bluuebunny/crossref_metadata_2025_split huggingface dataset:
Withdrawal Assessment Tool-1 Monitoring in PICU: A Multicenter Study on Iatrogenic Withdrawal Syndrome
Authors: Amigoni Angela , Mondardini Maria Cristina , Vittadello Ilaria , Zaglia Federico , Rossetti Emanuele , Vitale Francesca , Ferrario Stefania , Savron Fabio , Coffaro Giancarlo , Brugnaro Luca , Amato Roberta , Wolfler Andrea , Franck Linda S. 
Published: February 2017

Objectives:
Withdrawal syndrome is an adverse reaction of analgesic and sedative therapy, with a reported occurrence rate between 17% and 57% in critically ill children. Although some factors related to the development of withdrawal syndrome have been identified, there is weak evidence for the effectiveness of preventive and therapeutic strategies. The main aim of this study was to evaluate the frequency of withdrawal syndrome in Italian PICUs, using a validated instrument. We also analyzed differences in patient characteristics, analgesic and sedative treatment, and patients’ outcome between patients with and without withdrawal syndrome.

Design:
Observational multicenter prospective study.

Setting:
Eight Italian PICUs belonging to the national PICU network Italian PICU network.

Patients:
One hundred thirteen patients, less than 18 years old, mechanically ventilated and treated with analgesic and sedative therapy for five or more days. They were admitted in PICU from November 2012 to May 2014.

Interventions:
Symptoms of withdrawal syndrome were monitored with Withdrawal Assessment Tool-1 scale.

Measurements and Main Results:
The occurrence rate of withdrawal syndrome was 64.6%. The following variables were significantly different between the patients who developed withdrawal syndrome and those who did not: type, duration, and cumulative dose of analgesic therapy; duration and cumulative dose of sedative therapy; clinical team judgment about analgesia and sedation’s difficulty; and duration of analgesic weaning, mechanical ventilation, and PICU stay. Multivariate logistic regression analysis revealed that patients receiving morphine as their primary analgesic were 83% less likely to develop withdrawal syndrome than those receiving fentanyl or remifentanil.

Conclusions:
Withdrawal syndrome was frequent in PICU patients, and patients with withdrawal syndrome had prolonged hospital treatment. We suggest adopting the lowest effective dose of analgesic and sedative drugs and frequent reevaluation of the need for continued use. Further studies are necessary to define common preventive and therapeutic strategies.
HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa
Authors: Kityo Cissy , Thompson Jennifer , Nankya Immaculate , Hoppe Anne , Ndashimye Emmanuel , Warambwa Colin , Mambule Ivan , van Oosterhout Joep J. , Wools-Kaloustian Kara , Bertagnolio Silvia , Easterbrook Philippa J. , Mugyenyi Peter , Walker A. Sarah , Paton Nicholas I. ,   for the Europe Africa Research Network for Evaluation of Second-line Therapy (EARNEST) Trial Team
Published: February 2017

Objective:
To determine drug resistance mutation (DRM) patterns in a large cohort of patients failing nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy regimens in programs without routine viral load (VL) monitoring and to examine intersubtype differences in DRMs.

Design:
Sequences from 787 adults/adolescents who failed an NNRTI-based first-line regimen in 13 clinics in Uganda, Kenya, Zimbabwe, and Malawi were analyzed. Multivariable logistic regression was used to determine the association between specific DRMs and Stanford intermediate-/high-level resistance and factors including REGA subtype, first-line antiretroviral therapy drugs, CD4, and VL at failure.

Results:
The median first-line treatment duration was 4 years (interquartile range 30–43 months); 42% of participants had VL ≥100,000 copies/mL and 63% participants had CD4 <100 cells/mm3. Viral subtype distribution was A1 (40%; Uganda and Kenya), C (31%; Zimbabwe and Malawi), and D (25%; Uganda and Kenya), and recombinant/unclassified (5%). In general, DRMs were more common in subtype-C than in subtype-A and/or subtype-D (nucleoside reverse transcriptase inhibitor mutations K65R and Q151M; NNRTI mutations E138A, V106M, Y181C, K101E, and H221Y). The presence of tenofovir resistance was similar between subtypes [P (adjusted) = 0.32], but resistance to zidovudine, abacavir, etravirine, or rilpivirine was more common in subtype-C than in subtype-D/subtype-A [P (adjusted) < 0.02].

