High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation.

By developing a high-density murine immunophenotyping platform compatible with high-throughput genetic screening, we have established profound contributions of genetics and structure to immune variation (http://www.immunophenotype.org). Specifically, high-throughput phenotyping of 530 unique mouse gene knockouts identified 140 monogenic 'hits', of which most had no previous immunologic association. Furthermore, hits were collectively enriched in genes for which humans show poor tolerance to loss of function. The immunophenotyping platform also exposed dense correlation networks linking immune parameters with each other and with specific physiologic traits. Such linkages limit freedom of movement for individual immune parameters, thereby imposing genetically regulated 'immunologic structures', the integrity of which was associated with immunocompetence. Hence, we provide an expanded genetic resource and structural perspective for understanding and monitoring immune variation in health and disease.

Short-Term Outcomes and Patient Perceptions after Paramedic Non-Transport during the COVID-19 Pandemic.

BACKGROUND: EMS frequently encounter patients who decline transport, yet there are little data to inform the safety of patient and/or paramedic-initiated assess, treat, and refer (ATR) protocols. We determined patient decision-making and short-term outcomes after non-transport by EMS during the COVID-19 pandemic. METHODS: This was a prospective, observational study of a random sample of patients evaluated and not transported by EMS from August 2020 to March 2021. From the EMS database, we randomly selected a daily sample of adult patients with disposition of ATR. We excluded patients dispositioned against medical advice (AMA) and those in police custody. Investigators contacted patients by phone to administer a standardized survey regarding decision-making, symptom progression, follow-up care, and satisfaction with non-transport decision. We also determined the proportion of patients who re-contacted 9-1-1 within 72 h, and unexpected deaths within 72 h using coroner data. Descriptive statistics were calculated. RESULTS: Of 4613 non-transported patients, 3330 (72%) patients for whom the disposition was ATR were included. Patients were 46% male with a median age of 49 (inter-quartile range (IQR) 31-67). Median vital signs measurements fell within the normal range. Investigators successfully contacted 584/3330 patients (18%). The most common reason for failure was lack of accurate phone number. The most common reasons patients reported for not going to the ED on initial encounter were: felt reassured after the paramedic assessment (151/584, 26%), medical complaint resolved (113/584, 19%), paramedic suggested transport was not required (73/584, 13%), concern for COVID-19 exposure (57/584, 10%), and initial concern was not medical (46/584, 8%). Ninety-five percent (552/584) were satisfied with the non-transport decision and 49% (284/584) had sought follow-up care. The majority (501/584, 86%) reported equal, improved, or resolved symptoms, while 80 patients (13%) reported worse symptoms, of whom (64/80, 80%) remained satisfied with the non-transport decision. Overall, there were 154 of 3330 (4.6%) 9-1-1 recontacts within 72 h. Based on coroner data, three unexpected deaths (0.09%) occurred within 72 h of the initial EMS calls. CONCLUSION: Paramedic disposition by ATR protocols resulted in a low rate of 9-1-1 recontact. Unexpected deaths were extremely rare. Patient satisfaction with the non-transport decision was high.

Bioinductive Patch as an Augmentation for Rotator Cuff Repair, a Systematic Review and Meta-Analysis.

