Use of Eltrombopag to Improve Thrombocytopenia and Tranfusion Requirement in Anti-CD19 CAR-T Cell-Treated Patients.

Background/Objectives: Immune effector cell-associated hematotoxicity (ICAHT) is a frequent adverse event after chimeric antigen receptor (CAR)-T cell therapy. Grade ≥ 3 thrombocytopenia occurs in around one-third of patients, and many of them become platelet transfusion-dependent. Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) able to accelerate megakaryopoiesis, which has been used successfully in patients with bone marrow failure and immune thrombocytopenia (ITP). Its role in managing thrombocytopenia and other cytopenias in CAR-T cell-treated patients has been scarcely addressed. Our aim was to report the safety and efficacy of this approach in patients included in the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC) registry. Methods: This is a retrospective, multicenter, observational study. Patients who developed platelet transfusion dependence subsequently to CAR-T cells and received eltrombopag to improve platelet counts were recruited in 10 Spanish hospitals. Results: Thirty-eight patients were enrolled and followed up for a median (interquartile range [IQR]) of 175 (99, 489) days since CAR-T cell infusion. At the moment eltrombopag was indicated, 18 patients had thrombocytopenia and another severe cytopenia, while 8 patients had severe pancytopenia. After 32 (14, 38) days on eltrombopag, 29 (76.3%) patients recovered platelet transfusion independence. The number of platelet units transfused correlated with the time needed to restore platelet counts higher than 20 × 109/L (Rho = 0.639, p < 0.001). Non-responders to eltrombopag required more platelet units (58 [29, 69] vs. 12 [6, 26] in responders, p = 0.002). Nineteen out of twenty-three (82.6%) patients recovered from severe neutropenia after 22 (11, 31) days on eltrombopag. Twenty-nine out of thirty-five (82.9%) patients recovered red blood cell (RBC) transfusion independence after 29 (17, 44) days. Seven patients recovered all cell lineages while on treatment. No thromboembolic events were reported. Only two transient toxicities (cholestasis, hyperbilirubinemia) were reported during eltrombopag treatment, none of which compelled permanent drug withdrawal. Conclusions: Eltrombopag could be safely used to manage thrombocytopenia and accelerate transfusion independence in CAR-T cell-treated patients.

Dose-response relationship of high-intensity training on global cognition in older adults with mild cognitive impairment or dementia: a systematic review with meta-analysis - the ACHIEVE-Study.

BACKGROUND: The prevalence of mild cognitive impairment (MCI) and its subsequent progression to dementia has increased progression to dementia has increased worldwide, making it a topic of interest. of interest, and it has been observed that approximately 23% of cases are avoidable through preventable through vigorous exercise. METHODS: A systematic review with meta-analysis was conducted by searching in the PubMed, Scopus, CINAHL, and Web of Science databases. For inclusion, studies had to incorporate High Intensity Training (HIT) as a primary or significant component of the overall intervention for older adults with MCI. Out of the 611 articles identified, 14 randomized clinical trials met the criteria for inclusion in the review. RESULTS: Fourteen trials were included in the systematic review, and seven were included in the meta-analysis. A total of 1839 participants were included in the studies, with 1014 receiving a high-intensity training-based intervention, and 998 were considered in the meta-analysis. Compared to usual care or sedentary activities, the high-intensity training interventions had a positive effect on cognition, either improving it or delaying the decline (g = 0.710 (95% CI: 0.191 - 1.229; p = 0.007). Additionally, the meta-analysis determined that a frequency of 3 sessions per week (g = 0.964, CI = 0.091 - 1.837, p = 0.030) of approximately 60 minutes (g = 0.756, CI = 0.052 - 1.460, p = 0.035) each was the best dose to obtain better effects on global cognition. CONCLUSION: Low-frequency and short-duration high-intensity training interventions are sufficient to improve or at least delay the decline in global cognition.

Effects of Dance-Based Aerobic Training on Mental Health and Quality of Life in Older Adults with Mild Cognitive Impairment.

