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Background: Primary hyperparathyroidism predominately affects women who are postmenopausal and causes complications, including fragility fractures. Its treatment is parathyroidectomy, which is associated with low complication and >95% cure rates. Considering fractures are associated with premature death, we aimed to determine whether the surgical management of individuals with biochemical diagnosis of primary hyperparathyroidism was associated with a reduction in fracture risk., Methods: In this population-based cohort study, we used administrative health databases to identify adults ≥18 year old who were biochemically diagnosed with primary hyperparathyroidism between 2007 and 2016 in Ontario. Patients were included if their calcium was ≥2.6 mmol/L (≥10.42 mg/dL) with a concurrent parathyroid hormone of ≥2.2 pmol/L (≥20.75 pg/mL). We followed patients and compared the incidence of fractures between those with and without parathyroidectomy. To control for potential confounding, we used inverse probability of treatment weighting to estimate the average treatment effect in the treated. Fine-Gray competing risk regression models were used to determine the association between surgery and time to fracture., Results: In a cohort of 28,059 with a biochemical diagnosis of primary hyperparathyroidism, the mean age (standard deviation) was 65 years (14.2 years), and 75% (n = 21,139) were female. Only 12.6% (n = 3,523) underwent parathyroidectomy. Weighted fracture cumulative incidence at 12 years postdiagnosis was 10.17% (n = 182) in surgical patients and 14.04% (n = 2,004) in nonsurgical patients. Parathyroidectomy prevented 1 fracture for every 26 surgeries performed (weighted risk difference, 3.87%, 95% confidence interval, 0.96%-6.62%) and reduced the hazard of fracture by 22% (weighted hazard ratio, 0.78; 95% confidence interval, 0.64-0.95)., Conclusion: In a large, publicly funded health system, parathyroidectomy significantly reduced the short- and long-term risk of fragility fractures in patients with primary hyperparathyroidism., Competing Interests: Conflict of Interest/Disclosure The authors have no conflicts of interests or disclosures to report., (Copyright © 2024. Published by Elsevier Inc.)

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (Mtb) poses a significant threat to health globally. During searching for new chemical entities regulating MDR- and XDR-Mtb, chemical investigation of the black oil beetle gut bacterium Micromonospora sp. GR10 led to the discovery of eight new members of arenicolides along with the identification of arenicolide A (Ar-A, 1), which was a previously reported macrolide with incomplete configuration. Genomic analysis of the bacterial strain GR10 revealed their putative biosynthetic pathway. Quantum mechanics-based computation, chemical derivatizations, and bioinformatic analysis established the absolute stereochemistry of Ar-A and arenicolides D-K (Ar-D-K, 2-9) completely for the first time. Biological studies of 1-9 revealed their antimicrobial activity against MDR and XDR strains of Mtb. Ar-A had the most potent in vitro antimicrobial efficacy against MDR- and XDR-Mtb. Mechanistically, Ar-A induced ATP depletion and destabilized Mtb cell wall, thereby inhibiting growth. Notably, Ar-A exerted a significant antimicrobial effect against Mtb in macrophages, was effective in the treatment of Mtb infections, and showed a synergistic effect with amikacin (AMK) in a mouse model of MDR-Mtb lung infection. Collectively, our findings indicate Ar-A to be a promising drug lead for drug-resistant tuberculosis., (© 2024 Wiley-VCH GmbH.)

Aim: To investigate the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors in liver transplant (LT) recipients with diabetes., Methods: A single-centre, retrospective analysis of prospectively collected data from an LT recipient database (1990-2023) was conducted. We included adults with pre-existing diabetes and post-transplant diabetes, newly started on GLP-1RAs and/or SGLT2 inhibitors after LT. Metabolic and biochemical parameters and outcomes were collected for up to 12 months after starting medications and were compared to those in patients receiving dipeptidyl peptidase-4 (DPP-4) inhibitors. Statistical analysis included descriptive statistics and linear mixed models., Results: We included participants on GLP-1RAs (n = 46), SGLT2 inhibitors (n = 87), combination therapy (n = 12), and a DPP-4 inhibitor comparator (n = 217). Both GLP-1RAs and combination therapy decreased mean glycated haemoglobin (HbA1c) levels, and combination therapy remained significant when adjusted for DPP-4 inhibitor treatment (-3.5%, 95% CI [-6.1, -0.95]; p = 0.0089) at 12 months. All three groups had significant decreases in mean weight and body mass index, but these remained significant in the GLP-1RA (-5.2 kg, 95% CI [-8.7, -1.7], p = 0.0039 and 1.99 kg/m 2 , 95% CI [-3.4, -0.6], p = 0.0048) and combination therapy groups (-5.4 kg, 95% CI [-10.5, -0.36], p = 0.04 and -3.4 kg/m 2 , 95% CI [-5.5, -1.3], p = 0.0015) when adjusted for DPP-4 inhibitor treatment at 12 months. Alanine aminotransferase levels decreased with GLP-1RA and combination therapy. There were two (1.4%) cases of graft rejection., Conclusion: We found that GLP-1RAs, SGLT2 inhibitors, and their combination, led to significant weight loss in LT recipients with diabetes. Combination therapy, in particular, lowered HbA1c and alanine aminotransferase levels compared to DPP-4 inhibitors. Further studies are needed to assess long-term safety and efficacy., (© 2024 John Wiley & Sons Ltd.)

Objective: High-resolution manometry (HRM) provides measures of esophageal function which are used to classify esophageal motility disorders based on the Chicago Classification system. Upper esophageal sphincter (UES) measures are obtained from HRM, but are not included in the classification system, rendering the relationship between UES measures and esophageal motility disorders unclear. Furthermore, changes in the acceptable amount of esophageal dysfunction between versions of this classification system has created controversy. The objective of this study was to determine the relationship between UES measures and esophageal function., Study Design: Cross-sectional study., Setting: Referral centre., Methods: HRM studies from the Calgary Gut Motility Center were reviewed for UES mean basal pressure, mean residual pressure, relaxation time-to-nadir, relaxation duration, and recovery time. Patients were grouped by number of failed swallows according to different iterations of the Chicago Classification: 0 to 4 (Group 1), 5 to 7 (Group 2), and 8 to 10 (Group 3)., Results: 2114 patients (65.1% female, median age 56 y) were included. There were significant increases in UES mean basal pressure (P < .001), mean residual pressure (P < .001), relaxation duration (P < .001), and recovery time (P < .001) between groups. Positive correlations existed between number of failed swallows and UES mean basal pressure (r = 0.143; P < .001), mean residual pressure (r = 0.201; P < .001), relaxation duration (r = 0.145; P < .001), and recovery time (r = 0.168; P < .001)., Conclusions: Differences in UES measures exist among patients with failed swallows, with a positive correlation between UES dysfunction and increasing dysmotility. Our findings illustrate that UES measures are closely related to esophageal function, and that even minor esophageal dysfunction is related to UES dysfunction., (© 2024 The Author(s). Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

The differences in the proteolytic patterns and shear force of pork and beef during aging were evaluated. Pork and beef semitendinosus muscles were obtained at 24 and 48 h postmortem, respectively, and aged at 4°C for 0 (Day 0), 7 (Day 7), and 14 days (Day 14). Changes in the electrical conductivity were observed in pork on Day 7 and beef on Day 14. The calpain activity increased in pork (p<0.05) after 14 days of aging, whereas that of beef decreased on Day 7 (p<0.05). The cathepsin B activity in pork and beef increased between Day 7 and 14 (p<0.05). The content of α-amino group in the 10% trichloroacetic acid-soluble fraction increased between Day 7 and 14 in pork (p<0.05), but increased steadily in beef throughout aging (p<0.05). The electrophoretogram of the myofibrillar proteins revealed a 30 kDa protein band only in the beef lane on Day 14. The cooked pork had no significant changes in the shear force during aging periods (p>0.05), while the gradual decrease in the shear force with the increasing aging periods was shown in the cooked beef (p<0.05). Circular dichroism analysis of myosin extracts from pork and beef revealed thermal denaturation temperatures of 55°C and 58°C, respectively. This study highlights the different post-mortem proteolytic patterns and thermal denaturation temperatures of myosin in pork and beef semitendinosus muscles, which contribute to distinct changes in the shear force during aging between pork and beef., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Brett Cronin and Orestes O'Brien are Editorial Board Members for JCVA and was not involved in the editorial review or the decision to publish this article.

