bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct stages in the recognition, sorting, and packaging of proTGFα into COPII-coated transport vesicles
Authors: Zhang Pengcheng , Schekman Randy
Published: April 2016

In addition to its role in forming vesicles from the endoplasmic reticulum (ER), the coat protein complex II (COPII) is also responsible for selecting specific cargo proteins to be packaged into COPII transport vesicles. Comparison of COPII vesicle formation in mammalian systems and in yeast suggested that the former uses more elaborate mechanisms for cargo recognition, presumably to cope with a significantly expanded repertoire of cargo that transits the secretory pathway. Using proTGFα, the transmembrane precursor of transforming growth factor α (TGFα), as a model cargo protein, we demonstrate in cell-free assays that at least one auxiliary cytosolic factor is specifically required for the efficient packaging of proTGFα into COPII vesicles. Using a knockout HeLa cell line generated by CRISPR/Cas9, we provide functional evidence showing that a transmembrane protein, Cornichon-1 (CNIH), acts as a cargo receptor of proTGFα. We show that both CNIH and the auxiliary cytosolic factor(s) are required for efficient recruitment of proTGFα to the COPII coat in vitro. Moreover, we provide evidence that the recruitment of cargo protein by the COPII coat precedes and may be distinct from subsequent cargo packaging into COPII vesicles.
Rational bases for the use of the Immunoscore in routine clinical settings as a prognostic and predictive biomarker in cancer patients
Authors: Kirilovsky Amos , Marliot Florence , El Sissy Carine , Haicheur Nacilla , Galon Jérôme , Pagès Franck
Published: April 2016

The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumor, nodes, metastasis (TNM) classification system based on tumor features is used for prognosis estimation and treatment recommendations in most cancers. However, the clinical outcome can vary significantly among patients within the same tumor stage and TNM classification does not predict response to therapy. Therefore, many efforts have been focused on the identification of new markers. Multiple tumor cell-based approaches have been proposed but very few have been translated into the clinic. The recent demonstration of the essential role of the immune system in tumor progression has allowed great advances in the understanding of this complex disease and in the design of novel therapies. The analysis of the immune infiltrate by imaging techniques in large patient cohorts highlighted the prognostic impact of the in situ immune cell infiltrate in tumors. Moreover, the characterization of the immune infiltrates (e.g. type, density, distribution within the tumor, phenotype, activation status) in patients treated with checkpoint-blockade strategies could provide information to predict the disease outcome. In colorectal cancer, we have developed a prognostic score (‘Immunoscore’) that takes into account the distribution of the density of both CD3 + lymphocytes and CD8 + cytotoxic T cells in the tumor core and the invasive margin that could outperform TNM staging. Currently, an international retrospective study is under way to validate the Immunoscore prognostic performance in patients with colon cancer. The use of Immunoscore in clinical practice could improve the patients’ prognostic assessment and therapeutic management.
Text mining for precision medicine: automating disease-mutation relationship extraction from biomedical literature
Authors: Singhal Ayush , Simmons Michael , Lu Zhiyong
Published: April 2016

Objective Identifying disease-mutation relationships is a significant challenge in the advancement of precision medicine. The aim of this work is to design a tool that automates the extraction of disease-related mutations from biomedical text to advance database curation for the support of precision medicine.

Materials and Methods We developed a machine-learning (ML) based method to automatically identify the mutations mentioned in the biomedical literature related to a particular disease. In order to predict a relationship between the mutation and the target disease, several features, such as statistical features, distance features, and sentiment features, were constructed. Our ML model was trained with a pre-labeled dataset consisting of manually curated information about mutation-disease associations. The model was subsequently used to extract disease-related mutations from larger biomedical literature corpora.

Results The performance of the proposed approach was assessed using a benchmarking dataset. Results show that our proposed approach gains significant improvement over the previous state of the art and obtains F-measures of 0.880 and 0.845 for prostate and breast cancer mutations, respectively.

Discussion To demonstrate its utility, we applied our approach to all abstracts in PubMed for 3 diseases (including a non-cancer disease). The mutations extracted were then manually validated against human-curated databases. The validation results show that the proposed approach is useful in a real-world setting to extract uncurated disease mutations from the biomedical literature.

Conclusions The proposed approach improves the state of the art for mutation-disease extraction from text. It is scalable and generalizable to identify mutations for any disease at a PubMed scale.
Management of Urinary and Bowel Dysfunction in Multiple Sclerosis
Authors: Choi Judy M. , Kim Ja-Hong
Published: April 2016

Bladder and bowel dysfunction caused by multiple sclerosis is common and can cause considerable distress to a patient’s quality of life. Voiding dysfunction may comprise the initial presenting symptom in up to 15% of patients with multiple sclerosis, usually in the form of acute urinary retention or new-onset urinary urgency and frequency. The severity of the dysfunction and impact on daily activities are closely related to the patient’s general neurologic disability. Effective management options should be based on the patient’s overall functional status. The goal of this chapter is to provide a comprehensive algorithm for the diagnosis and management of urinary and bowel symptoms in patients with multiple sclerosis.
Sleep Disorders in Multiple Sclerosis
Authors: Braley Tiffany J. , Avidan Alon Y.
Published: April 2016

