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Purpose: This study assessed the efficacy, safety, and pharmacokinetics of adavosertib in combination with four chemotherapy agents commonly used in patients with primary platinum-resistant ovarian cancer. Patients and Methods: Women with histologically or cytologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer with measurable disease were enrolled between January 2015 and January 2018 in this open-label, four-arm, multicenter, phase II study. Patients received adavosertib (oral capsules, 2 days on/5 days off or 3 days on/4 days off) in six cohorts from 175 mg once daily to 225 mg twice daily combined with gemcitabine, paclitaxel, carboplatin, or pegylated liposomal doxorubicin. The primary outcome measurement was overall response rate. Results: Three percent of patients (3/94) had confirmed complete response and 29% (27/94) had confirmed partial response. The response rate was highest with carboplatin plus weekly adavosertib, at 66.7%, with 100% disease control rate, and median progression-free survival of 12.0 months. The longest median duration of response was in the paclitaxel cohort (12.0 months). The most common grade ≥3 adverse events across all cohorts were neutropenia [45/94 (47.9%) patients], anemia [31/94 (33.0%)], thrombocytopenia [30/94 (31.9%)], and diarrhea and vomiting [10/94 (10.6%) each]. Conclusions: Adavosertib showed preliminary efficacy when combined with chemotherapy. The most promising treatment combination was adavosertib 225 mg twice daily on days 1–3, 8–10, and 15–17 plus carboplatin every 21 days. However, hematologic toxicity was more frequent than would be expected for carboplatin monotherapy, and the combination requires further study to optimize the dose, schedule, and supportive medications.

Introduction:This document provides an update to the 2015 consensus statement with new content on inpatient utilization, procedural data, and compensation. The full document is available on...

Background It has been observed that gluteal-femoral adipose tissue has a protective effect against risk factors for cardiovascular disease but has not yet been concluded how different evaluation methods of fat distribution affect the results. Methods To test the hypothesis that B-mode ultrasound-measured subcutaneous adipose tissue distribution is associated with cardiovascular risk factors, 326 Japanese unmedicated postmenopausal women aged 50–70 years were analyzed. Subcutaneous adipose tissue thickness at 6 sites (anterior and posterior aspects of trunk, upper-arm, and thigh) and serum total (TC) and high-density lipoprotein cholesterol (HDLC) was measured, and a ratio of HDLC to TC (HDLC/TC) was calculated. We used Bayesian linear regression with 4 separate models with each model predicting HDLC/TC. Results Our first model provided evidence for an inverse correlation (r = –0.23) between ultrasound measured body fat (6 site measurement) and HDLC/TC. The second model noted evidence for an inverse correlation between trunk fat and HDLC/TC and found evidence for the null with respect to the correlation between thigh fat and HDLC/TC. Therefore, we added thigh fat to the null model to produce Distribution Model 2. Within this model, we noted an inverse correlation (r = –0.353) between trunk fat and HDLC/TC. Our last model determined that within the trunk fatness, the abdominal area (anterior trunk) was a larger predictor than the subscapular site (posterior trunk). Conclusion These results support the evidence that ultrasound-measured abdominal subcutaneous adipose tissue thickness is a non-invasive predictor for monitoring the risk for dyslipidemia in postmenopausal women.

The purpose was to examine the effect of isometric handgrip exercise with and without blood flow restriction on exercise-induced hypoalgesia at a local and non-local site, and its underlying mechanisms. Sixty participants (21 males & 39 females, 18-35 years old) completed 3 trials: four sets of 2-minute isometric handgrip exercise at 30% of maximum handgrip strength; isometric handgrip exercise with blood flow restriction at 50% of arterial occlusion pressure; and a non-exercise time-matched control. Pain thresholds increased similarly in both exercise conditions at a local (exercise conditions: ~0.45 kg/cm2, control: ~-0.04 kg/cm2) and non-local site (exercise conditions: ~0.37 kg/cm2, control: ~-0.16 kg/cm2). Blood flow restriction induced greater feelings of discomfort compared to exercise alone [median difference (95% credible interval) of 4.5 (0.5, 8.6) arbitrary units]. Blood pressure increased immediately after exercise (systolic: 10.3 mmHg, diastolic: 7.7 mmHg) and decreased in recovery. There was no within participant correlation between changes in discomfort and pressure pain threshold. A bout of isometric handgrip exercise with or without blood flow restriction can provide exercise-induced hypoalgesia at a local and non-local site. However, discomfort and changes in systolic blood pressure do not explain this response.

The field of genomics is the principal avenue in the ongoing development of precision/personalised medicine for a variety of health conditions. However, relating genes to outcomes is notoriously complex, especially when considering that other variables can change, or moderate, gene-outcome associations. Here, we comprehensively discuss moderation of gene-outcome associations in the context of traumatic brain injury (TBI), a common, chronically debilitating, and costly neurological condition that is under complex polygenic influence. We focus our narrative review on single nucleotide polymorphisms (SNPs) of three of the most studied genes (apolipoprotein E, brain-derived neurotrophic factor, and catechol-O-methyltransferase) and on three demographic variables believed to moderate associations between these SNPs and TBI outcomes (age, biological sex, and ethnicity). We speculate on the mechanisms which may underlie these moderating effects, drawing widely from biomolecular and behavioural research (n = 175 scientific reports) within the TBI population (n = 72) and other neurological, healthy, ageing, and psychiatric populations (n = 103). We conclude with methodological recommendations for improved exploration of moderators in future genetics research in TBI and other populations.

Background Mesenchymal stem cells have been proven to promote cellular recruitment and remodeling during healing. Considering challenges encountered in the healing process of esophageal injury, we sought to evaluate the effect of human adipose derived stem cells (hASC) on esophageal injury with stent and to assess the feasibility of submucosal hASC injection as a mechanism of delivery. Methods An intrabdominal esophagotomy was created in rodents with placement of an expandable fully covered metal esophageal stent. A submucosal injection of 2 × 106 hASC was delivered in experimental animals. Animals were sacrificed on postoperative day 3 (POD3) or 7 (POD7). Macroscopic, immunohistochemical and immunofluorescence analyses were conducted to assess for markers of healing and viability of transplanted cells. Results hASC were identified within submucosal and muscular layers with proliferation demonstrated in respective areas on anti-Ki67 stained sections. Lower adhesion and abscess scores were observed in hASC specimens without significant statistical difference. Prevalence of submucosal collagen was increased in samples treated with hASC compared to control, with abundant collagen deposition demonstrated within the POD7 group. Granulation tissue at the site of esophageal injury was more prominent in tissue sections treated with hASC compared to control, with significantly higher density at POD3 (control 1.94 versus hASC 2.83, P Conclusions Presence of hASC at the site of an esophageal injury may enhance wound healing predominantly through increased granulation and decreased inflammation in conjunction with esophageal stent placement. Targeted submucosal injection at the time of esophageal stent placement is an effective delivery method of hASC therapy.

Objective To compare racial differences in male fertility history and treatment. Design Retrospective review of prospectively collected data. Setting North American reproductive urology centers. Patient(s) Males undergoing urologist fertility evaluation. Intervention(s) None. Main Outcome Measure(s) Demographic and reproductive Andrology Research Consortium data. Result(s) The racial breakdown of 6,462 men was: 51% White, 20% Asian/Indo-Canadian/Indo-American, 6% Black, 1% Indian/Native, Conclusion(s) Racial differences exist for males undergoing fertility evaluation by a reproductive urologist. Better understanding of these differences in history in conjunction with societal and biologic factors can guide personalized care, as well as help to better understand and address disparities in access to fertility evaluation and treatment.

