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The interplay of gut microbiota, host metabolism, and metabolic health has gained increased attention. Gut microbiota may play a regulatory role in gastrointestinal health, substrate metabolism, and peripheral tissues including adipose tissue, skeletal muscle, liver, and pancreas via its metabolites short-chain fatty acids (SCFA). Animal and human data demonstrated that, in particular, acetate beneficially affects host energy and substrate metabolism via secretion of the gut hormones like glucagon-like peptide-1 and peptide YY, which, thereby, affects appetite, via a reduction in whole-body lipolysis, systemic pro-inflammatory cytokine levels, and via an increase in energy expenditure and fat oxidation. Thus, potential therapies to increase gut microbial fermentation and acetate production have been under vigorous scientific scrutiny. In this review, the relevance of the colonically and systemically most abundant SCFA acetate and its effects on the previously mentioned tissues will be discussed in relation to body weight control and glucose homeostasis. We discuss in detail the differential effects of oral acetate administration (vinegar intake), colonic acetate infusions, acetogenic fiber, and acetogenic probiotic administrations as approaches to combat obesity and comorbidities. Notably, human data are scarce, which highlights the necessity for further human research to investigate acetate’s role in host physiology, metabolic, and cardiovascular health.

Microbial-derived short-chain fatty acids (SCFA) acetate, propionate and butyrate may provide a link between gut microbiota and whole-body insulin sensitivity (IS). In this cross-sectional study (160 participants, 64% male, BMI: 19.2–41.0 kg/m 2 , normal or impaired glucose metabolism), associations between SCFA (faecal and fasting circulating) and circulating metabolites, substrate oxidation and IS were investigated. In a subgroup (n = 93), IS was determined using a hyperinsulinemic-euglycemic clamp. Data were analyzed using multiple linear regression analysis adjusted for sex, age and BMI. Fasting circulating acetate, propionate and butyrate concentrations were positively associated with fasting GLP-1 concentrations. Additionally, circulating SCFA were negatively related to whole-body lipolysis (glycerol), triacylglycerols and free fatty acids levels (standardized (std) β adjusted (adj) −0.190, P = 0.023; std β adj −0.202, P = 0.010; std β adj −0.306, P = 0.001, respectively). Circulating acetate and propionate were, respectively, negatively and positively correlated with IS (M-value: std β adj −0.294, P < 0.001; std β adj 0.161, P = 0.033, respectively). We show that circulating rather than faecal SCFA were associated with GLP-1 concentrations, whole-body lipolysis and peripheral IS in humans. Therefore, circulating SCFA are more directly linked to metabolic health, which indicates the need to measure circulating SCFA in human prebiotic/probiotic intervention studies as a biomarker/mediator of effects on host metabolism.

The incidence of MASLD and MASH-associated fibrosis is rapidly increasing worldwide. Drug therapy is hampered by large patient variability and partial representation of human MASH fibrosis in preclinical models. Here, we investigated the mechanisms underlying patient heterogeneity using a discovery dataset and validated in distinct human transcriptomic datasets, to improve patient stratification and translation into subgroup specific patterns. Patient stratification was performed using weighted gene co-expression network analysis (WGCNA) in a large public transcriptomic discovery dataset (n = 216). Differential expression analysis was performed using DESeq2 to obtain differentially expressed genes (DEGs). Ingenuity Pathway analysis was used for functional annotation. The discovery dataset showed relevant fibrosis-related mechanisms representative of disease heterogeneity. Biological complexity embedded in genes signature was used to stratify discovery dataset into six subgroups of various sizes. Of note, subgroup-specific DEGs show differences in directionality in canonical pathways (e.g. Collagen biosynthesis, cytokine signaling) across subgroups. Finally, a multiclass classification model was trained and validated in two datasets. In summary, our work shows a potential alternative for patient population stratification based on heterogeneity in MASLD-MASH mechanisms. Future research is warranted to further characterize patient subgroups and identify protein targets for virtual screening and/or in vitro validation in preclinical models.