This chapter summarizes information about sleep disorders commonly experienced by patients with multiple sclerosis. Detailed reviews of insomnia, motor disorders of sleep (including restless legs syndrome or Willis-Ekbom disease), sleep-disordered breathing, REM sleep behavior disorder, and narcolepsy are presented. The epidemiology, pathophysiology, and clinical presentations of each sleep disorder are discussed, with emphasis placed on clinical features of multiple sclerosis that may exacerbate or mimic these conditions. Each section also includes a comprehensive review of the diagnostic approaches and treatments for each condition, within the context of symptoms related to multiple sclerosis that may influence diagnosis or treatment. An approach is suggested to distinguish symptoms of fatigue from those of hypersomnolence.
Employment and Career Development Considerations
Authors: Nissen Steven W. , Rumrill Phillip D.
Published: April 2016

This chapter examines the impact of multiple sclerosis on employment and career development among patients with the disease. The labor force participation statistics for people with multiple sclerosis are presented, along with summaries of research findings regarding the factors associated with employment status in this patient group. Two federal laws have been enacted to provide employment protections for people with multiple sclerosis. An overview of these laws-namely, the Americans with Disabilities Act and the Family and Medical Leave Act-is provided. The chapter concludes with descriptions of several programs and resources that exist to aid people with multiple sclerosis in their employment pursuits.
Immunotherapy in critical illness
Authors: Volk Hans-Dieter , Akyüz Levent
Published: April 2016

Immunotherapy in critically-ill patients is only feasible at clinical experimental level; no therapy has been approved so far. To develop a potential therapeutic strategy we need to know the pathogen, immune status of the patient, and interaction between the particular pathogen and immune cells to readjust the patient´s individually imbalanced immunological responsiveness. Giving the right treatment at the right time is crucial for a better outcome and the best economic use of resources. The process starts by matching the therapeutic selection to the clinical need. Personalized immunotherapy, highly dependent on the available biomarker, is required. Future studies on new immunotherapeutic approaches in critically-ill patients can only be interpreted in combination with immunological biomarker analyses. Immune modulation is a promising approach despite many disappointing results and there is a clear need for immunological stratification of critically-ill patients for improved efficacy. The search continues for new clinical endpoints in surviving patients with medical and health-economical impact.
Respiratory system compliance and resistance in the critically ill
Authors: Cordioli Ricardo Luiz , Brochard Laurent
Published: April 2016

Under mechanical ventilation, monitoring of respiratory mechanics is fundamental, especially in patients with abnormal mechanics. In order to appropriately set the ventilator, clinicians need to understand the relationship between pressure, volume and flow. To move air in and out the thorax, energy must be dissipated against elastic and resistive forces. Elastance is the pressure to volume ratio and necessitates an end inspiratory occlusion to measure the so-called plateau pressure. Resistance is the ratio between pressure dissipated and mean gas flow. Finally, the total positive end expiratory pressure must be measured with an end expiratory occlusion. Volume-controlled ventilation is the recommended mode to assess respiratory mechanics of a passive patient. Clinicians must be aware that both chest wall and lung participate in forces imposed by the respiratory system. An oesophageal catheter can estimate pleural pressure, and used to partition the respective role of the lung and the chest wall.
Pathophysiology of severe capillary leak
Authors: Harrois Anatole , Duranteau Jacques
Published: April 2016

Severe capillary leak plays an important role in the pathogenesis of several inflammatory syndromes, including sepsis, acute lung injury, and shock syndromes. Microvascular leak is caused by an increase in endothelial permeability. This is due to a range of inflammatory mediators that destabilize endothelial junctions, thereby causing tissue oedema with potential harmful effects on tissue oxygenation and organ function. Tissue oedema can impair tissue oxygenation by increasing the distance required for the diffusion of oxygen to cells, and by decreasing microvascular perfusion due to an increase in interstitial pressure. Better understanding of the pathogenesis of microvascular permeability may lead to new therapies targeting the microvascular barrier in sepsis and the acute respiratory distress syndrome.
Five-Year Outcome Analysis of Intertrochanteric Femur Fractures: A Prospective Randomized Trial Comparing a 2-Screw and a Single-Screw Cephalomedullary Nail
Authors: Berger-Groch Josephine , Rupprecht Martin , Schoepper Steffen , Schroeder Malte , Rueger Johannes Maria , Hoffmann Michael
Published: April 2016

Objectives:

To compare the radiological and functional outcome after fixation of intertrochanteric fractures (IF) using either an integrated 2-screw cephalomedullary nail [InterTan (IT); Smith & Nephew] or a single-screw device [Gamma3 (G3); Stryker] with a 5-year follow-up.

Design:

Prospective, randomized.

Settings:

A single-center study.

Patients:

One hundred four patients with a mean age of 81.2 ± 9.2 years were included, 33 patients were available for the final 5-year follow-up, 63 patients died, and 8 patients were lost for follow-up.

Intervention:

Internal fixation of intertrochaneteric femur fractures using a cephalomedullary nail with either a single screw or an integrated 2-screw system.

Main Outcome Measurements:

Length of hospital stay, SF-36-questionnaire, Harris-Hip-Score, radiographs.

