Running Event, Age, and Competitive Level as Predictors of Dual-Energy X-Ray Absorptiometry-Derived Body Composition and Bone Health Markers in Female Runners.

ABSTRACT: Wilson, LJ and Curtis, C. Running event, age, and competitive level as predictors of dual-energy x-ray absorptiometry-derived body composition and bone health markers in female runners. J Strength Cond Res XX(X): 000-000, 2024-The aim of this study was to assess the impact of running discipline, competitive level (COMP), and age on body composition measures in female athletes. A total of n = 51 female runners (age: 30.9 ± 5.7 years, stature: 166.7 ± 5.7 cm, and body mass (BM): 57.1 ± 8.2 kg) completed a full-body dual-energy x-ray absorptiometry (DXA) scan in a cross-sectional design. One-way ANOVA or Kruskal-Wallis was used to identify differences in DXA measures and independent variables. Stepwise regression determined the contribution of independent variables on DXA measures. Body fat percentage (BF%) and fat mass (FM) differed based on COMP (BF%: H(2) = 17.451; FM: H(2) = 17.406, both p ≤ 0.0001). Competitive level modestly predicted BF% and FM (BF%: R2adj = 0.316, F(1,50) = 22.660; FM: R2adj = 0.300, F(1,50) = 21.029, both p ≤ 0.0001). Bone mineral density (BMD) and BMD Z-score (BMDZ) did not differ between age, running discipline, or COMP (age: BMD: F(2,50) = 2.825, BMDZ: F(2,50) = 2.215; running discipline: BMD: F(3,50) = 1.145, BMDZ: F(3,50) = 1.474; COMP: BMD: F(2,50) = 0.074, BMDZ: F(2,50) = 1.297, all p ≤ 0.05). Age and running discipline modestly predicted BMD and BMDZ (BMD: R2adj = 0.179, F(1,50) = 5.264; BMDZ: R2adj = 0.173, F(1,50) = 4.545, both p ≤ 0.05). These findings indicate COMP may be a predictor of BF% and FM. Age and running discipline appear predictors of bone health markers. Such findings may enable medical and sport science practitioners to tailor interventions relating to realization of training adaptations, performance, and health.

The effects of food insecurity on hepatic steatosis and fibrosis in people with HIV.

BACKGROUND & AIMS: Food insecurity (FI) is a risk factor for nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis in the general population, but its impact on liver disease in people with HIV (PWH) is unknown. METHODS: We examined the association of FI with prevalence of NAFLD and fibrosis in a diverse cohort of PWH. PWH aged ≥18 years on antiretroviral therapy, HIV RNA<200 copies/mL, and without other known liver diseases were screened for NAFLD (CAP≥263 decibels/meter) and advanced fibrosis (LSM≥11 kilopascals) by vibration controlled transient elastography at eight US centers. Participants were categorized as food insecure using the Six-Item Short Form Household Food Security Survey. We used multivariable logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) of NAFLD and advanced fibrosis by FI status. RESULTS: Among 654 PWH, NAFLD was present in 348 (53%) and advanced fibrosis in 41 (6%). FI was present in 203 (31%) of participants, including 97/348 (28%) with NAFLD and 18/41 (44%) with advanced fibrosis. In multivariable analysis, FI was associated with lower odds of NAFLD (OR=0.57,95%CI:0.37-0.88) and a greater, but nonsignificant, odds of advanced fibrosis (OR=1.38,95%CI:0.65-2.90). We identified a significant interaction between FI and diabetes (p=0.02) on fibrosis risk, with a greater odds of fibrosis among food insecure PWH and diabetes (OR=3.83,95%CI:1.15-12.73) but not among food insecure nondiabetics (OR=1.12,95%CI:0.47-2.98). CONCLUSIONS: FI is highly prevalent among PWH and associated with lower odds of NAFLD, and among PWH with diabetes, a greater odds of advanced fibrosis. FI may contribute to hepatic fibrosis through mechanisms other than steatosis in PWH.

PNPLA3 rs738409, age, diabetes, sex, and advanced fibrosis jointly contribute to the risk of major adverse liver outcomes in metabolic-associated steatotic liver disease.