This study investigated the relationship of carcass characteristics such as hot carcass weight and back fat thickness (BFT) and the pH of s emispinalis capitis (SC) with the cooking loss (CL) of pork shoulder butt and the CL and Warner-Bratzler shear force (WBSF) of belly. BFT was correlated with the CLs of the butt slices ( r s  = -0.30) and the belly slices ( r s  = -0.27 to -0.32). The pH of the SC muscle showed a correlation with the CLs of the butt slices ( r s  = -0.45) and the belly slices of the 6th and 11th thoracic vertebrae ( r s  = -0.28 to -0.33). Additionally, the correlations ( r s  = 0.62 to 0.77) were observed in the CLs among the belly slices. However, the WBSF of the belly slices did not show correlations with others. Therefore, the pH of the SC muscle as well as BFT can be used to obtain information on the CL of shoulder butts and bellies in carcasses., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Quantitative monitoring of cytomegalovirus (CMV) DNAemia in venous blood is standard in solid organ transplant recipients (SOTr) but is limited by the need for phlebotomy facilities and personnel. The aim of the study was to evaluate the Tasso+ capillary blood (CB) self-collection device for quantitation of plasma CMV DNAemia. Thirty adult SOTr with suspected CMV DNAemia were enrolled to have a supervised Tasso+ CB sample collection within 24 h of a venous sample. CMV DNA was quantitated in paired samples by using the Abbott M2000 Real-Time qPCR instrument. The participants were provided with a study-specific survey that measured patient acceptability of the Tasso+ device compared with venipuncture. A Tasso + CB sample was successfully collected in 28/30 (93%) patients, and 44 paired samples were analyzed. Concordance for detection of CMV DNAemia above the limit of detection (LOD) was 91% (42/44), and the Tasso + CB sample was estimated to be 95% sensitive at a viral load (VL) of 308 IU/mL. Among samples with a quantifiable DNAemia result with both methods ( N = 31), there was excellent correlation between methods (Spearman R 2 = 0.99). The difference in CMV VL between venous and Tasso+ CB samples was not dependent on time ( P > 0.1). Of 12 who completed the survey, 11 (92%) expressed a preference for Tasso+ CB collection over venipuncture. Collection of CB with the Tasso+ device is feasible, patient-acceptable, and yields generally comparable CMV DNAemia load to standard venous samples, but with lower sensitivity. Future studies to optimize and evaluate this methodology for patient self-collected samples are warranted., Importance: We evaluate an FDA-cleared blood self-collection device (Tasso+) and demonstrate that it is patient-acceptable and yields a liquid blood sample with quantitative CMV DNAemia results comparable to those of standard venipuncture samples. This opens up possibilities for self-blood collection to monitor for CMV and potentially other viruses in transplant and other at-risk populations., Competing Interests: The authors declare no conflict of interest.

Disability awareness and competency trainings are an important component of addressing ableism and health equity in the health promotion context. This commentary describes our process of developing, implementing, and refining a disability competency training, the Inclusive Community Exercise Training, for community-based group exercise instructors. The training originated from a partnership between academic researchers, community organizations, and individuals with disabilities. After initial pilot testing, we used feedback from participants to enhance the training. To optimize successful dissemination of this training, we utilized the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, which is widely used in public health. The revision process focused on generalizing content to suit a wider audience, utilizing an eLearning platform for dissemination, and optimizing interactivity to improve learning effectiveness. The commentary emphasizes the lessons learned and the significance of systematic program revision, considering diverse expertise, content tailoring, and the benefits of accessible eLearning platforms., (Published by Elsevier Inc.)

Background: This study investigated a stress management exercise program's effect on mental health, muscle pain, and autonomic nervous system activity in adults exposed to chronic stress., Methods: Thirty mothers between 40 to 59 years old raising children with disabilities were equally allocated into the yoga (YG) or control group (CG). The YG participated in 16 prop-assisted yoga sessions twice weekly for eight weeks, focusing on relaxing and strengthening neck, shoulder, back, and waist stress-related muscles. The Beck Depression Inventory, State-Trait Anxiety Inventory, Parenting Stress Scale, Stress Response Inventory, and Brief Resilience Scale assessed mental health variable changes. Visual Analog Scales (VAS) were used to self-report neck, shoulders, back, and waist pain and assess stress, anxiety, relaxation, and confidence. We also measured pain, psychological VAS, and Heart Rate Variability (HRV) immediately before and after each yoga session., Results: The YG exhibited significant reductions in muscle pain, depression, stress response, fatigue, and frustration, whereas the CG expressed no change. Prop-assisted yoga immediately improved pain and psychological VAS. HRV analyses revealed instantly reduced heart rates and an R-R interval and standard deviation normal to normal (SDNN) increase., Conclusions: Prop-assisted yoga may serve as a viable, safe, and efficient alternative therapeutic modality for managing chronic stress-related conditions.

Objective: The prevalence of metabolic diseases is increasing globally at an alarming rate; thus, it is essential that effective, accessible, low-cost therapeutics are developed. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that tightly regulate glucose homeostasis and lipid metabolism and are important drug targets for the treatment of type 2 diabetes and dyslipidemia. We previously identified LDT409, a fatty acid-like compound derived from cashew nut shell liquid, as a novel pan-active PPARα/γ/δ compound. Herein, we aimed to assess the efficacy of LDT409 in vivo and investigate the molecular mechanisms governing the actions of the fatty acid mimetic LDT409 in diet-induced obese mice., Methods: C57Bl/6 mice (6-11-month-old) were fed a chow or high fat diet (HFD) for 4 weeks; mice thereafter received once daily intraperitoneal injections of vehicle, 10 mg/kg Rosiglitazone, 40 mg/kg WY14643, or 40 mg/kg LDT409 for 18 days while continuing the HFD. During treatments, body weight, food intake, glucose and insulin tolerance, energy expenditure, and intestinal lipid absorption were measured. On day 18 of treatment, tissues and plasma were collected for histological, molecular, and biochemical analysis., Results: We found that treatment with LDT409 was effective at reversing HFD-induced obesity and associated metabolic abnormalities in mice. LDT409 lowered food intake and hyperlipidemia, while improving insulin tolerance. Despite being a substrate of both PPARα and PPARγ, LDT409 was crucial for promoting hepatic fatty acid oxidation and reducing hepatic steatosis in HFD-fed mice. We also highlighted a role for LDT409 in white and brown adipocytes in vitro and in vivo where it decreased fat accumulation, increased lipolysis, induced browning of WAT, and upregulated thermogenic gene Ucp1. Remarkably, LDT409 reversed HFD-induced weight gain back to chow-fed control levels. We determined that the LDT409-induced weight-loss was associated with a combination of increased energy expenditure (detectable before weight loss was apparent), decreased food intake, increased systemic fat utilization, and increased fecal lipid excretion in HFD-fed mice., Conclusions: Collectively, LDT409 represents a fatty acid mimetic that generates a uniquely favorable metabolic response for the treatment of multiple abnormalities including obesity, dyslipidemia, metabolic dysfunction-associated steatotic liver disease, and diabetes. LDT409 is derived from a highly abundant natural product-based starting material and its development could be pursued as a therapeutic solution to the global metabolic health crisis., Competing Interests: Declaration of competing interest CLC, LASR, and LM are co-authors on a patent related to this work. They wish to pursue collaborations to further develop LDT409 as an orally bioavailable low-cost therapy to treat obesity-related metabolic disease., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Bloodstream infections (BSIs) are a leading cause of hospitalizations and mortality among patients receiving hemodialysis (HD) therapy, especially those with a central venous catheter (CVC) for dialysis access. The use of chlorhexidine impregnated catheter caps (ClearGuard) has been associated with a decrease in the rate of HD catheter-related BSIs (CA-BSIs) in adults; similar data have not been published for children., Methods: We compared CA-BSI data from participating centers within the Standardizing Care to Improve Outcomes in Pediatric Endstage Kidney Disease (SCOPE) collaborative based on the center's use of ClearGuard caps for patients with HD catheter access. Centers were characterized as ClearGuard (CG) or non-ClearGuard (NCG) centers, with CA-BSI data pre- and post-CG implementation reviewed. All positive blood cultures in participating centers were reported to the SCOPE collaborative and adjudicated by an infectious disease physician., Results: Data were available from 1786 SCOPE enrollment forms completed January 2016-January 2022. January 2020 served as the implementation date for analyzing CG versus NCG center data, with this being the time when the last CG center underwent implementation. Post January 2020, there was a greater decrease in the rate of HD CA-BSI in CG centers versus NCG centers, with a decrease from 1.18 to 0.23 and 0.41 episodes per 100 patient months for the CG and NCG centers, respectively (p = 0.002)., Conclusions: Routine use of ClearGuard caps in pediatric dialysis centers was associated with a reduction of HD CA-BSI rates in pediatric HD patients., (© 2024. The Authors.)