(1) Background: Mild cognitive impairment in older adults is a condition characterized by a decrease in mental abilities that affects their quality of life. The aim of this study is to evaluate the effects of an aerobic training program based on dance on depression, sleep quality, and quality of life in older adults with mild cognitive impairment. (2) Methods: This study employed a randomized controlled trial design with a total of 92 older adults with cognitive impairment, randomly assigned to an experimental group (n = 47) undergoing dance-based aerobic training and a control group (n = 45) who did not receive any intervention. Depression was assessed using the Yesavage Geriatric Depression Scale, sleep quality through the Pittsburgh Sleep Quality Index (PSQI), and quality of life through the SF-36 questionnaire. (3) Results: Statistically significant improvements were observed in depression (t(46) = 4.783, p = 0.000) and in the PSQI domains: subjective sleep quality (t(46) = 3.333, p = 0.002, and Cohen's d = 0.35), sleep duration (t(46) = 5.511, p = 0.000, and Cohen's d = 0.73) and PSQI total score (t(46) = 2.116, p = 0.040, and Cohen's d = 0.20). Regarding quality of life, improvements were observed in all domains of the questionnaire: the general health (t(46) = -9.374, p = 0.000, and Cohen's d = 0.03), physical function (t(46) = -9.374, p = 0.000, and Cohen's d = 0.03), the physical role (t(46) = -5.954, p = 0.000, and Cohen's d = 1.06), the emotional role (t(46) = -6.200, p = 0.000, and Cohen's d = 0.80), social function (t(46) = -5.585, p = 0.000, and Cohen's d = 0.53), physical pain, (t(46) = -9.224, p = 0.000, and Cohen's d = 1.04), vitality (t(46) = 2.289, p = 0.027, and Cohen's d = 1.27), mental health, (t(46) = -7.985, p = 0.000, and Cohen's d = 1.33), the physical summary component, (t(46) = -13.532, p = 0.000, and Cohen's d = 1.81), and in the mental summary component (t(46) = -10.6 81, p = 0.000, and Cohen's d = 0.06); (4) Conclusions: The results of the present study showed that they suggest that a dance-based aerobic training program improves mental health and quality of life in older people with mild cognitive impairment, providing a non-pharmacological approach to improve general well-being in this population.

Retrospective Study of the Epidemiological-Clinical Characteristics of Burns Treated in a Hospital Emergency Service (2018-2022).

BACKGROUND: Burns are a common and severe medical emergency requiring immediate specialized care to minimize damage and prevent complications. Burn severity depends on depth, extent, and location, with more complex care needed for burns on critical areas or extensive burns. Nursing is essential in burn management, providing immediate care, adapting treatments, managing pain, preventing infections, and offering emotional support for recovery. The study aims to analyse the epidemiological and clinical characteristics of burns treated at the Hospital Emergency Department of the Hospital Complex of Cáceres (Spain) from January 2018 to December 2022. It looks at factors like gender, age, hospital stay duration, emergency type (paediatric or adult), main diagnosis, skin thickness, burn degree, affected body areas, percentage of body surface area burned, and treatment types. It also investigates how treatment varies by gender, age, skin thickness, and burn severity. The relevance of this research lies in the fact that periodic epidemiological studies are essential to monitor changes in diseases, evaluate the effectiveness of interventions, detect outbreaks quickly, update knowledge on risk factors, and guide health policy decisions. This ensures an adapted and effective response to the needs of the population. METHODS: Retrospective, observational study that analysed burn cases treated at the Hospital Complex of Cáceres (Spain) 2018-2022. Inclusion criteria were based on ICD-10 codes for burns, excluding severe cases not treated in this service. Data were analysed using descriptive statistics, Student's t-tests, Chi-square tests, and ANOVA. RESULTS: 220 patients surveyed, with a mean age of 47 years and 60.9% male. Most burns (95.5%) affected the external body surface, with a mean hospital stay of 7.86 days. Medical treatment was provided to 75.5% of patients, and 24.5% required surgical intervention. Significant differences in treatment procedures were observed according to age, skin thickness, and burn degree. Older patients had more procedures and longer hospital stays. Excision and transfer procedures were more common in full-thickness and severe burns. CONCLUSIONS: The findings align with previous research on burn demographics and treatment approaches. Treatment differences by age and burn severity highlight the need for tailored interventions. The study underscores the importance of comprehensive burn management, including psychological support for improved long-term outcomes. Further research could explore the impact of socio-economic factors on burn incidence and treatment. This study was not registered.

