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OBJECTIVE To provide updated information on the distribution of histopathologic types of primary pulmonary neoplasia in dogs and evaluate the effect of postoperative adjuvant chemotherapy in dogs with pulmonary carcinoma. ANIMALS 340 dogs. PROCEDURES Medical records of dogs that underwent lung lobectomy for removal of a primary pulmonary mass were reviewed, and histopathologic type of lesions was determined. The canine lung carcinoma stage classification system was used to determine clinical stage for dogs with pulmonary carcinoma. RESULTS Pulmonary carcinoma was the most frequently encountered tumor type (296/340 [87.1%]), followed by sarcoma (26 [7.6%]), adenoma (11 [3.2%]), and pulmonary neuroendocrine tumor (5 [1.5%]); there was also 1 plasmacytoma and 1 carcinosarcoma. Twenty (5.9%) sarcomas were classified as primary pulmonary histiocytic sarcoma. There was a significant difference in median survival time between dogs with pulmonary carcinomas (399 days), dogs with histiocytic sarcomas (300 days), and dogs with neuroendocrine tumors (498 days). When dogs with pulmonary carcinomas were grouped on the basis of clinical stage, there were no significant differences in median survival time between dogs that did and did not receive adjuvant chemotherapy. CLINICAL RELEVANCE Results indicated that pulmonary carcinoma is the most common cause of primary pulmonary neoplasia in dogs; however, nonepithelial tumors can occur. Survival times were significantly different between dogs with pulmonary carcinoma, histiocytic sarcoma, and neuroendocrine tumor, emphasizing the importance of recognizing the relative incidence of these various histologic diagnoses. The therapeutic effect of adjuvant chemotherapy in dogs with pulmonary carcinoma remains unclear and warrants further investigation.

Physicians often make diagnosis and treatment decisions based on incomplete data. That is why we practice medicine. We use accumulated knowledge and prior experience, individual and collective, to restore form and function of our patients to return them to normalcy with continued, durable homeostasis. However, due to the complex nature, our diagnosis may be wrong and our treatments ineffective or even harmful. The history of medicine and surgery is replete with such examples from snake oil and bloodletting to Halstedian radical mastectomy. Without knowing the governing dynamics, the cause-effect relationship is often obscure. Prospective, blinded, placebo-controlled trials provide the highest level of evidence, like the COVID vaccine trials, to determine if a treatment works. However, trials cannot explain in detail how and why a treatment works, or why it does not. Variabilities and uncertainty abound and require the correct mathematical methods to tease out the signal from the noise, causality from association. Collectively, statistics is the science of uncertainty and the extraction of reliable, useful information from raw data. The objectives of this review are to provide craniofacial surgeons with a primer in descriptive statistics: how to design investigations, collect, prepare, present, and interpret clinical data. Since large datasets at regional and national depositories represent powerful and valuable resources, and that their proper use requires a working knowledge in epidemiology, we included sections on incidence, prevalence, sensitivity, and specificity regarding diagnosis, treatments, and testing.

Voxel-based morphometry (VBM) studies of gray matter volume (GMV) in psychopathy have produced inconsistent results and few have been replicated. Therefore, to clarify GMV abnormalities associated with psychopathy as operationalized by Hare (2003), we conducted a meta-analysis of VBM studies using both categorical and dimensional analyses. We identified seven studies eligible for the categorical meta-analysis (136 men with psychopathy vs 150 male controls) and 11 studies (N = 519) eligible for dimensional metaregressions. First, we used seed-based d mapping with permutation of subject images for voxel-based meta-analyses. Statistical parametric maps of GMV were available for four (57%) of the studies included in the categorical meta-analysis and for five (45%) of the studies included in the dimensional metaregression analyses, with peak coordinates available for the remaining studies. Second, we used metadata of a large-scale neuroimaging database to provide an objective and quantitative account of psychological processes attributed to the brain regions we identified in our group meta-analysis and metaregressions. Men with psychopathy exhibited reliable GMV abnormalities circumscribed to the left hemisphere in the dorsolateral prefrontal cortex and the medial orbitofrontal cortex. Total psychopathy scores and Factors 1 and 2 scores were all related to decreased GMV within those two prefrontal regions, as well as decreased GMV in a wider set of regions encompassing midline, temporal, parietal, occipital, and subcortical structures. We discuss how decreased GMV in those regions likely account for the impairments in the emotion, cognition, action, and perception domains seen in the disorder. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background The coronavirus disease 2019 pandemic spread to >200 countries in Methods Given high residence hall student density, the University of Colorado Boulder established a mandatory weekly screening test program. We analyzed longitudinal data from 6408 students and identified 116 likely transmission events in which a second roommate tested positive within 14 days of the index roommate. Results Although the infection rate was lower in single-occupancy rooms (10%) than in multiple-occupancy rooms (19%), interroommate transmission occurred only about 20% of the time. Cases were usually asymptomatic at the time of detection. Notably, individuals who likely transmitted had an average viral load approximately 6.5-fold higher than individuals who did not (mean quantification cycle [Cq], 26.2 vs 28.9). Although students with diagnosed SARS-CoV-2 infection moved to isolation rooms, there was no difference in time to isolation between cases with or without interroommate transmission. Conclusions This analysis argues that interroommate transmission occurs infrequently in residence halls and provides strong correlative evidence that viral load is proportional to transmission probability.

The use of simulated patients (SPs) in pharmacy practice research has become an established method to observe practice. The reliability of data reported using this method in comparison to pharmacy staff self-reported behaviour has yet to be ascertained.To compare the inter-rater agreement of pharmacy staff and SP-reported data to researcher-reported data from audio recordings of SP encounters.A dataset of 352 audio-recorded SP encounters was generated in March-October 2015 by 61 undergraduate pharmacy students completing SP visits to 36 community pharmacies in Sydney, Australia. Post-visit scores were recorded on data collection forms by SPs. Staff completed self-assessments on identical forms immediately after the encounter. Two-hundred-and-seventy visits were randomly selected as the sample for this study, where the researcher independently scored encounters via audio recordings. Inter-rater agreement was calculated through intra-class correlation (ICC) and weighted kappa analyses.Analysis of staff scores returned ICC values of 0.48 (95% CI:0.38-0.56; p 0.001) for information gathering and 0.63 (95% CI:0.55-0.70; p 0.001) for total score. Weighted kappa for information rating was 0.30 (95% CI:0.21-0.38; p 0.001) and 0.43 (95% CI:0.34-0.51; p 0.001) for overall outcome. ICC values for SPs were 0.91 (95% CI:0.88-0.93; p 0.001) and 0.90 (95% CI:0.87-0.92; p 0.001) for information gathering and total scores respectively. Weighted kappa values were 0.44 (95% CI:0.37-0.52; p 0.001) for information rating and 0.63 (95% CI:0.55-0.70; p 0.001) for overall outcome.Pharmacy staff self-reported their behaviour with a poor degree of reliability. Conversely, SPs had a high level of agreement with the researcher scoring from audio recordings. Disagreement for both groups of raters was most apparent in rating the information provided and overall appropriateness of outcome. Future research should investigate this discrepancy between staff-reported behaviour and actual behaviour and consider the implications of this discrepancy in the interpretation of self-reported data.

Background Vertebral compression fractures (VCFs) are the most common among all osteoporotic fractures. The body may compensate to the kyphosis from vertebral compression fractures with lordosis of the adjacent spinal segments, rotation of the pelvis, knee flexion and ankle dorsiflexion. However, the detailed degree of body compensation, especially the lower limb, remains uncertain. Herein, the aim of this study is to investigate the values of global sagittal alignments (GSA) parameters, including the spine, pelvis and lower limbs, in patients with and without VCFs, as well as to evaluate the effect of VCFs on various quality of life (QoL) parameters. Methods A cross-sectional study was conducted from May 2015 to June 2018. A total of 142 patients with VCFs aged over 60 years old and 108 age-matched asymptomatic controls were recruited. Whole body sagittal alignment including thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), sagittal vertical axis (SVA), T1-pelvic angle (TPA), knee-flex angle (KA) and ankle-flex angle (AA) were measured. In addition, lower back pain and quality of life were assessed using self-reported questionnaires. Results Compared to asymptomatic controls, patients with VCF showed significantly greater TK (33.4o ± 16.4o vs 28.4o ± 11.4o; p o ± 10.5o vs 16.6o ± 8.9o; p o ± 11.8o vs 45.8o ± 12.0o; p p o ± 10.8o vs 14.8o ± 8.6o; p o ± 7.8o vs 6.0o ± 6.4o; p o ± 3.9o vs 4.8o ± 3.6o; p p p p Conclusion This is the first study to illustrate the abnormal lower limb alignment exhibited in patients with VCF. Patients with VCF showed an overall worse global sagittal alignment and decreased quality of life. Poorer global sagittal alignment of VCF patients also imply worse quality of life and more severe VCF.

