Effects of Diathermy on Pain in Women with Fibromyalgia: A Randomized Controlled Trial.

(1) Background: The main characteristic of fibromyalgia (FM) is generalized musculoskeletal pain. This may be accompanied by muscle and joint stiffness, sleep and mood disorders, anxiety and depression, cognitive dysfunction, and chronic fatigue. It is endemic in developed countries, with a higher prevalence among women than men, and its etiology is still unknown. Diagnosis is made based on chronic generalized pain and through the presence of tender points. The objective of this study was to analyze the efficacy of diathermy on pain in patients with fibromyalgia. (2) Methods: A single, blind, randomized experimental study was developed with a sample of 31 participants. Measurements were taken and recorded at three different intervals using the following measurement tools: the pressure pain threshold (PPT) at the tender points (TP) of the right and left trochanteric prominence with an algometer, the pain measurement scale, the Fibromyalgia Impact Questionnaire, the sleep quality index (PSQI, Pittsburgh), the Multidimensional Fatigue Inventory (MFI-S), and the scale for anxiety and depression (Hospital Anxiety and Depression Scale). Sociodemographic data were collected through Google Forms (age, height, weight, Body Mass Index). The intervention took place twice weekly across four weeks of sessions. (3) Results: Statistically significant results were obtained in the right and left trochanter PPT, as well as for anxiety and fatigue in the experimental group. The results obtained show that this treatment has managed to improve the quality of sleep, the impact of disease, chronic fatigue, and anxiety in patients with FM. (4) Conclusions: Diathermy is a tool that can help reduce pain. It can also improve the baseline levels of chronic fatigue, anxiety, the impact of the disease, and sleep quality in patients with fibromyalgia.

Glucose Disorders.

Glucose disorders are the most common endocrine condition in the primary care setting. The conditions overlap and are better viewed as a spectrum rather than discrete entities. Multiple treatment agents are now available for diabetes mellitus which include long-acting and short-acting insulins and medications targeting the various pathways of diabetes including liver gluconeogenesis, increasing peripheral insulin sensitivity, stimulating pancreatic insulin production, eliminating glucose renally, decreasing carbohydrate gastrointestinal absorption, and targeting the body's incretin system. Various endocrine conditions can cause secondary hyperglycemia or hypoglycemia. Medications and physiologic stress can affect glucose levels. Genetic syndromes causing enzyme deficiencies underlie a small portion of glucose disorders.

Effects of ß-Alanine Supplementation on Subjects Performing High-Intensity Functional Training.

BACKGROUND: ß-alanine, a non-essential amino acid found in the diet and produced through nucleotide catabolism, is significant for muscle performance due to its role in carnosine synthesis. This study aims to assess the impact of a 4-week ß-alanine supplementation on neuromuscular fatigue in individuals engaging in High-Intensity Functional Training (HIFT) and its subsequent effect on sports performance, distinguishing between central fatigue from the CNS and peripheral fatigue from the muscular system. MATERIALS AND METHODS: This study (a randomized controlled trial) comprised a total of 27 subjects, who were divided into two groups. Group A (the control group) was administered sucrose powder, while Group B (the experimental group) was given ß-alanine powder. The subjects were randomly assigned to either the experimental or control groups. This study lasted four weeks, during which both groups participated in high-intensity interval training (HIFT) on the first day to induce fatigue and work close to their VO2 max. RESULTS: Statistically significant changes were in the sports performance variables, specifically vertical jump and jumping power (p = 0.027). These changes were observed only in the group that had been supplemented with ß-alanine. Nevertheless, no alterations were observed in any other variables, including fatigue, metabolic intensity of exercise, or perceived intensity (p > 0.05). CONCLUSIONS: A four-week ß-alanine intake program demonstrated an improvement in the capacity of subjects, as evidenced by enhanced vertical jump and power performance. Nevertheless, it does result in discernible alterations in performance.

Artificial intelligence-assisted identification and retrieval of chronic hepatitis C patients lost to follow-up in the health area of Pontevedra and O Salnés (Spain).

