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- Comparison of Nonprecious Metal Cathode Materials for Methane Production by Electromethanogenesis.Siegert M, Yates MD, Call DF, Zhu X, Spormann A, Logan BEACS Sustain Chem Eng
- Relating prognosis in chromophobe renal cell carcinoma to the chromophobe tumor grading system.Weinzierl EP, Thong AE, McKenney JK, Jeon SH, Chung BIKorean J Urol
- Gastrointestinal ulcers, role of aspirin, and clinical outcomes: pathobiology, diagnosis, and treatment.Cryer B, Mahaffey KWJ Multidiscip Healthc
- Obligate progression precedes lung adenocarcinoma dissemination.Caswell DR, Chuang CH, Yang D, Chiou SH, Cheemalavagu S, Kim-Kiselak C, Connolly A, Winslow MMCancer Discov
- Highly Stretchable Transistors Using a Microcracked Organic Semiconductor.Chortos A, Lim J, To JW, Vosgueritchian M, Dusseault TJ, Kim TH, Hwang S, Bao ZAdv Mater
- JMJD5 regulates cell cycle and pluripotency in human embryonic stem cells.Zhu H, Hu S, Baker JStem Cells
- What influences youth to operate all-terrain vehicles safely?Grummon AH, Heaney CA, Dellinger WA, Wilkins JRHealth Educ Res
- Malignant transformation of infantile hemangioma to angiosarcoma: Response to chemotherapy with bevacizumab.Jeng MR, Fuh B, Blatt J, Gupta A, Merrow AC, Hammill A, Adams DPediatr Blood Cancer
- Diabetes Irreversibly Depletes Bone Marrow-Derived Mesenchymal Progenitor Cell Subpopulations.Januszyk M, Sorkin M, Glotzbach JP, Vial IN, Maan Z, Rennert RC, Duscher D, Thangarajah H, Longaker MT, Butte AJ, Gurtner GCDiabetes
- Large-scale assessment of mediterranean marine protected areas effects on fish assemblages.Guidetti P, Baiata P, Ballesteros E, Di Franco A, Hereu B, Macpherson E, Micheli F, Pais A, Panzalis P, Rosenberg AA, Zabala M, Sala EPLoS One
- Characterizing the Relationship Between Free Drug Samples and Prescription Patterns for Acne Vulgaris and Rosacea.Hurley MP, Stafford RS, Lane ATJAMA Dermatol
- Two Different Scenarios of Squamous Cell Carcinoma Within Advanced Basal Cell Carcinomas: Cases Illustrating the Importance of Serial Biopsy During Vismodegib Usage.Zhu GA, Sundram U, Chang ALJAMA Dermatol
- The Potential of Accelerating Early Detection of Autism through Content Analysis of YouTube Videos.Fusaro VA, Daniels J, Duda M, Deluca TF, D'Angelo O, Tamburello J, Maniscalco J, Wall DPPLoS One
- Population-Level Correlates of Preterm Delivery among Black and White Women in the U.S.Carmichael SL, Cullen MR, Mayo JA, Gould JB, Loftus P, Stevenson DK, Wise PH, Shaw GMPLoS One
- Serum inflammatory mediators as markers of human lyme disease activity.Soloski MJ, Crowder LA, Lahey LJ, Wagner CA, Robinson WH, Aucott JNPLoS One
- An economical training model to teach and practice deep inferior epigastric artery perforator dissection.Nykiel M, Wong R, Lee GAnn Plast Surg
- Changing attitudes toward hand allotransplantation among north american hand surgeons.Bertrand AA, Sen S, Otake LR, Lee GKAnn Plast Surg
- Outcomes of breast reconstruction in breast cancer patients with a history of mantle radiation for hodgkin lymphoma.Wong RK, Morrison SD, Momeni A, Nykiel M, Lee GKAnn Plast Surg
- Modification of the Tube-in-Tube Pedicled Anterolateral Thigh Flap for Total Phalloplasty: The Mushroom Flap.Morrison SD, Son J, Song J, Berger A, Kirby J, Ahdoot M, Lee GKAnn Plast Surg
- Predicting biodiversity change and averting collapse in agricultural landscapes.Mendenhall CD, Karp DS, Meyer CF, Hadly EA, Daily GCNature
- Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq.Treutlein B, Brownfield DG, Wu AR, Neff NF, Mantalas GL, Espinoza FH, Desai TJ, Krasnow MA, Quake SRNature
- Unravelling mechanisms of p53-mediated tumour suppression.Bieging KT, Mello SS, Attardi LDNat Rev Cancer
- Disrupted lung development and bronchopulmonary dysplasia: opportunities for lung repair and regeneration.Baker CD, Alvira CMCurr Opin Pediatr
- Prenatal imaging and postnatal presentation, diagnosis and management of congenital lung malformations.Wall J, Coates ACurr Opin Pediatr
- Mechanical offloading of incisional wounds is associated with transcriptional downregulation of inflammatory pathways in a large animal model.Januszyk M, Wong VW, Bhatt KA, Vial IN, Paterno J, Longaker MT, Gurtner GCOrganogenesis
- Invasive Coronary Microcirculation Assessment.Kobayashi Y, Fearon WFCirc J
- Trajectories of positive aging: observations from the women's health initiative study.Zaslavsky O, Cochrane BB, Woods NF, Lacroix AZ, Liu J, Herting JR, Goveas JS, Johnson KC, Kuller LH, Martin LW, Michael YL, Robinson JG, Stefanick M, Tinker LFInt Psychogeriatr
- Epigenetic reprogramming reverses the malignant epigenotype of the MMP/TIMP axis genes in tumor cells.Zhang S, Zhong B, Chen M, Yang L, Yang G, Li Y, Wang H, Wang G, Li W, Cui J, Hoffman AR, Hu JInt J Cancer
- Comparison of tricalcium phosphate cement and cancellous autograft as bone void filler in acetabular fractures with marginal impaction.Leucht P, Castillo AB, Bellino MJInjury
Comparison of Nonprecious Metal Cathode Materials for Methane Production by Electromethanogenesis.