BACKGROUND: Employees with psychiatric disabilities experience a great amount of workplace challenges such as lacking workplace supports and job accommodations. There is a lack of research surrounding job accommodations for persons with psychiatric disabilities within the United States. Thus, research is warranted to understand how to meet the needs of this population via accommodations. OBJECTIVE: This study examined barriers and facilitators to requesting accommodations among employees with psychiatric disabilities through a qualitative approach. METHODS: This study recruited 120 participants from multiple agencies serving individuals with psychiatric disabilities in the United States. Themes regarding barriers and facilitators were identified using the conventional content analysis approach. RESULTS: The most commonly identified themes were employees’ fear and anxiety negatively impacting accommodation seeking behaviors, employer discrimination and non-inclusive workplace culture, and employers lack knowledge of disabilities and ADA. Participants also identified positive experiences in requesting accommodations. CONCLUSION: Rehabilitation professionals and employers may utilize current findings, facilitate a positive and inclusive workplace environment and assist employees with disabilities to take full advantage of workplace resources and job accommodation to exert their potentials.

Gonzalez, AM, Accetta, MR, Spitz, RW, Mangine, GT, Ghigiarelli, JJ, and Sell, KM. Red spinach extract supplementation improves cycle time trial performance in recreationally active men and women. J Strength Cond Res XX(X): 000–000, 2019—To examine the effects of short-term red spinach extrac

Bell, ZW, Spitz, RW, Wong, V, Yamada, Y, Song, JS, Abe, T, and Loenneke, JP. Can individuals be taught to sense the degree of vascular occlusion? A comparison of methods and implications for practical blood flow restriction. J Strength Cond Res 36(12): 3359-3365, 2022-The study objective was to determine whether subjects could be conditioned to a relative blood flow restriction pressure in the lower body and compare 2 separate conditioning methods (unconstrained vs. constrained). Thirty-five subjects completed 4 visits, involving measurements for arterial occlusion and pressure estimations at 5 minutes and 24 hours after conditioning. The constrained method involved applying 40% of measured arterial occlusion 11 times, along with 10% above and below this pressure. The unconstrained method was time-matched, involving a series of inflations to 40% arterial occlusion for 12 seconds and then deflated for 22 seconds. Data are presented as mean differences (95% credible interval) unless otherwise noted. The absolute error between conditioning methods was found to be similar at 5 minutes (-1.1 [-5.9, 3.7] mm Hg) and 24 hours (-2.4 [-7, 2.2] mm Hg) after conditioning. The constant error differed between methods at 5 minutes [-8.2 (-14.4, -1.9) mm Hg] but was similar at 24 hours (-2.5 [-8.5, 3.6] mm Hg; H0: 0.680; H1: 0.068; and H2: 0.252) after conditioning. The bias and 95% limits of agreement for the unconstrained method were -3.9 (-33.8, 25.9) mm Hg at 5 minutes and -2.9 (-32, 26.1) mm Hg at 24 hours. The agreement for the constrained method was 4.2 (-28, 36.5) mm Hg at 5 minutes and -0.54 (-37.3, 36.2) mm Hg at 24 hours. Conditioning methods produced similar levels of absolute error, indicating that either method may offer a viable means of pressure application. Most estimates were between 20 and 60% of arterial occlusion pressure. Additional conditioning sessions may be needed to narrow this range at the individual level.

3d printing is capable of providing dose individualization for pediatric medicines and translating the precision medicine approach into practical application. In pediatrics, dose individualization and preparation of small dosage forms is a requirement for successful therapy, which is frequently not possible due to the lack of suitable dosage forms. For precision medicine, individual characteristics of patients are considered for the selection of the best possible API in the most suitable dose with the most effective release profile to improve therapeutic outcome. 3d printing is inherently suitable for manufacturing of individualized medicines with varying dosages, sizes, release profiles and drug combinations in small batch sizes, which cannot be manufactured with traditional technologies. However, understanding of critical quality attributes and process parameters still needs to be significantly improved for this new technology. To ensure health and safety of patients, cleaning and process validation needs to be established. Additionally, adequate analytical methods for the in-process control of intermediates, regarding their printability as well as control of the final 3d printed tablets considering any risk of this new technology will be required. The PolyPrint consortium is actively working on developing novel polymers for fused deposition modeling (FDM) 3d printing, filament formulation and manufacturing development as well as optimization of the printing process, and the design of a GMP-capable FDM 3d printer. In this manuscript, the consortium shares its views on quality aspects and measures for 3d printing from drug-loaded filaments, including formulation development, the printing process, and the printed dosage forms. Additionally, engineering approaches for quality assurance during the printing process and for the final dosage form will be presented together with considerations for a GMP-capable printer design.

When the Covid-19 pandemic hit Israel in March 2020 and the government imposed a number of lockdowns, Haredi (ultra-Orthodox) rabbis instructed their followers to continue attending synagogues and engage in Torah study. As a result, the relative number of COVID-19 infections and fatalities in the Haredi community was higher than that of the Israeli population as a whole. This article examines the role of the mass media during the crisis in Israel’s largest Haredi city of Bnei Beraq, via interviews with 405 of the city’s residents. It shows that despite rabbinic bans on exposure to the secular media and to the Internet, many Haredim were exposed to them and hence less dependent on the Haredi media. [ABSTRACT FROM AUTHOR] Copyright of Israel Affairs is the property of Routledge and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We present an analysis tool for subgroup identification in medical research based on feature analysis. Our use case is intracranial aneurysms. In the tool, an aneurysm-of-interest’s most similar aneurysms within a database are found. Similarity is defined via user-selected parameters, which can be entirely arbitrary. Different interactive outputs and visualizations include a heatmap view and a graph, which give an intuitive feedback to support researchers in the consideration of research questions, which in the present use case often relate to rupture risk analysis. The tool was evaluated with a pilot study and phantom database and received favorable results for its requirements of reliability and appropriate and clear outputs.

The discovery of community structures in social networks has gained significant attention since it is a fundamental problem in understanding the networks' topology and functions. However, most social network data are collected from partially observable networks with both missing nodes and edges. In this paper, we address a new problem of detecting overlapping community structures in the context of such an incomplete network, where communities in the network are allowed to overlap since nodes belong to multiple communities at once. To solve this problem, we introduce KroMFac, a new framework that conducts community detection via regularized nonnegative matrix factorization (NMF) based on the Kronecker graph model. Specifically, from an inferred Kronecker generative parameter matrix, we first estimate the missing part of the network. As our major contribution to the proposed framework, to improve community detection accuracy, we then characterize and select influential nodes (which tend to have high degrees) by ranking, and add them to the existing graph. Finally, we uncover the community structures by solving the regularized NMF-aided optimization problem in terms of maximizing the likelihood of the underlying graph. Furthermore, adopting normalized mutual information (NMI), we empirically show superiority of our KroMFac approach over two baseline schemes by using both synthetic and real-world networks., Comment: 24 pages, 8 figures, 5 tables; to appear in the ACM Transactions on Knowledge Discovery from Data (Please cite our journal version that will appear in an upcoming issue.)

