bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of Subjective Hospital Compare Metrics With Objective Outcomes of Cranial Neurosurgical Procedures in New York State
Authors: Bekelis Kimon , Missios Symeon , Coy Shannon , Rahmani Redi , MacKenzie Todd A. , Asher Anthony L.
Published: February 2017

BACKGROUND:Public reporting is at the forefront of health care reform.

OBJECTIVE:To investigate whether patient satisfaction as expressed in a public reporting platform correlates with objective outcomes for cranial neurosurgery patients.

METHODS:We performed a cohort study involving patients undergoing cranial neurosurgery from 2009 to 2013 who were registered in the Statewide Planning and Research Cooperative System database. This cohort was merged with the corresponding data from the Centers for Medicare and Medicaid Services Hospital Compare website. The association of patient satisfaction metrics with outcomes was examined with the use of a propensity-adjusted regression model.

RESULTS:Overall, 19 591 patients underwent cranial neurosurgery during the study. Using a propensity-adjusted multivariable regression analysis, we demonstrated that hospitals with a greater percentage of patient-assigned “high” scores had decreased mortality (OR, 0.60; 95% CI, 0.53-0.67), rate of discharge to rehabilitation (OR, 0.93; 95% CI, 0.88-0.98), length of stay (adjusted difference, –1.29; 95% CI, –1.46 to –1.13), and hospitalization charges (adjusted difference, –23%; 95% CI, –36% to –9%) after cranial neurosurgery. Similar associations were identified for hospitals with a higher percentage of patients, who would recommend these institutions to others.

CONCLUSION:In a Centers for Medicare and Medicaid Services Hospital Compare–Statewide Planning and Research Cooperative System merged dataset, we observed an association of higher performance in patient satisfaction measures with decreased mortality, rate of discharge to rehabilitation, hospitalization charges, and length of stay.
Lumbar Spinal Stenosis Associated With Degenerative Lumbar Spondylolisthesis: A Systematic Review and Meta-analysis of Secondary Fusion Rates Following Open vs Minimally Invasive Decompression
Authors: Schöller Karsten , Alimi Marjan , Cong Guang-Ting , Christos Paul , Härtl Roger
Published: February 2017

BACKGROUND: Decompression without fusion is a treatment option in patients with lumbar spinal stenosis (LSS) associated with stable low-grade degenerative spondylolisthesis (DS). A minimally invasive unilateral laminotomy (MIL) for “over the top” decompression might be a less destabilizing alternative to traditional open laminectomy (OL).

OBJECTIVE: To review secondary fusion rates after open vs minimally invasive decompression surgery.

METHODS: We performed a literature search in Pubmed/MEDLINE using the keywords “lumbar spondylolisthesis” and “decompression surgery.” All studies that separately reported the outcome of patients with LSS+DS that were treated by OL or MIL (transmuscular or subperiosteal route) were included in our systematic review and meta-analysis. The primary end point was secondary fusion rate. Secondary end points were total reoperation rate, postoperative progression of listhetic slip, and patient satisfaction.

RESULTS: We identified 37 studies (19 with OL, 18 with MIL), with a total of 1156 patients, that were published between 1983 and 2015. The studies’ evidence was mostly level 3 or 4. Secondary fusion rates were 12.8% after OL and 3.3% after MIL; the total reoperation rates were 16.3% after OL and 5.8% after MIL. In the OL cohort, 72% of the studies reported a slip progression compared to 0% in the MIL cohort, respectively. After OL, satisfactory outcome was 62.7% compared to 76% after MIL.

CONCLUSION: In patients with LSS and DS, minimally invasive decompression is associated with lower reoperation and fusion rates, less slip progression, and greater patient satisfaction than open surgery.
Long-term Outcome After Multiple Burr Hole Surgery in Children With Moyamoya Angiopathy: A Single-Center Experience in 108 Hemispheres
Authors: Blauwblomme Thomas , Mathon Bertrand , Naggara Olivier , Kossorotoff Manoelle , Bourgeois Marie , Puget Stéphanie , Meyer Philippe , Brousse Valentine , de Montalembert Marianne , Brunelle Francis , Zerah Michel , Sainte-Rose Christian
Published: February 2017

BACKGROUND: Multiple burr hole (MBH) surgery is a simple, safe, and effective indirect technique of revascularization in moyamoya angiopathy (MM). However, it is not yet recognized as a first-line treatment.

OBJECTIVE: To assess the long-term outcome and perioperative complications in a large single-center cohort of children with MM who underwent burr hole surgery.

METHODS: This study is a retrospective analysis of children who underwent surgery for MM in a national reference center for pediatric stroke between 1999 and 2015. Sixty-four children (108 hemispheres, median age 7 years) were consecutively treated. The indication for revascularization was previous stroke or transient ischemic attack (TIA) or rapidly progressive disease on brain magnetic resonance imaging (MRI) and digital subtraction angiography. Children were followed with clinical examinations, telephone interviews, and MRI with any clinical recurrence of stroke or TIA used as the primary endpoint. Surgical mortality and morbidity were documented.