Conclusions:
Non-B subtypes differ in DRMs at first-line failure, which impacts on residual nucleoside reverse transcriptase inhibitor and NNRTI susceptibility. In particular, higher rates of etravirine and rilpivirine resistance in subtype-C may limit their potential utility in salvage regimens.
Direct Targeting of Macrophages With Methylglyoxal-Bis-Guanylhydrazone Decreases SIV-Associated Cardiovascular Inflammation and Pathology
Authors: Walker Joshua A. , Miller Andrew D. , Burdo Tricia H. , McGrath Michael S. , Williams Kenneth C. 
Published: February 2017

Background:Despite effective combination antiretroviral therapy, HIV-infected individuals develop comorbidities, including cardiovascular disease, where activated macrophages play a key role. To date, few therapies target activated monocytes and macrophages.Methods:We evaluated a novel oral form of the polyamine biosynthesis inhibitor methylglyoxal-bis-guanylhydrazone (MGBG) on cardiovascular inflammation, carotid artery intima–media thickness (cIMT), and fibrosis in a simian immunodeficiency virus infection model of AIDS. Eleven simian immunodeficiency virus–infected animals received MGBG (30 mg/kg) once daily and 8 received a placebo control both beginning at 21 days postinfection (dpi). Animals were time sacrificed at 49 days post infection (dpi), when their matched placebo controls developed AIDS (63, 70, 77, 80), or at the study end-point (84 dpi). Aorta, carotid artery, and cardiac tissues were analyzed. Quantitative analyses of macrophage populations and T lymphocytes were done and correlated with cIMT and fibrosis.Results:MGBG treatment resulted in 2.19-fold (CD163+), 1.86-fold (CD68+), 2.31-fold (CD206+), and 2.12-fold (MAC387+) decreases in macrophages in carotid arteries and significant 2.07-fold (CD163+), 1.61-fold (CD68+), 1.95-fold (MAC387+), and 1.62-fold (CD206+) decreases in macrophages in cardiac tissues. cIMT (1.49-fold) and fibrosis (2.05-fold) also were significantly decreased with MGBG treatment. Numbers of macrophage and the degree of fibrosis in treated animals were similar to uninfected animals. A positive correlation between decreased macrophage in the carotid artery and cIMT, and cardiac macrophages and fibrosis was found.Conclusions:These data demonstrate that directly targeting macrophages with MGBG can reduce cardiovascular inflammation, cIMT, and fibrosis. They suggest that therapies targeting macrophages with HIV could be used in conjunction with combination antiretroviral therapy.
Impact of HIV and Atiretroviral Therapy on Neurocognitive Outcomes Among School-Aged Children
Authors: Brahmbhatt Heena , Boivin Michael , Ssempijja Victor , Kagaayi Joseph , Kigozi Godfrey , Serwadda David , Violari Avy , Gray Ronald H. 
Published: February 2017

Introduction:
The impact of HIV infection and antiretroviral therapy (ART) on neurocognitive outcomes among children aged 7–14 years was assessed. We hypothesized that ART would ameliorate neurocognitive sequelae of HIV infection.

Methods:
HIV-positive and HIV-negative mother–child pairs from the Rakai Community Cohort Study and ART clinics in Rakai, Uganda, were followed prospectively for 4 years. Exposures were stratified as: perinatally HIV infected, perinatally HIV exposed but uninfected, and HIV unexposed and uninfected. The Kaufman Assessment Battery for Children assessed sequential and simultaneous processing, learning, planning, knowledge, and fluid crystalized index for overall functioning. Multivariable generalized linear models estimated adjusted prevalence rate ratios by age.

Results:
Of the 370 mother–child pairs, 55% were HIV unexposed and uninfected, 7% were perinatally HIV exposed but uninfected, and 37.9% were perinatally HIV infected. Among HIV-infected children, longer duration of ART was associated with a significant improvement of sequential processing skills (adjusted prevalence rate ratios 25–36 months: 0.55, 95% confidence interval [CI]: 0.34 to 0.9; 37–48 months: 0.39, 95% CI: 0.2 to 0.76; 49+ months: 0.23, 95% CI: 0.1 to 0.54). Each additional year of schooling was associated with a 30%–40% decrease of impairment for all neurocognitive measures assessed. Healthier children (higher age-standardized height and weight) had improved sequential and simultaneous processing and overall fluid crystalized index.