Background and Aims: Endoscopic treatment is a definitive and cost-effective management strategy for early neoplasia in Barrett's oesophagus (BE). However, little is known of its impact on quality of life (QoL). This study reports outcomes of endoscopic eradication treatment (EET), focusing on QoL and costs in a Canadian tertiary referral centre., Methods: A retrospective cohort study using a prospectively maintained clinical database captured validated QoL metrics during and at the end of EET, risk factors for BE, treatment response, complications, costs, and follow-up response of all treated Barrett patients in Calgary and Southern Alberta, Canada., Results: A total of 147 BE patients were treated from 2013 to 2021. All patients showed significant improvement in almost all QoL parameters except depression. There was significant improvement in 7 of the 8 QoL metrics in those who achieved complete eradication of intestinal metaplasia (CEIM). EET was successful in achieving complete eradication of dysplasia (CED) and CEIM in 93.4% and 74.3% of patients, respectively, with a median of 3 radio frequency ablation treatments. Longer circumferential segments of BE (Cx) predicted a lower likelihood of achieving CEIM. The average total cost to achieve CED and CEIM were $10 414.58 and $9347.93CAD, respectively (compared to oesophagectomy estimated at $58 332.30 CAD)., Conclusion: This Canadian cohort reports significant post-treatment improvement in QoL parameters in patients treated to CEIM or CED over an 8-year period. EET for BE eradication is cost-effective compared to oesophagectomy. There was a low rate of complications and recurrence post-CEIM., Competing Interests: This research did not receive any specific grant from funding agencies in the public, commercial, or non-profit sectors. Authors C.A., S.C., M.G., and P.B. have received honoraria payments for lectures and presentations on Barrett’s and non-Barrett’s related talks. C.A. reports leadership role and stock options in Alimetry and Nimble Science. S.C. reports institutional Grants from Bristol-Myers Squibb Canada, Genfit, Allergan, Sequana Medical Inc., Axcella Health Inc., AstraZeneca, Merck, Ipsen, Gilead Sciences of Canada and consulting fees from Intercept Pharmaceuticals, AstraZeneca, and Novo Nordisk. P.B. reports consulting fees from AMT Vantage Endoscopy. M.G. reports travel expenses from Pentax. All other authors have no conflict of interest to report., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

This study aimed to develop a novel pH-modified nanoparticle with improved solubility and oral bioavailability of poorly water-soluble celecoxib by modifying the microenvironmental pH. After assessing the impact of hydrophilic polymers, surfactants and alkaline pH modifiers on the drug solubility, copovidone, sodium lauryl sulfate (SLS) and meglumine were chosen. The optimal formulation of solvent-evaporated, surface-attached and pH-modified nanoparticles composed of celecoxib/copovidone/SLS/meglumine at weight ratios of 1:1:0.2:0, 1:0.375:1.125:0 and 1:1:1:0.2:0.02, respectively, were manufactured using spray drying technique. Their physicochemical characteristics, solubility, dissolution and pharmacokinetics in rats were evaluated compared to the celecoxib powder. The solvent-evaporated and pH-modified nanoparticles converted a crystalline to an amorphous drug, resulting in a spherical shape with a reduced particle size compared to celecoxib powder. However, the surface-attached nanoparticles with insignificant particle size exhibited the unchangeable crystalline drug. All of them gave significantly higher solubility, dissolution, and oral bioavailability than celecoxib powder. Among them, the pH-modified nanoparticles demonstrated the most significant improvement in solubility (approximately 1600-fold) and oral bioavailability (approximately 4-fold) compared to the drug powder owing to the alkaline microenvironment formation effect of meglumine and the conversion to the amorphous drug. Thus, the pH-modified nanoparticle system would be a promising strategy for improving the solubility and oral bioavailability of poorly water-soluble and weakly acidic celecoxib., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study proposes a titanium silicide (TiSi 2 ) recombination layer for perovskite/tunnel oxide passivated contact (TOPCon) 2-T tandem solar cells as an alternative to conventional transparent conductive oxide (TCO)-based recombination layers. TiSi 2 was formed while TiO 2 was made by oxidizing a Ti film deposited on the p + -Si layer. The reaction formation mechanism was proposed based on the diffusion theory supported by experimental results. The optical and electrical properties of the TiSi 2 layer were optimized by controlling the initial Ti thicknesses (5-100 nm). With the initial Ti of 50 nm, the lowest reflectance and highly ohmic contact between the TiO 2 and p + -Si layers with a contact resistivity of 161.48 mΩ·cm 2 were obtained. In contrast, the TCO interlayer shows Schottky behavior with much higher contact resistivities. As the recombination layer of TiSi 2 and the electron transport layer of TiO 2 are formed simultaneously, the process steps become simpler. Finally, the MAPbI 3 /TOPCon tandem device yielded an efficiency of 16.23%, marking the first reported efficiency for a device including a silicide-based interlayer.

Background and Aim: Rectal hyposensitivity (RH) is common in constipation and often coexists with functional defecatory disorder (FDD). Rectal sensory thresholds are routinely evaluated with the anorectal manometry probe; however, the gold standard for the assessment of rectal sensitivity is with a barostat, use of which is limited by time constraints and availability. A novel rapid barostat bag (RBB) may facilitate measurements of rectal sensitivity. The aim is to evaluate the relationship between RH (measured by the RBB) and FDD (defined as any minor disorder of rectoanal coordination by the London classification) in constipated patients., Methods: Consecutive constipated patients referred for anorectal function testing underwent anorectal manometry with the 3D-HDAM probe as well as rectal sensation testing with the RBB pump. RH was defined by volume to first sensation >30%, urge to defecate >80%, or discomfort >100% (normalized to rectal capacity)., Results: Fifty-three percent of constipated patients had RH. Patients with FDD had a significantly increased volume to first sensation (134.5 mL vs 102.0, P = 0.02), urge to defecate (187.0 mL vs 149.0, P = 0.04), and rectal capacity (253.5 mL vs 209.0, P = 0.04) compared to constipated patients without FDD. There was no difference in normalized sensory thresholds (percent of rectal capacity) nor the prevalence of hyposensitivity to each sensory threshold nor overall hyposensitivity., Conclusion: Patients with FDD, when measured with the RBB, have increased sensory thresholds on volumetric distension, but RH was not observed when sensory threshold volume were normalized to rectal capacity. This may reflect "secondary" RH due to altered rectal biomechanics., (© 2024 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Lipid accumulation in macrophages (Mφs) is a hallmark of atherosclerosis. Yet, how lipid loading modulates Mφ inflammatory responses remains unclear. We endeavored to gain mechanistic insights into how pre-loading with free cholesterol modulates Mφ metabolism upon LPS-induced TLR4 signaling. We found that activities of prolyl hydroxylases (PHDs) and factor inhibiting HIF (FIH) are higher in cholesterol loaded Mφs post-LPS stimulation, resulting in impaired HIF-1α stability, transactivation capacity and glycolysis. In RAW264.7 cells expressing mutated HIF-1α proteins resistant to PHDs and FIH activities, cholesterol loading failed to suppress HIF-1α function. Cholesterol accumulation induced oxidative stress that enhanced NRF2 protein stability and triggered a NRF2-mediated antioxidative response prior to and in conjunction with LPS stimulation. LPS stimulation increased NRF2 mRNA and protein expression, but it did not enhance NRF2 protein stability further. NRF2 deficiency in Mφs alleviated the inhibitory effects of cholesterol loading on HIF-1α function. Mutated KEAP1 proteins defective in redox sensing expressed in RAW264.7 cells partially reversed the effects of cholesterol loading on NRF2 activation. Collectively, we showed that cholesterol accumulation in Mφs induces oxidative stress and NRF2 stabilization, which when combined with LPS-induced NRF2 expression leads to enhanced NRF2-mediated transcription that ultimately impairs HIF-1α-dependent glycolytic and inflammatory responses., (© 2024. The Author(s).)

Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting approximately 20% of children globally. While studies have been conducted elsewhere, air pollution and weather variability is not well studied in the tropics. This time-series study examines the association between air pollution and meteorological factors with the incidence of outpatient visits for AD obtained from the National Skin Centre (NSC) in Singapore. The total number of 1,440,844 consultation visits from the NSC from 2009 to 2019 was analysed. Using the distributed lag non-linear model and assuming a negative binomial distribution, the short-term temporal association between outpatient visits for AD and air quality and meteorological variability on a weekly time-scale were examined, while adjusting for long-term trends, seasonality and autocorrelation. The analysis was also stratified by gender and age to assess potential effect modification. The risk of AD consultation visits was 14% lower (RR 10th percentile : 0.86, 95% CI 0.78-0.96) at the 10th percentile (11.9 µg/m 3 ) of PM 2.5 and 10% higher (RR 90th percentile : 1.10, 95% CI 1.01-1.19) at the 90th percentile (24.4 µg/m 3 ) compared to the median value (16.1 µg/m 3 ). Similar results were observed for PM 10 with lower risk at the 10th percentile and higher risk at the 90th percentile (RR 10th percentile : 0.86, 95% CI 0.78-0.95, RR 90th percentile : 1.10, 95% CI 1.01-1.19). For rainfall for values above the median, the risk of consultation visits was higher up to 7.4 mm in the PM 2.5 model (RR 74th percentile : 1.07, 95% CI 1.00-1.14) and up to 9 mm in the PM 10 model (RR 80th percentile : 1.12, 95% CI 1.00-1.25). This study found a close association between outpatient visits for AD with ambient particulate matter concentrations and rainfall. Seasonal variations in particulate matter and rainfall may be used to alert healthcare providers on the anticipated rise in AD cases and to time preventive measures to reduce the associated health burden., (© 2024. The Author(s).)

Breast cancer is the most common type of cancer in women, and early abnormality detection using mammography can significantly improve breast cancer survival rates. Diverse datasets are required to improve the training and validation of deep learning (DL) systems for autonomous breast cancer diagnosis. However, only a small number of mammography datasets are publicly available. This constraint has created challenges when comparing different DL models using the same dataset. The primary contribution of this study is the comprehensive description of a selection of currently available public mammography datasets. The information available on publicly accessible datasets is summarized and their usability reviewed to enable more effective models to be developed for breast cancer detection and to improve understanding of existing models trained using these datasets. This study aims to bridge the existing knowledge gap by offering researchers and practitioners a valuable resource to develop and assess DL models in breast cancer diagnosis., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

In the classical insulin target tissues of liver, muscle, and adipose tissue, chronically elevated levels of free fatty acids (FFA) impair insulin signaling. Insulin signaling molecules are also present in β-cells where they play a role in β-cell function. Therefore, inhibition of the insulin/insulin-like growth factor 1 pathway may be involved in fat-induced β-cell dysfunction. To address the role of β-cell insulin resistance in FFA-induced β-cell dysfunction we co-infused bisperoxovanadate (BPV) with oleate or olive oil for 48 hours in rats. BPV, a tyrosine phosphatase inhibitor, acts as an insulin mimetic and is devoid of any antioxidant effect that could prevent β-cell dysfunction, unlike most insulin sensitizers. Following fat infusion, rats either underwent hyperglycemic clamps for assessment of β-cell function in vivo or islets were isolated for ex vivo assessment of glucose-stimulated insulin secretion (GSIS). We also incubated islets with oleate or palmitate and BPV for in vitro assessment of GSIS and Akt (protein kinase B) phosphorylation. Next, mice with β-cell specific deletion of PTEN (phosphatase and tensin homolog; negative regulator of insulin signaling) and littermate controls were infused with oleate for 48 hours, followed by hyperglycemic clamps or ex vivo evaluation of GSIS. In rat experiments, BPV protected against fat-induced impairment of β-cell function in vivo, ex vivo, and in vitro. In mice, β-cell specific deletion of PTEN protected against oleate-induced β-cell dysfunction in vivo and ex vivo. These data support the hypothesis that β-cell insulin resistance plays a causal role in FFA-induced β-cell dysfunction., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD) and progresses faster in males than in females. We identify sex-based differences in kidney metabolism and in the blood metabolome of male and female individuals with diabetes. Primary human proximal tubular epithelial cells (PTECs) from healthy males displayed increased mitochondrial respiration, oxidative stress, apoptosis, and greater injury when exposed to high glucose compared with PTECs from healthy females. Male human PTECs showed increased glucose and glutamine fluxes to the TCA cycle, whereas female human PTECs showed increased pyruvate content. The male human PTEC phenotype was enhanced by dihydrotestosterone and mediated by the transcription factor HNF4A and histone demethylase KDM6A. In mice where sex chromosomes either matched or did not match gonadal sex, male gonadal sex contributed to the kidney metabolism differences between males and females. A blood metabolomics analysis in a cohort of adolescents with or without diabetes showed increased TCA cycle metabolites in males. In a second cohort of adults with diabetes, females without DKD had higher serum pyruvate concentrations than did males with or without DKD. Serum pyruvate concentrations positively correlated with the estimated glomerular filtration rate, a measure of kidney function, and negatively correlated with all-cause mortality in this cohort. In a third cohort of adults with CKD, male sex and diabetes were associated with increased plasma TCA cycle metabolites, which correlated with all-cause mortality. These findings suggest that differences in male and female kidney metabolism may contribute to sex-dependent outcomes in DKD.

