bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recreational concentrations of alcohol enhance synaptic inhibition of cerebellar unipolar brush cells via pre- and postsynaptic mechanisms
Authors: Richardson Ben D. , Rossi David J. 
Published: April 2017

Variation in cerebellar sensitivity to alcohol/ethanol (EtOH) is a heritable trait associated with alcohol use disorder in humans and high EtOH consumption in rodents, but the underlying mechanisms are poorly understood. A recently identified cellular substrate of cerebellar sensitivity to EtOH, the GABAergic system of cerebellar granule cells (GCs), shows divergent responses to EtOH paralleling EtOH consumption and motor impairment phenotype. Although GCs are the dominant afferent integrator in the cerebellum, such integration is shared by unipolar brush cells (UBCs) in vestibulocerebellar lobes. UBCs receive both GABAergic and glycinergic inhibition, both of which may mediate diverse neurological effects of EtOH. Therefore, the impact of recreational concentrations of EtOH (~10–50 mM) on GABAAreceptor (GABAAR)- and glycine receptor (GlyR)-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) of UBCs in cerebellar slices was characterized. Sprague-Dawley rat (SDR) UBCs exhibited sIPSCs mediated by GABAARs, GlyRs, or both, and EtOH dose-dependently (10, 26, 52 mM) increased their frequency and amplitude. EtOH increased the frequency of glycinergic and GABAergic sIPSCs and selectively enhanced the amplitude of glycinergic sIPSCs. This GlyR-specific enhancement of sIPSC amplitude resulted from EtOH actions at presynaptic Golgi cells and via protein kinase C-dependent direct actions on postsynaptic GlyRs. The magnitude of EtOH-induced increases in UBC sIPSC activity varied across SDRs and two lines of mice, in parallel with their respective alcohol consumption/motor impairment phenotypes. These data indicate that Golgi cell-to-UBC inhibitory synapses are targets of EtOH, which acts at pre- and postsynaptic sites, via Golgi cell excitation and direct GlyR enhancement.NEW & NOTEWORTHY Genetic variability in cerebellar alcohol/ethanol sensitivity (ethanol-induced ataxia) predicts ethanol consumption phenotype in rodents and humans, but the cellular and molecular mechanisms underlying genetic differences are largely unknown. Here it is demonstrated that recreational concentrations of alcohol (10–30 mM) enhance glycinergic and GABAergic inhibition of unipolar brush cells through increases in glycine/GABA release and postsynaptic enhancement of glycine receptor-mediated responses. Ethanol effects varied across rodent genotypes parallel to ethanol consumption and motor sensitivity phenotype.
Mechanism of plasmin generation by S100A10
Authors: Miller Victoria A. , Madureira Patricia A. , Kamaludin Ain Adilliah , Komar Jeffrey , Sharma Vandna , Sahni Girish , Thelwell Craig , Longstaff Colin , Waisman David M. 
Published: April 2017

SummaryPlasminogen (Pg) is cleaved to form plasmin by the action of specific plasminogen activators such as the tissue plasminogen activator (tPA). Although the interaction of tPA and Pg with the surface of the fibrin clot has been well characterised, their interaction with cell surface Pg receptors is poorly understood. S100A10 is a cell surface Pg receptor that plays a key role in cellular plasmin generation. In the present report, we have utilised domain-switched/deleted variants of tPA, truncated plasminogen variants and S100A10 site-directed mutant proteins to define the regions responsible for S100A10-dependent plasmin generation. In contrast to the established role of the finger domain of tPA in fibrin-stimulated plasmin generation, we show that the kringle-2 domain of tPA plays a key role in S100A10-dependent plasmin generation. The kringle-1 domain of plasminogen, indispensable for fibrin-binding, is also critical for S100A10-dependent plasmin generation. S100A10 retains activity after substitution or deletion of the carboxyl-terminal lysine suggesting that internal lysine residues contribute to its plasmin generating activity. These studies define a new paradigm for plasminogen activation by the plasminogen receptor, S100A10.
Determinants of Acute and Late Pulmonary Vein Reconnection in Contact Force–Guided Pulmonary Vein Isolation
Authors: El Haddad Milad , Taghji Philippe , Phlips Thomas , Wolf Michael , Demolder Anthony , Choudhury Rajin , Knecht Sébastien , Vandekerckhove Yves , Tavernier Rene , Nakagawa Hiroshi , Duytschaever Mattias 
Published: April 2017

Background—
Pulmonary vein reconnection (PVR) still determines recurrences of atrial fibrillation after contact force (CF)–guided pulmonary vein isolation. We studied whether acute PVR (adenosine and waiting time) and late PVR (at repeat) are explained by incomplete transmurality and contiguity within the deployed radiofrequency circle.

