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Aryan Haratian, Katie Yensen, Jennifer A Bell, Laith K Hasan, Tara Shelby, Brandon Yoshida, Ioanna K Bolia, Alexander E Weber, Frank A Petrigliano USC Epstein Family Center for Sports Medicine at Keck Medicine of USC, Los Angeles, CA, USACorrespondence: Frank A PetriglianoUSC Epstein Family Center for Sports Medicine at Keck Medicine of USC, 1520 San Pablo Street, Suite 2000, Los Angeles, CA, 90033, USATel +1 323 442-5822Email fpetrigliano@gmail.comAbstract: Shoulder instability is a relatively common injury especially in the young athletic population and its surgical management continues to remain a controversial topic in sports medicine orthopedics. Anterior instability is the most common type encountered and is estimated to have an incidence rate of 0.08 per 1000 person–years in the general population; however, this figure is likely higher in the young athletic population. While in recent practice, arthroscopic surgery has become the new gold standard for management, reported failure rates as high as 26% and high recurrence rates in specific subpopulations such as young men in high collision sports have led to the consideration of alternative open procedures such as open Bankart repair, Latarjet, capsular shift, and glenoid bone grafting. These procedures may be preferred in specific patient subgroups such as young athletes involved in contact sports and those with Hill–Sachs defects and multidirectional instability, with postoperative recurrence rates of instability as low as 10%. The purpose of this review is to provide an overview of different open surgical techniques in the management of shoulder instability and summarize patient outcomes including recurrence rates for shoulder instability, return to sport, range of motion (ROM), muscle strength, and complications either individually by procedure or in comparison with other techniques, with special focus on their impact in the athletic population.Keywords: open shoulder stabilization, athletes, anterior instability, open Bankart repair, open Latarjet, open capsular shift

Ioanna K Bolia, Aryan Haratian, Jennifer A Bell, Laith K Hasan, Nima Saboori, Ryan Palmer, Frank A Petrigliano, Alexander E Weber USC Epstein Family Center for Sports Medicine at Keck Medicine of USC, Los Angeles, CA, USACorrespondence: Alexander E WeberUSC Epstein Family Center for Sports Medicine at Keck Medicine of USC, 1520 San Pablo Street, Suite 2000, Los Angeles, CA, 90033, USAEmail weber.ae@gmail.comAbstract: Anterior cruciate ligament reconstructions (ACLR) are a relatively common procedure in orthopedic sports medicine with an estimated 130,000 arthroscopic operations performed annually. Most procedures are carried out on an outpatient basis, and though success rates of ACLR are as high as 95%, pain remains the most common postoperative complication delaying patient discharge, and thereby increasing the costs associated with patient care. Despite the success and relative frequency of ACLR surgery, optimal and widely accepted strategies and regimens for controlling perioperative pain are not well established. In recent years, the paradigm of pain control has shifted from exclusively utilizing opiates and opioid medications in the acute postoperative period to employing other agents and techniques including nerve blocks, intra-articular and periarticular injections of local anesthetic agents, NSAIDs, and less commonly, ketamine, tranexamic acid (TXA), sedatives, gabapentin, and corticosteroids. More often, these agents are now used in combination and in synergy with one another as part of a multimodal approach to pain management in ACLR, with the goal of reducing postoperative pain, opioid consumption, and the incidence of delayed hospital discharge. The purpose of this review is to consolidate current literature on various agents involved in the management of postoperative pain following ACLR, including the role of classically used opiate and opioid medications, as well as to describe other drugs currently utilized in practice either individually or in conjunction with other agents as part of a multimodal regimen in pain management in ACLR.Keywords: anterior cruciate ligament reconstruction, ACL, postoperative pain, patient outcomes, multimodal pain management