This study aimed to compare the change in levels of several laboratory values and the development of adverse events using two commonly used intramuscular testosterone therapy regimens. Men were included if they were 18 years or older and received one of the following testosterone therapy regimens: 100 mg intramuscular once weekly or 200 mg intramuscular once every other week. Primary outcomes were relative changes in total testosterone, free testosterone, estradiol, prostate-specific antigen, and hematocrit at 6 months after initiation of testosterone therapy. Secondary outcomes were any significant rises in estradiol, hematocrit, prostate-specific antigen, and any other treatment-related adverse events requiring cessation of testosterone therapy. A total of 263 men were enrolled. In a subanalysis of men who had a baseline hematocrit below 54% before intramuscular testosterone therapy initiation, we found the following: men who received 100 mg weekly injections were significantly less likely to have hematocrit levels rising above 54% (1/102 (1%) vs. 4/51 (8%); p = 0.023). No significant differences were recorded in the increase in total testosterone, free testosterone, prostate-specific antigen, and estradiol levels between both groups. A higher average serum testosterone over the dosing interval seen with the 200 mg regimen appears to be associated with a higher risk of erythrocytosis.

Viral infections are known to modulate the upper respiratory tract microbiome, but few studies have addressed differences in the nasopharyngeal microbiome following SARS-CoV-2 infection. Using nasopharyngeal swab medical waste samples from 79 confirmed SARS-CoV-2 positive and 20 SARS-CoV-2 negative patients, we assessed microbiome composition with metagenomic sequencing. COVID-19 status and breathing assistive device use was associated with differences in beta diversity, principal component analyses, community composition and abundance of several species. Serratia more frequently appeared in COVID-19 patient samples compared to negative patient samples, and Serratia, Streptococcus, Enterobacter, Veillonella, Prevotella, and Rothia appeared more frequently in samples of those who used breathing assistive devices. Smoking and age were associated with differences in alpha diversity. Cross-sectional differences in the microbiome were apparent with SARS-CoV-2 infection, but longitudinal studies are needed to understand the dynamics of viral and breathing treatment modulation of microbes.

s Objective To review past literature regarding exercise-induced hypoalgesia and pain reduction following blood flow restriction interventions, and to discuss potential mechanisms as well as future considerations towards the efficacy of blood flow restriction in pain reduction following exercise. Methods To be eligible for inclusion, studies had to include acute exercise, or long-term training interventions, with blood flow restriction, along with including pre and post intervention pain measurements. Results A total of 13 studies met the inclusion criteria. Among these 13 studies, 3 studies examined exercise-induced hypoalgesia after an acute bout of resistance exercise with blood flow restriction, and 10 studies investigated pain reduction following long-term blood flow restriction training. Conclusions Existing literature suggests that low load resistance exercise with blood flow restriction may serve as an effective pain management method for those who are unable or unwilling to train with high loads. Several potential mechanisms have been suggested, however, the roles of these mechanisms are still unclear and require further clarification. Future research should consider implementing different methods of blood flow restriction application, and research study design to clarify the utility and efficacy of blood flow restriction as a pain management tool, by itself or in combination with exercise.

Background and objectivesFatigue and sleep disturbance are debilitating problems following brain injury and there are no established treatments. Building on demonstrated efficacy of blue light delivered via a lightbox in reducing fatigue and daytime sleepiness after TBI, this study evaluated the efficacy of a novelin-homelight intervention in alleviating fatigue, sleep disturbance, daytime sleepiness and depressive symptoms, and in improving psychomotor vigilance and participation in daily productive activity, following injuryMethodsThe impact of exposure to a dynamic light intervention (Treatment) was compared to usual lighting (Control) in a randomized within-subject, crossover trial. Outcomes were fatigue (primary outcome), daytime sleepiness, sleep disturbance, insomnia symptoms, psychomotor vigilance, mood and activity levels. Participants (N = 24,M ± SDage = 44.3 ± 11.4) had mild-severe TBI or stroke > 3 months previously, and self-reported fatigue (Fatigue Severity Scale ≥ 4). Following 2-week baseline, participants completed each condition for 2 months in counter-balanced order, with 1-month follow-up. Treatment comprised daytime blue-enriched white light (CCT > 5000 K) and blue-depleted light (ResultsRandom-effects mixed-model analysis showed no significantly greater change in fatigue on the Brief Fatigue Inventory during Treatment, but a medium effect size of improvement (p = .33,d = -0.42). There were significantly greater decreases in sleep disturbance (p = .004), insomnia symptoms (p = .036), reaction time (p = .004) and improvements in productive activity (p = .005) at end of Treatment relative to Control, with large effect sizes (d > 0.80). Changes in other outcomes were non-significant.ConclusionsThis pilot study provides preliminary support forin-homedynamic light therapy to address sleep-related symptoms in acquired brain injury.Trial registrationThis trial was registered with the Australian and New Zealand Clinical Trials Registry on 13 June 2017,www.anzctr.org.au, ACTRN12617000866303.

Muscle quality is typically defined as muscle strength relative to muscle size. Echo intensity has gained popularity as an index of skeletal muscle quality. There is common agreement that muscle size is related to strength at baseline and echo intensity is purported to impact this relationship. Thus, the purpose of this study was to examine whether echo intensity can be used as a physiological marker for muscle quality by investigating the moderating effect of echo intensity on the relationship between muscle size and strength. A sample of 96 participants was used for the upper body analysis and a separate sample of 96 participants was used for the lower body analysis. Echo intensity, muscle thickness, and strength measurements were measured on each limb. For strength, participants performed unilateral elbow flexion (upper body analysis) and knee extension (lower body analysis) to quantify 1-repetition maximum. Muscle thickness and echo intensity were determined from images captured using B-mode ultrasound. Muscle size correlated with muscle strength for all limbs. However, the relationship between muscle size and strength was not significantly moderated by echo intensity for Arm 1 (b = 0.042, p = 0.54) or Arm 2 (b = −0.002, p = 0.97). At the proximal site, no significant moderating effect of echo intensity was found in Leg 1 (b = 0.037, p = 0.67) or Leg 2 (b = −0.085, p = 0.29). Similarly, no significant moderating effect was observed at the distal site for Leg 1 (b = 0.03, p = 0.69) or Leg 2 (b = −0.026, p = 0.75). The results would indicate that the relationship between muscle size and strength does not depend on echo intensity. Therefore, the use of echo intensity as an index of muscle quality in healthy young adults may need to be reconsidered.

Background: In 2016, Sight for All United (SFAU) was founded in the Mahoning Valley of Ohio with the mission of improving access to care and maximizing the visual potential of the underserved. Methods: A retrospective chart review was conducted on patients served by SFAU from January 2016 through August 2020. Socioeconomic information, type of service, cost, and dollar amount paid were collected for patients. The data were analyzed with descriptive statistics and mapped with Esri ArcGIS. Results: A total of 1327 patients received assistance through the medical assistance and school vision programs. In the medical assistance program, 222 patients (mean age 50 years, 57% female) completed applications and 37% (83 patients) were in a household of 3 or more people. Median yearly income was $18 504, 134% above the federal poverty level by household size. The most common surgical services were cataract surgery (101) and vitreoretinal care (17). The most common medical services were eye exams (79) and spectacles (76). Estimated value of medical services provided was $367 249; actual cost was $93 746. The school vision program provided 1105 eye exams, 1514 pairs of spectacles, and 1 cataract surgery with an estimated value of $133 692. Conclusion: Sight for All United provided $500 941 of vision services to its patients since 2016 while dispersing less than $100 000 of donated dollars through collaboration with eye care providers, community resources, and national foun-dations. This study demonstrates the impact vision foundations managed by local eye care providers can have on the needs in their community in a cost-effective and efficient way.