OBJECTIVE: Direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) infection offer an opportunity to eliminate the disease. This study aimed to identify and relink to care HCV patients previously lost to medical follow-up in the health area of Pontevedra and O Salnés (Spain) using an artificial intelligence-assisted system. PATIENTS AND METHODS: Active retrospective search of previously diagnosed HCV cases recorded in the Galician Health Service proprietary health information exchange database using the Herramientas para la EXplotación de la INformación (HEXIN) application. RESULTS AND CONCLUSIONS: Out of 99 lost patients identified, 64 (64.6%) were retrieved. Of these, 62 (96.88%) initiated DAA treatment and 54 patients (87.1%) achieved a sustained virological response. Mean time from HCV diagnosis was over 10 years. Main reasons for loss to follow-up were fear of possible adverse effects of treatment (30%) and mobility impediments (21%). Among the retrieved patients, almost one in three presented advanced liver fibrosis (F3) or cirrhosis (F4) at evaluation. In sum, HCV patients lost to follow-up can be retrieved by screening past laboratory records. This strategy promotes the achievement of HCV elimination goals.

Catheter directed therapy in high-risk pulmonary embolism: Analysis of 9 cases. / Terapia dirigida por catéter en embolia pulmonar de alto riesgo: análisis de 9 casos.

BACKGROUND: Mechanical thrombectomy is a useful technique in patients with high-risk pulmonary embolism. It is indicated as an alternative to systemic fibrinolysis when it is contraindicated or as an adjuvant therapy when it fails. OBJECTIVE: To describe clinical characteristics, evolution and survival of patients with high-risk pulmonary embolism who have undergone mechanical thrombectomy. METHOD: Single-center retrospective descriptive study of consecutive patients who underwent mechanical thrombectomy. Demographic, clinical and survival variables were analyzed. RESULTS: 9 patients were included (56% men, 44% women). All patients had pulmonary artery pressure assessed using a Swan-Ganz catheter before thrombectomy. The median pulmonary artery pressure before the procedure was 46mmHg (51-38mmHg). Systemic fibrinolysis was also performed in 5 cases, in 2 of them in the setting of cardiorespiratory arrest, without hemorrhagic complications. No patient died during hospitalization. Survival one month after the procedure was 100%. CONCLUSIONS: In our series, mechanical thrombectomy is a useful technique as an alternative to systemic fibrinolysis or as an adjuvant therapy to it.

Pigmented acuminated condylomas seborrhoeic keratosis-like: a new entity?

BACKGROUND: Condyloma acuminatum is caused by human papillomavirus (HPV), which typically presents as excrescent, pedunculated, papillomatous lesions which may be of a pale colour. On rare occasions, we have observed pigmented genital lesions that are similar to seborrhoeic keratoses, but with histological findings of condyloma acuminatum and positive genotyping for HPV. We have termed these 'seborrhoeic keratosis-like' type condylomas. METHODS: This is an observational retrospective study. The following clinical data were collected: age, sex, time of evolution, location, isolated or multiple lesions, monomorphous or polymorphous/mixed lesions. HPV genotyping was performed in all cases, and excision for histological study in eight cases. RESULTS: A total of 31 patients were diagnosed with this type of pigmented condylomata acuminata. Of these, 16 had isolated lesions (less than five lesions) and 15 had multiple lesions. 67% of the lesions exhibited slow growth, with an evolution period of greater than 1 year. The most frequent location was the base of the penis and pubis. HPV genotyping of the lesions was positive in all cases, with the HPV-6 genotype predominating (28 cases, 90.3%). The lesions exhibited dermoscopic differences from other pigmented lesions and histological findings attributable to HPV infection (pseudoparakeratosis, koilocytosis, etc) and others similar to those observed in seborrhoeic keratoses. CONCLUSIONS: A total of 31 patients were diagnosed with pigmented verrucous lesions, excrescents, isolated or multiple, in the genital region. These lesions exhibited clinical characteristics similar to seborrhoeic keratoses, with positive genotyping for HPV. In the majority of cases, the genotype was HPV-6. These lesions have been named 'pigmented condylomata acuminata seborrhoeic keratosis-like'. Only 10 cases of these lesions have been described in the literature.

A 6-month educational program improves sleep behaviour in community-dwelling frail older adults: A randomised controlled trial.