The differential illusion memory for high-associated abstract concepts (DIM-HA) effect.

A vast body of evidence has shown that concrete concepts are processed faster and more accurately than abstract concepts in a variety of cognitive tasks. This phenomenon is widely known as the concreteness effect, and explanations for its occurrence seem to reflect differences in processing and organization for both types of representations. While there is considerable evidence to support this concreteness effect, the nature of these differences is still controversial. In developing an explanation, we have proposed a relatively different approach from a false memory perspective using the Deese-Roediger-McDermott paradigm. To explore the implications of the association in creating false memories, we explore behavioral and electrophysiologically the false memory effect, where targets were manipulated according to their association strength and their concreteness. Results showed that false recognition rates differed significantly between concrete and abstract critical words when they were associated strongly with their respective lists, which led to a higher proportion of abstract false alarms both in behavioral and electrophysiological experiments. The principal outcome, which was called the DIM-HA effect, was discussed in terms of theories of associative activation and qualitatively different representation.

Genetic Characterization of African Swine Fever Italian Clusters in the 2022-2023 Epidemic Wave by a Multi-Gene Approach.

The first report of African swine fever virus (ASFV) genotype II in Italy in 2022 marked the beginning of a significant invasion in at least eight Italian regions with different infection clusters. In this study, we used the multi-gene approach to investigate the epidemiological associations between ASFV strains causing cases and outbreaks in wild boar and pigs in Italy from January 2022 to the end of 2023. Our results confirm that all the tested ASFV-positive Italian samples belonged to genotype II and show high homology with genotype II ASFV sequences previously collected in Eurasian countries. Molecular characterization revealed the presence of four genetic groups in Italy. The majority of African swine fever (ASF) samples analyzed in the current study (72%) belonged to genetic group 3, which was the most representative in Europe. The results also provide evidence of the prevalence of genetic group 19 (15.9%). In addition, we identified new putative genetic groups, genetic group 25 (9.1%) and genetic group 26 (3.0%), which have never been described before. This is the first detailed report on the molecular characterization of more than 130 ASFV strains circulating in Italy.

Modulation of the K/BxN arthritis mouse model and the effector functions of human fibroblast-like synoviocytes by liver X receptors.

The role of liver X receptors (LXR) in rheumatoid arthritis (RA) remains controversial. We studied the effect of LXR agonists on fibroblast-like synoviocytes (FLS) from RA patients and the K/BxN arthritis model in LXRα and ß double-deficient (Nr1h2/3-/-) mice. Two synthetic LXR agonists, GW3965 and T0901317, were used to activate LXRs and investigate their effects on cell growth, proliferation and matrix metalloproteinases, and chemokine production in cultured FLS from RA patients. The murine model K/BxN serum transfer of inflammatory arthritis in Nr1h2/3-/- animals was used to investigate the role of LXRs on joint inflammation in vivo. LXR agonists inhibited the FLS proliferative capacity in response to TNF, the chemokine-induced migration, the collagenase activity in FLS supernatant and FLS CXCL12 production. In the K/BxN mouse model, Nr1h2/3-/- animals showed aggravated arthritis, histological inflammation, and joint destruction, as well as an increase in synovial metalloproteases and expression of proinflammatory mediators such as IL-1ß and CCL2 in joints compared with wild type animals. Taken together, these data underscore the importance of LXRs in modulating the joint inflammatory response and highlight them as potential therapeutic targets in RA.

Effect of combined physical-cognitive training on the functional and cognitive capacity of older people with mild cognitive impairment: a randomized controlled trial.

