Lane Medical Library

The geometric increase in meta-analyses from china in the genomic era.

PLoS One. 2013;8(6):e65602

Authors: Ioannidis JP, Chang CQ, Lam TK, Schully SD, Khoury MJ

Abstract
Meta-analyses are increasingly popular. It is unknown whether this popularity is driven by specific countries and specific meta-analyses types. PubMed was used to identify meta-analyses since 1995 (last update 9/1/2012) and catalogue their types and country of origin. We focused more on meta-analyses from China (the current top producer of meta-analyses) versus the USA (top producer until recently). The annual number of meta-analyses from China increased 40-fold between 2003 and 2011 versus 2.4-fold for the USA. The growth of Chinese meta-analyses was driven by genetics (110-fold increase in 2011 versus 2003). The HuGE Navigator identified 612 meta-analyses of genetic association studies published in 2012 from China versus only 109 from the USA. We compared in-depth 50 genetic association meta-analyses from China versus 50 from USA in 2012. Meta-analyses from China almost always used only literature-based data (92%), and focused on one or two genes (94%) and variants (78%) identified with candidate gene approaches (88%), while many USA meta-analyses used genome-wide approaches and raw data. Both groups usually concluded favorably for the presence of genetic associations (80% versus 74%), but nominal significance (P<0.05) typically sufficed in the China group. Meta-analyses from China typically neglected genome-wide data, and often included candidate gene studies published in Chinese-language journals. Overall, there is an impressive rise of meta-analyses from China, particularly on genetic associations. Since most claimed candidate gene associations are likely false-positives, there is an urgent global need to incorporate genome-wide data and state-of-the art statistical inferences to avoid a flood of false-positive genetic meta-analyses.

PMID: 23776510 [PubMed - in process]

Urine bisphenol-a level in relation to obesity and overweight in school-age children.

PLoS One. 2013;8(6):e65399

Authors: Li DK, Miao M, Zhou Z, Wu C, Shi H, Liu X, Wang S, Yuan W

Abstract
Bisphenol-A (BPA) is a potential endocrine disruptor impacting metabolic processes and increasing the risk of obesity. To determine whether urine BPA level is associated with overweight/obesity in school-age children, we examined 1,326 students in grades 4-12 from three schools (one elementary, one middle, and one high school) in Shanghai. More than 98% of eligible students participated. Total urine BPA concentration was measured and anthropometric measures were taken by trained research staff. Information on risk factors for childhood obesity was collected for potential confounders. Age- and gender-specific weight greater than 90(th) percentile of the underlying population was the outcome measure. After adjustment for potential confounders, a higher urine BPA level (≥2 µg/L), at the level corresponding to the median urine BPA level in the U.S. population, was associated with more than two-fold increased risk of having weight >90(th) percentile among girls aged 9-12 (adjusted odds ratio (aOR) = 2.32, 95% confidence interval: 1.15-4.65). The association showed a dose-response relationship with increasing urine BPA level associated with further increased risk of overweight (p = 0.006 for trend test). Other anthropometric measures of obesity showed similar results. The same association was not observed among boys. This gender difference of BPA effect was consistent with findings from experimental studies and previous epidemiological studies. Our study suggests that BPA could be a potential new environmental obesogen. Widespread exposure to BPA in the human population may also be contributing to the worldwide obesity epidemic.

PMID: 23776476 [PubMed - in process]

Archaeological shellfish size and later human evolution in Africa.

Proc Natl Acad Sci U S A. 2013 Jun 17;

Authors: Klein RG, Steele TE

Abstract
Approximately 50 ka, one or more subgroups of modern humans expanded from Africa to populate the rest of the world. Significant behavioral change accompanied this expansion, and archaeologists commonly seek its roots in the African Middle Stone Age (MSA; ∼200 to ∼50 ka). Easily recognizable art objects and "jewelry" become common only in sites that postdate the MSA in Africa and Eurasia, but some MSA sites contain possible precursors, especially including abstractly incised fragments of ocher and perforated shells interpreted as beads. These proposed art objects have convinced most specialists that MSA people were behaviorally (cognitively) modern, and many argue that population growth explains the appearance of art in the MSA and its post-MSA florescence. The average size of rocky intertidal gastropod species in MSA and later coastal middens allows a test of this idea, because smaller size implies more intense collection, and more intense collection is most readily attributed to growth in the number of human collectors. Here we demonstrate that economically important Cape turban shells and limpets from MSA layers along the south and west coasts of South Africa are consistently and significantly larger than turban shells and limpets in succeeding Later Stone Age (LSA) layers that formed under equivalent environmental conditions. We conclude that whatever cognitive capacity precocious MSA artifacts imply, it was not associated with human population growth. MSA populations remained consistently small by LSA standards, and a substantial increase in population size is obvious only near the MSA/LSA transition, when it is dramatically reflected in the Out-of-Africa expansion.

PMID: 23776248 [PubMed - as supplied by publisher]

Single-molecule spectroscopy reveals photosynthetic LH2 complexes switch between emissive states.

Proc Natl Acad Sci U S A. 2013 Jun 17;

Authors: Schlau-Cohen GS, Wang Q, Southall J, Cogdell RJ, Moerner WE

Abstract
Photosynthetic organisms flourish under low light intensities by converting photoenergy to chemical energy with near unity quantum efficiency and under high light intensities by safely dissipating excess photoenergy and deleterious photoproducts. The molecular mechanisms balancing these two functions remain incompletely described. One critical barrier to characterizing the mechanisms responsible for these processes is that they occur within proteins whose excited-state properties vary drastically among individual proteins and even within a single protein over time. In ensemble measurements, these excited-state properties appear only as the average value. To overcome this averaging, we investigate the purple bacterial antenna protein light harvesting complex 2 (LH2) from Rhodopseudomonas acidophila at the single-protein level. We use a room-temperature, single-molecule technique, the anti-Brownian electrokinetic trap, to study LH2 in a solution-phase (nonperturbative) environment. By performing simultaneous measurements of fluorescence intensity, lifetime, and spectra of single LH2 complexes, we identify three distinct states and observe transitions occurring among them on a timescale of seconds. Our results reveal that LH2 complexes undergo photoactivated switching to a quenched state, likely by a conformational change, and thermally revert to the ground state. This is a previously unobserved, reversible quenching pathway, and is one mechanism through which photosynthetic organisms can adapt to changes in light intensities.

PMID: 23776245 [PubMed - as supplied by publisher]

Underconnectivity between voice-selective cortex and reward circuitry in children with autism.