BACKGROUND: The prevalence of sleep-related issues among older adults is a significant concern, with half of the older population reporting these problems. Consequently, strategies to improve sleep are needed for this population. This study aims to assess the effects of a health educational program on sleep behaviour among pre-frail or frail older adults residing in the community and to explore possible associations with frailty. METHODS: This randomised controlled trial (NCT05610605) included a total of 197 community-dwelling older adults with frailty/pre-frailty, divided into control (n = 88) and educational (n = 109) groups, were assessed at baseline, after the 6-month educational program (6 months), and 6 months after the intervention (12 months). The intervention comprised four group sessions and six follow-up phone calls, focusing on frailty, physical activity, dietary habits, and cognitive training. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) and wrist-worn accelerometry. RESULTS: At 6 months, a significant time-by-group interaction was found for self-reported [ß = -0.449, 95%CI (-0.844, -0.053), p = 0.026] and accelerometer-measured [ß = 0.505, 95%CI (0.085, 0.926), p = 0.019] sleep efficiency, showing improved sleep efficiency in the intervention group vs. controls. A significant time-by-group interaction at 6 months was noted for sleep awakenings [ß = -0.402, 95%CI (-0.825, -0.020), p = 0.047]. The educational program led to a significant decrease in awakenings, while the control group experienced an increase. The change in the number of awakenings (Rs = 0.183, p = 0.020) at 6 months was significantly associated with changes in frailty. Moreover, a significant time-by-group interaction was reported at the 12-month assessment [ß = -0.449, 95%CI (-0.844, -0.053), p = 0.026] for self-reported sleep quality, indicating better results in the intervention group compared to controls. CONCLUSION: The educational program improved sleep quality and sleep efficiency while reducing the number of awakenings per night among community-dwelling frail older adults, offering a practical approach to addressing sleep-related challenges in this demographic.

Tissue explants as tools for studying the epigenetic modulation of the GH-IGF-I axis in farmed fish.

Somatic growth in vertebrates is mainly controlled by the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. The role of epigenetic mechanisms in regulating this axis in fish is far from being understood. This work aimed to optimize and evaluate the use of short-term culture of pituitary and liver explants from a farmed fish, the gilthead seabream Sparus aurata, for studying epigenetic mechanisms involved in GH/IGF-I axis regulation. Our results on viability, structure, proliferation, and functionality of explants support their use in short-term assays. Pituitary explants showed no variation in gh expression after exposure to the DNA methylation inhibitor decitabine (5-Aza-2'-deoxycytidine; DAC), despite responding to DAC by changing dnmt3bb and tet1 expression, and TET activity, producing an increase in overall DNA hydroxymethylation. Conversely, in liver explants, DAC had no effects on dnmt s and tet s expression or activity, but modified the expression of genes from the GH-IGF-I axis. In particular, the expression of igfbp2a was increased and that of igfbp4, ghri and ghrii was decreased by DAC as well as by genistein, which is suggestive of impaired growth. While incubation of liver explants with S-adenosylmethionine (SAM) produced no clear effects, it is proposed that nutrients must ensure the methylation milieu within the liver in the fish to sustain proper growth, which need further in vivo verification. Pituitary and liver explants from S. aurata can be further used as described herein for the screening of inhibitors or activators of epigenetic regulators, as well as for assessing epigenetic mechanisms behind GH-IGF-I variation in farmed fish.

Miniprotein engineering for inhibition of PD-1/PD-L1 interaction.

Miniproteins constitute an excellent basis for the development of structurally demanding functional molecules. The engrailed homeodomain, a three-helix-containing miniprotein, was applied as a scaffold for constructing programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) interaction inhibitors. PD-L1 binders were initially designed using the computer-aided approach and subsequently optimized iteratively. The conformational stability was assessed for each obtained miniprotein using circular dichroism spectroscopy, indicating that numerous mutations could be introduced. The formation of a sizable hydrophobic surface at the inhibitor that fits the molecular target imposed the necessity for the incorporation of additional charged amino acid residues to retain its appropriate solubility. Finally, the miniprotein effectively binding to PD-L1 (KD = 51.4 nM) that inhibits PD-1/PD-L1 interaction in cell-based studies with EC50 = 3.9 µM, was discovered.