Results:

SF-36 index at 6 months indicated that 93% of the IT group returned to their prefracture status compared with only 80% in the G3 group. For the mental health SF-36 index, the IT patients showed a significant increased level 6 months after the index procedure (IT: P = 0.02; G3: P = 0.20). The length of hospital stay was significantly (P = 0.03) shorter in the IT group. After 5 years however, neither group had significant implant-related complications or differences in terms of functional outcome.

Conclusions:

Regarding functional outcome and hospital stay, the IT collective performed better in the 6-month follow-up. After 5 years, no significant differences were recorded.

Level of Evidence:

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Time-Dependent Effectiveness of Locally Applied Vancomycin Powder in a Contaminated Traumatic Orthopaedic Wound Model
Authors: Tennent David J. , Shiels Stefanie M. , Sanchez Carlos J. , Niece Krista L. , Akers Kevin S. , Stinner Daniel J. , Wenke Joseph C.
Published: April 2016

Objectives:

To evaluate the effectiveness of locally applied vancomycin powder at different times postinfection in a contaminated traumatic animal model.

Methods:

This study used an established segmental defect rat femur model contaminated with Staphylococcus aureus UAMS-1 followed by treatment at 6 or 24 hours postinfection. Three treatments were evaluated: debridement and irrigation alone (control group) or in combination with either vancomycin powder or vancomycin-impregnated poly(methyl methacrylate) beads. Serum vancomycin levels were determined at scheduled time points over 14 days; bone, surrounding muscle, and implants were harvested for bacterial and inflammatory analyses.

Results:

Locally applied vancomycin powder and impregnated beads significantly reduced bacteria both within the bone and implant when treatment was performed at 6 hours. Delaying treatment to 24 hours significantly reduced the therapeutic efficacy of locally applied vancomycin of both groups. Serum vancomycin levels were detectable in all animals treated with vancomycin powder at 24 hours, but absorption was negligible from beads. At 14 days, vancomycin was detectable in the surrounding musculature of all animals and in serum of 20% of animals treated with vancomycin powder.

Conclusions:

This study suggests that vancomycin powder is a promising adjunctive therapy for preventing infection in traumatic wounds when treatment is performed early. This time-dependent effectiveness of vancomycin powder is similar to that observed with systemic and other local delivery adjuncts, which is likely attributable to biofilm formation after contamination, conferring intrinsic recalcitrance to antimicrobials.
Ketorolac Administered in the Recovery Room for Acute Pain Management Does Not Affect Healing Rates of Femoral and Tibial Fractures
Authors: Donohue David , Sanders Drew , Serrano-Riera Rafa , Jordan Charles , Gaskins Roger , Sanders Roy , Sagi H. Claude
Published: April 2016

Objectives:

To determine whether ketorolac administered in the immediate perioperative period affects the rate of nonunion in femoral and tibial shaft fractures.

Design:

Retrospective comparative study.

Setting:

Single Institution, Academic Level 1 Trauma Center.

Patients:

Three hundred and thirteen skeletally mature patients with 137 femoral shaft (OTA 32) and 191 tibial shaft (OTA 42) fractures treated with intramedullary rod fixation.

Intervention:

Eighty patients with 33 femoral shaft and 52 tibial shaft fractures were administered ketorolac within the first 24 hours after surgery (group 1—study group). Two-hundred thirty-three patients with 104 femoral shaft and 139 tibial shaft fractures were not (group 2—control group).

Main Outcome Measurements:

Rate of reoperation for repair of a nonunion and time to union.

Results:

Average time to union of the femur was 147 days for group 1 and 159 days for group 2 (P = 0.57). Average time to union of the tibia was 175 days for group 1 and 175 days for group 2 (P = 0.57). There were 3 femoral nonunions (9%) in group 1 and eleven femoral nonunions (11.6%) in group 2 (P = 1.00). There were 3 tibial nonunions (5.8%) in group 1 and 17 tibial nonunions (12.2%) in group 2 (P = 0.29). The average dose of ketorolac for patients who healed their fracture was 85 mg, whereas it was 50 mg for those who did not (P = 0.27). All patients with a nonunion in the study group were current smokers.

Conclusions:

Ketorolac administered in the first 24 hours after fracture repair for acute pain management does not seem to have a negative impact on time to healing or incidence of nonunion for femoral or tibial shaft fractures.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
STAT3 Suppression Is Involved in the Protective Effect of SIRT6 Against Cardiomyocyte Hypertrophy
Authors: Zhang Xiaoying , Li Wei , Shen Peiye , Feng Xiaojun , Yue Zhongbao , Lu Jing , You Jia , Li Jingyan , Gao Hui , Fang Shi , Li Zhuoming , Liu Peiqing
Published: April 2016