Adolescent idiopathic scoliosis (AIS) is the most common spinal disorder in children. A severity index was recently proposed to identify the stable from the progressive scoliosis at the first standardized biplanar radiographic exam. The aim of this work was to extend the validation of the severity index and to determine if curve location influences its predictive capabilities. AIS patients with Cobb angle between 10° and 25°, Risser 0–2, and no previous treatment were included. They underwent standing biplanar radiography and 3D reconstruction of the spine and pelvis, which allowed to calculate their severity index. Patients were grouped by curve location (thoracic, thoracolumbar, lumbar). Patients were followed up until skeletal maturity (Risser ≥ 3) or brace prescription. Their outcome was compared to the prediction made by the severity index. In total, 205 AIS patients were included; 82% of them (155/189, 95% confidence interval [74–90%]) were correctly classified by the index, while 16 patients were unclassified. Positive predictive ratio was 78% and negative predictive ratio was 86%. Specificity (78%) was not significantly affected by curve location, while patients with thoracic and lumbar curves showed higher sensitivity (≥ 89%) than those with thoracolumbar curves (74%). In this multicentric cohort of 205 patients, the severity index was used to predict the risk of progression from mild to moderate scoliosis, with similar results of typical major curve types. This index represents a novel tool to aid the clinician and the patient in the modulation of the follow-up and, for progressive patients, their decision for brace treatment. • The severity index of adolescent idiopathic scoliosis has the potential to detect patients with progressive scoliosis as early as the first exam. • Out of 205 patients, 82% were correctly classified as either stable or progressive by the severity index. • The location of the main curve had small effect on the predictive capability of the index.

Introduction Diabetes and bone health are closely related. We examined the incidence and risk factors of hip fractures in Chinese patients with type 2 diabetes (T2D). Materials and Methods In this prospective cohort, we consecutively enrolled 22,325 adults with T2D above the age of 40 years in the Hong Kong Diabetes Register between 1994 and 2015 with crude hip fracture incidence rate censored in 2017. Results At baseline, the mean age of this cohort was 60.9 ± 10.5 years (mean duration of diabetes 6 years, 52.4% male). During a mean ± standard deviation (SD) follow‐up period of 8.7 ± 5.2 years with 193,553 person‐years, 603 patients were hospitalized due to hip fractures with an incidence (95% confidence interval, CI) of 315.1 (290.4–341.3) per 100,000 person‐years. On multivariable analysis with competing death risk adjusted, the independent hazard ratios (95% CI) for hip fractures in T2D were 2.01 (1.61–2.51) for female sex, 1.08 (1.07–1.09) for age, 0.93 (0.90–0.95) for body mass index, 1.52 (1.25–1.85) for albuminuria and 1.12 (1.02–1.23) for low density lipoprotein‐cholesterol. In men, the 30‐day, 1‐year and 5‐year post‐hip fracture mortality rate (95% CI) were 5.8 (2.4–9.1) %, 29.2 (22.3–35.5) % and 65.9 (57.3–72.8) % respectively. The corresponding rates in women were 3.4 (1.6–5.1) %, 18.6 (14.7–22.4) %, and 46.8 (40.9–52.1) %. Conclusions Southern Chinese patients with T2D have a high risk of hip fracture associated with suboptimal cardiometabolic‐renal risk factors and a high post‐fracture mortality rate. The effects of improving modifiable risk factors on bone health warrants further evaluation., With prospective follow up of nearly 9 years, we identified several risk factors associated with increase hip fracture incidence in Southern Chinese patients with type 2 diabetes in the Hong Kong Diabetes Register. These include female sex, age, body mass index, albuminuria and low density lipoprotein.

The association between the risk of fractures and suboptimal vitamin D (Vit-D) status remains controversial in children. This meta-analysis suggested that serum 25(OH)Vit-D levels were lower in pediatric cases with fractures. 25-hydroxyvitamin D (25(OH)Vit-D) levels less than 50 nmol/L were associated with increased fracture risk in children. This study aimed to assess the association between serum 25(OH)Vit-D and the risk of fractures in children, and to explore the sources of heterogeneity and investigate their impact on results. Systematic review and meta-analysis were conducted for observational studies comparing serum 25(OH)Vit-D levels between fracture and non-fracture pediatric cases. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Analysis on 17 case-control and 6 cross-sectional studies (2929 fracture cases and 5000 controls) suggested that 25(OH)Vit-D was lower in fracture cases than in controls (pooled mean difference (MD) = − 3.51 nmol/L; 95% confidence interval (CI): − 5.60 to − 1.42) with a heterogeneity (I2) of 73.9%. The sensitivity analysis which merged the case-control studies that had a NOS score ≥ 4 showed a pooled MD of − 4.35 nmol/L (95% CI: − 6.64 to − 2.06) with a heterogeneity (I2) of 35.9%. Pooled odds ratio of fracture in subjects with 25(OH)Vit-D ≤ 50 nmol/L compared to subjects with 25(OH)Vit-D > 50 nmol/L was 1.29 (95% CI: 1.10 to 1.53; I2 < 1%). This study indicated that serum 25(OH)Vit-D levels were lower in pediatric patients with fractures. 25(OH)Vit-D ≤ 50 nmol/L was associated with increased fracture risk in children.

Author(s): Jabola, Raymond; Boswell, Benjamin; Lutz, Robert H.; Casey, Jack; Ceraulo, Anthony | Abstract: Introduction: Spinal cord injuries are a common reason for presentation to the emergency department (ED). Sports-related spinal injuries are one of the least common spinal injuries, falling behind vehicular accidents, acts of violence, and falls.Case Report: This case report describes a case of transient quadriplegia in a 17-year-old male who presented to the ED after a helmet-to-helmet collision while participating in football.Conclusion: Emergency physicians should be cognizant of potential spinal cord injury using clinical decision tools and radiologic imaging to properly disposition a patient presenting with cervical spine injury.

ObjectivesWe assessed whether the presence and character of a cardiac murmur in adolescents were associated with structural heart disease that confers risk of sudden cardiac death (SCD).MethodsWe performed a retrospective analysis of 15 141 adolescents age 12–19 who underwent a heart screen with history, physical examination and ECG. Participants with any screening abnormality underwent an echocardiogram for the assessment of structural heart disease. Murmurs were classified as physiological or pathological according to standard clinical criteria, and participants with murmurs were compared with a comparison group without murmurs. The primary outcome was echocardiogram-detected structural heart disease associated with SCD.Results905 participants with a cardiac murmur (mean age 15.8; 58% male) and 4333 participants without a murmur (comparison group; mean age 15.8; 55% male) had an echocardiogram to detect structural heart disease. 743 (82%) murmurs were described as physiological and 162 (18%) as pathological. Twenty-five (2.8%) participants with murmurs and 61 (1.4%) participants without murmurs had structural heart disease. Three (0.3%) participants in the murmur group were diagnosed with hypertrophic cardiomyopathy (HCM) which was the only identified condition associated with SCD. Two participants with HCM had physiological murmurs, one had a pathological murmur, and all three had an abnormal ECG. The most common minor structural heart disease was bicuspid aortic valve in both the murmur (7; 0.8%) and comparison (20; 0.5%) groups. The positive predictive value of physiological versus pathological murmurs for identifying any structural heart disease was 2.4% versus 4.3% (p=0.21), respectively. The positive predictive value of having any murmur versus no murmur for identifying structural heart disease was 2.8% versus 1.4% (p=0.003), respectively.ConclusionsIn adolescents, the traditional classification of cardiac murmurs as ‘physiologic’ or ‘pathologic’ does not differentiate for structural heart disease that puts individuals at risk for SCD. We recommend ECG evaluation in all patients with a cardiac murmur found during preparticipation screening to increase detection of HCM.

