bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nicotinamide riboside, a form of vitamin B3 and NAD+ precursor, relieves the nociceptive and aversive dimensions of paclitaxel-induced peripheral neuropathy in female rats
Authors: Hamity Marta V. , White Stephanie R. , Walder Roxanne Y. , Schmidt Mark S. , Brenner Charles , Hammond Donna L. 
Published: February 2017

Abstract
Injury to sensory afferents may contribute to the peripheral neuropathies that develop after administration of chemotherapeutic agents. Manipulations that increase levels of nicotinamide adenine dinucleotide (NAD+) can protect against neuronal injury. This study examined whether nicotinamide riboside (NR), a third form of vitamin B3 and precursor of NAD+, diminishes tactile hypersensitivity and place escape–avoidance behaviors in a rodent model of paclitaxel-induced peripheral neuropathy. Female Sprague-Dawley rats received 3 intravenous injections of 6.6 mg/kg paclitaxel over 5 days. Daily oral administration of 200 mg/kg NR beginning 7 days before paclitaxel treatment and continuing for another 24 days prevented the development of tactile hypersensitivity and blunted place escape–avoidance behaviors. These effects were sustained after a 2-week washout period. This dose of NR increased blood levels of NAD+ by 50%, did not interfere with the myelosuppressive effects of paclitaxel, and did not produce adverse locomotor effects. Treatment with 200 mg/kg NR for 3 weeks after paclitaxel reversed the well-established tactile hypersensitivity in a subset of rats and blunted escape–avoidance behaviors. Pretreatment with 100 mg/kg oral acetyl-l-carnitine (ALCAR) did not prevent paclitaxel-induced tactile hypersensitivity or blunt escape–avoidance behaviors. ALCAR by itself produced tactile hypersensitivity. These findings suggest that agents that increase NAD+, a critical cofactor for mitochondrial oxidative phosphorylation systems and cellular redox systems involved with fuel utilization and energy metabolism, represent a novel therapeutic approach for relief of chemotherapy-induced peripheral neuropathies. Because NR is a vitamin B3 precursor of NAD+ and a nutritional supplement, clinical tests of this hypothesis may be accelerated.
High Incidence and Prevalence of Drug-Related Movement Disorders in Young Patients With Psychotic Disorders
Authors: Mentzel Thierry Q. , Lieverse Ritsaert , Bloemen Oswald , Viechtbauer Wolfgang , van Harten Peter N. ,   The Genetic Risk and Outcome of Psychosis (GROUP) Investigators
Published: February 2017

Abstract

Background
Drug-related movement disorders (DRMDs) reduce quality of life and contribute to medication noncompliance of patients with psychotic disorders. Little is known about the epidemiology of DRMDs in relatively young patients a few years after onset of psychosis. This is an important period to study, as the impact of the antipsychotic treatment on the long-term potentiation of the neural pathways associated with psychotic disorders and DRMDs is still minimal. This study investigated the prevalence, incidence, persistence, and clinical correlates of DRMDs in patients during their first years after disease onset.

Methods
The Genetic Risk and Outcome of Psychosis study is a longitudinal study of 1120 relatively young patients with nonaffective psychosis and a mean age and illness duration of 27 and 4 years, respectively. The following drug-related movement disorders were assessed at baseline and at the 3-year follow-up: parkinsonism, akathisia, tardive dyskinesia, and tardive dystonia. We determined prevalence, incidence, and persistence and investigated clinical correlates at and over the baseline and follow-up assessment.

Results
Patients' mean age and illness duration at baseline were 27.1 and 4.3 years, respectively. In 4 patients, 1 developed a DRMD over the 3-year study period. Prevalence, incidence, and persistence rates were highest for parkinsonism (32%, 21%, and 53%) followed by akathisia (9%, 5%, and 17%) and tardive dyskinesia (4%, 3%, and 20%). Significant associations were found between DRMDs and the patients' age, IQ, and psychopathology.

Conclusions
The prevalence, persistence, and incidence of DRMDs in this sample were high despite the relatively young age, recent onset of the disorder, and treatment primarily with second-generation antipsychotics. These findings emphasize that screening, diagnosis, and treatment of DRMDs are still important.
Factors Associated With Peer Victimization Among Adolescents in Taiwan
Authors: Huang Hui-Wen , Chen Jyu-Lin , Wang Ruey-Hsia 
Published: February 2017

ABSTRACT

Background:
Adolescents who have experienced peer victimization face a higher risk of negative health outcomes. However, little is known about the factors that are associated with peer victimization among adolescents in Taiwan.

