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Abstract Background Fibrosis is defined as an excessive accumulation of extracellular matrix (ECM) components. Many organs are subjected to fibrosis including the lung, liver, heart, skin, kidney, and muscle. Muscle fibrosis occurs in response to trauma, aging, or dystrophies and impairs muscle function. Fibrosis represents a hurdle for the treatment of human muscular dystrophies. While data on the mechanisms of fibrosis have mostly been investigated in mice, dystrophic mouse models often do not recapitulate fibrosis as observed in human patients. Consequently, the cellular and molecular mechanisms that lead to fibrosis in human muscle still need to be identified. Methods Combining mass cytometry, transcriptome profiling, in vitro co‐culture experiments, and in vivo transplantation in immunodeficient mice, we investigated the role and nature of nonmyogenic cells (fibroadipogenic progenitors, FAPs) from human fibrotic muscles of healthy individuals (FibMCT) and individuals with oculopharyngeal muscular dystrophy (OPMD; FibMOP), as compared with nonmyogenic cells from human nonfibrotic muscle (MCT). Results We found that the proliferation rate of FAPs from fibrotic muscle is 3–4 times higher than those of FAPs from nonfibrotic muscle (population doubling per day: MCT 0.2 ± 0.1, FibMCT 0.7 ± 0.1, and FibMOP 0.8 ± 0.3). When cocultured with muscle cells, FAPs from fibrotic muscle impair the fusion index unlike MCT FAPs (myoblasts alone 57.3 ± 11.1%, coculture with MCT 43.1 ± 8.9%, with FibMCT 31.7 ± 8.2%, and with FibMOP 36.06 ± 10.29%). We also observed an increased proliferation of FAPs from fibrotic muscles in these co‐cultures in differentiation conditions (FibMCT +17.4%, P

Abstract Objectives To assess whether prevailing antipsychotic use rates in community nursing homes (CNH) influence new initiation of antipsychotics and diagnosis with antipsychotic indications among Veterans. Methods We used linked 2013–2016 Veterans Administration (VA) data, Medicare claims, Nursing Home Compare, and Minimum Data Set (MDS) assessments. The exposure was the proportion (in quintiles) of all CNH residents prescribed antipsychotics in the quarter preceding a Veteran's admission date. Using adjusted logistic regression, we analyzed two outcomes measured using MDS: antipsychotic initiation, and new diagnosis of an antipsychotic quality‐measure exclusionary condition (i.e., schizophrenia, Tourette's syndrome, or Huntington's disease). Results Among 8201 Veterans without an indication for antipsychotics at baseline, 21.1% initiated antipsychotics and 3.5% were newly diagnosed with any exclusionary diagnosis after CNH admission. Schizophrenia accounted for almost all (96.8%) the new diagnoses. Antipsychotic initiation increased with higher CNH antipsychotic use rates: OR = 2.55, 95% CI: 2.08–‐3.12, quintile 5 versus 1. CNHs with the highest prevalent use of antipsychotics were associated with increased odds of Veterans acquiring an exclusionary diagnosis (OR = 2.09, 95% CI: 1.32–3.32, quintile 5 vs. 1). Conclusions Incident antipsychotic use is common among Veterans admitted to CNHs. CNH antipsychotic prescribing practices are associated with Veterans being newly diagnosed with antipsychotic prescription indications, primarily schizophrenia.

We examined gender differences in appetite sensations when exposed to Mediterranean diet (MedDiet) meals and determined whether there are gender differences in the change in the satiating properties of the MedDiet over time. Thirty-eight men and 32 premenopausal women consumed a 4-week isoenergetic MedDiet under controlled conditions. Visual analogue scales were used to measure perceived appetite sensations before and immediately after each meal consumed over the course of one day (Wednesday) of the first and the fourth week of intervention. Women reported greater decreases for desire to eat, hunger, and appetite score than men in response to the consumption of the MedDiet meals (gender-by-meal interactions, resp., P=0.04, P=0.048, and P=0.03). Fullness and prospective food consumption responses did not significantly differ between men and women. Between the first and the fourth week of intervention, premeal prospective food consumption increased with time in men (P=0.0007) but not in women (P=0.84; P for gender-by-time interaction = 0.04). These results indicate gender differences in appetite sensations when exposed to the MedDiet. These results may be useful in order to have a better understanding of gender issues for body weight management.