Methods and Results—

We analyzed 42 CF-guided ipsilateral pulmonary vein isolation procedures. For each radiofrequency tag within the circle, we collected data reflecting lesion depth (time of application, power, impedance drop [Δ-Imp], CF, force–time integral [FTI], and ablation index [AI]) and contiguity (automated interlesion distance [ILD]). Ablation line contiguity index (ALCI) was developed as a novel automated algorithm combining depth and contiguity into one single criterion. Each circle was subdivided into 10 segments. For each segment, we determined its weakest link by annotating time
min
, power
min
, Δ-Imp
min
, CF
min
, FTI
min
, AI
min
, ILD
max
, and ALCI
min
. Compared with segments without PVR (n=758), PVR segments (n=44) were characterized by lower Δ-Imp
min
(4.8 versus 7.4 Ω), CF
min
(8.5 versus 11.8 g), FTI
min
(351 versus 473 gs), AI
min
(367 versus 408 arbitrary unit [au]), and higher ILD
max
(6.8 versus 5.5 mm). ALCI
min
was significantly lower in segments with PVR (74% versus 104%;
P
<0.001) and was associated with the highest accuracy to predict durable segments (area under the curve=0.73).

Conclusions—
In CF-guided pulmonary vein isolation, PVR is explained by lack of both lesion depth and contiguity within the deployed radiofrequency circle. ALCI, a novel measure combining contiguity and depth, is the most accurate predictor for durable segments. By avoiding weak links in the ablation chain, ALCI-guided ablation is expected to improve success rate of point-by-point radiofrequency ablation.
The Sensitivity of Orographic Precipitation to Flow Direction: An Idealized Modeling Approach
Authors: Picard Lee , Mass Clifford 
Published: April 2017

Abstract
A major question regarding orographic precipitation is its sensitivity to flow direction, with some research suggesting substantial sensitivity. To examine this issue, this paper describes a full physics model with realistic three-dimensional terrain that is forced by a single input sounding. This system is used to investigate the sensitivity of orographic precipitation to wind direction over the Pacific Northwest for conditions approximating an atmospheric river. The model results show considerable modulation of regional precipitation as flow direction changes, with results for four Washington State river drainages agreeing well with previous observational studies. It is shown that precipitation amounts over such drainages can vary substantially with very small changes in the direction of the incoming flow. To explore the origin of directional sensitivity of precipitation over the Olympic Mountains of western Washington State, additional experiments were carried out using modified terrain fields with smoothed or idealized Olympic Mountains, or with nearby orography removed. These simulations suggest that the sensitivity of Olympic Mountain precipitation to wind direction is more strongly modulated by the presence of surrounding orography than by the specific geometry of the Olympic Mountains.
Use of FDG PET/CT in identification of bone marrow involvement in diffuse large B cell lymphoma and follicular lymphoma: comparison with iliac crest bone marrow biopsy
Authors: Teagle Alexandra R , Barton Hannah , Charles-Edwards Elizabeth , Dizdarevic Sabina , Chevassut Timothy 
Published: April 2017