Purpose:
The aim of this study was to examine the factors related to peer victimization among Taiwanese adolescents.

Methods:
A cross-sectional design was employed. Three hundred seventy-seven adolescents aged 13–16 years from seven middle schools in southern Taiwan were recruited as participants. Validated, self-reported questionnaires were used to gather data on demographic characteristics, resilience, peer relationship, parental monitoring, school connectedness, social support, and peer victimization. Logistic regression analysis was used to examine the factors that were related to peer victimization.

Results:
About 17% (n = 64) of the participants experienced peer victimization during the previous 1-year period. Logistic regression analysis indicated that parental monitoring of daily life, school connectedness, and peer support were significant predictors of a reduced risk of peer victimization. The final model explained 23.1% of the total variance in less peer victimization and predicted 80.1% of peer victimization.

Conclusions/Implications for Practice:
School connectedness and peer support were identified as important factors facilitating the avoidance of peer victimization among adolescents in Taiwan. Healthcare providers and school personnel should consider school-based programs to improve school connectedness and to build an atmosphere of peer support to reduce peer victimization. Educating parents to monitor their adolescents’ daily activities is also encouraged in concert with these school-based programs.
High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection
Authors: Kessing Cari F. , Spudich Serena , Valcour Victor , Cartwright Pearline , Chalermchai Thep , Fletcher James L. K. , Takata Hiroshi , Nichols Carmen , Josey Benjamin J. , Slike Bonnie , Krebs Shelly J. , Sailsuta Napapon , Lerdlum Sukalaya , Jagodzinski Linda , Tipsuk Somporn , Suttichom Duanghathai , Rattanamanee Somprartthana , Zetterberg Henrik , Hellmuth Joanna , Phanuphak Nittaya , Robb Merlin L. , Michael Nelson L. , Ananworanich Jintanat , Trautmann Lydie ,   on behalf of the RV254/SEARCH 010/011/013 Study Teams
Published: February 2017

Background:Central nervous system (CNS) infiltration by CD8+T cells is associated with neuroinflammation in many neurodegenerative diseases, including HIV-associated dementia. However, the role of CD8+T cells in the CNS during acute HIV infection (AHI) is unknown.Methods:We analyzed the phenotype, gene expression, T cell receptor (TCR) repertoire, and HIV specificity of CD8+T cells in cerebrospinal fluid (CSF) of a unique cohort captured during the earliest stages of AHI (n = 26), chronic (n = 23), and uninfected (n = 8).Results:CSF CD8+T cells were elevated in AHI compared with uninfected controls. The frequency of activated CSF CD8+T cells positively correlated to CSF HIV RNA and to markers of CNS inflammation. In contrast, activated CSF CD8+T cells during chronic HIV infection were associated with markers of neurological injury and microglial activation. CSF CD8+T cells in AHI exhibited increased functional gene expression profiles associated with CD8+T cells effector function, proliferation, and TCR signaling, a unique restricted TCR Vbeta repertoire and contained HIV-specific CD8+T cells directed to unique HIV epitopes compared with the periphery.Conclusions:These results suggest that CSF CD8+T cells in AHI expanding in the CNS are functional and directed against HIV antigens. These cells could thus play a beneficial role protective of injury seen in chronic HIV infection if combination antiretroviral therapy is initiated early.
Longitudinal Assessment of Proximal Tubular Dysfunction in HIV Seropositive and Seronegative Persons: Correlates and Implications
Authors: Sheets Kerry M. , Atta Mohamed G. , Fine Derek M. , Zook Katie , Mcfall Allison M. , Estrella Michelle M. , Schwartz George J. , Lucas Gregory M. 
Published: February 2017