Victoria Forcina,1 Branavan Vakeesan,1 Chelsea Paulo,1 Laura Mitchell,1 Jennifer AH Bell,2 Seline Tam,1 Kate Wang,1 Abha A Gupta,1,3,4 Jeremy Lewin1,3,5 1Adolescent and Young Adult Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada; 2Joint Center for Bioethics, University of Toronto, Toronto, ON, Canada; 3Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada; 4Division of Hematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; 5ONTrac, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia Purpose: Although cancer clinical trials (CT) offer opportunities for novel treatments that may lead to improved outcomes, adolescents and young adults (AYA) are less likely to participate in these trials as compared to younger children and older adults. We aimed to identify the perceptions and attitudes toward CT in AYA that influence trial participation. Materials and methods: A systematic review of cancer literature was conducted that assessed perceptions and attitudes toward CT enrollment limited to AYA patients (defined as age 15–39). We estimated the frequency of identified themes by pooling identified studies. Results: In total, six original research articles were identified that specifically addressed perceptions or attitudes that influenced CT participation in AYA patients. Three studies were conducted at pediatric centers – one at an AYA unit, one at an adult cancer hospital, and one was registry based. Major themes identified for CT acceptability included: hope for positive clinical affect, altruism, and having autonomy. Potential deterrents included: prolonged hospitalization, worry of side effects, and discomfort with experimentation. Conclusion: Limited information is available with regard to the perceptions and attitudes toward CT acceptability among AYA patients, especially those treated at adult cancer centers, which prevents generalization of data and themes. Future research assessing strategies for understanding and supporting CT decision-making processes among AYA represents a key focus for future funding to improve CT enrollment. Keywords: adolescent and young adult, clinical trials, barriers, psychosocial, cancer

Objective: To determine whether the obesity-related decrement in fatty acid oxidation (FAO) in primary human skeletal muscle cells (HSkMC) is linked with lower mitochondrial content and whether this deficit could be corrected via overexpression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha). Research Design and Methods: FAO was studied in HSkMC from lean (BMI 22.4 +/- 0.9 kg/m(2); N = 12) and extremely obese (45.3 +/- 1.4 kg/m(2); N = 9) subjects. Recombinant adenovirus was used to increase HSkMC PGC-1alpha expression (3.5- and 8.0-fold), followed by assessment of mitochondrial content (mtDNA and cytochrome C oxidase IV [COXIV]), complete ((14)CO(2) production from labeled oleate), and incomplete (acid soluble metabolites [ASM]) FAO, and glycerolipid synthesis. Results: Obesity was associated with a 30% decrease (P < 0.05) in complete FAO, which was accompanied by higher relative rates of incomplete FAO ([(14)C]ASM production/(14)CO(2)), increased partitioning of fatty acid toward storage, and lower (P < 0.05) mtDNA (-27%), COXIV (-35%), and mitochondrial transcription factor (mtTFA) (-43%) protein levels. PGC-1alpha overexpression increased (P < 0.05) FAO, mtDNA, COXIV, mtTFA, and fatty acid incorporation into triacylglycerol in both lean and obese groups. Perturbations in FAO, triacylglycerol synthesis, mtDNA, COXIV, and mtTFA in obese compared with lean HSkMC persisted despite PGC-1alpha overexpression. When adjusted for mtDNA and COXIV content, FAO was equivalent between lean and obese groups. Conclusion: Reduced mitochondrial content is related to impaired FAO in HSkMC derived from obese individuals. Increasing PGC-1alpha protein levels did not correct the obesity-related absolute reduction in FAO or mtDNA content, implicating mechanisms other than PGC-1alpha abundance. [ABSTRACT FROM AUTHOR]

Abstract Background The field of interventional cardiovascular MRI is hampered by the unavailability of active guidewires that are both safe and conspicuous. Heating of conductive guidewires is difficult to predict in vivo and disruptive to measure using external probes. We describe a clinical-grade 0.035” (0.89 mm) guidewire for MRI right and left heart catheterization at 1.5 T that has an internal probe to monitor temperature in real-time, and that has both tip and shaft visibility as well as suitable flexibility. Methods The design has an internal fiberoptic temperature probe, as well as a distal solenoid to enhance tip visibility on a loopless antenna. We tested different tip-solenoid configurations to balance heating and signal profiles. We tested mechanical performance in vitro and in vivo in comparison with a popular clinical nitinol guidewire. Results The solenoid displaced the point of maximal heating (“hot spot”) from the tip to a more proximal location where it can be measured without impairing guidewire flexion. Probe pullback allowed creation of lengthwise guidewire temperature maps that allowed rapid evaluation of design prototypes. Distal-only solenoid attachment offered the best compromise between tip visibility and heating among design candidates. When fixed at the hot spot, the internal probe consistently reflected the maximum temperature compared external probes. Real-time temperature monitoring was performed during porcine left heart catheterization. Heating was negligible using normal operating parameters (flip angle, 45°; SAR, 1.01 W/kg); the temperature increased by 4.2°C only during high RF power mode (flip angle, 90°; SAR, 3.96 W/kg) and only when the guidewire was isolated from blood cooling effects by an introducer sheath. The tip flexibility and in vivo performance of the final guidewire design were similar to a popular commercial guidewire. Conclusions We integrated a fiberoptic temperature probe inside a 0.035” MRI guidewire. Real-time monitoring helps detect deleterious heating during use, without impairing mechanical guidewire operation, and without impairing MRI visibility. We therefore need not rely on prediction to ensure safe clinical operation. Future implementations may modulate specific absorption rate (SAR) based on temperature feedback.