The activation of signal transducer and activator of transcription 3 (STAT3) is critical for the development of cardiac hypertrophy and heart failure. Sirtuin 6 (SIRT6) protects cardiomyocytes from hypertrophy. This study focused on the association between SIRT6 and STAT3 in the regulation of cardiomyocyte hypertrophy. In the phenylephrine (PE)-induced hypertrophic cardiomyocyte model and in the hearts of isoprenaline-induced cardiac hypertrophic rat model, the mRNA and protein expressions of STAT3 and its phosphorylated level at tyrosine 705 (P-STAT3) were significantly increased. By contrast, the deacetylation activity of SIRT6 was weakened without altering its protein expression. In addition, the nuclear localization of STAT3 and P-STAT3 was enhanced by PE, suggesting that STAT3 was activated in cardiomyocyte hypertrophy. Adenovirus infection–induced SIRT6 overexpression repressed the activation of STAT3 by decreasing its mRNA and protein levels, by suppressing its transcriptional activity, and by hindering the expressions of its target genes. Moreover, the effect of SIRT6 overexpression on eliminating PE-induced expressions of hypertrophic biomarkers, such as atrial natriuretic factor and brain natriuretic peptide, was reversed by STAT3 overexpression. Likewise, SIRT6 knockdown–induced upregulation of atrial natriuretic factor and brain natriuretic peptide was reversed by STAT3 silencing. These observations suggest that the antihypertrophic effect of SIRT6 involves STAT3 suppression. In conclusion, SIRT6 prevents PE-induced activation of STAT3 in cardiomyocyte hypertrophy; the inhibitory effect of SIRT6 on STAT3 contributes to cardiac protection.
Constraint-induced movement therapy as a rehabilitation intervention for upper extremity in stroke patients: systematic review and meta-analysis
Authors: Etoom Mohammad , Hawamdeh Mohannad , Hawamdeh Ziad , Alwardat Mohammad , Giordani Laura , Bacciu Serenella , Scarpini Claudia , Foti Calogero
Published: April 2016

Constraint-induced movement therapy (CIMT) is a neurorehabilitation technique designed to improve upper extremity motor functions after stroke. This review aimed to investigate evidence of the effect of CIMT on upper extremity in stroke patients and to identify optimal methods to apply CIMT. Four databases (MEDLINE, EMBASE, CINHAL, and PEDro) and reference lists of relevant articles and reviews were searched. Randomized clinical trials that studied the effect of CIMT on upper extremity outcomes in stroke patients compared with other rehabilitative techniques, usual care, or no intervention were included. Methodological quality was assessed using the PEDro score. The following data were extracted for each trial: patients’ characteristics, sample size, eligibility criteria, protocols of CIMT and control groups, outcome measurements, and the PEDro score. A total of 38 trials were identified according to the inclusion criteria. The trials included were heterogeneous in CIMT protocols, time since stroke, and duration and frequency of treatment. The pooled meta-analysis of 36 trials found a heterogeneous significant effect of CIMT on upper extremity. There was no significant effect of CIMT at different durations of follow-up. The majority of included articles did not fulfill powered sample size and quality criteria. The effect of CIMT changed in terms of sample size and quality features of the articles included. These meta-analysis findings indicate that evidence for the superiority of CIMT in comparison with other rehabilitative interventions is weak. Information on the optimal dose of CIMT and optimal time to start CIMT is still limited.
External Volume Expansion in Irradiated Tissue: Effects on the Recipient Site
Authors: Chin Michael S. , Lujan-Hernandez Jorge , Babchenko Oksana , Bannon Elizabeth , Perry Dylan J. , Chappell Ava G. , Lo Yuan-Chyuan , Fitzgerald Thomas J. , Lalikos Janice F.
Published: April 2016

Background:

External volume expansion prepares recipient sites to improve outcomes of fat grafting. For patients receiving radiotherapy after mastectomy, results with external volume expansion vary, and the relationship between radiotherapy and expansion remains unexplored. Thus, the authors developed a new translational model to investigate the effects in chronic skin fibrosis after radiation exposure.

Methods:

Twenty-four SKH1-E mice received 50 Gy of β-radiation to each flank and were monitored until fibrosis developed (8 weeks). External volume expansion was then applied at −25 mmHg to one side for 6 hours for 5 days. The opposite side served as the control. Perfusion changes were assessed with hyperspectral imaging. Mice were euthanized at 5 (n = 12) and 15 days (n = 12) after the last expansion application. Tissue samples were analyzed with immunohistochemistry for CD31 and Ki67, Masson trichrome for skin thickness, and picrosirius red to analyze collagen composition.

Results:

All animals developed skin fibrosis 8 weeks after radiotherapy and became hypoperfused based on hyperspectral imaging. Expansion induced edema on treated sides after stimulation. Perfusion was decreased by 13 percent on the expansion side (p < 0.001) compared with the control side for 5 days after stimulation. Perfusion returned to control-side levels by day 15. Dermal vasculature increased 38 percent by day 15 (p < 0.01) in expansion versus control. No difference was found in collagen composition.

Conclusions:

External volume expansion temporarily reduces perfusion, likely because of transient ischemia or edema. Together with mechanotransduction, these effects encourage a proangiogenic and proliferative environment in fibrotic tissue after radiotherapy in the authors’ mouse model. Further studies are needed to assess these changes in fat graft retention.
Big Data and Machine Learning in Plastic Surgery: A New Frontier in Surgical Innovation
Authors: Kanevsky Jonathan , Corban Jason , Gaster Richard , Kanevsky Ari , Lin Samuel , Gilardino Mirko
Published: April 2016