INTRODUCTION: Rotator cuff tears (RCTs) are a prevalent cause of shoulder pain and dysfunction. For those who fail initial conservative treatment, operative intervention can be pursued. A significant and common complication after rotator cuff repair (RCR) is retearing or non-healing. Numerous augmentations to traditional suture RCR have been studied. Of these, the Smith+Nephew Regeneten bioinductive collagen patch has had promising initial results; however, analytic data for its use is lacking, and there is no meta-analysis comparing the available data to historical RCR outcomes. METHODS: A PRISMA-guided literature search was conducted using Ovid MEDLINE, PubMED, Cochrane, and ClinicalTrials.gov. 13 studies met inclusion and exclusion criteria. Only clinical trials on full and partial-thickness tears were included. American Shoulder and Elbow Surgeon score (ASES), Constant-Murley score (CMS), the visual analog scale for pain (VAS), the minimal clinically important difference (MCID), tendon thickness, and complication rates were primary outcomes of interest. A meta-analysis was performed to determine the overall complication and retear rate from the included studies. RESULTS: ASES, CMS, and VAS improved significantly in all studies that reported them, and most patients achieved MCID. Patient-reported outcome measure (PROM) improvements were similar to historical improvements in standard RCR, and a similar proportion of patients achieved MCID after standard repair. Tendon thickness improved significantly and to a similar degree as standard RCR. Overall retear rate after full thickness RCR augmented with the bioinductive patch was 8.3%. For partial thickness RCR, total retear rate of 1.1% across all patients. The overall complication rate with the bioinductive patch was 15.5% across all full-thickness RCR studies and 16.2% in partial thickness RCR. We found overall retear rate to be lower after augmentation with the bioinductive patch compared to traditional repair; however, the overall complication rate was similar for full-thickness tears and higher for partial-thickness tears. Lastly, adverse reactions to the bioinductive patch were noted at 0.2%. CONCLUSIONS: The bioinductive collagen patch appears to be a safe augmentation for rotator cuff repair. Patients are likely to experience significant subjective improvement in PROMs and significant increases in tendon thickness. Retear rate has been a concern after RCR for decades, and the bioinductive patch may help mitigate this risk. There is a lack of case-control studies comparing the bioinductive patch to traditional suture RCR. Such data is needed to better determine the role of the bioinductive patch in the treatment of full and partial-thickness rotator cuff repairs.

2015-2021 Industry Payments to Pediatric Orthopaedic Surgeons: Analysis of Trends and Characteristics of Top-earning Surgeons.

BACKGROUND: Analysis of industry payments to pediatric orthopaedic surgeons last occurred in 2017. We investigated payments to pediatric orthopaedic surgeons from 2015 to 2021 to understand surgeon characteristics associated with increased industry payments. METHODS: Open Payments Database datasets from 2015 to 2021 were queried for nonresearch payments to pediatric orthopaedic surgeons. Annual aggregates and subcategories were recorded. For surgeons receiving payments in 2021, the Hirsch index (h-index), gender, and US census division were found using the Scopus database, Open Payments Database, and online hospital profiles, respectively. χ 2 , Fisher exact, Mann-Whitney U , and t tests were used to compare surgeons in the top 25%, 10%, and 5% payment percentiles to the bottom 75%, 90%, and 95%, respectively. RESULTS: Payments rose 125% from 2015 to 2021. Education, royalties, and faculty/speaker increased most, while travel/lodging, honoraria, charitable contributions, and ownership interest decreased. Only royalties increased from 2019 to 2021. In 2021, of 419 pediatric orthopaedic surgeons receiving industry payments, men received greater median aggregate payments than women ($379.03 vs. $186.96, P =0.047). There were no differences in gender proportions between the top 75% and bottom 25% ( P =0.054), top 10% and bottom 90% ( P =0.235), and top 5% and bottom 95% ( P =0.280) earning comparison groups. The h-index was weakly positively correlated with industry payments ( rs =0.203, P <0.001). Mean h-indices in the 75th ( P <0.001, 95% CI: 2.62-7.65), 90th ( P =0.001, 95% CI: 3.28-13.03), and 95th ( P =0.005, 95% CI: 4.25-21.11) percentiles were significantly higher. Proportions of surgeons from the Middle Atlantic and West South Central in the 90th ( P =0.025) and 95th percentiles ( P =0.033), respectively, were significantly lower compared to all other regions. A higher proportion of surgeons from the Pacific were placed in the 90th ( P =0.004) and 95th ( P =0.024) percentiles. CONCLUSIONS: Industry payments to pediatric orthopaedic surgeons rose from 2015 to 2021. Most categories fell from 2019 to 2021, which may be related to the SARS-CoV-19 pandemic. In 2021, though gender was not related to aggregate payment percentile, location in select US census divisions and h-index was. LEVEL OF EVIDENCE: Level II-Retrospective study.

Pediatric Type I Open Both Bone Forearm Fractures: Predicting Failure of Nonoperative Management.