Proc Natl Acad Sci U S A. 2013 Jun 17;

Authors: Abrams DA, Lynch CJ, Cheng KM, Phillips J, Supekar K, Ryali S, Uddin LQ, Menon V

Abstract
Individuals with autism spectrum disorders (ASDs) often show insensitivity to the human voice, a deficit that is thought to play a key role in communication deficits in this population. The social motivation theory of ASD predicts that impaired function of reward and emotional systems impedes children with ASD from actively engaging with speech. Here we explore this theory by investigating distributed brain systems underlying human voice perception in children with ASD. Using resting-state functional MRI data acquired from 20 children with ASD and 19 age- and intelligence quotient-matched typically developing children, we examined intrinsic functional connectivity of voice-selective bilateral posterior superior temporal sulcus (pSTS). Children with ASD showed a striking pattern of underconnectivity between left-hemisphere pSTS and distributed nodes of the dopaminergic reward pathway, including bilateral ventral tegmental areas and nucleus accumbens, left-hemisphere insula, orbitofrontal cortex, and ventromedial prefrontal cortex. Children with ASD also showed underconnectivity between right-hemisphere pSTS, a region known for processing speech prosody, and the orbitofrontal cortex and amygdala, brain regions critical for emotion-related associative learning. The degree of underconnectivity between voice-selective cortex and reward pathways predicted symptom severity for communication deficits in children with ASD. Our results suggest that weak connectivity of voice-selective cortex and brain structures involved in reward and emotion may impair the ability of children with ASD to experience speech as a pleasurable stimulus, thereby impacting language and social skill development in this population. Our study provides support for the social motivation theory of ASD.

PMID: 23776244 [PubMed - as supplied by publisher]

Endoscopic Hydroxyapatite Augmentation for Patulous Eustachian Tube.

Laryngoscope. 2013 Jun 18;

Authors: Vaezeafshar R, Turner JH, Li G, Hwang PH

Abstract
OBJECTIVES/HYPOTHESIS: To evaluate the safety and efficacy of endoscopic calcium hydroxyapatite injection in patients with patulous Eustachian tube. STUDY DESIGN: Retrospective case series. METHODS: Fourteen patients diagnosed with patulous Eustachian tube (PET) underwent endoscopic hydroxyapatite injection under general anesthesia. All patients had at least two of three major PET symptoms including voice autophony, breathing autophony, or aural fullness/pressure. Patients were evaluated postoperatively with nasal endoscopy and a symptom questionnaire. RESULTS: Endoscopic Eustachian tube injection was performed in a total of 23 sides in 14 patients with an average volume of 2.1 cc injected per side. Mean follow-up was 17.5 months. The most common symptoms reported preoperatively were voice autophony (96%), breathing autophony (91%), and ear fullness (83%). A complete or significant response to treatment was noted in 13/22 sides with voice autophony (59%), 12/21 sides with breathing autophony (57%), and 12/19 sides with ear fullness (63%). All complete or significant symptom improvements remained durable through the entirety of the follow-up period. Four sides that had temporary or no improvement with treatment underwent repeat injection but did not achieve additional improvement. No intraoperative or postoperative complications were observed. CONCLUSION: Endoscopic hydroxyapatite injection of the Eustachian tube is a minimally invasive procedure that provided significant or complete relief of autophony and ear fullness in 57% to 63% of sides treated. The procedure is well tolerated and can be performed safely under endoscopic visualization. Hydroxyapatite injection may be a satisfactory alternative to more invasive treatments for PET. LEVEL OF EVIDENCE: 4. Laryngoscope, 2013.

PMID: 23775903 [PubMed - as supplied by publisher]

Comet-FISH with strand-specific probes reveals transcription-coupled repair of 8-oxoGuanine in human cells.

Nucleic Acids Res. 2013 Jun 17;

Authors: Guo J, Hanawalt PC, Spivak G

Abstract
Oxidized bases in DNA have been implicated in cancer, aging and neurodegenerative disease. We have developed an approach combining single-cell gel electrophoresis (comet) with fluorescence in situ hybridization (FISH) that enables the comparative quantification of low, physiologically relevant levels of DNA lesions in the respective strands of defined nucleotide sequences and in the genome overall. We have synthesized single-stranded probes targeting the termini of DNA segments of interest using a polymerase chain reaction-based method. These probes facilitate detection of damage at the single-molecule level, as the lesions are converted to DNA strand breaks by lesion-specific endonucleases or glycosylases. To validate our method, we have documented transcription-coupled repair of cyclobutane pyrimidine dimers in the ataxia telangiectasia-mutated (ATM) gene in human fibroblasts irradiated with 254 nm ultraviolet at 0.1 J/m(2), a dose ∼100-fold lower than those typically used. The high specificity and sensitivity of our approach revealed that 7,8-dihydro-8-oxoguanine (8-oxoG) at an incidence of approximately three lesions per megabase is preferentially repaired in the transcribed strand of the ATM gene. We have also demonstrated that the hOGG1, XPA, CSB and UVSSA proteins, as well as actively elongating RNA polymerase II, are required for this process, suggesting cross-talk between DNA repair pathways.

PMID: 23775797 [PubMed - as supplied by publisher]

C1q Assay for the Detection of Complement Fixing Antibody to HLA Antigens.

Methods Mol Biol. 2013;1034:305-11

Authors: Chen G, Tyan DB

Abstract
Solid phase Luminex(®) and flow cytometric single antigen bead assays offer exquisite sensitivity and specificity for HLA antibody detection. Unlike the historical complement-dependent cytotoxicity (CDC) method, these assays do not distinguish complement fixing from non-complement fixing antibody, the former of which are considered the most clinically relevant in the peri-transplant period. This chapter describes a novel solid phase C1q binding assay to distinguish HLA antibodies that can bind the first component of complement (C1q). These antibodies have the capacity to initiate the complement cascade irrespective of whether that actually occurs. The C1q assay detects many more complement fixing antibodies than are observed by the less sensitive and less specific CDC assay.

PMID: 23775744 [PubMed - in process]

Lumican Exhibits Anti-Angiogenic Activity in a Context Specific Manner.

Cancer Microenviron. 2013 Jun 18;

Authors: Sharma B, Ramus MD, Kirkwood CT, Sperry EE, Chu PH, Kao WW, Albig AR

Abstract
A series of overexpression studies have shown that lumican suppresses angiogenesis in tumors produced from pancreatic adenocarcinoma, fibrosarcoma, and melanoma tumor cells. Despite lumican's anti-angiogenic activity, a clear correlation of differential expression of lumican in various cancers and cancer malignancy has failed to emerge. Therefore, we hypothesized that either 1.) endogenously expressed lumican is not anti-angiogenic or alternatively that 2.) lumican exhibits angiostatic activity only in limited microenvironments. Previously, lumican was shown to suppress tumor growth and angiogenesis in subcutaneously injected PanO2 pancreatic adenocarcinoma cells. Therefore, to determine if endogenously expressed lumican is anti-angiogenic we subcutaneously injected PanO2 cells into wild-type and lumican knockout mice and compared tumor growth and vascular densities of the resulting tumors. We found that tumors grown in lumican knockout animals were larger and contained significantly elevated vascular densities compared to those grown in wild-type mice. Interestingly however lumican knockout animals did not exhibit enhanced angiogenesis in aortic ring assays, matrigel plugs, or healing wound biopsies raising the possibility that lumican suppresses angiogenesis only in tumor microenvironments. To test this possibility, we sought a tumor model wherein lumican did not exhibit anti-angiogenic activity. Utilizing the 4T1 breast cancer model, we found that lumican suppressed 4T1 tumor growth and lung metastasis, but not angiogenesis. In conclusion, these results show that the angiostatic activity of lumican is dependent on currently undefined microenvironmental cues and therefore helps to understand why differential expression of lumican does not consistently correlate with human tumor malignancy.

