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- A not-so-systematic review - The authors respond.Ebrahim S, Mollon B, Bance S, Busse JW, Bhandari MCan J Surg
- Social Integration and Mortality in Patients With Coronary Heart Disease: Findings From the Heart and Soul Study.Kreibig SD, Whooley MA, Gross JJPsychosom Med
- Risk of Narcolepsy Associated with Inactivated Adjuvanted (AS03) A/H1N1 (2009) Pandemic Influenza Vaccine in Quebec.Montplaisir J, Petit D, Quinn MJ, Ouakki M, Deceuninck G, Desautels A, Mignot E, De Wals PPLoS One
- Electroencephalographic Variation during End Maintenance and Emergence from Surgical Anesthesia.Chander D, García PS, MacColl JN, Illing S, Sleigh JWPLoS One
- Endoscopists can sustain high performance for the optical diagnosis of colorectal polyps following standardized and continued training.McGill SK, Soetikno R, Rastogi A, Rouse RV, Sato T, Bansal A, McQuaid K, Kaltenbach TEndoscopy
- The Strange Allure of State "Right-to-Try" Laws.Zettler PJ, Greely HTJAMA Intern Med
- Casein Kinase 2: a novel player in glioblastoma therapy and cancer stem cells.Agarwal M, Nitta RT, Li GJ Mol Genet Med
- Complications following primary and revision transsphenoidal surgeries for pituitary tumors.Krings JG, Kallogjeri D, Wineland A, Nepple KG, Piccirillo JF, Getz AELaryngoscope
- P-Wave Characteristics on Routine Preoperative Electrocardiogram Improve Prediction of New-Onset Postoperative Atrial Fibrillation in Cardiac Surgery.Wong JK, Lobato RL, Pinesett A, Maxwell BG, Mora-Mangano CT, Perez MVJ Cardiothorac Vasc Anesth
- The dilemma of vaginal breech delivery worldwide.Weiniger CF, Carvalho BLancet
- Neuroprotective effects of aldehyde dehydrogenase 2 activation in rotenone-induced cellular and animal models of parkinsonism.Chiu CC, Yeh TH, Lai SC, Wu-Chou YH, Chen CH, Mochly-Rosen D, Huang YC, Chen YJ, Chen CL, Chang YM, Wang HL, Lu CSExp Neurol
- NADPH oxidases: an overview from structure to innate immunity-associated pathologies.Panday A, Sahoo MK, Osorio D, Batra SCell Mol Immunol
- Engineering a vascularized collagen-β-tricalcium phosphate graft using an electrochemical approach.Kang Y, Mochizuki N, Khademhosseini A, Fukuda J, Yang YActa Biomater
- Predicting water quality at Santa Monica Beach: Evaluation of five different models for public notification of unsafe swimming conditions.Thoe W, Gold M, Griesbach A, Grimmer M, Taggart ML, Boehm ABWater Res
- Correlation of Continuous Glucose Monitoring Profiles with Pregnancy Outcomes in Nondiabetic Women.Sung JF, Kogut EA, Lee HC, Mannan JL, Navabi K, Taslimi MM, El-Sayed YYAm J Perinatol
- Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress.Myers AJ, Williams L, Gatt JM, McAuley-Clark EZ, Dobson-Stone C, Schofield PR, Nemeroff CBJ Psychiatr Res
- Protein corona change the drug release profile of nanocarriers: The "overlooked" factor at the nanobio interface.Behzadi S, Serpooshan V, Sakhtianchi R, Müller B, Landfester K, Crespy D, Mahmoudi MColloids Surf B Biointerfaces
- Vorapaxar in patients with peripheral artery disease and acute coronary syndrome: Insights from Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER).Jones WS, Tricoci P, Huang Z, Moliterno DJ, Harrington RA, Sinnaeve PR, Strony J, Van de Werf F, White HD, Held C, Armstrong PW, Aylward PE, Chen E, Patel MR, Mahaffey KWAm Heart J
- Reasons for warfarin discontinuation in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF).O'Brien EC, Simon DN, Allen LA, Singer DE, Fonarow GC, Kowey PR, Thomas LE, Ezekowitz MD, Mahaffey KW, Chang P, Piccini JP, Peterson EDAm Heart J
- Shiny-phyloseq: Web Application for Interactive Microbiome Analysis with Provenance Tracking.McMurdie PJ, Holmes SBioinformatics
- Residential agricultural pesticide exposures and risk of selected congenital heart defects among offspring in the San Joaquin Valley of California.Carmichael SL, Yang W, Roberts E, Kegley SE, Padula AM, English PB, Lammer EJ, Shaw GMEnviron Res
- Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma.Cerhan JR, Berndt SI, Vijai J, Ghesquières H, McKay J, Wang SS, Wang Z, Yeager M, Conde L, de Bakker PI, Nieters A, Cox D, Burdett L, Monnereau A, Flowers CR, De Roos AJ, Brooks-Wilson AR, Lan Q, Severi G, Melbye M, Gu J, Jackson RD, Kane E, Teras LR, Purdue MP, Vajdic CM, Spinelli JJ, Giles GG, Albanes D, Kelly RS, Zucca M, Bertrand KA, Zeleniuch-Jacquotte A, Lawrence C, Hutchinson A, Zhi D, Habermann TM, Link BK, Novak AJ, Dogan A, Asmann YW, Liebow M, Thompson CA, Ansell SM, Witzig TE, Weiner GJ, Veron AS, Zelenika D, Tilly H, Haioun C, Molina TJ, Hjalgrim H, Glimelius B, Adami HO, Bracci PM, Riby J, Smith MT, Holly EA, Cozen W, Hartge P, Morton LM, Severson RK, Tinker LF, North KE, Becker N, Benavente Y, Boffetta P, Brennan P, Foretova L, Maynadie M, Staines A, Lightfoot T, Crouch S, Smith A, Roman E, Diver WR, Offit K, Zelenetz A, Klein RJ, Villano DJ, Zheng T, Zhang Y, Holford TR, Kricker A, Turner J, Southey MC, Clavel J, Virtamo J, Weinstein S, Riboli E, Vineis P, Kaaks R, Trichopoulos D, Vermeulen RC, Boeing H, Tjonneland A, Angelucci E, Di Lollo S, Rais M, Birmann BM, Laden F, Giovannucci E, Kraft P, Huang J, Ma B, Ye Y, Chiu BC, Sampson J, Liang L, Park JH, Chung CC, Weisenburger DD, Chatterjee N, Fraumeni JF, Slager SL, Wu X, de Sanjose S, Smedby KE, Salles G, Skibola CF, Rothman N, Chanock SJNat Genet
- Retrospective studies provide valuable information.Riley EAnaesthesia
- Quantifying soft tissue loss in the aging male face using magnetic resonance imaging.Wysong A, Kim D, Joseph T, MacFarlane DF, Tang JY, Gladstone HBDermatol Surg
- A novel, catheter-based approach to left ventricular assist device deactivation after myocardial recovery.Zeigler SM, Sheikh AY, Lee PH, Desai J, Banerjee D, Oyer P, Dake MD, Ha RVAnn Thorac Surg
- Off-label use of recombinant human factor VIIa.Goodnough LT, Levy JHAnn Thorac Surg
- Pumping it up! Angiogenesis and muscle deconditioning in pulmonary hypertension.de Jesus Perez VAAm J Respir Crit Care Med
- Connectivity strength of dissociable striatal tracts predict individual differences in temporal discounting.van den Bos W, Rodriguez CA, Schweitzer JB, McClure SMJ Neurosci
- Longitudinal profiles of adaptive behavior in fragile X syndrome.Klaiman C, Quintin EM, Jo B, Lightbody AA, Hazlett HC, Piven J, Hall SS, Reiss ALPediatrics
- Gestational age and risk of venous thromboembolism from birth through young adulthood.Zöller B, Li X, Sundquist J, Sundquist K, Crump CPediatrics
- Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer.Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, Church JM, Dominitz JA, Johnson DA, Kaltenbach T, Levin TR, Lieberman DA, Robertson DJ, Syngal S, Rex DKAm J Gastroenterol
- Prevention of traumatic stress in mothers of preterms: 6-month outcomes.Shaw RJ, St John N, Lilo E, Jo B, Benitz W, Stevenson DK, Horwitz SMPediatrics
- Sustaining pressure ulcer best practices in a high-volume cardiac care environment.Paul R, McCutcheon SP, Tregarthen JP, Denend LT, Zenios SAAm J Nurs
- Decreasing handoff-related care failures in children's hospitals.Bigham MT, Logsdon TR, Manicone PE, Landrigan CP, Hayes LW, Randall KH, Grover P, Collins SB, Ramirez DE, O'Guin CD, Williams CI, Warnick RJ, Sharek PJPediatrics
- A meta-analysis of surgical versus nonsurgical management of recurrent thymoma.Hamaji M, Ali SO, Burt BMAnn Thorac Surg
- Mechanically triggered heterolytic unzipping of a low-ceiling-temperature polymer.Diesendruck CE, Peterson GI, Kulik HJ, Kaitz JA, Mar BD, May PA, White SR, Martínez TJ, Boydston AJ, Moore JSNat Chem
- Human NK cells licensed by killer Ig receptor genes have an altered cytokine program that modifies CD4+ T cell function.Lin L, Ma C, Wei B, Aziz N, Rajalingam R, Yusung S, Erlich HA, Trachtenberg EA, Targan SR, McGovern DP, Heath JR, Braun JJ Immunol
- Chemically defined generation of human cardiomyocytes.Burridge PW, Matsa E, Shukla P, Lin ZC, Churko JM, Ebert AD, Lan F, Diecke S, Huber B, Mordwinkin NM, Plews JR, Abilez OJ, Cui B, Gold JD, Wu JCNat Methods
- A balance between B cell receptor and inhibitory receptor signaling controls plasma cell differentiation by maintaining optimal Ets1 levels.Luo W, Mayeux J, Gutierrez T, Russell L, Getahun A, Müller J, Tedder T, Parnes J, Rickert R, Nitschke L, Cambier J, Satterthwaite AB, Garrett-Sinha LAJ Immunol
- A detailed staging scheme for late larval development in Strongylocentrotus purpuratus focused on readily-visible juvenile structures within the rudiment.Heyland A, Hodin JBMC Dev Biol
- SCAI/AATS/ACC/STS operator and institutional requirements for transcatheter valve repair and replacement: Part II. Mitral valve.Tommaso CL, Fullerton DA, Feldman T, Dean LS, Hijazi ZM, Horlick E, Weiner BH, Zahn E, Cigarroa JE, Ruiz CE, Bavaria J, Mack MJ, Cameron DE, Bolman RM, Miller DC, Moon MR, Mukherjee D, Trento A, Aldea GS, Bacha EA, Society for Cardiovascular Angiography and Interventions, American Association for Thoracic Surgery, American College of Cardiology, Society of Thoracic SurgeonsAnn Thorac Surg
- Combined elevated midpregnancy tumor necrosis factor alpha and hyperlipidemia in pregnancies resulting in early preterm birth.Jelliffe-Pawlowski LL, Ryckman KK, Bedell B, O'Brodovich HM, Gould JB, Lyell DJ, Borowski KS, Shaw GM, Murray JC, Stevenson DKAm J Obstet Gynecol
- Signal recognition particle-ribosome binding is sensitive to nascent chain length.Noriega TR, Tsai A, Elvekrog MM, Petrov A, Neher SB, Chen J, Bradshaw N, Puglisi JD, Walter PJ Biol Chem
- Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices.Ascheim DD, Gelijns AC, Goldstein D, Moye LA, Smedira N, Lee S, Klodell CT, Szady A, Parides MK, Jeffries NO, Skerrett D, Taylor DA, Rame JE, Milano C, Rogers JG, Lynch J, Dewey T, Eichhorn E, Sun B, Feldman D, Simari R, O'Gara PT, Taddei-Peters WC, Miller MA, Naka Y, Bagiella E, Rose EA, Woo YJCirculation
- Association between maternal characteristics, abnormal serum aneuploidy analytes, and placental abruption.Blumenfeld YJ, Baer RJ, Druzin ML, El-Sayed YY, Lyell DJ, Faucett AM, Shaw GM, Currier RJ, Jelliffe-Pawlowski LLAm J Obstet Gynecol
- Insulin secretory function: not a simple measurement.Reaven GJ Intern Med
- A general protocol for the generation of Nanobodies for structural biology.Pardon E, Laeremans T, Triest S, Rasmussen SG, Wohlkönig A, Ruf A, Muyldermans S, Hol WG, Kobilka BK, Steyaert JNat Protoc
- Current methods in the molecular typing of Mycobacterium tuberculosis and other mycobacteria.Jagielski T, van Ingen J, Rastogi N, Dziadek J, Mazur PK, Bielecki JBiomed Res Int
- A mouse model of permanent focal ischemia: distal middle cerebral artery occlusion.Doyle KP, Buckwalter MSMethods Mol Biol
- Reply to Breschan et al, re 'central venus catheter placement in children'.Kamra K, Hammer GPaediatr Anaesth
- Contemporary incidence, predictors, and outcomes of acute kidney injury in patients undergoing percutaneous coronary interventions: insights from the NCDR Cath-PCI registry.Tsai TT, Patel UD, Chang TI, Kennedy KF, Masoudi FA, Matheny ME, Kosiborod M, Amin AP, Messenger JC, Rumsfeld JS, Spertus JAJACC Cardiovasc Interv
- Aftermath of Typhoon Haiyan: the imminent epidemic of waterborne illnesses in Leyte, Philippines.Dolhun EDisaster Med Public Health Prep
- NIR-light-induced surface-enhanced Raman scattering for detection and photothermal/photodynamic therapy of cancer cells using methylene blue-embedded gold nanorod@SiO2 nanocomposites.Seo SH, Kim BM, Joe A, Han HW, Chen X, Cheng Z, Jang ESBiomaterials
- Reversible cerebral vasoconstriction syndrome and bilateral vertebral artery dissection presenting in a patient after cesarean section.Mitchell LA, Santarelli JG, Singh IP, Do HMJ Neurointerv Surg
- Diagnostic and Statistical Manual of Mental Disorders: the solution or the problem?Reiff MI, Feldman HMJ Dev Behav Pediatr
- Evidence-based de-implementation for contradicted, unproven, and aspiring healthcare practices.Prasad V, Ioannidis JPImplement Sci
- Prevention of high altitude illness.Zafren KTravel Med Infect Dis
- The symptom cluster-based approach to individualize patient-centered treatment for major depression.Lin SY, Stevens MBJ Am Board Fam Med
- The role of Ryk and Ror receptor tyrosine kinases in Wnt signal transduction.Green J, Nusse R, van Amerongen RCold Spring Harb Perspect Biol
- Incorporation of flexible objectives and time-linked simulation with flux balance analysis.Birch EW, Udell M, Covert MWJ Theor Biol
- Utilizing combinatorial chemistry and rational design: peptidic tweezers with nanomolar affinity to DNA can be transformed into efficient vectors for gene delivery by addition of a lipophilic tail.Kuchelmeister HY, Karczewski S, Gutschmidt A, Knauer S, Schmuck CAngew Chem Int Ed Engl
- Auditory cortex activation to natural speech and simulated cochlear implant speech measured with functional near-infrared spectroscopy.Pollonini L, Olds C, Abaya H, Bortfeld H, Beauchamp MS, Oghalai JSHear Res
- Safety and efficacy of low-dose paclitaxel utilizing the cobra-P drug-eluting stent system with a novel biodegradable coating in de novo coronary lesions: the PLUS-ONE first-in-man study.Calderas C, Condado JF, Condado JA, Flores A, Mueller A, Thomas J, Nakatani D, Honda Y, Waseda K, Fitzgerald PCardiovasc Revasc Med
- The relationship between male BMI and waist circumference on semen quality: data from the LIFE study.Eisenberg ML, Kim S, Chen Z, Sundaram R, Schisterman EF, Buck Louis GMHum Reprod
- Integration of palliative care into emergency medicine: the Improving Palliative Care in Emergency Medicine (IPAL-EM) collaboration.Lamba S, DeSandre PL, Todd KH, Bryant EN, Chan GK, Grudzen CR, Weissman DE, Quest TE, Improving Palliative Care in Emergency Medicine BoardJ Emerg Med
- Evaluating noncoding nucleotide repeat expansions in amyotrophic lateral sclerosis.Figley MD, Thomas A, Gitler ADNeurobiol Aging
- Tissue engineering in flexor tendon surgery: current state and future advances.Galvez MG, Crowe C, Farnebo S, Chang JJ Hand Surg Eur Vol
- An integrated model of stomatal development and leaf physiology.Dow GJ, Bergmann DC, Berry JANew Phytol
- Blood collection tube-related alterations in analyte concentrations in quality control material and serum specimens.Bowen RA, Sattayapiwat A, Gounden V, Remaley ATClin Biochem
- Use of eculizumab and plasma exchange in successful combined liver-kidney transplantation in a case of atypical HUS associated with complement factor H mutation.Tran H, Chaudhuri A, Concepcion W, Grimm PCPediatr Nephrol
- The physiological importance of developmental mechanisms that enforce proper stomatal spacing in Arabidopsis thaliana.Dow GJ, Berry JA, Bergmann DCNew Phytol
- A systematic comparison between 1-D and 3-D hemodynamics in compliant arterial models.Xiao N, Alastruey J, Alberto Figueroa CInt J Numer Method Biomed Eng
- Moderate hypothermia inhibits brain inflammation and attenuates stroke-induced immunodepression in rats.Gu LJ, Xiong XX, Ito T, Lee J, Xu BH, Krams S, Steinberg GK, Zhao HCNS Neurosci Ther
- Marine protected areas facilitate parasite populations among four fished host species of central Chile.Wood CL, Micheli F, Fernández M, Gelcich S, Castilla JC, Carvajal JJ Anim Ecol
- Acute uremia suppresses leucine-induced signal transduction in skeletal muscle.McIntire KL, Chen Y, Sood S, Rabkin RKidney Int
- A simple method for purification of vestibular hair cells and non-sensory cells, and application for proteomic analysis.Herget M, Scheibinger M, Guo Z, Jan TA, Adams CM, Cheng AG, Heller SPLoS One
- NIPT in a clinical setting: an analysis of uptake in the first months of clinical availability.Taylor JB, Chock VY, Hudgins LJ Genet Couns
- Knowledge and attitudes of anesthesia providers about noncardiac surgery in adults with congenital heart disease.Maxwell BG, Williams GD, Ramamoorthy CCongenit Heart Dis
- Transcatheter device closure of a congenital aortic-left atrial tunnel.Sun HY, Buccola KJ, Punn R, Silverman NH, Peng LF, Perry SB, Balasubramanian SCongenit Heart Dis
- Traumatic lacerations: what are the risks for infection and has the 'golden period' of laceration care disappeared?Quinn JV, Polevoi SK, Kohn MAEmerg Med J
A not-so-systematic review - The authors respond.