Abstract Background How socio-demographic factors influence women's autonomy in decision making on health care including purchasing goods and visiting family and relatives are very poorly studied in Nepal. This study aims to explore the links between women's household position and their autonomy in decision making. Methods We used Nepal Demographic Health Survey (NDHS) 2006, which provided data on ever married women aged 15-49 years (n = 8257). The data consists of women's four types of household decision making; own health care, making major household purchases, making purchase for daily household needs and visits to her family or relatives. A number of socio-demographic variables were used in multivariable logistic regression to examine the relationship of these variables to all four types of decision making. Results Women's autonomy in decision making is positively associated with their age, employment and number of living children. Women from rural area and Terai region have less autonomy in decision making in all four types of outcome measure. There is a mixed variation in women's autonomy in the development region across all outcome measures. Western women are more likely to make decision in own health care (1.2-1.6), while they are less likely to purchase daily household needs (0.6-0.9). Women's increased education is positively associated with autonomy in own health care decision making (p < 0.01), however their more schooling (SLC and above) shows non-significance with other outcome measures. Interestingly, rich women are less likely to have autonomy to make decision in own healthcare. Conclusions Women from rural area and Terai region needs specific empowerment programme to enable them to be more autonomous in the household decision making. Women's autonomy by education, wealth quintile and development region needs a further social science investigation to observe the variations within each stratum. A more comprehensive strategy can enable women to access community resources, to challenge traditional norms and to access economic resources. This will lead the women to be more autonomous in decision making in the due course.

Abstract Background Statistical methods to tentatively identify differentially expressed genes in microarray studies typically assume larger sample sizes than are practical or even possible in some settings. Results The performance of several probe-level and probeset models was assessed graphically and numerically using three spike-in datasets. Based on the Affymetrix GeneChip, a novel nested factorial model was developed and found to perform competitively on small-sample spike-in experiments. Conclusions Statistical methods with test statistics related to the estimated log fold change tend to be more consistent in their performance on small-sample gene expression data. For such small-sample experiments, the nested factorial model can be a useful statistical tool. This method is implemented in freely-available R code (affyNFM), available with a tutorial document at http://www.stat.usu.edu/~jrstevens.

Abstract Background Maternal mortality is too rare in high income countries to be used as a marker of the quality of maternity care. Consequently severe maternal morbidity has been suggested as a better indicator. Using the maternal morbidity outcome indicator (MMOI) developed and validated for use in routinely collected population health data, we aimed to determine trends in severe adverse maternal outcomes during the birth admission and in particular to examine the contribution of postpartum haemorrhage (PPH). Methods We applied the MMOI to the linked birth-hospital discharge records for all women who gave birth in New South Wales, Australia from 1999 to 2004 and determined rates of severe adverse maternal outcomes. We used frequency distributions and contingency table analyses to examine the association between adverse outcomes and maternal, pregnancy and birth characteristics, among all women and among only those with PPH. Using logistic regression, we modelled the effects of these characteristics on adverse maternal outcomes. The impact of adverse outcomes on duration of hospital admission was also examined. Results Of 500,603 women with linked birth and hospital records, 6242 (12.5 per 1,000) suffered an adverse outcome, including 22 who died. The rate of adverse maternal outcomes increased from 11.5 in 1999 to 13.8 per 1000 deliveries in 2004, an annual increase of 3.8% (95%CI 2.3–5.3%). This increase occurred almost entirely among women with a PPH. Changes in pregnancy and birth factors during the study period did not account for increases in adverse outcomes either overall, or among the subgroup of women with PPH. Among women with severe adverse outcomes there was a 12% decrease in hospital days over the study period, whereas women with no severe adverse outcome occupied 23% fewer hospital days in 2004 than in 1999. Conclusion Severe adverse maternal outcomes associated with childbirth have increased in Australia and the increase was entirely among women who experienced a PPH. Reducing or stabilising PPH rates would halt the increase in adverse maternal outcomes.