RESULTS: Sixty-four patients were operated (bilateral MBH n = 39, unilateral procedure n = 25). At a mean follow-up of 4.2 years and 270.6 patient years, 89.1% of patients had not suffered any recurrent stroke or TIA. A second surgery was required in 5 cases after unilateral revascularization, and in 3 cases after bilateral MBH. Mortality associated with the procedure was 0. Postoperative Matsushima angiographic grading was the only predictive factor of ischemic recurrence (P = .036).

CONCLUSION: In pediatric MM, MBH compares favorably to other indirect or direct revascularization techniques in children in the prevention of stroke or TIA.
Clinical and Mucosal Immune Correlates of HIV-1 Semen Levels in Antiretroviral-Naive Men
Authors: Osborne Brendan J. W. , Marsh Angie K. , Huibner Sanja , Shahabi Kamnoosh , Liu Cindy , Contente Tania , Nagelkerke Nico J. D. , Kovacs Colin , Benko Erika , Price Lance , MacDonald Kelly S. , Kaul Rupert
Published: February 2017

Background

This study was done to characterize parameters associated with semen human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) viral load (VL) variability in HIV-infected, therapy-naive men.

Methods

Paired blood and semen samples were collected from 30 HIV-infected, therapy-naive men who have sex with men, and 13 participants were observed longitudinally for up to 1 year. Human immunodeficiency virus RNA, bacterial load by 16S RNA, herpesvirus (Epstein-Barr virus and cytomegalovirus [CMV]) shedding, and semen cytokines/chemokines were quantified, and semen T-cell subsets were assessed by multiparameter flow cytometry.

Results

Semen HIV RNA was detected at 93% of visits, with >50% of men shedding high levels of virus (defined as >5000 copies/mL). In the baseline cross-sectional analysis, an increased semen HIV VL correlated with local CMV reactivation, the semen bacterial load, and semen inflammatory cytokines, particularly interleukin (IL)-8. T cells in semen were more activated than blood, and there was an increased frequency of Th17 cells and γδ-T-cells. Subsequent prospective analysis demonstrated striking interindividual variability in HIV and CMV shedding patterns, and only semen IL-8 levels and the blood VL were independently associated with semen HIV levels.

Conclusions

Several clinical and immune parameters were associated with increased HIV semen levels in antiretroviral therapy-naive men, with induction of local proinflammatory cytokines potentially acting as a common pathway.
A Narrative Review of the Evidence on the Efficacy of Dexamethasone on Postoperative Analgesic Consumption
Authors: Batistaki Chrysanthi , Kaminiotis Evagelia , Papadimos Thomas , Kostopanagiotou Georgia
Published: February 2017

Objectives:

The effect of dexamethasone on analgesic consumption has not been adequately studied. The aim of this review was to investigate recent literature regarding the possible effect of dexamethasone on postoperative analgesic consumption.

Methods:

Critical review of randomized trials and prospective consecutive studies investigating the postoperative analgesic effect of dexamethasone was performed. Only studies published during 2006 to 2015 were included.

Results:

Forty-one studies met the inclusion criteria; 33 in adults and 8 in children (9 in general surgery, 8 in gynecologic/breast surgery, 8 in orthopedic/spinal surgery, 8 in head/neck surgery, 7 in children’s tonsillectomy, and 1 in children’s orchiopexy). Literature review demonstrated that dexamethasone can decrease analgesic requirements in patients undergoing laparoscopic cholecystectomies, laparoscopic gynecologic and breast surgery; whereas there is no consensus regarding orthopedic procedures, with positive evidence mostly regarding spinal surgeries. The efficacy of dexamethasone during head and neck surgery is not conclusive; however, its use before thyroid surgery may be beneficial. In children a beneficial impact of dexamethasone administration was revealed on posttonsillectomy reduction of analgesic needs. Studies on other kinds of operations in children are lacking.

Conclusions:

Dexamethasone administered at a dose of 8 mg before surgical incision may be beneficial in laparoscopic cholecystectomies, thyroid, laparoscopic gynecologic and breast surgery, and tonsillectomies in children. Dexamethasone’s potential impact on reducing postoperative analgesic requirements should be investigated in more detail in a systematic manner, to support its use in other kinds of operations.
Gray Matter Abnormalities Associated With Chronic Back Pain
Authors: Yuan CongHu , Shi HaiCun , Pan PingLei , Dai ZhenYu , Zhong JianGuo , Ma HaiRong , Sheng LiQin
Published: February 2017

Background:

Studies employing voxel-based morphometry have reported inconsistent findings on the association of gray matter (GM) abnormalities with chronic back pain (CBP). We, therefore, performed a meta-analysis of available studies to identify the most consistent GM regions associated with CBP.

Methods:

The PubMed, Embase, and Web of Science databases were searched from January 2000 to May 29, 2016. Comprehensive meta-analyses of whole-brain voxel-based morphometry studies to identify the most robust GM abnormalities in CBP were conducted using the Seed-based d Mapping software package.

Results:

A total of 10 studies, comprising 293 patients with CBP and 624 healthy controls, were included in the meta-analyses. The most robust findings of regional GM decreases in patients with CBP compared with healthy controls were identified in the bilateral medial prefrontal cortex extending to the anterior cingulate cortex, the right medial prefrontal cortex extending to the orbitofrontal cortex. Regional GM decreases in the left anterior insula were less robustly observed.