Can J Surg. 2014 Oct;57(5):E152-E153
Authors: Ebrahim S, Mollon B, Bance S, Busse JW, Bhandari M
PMID: 25265120 [PubMed - as supplied by publisher]
Social Integration and Mortality in Patients With Coronary Heart Disease: Findings From the Heart and Soul Study.
Psychosom Med. 2014 Sep 26;
Authors: Kreibig SD, Whooley MA, Gross JJ
OBJECTIVE: To determine why lower social integration predicts higher mortality in patients with coronary heart disease (CHD).
METHODS: The association between social integration and mortality was examined prospectively in 1019 outpatients with stable CHD from the Heart and Soul Study. Baseline social integration was assessed with the Berkman Social Network Index. Cox proportional hazards models were used to determine the extent to which demographic and disease-relevant confounders and potential biological, behavioral, and psychological mediators explained the association between social integration and mortality.
RESULTS: During a mean (standard deviation) follow-up period of 6.7 (2.3) years, the age-adjusted annual rate of mortality was 6.3% among socially isolated patients and 4.1% among nonisolated patients (age-adjusted hazard ratio [HR] = 1.61, 95% confidence interval [CI] = 1.26-2.05, p < .001). After adjustment for demographic and disease-relevant confounders, socially isolated patients had a 50% greater risk of death than did nonisolated patients (HR = 1.50, 95% CI = 1.07-2.10). Separate adjustment for potential biological (HR = 1.53, CI = 1.05-2.25) and psychological mediators (HR = 1.52, CI = 1.08-2.14) did not significantly attenuate this association, whereas adjustment for potential behavioral mediators did (HR = 1.30, CI = 0.91-1.86). C-reactive protein and hemoglobin A1c were identified as important biological and omega-3 fatty acids, smoking, and medication adherence as important behavioral potential mediators, with smoking making the largest contribution.
CONCLUSIONS: In this sample of outpatients with baseline stable CHD, the association between social integration and mortality was largely explained by health-related behavioral pathways, particularly smoking.
PMID: 25264970 [PubMed - as supplied by publisher]
Risk of Narcolepsy Associated with Inactivated Adjuvanted (AS03) A/H1N1 (2009) Pandemic Influenza Vaccine in Quebec.
PLoS One. 2014;9(9):e108489
Authors: Montplaisir J, Petit D, Quinn MJ, Ouakki M, Deceuninck G, Desautels A, Mignot E, De Wals P
CONTEXT: An association between an adjuvanted (AS03) A/H1N1 pandemic vaccine and narcolepsy has been reported in Europe.
OBJECTIVE: To assess narcolepsy risk following administration of a similar vaccine in Quebec.
DESIGN: Retrospective population-based study.
SETTING: Neurologists and lung specialists in the province were invited to report narcolepsy cases to a single reference centre.
POPULATION: Patients were interviewed by two sleep experts and standard diagnostic tests were performed. Immunization status was verified in the provincial pandemic influenza vaccination registry.
MAIN OUTCOME MEASURES: Confirmed narcolepsy with or without cataplexy with onset of excessive daytime sleepiness between January 1st, 2009, and December 31st, 2010. Relative risks (RRs) were calculated using a Poisson model in a cohort analysis, by a self-controlled case series (SCCS) and a case-control method.
RESULTS: A total of 24 cases were included and overall incidence rate was 1.5 per million person-years. A cluster of 7 cases was observed among vaccinated persons in the winter 2009-2010. In the primary cohort analysis, 16-week post-vaccination RR was 4.32 (95% CI: 1.50-11.12). RR was 2.07 (0.70-6.17) in the SCCS, and 1.48 (0.37-7.03) using the case-control method. Estimates were lower when observation was restricted to the period of pandemic influenza circulation, and tended to be higher in persons <20 years old and for cataplexy cases.
CONCLUSIONS: Results are compatible with an excess risk of approximately one case per million vaccine doses, mainly in persons less than 20 years of age. However, a confounding effect of the influenza infection cannot be ruled out.
PMID: 25264897 [PubMed - as supplied by publisher]
Electroencephalographic Variation during End Maintenance and Emergence from Surgical Anesthesia.
PLoS One. 2014;9(9):e106291
Authors: Chander D, García PS, MacColl JN, Illing S, Sleigh JW
The re-establishment of conscious awareness after discontinuing general anesthesia has often been assumed to be the inverse of loss of consciousness. This is despite the obvious asymmetry in the initiation and termination of natural sleep. In order to characterize the restoration of consciousness after surgery, we recorded frontal electroencephalograph (EEG) from 100 patients in the operating room during maintenance and emergence from general anesthesia. We have defined, for the first time, 4 steady-state patterns of anesthetic maintenance based on the relative EEG power in the slow-wave (<14 Hz) frequency bands that dominate sleep and anesthesia. Unlike single-drug experiments performed in healthy volunteers, we found that surgical patients exhibited greater electroencephalographic heterogeneity while re-establishing conscious awareness after drug discontinuation. Moreover, these emergence patterns could be broadly grouped according to the duration and rapidity of transitions amongst these slow-wave dominated brain states that precede awakening. Most patients progressed gradually from a pattern characterized by strong peaks of delta (0.5-4 Hz) and alpha/spindle (8-14 Hz) power ('Slow-Wave Anesthesia') to a state marked by low delta-spindle power ('Non Slow-Wave Anesthesia') before awakening. However, 31% of patients transitioned abruptly from Slow-Wave Anesthesia to waking; they were also more likely to express pain in the post-operative period. Our results, based on sleep-staging classification, provide the first systematized nomenclature for tracking brain states under general anesthesia from maintenance to emergence, and suggest that these transitions may correlate with post-operative outcomes such as pain.
PMID: 25264892 [PubMed - as supplied by publisher]
Endoscopists can sustain high performance for the optical diagnosis of colorectal polyps following standardized and continued training.
Endoscopy. 2014 Sep 29;
Authors: McGill SK, Soetikno R, Rastogi A, Rouse RV, Sato T, Bansal A, McQuaid K, Kaltenbach T
Background and study aims: The learning curve for optical diagnosis of colorectal polyps with the narrow-band imaging (NBI) is unknown. To forego histological analysis of diminutive polyps diagnosed optically with high confidence, guidelines recommend ≥ 90 % negative predictive value (NPV) and concordance of ≥ 90 % for surveillance intervals predicted optically and histologically. We aimed to study the learning of optical diagnosis for colorectal polyps. Patients and methods: We studied five endoscopists as part of a randomized multisite trial comparing near-focus and standard-focus views for optical diagnosis. They trained using a computer-based module, followed by 10 real-time colonoscopies with pathology correlation. Endoscopists then optically diagnosed and resected all the polyps found during 558 consecutive colonoscopies, and diagnoses were compared with pathology. Endoscopists repeated the training module at the study midpoint. NPV and concordance of surveillance intervals for diminutive polyps diagnosed optically with high confidence were measured over time. Results: Endoscopists showed high diagnostic performance, with a nonsignificant trend toward higher NPV in the second half of the study. For the 445 polyps in the standard-view arm, the NPV was 88.0 % (95 %CI 75.7 % - 95.5 %) in the first half and 95.8 % (88.3 % - 99.1 %) in the second; P = 0.7. Three endoscopists in the first half and four in the second achieved > 90 % NPV. Concordance of surveillance intervals was identical in the first and second halves at 98.1 % (95 %CI 93.3 % - 99.8 %). Conclusions: High NPV for the prediction of non-neoplasms with NBI was achieved and maintained in this group of endoscopists who participated in standardized and continued training. Both NPV and surveillance interval agreement indicated high performance in the optical diagnosis of colorectal polyps and exceeded thresholds.
PMID: 25264764 [PubMed - as supplied by publisher]
The Strange Allure of State "Right-to-Try" Laws.
JAMA Intern Med. 2014 Sep 29;
Authors: Zettler PJ, Greely HT
PMID: 25264589 [PubMed - as supplied by publisher]
Casein Kinase 2: a novel player in glioblastoma therapy and cancer stem cells.
J Mol Genet Med. 2013 Dec 9;8(1)
Authors: Agarwal M, Nitta RT, Li G
Casein kinase 2 (CK2) is an oncogenic protein kinase which contributes to tumor development, proliferation, and suppression of apoptosis in multiple cancer types. The mechanism by which CK2 expression and activity leads to tumorigenesis in glioblastoma (GBM), a stage IV primary brain tumor, is being studied. Recent studies demonstrate that CK2 plays an important role in GBM formation and growth through the inhibition of tumor suppressors and activation of oncogenes. In addition, intriguing new reports indicate that CK2 may regulate GBM formation in a novel manner; CK2 may play a critical role in cancer stem cell (CSC) maintenance. Since glial CSCs have the ability to self-renew and initiate tumor growth, new treatments which target these CSCs are needed to treat this fatal disease. Inhibition of CK2 is potentially a novel method to inhibit GBM growth and reoccurrence by targeting the glial CSCs. A new, orally available, selective CK2 inhibitor, CX-4945 has had promising results when tested in cancer cell lines, in vivo xenograft models, and human clinical trials. The development of CK2 targeted inhibitors, starting with CX-4945, may lead to a new class of more effective cancer therapies.
PMID: 25264454 [PubMed - as supplied by publisher]
Complications following primary and revision transsphenoidal surgeries for pituitary tumors.
Laryngoscope. 2014 Sep 27;
Authors: Krings JG, Kallogjeri D, Wineland A, Nepple KG, Piccirillo JF, Getz AE
OBJECTIVES/HYPOTHESIS: This study aimed to determine the incidence of major complications following both primary and revision transsphenoidal pituitary surgery. Major complications included endocrinopathic, skull base, orbital, hemorrhagic and thromboembolic complications, respiratory failure, and death. Secondarily, this study aimed to examine factors associated with the occurrence of complications.
STUDY DESIGN: Retrospective cohort analysis of California and Florida all-payer databases from 2005 to 2008.
METHODS: The major complication rate following both primary and revision transsphenoidal pituitary surgery was calculated. Bivariate analyses were performed to investigate the relationship of patient characteristics with complication occurrence, and a multivariate model was constructed to determine risk factors associated with these complications.
RESULTS: There were 5,277 primary cases and 192 revision cases that met inclusion criteria. There was a nonsignificant absolute difference of 3.09% (95% confidence interval [CI]: -11.00 to 16.14) between the rate of complications following primary (n = 443, 8.39%) and revision (n = 22, 11.46%) surgeries. Multivariate analyses showed that patients with Medicare (odds ratio [OR]:1.74, 95% CI: 1.17 to 2.61), Medicaid (OR: 2.13, 95% CI: 1.59 to 2.86), or a malignant neoplasm (OR: 3.10, 95% CI: 1.62 to 5.93) were more likely to have complications.
CONCLUSIONS: The rate of major complications following transsphenoidal pituitary surgery is lower than earlier retrospective reports. The overall complication rate following revision surgery was not significantly different from primary surgery. Insurance status and a diagnosis of a malignant neoplasm were associated with a higher rate of complications.
LEVEL OF EVIDENCE: 2C Laryngoscope, 2014.
PMID: 25263939 [PubMed - as supplied by publisher]
P-Wave Characteristics on Routine Preoperative Electrocardiogram Improve Prediction of New-Onset Postoperative Atrial Fibrillation in Cardiac Surgery.
J Cardiothorac Vasc Anesth. 2014 Sep 25;
Authors: Wong JK, Lobato RL, Pinesett A, Maxwell BG, Mora-Mangano CT, Perez MV
OBJECTIVE: To test the hypothesis that including preoperative electrocardiogram (ECG) characteristics with clinical variables significantly improves the new-onset postoperative atrial fibrillation prediction model.
DESIGN: Retrospective analysis.
SETTING: Single-center university hospital.
PARTICIPANTS: Five hundred twenty-six patients,≥18 years of age, who underwent coronary artery bypass grafting, aortic valve replacement, mitral valve replacement/repair, or a combination of valve surgery and coronary artery bypass grafting requiring cardiopulmonary bypass.
INTERVENTIONS: Retrospective review of medical records.
MEASUREMENTS AND MAIN RESULTS: Baseline characteristics and cardiopulmonary bypass times were collected. Digitally-measured timing and voltages from preoperative electrocardiograms were extracted. Postoperative atrial fibrillation was defined as atrial fibrillation requiring therapeutic intervention. Two hundred eight (39.5%) patients developed postoperative atrial fibrillation. Clinical predictors were age, ejection fraction<55%, history of atrial fibrillation, history of cerebral vascular event, and valvular surgery. Three ECG parameters associated with postoperative atrial fibrillation were observed: Premature atrial contraction, p-wave index, and p-frontal axis. Adding electrocardiogram variables to the prediction model with only clinical predictors significantly improved the area under the receiver operating characteristic curve, from 0.71 to 0.78 (p<0.01). Overall net reclassification improvement was 0.059 (p = 0.09). Among those who developed postoperative atrial fibrillation, the net reclassification improvement was 0.063 (p = 0.03).