HB-EGF activates EGFR to induce reactive neural stem cells in the mouse hippocampus after seizures.

Hippocampal seizures mimicking mesial temporal lobe epilepsy cause a profound disruption of the adult neurogenic niche in mice. Seizures provoke neural stem cells to switch to a reactive phenotype (reactive neural stem cells, React-NSCs) characterized by multibranched hypertrophic morphology, massive activation to enter mitosis, symmetric division, and final differentiation into reactive astrocytes. As a result, neurogenesis is chronically impaired. Here, using a mouse model of mesial temporal lobe epilepsy, we show that the epidermal growth factor receptor (EGFR) signaling pathway is key for the induction of React-NSCs and that its inhibition exerts a beneficial effect on the neurogenic niche. We show that during the initial days after the induction of seizures by a single intrahippocampal injection of kainic acid, a strong release of zinc and heparin-binding epidermal growth factor, both activators of the EGFR signaling pathway in neural stem cells, is produced. Administration of the EGFR inhibitor gefitinib, a chemotherapeutic in clinical phase IV, prevents the induction of React-NSCs and preserves neurogenesis.

Cryogenic electron microscopy reveals morphologically distinct subtypes of extracellular vesicles among porcine ejaculate fractions.

Seminal plasma (SP) is rich in extracellular vesicles (EVs), which are still poorly studied, especially in livestock species. To better understand their functional role in both spermatozoa and endometrial epithelial cells, proper characterization of EVs is an essential step. The objective was to phenotypically characterize porcine seminal EVs (sEVs) using cryogenic electron microscopy (cryo-EM), which allows visualization of EVs in their native state. Porcine ejaculates are released in fractions, each containing SP from different source. This allows characterization sEVs released from various male reproductive tissues. Two experiments were performed, the first with SP from the entire ejaculate (n:6) and the second with SP from three ejaculate fractions (n:15): the first 10 mL of the sperm-rich ejaculate fraction (SRF-P1) with SP mainly from the epididymis, the remainder of the SRF (SRF-P2) with SP mainly from the prostate, and the post-SRF with SP mainly from the seminal vesicles. The sEVs were isolated by size exclusion chromatography and 1840 cryo-EM sEV images were acquired using a Jeol-JEM-2200FS/CR-EM. The size, electron density, complexity, and peripheral corona layer were measured in each sEV using the ImageJ software. The first experiment showed that sEVs were structurally and morphologically heterogeneous, although most (83.1%) were small (less than 200 nm), rounded, and poorly electrodense, and some have a peripheral coronal layer. There were also larger sEVs (16.9%) that were irregularly shaped, more electrodense, and few with a peripheral coronal layer. The second experiment showed that small sEVs were more common in SRF-P1 and SRF-P2, indicating that they originated mainly from the epididymis and prostate. Large sEVs were more abundant in post-SRF, indicating that they originated mainly from seminal vesicles. Porcine sEVs are structurally and morphologically heterogeneous. This would be explained by the diversity of reproductive organs of origin.

Distribution of Main Bioactive Compounds from Saffron Species as a Function of Infusion Temperature and Time in an Oil/Water System.

Most research on saffron has focused on its composition and beneficial effects, while the culinary perspective to enhance its gastronomic potential remains unexplored. This study aims to define the transfer of the main compounds responsible for color, flavor, and aromatic properties, evaluating three critical variables: temperature (60 °C, 80 °C and 100 °C), infusion time (ranging from 10 to 30 min), and the composition of the medium (water, oil, and water/oil). Samples were analyzed using the LC-QTOF MS/MS and ISO 3632-1:2011 methods. The major compounds were crocins, including trans-crocin and picrocrocin. Among the flavonoids, kaempferol 3-O-sophoroside stands out. Regarding extraction conditions, crocins, glycoside flavonoids, and picrocrocin were enhanced in water, the former in 100% water and at low temperatures, while picrocrocin proved to be the most stable compound with extraction favored at high temperatures. The variable with the greatest incidence of picrocrocin isolation seemed to be the concentration of water since water/oil compositions reported higher concentrations. Safranal and kaempferol were enriched in the oil phase and at lower temperatures. This study provides a chemical interpretation for the appropriate gastronomic use of saffron according to its versatility. Finally, the determination of safranal using the ISO method did not correlate with that obtained using chromatography.