BACKGROUND: In recent years, nonoperative treatment of pediatric type I open both bone forearm fractures (OBBFFs) with bedside irrigation, antibiotics, closed reduction, and casting has yielded low infection rates. However, risk factors for failure of type I OBBFF closed reduction have not been well described. Our purpose was to describe management of patients with type I OBBFFs at our institution and determine what factors are associated with failure of closed reduction in this population. METHODS: This was a review of patients between 5 and 15 years of age who received initial nonoperative management for type I OBBFFs at one institution between 2015 and 2021. Primary outcome was success or failure of nonoperative management (defined as progression to surgical management). Secondary outcomes included infections, compartment syndromes, and neuropraxias. Other variables of interest were demographic information, prereduction and postreduction translation and angulation of the radius and ulna, cast index, and antibiotic administration. RESULTS: Sixty-one patients (67.7% male) with 62 type I OBBFFs were included in this study. Following initial nonoperative management, 55 injuries (88.7%) were successfully treated in casts, while the remaining 7 (11.3%) required surgical intervention following loss of acceptable reduction in cast. Median cast index (0.84, IQR 0.8 to 0.9 vs. 0.75, IQR 0.7-0.8, P =0.020) and postreduction radius translation on anteroposterior films (32.0%, IQR 17.0% to 40.0% vs. 5.0%, IQR 0.0% to 26.0%, P =0.020) were higher among those who failed nonoperative management. Multivariable logistic regression models identified increased odds of failure for every SD (0.7) increase in cast index (OR 3.78, P =0.023, 95% CI: 1.4-14.3) and 25% increase in postreduction radius translation on anteroposterior films (OR 7.39, P =0.044, 95% CI 1.2-70.4). No infections or compartment syndromes and 2 transient ulnar neuropraxias occurred. CONCLUSIONS: Closed reduction of type I OBBFFs was successful in 88.7% of cases. There were no infections after nonoperative management. Increases in cast index of 0.7 and postreduction radius translation on anteroposterior radiographs of 25% were associated with increased likelihood of failure, thus requiring surgery; age was not. LEVEL OF EVIDENCE: Level IV-retrospective comparative study.

Two AIS Cases, 2 Surgeons, 1 Operating Room, 1 Day: Faster and Safer Than 1 Case in a Day.

BACKGROUND: To lessen surgical times for patients with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal instrumentation and fusion (PSIF), our department developed a quality improvement initiative where 2 AIS cases were completed in 1 day by the same 2 surgeons operating together in 1 operating room (OR). We describe the results of this initiative, comparing operative times and outcomes to cases of these surgeons operating individually. METHODS: From 2017 to 2023, patients aged 10 to 18 years with AIS undergoing PSIF were prospectively enrolled for "Two Spine Tuesday." Patients were matched by age, sex, curve severity, and number of levels fused to historical AIS controls. Outcomes included surgery time, total OR time, estimated blood loss (EBL), volume of cell saver transfused, allogenic blood transfusion, length of stay, 90-day readmissions, Clavien-Dindo-Sink Complication Classification System complication rates, and percentage who achieved the minimal clinically important difference (MCID) for SRS-22. RESULTS: Fifty-five patients composing the 2-spine group (group 2) were compared with 55 historical sex-matched and age-matched controls (group 1). Major coronal curve and average number of levels fused were similar between groups. Overall surgery time (203 vs. 296 min, P<0.001), total OR time (P<0.001), and EBL (400 vs. 550 mL, P<0.001) were lower for group 2. Group 2 had fewer complications [n=17 (31%) vs. n=28 (51%), P=0.03]. CONCLUSIONS: Performing 2 AIS cases in 1 OR by 2 surgeons the same day resulted in shorter surgery times, less total time in the operating room, lower complication rates, and less blood loss compared with single-surgeon matched controls. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Use of i-Gel Supraglottic Airway in a Simulated Cardiac Arrest Resuscitation During Boat Rescue Transport by Los Angeles County Fire Lifeguard Division: A Proof-of-Concept Study.

OBJECTIVE: The Los Angeles County Fire Department Lifeguard Division responds to water rescues and medical and dive emergencies across 72 miles of Southern California coastline and Catalina Island. Limited advanced life support resources make cardiac arrest resuscitations logistically challenging during transport to shore or the hyperbaric chamber. This proof-of-concept study looked to determine if an i-Gel (Intersurgical Complete Respiratory Systems, Wokingham, Berkshire, UK) supraglottic airway device would either become dislodged or compromise ventilations during prolonged resuscitation at high speeds over open water with an ongoing automatic chest compression device (ACCD). METHODS: A simulated resuscitation was performed on the Los Angeles County Lifeguard rescue boat while underway at speeds up to 25 knots. A LUCAS ACCD (Jolife AB, Ideon Science Park, Lund, Sweden) and a size 3 i-Gel were used. The volume of ventilations and depth of compressions were continuously monitored using the AmbuMan Advanced manikin (Ambu, Ballerup, Denmark). RESULTS: The i-Gel supraglottic airway device delivered appropriate ventilations measuring between 300 and 400 mL/breath when delivered on the upstroke of compression. The i-Gel did not dislodge during transport. CONCLUSION: The i-Gel supraglottic airway device appears to provide adequate ventilations without dislodgment during ongoing compressions with an ACCD during high-speed water transport.