Conclusions:

The present study demonstrates a pattern of GM alterations in CBP. These data further advance our understanding of the pathophysiology of CBP.
The Untapped Potential of Patient and Family Engagement in the Organization of Critical Care
Authors: Haines Kimberley J. , Kelly Phillipa , Fitzgerald Peter , Skinner Elizabeth H. , Iwashyna Theodore J.
Published: February 2017

Objective:

There is growing interest in patient and family participation in critical care—not just as part of the bedside, but as part of educational and management organization and infrastructure. This offers tremendous opportunities for change but carries risk to patients, families, and the institution. The objective is to provide a concise definitive review of patient and family organizational participation in critical care as a high-risk population and other vulnerable groups. A pragmatic, codesigned model for critical care is offered as a suggested approach for clinicians, researchers, and policy-makers.

Data Sources:

To inform this review, a systematic search of Ovid Medline, PubMed, and Embase was undertaken in April 2016 using the MeSH terms: patient participation and critical care. A second search was undertaken in PubMed using the terms: patient participation and organizational models to search for other examples of engagement in vulnerable populations. We explicitly did not seek to include discussions of bedside patient-family engagement or shared decision-making.

Study Selection:

Two reviewers screened citations independently. Included studies either actively partnered with patients and families or described a model of engagement in critical care and other vulnerable populations.

Data Extraction:

Data or description of how patient and family engagement occurred and/or description of model were extracted into a standardized form.

Data Synthesis:

There was limited evidence of patient and family engagement in critical care although key recommendations can be drawn from included studies. Patient and family engagement is occurring in other vulnerable populations although there are few described models and none which address issues of risk.

Conclusions:

A model of patient and family engagement in critical care does not exist, and we propose a pragmatic, codesigned model that takes into account issues of psychologic safety in this population. Significant opportunity exists to document processes of engagement that reflect a changing paradigm of healthcare delivery.
A Novel Fusion Antibody Exhibits Antiangiogenic Activity and Stimulates NK Cell-mediated Immune Surveillance Through Fused NKG2D Ligand
Authors: Acheampong Desmond O. , Tang Mingying , Wang Youfu , Zhao Xin , Xie Wei , Chen Zhiguo , Tian Wenzhi , Wang Min , Zhang Juan
Published: February 2017

A single-chain variable fragment (scFv) targeting vascular endothelial growth factor receptor 2 was previously generated from a phage display library in our laboratory. However, it has shortened half-life and lacks Fc fragment for effector cell recognition. To address these challenges, a ligand of NK-cell receptor NKG2D was fused to the scFv and created a fusion protein scFv-major histocompatibility complex class I-related chain A (MICA), which is expected to recognize tumor cells through the scFv moiety and stimulate NK cells through the MICA. The fusion protein demonstrated specific binding to both vascular endothelial growth factor receptor 2 and NKG2D in protein-based and cell-based assays. In addition, it demonstrated antiangiogenic activities including restraining the proliferation, migration, transwell invasion, and tube formation of human umbilical vein endothelial cells. Furthermore, the fusion protein exhibited significant cytotoxicity on K562, MDA-MB-435, and B16F10 cells and triggered NK92 cell-mediated cytotoxicity on MDA-MB-435 cells by stimulating the release of significant cytokines. The fusion protein targeting strategy, therefore, provides a means to engage lymphocyte effector cells against tumor specific antigen overexpressing tumor cells.
Altered integrin expression patterns shown by microarray in human cutaneous melanoma
Authors: Vizkeleti Laura , Kiss Timea , Koroknai Viktoria , Ecsedi Szilvia , Papp Orsolya , Szasz Istvan , Adany Roza , Balazs Margit
Published: February 2017

A large variety of molecular pathways in melanoma progression suggests that no individual molecular alteration is crucial in itself. Our aim was to define the molecular alterations underlying metastasis formation. Gene expression profiling was performed using microarray and qRT-PCR to define alterations between matched primary and metastatic melanoma cell lines. These data were integrated with publicly available unmatched tissue data. The invasiveness of cell lines was determined by Matrigel invasion assays and invasive clones from primary melanoma-derived cell lines were also selected. Two metastatic cell line models were created: the regional lymph node WM983A–WM983AINV–WM983B and the distant lung WM793B–WM793BINV–1205Lu metastatic models. The majority of metastasis genes were downregulated and enriched in adhesion and ITGA6-B4 pathways. Upregulation of immune pathways was characteristic of distant metastases, whereas increased Rap1 signaling was specific for regional (sub)cutaneous metastases. qRT-PCR analysis of selected integrins (A2, A3, A4, A9, B5, B8, A6, B1, and B3) highlighted the possible importance of ITGA3/4 and B8 in the metastatic process, distinguishing regional and distant metastases. We identified functionally relevant gene clusters that influenced metastasis formation. Our data provide further evidence that integrin expression patterns may be important in distant metastasis formation.
BRAF inhibitor discontinuation and rechallenge in advanced melanoma patients with a complete initial treatment response
Authors: Desvignes Céline , Abi Rached Henry , Templier Carole , Drumez Elodie , Lepesant Pauline , Desmedt Eve , Mortier Laurent
Published: February 2017