Background:Proximal tubular dysfunction (PTD) is common in HIV-positive persons and has been associated with tenofovir disoproxil fumarate (TDF). However, few studies have assessed the natural history PTD in HIV-positive and -negative individuals, or the association of PTD with the subsequent trajectory of directly measured glomerular filtration rate (mGFR).Methods:We followed 192 HIV-positive and 100 HIV-negative, nondiabetic participants for 3 years. We measured 3 PTD markers (normoglycemic glycosuria, fractional excretion of phosphorus, and tubular proteinuria) and mGFR (by iohexol disappearance from serum) annually. We used univariate and multivariate generalized estimating equation logistic regression to identify factors associated with PTD across all visits and linear mixed effects models to assess the association between baseline PTD and mGFR slope.Results:Compared with HIV-negative participants, HIV-positive persons that were not taking antiretroviral therapy were at increased risk of PTD (adjusted odds ratio 3.33; 95% confidence interval: 1.65 to 6.71), whereas those taking a TDF-based or a TDF-sparing regimen were not at significantly increased risk of PTD. Among HIV-positive participants, uncontrolled viremia was a strong correlate of PTD. Forty-nine of 55 (89%) participants with PTD at baseline had at least 1 subsequent visit without PTD. There was no association between baseline PTD and rate of decline in mGFR over time.Conclusions:Poorly controlled HIV may be a stronger risk factor for PTD than TDF use. The individual-level variability of the PTD markers over time was high, potentially limiting their usefulness for routine screening in unselected patients. Baseline PTD was not associated with subsequent mGFR slope.
Neutralizing and Targeting Properties of a New Set of α4β7-Specific Antibodies Are Influenced by Their Isotype
Authors: Girard Alexandre , Jelicic Katija , Van Ryk Don , Rochereau Nicolas , Cicala Claudia , Arthos James , Noailly Blandine , Genin Christian , Verrier Bernard , Laurant Stephanie , Razanajaoana-Doll Diane , Pin Jean-Jacques , Paul Stéphane 
Published: February 2017

Abstract:
The homing of lymphocytes to the mucosa is mainly controlled by α4β7 integrin, and it is amplified during gut chronic inflammation, as occurs with HIV and/or inflammatory bowel diseases. We designed and applied an improved immunization strategy based on an innovative selection process to isolate new α4β7+ lymphocyte–specific monoclonal antibodies that are able to prevent their migration into inflamed gut tissues and/or to counteract HIV infection in vitro. First, 5 monoclonal antibodies (1 IgA, 1 IgM, and 4 IgGs) were selected based on their capacity to recognize α4 or β7 homodimers and α4β7 heterodimers in transfected human cells. Their ability to block gp120/α4β7 or MAdCAM-1/α4β7 interactions was then measured in vitro with human T and B lymphocytes. In vitro, the anti-α4β7 IgA isotype was found to have the highest affinity for the α4β7 heterodimer, and it significantly reduced HIV replication in retinoic acid–treated α4β7hi CD4+ human T cells. This α4β7-specific IgA also displayed a high avidity for human and mouse α4β7+ lymphocytes in both mouse and human inflammatory colitis tissues. These new antibodies, and in particular those with mucosa-targeting isotypes such as IgA, could therefore be potential novel therapeutic tools for treating HIV and inflammatory bowel disease.
Vitamin A and D Deficiencies Associated With Incident Tuberculosis in HIV-Infected Patients Initiating Antiretroviral Therapy in Multinational Case-Cohort Study
Authors: Tenforde Mark W. , Yadav Ashish , Dowdy David W. , Gupte Nikhil , Shivakoti Rupak , Yang Wei-Teng , Mwelase Noluthando , Kanyama Cecilia , Pillay Sandy , Samaneka Wadzanai , Santos Breno , Poongulali Selvamuthu , Tripathy Srikanth , Riviere Cynthia , Berendes Sima , Lama Javier R. , Cardoso Sandra W. , Sugandhavesa Patcharaphan , Christian Parul , Semba Richard D. , Campbell Thomas B. , Gupta Amita ,   the NWCS319 and ACTG 5175 study team
Published: February 2017

Introduction:
Numerous micronutrients have immunomodulatory roles that may influence risk of tuberculosis (TB), but the association between baseline micronutrient deficiencies and incident TB after antiretroviral therapy (ART) initiation in HIV-infected individuals is not well characterized.

Methods:
We conducted a case-cohort study (n = 332) within a randomized trial comparing 3 ART regimens in 1571 HIV treatment-naive adults from 9 countries. A subcohort of 30 patients was randomly selected from each country (n = 270). Cases (n = 77; main cohort = 62, random subcohort = 15) included patients diagnosed with TB by 96 weeks post-ART initiation. We determined pretreatment concentrations of vitamin A, carotenoids, vitamin B6, vitamin B12, vitamin D, vitamin E, and selenium. We measured associations between pretreatment micronutrient deficiencies and incident TB using Breslow-weighted Cox regression models.

Results:
Median pretreatment CD4+ T-cell count was 170 cells/mm3; 47.3% were women; and 53.6% Black. In multivariable models after adjusting for age, sex, country, treatment arm, previous TB, baseline CD4 count, HIV viral load, body mass index, and C-reactive protein, pretreatment deficiency in vitamin A (adjusted hazard ratio, aHR 5.33, 95% confidence interval, CI: 1.54 to 18.43) and vitamin D (aHR 3.66, 95% CI: 1.16 to 11.51) were associated with TB post-ART.