BACKGROUND AND AIMS: The patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 variant is associated with Steatotic Liver Disease (SLD) and its progression. We examined the association between PNPLA3 and the development of major adverse liver outcomes (MALO) and how non-modifiable and modifiable conditions modify this relationship. APPROACH AND RESULTS: 2,075 adults with biopsy-confirmed Metabolic-Associated SLD (MASLD) were enrolled in the MASLD CRN studies and followed prospectively until death, transplant, or withdrawal of consent. 104 MALOs were recorded during an average of 4.3 years. PNPLA3 G-allele (Adj. SubHazard ratio (sHR): 1.4, 95% confidence interval (CI): 1.07-1.8), advanced fibrosis (AF) (Adj. sHR: 7.8, 95% CI: 4.4-13.8), age >60 years (Adj. sHR: 2.9, 95% CI: 1.3-6.8), and type 2 diabetes mellitus (T2DM) (Adj. sHR: 2.8, 95% CI: 1.8-4.2) were associated with MALO. Among participants with AF, those carrying the G-allele displayed the highest cumulative incidence of MALO (85%) vs. noncarriers (53%), p=0.03, and p value for interaction<0.01. The strength of the association between PNPLA3 and MALO was statistically significantly greater among older than 60 years (sHR: 2.1, 95% CI: 1.5-2.8), women (sHR: 1.4, 95% CI: 1.1-1.9), and those with AF (sHR: 1.9, 95% CI: 1.5-2.4) or T2DM (sHR: 2.1, 95% CI: 1.5-2.8) as compared with their counterparts, p value for interaction between PNPLA3 and each factor<0.01. CONCLUSIONS: The deleterious effects of PNPLA3 rs738409 on the risk of MALO are significantly worsened by advanced fibrosis, age, T2DM, and sex.

Seasonal Variation and Positional Differences in Anthropometry, Strength, and Power Characteristics in English Premiership Women's Rugby Union Players.

ABSTRACT: Yao, X, Austerberry, A, Bishop, C, Wilson, L, Chiang, C-Y, and Turner, A. Seasonal variation and positional differences in anthropometry, strength, and power characteristics in English premiership women's rugby union players. J Strength Cond Res 38(5): 924-931, 2024-Women's rugby is a collision sport that relies heavily on body composition and physical characteristics of strength and power to achieve competitive success. Furthermore, the seasonal nature presents a variety of physical challenges that can cause fluctuations in a player's physical development. Therefore, the purpose of this study was to determine the differences in anthropometry, strength, and power characteristics between forwards and backs in women's rugby union athletes in England and to identify changes throughout a season. Forty-seven players were recruited from the English premiership women's rugby during the 2020-2021 season. Players were split into forwards and backs and underwent body composition testing by dual-energy X-ray absorptiometry and strength and power tests (countermovement jump, drop jump [DJ], and isometric midthigh pull) on 3 separate occasions (preseason, midseason, postseason). Overall, forwards had significantly (p < 0.01) higher body mass, fat mass, lean mass [LM], bone mineral content, and take off momentum, and backs had significantly higher (p < 0.01, d > 0.5) jump height, reactive strength, and shorter DJ contact time. When observing seasonal changes, there were statistically significant differences (p < 0.01) or moderate-to-large practical differences (d > 0.5) in LM, reactive strength index modified, time to take-off, and DJ flight time [FT] among forwards when comparing 3 testing time frames. For backs, statistically significant differences (p < 0.01) or moderate-to-large practical differences (d > 0.5) were reported in LM and DJ FT throughout the season. In conclusion, the strength and power testing and characteristics shown in this study could support coaches and junior women's rugby athletes to have a basic understanding of English premiership physical standards.

Investigating the Relationship Between Rare Genetic Variants and Fibrosis in Pediatric Nonalcoholic Fatty Liver Disease.

Background and Aims: Nonalcoholic Fatty Liver Disease (NAFLD) is a complex human disease. Common genetic variation in the patatin-like phospholipase domain containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) genes have been associated with an increased risk of developing NAFLD, nonalcoholic steatohepatitis (NASH), and fibrosis in adults. The role of rare genetic variants in the development and progression of NAFLD in children is not well known. We aimed to explore the role of rare genetic variants in pediatric patients with advanced fibrosis. Methods: Whole exome sequencing data was generated for 229 pediatric patients diagnosed with NAFLD recruited from the NASH Clinical Research Network (NASH CRN). Case-control single variant and gene-based collapsing analyses were used to test for rare variants that were enriched or depleted within the pediatric NAFLD cohort specifically for advanced fibrosis (cases) versus those without fibrosis (controls) or six other histologic characteristics. Exome data from non-NAFLD population controls were also used for additional analyses. All results were adjusted for multiple testing using a Bonferroni correction. Results: No genome-wide significant associations were found between rare variation and presence of advanced fibrosis or NASH, nor the severity of steatosis, inflammation, or hepatocellular ballooning. Significantly, no enrichment of rare variants in PNPLA3 or TM6SF2 was observed across phenotypes. Conclusion: In a cohort of children with histologically proven NAFLD, no genome-wide significant associations were found between rare genetic variation and advanced fibrosis or six other histologic features. Of particular interest was the lack of association with genes of interest in adults: PNPLA3 and TM6SF2, though limitations in sample size may reduce the ability to detect associations, particularly with rare variation.