BRAF inhibitors (BRAFi), a targeted therapy, are used to treat metastatic late-stage melanomas harbouring the BRAF-V600 mutation (found in about 50% of melanomas). The targeted therapy is generally maintained until tumour progression or major toxicity occurs, although responses are often limited in time. It is unknown whether melanoma patients achieving a complete response with targeted therapy can safely discontinue treatment. We retrospectively observed the clinical course of patients with metastatic melanoma who discontinued BRAFi therapy after achieving a complete response and those with an incomplete response combined with surgical removal of the remaining tumours. We also evaluated the effectiveness of BRAFi in these patients after recurrence. In 11 patients, the best response was diagnosed after a median BRAFi treatment duration of 105 (29–341) days. The median follow-up after BRAFi initiation was 769 (435–1765) days. Recurrence was observed in all 11 patients (100%), median: 82 (27–322) days. Five patients achieved a complete response, with a median progression-free survival after cessation of 136.5 (34–322) days versus 82 (27–144) days for six patients with an incomplete response combined with surgical removal of remaining tumours. Baseline characteristics and time to best response and to discontinuation did not influence the rate of relapse. Subsequently, eight patients were rechallenged with a BRAFi. The median progression-free survival time after BRAFi rechallenge was 222.5 (15–425) days. The three remaining patients received treatments other than BRAFi. Our findings may be valuable with respect to ongoing clinical trials of combinations of targeted therapies and immunomodulatory antibodies.
Methodology and Reporting of Mobile Health and Smartphone Application Studies for Schizophrenia
Authors: Torous John , Firth Joseph , Mueller Nora , Onnela J. P. , Baker Justin T.
Published: February 2017

The increasing prevalence of mobile devices among patients of all demographic groups has the potential to transform the ways we diagnose, monitor, treat, and study mental illness. As new tools and technologies emerge, clinicians and researchers are confronted with an increasing array of options both for clinical assessment, through digital capture of the essential behavioral elements of a condition, and for intervention, through formalized treatments, coaching, and other technology-assisted means of patient communication. And yet, as with any new set of tools for the assessment or treatment of a medical condition, establishing and adhering to reporting guidelines—that is, what works and under what conditions—is an essential component of the translational research process. Here, using the recently published World Health Organization mHealth Evaluation, Reporting and Assessment guidelines for evaluating mobile health applications, we review the methodological strengths and weaknesses of existing studies on smartphones and wearables for schizophrenia. While growing evidence supports the feasibility of using mobile tools in severe mental illness, most studies to date failed to adequately report accessibility, interoperability, costs, scalability, replicability, data security, usability testing, or compliance with national guidelines or regulatory statutes. Future research efforts addressing these specific gaps in the literature will help to advance our understanding and to realize the clinical potential of these new tools of psychiatry.
AGE-RELATED CHANGES IN CHOROIDAL VASCULAR DENSITY OF HEALTHY SUBJECTS BASED ON IMAGE BINARIZATION OF SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY
Authors: Ruiz-Medrano Jorge , Ruiz-Moreno José M. , Goud Abhilash , Vupparaboina Kiran Kumar , Jana Soumya , Chhablani Jay
Published: February 2017

Purpose:

To analyze the vascular density of the choroid in a healthy population using swept-source optical coherence tomography.

Methods:

A cross-sectional, noninterventional study. Inclusion criteria: best-corrected visual acuity between 20/20 and 20/25, spherical equivalent between ±3 diopters, no systemic or ocular diseases, and ages ranging between 3 and 85 years. One hundred and thirty-six eyes from 136 subjects were analyzed, 86 eyes (63.2%) were from male and 50 eyes (36.8%) from female subjects. The eyes were divided into different age groups to analyze the possible age-related changes. Twelve-millimeter horizontal, fovea-centered B-scans were used. Choroidal stroma and vessel area analysis involved automated segmentation and binarization using validated algorithms.

Results:

Mean age was 33.1 ± 24.5 years. Mean choroidal area was 0.5554 ± 0.1377 mm2. Mean stromal area was 0.2524 ± 0.0762 mm2, and mean vascular region area was 0.3029 ± 0.0893 mm2. The percentage of choroidal vascularity (vascular area/total area) was 54.40 ± 8.35%. Choroid area, vascular region, and percentage of choroidal vascular density were statistically higher in the <18-year-old group versus the >18-year-old group (P < 0.001). The stromal region was not different (P = 0.46). In the same way, choroid area, vascular region, and percentage of choroidal vascular density between the 5 age groups were statistically different (P < 0.001), showing larger figures in the 0 to 10-year-old group, but not stromal region (P = 0.71). There were no gender-related differences.

Conclusion:

The luminal area and the percentage of vascular/total area decrease with increasing age, while the stromal area remains stable.
Osteogenic Differentiation of MSCs on Fibronectin-Coated and nHA-Modified Scaffolds
Authors: Mohamadyar-Toupkanlou Farzaneh , Vasheghani-Farahani Ebrahim , Hanaee-Ahvaz Hana , Soleimani Masoud , Dodel Masumeh , Havasi Parvaneh , Ardeshirylajimi Abdolreza , Taherzadeh Elham Sadat
Published: February 2017