Medical decision-making is increasingly based on quantifiable data. From the moment patients come into contact with the health care system, their entire medical history is recorded electronically. Whether a patient is in the operating room or on the hospital ward, technological advancement has facilitated the expedient and reliable measurement of clinically relevant health metrics, all in an effort to guide care and ensure the best possible clinical outcomes. However, as the volume and complexity of biomedical data grow, it becomes challenging to effectively process “big data” using conventional techniques. Physicians and scientists must be prepared to look beyond classic methods of data processing to extract clinically relevant information. The purpose of this article is to introduce the modern plastic surgeon to machine learning and computational interpretation of large data sets. What is machine learning? Machine learning, a subfield of artificial intelligence, can address clinically relevant problems in several domains of plastic surgery, including burn surgery; microsurgery; and craniofacial, peripheral nerve, and aesthetic surgery. This article provides a brief introduction to current research and suggests future projects that will allow plastic surgeons to explore this new frontier of surgical science.
Collagen and Fractionated Platelet-Rich Plasma Scaffold for Dermal Regeneration
Authors: Houdek Matthew T. , Wyles Cody C. , Stalboerger Paul G. , Terzic Andre , Behfar Atta , Moran Steven L.
Published: April 2016

Background:

Current options for in vivo regeneration of dermal tissue remain limited. The purpose of this study was to engineer a unique scaffold capable of recruiting dermal stem cells from adjacent tissue, thus circumventing the need to seed the scaffolds with stem cells before implantation, leading to skin regeneration.

Methods:

A hydrogel scaffold was created through combination of type I collagen along with fractionated platelet-rich plasma. This was compared to a control hydrogel consisting of type I collagen and fetal bovine serum. Hydrogels were cultured with fresh human skin tissue and incubated with supplemental media. Gels were digested weekly for cellular content as examined by flow cytometry at the 4- and 8-week time points. The fractionated platelet-rich plasma and collagen gels were then implanted onto full-thickness skin defects on the backs of rats and compared to wounds healing by secondary intention. Wound area was evaluated for epithelialization and neovascularization.

Results:

Platelet-rich plasma fractionation increased platelet-derived growth factors. In contrast to collagen scaffolds, fractionated platelet-rich plasma–supplemented scaffolds recruited more dermal-derived stem cells from fresh skin tissue compared with collagen hydrogels at the 4- and 8-week time points. Furthermore, fractionated platelet-rich plasma–supplemented hydrogels accelerated wound healing, angiogenesis, and hair and sweat gland formation, ultimately regenerating a dermis-like tissue.

Conclusions:

Generation of hydrogels with fractionated platelet-rich plasma was able to improve cellular recruitment and growth and differentiation of dermal-derived stem cells, leading to hair growth and sweat gland formation. This provides a novel approach to regenerate skin for treating large defects.
Global Aesthetics Consensus: Hyaluronic Acid Fillers and Botulinum Toxin Type A—Recommendations for Combined Treatment and Optimizing Outcomes in Diverse Patient Populations
Authors: Sundaram Hema , Liew Steven , Signorini Massimo , Vieira Braz André , Fagien Steven , Swift Arthur , De Boulle Koenraad L. , Raspaldo Hervé , Trindade de Almeida Ada R. , Monheit Gary
Published: April 2016

Background:

Combination of fillers and botulinum toxin for aesthetic applications is increasingly popular. Patient demographics continue to diversify, and include an expanding population receiving maintenance treatments over decades.

Methods:

A multinational panel of plastic surgeons and dermatologists convened the Global Aesthetics Consensus Group to develop updated guidelines with a worldwide perspective for hyaluronic acid fillers and botulinum toxin. This publication considers strategies for combined treatments, and how patient diversity influences treatment planning and outcomes.

Results:

Global Aesthetics Consensus Group recommendations reflect increased use of combined treatments in the lower and upper face, and some midface regions. A fully patient-tailored approach considers physiologic and chronologic age, ethnically associated facial morphotypes, and aesthetic ideals based on sex and culture. Lower toxin dosing, to modulate rather than paralyze muscles, is indicated where volume deficits influence muscular activity. Combination of toxin with fillers is appropriate for several indications addressed previously with toxin alone. New scientific data regarding hyaluronic acid fillers foster an evidence-based approach to selection of products and injection techniques. Focus on aesthetic units, rather than isolated rhytides, optimizes results from toxin and fillers. It also informs longitudinal treatment planning, and analysis of toxin nonresponders.

Conclusions:

The emerging objective of injectable treatment is facial harmonization rather than rejuvenation. Combined treatment is now a standard of care. Its use will increase further as we refine the concept that aspects of aging are intimately related, and that successful treatment entails identifying and addressing the primary causes of each.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Total Face, Eyelids, Ears, Scalp, and Skeletal Subunit Transplant Research Procurement: A Translational Simulation Model
Authors: Sosin Michael , Ceradini Daniel J. , Hazen Alexes , Sweeney Nicole G. , Brecht Lawrence E. , Levine Jamie P. , Staffenberg David A. , Saadeh Pierre B. , Bernstein G. Leslie , Rodriguez Eduardo D.
Published: April 2016

Background:

Cadaveric face transplant models are routinely used for technical allograft design, perfusion assessment, and transplant simulation but are associated with substantial limitations. The purpose of this study was to describe the experience of implementing a translational donor research facial procurement and solid organ allograft recovery model.

Methods:

Institutional review board approval was obtained, and a 49-year-old, brain-dead donor was identified for facial vascularized composite allograft research procurement. The family generously consented to donation of solid organs and the total face, eyelids, ears, scalp, and skeletal subunit allograft.

