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© 2014 Macmillan Publishers Limited. All rights reserved.The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of ra

A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (herein termed autism), the nature of the allelic spectrum is uncertain. Individual risk-associated genes have been identified from

Background: Although mechanical circulatory support might not increase the number of adults surviving to transplantation, because of the shortage of donor organs, the situation might be different for children. Our aim was to assess the effect of mechanical assist devices to bridge children with end-stage cardiomyopathy to heart transplantation. Methods: A 5-year retrospective review was undertaken with data from the UK paediatric transplant programme and from bridging to transplant done at two paediatric transplant centres in the UK. Findings: Between Jan 1, 1998 and Dec 31, 2002, 22 children with end-stage cardiomyopathy, median age 5.7 years (range 1.2-17), were supported by a mechanical assist device as a bridge to first heart transplantation, with a 77% survival rate to hospital discharge. Nine were supported by a paracorporeal ventricular assist device, six received transplantation, five survived to discharge (55%), with one late death. 13 were supported by extra-corporeal membrane oxygenation, and 12 were transplanted and survived to discharge (92%) with one late death. With urgent listing, the median waiting time for a heart was 7.5 days (range 1.5-22 days). The correlation between the proportion of patients bridged to transplantation and the proportion of patients dying while on the transplant waiting list was r=-0.93, p=0.02. Interpretation: Our findings lend support to the hypothesis that a national mechanical assist programme to bridge children to transplantation can minimise the number dying while on the heart transplant waiting list. In the context of urgent listing and a short waiting time, extra-corporeal membrane oxygenation seems to provide the safest form of support. [ABSTRACT FROM AUTHOR]

Background: There are few empirical data to support the claim that weight loss improves coronary heart disease (CHD) risk factors in postmenopausal women; nor is it known if there are racial differences in changes of body fat distribution, lipids, glucose tolerance, and blood pressure with weight loss. This study determined the efficacy of a lifestyle weight loss intervention in reducing total and abdominal obesity and improving CHD risk factors in obese Caucasian and African-American postmenopausal women.Methods: Body composition (dual-energy x-ray absorptiometry), abdominal fat areas (computed tomography scan), lipoprotein lipids, insulin, glucose tolerance, and blood pressure were measured before and after 6 months of hypocaloric diet and low-intensity walking in 76 overweight or obese (body mass index > 25 kg/m(2)), Caucasian (72%) or African-American (28%), postmenopausal (age = 60 +/- 5 years) women who completed the study.Results: Absolute amount of body weight lost was similar in Caucasians (-5.4 +/- 3.6 kg) and African Americans (-3.9 +/- 3.6 kg), but Caucasian women lost relatively more fat mass (p <.05). Both groups decreased their subcutaneous abdominal fat, and Caucasian women decreased their visceral fat area, but there were no racial differences in the magnitude of abdominal fat lost. The intervention decreased triglyceride and increased high-density lipoprotein and high-density lipoprotein 2 cholesterol in both races, and it decreased total and low-density lipoprotein cholesterol in Caucasian women (p <.05-.0001). Fasting glucose and glucose area during the oral glucose tolerance test decreased (p <.0001) in Caucasian women, whereas insulin area decreased in both Caucasian (p <.01) and African-American (p <.05) women. Blood pressure decreased the most in women with higher blood pressures at baseline. Changes in lipids, fasting glucose and insulin, their responses during the oral glucose tolerance test, and blood pressure were not different between racial groups.Conclusions: Weight loss achieved through a lifestyle intervention of energy restriction and increased physical activity is an equally effective therapy in African-American and Caucasian obese, postmenopausal women for improving glucose and lipid CHD risk factors. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of weight loss vs aerobic exercise training on coronary artery disease risk factors in healthy sedentary, obese, middle-aged and older men.Design: Randomized controlled trial.Subjects: A total of 170 obese (body mass index, 30 +/- 1 kg/m2 [mean +/- SEM]), middle-aged and older (61 +/- 1 years) men.Interventions: A 9-month diet-induced weight loss interventions, 9-month aerobic exercise training program, and a weight-maintenance control group.Main Outcome Measures: Change in body composition, maximal aerobic capacity (V02 max), blood pressure, lipoprotein concentrations, and glucose tolerance.Results: Forty-four of 73 men randomized to weight loss completed the intervention and had a 10% mean reduction in weight (- 9.5 +/- 0.7 kg; P < .001), with no 22 change in VO2 max. Forty-nine of 71 men randomized to aerobic exercise completed the intervention, increased their VO2 max by a mean of 17% (P < .001), and did not change their weight, whereas the 18 men who completed in the control group had no significant changes in body composition or VO2 max. Weight loss decreased fasting glucose concentrations by 2%, insulin by 18%, and glucose and insulin areas during the oral glucose tolerance test (OGTT) by 8% and 26%, respectively (P < .01). By contrast, aerobic exercise did not improve fasting glucose or insulin concentrations or glucose responses during the OGTT but decreased insulin areas by 17% (P < .001). In analysis of variance, the decrement in fasting glucose and insulin levels and glucose areas with intervention differed between weight loss and aerobic exercise when compared with the control group (P < .05). Similarly, weight loss but not aerobic exercise increased high-density lipoprotein cholesterol levels (+ 13%) and decreased blood pressure compared with the control group. In multiple regression analyses, the improvement in lipoprotein and glucose metabolism was related primarily to the reduction in obesity.Conclusions: These results suggest that weight loss is the preferred treatment to improve coronary artery disease risk factors in overweight, middle-aged and older men. [ABSTRACT FROM AUTHOR]