BACKGROUND: The increase in population aging highlights the growing prevalence of mild cognitive impairment, prompting the adoption of interventions that combine physical exercise and cognitive training to improve health and cognitive performance in older adults. The aim of this study was to analyze the efficacy of a combined program on physical and cognitive health in older people with cognitive impairment. METHODS: A 12-week randomized controlled clinical trial involving 95 participants (aged 72.12 ± 4.25 years), 47 individuals participated in a control group (CG) that only underwent cognitive stimulation, while 48 individuals were in an experimental group (EG) that participated in a combined program. Balance was measured using the Tinetti scale, upper body strength was assessed with the arm curl test, lower body strength was evaluated with the 30-s chair stand test, flexibility was tested using the back scratch test and chair sit-and-reach test, physical function was measured with the Timed Up and Go test, cognitive function was assessed using the Mini Mental State Examination, cognitive impairment was evaluated with the Montreal Cognitive Assessment, verbal fluency was tested with the Isaac test, and executive functions were assessed using the Trail Making Test. RESULTS: The results of the study show significant improvements in both physical and cognitive aspects, such as balance, gait, upper and lower body strength, flexibility, physical function, cognitive function, cognitive impairment, verbal fluency, and executive functions in the group that carried out the intervention compared to the control group. CONCLUSION: A combined program for older individuals with mild cognitive impairment leads to enhancements in physical and cognitive health. These improvements underscore the importance of integrating physical exercise with cognitive training as an effective strategy for enhancing overall health and quality of life in older adults. TRIAL REGISTRATION: NCT05503641.

Impact of fluazuron on oocyte maturation: May the antiparasitic affect bovine reproduction?

Fluazuron is a novel veterinary pour-on antitick formulation which can be applied simultaneously with bovine reproduction management strategies. Considering the economic importance of the livestock industry in many countries, it is important to know whether antiparasitics such as fluazuron may cause embryonic loss. The aim of this study was to evaluate the toxicological effect of fluazuron on bovine oocytes during in vitro maturation. The best fluazuron concentrations were determined in a preliminary experiment on Chinese hamster ovary (CHO)-K1 cells and further used to compare fluazuron toxicity in both study models. Results of the annexin V and alkaline single cell gel electrophoresis assays demonstrated that fluazuron caused cytotoxicity and genotoxicity in bovine cumulus cells at all the concentrations tested (50, 75 and 100 µg fluazuron/mL). The evaluation of cortical granules and mitochondria distribution showed that cytoplasmic maturation was not affected by fluazuron treatment. However, a decrease in metaphase II + polar body, degenerate oocytes as well as disorganized chromatin in polar body were observed at all concentrations tested. Whereas the fertilization process was not altered by 50 µg/mL fluazuron, the embryo development rate decreased significantly. No significant differences were observed in any of the oxidative stress parameters assessed. This study contributes to a better understanding of fluazuron in bovines, suggesting that the antiparasitic may affect bovine reproduction and might cause embryo loss.

Prospective One-Health investigation into low-abundant extended-spectrum ß-lactamase producing Enterobacterales enables detection of potential dissemination events and persistence.