PMID: 23775523 [PubMed - as supplied by publisher]

Processive ATP-driven disassembly of SNARE complexes by the N-ethylmaleimide sensitive factor molecular machine.

J Biol Chem. 2013 Jun 17;

Authors: Cipriano DJ, Jung J, Vivona S, Fenn TD, Brunger AT, Bryant Z

Abstract
SNARE proteins promote membrane fusion by forming a 4-stranded parallel helical bundle that brings the membranes into close proximity. Post fusion, the complex is disassembled by an AAA+ ATPase called N-ethylmaleimide sensitive factor (NSF). We present evidence that NSF uses a processive unwinding mechanism to disassemble SNARE proteins. Using a real-time disassembly assay based on fluorescence dequenching, we correlate NSF-driven disassembly rates with the SNARE-activated ATPase activity of NSF. Neuronal SNAREs activate the ATPase rate of NSF by ~26-fold. One SNARE complex takes an average of ~5 seconds to disassemble in a process that consumes ~50 ATP. Investigations of substrate requirements show that NSF is capable of disassembling a truncated SNARE substrate consisting of only the core SNARE domain, but not an unrelated four-stranded coiled coil. NSF can also disassemble an engineered double-length SNARE complex, suggesting a processive unwinding mechanism. We further investigated processivity using single turnover experiments, which show that SNAREs can be unwound in a single encounter with NSF. We propose a processive helicase-like mechanism for NSF in which ~1 residue is unwound for every hydrolyzed ATP molecule.

PMID: 23775070 [PubMed - as supplied by publisher]

Deconstructing the complexity of PTSD in cancer.

Nat Rev Clin Oncol. 2013 Jun 18;

Authors: Palesh O, Koopman C

PMID: 23774643 [PubMed - as supplied by publisher]

Throwing out the Bayesian baby with the optimal bathwater: Response to.

Cognition. 2013 Jun 14;128(3):417-423

Authors: Frank MC

Abstract
A recent probabilistic model unified findings on sequential generalization ("rule learning") via independently-motivated principles of generalization (Frank & Tenenbaum, 2011). Endress critiques this work, arguing that learners do not prefer more specific hypotheses (a central assumption of the model), that "common-sense psychology" provides an adequate explanation of rule learning, and that Bayesian models imply incorrect optimality claims but can be fit to any pattern of data. Endress's response raises useful points about the importance of mechanistic explanation, but the specific critiques of our work are not supported. More broadly, I argue that Endress undervalues the importance of formal models. Although probabilistic models must meet a high standard to be used as evidence for optimality claims, they nevertheless provide a powerful framework for describing cognition.

PMID: 23774636 [PubMed - as supplied by publisher]

The author replies.

Crit Care Med. 2013 Jul;41(7):e144-5

Authors: Barr J

PMID: 23774371 [PubMed - in process]

Reduction of subjective distress in CBT for childhood OCD: Nature of change, predictors, and relation to treatment outcome.

J Anxiety Disord. 2013 May 21;

Authors: Kircanski K, Wu M, Piacentini J

Abstract
Little research has investigated changes in subjective distress during cognitive-behavioral therapy (CBT) for anxiety disorders in youth. In the current study, 40 youth diagnosed with primary obsessive-compulsive disorder (OCD; M age=11.9 years, 60% male, 80% Caucasian) and 36 parent informants completed separate weekly ratings of child distress for each OC symptom during a 12-session course of CBT. Between-session changes in distress were calculated at the start of, on average throughout, and at the end of treatment. On average throughout treatment, child- and parent-reported decreases in child distress were significant. Baseline OCD severity, functional impairment, and internalizing symptoms predicted degree of change in child distress. Additionally, greater decreases in child distress were predictive of more improved clinical outcomes. Findings advance our understanding of the strengths and limitations of this clinical tool. Future studies should examine youth distress change between and within CBT sessions across both subjective and psychophysiological levels of analysis.

PMID: 23774008 [PubMed - as supplied by publisher]

Differentiating the roles of STAT5B and STAT5A in human CD4(+) T cells.

Clin Immunol. 2013 May 5;148(2):227-236

Authors: Jenks JA, Seki S, Kanai T, Huang J, Morgan AA, Scalco RC, Nath R, Bucayu R, Wit JM, Al-Herz W, Ramadan D, Jorge AA, Bacchetta R, Hwa V, Rosenfeld R, Nadeau KC

Abstract
STAT5A and STAT5B are highly homologous proteins whose distinctive roles in human immunity remain unclear. However, STAT5A sufficiency cannot compensate for STAT5B defects, and human STAT5B deficiency, a rare autosomal recessive primary immunodeficiency, is characterized by chronic lung disease, growth failure and autoimmunity associated with regulatory T cell (Treg) reduction. We therefore hypothesized that STAT5A and STAT5B play unique roles in CD4(+) T cells. Upon knocking down STAT5A or STAT5B in human primary T cells, we found differentially regulated expression of FOXP3 and IL-2R in STAT5B knockdown T cells and down-regulated Bcl-X only in STAT5A knockdown T cells. Functional ex vivo studies in homozygous STAT5B-deficient patients showed reduced FOXP3 expression with impaired regulatory function of STAT5B-null Treg cells, also of increased memory phenotype. These results indicate that STAT5B and STAT5A act partly as non-redundant transcription factors and that STAT5B is more critical for Treg maintenance and function in humans.

PMID: 23773921 [PubMed - as supplied by publisher]

Foot and ankle injuries in sport: imaging correlation with arthroscopic and surgical findings.

Clin Sports Med. 2013 Jul;32(3):525-57

Authors: Hunt KJ, Githens M, Riley GM, Kim M, Gold GE

Abstract
Foot and ankle injuries are common in sport. Although many available imaging techniques can be useful in identifying and classifying injuries, magnetic resonance imaging (MRI) provides high levels of sensitivity and specificity for articular and soft-tissue injuries. Arthroscopic and minimally invasive treatment techniques for foot and ankle injuries are rapidly evolving, minimizing morbidity and improving postoperative rehabilitation and return to play. Correlation between MRI and surgical findings can aid in both accessing and treating pathologic processes and structures.

PMID: 23773880 [PubMed - in process]

Hip-femoral acetabular impingement.

Clin Sports Med. 2013 Jul;32(3):409-25

Authors: Anderson CN, Riley GM, Gold GE, Safran MR

Abstract
Magnetic resonance imaging (MRI) has become a valuable technology for the diagnosis and treatment of femoroacetabular impingement (FAI). This article reviews the basic pathophysiology of FAI, as well as the techniques and indications for MRI and magnetic resonance arthrography. Normal MRI anatomy of the hip and pathologic MRI anatomy associated with FAI are also discussed. Several case examples are presented demonstrating the diagnosis and treatment of FAI.

PMID: 23773875 [PubMed - in process]

The subventricular zone neural progenitor cell hypothesis in glioblastoma: epiphany, trojan horse, or cheshire fact?

Int J Radiat Oncol Biol Phys. 2013 Jul 15;86(4):606-8

Authors: Gibbs IC, Haas-Kogan D, Terezakis S, Kavanagh BD

PMID: 23773389 [PubMed - in process]

A content analysis of posthumous sperm procurement protocols with considerations for developing an institutional policy.