ExAblate received FDA approval for treatment of a range of movement disorders in 2016, including tremor-dominant Parkinson’s disease (TDPD), dyskinetic PD, and essential tremor. This incisionless device allows for magnetic resonance-guided focused ultrasound (MRgFUS) for ablation of several regions of interest. Current studies should aim to measure pre- and post-operative neurocognitive functioning to better understand MRgFUS in PD and how it compares to deep brain stimulation, which has known cognitive risks among certain populations. PubMed, CINAHL, PsycINFO, and Cochrane Library databases were searched from January 2016 to January 2020. Guidelines for Preferred Reporting Items for Systematic Review and Meta-Analyses were used to review clinical trials comprehensively assessing pre- and post-operative neurocognitive functioning in PD patients undergoing MRgFUS. Due to limited extant literature in this area, TDPD was expanded to PD with severe dyskinesia. Twenty-two abstracts were reviewed following removal of duplicates. After full-text review of eight articles, only two studies included comprehensive neuropsychological evaluations of PD patients undergoing MRgFUS thalamotomy or pallidotomy. Most excluded studies used only brief cognitive screeners to assess functioning. Cognitive declines appear to be minimal following MRgFUS in PD, with exceptions in verbal fluency and inhibition. These results are limited by sample size and sample diversity. Significant methodological gaps were inadvertently discovered. Few studies to-date have administered comprehensive neuropsychological batteries to ascertain MRgFUS risks to neurocognitive functioning in PD. Studies must extend beyond brief screeners when assessing PD populations vulnerable to decline. Furthermore, consensus on a comprehensive battery would better serve replicability and the ability to engage in useful meta-analyses.

STUDY DESIGN A case-control association study. OBJECTIVES The aim of this study was to investigate whether CHD7 was associated with adolescent idiopathic scoliosis in Chinese Han population and to further explore the functional role of CHD7 in the development of adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA Several studies have explored the association of CHD7 with scoliosis in patients of European descent, while the results were inconsistent. There was a lack of study investigating the association of CHD7 with AIS in Chinese Han population. METHODS Variants within CHD7 were genotyped in 965 AIS patients and 976 healthy controls. Whole exome sequencing was performed in 96 AIS patients. Paraspinal muscles of 43AIS patients and 38 lumbar disc herniation patients were collected for the evaluation of the gene expression. Intergroup comparison was performed with the χ2 test for genotyping data or Student t test for tissue expression. The relationship of CHD7 expression with clinical phenotypes was determined by the Pearson correlation. RESULT Variant rs121434341 of CHD7 was significantly associated with AIS. AIS patients were found to have a remarkable higher frequency of allele G when compared with healthy controls (2.89% vs. 1.57%, P = 0.0018), with an odds ratio value of 1.89. A pathogenic mutation affecting normal splicing was identified in a patient. Moreover, the expression level of CHD7 in AIS patients was significantly lower than in the controls (0.0008437 ± 0.00004583 vs. 0.001129 ± 0.00003773, P

Objective: Activation of the maternal immune (MIA) system while pregnant can have significant effects on fetal development. Here, the authors sought to examine MIA and its effects on fetal craniofacial formation. As a measure of MIA, data on maternal influenza infection was used, as influenza occurs in a predictive fashion, is not vertically transmitted, and is found to generate a robust maternal immune response. Thus, this study measures the association of the incidence of influenza infection in the United States with the incidence of craniofacial congenital deficits—specifically encephalocele and microtia. Methods: The National Inpatient Sample Database (NIS) was referenced to identify national estimates of infants born with each disease from 2004 to 2013. The gross monthly disease incidences were adjusted based on the number of newborns each month. The National Respiratory and Enteric Virus Surveillance System’s FluView database from the CDC was used to obtain influenza data from 2003 to 2013. Mixed effect logistic regression analyses were conducted to find the association between influenza occurrence and each disease, specifically an odds ratio (OR). Results: There were 2858 infants born with encephalocele and 3371 born with microtia from January 2004 to December 2013. Microtia showed no statistically significant correlation with influenza rates and served as a methodologic control. Encephalocele, however, showed a strong correlation with influenza infection specifically during the eighth month of pregnancy (OR = 34.538, 95% confidence interval: 3.815-312.681). Conclusion: This study shows a strong correlation between maternal influenza infection during the eighth month of pregnancy and encephalocele incidence. This suggests that there is an additional trigger for encephalocele development towards the end of the pregnancy not currently understood in the literature. Although there appears to be a connection between MIA and encephalocele formation, more research is needed to confirm this theory.

Objective: Maternal immune activation secondary to influenza infection during critical periods of fetal development is a significant risk factor for neuropsychiatric and neurodevelopmental disorders. The association between influenza and craniosynostosis is not well documented. We investigate the association between the incidence of influenza infection and incidence of craniosynostosis in the United States. Materials and Methods: Retrospective population-based observational study spanning using the National Inpatient Sample Database, the United States Center for Disease Control and Prevention FluView databases, including infants born with craniosynostosis in the United States from 2004 to 2013 and monthly influenza incidence in the United States from 2003 to 2013. Mixed-effects logistic regression tested the association between 2 variables: national influenza incidences and rate of craniosynostosis. Odds ratios were calculated for the occurrence of craniosynostosis in relation to previous months’ flu incidence. E-values were calculated to evaluate unmeasured confounders. Results: Retrospective analysis performed on 45 356 newborns with craniosynostosis. Mixed-effects logistic regression revealed for each additional influenza case per 1000 people, the odds of craniosynostosis event occurring 6 months later increased by 3.4 (adjusted P = .009, OR = 3.444, CI = 1.756-6.754). For each additional influenza case per 1000 people, the odds of craniosynostosis event occurring 7 and 2 months later decreased by 3.8 and 6.1, respectively (OR = 0.262 and 0.165; adjusted P value = .007 and

Objective: Viral infections during pregnancy can cause disturbance in normal craniofacial morphogenesis. While some pathogens such as cytomegalovirus and herpes simplex are familiar to us, others remain obscure. This review examines the arbovirus-induced cranial deformities and combines biomechanics with growth dynamics to gain a deeper appreciation of this complex morphogenetic process. Materials and Methods: Using Wolfram Alpha, we analyzed the impact of cell population changes. The growth dynamics of the brain, and thus the size of the calvarium, followed 2 potential logistic curves: compensated and uncompensated. To understand the potential mechanism of cell loss, we performed literature review on maternal immune activation and viral tropism for neurons and glial cells. Results: With arboviral infections such as Zika, uncompensated loss of cells during the critical phases of fetal brain development reduces the intracranial mass and therefore decreases the tensile stress across the cranial sutures. The deflationary effect produces microcephaly by subduction and reduced osteogenesis seen clinically in these infants. Conclusion: Many viral infections cause intense maternal immune activation, some have neurotropism and can result in cell loss within the developing cranium. Unable to overcome this loss, the cranium assumes a new, abnormal shape and volume. Secondary calvarial deformities is due to, and should not cause, changes in brain development.

This review attempts to examine two key elements in the evolution of cognitive impairment in the elderly who develop heart failure. First, major left side heart parts can structurally and functionally deteriorate from aging wear and tear to provoke hemodynamic instability where heart failure worsens or is initiated; second, heart failure is a major inducer of cognitive impairment and Alzheimer's disease in the elderly. In heart failure, when the left ventricular myocardium of an elderly person does not properly contract, it cannot pump out adequate blood to the brain, raising the risk of cognitive impairment due to the intensification of chronic brain hypoperfusion. Chronic brain hypoperfusion originates from chronically reduced cardiac output which progresses as heart failure worsens. Other left ventricular heart parts, including atrium, valves, myocardium, and aorta can contribute to the physiological shortfall of cardiac output. It follows that hemodynamic instability and perfusion changes occurring from the aging heart's blood pumping deficiency will, in time, damage vulnerable brain cells linked to specific cognitive regulatory sites, diminishing neuronal energy metabolism to a level where progressive cognitive impairment is the outcome. Could cognitive impairment progress be reversed with a heart transplant? Evidence is presented detailing the errant hemodynamic pathways leading to cognitive impairment during aging as an offshoot of inefficient structural and functional heart parts and their contribution to heart failure.