CONCLUSION: Several p-wave characteristics are independently associated with postoperative atrial fibrillation. Addition of these parameters improves the postoperative atrial fibrillation prediction model.
PMID: 25263779 [PubMed - as supplied by publisher]
The dilemma of vaginal breech delivery worldwide.
Lancet. 2014 Sep 27;384(9949):1183
Authors: Weiniger CF, Carvalho B
PMID: 25263673 [PubMed - in process]
Neuroprotective effects of aldehyde dehydrogenase 2 activation in rotenone-induced cellular and animal models of parkinsonism.
Exp Neurol. 2014 Sep 25;
Authors: Chiu CC, Yeh TH, Lai SC, Wu-Chou YH, Chen CH, Mochly-Rosen D, Huang YC, Chen YJ, Chen CL, Chang YM, Wang HL, Lu CS
Many studies have shown that mitochondrial aldehyde dehydrogenase 2 (ALDH2) functions as a cellular protector against oxidative stress by detoxification of cytotoxic aldehydes. Within dopaminergic neurons, dopamine is metabolized by monoamine oxidase to yield 3,4-dihydroxyphenylacetaldehyde (DOPAL) then converts to a less toxic acid product by ALDH. The highly toxic and reactive DOPAL has been hypothesized to contribute to the selective neurodegeneration in Parkinson's disease (PD). In this study, we investigated the neuroprotective mechanism and therapeutic effect of ALDH2 in rotenone models for parkinsonism. Overexpression of wild-type ALDH2 gene, but not the enzymatically deficient mutant ALDH2*2 (E504K), reduced rotenone-induced cell death. Application of a potent activator of ALDH2, Alda-1, was effective in protecting against rotenone-induced apoptotic cell death in both SH-SY5Y cells and primary cultured substantia nigra (SN) dopaminergic neurons. In addition, intraperitoneal administration of Alda-1 significantly reduced rotenone- or MPTP-induced death of SN tyrosine hydroxylase (TH)-positive dopaminergic neurons. The attenuation of rotenone-induced apoptosis by Alda-1 resulted from decreasing ROS accumulation, reversal of mitochondrial membrane potential depolarization, and inhibition of activation of proteins related to mitochondrial apoptotic pathway. The present study demonstrates that ALDH2 plays a crucial role in maintaining normal mitochondrial function to protect against neurotoxicity and that Alda-1 is effective in ameliorating mitochondrial dysfunction and inhibiting mitochondria-mediated apoptotic pathway. These results indicate that ALDH2 activation could be a neuroprotective therapy for PD.
PMID: 25263579 [PubMed - as supplied by publisher]
NADPH oxidases: an overview from structure to innate immunity-associated pathologies.
Cell Mol Immunol. 2014 Sep 29;
Authors: Panday A, Sahoo MK, Osorio D, Batra S
Oxygen-derived free radicals, collectively termed reactive oxygen species (ROS), play important roles in immunity, cell growth, and cell signaling. In excess, however, ROS are lethal to cells, and the overproduction of these molecules leads to a myriad of devastating diseases. The key producers of ROS in many cells are the NOX family of NADPH oxidases, of which there are seven members, with various tissue distributions and activation mechanisms. NADPH oxidase is a multisubunit enzyme comprising membrane and cytosolic components, which actively communicate during the host responses to a wide variety of stimuli, including viral and bacterial infections. This enzymatic complex has been implicated in many functions ranging from host defense to cellular signaling and the regulation of gene expression. NOX deficiency might lead to immunosuppression, while the intracellular accumulation of ROS results in the inhibition of viral propagation and apoptosis. However, excess ROS production causes cellular stress, leading to various lethal diseases, including autoimmune diseases and cancer. During the later stages of injury, NOX promotes tissue repair through the induction of angiogenesis and cell proliferation. Therefore, a complete understanding of the function of NOX is important to direct the role of this enzyme towards host defense and tissue repair or increase resistance to stress in a timely and disease-specific manner.Cellular & Molecular Immunology advance online publication, 29 September 2014; doi:10.1038/cmi.2014.89.
PMID: 25263488 [PubMed - as supplied by publisher]
Engineering a vascularized collagen-β-tricalcium phosphate graft using an electrochemical approach.
Acta Biomater. 2014 Sep 25;
Authors: Kang Y, Mochizuki N, Khademhosseini A, Fukuda J, Yang Y
Vascularization of three-dimensional large synthetic grafts for tissue regeneration remains a significant challenge. Here we demonstrate an electrochemical approach, named as cell electrochemical detachment (CED) technique,to form an integral endothelium and use it to prevascularize a collagen-β-tricalcium phosphate (β-TCP) graft. The CED technique electrochemically detached an integral endothelium from a gold-coated glass rod to a collagen infiltrated, channeled, macroporous β-TCP scaffold, forming an endothelium-lined microchannel containing graft upon removal of the rod. The in vitro results from static and perfusion culture show that the endothelium robustly emanated microvascular sprouting and prevascularized the entire collagen/β-TCP integrated graft. The in vivo subcutaneous implantation studies show that the prevascularized collagen/β-TCP grafts established blood flow originating from the endothelium-lined microchannel within a week, and the blood flow covered more areas in the graft over time. In addition, many blood vessels invaded the prevascularized collagen/β-TCP graft and the in vitro preformed microvascular networks anastomosed with the host vasculature, while collagen alone without the support of rigid ceramic scaffold showed less blood vessel invasion and anastomosis. These results suggest promising strategy for effectively vascularizing large tissue-engineered grafts by integrating multiple hydrogel-based CED-engineered endothelium-lined microchannels into a rigid channeled macroporous scaffold.
PMID: 25263031 [PubMed - as supplied by publisher]
Predicting water quality at Santa Monica Beach: Evaluation of five different models for public notification of unsafe swimming conditions.
Water Res. 2014 Sep 16;67C:105-117
Authors: Thoe W, Gold M, Griesbach A, Grimmer M, Taggart ML, Boehm AB
Bathing beaches are monitored for fecal indicator bacteria (FIB) to protect swimmers from unsafe conditions. However, FIB assays take ∼24 h and water quality conditions can change dramatically in that time, so unsafe conditions cannot presently be identified in a timely manner. Statistical, data-driven predictive models use information on environmental conditions (i.e., rainfall, turbidity) to provide nowcasts of FIB concentrations. Their ability to predict real time FIB concentrations can make them more accurate at identifying unsafe conditions than the current method of using day or older FIB measurements. Predictive models are used in the Great Lakes, Hong Kong, and Scotland for beach management, but they are presently not used in California - the location of some of the world's most popular beaches. California beaches are unique as point source pollution has generally been mitigated, the summer bathing season receives little to no rainfall, and in situ measurements of turbidity and salinity are not readily available. These characteristics may make modeling FIB difficult, as many current FIB models rely heavily on rainfall or salinity. The current study investigates the potential for FIB models to predict water quality at a quintessential California Beach: Santa Monica Beach. This study compares the performance of five predictive models, multiple linear regression model, binary logistic regression model, partial least square regression model, artificial neural network, and classification tree, to predict concentrations of summertime fecal coliform and enterococci concentrations. Past measurements of bacterial concentration, storm drain condition, and tide level are found to be critical factors in the predictive models. The models perform better than the current beach management method. The classification tree models perform the best; for example they correctly predict 42% of beach postings due to fecal coliform exceedances during model validation, as compared to 28% by the current method. Artificial neural network is the second best model which minimizes the number of incorrect beach postings. The binary logistic regression model also gives promising results, comparable to classification tree, by adjusting the posting decision thresholds to maximize correct beach postings. This study indicates that predictive models hold promise as a beach management tool at Santa Monica Beach. However, there are opportunities to further refine predictive models.
PMID: 25262555 [PubMed - as supplied by publisher]
Correlation of Continuous Glucose Monitoring Profiles with Pregnancy Outcomes in Nondiabetic Women.
Am J Perinatol. 2014 Sep 28;
Authors: Sung JF, Kogut EA, Lee HC, Mannan JL, Navabi K, Taslimi MM, El-Sayed YY
Objective To determine whether hyperglycemic excursions detected by continuous glucose monitoring (CGM) correlate with birth weight percentile and other pregnancy outcomes, and whether CGM correlates better with these outcomes than a single glucose value from a 1-hour glucose challenge test (GCT). Study Design This was a prospective observational study of 55 pregnant patients without preexisting diabetes, who wore a CGM device for up to 7 days, between 24 and 28 weeks' gestation. The area under the curve (AUC) of hyperglycemic excursions above various thresholds (110, 120, 130, 140, and 180 mg/dL) was calculated. These AUC values, and results from a standard 50-g GCT, were correlated with our primary outcome of birth weight percentile, and secondary outcomes of unplanned operative delivery, pregnancy complications, delivery complications, fetal complications, and neonatal complications. Results A consistent correlation was seen between all AUC thresholds and birth weight percentile (r = 0.29, p < 0.05 for AUC-110, -120, -130, and -140; r = 0.25, p = 0.07 for AUC-180). This correlation was stronger than that of 1-hour oral GCT (r = - 0.02, p = 0.88). There was no association between AUC values and other outcomes. Conclusions Among nondiabetic pregnant patients, hyperglycemic excursions detected by CGM show a stronger correlation to birth weight percentile than blood glucose values obtained 1-hour after a 50-g oral GCT.
PMID: 25262455 [PubMed - as supplied by publisher]
Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress.
J Psychiatr Res. 2014 Sep 16;
Authors: Myers AJ, Williams L, Gatt JM, McAuley-Clark EZ, Dobson-Stone C, Schofield PR, Nemeroff CB
BACKGROUND: Oxytocin is a neuropeptide that is involved in the regulation of mood, anxiety and social biology. Genetic variation in the oxytocin receptor gene (OXTR) has been implicated in anxiety, depression and related stress phenotypes. It is not yet known whether OXTR interacts with other risk factors such as early life trauma to heighten the severity of experienced anxiety and depression.
METHODS: In this study, we examined genotypes in 653 individuals and tested whether SNP variation in OXTR correlates with severity of features of self-reported experience on the Depression Anxiety and Stress Scale (DASS), and whether this correlation is enhanced when early life trauma is taken into account. We also assessed the effects of OXTR SNPs on RNA expression levels in two separate brain tissue cohorts totaling 365 samples.
RESULTS: A significant effect of OXTR genotype on DASS anxiety, stress and depression scores was found and ELS events, in combination with several different OXTR SNPs, were significantly associated with differences in DASS scores with one SNP (rs139832701) showing significant association or a trend towards association for all three measures. Several OXTR SNPs were correlated with alterations in OXTR RNA expression and rs3831817 replicated across both sets of tissues.
CONCLUSIONS: These results support the hypothesis that the oxytocin system plays a role in the pathophysiology of mood and anxiety disorders.
PMID: 25262417 [PubMed - as supplied by publisher]
Protein corona change the drug release profile of nanocarriers: The "overlooked" factor at the nanobio interface.
Colloids Surf B Biointerfaces. 2014 Sep 16;
Authors: Behzadi S, Serpooshan V, Sakhtianchi R, Müller B, Landfester K, Crespy D, Mahmoudi M
The emergence of nanocarrier systems in drug delivery applications has ushered in rapid development of new classes of therapeutic agents which can provide an essential breakthrough in the fight against refractory diseases. However, successful clinical application of nano-drug delivery devices has been limited mainly due to the lack of control on sustained release of therapeutics from the carriers. A wide range of sophisticated approaches employs the formation of crosslinkable, non-crosslinkable, stimuli-responsive polymer nanocarriers in order to enhance their delivery efficiency. Despite the extensive research conducted on the development of various nanocarriers, the effect of the biological milieu on the drug release profile of these constructs is not yet fully investigated. In particular, the formation of a protein corona on the surface of nanocarriers, when they interact with living organisms in vivo is largely decisive for their biological function. Using a number of synthetized (i.e., superparamagnetic iron oxide nanoparticles and polymeric nanocapsules) and commercialized nanocarriers (i.e., Abraxane(®), albumin-bound paclitaxel drug), this study demonstrates that the protein corona can shield the nanocarriers and, consequently, alters the release profile of the drugs from the nanocarriers. More specifically, the protein corona could significantly reduce the burst effect of either protein conjugated nanocarriers or carriers with surface loaded drug (i.e., SPIONs). However, the corona shell only slightly changed the release profile of polymeric nanocapsules. Therefore, the intermediary, buffer effect of the protein shells on the surface of nanoscale carriers plays a crucial role in their successful high-yield applications in vivo.
PMID: 25262409 [PubMed - as supplied by publisher]
Vorapaxar in patients with peripheral artery disease and acute coronary syndrome: Insights from Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER).
Am Heart J. 2014 Oct;168(4):588-96
Authors: Jones WS, Tricoci P, Huang Z, Moliterno DJ, Harrington RA, Sinnaeve PR, Strony J, Van de Werf F, White HD, Held C, Armstrong PW, Aylward PE, Chen E, Patel MR, Mahaffey KW
BACKGROUND: In the TRACER trial, vorapaxar, a protease-activated receptor-1 antagonist, plus standard care in non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients did not significantly reduce the primary composite end point but reduced a key secondary end point and significantly increased bleeding. History of peripheral artery disease (PAD) was a risk-enrichment inclusion criterion. We investigated the efficacy and safety of vorapaxar in NSTE ACS patients with documented PAD.
METHODS: TRACER was a double-blind, randomized trial comparing vorapaxar with placebo in 12,944 patients with NSTE ACS.
RESULTS: In total, 936 (7.2%) patients had a history of PAD. Ischemic events occurred more frequently among patients with PAD (25.3%) versus no PAD (12.2%, P < .001), and Global Use of Strategies to Open Occluded Coronary Arteries moderate/severe bleeding was more common in PAD (9.1%) versus no PAD (5.0%, P = .004). Similar rates of the composite end point (cardiovascular death, myocardial infarction, or stroke) occurred in patients with PAD treated with vorapaxar and placebo (21.7% vs 24.8%, P interaction = .787). Patients with PAD treated with vorapaxar, when compared with placebo, also had a numerical reduction in peripheral revascularization procedures (8.1% vs 9.0%, P = .158) and a lower extremity amputation rate (0.9% vs 1.5%, P = .107). Vorapaxar increased Global Use of Strategies to Open Occluded Coronary Arteries moderate/severe bleeding similarly in patients with PAD (hazard ratio 1.47, 95% CI 0.89-2.45) and without (hazard ratio 1.48, 95% CI 1.22-1.79; P interaction = .921).
CONCLUSIONS: Patients with NSTE ACS and PAD were at increased risk for ischemic events. Lower rates of ischemic end points, peripheral revascularization, and amputation with vorapaxar did not reach statistical significance but warrant further investigation. Vorapaxar increased bleeding in both patients with and without PAD at a similar magnitude of risk.
PMID: 25262270 [PubMed - in process]
Reasons for warfarin discontinuation in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF).
Am Heart J. 2014 Oct;168(4):487-94
Authors: O'Brien EC, Simon DN, Allen LA, Singer DE, Fonarow GC, Kowey PR, Thomas LE, Ezekowitz MD, Mahaffey KW, Chang P, Piccini JP, Peterson ED
BACKGROUND: Warfarin reduces thromboembolic risks in atrial fibrillation (AF), but therapeutic durability remains a concern.
METHODS: We used clinical data from ORBIT-AF, a nationwide outpatient AF registry conducted at 176 sites with follow-up data at 6 and 12 months, to examine longitudinal patterns of warfarin discontinuation. We estimated associations between patient and provider characteristics and report of any warfarin discontinuation using discrete time proportional odds models.