Fertil Steril. 2013 Jun 14;

Authors: Bahm SM, Karkazis K, Magnus D

Abstract
OBJECTIVE: To identify and analyze existing posthumous sperm procurement (PSP) protocols in order to outline central themes for institutions to consider when developing future policies. DESIGN: Qualitative content analysis. SETTING: Large academic institutions across the United States. PATIENT(S): N/A. INTERVENTION(S): We performed a literature search and contacted 40 institutions to obtain nine full PSP protocols. We then performed a content analysis on these policies to identify major themes and factors to consider when developing a PSP protocol. MAIN OUTCOME MEASURE(S): Presence of a PSP policy. RESULT(S): We identified six components of a thorough PSP protocol: Standard of Evidence, Terms of Eligibility, Sperm Designee, Restrictions on Use in Reproduction, Logistics, and Contraindications. We also identified two different approaches to policy structure. In the Limited Role approach, institutions have stricter consent requirements and limit their involvement to the time of procurement. In the Family-Centered approach, substituted judgment is permitted but a mandatory wait period is enforced before sperm use in reproduction. CONCLUSION(S): Institutions seeking to implement a PSP protocol will benefit from considering the six major building blocks of a thorough protocol and where they would like to fall on the spectrum from a Limited Role to a Family-Centered approach.

PMID: 23773314 [PubMed - as supplied by publisher]

Ambient air pollution and traffic exposures and congenital heart defects in the san joaquin valley of california.

Paediatr Perinat Epidemiol. 2013 Jul;27(4):329-39

Authors: Padula AM, Tager IB, Carmichael SL, Hammond SK, Yang W, Lurmann F, Shaw GM

Abstract
BACKGROUND: Congenital anomalies are a leading cause of infant morbidity and mortality. Studies suggest associations between environmental contaminants and some anomalies, although evidence is limited.
METHODS: We used data from the California Center of the National Birth Defects Prevention Study and the Children's Health and Air Pollution Study to estimate the odds of 27 congenital heart defects with respect to quartiles of seven ambient air pollutant and traffic exposures in California during the first 2 months of pregnancy, 1997-2006 (n = 822 cases and n = 849 controls).
RESULTS: Particulate matter < 10 microns (PM10 ) was associated with pulmonary valve stenosis [adjusted odds ratio (aOR)Fourth Quartile  = 2.6] [95% confidence intervals (CI) 1.2, 5.7] and perimembranous ventricular septal defects (aORThird Quartile  = 2.1) [95% CI 1.1, 3.9] after adjusting for maternal race/ethnicity, education and multivitamin use. PM2.5 was associated with transposition of the great arteries (aORThird Quartile  = 2.6) [95% CI 1.1, 6.5] and inversely associated with perimembranous ventricular septal defects (aORFourth Quartile  = 0.5) [95% CI 0.2, 0.9]. Secundum atrial septal defects were inversely associated with carbon monoxide (aORFourth Quartile  = 0.4) [95% CI 0.2, 0.8] and PM2.5 (aORFourth Quartile  = 0.5) [95% CI 0.3, 0.8]. Traffic density was associated with muscular ventricular septal defects (aORFourth Quartile  = 3.0) [95% CI 1.2, 7.8] and perimembranous ventricular septal defects (aORThird Quartile  = 2.4) [95% CI 1.3, 4.6], and inversely associated with transposition of the great arteries (aORFourth Quartile  = 0.3) [95% CI 0.1, 0.8].
CONCLUSIONS: PM10 and traffic density may contribute to the occurrence of pulmonary valve stenosis and ventricular septal defects, respectively. The results were mixed for other pollutants and had little consistency with previous studies.

PMID: 23772934 [PubMed - in process]

A multicenter, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia.

Transfusion. 2013 Jun 17;

Authors: Onken JE, Bregman DB, Harrington RA, Morris D, Acs P, Akright B, Barish C, Bhaskar BS, Smith-Nguyen GN, Butcher A, Koch TA, Goodnough LT

Abstract
BACKGROUND: Many patients receiving oral iron for iron deficiency anemia (IDA) cannot tolerate or fail to respond to therapy, and existing intravenous (IV) iron formulations often require repeated administrations. Ferric carboxymaltose (FCM), a nondextran IV formulation, permits larger single doses. STUDY DESIGN AND METHODS: We evaluated FCM versus oral iron in IDA patients. After 14 days of oral iron, 507 participants responding inadequately to oral iron (hemoglobin [Hb] increase <1 g/dL; Cohort 1) were assigned to Group A (two doses of FCM, 750 mg, 1 week apart) or Group B (oral iron, 325 mg, 3 × day for 14 additional days). Also, 504 subjects not appropriate for oral iron (Cohort 2) were assigned to Group C (FCM as above) or Group D (standard-of-care IV iron). The primary efficacy endpoint was change to highest observed Hb from baseline to Day 35. The composite safety endpoint included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina, heart failure, arrhythmias, and hyper- or hypotensive events. RESULTS: Mean (± standard deviation [SD]) Hb increase was significantly greater in Group A-FCM than Group B-oral iron: 1.57 (±1.19) g/dL versus 0.80 (±0.80) g/dL (p = 0.001). Post hoc comparison of Group C-FCM and Group D-IV standard of care also demonstrated significant mean (±SD) increase in Hb from baseline to highest value by Day 35 in Group C versus Group D: 2.90 (±1.64) g/dL versus 2.16 (±1.25) g/dL (p = 0.001). Safety endpoints occurred in 17 of 499 (3.4%) participants receiving FCM versus 16 of 498 (3.2%) in comparator groups. CONCLUSION: Two 750-mg FCM infusions are safe and superior to oral iron in increasing Hb levels in IDA patients with inadequate oral iron response.

PMID: 23772856 [PubMed - as supplied by publisher]

Assessing extracellular fluid volume in breast cancer lymphedema.

Lymphat Res Biol. 2013 Jun;11(2):65

Authors: Rockson SG

PMID: 23772714 [PubMed - in process]

Cochlear implant considerations in children with additional disabilities.

Curr Otorhinolaryngol Rep. 2013 Jun 1;1(2):61-68

Authors: Corrales CE, Oghalai JS

Abstract
Early identification and management of disabilities in children are essential to reduce long-term developmental sequelae. Many of the causes of hearing loss also produce cognitive delays resulting in a large number of children with both deafness and developmental disabilities. Children who have hearing loss and additional disabilities require complex, individualized therapy to maximize their long-term quality of life. Hearing loss is often detected early because of widespread newborn hearing screening programs and the decision for cochlear implantation in children presenting with multiple medical and developmental disorders is still evolving. This article will review the literature regarding cochlear implant considerations in children with additional developmental disabilities in areas of family perception, speech and language development, cognitive development including adaptive behavior and intelligence, communication and functional skills, auditory outcomes, quality of life outcomes, predictors of outcomes and realistic expectations after cochlear implantation.

PMID: 23772353 [PubMed - as supplied by publisher]

Genetic risk variants in African Americans with multiple sclerosis.