Environmental surveillance of antimicrobial resistance (AMR), perspectives from a national environmental regulator in 2023.

The development, and in some cases increasing prevalence, of resistance to antimicrobials used in clinical and veterinary settings has long been recognised. In recent years, the concept of 'One Health' has added recognition of the role that the environment plays in health protection along with the need for protection of the health of the environment itself. Organisations including the World Health Organization, United Nations Environment Programme, and national governments have identified a need for surveillance of antimicrobial resistance in the environment to sit alongside the surveillance carried out in clinical, veterinary and food sectors. However, having recognised the need for environmental surveillance there are multiple challenges in deciding what this should entail. For example, what pathogens or genes to monitor, who or what we wish to protect and what measures we wish to enable to decrease infection risks. That might include sampling near a source of resistant organisms entering the environment or conversely sampling where the exposure actually occurs. Choices need to be made at both policy and technical levels based on the detailed purposes of surveillance. This paper discusses these issues from the perspective of a national environmental regulator.

Perceived effectiveness of video interviews for orthopaedic surgery residency during COVID-19.

BACKGROUND: During the 2020-21 residency interview season, interviews were conducted through virtual platforms due to the COVID-19 pandemic. The purpose of this study is to assess the general perceptions of applicants, residents and attendings at a single, large, metropolitan orthopaedic residency with regards to the video interview process before and after the interview season. METHODS: Surveys were sent to all orthopaedic applicants, residents, and attendings before the interview season. Applicants who received interviews and responded to the first survey (46) and faculty who responded to the first survey (28) were sent a second survey after interviews to assess how their perceptions of video interviews changed. RESULTS: Initially, 50% of applicants (360/722) and 50% of faculty and residents (28/56) responded before interview season. After interviews, 55% of interviewees (25/46) and 64% of faculty and residents (18/28) responded. Before interviews, 91% of applicants stated they would prefer in-person interviews and 71% were worried that video interviews would prevent them from finding the best program fit. Before interviews, 100% of faculty and residents stated they would rather conduct in-person interviews and 86% felt that residencies would be less likely to find applicants who best fit the program. Comparing responses before and after interviews, 16% fewer applicants (p = 0.01) perceived that in-person interviews provide a better sense of a residency program and faculty and residents' perceived ability to build rapport with interviewees improved in 11% of respondents (p = 0.01). However, in-person interviews were still heavily favored by interviewees (84%) and faculty and residents (88%) after the interview season. CONCLUSIONS: In-person interviews for Orthopaedic Surgery Residency are perceived as superior and are preferred among the overwhelming majority of applicants, residents, and interviewers. Nevertheless, perceptions toward video interviews improved in certain domains after interview season, identifying potential areas of improvement and alternative interview options for future applicants.

Characterizing preoperative expectations for patients undergoing reverse total shoulder arthroplasty.

