bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential impact of psychological and psychophysical stress on low back pain in mice
Authors: La Porta Carmen , Tappe-Theodor Anke 
Published: March 2020

Abstract
Low back pain (LBP) is a highly prevalent and disabling condition whose initiating factors are poorly understood. It is known that psychological and physical stress is associated with LBP but the causal relationship, mechanisms, and mediators have not been elucidated, and a preclinical model enabling the investigation of causality and thereby critically contributing to clinical translation does not exist. In this study, we first established and characterized a myofascial LBP model in mice based on nerve growth factor (NGF) injection into the low back muscles. Second, we investigated the effect of 2 different stress paradigms on this mouse LBP model by applying the chronic unpredictable stress and vertical chronic restraint stress (vCRS) paradigms, to mimic psychological and psychophysical stress, respectively. In these studies, we combined longitudinal behavioral tests with gene and protein expression analysis in the muscle, dorsal root ganglia, and spinal cord. Nerve growth factor-induced LBP was characterized by long-lasting local and plantar mechanical hypersensitivity, cold hyperalgesia, decreased grip strength and wheel running activity, and time-dependent changes of neuropeptide and glial markers in the spinal cord. Interestingly, the exposure to chronic unpredictable stress slightly worsened pain behavior, whereas vCRS primed and highly aggravated pain in this LBP model, by causing per se the intramuscular upregulation of endogenous NGF and increased spinal astrocyte expression. Our mouse model, particularly the combination of NGF injection and vCRS, suggests that similar mechanisms are important in nonspecific LBP and might help to investigate certain aspects of stress-induced exacerbation of pain.
Radiation enteritis: from diagnosis to management
Authors: Hale Melissa Fay 
Published: March 2020

Purpose of review
As cancer treatments improve more patients than ever are living for longer with the side effects of these treatments. Radiation enteritis is a heterogenous condition with significant morbidity. The present review aims to provide a broad overview of the condition with particular attention to the diagnosis and management of the condition.

Recent findings
Radiation enteritis appears to be more prevalent than originally thought because of patient underreporting and a lack of clinician awareness. Patient-related and treatment-related risk factors have now been identified and should be modified where possible. Medical and surgical factors have been explored, but manipulation of the gut microbiota offers one of the most exciting recent developments in disease prevention. Diagnosis and treatment are best approached in a systematic fashion with particular attention to the exclusion of recurrent malignancy and other gastrointestinal conditions. Surgery and endoscopy both offer opportunities for management of the complications of radiation enteritis. Experimental therapies offer hope for future management of radiation enteritis but large-scale human trials are needed.

Summary
Radiation enteritis is an important clinical problem, but awareness is lacking amongst patients and physicians. Clinical guidelines would allow standardised management which may improve the burden of the disease for patients.
Body Composition Using Air Displacement Plethysmography in Children With Inflammatory Bowel Disease
Authors: Dhaliwal Jasbir , Martincevic Inez , Williams Brock , Frost Karen , Uusoue Krista , Arpino Valerie , Church Peter , Walters Thomas D. , Griffiths Anne M. , Mouzaki Marialena 
Published: March 2020

ABSTRACTObjective:The aim of the study was to assess the body composition of children with inflammatory bowel disease (IBD) and to study the accuracy of clinically available tools in predicting excess body fatness. We aimed at also exploring the influence of adiposity on pharmacokinetics during early Infliximab exposure.Methods:Prospective cohort study in 5‐ to 17‐year‐old children with IBD initiating Infliximab therapy. Patient demographic, phenotypic, and laboratory data at the time of Infliximab initiation were recorded. Body composition was assessed using air displacement plethysmography (ADP). fat mass index (FMI = fat mass [kg]/(height [m])2) was calculated to determine excess adiposity (defined as FMI ≥75th centile). Anthropometrics (weight, height, mid upper arm circumference [MUAC] and triceps skin fold thickness [TSF]) were obtained and MUAC and TSF measurements were used to calculate arm fat area (AFA) and arm muscle area z‐scores. Statistical analysis was applied as appropriate.Results:Fifty‐three (68% male; 55% Crohn disease [CD], 45% ulcerative colitis [UC], median [IQR] age 15 [13–16] years) children with IBD were included. Twenty‐four percentage of children with IBD (21% CD, 29% UC) had excess adiposity. Four children (31%) with FMI ≥75th centile were not identified by body mass index (BMI) alone (kappa of 0.60), and 2 children (15%) were not identified by AFA z‐score alone. The intra‐ and interobserver reliability of MUAC and TSFT measurements was excellent. There was no difference in Infliximab trough levels at the end of induction between those with FMI less than or ≥75th centile.Conclusions:Excess adiposity affects approximately 1 in 4 young patients with IBD and can be missed by routine obesity screening. Our exploratory study did not raise concerns of underexposure to infliximab in those children with excess adiposity during early drug exposure.
Rules Are Meant to Be Broken
Authors: Clark Susannah J. , Staffa Steven J. , Ngo Peter D. , Yasuda Jessica L. , Zendejas Benjamin , Hamilton Thomas E. , Jennings Russell W. , Manfredi Michael A. 
Published: March 2020