Non-Hispanic Black persons with nonalcoholic fatty liver disease have lower rates of advanced fibrosis, cirrhosis, and liver-related events even after controlling for clinical risk factors and PNPLA3 genotype.

BACKGROUND AIMS: Nonalcoholic fatty liver disease (NAFLD) is less frequent in non-Hispanic persons (NHB) but there are knowledge gaps in our understanding of disease severity and outcomes of NAFLD in NHB. We compared liver histology and clinical outcomes of NAFLD in NHB and non-Hispanic White adults (NHW). METHODS: We compared liver histology and outcomes of 109 NHB and 1910 NHW adults with biopsy proven NAFLD participating in the Nonalcoholic Steatohepatitis Clinical Research Network observational studies. The relationship between self-reported NHB race/ethnicity and advanced fibrosis was assessed via multivariable logistic regression after controlling for clinical co-variates and PNPLA3 genotype. RESULTS: NHB and NHW with NAFLD had similar NAFLD activity scores (NAS, 4.4 vs 4.3, p=0.87) and proportions with definite NASH (59% vs 58%, p=1.0), but NHB had significantly lower rates of advanced fibrosis (22% vs 34%, p=0.01) or cirrhosis (4.6% vs 12.1%, p=0.010). Compared to NHW, NHB had significantly lower frequency of advanced fibrosis (OR: 0.48, 95% CI:.27-0.86, p=0.01). In a comparison between 24 NHB and 655 NHW with advanced fibrosis, the NAS (5.6 vs 4.9, p=0.01) and lobular inflammation grade (2.2 vs 1.7, p<0.002) were significantly higher among NHB with advanced fibrosis. One NHB and 23 NHW died during follow-up (0.30 vs 0.28 per 100 person-year follow-up). Seven and zero liver-related deaths occurred in NHW and NHB with NAFLD respectively. CONCLUSION: The risk of advanced fibrosis in NHB with NAFLD is significantly lower, after controlling for clinical risk factors and PNPLA3 genotype. Although their risk for advanced fibrosis was low, NHB with NAFLD and advanced fibrosis had higher NAS and lobular inflammation, indicating a difference in their relationship between necroinflammation and fibrosis.

ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer.

Immune checkpoint blockade has yet to produce robust anti-cancer responses for prostate cancer. Sialyltransferases have been shown across several solid tumours, including breast, melanoma, colorectal and prostate to promote immune suppression by synthesising sialoglycans, which act as ligands for Siglec receptors. We report that ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) levels negatively correlate with androgen signalling in prostate tumours. We demonstrate that ST3Gal1 plays an important role in modulating tumour immune evasion through the synthesises of sialoglycans with the capacity to engage the Siglec-7 and Siglec-9 immunoreceptors preventing immune clearance of cancer cells. Here, we provide evidence of the expression of Siglec-7/9 ligands and their respective immunoreceptors in prostate tumours. These interactions can be modulated by enzalutamide and may maintain immune suppression in enzalutamide treated tumours. We conclude that the activity of ST3Gal1 is critical to prostate cancer anti-tumour immunity and provide rationale for the use of glyco-immune checkpoint targeting therapies in advanced prostate cancer.

Single cell atlas of human gastric muscle immune cells and macrophage-driven changes in idiopathic gastroparesis.

Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with the enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45+ cells obtained from the gastric tissue of 20 subjects. We demonstrate 11 immune cell clusters with T cells being most abundant followed by myeloid cells. The proportions of cells belonging to the 11 clusters were similar between IG and controls. However, 9/11 clusters showed 578-11,429 differentially expressed genes. In IG, MM had decreased expression of tissue-protective and microglial genes and increased the expression of monocyte trafficking and stromal activating genes. Furthermore, in IG, IL12 mediated JAK-STAT signaling involved in the activation of tissue-resident macrophages and Eph-ephrin signaling involved in monocyte chemotaxis were upregulated. Patients with IG had a greater abundance of monocyte-like cells. These data further link immune dysregulation to the pathophysiology of gastroparesis.