RESULTS: Of 10,132 AF patients enrolled in ORBIT-AF from June 2010 to August 2011, 6,110 (60.3%) were prescribed warfarin, had follow-up data, and were not switched to an alternative oral anticoagulant enrolled from June 2010 to August 2011. Over 1 year, 617 patients (10.1% of baseline warfarin users) discontinued warfarin therapy. Among incident warfarin users (starting therapy within 1 year of baseline survey), warfarin discontinuation rates rose to 17.1%. The most commonly reported reasons for warfarin discontinuation were physician preference (47.7%), patient refusal/preference (21.1%), bleeding event (20.2%), frequent falls/frailty (10.8%), high bleeding risk (9.8%), and patient inability to adhere to/monitor therapy (4.7%). In multivariable analysis, the factors most strongly associated with warfarin discontinuation were bleeding hospitalization during follow-up (odds ratio 10.91, 95% CI 7.91-15.03), prior catheter ablation (1.83, 1.37-2.45), noncardiovascular/nonbleeding hospitalization (1.77, 1.40-2.24), cardiovascular hospitalization (1.64, 1.33-2.03), and permanent AF (0.25, 0.17-0.36).
CONCLUSIONS: Discontinuation of warfarin is common among patients with AF, particularly among incident users. Warfarin is most commonly discontinued because of physician preference, patient refusal, and bleeding events.
PMID: 25262258 [PubMed - in process]
Shiny-phyloseq: Web Application for Interactive Microbiome Analysis with Provenance Tracking.
Bioinformatics. 2014 Sep 26;
Authors: McMurdie PJ, Holmes S
SUMMARY: We have created a Shiny-based web application, called Shiny-phyloseq, for dynamic interaction with microbiome data that runs on any modern web-browser, and requires no programming to use - increasing the accessibility and decreasing the entrance requirement to using phyloseq and related R tools. Along with a data- and context-aware dynamic interface for exploring the effects of parameter and method choices, Shiny-phyloseq also records the complete user-input and subsequent graphical results of a user's session, allowing the user to archive, share, and reproduce the sequence of steps that created their result - without writing any new code themselves. Availability and Implementation: Shiny-phyloseq is implemented entirely in the R language. It can be hosted/launched by any system with R installed, including Windows, Mac OS, and most Linux distributions. Information technology administrators can also host Shiny-phyloseq from a remote server, in which case users need only have a web-browser installed. Shiny-phyloseq is provided free of charge under a GPL-3 open-source license through GitHub at http://joey711.github.io/shiny-phyloseq/.
PMID: 25262154 [PubMed - as supplied by publisher]
Residential agricultural pesticide exposures and risk of selected congenital heart defects among offspring in the San Joaquin Valley of California.
Environ Res. 2014 Sep 25;135C:133-138
Authors: Carmichael SL, Yang W, Roberts E, Kegley SE, Padula AM, English PB, Lammer EJ, Shaw GM
BACKGROUND: Pesticide exposures are ubiquitous and of substantial public concern. We examined the potential association of congenital heart defects with residential proximity to commercial agricultural pesticide applications in the San Joaquin Valley, California.
METHODS: Study subjects included 569 heart defect cases and 785 non-malformed controls born from 1997 to 2006 whose mothers participated in a population-based case-control study. Associations with any versus no exposure to physicochemical groups of pesticides and specific chemicals were assessed using logistic regression adjusted for relevant covariates, for 8 heart defect phenotypes that included ≥50 cases and pesticide exposures with ≥5 exposed cases and controls, which resulted in 235 comparisons.
RESULTS: 38% of cases and controls were classified as exposed to pesticides within a 500m radius of mother׳s address during a 3-month periconceptional window. Adjusted odds ratios (AORs) with 95% CIs excluding 1.0 were observed for 18 comparisons; all were >1 and ranged from 1.9 to 7.1. They included tetralogy of Fallot (n=101 cases) and neonicotinoids; hypoplastic left heart syndrome (n=59) and strobins; coarctation of the aorta (n=74) and pyridazinones; pulmonary valve stenosis (n=53) and bipyridyliums and organophosphates; ventricular septal defects (n=93) and avermectins and pyrethroids; and atrial septal defects (n=132) and dichlorphenoxy acid or esters, organophosphates, organotins, and pyrethroids. No AORs met both of these criteria for d-transposition of the great arteries (n=58) or heterotaxia (n=53).
CONCLUSIONS: Most pesticides were not associated with increased risk of specific heart defect phenotypes. For the few that were associated, results should be interpreted with caution until replicated in other study populations.
PMID: 25262086 [PubMed - as supplied by publisher]
Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma.
Nat Genet. 2014 Sep 28;
Authors: Cerhan JR, Berndt SI, Vijai J, Ghesquières H, McKay J, Wang SS, Wang Z, Yeager M, Conde L, de Bakker PI, Nieters A, Cox D, Burdett L, Monnereau A, Flowers CR, De Roos AJ, Brooks-Wilson AR, Lan Q, Severi G, Melbye M, Gu J, Jackson RD, Kane E, Teras LR, Purdue MP, Vajdic CM, Spinelli JJ, Giles GG, Albanes D, Kelly RS, Zucca M, Bertrand KA, Zeleniuch-Jacquotte A, Lawrence C, Hutchinson A, Zhi D, Habermann TM, Link BK, Novak AJ, Dogan A, Asmann YW, Liebow M, Thompson CA, Ansell SM, Witzig TE, Weiner GJ, Veron AS, Zelenika D, Tilly H, Haioun C, Molina TJ, Hjalgrim H, Glimelius B, Adami HO, Bracci PM, Riby J, Smith MT, Holly EA, Cozen W, Hartge P, Morton LM, Severson RK, Tinker LF, North KE, Becker N, Benavente Y, Boffetta P, Brennan P, Foretova L, Maynadie M, Staines A, Lightfoot T, Crouch S, Smith A, Roman E, Diver WR, Offit K, Zelenetz A, Klein RJ, Villano DJ, Zheng T, Zhang Y, Holford TR, Kricker A, Turner J, Southey MC, Clavel J, Virtamo J, Weinstein S, Riboli E, Vineis P, Kaaks R, Trichopoulos D, Vermeulen RC, Boeing H, Tjonneland A, Angelucci E, Di Lollo S, Rais M, Birmann BM, Laden F, Giovannucci E, Kraft P, Huang J, Ma B, Ye Y, Chiu BC, Sampson J, Liang L, Park JH, Chung CC, Weisenburger DD, Chatterjee N, Fraumeni JF, Slager SL, Wu X, de Sanjose S, Smedby KE, Salles G, Skibola CF, Rothman N, Chanock SJ
Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.
PMID: 25261932 [PubMed - as supplied by publisher]
Retrospective studies provide valuable information.
Anaesthesia. 2014 Sep;69(9):1052-3
Authors: Riley E
PMID: 25117013 [PubMed - indexed for MEDLINE]
Quantifying soft tissue loss in the aging male face using magnetic resonance imaging.
Dermatol Surg. 2014 Jul;40(7):786-93
Authors: Wysong A, Kim D, Joseph T, MacFarlane DF, Tang JY, Gladstone HB
BACKGROUND: Quantitative data on soft tissue aging of the face are scarce, particularly in men.
OBJECTIVE: Magnetic resonance imaging (MRI) was used to quantify and compare facial soft tissue loss in men.
MATERIALS AND METHODS: Two thousand thirty-seven MRIs were screened and 30 male subjects were divided into young, middle, and old-aged groups. A blinded radiologist measured temporal, infraorbital, and medial and lateral cheek areas.
RESULTS: The mean thickness of the subcutaneous tissue in the temporal area was 12.5, 10.9, and 9.6 mm in the young, middle, and older age groups, respectively (p < .001). A 40% reduction in the skin thickness was seen in the infraorbital areas. Finally, a decrease of 1.5 and 2.7 mm in medial cheeks (p < .001), and 0.9 and 1.6 mm (p = .03) in lateral cheeks were measured in middle and old age groups.
CONCLUSION: A steady and significant decline in the soft tissue thickness was noted at all measured sites in men over time. These findings are in contrast to our recently study in women showing dramatic loss of soft tissue between the ages of 30 and 60 with no significant differences between the middle and old-aged groups. These results have implications for volume correction and maintenance of a youthful appearance in the aging male face.
PMID: 25111352 [PubMed - indexed for MEDLINE]
A novel, catheter-based approach to left ventricular assist device deactivation after myocardial recovery.
Ann Thorac Surg. 2014 Aug;98(2):710-3
Authors: Zeigler SM, Sheikh AY, Lee PH, Desai J, Banerjee D, Oyer P, Dake MD, Ha RV
We describe a case of catheter-based embolization and deactivation of a left ventricular assist device using an Amplatzer plug for a patient demonstrating myocardial recovery after diagnosis of nonischemic cardiomyopathy. This procedure can provide a minimally invasive, low morbidity solution for patients wishing to be separated from left ventricular assist device support who want to avoid invasive surgery for device removal.
PMID: 25087798 [PubMed - indexed for MEDLINE]
Off-label use of recombinant human factor VIIa.
Ann Thorac Surg. 2014 Aug;98(2):393-5
Authors: Goodnough LT, Levy JH
PMID: 25087781 [PubMed - indexed for MEDLINE]
Pumping it up! Angiogenesis and muscle deconditioning in pulmonary hypertension.
Am J Respir Crit Care Med. 2014 Aug 1;190(3):250-1
Authors: de Jesus Perez VA
PMID: 25084260 [PubMed - indexed for MEDLINE]
Connectivity strength of dissociable striatal tracts predict individual differences in temporal discounting.
J Neurosci. 2014 Jul 30;34(31):10298-310
Authors: van den Bos W, Rodriguez CA, Schweitzer JB, McClure SM
Large individual differences exist in the ability to delay gratification for the sake of satisfying longer-term goals. These individual differences are commonly assayed by studying intertemporal preferences, as revealed by choices between immediate and delayed rewards. In the brain, reward-based and goal-oriented decisions are believed to rely on the striatum and its interactions with other cortical and subcortical networks. However, it remains unknown which specific cortical-striatal tracts are involved in intertemporal decision making. We use connectivity analyses in both structural and functional MRI to further our understanding of the relationship between distinct corticostriatal networks and intertemporal preferences in humans. Our results revealed distinct striatal pathways that are differentially related to delay discounting. Structural and functional connectivity between striatum and lateral prefrontal cortex was associated with increased patience, whereas connectivity between subcortical areas and striatum was associated with increased impulsivity. These findings provide novel insights into how the anatomy and functioning of striatal circuits mediate individual differences in intertemporal choice.
PMID: 25080591 [PubMed - indexed for MEDLINE]
Longitudinal profiles of adaptive behavior in fragile X syndrome.
Pediatrics. 2014 Aug;134(2):315-24
Authors: Klaiman C, Quintin EM, Jo B, Lightbody AA, Hazlett HC, Piven J, Hall SS, Reiss AL
OBJECTIVE: To examine longitudinally the adaptive behavior patterns in fragile X syndrome.
METHOD: Caregivers of 275 children and adolescents with fragile X syndrome and 225 typically developing children and adolescents (2-18 years) were interviewed with the Vineland Adaptive Behavior Scales every 2 to 4 years as part of a prospective longitudinal study.
RESULTS: Standard scores of adaptive behavior in people with fragile X syndrome are marked by a significant decline over time in all domains for males and in communication for females. Socialization skills are a relative strength as compared with the other domains for males with fragile X syndrome. Females with fragile X syndrome did not show a discernible pattern of developmental strengths and weaknesses.
CONCLUSIONS: This is the first large-scale longitudinal study to show that the acquisition of adaptive behavior slows as individuals with fragile X syndrome age. It is imperative to ensure that assessments of adaptive behavior skills are part of intervention programs focusing on childhood and adolescence in this condition.
PMID: 25070318 [PubMed - indexed for MEDLINE]
Gestational age and risk of venous thromboembolism from birth through young adulthood.
Pediatrics. 2014 Aug;134(2):e473-80
Authors: Zöller B, Li X, Sundquist J, Sundquist K, Crump C
BACKGROUND: Preterm birth has been associated with increased risk of venous thromboembolism (VTE) in infancy, but the longer-term risk is unknown. Our aim was to examine this association from birth through young adulthood.
METHODS: National cohort study of 3,571,574 individuals who were live-born in Sweden from 1973 through 2008, including 206,844 born preterm (gestational age <37 weeks), and followed up to 2010 (ages 0-38 years). The main outcome was VTE.
RESULTS: A total of 7519 (0.2%) individuals were diagnosed with VTE in 70.8 million person-years of follow-up. Low gestational age at birth was associated with VTE in infancy (ages <1 year: adjusted hazard ratio 47.16 [95% confidence interval 21.30-104.42] for 22 to 27 weeks, 5.54 [2.53-12.12] for 28 to 33 weeks, 3.54 [2.07-6.06] for 34 to 36 weeks, 1.00 for 37 to 41 weeks [reference]), early childhood (ages 1-5 years), and young adulthood (ages 18-38 years: adjusted hazard ratio 2.76 [1.43-5.31] for 22 to 27 weeks, 1.53 [1.24-1.89] for 28 to 33 weeks, 1.24 [1.10-1.40] for 34 to 36 weeks, and 1.00 for 37 to 41 weeks [reference]), but not in late childhood (ages 6-12 years). Very preterm (<34 weeks) but not late preterm birth (34-36 weeks) was also associated with VTE in adolescence (ages 13-17 years). After further adjustment for comorbidities, these associations were attenuated, but most remained significantly elevated.
CONCLUSIONS: In this large national cohort, low gestational age at birth was associated with increased risk of VTE in infancy, early childhood, and young adulthood.
PMID: 25070308 [PubMed - indexed for MEDLINE]
Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer.
Am J Gastroenterol. 2014 Aug;109(8):1159-79
Authors: Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, Church JM, Dominitz JA, Johnson DA, Kaltenbach T, Levin TR, Lieberman DA, Robertson DJ, Syngal S, Rex DK
The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients at risk for and affected with Lynch syndrome as follows: Figure 1 provides a colorectal cancer risk assessment tool to screen individuals in the office or endoscopy setting; Figure 2 illustrates a strategy for universal screening for Lynch syndrome by tumor testing of patients diagnosed with colorectal cancer; Figures 3,4,5,6 provide algorithms for genetic evaluation of affected and at-risk family members of pedigrees with Lynch syndrome; Table 10 provides guidelines for screening at-risk and affected persons with Lynch syndrome; and Table 12 lists the guidelines for the management of patients with Lynch syndrome. A detailed explanation of Lynch syndrome and the methodology utilized to derive these guidelines, as well as an explanation of, and supporting literature for, these guidelines are provided.
PMID: 25070057 [PubMed - indexed for MEDLINE]
Prevention of traumatic stress in mothers of preterms: 6-month outcomes.
Pediatrics. 2014 Aug;134(2):e481-8
Authors: Shaw RJ, St John N, Lilo E, Jo B, Benitz W, Stevenson DK, Horwitz SM
OBJECTIVE: Symptoms of posttraumatic stress disorder are a well-recognized phenomenon in mothers of preterm infants, with implications for maternal health and infant outcomes. This randomized controlled trial evaluated 6-month outcomes from a skills-based intervention developed to reduce symptoms of posttraumatic stress disorder, anxiety, and depression.
METHODS: One hundred five mothers of preterm infants were randomly assigned to (1) a 6- or 9-session intervention based on principles of trauma-focused cognitive behavior therapy with infant redefinition or (2) a 1-session active comparison intervention based on education about the NICU and parenting of the premature infant. Outcome measures included the Davidson Trauma Scale, the Beck Depression Inventory II, and the Beck Anxiety Inventory. Participants were assessed at baseline, 4 to 5 weeks after birth, and 6 months after the birth of the infant.
RESULTS: At the 6-month assessment, the differences between the intervention and comparison condition were all significant and sizable and became more pronounced when compared with the 4- to 5-week outcomes: Davidson Trauma Scale (Cohen's d = -0.74, P < .001), Beck Anxiety Inventory (Cohen's d = -0.627, P = .001), Beck Depression Inventory II (Cohen's d = -0.638, P = .002). However, there were no differences in the effect sizes between the 6- and 9-session interventions.