Background Non-Hodgkin’s lymphoma (NHL) accounts for around 4% of new cancer cases annually. Bone marrow involvement is important for staging and management. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is used increasingly to identify this, in addition to bone marrow biopsy (BMB), which is seen as “gold” reference standard. Purpose To compare determination of bone marrow involvement by FDG PET/CT against BMB in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Material and Methods This was a retrospective study of patients with histologically confirmed NHL at a single UK cancer center undergoing pre-treatment FDG PET/CT and BMB between June 2010 and February 2013. Information was collected from patient notes, cancer registry, histological and imaging reports. Diagnostic accuracy of FDG PET/CT was determined, compared to BMB as the reference standard. Results Twenty-four patients with DLBCL and 12 with FL were included. Five DLBCL patients had bone marrow involvement on PET/CT; all were confirmed on BMB. Three FL patients had marrow involvement on PET/CT but not on BMB; one FL patient had positive BMB but negative PET/CT. Using BMB as the reference standard, the sensitivity and specificity of FDG PET/CT for detecting bone marrow involvement in DLBCL were 100% and 100%, respectively, and in FL were 0% and 72.7%, respectively. Conclusion FDG PET/CT is accurate for detection of bone marrow involvement in newly diagnosed DLBCL, but not FL. In DLBCL, positive FDG PET/CT may negate the need for routine BMB, although BMB in addition or combination may be appropriate if this would influence management or prognosis.
Randomized controlled trial of a home-based palliative approach for people with severe multiple sclerosis
Authors: Solari Alessandra , Giordano Andrea , Patti Francesco , Grasso Maria Grazia , Confalonieri Paolo , Palmisano Lucia , Ponzio Michela , Borreani Claudia , Rosato Rosalba , Veronese Simone , Zaratin Paola , Battaglia Mario Alberto ,   on behalf of the PeNSAMI Project
Published: April 2017

Background: Evidence on the efficacy of palliative care in persons with severe multiple sclerosis (MS) is scarce. Objective: To assess the efficacy of a home-based palliative approach (HPA) for adults with severe MS and their carers. Methods: Adults with severe MS-carer dyads were assigned (2:1 ratio) to either HPA or usual care (UC). At each center, a multi-professional team delivered the 6-month intervention. A blind examiner assessed dyads at baseline, 3 months, and 6 months. Primary outcome measures were Palliative care Outcome Scale-Symptoms-MS (POS-S-MS) and Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW, not assessed in severely cognitively compromised patients). Results: Of 78 dyads randomized, 76 (50 HPA, 26 UC) were analyzed. Symptom burden (POS-S-MS) significantly reduced in HPA group compared to UC ( p = 0.047). Effect size was 0.20 at 3 months and 0.32 at 6 months, and statistical significance was borderline in per-protocol analysis ( p = 0.062). Changes in SEIQoL-DW index did not differ in the two groups, as changes in secondary patient and carer outcomes. Conclusion: HPA slightly reduced symptoms burden. We found no evidence of HPA efficacy on patient quality of life and on secondary outcomes.
Cardiorespiratory fitness, cognition and brain structure after TIA or minor ischemic stroke
Authors: Boss H Myrthe , Van Schaik Sander M , Witkamp Theo D , Geerlings Mirjam I , Weinstein Henry C , Van den Berg-Vos Renske M 
Published: April 2017

Background It is not known whether cardiorespiratory fitness is associated with better cognitive performance and brain structure in patients with a TIA or minor ischemic stroke. Aims To examine the association between cardiorespiratory fitness, cognition and brain structure in patients with a TIA and minor stroke. Methods The study population consisted of patients with a TIA or minor stroke with a baseline measurement of the peak oxygen consumption, a MRI scan of brain and neuropsychological assessment. Composite z-scores were calculated for the cognitive domains attention, memory and executive functioning. White matter hyperintensities, microbleeds and lacunes were rated visually. The mean apparent diffusion coefficient was measured in regions of interest in frontal and occipital white matter and in the centrum semiovale as a marker of white matter structure. Normalized brain volumes were estimated by use of Statistical Parametric Mapping. Results In 84 included patients, linear regression analysis adjusted for age, sex and education showed that a higher peak oxygen consumption was associated with higher cognitive z-scores, a larger grey matter volume (B = 0.15 (95% CI 0.05; 0.26)) and a lower mean apparent diffusion coefficient (B = −.004 (95% CI −.007; −.001)). We found no association between the peak oxygen consumption and severe white matter hyperintensities, microbleeds, lacunes and total brain volume. Conclusions These data suggest that cardiorespiratory fitness is associated with better cognitive performance, greater grey matter volume and greater integrity of the white matter in patients with a TIA or minor ischemic stroke. Further prospective trials are necessary to define the effect of cardiorespiratory fitness on cognition and brain structure in patients with TIA or minor stroke.
Major depressive disorder with religious struggle and completed suicide after hair transplantation
Authors: Ceylan Mehmet Emin , Önen Ünsalver Barış , Evrensel Alper 
Published: April 2017