Background: The purposes of this study were to identify predictors of increased claudication distances following exercise rehabilitation in peripheral arterial occlusive disease (PAOD) patients with intermittent claudication and determine whether improved claudication distances translated into increased free-living daily physical activity in the community setting.Methods: Sixty-three patients were recruited (age, 68+/-1 years, mean +/- standard error). Patients were characterized on treadmill claudication distances, walking economy, peripheral circulation, cardiopulmonary function, self-perceived ambulatory function, body composition, baseline comorbidities, and free-living daily physical activity before and after a 6-month treadmill exercise program.Results: Exercise rehabilitation increased distance to onset of claudication pain by 115% (178+/-22 m to 383+/-34 m; p < .001) and distance to maximal claudication pain by 65% (389+/-29 m to 641+/-34 m; p < .001). The increased distance to onset of pain was independently related to a 27% increase in calf blood flow (r = .42, p < .001) and to baseline age (r = -.26, p < .05), and the increased distance to maximal pain was predicted by a 10% increase in peak oxygen uptake (r = .41, p < .001) and by a 10% improvement in walking economy (r = -.34, p < .05). Free-living daily physical activity increased 31% (337+/-29 kcal/day to 443+/-37 kcal/day; p < .001) and was related to the increases in treadmill distances to onset (r = .24, p < .05) and to maximal pain (r = .45, p < .001).Conclusions: Increased claudication distances following exercise rehabilitation are mediated through improvements in peripheral circulation, walking economy, and cardiopulmonary function, with younger patients having the greatest absolute ambulatory gains. Furthermore, improved symptomatology translated into enhanced community-based ambulation. [ABSTRACT FROM AUTHOR]

Background: We evaluated the effect of weight loss (WL) or aerobic exercise (AEX) on pulmonary function in middle-aged and older (46-80 years) obese, sedentary men to determine the effect of reductions in body weight and increases in cardiorespiratory fitness on pulmonary function.Methods: Subjects were randomly assigned to WL (n = 73), AEX (n = 71), or control (n = 26) groups. Maximal oxygen uptake (VO2max), body composition and anthropometrics, pulmonary function, and arterial blood gases were measured at baseline and after interventions.Results: The 35 subjects who completed WL decreased weight by 11%, body fat percentage by 21% (p < .001), waist circumference by 8%, waist-hip ratio by 2%, and fat-free mass by 3% (p < .05). This resulted in a 3% increase in forced vital capacity (FVC) (4.08 +/- 0.71 L vs 4.21 +/- 0.76 L), a 5% increase in total lung capacity (6.62 +/- 0.99 L vs 6.94 +/- 0.99 L), an 18% increase in functional residual capacity (3.09 +/- 0.58 L vs 3.66 +/- 0.79 L), and an 8% increase in residual volume (2.20 +/- 0.44 L vs 2.37 +/- 0.52 L), with no change in forced expiratory volume in one second (FEV1), FEV1/FVC ratio, or carbon monoxide diffusing capacity. The change in FVC correlated with change in body weight (r = -.34, p < .05). The 38 subjects who completed AEX increased VO2max by 14%, with no change in pulmonary function. There were no changes in 8 control subjects.Conclusions: WL changes static lung volumes, not dynamic pulmonary function, in middle-aged and older, moderately obese, sedentary men. Some of the alterations in static lung function associated with aging may be due to the development of obesity and are modifiable by WL. [ABSTRACT FROM AUTHOR]