ABSTRACTBackground and Aims:The “rule of 3” is a 40‐year‐old expert opinion that suggests dilating an esophageal stricture more than 3 mm is unsafe. Few studies have evaluated this tenet, and do not specify how much larger than 3 mm is reasonable. Our aim was to determine the optimal point for maximum dilation diameter with acceptable risk in a pediatric population.Methods:A retrospective review in pediatric patients with esophageal strictures was performed. The number of millimeters the stricture was dilated, defined as delta dilation diameter (ΔDD), was determined by subtracting the initial stricture diameter from the diameter of the largest balloon used. Receiver operating characteristic curve analysis was used to evaluate the discriminatory ability of ΔDD. Youden J index was used to identify optimal cut‐point in predicting perforation.Results:Two hundred eighty‐four patients underwent 1384 balloon dilations. Overall perforation rate was 1.66%. There were 8 perforations in 1075 dilations with ΔDD ≤5 mm (0.7%) and 15 perforations in 309 dilations with ΔDD >5 mm (4.9%). Youden J index found an optimal cutoff to be at a ΔDD of ≤5 mm. The cumulative rate of perforation for all dilations ≤5 mm was 0.74% whereas the cumulative risk of perforation for all dilations ≥6 mm was 4.85% (P < 0.001).Conclusions:Balloon dilations that expand the initial esophageal anastomosis ≤5 mm in a pediatric population appear to not unduly increase the risk of perforation. Further prospective studies are needed to further investigate the potential for a new rule of 5 for balloon dilation.
Effectivity of Pancreatic Enzyme Replacement Therapy in Malnourished Children
Authors: Güven Burcu , Demir Mis Mevsim , Karaman Kamuran , Şahin Yaşar Akkiz 
Published: March 2020

ABSTRACTObjective:Malnutrition is commonly seen in children with exocrine pancreatic insufficiency (EPI). Pancreatic enzyme replacement therapy (PERT) is the mainstay treatment of acute malnutrition in children detected with a disease closely associated with EPI (eg, cystic fibrosis). The effectiveness of PERT in children with malnutrition without any chronic disease, however, remains unclear. The aim of this study was to investigate the effectiveness of PERT on weight gain and EPI in children classified as moderately and severely malnourished according to the World Health Organization (WHO) classification.Materials and Methods:The study included a total of 40 children aged 2‐16 years who were classified as moderately and severely malnourished according to the WHO classification. The patients were randomly divided into 2 groups: PERT group (n = 20) received 2000 U lipase/kg/day (in 4 doses) in addition to hypercaloric enteral supplements and control group received hypercaloric enteral supplements only. In both groups, anthropometric measurements and the assessment of fecal elastase‐1 (FE‐1) levels were performed both at first admission and at the end of the 8‐week treatment period.Results:On the basis of WHO classification, 10 (25%) children were classified as severely malnourished and 30 (75%) children as moderately malnourished. EPI was detected in all the patients, among whom 24 (60%) patients had severe EPI. At the end of the treatment, body weight, height, and body mass index (BMI) increased significantly in both groups compared to their pre‐treatment values, whereas no significant difference was found with regard to waist circumference (WC) and FE‐1 levels. Similarly, no significant difference was found between pre‐ and posttreatment measurements of PERT and control groups (P > 0.05) and between pre‐ and posttreatment measurements of patients with moderate and severe malnutrition (P > 0.05).Conclusions:Malnutrition remains a serious public health problem, and thus, the development of novel treatment methods is highly essential. PERT is one of the most commonly considered alternatives, although there is little documentation of PERT in the literature. In the present study, although PERT resulted in higher weight gain, it established no significant difference between the 2 groups.
Cystic Fibrosis‐related Liver Disease is Associated With Increased Disease Burden and Endocrine Comorbidities
Authors: Singh Harveen , Coffey Michael J. , Ooi Chee Y. 
Published: March 2020