Previous studies demonstrated that the non-thermal effects of pulsed electric fields can promote protein glycation below 40 °C, but it does not always enhance the emulsifying properties of proteins, such as in the bovine serum albumin/glucose model. Therefore, the aim of this study was to investigate the impact of non-thermal effects on the glucose glycation and emulsification properties of bovine serum albumin at 90 °C. The results of circular dichroism, surface hydrophobicity, and molecular dynamics simulations showed that the polarization effect increased the degree of glycation of bovine serum albumin-glucose conjugates from 12.82 % to 21.10 % by unfolding protein molecule, while the emulsifying stability index was increased from 79.17 to 100.73 compared with the control. Furthermore, the results of principal component analysis and Pearson correlation analysis indicated that the ionization effect and the free radicals generated by pulsed electric fields significantly (p < 0.05) inhibited browning and reduced free sulfhydryl content. This study demonstrated that pulsed electric fields combined with heating can prepare glycated proteins with good emulsifying properties in a short period of time and at temperatures lower than conventional heating while reducing energy consumption. This processing strategy has potential applications in improving the emulsifying performance of highly stable proteins., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The accumulation of lipid and the formation of macrophage foam cells is a hallmark of atherosclerosis, a chronic inflammatory disease. To better understand the role of macrophage lipid accumulation in inflammation during atherogenesis, we studied early molecular events that follow the accumulation of oxidized low-density lipoprotein (oxLDL) in cultured mouse macrophages. We previously showed that oxLDL accumulation downregulates the inflammatory response in conjunction with downregulation of late-phase glycolysis. In this study, we show that within hours after LPS stimulation, macrophages with accumulated oxLDL maintain early-phase glycolysis but selectively downregulate activation of AKT2, one of three AKT isoforms. The inhibition of AKT2 activation reduced LPS-induced ATP citrate lyase activation, acetyl-CoA production, and acetylation of histone 3 lysine 27 (H3K27ac) in certain inflammatory gene promoters. In contrast to oxLDL, multiple early LPS-induced signaling pathways were inhibited in macrophages with accumulated cholesterol, including TBK1, AKT1, AKT2, MAPK, and NF-κB, and early-phase glycolysis. The selective inhibition of LPS-induced AKT2 activation was dependent on the generation of mitochondrial oxygen radicals during the accumulation of oxLDL in macrophages prior to LPS stimulation. This is consistent with increased oxidative phosphorylation, fatty acid synthesis, and oxidation pathways found by comparative transcriptomic analyses of oxLDL-loaded versus control macrophages. Our study shows a functional connection between oxLDL accumulation, inactivation of AKT2, and the inhibition of certain inflammatory genes through epigenetic changes that occur soon after LPS stimulation, independent of early-phase glycolysis., (Copyright © 2024 The Authors.)

Silicon carbide (SiC) wafers have attracted attention as a material for advanced power semiconductor device applications due to their high bandgap and stability at high temperatures and voltages. However, the inherent chemical and mechanical stability of SiC poses significant challenges in the chemical mechanical planarization (CMP) process, an essential step in reducing defects and improving surface flatness. SiC exhibits different mechanical and chemical properties depending on SiC terminal faces, affecting SiC oxidation behavior during the CMP process. Here, we investigate the process of oxide layer formation during the CMP process and how it relates to the SiC terminal faces. The results show that under the same conditions, the C-terminated face (C-face) exhibits higher oxidation reaction kinetics than the Si-terminated face (Si-face), forming an oxide layer of finer particles. Due to the different oxidation kinetic tendencies, the oxide layer formed on the C-face has a higher friction coefficient and more defects than the oxide layer formed on the Si-face. This results in a higher removal rate during CMP for the C-face than the Si-face. Furthermore, by controlling the physicochemical properties of the oxide film, high removal rates can be achieved by friction with the pad alone, without the need for nanoparticle abrasives., (© 2023. The Author(s).)

Caspases are cysteine-aspartic proteases that were initially discovered to play a role in apoptosis. However, caspase 8, in particular, also has additional nonapoptotic roles, such as in inflammation. Adipocyte cell death and inflammation are hypothesized to be initiating pathogenic factors in type 2 diabetes. Here, we examined the pleiotropic role of caspase 8 in adipocytes and obesity-associated insulin resistance. Caspase 8 expression was increased in adipocytes from mice and humans with obesity and insulin resistance. Treatment of 3T3-L1 adipocytes with caspase 8 inhibitor Z-IETD-FMK decreased both death receptor-mediated signaling and targets of nuclear factor κ-light-chain-enhancer of activated B (NF-κB) signaling. We generated novel adipose tissue and adipocyte-specific caspase 8 knockout mice (aP2Casp8-/- and adipoqCasp8-/-). Both males and females had improved glucose tolerance in the setting of high-fat diet (HFD) feeding. Knockout mice also gained less weight on HFD, with decreased adiposity, adipocyte size, and hepatic steatosis. These mice had decreased adipose tissue inflammation and decreased activation of canonical and noncanonical NF-κB signaling. Furthermore, they demonstrated increased energy expenditure, core body temperature, and UCP1 expression. Adipocyte-specific activation of Ikbkb or housing mice at thermoneutrality attenuated improvements in glucose tolerance. These data demonstrate an important role for caspase 8 in mediating adipocyte cell death and inflammation to regulate glucose and energy homeostasis., Article Highlights: Caspase 8 is increased in adipocytes from mice and humans with obesity and insulin resistance. Knockdown of caspase 8 in adipocytes protects mice from glucose intolerance and weight gain on a high-fat diet. Knockdown of caspase 8 decreases Fas signaling, as well as canonical and noncanonical nuclear factor κ-light-chain-enhancer of activated B (NF-κB) signaling in adipose tissue. Improved glucose tolerance occurs via reduced activation of NF-κB signaling and via induction of UCP1 in adipocytes., (© 2023 by the American Diabetes Association.)

Objective: To examine the prognostic value of electroneuronography (ENoG) in predicting functional recovery in severe cases of acute facial palsy., Methods: Patients with severe degrees of facial palsy (initial House-Brackmann [HB] grades IV to VI) with available electrodiagnostic studies conducted 2-4 weeks after symptom onset were reviewed retrospectively. The patients were categorized into "good recovery" and "poor recovery" groups, with the former showing mild to no dysfunction (HB I to III) and the latter exhibiting moderate to severe dysfunction (HB IV to VI) on follow-up evaluation, 2 months after onset. ENoG amplitudes in four facial muscles (frontalis, nasalis, orbicularis oculi, and orbicularis oris), as well as age, sex, affected side, disease etiology, comorbidities, and laboratory findings, were compared between the two groups., Results: Thirty-seven patients were included. Twenty-nine of the patients showed "good recovery," and eight showed "poor recovery" at 2 months after symptom onset. Univariate analysis yielded no significant difference in age, sex, affected side, disease etiology, comorbidities, and laboratory findings between the two groups. Preserved ENoG amplitudes (individual, average, and trimmed means) were significantly higher in the good recovery group than in the poor recovery group (p<0.005). Sex (p=0.038) and the ENoG of the nasalis muscle, acquired 2-4 weeks from symptom onset (p=0.004), showed significant differences in multivariate regression analysis., Conclusion: This study suggests that the female sex and lower ENoG of the nasalis muscle, acquired 2-4 weeks from symptom onset, have negative prognostic value for the 2-month functional outcome of severe facial palsy cases.

Lipid accumulation in macrophages (Mφs) is a hallmark of atherosclerosis, yet how lipid accumulation affects inflammatory responses through rewiring of Mφ metabolism is poorly understood. We modeled lipid accumulation in cultured wild-type mouse thioglycolate-elicited peritoneal Mφs and bone marrow-derived Mφs with conditional (Lyz2-Cre) or complete genetic deficiency of Vhl, Hif1a, Nos2, and Nfe2l2. Transfection studies employed RAW264.7 cells. Mφs were cultured for 24 h with oxidized low-density lipoprotein (oxLDL) or cholesterol and then were stimulated with LPS. Transcriptomics revealed that oxLDL accumulation in Mφs downregulated inflammatory, hypoxia, and cholesterol metabolism pathways, whereas the antioxidant pathway, fatty acid oxidation, and ABC family proteins were upregulated. Metabolomics and extracellular metabolic flux assays showed that oxLDL accumulation suppressed LPS-induced glycolysis. Intracellular lipid accumulation in Mφs impaired LPS-induced inflammation by reducing both hypoxia-inducible factor 1-α (HIF-1α) stability and transactivation capacity; thus, the phenotype was not rescued in Vhl-/- Mφs. Intracellular lipid accumulation in Mφs also enhanced LPS-induced NF erythroid 2-related factor 2 (Nrf2)-mediated antioxidative defense that destabilizes HIF-1α, and Nrf2-deficient Mφs resisted the inhibitory effects of lipid accumulation on glycolysis and inflammatory gene expression. Furthermore, oxLDL shifted NADPH consumption from HIF-1α- to Nrf2-regulated apoenzymes. Thus, we postulate that repurposing NADPH consumption from HIF-1α to Nrf2 transcriptional pathways is critical in modulating inflammatory responses in Mφs with accumulated intracellular lipid. The relevance of our in vitro models was established by comparative transcriptomic analyses, which revealed that Mφs cultured with oxLDL and stimulated with LPS shared similar inflammatory and metabolic profiles with foamy Mφs derived from the atherosclerotic mouse and human aorta., (Copyright © 2023 by The American Association of Immunologists, Inc.)