Objectives: Psychological outcomes of aesthetic surgical procedures like hair transplantation are mostly positive including decreased anxiety, depression and social phobia and increased general well-being, self-efficacy and self-esteem. However, some patients may suffer from post-surgical depression and post-surgical increased suicide rates have been reported for breast augmentation patients. Difficulty adapting to the new image, unfulfilled psychological needs expected to be met by the surgery, side effects of the surgery like tissue swelling or bruising, uncontrolled pain, presence of body dysmorphic disorder and previous history of mood disorder may be some of the risk factors for post-surgical depression. Methods: Here, we present a case without prior psychiatric history who developed major depressive disorder after hair transplantation and died of suicide. Results: He started experiencing religious struggle related to his decision about the hair transplant which he interpreted as acting against God’s will. While religious involvement has been reported to be a protective factor against depression, spiritual struggle, which includes religious guilt, has been described as an important risk factor for depression, hopelessness and suicidality which might explain the severity of depression in our patient. Conclusions: This case highlights the importance of a detailed psychiatric evaluation and exploration of religious concerns of any patient before any type of aesthetic surgery. Major depressive disorder is a treatable condition; however, mild depression can go unnoticed. Religious belief and related religious practices affect an individual’s personal health attitudes; therefore, we think that every physician is needed to explore the religious concerns of any patient during any medical examination or surgical procedure. Relevant religious authorities should be consulted when necessary.
Risk and Cost of Reoperation After Single-Level Posterior Cervical Foraminotomy: A Large Database Study
Authors: Sayari Arash J. , Tuchman Alexander , Cohen Jeremiah R. , Hsieh Patrick C. , Buser Zorica , Wang Jeffrey C. 
Published: April 2017

Study Design: Retrospective cohort study. Objective: To examine the risk of undergoing another cervical spine surgery after single-level posterior cervical foraminotomy (PCF) and analyze the costs of such reoperations. Methods: Using the PearlDiver database, we created database algorithms to identify cohorts of patients who underwent single-level PCF and also had various reoperations of interest, within 1, 2, and 4 years of follow-up. We also identified the per-patient average charge (PPAC) for each reoperation cohort. Results: In the Medicare cohort, the incidence of any reoperation was 8.3%, 9.8%, and 10.5% within 1, 2, and 4 years of follow-up, respectively. The PPAC was $8520 for the initial PCF procedure. When a second cervical surgery was performed, the PPAC was $70 349 for anterior fusion, $15 760 for posterior decompression alone, and $77 976 for posterior decompression and fusion. In the UnitedHealth cohort, the incidence of any reoperation was 13.6%, 16.7%, and 17.0% within 1, 2, and 4 years of follow-up, respectively. Conclusions: The overall incidence of another cervical spine operation was slightly higher in the Medicare population to that in previous literature, but much higher in the UnitedHealth population. The most common reoperation after PCF varied between the Medicare and UnitedHealth datasets, and costs varied widely based on the procedure performed. This study provides pertinent information that surgeons can use to discuss the risk of reoperation with their patients.
The Burden of Spine Fractures in India
Authors: Aleem Ilyas S. , DeMarco Dylan , Drew Brian , Sancheti Parag , Shetty Vijay , Dhillon Mandeep , Foote Clary J. , Bhandari Mohit 
Published: April 2017

Study Design: Prospective cohort study. Objectives: The objectives of this study were (1) to determine the characteristics of patients sustaining spinal trauma in India and (2) to explore the association between patient or injury characteristics and outcomes after spinal trauma. Methods: In affiliation with the ongoing INternational ORthopaedic MUlticentre Study (INORMUS), 192 patients with spinal injuries were recruited during an 8-week period (November 2011 to June 2012) from 14 hospitals in India and followed for 30-days. The primary outcome was a composite of mortality, complications, and reoperation. This was regressed on a set of 13 predictors in a multiple logistic regression model. Results: Most patients were middle-aged (mean age = 51.0 years; median age = 55.5 years; range = 18.0 to 72.0 years), male (60.4%), injured from falls (72.4%), and treated in a private setting (59.9%). Fractures in the lumbar region (51.0%) were most common, followed by thoracic (30.7%) and cervical (18.2%). More than 1 in 5 (21.6%) patients experienced a treatment delay greater than 24 hours, and 36.5% arrived by ambulance. Thirty-day mortality and complication rates were 2.6% and 10.0%, respectively. Care in the public hospital system (odds ratio [OR] = 6.7, 95% CI = 1.1-41.6), chest injury (OR = 11.1, 95% CI = 1.8-66.9), and surgical intervention (OR = 4.8, 95% CI = 1.2-19.6) were independent predictors of major complications. Conclusions: Treatment in the public health care system, increased severity of injury, and surgical intervention were associated with increased risk of major complications following spinal trauma. The need for a large-scale, prospective, multicenter study taking into account spinal stability and neurologic status is feasible and warranted.
Long-term effects of severe acute malnutrition on lung function in Malawian children: a cohort study
Authors: Lelijveld Natasha , Kerac Marko , Seal Andrew , Chimwezi Emmanuel , Wells Jonathan C. , Heyderman Robert S. , Nyirenda Moffat J. , Stocks Janet , Kirkby Jane 
Published: April 2017