The purpose of this meta-analysis was to examine the effects of blood flow restriction training on resting blood pressure and heart rate. A meta-analysis was completed in May 2020 including all previously published papers on blood flow restriction and was analyzed using a random effects model. To be included, studies needed to implement a blood flow restriction protocol compared to the same exercise protocol without restriction. A total of four studies met the inclusion criteria for quantitative analysis including four effect sizes for resting systolic blood pressure, four effect sizes for resting diastolic blood pressure, and three effect sizes for resting heart rate. There was evidence of a difference [mean difference (95 CI)] in resting systolic blood pressure between training with and without blood flow restriction [4.2 (0.3, 8.0) mmHg, p = 0.031]. No significant differences were observed when comparing resting diastolic blood pressure [1.2 (-1, 3.5) mmHg p = 0.274] and resting heart rate [-0.2 (-4.7, 4.1) bpm, p = 0.902] between chronic exercise with and without blood flow restriction. These results indicate that training with blood flow restriction may elicit an increase in resting systolic blood pressure. However, lack of data addressing this topic makes any conclusion speculative. Based on the results of the present study along with the overall lack of long-term data, it is suggested that future research on this topic is warranted. Recommendations include making changes in resting blood pressure a primary outcome and increasing the sample size of the interventions.

Context: Preeclampsia is a multisystem endothelial disease characterized by hypertension of pregnancy and glomeruloendotheliosis resulting in significant proteinuria. These days, the weight determination of urinary proteins by 24-hour proteinuria (P24) remains the reference method for biologically confirming this condition. However, the completion of the exam appears to be very burdensome with a long waiting period for results. Hence the need to use a simple alternative method such as the proteinuria / creatininuria ratio (PCR). Aims: Improve the diagnosis and management of preeclampsia by using a simple, less restrictive but reliable diagnostic method. Methodology: The study compared the results obtained from P24 versus PCR in confirming the diagnosis of preeclampsia in 149 Congolese women in whom the disease was suspected thanks to the urine dipstick. The cut-off values used for the diagnosis of preeclampsia were, for P24, a proteinuria> 300 mg / 24 h and for PCR a value> 30 mg / mmol. Results: Of the 149 pregnant women in whom the diagnosis of preeclampsia was suspected using the urine dipstick, only 85.9% had a P24> 300 mg. This diagnostic confirmation rate was similar to that obtained with PCR (86.6%). A linear correlation was found between P24 and PCR in the quantification of proteinuria and in the diagnosis of preeclampsia (r² = 0.627, p

Exercise and low-calorie diets are common approaches taken to produce an energy deficit for weight loss in obesity. Changes in visceral and abdominal subcutaneous fat associated with weight loss are important questions but have not yet been concluded. We investigated the relationship between changes in visceral (VAT) and subcutaneous adipose tissue (SAT) areas obtained by abdominal imaging with the change in total body fat. The relevant databases were searched through January 2021 according to the PRISMA guidelines. Sixty-five studies were included. We found that the change in total body fat was associated with changes in both VAT and abdominal SAT areas, but the relationship between total body fat and the abdominal SAT area appeared stronger. Baseline values of VAT and abdominal SAT area were similar in the three treatment groups (calorie restriction, calorie restriction plus exercise, and exercise alone). The reduction in abdominal SAT area for a loss of 1 kg of total body fat was about 10 cm2, which was similar among all the treatments. The change in VAT area (−26.3 cm2) was a similar level as the change in abdominal SAT area (−31.5 cm2) in the exercise, whereas in the calorie restriction with and without exercise, the change in VAT area (−33.6 and −51.6 cm2, respectively) was approximately half of the reduction of SAT area (−65.1 and −87.2 cm2, respectively). Absolute changes in VAT and abdominal SAT areas might differ between interventions for the exercise and calorie restriction with and without exercise.

Background Anterior cervical discectomy and fusion (ACDF) has conventionally been performed using an allograft cage with a plate-and-screw construct. Recently, standalone cages have gained popularity due to theorized decreases in operative time and postoperative dysphagia. Few studies have compared these outcomes. Here, we directly compare the outcomes of plated versus standalone ACDF constructs. Methods A single-center retrospective review of patients undergoing ACDF after June 2011 with at least 6 months of follow up was conducted. Clinical outcomes were analyzed and compared between standalone and plated constructs. Multivariate regression analysis of the primary outcome, need for revision surgery, as well as several secondary outcomes, procedure duration, estimated blood loss (EBL), length of hospital stay, disposition, and incidence of dysphagia, hoarseness, or surgical site infection, was completed. Results A total of 321 patients underwent ACDF and met inclusion-exclusion criteria, with mean follow-up duration of 20 months. Forty-six (14.3%) patients received standalone constructs, while 275 (85.7%) received plated constructs. Fourteen (4.4%) total revisions were necessary, 4 in the standalone group and 10 in the plated group, yielding revision rates of 8.7% and 3.6%, respectively (P = .125). Mean EBL was 98 mL in the standalone group and 63 mL in the plated group (P = .001). Mean procedure duration was 147 minutes in the standalone group and 151 minutes in the plated group (P = .800). Mean hospital stay was 3.6 days in the standalone group and 2.5 days in the plated group (P = .270). There was no significant difference in incidence of dysphagia (P = .700) or hoarseness (P = .700). Conclusions Standalone ACDF demonstrates higher, but not statistically significant, revision rates than plate-and-screw constructs, without the hypothesized decreased incidence of dysphagia or hoarseness and without decreased procedure duration or EBL. Surgeons may consider limiting use of these constructs to cases of adjacent segment disease. Larger studies with longer follow up are necessary to make more definitive conclusions. Level of Evidence 4. Clinical Relevance This study will help spine surgeons decide between using standalone or cage-and-plate constructs for ACDF.

The emergence of the COVID-19 pandemic and subsequent public health emergency (PHE) have propelled telemedicine several years into the future. With the rapid adoption of this technology came socioeconomic inequities as minority communities disproportionately have yet to adopt telemedicine. Telemedicine offers solutions to patient access issues that have plagued urology, helping address physician shortages in rural areas and expanding the reach of urologists. The Centers for Medicare & Medicaid Services have adopted changes to expand coverage for telemedicine services. The expectation is that telemedicine will continue to be a mainstay in the health care system with gradual expansion in utilization.

Background Ventricular assist device (VAD) implantation has become an established treatment strategy for the increasing number of patients with advanced heart failure. Adequate patient self-management becomes essential to prevent adverse events, which could diminish expected outcomes and survival for patients on VAD support. Objectives The aim of this study was to provide an overview of the current state of evidence concerning self-management in VAD patients through a systematized search and mapping of the literature. Methods Following the scoping review process, a comprehensive literature search (PubMed, PsychInfo), tabular synthesis of included articles, and data analysis of synthesized findings were performed. Results Overall, twenty articles were included. Results describe the complexity of regular self-management tasks and give direction for specific self-management training. Conclusions This article represents the first comprehensive overview of available evidence suggesting the need for development and implementation of evidence-based, patient self-management curricula with therapeutic regimen for VAD patients.