Background: Lipoprotein lipids in older individuals are affected by family history of coronary artery disease (CAD), obesity, diet, and physical activity habits.Methods: The relationship of obesity and physical fitness (VO2max) to lipoprotein lipids and postheparin lipases was examined in a cross-sectional study of 12 lean (LS) and 26 obese (OS) sedentary men and 18 master athletes (MAs) aged 65+/-1 years (mean +/- SE). The men were healthy, had no family history of CAD, and were weight stable on AHA diets at the time of study.Results: VO2max was similar in LS and OS men but higher in the MAs. The OS men had a higher percentage of body fat (%BF), waist circumference, and waist:hip ratio (WHR) than the MA and LS men, but MA and LS men differed only in waist circumference. Total and LDL-C levels were comparable, but HDL-C, HDL2-C, and %HDL2b subspecies were higher in MAs than in OS and LS men, and in LS than in OS men. Triglyceride (TG) was similar in MAs and LS men but higher in OS men. Across groups, two multiple regression analyses models (VO2max, %BF, and WHR or waist circumference) showed that %BF and VO2max independently predicted HDL-C and HDL2, whereas WHR predicted TG (r2 = .45) more strongly than waist circumference (r2 = .39). Postheparin lipoprotein lipase activity (LPL) was comparable among groups and correlated independently with VO2max. Total postheparin lipolytic activity (PHLA), hepatic lipase activity (HL), and HL:PHLA ratio were similar in MAs and LS men but higher in OS men. In both multiple regression analysis models, only %BF predicted HL activity and the HL:PHLA ratio. The HL:PHLA ratio independently predicted HDL-C, HDL2-C, %HDL2b, %HDL3 subspecies, and the cholesterol:HDL-C ratio, whereas LPL activity predicted TG.Conclusions: Increased fitness and reduced total and abdominal fatness in MAs are associated with lower HL and higher LPL activities, which may mediate their higher HDL-C and lower TG levels relative to their sedentary peers. [ABSTRACT FROM AUTHOR]

High-physical activity levels are associated with reduced risk of symptomatic coronary artery disease (CAD). However, there are a number of reports of exercise-related sudden death and myocardial infarction in aerobically trained athletes. This study compared the prevalence of exercise-induced silent myocardial ischemia on maximum graded exercise tests with tomographic thallium scintigraphy in 70 master male athletes (63 +/- 6 years, mean +/- SD) (maximum aerobic capacity, VO2max >40 ml/kg/min) and in 85 healthy untrained men (61 +/- 7 years) with no history of CAD. The prevalence of silent ischemia (exercise-induced ST-segment depression on electrocardiogram and perfusion abnormalities on thallium scintigraphy) was similar in athletes and untrained men; 16% of the athletes (11 of 70) had silent ischemia compared with 21% of the untrained men (chi-square = 0.81, p = 0.36). No athletes had hyperlipidemia, systemic hypertension, or diabetes mellitus. However, the apolipoprotein E4 allele was present in 9 of the 11 athletes with silent ischemia compared with 2 of 32 athletes with normal exercise tests (chi-square = 24, p = 0.0001). These results suggest that older male athletes with the apolipoprotein E4 allele are at increased risk for the development of exercise-induced silent ischemia. [ABSTRACT FROM AUTHOR]

Abusive Head Trauma (AHT) results in more child fatalities than any other form of physical abuse and is associated with significant risk of morbidity for survivors. The diagnosis of AHT is made like any other complex medical condition and is based on a constellation of findings within the context of a reported history provided by the patient's caregiver(s). A standardized process with careful consideration of a differential diagnosis and utilization of a multidisciplinary team is essential. This article explores the history of the diagnosis of AHT, reviews the scientific basis for potential mechanisms, references the recommended medical evaluation, describes common findings, and the importance of early and accurate diagnosis.

This pilot study explored female caregiver's perception of their child's behaviors during sexual abuse evaluations. We compared reports by caregivers with histories of their own child sexual abuse (PCSA) to caregivers with no prior history of child sexual abuse (NPCSA) regarding their 1) child's sexualized behaviors and (2) perceptions of whether their child had been sexually abused. Forty-four caregivers met inclusion criteria. Ninety-five percent of PCSA caregivers versus 21% of NPCSA caregivers reported at least one behavior from the Child Sexual Behavior Inventory. Our findings identified that PCSA caregivers reported more sexualized behaviors for their children overall, potentially contributing to their perception that their child had been sexually abused. This pilot study demonstrated that caregivers were able to tolerate answering questions about their own history of child abuse. Parents should be asked these questions as this may influence perceptions of their child's behaviors and possible sexual abuse.