CONCLUSIONS: A brief 6-session intervention based on principles of trauma-focused cognitive behavior therapy was effective at reducing symptoms of trauma, anxiety, and depression in mothers of preterm infants. Mothers showed increased benefits at the 6-month follow-up, suggesting that they continue to make use of techniques acquired during the intervention phase.
PMID: 25049338 [PubMed - indexed for MEDLINE]
Sustaining pressure ulcer best practices in a high-volume cardiac care environment.
Am J Nurs. 2014 Aug;114(8):34-44; quiz 45-6
Authors: Paul R, McCutcheon SP, Tregarthen JP, Denend LT, Zenios SA
\Narayana Hrudayalaya Cardiac Hospital (NHCH) in Bangalore, India (now known as the Narayana Institute of Cardiac Sciences), is one of the world's largest and busiest cardiac hospitals. In early 2009, NHCH experienced a sharp increase in the number of surgical procedures performed and a corresponding rise in hospital-acquired pressure ulcers. The hospital sought to reduce pressure ulcer prevalence by implementing a portfolio of quality improvement strategies. Baseline data showed that, over the five-month observation period, an average of 6% of all adult and pediatric surgical patients experienced a pressure ulcer while recovering in the NHCH intensive therapy unit (ITU). Phase 1 implementation efforts, which began in January 2010, focused on four areas: raising awareness, increasing education, improving documentation and communication, and implementing various preventive practices. Phase 2 implementation efforts, which began the following month, focused on changing operating room practices. The primary outcome measure was the weekly percentage of ITU patients with pressure ulcers. By July 2010, that percentage was reduced to zero; as of April 1, 2014, the hospital has maintained this result. Elements that contributed significantly to the program's success and sustainability include strong leadership, nurse and physician involvement, an emphasis on personal responsibility, improved documentation and communication, ongoing training and support, and a portfolio of low-tech changes to core workflows and behaviors. Many of these elements are applicable to U.S. acute care environments.
PMID: 25036664 [PubMed - indexed for MEDLINE]
Decreasing handoff-related care failures in children's hospitals.
Pediatrics. 2014 Aug;134(2):e572-9
Authors: Bigham MT, Logsdon TR, Manicone PE, Landrigan CP, Hayes LW, Randall KH, Grover P, Collins SB, Ramirez DE, O'Guin CD, Williams CI, Warnick RJ, Sharek PJ
BACKGROUND AND OBJECTIVE: Patient handoffs in health care require transfer of information, responsibility, and authority between providers. Suboptimal patient handoffs pose a serious safety risk. Studies demonstrating the impact of improved patient handoffs on care failures are lacking. The primary objective of this study was to evaluate the effect of a multihospital collaborative designed to decrease handoff-related care failures.
METHODS: Twenty-three children's hospitals participated in a quality improvement collaborative aimed at reducing handoff-related care failures. The improvement was guided by evidence-based recommendations regarding handoff intent and content, standardized handoff tools/methods, and clear transition of responsibility. Hospitals tailored handoff elements to locally important handoff types. Handoff-related care failures were compared between baseline and 3 intervention periods. Secondary outcomes measured compliance to specific change package elements and balancing measure of staff satisfaction.
RESULTS: Twenty-three children's hospitals evaluated 7864 handoffs over the 12-month study period. Handoff-related care failures decreased from baseline (25.8%) to the final intervention period (7.9%) (P < .05). Significant improvement was observed in every handoff type studied. Compliance to change package elements improved (achieving a common understanding about the patient from 86% to 96% [P < .05]; clear transition of responsibility from 92% to 96% [P < .05]; and minimized interruptions and distractions from 84% to 90% [P < .05]) as did overall satisfaction with the handoff (from 55% to 70% [P < .05]).
CONCLUSIONS: Implementation of a standardized evidence-based handoff process across 23 children's hospitals resulted in a significant decrease in handoff-related care failures, observed over all handoff types. Compliance to critical components of the handoff process improved, as did provider satisfaction.
PMID: 25002665 [PubMed - indexed for MEDLINE]
A meta-analysis of surgical versus nonsurgical management of recurrent thymoma.
Ann Thorac Surg. 2014 Aug;98(2):748-55
Authors: Hamaji M, Ali SO, Burt BM
This meta-analysis was designed to determine the effect of surgical and nonsurgical approaches on 5-year and 10-year overall survival (OS) in patients with recurrent thymoma. PubMed, Scopus, and the Journal of Japanese Association for Chest Surgery were queried, and 11 studies were eligible. Our meta-analysis using a random-effect model revealed significant differences in the rates of 5- and 10-year OS after thymectomy and in 5-year OS after recurrence, favoring surgically managed patients. Surgical resection may be associated with improved long-term survival and should be considered for patients with recurrent thymoma.
PMID: 24980604 [PubMed - indexed for MEDLINE]
Mechanically triggered heterolytic unzipping of a low-ceiling-temperature polymer.
Nat Chem. 2014 Jul;6(7):623-8
Authors: Diesendruck CE, Peterson GI, Kulik HJ, Kaitz JA, Mar BD, May PA, White SR, Martínez TJ, Boydston AJ, Moore JS
Biological systems rely on recyclable materials resources such as amino acids, carbohydrates and nucleic acids. When biomaterials are damaged as a result of aging or stress, tissues undergo repair by a depolymerization-repolymerization sequence of remodelling. Integration of this concept into synthetic materials systems may lead to devices with extended lifetimes. Here, we show that a metastable polymer, end-capped poly(o-phthalaldehyde), undergoes mechanically initiated depolymerization to revert the material to monomers. Trapping experiments and steered molecular dynamics simulations are consistent with a heterolytic scission mechanism. The obtained monomer was repolymerized by a chemical initiator, effectively completing a depolymerization-repolymerization cycle. By emulating remodelling of biomaterials, this model system suggests the possibility of smart materials where aging or mechanical damage triggers depolymerization, and orthogonal conditions regenerate the polymer when and where necessary.
PMID: 24950333 [PubMed - indexed for MEDLINE]
Human NK cells licensed by killer Ig receptor genes have an altered cytokine program that modifies CD4+ T cell function.
J Immunol. 2014 Jul 15;193(2):940-9
Authors: Lin L, Ma C, Wei B, Aziz N, Rajalingam R, Yusung S, Erlich HA, Trachtenberg EA, Targan SR, McGovern DP, Heath JR, Braun J
NK cells are innate immune cells known for their cytolytic activities toward tumors and infections. They are capable of expressing diverse killer Ig-like receptors (KIRs), and KIRs are implicated in susceptibility to Crohn's disease (CD), a chronic intestinal inflammatory disease. However, the cellular mechanism of this genetic contribution is unknown. In this study, we show that the "licensing" of NK cells, determined by the presence of KIR2DL3 and homozygous HLA-C1 in host genome, results in their cytokine reprogramming, which permits them to promote CD4(+) T cell activation and Th17 differentiation ex vivo. Microfluidic analysis of thousands of NK single cells and bulk secretions established that licensed NK cells are more polarized to proinflammatory cytokine production than unlicensed NK cells, including production of IFN-γ, TNF-α, CCL-5, and MIP-1β. Cytokines produced by licensed NK augmented CD4(+) T cell proliferation and IL-17A/IL-22 production. Ab blocking indicated a primary role for IFN-γ, TNF-α, and IL-6 in the augmented T cell-proliferative response. In conclusion, NK licensing mediated by KIR2DL2/3 and HLA-C1 elicits a novel NK cytokine program that activates and induces proinflammatory CD4(+) T cells, thereby providing a potential biologic mechanism for KIR-associated susceptibility to CD and other chronic inflammatory diseases.
PMID: 24935928 [PubMed - indexed for MEDLINE]
Chemically defined generation of human cardiomyocytes.
Nat Methods. 2014 Aug;11(8):855-60
Authors: Burridge PW, Matsa E, Shukla P, Lin ZC, Churko JM, Ebert AD, Lan F, Diecke S, Huber B, Mordwinkin NM, Plews JR, Abilez OJ, Cui B, Gold JD, Wu JC
Existing methods for human induced pluripotent stem cell (hiPSC) cardiac differentiation are efficient but require complex, undefined medium constituents that hinder further elucidation of the molecular mechanisms of cardiomyogenesis. Using hiPSCs derived under chemically defined conditions on synthetic matrices, we systematically developed an optimized cardiac differentiation strategy, using a chemically defined medium consisting of just three components: the basal medium RPMI 1640, L-ascorbic acid 2-phosphate and rice-derived recombinant human albumin. Along with small molecule-based induction of differentiation, this protocol produced contractile sheets of up to 95% TNNT2(+) cardiomyocytes at a yield of up to 100 cardiomyocytes for every input pluripotent cell and was effective in 11 hiPSC lines tested. This chemically defined platform for cardiac specification of hiPSCs will allow the elucidation of cardiomyocyte macromolecular and metabolic requirements and will provide a minimal system for the study of maturation and subtype specification.
PMID: 24930130 [PubMed - indexed for MEDLINE]
A balance between B cell receptor and inhibitory receptor signaling controls plasma cell differentiation by maintaining optimal Ets1 levels.
J Immunol. 2014 Jul 15;193(2):909-20
Authors: Luo W, Mayeux J, Gutierrez T, Russell L, Getahun A, Müller J, Tedder T, Parnes J, Rickert R, Nitschke L, Cambier J, Satterthwaite AB, Garrett-Sinha LA
Signaling through the BCR can drive B cell activation and contribute to B cell differentiation into Ab-secreting plasma cells. The positive BCR signal is counterbalanced by a number of membrane-localized inhibitory receptors that limit B cell activation and plasma cell differentiation. Deficiencies in these negative signaling pathways may cause autoantibody generation and autoimmune disease in both animal models and human patients. We have previously shown that the transcription factor Ets1 can restrain B cell differentiation into plasma cells. In this study, we tested the roles of the BCR and inhibitory receptors in controlling the expression of Ets1 in mouse B cells. We found that Ets1 is downregulated in B cells by BCR or TLR signaling through a pathway dependent on PI3K, Btk, IKK2, and JNK. Deficiencies in inhibitory pathways, such as a loss of the tyrosine kinase Lyn, the phosphatase Src homology region 2 domain-containing phosphatase 1 (SHP1) or membrane receptors CD22 and/or Siglec-G, result in enhanced BCR signaling and decreased Ets1 expression. Restoring Ets1 expression in Lyn- or SHP1-deficient B cells inhibits their enhanced plasma cell differentiation. Our findings indicate that downregulation of Ets1 occurs in response to B cell activation via either BCR or TLR signaling, thereby allowing B cell differentiation and that the maintenance of Ets1 expression is an important function of the inhibitory Lyn → CD22/SiglecG → SHP1 pathway in B cells.
PMID: 24929000 [PubMed - indexed for MEDLINE]
A detailed staging scheme for late larval development in Strongylocentrotus purpuratus focused on readily-visible juvenile structures within the rudiment.
BMC Dev Biol. 2014;14:22
Authors: Heyland A, Hodin J
BACKGROUND: The purple sea urchin, Strongylocentrotus purpuratus, has long been the focus of developmental and ecological studies, and its recently-sequenced genome has spawned a diversity of functional genomics approaches. S. purpuratus has an indirect developmental mode with a pluteus larva that transforms after 1-3 months in the plankton into a juvenile urchin. Compared to insects and frogs, mechanisms underlying the correspondingly dramatic metamorphosis in sea urchins remain poorly understood. In order to take advantage of modern techniques to further our understanding of juvenile morphogenesis, organ formation, metamorphosis and the evolution of the pentameral sea urchin body plan, it is critical to assess developmental progression and rate during the late larval phase. This requires a staging scheme that describes developmental landmarks that can quickly and consistently be used to identify the stage of individual living larvae, and can be tracked during the final two weeks of larval development, as the juvenile is forming.
RESULTS: Notable structures that are easily observable in developing urchin larvae are the developing spines, test and tube feet within the juvenile rudiment that constitute much of the oral portion of the adult body plan. Here we present a detailed staging scheme of rudiment development in the purple urchin using soft structures of the rudiment and the primordia of these juvenile skeletal elements. We provide evidence that this scheme is robust and applicable across a range of temperature and feeding regimes.
CONCLUSIONS: Our proposed staging scheme provides both a useful method to study late larval development in the purple urchin, and a framework for developing similar staging schemes across echinoderms. Such efforts will have a high impact on evolutionary developmental studies and larval ecology, and facilitate research on this important deuterostome group.
PMID: 24886415 [PubMed - indexed for MEDLINE]
SCAI/AATS/ACC/STS operator and institutional requirements for transcatheter valve repair and replacement: Part II. Mitral valve.
Ann Thorac Surg. 2014 Aug;98(2):765-77
Authors: Tommaso CL, Fullerton DA, Feldman T, Dean LS, Hijazi ZM, Horlick E, Weiner BH, Zahn E, Cigarroa JE, Ruiz CE, Bavaria J, Mack MJ, Cameron DE, Bolman RM, Miller DC, Moon MR, Mukherjee D, Trento A, Aldea GS, Bacha EA, Society for Cardiovascular Angiography and Interventions, American Association for Thoracic Surgery, American College of Cardiology, Society of Thoracic Surgeons
PMID: 24835557 [PubMed - indexed for MEDLINE]
Combined elevated midpregnancy tumor necrosis factor alpha and hyperlipidemia in pregnancies resulting in early preterm birth.
Am J Obstet Gynecol. 2014 Aug;211(2):141.e1-9
Authors: Jelliffe-Pawlowski LL, Ryckman KK, Bedell B, O'Brodovich HM, Gould JB, Lyell DJ, Borowski KS, Shaw GM, Murray JC, Stevenson DK
OBJECTIVE: The objective of the study was to determine whether pregnancies resulting in early preterm birth (PTB) (<30 weeks) were more likely than term pregnancies to have elevated midtrimester serum tumor necrosis factor alpha (TNF-α) levels combined with lipid patterns suggestive of hyperlipidemia.
STUDY DESIGN: In 2 nested case-control samples drawn from California and Iowa cohorts, we examined the frequency of elevated midpregnancy serum TNF-α levels (in the fourth quartile [4Q]) and lipid patterns suggestive of hyperlipidemia (eg, total cholesterol, low-density-lipoproteins, or triglycerides in the 4Q, high-density lipoproteins in the first quartile) (considered independently and by co-occurrence) in pregnancies resulting in early PTB compared with those resulting in term birth (n = 108 in California and n = 734 in Iowa). Odds ratios (ORs) and 95% confidence intervals (CIs) estimated in logistic regression models were used for comparisons.
RESULTS: Early preterm pregnancies were 2-4 times more likely than term pregnancies to have a TNF-α level in the 4Q co-occurring with indicators of hyperlipidemia (37.5% vs 13.9% in the California sample (adjusted OR, 4.0; 95% CI, 1.1-16.3) and 26.3% vs 14.9% in the Iowa sample (adjusted OR, 2.7; 95% CI, 1.1-6.3). No differences between early preterm and term pregnancies were observed when TNF-α or target lipid abnormalities occurred in isolation. Observed differences were not explicable to any maternal or infant characteristics.
CONCLUSION: Pregnancies resulting in early PTB were more likely than term pregnancies to have elevated midpregnancy TNF-α levels in combination with lipid patterns suggestive of hyperlipidemia.
PMID: 24831886 [PubMed - indexed for MEDLINE]
Signal recognition particle-ribosome binding is sensitive to nascent chain length.
J Biol Chem. 2014 Jul 11;289(28):19294-305
Authors: Noriega TR, Tsai A, Elvekrog MM, Petrov A, Neher SB, Chen J, Bradshaw N, Puglisi JD, Walter P
The signal recognition particle (SRP) directs ribosome-nascent chain complexes (RNCs) displaying signal sequences to protein translocation channels in the plasma membrane of prokaryotes and endoplasmic reticulum of eukaryotes. It was initially proposed that SRP binds the signal sequence when it emerges from an RNC and that successful binding becomes impaired as translation extends the nascent chain, moving the signal sequence away from SRP on the ribosomal surface. Later studies drew this simple model into question, proposing that SRP binding is unaffected by nascent chain length. Here, we reinvestigate this issue using two novel and independent fluorescence resonance energy transfer assays. We show that the arrival and dissociation rates of SRP binding to RNCs vary according to nascent chain length, resulting in the highest affinity shortly after a functional signal sequence emerges from the ribosome. Moreover, we show that SRP binds RNCs in multiple and interconverting conformations, and that conversely, RNCs exist in two conformations distinguished by SRP interaction kinetics.