Conclusions:
Sequential processing skills of working memory improved with prolonged ART, and increased duration of schooling was associated with a reduction of neurocognitive impairment. Early initiation and sustained use of ARTs and longer schooling are needed to reduce neurocognitive impairment among HIV-infected school-aged children.
Project Engage: Snowball Sampling and Direct Recruitment to Identify and Link Hard-to-Reach HIV-Infected Persons Who Are Out of Care
Authors: Wohl Amy Rock , Ludwig-Barron Natasha , Dierst-Davies Rhodri , Kulkarni Sonali , Bendetson Jesse , Jordan Wilbert , Bolan Robert , Smith Terry , Cunningham William , Pérez Mario J. 
Published: February 2017

Introduction:
Innovative strategies are needed to identify and link hard-to-find persons living with HIV (PLWH) who are out of care (OOC). Project Engage, a health department–based project in Los Angeles County, used a mixed-methods approach to locate and provide linkage for PLWH who have limited contact with HIV medical and nonmedical services.

Methods:
Incentivized social network recruitment (SNR) and direct recruitment (DR) was used to identify eligible OOC alters for a linkage intervention that included HIV clinic selection, appointment and transportation support, reminder calls/texts, and clinic navigation.

Results:
Between 2012 and 2015, 112 alters were identified using SNR (n = 74) and DR (n = 38). Most alters were male (80%), African American (38%), and gay (60%). Sizable percentages were homeless (78%), had engaged in sex work (32%) in the previous 6 months, had injected drugs (47%), were incarcerated in the previous 12 months (50%), and had only received HIV care during the previous 5 years while incarcerated (24%). SNR alters were more likely than DR alters to be African American, uninsured, unemployed, homeless, sex workers, injection drug users, recently incarcerated, and have unmet service needs. Alters linked to care within 3 (69%), 4–6 (5%), and 7–12 months (8%), and 72% were retained at 6–12 months. The percent virally suppressed increased (27% vs. 41%) and the median viral load decreased (P = 0.003) between linkage and follow-up at 6–12 months.

Discussion:
The alternative approaches presented were effective at locating marginalized HIV-positive persons who are OOC for linkage and retention. The SNR approach was most successful at identifying alters with serious social challenges and gaps in needed medical/ancillary services.
Preoperative Axillary Lymph Node Evaluation in Breast Cancer
Authors: Choi Hee Young , Park Minho , Seo Mirinae , Song Eunjee , Shin So Youn , Sohn Yu-Mee 
Published: February 2017

Abstract
Axillary lymph node (ALN) status is an important prognostic factor for overall breast cancer survival. In current clinical practice, ALN status is evaluated before surgery via multimodal imaging and physical examination. Mammography is typically suboptimal for complete ALN evaluation. Currently, ultrasonography is widely used to evaluate ALN status; nonetheless, results may vary according to operator. Ultrasonography is the primary imaging modality for evaluating ALN status. Other imaging modalities including contrast-enhanced magnetic resonance imaging, computed tomography, and positron emission tomography/computed tomography can play additional roles in axillary nodal staging.
The purpose of this article is (1) to review the strengths and weaknesses of current imaging modalities for nodal staging in breast cancer patients and (2) to discuss updated guidelines for ALN management with regard to preoperative ALN imaging.
Oral Polyphosphate Suppresses Bacterial Collagenase Production and Prevents Anastomotic Leak Due to Serratia marcescens and Pseudomonas aeruginosa
Authors: Hyoju Sanjiv K. , Klabbers Robin E. , Aaron Melissa , Krezalek Monika A. , Zaborin Alexander , Wiegerinck Mara , Hyman Neil H. , Zaborina Olga , Van Goor Harry , Alverdy John C. 
Published: February 2017

Objective:
The objective of this study was to determine the effect of polyphosphate on intestinal bacterial collagenase production and anastomotic leak in mice undergoing colon surgery.

Background:
We have previously shown that anastomotic leak can be caused by intestinal pathogens that produce collagenase. Because bacteria harbor sensory systems to detect the extracellular concentration of phosphate which controls their virulence, we tested whether local phosphate administration in the form of polyphosphate could attenuate pathogen virulence and prevent leak without affecting bacterial growth.