Background Perforated gastric ulcers are surgical emergencies with paucity of data on the preferred treatment modality of resection versus omental patch. We aim to compare outcomes with ulcer repair and gastric resection surgeries in perforated gastric ulcers after systematic review of literature. Methods A systematic literature search was performed for publications in PubMed Medline, Embase, and Cochrane Central Register of Controlled Trials. We included all studies which compared ulcer repair vesus gastric resection surgeries for perforated gastric ulcers. We excluded studies which did not separate outcomes gastric and duodenal ulcer perforations. Results The search included nine single-institution retrospective reviews comparing ulcer repair (449 patients) versus gastric resection surgeries (212 patients). Meta-analysis was restricted to perforated gastric ulcers and excluded perforated duodenal ulcers. The majority of these studies did not control for baseline characteristics, and surgical strategies were often chosen in a non-randomized manner. All of the studies included were at high risk of bias. The overall odds ratio of mortality in ulcer repair surgery compared to gastric resection surgery was 1.79, with 95% CI 0.72 to 4.43 and p-value 0.209. Conclusion In this meta-analysis, there was no difference in mortality between the two surgical groups. The overall equivalence of clinical outcomes suggests that gastric resection is a potentially viable alternative to ulcer repair surgery and should not be considered a secondary strategy. We would recommend a multicenter randomized control trial to evaluate the surgical approach that yields superior outcomes. Level of evidence Systematic review and meta-analysis, level III.

Purpose To apply a deep learning algorithm for automated, objective, and comprehensive quantification of OCT scans to a large real-world dataset of eyes with neovascular age-related macular degeneration (AMD) and make the raw segmentation output data openly available for further research. Design Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database. Participants A total of 2473 first-treated eyes and 493 second-treated eyes that commenced therapy for neovascular AMD between June 2012 and June 2017. Methods A deep learning algorithm was used to segment all baseline OCT scans. Volumes were calculated for segmented features such as neurosensory retina (NSR), drusen, intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), retinal pigment epithelium (RPE), hyperreflective foci (HRF), fibrovascular pigment epithelium detachment (fvPED), and serous PED (sPED). Analyses included comparisons between first- and second-treated eyes by visual acuity (VA) and race/ethnicity and correlations between volumes. Main Outcome Measures Volumes of segmented features (mm3) and central subfield thickness (CST) (μm). Results In first-treated eyes, the majority had both IRF and SRF (54.7%). First-treated eyes had greater volumes for all segmented tissues, with the exception of drusen, which was greater in second-treated eyes. In first-treated eyes, older age was associated with lower volumes for RPE, SRF, NSR, and sPED; in second-treated eyes, older age was associated with lower volumes of NSR, RPE, sPED, fvPED, and SRF. Eyes from Black individuals had higher SRF, RPE, and serous PED volumes compared with other ethnic groups. Greater volumes of the majority of features were associated with worse VA. Conclusions We report the results of large-scale automated quantification of a novel range of baseline features in neovascular AMD. Major differences between first- and second-treated eyes, with increasing age, and between ethnicities are highlighted. In the coming years, enhanced, automated OCT segmentation may assist personalization of real-world care and the detection of novel structure–function correlations. These data will be made publicly available for replication and future investigation by the AMD research community.

Background Robotic and laparoscopic hepatectomies having increased utilization as minimally invasive techniques are explored for hepatobiliary malignancies. Although the data on outcomes from these 2 approaches are emerging, the cost-benefit analysis of these approaches remains sparse. This study compares the costs associated with robotic vs. laparoscopic liver resections, taking into account 30-day complications. Methods Using the American College of Surgeons National Surgical Quality Improvement Program database, a propensity-matched cohort of patients with laparoscopic or robotic liver resections between 2014 and 2017 was identified. Costs were assigned to perioperative variables, including operating room (OR) time, length of stay, blood transfusions, and 30-day complications. Cost estimates were obtained from the Centers for Medicare and Medicaid Services billing data (2017), American Hospital Association data (2017), relevant literature, and local institutional cost data. Results In our matched cohort of 454 patients (227 per group), total costs associated with laparoscopic liver resections were estimated at $5.5 M ($24 K per patient) vs. $6.8 M ($29.8 K per patient) for robotic liver resections (21.3% difference, P < .001). The higher cost associated with robotic hepatectomies was related to blood transfusions ($22.0 K vs. $12.1 K, P = .02), length of stay ($2.05 M vs. $1.76 M, P = .046), and OR time ($4.01 M vs. $3.24 M, P < .0001). Discussion Robotic hepatectomies were associated with higher costs compared to laparoscopic hepatectomies. The 2 major contributors to the cost disparity were increased OR time and increased length of stay. Future studies are warranted to analyze high-volume Minimally Invasive Surgery surgeons’ impact in specialty centers on potentially mitigating this current cost disparity.

This prospective controlled study examined long-term trajectories of neuropsychological performance in individuals with traumatic brain injury (TBI) compared to healthy controls, and the impact of IQ, age at injury, time since injury, and injury severity on change over time. Fifty-three individuals with moderate to severe TBI (60.37% male

Refugee youth face sexual health challenges, and research investigating contributing factors has primarily focused on identifying contextual barriers. However, it is also important to investigate protective factors, as well as how risk and protective factors work together across contexts. The present study explored both contextual facilitators and barriers to refugee young women’s sexual health and how these factors intersect to influence behavior. Interviews were conducted with twelve female refugees ages 18-24. Participants’ countries of origin included Burma, Central African Republic, the Democratic Republic of Congo, and Somalia; most participants had lived in the United States for over five years. Data were analyzed using thematic text analysis and narrative analysis. Findings revealed four primary themes: sex/relationship restrictions, judgment/disapproval, support, and youth outcomes. Themes varied by context (e.g., family, peers, religion, culture) and were related to one another in important ways, such that refugee young women who violate sociocultural sex/relationship expectations experience actual or anticipated judgment from others, which leads to fear, embarrassment, and risky sexual behavior. However, participants also shared that social and institutional support would contribute to improved sexual health outcomes. Findings highlight the importance of considering refugee young women’s sociocultural contexts when addressing sexual health challenges.

Objective This study compared traumatic brain injury (TBI) outcomes from 2 cohorts: the National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems (TBIMS) in the United States and Longitudinal Head Injury Outcome Study conducted in Victoria, Australia, by the Monash Epworth Rehabilitation Research Centre (MERRC). Design Cohort study with 1- and 2-year follow-up. Setting Acute trauma care and inpatient rehabilitation with follow-up. Participants Patients (N=1056) with moderate-severe TBI admitted in 2000-2012 to inpatient rehabilitation after motor vehicle–related collisions, who completed follow-up, were matched using 1:2 matching algorithm based on age at injury, days of posttraumatic amnesia, and years education, resulting in groups of 352 (MERRC) and 704 patients (TBIMS). Intervention The cohorts had received acute trauma care and inpatient rehabilitation for a median 38 (MERRC) or 33 days (TBIMS). The MERRC group also had routine access to community-based support and rehabilitation for return to work or school, attendant care, and home help as justified, funded by an accident compensation system, whereas the TBIMS cohort had variable access to these services. Main Outcome Measures Outcomes were assessed 1 and 2 years post injury in terms of employment, living situation, marital status, and Glasgow Outcome Scale-Extended (GOS-E) scores. Results At 2 years post injury, MERRC participants were more likely to be competitively employed. At both 1 and 2 years post injury, MERRC participants were more likely to be married and living independently. On GOS-E, the TBIMS group had higher percentages of patients in Lower Severe Disability/Vegetative State and Upper Good Recovery than MERRC participants, whereas the MERRC cohort had higher percentages of Lower Moderate Disability than TBIMS. Conclusions Findings may suggest that routine provision of community-based supports could confer benefits for long-term TBI outcomes. Further studies documenting rehabilitation services are needed to explore this.