ACS Sustain Chem Eng. 2014 Apr 7;2(4):910-917
Authors: Siegert M, Yates MD, Call DF, Zhu X, Spormann A, Logan BE
In methanogenic microbial electrolysis cells (MMCs), CO2 is reduced to methane using a methanogenic biofilm on the cathode by either direct electron transfer or evolved hydrogen. To optimize methane generation, we examined several cathode materials: plain graphite blocks, graphite blocks coated with carbon black or carbon black containing metals (platinum, stainless steel or nickel) or insoluble minerals (ferrihydrite, magnetite, iron sulfide, or molybdenum disulfide), and carbon fiber brushes. Assuming a stoichiometric ratio of hydrogen (abiotic):methane (biotic) of 4:1, methane production with platinum could be explained solely by hydrogen production. For most other materials, however, abiotic hydrogen production rates were insufficient to explain methane production. At -600 mV, platinum on carbon black had the highest abiotic hydrogen gas formation rate (1600 ± 200 nmol cm(-3) d(-1)) and the highest biotic methane production rate (250 ± 90 nmol cm(-3) d(-1)). At -550 mV, plain graphite (76 nmol cm(-3) d(-1)) performed similarly to platinum (73 nmol cm(-3) d(-1)). Coulombic recoveries, based on the measured current and evolved gas, were initially greater than 100% for all materials except platinum, suggesting that cathodic corrosion also contributed to electromethanogenic gas production.
PMID: 24741468 [PubMed - as supplied by publisher]
Relating prognosis in chromophobe renal cell carcinoma to the chromophobe tumor grading system.
Korean J Urol. 2014 Apr;55(4):239-44
Authors: Weinzierl EP, Thong AE, McKenney JK, Jeon SH, Chung BI
PURPOSE: The chromophobe subtype of renal cell carcinoma (chRCC) has generally been associated with a better prognosis than the clear cell type; however, debate continues as to absolute prognosis as well as the significance of certain prognostic variables. We investigated the significance of pathologic stage and a recently proposed chromophobe tumor grading (CTG) scheme in predicting chRCC outcomes.
MATERIALS AND METHODS: All available chRCCs were identified from our surgical pathology archives from 1987-2010. Original slides were reviewed to verify diagnoses and stage, and each case was graded following a novel chromophobe tumor grade system criteria. Disease status was obtained from a clinical outcome database, and cancer specific deaths and recurrences were recorded.
RESULTS: Eighty-one cases of chRCC were identified, and 73 had adequate follow-up information available. There were only 3 instances of cancer related recurrence or mortality, which included 1 disease specific mortality and 2 disease recurrences. Pathologic stage and CTG 3 were found to be significantly associated with the recurrences or death from chRCC, but there was no association with CTG 1 and CTG 2.
CONCLUSIONS: chRCC is associated with a very low rate of cancer specific events (4.1%) even at a tertiary referral center. In our study, pathologic stage and CTG 3, but not CTG 1 or 2, were significantly associated with the development of these events.
PMID: 24741411 [PubMed]
Gastrointestinal ulcers, role of aspirin, and clinical outcomes: pathobiology, diagnosis, and treatment.
J Multidiscip Healthc. 2014;7:137-146
Authors: Cryer B, Mahaffey KW
Peptic ulcer disease is a major cause of morbidity and mortality in the US with more than six million diagnoses annually. Ulcers are reported as the most common cause of hospitalization for upper gastrointestinal (GI) bleeding and are often a clinical concern due to the widespread use of aspirin and nonsteroidal anti-inflammatory drugs, both of which have been shown to induce ulcer formation. The finding that Helicobacter pylori infection (independent of aspirin use) is associated with the development of ulcers led to a more thorough understanding of the causes and pathogenesis of ulcers and an improvement in therapeutic options. However, many patients infected with H. pylori are asymptomatic and remain undiagnosed. Complicating matters is a current lack of understanding of the association between aspirin use and asymptomatic ulcer formation. Low-dose aspirin prescriptions have increased, particularly for cardioprotection. Unfortunately, the GI side effects associated with aspirin therapy continue to be a major complication in both symptomatic and asymptomatic patients. These safety concerns should be important considerations in the decision to use aspirin and warrant further education. The medical community needs to continue to improve awareness of aspirin-induced GI bleeding to better equip physicians and improve care for patients requiring aspirin therapy.
PMID: 24741318 [PubMed - as supplied by publisher]
Obligate progression precedes lung adenocarcinoma dissemination.
Cancer Discov. 2014 Apr 16;
Authors: Caswell DR, Chuang CH, Yang D, Chiou SH, Cheemalavagu S, Kim-Kiselak C, Connolly A, Winslow MM
Despite its clinical importance, very little is known about the natural history and molecular underpinnings of lung cancer dissemination and metastasis. Here we employed a genetically-engineered mouse model of metastatic lung adenocarcinoma in which cancer cells are fluorescently marked to determine whether dissemination is an inherent ability or a major acquired phenotype during lung adenocarcinoma metastasis. We find very little evidence for dissemination from oncogenic Kras-driven hyperplasias or most adenocarcinomas. p53 loss is insufficient to drive dissemination but rather enables rare cancer cells in a small fraction of primary adenocarcinomas to gain alterations that drive dissemination. Molecular characterization of disseminated tumors cells indicates that down-regulation of the transcription factor Nkx2-1 precedes dissemination. Finally, we show that metastatic primary tumors possess a highly proliferative sub-population of cells with characteristics matching those of disseminating cells. We propose that dissemination is a major hurdle during the natural course of lung adenocarcinoma metastasis.
PMID: 24740995 [PubMed - as supplied by publisher]
Highly Stretchable Transistors Using a Microcracked Organic Semiconductor.
Adv Mater. 2014 Apr 17;
Authors: Chortos A, Lim J, To JW, Vosgueritchian M, Dusseault TJ, Kim TH, Hwang S, Bao Z
Organic transistors with elastic conductors and dielectrics can be stretched up to 250% strain while maintaining the transistor characteristics. Strain-independent properties can be achieved after an initial "programming" cycle that causes the formation of microcracks in the semiconductor. The change in mobility with strain follows the same trend in different stretching directions.