BACKGROUND: There remains a paucity of information analyzing which factors most influence preoperative expectations for patients undergoing reverse total shoulder arthroplasty (RTSA). The purposes of our study were to characterize preoperative patient expectations for those scheduled to undergo RTSA and to determine the impact of demographic factors, shoulder function, and shoulder pain on these preoperative expectations. METHODS: Patients were prospectively recruited into the study if they were scheduled to undergo an elective unilateral primary RTSA for a diagnosis of glenohumeral arthritis. Preoperative patient expectations were evaluated using the Hospital for Special Surgery's Shoulder Surgery Expectation Survey. Patients also completed the American Shoulder and Elbow Surgeons shoulder score, the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function-Upper Extremity computer adaptive test (version 2.0), the PROMIS Pain Interference (PI) computer adaptive test (version 1.1), the PROMIS Depression computer adaptive test (version 1.0), visual analog scores, and an itemized satisfaction questionnaire, which paralleled the Hospital for Special Surgery's Shoulder Surgery Expectation Survey. Demographic data and preoperative shoulder range of motion (ROM) were also recorded. RESULTS: A total of 107 patients scheduled to undergo RTSA were included in the study. Relief of daytime pain (n = 91, 85%), improvement in self-care (n = 86, 80%), and improvement in shoulder ROM (n = 85, 79%) were most commonly cited as "very important" expectations. In the item-specific analysis, lower PROMIS Upper Extremity scores were correlated with greater expectations for the ability to reach sideways (P = .015) and the ability to perform daily activities (P = .018). Patients with lower shoulder ROM had greater expectations for improved shoulder ROM (internal rotation with arm at 90°, P = .004) and an improved ability to perform daily activities (forward elevation, P = .038; abduction, P = .009). In the cumulative analysis, a greater number of very important expectations was associated with African American race (P = .013), higher PROMIS PI score (r = 0.351, P = .004), and lower overall preoperative satisfaction (r = 0.334, P < .001). CONCLUSION: Patients scheduled to undergo RTSA have the greatest expectations for relief of daytime pain, improvement in self-care, and improvement in shoulder ROM. Patients with limited preoperative ROM have greater expectations for improvement in self-care and the ability to perform daily activities in addition to expectations for improvement in shoulder ROM. Greater overall expectations for surgery were not associated with preoperative physical function but were instead associated with lower preoperative satisfaction and higher PROMIS PI scores.

The impact of external beam radiation therapy on shoulder surgical outcomes: a case series study.

HYPOTHESIS: External beam radiation therapy (XRT) is a commonly used treatment adjunct in patients with breast cancer and is known to cause soft tissue dysfunction. However, data on XRT as a preoperative risk factor for shoulder surgery is limited. The purpose of this study was to assess whether prior history of breast cancer treated with XRT has an impact on surgical complications or outcomes. We hypothesize that patients treated with XRT will have a higher rate of surgical complications and lower outcomes. METHODS: A 20-year retrospective chart review across a large, academic health care system was performed. Inclusion criterion comprised any patient with history of breast cancer of the upper-outer or axillary region treated with XRT. Patients also must have undergone a surgical procedure to the ipsilateral shoulder with at least 1-year postoperative follow-up. Patients were stratified by demographics, hand dominance, and surgery type. Postoperative outcomes including range of motion (ROM) and visual analog scale (VAS) scores for pain were also collected. RESULTS: Eighteen patients were identified (100% female) with an average age of 66.3 years (standard deviation 10.5 years). Ten shoulders underwent rotator cuff repair (RCR), 4 total shoulder arthroplasty (TSA), 3 reverse shoulder arthroplasty (RSA), and 1 arthroscopic superior labrum anterior to posterior (SLAP) repair. Four patients treated with RCR (40%) experienced postoperative complications related to their procedure. These included scapular winging, adhesive capsulitis, stiffness, and one retear. Two patients treated with shoulder arthroplasty (28.6%) experienced postoperative complications that included lymphedema and periprosthetic fracture following a mechanical fall in one RSA patient and periprosthetic infection in a TSA patient. ROM across all groups improved, most significantly in forward flexion and internal rotation among RCR patients (P < .001). Furthermore, a statistically significant improvement in VAS scores was achieved in each group (6.2 ± 2.14 preoperation, 1.06 ± 1.75 postoperation; P < .001). CONCLUSION: When compared to national averages, complication rates in our cohort were higher (40% vs. 10%-17% in RCR patients and 28.6% vs. 4%-14% in arthroplasty patients). On further scrutiny, many of these complications were independent of a history of XRT and many resolved with appropriate therapy. Most importantly, functional outcomes as measured by ROM and pain scores showed appropriate improvement consistent with normal populations without history of XRT. Thus, our results suggest that performing shoulder surgery after ipsilateral XRT for breast cancer is likely safe and may offer improved pain and ROM compared to forgoing surgery without necessarily increasing the risk for postoperative complication.

Targeting T-cell oxidative metabolism to improve influenza survival in a mouse model of obesity.