Abstract Background In studies where microsatellite markers are employed, it is essential that the primers designed will reliably and consistently amplify target loci. In populations conforming to Hardy-Weinberg equilibrium (HWE), screening for unreliable markers often relies on the identification of heterozygote deficiencies and subsequent departures from HWE. However, since many populations naturally deviate from HWE, such as many marine invertebrates, it can be difficult to distinguish heterozygote deficiencies resulting from unreliable markers from natural processes. Thus, studies of populations that are suspected to deviate from HWE naturally would benefit from a method to validate genotype data-sets and test the reliability of the designed primers. Levels of heterozygosity are reported for the prosobranch mollusc Hydrobia ulvae (Pennant) together with a method of genotype validation and primer assessment that utilises two primer sets for each locus. Microsatellite loci presented are the first described for the species Hydrobia ulvae; the five loci presented will be of value in further study of populations of H. ulvae. Results We have developed a novel method of testing primer reliability in naturally heterozygote deficient populations. After the design of an initial primer set, genotyping in 48 Hydrobia ulvae specimens using a single primer set (Primer set_A) revealed heterozygote deficiency in six of the seven loci examined. Redesign of six of the primer pairs (Primer set_B), re-genotyping of the successful individuals from Primer set_A using Primer set_B, and comparison of genotypes between the two primer sets, enabled the identification of two loci (Hulv-06 & Hulv-07) that showed a high degree of discrepancy between primer sets A and B (0% & only 25% alleles matching, respectively), suggesting unreliability in these primers. The discrepancies included changes from heterozygotes to homozygotes or vice versa, and some individuals who also displayed new alleles of unexpected sizes. Of the other four loci examined (Hulv-01, Hulv-03, Hulv-04, & Hulv-05), all showed more than 95% agreement between primer sets. Hulv-01, Hulv-03, & Hulv-05 displayed similar levels of heterozygosity with both primer sets suggesting that these loci are indeed heterozygote deficient, while Hulv-08 showed no deficiency in either primer set. Conclusion The simple method described to identify unreliable markers will prove a useful technique for many population studies, and also emphasises the dangers in using a single primer set and assuming marker reliability in populations shown to naturally deviate from HWE.

Avian haemosporidians are a diverse group of protozoan parasites that infect a wide range of host species. Waterfowl are an ecologically and economically important group of hosts that have been underrepresented in studies of haemosporidians. Diving ducks have unique life history traits, and morphological, behavioral, and dietary differences separate them from more common dabbling ducks. Greater scaup (Aythya marila) and lesser scaup (Aythya affinis) are closely related diving ducks with declining population trends in North America. To better understand the diversity of haemosporidians within diving ducks and factors related to host infections in scaup, we surveyed 82 hunter-donated waterfowl from 8 species of divers, sea ducks, and dabblers from Green Bay, Wisconsin from 2019 to 2021. We used molecular detection methods and phylogenetic and statistical analyses to describe the diversity, host associations, and prevalence of haemosporidians. We detected 14 unique genetic lineages of haemosporidians, including 4 novel lineages. We identified at least 1 lineage of haemosporidian in each of the 8 host species of divers, sea ducks, and dabblers examined. Lesser scaup had more diverse haemosporidian communities than did greater scaup, but lineages showed no clustering among these hosts when incorporated in phylogenetic analyses with lineages from other Nearctic waterfowl. Female lesser scaup had the highest infection prevalence, but there was no effect of host age or year of sampling. Our findings underscore the importance of species and sex differences that could lead to a higher risk of infections. Our results also fill an important geographical sampling gap for haemosporidians along a key migratory route. Increased monitoring of haemosporidians in waterfowl could contribute to insights into parasite evolution and ecology and the conservation and management of host populations., (© American Society of Parasitologists 2024.)