Neurology. 2013 Jun 14;

Authors: Isobe N, Gourraud PA, Harbo HF, Caillier SJ, Santaniello A, Khankhanian P, Maiers M, Spellman S, Cereb N, Yang S, Pando MJ, Piccio L, Cross AH, De Jager PL, Cree BA, Hauser SL, Oksenberg JR

Abstract
OBJECTIVES: To assess the association of established multiple sclerosis (MS) risk variants in 3,254 African Americans (1,162 cases and 2,092 controls). METHODS: Human leukocyte antigen (HLA)-DRB1, HLA-DQB1, and HLA-A alleles were typed by molecular techniques. Single nucleotide polymorphism (SNP) genotyping was conducted for 76 MS-associated SNPs and 52 ancestry informative marker SNPs selected throughout the genome. Self-declared ancestry was refined by principal component analysis of the ancestry informative marker SNPs. An ancestry-adjusted multivariate model was applied to assess genetic associations. RESULTS: The following major histocompatibility complex risk alleles were replicated: HLA-DRB1*15:01 (odds ratio [OR] = 2.02 [95% confidence interval: 1.54-2.63], p = 2.50e-07), HLA-DRB1*03:01 (OR = 1.58 [1.29-1.94], p = 1.11e-05), as well as HLA-DRB1*04:05 (OR = 2.35 [1.26-4.37], p = 0.007) and the African-specific risk allele of HLA-DRB1*15:03 (OR = 1.26 [1.05-1.51], p = 0.012). The protective association of HLA-A*02:01 was confirmed (OR = 0.72 [0.55-0.93], p = 0.013). None of the HLA-DQB1 alleles were associated with MS. Using a significance threshold of p < 0.01, outside the major histocompatibility complex region, 8 MS SNPs were also found to be associated with MS in African Americans. CONCLUSION: MS genetic risk in African Americans only partially overlaps with that of Europeans and could explain the difference of MS prevalence between populations.

PMID: 23771490 [PubMed - as supplied by publisher]

Imaging currents in HgTe quantum wells in the quantum spin Hall regime.

Nat Mater. 2013 Jun 16;

Authors: Nowack KC, Spanton EM, Baenninger M, König M, Kirtley JR, Kalisky B, Ames C, Leubner P, Brüne C, Buhmann H, Molenkamp LW, Goldhaber-Gordon D, Moler KA

Abstract
The quantum spin Hall (QSH) state is a state of matter characterized by a non-trivial topology of its band structure, and associated conducting edge channels. The QSH state was predicted and experimentally demonstrated to be realized in HgTe quantum wells. The existence of the edge channels has been inferred from local and non-local transport measurements in sufficiently small devices. Here we directly confirm the existence of the edge channels by imaging the magnetic fields produced by current flowing in large Hall bars made from HgTe quantum wells. These images distinguish between current that passes through each edge and the bulk. On tuning the bulk conductivity by gating or raising the temperature, we observe a regime in which the edge channels clearly coexist with the conducting bulk, providing input to the question of how ballistic transport may be limited in the edge channels. Our results represent a versatile method for characterization of new QSH materials systems.

PMID: 23770727 [PubMed - as supplied by publisher]

Assessment of Homology Templates and an Anesthetic Binding Site within the γ-Aminobutyric Acid Receptor.

Anesthesiology. 2013 Jun 13;

Authors: Bertaccini EJ, Yoluk O, Lindahl ER, Trudell JR

Abstract
BACKGROUND:: Anesthetics mediate portions of their activity via modulation of the γ-aminobutyric acid receptor (GABAaR). Although its molecular structure remains unknown, significant progress has been made toward understanding its interactions with anesthetics via molecular modeling. METHODS:: The structure of the torpedo acetylcholine receptor (nAChRα), the structures of the α4 and β2 subunits of the human nAChR, the structures of the eukaryotic glutamate-gated chloride channel (GluCl), and the prokaryotic pH-sensing channels, from Gloeobacter violaceus and Erwinia chrysanthemi, were aligned with the SAlign and 3DMA algorithms. A multiple sequence alignment from these structures and those of the GABAaR was performed with ClustalW. The Modeler and Rosetta algorithms independently created three-dimensional constructs of the GABAaR from the GluCl template. The CDocker algorithm docked a congeneric series of propofol derivatives into the binding pocket and scored calculated binding affinities for correlation with known GABAaR potentiation EC50s. RESULTS:: Multiple structure alignments of templates revealed a clear consensus of residue locations relevant to anesthetic effects except for torpedo nAChR. Within the GABAaR models generated from GluCl, the residues notable for modulating anesthetic action within transmembrane segments 1, 2, and 3 converged on the intersubunit interface between α and β subunits. Docking scores of a propofol derivative series into this binding site showed strong linear correlation with GABAaR potentiation EC50. CONCLUSION:: Consensus structural alignment based on homologous templates revealed an intersubunit anesthetic binding cavity within the transmembrane domain of the GABAaR, which showed a correlation of ligand docking scores with experimentally measured GABAaR potentiation.

PMID: 23770602 [PubMed - as supplied by publisher]

Specific Kinematics and Motor-Related Neurons for Aversive Chemotaxis in Drosophila.

Curr Biol. 2013 Jun 11;

Authors: Gao XJ, Potter CJ, Gohl DM, Silies M, Katsov AY, Clandinin TR, Luo L

Abstract
BACKGROUND: Chemotaxis, the ability to direct movements according to chemical cues in the environment, is important for the survival of most organisms. The vinegar fly, Drosophila melanogaster, displays robust olfactory aversion and attraction, but how these behaviors are executed via changes in locomotion remains poorly understood. In particular, it is not clear whether aversion and attraction bidirectionally modulate a shared circuit or recruit distinct circuits for execution. RESULTS: Using a quantitative behavioral assay, we determined that both aversive and attractive odorants modulate the initiation and direction of turns but display distinct kinematics. Using genetic tools to perturb these behaviors, we identified specific populations of neurons required for aversion, but not for attraction. Inactivation of these populations of cells affected the completion of aversive turns, but not their initiation. Optogenetic activation of the same populations of cells triggered a locomotion pattern resembling aversive turns. Perturbations in both the ellipsoid body and the ventral nerve cord, two regions involved in motor control, resulted in defects in aversion. CONCLUSIONS: Aversive chemotaxis in vinegar flies triggers ethologically appropriate kinematics distinct from those of attractive chemotaxis and requires specific motor-related neurons.

PMID: 23770185 [PubMed - as supplied by publisher]

Asynchronous Broadband Signals Are the Principal Source of the BOLD Response in Human Visual Cortex.

Curr Biol. 2013 Jun 11;

Authors: Winawer J, Kay KN, Foster BL, Rauschecker AM, Parvizi J, Wandell BA

Abstract
BACKGROUND: Activity in the living human brain can be studied using multiple methods, spanning a wide range of spatial and temporal resolutions. We investigated the relationship between electric field potentials measured with electrocorticography (ECoG) and the blood oxygen level-dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI). We set out to explain the full set of measurements by modeling the underlying neural circuits. RESULTS: ECoG responses in visual cortex can be separated into two visually driven components. One component is a specific temporal response that follows each stimulus contrast reversal ("stimulus locked"); the other component is an increase in the response variance ("asynchronous"). For electrodes in visual cortex (V1, V2, V3), the two measures respond to stimuli in the same region of visual space, but they have different spatial summation properties. The stimulus-locked ECoG component sums contrast approximately linearly across space; spatial summation in the asynchronous ECoG component is subadditive. Spatial summation measured using BOLD closely matches the asynchronous component. We created a neural simulation that accurately captures the main features of the ECoG time series; in the simulation, the stimulus-locked and asynchronous components arise from different neural circuits. CONCLUSIONS: These observations suggest that the two ECoG components arise from different neural sources within the same cortical region. The spatial summation measurements and simulations suggest that the BOLD response arises primarily from neural sources that generate the asynchronous broadband ECoG component.