Objective. To document sex differences in the impact of the Mediterranean diet (MedDiet) on glucose/insulin homeostasis and to verify whether these sex-related effects were associated with changes in nonesterified fatty acids (NEFA). Methods. All foods were provided to 38 men and 32 premenopausal women (24–53 y) during 4 weeks. Variables were measured during a 180 min OGTT before and after the MedDiet. Results. A sex-by-time interaction for plasma insulin iAUC was found (men: −17.8%, P=0.02; women: +9.4%, P=0.63; P for sex-by-time interaction = 0.005). A sex-by-time interaction was also observed for insulin sensitivity (Cederholm index, P=0.03), for which only men experienced improvements (men: +8.1%, P=0.047; women: −5.9%, P=0.94). No sex difference was observed for glucose and C-peptide responses. Trends toward a decrease in NEFA AUC (P=0.06) and an increase in NEFA suppression rate (P=0.06) were noted, with no sex difference. Changes in NEFA were not associated with change in insulin sensitivity. Conclusions. Results suggest that the more favorable changes in glucose/insulin homeostasis observed in men compared to women in response to the MedDiet are not explained by sex differences in NEFA response. This clinical trial is registered with clinicaltrials.gov NCT01293344.

We investigated the impact of abdominal obesity status on the cardiovascular response to a fully controlled 4-week isoenergetic Mediterranean diet (MedDiet). Thirty-eight abdominally obese individuals (waist circumference >102 cm in men and >88 cm in women) and thirty-one nonabdominally obese individuals were recruited and studied before and after the MedDiet. All analyses were adjusted for the slight decrease in body weight, which occurred during the MedDiet (mean: 0.9±1.2 kg). A group by time interaction was noted for waist circumference (P=0.02), abdominally obese subjects showing a significant decrease and nonabdominally obese subjects a nonsignificant increase (resp., −1.1 and +0.3%). The MedDiet resulted in decreases in total cholesterol, LDL-C, HDL-C, apolipoprotein B, A-1, and A-2, total cholesterol/HDL-C ratio, LDL-C/HDL-C ratio, and systolic and diastolic blood pressure (time effect: P

Fabry disease (FD) is an X-linked disease characterized by an accumulation of glycosphingolipids, notably of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3) leading to renal failure, cardiomyopathy, and cerebral strokes. Inflammatory processes are involved in the pathophysiology. We investigated the immunological phenotype of peripheral blood mononuclear cells in Fabry patients depending on the clinical phenotype, treatment, Gb3, and lysoGb3 levels and the presence of anti-drug antibodies (ADA). Leucocytes from 41 male patients and 20 controls were analyzed with mass cytometry using both unsupervised and supervised algorithms. FD patients had an increased expression of CD27 and CD28 in memory CD45- and CD45 + CCR7-CD4 T cells (respectively p < 0.014 and p < 0.02). Percentage of CD45RA-CCR7-CD27 + CD28+ cells in CD4 T cells was correlated with plasma lysoGb3 (r = 0.60; p = 0.0036) and phenotype (p < 0.003). The correlation between Gb3 and CD27 in CD4 T cells almost reached significance (r = 0.33; p = 0.058). There was no immune profile associated with the presence of ADA. Treatment with agalsidase beta was associated with an increased proportion of Natural Killer cells. These findings provide valuable insights for understanding FD, linking Gb3 accumulation to inflammation, and proposing new prognostic biomarkers., (© 2024 SSIEM.)