PMID: 24740928 [PubMed - as supplied by publisher]
JMJD5 regulates cell cycle and pluripotency in human embryonic stem cells.
Stem Cells. 2014 Apr 16;
Authors: Zhu H, Hu S, Baker J
In mammalian embryos, embryonic stem cells and induced pluripotent cells, a shortened G1 phase is correlated with the pluripotent state. To molecularly define this phase, we compared transcripts from the shortened G1 of human embryonic stem cells (hESCs) with those from the longer G1 of derived endoderm. We identified JMJD5, a JmjC (Jumonji C) domain containing protein that, when depleted in hESCs, causes the accumulation of cells in G1 phase, loss of pluripotency and subsequent differentiation into multiple lineages, most prominently ectoderm and trophectoderm. Further, we demonstrate that the JMJD5 phenotype is caused by the upregulation of CDKN1A (p21), as depleting both JMJD5 and CDKN1A (p21) in hESCs restores the rapid G1 phase and rescues the pluripotent state. Overall, we provide genetic and biochemical evidence that the JMJD5/CDKN1A (p21) axis is essential to maintaining the short G1 phase which is critical for pluripotency in hESCs. Stem Cells 2014.
PMID: 24740926 [PubMed - as supplied by publisher]
What influences youth to operate all-terrain vehicles safely?
Health Educ Res. 2014 Apr 16;
Authors: Grummon AH, Heaney CA, Dellinger WA, Wilkins JR
The operation of all-terrain vehicles (ATVs) by youth has contributed to the incidence of serious and fatal injuries among children. This study explored factors related to the frequency with which youth wore a helmet and refrained from engaging in three risky driving behaviors (driving at risky speeds, on paved roads and on unfamiliar terrain) while operating an ATV. Youth (n = 248) aged 9-14 from central Ohio and one of their parents completed self-report measures of ATV safety behaviors, youth general propensity for risk taking, protection motivation and parental behaviors to facilitate youth safety. Data from two focus groups provided insight on quantitative results. Analyses revealed considerable variation in the frequency with which youth performed the safety behaviors, with 13- and 14-year-olds reporting less frequent safe behavior than 9- to 12-year-olds. Multiple regression analyses suggested that parental behaviors, such as providing reminders to wear a helmet, were associated with more frequent helmet use but were not associated with risky driving behaviors. Youth's general propensity toward risk taking was not associated with helmet use and only associated with riskydriving behaviors among the 13- and 14-year-olds. Self-efficacy was an important predictor across both age groups and behaviors. Implications for injury prevention are discussed.
PMID: 24740837 [PubMed - as supplied by publisher]
Malignant transformation of infantile hemangioma to angiosarcoma: Response to chemotherapy with bevacizumab.
Pediatr Blood Cancer. 2014 Apr 17;
Authors: Jeng MR, Fuh B, Blatt J, Gupta A, Merrow AC, Hammill A, Adams D
We describe a child initially diagnosed with multi-focal infantile hemangioma (cutaneous, hepatic, pulmonary), a benign vascular lesion, which underwent malignant transformation to angiosarcoma. The use of anti-angiogenic agents, such as bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, has been reported in adults with angiosarcoma. Treatment with chemotherapy (gemcitabine and docetaxel) and bevacizumab resulted in disease response with progression free survival of 12 months. This report describes the response to chemotherapy and bevacizumab in a child with angiosarcoma and highlights the potential for malignant transformation of benign vascular lesions and the need for careful monitoring. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
PMID: 24740626 [PubMed - as supplied by publisher]
Diabetes Irreversibly Depletes Bone Marrow-Derived Mesenchymal Progenitor Cell Subpopulations.
Diabetes. 2014 Apr 16;
Authors: Januszyk M, Sorkin M, Glotzbach JP, Vial IN, Maan Z, Rennert RC, Duscher D, Thangarajah H, Longaker MT, Butte AJ, Gurtner GC
Diabetic vascular pathology is largely attributable to impairments in tissue recovery from hypoxia. Circulating progenitor cells have been postulated to play a role in ischemic recovery and deficiencies in these cells have been well described in diabetic patients. Here, we examine bone marrow-derived mesenchymal progenitor cells (BM-MPCs) that have previously been shown to be important for new blood vessel formation, and demonstrate significant deficits in the context of diabetes. Further, we determine that this dysfunction is attributable to intrinsic defects in diabetic BM-MPCs that are not correctable by restoring glucose homeostasis. We identify two transcriptionally distinct subpopulations that are selectively depleted by both type 1 and type 2 diabetes, and these subpopulations have pro-vasculogenic expression profiles, suggesting that they are vascular progenitor cells. These results suggest that the clinically observed deficits in progenitor cells may be attributable to selective and irreversible depletion of progenitor cell subsets in patients with diabetes.
PMID: 24740572 [PubMed - as supplied by publisher]
Large-scale assessment of mediterranean marine protected areas effects on fish assemblages.
PLoS One. 2014;9(4):e91841
Authors: Guidetti P, Baiata P, Ballesteros E, Di Franco A, Hereu B, Macpherson E, Micheli F, Pais A, Panzalis P, Rosenberg AA, Zabala M, Sala E
Marine protected areas (MPAs) were acknowledged globally as effective tools to mitigate the threats to oceans caused by fishing. Several studies assessed the effectiveness of individual MPAs in protecting fish assemblages, but regional assessments of multiple MPAs are scarce. Moreover, empirical evidence on the role of MPAs in contrasting the propagation of non-indigenous-species (NIS) and thermophilic species (ThS) is missing. We simultaneously investigated here the role of MPAs in reversing the effects of overfishing and in limiting the spread of NIS and ThS. The Mediterranean Sea was selected as study area as it is a region where 1) MPAs are numerous, 2) fishing has affected species and ecosystems, and 3) the arrival of NIS and the northward expansion of ThS took place. Fish surveys were done in well-enforced no-take MPAs (HP), partially-protected MPAs (IP) and fished areas (F) at 30 locations across the Mediterranean. Significantly higher fish biomass was found in HP compared to IP MPAs and F. Along a recovery trajectory from F to HP MPAs, IP were similar to F, showing that just well enforced MPAs triggers an effective recovery. Within HP MPAs, trophic structure of fish assemblages resembled a top-heavy biomass pyramid. Although the functional structure of fish assemblages was consistent among HP MPAs, species driving the recovery in HP MPAs differed among locations: this suggests that the recovery trajectories in HP MPAs are likely to be functionally similar (i.e., represented by predictable changes in trophic groups, especially fish predators), but the specific composition of the resulting assemblages may depend on local conditions. Our study did not show any effect of MPAs on NIS and ThS. These results may help provide more robust expectations, at proper regional scale, about the effects of new MPAs that may be established in the Mediterranean Sea and other ecoregions worldwide.