PMID: 23770184 [PubMed - as supplied by publisher]

Respiratory-Mode Display of Echocardiographic Images Highlights Effects of Pericardial Disease.

JACC Cardiovasc Imaging. 2013 Jun 8;

Authors: McConnell MV, Wu HH

PMID: 23769491 [PubMed - as supplied by publisher]

Ultrasonographic evaluation of malignant and normal cervical lymph nodes.

Semin Ultrasound CT MR. 2013 Jun;34(3):236-47

Authors: Giacomini CP, Jeffrey RB, Shin LK

Abstract
Head and neck malignancies, including squamous cell carcinoma, lymphoma, and thyroid cancer, are a major cause of morbidity and mortality worldwide and frequently present with cervical lymphadenopathy. Distinguishing normal from malignant lymph nodes is critical for accurate staging, prognosis, and determination of optimal therapeutic options. Gray-scale, power, and color Doppler ultrasonography offers an inexpensive yet effective method in identifying abnormal cervical lymph nodes. Sonographic nodal features that should be assessed include size, shape, echotexture (including microcalcifications and cystic changes), presence of an echogenic hilus, and vascularity. Although no single sonographic feature can accurately distinguish malignant from normal nodes, a combination of these characteristics can help to make this determination.

PMID: 23768890 [PubMed - in process]

Pitfalls in sonographic evaluation of thyroid abnormalities.

Semin Ultrasound CT MR. 2013 Jun;34(3):226-35

Authors: Patel BN, Kamaya A, Desser TS

Abstract
Ultrasound of the thyroid has become increasingly common, with evaluation of thyroid nodules representing the main indication for its use. While detection of thyroid nodules with modern high-resolution sonographic equipment is generally not a challenge, pitfalls may occur by which normal structures or pathology in neighboring organs are mistaken for thyroid nodules. Numerous reports in the literature describe various sonographic features of nodules in an attempt to stratify lesions into benign or malignant categories. While neither nodule size nor number is reliable, echogenicity, microcalcifcation, shape, and composition have been reported to be helpful in classifying thyroid nodules. No single feature should be used in isolation, and consensus guidelines have been established as to when fine-needle aspiration is indicated. Pitfalls remain in the evaluation of thyroid nodules demonstrating atypical features, such as cystic papillary carcinomas. Focal presentation of typically diffuse processes, such as Graves' disease and Hashimoto thyroiditis, may mimic malignant nodules, but carcinomas occur in these settings as well as in a background of normal thyroid parenchyma. Finally, because ultrasound is commonly used for surveillance of patients with thyroid carcinoma after thyroidectomy, sonographers should be familiar with the ultrasound appearance of disease recurrence and its mimics.

PMID: 23768889 [PubMed - in process]

Convergent antibody signatures in human dengue.

Cell Host Microbe. 2013 Jun 12;13(6):691-700

Authors: Parameswaran P, Liu Y, Roskin KM, Jackson KK, Dixit VP, Lee JY, Artiles KL, Zompi S, Vargas MJ, Simen BB, Hanczaruk B, McGowan KR, Tariq MA, Pourmand N, Koller D, Balmaseda A, Boyd SD, Harris E, Fire AZ

Abstract
Dengue is the most prevalent mosquito-borne viral disease in humans, and the lack of early prognostics, vaccines, and therapeutics contributes to immense disease burden. To identify patterns that could be used for sequence-based monitoring of the antibody response to dengue, we examined antibody heavy-chain gene rearrangements in longitudinal peripheral blood samples from 60 dengue patients. Comparing signatures between acute dengue, postrecovery, and healthy samples, we found increased expansion of B cell clones in acute dengue patients, with higher overall clonality in secondary infection. Additionally, we observed consistent antibody sequence features in acute dengue in the highly variable major antigen-binding determinant, complementarity-determining region 3 (CDR3), with specific CDR3 sequences highly enriched in acute samples compared to postrecovery, healthy, or non-dengue samples. Dengue thus provides a striking example of a human viral infection where convergent immune signatures can be identified in multiple individuals. Such signatures could facilitate surveillance of immunological memory in communities.

PMID: 23768493 [PubMed - in process]

Some first steps toward responsible use of cognitive-enhancing drugs by the healthy.

Am J Bioeth. 2013 Jul;13(7):39-41

Authors: Greely HT

PMID: 23767438 [PubMed - in process]

Overthrowing the tyranny of the journal impact factor.

Am J Bioeth. 2013 Jul;13(7):1-2

Authors: Magnus D

PMID: 23767427 [PubMed - in process]

Comparative effectiveness of coronary artery bypass grafting and percutaneous coronary intervention for multivessel coronary disease in a community-based population with chronic kidney disease.

Am Heart J. 2013 May;165(5):800-8, 808.e1-2

Authors: Chang TI, Leong TK, Kazi DS, Lee HS, Hlatky MA, Go AS

Abstract
BACKGROUND: Randomized clinical trials comparing coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) have largely excluded patients with chronic kidney disease (CKD), leading to uncertainty about the optimal coronary revascularization strategy. We sought to test the hypothesis that an initial strategy of CABG would be associated with lower risks of long-term mortality and cardiovascular morbidity compared with PCI for the treatment of multivessel coronary heart disease in the setting of CKD.
METHODS: We created a propensity score-matched cohort of patients aged ≥30 years with no prior dialysis or renal transplant who received multivessel coronary revascularization between 1996 and 2008 within a large integrated health care delivery system in northern California. We used extended Cox regression to examine death from any cause, acute coronary syndrome, and repeat revascularization.
RESULTS: Coronary artery bypass grafting was associated with a significantly lower adjusted rate of death than PCI across all strata of estimated glomerular filtration rate (eGFR) (in mL/min per 1.73 m(2)): the adjusted hazard ratio (HR) was 0.81, 95% CI 0.68 to 1.00 for patients with eGFR ≥60; HR 0.73 (CI 0.56-0.95) for eGFR of 45 to 59; and HR 0.87 (CI 0.67-1.14) for eGFR <45. Coronary artery bypass grafting was also associated with significantly lower rates of acute coronary syndrome and repeat revascularization at all levels of eGFR compared with PCI.
CONCLUSIONS: Among adults with and without CKD, multivessel CABG was associated with lower risks of death and coronary events compared with multivessel PCI.

PMID: 23622918 [PubMed - indexed for MEDLINE]

A brain area for visual numerals.