Diagnostic Ability of Simple Noninvasive Blood Tests to Predict Increased Liver Stiffness in People Living With HIV and Steatotic Liver Disease.

INTRODUCTION: Steatotic liver disease is common in people with HIV (PWH). Identifying those with advanced fibrosis (AF, bridging fibrosis or cirrhosis), F3-4, is important. We aimed to examine the performance of FIB-4 and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) in PWH to identify those with AF assessed by liver stiffness measurement (LSM). METHODS: We prospectively collected data on adults participating in 2 National Institute of Health-sponsored HIV NAFLD networks. All had HIV on antiretroviral therapy (ART) ≥6 months with HIV RNA <200 copies/mL. Those with viral hepatitis, other liver disease, excessive alcohol use, or hepatic decompensation were excluded. Vibration-controlled transient elastrography for LSM was performed, and AF defined as ≥11 kPa was compared with FIB-4 and NFS at predefined thresholds (<1.3 and >2.67 for FIB-4 and <-1.455 and >0.675 for NFS). RESULTS: A total of 1,065 participants were analyzed: mean age 51.6 years, 74% male, 28% White, 46% Black, 22% Hispanic, with 34% overweight (body mass index 25-29 kg/m 2 ) and 43% obese (body mass index ≥30 kg/m 2 ). Features of the metabolic syndrome were common: hyperlipidemia 35%, type 2 diabetes 17%, and hypertension 48%. The median CD4 + T-cell count was 666 cells/mm 3 , 74% had undetectable HIV RNA, and duration of HIV-1 was 17 years with most taking a nucleoside reverse transcriptase inhibitor (92%) and an integrase inhibitor (83%). The mean LSM was 6.3 kPa, and 6.3% had AF. The area under the receiver characteristic curve for FIB-4 and NFS to identify AF were 0.70 and 0.75, respectively. While both had high negative predictive values (97%-98%), the sensitivity at low thresholds and specificity at high thresholds were 64% and 97% for FIB-4 and 80% and 96% for NFS, respectively. Neither FIB-4 nor NFS at either threshold had good positive predictive value to detect AF. DISCUSSION: FIB-4 and NFS have excellent specificity and negative predictive value for detecting AF, and thus can be used as screening tools in PWH to exclude those with AF who do not need further testing (LSM) or referral to hepatologist.

Comparison of different porcine models simulating myocardial cold ischemia of pediatric donor hearts.

BACKGROUND: Our team previously identified a stem cell-derived cardioprotective additive that can be added to standard cardioplegia to extend myocardial viability during prolonged myocardial cold ischemic time (CIT) in rodent models. The purpose of this study was to utilize a porcine model to compare in-vivo versus ex-vivo porcine simulation of CIT that accompanies cardiac transplantation in humans, in order to determine an optimal method for translation of our studies to larger animals. METHODS: Eight 39-55 kg Yorkshire X pigs were randomly assigned to either in-vivo or ex-vivo simulation. After administration of general anesthesia and endotracheal intubation, baseline measurement of left ventricular performance was obtained via transesophageal echocardiography (TEE). After midline sternotomy and heparin administration, the aorta was cross-clamped and two liters of HTK-Custodiol were introduced via the aortic root. The in-vivo method utilized cold ischemic heart storage in the chest cavity while supporting the experimental animal with cardiopulmonary bypass (CPB). The ex-vivo method involved standard cardiac procurement, cold ischemic storage outside of the body, and subsequent cardiac reperfusion utilizing cardiac reanimation in a Langendorff heart perfusion mode. After CIT, measurements of post-ischemic left ventricular performance were obtained via echocardiography. Results are presented as: Mean ± Standard Deviation (Median, Minimum-Maximum). RESULTS: Weight (kilograms) was similar in the in-vivo group and the ex-vivo group: 44 ± 1.8 (44, 42-46) versus 44 ± 5.1 (43.5, 39-51), respectively. Cold ischemic time (minutes) was longer in the ex-vivo group: 360 ± 0 (360, 360-360) versus 141 ± 26.7 (149, 102-163). Temperature (degrees Celsius) was colder in the ex-vivo group: 8 ± 0 (8, 8-8) versus 16.5 ± 4.2 (16, 12-16).In the in-vivo group, baseline ejection fraction and ejection fraction after CIT were: 48.25% ± 14.95% (48.5%, 33%-63%) and 41.25% ± 22.32% (41.5%, 20%-62%), respectively. In the ex-vivo group, baseline ejection fraction and ejection fraction after CIT were: 56.4% ± 5.9% (57%, 50%-67%) and 60.4% ± 7.7% (61.5%, 51.9%-67%), respectively. CONCLUSION: The ex-vivo technique is suitable to evaluate cardioplegia additives that may substantially extend myocardial tolerance to cold ischemia.