The increasing demand for biocompatible bone substitutes has made it a priority to tissue engineering and regenerative medicine scientists. Combination of minerals, growth factors, and extracellular matrix (ECM) proteins with nanofibrous scaffolds is a potential promising strategy for bone reconstruction and clinical applications. In this study, nanohydroxyapatite (nHA) was incorporated in electrospun nanofibrous polycaprolactone (PCL) scaffolds coated with fibronectin (Fn). The potential bone regeneration capacities of these scaffolds were evaluated in vitro and in vivo using mouse mesenchymal stem cells (mMSCs). The interconnected pores and proper mechanical characteristics of the fabricated electrospun PCL mats in combination with nHA and Fn provided suitable environment for cell attachment, proliferation, and enhanced osteogenic differentiation. The synergistic effect of Fn and nHA on the both in vitro and in vivo increase of calcium deposition was assessed by biochemical analysis. In addition, alkaline phosphatase (ALP) activity in nHA-incorporated PCL scaffold (PCL/nHA) and Fn-coated PCL/nHA (PCL/nHA/Fn) were significantly higher in comparison to the control group. Quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) analyses of important bone-related genes (ALP, osteocalcin, osteopontin, and Runx2) revealed that Fn has additive effect on promoting the osteogenic differentiation. The aforementioned results indicated that nanofibrous PCL/nHA scaffold coated with Fn is a promising candidate for bone-tissue engineering applications.
Is there still a role for hypothermia in neurocritical care?
Authors: Frank Florian , Broessner Gregor
Published: February 2017

Purpose of review

Therapeutic hypothermia (i.e. induced body core temperature ≈ 33–35°C) in neurological patients with cerebrovascular disease and traumatic brain injury is a controversially discussed issue in the literature. In this review, we have included the most recently published research covering the use of therapeutic hypothermia and targeted temperature management in neurologic diseases and translated the results into a clinical decision support for the professional healthcare community.

Recent findings

Recent findings from large multicenter studies investigating therapeutic hypothermia in patients with various acute neurologic diseases have revealed that although short-term and long-term temperature modulation on different temperature levels is feasible with the latest device technology, the effect on outcome is controversial.

There is overwhelming evidence that fever is an independent predictor of morbidity and mortality in patients with acute severe neurologic diseases. Although therapeutic hypothermia has been proven to be a potent neuroprotective measure acting on various levels in animal models, many questions such as optimal depth of target temperature, speed of rewarming, duration of cooling and management of side-effects accompanying therapeutic hypothermia are unresolved in human. Therefore, the application of therapeutic hypothermia outside of strictly supervised clinical trials must be carefully considered.
Diagnosis of a malignant adrenal mass: the role of urinary steroid metabolite profiling
Authors: Bancos Irina , Arlt Wiebke
Published: February 2017

Purpose of review

Adrenal masses are highly prevalent, found in 5% of the population. Differentiation of benign adrenocortical adenoma from adrenocortical carcinoma is currently hampered by the poor specificity and limited evidence base of imaging tests. This review summarizes the results of studies published to date on urine steroid metabolite profiling for distinguishing benign from malignant adrenal masses.

Recent findings

Three studies have described cohorts of at least 100 patients with adrenal tumors showing significant differences between urinary steroid metabolite excretions according to the nature of the underlying lesion, suggesting significant value of steroid metabolite profiling as a highly accurate diagnostic test.

Steroid profiling is emerging as a powerful novel diagnostic tool with a significant potential for improving the management for patients with adrenal tumors. Although the current studies use gas chromatography–mass spectrometry for proof of concept, widespread use of the method in routine clinical care will depend on transferring the approach to high-throughput tandem mass spectrometry platforms. The use of computational data analysis in conjunction with urine steroid metabolite profiling, that is, steroid metabolomics, adds accuracy and precision.
Clinical significance of 11-oxygenated androgens
Authors: Turcu Adina F. , Auchus Richard J.
Published: February 2017

Purpose of review

The adrenal gland is considered a source of weak androgens, such as dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione. Emerging evidence proposes a set of 11-oxygenated 19-carbon (11oxC19) adrenal-derived steroids as clinically important androgens. Such steroids include 11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone, and 11-ketotestosterone. The present review will discuss the synthesis, androgenic activity, and clinical implications of the 11oxC19 steroids.

Recent findings

The clinical relevance of the 11oxC19 steroids resides in two key characteristics: the synthesis of all 11oxC19 originates predominantly in the adrenal cortex, and 11-ketotestosterone and its 5α-reduced metabolite, 11-ketodihydrotestosterone are potent agonists of the human androgen receptor, similar to the classic androgens testosterone and dihydrotestosterone, respectively. Recent studies have demonstrated higher than normal circulating levels of 11oxC19 steroids in patients with 21-hydroxylase deficiency and in polycystic ovary syndrome. The 11oxC19 steroids are also thought to contribute to castration-resistant prostate cancer progression. In addition, the 11oxC19 steroids might have clinical implications in adrenarche and postmenopausal women.

Future prospective studies are needed to establish the clinical utility of the 11oxC19 steroids for individualized patient care. Preliminary data suggest that these biomarkers hold promise to improve the evaluation and management of androgen excess disorders.
Chronic Health Outcomes and Prescription Drug Copayments in Medicaid
Authors: Kostova Deliana , Fox Jared
Published: February 2017

Background:

Prescription drug copayments and cost-sharing have been linked to reductions in prescription drug use and expenditures. However, little is known about their effect on specific health outcomes.