This article provides an historical review of child maltreatment, focusing on the three most common subtypes: physical abuse, sexual abuse, and neglect. The evolution of recognizing, evaluating, and accurately diagnosing child maltreatment is described. Over time, the establishment of multidisciplinary teams, mandatory reporting, and Child Abuse Pediatrics as a subspecialty of pediatrics has improved the training, research, and clinical diagnosis for all forms of child maltreatment. These advancements have set clinical standards to ensure accurate diagnosis, prevent the misdiagnosis of child abuse and neglect, and continually improve the systems meant to protect children. The expansion of knowledge of child maltreatment continues with attention on early detection of children at risk of developing lifelong physical, psychological, and behavioral consequences from trauma associated with all forms of child maltreatment.

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Stochasticity from gene expression in single cells is known to drive metabolic heterogeneity at the level of cellular populations, which is understood to have important consequences for issues such as microbial drug tolerance and treatment of human diseases like cancer. Despite considerable advancements in profiling the genomes, transcriptomes, and proteomes of single cells, it remains difficult to experimentally characterize their metabolism at the genome scale. Computational methods could bridge this gap toward a systems understanding of single-cell biology. To address this challenge, we developed stochastic simulation algorithm with flux-balance analysis embedded (SSA-FBA), a computational framework for simulating the stochastic dynamics of the metabolism of individual cells using genome-scale metabolic models with experimental estimates of gene expression and enzymatic reaction rate parameters. SSA-FBA extends the constraint-based modeling formalism of metabolic network modeling to the single-cell regime, enabling simulation when experimentation is intractable. We also developed an efficient implementation of SSA-FBA that leverages the topology of embedded flux-balance analysis models to significantly reduce the computational cost of simulation. As a preliminary case study, we built a reduced single-cell model of Mycoplasma pneumoniae and used SSA-FBA to illustrate the role of stochasticity on the dynamics of metabolism at the single-cell level., (Copyright © 2021 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to determine the prevalence of rib fractures (RFs) identified by chest x-ray (CXR) among children younger than 2 years who sustained accidental versus nonaccidental injuries. It is hypothesized that RFs are uncommon among all accidental pediatric trauma mechanisms (eg, falls, motor vehicle crashes) as compared with the prevalence of RFs in the setting of nonaccidental trauma (NAT)., Methods: A retrospective chart review of sequential CXRs of children younger than 2 years evaluated at a pediatric level 1 trauma center for accidental trauma and possible NAT was conducted from January 1, 2011, to October 31, 2016. Data collected included demographics, CXR indication and findings, history of cardiopulmonary resuscitation, trauma mechanism, associated injuries, final diagnoses, and outcomes., Results: Two (<1%) of 226 CXRs obtained to evaluate accidental trauma demonstrated acute RFs. Ten (19.6%) of 51 CXRs obtained in the setting of concern for NAT revealed RFs (9/10 identified only healing RFs and 1/10 identified acute RFs). Among patients with a final diagnosis of NAT (ie, not neglect, accidental trauma, etc; n = 38), the overall prevalence increased to 26.3%., Conclusions: The presence of RFs in pediatric accidental trauma is uncommon even in the setting of high-force mechanisms, and when identified, these RFs are acute. Comparatively, the overall prevalence of RFs identified on CXR among cases with a final diagnosis of NAT was much higher and almost exclusively healing RFs. These data provide support that identification of RFs is highly concerning for NAT even if an accidental mechanism is provided. When RFs are identified, a full NAT work-up should be considered., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Substance use and abuse have been documented as both a risk factor in and consequence of involvement in domestic minor sex trafficking (DMST). Domestic minor sex trafficking is defined as the commercial sexual exploitation of children in exchange for money, food, shelter, or any other valued entity. The current investigation sought to describe substance use in a cohort of DMST patients who present for medical evaluation. Findings revealed that 68 patients referred for DMST involvement reported high rates of alcohol/substance use and parental substance abuse. Further, many patients who had a urine toxicology screen had a positive result, most often identifying the presence of cannabinoids. Our data may inform the importance of comprehensive assessments and specialized interventions for substance abuse in this unique patient population., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Close medical follow-up after pediatric acute sexual assault is recommended and may mitigate adverse consequences and decrease long-term comorbidities. The objectives are to (1) examine adherence to a comprehensive outpatient medical follow-up protocol after evaluation in the emergency department in a pediatric population and (2) identify characteristics associated with patient adherence to inform the utilization of a medical follow-up protocol after pediatric acute sexual assault., Methods: A retrospective medical record review was conducted of patients younger than 18 years presenting to the emergency department from January 1, 2010, to December 31, 2013, with a discharge diagnosis suggestive of sexual assault/abuse. We examined differences in demographics, assault characteristics, and medical/legal needs of patients who were evaluated in follow-up versus patients who were not., Results: Of 182 patients, 60.4% completed follow-up appointments with the child protection center. Younger patients had follow-up rates higher than older patients (70.2% vs 50%; odds ratio [OR], 0.42). For patients where child protective services or law enforcement were called, follow-up rates were 74.2% and 64.7%, respectively (OR, 2.5; OR, 3.1). All patients with anogenital injuries on initial examination were seen in follow-up. The majority of patients who followed-up were accompanied by a caregiver/relative (95%)., Conclusions: (1) Caregivers should be integrated into the evaluation to facilitate compliance with follow-up; (2) child abuse specialists may be consulted to facilitate specific interventions and recommendations; (3) professionals should work as a multidisciplinary team; and (4) the patient's psychological status should be evaluated, and mental health interventions recommended., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The metabolic syndrome (MetS) is a systemic disorder associated with reduced atheroprotective gynoid fat and bone mineral content (BMC). The goal of this pilot study was to assess whether administration of icosapent ethyl (IPE), a purified formulation of eicosapentaenoic acid, would maintain gynoid fat and BMC over a 9-month treatment period., Methods: Patients with MetS aged ≥40 years were randomly assigned to receive 4 g daily of IPE (2 g BID with food) or placebo (paraffin oil 2 g BID with food) for 9 months. Data were collected at baseline and 9 months later. The data included anthropometric measures, biochemical analysis, and whole body fat mass, including gynoid fat. Bone mineral density and BMC were measured by using dual-energy X-ray absorptiometry. A two-tailed P value ≤ 0.05 was considered statistically significant., Findings: The study sample consisted of 13 patients with MetS (mean age, 61.6 years; age range, 44-77 years; 77% female and 23% male). Compared with the IPE group, the placebo group experienced statistically significant mean reductions in percent gynoid fat (pre/post, 46.8%-43.5%; P = 0.02), BMC (pre/post, 2461 g-2423 g; P = 0.02), and bone mineral density (pre/post, 1.24 g/cm 2 to 1.22 g/cm 2 ; P = 0.05) over the 9-month study period., Implications: The results of this pilot study raise the possibility that IPE supplementation may preserve gynoid fat distribution and bone mineral health in patients with MetS. Larger, randomized longitudinal studies are necessary to determine the potential long-term metabolic benefits of IPE treatment., (Published by Elsevier Inc.)