BACKGROUND: Following a one-health approach, we sought to determine reservoirs of extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales (ESBL-PE), other than Escherichia coli or Klebsiella pneumoniae complex species (i.e., low-abundant species), and their associated ESBL genes and plasmid-replicon profiles. METHODS: From 06/2017-05/2019, ESBL-PE isolates were recovered from clinical samples routinely collected at the University Hospital Basel (Basel, Switzerland), as well as from wastewater and foodstuffs collected monthly at predefined locations throughout the city of Basel. Whole-genome sequencing was performed for characterization of ESBL-PE isolates. RESULTS: Among 1634 isolates recovered, 114 (7%) belonged to 17 low-abundant ESBL-PE species. Seven species originated from more than one compartment, mainly from clinical and wastewater samples (6/17). Sixteen different ESBL genes were identified, with blaCTX-M-15 (27%), blaFONA-6 (23%) and blaSHV-12 (16%) being most frequent. The blaCTX-M-1 gene was the only ESBL gene recovered from all three compartments. Putative plasmids constituted 60% of ESBL gene-containing contigs, while chromosomes comprised 40%. Foodstuff isolates showed the highest proportion (91%, 41/45) of ESBL genes located on chromosomes, whereas wastewater isolates had the highest proportion (95%, 37/39) of putative plasmids. Multi-replicon combinations were identified in 81% of the isolates. Epidemiological links were found among some clinical and wastewater isolates. CONCLUSIONS: The dominance of blaCTX-M-15 among low-abundant ESBL-PE species supports its species-independent transmission potential beyond the E. coli and K. pneumoniae complex, and blaCTX-M-1 may be transmitted between strains recovered from different compartments. The substantial overlap between low-abundant ESBL-PE present in wastewater and clinical samples supports the utility of wastewater surveillance for antibiotic resistance monitoring.

Candida spp.: the burden of a microorganism in a microbiology department.

There is no precise information available on the entire workload of isolating a specific microorganism in a clinical microbiology laboratory, and the costs associated with it have not been specifically estimated. In this descriptive retrospective study conducted at the microbiology department of a general teaching hospital from January 2021 to December 2022, we assessed the workload associated with identifying Candida species in all types of clinical samples and patients. Costs were estimated from data obtained from the hospital's finance department and microbiology laboratory cost records. In 2 years, 1,008,231 samples were processed at our microbiology department, of which 8,775 had one or more Candida spp. isolates (9,683 total isolates). Overall, 5,151 samples with Candida spp. were identified from 2,383 inpatients. We isolated Candida spp. from 515.3 samples/100,000 population/year and from 92 samples/1,000 hospital admissions/year. By sample type, 90.8% were superficial, mainly mucosal. Only 9.1% Candida spp. were isolated from deep, usually sterile, samples, being mostly from ordinarily sterile fluids. Candida albicans was the main species (58.5%) identified, followed by C. parapsilosis complex, C. glabrata, C. tropicalis, and C. krusei. In admitted patients, the incidences of samples with Candida spp. isolates were 302.7 samples/100,000 population/year and 54 samples/1,000 admissions/year. The average cost of isolating and identifying Candida spp. was estimated at 25€ per culture-positive sample. To our knowledge, this is the first attempt to gage the workload and costs of Candida spp. isolation at a hospital microbiology department. These data can help assess the burden and significance of Candida isolation at other institutions and also help design measures for streamlining. IMPORTANCE: We believe that this work is of interest because at present, there is no really accurate information available on the total workload involved in isolating a specific microorganism in a clinical microbiology laboratory. The costs related to this have also not been described. We have described the unrestricted workload of Candida spp. in all types of samples for all types of species and patients. We believe that this information would be necessary to collect and share this information as well as to collect it in a standardized way to know the current situation of Candida spp. workload in all clinical microbiology laboratories.

Risk factors of death or chronic renal replacement therapy requirements in patients with thrombotic microangiopathies without ADAMTS-13 deficiency.

Thrombotic microangiopathy (TMA), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and multisystem organ dysfunction, is a life-threatening disease. Patients with TMA who do not exhibit a severe ADAMTS-13 deficiency (defined as a disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13 activity ≥10%: TMA-13n) continue to experience elevated mortality rates. This study explores the prognostic indicators for augmented mortality risk or necessitating chronic renal replacement therapy (composite outcome: CO) in TMA-13n patients. We included 42 TMA-13n patients from January 2008 to May 2018. Median age of 41 years and 60% were female. At presentation, 62% required dialysis, and 57% warranted intensive care unit admission. CO was observed in 45% of patients, including a 9-patient mortality subset. Multivariate logistic regression revealed three independent prognostic factors for CO: early administration of eculizumab (median time from hospitalization to eculizumab initiation: 5 days, range 0-19 days; odds ratio [OR], 0.14; 95% confidence interval [CI], 0.02-0.94), presence of neuroradiological lesions (OR, 6.67; 95% CI, 1.12-39.80), and a PLASMIC score ≤4 (OR, 7.39; 95% CI, 1.18-46.11). In conclusion, TMA-13n patients exhibit a heightened risk of CO in the presence of low PLASMIC scores and neuroradiological lesions, while early eculizumab therapy was the only protective factor.