Results:

The successful sequence of computed tomographic scanning, fabrication and postprocessing of patient-specific cutting guides, tracheostomy placement, preoperative fluorescent angiography, silicone mask facial impression, donor facial allograft recovery, postprocurement fluorescent angiography, and successful recovery of kidneys and liver occurred without any donor instability. Preservation of the bilateral external carotid arteries, facial arteries, occipital arteries, and bilateral thyrolinguofacial and internal jugular veins provided reliable and robust perfusion to the entirety of the allograft. Total time of facial procurement was 10 hours 57 minutes.

Conclusions:

Essential to clinical face transplant outcomes is the preparedness of the institution, multidisciplinary face transplant team, organ procurement organization, and solid organ transplant colleagues. A translational facial research procurement and solid organ recovery model serves as an educational experience to modify processes and address procedural, anatomical, and logistical concerns for institutions developing a clinical face transplantation program. This methodical approach best simulates the stressors and challenges that can be expected during clinical face transplantation.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Social Capital is Associated With Late HIV Diagnosis: An Ecological Analysis
Authors: Ransome Yusuf , Galea Sandro , Pabayo Roman , Kawachi Ichiro , Braunstein Sarah , Nash Denis
Published: April 2016

Background:

Late HIV diagnosis is associated with higher medical costs, early mortality among individuals, and HIV transmission in the population. Even under optimal configurations of stable or declining HIV incidence and increase in HIV case findings, no change in proportion of late HIV diagnosis is projected after year 2019. We investigated the association among social capital, gender, and late HIV diagnosis.

Methods:

We conduct ecological analyses (ZIP code, N = 166) using negative binomial regression of gender-specific rates of late HIV diagnoses (an AIDS defining illness or a CD4 count ≤200 cell/μL within 12 months of a new HIV diagnosis) in 2005 and 2006 obtained from the New York City HIV Surveillance Registry, and social capital indicators (civic engagement, political participation, social cohesion, and informal social control) from the New York Social Indicators Survey, 2004.

Results:

Overall, low to high political participation and social cohesion corresponded with significant (P < 0.0001) decreasing trends in late HIV diagnosis rates. Among men [relative risk (RR) = 0.66, 95% CI: (0.47 to 0.98)] and women [RR = 0.43, 95% CI: (0.28 to 0.67)], highest political participation was associated with lower relative odds of late HIV diagnosis, independent of income inequality. Highest informal social control [RR = 0.67, 95% CI: (0.48 to 0.93)] among men only and moderate social cohesion [RR = 0.71, 95% CI: (0.55 to 0.92)] among women only were associated with the outcome adjusting for social fragmentation, income inequality, and racial composition.

Discussion:

The magnitude of association between social capital and late HIV diagnosis varies by gender and by social capital indicator.
Ultrabrief Electroconvulsive Therapy for Manic Episodes of Bipolar Disorder
Authors: Anand Sandip
Published: April 2016

Right unilateral ultrabrief-pulse electroconvulsive therapy (RUL-UB ECT) is gaining popularity and is being used for the treatment of severe major depression. Though brief pulse-width ECT has shown to have robust antimanic effects, the efficacy of UB ECT for mania has not been studied, and there are very few reports on its use in mania. A brief case series of 3 patients with manic episode of bipolar disorder who were treated with RUL-UB ECT is presented here. The successful treatment of 2 patients in this report suggests that some manic episodes can be rapidly and effectively treated with RUL-UB ECT.
Police integrity in South Africa: a tale of three police agency types
Authors: Ivković Sanja Kutnjak , Sauerman Adri
Published: April 2016

Purpose

– Following the theory of police integrity, the purpose of this paper is to explore empirically the contours of police integrity in South Africa using survey of the three South African police agency types.

Design/methodology/approach

– During the period from 2010 to 2012, a police integrity survey was used to measure the contours of police integrity among 871 police officers across South Africa, covering all three police agency types. The questionnaire contains descriptions of 11 scenarios, covering different forms of police misconduct, followed by seven questions measuring officer views of scenario seriousness, the appropriate and expected discipline, and willingness to report the misconduct.

Findings

– The results show that the respondents from the three police agency types were about equally likely to recognize behaviors as rule-violating and, in most scenarios, evaluated these scenarios to be of the same level of seriousness. The contours of the code of silence were very similar as well. The authors found the largest and most systematic differences in the respondents’ perceptions of disciplinary environment, with the traffic respondents expecting harsher disciplinary environments than either the South African Police Service or metro police respondents.

Research limitations/implications

– Similar sample group sizes would have been preferred, although the current sample group proportions are certainly representative of a collective, agency size comparison.

Practical implications

– Although the respondents from the three police agency types expressed similar views of misconduct seriousness and their willingness to report, and were as likely to recognize these behaviors as rule-violating, their views depicted markedly different disciplinary environments. These results clearly support the critical importance of consistent enforcement of official rules.

Originality/value

– Whereas several integrity studies have explored the country’s national police service, empirical studies on the integrity of the other South African police agency types are non-existent.
Police officer integrity: a partial replication and extension
Authors: Lim Hyeyoung , Sloan John J.
Published: April 2016

Purpose

– The purpose of this paper is to partially replicate and extend the work of Klockarset al.and others on police integrity by examining how individual, organizational, and ecological factors affect police supervisors’ perceptions of police misconduct and willingness to report fellow officers’ misconduct.