PMID: 24808175 [PubMed - indexed for MEDLINE]
Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices.
Circulation. 2014 Jun 3;129(22):2287-96
Authors: Ascheim DD, Gelijns AC, Goldstein D, Moye LA, Smedira N, Lee S, Klodell CT, Szady A, Parides MK, Jeffries NO, Skerrett D, Taylor DA, Rame JE, Milano C, Rogers JG, Lynch J, Dewey T, Eichhorn E, Sun B, Feldman D, Simari R, O'Gara PT, Taddei-Peters WC, Miller MA, Naka Y, Bagiella E, Rose EA, Woo YJ
BACKGROUND: Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contribute to myocardial recovery. This trial explores the safety and efficacy of this strategy.
METHODS AND RESULTS: In this multicenter, double-blind, sham-procedure controlled trial, 30 patients were randomized (2:1) to intramyocardial injection of 25 million MPCs or medium during LVAD implantation. The primary safety end point was incidence of infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization (90 days after randomization). Key efficacy end points were functional status and ventricular function while temporarily weaned from LVAD support (90 days after randomization). Patients were followed up until transplant or 12 months after randomization, whichever came first. Mean age was 57.4 (±13.6) years, mean left ventricular ejection fraction was 18.1%, and 66.7% were destination therapy LVADs. No safety events were observed. Successful temporary LVAD weaning was achieved in 50% of MPC and 20% of control patients at 90 days (P=0.24); the posterior probability that MPCs increased the likelihood of successful weaning was 93%. At 90 days, 3 deaths (30%) occurred in control patients, and none occurred in MPC patients. Mean left ventricular ejection fraction after successful wean was 24.0% (MPC=10) and 22.5% (control=2; P=0.56). At 12 months, 30% of MPC patients and 40% of control patients were successfully temporarily weaned from LVAD support (P=0.69), and 6 deaths (30%) occurred in MPC patients. Donor-specific HLA sensitization developed in 2 MPC and 3 control patients and resolved by 12 months.
CONCLUSIONS: In this preliminary trial, administration of MPCs appeared to be safe, and there was a potential signal of efficacy. Future studies will evaluate the potential for higher or additional doses to enhance the ability to wean LVAD recipients off support.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01442129.
PMID: 24682346 [PubMed - indexed for MEDLINE]
Association between maternal characteristics, abnormal serum aneuploidy analytes, and placental abruption.
Am J Obstet Gynecol. 2014 Aug;211(2):144.e1-9
Authors: Blumenfeld YJ, Baer RJ, Druzin ML, El-Sayed YY, Lyell DJ, Faucett AM, Shaw GM, Currier RJ, Jelliffe-Pawlowski LL
OBJECTIVE: The objective of the study was to examine the association between placental abruption, maternal characteristics, and routine first- and second-trimester aneuploidy screening analytes.
STUDY DESIGN: The study consisted of an analysis of 1017 women with and 136,898 women without placental abruption who had first- and second-trimester prenatal screening results, linked birth certificate, and hospital discharge records for a live-born singleton. Maternal characteristics and first- and second-trimester aneuploidy screening analytes were analyzed using logistic binomial regression.
RESULTS: Placental abruption was more frequent among women of Asian race, age older than 34 years, women with chronic and pregnancy-associated hypertension, preeclampsia, preexisting diabetes, previous preterm birth, and interpregnancy interval less than 6 months. First-trimester pregnancy-associated plasma protein-A of the fifth percentile or less, second-trimester alpha fetoprotein of the 95th percentile or greater, unconjugated estriol of the fifth percentile or less, and dimeric inhibin-A of the 95th percentile or greater were associated with placental abruption as well. When logistic models were stratified by the presence or absence of hypertensive disease, only maternal age older than 34 years (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.0-2.0), pregnancy-associated plasma protein-A of the 95th percentile or less (OR, 1.9; 95% CI, 1.2-3.1), and alpha fetoprotein of the 95th percentile or greater (OR, 2.3; 95% CI, 1.4-3.8) remained statistically significantly associated for abruption.
CONCLUSION: In this large, population-based cohort study, abnormal maternal aneuploidy serum analyte levels were associated with placental abruption, regardless of the presence of hypertensive disease.
PMID: 24631707 [PubMed - indexed for MEDLINE]
Insulin secretory function: not a simple measurement.
J Intern Med. 2014 Sep;276(3):308-9
Authors: Reaven G
PMID: 24612222 [PubMed - indexed for MEDLINE]
A general protocol for the generation of Nanobodies for structural biology.
Nat Protoc. 2014 Mar;9(3):674-93
Authors: Pardon E, Laeremans T, Triest S, Rasmussen SG, Wohlkönig A, Ruf A, Muyldermans S, Hol WG, Kobilka BK, Steyaert J
There is growing interest in using antibodies as auxiliary tools to crystallize proteins. Here we describe a general protocol for the generation of Nanobodies to be used as crystallization chaperones for the structural investigation of diverse conformational states of flexible (membrane) proteins and complexes thereof. Our technology has a competitive advantage over other recombinant crystallization chaperones in that we fully exploit the natural humoral response against native antigens. Accordingly, we provide detailed protocols for the immunization with native proteins and for the selection by phage display of in vivo-matured Nanobodies that bind conformational epitopes of functional proteins. Three representative examples illustrate that the outlined procedures are robust, making it possible to solve by Nanobody-assisted X-ray crystallography in a time span of 6-12 months.
PMID: 24577359 [PubMed - indexed for MEDLINE]
Current methods in the molecular typing of Mycobacterium tuberculosis and other mycobacteria.
Biomed Res Int. 2014;2014:645802
Authors: Jagielski T, van Ingen J, Rastogi N, Dziadek J, Mazur PK, Bielecki J
In the epidemiology of tuberculosis (TB) and nontuberculous mycobacterial (NTM) diseases, as in all infectious diseases, the key issue is to define the source of infection and to disclose its routes of transmission and dissemination in the environment. For this to be accomplished, the ability of discerning and tracking individual Mycobacterium strains is of critical importance. Molecular typing methods have greatly improved our understanding of the biology of mycobacteria and provide powerful tools to combat the diseases caused by these pathogens. The utility of various typing methods depends on the Mycobacterium species under investigation as well as on the research question. For tuberculosis, different methods have different roles in phylogenetic analyses and person-to-person transmission studies. In NTM diseases, most investigations involve the search for environmental sources or phylogenetic relationships. Here, too, the type of setting determines which methodology is most suitable. Within this review, we summarize currently available molecular methods for strain typing of M. tuberculosis and some NTM species, most commonly associated with human disease. For the various methods, technical practicalities as well as discriminatory power and accomplishments are reviewed.
PMID: 24527454 [PubMed - indexed for MEDLINE]
A mouse model of permanent focal ischemia: distal middle cerebral artery occlusion.
Methods Mol Biol. 2014;1135:103-10
Authors: Doyle KP, Buckwalter MS
Here we provide a standardized protocol for performing distal middle cerebral artery occlusion (DMCAO) in mice. DMCAO is a method of inducing permanent focal ischemia that is commonly used as a rodent stroke model. To perform DMCAO a temporal craniotomy is performed, and the middle cerebral artery (MCA) is permanently ligated at a point downstream of the lenticulostriate branches. The size of the lesion produced by this surgery is strain dependent. In C57BL/6J mice, DMCAO produces an infarct predominantly restricted to the barrel region of the somatosensory cortex, but in BALB/cJ mice, DMCAO generates a much larger lesion that incorporates more of the somatosensory cortex and part of the M1 region of the motor cortex. The larger lesion produced by DMCAO in BALB/cJ mice produces a clearer sensorimotor deficit, which is useful for investigating recovery from stroke. We also describe how to modify DMCAO in C57BL/6J mice with the application of hypoxia to generate a lesion and sensorimotor deficit that are similar in size to those produced by DMCAO alone in BALB/cJ mice. This is extremely useful for stroke experiments that require a robust sensorimotor deficit in transgenic mice created on a C57BL/6J background.
PMID: 24510858 [PubMed - indexed for MEDLINE]
Reply to Breschan et al, re 'central venus catheter placement in children'.
Paediatr Anaesth. 2014 Mar;24(3):345
Authors: Kamra K, Hammer G
PMID: 24467577 [PubMed - indexed for MEDLINE]
Contemporary incidence, predictors, and outcomes of acute kidney injury in patients undergoing percutaneous coronary interventions: insights from the NCDR Cath-PCI registry.
JACC Cardiovasc Interv. 2014 Jan;7(1):1-9
Authors: Tsai TT, Patel UD, Chang TI, Kennedy KF, Masoudi FA, Matheny ME, Kosiborod M, Amin AP, Messenger JC, Rumsfeld JS, Spertus JA
OBJECTIVES: This study sought to examine the contemporary incidence, predictors and outcomes of acute kidney injury in patients undergoing percutaneous coronary interventions.
BACKGROUND: Acute kidney injury (AKI) is a serious and potentially preventable complication of percutaneous coronary interventions (PCIs) that is associated with adverse outcomes. The contemporary incidence, predictors, and outcomes of AKI are not well defined, and clarifying these can help identify high-risk patients for proactive prevention.
METHODS: A total of 985,737 consecutive patients underwent PCIs at 1,253 sites participating in the National Cardiovascular Data Registry Cath-PCI registry from June 2009 through June 2011. AKI was defined on the basis of changes in serum creatinine level in the hospital according to the Acute Kidney Injury Network (AKIN) criteria. Using multivariable regression analyses with generalized estimating equations, we identified patient characteristics associated with AKI.
RESULTS: Overall, 69,658 (7.1%) patients experienced AKI, with 3,005 (0.3%) requiring new dialysis. On multivariable analyses, the factors most strongly associated with development of AKI included ST-segment elevation myocardial infarction (STEMI) presentation (odds ratio [OR]: 2.60; 95% confidence interval [CI]: 2.53 to 2.67), severe chronic kidney disease (OR: 3.59; 95% CI: 3.47 to 3.71), and cardiogenic shock (OR: 2.92; 95% CI: 2.80 to 3.04). The in-hospital mortality rate was 9.7% for patients with AKI and 34% for those requiring dialysis compared with 0.5% for patients without AKI (p < 0.001). After multivariable adjustment, AKI (OR: 7.8; 95% CI: 7.4 to 8.1, p < 0.001) and dialysis (OR: 21.7; 95% CI: 19.6 to 24.1; p < 0.001) remained independent predictors of in-hospital mortality.
CONCLUSIONS: Approximately 7% of patients undergoing a PCI experience AKI, which is strongly associated with in-hospital mortality. Defining strategies to minimize the risk of AKI in patients undergoing PCI are needed to improve the safety and outcomes of the procedure.
PMID: 24456715 [PubMed - indexed for MEDLINE]
Aftermath of Typhoon Haiyan: the imminent epidemic of waterborne illnesses in Leyte, Philippines.
Disaster Med Public Health Prep. 2013 Dec;7(6):547-8
Authors: Dolhun E
PMID: 24444130 [PubMed - indexed for MEDLINE]
NIR-light-induced surface-enhanced Raman scattering for detection and photothermal/photodynamic therapy of cancer cells using methylene blue-embedded gold nanorod@SiO2 nanocomposites.
Biomaterials. 2014 Mar;35(10):3309-18
Authors: Seo SH, Kim BM, Joe A, Han HW, Chen X, Cheng Z, Jang ES
Methylene blue-loaded gold nanorod@SiO2 (MB-GNR@SiO2) core@shell nanoparticles are synthesized for use in cancer imaging and photothermal/photodynamic dual therapy. For the preparation of GNR@SiO2 nanoparticles, we found that the silica coating rate of hexadecylcetyltrimethylammonium bromide (CTAB)-capped GNRs is much slower than that of PEGylated GNRs due to the densely coated CTAB bilayer. Encapsulated MB molecules have both monomer and dimer forms that result in an increase in the photosensitizing effect through different photochemical pathways. As a consequence of the excellent plasmonic properties of GNRs at near-infrared (NIR) light, the embedded MB molecules showed NIR light-induced SERS performance with a Raman enhancement factor of 3.0 × 10(10), which is enough for the detection of a single cancer cell. Moreover, the MB-GNR@SiO2 nanoparticles exhibit a synergistic effect of photodynamic and photothermal therapies of cancer under single-wavelength NIR laser irradiation.
PMID: 24424205 [PubMed - indexed for MEDLINE]
Reversible cerebral vasoconstriction syndrome and bilateral vertebral artery dissection presenting in a patient after cesarean section.
J Neurointerv Surg. 2014 Jan;6(1):e5
Authors: Mitchell LA, Santarelli JG, Singh IP, Do HM
Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden-onset thunderclap headache and focal neurologic deficits. Once thought to be a rare syndrome, more advanced non-invasive imaging has led to an increase in RCVS diagnosis. Unilateral vertebral artery dissection has been described in fewer than 40% of cases of RCVS. Bilateral vertebral artery dissection has rarely been reported. We describe the case of a patient with RCVS and bilateral vertebral artery dissection presenting with an intramedullary infarct treated successfully with medical management and careful close follow-up. This rare coexistence should be recognized as the treatment differs.
PMID: 24415454 [PubMed - indexed for MEDLINE]
Diagnostic and Statistical Manual of Mental Disorders: the solution or the problem?
J Dev Behav Pediatr. 2014 Jan;35(1):68-70
Authors: Reiff MI, Feldman HM
PMID: 24399102 [PubMed - indexed for MEDLINE]
Evidence-based de-implementation for contradicted, unproven, and aspiring healthcare practices.
Implement Sci. 2014;9:1
Authors: Prasad V, Ioannidis JP
Abandoning ineffective medical practices and mitigating the risks of untested practices are important for improving patient health and containing healthcare costs. Historically, this process has relied on the evidence base, societal values, cultural tensions, and political sway, but not necessarily in that order. We propose a conceptual framework to guide and prioritize this process, shifting emphasis toward the principles of evidence-based medicine, acknowledging that evidence may still be misinterpreted or distorted by recalcitrant proponents of entrenched practices and other biases.
PMID: 24398253 [PubMed - indexed for MEDLINE]
Prevention of high altitude illness.
Travel Med Infect Dis. 2014 Jan-Feb;12(1):29-39
Authors: Zafren K
High altitude illness - Acute Mountain Sickness (AMS), High Altitude Cerebral Edema (HACE) and High Altitude Pulmonary Edema (HAPE) - can be prevented or limited in severity by gradual ascent and by pharmacologic methods. The decision whether to use pharmacologic prophylaxis depends on the ascent rate and an individual's previous history of altitude illness. This review discusses risk stratification to determine whether to use pharmacologic prophylaxis and recommends specific drugs, especially acetazolamide, dexamethasone and nifedipine. This review also evaluates non-recommended drugs. In addition, this review suggests non-pharmacologic methods of decreasing the risk of severe altitude illness. There are also brief sections on how to decrease sleep disturbance at high altitude, travel to high altitude for patients with pre-existing illness and advice for travelers ascending to high altitude.
PMID: 24393671 [PubMed - indexed for MEDLINE]
The symptom cluster-based approach to individualize patient-centered treatment for major depression.