The COVID-19 pandemic has been met with studies on risk factors, characteristics, and clinical course. Among these characteristics are neurologic symptoms, which may provide improved insight into the mechanisms of this novel virus and the brain's susceptibility to infectious diseases. This article aims to discuss 1) findings related to neurologic complications, 2) how they connect to and are bidirectionally impacted by bioimmunology, 3) how this combination of biological mechanisms impact and are impacted by psychosocial stressors, and 4) the importance of considering potential neurodegenerative consequences of COVID-19. Longitudinal studies on neuropathology and cognition are critical to avoiding premature conclusions related to long-term neurologic effects.

Context Glucagon acts reciprocally with insulin to regular blood glucose. However, the effect of glucagon on cardiovascular disease has not been widely studied. It has been suggested that insulin may increase the risk of ischemic heart disease. Objective To investigate whether glucagon, the main counteracting hormone of insulin, plays a role in development of ischemic heart disease. Design, Setting, and Participants In this 2-sample Mendelian randomization study, we estimated the causal effect of glucagon on ischemic heart disease and its risk factors using the inverse-variance weighted method with multiplicative random effects and multiple sensitivity analyses. Genetic associations with glucagon and ischemic heart disease and its risk factors, including type 2 diabetes and fasting insulin, were obtained from publicly available genome-wide association studies. Main Outcome Measure Odds ratio for ischemic heart disease and its risk factors per 1 standard deviation change in genetically predicted glucagon. Results Twenty-four single-nucleotide polymorphisms strongly (P < 5 × 10−6) and independently (r2 < 0.05) predicting glucagon were obtained. Genetically predicted higher glucagon was associated with an increased risk of ischemic heart disease (inverse-variance weighted odds ratio, 1.03; 95% confidence interval, 1.0003-1.05) but not with type 2 diabetes (inverse-variance weighted odds ratio, 0.998, 95% confidence interval, 0.97-1.03), log-transformed fasting insulin (inverse-variance weighted beta, 0.002, 95% confidence interval, -0.01 to 0.01), other glycemic traits, blood pressure, reticulocyte, or lipids. Conclusion Glucagon might have an adverse impact on ischemic heart disease. Relevance of the underlying pathway to existing and potential interventions should be investigated.

BACKGROUND Over the past 20 years, innovations in microsurgical technique have coincided with advances in orthoplastic approaches. However, no single algorithm exists to guide management of limb salvage versus amputation. As such, one would expect these procedures to be performed at equal rates given studies showing similar outcomes. Anecdotally, the observation at the authors' institution is that amputations are being performed more frequently. The purpose of this study was to determine trends in lower extremity trauma management. METHODS A retrospective cohort study was conducted at a Level I trauma center on patients with Gustilo type IIIB/IIIC lower extremity trauma from 2005 to 2014. Overall, 148 patients were included. Patients were subdivided into amputation (n = 69) and reconstruction (n = 79) cohorts. The Spearman rank correlation coefficient was used to compare trends in amputation and reconstruction groups. Plastic surgery consultation data were analyzed using the Mann-Whitney U and chi-square tests and the Pearson correlation coefficient. RESULTS Amputation was performed more frequently over the study period (r = 0.292; p < 0.001). Plastic surgeons were consulted in 67.5 percent of cases. A plastic surgery consultation was obtained in only 30 percent of amputation cases (p < 0.001). CONCLUSIONS Although the data show a trend toward amputation and a shift in management of lower extremity trauma, the observed trend may be attributable in part to deviation from an orthoplastic approach to lower extremity trauma. However, lower extremity reconstruction remains a viable option in select patients, and advances in microsurgery can provide excellent outcomes in the face of severe lower extremity trauma.

An 8-year-old, Caucasian, and right-handed female presented for a baseline neuropsychological evaluation due to diagnosis of electrical status epilepticus during sleep (ESES) preceded by postictal, late-night discovery of the patient on the floor and subsequent overnight electroencephalography. This first recognized seizure was tonic-clonic. The patient was born at 39 weeks gestation weighing approximately 5 lb, subsequently spending 48 h in NICU due to low birth weight and hypoglycemia. Developmental milestones were recalled within normal limits (WNL). The patient is prescribed levetiracetam, clobazam, and acetazolamide and has undergone multiple EEGs since diagnosis. Remaining medical history unremarkable including absence of known head trauma. Family history is remarkable for anxiety and developmental disability. Tests suggest global impairment, particularly in motor abilities and processing speed. Academic achievement is average across basic reading and writing, but verbal learning and memory are significantly diminished unless in story form. Evidence of impulsivity and inattention were present along with deficits in mathematics. Affect recognition was intact and tests of cognitive flexibility and planning were discontinued. ESES generally presents early and results in neuropsychological deficits that are dependent upon length of condition and frequency and intensity of seizures. While deficits may improve when ESES subsides in pre-pubescence, some may persist into adulthood with high outcome variability. Baseline and ongoing neuropsychological testing are critical to early, targeted interventions and ongoing care. When early baselines are not feasible, it is important to construct a detailed, data-driven conceptualization to accommodate potential factors involved in notable deficits.

INTRODUCTION Autologous fat grafting (AFG) is a popular and effective method of breast reconstruction after mastectomy; however, the oncological safety of AFG remains in question. The aim of this study was to determine whether AFG increases the risk of cancer recurrence in the reconstructed breast. METHODS A matched, case-control study was conducted from 2000 to 2017 at the senior author's institution. Inclusion was limited to female patients who underwent mastectomy and breast reconstruction with or without AFG. Data were further subdivided at the breast level. χ analyses were used to test the association between AFG status and oncologic recurrence. A Cox proportional-hazards model was constructed to assess for possible differences in time to oncologic recurrence. The probability of recurrence was determined by Kaplan-Meier analyses and confirmed with log-rank testing. RESULTS Overall, 428 breasts met study criteria. Of those, 116 breasts (27.1%) received AFG, whereas 312 (72.9%) did not. No differences in the rates of oncologic recurrence were found between the groups (8.2% vs 9.0%, P < 1.000). Unadjusted (hazard ratio = 1.03, confidence interval = 0.41-2.60, P < 0.957) and adjusted hazard models showed no statistically significant increase in time to oncologic recurrence when comparing AFG to non-AFG. In addition, no statistical differences in disease-free survival were found (P = 0.96 by log rank test). CONCLUSION Autologous fat grafting for breast reconstruction is oncologically safe and does not increase the likelihood of oncologic recurrence. Larger studies (eg, meta analyses) with longer follow-up are needed to further elucidate the long-term safety of AFG as a reconstructive adjunct.

With an aging population, cost containment and improved outcomes will be crucial for a sustainable healthcare ecosystem. Current data demonstrate great variation in payments for procedures and diagnostic workup of benign prostatic hyperplasia (BPH). To help determine the best financial value in BPH care, we sought to analyze the major drivers of total payments in BPH. Commercial and Medicare claims from the Truven Health Analytics Markestscan® database for the Austin, Texas Metropolitan Service Area from 2012 to 2014 were queried for encounters with diagnosis and procedural codes related to BPH. Linear regression was utilized to assess factors related to BPH-related payments. Payments were then compared between surgical patients and patients managed with medication alone. Major drivers of total payments in BPH care were operative, namely transurethral resection of prostate (TURP) [$2778, 95% CI ($2385–$3171), p

Chronic Azithromycin (AZM) is a common treatment for lung infection. Among adults at risk of cardiac events, AZM use has been associated with cardiovascular harm. We assessed cardiovascular safety of AZM among children with CF, as a secondary analysis of a placebo-controlled, clinical trial, in which study drug was taken thrice-weekly for a planned 18 months. Safety assessments using electrocardiogram (ECG) occurred at study enrollment, and then after 3 weeks and 18 months of participation. Among 221 study participants with a median of 18 months follow-up, increased corrected QT interval (QTc) of ≥30 msec was rare, at 3.4 occurrences per 100 person-years; and incidence of QTc prolongation was no higher in the AZM arm than the placebo arm (1.8 versus 5.4 per 100 person-years). No persons experienced QTc intervals above 500 msec. Long-term chronic AZM use was not associated with increased QT prolongation.