Reliability of near-infrared spectroscopy in measuring muscle oxygenation during squat exercise.

Monitoring of changes in skeletal muscle oxygenation during exercise has increased in recent years. Tissue oxygenation, which is related to fatigue and muscle hypertrophy, is often measured using near-infrared spectroscopy (NIRS). OBJECTIVES: This study aimed to determine the test-retest reliability of a non-portable NIRS (NIRO200Nx) during the full-squat exercise and recovery in young healthy men. DESIGN: Twenty-five male participants (21.8 ±â€¯2.6 years) were recruited for this original research. Each participant completed an 8-repetition test with a load that elicited a velocity of 1 m·s-1. The test was conducted twice, with a 48-hour washout period between sessions. METHODS: The NIRS measured the changes of oxygenated-Hemoglobin (O2Hb), deoxygenated-Hemoglobin (HHb) and Tissue Oxygenation Index (TOI) in both Vastus Lateralis and Vastus Medialis during rest, exercise, and recovery. Coefficient of Variation (CV), Standard Error Measurement (SEM) and Intraclass Correlation Coefficient (ICC) were used to evaluate the reliability of the data. Significance was set at p < 0.05. RESULTS: The results indicated that TOI had good to acceptable absolute reliability (CVTOI = 2.7-10.2 %). A good relative relativity for the overall test was found for Vastus Medialis O2Hb (ICC = 0.851), HHb (ICC = 0.852), and TOI (ICC = 0.864), and Vastus Lateralis O2Hb (ICC = 0.898), HHb (ICC = 0.899), and TOI (ICC = 0.897). CONCLUSIONS: We conclude that NIRO200Nx is a reliable instrument for measuring muscle oxygen saturation through the TOI parameter in not-to-failure dynamic resistance exercises (1 set of 8 reps against ∼40 % 1 repetition maximum). Tissue oxygenation assessment could be a new way of individualizing exercise through dynamic resistance exercises.

Risk factors associated with radiological and clinical recurrences after laparoscopic repair of large hiatal hernia with TiO2Mesh™ reinforcement.

INTRODUCTION: Laparoscopic repair of large para-esophageal hiatal hernias (LPHH) remains controversial. Several meta-analyses suggest hiatus reinforcement with mesh has better outcomes over cruroplasty in terms of less recurrence. The aim of this study was to evaluate the medium-term results of treating LPHH with a biosynthetic monofilament polypropylene mesh coated with titanium dioxide to enhance biocompatibility (TiO2Mesh™). METHODS: A retrospective observational study, using data extracted from a prospectively collected database was performed at XXX from December 2014 to June 2023. Included participants were all patients who underwent laparoscopic repair of large (> 5 cm) type III hiatal hernia in which a TiO2Mesh™ was used. The results of the study, including clinical and radiological recurrences as well as mesh-related morbidity, were analyzed. RESULTS: Sixty-seven patients were finally analyzed. Laparoscopic approach was attempted in all but conversion was needed in one patient because of bleeding in the lesser curvature. With a median follow-up of 41 months (and 10 losses to follow-up), 22% of radiological recurrences and 19.3% of clinical recurrences were described. Regarding complications, one patient presented morbidity associated with the mesh (mesh erosion requiring endoscopic extraction). Recurrent hernia repair was an independent factor of clinical recurrence (OR 4.57 95% CI (1.28-16.31)). CONCLUSION: LPHH with TiO2Mesh™ is safe and feasible with a satisfactory medium-term recurrence and a low complication rate. Prospective randomized studies are needed to establish the standard repair of LPHH.

Shedding Light on Dark Chemical Matter: The Discovery of a SARS-CoV-2 Mpro Main Protease Inhibitor through Intensive Virtual Screening and In Vitro Evaluation.