Design/methodology/approach

– Surveys containing 17 scenarios developed by Klockarset al.(2000, 2004, 2006) were administered to 553 ranking officers attending training at the Bill Blackwood Law Enforcement Management Institute of Texas from June 1, 2009 to March 1, 2010 and employed by municipal police departments, county sheriff’s departments, and constable agencies.

Findings

– Results suggest that individual and organizational factors affect supervisor willingness to blow the whistle on underling misconduct, although their effects varied by seriousness of the behavior.

Originality/value

– The current project partially replicates and extends prior studies of factors affecting police integrity by surveying supervisors, measuring their willingness to whistle blow, and including variables in statistical models that prior studies have not included.
Citrus Tachibana Leaf Extract Mitigates Symptoms of Food Allergy by Inhibiting Th2‐Associated Responses
Authors: Chung Min‐Yu , Shin Hee Soon , Choi Dae Woon , Shon Dong‐Hwa
Published: April 2016

Although the incidence of food allergy continues to rise, there have been no effective therapeutic strategies. Citrus fruits contain a number of bioactive flavonoids with immune‐regulatory functions. The objective of this study was to determine whether Citrus tachibana (fruit body with peel, leaves, and branch) can protect against the development of food allergy and the mechanism behind it, and to identify the active compound(s) responsible. We found that C. tachibana leaf extract (CLE) mitigated ovalbumin (OVA)‐induced food allergy symptoms including increased rectal temperature, diarrhea, and anaphylaxis. This mitigation was likely due to CLE‐mediated decreases in cytokine release from T‐helper 2 cells (Th2 cells) in mesenteric lymph nodes. Moreover, higher levels of CLE attenuated systemic Th2 cell–mediated responses in mouse splenocytes sensitized with OVA+Alum. This was evidenced by CLE‐mediated reductions in Th2 cytokine release, including interleukin (IL)‐4, IL‐5, and IL‐13, but not the Th1 cytokines IL‐12 and interferon (IFN)‐γ, which was attributable to decreased gene expression levels. We also identified kaempferol as the most potent compound for reducing Th2‐associated responses in splenocytes. The findings of this study suggest that CLE suppresses Th2‐cell–mediated immune responses, contributing to alleviation of food allergy symptoms, and that kaempferol is a flavonoid with potential antiallergenic activity that targets Th2 cell–induced responses.
Microbial Community Composition Associated with Maotai Liquor Fermentation
Authors: Wang Qiang , Zhang Hongxun , Liu Xiu
Published: April 2016

The solid‐state fermentation state of Chinese Maotai liquor involves the interaction of several complex microbial communities leading to the generation of the most complex liquor fermentation system in the world and contributes to the unique flavor and aroma of the liquor. In this study, total DNA was extracted from 3 fermented grain samples (FG1, FG2, and FG3) and 12 environmental samples, including Daqu (DA1, DA2, DA3, and DA4), cellar mud (CS1, CS2, and CS3), soil (SL1 and SL2), air (A1 and A2), and sorghum (SH), and the 16S and 18S rRNA genes were amplified. The distribution of typical microorganisms in the samples was analyzed using nested PCR‐denaturing gradient gel electrophoresis, while quantitative PCR amplification of 16S rRNA and internal transcribed spacer genes was performed to estimate the microbial abundance present in each sample. The results indicated that Daqu was the primary source of bacteria, followed by the air, soil, and sorghum samples, while the majority of the fungi responsible for Maotai liquor fermentation were from Daqu and sorghum. Highest bacterial concentrations were found in fermented grains, followed by Daqu and sorghum, while the highest fungal concentrations were found in Daqu, followed by sorghum and an air sample from outside the liquor production area. The findings of this study may provide information regarding the mechanisms responsible for flavor development in Maotai liquor, and may be used to further optimize the traditional art of making liquor.
The Genetics of Fetal Alcohol Spectrum Disorders
Authors: Eberhart Johann K. , Parnell Scott E.
Published: April 2016

The term “fetal alcohol spectrum disorders” (FASD) defines the full range of ethanol (EtOH)‐induced birth defects. Numerous variables influence the phenotypic outcomes of embryonic EtOH exposure. Among these variables, genetics appears to play an important role, yet our understanding of the genetic predisposition to FASD is still in its infancy. We review the current literature that relates to the genetics of FASD susceptibility and gene–EtOH interactions. Where possible, we comment on potential mechanisms of reported gene–EtOH interactions. Early indications of genetic sensitivity to FASD came from human and animal studies using twins or inbred strains, respectively. These analyses prompted searches for susceptibility loci involved in EtOH metabolism and analyses of candidate loci, based on phenotypes observed in FASD. More recently, genetic screens in animal models have provided an additional insight into the genetics of FASD. Understanding FASD requires that we understand the many factors influencing phenotypic outcome following embryonic EtOH exposure. We are gaining ground on understanding some of the genetics behind FASD, yet much work remains to be carried out. Coordinated analyses using human patients and animal models are likely to be highly fruitful in uncovering the genetics behind FASD.
Interplay of dysphoria and anxiety sensitivity in relation to emotion regulatory cognitions of smoking among treatment‐seeking smokers
Authors: Garey Lorra , Bakhshaie Jafar , Brandt Charles P. , Langdon Kirsten J. , Kauffman Brooke Y. , Schmidt Norman B. , Leventhal Adam M. , Zvolensky Michael J.
Published: April 2016

Background and Objectives

There is evidence that anxiety sensitivity (AS) plays a role in the maintenance of smoking, yet there is little understanding of how AS interplays with other affective symptomatology variables that are also related to smoking, such as dysphoria. Therefore, the current cross‐sectional study evaluated the interactive effects of AS and dysphoria on emotion regulatory cognitions, including smoking negative affect reduction expectancies, perceived barriers for cessation, and smoking‐specific experiential avoidance.