Antimullerian Hormone, a Marker of Ovarian Reserve, Is Protective Against Presence and Severity of NASH in Premenopausal Women.

BACKGROUND & AIMS: Antimüllerian hormone (AMH) is a marker of ovarian reserve with emerging data linking lower levels to some metabolic and inflammatory diseases in women. Whether AMH levels influence nonalcoholic fatty liver disease (NAFLD) is unknown. METHODS: Leveraging the NASH Clinical Research Network we determined the association of AMH levels within 6 months of liver biopsy with presence and severity of histologic measures of NAFLD in premenopausal women. Outcomes included presence of nonalcoholic steatohepatitis (NASH), presence and severity of fibrosis, and NAFLD Activity Score and its components. Logistic and ordinal logistic regression models were adjusted for age, race/ethnicity, homeostatic model assessment for insulin resistance, body mass index, dyslipidemia, polycystic ovary syndrome, estrogen-progestin use, and menstrual cyclicity. RESULTS: Median cohort age was 35 years; 73% were white and 24% Hispanic. Thirty-three percent had diabetes, 81% had obesity, and 95% had dyslipidemia. On biopsy 71% had NASH, 68% had any fibrosis, and 15% had advanced fibrosis. On adjusted analysis (n = 205), higher AMH quartiles were inversely associated with NAFLD histology including prevalent NASH (adjusted odds ratio [AOR], 0.64; 95% confidence interval [CI], 0.41-1.00), NAFLD Activity Score ≥5 (AOR, 0.52; 95% CI, 0.35-0.77), Mallory hyaline (AOR, 0.54; 95% CI, 0.35-0.82), and higher fibrosis stage (AOR, 0.70; 95% CI, 0.51-0.98). The protective effects of AMH were more pronounced among women without polycystic ovary syndrome (n = 164), including lower odds of NASH (AOR, 0.53; 95% CI, 0.32-0.90) and any NASH fibrosis (AOR, 0.54; 95% CI, 0.32-0.93). CONCLUSIONS: AMH may reflect a unique biomarker of NASH in premenopausal women and findings suggest a novel link between reproductive aging and histologic severity of NAFLD in women.

Topical application of L-Menthol - Physiological and genetic considerations to assist in developing female athlete research: A narrative review.

L-menthol is a cyclic monoterpene derived from aromatic plants, which gives a cooling sensation upon application. With this in mind, L-menthol is beginning to be considered as a potential ergogenic aid for exercise and sporting competitions, particularly in hot environments, however female-specific research is lacking. The aim of this narrative review is to summarize available literature relating to topical application of L-menthol and provide commentary on avenues of consideration relating to future research developments of topical L-menthol in female athletes. From available studies in male participants, L-menthol topical application results in no endurance exercise performance improvements, however decreases in thermal sensation are observed. Mixed results are observed within strength performance parameters. Several genetic variations and single nucleotide polymorphisms have been identified in relation to sweat production, fluid loss and body mass changes - factors which may influence topical application of L-menthol. More specifically to female athletes, genetic variations relating to sweat responses and skin thickness, phases of the menstrual cycle, and body composition indices may affect the ergogenic effects of L-menthol topical application, via alterations in thermogenic responses, along with differing tissue distribution compared to their male counterparts. This narrative review concludes that further development of female athlete research and protocols for topical application of L-menthol is warranted due to physiological and genetic variations. Such developments would benefit research and practitioners alike with further personalized sport science strategies around phases of the menstrual cycle and body composition indices, with a view to optimize ergogenic effects of L-menthol.