Like many scientific disciplines, dynamical biochemical modeling is hindered by irreproducible results. This limits the utility of biochemical models by making them difficult to understand, trust, or reuse. We comprehensively list the best practices that biochemical modelers should follow to build reproducible biochemical model artifacts-all data, model descriptions, and custom software used by the model-that can be understood and reused. The best practices provide advice for all steps of a typical biochemical modeling workflow in which a modeler collects data; constructs, trains, simulates, and validates the model; uses the predictions of a model to advance knowledge; and publicly shares the model artifacts. The best practices emphasize the benefits obtained by using standard tools and formats and provides guidance to modelers who do not or cannot use standards in some stages of their modeling workflow. Adoption of these best practices will enhance the ability of researchers to reproduce, understand, and reuse biochemical models., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Domestic minor sex trafficking (DMST) is an increasingly recognized traumatic crime premised upon the control, abuse, and exploitation of youth. By definition, DMST is the "recruitment, harboring, transportation, provision, or obtaining of a person for the purpose of a commercial sex act" within domestic borders, in which the person is a U.S. citizen or lawful permanent resident under the age of 18 years. The present study described the demographics, psychosocial features, and trafficking experiences (e.g., environments of recruitment, relationship to trafficker, solicitation) of DMST victims. A total of 25 medical records of patients under the age of 18 who disclosed their involvement in DMST to medical providers between August 1, 2013, and November 30, 2015, were retrospectively reviewed. The majority of patients were female, and the mean age was 15.4 years old. Most patients lived at home and/or were accompanied at the evaluation by a parent/guardian. High rates of alcohol or substance use/abuse (92%), being placed in a group home or child protective services (CPS) custody (28%), a history of runaway behavior (60%), and/or exposure to other child maltreatment (88%) were identified. Our data indicated variation in reported trafficking experiences; however, patients commonly reported an established relationship with their trafficker (60%) and recruitment occurred primarily as a result of financial motivation (52%). Patients were prevalently recruited in settings where there were face-to-face interactions (56%), whereas the solicitation of sex-buyers occurred primarily online (92%). Victims who disclosed involvement in DMST had complicated psychosocial histories that may have rendered them susceptible to their exploitation, and reported a variety of DMST experiences perpetuated by traffickers. Although preliminary in nature, this study provided empirical evidence of the predisposing factors, motivations, and experiences of victimized youth uniquely from the perspective of patients who sought medical care.