Objective:

To evaluate the association between prescription drug copayments and uncontrolled hypertension, uncontrolled hypercholesterolemia, and prescription drug utilization among Medicaid beneficiaries with these conditions.

Subjects:

Select adults aged 20–64 from NHANES 1999–2012 in 18 states.

Measures:

Uncontrolled hypertension, uncontrolled hypercholesterolemia, and taking medication for each of these conditions.

Research Design:

A differencing regression model was used to evaluate health outcomes among Medicaid beneficiaries in 4 states that introduced copayments during the study period, relative to 2 comparison groups—Medicaid beneficiaries in 14 states unaffected by shifts in copayment policy, and a within-state counterfactual group of low-income adults not on Medicaid, while controlling for individual demographic factors and unobserved state-level characteristics.

Results:

Although uncontrolled hypertension and hypercholesterolemia declined among all low-income persons during the study period, the trend was less pronounced in Medicaid beneficiaries affected by copayments. After netting out concurrent trends in health outcomes of low-income persons unaffected by Medicaid copayment changes, we estimated that introduction of drug copayments in Medicaid was associated with an average rise in uncontrolled hypertension and uncontrolled hypercholesterolemia of 7.7 and 13.2 percentage points, respectively, and with reduced drug utilization for hypercholesterolemia.

Conclusions:

As Medicaid programs change in the years following the Affordable Care Act, prescription drug copayments may play a role as a lever for controlling hypertension and hypercholesterolemia at the population level.
Use of Sirolimus (Rapamycin) for Treatment of Cytopenias and Lymphoproliferation Linked to Autoimmune Lymphoproliferative Syndrome (ALPS). Two Case Reports
Authors: Cayrol Julie , Garrido Colino Carmen
Published: February 2017

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte apoptosis. Children present with chronic nonmalignant lymphadenopathy, hepatosplenomegaly, and autoimmune cytopenias. Recent advances show efficacy of treatment with immunosuppressive drugs. Sirolimus, an mammalian target of rapamycin inhibitor, improves autoimmune cytopenias and lymphoproliferation, with a safe profile. We present 2 patients, a 5-year-old girl and 15-year-old boy, diagnosed with ALPS with initial partial response to steroid treatment. Autoimmune cytopenias and lymphoproliferation then became refractory to treatment, with recurrence of symptoms. In both cases, treatment with sirolimus was started, with a rapid response, complete remission of cytopenias, and resolution of lymphoproliferation, with no significant adverse effects. Conclusion: sirolimus is an effective and safe drug for controlling children with cytopenias and lymphoproliferation linked to ALPS.
Defining Potentially Preventable Adverse Outcomes in Medicare Elective Lung Resections
Authors: Fry Donald E. , Pine Michael , Nedza Susan M. , Locke David G. , Reband Agnes M. , Pine Gregory
Published: February 2017

Objective

The aims of the study were to develop risk-adjusted models and apply them for comparisons of hospital performance to define potentially preventable adverse outcomes (OAs) in Medicare lung resection surgery.

Methods

The Medicare Limited Data Set for 2010–2012 was used to design predictive risk models for the four OAs of inpatient deaths, prolonged length-of-stay outliers, 90-day postdischarge deaths without hospital readmission, and 90-day readmissions after removal of unrelated readmission events. The probability of adverse events for each hospital was used to compute the hospital-specific standard deviation (SD) tailored to patient risk profiles. Observed versus predicted adverse events divided by the hospital-specific SD identified the z score for each hospital. Risk-adjusted OA rates were then computed for comparing hospital performance.

Results

A total of 39,405 lung resection patients from 739 hospitals had 768 inpatient deaths (1.9%), 3147 had prolonged LOS (8.0%), 514 had 90-day postdischarge deaths without readmission (1.3 %), and 7701 had one or more 90-day readmissions (19.5%); 10,924 patients (27.7%) had one or more of these OAs. Twenty-six hospitals were two SDs better than predicted and 34 hospitals were two SDs poorer than predicted. When evaluated by deciles of risk-adjusted OAs, the top performing decile of hospitals had rates of 14.3% and the poorest performing decile had OA rates of 41.0%.

Conclusions

The differences in risk-adjusted comparative outcomes between top- and suboptimal-performing hospitals in lung resections define the potential opportunities for care improvement. Identification of risk factors associated with OAs and causes for readmissions provides direction for specific areas of care redesign for improvement.
Lowering Perfusate Temperature From 37°C to 32°C Diminishes Function in a Porcine Model of Ex Vivo Kidney Perfusion
Authors: Adams Thomas D. , Patel Meeta , Hosgood Sarah A. , Nicholson Michael L.
Published: February 2017

Background

Ex vivo perfusion (EVP) is a novel method of preservation. However, optimal perfusion conditions remain undetermined. Reducing the temperature of the perfusate to subnormothermia may be beneficial during EVP and improve early graft function. The aim of this study was to investigate whether subnormothermia would influence the conditioning effect of EVP when compared with normothermic perfusion, and standard cold static storage (CS).

Methods

Porcine kidneys underwent static CS for 23 hours followed by 1 hour of EVP using leukocyte-depleted blood at a mean temperature of 32°C or 37°C. After this, kidneys were reperfused with whole autologous blood at 37°C for 3 hours to assess renal function and injury. These were compared with a control group that underwent 24 hours CS.