The development of specific antiviral therapies targeting SARS-CoV-2 remains fundamental because of the continued high incidence of COVID-19 and limited accessibility to antivirals in some countries. In this context, dark chemical matter (DCM), a set of drug-like compounds with outstanding selectivity profiles that have never shown bioactivity despite being extensively assayed, appears to be an excellent starting point for drug development. Accordingly, in this study, we performed a high-throughput screening to identify inhibitors of the SARS-CoV-2 main protease (Mpro) using DCM compounds as ligands. Multiple receptors and two different docking scoring functions were employed to identify the best molecular docking poses. The selected structures were subjected to extensive conventional and Gaussian accelerated molecular dynamics. From the results, four compounds with the best molecular behavior and binding energy were selected for experimental testing, one of which presented inhibitory activity with a Ki value of 48 ± 5 µM. Through virtual screening, we identified a significant starting point for drug development, shedding new light on DCM compounds.

Metabolic dysregulation of tricarboxylic acid cycle and oxidative phosphorylation in glioblastoma.

Glioblastoma multiforme (GBM) exhibits genetic alterations that induce the deregulation of oncogenic pathways, thus promoting metabolic adaptation. The modulation of metabolic enzyme activities is necessary to generate nucleotides, amino acids, and fatty acids, which provide energy and metabolic intermediates essential for fulfilling the biosynthetic needs of glioma cells. Moreover, the TCA cycle produces intermediates that play important roles in the metabolism of glucose, fatty acids, or non-essential amino acids, and act as signaling molecules associated with the activation of oncogenic pathways, transcriptional changes, and epigenetic modifications. In this review, we aim to explore how dysregulated metabolic enzymes from the TCA cycle and oxidative phosphorylation, along with their metabolites, modulate both catabolic and anabolic metabolic pathways, as well as pro-oncogenic signaling pathways, transcriptional changes, and epigenetic modifications in GBM cells, contributing to the formation, survival, growth, and invasion of glioma cells. Additionally, we discuss promising therapeutic strategies targeting key players in metabolic regulation. Therefore, understanding metabolic reprogramming is necessary to fully comprehend the biology of malignant gliomas and significantly improve patient survival.

Efficacy and safety of sagittal synostosis surgery in older (> 12 months) patients: a systematic review and meta-analysis.

PURPOSE: Sagittal synostosis is the most common isolated craniosynostosis. Surgical treatment of this synostosis has been extensively described in the global literature, with promising outcomes when it is performed in the first 12 months of life. However, in some cases, patients older than 12 months arrive at the craniofacial center with this synostosis. A comprehensive study on efficacy and perioperative outcomes has yet to be fully explored in this population. This systematic review and meta-analysis aimed to assess the available evidence of surgical outcomes for the treatment of sagittal synostosis among older patients to analyze the efficacy and safety of synostosis surgery in this unique population. METHODS: PubMed, Embase, and Scopus were searched for studies published from inception to March 2024 reporting surgical outcomes of synostosis surgery in older patients (> 12 months) with isolated sagittal synostosis. The main outcome was the reoperation rate, with secondary endpoints including transfusion rates, aesthetic outcomes, and surgical complications. RESULTS: Nine studies were included in the final analysis. The pooled proportion of the reoperation rate was 1%. The rate of excellent aesthetic results was 95%. The need for transfusion associated with the procedures was 86%, and finally, surgical complications attained a pooled ratio of 2%, indicating minimal morbidity associated with the surgical repair. CONCLUSION: Sagittal synostosis surgery is a safe and effective procedure to perform in older patients; this meta-analysis suggests that open surgery confers a significant rate of excellent aesthetic results with a low reoperation rate and minimal complications associated with the intervention. Future research with direct comparisons among different techniques will validate the findings of this study, which will all contribute to the rigor of synostosis management.

Multidimensional associations of physical performance, balance, wellness and daily activities with frailty in older adults with coexisting frailty and diabetes.