Pharmaceutical and Trace Metal Interaction within the Water-Soil-Plant Continuum: Implications for Human and Soil Health.

Unplanned water reuse for crop irrigation may pose a global health risk due to the entry of contaminants into the food chain, undesirable effects on crop quality, and impact on soil health. In this study, we evaluate the impact derived from the co-occurrence of pharmaceuticals (Phs), trace metals (TMs), and one metalloid within the water-soil-plant continuum through bioassay experiments with Lactuca sativa L. Results indicate that the co-occurrence of Phs and TMs has synergistic or antagonistic effects, depending on target contaminants and environmental compartments. Complex formations between drugs and TMs may be responsible for enhanced sorption onto the soil of several Phs and TMs. Concerning plant uptake, the co-occurrence of Phs and TMs exerts antagonistic and synergistic effects on carbamazepine and diazepam, respectively. With the exception of Cd, drugs exert an antagonistic effect on TMs, negatively affecting their uptake and translocation. Drug contents in lettuce edible parts do not pose any threat to human health, but Cd levels exceed the maximum limits set for leafy vegetable foodstuffs. Under Ph-TM conditions, lettuce biomass decreases, and a nutrient imbalance is observed. Soil enzyme activity is stimulated under Ph-TM conditions (ß-galactosidase) and Ph and Ph-TM conditions (urease and arylsulfatase), or it is not affected (phosphatase).

BRAF mutational status is associated with survival outcomes in locally advanced resectable and metastatic NSCLC.

BACKGROUND: Immunotherapy-based treatments have demonstrated high efficacy in patients with advanced and locally advanced non-small-cell lung cancer (NSCLC). BRAF mutations affect a small but significant fraction of NSCLC. The efficacy of these therapies in this subgroup of patients is unknown. MATERIALS AND METHODS: Plasma and tissue samples from 116 resectable stage IIIA/B NSCLC patients, included in NADIM and NADIM II clinical trials (NADIM cohort), and from a prospective academic cohort with 84 stage IV NSCLC patients (BLI-O cohort), were analyzed by next-generation sequencing. RESULTS: The p.G464E, p.G466R, p.G466V, p.G469V, p.L597Q, p.T599I, p.V600E (n = 2) BRAF mutations, were identified in four (3.45 %) samples from the NADIM cohort, all of which were cases treated with neoadjuvant chemoimmunotherapy (CH-IO), and four (4.76 %) samples from the BLI-O cohort, corresponding to cases treated with first-line immunotherapy (n = 2) or CH-IO (n = 2). All these patients were alive and had no evidence of disease at data cut-off. Conversely, patients with BRAF wild-type (wt) tumors in the BLI-O cohort had a median progression-free survival (PFS) of 5.49 months and a median overall survival (OS) of 12.00 months (P-LogRank = 0.013 and 0.046, respectively). Likewise, PFS and OS probabilities at 36 months were 60.5 % and 76.1 % for patients with BRAF-wt tumors in the NADIM cohort. The pathological complete response (pCR) rate after neoadjuvant CH-IO in patients with BRAF-positive tumors (n = 4) was 100 %, whereas the pCR rate in the BRAF-wt population was 44.3 % (RR: 2.26; 95 % CI: 1.78-2.85; P < 0.001). CONCLUSION: BRAF mutations may be a good prognostic factor for advanced and locally advanced NSCLC patients undergoing immunotherapy-based treatments.

Exercise and Nutrition in the Mental Health of the Older Adult Population: A Randomized Controlled Clinical Trial.