When delivering cells on a scaffold to treat a bone defect, the cell seeding technique determines the number and distribution of cells within a scaffold, however the optimal technique has not been established. This study investigated if human adipose-derived stem cells (ASCs) transduced with a lentiviral vector to overexpress bone morphogenetic protein 2 (BMP-2) and loaded on a scaffold using dynamic orbital shaker could reduce the total cell dose required to heal a critical sized bone defect when compared with static seeding. Human ASCs were loaded onto a collagen/biphasic ceramic scaffold using static loading and dynamic orbital shaker techniques, compared with our labs standard loading technique, and implanted into femoral defects of nude rats. Both a low dose and standard dose of transduced cells were evaluated. Outcomes investigated included BMP-2 production, radiographic healing, micro-computerized tomography, histologic assessment, and biomechanical torsional testing. BMP-2 production was higher in the orbital shaker cohort compared with the static seeding cohort. No statistically significant differences were noted in radiographic, histomorphometric, and biomechanical outcomes between the low-dose static and dynamic seeding groups, however the standard-dose static seeding cohort had superior biomechanical properties. The standard-dose 5 million cell dose standard loading cohort had superior maximum torque and torsional stiffness on biomechanical testing. The use of orbital shaker technique was labor intensive and did not provide equivalent biomechanical results with the use of fewer cells., (© 2024 Wiley Periodicals LLC.)

Matrix stiffening by lysyl oxidase-like 2 (LOXL2)-mediated collagen cross-linking is proposed as a core feedforward mechanism that promotes fibrogenesis. Failure in clinical trials of simtuzumab (the humanized version of AB0023, a monoclonal antibody against human LOXL2) suggested that targeting LOXL2 may not have disease relevance; however, target engagement was not directly evaluated. We compare the spatial transcriptome of active human lung fibrogenesis sites with different human cell culture models to identify a disease-relevant model. Within the selected model, we then evaluate AB0023, identifying that it does not inhibit collagen cross-linking or reduce tissue stiffness, nor does it inhibit LOXL2 catalytic activity. In contrast, it does potently inhibit angiogenesis consistent with an alternative, non-enzymatic mechanism of action. Thus, AB0023 is anti-angiogenic but does not inhibit LOXL2 catalytic activity, collagen cross-linking, or tissue stiffening. These findings have implications for the interpretation of the lack of efficacy of simtuzumab in clinical trials of fibrotic diseases., Competing Interests: Declaration of interests M.G.J., D.E.D., and Y.W. acknowledge grants from Boehringer Ingelheim. D.E.D. is co-founder of, shareholder in, and consultant to Synairgen Research Ltd. M.G.J. acknowledges consultancy fees from Skyhawk Therapeutics. J.J.W.R., K.L., and P.D.M. are current employees of Synairgen Research Ltd. L.R. acknowledges grants from Boehringer Ingelheim and consultancy fees from Biogen, Celgene, Boehringer Ingelheim, Roche, Pliant Therapeutics, BMS, CSL Behring, FibroGen, Veracyte, and Chiesi., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Adiposity shows opposing associations with mortality within COVID-19 versus non-COVID-19 respiratory conditions. We assessed the likely causality of adiposity for mortality among intensive care patients with COVID-19 versus non-COVID-19 by examining the consistency of associations across temporal and geographical contexts where biases vary., Methods: We used data from 297 intensive care units (ICUs) in England, Wales, and Northern Ireland (Intensive Care National Audit and Research Centre Case Mix Programme). We examined associations of body mass index (BMI) with 30-day mortality, overall and by date and region of ICU admission, among patients admitted with COVID-19 (N = 34,701; February 2020-August 2021) and non-COVID-19 respiratory conditions (N = 25,205; February 2018-August 2019)., Results: Compared with non-COVID-19 patients, COVID-19 patients were younger, less often of a white ethnic group, and more often with extreme obesity. COVID-19 patients had fewer comorbidities but higher mortality. Socio-demographic and comorbidity factors and their associations with BMI and mortality varied more by date than region of ICU admission. Among COVID-19 patients, higher BMI was associated with excess mortality (hazard ratio (HR) per standard deviation (SD) = 1.05; 95% CI = 1.03-1.07). This was evident only for extreme obesity and only during February-April 2020 (HR = 1.52, 95% CI = 1.30-1.77 vs. recommended weight); this weakened thereafter. Among non-COVID-19 patients, higher BMI was associated with lower mortality (HR per SD = 0.83; 95% CI = 0.81-0.86), seen across all overweight/obesity groups and across dates and regions, albeit with a magnitude that varied over time., Conclusions: Obesity is associated with higher mortality among COVID-19 patients, but lower mortality among non-COVID-19 respiratory patients. These associations appear vulnerable to confounding/selection bias in both patient groups, questioning the existence or stability of causal effects., (© 2024. The Author(s).)