Method

A total of 448 adult treatment‐seeking daily smokers, who responded to study advertisements, were recruited to participate in a smoking cessation treatment trial (47.8% female; Mage = 37.2, SD = 13.5). The current study utilized self‐report baseline data from trial participants.

Results

After accounting for covariates, simple slope analyses revealed that AS was positively related to negative affect reduction expectancies (β = .03, p = .01), perceived barriers to cessation (β = .22, p = .002), and smoking avoidance and inflexibility (β = .07, p = .04), among smokers with lower (vs. higher) levels of dysphoria.

Conclusions

The current findings suggest that higher levels of dysphoria may mitigate the relation between AS and emotion regulatory cognitions of smoking.

Scientific Significance

The current findings highlight the unique and additive clinical relevance of AS and dysphoria regarding emotion regulatory smoking cognitions that may impede quit success. (Am J Addict 2016;25:267–274)
TRPV4 channels in the human urogenital tract play a role in cell junction formation and epithelial barrier
Authors: Janssen D. A. W. , Jansen C. J. F. , Hafmans T. G. , Verhaegh G. W. , Hoenderop J. G. , Heesakkers J. P. F. A. , Schalken J. A.
Published: April 2016

Aim

The molecular interactions between transient receptor potential vanilloid subtype 4 channels (TRPV4) and cell junction formation were investigated in the human and mouse urogenital tract.

Materials and Methods

A qualitative study was performed to investigate TRPV4 channels, adherence junctions (AJs) and tight junctions (TJs) in kidney, ureter and bladder tissues from humans and wild‐type and transgenic TRPV4 knockout (−/−) mice with immunohistochemistry, Western blotting, immunoprecipitation and reverse trasnscription‐PCR. Cell junction formation in the wild‐type and TRPV4 knockout (−/−) mouse was evaluated with immunohistochemistry and transmission electron microscope (TEM) techniques.

Results

TRPV4 channels are predominantly located in membranes of epithelial cells of the bladder, ureter and the collecting ducts of the kidney. There is a molecular interaction between the TRPV4 channel and the AJ. TEM evaluation showed that AJ formation is disrupted in the TRPV4 −/− mouse resulting in deficient intercellular connections and integrity of the epithelium.

Conclusions

TRPV4 is believed to be a mechanoreceptor in the bladder. This study demonstrates that TRPV4 is also involved in intercellular connectivity and structural integrity of the epithelium.
Influence of river channelization and the invasive shrub, Ligustrum sinense, on oak (Quercus spp.) growth rates in bottomland hardwood forests
Authors: Foard Meghan , Burnette Dorian J. , Burge David R. L. , Marsico Travis D.
Published: April 2016

Question

Do river channelization and a common invasive shrub, Ligustrum sinense Lour. (Chinese privet), affect tree growth rates in forested riverine wetlands?

Location

Three sites along the Wolf River, in and near Memphis, Tennessee, USA.

Methods

We cored and analysed 83 oak trees within three study sites. Correlations of river channelization and climatic variables with basal area increments (BAI) and detrended BAI (SFS) were analysed to investigate channelization effects. Significant correlations were removed from BAI chronologies (BAI‐HR) to isolate the effect of L. sinense. We investigated effects of L. sinense on tree growth using a before–after/control–impact (BACI) experimental design with one location impacted by invasion (INV), two control locations that were not invaded (NON and REF) and covariates of tree age and size. We conducted a two‐factor mixed effects ANCOVA to determine if there was a significant interaction (BACI) effect.

Results

Channelization promoted faster canopy oak growth in all sites, spring drought significantly slowed growth in NON, while summer precipitation promoted wood production in NON. Investigation of L. sinense impact on tree growth revealed a significant BACI effect, such that trees in INV grew slower after invasion than trees in the non‐invaded control sites (NON and REF).

Conclusions

We suggest that faster growth after channelization may be a consequence of increased aerobic conditions, by enabling higher oxygen availability to tree roots. However, many of the obligate bottomland tree species struggle to regenerate in drier, post‐channelized conditions. Thus, native drought‐tolerant species may have an advantage in the sub‐canopy and regeneration layers of these altered forests. Instead, L. sinense, an invasive and drought‐tolerant species, has invaded most locations adjacent to the channelized portion of the Wolf River. L. sinense presence reduces the channelization advantage by slowing growth of canopy oaks and possibly contributing to accelerated mortality. These results suggest an emerging shift to a commonly held paradigm with respect to invasive shrub species. Not only do invasive shrubs crowd out other small woody species and herbaceous plants, but they also have the ability to impact the structure of the forest canopy.