J Am Board Fam Med. 2014 Jan-Feb;27(1):151-9
Authors: Lin SY, Stevens MB
Unipolar major depressive disorder is a common, disabling, and costly disease that is the leading cause of ill health, early death, and suicide in the United States. Primary care doctors, in particular family physicians, are the first responders in this silent epidemic. Although more than a dozen different antidepressants in 7 distinct classes are widely used to treat depression in primary care, there is no evidence that one drug is superior to another. Comparative effectiveness studies have produced mixed results, and no specialty organization has published recommendations on how to choose antidepressants in a rational, evidence-based manner. In this article we present the theory and evidence for an individualized, patient-centered treatment model for major depression designed around a targeted symptom cluster-based approach to antidepressant selection. When using this model for healthy adults with major depressive disorder, the choice of antidepressants should be guided by the presence of 1 of 4 common symptom clusters: anxiety, fatigue, insomnia, and pain. This model was built to foster future research, provide a logical framework for teaching residents how to select antidepressants, and equip primary care doctors with a structured treatment strategy to deliver optimal patient-centered care in the management of a debilitating disease: major depressive disorder.
PMID: 24390897 [PubMed - indexed for MEDLINE]
The role of Ryk and Ror receptor tyrosine kinases in Wnt signal transduction.
Cold Spring Harb Perspect Biol. 2014 Feb;6(2)
Authors: Green J, Nusse R, van Amerongen R
Receptor tyrosine kinases of the Ryk and Ror families were initially classified as orphan receptors because their ligands were unknown. They are now known to contain functional extracellular Wnt-binding domains and are implicated in Wnt-signal transduction in multiple species. Although their signaling mechanisms still remain to be resolved in detail, both Ryk and Ror control important developmental processes in different tissues. However, whereas many other Wnt-signaling responses affect cell proliferation and differentiation, Ryk and Ror are mostly associated with controlling processes that rely on the polarized migration of cells. Here we discuss what is currently known about the involvement of this exciting class of receptors in development and disease.
PMID: 24370848 [PubMed - indexed for MEDLINE]
Incorporation of flexible objectives and time-linked simulation with flux balance analysis.
J Theor Biol. 2014 Mar 21;345:12-21
Authors: Birch EW, Udell M, Covert MW
We present two modifications of the flux balance analysis (FBA) metabolic modeling framework which relax implicit assumptions of the biomass reaction. Our flexible flux balance analysis (flexFBA) objective removes the fixed proportion between reactants, and can therefore produce a subset of biomass reactants. Our time-linked flux balance analysis (tFBA) simulation removes the fixed proportion between reactants and byproducts, and can therefore describe transitions between metabolic steady states. Used together, flexFBA and tFBA model a time scale shorter than the regulatory and growth steady state encoded by the biomass reaction. This combined short-time FBA method is intended for integrated modeling applications to enable detailed and dynamic depictions of microbial physiology such as whole-cell modeling. For example, when modeling Escherichia coli, it avoids artifacts caused by low-copy-number enzymes in single-cell models with kinetic bounds. Even outside integrated modeling contexts, the detailed predictions of flexFBA and tFBA complement existing FBA techniques. We show detailed metabolite production of in silico knockouts used to identify when correct essentiality predictions are made for the wrong reason.
PMID: 24361328 [PubMed - indexed for MEDLINE]
Utilizing combinatorial chemistry and rational design: peptidic tweezers with nanomolar affinity to DNA can be transformed into efficient vectors for gene delivery by addition of a lipophilic tail.
Angew Chem Int Ed Engl. 2013 Dec 23;52(52):14016-20
Authors: Kuchelmeister HY, Karczewski S, Gutschmidt A, Knauer S, Schmuck C
PMID: 24353227 [PubMed - indexed for MEDLINE]
Auditory cortex activation to natural speech and simulated cochlear implant speech measured with functional near-infrared spectroscopy.
Hear Res. 2014 Mar;309:84-93
Authors: Pollonini L, Olds C, Abaya H, Bortfeld H, Beauchamp MS, Oghalai JS
The primary goal of most cochlear implant procedures is to improve a patient's ability to discriminate speech. To accomplish this, cochlear implants are programmed so as to maximize speech understanding. However, programming a cochlear implant can be an iterative, labor-intensive process that takes place over months. In this study, we sought to determine whether functional near-infrared spectroscopy (fNIRS), a non-invasive neuroimaging method which is safe to use repeatedly and for extended periods of time, can provide an objective measure of whether a subject is hearing normal speech or distorted speech. We used a 140 channel fNIRS system to measure activation within the auditory cortex in 19 normal hearing subjects while they listed to speech with different levels of intelligibility. Custom software was developed to analyze the data and compute topographic maps from the measured changes in oxyhemoglobin and deoxyhemoglobin concentration. Normal speech reliably evoked the strongest responses within the auditory cortex. Distorted speech produced less region-specific cortical activation. Environmental sounds were used as a control, and they produced the least cortical activation. These data collected using fNIRS are consistent with the fMRI literature and thus demonstrate the feasibility of using this technique to objectively detect differences in cortical responses to speech of different intelligibility.
PMID: 24342740 [PubMed - indexed for MEDLINE]
Safety and efficacy of low-dose paclitaxel utilizing the cobra-P drug-eluting stent system with a novel biodegradable coating in de novo coronary lesions: the PLUS-ONE first-in-man study.
Cardiovasc Revasc Med. 2014 Jan;15(1):18-22
Authors: Calderas C, Condado JF, Condado JA, Flores A, Mueller A, Thomas J, Nakatani D, Honda Y, Waseda K, Fitzgerald P
BACKGROUND: The Cobra-P drug-eluting stent (DES) system consists of cobalt chromium alloy with bio-absorbable siloxane sol-gel matrix coating that elutes low dose paclitaxel within 6 months. The aim of this first-in-man trial was to evaluate the safety and performance of 2 doses of the Cobra-P DES.
METHODS: A total of 60 lesions (54 patients) were sequentially assigned to 2 different paclitaxel doses: group A (3.7 μg/18mm, n=30) or group B (8 μg/18mm, n=30). The primary endpoint was MACE at 4 months defined as cardiac death, myocardial infarction, and target lesion revascularization.
RESULTS: Patient and lesion characteristics were matched between the 2 groups except for male sex. MACE at 4 months was 3.3% and 0% respectively (P=1.000) and at 1-year follow-up remained unchanged. In-stent late loss at 4 months was similar in both groups (0.36 ± 0.30mm and 0.34 ± 0.20mm P=.773).
CONCLUSIONS: In this FIM study, implantation of the Cobra-P low dose paclitaxel-eluting stent with a bioabsorbable sol-gel coating was proven to be feasible and safe. Moderate neointimal proliferation was observed as well as an acceptable MACE rate up to 1 year.
PMID: 24315045 [PubMed - indexed for MEDLINE]
The relationship between male BMI and waist circumference on semen quality: data from the LIFE study.
Hum Reprod. 2014 Feb;29(2):193-200
Authors: Eisenberg ML, Kim S, Chen Z, Sundaram R, Schisterman EF, Buck Louis GM
STUDY QUESTION: What is the relationship between body size, physical activity and semen parameters among male partners of couples attempting to become pregnant?
SUMMARY ANSWER: Overweight and obesity are associated with a higher prevalence of low ejaculate volume, sperm concentration and total sperm count.
WHAT IS KNOWN ALREADY: Higher BMI is associated with impaired semen parameters, while increasing waist circumference (WC) is also associated with impaired semen parameters in infertile men.
STUDY DESIGN, SIZE, DURATION: Data from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study were utilized. The LIFE study is a population-based prospective cohort of 501 couples attempting to conceive in two geographic areas (Texas and Michigan, USA) recruited in 2005-2009. Couples were recruited from four counties in Michigan and 12 counties in Texas to ensure a range of environmental exposures and lifestyle characteristics. In person interviews were conducted to ascertain demographic, health and reproductive histories followed by anthropometric assessment.
PARTICIPANTS/MATERIALS, SETTING, METHODS: We categorized BMI (kg/m(2)) as <25.0 (underweight and normal), 25.0-29.9 (overweight) 30.0-34.9 (obese, class I) and ≥35 (obese, class II) for analysis. Data were available for analysis in 468 men (93% participation), with a mean ± SD age of 31.8 ± 4.8 years, BMI of 29.8 ± 5.6 kg/m(2) and WC of 100.8 ± 14.2 cm. The majority of the cohort (82%) was overweight or obese with 58% reporting physical activity <1 time/week. The median sperm concentration for the men in the cohort was 60.2 M/ml with 8.6% having oligospermia (<15 M/ml).
MAIN RESULTS AND THE ROLE OF CHANCE: When examining semen parameters, ejaculate volume showed a linear decline with increasing BMI and WC (P < 0.01). Similarly, the total sperm count showed a negative linear association with WC (P < 0.01). No significant relationship was seen between body size (i.e. BMI or WC) and semen concentration, motility, vitality, morphology or DNA fragmentation index. The percentage of men with abnormal volume, concentration and total sperm increased with increasing body size (P < 0.05). No relationship between physical activity and semen parameters was identified.
LIMITATIONS, REASONS FOR CAUTION: Our cohort was largely overweight and sedentary, which may result in limited external validity, i.e. generalizability. The lack of physical activity did preclude examination of exercise more frequently than once per week, thus our ability to examine more active individuals is limited.
WIDER IMPLICATIONS OF THE FINDINGS: Body size (as measured by BMI or WC) is negatively associated with semen parameters with little influence of physical activity. Our findings are the first showing a relationship between WC and semen parameters in a sample of men without known infertility. Given the worldwide obesity epidemic, further study of the role of weight loss to improve semen parameters is warranted.
STUDY FUNDING/COMPETING INTEREST(S): Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contracts #N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). There are no competing interests.
PMID: 24306102 [PubMed - indexed for MEDLINE]
Integration of palliative care into emergency medicine: the Improving Palliative Care in Emergency Medicine (IPAL-EM) collaboration.
J Emerg Med. 2014 Feb;46(2):264-70
Authors: Lamba S, DeSandre PL, Todd KH, Bryant EN, Chan GK, Grudzen CR, Weissman DE, Quest TE, Improving Palliative Care in Emergency Medicine Board
BACKGROUND: Emergency department (ED) providers commonly care for seriously ill patients who suffer from advanced, chronic, life-limiting illnesses in addition to those that are acutely ill or injured. Both the chronically ill and those who present in extremis may benefit from application of palliative care principles.
CASE REPORT: We present a case highlighting the opportunities and need for better integration of emergency medicine and palliative care.
DISCUSSION: We offer practical guidelines to the ED faculty/administrators who seek to enhance the quality of patient care in their own unique ED setting by starting an initiative that better integrates palliative principles into daily practice. Specifically, we outline four things to do to jumpstart this collaborative effort.
CONCLUSION: The Improving Palliative Care in Emergency Medicine project sponsored by the Center to Advance Palliative Care is a resource that assists ED health care providers with the process and structure needed to integrate palliative care into the ED setting.
PMID: 24286714 [PubMed - indexed for MEDLINE]
Evaluating noncoding nucleotide repeat expansions in amyotrophic lateral sclerosis.
Neurobiol Aging. 2014 Apr;35(4):936.e1-4
Authors: Figley MD, Thomas A, Gitler AD
Intermediate-length polyglutamine expansions in ataxin 2 are a risk factor for amyotrophic lateral sclerosis (ALS). The polyglutamine tract is encoded by a trinucleotide repeat in a coding region of the ataxin 2 gene (ATXN2). Noncoding nucleotide repeat expansions in several genes are also associated with neurodegenerative and neuromuscular diseases. For example, hexanucleotide repeat expansions located in a noncoding region of C9ORF72 are the most common cause of ALS. We sought to assess a potential larger role of noncoding nucleotide repeat expansions in ALS. We analyzed the nucleotide repeat lengths of 6 genes (ATXN8, ATXN10, PPP2R2B, NOP56, DMPK, and JPH3) that have previously been associated with neurologic or neuromuscular disorders, in several hundred sporadic patients with ALS and healthy control subjects. We report no association between ALS and repeat length in any of these genes, suggesting that variation in the noncoding repetitive regions in these genes does not contribute to ALS.
PMID: 24269018 [PubMed - indexed for MEDLINE]
Tissue engineering in flexor tendon surgery: current state and future advances.
J Hand Surg Eur Vol. 2014 Jan;39(1):71-8
Authors: Galvez MG, Crowe C, Farnebo S, Chang J
Tissue engineering of flexor tendons addresses a challenge often faced by hand surgeons: the restoration of function and improvement of healing with a limited supply of donor tendons. Creating an engineered tendon construct is dependent upon understanding the normal healing mechanisms of the tendon and tendon sheath. The production of a tendon construct includes: creating a three-dimensional scaffold; seeding cells within the scaffold; encouraging cellular growth within the scaffold while maintaining a gliding surface; and finally ensuring mechanical strength. An effective construct incorporates these factors in its design, with the ultimate goal of creating tendon substitutes that are readily available to the reconstructive hand surgeon.
PMID: 24262584 [PubMed - indexed for MEDLINE]
An integrated model of stomatal development and leaf physiology.
New Phytol. 2014 Mar;201(4):1218-26
Authors: Dow GJ, Bergmann DC, Berry JA
• Stomatal conductance (g(s)) is constrained by the size and number of stomata on the plant epidermis, and the potential maximum rate of g(s) can be calculated based on these stomatal traits (Anatomical g(smax)). However, the relationship between Anatomical g(smax) and operational g(s) under atmospheric conditions remains undefined. • Leaf-level gas-exchange measurements were performed for six Arabidopsis thaliana genotypes that have different Anatomical g(smax) profiles resulting from mutations or transgene activity in stomatal development. • We found that Anatomical g(smax) was an accurate prediction of g(s) under gas-exchange conditions that maximized stomatal opening, namely high-intensity light, low [CO₂], and high relative humidity. Plants with different Anatomical g(smax) had quantitatively similar responses to increasing [CO₂] when g(s) was scaled to Anatomical g(smax). This latter relationship allowed us to produce and test an empirical model derived from the Ball-Woodrow-Berry equation that estimates g(s) as a function of Anatomical g(smax), relative humidity, and [CO₂] at the leaf. • The capacity to predict operational g(s) via Anatomical g(smax) and the pore-specific short-term response to [CO₂] demonstrates a precise link between stomatal development and leaf physiology. This connection should be useful to quantify the gas flux of plants in past, present, and future CO₂ regimes based upon the anatomical features of stomata.
PMID: 24251982 [PubMed - indexed for MEDLINE]
Blood collection tube-related alterations in analyte concentrations in quality control material and serum specimens.
Clin Biochem. 2014 Feb;47(3):150-7
Authors: Bowen RA, Sattayapiwat A, Gounden V, Remaley AT
OBJECTIVES: Several previous studies have described the effects of interfering substances on clinical assay results; however, the effects of exogenous substances, particularly additives from blood collection tubes on quality control (QC) specimens and serum specimens have not been well examined. This study examines the effects of blood-collection tube additives on total triiodothyronine (TT3), and thyroxine (TT4), cortisol, and routine clinical chemistry tests in QC and serum specimens from apparently healthy volunteers.
METHODS: QC and serum specimens were poured or collected into different blood collection tubes. TT3 and TT4, cortisol, and routine chemistry tests were analyzed from the different blood-collection tube types.
RESULTS: The findings of this study demonstrate statistically and/or clinically significant blood collection tube-related alterations in the TT3, TT4, and cortisol concentrations of QC specimens and TT4 concentrations from serum specimens.
CONCLUSIONS: These findings have important implications for clinical laboratories, demonstrating that QC specimens should ideally, like patients' specimens, be poured into blood collection tubes. This strategy would reveal any adverse effects caused by blood collection tubes, which otherwise would not likely be detected by most routine QC practices. The results of this study also show the importance of producing blood collection tubes that contain additives that are truly inert and do not adversely affect clinical laboratory testing.
PMID: 24240064 [PubMed - indexed for MEDLINE]
Use of eculizumab and plasma exchange in successful combined liver-kidney transplantation in a case of atypical HUS associated with complement factor H mutation.