Methods:
Groups of mice underwent a colorectal anastomosis which was then exposed to collagenolytic strains of either Serratia marcescens or Pseudomonas aeruginosa via enema. Mice were then randomly assigned to drink water or water supplemented with a 6-mer of polyphosphate (PPi-6). All mice were sacrificed on postoperative day 10 and anastomoses assessed for leakage, the presence of collagenolytic bacteria, and anastomotic PPi-6 concentration.

Results:
PPi-6 markedly attenuated collagenase and biofilm production, and also swimming and swarming motility in both S. marcescens and P. aeruginosa while supporting their normal growth. Mice drinking PPi-6 demonstrated increased levels of PPi-6 and decreased colonization of S. marcescens and P. aeruginosa, and collagenase activity at anastomotic tissues. PPi-6 prevented anastomotic abscess formation and leak in mice after anastomotic exposure to S. marcescens and P. aeruginosa.

Conclusions:
Polyphosphate administration may be an alternative approach to prevent anastomotic leak induced by collagenolytic bacteria with the advantage of preserving the intestinal microbiome and its colonization resistance.
Detection of Donor-Derived Microparticles in the Peripheral Blood of a Hand Transplant Recipient During Rejection
Authors: Kim Joseph Y. , Kelesidis Theodoros , Yang Otto O. 
Published: February 2017

Background
Microparticles (MPs) are released from the plasma membrane of activated or dying cells and bear surface molecules from those cells. We examined whether donor-derived MPs in the peripheral blood of the recipient could serve as a marker of tissue damage due to rejection of a transplanted hand.

Methods
Platelet-free plasma from the recipient of the transplanted hand was analyzed for MPs bearing the donor-specific HLA molecule A*02 using flow cytometry. Rejection status of the transplanted hand was monitored by histopathology of skin punch biopsies.

Results
Donor-specific MPs expressing HLA A*02 were quantifiable in the peripheral blood of the recipient. Levels of these MPs increased with worsening rejection of the transplanted hand.

Conclusions
These findings demonstrate the ability to detect donor specific MPs through staining of graft cell-specific HLA and promote further investigation into the potential utility of flow cytometry for donor-derived MPs as a noninvasive tool to assess rejection in solid organ transplantation patients.
Development and Validation of the Kidney Transplant Understanding Tool (K-TUT)
Authors: Rosaasen Nicola , Taylor Jeff , Blackburn David , Mainra Rahul , Shoker Ahmed , Mansell Holly 
Published: February 2017

Background
Several educational interventions have been designed to improve patient knowledge before and after kidney transplantation. However, evaluation of such interventions has been difficult because validated instruments to measure knowledge-based outcomes in this population have not been developed.

Objective
To create a tool to measure patient knowledge of kidney transplantation and to evaluate its validity.

Methods
The Kidney Transplant Understanding Tool (K-TUT) was created using a stepwise iterative process. Experts in the field and transplant recipients were consulted to establish content validity. The K-TUT consists of 9 true/false and 13 multiple-choice questions, and scores are based on the number correct answers [YES/NO format] of 69 items. The questionnaire was piloted in a study that also measured health literacy (via the Short Test of Functional Health Literacy) in transplant candidates, whereas the main survey was mailed to transplant recipients. Test-retest was performed, and completed surveys were analyzed for internal consistency, construct validity, floor and ceiling effects, and reproducibility.

Results
Surveys were offered to 106 pretransplant patients and 235 in the posttransplant period, and response rates were 38.7% (41/106) and 63.4% (149/235), respectively. The mean corrected scores were 53.1 ± 8.5 (77%) and 56.2 ± 6.3 (81%), respectively. Test-retest was performed over 20% of both cohorts and percent agreement ranged between 70% and 100% in the pretransplant group and 66% and 100% in the posttransplant group. Cronbach α ranged from 0.794 to 0.875 in all cohorts indicating favorable internal consistency. Increased health literacy in the pretransplant group was significantly associated with increased knowledge (r = 0.52; P < 0.001), suggestive of construct validity, and the absence of floor and ceiling effects was positive. The majority of transplant recipients (98/148, 67%) believed the questionnaire adequately assessed transplant knowledge, about a quarter (36/148, 24.3%) were “unsure,” and 85% (126/148) agreed that no questions should be removed.