A subset (35%) of triple-negative breast cancers (TNBCs) expresses androgen receptor (AR) activity. However, clinical trials with antiandrogen drugs have shown limited efficacy, with about a 19% clinical benefit rate. We investigated the therapeutic enhancement of antiandrogens as radiosensitizers in combination with (18)F-FDG in TNBC. Methods: We screened 5 candidate drugs to evaluate shared toxicity when combined with either (18)F-FDG, x-rays, or ultraviolet radiation, at doses below their respective half-maximal inhibitory concentrations. Cytotoxic enhancement of antiandrogen in combination with (18)F-FDG was evaluated using cell proliferation and DNA damage assays. Finally, the therapeutic efficacy of the combination treatment was evaluated in mouse tumor models of TNBC and prostate cancer. Results: Bicalutamide, an antiandrogen drug, was found to share similar toxicity in combination with either (18)F-FDG or x-rays, indicating its sensitivity as a radiosensitizer to (18)F-FDG. Cell proliferation assays demonstrated selective toxicity of combination bicalutamide-(18)F-FDG in AR-positive 22RV1 and MDA-MB-231 cells in comparison to AR-negative PC3 cells. Quantitative DNA damage and cell cycle arrest assays further confirmed radiation-induced damage to cells, suggesting the role of bicalutamide as a radiosensitizer to (18)F-FDG–mediated radiation damage. Animal studies in MDA-MB-231, 22RV1, and PC3 mouse tumor models demonstrated significant attenuation of tumor growth through combination of bicalutamide and (18)F-FDG in the AR-positive model in comparison to the AR-negative model. Histopathologic examination corroborated the in vitro and in vivo data and confirmed the absence of off-target toxicity to vital organs. Conclusion: These data provide evidence that (18)F-FDG in conjunction with antiandrogens serving as radiosensitizers has utility as a radiotherapeutic agent in the ablation of AR-positive cancers.

This document was prepared by the DUNE collaboration using the resources of the Fermi National Accelerator Laboratory (Fermilab), a U.S. Department of Energy, Office of Science, HEP User Facility. Fermilab is managed by Fermi Research Alliance, LLC (FRA), acting under Contract No. DE-AC02-07CH11359. The DUNE collaboration also acknowledges the international, national, and regional funding agencies supporting the institutions who have contributed to completing this Technical Design Report., The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. DUNE is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. Central to achieving DUNE's physics program is a far detector that combines the many tens-of-kiloton fiducial mass necessary for rare event searches with sub-centimeter spatial resolution in its ability to image those events, allowing identification of the physics signatures among the numerous backgrounds. In the single-phase liquid argon time-projection chamber (LArTPC) technology, ionization charges drift horizontally in the liquid argon under the influence of an electric field towards a vertical anode, where they are read out with fine granularity. A photon detection system supplements the TPC, directly enhancing physics capabilities for all three DUNE physics drivers and opening up prospects for further physics explorations. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. Volume IV presents an overview of the basic operating principles of a single-phase LArTPC, followed by a description of the DUNE implementation. Each of the subsystems is described in detail, connecting the high-level design requirements and decisions to the overriding physics goals of DUNE., Fermi Research Alliance, LLC (FRA) DE-AC02-07CH11359

Without insights into the threats affecting species across their distributions and throughout their annual cycles, effective conservation management cannot be applied. The Whenua Hou diving petrel Pelecanoides whenuahouensis (WHDP) is a Critically Endangered small seabird whose offshore habits and threats are poorly understood. We tracked WHDPs year-round in 2015/16, 2017/18, and 2018/19 using global location-sensing immersion loggers to identify offshore distribution, movements, behaviour, and overlap with commercial fishing effort. During the breeding period, WHDPs ranged from southern Aotearoa (New Zealand) to Maukahuka (Auckland Islands). After breeding, WHDPs migrated southwest towards the Polar Front south of Australia, exhibited clockwise movements, and returned to their breeding grounds via the Subantarctic Front. During the non-breeding period, WHDPs exhibited extreme aquatic behaviour and spent >95% of their time on, or under, water. The core areas used consistently during breeding and non-breeding periods warrant listing as Important Bird and Biodiversity Areas. Spatiotemporal overlap of commercial fishing effort with breeding distributions was considerable (35%), in contrast with non-breeding distributions (0%). Spatial restrictions of anthropogenic activity around the breeding colony during the breeding period could help protect WHDPs, but such measures should be subjected to a structured decision-making framework. Our results illustrate the importance of year-round studies to inform conservation of marine species.

Background Cockayne syndrome is a progressive multisystem genetic disorder linked to defective DNA repair and transcription. This rare condition encompasses a very wide spectrum of clinical severity levels ranging from severe prenatal onset to mild adult-onset subtypes. The rarity, complexity and variability of the disease make early diagnosis and severity assessment difficult. Based on similar approaches in other neurodegenerative disorders, we propose to validate diagnostic and severity scores for Cockayne syndrome. Methods Clinical, imaging and genetic data were retrospectively collected from 69 molecularly confirmed CS patients. A clinical diagnostic score and a clinical-radiological diagnostic score for CS were built using a multivariable logistic regression model with a stepwise variable selection procedure. A severity score for CS was designed on five items (head circumference, growth failure, neurosensorial signs, motor autonomy, communication skills) and validated by comparison with classical predefined severity subtypes of CS. Results Short stature, enophtalmos, hearing loss, cataracts, cutaneous photosensitivity, frequent dental caries, enamel hypoplasia, morphological abnormalities of the teeth, areflexia and spasticity were included in the clinical diagnostic score as being the most statistically relevant criteria. Appropriate weights and thresholds were assigned to obtain optimal sensitivity and specificity (95.7% and 86.4% respectively). The severity score was shown to be able to quantitatively differentiate classical predefined subtypes of CS and confirmed the continuous distribution of the clinical presentations in CS. Longitudinal follow-up of the severity score was able to reflect the natural course of the disease. Conclusion The diagnostic and severity scores for CS will facilitate early diagnosis and longitudinal evaluation of future therapeutic interventions. Prospective studies will be needed to confirm these findings.

Paroxysmal dyskinesias (PD) are rare movement disorders characterized by recurrent attacks of dystonia, chorea, athetosis, or their combination, with large phenotypic and genetic heterogeneity. 3-Hydroxy-isobutyryl-CoA hydrolase (HIBCH) deficiency is a neurodegenerative disease characterized in most patients by a continuous decline in psychomotor abilities or a secondary regression triggered by febrile infections and metabolic crises.We describe two PD patients from two pedigrees, both carrying a homozygous c.913A > G, p.Thr305Ala mutation in the HIBCH gene, associated with an unusual clinical presentation. The first patient presented in the second year of life with right paroxysmal hemidystonia lasting for 30 minutes, without any loss of consciousness and without any triggering factor. The second patient has presented since the age of 3 recurrent exercise-induced PD episodes which have been described as abnormal equinovarus, contractures of the lower limbs, lasting for 1 to 4 hours, associated with choreic movements of the hands. Their neurological examination and metabolic screening were normal, while brain magnetic resonance imaging showed abnormal signal of the pallidi.We suggest that HIBCH deficiency, through the accumulation of metabolic intermediates of the valine catabolic pathway, leads to a secondary defect in respiratory chain activity and pyruvate dehydrogenase (PDH) activity and to a broad phenotypic spectrum ranging from Leigh syndrome to milder phenotypes. The two patients presented herein expand the spectrum of the disease to include unusual paroxysmal phenotypes and HIBCH deficiency should be considered in the diagnostic strategy of PD to enable adequate preventive treatment.