Pediatr Nephrol. 2014 Mar;29(3):477-80
Authors: Tran H, Chaudhuri A, Concepcion W, Grimm PC
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) evolves into end-stage renal failure in nearly half of affected patients and is associated with defective regulation of the alternative complement pathway. Patients with a complement factor H (CFH) mutation have a 30-100% risk of graft loss due to aHUS recurrence or graft thrombosis. Since CFH is produced predominantly by the liver, combined liver-kidney transplant is a curative treatment option. One major unexpected risk includes liver failure secondary to uncontrolled complement activation. We report a successful combined liver-kidney transplantation with perioperative plasma exchange and use of the humanized anti-C5 monoclonal antibody eculizumab.
CASE DIAGNOSIS/TREATMENT: An 11-month-old female presented with oliguric renal failure after 3 weeks of flu-like symptoms in the absence of diarrhea. Following the identification of Escherichia coli 0157:H7 in her stool, she was discharged home on peritoneal dialysis with a diagnosis of Shiga toxin-associated HUS. Three months later, she developed severe anemia, thrombocytopenia, and neurological involvement. aHUS was diagnosed and confirmed, and genetic testing revealed a mutation in CFH SCR20. Once donor organs became available, she received preoperative plasma exchange followed by eculizumab infusion with intra-operative fresh frozen plasma prior to combined liver-kidney transplant. At 19 months post-transplant, she continues to have excellent allograft and liver function without signs of disease recurrence.
CONCLUSION: Perioperative use of eculizumab in conjunction with plasma exchange during simultaneous liver-kidney transplant can be used to inhibit terminal complement activity, thereby optimizing successful transplantation by reducing the risk of graft thrombosis.
PMID: 24221349 [PubMed - indexed for MEDLINE]
The physiological importance of developmental mechanisms that enforce proper stomatal spacing in Arabidopsis thaliana.
New Phytol. 2014 Mar;201(4):1205-17
Authors: Dow GJ, Berry JA, Bergmann DC
• Genetic and cell biological mechanisms that regulate stomatal development are necessary to generate an appropriate number of stomata and enforce a minimum spacing of one epidermal cell between stomata. The ability to manipulate these processes in a model plant system allows us to investigate the physiological importance of stomatal patterning and changes in density, therein testing underlying theories about stomatal biology. • Twelve Arabidopsis thaliana genotypes that have varied stomatal characteristics as a result of mutations or transgenes were analyzed in this study. Stomatal traits were used to categorize the genotypes and predict maximum stomatal conductance to water vapor (Anatomical g(smax)) for individuals. Leaf-level gas-exchange measurements determined Diffusive g(smax), net carbon assimilation (A), water-use efficiency (WUE), and stomatal responses to increasing CO₂ concentration. Genotypes with proper spacing (< 5% of stomata in clusters) achieved Diffusive g(smax) values comparable to Anatomical g(smax) across a 10-fold increase in stomatal density, while lines with patterning defects (> 19% clustering) did not. • Genotypes with clustering also had reduced A and impaired stomatal responses, while WUE was generally unaffected by patterning. • Consequently, optimal function per stoma was dependent on maintaining one epidermal cell spacing and the physiological parameters controlled by stomata were strongly correlated with Anatomical g(smax).
PMID: 24206523 [PubMed - indexed for MEDLINE]
A systematic comparison between 1-D and 3-D hemodynamics in compliant arterial models.
Int J Numer Method Biomed Eng. 2014 Feb;30(2):204-31
Authors: Xiao N, Alastruey J, Alberto Figueroa C
We present a systematic comparison of computational hemodynamics in arteries between a one-dimensional (1-D) and a three-dimensional (3-D) formulation with deformable vessel walls. The simulations were performed using a series of idealized compliant arterial models representing the common carotid artery, thoracic aorta, aortic bifurcation, and full aorta from the arch to the iliac bifurcation. The formulations share identical inflow and outflow boundary conditions and have compatible material laws. We also present an iterative algorithm to select the parameters for the outflow boundary conditions by using the 1-D theory to achieve a desired systolic and diastolic pressure at a particular vessel. This 1-D/3-D framework can be used to efficiently determine material and boundary condition parameters for 3-D subject-specific arterial models with deformable vessel walls. Finally, we explore the impact of different anatomical features and hemodynamic conditions on the numerical predictions. The results show good agreement between the two formulations, especially during the diastolic phase of the cycle.
PMID: 24115509 [PubMed - indexed for MEDLINE]
Moderate hypothermia inhibits brain inflammation and attenuates stroke-induced immunodepression in rats.
CNS Neurosci Ther. 2014 Jan;20(1):67-75
Authors: Gu LJ, Xiong XX, Ito T, Lee J, Xu BH, Krams S, Steinberg GK, Zhao H
AIMS: Stroke causes both brain inflammation and immunodepression. Mild-to-moderate hypothermia is known to attenuate brain inflammation, but its role in stroke-induced immunodepression (SIID) of the peripheral immune system remains unknown. This study investigated the effects in rats of moderate intra-ischemic hypothermia on SIID and brain inflammation.
METHODS: Stroke was induced in rats by permanent distal middle cerebral artery occlusion combined with transient bilateral common carotid artery occlusion, while body temperature was reduced to 30°C. Real-time PCR, flow cytometry, in vitro T-cell proliferation assays, in vivo delayed-type hypersensitivity (DTH) reaction and confocal microscopy were used to study SIID and brain inflammation.
RESULTS: Brief intra-ischemic hypothermia helped maintain certain leukocytes in the peripheral blood and spleen and enhanced T-cell proliferation in vitro and delayed-type hypersensitivity in vivo, suggesting that hypothermia reduces SIID. In contrast, in the brain, brief intra-Ischemic hypothermia inhibited mRNA expression of anti-inflammatory cytokine IL-10 and proinflammatory mediators INF-γ, TNF-α, IL-2, IL-1β and MIP-2. Brief intra-Ischemic hypothermia also attenuated the infiltration of lymphocytes, neutrophils (MPO(+) cells) and macrophages (CD68(+) cells) into the ischemic brain, suggesting that hypothermia inhibited brain inflammation.
CONCLUSIONS: Brief intra-ischemic hypothermia attenuated SIID and protected against acute brain inflammation.
PMID: 23981596 [PubMed - indexed for MEDLINE]
Marine protected areas facilitate parasite populations among four fished host species of central Chile.
J Anim Ecol. 2013 Nov;82(6):1276-87
Authors: Wood CL, Micheli F, Fernández M, Gelcich S, Castilla JC, Carvajal J
1. Parasites comprise a substantial proportion of global biodiversity and exert important ecological influences on hosts, communities and ecosystems, but our knowledge of how parasite populations respond to human impacts is in its infancy. 2. Here, we present the results of a natural experiment in which we used a system of highly successful marine protected areas and matched open-access areas in central Chile to assess the influence of fishing-driven biodiversity loss on parasites of exploited fish and invertebrate hosts. We measured the burden of gill parasites for two reef fishes (Cheilodactylus variegatus and Aplodactylus punctatus), trematode parasites for a keyhole limpet (Fissurella latimarginata), and pinnotherid pea crab parasites for a sea urchin (Loxechinus albus). We also measured host density for all four hosts. 3. We found that nearly all parasite species exhibited substantially greater density (# parasites m(-2)) in protected than in open-access areas, but only one parasite species (a gill monogenean of C. variegatus) was more abundant within hosts collected from protected relative to open-access areas. 4. These data indicate that fishing can drive declines in parasite abundance at the parasite population level by reducing the availability of habitat and resources for parasites, but less commonly affects the abundance of parasites at the infrapopulation level (within individual hosts). 5. Considering the substantial ecological role that many parasites play in marine communities, fishing and other human impacts could exert cryptic but important effects on marine community structure and ecosystem functioning via reductions in parasite abundance.
PMID: 23855822 [PubMed - indexed for MEDLINE]
Acute uremia suppresses leucine-induced signal transduction in skeletal muscle.
Kidney Int. 2014 Feb;85(2):374-82
Authors: McIntire KL, Chen Y, Sood S, Rabkin R
Adequate nutrient intake in acute uremia is a key part of patient management especially as food utilization is usually impaired. Leucine is important as it comprises about one-fifth of essential amino acid needs and, apart from serving as a substrate, it directly activates the mTOR signaling pathway stimulating protein synthesis and inhibiting autophagy. Here we tested whether leucine activation of the mTOR signaling pathway in muscle is severely disrupted in acute uremia. Several abnormalities were identified in bilateral ureteral ligated (model of acute uremia) compared to sham-operated pair-fed control rats. Levels of several signaling proteins increased significantly while leucine-induced phosphorylation of mTOR and downstream proteins, 4e-BP1 and S6K1, was completely suppressed. Levels of LC3B-II, a specific autophagosomal membrane-associated protein used as a marker of autophagy, increased threefold in uremia. Furthermore, while leucine suppressed LC3B-II levels in controls, it failed to do so in uremic rats. Muscle IL-6 mRNA levels increased, while IGF-1 mRNA levels decreased in uremia. These findings establish that, in acute uremia, severe resistance to leucine-induced activation of the mTOR anabolic signaling pathway develops. Thus, leucine resistance, together with the reduction in IGF-1 and increase in IL-6 expression, may explain why the anabolic effect of nutritional therapy is diminished in acute uremic patients.
PMID: 23783244 [PubMed - indexed for MEDLINE]
A simple method for purification of vestibular hair cells and non-sensory cells, and application for proteomic analysis.
PLoS One. 2013;8(6):e66026
Authors: Herget M, Scheibinger M, Guo Z, Jan TA, Adams CM, Cheng AG, Heller S
Mechanosensitive hair cells and supporting cells comprise the sensory epithelia of the inner ear. The paucity of both cell types has hampered molecular and cell biological studies, which often require large quantities of purified cells. Here, we report a strategy allowing the enrichment of relatively pure populations of vestibular hair cells and non-sensory cells including supporting cells. We utilized specific uptake of fluorescent styryl dyes for labeling of hair cells. Enzymatic isolation and flow cytometry was used to generate pure populations of sensory hair cells and non-sensory cells. We applied mass spectrometry to perform a qualitative high-resolution analysis of the proteomic makeup of both the hair cell and non-sensory cell populations. Our conservative analysis identified more than 600 proteins with a false discovery rate of <3% at the protein level and <1% at the peptide level. Analysis of proteins exclusively detected in either population revealed 64 proteins that were specific to hair cells and 103 proteins that were only detectable in non-sensory cells. Statistical analyses extended these groups by 53 proteins that are strongly upregulated in hair cells versus non-sensory cells and vice versa by 68 proteins. Our results demonstrate that enzymatic dissociation of styryl dye-labeled sensory hair cells and non-sensory cells is a valid method to generate pure enough cell populations for flow cytometry and subsequent molecular analyses.
PMID: 23750277 [PubMed - indexed for MEDLINE]
NIPT in a clinical setting: an analysis of uptake in the first months of clinical availability.
J Genet Couns. 2014 Feb;23(1):72-8
Authors: Taylor JB, Chock VY, Hudgins L
The objective of our study was to describe the clinical experience in offering noninvasive prenatal testing (NIPT) for aneuploidy to pregnant patients, highlighting the clinical utility, barriers to acceptance and limitations of this novel test. Data were collected from 961 patients offered NIPT from 3/1/12 to 9/30/12. Univariate and multivariate logistic regression analysis was performed. Twenty-eight percent of patients elected NIPT and 72 % declined. Women continue to elect less sensitive and less specific screening through biochemical markers and nuchal translucency. Women considering all options at average risk for aneuploidy were less likely to accept NIPT testing than women who had a risk adjustment from an ultrasound marker or routine screening test. In our multi-ethnic population, Filipina women were significantly less likely to elect NIPT compared to other ethnicities. Five percent of NIPT ordered failed analysis. Several chromosome abnormalities were detected through CVS or amniocentesis that would not have been detected by NIPT. Even though NIPT offers a non-invasive, highly sensitive and specific analysis for aneuploidy, the majority of women in our study declined this option. NIPT should be offered in the context of genetic counseling so that women understand the limitations of the testing and make an educated decision about the testing option best suited to their situation.
PMID: 23723049 [PubMed - indexed for MEDLINE]
Knowledge and attitudes of anesthesia providers about noncardiac surgery in adults with congenital heart disease.
Congenit Heart Dis. 2014 Jan-Feb;9(1):45-53
Authors: Maxwell BG, Williams GD, Ramamoorthy C
OBJECTIVE: To examine the knowledge and attitudes of anesthesia providers in relation to the care of adult congenital heart disease (ACHD) patients presenting for noncardiac surgery.
DESIGN/SETTING: A novel survey was designed and administered to 168 anesthesiologists across a single academic department in a range of practice environments.
OUTCOME MEASURES: Survey responses, including true/false, multiple choice, and Likert scale questions.
RESULTS: A total of 118 anesthesiologists (response rate = 70%) completed the survey. Knowledge scores ranged from 0 to 19 (median [interquartile range] = 7 [5-13]) out of a possible maximum of 20. Total knowledge scores differed significantly by fellowship background (P = .004), with higher scores in those with cardiac (11 [7-15], P = .005) and pediatric (12 [6-15], P = .001) fellowship training, but not in those with critical care, obstetric, regional, or pain management training. Scores also differed by frequency of providing care for cardiopulmonary bypass cases and frequency of providing care for patients under 2 years of age (P < .001 for both), but not by gender or years removed from residency. Respondents reported only moderate levels of comfort with a range of questions about providing perioperative or obstetric care to ACHD patients, with decreasing levels of comfort reported in patients with more complex lesions.
CONCLUSIONS: Within the context of the limitations of a single-institution survey design, the low levels of knowledge and comfort we observed suggest that providers may benefit from improved training and protocols for ensuring adequate preparedness for the care of ACHD patients.
PMID: 23648140 [PubMed - indexed for MEDLINE]
Transcatheter device closure of a congenital aortic-left atrial tunnel.
Congenit Heart Dis. 2014 Jan-Feb;9(1):E23-6
Authors: Sun HY, Buccola KJ, Punn R, Silverman NH, Peng LF, Perry SB, Balasubramanian S
Rare cases of aortic-left atrial tunnel exist in the literature. This case report highlights the echocardiographic characterization of this vascular anomaly and provides the first description of an aortic-left atrial tunnel closed by interventional cardiac catheterization in a pediatric patient.
PMID: 23601836 [PubMed - indexed for MEDLINE]
Traumatic lacerations: what are the risks for infection and has the 'golden period' of laceration care disappeared?
Emerg Med J. 2014 Feb;31(2):96-100
Authors: Quinn JV, Polevoi SK, Kohn MA
OBJECTIVE: To determine risk factors associated with infection and traumatic lacerations and to see if a relationship exists between infection and time to wound closure after injury.
METHODS: Consecutive patients presenting with traumatic lacerations at three diverse emergency departments were prospectively enrolled and 27 variables were collected at the time of treatment. Patients were followed for 30 days to determine the development of a wound infection and desire for scar revision.
RESULTS: 2663 patients completed follow-up and 69 (2.6%, 95% CI 2.0% to 3.3%) developed infection. Infected wounds were more likely to receive a worse cosmetic rating and more likely to be considered for scar revision (RR 2.6, 95% CI 1.7 to 3.9). People with diabetes (RR 2.70, 95% CI 1.1 to 6.5), lower extremity lacerations (RR 4.1, 95% CI 2.5 to 6.8), contaminated lacerations (RR 2.0, 95% CI 1.2 to 3.4) and lacerations greater than 5 cm (RR 2.9, 95% CI 1.6 to 5.2) were more likely to develop an infection. There were no differences in the infection rates for lacerations closed before 3% (95% CI 2.3% to 3.8%) or after 1.2% (95% CI 0.03% to 6.4%) 12 h.
CONCLUSIONS: Diabetes, wound contamination, length greater than 5 cm and location on the lower extremity are important risk factors for wound infection. Time from injury to wound closure is not as important as previously thought. Improvements in irrigation and decontamination over the past 30 years may have led to this change in outcome.
PMID: 23314208 [PubMed - indexed for MEDLINE]
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