J Neurosci. 2013 Apr 17;33(16):6709-15

Authors: Shum J, Hermes D, Foster BL, Dastjerdi M, Rangarajan V, Winawer J, Miller KJ, Parvizi J

Abstract
Is there a distinct area within the human visual system that has a preferential response to numerals, as there is for faces, words, or scenes? We addressed this question using intracranial electrophysiological recordings and observed a significantly higher response in the high-frequency broadband range (high γ, 65-150 Hz) to visually presented numerals, compared with morphologically similar (i.e., letters and false fonts) or semantically and phonologically similar stimuli (i.e., number words and non-number words). Anatomically, this preferential response was consistently localized in the inferior temporal gyrus and anterior to the temporo-occipital incisure. This region lies within or close to the fMRI signal-dropout zone produced by the nearby auditory canal and venous sinus artifacts, an observation that may account for negative findings in previous fMRI studies of preferential response to numerals. Because visual numerals are culturally dependent symbols that are only learned through education, our novel finding of anatomically localized preferential response to such symbols provides a new example of acquired category-specific responses in the human visual system.

PMID: 23595729 [PubMed - indexed for MEDLINE]

Structural and rheological properties of meibomian lipid.

Invest Ophthalmol Vis Sci. 2013;54(4):2720-32

Authors: Rosenfeld L, Cerretani C, Leiske DL, Toney MF, Radke CJ, Fuller GG

Abstract
PURPOSE: We explore the unique rheological and structural properties of human and bovine meibomian lipids to provide insight into the physical behavior of the human tear-film lipid layer (TFLL).
METHODS: Bulk rheological properties of pooled meibomian lipids were measured by a commercial stress-controlled rheometer; a home-built interfacial stress rheometer (ISR) probed the interfacial viscoelasticity of spread layers of meibomian lipids. Small- and wide-angle x-ray scattering detected the presence and melting of dispersed crystal structures. Microscope examination under cross polarizers provided confirmation of ordered crystals. A differential scanning calorimeter (DSC) analyzed phase transitions in bulk samples of bovine meibum.
RESULTS: Bulk and interfacial rheology measurements show that meibum is extremely viscous and highly elastic. It is also a non-Newtonian, shear-thinning fluid. Small- and wide-angle x-ray diffraction (SAXS and WAXS), as well as differential scanning calorimetry (DSC) and polarizing microscopy, confirm the presence of suspended lamellar-crystal structures at physiologic temperature.
CONCLUSIONS: We studied meibum architecture and its relation to bulk and interfacial rheology. Bovine and human meibomian lipids exhibit similar physical properties. From all structural probes utilized, we find a melt transition near eye temperature at which lamellar crystals liquefy. Our proposed structure for the tear-film lipid layer at physiologic temperature is a highly viscoelastic, shear-thinning liquid suspension consisting of lipid lamellar-crystallite particulates immersed in a continuous liquid phase with no long-range order. When spread over on-eye tear, the TFLL is a duplex film that exhibits bulk liquid properties and two separate interfaces, air/lipid and water/lipid, with aqueous protein and surfactantlike lipids adsorbed at the water/lipid surface.

PMID: 23513065 [PubMed - indexed for MEDLINE]

A prospective randomized trial of ultrasound- vs landmark-guided central venous access in the pediatric population.

J Am Coll Surg. 2013 May;216(5):939-43

Authors: Bruzoni M, Slater BJ, Wall J, St Peter SD, Dutta S

Abstract
BACKGROUND: The purpose of this prospective randomized study was to compare landmark- to ultrasound-guided central venous access when performed by pediatric surgeons. The American College of Surgeons advocates for use of ultrasound in central venous catheter placement; however, this is not universally embraced by pediatric surgeons. Complication risk correlates positively with number of venous cannulation attempts.
STUDY DESIGN: With IRB approval, a randomized prospective study of children under 18 years of age undergoing tunneled central venous catheter placement was performed. Patient accrual was based on power analysis. Exclusion criteria included known nonpatency of a central vein or coagulopathy. After randomization, the patients were assigned to either ultrasound-guided internal jugular vein access or landmark-guided subclavian/internal jugular vein access. The primary outcomes measure was number of attempts at venous cannulation. Secondary outcomes measures included: access times, number of arterial punctures, and other complications. Continuous variables were compared using 2-tailed Student's t-test. Discrete variables were analyzed with chi-square. Significance was defined as p < 0.05.
RESULTS: There were 150 patients enrolled between April 2008 and September 2011. There was no difference when comparing demographic data. Success at first attempt was achieved in 65% of patients in the ultrasound group vs 45% in the landmark group (p = 0.021). Success within 3 attempts was achieved in 95% of ultrasound group vs 74% of landmark group (p = 0.0001).
CONCLUSIONS: Ultrasound reduced the number of cannulation attempts necessary for venous access. This indicates a potential to reduce complications when ultrasound is used by pediatric surgeons.

PMID: 23478546 [PubMed - indexed for MEDLINE]

Systematic identification of interaction effects between genome- and environment-wide associations in type 2 diabetes mellitus.

Hum Genet. 2013 May;132(5):495-508

Authors: Patel CJ, Chen R, Kodama K, Ioannidis JP, Butte AJ

Abstract
Diseases such as type 2 diabetes (T2D) result from environmental and genetic factors, and risk varies considerably in the population. T2D-related genetic loci discovered to date explain only a small portion of the T2D heritability. Some heritability may be due to gene-environment interactions. However, documenting these interactions has been difficult due to low availability of concurrent genetic and environmental measures, selection bias, and challenges in controlling for multiple hypothesis testing. Through genome-wide association studies (GWAS), investigators have identified over 90 single nucleotide polymorphisms (SNPs) associated to T2D. Using a method analogous to GWAS [environment-wide association study (EWAS)], we found five environmental factors associated with the disease. By focusing on risk factors that emerge from GWAS and EWAS, it is possible to overcome difficulties in uncovering gene-environment interactions. Using data from the National Health and Nutrition Examination Survey (NHANES), we screened 18 SNPs and 5 serum-based environmental factors for interaction in association to T2D. We controlled for multiple hypotheses using false discovery rate (FDR) and Bonferroni correction and found four interactions with FDR <20 %. The interaction between rs13266634 (SLC30A8) and trans-β-carotene withstood Bonferroni correction (corrected p = 0.006, FDR <1.5 %). The per-risk-allele effect sizes in subjects with low levels of trans-β-carotene were 40 % greater than the marginal effect size [odds ratio (OR) 1.8, 95 % CI 1.3-2.6]. We hypothesize that impaired function driven by rs13266634 increases T2D risk when combined with serum levels of nutrients. Unbiased consideration of environmental and genetic factors may help identify larger and more relevant effect sizes for disease associations.

PMID: 23334806 [PubMed - indexed for MEDLINE]

The seed and the soil: optimizing stem cells and their environment for tissue regeneration.

Ann Plast Surg. 2013 Feb;70(2):235-9

Authors: Hyun JS, Montoro DT, Lo DD, Flynn RA, Wong V, Chung MT, Longaker MT, Wan DC

Abstract
The potential for stem cells to serve as cellular building blocks for reconstruction of complex defects has prompted significant enthusiasm in the field of regenerative medicine. Clinical application, however, is still limited, as implantation of cells into hostile wound environments may greatly hinder their tissue forming capacity. To circumvent this obstacle, novel approaches have been developed to manipulate both the stem cell itself and its surrounding environmental niche. By understanding this paradigm of seed and soil optimization, innovative strategies may thus be developed to harness the true promise of stem cells for tissue regeneration.