Tracheoesophageal fistula (TEF) is an abnormal connection between the trachea and esophagus. Rare acquired TEF arises from trauma, caustic fluids ingestion, and iatrogenic injuries (ventilation, esophageal atresia repair, radiation, or tracheal/esophageal stents). We discuss the diagnosis, anesthetic management, and surgical correction of battery swallow‐induced TEF, not previously reported in the pediatric anesthesia and otorhinolaryngology literatures., Battery swallow‐induced tracheoesophageal fistula (TEF) is a rare, life‐threatening condition with increasing incidence requiring adequate preparation, understanding of TEF anatomy, and excellent communication among all involved in the care of these pediatric critical airways.

Background: Adolescent idiopathic scoliosis (AIS) patients have lower physical activity levels than normal adolescents, and there is an association with poorer bone and muscle health. This study evaluated the effects of a home-based exercise intervention (E-Fit) on bone mineral density (BMD), muscle function, and quality of life (QoL) in AIS-affected girls. Methods: A total of 40 AIS females aged 11 to 14 years were randomly assigned to the E-Fit or control group. The E-Fit group performed modified 7-min high-intensity interval training (HIIT) 5 days per week for 6 months. Outcome measures including BMD using dual-energy X-ray absorptiometry (DXA), muscle strength and endurance tests, physical activity levels, and QoL using self-reported questionnaires were assessed at baseline and at 6-month and 12-month follow-up. Results: In total, 14 patients in the E-Fit and 16 in the control group completed the study. The E-Fit group showed a marginally significant interaction effect in the whole body areal BMD at the 6- (p = 0.096) and 12-month follow-ups (p = 0.085). The left arm lean mass in the E-Fit group showed a statistically significant interaction effect between the 6- and 12-month follow-ups (p = 0.046). The E-Fit group showed improvements in physical activity participation, as measured by the Modified Baecke Questionnaire (MBQ), with a significant interaction effect in work index (p = 0.043), sport index (p = 0.050), and total score (p = 0.016) from baseline to the 12-month follow-up. Improvement on self-image were noted in E-Fit group across time. Conclusions: The present results provided some evidence to support the positive benefits of E-Fit for bone health and muscle function in AIS girls.

BackgroundAcute respiratory distress syndrome (ARDS) is a life-threatening clinical syndrome whose potential to become one of the most grievous challenges of the healthcare system evidenced by the COVID-19 pandemic. Considering the lack of target-specific treatment for ARDS, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve quality of life and outcomes for ARDS patients. ARDS is a systemic inflammatory disease starting with the pulmonary system and involves all other organs in a morbid bidirectional fashion. Mounting evidence including our findings supporting the notion that cannabinoids have potential to be targeted as regulatory therapeutic modalities in the treatment of inflammatory diseases. Therefore, it is plausible to test their capabilities as alternative therapies in the treatment of ARDS. In this study, we investigated the potential protective effects of cannabichromene (CBC) in an experimental model of ARDS.MethodsWe used, for the first time, an inhalant CBC treatment as a potential therapeutic target in a murine model of ARDS-like symptoms. ARDS was induced by intranasal administration of Poly(I:C), a synthetic mismatched double-stranded RNA, into the C57BL/6 mice (6–10 male mice/group, including sham, placebo, and CBC treated), three once-daily doses followed by a daily dose of inhalant CBC or placebo for the period of 8 days starting the first dose 2 h after the second Poly(I:C) treatment. We employed histologic, immunohistochemistry, and flow cytometry methods to assess the findings. Statistical analysis was performed by using one way analysis of variance (ANOVA) followed by Newman–Keuls post hoc test to determine the differences among the means of all experimental groups and to establish significance (p< 0.05) among all groups.ResultsOur data showed that CBC was able to reverse the hypoxia (increasing blood O2saturation by 8%), ameliorate the symptoms of ARDS (reducing the pro-inflammatory cytokines by 50% in lung and blood), and protect the lung tissues from further destruction. Further analysis showed that CBC may wield its protective effects through transient receptor potential (TRP) cation channels, TRPA1 and TRPV1, increasing their expression by 5-folds in lung tissues compared to sham and untreated mice, re-establishing the homeostasis and immune balance.ConclusionOur findings suggest that inhalant CBC may be an effective alternative therapeutic target in the treatment of ARDS. In addition, Increased expression of TRPs cation channels after CBC treatment proposes a novel role for TRPs (TRPA1 and TRPV2) as new potential mechanism to interpret the beneficial effects of CBC as well as other cannabinoids in the treatment of ARDS as well as other inflammatory diseases. Importantly, delivering CBC through an inhaler device is a translational model supporting the feasibility of trial with human subjects, authorizing further research.

Previous studies have reported abnormal muscle morphology and functions in patients with adolescent idiopathic scoliosis (AIS). To answer whether such abnormalities could be reflected in their circulation and their clinical implication for predicting curve progression to the surgical threshold, this preliminary study explored the presence of baseline muscle-related proteins and their association with curve progression. Plasma samples were collected at the first clinical visit for AIS, with patients divided into non-progressive or progressive groups (N = four and four) according to their Cobb angle in six-year follow-ups, with age- and sex-matched healthy subjects (N = 50). Then, the samples were subjected to isobaric tags for relative and absolute quantitation (iTRAQ) for global comparison of untargeted protein expression. Seventy-one differentially expressed proteins (DEPs) were found elevated in progressive AIS. Functional analysis showed that 18 of these are expressed in muscles and play an essential role in muscle activities. Among the muscle-related DEPs, α-actin had the highest fold change in progressive/non-progressive groups. This preliminary study firstly suggested higher circulating levels of muscle structural proteins in progressive AIS, indicating the likelihood of structural damage at the microscopic level and its association with progression to the surgical threshold. Further studies with larger sample sizes are warranted to validate these novel candidates for early diagnosis and predicting progression.

Ocular HSV-1 infection is a major cause of eye disease and innate and adaptive immunity both play a role in protection and pathology associated with ocular infection. Previously we have shown that M1-type macrophages are the major and earliest infiltrates into the cornea of infected mice. We also showed that HSV-1 infectivity in the presence and absence of M2-macrophages was similar to wild-type (WT) control mice. However, it is not clear whether the absence of M1 macrophages plays a role in protection and disease in HSV-1 infected mice. To explore the role of M1 macrophages in HSV-1 infection, we used mice lacking M1 activation (M1-/- mice). Our results showed that macrophages from M1-/- mice were more susceptible to HSV-1 infection in vitro than were macrophages from WT mice. M1-/- mice were highly susceptible to ocular infection with virulent HSV-1 strain McKrae, while WT mice were refractory to infection. In addition, M1-/- mice had higher virus titers in the eyes than did WT mice. Adoptive transfer of M1 macrophages from WT mice to M1-/- mice reduced death and rescued virus replication in the eyes of infected mice. Infection of M1-/- mice with avirulent HSV-1 strain KOS also increased ocular virus replication and eye disease but did not affect latency-reactivation seen in WT control mice. Severity of virus replication and eye disease correlated with significantly higher inflammatory responses leading to a cytokine storm in the eyes of M1-/- infected mice that was not seen in WT mice. Thus, for the first time, our study illustrates the importance of M1 macrophages specifically in primary HSV-1 infection, eye disease, and survival but not in latency-reactivation., Author summary Macrophages circulating in the blood or present in different tissues constitute an important barrier against infection. We previously showed that the absence of M2 macrophages does not impact HSV-1 infectivity in vivo. However, in this study we demonstrated an essential role of M1 macrophages in protection from primary HSV-1 replication, death, and eye disease but not in latency-reactivation.

Personal Breast Cancer (BC) Risk Assessments (PBCRA) have potential to stratify women into clinically-actionable BC risk categories. As this could involve population-wide genomic testing, women’s attitudes to PBCRA and views on acceptable implementation platforms must be considered to ensure optimal population participation. We explored these issues with 31 women with different BC risk profiles through semi-structured focus group discussions or interviews. Inductive thematic coding of transcripts was performed. Subsequently, women listed factors that would impact on their decision to participate. Participants’ attitudes to PBCRA were positive. Identified themes included that PBCRA acceptance hinges on result actionability. Women value the ability to inform decision-making. Participants reported anxiety, stress, and genetic discrimination as potential barriers. The age at which PBCRA was offered, ease of access, and how results are returned held importance. Most women value the opportunity for PBCRA to inform increased surveillance, while highlighting hesitance to accept reduced surveillance as they find reassurance in regular screening. Women with BRCA pathogenic variants value the potential for PBCRA to identify a lower cancer risk and potentially inform delayed prophylactic surgery. This study highlights complexities in adopting advances in BC early detection, especially for current users who value existing processes as a social good.