Background/Objectives: Preclinical models of liver fibrosis only partially mimic human disease processes. Particularly, traditional transforming growth factor beta 1 (TGFβ1)-induced hepatic stellate cell (HSC) models lack relevant processes, including hypoxia-induced pathways. Here, the ability of a hypoxia-mimicking compound (IOX2) to more accurately reflect the human fibrotic phenotype on a functional level was investigated. Methods: Human primary HSCs were stimulated (TGFβ1 +/− IOX2), and the cell viability and fibrotic phenotype were determined. The latter was assessed as protein levels of fibrosis markers—collagen, TIMP-1, and Fibronectin. Next-generation sequencing (NGS), differential expression analyses (DESeq2), and Ingenuity Pathway Analysis (IPA) were performed for mechanistic evaluation and biological annotation. Results: Stimulation with TGFβ1 + IOX2 significantly increased fibrotic marker levels. Also, fibrosis-related pathways were activated, and hypoxia-related genes and collagen modifications, such as crosslinking, increased dose-dependently. Comparative analysis with human fibrotic DEGs showed improved disease representation in the HSC model in the presence of IOX2. Conclusions: In conclusion, the HSC model better recapitulated liver fibrosis by IOX2 administration. Therefore, hypoxia-mimicking compounds hold promise for enhancing the translational value of in vitro fibrosis models, providing valuable insights in liver fibrosis pathogenesis and potential therapeutic strategies.

Microbially-produced acetate has been reported to beneficially affect metabolic health through effects on satiety, energy expenditure, insulin sensitivity, and substrate utilization. Here, we investigate the association between sex-specific concentrations of acetate and insulin sensitivity/resistance indices (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), circulating insulin and Matsuda Index) in the Diet, Obesity and Genes (DiOGenes) Dietary study at baseline and after a low-calorie diet (LCD, 800 kcal/d). In this analysis, 692 subjects (Body Mass Index >27 kg/m2) were included, who underwent an LCD for 8 weeks. Linear mixed models were performed, which were adjusted for mean acetate concentration, center (random factor), age, weight loss, and fat-free mass (FFM). At baseline, no associations between plasma acetate and insulin sensitivity/resistance indices were found. We found a slight positive association between changes in acetate and changes in HOMA-IR (stdβ 0.130, p = 0.033) in women, but not in men (stdβ −0.072, p = 0.310) independently of age, weight loss and FFM. We were not able to confirm previously reported associations between acetate and insulin sensitivity in this large European cohort. The mechanisms behind the sex-specific relationship between LCD-induced changes in acetate and insulin sensitivity require further study.

Empathy and assertiveness are two essential soft skills for any healthcare professional's competence and ethical development. It has been shown that empathy can be influenced throughout the training of a future healthcare professional, particularly during the clinical placement period. This research aims to assess fourth-year physiotherapy students' empathic and assertive development before and after clinical placement. A longitudinal observational study was conducted with fourth-year physiotherapy students during the academic year 2022/2023. A preliminary assessment of empathy and assertiveness levels was carried out before the start of the clinical placement and at the end of the placement using the Individual Reactivity Index to assess empathy and the Rathus Test to assess assertiveness. The results show a statistically significant difference ( p  ≤ 0.05) in both the empathy subscales of perspective-taking and empathic-concern between the pre- and postassessment, as well as an inverse correlation between the empathy subscale of personal distress and assertiveness. It is concluded that students show adequate results in empathy and assertiveness. However, there is some influence of clinical practice on the development of empathy, and future intervention studies need to be considered. Furthermore, students with higher levels of assertiveness have lower levels of personal distress, suggesting that assertiveness is closely related to empathy.

Magnetic nanoparticles such as cobalt ferrite are investigated under clinical hyperthermia conditions for the treatment of cancer. Cobalt ferrite nanoparticles (CFNPs) synthesized by the thermal decomposition method, using nonionic surfactant Triton-X100, possess hydrophilic polyethylene oxide chains acting as reducing agents for the cobalt and iron precursors. The monodispersed nanoparticles were of 10 nm size, as confirmed by high-resolution transmission electron microscopy (HR-TEM). The X-ray diffraction patterns of CFNPs prove the existence of cubic spinel cobalt ferrites. Cs-corrected scanning transmission electron microscopy–high-angle annular dark-field imaging (STEM–HAADF) of CFNPs confirmed their multi-twinned crystallinity due to the presence of atomic columns and defects in the nanostructure. Magnetic measurements proved that the CFNPs possess reduced remnant magnetization (MR/MS) (0.86), which justifies cubic anisotropy in the system. Microwave-based hyperthermia studies performed at 2.45 GHz under clinical conditions in physiological saline increased the temperature of the CFNP samples due to the transformation of radiation energy to heat. The specific absorption rate of CFNPs in physiological saline was 68.28 W/g. Furthermore, when triple-negative breast cancer cells (TNBC) in the presence of increasing CFNP concentration (5 mg/mL to 40 mg/mL) were exposed to microwaves, the cell cytotoxicity was enhanced compared to CFNPs alone.