Prevalence of steatotic liver disease, MASLD, MetALD and significant fibrosis in people with HIV in the United States.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed as a replacement term for NAFLD. AIMS: To assess the effects of this new nomenclature on the prevalence and distribution of different SLD categories in people with HIV (PWH) and identified factors associated with MASLD and clinically significant fibrosis (CSF). METHODS: PWH were prospectively enrolled from 9 US centres and underwent clinical evaluation and vibration-controlled transient elastography for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). SLD was defined as CAP ≥ 263 dB/m, CSF as LSM of ≥8 kPa, and advanced fibrosis (AF) as LSM ≥ 12 kPa. The prevalence of SLD, MASLD, metabolic dysfunction and alcohol-associated liver disease (MetALD), ALD, cryptogenic (cSLD), CSF and AF were determined. Uni- and multivariate logistic regression models were used to assess factors associated with MASLD and CSF risk. RESULTS: Of 1065 participants, 74% were male, mean (SD) age 51.6 ± 11.9 years, 46% non-Hispanic Black and 74% with undetectable HIV RNA. The prevalence of SLD was 52%, MASLD 39%, MetALD 10%, ALD 3%, CSF 15% and AF 4%. Only 0.6% had cSLD. Black race was protective whereas obesity, ALT and AST levels were associated with increased risk of MASLD and CSF in MASLD. HIV or antiretroviral therapy did not affect MASLD risk. CONCLUSIONS: MASLD and MetALD are the dominant causes of SLD in PWH, affecting almost half. Application of the new nomenclature resulted in minimal change in the proportion of patients with MASLD who would have been diagnosed previously with NAFLD.

The Role of Thymoma and Thymic Hyperplasia as Prognostic Risk Factors for Secondary Generalisation in Adults with Ocular Myasthenia Gravis: A Systematic Narrative Review.

Purpose: The conversion of ocular myasthenia gravis (OMG) to generalised myasthenia gravis (GMG) is reported to differ depending on the presence of generalisation risk factors (Mazzoli et al. 2018). Thymic pathology has been recognised as a potential risk factor for generalisation in the literature (Teo et al. 2017). Thymoma and thymic hyperplasia have yet to be examined as a risk factor for generalisation of OMG independently of other risk factors in the literature. Thus, the purpose of this review is to examine the literature to identify whether thymoma and thymic hyperplasia do increase the risk of OMG progressing to GMG. Methods: A literature search was carried out which employed a systematic approach. The search was undertaken using the following academic libraries: MEDLINE, Embase and Starplus. The search was limited to publications between the years 2001 to 2021. The search yielded 82 studies, which after the screening of titles and abstracts, left 62 studies for further analysis against the inclusion and exclusion criteria. Results: The review found thymoma to be associated with an increased risk of GMG development. However, there was a scarce amount of literature which investigated thymic hyperplasia. Therefore, a firm conclusion could not be made with regards to thymic hyperplasia and the risk of GMG development. Conclusions: This review provides evidence for the consideration of thymectomy early after thymomatous OMG diagnosis to prevent GMG conversion. As the review did not collect enough evidence to support the influence of thymic hyperplasia on OMG conversion, further research is required.

Youths Are Less Susceptible to Exercise-Induced Muscle Damage Than Adults: A Systematic Review With Meta-Analysis.

PURPOSE: This meta-analysis aimed to (1) provide a comparison of peak changes in indirect markers of exercise-induced muscle damage (EIMD) in youths versus adults and (2) determine if the involved limb moderated this effect. METHOD: Studies were eligible for inclusion if they (1) provided a human youth versus adult comparison; (2) provided data on muscle strength, soreness, or creatine kinase markers beyond ≥24 hours; and (3) did not provide a recovery treatment. Effect sizes (ES) were presented alongside 95% confidence intervals. RESULTS: EIMD exhibited larger effects on adults than in youths for muscle strength (ES = -2.01; P < .001), muscle soreness (ES = -1.52; P < .001), and creatine kinase (ES = -1.98; P < .001). The random effects meta-regression indicated that the effects of upper- and lower-limb exercise in youths and adults were significant for muscle soreness (coefficient estimate = 1.11; P < .001) but not for muscle strength or creatine kinase (P > .05). As such, the between-group effects for muscle soreness (ES = -2.10 vs -1.03; P < .05) were greater in the upper than lower limbs. CONCLUSION: The magnitude of EIMD in youths is substantially less than in their adult counterparts, and this effect is greater in upper than lower limbs for muscle soreness. These findings help guide practitioners who may be concerned about the potential impact of EIMD when training youth athletes.

Age, BMI, and Type 2 Diabetes Modify the Relationship Between PNPLA3 and Advanced Fibrosis in Children and Adults With NAFLD.