(1) Background: Global population aging is changing demographic structures and presents significant challenges for health systems, which must adapt to an increasingly elderly population. (2) Methods: The study employed a randomized controlled trial design with a total of 116 older adults aged 65 or older, randomly assigned to an experimental group (n = 57) undergoing a combined resistance program and Mediterranean diet program and a control group (n = 59) who did not receive any intervention. Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS), sleep quality through the Pittsburgh Sleep Quality Index (PSQI), and perceived stress using the Perceived Stress Scale (PSS). (3) Results: Statistically significant improvements (p < 0.05) were observed both within and between groups in anxiety (Cohen's d = 0.38 and 0.78, respectively), depression (Cohen's d = 0.56 and 0.18, respectively), perceived stress (Cohen's d = 0.15 and 0.39, respectively), and in the PSQI domains: subjective sleep quality (Cohen's d = 1.01 and 0.53, respectively), sleep duration (Cohen's d = 0.112 and 0.53, respectively), sleep disturbances (Cohen's d = 1.92 and 0.95, respectively), use of medications (Cohen's d = 0.34 and 0.40, respectively), and the PSQI total score (Cohen's d = 0.68 and 0.49, respectively). No significant differences were observed in sleep latency or daytime dysfunction. (4) Conclusions: The results of the present study suggest that resistance intervention may be an effective therapeutic option to improve mental health and sleep quality in older adults aged 65 or older, offering a non-pharmacological approach to improving overall well-being in this demographic.

Effects of a Yoga Program Combined with a Mediterranean Diet on Nutritional Status and Functional Capacity in Community-Dwelling Older Adults: A Randomized Controlled Clinical Trial.

(1) Background: With the aging population, effective interventions are needed to enhance the health of older adults. This study investigated the combined effects of yoga and the Mediterranean diet on various health outcomes in community-dwelling older adults; (2) Methods: The study employed a randomized controlled trial design with a total of 116 older adults randomized to an experimental group (n = 57) that underwent a combined yoga and Mediterranean diet program and a control group (n = 59) that did not receive any intervention. Nutritional status was assessed using the Mini Nutritional Assessment, flexibility with the Back Scratch Test and the Chair Sit-and-Reach Test, balance, gait, and fall risk with the Tinetti Scale, and muscle strength with a dynamometer and the 30 s Chair Stand Test; (3) Results: Regarding nutritional status, there were significant differences between the experimental group and the control group (Cohen's d = 0.02). The participants in the experimental group showed greater balance (11.12 ± 3.01 vs. 10.03 ± 2.35, Cohen's d = 0.41 and gait (7.63 ± 1.96 vs. 6.69 ± 2.50, Cohen's d = 0.44) with respect to the control group. In terms of flexibility, the experimental group showed statistically significant improvements in the right arm (Cohen's d = 0.43), left arm (Cohen's d = 0.64), right perineum (Cohen's d = 0.42), and left leg (Cohen's d = 0.37) Finally, in terms of strength, participants in the experimental group experienced statistically significant improvements in grip strength and lower body strength (Cohen's d = 0.39 and 0.81, respectively); (4) Conclusions: The study highlights the potential benefits of a 12-week intervention combining yoga with a Mediterranean diet to improve the health and functional capacities of community-dwelling older adults.

Yoga as a therapeutic approach to mental health in university students: a randomized controlled trial.

Objectives: The purpose of this study has been to analyze the efficacy of a yoga-based intervention on stress, emotional wellbeing, state anxiety and trait anxiety in university students. Methods: This study was a randomized controlled trial. The sample consisted of 129 university students, of which 65 underwent a yoga training for 12 weeks and a control group that did not carry out any type of intervention. The primary outcome was stress, which was collected through The Perceived Stress Scale (PSS). The secondary outcomes were emotional wellbeing which was measured through the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS), and anxiety through State-Trait Anxiety Inventory (STAI). All variables were measured before and after the intervention. Results: Participants in the experimental group showed statistically significant improvements in the primary outcome perceived stress (Cohen's d = 0.44) and the secondary outcomes emotional wellbeing (Cohen's d = 0.47), and both state anxiety (Cohen's d = 0.38) and trait anxiety (Cohen's d = 0.80) compared to the control group that did not carry out any type of physical training. Conclusion: This study demonstrated that a 12-week yoga intervention can significantly reduce perceived stress and anxiety, and improve emotional wellbeing in university students. Initially, the experimental group (EG) reported higher levels of stress and anxiety than the control group (CG), but after the intervention, the EG experienced significant improvements compared to the CG.