Having learners (K7–10) acquire system thinking skills is challenging. Together with teachers we deploy qualitative representations of complex systems to enable this learning process. Teachers select their own topics for their leaners to work on which makes that lessons vary in content depending on the teacher’s preference. Within this setting we face the challenge of adequately coaching learners while they create their knowledge models. For this, we use norm-model based feedback, ignoring learner specific information. Here we report the working and effectiveness of this approach.

The emergence of the COVID-19 pandemic has demanded the adoption of extraordinary measures of quarantine and social distancing, impacting educational institutions worldwide. Schools and campuses – which used to be spaces for social exchange – had to cease face-to-face instruction and shift to remote learning with no prior planning or training, which posed several challenges to education systems around the globe. In Latin America – responsible, today, for over half of the planet’s daily COVID-19-related deaths - this scenario is even more dramatic. The diverse socioeconomic levels of the student population is a major challenge for online teaching, as institutions cannot provide computer training, equipment and connectivity to all those in need. In spite of all challenges, universities which are part of AUSJAL (Association of Universities Entrusted to the Society of Jesus in Latin America) are making every effort to offer online classes during this pandemic, since education plays a pivotal role in these countries. This paper presents a selection of Design educational experiences conducted in AUSJAL universities during this pandemic. Design educators from Brazil, Colombia, Ecuador and Nicaragua present educational methods and strategies for dealing with this critical situation. In conclusion, we discuss how their innovative and engaging teaching ideas are paving the way towards not simply a new, but a “better normal” in Latin America.

What is the goal of your paper? What questions did you seek to answer? Digital health is an emerging discipline that utilizes hardware and software tools to improve healthcare delivery efficiency and accessibility. Technologies that fall under the digital health umbrella include mobile phone applications, telemedicine, and social media networks. The goal of this review is to highlight two mobile phone applications that were developed for premature ejaculation and Peyronie’s disease. Summarize the latest research on your topic. Through the course of our review, we aim to highlight how these applications were conceived, the manner in which users interface with these tools and future directions for these software solutions. We identified that patients and practitioners alike are creating digital health solutions based upon personal and clinical experiences. What answers did you find? What are the major takeaways/conclusions of your examination? What’s the impact on future research? The major takeaway of our examination is that digital health is an emerging area of innovation and investigation. Existing solutions however need further real-world evaluation to assess their clinical validity.

Background Duodenal adenocarcinoma treatment consists of either simple or radical surgical resection. Existing evidence suggests similar survival outcomes between the two but is limited by small numbers and single-institution analysis. We aim to compare survival after partial versus radical resection for duodenal adenocarcinoma using the National Cancer Database (NCDB). Methods Using NCDB results from 2004 to 2014, we compared patients with duodenal adenocarcinoma undergoing partial resection (n = 1247) and radical resection (n = 1240) by age, sex, facility type, facility location, cancer stage, cancer grade, lymph node sampling, node status, tumor size, margin status, neoadjuvant therapy, and adjuvant therapy using chi-square analysis. Survival was compared using propensity matching. Results Patients undergoing partial resection had overall earlier cancer stage, more favorable tumor grade, and were less likely to undergo lymph node sampling and neoadjuvant therapy. When overall survival was compared between the 2 propensity-matched groups, the median survival was 46.7 months after partial resection and 43.2 months after radical resection ( P = .329), and overall survival was similar between the 2 groups ( P = .894). The use of adjuvant therapy demonstrated improved survival over either surgery alone ( P < .0001, P = .0037). Conclusion Partial resection did not demonstrate worse survival outcomes than radical resection for duodenal adenocarcinoma. The use of adjuvant therapy in addition to surgery demonstrated improved survival regardless of surgery type and played a larger role in survival than the type of surgery. Our findings provide evidence to support the continued use of both partial and radical surgical resections to treat duodenal malignancy.

Purpose The majority of colorectal cancers are resistant to cancer immune checkpoint inhibitors. Ionizing radiation (IR) and several radiosensitizers, including PARP inhibitors, can enhance responsiveness to immune checkpoint inhibitors by potentially complementary mechanisms of action. We assessed the ability of radiation and PARP inhibition to induce proimmunogenic changes in tumor cells and enhance their in vivo responsiveness to anti-PD-1 antibodies. Methods and Materials We performed a candidate drug screen and used flow cytometry to assess effects of the PARP inhibitor veliparib on IR-mediated changes in MHC-1 antigen presentation and surface localization of immune-modulating proteins including PD-L1 and calreticulin in colorectal cancer tumor models. Reverse transcription polymerase chain reaction was used to assess the effects of veliparib and radiation on the expression of proinflammatory and immunosuppressive cytokines. The ability of concurrent PARP inhibition and subablative doses of radiation therapy to enhance in vivo responsiveness to anti-PD-1 antibodies was assessed using unilateral flank-tumor models with or without T-cell depletion. Results Veliparib was a potent radiosensitizer in both cell lines. Radiation increased surface localization of MHC-1 and PD-L1 in a dose-dependent manner, and veliparib pretreatment significantly enhanced these effects with high (8 Gy) but not with lower radiation doses. Enhancement of MHC-1 and PD-L1 surface localization by IR and IR+ veliparib remained significant 1, 3, and 7 days after treatment. IR significantly increased delayed tumoral expression of proinflammatory cytokines interferon-Ƴ and CXCL10 but had no significant effect on the expression of IL-6 or TGF-β. Concurrent administration of veliparib and subablative radiation therapy (8 Gy × 2) significantly prolonged anti-PD-1–mediated in vivo tumor growth delay and survival in both tumor models. Moreover, these effects were more pronounced in the microsatellite instability-mutated MC38 tumor model. Enhancement of anti-PD-1 mediated tumor growth delay with veliparib and IR was attenuated by CD8+ T-cell depletion. Conclusions We provide preclinical evidence for a novel therapeutic strategy to enhance responsiveness of colorectal tumors to immune checkpoint inhibitors.

Introduction The coronavirus disease 2019 (COVID-19) pandemic has expanded the utilization of telemedicine in clinical practice to minimize potential risks to both patients and providers. We aim to describe the perception of telemedicine by both surgical patients and providers to understand the preferences for future incorporation in future surgical practice. Methods An anonymous survey was administered to providers that transitioned clinic visits to telemedicine encounters since the start of the COVID-19 pandemic. In the second part of the study, patients who underwent video telemedicine appointments answered survey questions via telephone. Results Twenty-six out of 36 (72.7%) providers responded. Over 75% reported that they could effectively communicate with patients over telemedicine. Six (23.1%) reported that they could adequately assess surgical sites. Of 361 patients, 187 consented to the study (consent rate 51.8%). Among patients, the most common result to choose a telemedicine appointment was to avoid the risk of COVID-19 transmission (84, 44.9%), though the minority reported that they would choose telemedicine after the pandemic (64, 34.2%). Those patients who would choose an in-person visit were more likely to have a higher Charlson Comorbidity Score, body mass index, and use friends or family for transportation. In open-ended feedback, patients suggested that telemedicine would be better suited for long-term follow-up rather than the immediate postoperative setting. Conclusions Patients and providers reported a high degree of satisfaction using telemedicine during the COVID-19 pandemic but noted concern with limited physical examinations. Telemedicine may be suited for preoperative evaluation and medium-term and long-term postoperative follow-up for surgical patients.