PMID: 24740479 [PubMed - in process]
Characterizing the Relationship Between Free Drug Samples and Prescription Patterns for Acne Vulgaris and Rosacea.
JAMA Dermatol. 2014 Apr 16;
Authors: Hurley MP, Stafford RS, Lane AT
IMPORTANCE Describing the relationship between the availability of free prescription drug samples and dermatologists' prescribing patterns on a national scale can help inform policy guidelines on the use of free samples in a physician's office. OBJECTIVES To investigate the relationships between free drug samples and dermatologists' local and national prescribing patterns and between the availability of free drug samples and prescription costs. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study investigating prescribing practices for acne, a common dermatologic condition for which free samples are often available. The settings were, first, the offices of nationally representative dermatologists from the National Disease and Therapeutic Index (an IMS Health Incorporated database) and, second, an academic medical center clinic without samples. Participants were ambulatory patients who received a prescription from a dermatologist for a primary initial diagnosis of acne vulgaris or rosacea in 2010. MAIN OUTCOMES AND MEASURES National trends in dermatologist prescribing patterns, the degree of correlation between the availability of free samples and the prescribing of brand-name medications, and the mean cost of acne medications prescribed per office visit nationally and at an academic medical center without samples. RESULTS On a national level, the provision of samples with a prescription by dermatologists has been increasing over time, and this increase is correlated (r = 0.92) with the use of the branded generic drugs promoted by these samples. Branded and branded generic drugs comprised most of the prescriptions written nationally (79%), while they represented only 17% at an academic medical center clinic without samples. Because of the increased use of branded and branded generic drugs, the national mean total retail cost of prescriptions at an office visit for acne was conservatively estimated to be 2 times higher (approximately $465 nationally vs $200 at an academic medical center without samples). CONCLUSIONS AND RELEVANCE Free drug samples can alter the prescribing habits of physicians away from the use of less expensive generic medications. The benefits of free samples in dermatology must be weighed against potential negative effects on prescribing behavior and prescription costs.
PMID: 24740450 [PubMed - as supplied by publisher]
Two Different Scenarios of Squamous Cell Carcinoma Within Advanced Basal Cell Carcinomas: Cases Illustrating the Importance of Serial Biopsy During Vismodegib Usage.
JAMA Dermatol. 2014 Apr 16;
Authors: Zhu GA, Sundram U, Chang AL
IMPORTANCE Vismodegib is a Hedgehog signaling pathway inhibitor recently approved by the US Food and Drug Administration for advanced basal cell carcinoma. We present 2 cases of clinically significant squamous cell carcinoma within the tumor bed of locally advanced basal cell carcinoma found during vismodegib treatment. OBSERVATIONS The first case is that of a patient with locally advanced basal cell carcinoma responsive to vismodegib but with an enlarging papule within the tumor bed. On biopsy, this papule was an invasive acantholytic squamous cell carcinoma. The second case is that of a patient with Gorlin syndrome with a locally advanced basal cell carcinoma that was stable while the patient was receiving therapy with vismodegib for 2.5 years but subsequently increased in size. Biopsy specimens from this tumor showed invasive squamous cell carcinoma, spindle cell subtype. In both cases, the squamous cell carcinomas were surgically resected. CONCLUSIONS AND RELEVANCE These cases highlight the importance of repeated biopsy in locally advanced basal cell carcinomas in 2 clinical situations: (1) when an area within the tumor responds differentially to vismodegib, and (2) when a tumor stops being suppressed by vismodegib. Timely diagnosis of non-basal cell histologic characteristics is critical to institution of effective therapy.
PMID: 24740281 [PubMed - as supplied by publisher]
The Potential of Accelerating Early Detection of Autism through Content Analysis of YouTube Videos.
PLoS One. 2014;9(4):e93533
Authors: Fusaro VA, Daniels J, Duda M, Deluca TF, D'Angelo O, Tamburello J, Maniscalco J, Wall DP
Autism is on the rise, with 1 in 88 children receiving a diagnosis in the United States, yet the process for diagnosis remains cumbersome and time consuming. Research has shown that home videos of children can help increase the accuracy of diagnosis. However the use of videos in the diagnostic process is uncommon. In the present study, we assessed the feasibility of applying a gold-standard diagnostic instrument to brief and unstructured home videos and tested whether video analysis can enable more rapid detection of the core features of autism outside of clinical environments. We collected 100 public videos from YouTube of children ages 1-15 with either a self-reported diagnosis of an ASD (N = 45) or not (N = 55). Four non-clinical raters independently scored all videos using one of the most widely adopted tools for behavioral diagnosis of autism, the Autism Diagnostic Observation Schedule-Generic (ADOS). The classification accuracy was 96.8%, with 94.1% sensitivity and 100% specificity, the inter-rater correlation for the behavioral domains on the ADOS was 0.88, and the diagnoses matched a trained clinician in all but 3 of 22 randomly selected video cases. Despite the diversity of videos and non-clinical raters, our results indicate that it is possible to achieve high classification accuracy, sensitivity, and specificity as well as clinically acceptable inter-rater reliability with nonclinical personnel. Our results also demonstrate the potential for video-based detection of autism in short, unstructured home videos and further suggests that at least a percentage of the effort associated with detection and monitoring of autism may be mobilized and moved outside of traditional clinical environments.