Results

During EVP, kidneys perfused at 37°C had a higher level of renal blood flow and oxygen consumption compared with EVP at 32°C (P = 0.001, 0.002). During reperfusion, 32°C EVP kidneys had lower creatinine clearance and urine output than control (P = 0.023, 0.011) and a higher fractional excretion of sodium, serum potassium, and serum aspartate transaminase than 37°C EVP kidneys (P = 0.01, 0.023, 0.009).

Conclusions

Tubular and renal functions were better preserved by a near-physiological temperature of 37°C during 1 hour of EVP, when compared to EVP at 32°C or cold storage.
Mobility as the purpose of postural control
Authors: Mouel Charlotte Le , Brette Romain
Published: February 2017

Counteracting the destabilizing force of gravity is usually considered to be the main purpose of postural control. However, from the consideration of the mechanical requirements for movement, we argue that posture is adjusted in view of providing impetus for movement. Thus, we show that the posture that is usually adopted in quiet standing in fact allows torque for potential movement. Moreover, when performing a movement - either voluntarily or in response to an external perturbation - we show that the postural adjustments are organized both spatially and temporally so as to provide the required torque for the movement. Thus, when movement is performed skillfully, the force of gravity is not counteracted but actually used to provide impetus to movement. This ability to move one’s weight so as to exploit the torque of gravity seems to be dependent on development and skill learning, and is impaired in aging.
A Spatially Localized Architecture for Fast and Modular Computation at the Molecular Scale
Authors: Chatterjee Gourab , Dalchau Neil , Muscat Richard A. , Phillips Andrew , Seelig Georg
Published: February 2017

Cells use spatial constraints to control and accelerate the flow of information in enzyme cascades and signaling networks. Here we show that spatial organization can be a similarly powerful design principle for overcoming limitations of speed and modularity in engineered molecular circuits. We create logic gates and signal transmission lines by spatially arranging reactive DNA hairpins on a DNA origami. Signal propagation is demonstrated across transmission lines of different lengths and orientations, and logic gates are modularly combined into circuits that establish the universality of our approach. Because reactions preferentially occur between neighbors, identical DNA hairpins can be reused across circuits. Colocalization of circuit elements decreases computation time from hours to minutes compared to circuits with diffusible components. Detailed computational models enable predictive circuit design. We anticipate that our approach will motivate the use of spatial constraints in molecular engineering more broadly, bringing embedded molecular control circuits closer to applications.
The recombinase protein is a torque sensitive molecular switch
Authors: Atwell Scott X. , Dupont Aurélie , Migliozzi Daniel , Viovy Jean-Louis , Cappello Giovanni
Published: February 2017

How a nano-searcher finds its nano-target isa general problem in non-equilibrium statistical physics. It becomesvital when the searcher is a damaged DNA fragmenttrying to find its counterpart on the intact homologous chromosome. If the two copies are paired, that intact homologous sequence serves as a template to reconstitute the damaged DNA sequence, enabling the cell to survive without genetic mutations. To succeed, the search must stop only when the perfect homology is found. The biological process that ensures such a genomic integrity is calledHomologous Recombinationand is promoted by the Recombinase proteins. In this article, we use torque-sensitive magnetic tweezers to measure the free-energy landscape of the human Recombinase hRad51 protein assembled a DNA fragment. Based on our measurements we model the hRad51/DNA complex as an out-of-equilibrium two-state system and provide a thermodynamical description of Homologous Recombination. With this dynamical two-state model, we suggest a mechanism by which the recombinase proteins discriminate between homologous and a nonhomologous sequences.
The Sequence of 1504 Mutants in the Model Rice Variety Kitaake Facilitates Rapid Functional Genomic Studies
Authors: Li Guotian , Jain Rashmi , Chern Mawsheng , Pham Nikki T. , Martin Joel A. , Wei Tong , Schackwitz Wendy S. , Lipzen Anna M. , Duong Phat Q. , Jones Kyle C. , Jiang Liangrong , Ruan Deling , Bauer Diane , Peng Yi , Barry Kerrie W. , Schmutz Jeremy , Ronald Pamela C.
Published: February 2017

The availability of a whole-genome sequenced mutant population and the cataloging of mutations of each line at a single-nucleotide resolution facilitates functional genomic analysis. To this end, we generated and sequenced a fast-neutron-induced mutant population in the model rice cultivar Kitaake (Oryza sativa L. ssp. japonica), which completes its life cycle in 9 weeks. We sequenced 1,504 mutant lines at 45-fold coverage and identified 91,513 mutations affecting 32,307 genes, 58% of all rice genes. We detected an average of 61 mutations per line. Mutation types include single base substitutions, deletions, insertions, inversions, translocations, and tandem duplications. We observed a high proportion of loss-of-function mutations. Using this mutant population, we identified an inversion affecting a single gene as the causative mutation for the short-grain phenotype in one mutant line with a small segregating population. This result reveals the usefulness of the resource for efficient identification of genes conferring specific phenotypes. To facilitate public access to this genetic resource, we established an open access database called KitBase that provides access to sequence data and seed stocks, enabling rapid functional genomic studies of rice.