PMID: 23295233 [PubMed - indexed for MEDLINE]

A randomized comparison of long-and short-axis imaging for in-plane ultrasound-guided femoral perineural catheter insertion.

J Ultrasound Med. 2013 Jan;32(1):149-56

Authors: Mariano ER, Kim TE, Funck N, Walters T, Wagner MJ, Harrison TK, Giori N, Woolson S, Ganaway T, Howard SK

Abstract
OBJECTIVES: Continuous femoral nerve blocks provide effective analgesia after knee arthroplasty, and infusion effects depend on reliable catheter location. Ultrasound-guided perineural catheter insertion using a short-axis in-plane technique has been validated, but the optimal catheter location relative to target nerve and placement orientation remain unknown. We hypothesized that a long-axis in-plane technique for femoral perineural catheter insertion results in faster onset of sensory anesthesia compared to a short-axis in-plane technique.
METHODS: Preoperatively, patients receiving an ultrasound-guided nonstimulating femoral perineural catheter for knee surgery were randomly assigned to either the long-axis in-plane or short-axis in-plane technique. A local anesthetic was administered via the catheter after successful insertion. The primary outcome was the time to achieve complete sensory anesthesia. Secondary outcomes included the procedural time, the onset time of the motor block, pain and muscle weakness reported on postoperative day 1, and procedure-related complications.
RESULTS: The short-axis group (n = 23) took a median (10th-90th percentiles) of 9.0 (6.0-20.4) minutes compared to 6.0 (3.0-14.4) minutes for the long-axis group (n = 23; P = .044) to achieve complete sensory anesthesia. Short-axis procedures took 5.0 (4.0-7.8) minutes to perform compared to 9.0 (7.0-14.8) minutes for long-axis procedures (P < .001). In the short-axis group, 19 of 23 (83%) achieved a complete motor block within the testing period compared to 18 of 23 (78%) in the long-axis group (P = .813); short-axis procedures took 12.0 (6.0-15.0) minutes versus 15.0 (5.1-27.9) minutes for long-axis procedures (P = .048). There were no statistically significant differences in other secondary outcomes.
CONCLUSIONS: Long-axis in-plane femoral perineural catheters result in a slightly faster onset of sensory anesthesia, but placement takes longer to perform without other clinical advantages.

PMID: 23269720 [PubMed - indexed for MEDLINE]

Revitalizing long-acting reversible contraceptives in settings with high unmet need: a multicountry experience matching demand creation and service delivery.

Contraception. 2013 Feb;87(2):170-5

Authors: Blumenthal PD, Shah NM, Jain K, Saunders A, Clemente C, Lucas B, Jafa K, Eber M

Abstract
BACKGROUND: Contraception in many developing countries is characterized by high unmet need, irregular access, low utilization and presumed demand for long-acting reversible contraceptives (LARCs).
STUDY DESIGN: A 13-country initiative focused on increasing consumer demand and high quality services for intrauterine devices (IUDs) began in 2009. Services were provided through (a) private sector-franchised or affiliated clinics; (b) providers seconded to the public sector and (c) special "event" days. Client intake data are used to compare the profile of IUD acceptors with IUD users from representative national datasets of select countries, as well as examine trends in IUD uptake.
RESULTS: During 2009-2010, 575,601 IUDs were inserted across the 13 countries. Compared to national IUD users, users in this project were slightly younger and less educated. Among IUD acceptors, 24% used no modern method at the time of IUD initiation, and 28% reported injectable use in the three previous months.
CONCLUSIONS: Convenient, quality, affordable services with demand creation can result in significant uptake of LARCs in settings with low use.

PMID: 23153895 [PubMed - indexed for MEDLINE]

Case 7-2012. Airway management and perioperative decision making in the patient with severe pulmonary hypertension who requires emergency noncardiac surgery.

J Cardiothorac Vasc Anesth. 2012 Oct;26(5):940-4

Authors: Maxwell BG, Pearl RG, Kudelko KT, Zamanian RT, Hill CC

PMID: 22943790 [PubMed - indexed for MEDLINE]

A randomized controlled trial of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving decitabine.

Leuk Lymphoma. 2013 Feb;54(2):321-8

Authors: Greenberg PL, Garcia-Manero G, Moore M, Damon L, Roboz G, Hu K, Yang AS, Franklin J

Abstract
Patients with myelodysplastic syndrome (MDS) receiving hypomethylating agents commonly develop thrombocytopenia. This double-blind study evaluated the efficacy and safety of romiplostim, a peptibody protein that increases platelets, in patients with MDS receiving decitabine. Patients received romiplostim 750 μg (n = 15) or placebo (n = 14) and decitabine. Median platelet counts at the beginning of each decitabine cycle trended lower in placebo-treated than in romiplostim-treated patients. Bleeding events occurred in 43% of placebo-treated and 27% of romiplostim-treated patients, and platelet transfusions were administered to 57% of placebo-treated and 47% of romiplostim-treated patients. Overall clinical therapeutic response was achieved by 21% of placebo-treated and 33% of romiplostim-treated patients. Treatment was generally well tolerated. Progression to acute myeloid leukemia (AML) occurred in one patient per group. Adding romiplostim to decitabine treatment is well tolerated and may be beneficial, as indicated by trends toward higher platelet counts at the beginning of each treatment cycle and lower platelet transfusion rates and percentages of patients with bleeding events.

PMID: 22906162 [PubMed - indexed for MEDLINE]

Clinically meaningful reduction in pruritus in patients with cutaneous T-cell lymphoma treated with romidepsin.

Leuk Lymphoma. 2013 Feb;54(2):284-9

Authors: Kim YH, Demierre MF, Kim EJ, Lerner A, Rook AH, Duvic M, Robak T, Samtsov A, McCulloch W, Chen SC, Waksman J, Nichols J, Whittaker S

Abstract
Patients with cutaneous T-cell lymphoma (CTCL) frequently experience severe pruritus that can significantly impact their quality of life. Romidepsin is approved by the US Food and Drug Administration (FDA) for the treatment of patients with CTCL who have received at least one prior systemic therapy, with a reported objective response rate of 34%. In a phase 2 study of romidepsin in patients with CTCL (GPI-04-0001), clinically meaningful reduction in pruritus (CMRP) was evaluated as an indicator of clinical benefit by using a patient-assessed visual analog scale. To determine the effect of romidepsin alone, confounding pruritus treatments including steroids and antihistamines were prohibited. At baseline, 76% of patients reported moderate-to-severe pruritus; 43% of these patients experienced CMRP, including 11 who did not achieve an objective response. Median time to CMRP was 1.8 months, and median duration of CMRP was 5.6 months. Study results suggest that the clinical benefit of romidepsin may extend beyond objective responses.

PMID: 22839723 [PubMed - indexed for MEDLINE]

Literature review of various treatment plans and outcomes for brain metastases from colorectal cancer.

World Neurosurg. 2013 Mar-Apr;79(3-4):435-6

Authors: Murovic JA, Chang SD

PMID: 22381286 [PubMed - indexed for MEDLINE]