Early nutritional insults may increase risk of adult lung disease. We aimed to quantify the impact of severe acute malnutrition (SAM) on spirometric outcomes 7 years post-treatment and explore predictors of impaired lung function.Spirometry and pulse oximetry were assessed in 237 Malawian children (median age: 9.3 years) who had been treated for SAM and compared with sibling and age/sex-matched community controls. Spirometry results were expressed as z-scores based on Global Lung Function Initiative reference data for the African–American population.Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were low in all groups (mean FEV1z-score: −0.47 for cases, −0.48 for siblings, −0.34 for community controls; mean FVC z-score: −0.32, −0.38, and −0.15 respectively). There were no differences in spirometric or oximetry outcomes between SAM survivors and controls. Leg length was shorter in SAM survivors but inter-group sitting heights were similar. HIV positive status or female sex was associated with poorer FEV1, by 0.55 and 0.31 z-scores, respectively.SAM in early childhood was not associated with subsequent reduced lung function compared to local controls. Preservation of sitting height and compromised leg length suggest “thrifty” or “lung-sparing” growth. Female sex and HIV positive status were identified as potentially high-risk groups.
Unique Barriers to Care and Outcomes of Pediatric Acute Lymphoblastic Leukemia Treatment in Gaza City, Occupied Palestinian Territory
Authors: Mills David , Abushanab Salah , Elhaloul Awad , El Nuweiry Heiam , Shaaban Mohamad Abu , Salman Zeena 
Published: April 2017

Abstract 56 Background: Although cure rates for childhood acute lymphoblastic leukemia (ALL) in developed countries surpass 90%, 1 rates in resource-limited countries, to which barriers to care contribute, are as low as 35%. 2 In the Gaza Strip—a lower middle-income economy 3 —children face unique barriers to ALL treatment. We undertook this work to describe barriers to care for patients with pediatric ALL as well as treatment outcomes at the only pediatric oncology ward in the Gaza Strip. Methods: A comprehensive review of 131 charts was performed. Eighty-four patients met an inclusion criterion of diagnosis of ALL by bone marrow evaluation between 2010 and 2015 in children age < 12 years. Results: Eighty-four patients with ALL (T cell, 12 [14%]; pre-B cell, 72 [86%]) were stratified as being at standard (n = 64; 76%), intermediate (n = 3; 4%), or high risk (HR; n = 17; 20%). Of patients, 100% were referred to an international hospital for definitive diagnosis and induction therapy; 52% required at least one additional international hospital referral as a result of chemotherapy shortages (n = 8), methotrexate monitoring (n = 28), induction failure (n = 5), or relapse (n = 5). Three-year overall survival was 93% (CI, 82% to 97%), event free survival (EFS) was 80% (CI, 66% to 89%; events: death, induction failure, and relapse), and EFS of HR patients was 23% (CI, 4% to 51%). Conclusion: HR patients had extremely poor outcomes, even compared with those in other resource-limited settings. 4 Overall, patients experienced relatively high overall survival and EFS, which was likely confounded by exclusion of HR patients age > 12 years because of low pediatric age cutoff and missing charts. Barriers to care, including limited freedom of movement, contribute to delays in treatment, perhaps affecting outcomes of the HR cohort. An NGL–Ministry of Health partnership is addressing these barriers 5 by providing resources to decrease referrals. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from the authors.