Background: Atherosclerosis of the carotid bifurcation with plaque formation causes asymptomatic carotid artery stenosis (ACAS), which may also be associated with cerebral hypoperfusion. Cerebral hypoperfusion adversely affects multiple aspects of mobility and cognition. This study tests the hypothesis that community-dwelling older adults with a 50% or greater diameter-reducing ACAS will have mobility and cognitive impairments that heighten their risk for falls., Methods: Eighty community-dwelling adults completed a mobility assessment (Short Physical Performance Battery, Berg Balance Scale, Four Square Step Test, Dynamic Gait Index, Timed Up and Go, and gait speed), self-reported physical function (Activities-Specific Balance Confidence, SF-12 Physical Function Component), and cognitive tests (Mini-Mental State Examination). Falls were recorded for the past 6 months. Standardized carotid ultrasound examination classified participants into no stenosis (<50% diameter reduction) (n = 54), moderate stenosis (50%-69%) (n = 17), and high-grade stenosis (70%-99%) (n = 9) groups. Linear and logistic regression analyses determined the associations between these measures and the degree of stenosis (three groups)., Results: Logistic regression analysis showed their degree of stenosis was associated with reductions in mobility (Short Physical Performance Battery [P = .008], Berg Balance Scale [P = .0008], Four Square Step Test [P = .005], DGI [P = .0001], TUG [P = .0004], gait speed [P = .02]), perceived physical function (ABC [P < .0001], SF-12 Physical Function Component [P < .0001]), and cognition (MMSE [P = .003]). Adults with moderate- and high-grade stenosis had a greater incidence of falls compared with those without stenosis (relative risk, 2.86; P = .01). Results remained unchanged after adjustment for age, sex and cardiovascular risk factors., Conclusions: ACAS is associated with impaired mobility and cognition that are accompanied with increased fall risk. These impairments increased with worsening severity., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Study Objective: To compare characteristics of patients with confirmatory evidence (eg, disclosure, found by law enforcement) of domestic minor sex trafficking (DMST) involvement with those without confirmatory evidence but who were suspected of involvement., Design: A retrospective chart review was conducted of all patients referred for DMST involvement. Confirmed DMST patients were compared with suspected patients with regard to demographic, psychosocial, medical, and psychiatric variables., Setting: A child protection program at a children's hospital where patients are evaluated by child abuse pediatricians in outpatient, emergency department, and inpatient settings., Participants: Patients 11-17 years old referred for concern of DMST involvement between August 1, 2013 and July 1, 2016 were included. Patients self-disclosed, had reported with evidence, and/or had histories that placed them at high risk for DMST involvement., Interventions and Main Outcome Measures: We collected data on demographic, psychosocial, medical, and psychiatric variables from the medical records of patients referred for evaluation., Results: A total of 67 patients were included. No statistically significant differences were identified between the confirmed and suspected groups., Conclusion: Our preliminary data showed that confirmed and suspected patients presented with similar and high rates of concerning medical and psychosocial issues; therefore, medical providers should evaluate and treat all patients referred for DMST. Similar treatment includes referrals for psychological/substance abuse interventions, safety planning, and collaboration with a multidisciplinary team., (Copyright © 2019 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Objectives: To determine the prevalence of incidental rib fractures identified by chest radiograph (CXR) obtained for indications unrelated to accidental trauma or nonaccidental trauma (NAT), and describe the histories associated with cases of incidental rib fractures and their proposed etiologies. It is hypothesized that incidental rib fractures are rare and alternative explanations for rib fractures occasionally used in a medico-legal context such as minor accidental trauma, undiagnosed medical conditions, and transient metabolic bone disturbances are unlikely to be the etiology of incidental rib fractures., Study Design: A retrospective chart review of sequential CXRs of children ages 0 to <2 years was conducted from January 1, 2011 to October 31, 2016. CXRs were obtained in the emergency department, general pediatric or intensive care units, or outpatient pediatric clinics. Data collected included demographics, CXR indication and findings, history of cardiopulmonary resuscitation, laboratory and additional imaging results, and incidental rib fracture descriptions and proposed etiologies., Results: A total of 7530 patients underwent 9720 CXRs associated with unique clinical encounters. Five CXRs had incidental rib fractures identified, making the prevalence of CXRs with incidental rib fractures in this cohort <0.1%. Of 5 identified incidental cases, mean age was 3.6 months, 3 were concerning for NAT, 1 was confirmed NAT, and 1 had radiographic findings consistent with osteopenia of prematurity., Conclusions: Identification of incidental rib fracture on CXR is rare. When detected in the absence of corresponding trauma history and/or objective laboratory or radiographic metabolic abnormalities, work-up for NAT should be pursued., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The study is to compare the Modified Physical Performance Test (MPPT) and Short Physical Performance Battery (SPPB) as metrics of mobility and function in older men with peripheral arterial disease (PAD)., Materials and Methods: A total of 51 men (55-87 years) with PAD underwent functional testing including the SPPB, MPPT, Walking Impairment Questionnaire (WIQ), stair ascent, and 6-min walk distance. Individuals were grouped according to SPPB and MPPT scores as not limited on either, limited only on the MPPT, or limited on both., Results: The MPPT identified a higher proportion of patients as being functionally limited than the SPPB (p < 0.001). Men identified as limited only by the MPPT, and not the SPPB, were subsequently confirmed to have lower function on all measures compared to those not identified as limited by either the SPPB or the MPPT (p < 0.02)., Conclusions: These findings suggest the MPPT is an appropriate measure to identify early declines in men with PAD and may identify global disability better than SPPB. Implications for rehabilitation Individuals with peripheral arterial disease have low activity levels and are at risk for a loss of independence and global disability. Early detection of decline in mobility and global function would allow for interventions before large changes in ambulatory ability or a loss of functional independence occur. This study shows the Modified Physical Performance Test may be an appropriate test to identify early decline in function in men with peripheral arterial disease.