Background and Aims Empathy and assertiveness are two essential social skills for a health professional such as a physiotherapist and are necessary for developing moral thinking. Previous studies show that the development of empathy and other social skills improves as students progress in their studies. However, other authors show deterioration of empathy as students progress in their studies and acquire clinical experience. Training in soft skills, such as assertiveness, among health science students will have an impact on the quality of patient care. Effective communication, conflict resolution and the ability to work as part of a team are competencies that have been put to one side as a result of the recent COVID‐19 pandemic and it is important to resume training students in soft skills. The objective of this study is to investigate to determine the empathic and assertive state of physiotherapy university students. Methods A descriptive cross‐sectional study of physiotherapy university students was conducted in the 2022/2023 academic year. The Interpersonal Reactivity Index (IRI) scales for empathy and the Rathus test for assertiveness (RAS) were used as study tools. Finally, 127 students participated in the study, 52.91% of the total population of physiotherapy students. The questionnaire was available for 4 weeks in November and December 2022. Results The empathetic and assertive development of the students was found to be acceptable. Significant differences were also observed according to the gender variable in the students, with female students presenting better results (p = 0.01). Students who are working or have clinical experience in other professions score lower on the empathy personal distress subscale (p < 0.001). Conclusion Future research should be considered to help improve clinical and professional expertise in physiotherapy students about empathic and assertive development. The findings provide new evidence on the levels of empathy and assertiveness in physiotherapy students. Key points Fostering empathic attitudes in health sciences degrees is vital for humanized care, and empathy training should be considered fundamental until they become professionals. Significant differences were found in the personal distress empathy subscale concerning working while studying or previous health science jobs/experience. The personal distress empathy subscale showed a significant negative correlation with assertiveness.

Tuberculosis (TB) is a prevalent disease throughout the world. The extent of TB illness in childhood is not clear; recent data shows that 10-20% of the cases are found in children under 15 years old. In 2017, 1 million children developed the disease, of which 9% were co-infected with HIV. A cross-sectional study that analyzed 48 children diagnosed with HIV-infection in Guadalajara, Mexico. The tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube test (QFT) were performed and compared to diagnose latent TB infection (LTBI). The average age was 9 years old (± 4), with an age range of 1-16 years; the 6-12-year-old group predominated with 50% of cases. 27 patients (56%) were male; 83% had received the BCG vaccination and 23% had a history of being contacts of TB cases. In the study, 40 patients (83%) were without immunosuppression; seven (15%) with moderate immunosuppression, and only one patient had severe immunodeficiency. Overall, 3 of the 48 children (6.2%) had a positive TST, while 8 out of 48 (16.6%) had a positive QFT. The concordance between the two tests was 89.6% (43/48) with Kappa = 0.5 (95% CI, 0.14-0.85). The QFT test represents an opportunity in the diagnosis of LTBI, particularly in pediatric HIV- patients. This is the first study that compares the two tests (TST and QFT) in children with HIV-infection in Guadalajara, Mexico.

The simplest extension of the SM to account for the observed neutrino masses and mixings is the addition of at least two singlet fermions (or right-handed neutrinos). If their masses lie at or below the GeV scale, such new fermions would be produced in meson decays. Similarly, provided they are sufficiently heavy, their decay channels may involve mesons in the final state. Although the couplings between mesons and heavy neutrinos have been computed previously, significant discrepancies can be found in the literature. The aim of this paper is to clarify such discrepancies and provide consistent expressions for all relevant effective operators involving mesons with masses up to 2 GeV. Moreover, the effective Lagrangians obtained for both the Dirac and Majorana scenarios are made publicly available as FeynRules models so that fully differential event distributions can be easily simulated. As an application of our setup, we numerically compute the expected sensitivity of the DUNE near detector to these heavy neutral leptons.