Conclusions:
In a diverse cohort of HIV-infected adults from predominantly low- and middle-income countries, deficiencies in vitamin A and vitamin D at ART initiation were independently associated with increased risk of incident TB in the ensuing 96 weeks. Vitamin A and D may be important modifiable risk factors for TB in high-risk HIV-infected patients starting ART in resource-limited highly-TB-endemic settings.
Computed Tomography–Assisted Thoracoscopic Surgery
Authors: Kostrzewa Michael , Kara Kerim , Rathmann Nils , Tsagogiorgas Charalambos , Henzler Thomas , Schoenberg Stefan O. , Hohenberger Peter , Diehl Steffen J. , Roessner Eric D. 
Published: February 2017

Objectives
Minimally invasive resection of small, deep intrapulmonary lesions can be challenging due to the difficulty of localizing them during video-assisted thoracoscopic surgery (VATS). We report our preliminary results evaluating the feasibility of an image-guided, minimally invasive, 1-stop-shop approach for the resection of small, deep intrapulmonary lesions in a hybrid operating room (OR).

Materials and Methods
Fifteen patients (5 men, 10 women; mean age, 63 years) with a total of 16 solitary, deep intrapulmonary nodules of unknown malignant status were identified for intraoperative wire marking. Patients were placed on the operating table for resection by VATS. A marking wire was placed within the lesion under 3D laser and fluoroscopic guidance using a cone beam computed tomography system. Then, wedge resection by VATS was performed in the same setting without repositioning the patient.

Results
Complete resection with adequate safety margins was confirmed for all lesions. Marking wire placement facilitated resection in 15 of 16 lesions. Eleven lesions proved to be malignant, either primary or secondary; 5 were benign. Mean lesion size was 7.7 mm; mean distance to the pleural surface was 15.1 mm (mean lesion depth–diameter ratio, 2.2). Mean procedural time for marking wire placement was 35 minutes; mean VATS duration was 36 minutes.

Conclusions
Computed tomography–assisted thoracoscopic surgery is a new, safe, and effective procedure for minimally invasive resection of small, deeply localized intrapulmonary lesions. The benefits of computed tomography–assisted thoracoscopic surgery are 1. One-stop-shop procedure, 2. Lower risk for the patient (no patient relocation, no marking wire loss), and 3. No need to coordinate scheduling between the CT room and OR.
Time-Dependent Diffusion in Prostate Cancer
Authors: Lemberskiy Gregory , Rosenkrantz Andrew B. , Veraart Jelle , Taneja Samir S. , Novikov Dmitry S. , Fieremans Els 
Published: February 2017

Objective
Prior studies in prostate diffusion-weighted magnetic resonance imaging (MRI) have largely explored the impact of b-value and diffusion directions on estimated diffusion coefficient D. Here we suggest varying diffusion time, t, to study time-dependent D(t) in prostate cancer, thereby adding an extra dimension in the development of prostate cancer biomarkers.

Methods
Thirty-eight patients with peripheral zone prostate cancer underwent 3-T MRI using an external-array coil and a diffusion-weighted image sequence acquired for b = 0, as well as along 12 noncollinear gradient directions for b = 500 s/mm2 using stimulated echo acquisition mode (STEAM) diffusion tensor imaging (DTI). For this sequence, 6 diffusion times ranging from 20.8 to 350 milliseconds were acquired. Tumors were classified as low-grade (Gleason score [GS] 3 + 3; n = 11), intermediate-grade (GS 3 + 4; n = 16), and high-grade (GS ≥4 + 3; n = 11). Benign peripheral zone and transition zone were also studied.

Results
Apparent diffusion coefficient (ADC) D(t) decreased with increasing t in all zones of the prostate, though the rate of decay in D(t) was different between sampled zones. Analysis of variance and area under the curve analyses suggested better differentiation of tumor grades at shorter t. Fractional anisotropy (FA) increased with t for all regions of interest. On average, highest FA was observed within GS 3 + 3 tumors.