ABSTRACTBackground:Cystic fibrosis‐related liver disease (CFLD) is the leading nonpulmonary cause of mortality in cystic fibrosis (CF). We evaluated and compared the burden of disease and nonrespiratory comorbidities of those with severe CFLD and those without (noCFLD).Methods:A retrospective nationwide (Australia) longitudinal review (from 1998 to 2016) of severe CFLD patients compared with noCFLD controls (matched 1 : 1 for age, genotype, pancreatic insufficiency, and center).Results:One hundred sixty‐six patients with severe CFLD and 166 with noCFLD were identified. Forced expiratory volume in 1 second percentage of predicted (FEV1%) was significantly lower in CFLD than noCFLD across all ages (estimate [SE] −6.05% [2.12]; P = 0.004). Median (IQR) hospitalizations per patient per year were higher in CFLD than noCFLD for: respiratory indications (0.6 [0.2–1.3] vs 0.4 [0.1–0.9]; P = 0.002); gastrointestinal indications (0.09 [0–0.2] vs 0 [0–0.05]; P < 0.001); and other indications (0.05 [0–0.2] vs 0 [0–0.1]; P = 0.03). In the CFLD cohort, there was increased use of nasogastric (12.6% vs 5.4%; OR 2.51 [95% CI 1.06–6.46]; P = 0.03) and gastrostomy nutritional supplementation (22.9% vs 13.2%; OR 1.93 [95% CI 1.05–3.63]; P = 0.03). Additionally, the CFLD cohort had a higher frequency of bone diseases, osteopenia (26.5% vs 16.8%; OR 1.77 [95%CI 1.01–3.15]; P = 0.04) and osteoporosis (16.2% vs 8.4%; OR 2.1 [95% CI 1.01–4.52]; P = 0.04), as well as CF‐related diabetes (38.5% vs 19.2%; OR 2.61 [95% CI 1.55–4.47]; P = 0.001).Conclusions:Patients with severe CFLD have greater disease burden, with higher number of hospitalizations (both respiratory and nonrespiratory indications), nutritional interventions, and are at higher risk of CF‐related bone disease and diabetes.
Understanding the HIV Epidemic Among MSM in Baltimore: A Modeling Study Estimating the Impact of Past HIV Interventions and Who Acquired and Contributed to Infections
Authors: Silhol Romain , Boily Marie-Claude , Dimitrov Dobromir , German Danielle , Flynn Colin , Farley Jason E. , Gelman Marcy , Hughes James P. , Donnell Deborah , Adeyeye Adeola , Remien Robert H. , Beyrer Chris , Paz-Bailey Gabriela , Wejnert Cyprian , Mitchell Kate M. 
Published: March 2020

Introduction:
Men who have sex with men (MSM) in the United States are disproportionately affected by HIV. We estimated the impact of past interventions and contribution of different population groups to incident MSM HIV infections.

Setting:
Baltimore, US.

Methods:
We used a deterministic model, parameterized and calibrated to demographic and epidemic Baltimore MSM data, to estimate the fraction of HIV infections among MSM averted by condoms and antiretroviral therapy (ART) over 1984–2017 and the fraction of infections acquired and transmission contributed by MSM from different demographic groups and disease and care continuum stages over 10-year periods from 1988 to 2017, using population attributable fractions.

Results:
Condom use and ART averted 19% (95% uncertainty interval: 14%–25%) and 23% (15%–31%) of HIV infections that would have occurred since 1984 and 1996, respectively. Over 2008–2017, 46% (41%–52%) of incident infections were acquired by and 35% (27%–49%) of transmissions contributed by MSM aged 18–24 years (who constitute 27% of all MSM, 19% of HIV+ MSM). MSM with undiagnosed HIV infection, those with diagnosed infection but not in care, and those on ART contributed to 41% (31%–54%), 46% (25%–56%), and 14% (7%–28%) of transmissions, respectively.

Conclusion:
Condoms and ART have modestly impacted the HIV epidemic among Baltimore MSM to date. Interventions reaching MSM with diagnosed infection who are not in care should be implemented because the largest percentage of HIV transmissions among Baltimore MSM is attributed to this group.
The Efficacy of Over-the-Scope Clip Closure for Gastrointestinal Iatrogenic Perforation During Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography for Pancreaticobiliary Diseases
Authors: Iwasa Yuhei , Iwashita Takuji , Uemura Shinya , Mita Naoki , Iwata Keisuke , Yoshida Kensaku , Mukai Tsuyoshi , Yasuda Ichiro , Shimizu Masahito 
Published: March 2020

Background:
Intestinal perforation is a severe adverse event during pancreaticobiliary endoscopy. The use of over-the-scope clip (OTSC) has recently increased; however, the efficacy of OTSC during pancreaticobiliary endoscopy has not been well studied.