PMID: 24740236 [PubMed - in process]
Population-Level Correlates of Preterm Delivery among Black and White Women in the U.S.
PLoS One. 2014;9(4):e94153
Authors: Carmichael SL, Cullen MR, Mayo JA, Gould JB, Loftus P, Stevenson DK, Wise PH, Shaw GM
OBJECTIVE: This study examined the ability of social, demographic, environmental and health-related factors to explain geographic variability in preterm delivery among black and white women in the US and whether these factors explain black-white disparities in preterm delivery.
METHODS: We examined county-level prevalence of preterm delivery (20-31 or 32-36 weeks gestation) among singletons born 1998-2002. We conducted multivariable linear regression analysis to estimate the association of selected variables with preterm delivery separately for each preterm/race-ethnicity group.
RESULTS: The prevalence of preterm delivery varied two- to three-fold across U.S. counties, and the distributions were strikingly distinct for blacks and whites. Among births to blacks, regression models explained 46% of the variability in county-level risk of delivery at 20-31 weeks and 55% for delivery at 32-36 weeks (based on R-squared values). Respective percentages for whites were 67% and 71%. Models included socio-environmental/demographic and health-related variables and explained similar amounts of variability overall.
CONCLUSIONS: Much of the geographic variability in preterm delivery in the US can be explained by socioeconomic, demographic and health-related characteristics of the population, but less so for blacks than whites.
PMID: 24740117 [PubMed - in process]
Serum inflammatory mediators as markers of human lyme disease activity.
PLoS One. 2014;9(4):e93243
Authors: Soloski MJ, Crowder LA, Lahey LJ, Wagner CA, Robinson WH, Aucott JN
Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low) of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005) in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG), CXCL10 (IP-10) and CCL19 (MIP3B) were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p = 0.027 and p = 0.021 respectively). There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p = 0.01) and the decrease correlates with chemokine levels (p = 0.0375). The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations.
PMID: 24740099 [PubMed - in process]
An economical training model to teach and practice deep inferior epigastric artery perforator dissection.
Ann Plast Surg. 2014 May;72 Suppl 1:S66-70
Authors: Nykiel M, Wong R, Lee G
INTRODUCTION: Modern surgical training has placed a larger focus on procedural competency base training for surgical specialties. Although various simulators are in existence to teach laparoscopic skills, plastic surgery has a paucity of surgical training models.
METHODS AND MATERIALS: We developed a low-cost teaching model for the steps and techniques required in the deep inferior epigastric perforator flap and assessed the utility of this model with the resident surgeons using presurvey and postsurvey.
RESULTS: A total of 13 residents participated in the surgical skill exercise. The residents felt this exercise increased their proficiency in the steps and techniques required for a deep inferior epigastric perforator flap harvest [4 (0.4)].
CONCLUSIONS: Overall, residents felt this exercise should be included in the postgraduate years 1 and 2 educational curriculum.
PMID: 24740027 [PubMed - in process]
Changing attitudes toward hand allotransplantation among north american hand surgeons.
Ann Plast Surg. 2014 May;72 Suppl 1:S56-60
Authors: Bertrand AA, Sen S, Otake LR, Lee GK
OBJECTIVES: Although more than 70 hand transplants have been performed worldwide, the appropriate clinical indications for this operation are still being determined. Cost and patient exposure to the challenges of lifelong immunosuppression for what is a quality of life-improving (but not life-saving) operation are the focus of the ongoing discussion. A study performed in 2007 showed that surgeons' opinions on the issue varied widely. Recently, more information has been made available regarding long-term patient outcomes, and significant improvements in immunotherapy protocols have been reported. In light of this, we sought to examine changing attitudes regarding hand allotransplantation and its indications by surveying hand surgeons.
METHODS: An email-based survey was sent to members of the American Society for Surgery of the Hand. Demographic information and practice profiles were identified, followed by their risk assessment of hand allotransplants and endorsement of performing the operation in different clinical scenarios. Additional questions focused on the appropriate indications for hand allotransplantation, as well as the procedure's associated ethical and financial implications.
RESULTS: A total of 385 surgeons responded to the survey (14% response rate). The majority (82%) considered hand transplantation to be a high-risk operation (as opposed to 27% in hand replantation), with 78% citing lifelong immunosuppression as the primary factor impacting their overall risk assessment. The most commonly accepted indication for hand vascularized composite allotransplantation was loss of bilateral hands (80% in favor). Dominant hand loss (with an intact contralateral hand) was a far less frequently accepted indication (36% in favor). Patient adherence to immunosuppressive regimens (51%) and expectations of functional/aesthetic outcome (38%) were the most frequently chosen top psychosocial issues that must be addressed by the surgical/medical teams involved in the operation.
CONCLUSIONS: Our study's results demonstrate increasing overall support for hand allotransplantation and increasing acceptance of today's immunosuppressive regimens compared to prior literature. Bilateral hand loss remains the primary agreed-upon indication for transplantation. Despite increasing acceptance in the surgical community, the dangers of chronic immunosuppression, cost and patient adherence continue to be the primary concerns hindering its broader acceptance.
PMID: 24740026 [PubMed - in process]
Outcomes of breast reconstruction in breast cancer patients with a history of mantle radiation for hodgkin lymphoma.
Ann Plast Surg. 2014 May;72 Suppl 1:S46-50
Authors: Wong RK, Morrison SD, Momeni A, Nykiel M, Lee GK
BACKGROUND: Although mantle radiation (ie, extended field radiation) represented the standard of care in the past for Hodgkin disease, contemporary treatment of lymphoma consists of a multimodal approach with chemotherapy. Patients who were exposed to mantle radiation have a higher risk of breast cancer and are more susceptible to postoperative complications after breast reconstruction due to radiation. In this study, we present postoperative outcomes in patients with a history of mantle radiation who underwent mastectomy and breast reconstruction.