BACKGROUND & AIMS: PNPLA3 G-allele is an important determinant of disease severity in nonalcoholic fatty liver disease (NAFLD). Here, we investigated the effect of age, body mass index (BMI), and type 2 diabetes mellitus (T2DM) on the relationship between PNPLA3 G-allele and advanced fibrosis in adults and children with histologically characterized NAFLD. METHODS: A total of 1047 children and 2057 adults were included. DNA was genotyped for rs738409 in duplicate. Primary outcome of interest was advanced fibrosis (fibrosis stage ≥3). Regression analyses were performed after controlling for relevant covariates. An additive model was used to assess the effect of PNPLA3 G-allele (CC vs CG vs GG). RESULTS: PNPLA3 G-allele was significantly associated with advanced fibrosis in children (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.16-2.09) and adults (OR, 1.55; 95% CI, 1.16-1.54). Across the cohort, older age significantly increased the risk for advanced fibrosis for PNPLA3 CC (OR, 1.019; 95% CI, 1.013-1.026), CG (OR, 1.024; 95% CI, 1.018-1.030), and GG (OR, 1.03; 95% CI, 1.023-1.037) genotypes. BMI significantly increased the relationship between PNPLA3 genotypes and advanced fibrosis in children and adults. A BMI of 30 kg/m2 was the cutoff beyond which PNPLA3 G-allele had exponential effect on the risk for advanced fibrosis in children and adults. T2DM significantly worsened the relationship between PNPLA3 G-allele and advanced fibrosis in children and adults (interaction P < .01 for both). CONCLUSIONS: Age, BMI, and T2DM modify the risk of advanced fibrosis associated with PNPLA3 G-allele. Preventing or reversing T2DM and obesity in persons carrying PNPLA3 G-allele may lower the risk for advanced fibrosis in NAFLD.

Gender Minority Stress and Resilience Measure: A Meta-Analysis of the Associations with Mental Health in Transgender and Gender Diverse Individuals.

Transgender and gender diverse (TGD) individuals are more likely to experience mental health difficulties than cisgender individuals due to unique stressors related to their stigmatized gender identity and/or expression. This meta-analysis examined the associations between gender minority stressors and resilience factors, as measured by the Gender Minority Stress and Resilience Measure (GMSR; Testa et al., 2015), and two types of mental health symptoms (i.e., depression and anxiety). A comprehensive literature search and study inclusion process following PRISMA guidelines identified 69 sources, representing 47 unique samples. Mean effect sizes revealed significant positive associations between all GMSR minority stress subscales and anxiety and depression symptoms (rs = .22 to .40) with larger correlations for proximal stressors compared to distal stressors. The GMSR resilience subscales were significantly negatively correlated with anxiety and depression symptoms (rs = -.07 to -.16). These findings highlight the robust relationship between gender minority stressors and mental health symptoms among TGD individuals and indicate a need for addressing these stressors both by reducing exposure to external stressors and by addressing the internalization of those stressors in clinical settings. The small effects for the resilience subscales suggest a need to examine additional resilience factors that may be more pertinent to mental health among TGD individuals.

The economic value of insulin glargine 300 U/mL (Gla-300) in people ≥18 years of age with type 2 diabetes mellitus: a value-based economic model from a U.S. payer perspective.

AIMS: This study aimed to evaluate the value and affordability of insulin glargine 300 U/mL (Gla-300) in a budget impact model from a United States (U.S.) payer perspective by leveraging recent real-world evidence (RWE) studies and incorporating the recent insulin price caps where applicable. MATERIALS AND METHODS: An economic model for a hypothetical one million U.S. health-plan population was developed to assess the budgetary impact of therapeutic interchanges in either direction between the two long- and longer-acting basal insulins (BIs) for patients with type 2 diabetes over a three-year model horizon. The utilization of long-acting BIs, longer-acting BIs, biosimilar BIs, and insulin degludec (IDeg-100) were informed by IQVIA data and internal forecasting at Sanofi. The DELIVER-2 and DELIVER-naïve studies provided healthcare resource utilization (HCRU) parameters. In the model base case, 24% of patients switched from long-acting BIs to insulin glargine biosimilars, IDeg-100, and other longer-acting BIs (Gla-300) by projected year 3. RESULTS: The base case total costs were $10,145 per patient per year (PPPY) in year 3 for the cumulative population. When all patients switched to Gla-300, the total costs in year 3 were $8,799, reflecting a net savings of -$660 PPPY compared to the budget increase of $686 PPPY in the base case. However, the longer-acting to long-acting BIs reversal scenario demonstrated a budgetary decrease of $676 PPPY over the model horizon. The reduction in incremental PPPY cost of $93 was observed using net drug costs rather than wholesale acquisition costs (WAC). LIMITATIONS: The market shares for years 1-3 were based on expectations supported by the clinicians' expert opinions and were not obtained from real-world data. CONCLUSIONS: The economic value of increased utilization of Gla-300 was driven by the reduction in HCRU, costs and market shares assumptions. Budgetary reductions were achieved by switching patients from long-acting BIs to Gla-300.