Aims:
To evaluate the efficacy of OTSC for the closure of gastrointestinal iatrogenic perforation during pancreaticobiliary endoscopy.

Patients and Methods:
This was a retrospective multicenter cohort study conducted at 3 tertiary care centers. The inclusion criteria were patients who had gastrointestinal perforation during endoscopic procedures for pancreaticobiliary diseases and underwent perforation closure using OTSC. The primary outcome was the clinical success rate. Secondary outcomes were technical success rates, adverse event rates, and the duration until the start of oral intake after OTSC.

Results:
Ten patients were treated by OTSC from January 2013 to December 2017. In 2 out of 10, the perforations could not be closed completely. In the remaining 8, perforations were closed completely, but intestinal obstruction caused by OTSC occurred in 1 patient. The clinical success rate was 80% (8/10). The technical and adverse event rates were 80% (8/10) and 10% (1/10), respectively. A median resumption timing of oral intake was 5 days (range, 3 to 10 d).

Conclusion:
OTSC is considered as effective management for perforations during pancreaticobiliary endoscopy, although careful consideration is required for the indication of OTSC.
Therapeutic Potentials of Localized Blood–Brain Barrier Disruption by Noninvasive Transcranial Focused Ultrasound: A Technical Review
Authors: Cammalleri Amanda , Croce Phillip , Lee Wonhye , Yoon Kyungho , Yoo Seung-Schik 
Published: March 2020

Summary:
The demands for region-specific, noninvasive therapies for neurologic/psychiatric conditions are growing. The rise of transcranial focused ultrasound technology has witnessed temporary and reversible disruptions of the blood–brain barrier in the brain with exceptional control over the spatial precisions and depth, all in a noninvasive manner. Starting with small animal studies about a decade ago, the technique is now being explored in nonhuman primates and humans for the assessment of its efficacy and safety. The ability to transfer exogenous/endogenous therapeutic agents, cells, and biomolecules across the blood–brain barrier opens up new therapeutic avenues for various neurologic conditions, with a possibility to modulate the excitability of regional brain function. This review addresses the technical fundamentals, sonication parameters, experimental protocols, and monitoring techniques to examine the efficacy/safety in focused ultrasound–mediated blood–brain barrier disruption and discuss its potential translations to clinical use.
Nocturnal Rapid Eye Movement Sleep Without Atonia can Be a Diagnostic Parameter in Differentiating Narcolepsy Type 1 From Type 2
Authors: Yon Mehmet Ilker , Azman Filiz , Yon Merve Ecem , Tezer F. Irsel 
Published: March 2020

Purpose:
We aimed to compare rapid eye movement sleep without atonia (RSWA), tonic RSWA, and phasic RSWA indices during polysomnography as a potential biomarker between narcolepsy type 1 and type 2.

Methods:
Medical files, polysomnography, and multiple sleep latency tests of patients with narcolepsy were evaluated retrospectively. A total of three adolescents and 31 adult patients were included. We calculated the total number of rapid eye movement (REM) epochs with tonic and phasic activity in accordance with the American Academy of Sleep Medicine manual scoring rules, version 2.4. We defined tonic RSWA index as the ratio of total number of REM sleep stage epochs with only tonic activity to total REM sleep stage epochs, phasic RSWA index as the ratio of total number of REM sleep stage epochs with only phasic activity to total REM sleep stage epochs, and RSWA index as the ratio of total number of REM stage sleep epochs with RSWA to total REM sleep stage epochs on the polysomnography.

Results:
Clinically and polysomnographically diagnosed 25 patients with narcolepsy type 1 and 9 patients with narcolepsy type 2 were included. The median age of the subjects was 30 (10, 61) and 36 (18, 64), respectively. Eleven narcolepsy type 1 patients (44%) and 4 narcolepsy type 2 patients (44.44%) were women. The RSWA index of ≥ 3% yielded a sensitivity of 76% and specificity of 88.9% (AUC = 0.77 (0.09), 95% confidence interval = 0.58 to 0.97, p = 0.01), and the tonic RSWA index of ≥ 2.2% yielded a sensitivity of 72% and specificity of 77.8% (area under the curve = 0.74 (0.1), 95% confidence interval = 0.54–0.94, p = 0.03).