Treatment of post-allogeneic hematopoietic stem cell transplant cytopenias with sequential doses of multipotent mesenchymal stromal/stem cells.

BACKGROUND AIMS: Cytopenias after allogeneic stem cell transplantation (allo-SCT) are a common complication, the underlying pathogenic mechanisms of which remain incompletely understood. Multipotent mesenchymal stromal/stem cell (MSC) therapy has been successfully employed in the treatment of immune-related disorders and can aid in the restoration of the hematopoietic niche. METHODS: A phase II clinical trial to assess the efficacy and safety of administering four sequential doses of ex-vivo expanded bone marrow MSCs from a third-party donor to patients with persistent severe cytopenias after allo-SCT was performed. RESULTS: The overall response rate on day 90 was 75% among the 27 evaluable patients (comprising 12 complete responses, 8 partial responses, and 7 with no response). The median time to respond was 14.5 days. Responses were observed across different profiles, including single or multiple affected lineages, primary or secondary timing, and potential immune-mediated or post-infectious pathophysiology versus idiopathic origin. With a median follow-up for surviving patients of 85 months after MSC infusion, 53% of patients are alive. Notably, no adverse events related to MSC therapy were reported. CONCLUSIONS: In summary, the sequential infusion of third-party MSCs emerges as a viable and safe therapeutic option, exhibiting potential benefits for patients experiencing cytopenias following allo-SCT.

Lipid phase separation impairs membrane thickness sensing by the Bacillus subtilis sensor kinase DesK.

Membrane fluidity and thickness have emerged as crucial factors for the activity of and resistance to several antimicrobials. However, the lack of tools to study membrane fluidity and, in particular, thickness in living bacteria limits our understanding of this interplay. The Bacillus subtilis histidine kinase/phosphatase DesK is a molecular sensor that directly detects membrane thickness. It controls activity of DesR, which regulates expression of the lipid desaturase Des, known for its role in cold adaptation and daptomycin susceptibility. We hypothesized that this property could be exploited to develop biosensors and reporters for antibiotic-induced changes in membrane fluidity and thickness. To test this, we designed three assays based on the des system: activation of the Pdes promoter as reporter for membrane thickening, localization of DesK-GFP(green-fluorescent protein) as proxy for rigidified membrane domains, and antibiotic sensitivity of des, desK, and desR deletion mutants as readout for the importance of membrane rigidification/thickening under the tested condition. While we could not confirm the suitability of the des system as reporter for antibiotic-induced changes in membrane thickness, we did observe that des expression is only activated by mild temperature shocks, likely due to partitioning of the sensor DesK into fluid membrane domains upon phase separation, precluding effective thickness sensing under harsh cold shock and antibiotic stress conditions. Similarly, we did not observe any sensitivity of the deletion mutants to either temperature or antibiotic stress, raising the question to what extent the des system contributes to fluidity adaptation under these conditions. IMPORTANCE: The B. subtilis des system is a prime model for direct molecular membrane thickness sensor and, as such, has been well studied in vitro. Our study shows that our understanding of its function in vivo and its importance under temperature and antibiotic stress is still very limited. Specifically, our results suggest that (i) the des system senses very subtle membrane fluidity changes that escape detection by established fluidity reporters like laurdan; (ii) membrane thickness sensing by DesK is impaired by phase separation due to partitioning of the protein into the fluid phase; and (iii) fluidity adaptations by Des are too subtle to elicit growth defects under rigidifying conditions, raising the question of how much the des system contributes to adaptation of overall membrane fluidity.