Background: Poor functional status is a key marker of morbidity, yet is not routinely captured in clinical encounters. We developed and evaluated the accuracy of a machine learning algorithm that leveraged electronic health record (EHR) data to provide a scalable process for identification of functional impairment., Methods: We identified a cohort of patients with an electronically captured screening measure of functional status (Older Americans Resources and Services ADL/IADL) between 2018 and 2020 (N = 6484). Patients were classified using unsupervised learning K means and t-distributed Stochastic Neighbor Embedding into normal function (NF), mild to moderate functional impairment (MFI), and severe functional impairment (SFI) states. Using 11 EHR clinical variable domains (832 variable input features), we trained an Extreme Gradient Boosting supervised machine learning algorithm to distinguish functional status states, and measured prediction accuracies. Data were randomly split into training (80%) and test (20%) sets. The SHapley Additive Explanations (SHAP) feature importance analysis was used to list the EHR features in rank order of their contribution to the outcome., Results: Median age was 75.3 years, 62% female, 60% White. Patients were classified as 53% NF (n = 3453), 30% MFI (n = 1947), and 17% SFI (n = 1084). Summary of model performance for identifying functional status state (NF, MFI, SFI) was AUROC (area under the receiving operating characteristic curve) 0.92, 0.89, and 0.87, respectively. Age, falls, hospitalization, home health use, labs (e.g., albumin), comorbidities (e.g., dementia, heart failure, chronic kidney disease, chronic pain), and social determinants of health (e.g., alcohol use) were highly ranked features in predicting functional status states., Conclusion: A machine learning algorithm run on EHR clinical data has potential utility for differentiating functional status in the clinical setting. Through further validation and refinement, such algorithms can complement traditional screening methods and result in a population-based strategy for identifying patients with poor functional status who need additional health resources., (© 2023 The American Geriatrics Society.)

Competing Interests: Intérêts concurrents: Yasmin Nasser mentionne recevoir du soutien à la recherche, indépendamment des présents travaux, de la société Allergan à titre de chercheuse principale locale d’un essai clinique. Elle était conférencière dans le cadre d’un webinaire portant sur la douleur chronique pour les laboratoires AbbVie (2021) et elle a aussi participé à un comité consultatif pour la société Allergan (2020), indépendamment des présents travaux. Aucun autre intérêt concurrent n’a été déclaré.

Introduction: To date, most mammography-related AI models have been trained using either film or digital mammogram datasets with little overlap. We investigated whether or not combining film and digital mammography during training will help or hinder modern models designed for use on digital mammograms., Methods: To this end, a total of six binary classifiers were trained for comparison. The first three classifiers were trained using images only from Emory Breast Imaging Dataset (EMBED) using ResNet50, ResNet101, and ResNet152 architectures. The next three classifiers were trained using images from EMBED, Curated Breast Imaging Subset of Digital Database for Screening Mammography (CBIS-DDSM), and Digital Database for Screening Mammography (DDSM) datasets. All six models were tested only on digital mammograms from EMBED., Results: The results showed that performance degradation to the customized ResNet models was statistically significant overall when EMBED dataset was augmented with CBIS-DDSM/DDSM. While the performance degradation was observed in all racial subgroups, some races are subject to more severe performance drop as compared to other races., Discussion: The degradation may potentially be due to ( 1) a mismatch in features between film-based and digital mammograms ( 2) a mismatch in pathologic and radiological information. In conclusion, use of both film and digital mammography during training may hinder modern models designed for breast cancer screening. Caution is required when combining film-based and digital mammograms or when utilizing pathologic and radiological information simultaneously., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors AG declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Hwang, Trivedi, Brown-Mulry, Zhang, Nalla, Gastounioti, Gichoya, Seyyed-Kalantari, Banerjee and Woo.)

Alterations in the microbiome correlate with improved metabolism in patients following bariatric surgery. While fecal microbiota transplantation (FMT) from obese patients into germ-free (GF) mice has suggested a significant role of the gut microbiome in metabolic improvements following bariatric surgery, causality remains to be confirmed. Here, we perform paired FMT from the same obese patients (BMI > 40; four patients), pre- and 1 or 6 months post-Roux-en-Y gastric bypass (RYGB) surgery, into Western diet-fed GF mice. Mice colonized by FMT from patients' post-surgery stool exhibit significant changes in microbiota composition and metabolomic profiles and, most importantly, improved insulin sensitivity compared with pre-RYGB FMT mice. Mechanistically, mice harboring the post-RYGB microbiome show increased brown fat mass and activity and exhibit increased energy expenditure. Moreover, improvements in immune homeostasis within the white adipose tissue are also observed. Altogether, these findings point to a direct role for the gut microbiome in mediating improved metabolic health post-RYGB surgery., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background/objectives: The immunomodulatory effect of Platycodon grandiflorum (PG) has been reported, but studies on its mechanism are still lacking. This study was undertaken to confirm whether the hydrolyzed and fermented PG extract (HFPGE) obtained by adding hydrolysis and fermentation to the extraction process has an immune-enhancing effect in the in vivo system., Materials/methods: Five-week-old BALB/c mice were divided into 4 groups: normal control group (NOR), control group (CON), 150 mg/kg body weight (BW)/day HFPGE-treated group (T150), and 300 mg/kg BW/day HFPGE-treated group (T300). The mice were administered HFPGE for 4 weeks and intraperitoneally injected with cyclophosphamide (CPA, 80 mg/kg BW/day) on day 6, 7, and 8, respectively, to induce immunosuppression. The levels of immunoglobulins (Igs) and cytokines were measured in the serum. In splenocytes, proliferation and cytokine levels were measured., Results: Serum IgA, IgG, and IgM levels were observed to decrease after CPA treatment, which was recovered by HFPGE administration. The levels of serum interleukin (IL)-12, tumor necrosis factor (TNF)-α, IL-8, and transforming growth factor (TGF)-β were also decreased after exposure to CPA but increased after HFPGE administration. Decreased splenocyte proliferation was seen in CPA-treated mice, but was observed to increase in the T150 and T300 groups as compared to the NOR group. Compared to the CON group, splenocyte proliferation stimulated with concanavalin A (ConA) or lipopolysaccharide (LPS) in the HFPGE-treated groups was significantly increased. The cytokines secreted by ConA-stimulated splenocytes (IL-2, IL-12, interferon-γ, TNF-α) were increased in the T150 and T300 groups, and cytokines secreted by LPS-stimulated splenocytes (IL-4, IL-8, TGF-β) were also increased by HFPGE administration., Conclusion: These results suggest that HFPGE stimulates the immunity in immunosuppressed conditions, thereby enhancing the immune response. Therefore, it is expected that HFPGE has the potential to be used as functional food and medicine for immune recovery in various immunocompromised situations., Competing Interests: Conflict Interest: The authors declare no potential conflicts of interests., (©2023 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Purpose: To compare the clinical outcomes of intrascleral fixation of the three-piece intraocular lenses (IOLs) 2.5 mm posterior to the limbus with ciliary sulcus implantation and transscleral fixation 2.5 mm posterior to the limbus., Methods: Sixty-five eyes of 65 patients who underwent ciliary sulcus implantation or transscleral or intrascleral fixation of the AMO Sensar AR40e IOL were retrospectively reviewed. The postoperative refractive prediction error, back-calculated effective lens position (ELP), corrected distance visual acuity (CDVA), and postoperative residual cylinder were compared., Results: There were significant differences in the median (interquartile range) postoperative refractive prediction error (diopters [D]) among the three groups (p < 0.001): for ciliary sulcus implantation (33 eyes), -0.89 D (-1.21 to -0.56 D); for transscleral fixation (10 eyes), -0.40 D (-0.78 to -0.22 D); and for intrascleral fixation (22 eyes), 0.01 D (-0.28 to 0.34 D). Significant differences (p < 0.001) were observed in the median back-calculated ELP: for ciliary sulcus implantation, 4.35 mm (3.95 to 4.55 mm); for transscleral fixation, 4.51 mm (4.34 to 4.76 mm); and for intrascleral fixation, 4.90 mm (4.56 to 5.35 mm). There were no differences in the median postoperative CDVA (0, 0.10, and 0 logarithm of the minimum angle of resolution, respectively; p = 0.083) and the residual cylinder (-0.75, -1.50, and -0.63 D, respectively; p = 0.074) among three groups., Conclusions: Intrascleral fixation showed no myopic shift and the most posterior lens position, while ciliary sulcus implantation induced the greatest myopic shift and the most anterior lens position. However, there was no significant difference in the postoperative CDVA or astigmatism among the eyes with different IOL insertion methods, demonstrating good IOL stability and vision outcomes.