Conclusions
There is a measurable time dependence of ADC in prostate cancer, which is dependent on the underlying tissue and Gleason score. Therefore, there may be an optimal selection of t for prediction of tumor grade using ADC. Controlling t should allow ADC to achieve greater reproducibility between different sites and vendors. Intentionally varying t enables targeted exploration of D(t), a previously overlooked biophysical phenomenon in the prostate. Its further microstructural understanding and modeling may lead to novel diffusion-derived biomarkers.
Aggressive Surgical Management of Congenital Diaphragmatic Hernia: Worth the Effort?
Authors: Harting Matthew T. , Hollinger Laura , Tsao Kuojen , Putnam Luke R. , Wilson Jay M. , Hirschl Ronald B. , Skarsgard Erik D. , Tibboel Dick , Brindle Mary E. , Lally Pamela A. , Miller Charles C. , Lally Kevin P. 
Published: February 2017

Objective:
The objectives of this study were (i) to evaluate infants with congenital diaphragmatic hernia (CDH) that do not undergo repair, (ii) to identify nonrepair rate by institution, and (iii) to compare institutional outcomes based on nonrepair rate.

Background:
Approximately 20% of infants with CDH go unrepaired and the threshold to offer surgical repair is variable.

Methods:
Data were abstracted from a multicenter, prospectively collected database. Standard clinical variables, including repair (or nonrepair), and outcome were analyzed. Institutions were grouped based on volume and rate of nonrepair. Preoperative mortality predictors were identified using logistic regression, expected mortality for each center was calculated, and observed /expected (O/E) ratios were computed for center groups and compared by Kruskal-Wallis ANOVA.

Results:
A total of 3965 infants with CDH were identified and 691 infants (17.5%) were not repaired. Nonrepaired patients had lower Apgar scores (P < 0.05) and increased incidence of anomalies (P < 0.0001). Low-volume centers (“Lo”, n=44 total, < 10 CDH pts/yr) and high-volume centers (“Hi”, n = 21) had median nonrepair rates of 19.8% (range 0%–66.7%) and 16.7% (5.1%–38.5%), respectively. High-volume centers were further dichotomized by rate of nonrepair (HiLo = 5.1–16.7% and HiHi = 17.6–38.5%), leaving 3 groups: HiLo, HiHi, and Lo. Predictors of mortality were lower birth weight, lower Apgar scores, prenatal diagnosis, and presence of congenital anomalies. O/E ratios for mortality in the HiLo, HiHi, and Lo groups were 0.81, 0.94, and 1.21, respectively (P < 0.0001). For every 100 CDH patients, HiLo centers have 2.73 (2.4–3.1, 95% confidence interval) survivors beyond expectation.

Conclusions:
There are significant differences between repaired and nonrepaired CDH infants and significant center variation in rate of nonrepair exists. Aggressive surgical management, leading to a low rate of nonrepair, is associated with improved risk-adjusted mortality.
Modulating Portal Hemodynamics With Vascular Ring Allows Efficient Regeneration After Partial Hepatectomy in a Porcine Model
Authors: Bucur Petru O. , Bekheit Mohamed , Audebert Chloe , Othman Amnah , Hammad Seddik , Sebagh Mylene , Allard Marc-Antoine , Decante Benoît , Friebel Adrian , Miquelestorena-Standley Elodie , Drasdo Dirk , Hengstler Jan G. , Vignon-Clementel Irene E. , Vibert Eric 
Published: February 2017

Objective:
To investigate safety and efficacy of temporary portal hemodynamics modulation with a novel percutaneously adjustable vascular ring (MID-AVR) onto a porcine model of 75% hepatectomy.

Background:
Postoperative liver failure is a leading cause of mortality after major hepatectomy. Portal flow modulation is an increasingly accepted concept to prevent postoperative liver failure. Nonetheless, the current strategies have shortcomings.

Methods:
Resection was performed under hemodynamic monitoring in 17 large, white pigs allocated into 2 groups. Eight pigs had ring around the portal vein for 3 days with the aim of reducing changes in hemodynamics due to hepatectomy. Analysis of hemodynamics, laboratory, and histopathological parameters was performed.

Results:
Percutaneous inflation, deflation, and removal of the MID-AVR were safe. Two (25%) pigs in the MID-AVR group and 4 (45%) controls died before day 3 (P = NS). A moderate increase of portal flow rate per liver mass after resection was associated with better survival (P = 0.017). The portocaval pressure gradient was lower after hepatectomy in the MID-AVR group (P = 0.001). Postoperative serum bilirubin levels were lower in the MID-AVR group (P = 0.007 at day 5). In the MID-AVR group, the Ki67 index was significantly higher on day 3 (P = 0.043) and the architectural derangement was lower (P < 0.05). Morphometric quantification of the bile canaliculi revealed a significantly lower number of intersection branches (P < 0.05) and intersection nodes (P < 0.001) on day 7 compared with the preoperative specimen, in the control group. These differences were not found in the ring group.

Conclusions:
MID-AVR is safe for portal hemodynamics modulation. It might improve liver regeneration by protecting liver microarchitecture.