BACKGROUND: The coexistence of frailty and type 2 diabetes mellitus in the older population heightens the risk of adverse events. However, research on functional and wellness factors associated with frailty in this population is limited. PURPOSE: To investigate the associations of physical performance, functional dependency, physical activity, nutritional status, sleep, self-perceived health and depression with frailty in community-dwelling older adults with coexisting frailty and type 2 diabetes mellitus. DESIGN: Cross-sectional. METHODS: The study included 123 community-dwelling older adults (73.7 ± 6.0 years) with pre-frailty/frailty and type 2 diabetes mellitus. Physical performance (Short Physical Performance Battery), functional dependency (Barthel Index and Lawton & Brody), physical activity and inactivity (GeneActiv wrist-worn accelerometer), malnutrition risk (Mini Nutritional Assessment), sleep (Pittsburgh Sleep Quality Index), self-perceived health (EuroQoL 5-Dimension 3-Level) and depression (Yesavage 15-item-Geriatric-Depression-Scale) were evaluated through personal interviews. Principal component analysis (PCA) was performed to categorize the variables into components, and logistic regressions were used to propose the best-fitted model for each component. RESULTS: The PCA identified four components: (i) physical performance, with gait speed and leg mean velocity as the main variables associated with frailty; (ii) balance, showing significant associations with monopodal balance; (iii) daily activities, with moderate to vigorous physical activity and the Lawton and Brody score as the main variables associated with frailty within this component; and (iv) wellness factors, with nutritional status, self-perceived health and depression score as the primary variables associated with frailty. CONCLUSIONS: This research underscores the significance of physical function and daily activities as protective factors against frailty in community-dwelling older adults with coexisting frailty and type 2 diabetes mellitus. The health dimension contributes both protective and risk factors, emphasizing the need for comprehensive assessments in managing frailty in this population. REPORTING METHOD: The study adhered to the STROBE checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Lipidomics and biodistribution of extracellular vesicles-secreted by hepatocytes from Zucker lean and fatty rats.

Extracellular vesicles (EVs) have been involved in metabolic syndrome, although their specific role in the development of the pathology is still unknown. To further study the role of EVs, we have analysed by Raman tweezers microspectroscopy and mass spectrometry-based lipidomics the small EVs population secreted by fatty (ZF) and lean (ZL) hepatocytes obtained from Zucker rats. We have also explored in vivo and ex vivo biodistribution of these EVs through fluorine-18-radiolabelling using a positron emission tomography imaging. Based on the proportion of proteins to lipids and the types of lipids, our results indicate that within the range of small EVs, primary hepatocytes secrete different subpopulations of particles. These differences were observed in the enrichment of triglyceride species in EVs secreted by ZF hepatocytes. Biodistribution experiments showed accumulation in the brain, heart, lungs, kidney and specially in bladder after intravenous administration. In summary, we show that EVs released by a fatty hepatocytes carry a different lipid signature compared to their lean counterpart. Biodistribution experiment has shown no difference in the distribution of EVs secreted by ZF and ZL hepatocytes but has given us a first view of possible target organs for these particles. Our results might open a door to both pathology studies and therapeutic interventions.

Three-Dimensional Hepatocyte Spheroids: Model for Assessing Chemotherapy in Hepatocellular Carcinoma.

BACKGROUND: Three-dimensional cellular models provide a more comprehensive representation of in vivo cell properties, encompassing physiological characteristics and drug susceptibility. METHODS: Primary hepatocytes were seeded in ultra-low attachment plates to form spheroids, with or without tumoral cells. Spheroid structure, cell proliferation, and apoptosis were analyzed using histological staining techniques. In addition, extracellular vesicles were isolated from conditioned media by differential ultracentrifugation. Spheroids were exposed to cytotoxic drugs, and both spheroid growth and cell death were measured by microscopic imaging and flow cytometry with vital staining, respectively. RESULTS: Concerning spheroid structure, an active outer layer forms a boundary with the media, while the inner core comprises a mass of cell debris. Hepatocyte-formed spheroids release vesicles into the extracellular media, and a decrease in the concentration of vesicles in the culture media can be observed over time. When co-cultured with tumoral cells, a distinct distribution pattern emerges over the primary hepatocytes, resulting in different spheroid conformations. Tumoral cell growth was compromised upon antitumoral drug challenges. CONCLUSIONS: Treatment of mixed spheroids with different cytotoxic drugs enables the characterization of drug effects on both hepatocytes and tumoral cells, determining drug specificity effects on these cell types.