BACKGROUND: Obesity is associated with impaired primary and secondary immune responses to influenza infection, with T cells playing a critical role. T-cell function is highly influenced by the cellular metabolic state; however, it remains unknown how altered systemic metabolism in obesity alters T-cell metabolism and function to influence immune response. Our objective was to identify the altered cellular metabolic state of T cells from obese mice so that we may target T-cell metabolism to improve immune response to infection. METHODS: Mice were fed normal chow or high-fat diet for 18-19 weeks. Changes in T-cell populations were analyzed in both adipose tissue and spleens using flow cytometry. Splenic T cells were further analyzed for nutrient uptake and extracellular metabolic flux. As changes in T-cell mitochondrial oxidation were observed in obesity, obese mice were treated with metformin for 6 weeks and compared to lean control mice or obese mice undergoing weight loss through diet switch; immunity was measured by survival to influenza infection. RESULTS: We found changes in T-cell populations in adipose tissue of high-fat diet-induced obese mice, characterized by decreased proportions of Treg cells and increased proportions of CD8+ T cells. Activated CD4+ T cells from obese mice had increased glucose uptake and oxygen consumption rate (OCR), compared to T cells from lean controls, indicating increased mitochondrial oxidation of glucose. Treatment of isolated CD4+ T cells with metformin was found to inhibit OCR in vitro and alter the expression of several activation markers. Last, treatment of obese mice with metformin, but not weight loss, was able to improve survival to influenza in obesity. CONCLUSIONS: T cells from obese mice have an altered metabolic profile characterized by increased glucose oxidation, which can be targeted to improve survival against influenza infection.

Dietary R, S-1,3-butanediol diacetoacetate reduces body weight and adiposity in obese mice fed a high-fat diet.

The dietary R-3-hydroxybutyrate- R-1,3-butanediol monoester increases resting energy expenditure (REE) and markers of brown and white adipose thermogenesis in lean mice. The purpose of this investigation was to determine whether the ketone ester, R, S-1,3-butanediol diacetoacetate (BD-AcAc2), increases energy expenditure and markers of adipose tissue thermogenesis in the context of high-fat diet (HFD)-induced obesity. Thirty-five-week-old male C57BL/6J mice were placed on an ad libitum HFD (45% kcal) for 10 wk. The mice were then randomized to 1 of 3 groups ( n = 10 per group) for an additional 12 wk: 1) control (Con), continuous HFD, 2) pair-fed (PF) to ketone ester (KE); and 3) KE: HFD+30% energy from BD-AcAc2. Mean energy intake throughout the study was ∼26% lower in the KE compared to the Con group (8.2 ± 0.5 vs. 11.2 ± 0.7 kcal/d; P < 0.05). Final body weight (26.8 ± 3.6 vs. 34.9 ± 4.8 g; P < 0.001) and fat mass (5.2 ± 1.2 vs. 11.3 ± 4.5 g; P < 0.001) of the KE group was significantly lower than PF, despite being matched for energy provisions. Differences in body weight and adiposity were accompanied by higher REE and total energy expenditure in the KE group compared to PF after adjustment for lean body mass and fat-mass ( P = 0.001 and 0.007, respectively). Coupled or uncoupled mitochondrial respiratory rates in skeletal muscle were not different among groups, but markers of mitochondrial uncoupling and thermogenesis (uncoupling protein-1, deiodinase-2, and peroxisome proliferator-activated receptor γ coactivator-1α) were higher in interscapular brown adipose tissue (BAT) of mice receiving the KE diet. The absence of mitochondrial uncoupling in skeletal muscle and increased markers of mitochondrial uncoupling in BAT suggest that BD-AcAc2 initiates a transcriptional signature consistent with BAT thermogenesis in the context of HFD-induced obesity.-Davis, R. A. H., Deemer, S. E., Bergeron, J. M., Little, J. T., Warren, J. L., Fisher, G., Smith, D. L., Jr., Fontaine, K. R., Dickinson, S. L., Allison, D. B., Plaisance, E. P. Dietary R, S-1,3-butanediol diacetoacetate reduces body weight and adiposity in obese mice fed a high-fat diet.

What's in a Name? Evaluating the Public Stigma of Gambling Disorder.