METHODS: All patients at Stanford University Medical Center between January 2006 and December 2012 with a history of Hodgkin lymphoma treated with mantle radiation who received breast reconstruction were identified. A retrospective chart review was conducted analyzing patient demographics, history of Hodgkin treatment, type of reconstruction, follow-up, and complications. Complications were further classified into medical complications, donor-site complications, and recipient-site complications.
RESULTS: Sixteen patients with a history of Hodgkin disease and mantle radiation received breast reconstruction. The average age of the patients at their mastectomy was 46 (33-60) years, with the average age at the time of their mantle radiation of 20.5 (10-33) years with an average interval of radiation to breast cancer treatment of 24.8 (16-38) years. There were five unilateral and 11 bilateral reconstructions. All patients had immediate reconstruction with tissue expanders (14 patients) or autologous tissue (one muscle-sparing transverse rectus abdominis myocutaneous and one transverse upper gracilis flap). Eleven (69%) patients had postoperative complications. In the patients who had tissue expander reconstruction, there was an overall complication rate of 64%, which included capsular contracture (n = 5, 56%), mastectomy flap necrosis (n = 5, 56%), cellulitis (n = 4, 44%), seroma (n = 3, 33%), hematoma (n = 1, 11%), and chronic pain (n = 1, 11%). Three (two unilateral and one bilateral) tissue expander infections required removal of the expander and delayed reconstruction with a latissimus dorsi flap, whereas one patient with chronic pain and capsular contracture required a muscle-sparing transverse rectus abdominis myocutaneous for a unilateral implant failure.
CONCLUSIONS: Although the risk of complications associated with preoperative radiation is well documented, physicians and patients should be cognizant of the increased risk of complications after mantle radiation as it represents a unique modality of radiation exposure.
PMID: 24740024 [PubMed - in process]
Modification of the Tube-in-Tube Pedicled Anterolateral Thigh Flap for Total Phalloplasty: The Mushroom Flap.
Ann Plast Surg. 2014 May;72 Suppl 1:S22-6
Authors: Morrison SD, Son J, Song J, Berger A, Kirby J, Ahdoot M, Lee GK
BACKGROUND: Malformation or absence of the penis can lead to physical and psychological problems for male patients. Reconstruction of the phallus should optimally be completed in a single procedure, be aesthetically pleasing, retain erogenous and tactile sensation, enable micturition in the standing position, and allow for penetrative sexual intercourse. The tube-in-tube flap was described nearly 30 years ago and forms both a urethra and an outer penile shaft with a single flap. Here we present our modification of the original tube-in-tube design with the pedicled anterolateral thigh (ALT) flap and an extension for the neoglans, which we have termed the "mushroom flap" because of its shape and design.
METHODS: The flap is based on the ALT flap; however, the area that will become the neoglans is shaped with a semicircular extension, resembling the head of a mushroom. When the flap is tubularized, the neoglans has the proper anatomic landmarks such as the corona and more closely approximates a circumcised penis. When used in conjunction with the tube-in-tube design, the neophallus, neoglans, and neourethra can all be constructed in a single stage with a single flap.
RESULTS: We have performed total phalloplasties in three patients using the pedicled ALT flap, and the mushroom flap design evolved as we sought to improve the aesthetics of the neoglans. In comparing the aesthetic results among our patients as well as those published in the literature, the mushroom flap design seems to provide the most natural and aesthetically pleasing appearance.
CONCLUSIONS: The pedicled ALT flap can be used to reconstruct an entire penis, as well as a urethra, without the need for microsurgery. By modifying the original tube-in-tube design to include a semicircular extension (a.k.a. the "mushroom flap"), we feel that we have been able to achieve a more natural-appearing neoglans.
PMID: 24740021 [PubMed - in process]
Predicting biodiversity change and averting collapse in agricultural landscapes.
Nature. 2014 Apr 16;
Authors: Mendenhall CD, Karp DS, Meyer CF, Hadly EA, Daily GC
The equilibrium theory of island biogeography is the basis for estimating extinction rates and a pillar of conservation science. The default strategy for conserving biodiversity is the designation of nature reserves, treated as islands in an inhospitable sea of human activity. Despite the profound influence of islands on conservation theory and practice, their mainland analogues, forest fragments in human-dominated landscapes, consistently defy expected biodiversity patterns based on island biogeography theory. Countryside biogeography is an alternative framework, which recognizes that the fate of the world's wildlife will be decided largely by the hospitality of agricultural or countryside ecosystems. Here we directly test these biogeographic theories by comparing a Neotropical countryside ecosystem with a nearby island ecosystem, and show that each supports similar bat biodiversity in fundamentally different ways. The island ecosystem conforms to island biogeographic predictions of bat species loss, in which the water matrix is not habitat. In contrast, the countryside ecosystem has high species richness and evenness across forest reserves and smaller forest fragments. Relative to forest reserves and fragments, deforested countryside habitat supports a less species-rich, yet equally even, bat assemblage. Moreover, the bat assemblage associated with deforested habitat is compositionally novel because of predictable changes in abundances by many species using human-made habitat. Finally, we perform a global meta-analysis of bat biogeographic studies, spanning more than 700 species. It generalizes our findings, showing that separate biogeographic theories for countryside and island ecosystems are necessary. A theory of countryside biogeography is essential to conservation strategy in the agricultural ecosystems that comprise roughly half of the global land surface and are likely to increase even further.
PMID: 24739971 [PubMed - as supplied by publisher]
Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq.