Conclusions:
As an electrophysiological biomarker, RSWA and tonic RSWA indices can be sensitive and specific polysomnography parameters in distinguishing narcolepsy type 1 from narcolepsy type 2.
Vicarious trial-and-error is enhanced during deliberation in human virtual navigation in a translational neuroeconomic task
Authors: Huynh Thach , Alstatt Keanan , Abram Samantha , Schmitzer-Torbert Neil 
Published: March 2020

AbstractForaging tasks can provide valuable insights into decision-making, as animals choose how to allocate limited resources (such as time). In the “Restaurant Row” task, rodents move between several sites to obtain food rewards available after a variable delay, while in a translational version (the “Web-Surf”) lacking the navigation component, humans are offered short videos. Both tasks have provided novel insights into decision-making and have been applied to addiction vulnerability and the impact of drug exposure on decision-making. We tested new tasks (the “Movie Row” and “Candy Row”) which use virtual navigation to determine if the behavioral correlates of human decision-making are more broadly similar to those of rodents, and explored the relationship of task performance to smoking and obesity. Humans navigated a virtual maze presented on standard computers to obtain rewards (either short videos or candy) available after a variable delay. Behavior on the tasks replicated previous results for the Restaurant Row and Web-Surf. In conditions promoting deliberation, decision latency was elevated along with measures of vicarious trial-and-error (VTE), supporting VTE as a shared behavioral index of deliberation across species. Smoking status was not well-related to performance, while high BMI (>25) individuals showed reduced sensitivity to a sunk-costs measure and stronger sensitivity to offer value for offers below the preferred delay. These data support the Movie and Candy Row as translational tools to study decision-making during foraging in humans, providing convergent results with a rodent navigation task and demonstrating the potential to provide novel insights relevant to public health.
Polygenic Risk Score Modifies Risk of Coronary Artery Disease Conferred by Low-Density Lipoprotein Cholesterol
Authors: Bolli Alessandro , Di Domenico Paolo , Pastorino Roberta , Busby George , Bottà Giordano 
Published: March 2020

AbstractBackgroundAn individual’s lifetime risk of Coronary Artery Disease (CAD) is determined by a combination of genetic and lifestyle factors. Whilst adherence to a healthy lifestyle can help individuals with high genetic risk reduce their lifetime risk of CAD, the extent to which blood lipid levels affect CAD risk in individuals with varying genetic risk remains unknown. To explore how genetics, blood lipids and CAD risk interact, we derived a novel genome-wide polygenic risk score (PRS) for CAD. We then applied the PRS to individuals from the UK Biobank and divided them into Low PRS (bottom 10 percentiles of PRS distribution), Intermediate PRS (PRS in the 10th-90th percentiles), and High PRS (top 10 percentiles), and further stratified individuals by blood lipid levels.ResultsWe found that the elevated CAD risk conferred by high low-density lipoprotein cholesterol (LDL-C) was modified by the interaction with PRS (P-value interaction: <0.005). Individuals with High PRS and whose LDL-C was Borderline (between 130 and 160 mg/dL) had higher CAD relative risk (HR 3.10; 95% CI, 2.55-3.76) than those at Intermediate PRS whose LDL-C were Very High (>190 mg/dL; HR 2.77; 95% CI, 2.33-3.28). Furthermore, individuals with High PRS but whose lipid levels were below the following thresholds did not have a significantly increased risk for incident CAD: LDL-C <130 mg/dL, total Cholesterol (TC) <200 mg/dL, LDL-C:HDL <2.0 and TC:HDL <3.0. In addition, individuals with Low PRS and Very High LDL-C (>190 mg/dl) did not have increased CAD risk, which was comparable to individuals with Intermediate PRS and Optimal LDL-C (<130 mg/dL).ConclusionsOur results have important implications for the primary prevention of coronary artery disease. Currently, healthy individuals with Borderline LDL-C (130-159 mg/dL) are not considered to be at high risk of CAD. Here we demonstrate that the combination of Borderline LDL-C and High PRS results in CAD relative risk which is greater than individuals without high polygenic risk, but whose LDL-C levels are high enough for statins to be recommended (>190 mg/dL). This analysis therefore demonstrates that PRS can identify a proportion of the population who are at high-risk of CAD but who are invisible to current approaches for assessing CAD risk. Moreover, of perhaps greater significance is the evidence that individuals who have a combination of High PRS and Optimal blood lipid levels do not have greater risk of CAD than individuals without high polygenic risk and the same Optimal blood lipid levels. Our results suggest that high polygenic risk for CAD could be overcome by controlling blood lipid levels. We propose that incorporating PRS into CAD risk assessment early in life could allow individuals at high polygenic risk to benefit from tailored blood lipid guidelines and avoid lifetime exposure to potentially damaging PRS-dependent LDL-C levels.