Public stigma of gambling disorder has negative effects on the mental health and functioning of affected individuals and impedes treatment-seeking. One factor thought to be implicated in stigma is the label used to describe the condition. The aims of this research were to: (1) evaluate whether different labels for problematic gambling behavior influence public stigma; and (2) compare public stigma of gambling disorder to other health conditions. Separate samples of university student (Study 1) and general population (Study 2) participants were randomly assigned to label conditions and completed questionnaires assessing stigma and attitudes towards the assigned label. In Study 1, the eight conditions included four gambling labels (problem gambling, pathological gambling, gambling disorder, and gambling addiction) and four psychiatric or health comparison labels (depression, obsessive-compulsive disorder, alcohol use disorder, and asthma). In Study 2, compulsive buying disorder was added as a fifth psychiatric comparison for a total of nine conditions. The results indicated that the four gambling label conditions elicited similar attitudes and stigma. Those conditions were also more stigmatized than the depression, obsessive-compulsive disorder, and asthma conditions. The gambling conditions elicited similar stigmatizing attitudes as alcohol use disorder but were slightly more stigmatized than compulsive buying disorder, with these conditions showing both similarities and differences across the stigma-related outcomes. The results were largely consistent across both samples and contribute to knowledge of the nature and origins of gambling-related stigma.

Associations of human skeletal muscle fiber type and insulin sensitivity, blood lipids, and vascular hemodynamics in a cohort of premenopausal women.

PURPOSE: Cardiometabolic disease remains a leading cause of morbidity and mortality in developed nations. Consequently, identifying and understanding factors associated with underlying pathophysiological processes leading to chronic cardio metabolic conditions is critical. Metabolic health, arterial elasticity, and insulin sensitivity (SI) may impact disease risk, and may be determined in part by myofiber type. Therefore, the purpose of this study was to test the hypothesis that type I myofiber composition would be associated with high SI, greater arterial elasticity, lower blood pressure, and blood lipids; whereas, type IIx myofibers would be associated with lower SI, lower arterial elasticity, higher blood pressure, blood lipids. METHODS: Muscle biopsies were performed on the vastus lateralis in 16 subjects (BMI = 27.62 ± 4.71 kg/m2, age = 32.24 ± 6.37 years, 43% African American). The distribution of type I, IIa, and IIx myofibers was determined via immunohistochemistry performed on frozen cross-sections. Pearson correlation analyses were performed to assess associations between myofiber composition, SI, arterial elasticity, blood pressure, and blood lipid concentrations. RESULTS: The percentage of type I myofibers positively correlated with SI and negatively correlated with systolic blood pressure SBP, diastolic blood pressure, and mean arterial pressure (MAP); whereas, the percentage of type IIx myofibers were negatively correlated with SI and large artery elasticity, and positively correlated with LDL cholesterol, SBP, and MAP. CONCLUSIONS: These data demonstrate a potential link between myofiber composition and cardiometabolic health outcomes in a cohort of premenopausal women. Future research is needed to determine the precise mechanisms in which myofiber composition impacts the pathophysiology of impaired glucose and lipid metabolism, as well as vascular dysfunction.

The International Mouse Phenotyping Consortium Web Portal, a unified point of access for knockout mice and related phenotyping data.

The International Mouse Phenotyping Consortium (IMPC) web portal (http://www.mousephenotype.org) provides the biomedical community with a unified point of access to mutant mice and rich collection of related emerging and existing mouse phenotype data. IMPC mouse clinics worldwide follow rigorous highly structured and standardized protocols for the experimentation, collection and dissemination of data. Dedicated 'data wranglers' work with each phenotyping center to collate data and perform quality control of data. An automated statistical analysis pipeline has been developed to identify knockout strains with a significant change in the phenotype parameters. Annotation with biomedical ontologies allows biologists and clinicians to easily find mouse strains with phenotypic traits relevant to their research. Data integration with other resources will provide insights into mammalian gene function and human disease. As phenotype data become available for every gene in the mouse, the IMPC web portal will become an invaluable tool for researchers studying the genetic contributions of genes to human diseases.

A mouse informatics platform for phenotypic and translational discovery.