Nature. 2014 Apr 13;
Authors: Treutlein B, Brownfield DG, Wu AR, Neff NF, Mantalas GL, Espinoza FH, Desai TJ, Krasnow MA, Quake SR
The mammalian lung is a highly branched network in which the distal regions of the bronchial tree transform during development into a densely packed honeycomb of alveolar air sacs that mediate gas exchange. Although this transformation has been studied by marker expression analysis and fate-mapping, the mechanisms that control the progression of lung progenitors along distinct lineages into mature alveolar cell types are still incompletely known, in part because of the limited number of lineage markers and the effects of ensemble averaging in conventional transcriptome analysis experiments on cell populations. Here we show that single-cell transcriptome analysis circumvents these problems and enables direct measurement of the various cell types and hierarchies in the developing lung. We used microfluidic single-cell RNA sequencing (RNA-seq) on 198 individual cells at four different stages encompassing alveolar differentiation to measure the transcriptional states which define the developmental and cellular hierarchy of the distal mouse lung epithelium. We empirically classified cells into distinct groups by using an unbiased genome-wide approach that did not require a priori knowledge of the underlying cell types or the previous purification of cell populations. The results confirmed the basic outlines of the classical model of epithelial cell-type diversity in the distal lung and led to the discovery of many previously unknown cell-type markers, including transcriptional regulators that discriminate between the different populations. We reconstructed the molecular steps during maturation of bipotential progenitors along both alveolar lineages and elucidated the full life cycle of the alveolar type 2 cell lineage. This single-cell genomics approach is applicable to any developing or mature tissue to robustly delineate molecularly distinct cell types, define progenitors and lineage hierarchies, and identify lineage-specific regulatory factors.
PMID: 24739965 [PubMed - as supplied by publisher]
Unravelling mechanisms of p53-mediated tumour suppression.
Nat Rev Cancer. 2014 Apr 17;
Authors: Bieging KT, Mello SS, Attardi LD
p53 is a crucial tumour suppressor that responds to diverse stress signals by orchestrating specific cellular responses, including transient cell cycle arrest, cellular senescence and apoptosis, which are all processes associated with tumour suppression. However, recent studies have challenged the relative importance of these canonical cellular responses for p53-mediated tumour suppression and have highlighted roles for p53 in modulating other cellular processes, including metabolism, stem cell maintenance, invasion and metastasis, as well as communication within the tumour microenvironment. In this Opinion article, we discuss the roles of classical p53 functions, as well as emerging p53-regulated processes, in tumour suppression.
PMID: 24739573 [PubMed - as supplied by publisher]
Disrupted lung development and bronchopulmonary dysplasia: opportunities for lung repair and regeneration.
Curr Opin Pediatr. 2014 Apr 15;
Authors: Baker CD, Alvira CM
PURPOSE OF REVIEW: Advances in medical therapy have increased survival of extremely premature infants and changed the pathology of bronchopulmonary dysplasia (BPD) from one of acute lung injury to a disease of disrupted lung development. With this evolution, new questions emerge regarding the molecular mechanisms that control postnatal lung development, the effect of early disruptions of postnatal lung development on long-term lung function, and the existence of endogenous mechanisms that permit lung regeneration after injury.
RECENT FINDINGS: Recent data demonstrate that a significant component of alveolarization, the final stage of lung development, occurs postnatally. Further, clinical and experimental studies demonstrate that premature birth disrupts alveolarization, decreasing the gas exchange surface area of the lung and causing BPD. BPD is associated with significant short-term morbidity, and new longitudinal, clinical data demonstrate that survivors of BPD have long-standing deficits in lung function and may be at risk for the development of additional lung disease as adults. Unfortunately, current care is mainly supportive with few effective therapies that prevent or treat established BPD. These studies underscore the need to further elucidate the mechanisms that direct postnatal lung growth and develop innovative strategies to stimulate lung regeneration.
SUMMARY: Despite significant improvements in the care and survival of extremely premature infants, BPD remains a major clinical problem. Although efforts should remain focused on the prevention of preterm labor and BPD, novel research aimed at promoting postnatal alveolarization offers a unique opportunity to develop effective strategies to treat established BPD.
PMID: 24739494 [PubMed - as supplied by publisher]
Prenatal imaging and postnatal presentation, diagnosis and management of congenital lung malformations.
Curr Opin Pediatr. 2014 Apr 15;
Authors: Wall J, Coates A
PURPOSE OF REVIEW: Congenital lung malformations (CLMs) vary in their clinical presentation and severity. Increases in prenatal diagnosis, observed regression of certain lesions, and prognostic uncertainty are driving an evolution in management.
RECENT FINDINGS: There has been an increase in the early diagnosis of these malformations, a change that is attributable to the routine use of prenatal ultrasound. Although prenatal diagnosis of CLMs using ultrasound and MRI has increased, chest radiography and computed tomography still play important roles in diagnosis. The management of these lesions depends on the type of malformation and symptoms. The treatment of asymptomatic patients with lung malformations is controversial, because the prognosis of these lesions is largely unknown. Proponents of early intervention argue that the complications of CLM, which may include infection, pneumothorax, bleeding and malignant transformation, justify surgery. Advocates of conservative management note that some CLMs disappear postnatally, and that the long-term complication rate following surgery is unknown. There is a need to obtain natural history data regardless of the therapeutic recommendations.
SUMMARY: This article reviews the prenatal radiographic features and postnatal clinical findings of various CLMs and the dilemmas regarding treatment.
PMID: 24739492 [PubMed - as supplied by publisher]
Mechanical offloading of incisional wounds is associated with transcriptional downregulation of inflammatory pathways in a large animal model.
Organogenesis. 2014 Apr 16;10(2)
Authors: Januszyk M, Wong VW, Bhatt KA, Vial IN, Paterno J, Longaker MT, Gurtner GC
Cutaneous scarring is a major source of morbidity and current therapies to mitigate scar formation remain ineffective. Although wound fibrosis and inflammation are highly linked, only recently have mechanical forces been implicated in these pathways. Our group has developed a topical polymer device that significantly reduces post-injury scar formation via the manipulation of mechanical forces. Here we extend these studies to examine the genomewide transcriptional effects of mechanomodulation during scar formation using a validated large animal model, the red Duroc pig. We demonstrate that mechanical loading of incisional wounds upregulates expression of genes associated with inflammatory and fibrotic pathways, and that device-mediated offloading of these wounds reverses these effects. Validation studies are needed to clarify the clinical significanceof these findings.
PMID: 24739276 [PubMed - as supplied by publisher]
Invasive Coronary Microcirculation Assessment.