Conclusions
Although more study is warranted to further assess psychometric properties, the K-TUT appears to be a promising tool to measure transplant knowledge.
Evaluation of Carotid Ultrasonography Screening Among Kidney Transplant Candidates: A Single-Center, Retrospective Study
Authors: Rossitter Chad W. , Vigo Ronald B. , Gaber Ahmed Osama , Swan Joshua T. , Suki Wadi N. 
Published: February 2017

Background
Kidney transplant candidates undergo rigorous testing prior to clearance for transplantation. Because kidney transplant candidates may be at increased risk for carotid artery stenosis because of arteriosclerosis and atherosclerosis secondary to hypertension, vascular calcification, and diabetes, carotid ultrasound is often performed with the intent of preventing a cerebrovascular accident in the perioperative or posttransplant period. To our knowledge, there has not been a study investigating the utility of screening carotid ultrasonography in pretransplant candidates. The purpose of the present study was to investigate the yield of carotid ultrasonography in end-stage renal disease patients, at high risk for having clinically significant vascular disease evaluated at our center for kidney transplantation during the years 2009 to 2014.

Methods
Data for carotid ultrasound findings and risk factors for carotid artery disease were extracted from the medical records.

Results
A total of 882 patients were included in our study of which only 13 patients (1.47% of the cohort) had significant carotid artery stenosis (>70%) on ultrasound testing. Using multiple logistic regression on the outcome of carotid stenosis, congestive heart failure (adjusted odds ratio, 5.2), and peripheral vascular disease (adjusted odds ratio, 4.4) were positively associated with carotid stenosis.

Conclusions
The prevalence of significant carotid artery stenosis was only 1.47% in our cohort of kidney transplant candidates, and the routine use of carotid ultrasound testing in this population may not be an efficient use of clinical resources. Use of risk factors, such as congestive heart failure or peripheral vascular disease, may identify patients who are more likely to benefit from carotid ultrasonography screening.
Polarity sensitive probes for super resolution STED microscopy
Authors: Sezgin E , Schneider F , Zilles V , Garcia E , Waithe D , Klymchenko A S , Eggeling C 
Published: February 2017

AbstractThe lateral organization of molecules in the cellular plasma membrane plays an important role in cellular signaling. A critical parameter for membrane molecular organization is how the membrane lipids are packed (or ordered). Polarity sensitive dyes are powerful tools to characterize such lipid membrane order, employing for example confocal and two-photon microscopy. The investigation of potential lipid nanodomains, however, requires the use of super resolution microscopy. Here, we test the performance of the polarity sensitive membrane dyes Di-4-ANEPPDHQ, Di-4-AN(F)EPPTEA and NR12S in super resolution STED microscopy. Measurements on cell-derived membrane vesicles, in the plasma membrane of live cells, and on single virus particles show the high potential of these dyes for probing nanoscale membrane heterogeneity.
Investigating circadian rhythmicity in pain sensitivity using a neural circuit model for spinal cord processing of pain
Authors: Crodelle Jennifer A. , Piltz Sofia H. , Booth Victoria , Hagenauer Megan Hastings 
Published: February 2017

AbstractPrimary processing of painful stimulation occurs in the dorsal horn of the spinal cord. In this article, we introduce mathematical models of the neural circuitry in the dorsal horn responsible for processing nerve fiber inputs from noxious stimulation of peripheral tissues and generating the resultant pain signal. The differential equation models describe the average firing rates of excitatory and inhibitory interneuron populations, as well as the wide dynamic range (WDR) neurons whose output correlates with the pain signal. The temporal profile of inputs on the different afferent nerve fibers that signal noxious and innocuous stimulation and the excitability properties of the included neuronal populations are constrained by experimental results. We consider models for the spinal cord circuit in isolation and when top-down inputs from higher brain areas that modulate pain processing are included. We validate the models by replicating experimentally observed phenomena of A fiber inhibition of pain and wind-up. We then use the models to investigate mechanisms for the observed phase shift in circadian rhythmicity of pain that occurs with neuropathic pain conditions. Our results suggest that changes in neuropathic pain rhythmicity can occur through dysregulation of inhibition within the dorsal horn circuit.