The International Mouse Phenotyping Consortium (IMPC) is providing the world's first functional catalogue of a mammalian genome by characterising a knockout mouse strain for every gene. A robust and highly structured informatics platform has been developed to systematically collate, analyse and disseminate the data produced by the IMPC. As the first phase of the project, in which 5000 new knockout strains are being broadly phenotyped, nears completion, the informatics platform is extending and adapting to support the increasing volume and complexity of the data produced as well as addressing a large volume of users and emerging user groups. An intuitive interface helps researchers explore IMPC data by giving overviews and the ability to find and visualise data that support a phenotype assertion. Dedicated disease pages allow researchers to find new mouse models of human diseases, and novel viewers provide high-resolution images of embryonic and adult dysmorphologies. With each monthly release, the informatics platform will continue to evolve to support the increased data volume and to maintain its position as the primary route of access to IMPC data and as an invaluable resource for clinical and non-clinical researchers.

Routine.

Written a year and a half into the pandemic during a particularly difficult week, this poem explores the moral injury and emotional distress that emergency physicians encounter and must process daily. These repeated microtraumas throughout our day frequently contribute to depersonalization and it is important to recognize those factors that "break the routine" and help to improve physician well-being.

Carpal tunnel syndrome and sleep, a systematic review and meta-analysis.

BACKGROUND: The most common symptom and reason patients seek treatment for carpal tunnel syndrome is lack of sleep. Our purpose was to determine how much sleep-related symptoms of carpal tunnel syndrome improve after carpal tunnel release using validated patient-reported outcome measures (PROMs) and objective sleep data as primary measures of interest. METHODS: A PRISMA-guided literature search was conducted using Ovid MEDLINE, PubMed, Cochrane, and ClinicalTrials.gov. Only interventional clinical trials that examined primary outcome measures of interest were included. Patient-reported outcome measures underwent meta-analysis to determine how much scores improved following carpal tunnel release. RESULTS: The Pittsburgh Sleep Quality Index improved significantly after carpal tunnel release, by 4.43 points and 6.02 points at 1-3 and 6-12 months postoperatively, respectively, and continued to improve up to 2 years. Improvement on the Insomnia Severity Index after carpal tunnel release was also significant, with improvement up to 1 year postoperatively, by 8.54 points and 9.05 points at 1-3 and 6-12 months, respectively. Insomnia Severity Index scores improved significantly after splinting as well. CONCLUSIONS: The present meta-analysis determined to what extent patients can expect their sleep to improve after operative and non-operative intervention, as measured by various patient-reported outcome measures that assess sleep. The Pittsburgh Sleep Quality Index and Insomnia Severity Index correlated very well between studies and across hundreds of patients with carpal tunnel syndrome. Data are lacking to define the minimal clinically important difference and assess whether patients achieve a minimal clinically important difference for sleep questionnaires; more information on this topic is needed. LEVEL OF EVIDENCE: III.

Time-Dependent Bacterial Contamination of a Surgical Suction Tip.

Background: No in vitro surgical study has evaluated the time-dependent contamination of surgical suction tips compared with controls. Our purpose was to determine the difference in suction tip bacterial contamination rates between suction-positive and suction-negative tips. Materials and Methods: A matched-pair analysis of the contamination of surgical suction tips over a six-hour period was performed in two clean operating rooms. One suction tip was connected to standard wall suction (suction-positive group), with a matched control tip not connected to wall suction (suction-negative group). At time zero and then at hourly intervals for six hours, the distal 3 cm of suction tips were removed, placed in nutrient broth for 48 hours, then plate cultured. One hundred tips were collected for each time interval. Results: Eighty-two of 700 (11.7%) suction tips had bacterial contamination. Sixty-three (18.0%) of 350 suction-positive tips were contaminated, with 19 (5.4%) of the 350 suction-negative tips contaminated (χ2 = 26.7, p < 0.001). Suction tip contamination was time-dependent with the first significant difference between groups occurring after two hours of continuous suction (χ2 = 4.0, p = 0.04). Contamination rate in the suction-positive group increased significantly after one hour compared with time-zero controls (χ2 = 7.1, p = 0.008). There was no significant difference in frequency of positive cultures over time in the suction-negative group compared with time-zero controls. Conclusions: This is the first controlled laboratory study suggesting a time-dependent increase in positive suction tip cultures. From our data, operating room staff should have an awareness that suction tips represent a potential source of bacterial concentration. We recommend that when not in use, suction tip valves be closed if this feature is available, that hosing be manipulated to cease suction when not needed, that suckers be disconnected from tubing, or that suckers be exchanged at frequent intervals. Doing so may reduce bacterial contamination on the suction tip.