Circ J. 2014 Apr 16;
Authors: Kobayashi Y, Fearon WF
Assessment of the coronary microvasculature in the clinical setting is a key issue, given that microvascular dysfunction itself has a predictive value for cardiovascular events. The index of microcirculatory resistance (IMR) is an invasive method of interrogating the microvasculature and provides further insight into the physiology of cardiovascular diseases. It is simple and readily applicable in the cardiac catheterization laboratory where many patients first present for evaluation of their coronary circulation. In contrast to other invasive and non-invasive tests, this method is known to be stable and reproducible under various hemodynamics and even in the presence of epicardial coronary artery stenosis. IMR has been shown to have prognostic value in patients with ST-segment elevation myocardial infarction; therefore it can be a surrogate marker of cardiovascular events. At the same time, it has the potential to be a therapeutic as well as an investigational tool in the physiology of cardiovascular diseases. This review summarizes the development of IMR, tips and tricks for its measurement, and its usefulness in various clinical settings.
PMID: 24739222 [PubMed - as supplied by publisher]
Trajectories of positive aging: observations from the women's health initiative study.
Int Psychogeriatr. 2014 Apr 17;:1-12
Authors: Zaslavsky O, Cochrane BB, Woods NF, Lacroix AZ, Liu J, Herting JR, Goveas JS, Johnson KC, Kuller LH, Martin LW, Michael YL, Robinson JG, Stefanick M, Tinker LF
ABSTRACT Background: The purpose of this study was to describe the longitudinal trajectories and bidirectional relationships of the physical-social and emotional functioning (EF) dimensions of positive aging and to identify their baseline characteristics. Methods: Women age 65 and older who enrolled in one or more Women's Health Initiative clinical trials (WHI CTs) and who had positive aging indicators measured at baseline and years 1, 3, 6, and 9 were included in these analyses (N = 2281). Analytic strategies included latent class growth modeling to identify longitudinal trajectories and multinomial logistic regression to examine the effects of baseline predictors on these trajectories. Results: A five-trajectory model was chosen to best represent the data. For Physical-Social Functioning (PSF), trajectory groups included Low Maintainer (8.3%), Mid-Low Improver (10.4%), Medium Decliner (10.7%), Mid-High Maintainer (31.2%), and High Maintainer (39.4%); for EF, trajectories included Low Maintainer (3%), Mid-Low Improver (9%), Medium Decliner (7.7%), Mid-High Maintainer (22.8%), and High Maintainer (57.5%). Cross-classification of the groups of trajectories demonstrated that the impact of a high and stable EF on PSF might be greater than the reverse. Low depression symptoms, low pain, and high social support were the most consistent predictors of high EF trajectories. Conclusion: Aging women are heterogeneous in terms of positive aging indicators for up to 9 years of follow-up. Interventions aimed at promoting sustainable EF might have diffused effects on other domains of healthy aging.
PMID: 24739218 [PubMed - as supplied by publisher]
Epigenetic reprogramming reverses the malignant epigenotype of the MMP/TIMP axis genes in tumor cells.
Int J Cancer. 2014 Apr 1;134(7):1583-94
Authors: Zhang S, Zhong B, Chen M, Yang L, Yang G, Li Y, Wang H, Wang G, Li W, Cui J, Hoffman AR, Hu J
Cancer progression is characterized by extensive tumor invasion into the surrounding extracellular matrix (ECM) and migration to metastatic sites. The increased proteolytic degradation of the ECM during tumor invasion is directly dependent on the activity of matrix metalloproteinases (MMPs), counter-balanced by tissue inhibitors of matrix metalloproteinases (TIMPs). In this study, we found that unbalanced expression of MMP/TIMP axis genes in tumors was correlated with aberrant epigenotypes in the various gene promoters. The malignant epigenotypes could be therapeutically corrected by a simple defined factor-mediated reprogramming approach. Correction of the abnormal epigenotypes by nuclear remodeling leads to a rebalance in the gene expression profile, an alteration in tumor cell morphology, attenuation of tumor cell migration and invasion in vitro, and reduced tumorigenicity in nude mice. We further identified the downregulation of the MKK-p38 MAPK signal pathway as an important underlying mechanism for reduced tumorigenicity in this epigenetic reprogramming model. These data demonstrate that the malignant phenotypes seen in cancer can be corrected by a nuclear remodeling mechanism, thus highlighting a novel non-chemotherapeutic, non-radiotherapeutic approach for the treatment of cancer.
PMID: 24105737 [PubMed - indexed for MEDLINE]
Comparison of tricalcium phosphate cement and cancellous autograft as bone void filler in acetabular fractures with marginal impaction.
Injury. 2013 Jul;44(7):969-74
Authors: Leucht P, Castillo AB, Bellino MJ
OBJECTIVE: To compare clinical and radiological outcome between acetabular fractures with marginal impaction that were treated with either cancellous bone graft (CBG) or tricalcium phosphate cement (TPC) as bone void filler.
DESIGN: Retrospective study.
PATIENTS: Forty-three patients with acetabular fractures with marginal impaction.
INTERVENTION: Eighteen patients received cancellous bone graft and 25 patients received tricalcium phosphate cement as bone void filler.
MAIN OUTCOME MEASUREMENT: Clinical outcome was assessed using the Merle d'Aubigne score and Short-form-36. Radiographs were evaluated for postoperative reduction, arthritis grade and development of heterotopic ossification.
RESULTS: Forty-three patients met the inclusion criteria. There was no significant difference in the demographics, laterality, fracture type, associated injuries, surgical approach and postoperative quality of reduction between the groups. At final follow-up, a significantly higher number of patients in the cancellous bone graft group exhibited signs of moderate to severe post-traumatic arthritis (CBG: 6 (33%) vs. TPC: 4 (20%), p=0.007) and required a total hip arthroplasty (CBG: 4 (22.2%) vs. TPC: 1 (5%), p=0.08). There was no significant difference between the two groups in the SF-36 score and the modified Merle d'Aubigne score.
CONCLUSION: Patients with acetabular fractures with marginal impaction treated with tricalcium phosphate cement exhibit a significantly lower incidence of post-traumatic arthritis when compared to patients treated with cancellous bone graft.
LEVEL OF EVIDENCE: III.
PMID: 23684351 [PubMed - indexed for MEDLINE]