Objective: People living with severe and persistent mental illness experience poorer physical health, often due to medication and preventable lifestyle factors, and exacerbated by barriers to accessing healthcare services. Pharmacists are well-positioned to improve the physical and mental health of this population. However, little is known about pharmacists’ current practices when providing services to this population nor the impact of pharmacist-led interventions on consumer health outcomes. We undertook a systematic review to identify, describe and assess the effectiveness of pharmacist-led interventions for supporting people living with severe and persistent mental illness and the impact on consumer outcomes. Methods: MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, Scopus, Cochrane Library, International Pharmaceutical Abstracts and ProQuest Dissertations and Theses were searched between January 1990 and April 2020. Full-text studies exploring pharmacist-led interventions in any setting for people living with severe and persistent mental illness were included. A risk of bias assessment was conducted. Results: A total of 37 studies were included. More than half of the pharmacist interventions were multifaceted. The most common components of pharmacist-led interventions included education and/or patient counselling, providing recommendations to healthcare professionals and conducting medication reviews. Multifaceted interventions demonstrated improvements in clinical outcomes, whereas single interventions focused mostly on consumer-reported outcomes. The methodological quality of included studies was moderate-to-high risk of bias and there was considerable heterogeneity in the study design, interventions described, and outcomes reported. Conclusion: There is evidence that pharmacist-led interventions improve consumer-reported and clinical outcomes for people living with severe and persistent mental illness. Pharmacists are capable and have a role in supporting people living with severe and persistent mental illness, either individually or as interprofessional collaborators with other healthcare professionals. Future research should attempt to better understand which particular intervention components have the greatest impact and also evaluate the implementation and long-term sustainability of such interventions.

Background: Basal metabolic rate is associated with cancer, but these observations are open to confounding. Limited evidence from Mendelian randomization studies exists, with inconclusive results. Moreover, whether basal metabolic rate has a similar role in cancer for men and women independent of insulin-like growth factor 1 increasing cancer risk has not been investigated.Methods: We conducted a two-sample Mendelian randomization study using summary data from the UK Biobank to estimate the causal effect of basal metabolic rate on cancer. Overall and sex-specific analysis and multiple sensitivity analyses were performed including multivariable Mendelian randomization to control for insulin-like growth factor 1.Results: We obtained 782 genetic variants strongly (p-value < 5 × 10–8) and independently (r2 < 0.01) predicting basal metabolic rate. Genetically predicted higher basal metabolic rate was associated with an increase in cancer risk overall (odds ratio, 1.06; 95% confidence interval, 1.02–1.10) with similar estimates by sex (odds ratio for men, 1.07; 95% confidence interval, 1.002–1.14; odds ratio for women, 1.06; 95% confidence interval, 0.995–1.12). Sensitivity analyses including adjustment for insulin-like growth factor 1 showed directionally consistent results.Conclusion: Higher basal metabolic rate might increase cancer risk. Basal metabolic rate as a potential modifiable target of cancer prevention warrants further study.

Fragility fractures are related to the loss of bone integrity and deteriorated morphology of osteocytes. Our previous studies have reported that low-magnitude high-frequency vibration (LMHFV) promoted osteoporotic fracture healing. As osteocytes are known for mechanosensing and initiating bone repair, we hypothesized that LMHFV could enhance osteoporotic fracture healing through enhancing morphological changes in the osteocyte lacuna-canalicular network (LCN) and mineralization. A metaphyseal fracture model was established in female Sprague-Dawley rats to investigate changes in osteocytes and healing outcomes from early to late phase post-fracture. Our results showed that the LCN exhibited an exuberant outgrowth of canaliculi in the osteoporotic fractured bone at day 14 after LMHFV. LMHFV upregulated the E11, dentin matrix protein 1 (DMP1), and fibroblast growth factor 23 (FGF23), but downregulated sclerostin (Sost) in osteocytes. Moreover, LMHFV promoted mineralization with significant enhancements of Ca/P ratio, mineral apposition rate (MAR), mineralizing surface (MS/BS), and bone mineral density (BMD) in the osteoporotic group. Consistently, better healing was confirmed by microarchitecture and mechanical properties, whereas the enhancement in osteoporotic group was comparable or even greater than the normal group. This is the first report to reveal the enhancement effect of LMHFV on the osteocytes' morphology and functions in osteoporotic fracture healing.

Objective Women with early-onset oestrogen deficiency are at risk of reduced bone mineral density (BMD). We sought to assess fracture history and BMD in women with Turner syndrome (TS) and premature ovarian insufficiency (POI). Design A cross-sectional observational study. Patients Two hundred and sixty seven women with TS (median age 34.3 years) and 67 women with POI (median age 28.1 years). Measurements A questionnaire was used to collect data on fracture history, co-morbidities and drug history including age at first oestrogen exposure. Clinical data included height, weight, serum vitamin D and hip and spine T-scores, which were adjusted for height and age. Fractures were subdivided into major osteoporotic fractures (MOF) and 'other' fracture types. Results Overall fracture rate was similar in women with TS and POI (82 [30.5%] vs 22 [32.8%] respectively, P = .74). Compared to women with POI, those with TS had more fractures at MOF sites (30.2% vs 52.7%, P = .012) and fewer phalangeal fractures (27.9% vs 9.8%, P = .005). There was no difference in BMD between women who sustained a fracture compared to those who did not. Women with TS who fractured were more likely to suffer from hearing impairment compared to those with no fracture (62.2% vs 48.1%, P = .045). Conclusions TS is not associated with an overall excess risk of bone fracture. The higher rate of fractures at MOF sites in women with TS may be secondary to hearing impairment, thin cortical bone and abnormal bone remodelling.

The potential impacts of coal mining on health have been addressed by the application of impact assessment methodologies that use the results of qualitative and quantitative analyses to support their conclusions and recommendations. Although human epidemiological analyses can provide the most relevant measures of risk of health outcomes in populations exposed to coal mining by-products, this kind of studies are seldom implemented as part of the impact assessment methods. To review the use of human epidemiological analyses in the methods used to assess the impacts of coal mining, a systematic search in the peer review literature was implemented following the PRISMA protocol. A synthesis analysis identified the methods and the measures used in the selected publications to develop a thematic review and discussion. The major methodological approaches to assess the impacts of coal mining are environmental impact assessment (EIA), health impact assessment (HIA), social impact assessment (SIA) and environmental health impact assessment (EHIA). The measures used to assess the impacts of coal mining on health were classified as the estimates from non-human-based studies such as health risk assessment (HRA) and the measures of risk from human epidemiological analyses. The inclusion of human epidemiological estimates of the populations exposed, especially the general populations in the vicinity of the mining activities, is seldom found in impact assessment applications for coal mining. These methods rather incorporate HRA measures or other sources of evidence such as qualitative analyses and surveys. The implementation of impact assessment methods without estimates of the risk of health outcomes relevant to the potentially exposed populations affects their reliability to address the environmental and health impacts of coal mining. This is particularly important for EIA applications because these are incorporated in regulatory frameworks globally. The effective characterization of the impacts of coal mining on health requires quantitative estimates of the risk, including the risk measures from epidemiological analyses of relevant human health data.