Competing Interests: Competing interests: Yasmin Nasser reports receiving research support, outside of this work, from Allergan as local principal investigator on a clinical trial. She was a speaker for a webinar on chronic pain in inflammatory bowel disease for AbbVie (2021) and also participated on an advisory board for Allergan (2020), outside of this work. No other competing interests were declared.

Coliphage have been suggested as an alternative to fecal indicator bacteria for assessing recreational beach water quality, but it is unclear how frequently and at what types of beaches coliphage produces a different management outcome. Here we conducted side-by-side sampling of male-specific and somatic coliphage by the new EPA dead-end hollow fiber ultrafiltration (D-HFUF-SAL) method and Enterococcus at southern California beaches over two years. When samples were combined for all beach sites, somatic and male-specific coliphage both correlated with Enterococcus. When examined categorically, Enterococcus would have resulted in approximately two times the number of health advisories as somatic coliphage and four times that of male-specific coliphage,using recently proposed thresholds of 60 PFU/100 mL for somatic and 30 PFU/100 mL for male-specific coliphage. Overall, only 12% of total exceedances would have been for coliphage alone. Somatic coliphage exceedances that occurred in the absence of an Enterococcus exceedance were limited to a single site during south swell events, when this beach is known to be affected by nearby minimally treated sewage. Thus, somatic coliphage provided additional valuable health protection information, but may be more appropriate as a supplement to FIB measurements rather than as replacement because: (a) EPA-approved PCR methods for Enterococcus allow a more rapid response, (b) coliphage is more challenging owing to its greater sampling volume and laboratory time requirements, and (c) Enterococcus' long data history has yielded predictive management models that would need to be recreated for coliphage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Aims:  To evaluate the evidence and produce a summary and recommendations for the most common heart and lung applications of point-of-care ultrasound (PoCUS)., Methods:  We reviewed 10 clinical domains/questions related to common heart and lung applications of PoCUS. Following review of the evidence, a summary and recommendation were produced, including assignment of levels of evidence (LoE) and grading of the recommendation, assessment, development, and evaluation (GRADE). 38 international experts, the expert review group (ERG), were invited to review the evidence presented for each question. A level of agreement of over 75 % was required to progress to the next section. The ERG then reviewed and indicated their level of agreement regarding the summary and recommendation for each question (using a 5-point Likert scale), which was approved if a level of agreement of greater than 75 % was reached. A level of agreement was defined as a summary of "strongly agree" and "agree" on the Likert scale responses., Findings and Recommendations:  One question achieved a strong consensus for an assigned LoE of 3 and a weak GRADE recommendation (question 1). The remaining 9 questions achieved broad agreement with one assigned an LoE of 4 and weak GRADE recommendation (question 2), three achieving an LoE of 3 with a weak GRADE recommendation (questions 3-5), three achieved an LoE of 3 with a strong GRADE recommendation (questions 6-8), and the remaining two were assigned an LoE of 2 with a strong GRADE recommendation (questions 9 and 10)., Conclusion:  These consensus-derived recommendations should aid clinical practice and highlight areas of further research for PoCUS in acute settings., Competing Interests: A number of authors have declared potential conflicts of interest from the past three years:Bøetker, M.T. [royalties received from e-learning platform USabcd.org]; Connolly, J. [honoraria received from Sonosite FujiFilm UK, equipment loans from Canon Healthcare, Terason Ultrasound, EchoNous]; Gargani, L. [honoraria received from GE Healthcare, Philips Healthcare & Caption Health]; Jarman, R.D. [honoraria received from Sonosite FujiFilm UK, equipment loans from Canon Healthcare]; Kim, D. [medical advisor for Clarius Mobile Health]; Liu, R. [honoraria received from Philips Healthcare]; Olusanya, O. [honoraria received from GE Healthcare & Sonosite FujiFilm UK]; Peck, M. [honoraria received from GE Healthcare]., (Thieme. All rights reserved.)

Objective: To systematically review the effect of intrathecal baclofen pump insertion in children with cerebral palsy (CP) with respect to scoliosis., Methods: A systematic literature search was conducted in PubMed, Embase, Cochrane Library, and Google Scholar databases up to June 2022. The inclusion criteria were as follows: (1) studies with a quantitative study design; (2) studies with a study group of children with CP; (3) studies comparing scoliosis in children with and without an intrathecal baclofen pump; and (4) studies with Cobb's angle as a parameter., Results: Of the 183 studies found, four studies, all of which were retrospective comparative studies, met the aforementioned inclusion criteria. All studies were homogeneous (I2=0%, p=0.53) and intrathecal baclofen pump insertion accelerated the progression of scoliosis (standard mean difference=0.27; 95% confidence interval=0.07-0.48)., Conclusion: Intrathecal baclofen pumps have been used to alleviate spasticity in children with CP, thus aiding their daily activities and movements. However, their advantages and disadvantages should be reviewed after sufficient time considering the pumps' negative effect on the course of scoliosis.

Objective:  To evaluate the evidence and produce a summary and recommendations for the most common heart and lung point-of-care ultrasound (PoCUS)., Methods:  We reviewed 10 clinical domains/questions related to common heart and lung applications of PoCUS. Following review of the evidence, a summary and recommendations were produced, including assigning levels of evidence (LoE) and grading of recommendation, assessment, development, and evaluation (GRADE). 38 international experts, the expert review group (ERG), were invited to review the evidence presented for each question. A level of agreement of over 75 % was required to progress to the next section. The ERG then reviewed and indicated their level of agreement of the summary and recommendation for each question (using a 5-point Likert scale), which was approved in the case of a level of agreement of greater than 75 %. A level of agreement was defined as a summary of "strongly agree" and "agree" on the Likert scale responses., Findings and Recommendations:  One question achieved a strong consensus for an assigned LoE of 3 and a weak GRADE recommendation (question 1), the remaining 9 questions achieved broad agreement with an assigned LoE of 4 and a weak GRADE recommendation (question 2), three achieved an LoE of 3 with a weak GRADE recommendation (questions 3-5), three achieved an LoE of 3 with a strong GRADE recommendation (questions 6-8) and the remaining two were assigned an LoE of 2 with a strong GRADE recommendation (questions 9 and 10)., Conclusion:  These consensus-derived recommendations should aid clinical practice and highlight areas of further research for PoCUS in acute settings., Competing Interests: A number of authors have declared potential conflicts of interest from the past three years.Bøetker, M.T. [royalties received from e-learning platform USabcd.org];Connolly, J. [honoraria received from Sonosite FujiFilm UK, equipment loans from Canon Healthcare, Terason Ultrasound, EchoNous]; Gargani, L. [honoraria received from GE Healthcare, Philips Healthcare & Caption Health]; Jarman, R.D. [honoraria received from Sonosite FujiFilm UK, equipment loans from Canon Healthcare];Kim, D. [medical advisor for Clarius Mobile Health]; Liu, R. [honoraria received from Philips Healthcare];Olusanya, O. [honoraria received from GE Healthcare & Sonosite FujiFilm UK];Peck, M. [honoraria received from GE Healthcare]., (Thieme. All rights reserved.)