One-sentence summary

We have sequenced 1,504 mutant lines generated in the short life cycle rice variety Kitaake (9 weeks) and established a publicly available database, enabling rapid functional genomic studies of rice.
TheXChemExplorergraphical workflow tool for routine or large-scale protein–ligand structure determination
Authors: Krojer Tobias , Talon Romain , Pearce Nicholas , Collins Patrick , Douangamath Alice , Brandao-Neto Jose , Dias Alexandre , Marsden Brian , von Delft Frank
Published: February 2017

XChemExplorer(XCE) is a data-management and workflow tool to support large-scale simultaneous analysis of protein–ligand complexes during structure-based ligand discovery (SBLD). The user interfaces of established crystallographic software packages such asCCP4 [Winnet al.(2011),Acta Cryst.D67, 235–242] orPHENIX[Adamset al.(2010),Acta Cryst.D66, 213–221] have entrenched the paradigm that a `project' is concerned with solving one structure. This does not hold for SBLD, where many almost identical structures need to be solved and analysed quickly in one batch of work. Functionality to track progress and annotate structures is essential.XCEprovides an intuitive graphical user interface which guides the user from data processing, initial map calculation, ligand identification and refinement up until data dissemination. It provides multiple entry points depending on the need of each project, enables batch processing of multiple data sets and records metadata, progress and annotations in an SQLite database.XCEis freely available and works on any Linux and Mac OS X system, and the only dependency is to have the latest version ofCCP4 installed. The design and usage of this tool are described here, and its usefulness is demonstrated in the context of fragment-screening campaigns at the Diamond Light Source. It is routinely used to analyse projects comprising 1000 data sets or more, and therefore scales well to even very large ligand-design projects.
N-{2-[2-(5-Methyl-1H-pyrazol-3-yl)acetamido]phenyl}benzamide monohydrate
Authors: Chkirate Karim , Mague Joel T. , Sebbar Nada Kheira , Ouzidan Younes , Essassi El Mokhtar
Published: February 2017

The asymmetric unit of the title compound, C19H18N4O2·H2O, comprises the U-shaped pyrazole derivative and a solvent water molecule. The molecular conformation is partly determined by an intramolecular N—H...O hydrogen bond. The crystal packing is directed by an extensive network of O—H...O, N—H...O, N—H...N and C—H...O hydrogen bonds together with C—H...π(ring) contacts that generate a three-dimensional network.
4-Methylanilinium 3-carboxy-4-hydroxybenzenesulfonate
Authors: Kalaiyarasi S. , Suresh S. , Akilan R. , Kumar R. Mohan , Chakkaravarthi G.
Published: February 2017

In the title molecular salt, C7H10N+·C7H5O6S−, the anion is deprotonated at the hydroxy O atom of the sulfonate group. In the anion, an intra-ionic O—H...O hydrogen bond generates anS(6) graph-set motif. In the crystal, the inter-ionic N—H...O and O—H...O hydrogen bonds generate anR24(12) ring-set motif, linking the anions and cations into an infinite three-dimensional framework. The crystal structure also features C—H...π and π–π [centroid-to-centroid distance = 3.5946 (11) Å] interactions.
(E)-1-(3-Bromophenyl)-3-(4-nitrophenyl)prop-2-en-1-one
Authors: Harini K. S. , Quah Ching Kheng , Chidan Kumar C. S. , Chandraju S. , Lokanath N. K. , Naveen S. , Warad Ismail
Published: February 2017

The title compound, C15H10BrNO3, is close to planar, as seen by the dihedral angle of 3.32 (17)° between the bromophenyl and nitrophenyl rings. In the crystal, molecules are linked by weak C—H...O hydrogen bonds, forming chains propagating along thec-axis direction.
Role of basic psychological need satisfaction in retaining talent: an investigation in the Indian context
Authors: Rathi Neerpal , Lee Kidong
Published: February 2017

Purpose

The purpose of this paper is to investigate the association of the satisfaction of the basic psychological needs for competence, autonomy, and relatedness with affective commitment and turnover intentions among retail employees in India while also examining the mediating role of job satisfaction in these associations.

Design/methodology/approach

Research hypotheses were tested using a cross-organizational sample of 244 employees. Existing, established scales were used to measure the research constructs.

Findings

The results of this study show that the satisfaction of the needs for competence, autonomy, and relatedness was positively related to affective commitment and negatively related to turnover intentions. Moreover, the results indicate that job satisfaction mediated the association of basic psychological need satisfaction with affective commitment and turnover intentions.

Practical implications

This study highlights the significant role of basic psychological need satisfaction in retaining employees in a rapidly growing economy that is experiencing very high employee turnover. The findings of this study may be helpful for organizational leaders in taking appropriate actions to create working conditions that facilitate the satisfaction of employees’ basic psychological needs. Satisfaction of employees’ basic psychological needs at work may help in retaining them in the current economic scenario, which is witnessing very high employee turnover.

Originality/value

This research tested the applicability of basic psychological need satisfaction to Eastern collectivistic cultures, particularly to India. Recent socio-economic changes, unique workforce demographics and a predominantly collectivistic culture make India distinct from western and European countries, where most of the earlier research on understanding the nature, antecedents, and consequences of basic psychological need satisfaction has been conducted. This research provides an important contribution not only to basic psychological need satisfaction theory, but also to international business literature.