BACKGROUND Health care disparities in Appalachia are well documented. However, no previous studies have examined possible differences in the utilization of breast reconstruction (BR) in Appalachia. This study aims to determine if a disparity in BR utilization exists in women from Appalachia Kentucky. METHODS A retrospective, population-based cohort study was conducted from January 1, 2006, to December 31, 2015. The Kentucky Cancer Registry was queried to identify population-level data for female patients diagnosed with breast cancer and treated with mastectomy. A multivariate logistic regression model controlling for patient, disease, and treatment characteristics was constructed to predict the likelihood of BR. RESULTS Bivariate testing showed differences (P < 0.0001) in BR utilization between Appalachian and non-Appalachian women in Kentucky (15.0% and 26.3%, respectively). Multivariate analysis showed that women from Appalachia (odds ratio, 0.54; confidence interval (95), 0.48-0.61; P < 0.0001) were less likely to undergo BR than non-Appalachian women. Interestingly, the rate of BR increased over time in both Appalachian (r = 0.115; P < 0.0001) and non-Appalachian women (r = 0.148; P < 0.0001). CONCLUSIONS Despite the benefits of BR, women from Appalachia undergo BR at lower rates and are less likely to receive BR than non-Appalachian Kentuckians. Although the rates of BR increased over time in both populations, access to comprehensive breast cancer care remains a challenge for women from Kentucky's Appalachian region.

Increasing the feed efficiency of lean tissue gains is an important goal for improving sustainable pork production and profitability for swine producers. To study feed efficiency, genetic selection based on residual feed intake (RFI) was used to create two divergent lines. Low-RFI pigs consume less feed for equal weight gain compared with their less-efficient, high-RFI counterparts. As cortisol and insulin are important energy control and growth regulators, our objective was to evaluate the role of the adrenocorticotropic hormone (ACTH)-cortisol and the glucose-insulin axes in pigs divergently selected for RFI. Adrenocorticotropic hormone (0.2 IU/kg BW)-stimulated cortisol and non-esterified fatty acids (NEFA) concentrations and intravenous glucose tolerance test (IVGTT; 0.25 g/kg BW)-stimulated glucose, insulin, and NEFA concentrations were assessed in six low-RFI and six high-RFI gilts (68 ± 5.2 kg). Before the ACTH challenge, low-RFI gilts tended to have less baseline plasma cortisol (P = 0.08) but no difference in NEFA concentrations (P = 0.63) compared with high-RFI gilts. After the ACTH challenge, low-RFI gilts had less cortisol (P = 0.04) and NEFA concentrations (P = 0.05) compared with high-RFI gilts. Glucose, insulin, and NEFA concentrations did not differ between genetic lines before the IVGTT. After glucose infusion, low-RFI gilts had greater insulin concentrations (P = 0.003) but did not differ in glucose or NEFA concentrations compared with high-RFI gilts. These results indicate that genetic selection for reduced RFI (improved feed efficiency) resulted in less stress responsiveness and an increase in insulin after glucose infusion. These data have implications for identifying and selecting more feed efficient pigs and for understanding the physiological mechanisms underlying feed efficiency.

Background: Previous GWASs have revealed several susceptible variants associated with adolescent idiopathic scoliosis (AIS). Risk prediction based on these variants can potentially improve disease prognosis. We aimed to evaluate the combined effects of genetic factors on the development of AIS and to further develop a genetic predictive model. Methods: A total of 914 AIS patients and 1441 normal controls were included in the discovery stage, which was followed by the replication stage composed of 871 patients and 1239 controls. Genotyping assay was performed to analyze 10 previously reported susceptible variants, including rs678741 of LBX1, rs241215 of AJAP1, rs13398147 of PAX3, rs16934784 of BNC2, rs2050157 of GPR126, rs2180439 of PAX1, rs4940576 of BCL2, rs7593846 of MEIS1, rs7633294 of MAGI1 and rs9810566 of TNIK. Logistic regression analysis was performed to generate a risk predictive model. The predicted risk score was calculated for each participant in the replication stage. Results: The association of the 10 variants with AIS was successfully validated. The established model could explain approximately 7.9% of the overall variance. In the replication stage, patients were found to have a remarkably higher risk score as compared to the controls (44.2 ± 14.4 vs. 33.9 ± 12.5, p 40 in the patients than in the controls (59% vs. 28.9%, p Conclusion: Risk predictive model based on the previously reported genetic variants has a remarkable discriminative power. More clinical and genetic factors need to be studied, to further improve the probability to predict the onset of AIS.

It is well-documented that melatonin deficiency has been linked to the etiopathogenesis of adolescent idiopathic scoliosis. In this study, we intended to apply melatonin in melatonin-deficient mice to ascertain whether melatonin could reduce the incidence/severity of scoliosis, and investigate the role of melatonin on bone mineral density in scoliosis. A total of 80 mice were divided into 4 groups: 20 quadrupedal mice and 20 bipedal mice served as controls; 20 quadrupedal and 20 bipedal mice received oral melatonin (8 mg/kg BW) daily. After 5th, 10th, 15th and 20th weeks of treatment, radiographs and in vivo micro-CT were used to determine the incidence of scoliosis and bone qualities, respectively. Upon sacrifice, the levels of melatonin were measured in each group. At 20th week, the occurrence of scoliosis was 80%, 30%, 22% and 5% in bipedal, quadrupedal, bipedal + melatonin and quadrupedal + melatonin group, respectively. The trabecular bone quality of the vertebral body was significantly ameliorated in the melatonin-treated bipedal models. Likewise, the number of osteoclasts was significantly less in those treated with melatonin. Our results indicated that melatonin deficiency may be crucial for scoliotic development, and restoration of melatonin levels can prevent scoliotic development with the improvement in bone density.

Background Malignant melanoma is a complex malignancy with significant morbidity and mortality. The incidence continues to rise, and despite advances in treatment, the prognosis is poor. Thus, it is necessary to develop novel strategies to treat this aggressive cancer. Synthetic cannabinoids have been implicated in inhibiting cancer cell proliferation, reducing tumor growth, and reducing metastasis. We developed a unique study focusing on the effects of treatment with a cannabinoid derivative on malignant melanoma tumors in a murine model. Methods Murine B16F10 melanoma tumors were established subcutaneously in C57BL/6 mice. Mice were then treated with intraperitoneal injections of vehicle twice per week (control—group 1, n = 6), Cisplatin 5 mg/kg/wk (group 2; n = 6), and Cannabidiol (CBD) 5 mg/kg twice per week (group 3; n = 6). Tumors were measured and volume calculated as (4π/3) × (width/2)2 × (length/2). Tumor size and survival curves were measured. Results were compared using a one-way ANOVA with multiple comparison test. Results A significant decrease in tumor size was detected in mice treated with CBD when compared with the control group (P = 0.01). The survival curve of melanoma tumors treated with CBD increased when compared with the control group and was statistically significant (P = 0.04). The growth curve and survival curve of melanoma tumors treated with Cisplatin were significantly decreased and increased, respectively, when compared with the control and CBD-treated groups. Mice treated with Cisplatin demonstrated the longest survival time, but the quality of life and movement of CBD-treated mice were observed to be better. Conclusions We demonstrate a potential beneficial therapeutic effect of cannabinoids, which could influence the course of melanoma in a murine model. Increased survival and less tumorgenicity are novel findings that should guide research to better understand the mechanisms by which cannabinoids could be utilized as adjunctive treatment of cancer, specifically melanoma. Further studies are necessary to evaluate this potentially new and novel treatment of malignant melanoma.

Idiopathic Scoliosis (IS) is a relatively common condition and is estimated to affect as many as 3 % of youth aged 10–17 years (in the United States an estimated approximately 1.4 million otherwise healthy individuals). A clear understanding of the etiology will better direct optimization of evaluation, treatments and therapies, especially early treatments with less invasive methods. A mechanistic explanation of factors combining to initiate and then cause progression of this common condition-- in otherwise healthy pre-teenage and teenage patients--will be discussed. A recent well-designed structured systematic review states that ‘strong evidence is lacking for a consistent pattern of occurrence and any abnormality’, in other words there is no strong evidence for ‘other associated diagnoses’ in IS. And so, certain important inherent factors of IS merit greater discussion. Inherent, or intrinsic factors include: a natural susceptibility to develop a lateral and rotational deformity in the immature rapidly growing erect human spine, inherent torsion associated at the induction of deformity, biomechanics related to curve progression, and anthropology/bipedal gait. We know more today about factors related to the condition and its etiology than we have previously. Across multiple disciplines, a mechanistic approach to understanding the etiopathogenesis of IS, allows a reasonable ‘theory’ for IS etiology and its progression. We will discuss these inherent intrinsic factors in order to further add to our understanding of the theoretical etiopathogenesis. A better understanding of the etiology (and progression) may better direct ways to optimize evaluation, treatments and therapies, especially early treatments with less invasive methods.