Type 2 Diabetes (T2D) is a chronic and debilitating condition that can lead to severe macro or microvascular complications. To mitigate these complications, it is crucial to effectively manage blood glucose levels. When other treatments prove ineffective in achieving adequate glucose control, insulin-based therapy becomes necessary. However, insulin-based treatments often come with the risk of hypoglycemic episodes, which can lead to increased utilization of healthcare resources (HCRU) and have a negative impact on costs.This study aimed to assess the budgetary impact of higher market shares of longer-acting basal insulins (specifically insulin glargine Gla-300) compared to long-acting basal insulins, insulin glargine biosimilars, and insulin degludec (IDeg) in the treatment of T2D. The perspective taken was that of a U.S. payer, taking into account the recent insulin price caps where applicable.The economic benefit of increased utilization of Gla-300 was driven by reductions in HCRU, costs, and market share assumptions. This resulted in a budgetary increase of $686 per patient per year (PPPY). In an alternative scenario where all patients transitioned to Gla-300, it led to a net savings of $660 PPPY.These findings provide valuable insights for decision-makers and healthcare professionals when making choices related to formulary placement and treatment utilization.

Development of Fibro-PeN, a clinical prediction model for moderate-to-severe fibrosis in children with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Liver fibrosis is common in children with NAFLD and is an important determinant of outcomes. High-performing noninvasive models to assess fibrosis in children are needed. The objectives of this study were to evaluate the performance of existing pediatric and adult fibrosis prediction models and to develop a clinical prediction rule for identifying moderate-to-severe fibrosis in children with NAFLD. APPROACH AND RESULTS: We enrolled children with biopsy-proven NAFLD in the Nonalcoholic Steatohepatitis Clinical Research Network within 90 days of liver biopsy. We staged liver fibrosis in consensus using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. We evaluated existing pediatric and adult models for fibrosis and developed a new pediatric model using the least absolute shrinkage and selection operator with linear and spline terms for discriminating moderate-to-severe fibrosis from none or mild fibrosis. The model was internally validated with 10-fold cross-validation. We evaluated 1055 children with NAFLD, of whom 26% had moderate-to-severe fibrosis. Existing models performed poorly in classifying fibrosis in children, with area under the receiver operator curves (AUC) ranging from 0.57 to 0.64. In contrast, our new model, fibrosis in pediatric NAFLD was derived from fourteen common clinical variables and had an AUC of 0.79 (95% CI: 0.77-0.81) with 72% sensitivity and 76% specificity for identifying moderate-to-severe fibrosis. CONCLUSION: Existing fibrosis prediction models have limited clinical utility in children with NAFLD. Fibrosis in pediatric NAFLD offers improved performance characteristics for risk stratification by identifying moderate-to-severe fibrosis in children with NAFLD.

Sexual assault characteristics and posttraumatic stress symptoms among collegiate women: The role of posttraumatic cognitions.

Although it is well-established that sexual assault is a risk factor for posttraumatic stress symptoms (PTSS) and other negative mental health outcomes, research is needed to help identify which individuals are most likely to experience ongoing distress following sexual assault. Negative cognitions following trauma may be influenced by sexual assault characteristics and have been shown to be associated with PTSS. The present study examined whether sexual assault characteristics were associated with PTSS by way of posttraumatic cognitions in a sample of 475 female college students who had experienced a sexual assault since the age of 14 years. Participants completed an online survey that included questions about sexual assault characteristics (i.e., whether the perpetrator used force, whether they experienced a freeze response), posttraumatic cognitions, and PTSS. Path analysis revealed that survivors who indicated they froze during the assault reported higher levels of PTSS, total effect = .28, p < .001, direct effect = .19, p < .001; posttraumatic cognitions regarding others, indirect effect = .02, p = .047, and other-safety, indirect effect = .05, p = .003, partially accounted for this association. Only the direct effect of perpetrator use of force on PTSS was statistically significant, total effect = .23, p = .090, direct effect = .16, p = .009; none of the indirect effects were statistically significant, ps = .063-.669. The results support that assault characteristics are associated with postassault outcomes and are consistent with the cognitive model of posttraumatic stress disorder.