Lack of disability awareness of fitness professionals is a well-established barrier to exercise participation among people with disabilities that is likely related to the lack of disability awareness training for group fitness instructors. The purposes of this study were to develop, implement, and evaluate a disability awareness training for group fitness instructors. A 90-min video training and resource manual were developed. We recruited 10 group fitness instructors from one recreation center to participate. Participants completed baseline, posttraining, and 2-month follow-up testing on survey-based outcomes including disability attitudes, confidence in exercise adaptations, and training satisfaction. Participants' confidence to adapt fitness classes was significantly improved; however, disability attitudes were high in the pretest and not significantly different posttraining. Semistructured interviews were conducted posttraining and revealed three themes: Formal disability training is needed, Managing inclusive class dynamics, and Training suggestions and satisfaction. This training demonstrated a feasible intervention for increasing disability awareness among community-based group fitness instructors.

Neurodegenerative disorders are accompanied by neuronal degeneration and glial dysfunction, resulting in cognitive, psychomotor, and behavioral impairment. Multiple factors including genetic, environmental, metabolic, and oxidant overload contribute to disease progression. Recent evidences suggest that metabolic syndrome is linked to various neurodegenerative diseases. Metabolic syndrome (MetS) is known to be accompanied by symptoms such as hyperglycemia, abdominal obesity, hypertriglyceridemia, and hypertension. Despite advances in knowledge about the pathogenesis of neurodegenerative disorders, effective treatments to combat neurodegenerative disorders caused by MetS have not been developed to date. Insulin growth factor-1 (IGF-1) deficiency has been associated with MetS-related pathologies both in-vivo and in-vitro. IGF-1 is essential for embryonic and adult neurogenesis, neuronal plasticity, neurotropism, angiogenesis, metabolic function, and protein clearance in the brain. Here, we review the evidence for the potential therapeutic effects of IGF-1 in the neurodegeneration related to metabolic syndrome. We elucidate how IGF-1 may be involved in molecular signaling defects that occurs in MetS-related neurodegenerative disorders and highlight the importance of IGF-1 as a potential therapeutic target in MetS-related neurological diseases., (© 2023. The Author(s).)

Introduction: Point-of-care ultrasonography (POCUS) is a portable imaging technology used in clinical settings. There is a need for valid tools to assess clinical competency in POCUS in medical students. The primary aim of this study was to use Kane's framework to evaluate an interpretation-use argument (IUA) for an undergraduate POCUS assessment tool., Methods: Participants from Memorial University of Newfoundland, the University of Calgary, and the University of Ottawa were recruited between 2014 and 2018. A total of 86 participants and seven expert raters were recruited. The participants performed abdominal, sub-xiphoid cardiac, and aorta POCUS scans on a volunteer patient after watching an instruction video. The participant-generated POCUS images were assessed by the raters using a checklist and a global rating scale. Kane's framework was used to determine validity evidence for the scoring inference. Fleiss' kappa was used to measure agreement between seven raters on five questions that reflected clinical competence. The descriptive comments collected from the raters were systematically coded and analyzed., Results: The overall agreement between the seven raters on five questions on clinical competency ranged from fair to moderate (κ = 0.32 to 0.55). The themes from the qualitative data were poor image generation and interpretation (22%), items not applicable (20%), poor audio and video quality (20%), poor probe handling (10%), and participant did not verbalize findings (14%)., Conclusion: The POCUS assessment tool requires further modification and testing prior before it can be used for reliable undergraduate POCUS assessment., (© 2023. The Author(s).)

Conjugated polymer (CP)-based organic field-effect transistors (OFETs) have been considered a potential sensor platform for detecting gas molecules because they can amplify sensing signals by controlling the gate voltage. However, these sensors exhibit significantly poorer oxidizing gas sensing performance than their inorganic counterparts. This paper presents a high-performance nitric oxide (NO) OFET sensor consisting of a poly(3-hexylthiophene) (P3HT) film with an ultrathin nanoporous structure. The ultrathin nonporous structure of the P3HT film was created via deposition through the shear-coating-assisted phase separation of polymer blends and selective solvent etching. The ultrathin nonporous structure of the P3HT film enhanced NO gas diffusion, adsorption, and desorption, resulting in the ultrathin nanoporous P3HT-film-based OFET gas sensor exhibiting significantly better sensing performance than pristine P3HT-film-based OFET sensors. Additionally, upon exposure to 10 ppm NO at room temperature, the nanoporous P3HT-film-based OFET gas sensor exhibited significantly better sensing performance (i.e., responsivity ≈ 42%, sensitivity ≈ 4.7% ppm -1 , limit of detection ≈ 0.5 ppm, and response/recovery times ≈ 6.6/8.0 min) than the pristine P3HT-film-based OFET sensors.

Organic field-effect transistor (OFET) gas sensors based on conjugated polymer films have recently attracted considerable attention for use in environmental monitoring applications. However, the existing devices are limited by their poor sensing performance for gas analytes. This drawback is attributed to the low charge transport in and the limited charge-analyte interaction of the conjugated polymers. Herein, we demonstrate that the incorporation of graphitic carbon nitride (g-C₃N₄) into the conjugated polymer matrix can improve the sensing performance of OFET gas sensors. Moreover, the effect of graphitic carbon nitride (g-C₃N₄) on the gas sensing properties of OFET sensors based on poly(3-hexylthiophene) (P3HT), a conjugated polymer, was systematically investigated by changing the concentration of the g-C₃N₄ in the P3HT/g-C₃N₄ composite films. The obtained films were applied in OFET to detect NO gas at room temperature. In terms of the results, first, the P3HT/g-C₃N₄ composite films containing 10 wt.% g-C₃N₄ exhibited a maximum charge carrier mobility of ~1.1 × 10 -1 cm 2 V -1 S -1 , which was approximately five times higher than that of pristine P3HT films. The fabricated P3HT/g-C₃N₄ composite film based OFET sensors presented significantly enhanced NO gas sensing characteristics compared to those of the bare P3HT sensor. In particular, the sensors based on the P3HT/g-C₃N₄ (90/10) composite films exhibited the best sensing performance relative to that of the bare P3HT sensor when exposed to 10 ppm NO gas: responsivity = 40.6 vs. 18.1%, response time = 129 vs. 142 s, and recovery time = 148 vs. 162 s. These results demonstrate the enormous promise of g-C₃N₄ as a gas sensing material that can be hybridized with conjugated polymers to efficiently detect gas analytes.

Supplemental material is available for this article. Keywords: Mammography, Breast, Machine Learning © RSNA, 2023., Competing Interests: Disclosures of conflicts of interest: J.J.J. No relevant relationships. B.L.V. No relevant relationships. A.B. No relevant relationships. T.K. No relevant relationships. T.S. No relevant relationships. R.C. No relevant relationships. R.D. No relevant relationships. M.M. No relevant relationships. G.O. No relevant relationships. G.S. No relevant relationships. M.W. No relevant relationships. C.R.M. No relevant relationships. M.S.N. No relevant relationships. I.B. No relevant relationships. J.G. NSF and NIH grants; Nightingale Foundation grant; ACR AI Advisory group; SIIM director at large; HL7 board member; trainee editorial board member lead and associate editor for Radiology: Artificial Intelligence. H.T. Kheiron Medical Technologies, academic-industry collaboration; consultant for Arterys, Sirona Medical, and BioData Consortium; owner of Lightbox AI., (© 2023 by the Radiological Society of North America, Inc.)