Purpose: To compare the effects of adding a progressive multimodal rehabilitation program to usual care (MRP + UC) versus UC alone on 1) functional mobility, strength, endurance and 2) ventilator weaning and discharge status of patients with ICU-acquired weakness (ICUAW) receiving prolonged mechanical ventilation (PMV)., Methods: Randomized pilot trial of an individualized MRP + UC versus UC in middle-aged and older ICU survivors with ICUAW receiving PMV. Outcomes compare changes in strength, mobility, weaning success and discharge home from a long-term acute care hospital (LTACH) between the groups., Results: Eighteen males and 14 females (age 60.3 ± 11.9 years) who received PMV for ≥14 days were enrolled. Despite no significant differences between groups in the changes in handgrip, gait speed, short physical performance battery or 6-min walk distance after treatment, the MRP + UC group had greater weaning success (87% vs. 41%, p < 0.01), and more patients discharged home than UC (53 vs. 12%, p = 0.05). Post hoc analyses, combining patients based on successful weaning or discharge home, demonstrated significant improvements in strength, ambulation and mobility., Conclusion: The addition of an MRP that improves strength, physical function and mobility to usual physical therapy in LTACH patients with ICUAW is associated with greater weaning success and discharge home than UC alone., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Whole-cell computational models aim to predict cellular phenotypes from genotype by representing the entire genome, the structure and concentration of each molecular species, each molecular interaction, and the extracellular environment. Whole-cell models have great potential to transform bioscience, bioengineering, and medicine. However, numerous challenges remain to achieve whole-cell models. Nevertheless, researchers are beginning to leverage recent progress in measurement technology, bioinformatics, data sharing, rule-based modeling, and multi-algorithmic simulation to build the first whole-cell models. We anticipate that ongoing efforts to develop scalable whole-cell modeling tools will enable dramatically more comprehensive and more accurate models, including models of human cells., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Domestic minor sex trafficking (DMST) has become an increasingly recognized issue associated with both immediate and long-term physical and mental health consequences. Guidelines have focused on potential risk factors, recruitment practices, and health consequences for these youth assisting in identification and intervention efforts. However, recommendations have not been established for continuous medical intervention and follow-up for this vulnerable patient population that includes both patients involved in and at high risk for DMST. Our goal is to highlight preliminary recommendations for and the importance of medical visits for these youth. A comprehensive physical examination, STI testing and treatment, and pregnancy prevention options are important to address the patients' concerns for their body and identify acute and chronic injuries. Further, collaborating with other medical and non-medical providers can provide essential resources for the multifaceted needs of DMST patients.