Wong, V, Dankel, SJ, Spitz, RW, Bell, ZW, Viana, RB, Chatakondi, RN, Abe, T, and Loenneke, JP. The effect of blood flow restriction therapy on recovery after experimentally induced muscle weakness and pain. J Strength Cond Res 36(4): 1147-1152, 2022-The purpose was to determine if blood flow restriction with no external load could be used as a means of active therapy after experimentally induced fatigue and soreness. Twelve women and 7 men (aged 18-35 years) participated in a randomized controlled trial using a within-subject design. The study intervention was 3 consecutive visits. Visit 1 included the fatiguing/soreness-inducing protocol for the elbow flexors, which was performed only once during the study. Torque was measured before/after to confirm individuals began in a weakened state. Subjects then completed blood flow restriction therapy on one arm and the sham therapy on the other. Subjects performed elbow flexion/contraction with no external load on both arms. Torque was measured once more 10 minutes after the fatiguing/soreness-inducing protocol. Twenty-four hours later, soreness and torque were assessed in each arm, followed by another bout of therapy. Forty-eight hours after the initial visit, soreness and torque were measured again. There were no differences (median difference [95% credible interval]) in the recovery of torque between the blood flow restriction and sham therapy conditions at 10 minutes (0.5 [-2.7, 3.8] N·m), 24 hours (-2.34 [-6, 1.14] N·m), or 48 hours (-1.94 [-5.45, 1.33] N·m). There were also no differences in ratings of soreness at 24 hours (-2.48 [-10.05, 5.05]) or 48 hours (2.58 [-4.96, 10.09]). Our results indicate that this specific model of blood flow restriction therapy did not enhance the recovery of the muscle compared with a sham condition without the application of pressure.

Background Anastomotic leakage remains a dreaded complication after colorectal surgery. Stem-cell-based therapies have been shown to increase angiogenesis and cell proliferation. Objective The purpose of this research was to investigate the use of adipose-derived stem cells on the healing of ischemic colonic anastomoses in a rat model. Design This is an animal research study using xenotransplantation. Settings Male Wistar rats (300-400 g, n = 48) were purchased from a licensed breeder. Patients Adipose stem cells were isolated from the subcutaneous fat of healthy human donors. Interventions The rats underwent laparotomy with creation of an ischemic colorectal anastomosis created by ligation of mesenteric vessels. The animals were divided into 3 groups: control group with an ischemic anastomosis, vehicle-only group in which the ischemic anastomosis was treated with an absorbable gelatin sponge, and a treatment group in which the ischemic anastomosis was treated with an absorbable gelatin sponge plus adipose stem cells. Animals were killed at postoperative days 3 and 7. Main outcome measures Anastomotic leakage was defined as the finding of feculent peritonitis or perianastomotic abscess on necropsy. Rat mRNA expression was measured using real-time polymerase chain reaction. Results Adipose-derived stem cells significantly decreased anastomotic leakage when compared with control at both postoperative days 3 (25.0% vs 87.5%; p = 0.02) and 7 (25.0% vs 87.5%; p = 0.02). The use of an absorbable gelatin sponge alone had no effect on anastomotic leakage when compared with control and postoperative days 3 or 7. We found that stem cell-treated animals had a 5.9-fold and 7.4-fold increase in the expression of vascular endothelial growth factor when compared with control at 3 and 7 days; however, this difference was not statistically significant when compared with the absorbable gelatin sponge group. Limitations This is a preclinical animal research study using xenotransplantation of cultured stem cells. Conclusions Locally transplanted adipose stem cells enhance the healing of ischemic colorectal anastomoses and may be a novel strategy for reducing the risk of anastomotic leakage in colorectal surgery. See Video Abstract at http://links.lww.com/DCR/B203. EL TRANSPLANTE LOCAL DE CELULAS MADRE ADIPOSAS REDUCE LA FUGA ANASTOMOTICA EN LAS SUTURAS COLORRECTALES ISQUEMICAS: MODELO EN RATAS: Las fugas anastomoticas son una complicacion pusilanime despues de toda cirugia colorrectal. Se ha demostrado que el tratamiento con celulas madre aumenta la angiogenesis y la proliferacion celular.Investigar el uso de celulas madre derivadas de tejido adiposo en la cicatrizacion de una anastomosis colonica isquemica basada en ratas como modelo.Estudio de investigacion en animales utilizando xenotrasplantes.Adquisicion de tipicas ratas de laboratorio raza Wistar, todas machos (300-400 g, n = 48) de un criadero autorizado.Aislamiento de celulas madre de tipo adiposo del tejido celular subcutaneo en donantes humanos sanos.Las ratas se sometieron a laparotomia con la creacion de una anastomosis colorrectal isquemica obtenida mediante ligadura controlada de los vasos mesentericos correspondientes. Los animales se dividieron en tres grupos: grupo de control con anastomosis isquemica, grupo de vehiculo unico en el que la anastomosis isquemica se trato con una esponja de gelatina absorbible, y un grupo de tratamiento en el que la anastomosis isquemica se trato con una esponja de gelatina absorbible asociada a un vastago adiposo de celulas madre. Los animales fueron sacrificados el POD3 y el POD7.La fuga anastomotica fue definida como el hallazgo de peritonitis fecaloidea o absceso perianastomotico a la necropsia. La expresion de RNAm de las ratas se midio usando PCR en tiempo real.Las celulas madre derivadas de tejido adiposo disminuyeron significativamente la fuga anastomotica en comparacion con el grupo control tanto en el POD3 (25% frente a 87.5%, p = 0.02) como en el POD7 (25% frente a 87.5%, p = 0.02). El uso de una esponja de gelatina absorbible sola, no tuvo efecto sobre la fuga anastomotica en comparacion con los controles el POD3 o el POD7. Descubrimos que los animales tratados con celulas madre adiposas tenian un aumento de 5,9 y 7,4 veces en la expresion de VEGF en comparacion con el control a los 3 y 7 dias, respectivamente; sin embargo, esta diferencia no fue estadisticamente significativa en comparacion con el grupo de esponja de gelatina absorbible.Este es un estudio preclinico de investigacion en animales que utiliza xenotrasplantes de celulas madre adiposas cultivadas.Las celulas madre de tipo adiposo trasplantadas localmente mejoran la cicatrisacion en casos de anastomosis colorrectales isquemicas, y podrian convertirse en una nueva estrategia para reducir el riesgo de fugas anastomoticas en casos de cirugia colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B203. (Traduccion-Dr Xavier Delgadillo).

Purpose Medical case-based reasoning solves problems by applying experience gained from the outcome of previous treatments of the same kind. Particularly for complex treatment decisions, for example, incidentally found intracranial aneurysms (IAs), it can support the medical expert. IAs bear the risk of rupture and may lead to subarachnoidal hemorrhages. Treatment needs to be considered carefully, since it may entail unnecessary complications for IAs with low rupture risk. With a rupture risk prediction based on previous cases, the treatment decision can be supported. Methods We present an interactive visual exploration tool for the case-based reasoning of IAs. In presence of a new aneurysm of interest, our application provides visual analytics techniques to identify the most similar cases with respect to morphology. The clinical expert can obtain the treatment, including the treatment outcome, for these cases and transfer it to the aneurysm of interest. Our application comprises a heatmap visualization, an adapted scatterplot matrix and fully or partially directed graphs with a circle- or force-directed layout to guide the interactive selection process. To fit the demands of clinical applications, we further integrated an interactive identification of outlier cases as well as an interactive attribute selection for the similarity calculation. A questionnaire evaluation with six trained physicians was used. Result Our application allows for case-based reasoning of IAs based on a reference data set. Three classifiers summarize the rupture state of the most similar cases. Medical experts positively evaluated the application. Conclusion Our case-based reasoning application combined with visual analytic techniques allows for representation of similar IAs to support the clinician. The graphical representation was rated very useful and provides visual information of the similarity of the k most similar cases.