Significance We analyzed data from saliva-based COVID-19 screening deployed on the University of Colorado Boulder campus. Our dataset is unique in that all SARS-CoV-2−positive individuals reported no symptoms at the time of saliva collection, and therefore were infected but asymptomatic or presymptomatic. We found that 1) the distribution of viral loads observed in our asymptomatic college population was indistinguishable from what has been reported in hospitalized populations; 2) regardless of symptomatic status, approximately 50% of individuals who test positive for SARS-CoV-2 seem to be in noninfectious phases of the infection; and 3) just 2% of infected individuals carry 90% of the virions circulating within communities, serving as viral “supercarriers” and likely also superspreaders., We analyze data from the fall 2020 pandemic response efforts at the University of Colorado Boulder, where more than 72,500 saliva samples were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using qRT-PCR. All samples were collected from individuals who reported no symptoms associated with COVID-19 on the day of collection. From these, 1,405 positive cases were identified. The distribution of viral loads within these asymptomatic individuals was indistinguishable from what has been previously observed in symptomatic individuals. Regardless of symptomatic status, ∼50% of individuals who test positive for SARS-CoV-2 seem to be in noninfectious phases of the disease, based on having low viral loads in a range from which live virus has rarely been isolated. We find that, at any given time, just 2% of individuals carry 90% of the virions circulating within communities, serving as viral “supercarriers” and possibly also superspreaders.

STUDY DESIGN A genetic case-control study. OBJECTIVES To investigate whether the variants in BOC, SEC16B, and SH2D1B are sex-specifically and functionally associated with the susceptibility of adolescent idiopathic scoliosis (AIS) in Chinese Han population. SUMMARY OF BACKGROUND DATA A recent genome-wide association study identified three female-specific susceptibility loci of AIS in Japanese population. However, the association of these genes with AIS in other populations remains unclear. Further investigation of the functional role of the three genes was warranted. METHODS SNPs rs73235136, rs545608, and rs142502288 were genotyped in 1599 AIS patients and 2985 controls. Paraspinal muscle collected from 40 AIS and 30 lumber disc herniation patients during surgical interventions was used for gene expression analysis. The difference regarding genotype and allele frequency between patients and controls was analyzed by chi-square analysis. Expression of BOC and SEC16B was compared between AIS and lumber disc herniation patients by the Student t test. Pearson correlation analysis was performed to evaluate the relationship between gene expression level and clinical phenotypes. RESULTS SNPs rs73235136 of BOC and rs545608 of SEC16B were found to be remarkably associated with AIS only in females. Allele C of rs73235136 and allele G of rs545608 could significantly add to the risk of female AIS patients, with an odds ratio of 1.087 and 1.033, respectively. However, there was no significant difference between the male patients and controls regarding genotype or allele frequency of rs73235136 and rs545608. No polymorphism at rs142502288 was detected in either patients or controls, and all the subjects had genotype of AA. Moreover, tissue expression of BOC and SEC16B was significantly lower in AIS patients compared with controls. BOC expression was positively associated with bone mineral contents, and expression of SEC16B was negatively correlated with curve severity in AIS patients. CONCLUSION Female-specific variants in BOC and SEC16B were associated with AIS. Expression of BOC and SEC16B was significantly lower in AIS patients. The role of BOC and SEC16B in the development of AIS is worthy of further investigation.Level of Evidence: 3.

Background Osteoarthritis of the knee is a common degenerative joint disorder in our ageing population. A combination of thermal therapy with a self-management exercise have shown a positive effect in the management of osteoarthritis of the knee. This study aimed to compare the effectiveness of topical heat pack versus focal application of heat therapy at the acupressure points in the treatment of osteoarthritis of the knee. Methods A randomized controlled trial was conducted in 76 patients with osteoarthritis of the knee, diagnosed by an experienced orthopedic surgeon. Following inclusion and exclusion selection, patients were randomly allocated to group 1 (Heat pack) or group 2 (Thermal gun). All patients received 30 min of treatment in each session, twice a week for 4 weeks. They also received an education program and taught home knee exercises. Outcome measurements were the visual analog scale (VAS) for pain intensity, muscle power, knee ROM, WOMAC and SF-12v2. Results In the Thermal gun group, function and total scores (WOMAC) and Physical Composite Scale (SF-12v2) were significantly improved after 8 sessions. Quadriceps strength was significantly improved after 8 weeks (from 4.42 to 4.63; p = 0.02). In the Heat pack group, flexion was significantly improved after 8 sessions (p = 0.02). Mean VAS scores after Heat pack treatment was consistently better (lower) than mean VAS scores after Thermal gun treatment. Conclusion The combination of focal thermal therapy at acupressure points is a viable conservative treatment in osteoarthritis of the knee. The pressure at the acupressure points has a synergistic benefit than topical thermal therapy alone. Trial registration ClinicalTrials.gov, NCT04735029 Date of registration: February 2, 2021 (Retrospectively registered)

Objective The objective of this study was to characterize early and midterm outcomes after the Ross/Ross-Konno procedure performed in infancy for severe aortic valve disease. Methods Between January 1995 and December 2018, 35 infants younger than 1 year (13 neonates) underwent a Ross/Ross-Konno procedure. Patients were followed up to a median of 4.1 years (interquartile range [IQR], 2.6-9.5). Primary outcome measures were survival, early morbidity, freedom from reintervention and long-term functional and echocardiographic status. Results Median age at operation was 49 days (IQR, 17-135) and weight was 4 kg (IQR, 3.4-5.2). Thirty-one (89%) had undergone a previous procedure, including balloon valvuloplasty in 26 (74%). Thirty (86%) required annular enlargement (Konno incision). Five required concomitant aortic arch surgery (2 neonates, 3 infants). There were no early deaths, and 1 late death at 18 months. Freedom from reoperation was 85% (95% confidence interval [CI], 68%-93%) at 1 year, 76% (95% CI, 54%-88%) at 5 years, and 62% (95% CI, 36%-79%) at 10 years. One modified Konno was performed at 5 years after a Ross in infancy. Ten right ventricle to pulmonary artery conduits have required reintervention (2 percutaneous pulmonary valve implantations). One child required a permanent pacemaker for complete heart block. At latest follow-up, 32 (94%) of 34 survivors were asymptomatic. There was no significant change in neoaortic Z-scores between 6 weeks and latest follow-up. Conclusions The neonatal and infant Ross/Ross-Konno procedure can be performed with low mortality and achieves a stable left ventricular outflow tract. Significant early morbidity reflects the preoperative condition of the patients but definitive surgery of this type can be considered as a primary approach.

Scoliosis screening is important for timely initiation of brace treatment to mitigate curve progression in skeletally immature children and adolescents. School scoliosis screening programs in Hong Kong follow the protocol of referring children screened positive with a scoliometer and Moire topography for confirmatory standard radiography. Despite being highly sensitive (88%) in detecting those who require specialist referral, the screening program was found to have a false-positive rate >50%, which could lead to unnecessary X-ray radiation. Radiation-free ultrasound has been reported to be valid and reliable for quantitative assessment of curve severity in scoliosis patients. The aim of this prospective diagnostic accuracy study was to determine the accuracy of ultrasound in determining the threshold of referral that requires X-ray for children screened positive with the scoliometer and Moire topography. Our study recruited 442 schoolchildren with a mean Cobb angle of 14.0 ± 6.6°. The sensitivity and specificity of ultrasound in predicting the correct referral status, confirmed by X-ray, were 92.3% and 51.6%, with positive and negative predictive values of 29.0% and 96.9%, respectively. Receiver operating characteristic curve analysis revealed area under the curve values of 0.735 for ultrasound alone and 0.832 for ultrasound in combination with measurement of angle of trunk rotation. The finding supports the accuracy of using ultrasound to determine referral status, which could result in a >50% reduction of unnecessary radiation for children undergoing scoliosis screening.

Treatment section: Head and neck squamous cell carcinoma most commonly affects the oral cavity, oropharynx, and larynx. Traditional risk factors include tobacco, alcohol, and more recently high-risk strains of human papilloma virus (HPV). The mainstay of treatment includes surgery, radiation, and cytotoxic chemotherapy. Recent updates to diagnosis and staging criteria as well as primary treatment modalities are reviewed below for each head and neck subsite.