Objective: Resistance training (RT) reduces fatigue and improves physical function and quality of life (QOL) in breast cancer survivors (BCS). This may be related to reductions in systemic and tissue-specific inflammation. This pilot study examines the hypothesis that RT induces changes in systemic and tissue-specific inflammation that contribute to improvements in physical and behavioral function in postmenopausal BCS., Methods: Eleven BCS (60 ± 2 years old, body mass index 30 ± 1 kg/m, mean ± SEM) underwent assessments of fatigue (Piper Fatigue Scale), physical function, QOL (SF-36), glucose and lipid metabolism, and systemic, skeletal muscle, and adipose tissue inflammation (n = 9) before and after 16 weeks of moderate-intensity whole-body RT., Results: Muscle strength improved by 25% to 30% (P < 0.01), QOL by 10% (P = 0.04), chair stand time by 15% (P = 0.01), 6-minute walk distance by 4% (P = 0.03), and fatigue decreased by 58% (P < 0.01), fasting insulin by 18% (P = 0.04), and diastolic and systolic blood pressure by approximately 5% (P = 0.04) after RT. BCS with the worst fatigue and QOL demonstrated the greatest improvements (absolute change vs baseline: fatigue: r = -0.95, P < 0.01; QOL: r = -0.82, P < 0.01). RT was associated with an approximately 25% to 35% relative reduction in plasma and adipose tissue protein levels of proinflammatory interleukin (IL)-6sR, serum amyloid A, and tumor necrosis factor-α, and 75% relative increase in muscle pro-proliferative, angiogenic IL-8 protein content by 75% (all P < 0.05). BCS with the highest baseline proinflammatory cytokine levels had the greatest absolute reductions, and the change in muscle IL-8 correlated directly with improvements in leg press strength (r = 0.53, P = 0.04)., Conclusions: These preliminary results suggest that a progressive RT program effectively lowers plasma and tissue-specific inflammation, and that these changes are associated with reductions in fatigue and improved physical and behavioral function in postmenopausal BCS.

Whole-cell dynamical models of human cells are a central goal of systems biology. Such models could help researchers understand cell biology and help physicians treat disease. Despite significant challenges, we believe that human whole-cell models are rapidly becoming feasible. To develop a plan for achieving human whole-cell models, we analyzed the existing models of individual cellular pathways, surveyed the biomodeling community, and reflected on our experience developing whole-cell models of bacteria. Based on these analyses, we propose a plan for a project, termed the Human Whole-Cell Modeling Project , to achieve human whole-cell models. The foundations of the plan include technology development, standards development, and interdisciplinary collaboration.

Objective: To determine the 6-month follow-up effects after intentional 6-month weight loss alone (WL) and after weight loss with aerobic exercise (AEX + WL) on body composition, glucose metabolism, and cardiovascular disease risk factors in older postmenopausal women and to identify the mechanisms for weight regain., Methods: Women (n = 65, BMI > 25 kg/m 2 ) underwent maximal oxygen consumption testing, dual-energy x-ray absorptiometry, computed tomography scans, and oral glucose tolerance tests before and after 6 months of AEX + WL or WL and at 12 months ad libitum follow-up. Insulin sensitivity (M) (hyperinsulinemic-euglycemic clamp) was measured at baseline and 6 months. Thirty WL and thirty-five AEX + WL women completed a follow-up at 12 months., Results: Similar weight loss was observed (-8%) in both groups from 0 to 6 months. Total fat mass, fat-free mass, visceral fat area, subcutaneous abdominal and midthigh fat areas, fasting glucose, insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), insulin areas under the curve, and triglyceride levels decreased similarly after WL and AEX + WL and remained lower at 12 months than at baseline, despite weight regain at 12 months. Initial M was associated with weight regain (r = -0.40, P < 0.01). Weight regain was related to independent changes in leptin and HOMA-IR from 6 to 12 months in a multiple regression model (r = 0.77, P < 0.0001)., Conclusions: Reductions in body fat and improvements in insulin sensitivity after AEX + WL and WL were maintained at 12 months despite modest weight regain. Baseline insulin resistance partially predicted the magnitude of weight regain in postmenopausal women., (© 2017 The Obesity Society.)

After an acute sexual assault, children and adolescents often present for medical evaluation and treatment. Physicians have an important role in both the medical and legal components of these cases. Careful physical examination and questioning are important in determining the origin of the trauma. In the presented case report, genital trauma after an acute sexual assault was noted and attributed to the alleged offender's penis piercing. The genital trauma caused by the piercing provided physical evidence linking offender to victim and may have implications for the victim's risk of HIV infection and other blood borne pathogens., (Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)