Transcriptome Profiling Reveals Distinct Alterations in B-Cell Signature and Dysregulation of Peripheral B-Cell Subsets in Sickle Cell Anemia Patients.

INTRODUCTION: Sickle cell anemia (SCA) is characterized by immune system activation and heightened susceptibility to infections. We hypothesized that SCA patients exhibit transcriptional alterations in B-cell-related genes, impacting their peripheral B-cell compartment and leading to dysregulated humoral immunity and increased infection susceptibility. OBJECTIVE: Our objective was to conduct an in-silico analysis of whole blood transcriptomes from SCA patients and healthy controls obtained from public repositories. We aimed to identify alterations in the adaptive immune system and validate these findings in our own SCA patient cohort. METHODS: Bioinformatic analyses unveiled significant transcriptional alterations in B-cell signatures, developmental pathways, and signaling pathways. These results were validated in peripheral blood mononuclear cells from our SCA patient cohort and controls using real-time PCR and flow cytometry. RESULTS: Ninety genes exhibited differential expression, with 70 upregulated and 20 downregulated. Dysregulation in the B-cell compartment of SCA patients was evident, characterized by increased frequencies of immature and naive B-cells and decreased percentages of memory B-cell subsets compared to healthy controls. CONCLUSION: Our findings highlight previously unexplored transcriptional and quantitative alterations in peripheral B-cells among SCA patients. Understanding these changes sheds light on the mechanisms contributing to the heightened infection risk in this population. Future studies should delve deeper into these molecular changes to develop targeted interventions and therapeutic strategies aimed at mitigating infection susceptibility in individuals with SCA.

Closed-loop oxygen control for critically ill patients--A systematic review and meta-analysis.

BACKGROUND: The impact of closed-loop control systems to titrate oxygen flow in critically ill patients, including their effectiveness, efficacy, workload and safety, remains unclear. This systematic review investigated the utilization of closed-loop oxygen systems for critically ill patients in comparison to manual oxygen titration systems focusing on these topics. METHODS AND FINDINGS: A search was conducted across several databases including MEDLINE, CENTRAL, EMBASE, LILACS, CINAHL, LOVE, ClinicalTrials.gov, and the World Health Organization on March 3, 2022, with subsequent updates made on June 27, 2023. Evidence databases were searched for randomized clinical parallel or crossover studies investigating closed-loop oxygen control systems for critically ill patients. This systematic review and meta-analysis was performed following the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. The analysis was conducted using Review Manager software, adopting the mean difference or standardized mean difference with a 95% confidence interval (95% CI) for continuous variables or risk ratio with 95% CI for dichotomous outcomes. The main outcome of interest was the percentage of time spent in the peripheral arterial oxygen saturation target. Secondary outcomes included time for supplemental oxygen weaning, length of stay, mortality, costs, adverse events, and workload of healthcare professional. A total of 37 records from 21 studies were included in this review with a total of 1,577 participants. Compared with manual oxygen titration, closed-loop oxygen control systems increased the percentage of time in the prescribed SpO2 target, mean difference (MD) 25.47; 95% CI 19.7, 30.0], with moderate certainty of evidence. Current evidence also shows that closed-loop oxygen control systems have the potential to reduce the percentage of time with hypoxemia (MD -0.98; 95% CI -1.68, -0.27) and healthcare workload (MD -4.94; 95% CI -7.28, -2.61) with low certainty of evidence. CONCLUSION: Closed-loop oxygen control systems increase the percentage of time in the preferred SpO2 targets and may reduce healthcare workload. TRIAL REGISTRATION: PROSPERO: CRD42022306033.

Combined physical exercise re-synchronizes expression of Bmal1 and REV-ERBα and up-regulates apoptosis and metabolism in the prostate during aging.

BACKGROUND: Aging increases the prevalence of prostate cancer. The circadian clock coordinates metabolism, cell cycle, and tumor suppressor p53. Although physical exercise has several effects on preventing prostate diseases, its effect on regulating genes and proteins of the circadian rhythm of the prostate needs to be better evaluated. The present study verified expression of REV-ERBα (Nr1d1), Bmal1, apoptosis, tumor suppressors, energetic metabolism markers, and androgen receptors in the prostatic microenvironment in 18-month-old mice submitted to combined physical training. METHODS: C57BL/6 J mice were divided into 2 groups: 6 months-old (n = 10) and 18 months-old, (n = 20). The 18-month-old animals were divided into 2 subgroups: sedentary (n = 10, 18 m Sed) and submitted to combined physical training (n = 10, 18 m TR). Combined physical training protocol was performed by running on the treadmill (40-60 % of incremental load test) and climbing strength training (40-50 % of maximum repetition test), consisting of 5×/week (3 days aerobic and 2 days strength) for 3 weeks. The prostate was prepared for Western blot and RT-qPCR analysis, and the plasm was prepared for the biochemistry analysis. RESULTS: Combined physical exercise during aging led to increased levels of Bmal1 and decreased levels of REV-ERBα in the prostate. These results were accompanied by a reduction in the AMPK/SIRT1/PGC-1α proteins and an increase in the PI3K/AKT and p53/PTEN/caspase 3 pathways, promoting apoptotic potential. CONCLUSION: These findings suggest that strength and aerobic physical exercise may be preventive in the development of preneoplastic molecular alterations and age-related features by re-synchronizes Bmal1 and REV-ERBα in prostatic tissues.

Occurrence of Free-Living Amoebae in Non-Human Primate Gut.

The gut microbiome reflects health and predicts possible disease in hosts. A holistic view of this community is needed, focusing on identifying species and dissecting how species interact with their host and each other, regardless of whether their presence is beneficial, inconsequential, or detrimental. The distribution of gut-associated eukaryotes within and across non-human primates is likely driven by host behavior and ecology. To ascertain the existence of free-living amoebae (FLA) in the gut of wild and captive non-human primates, 101 stool samples were collected and submitted to culture-dependent microscopy examination and DNA sequencing. Free-living amoebae were detected in 45.4% (46/101) of fecal samples analyzed, and their morphological characteristics matched those of Acanthamoeba spp., Vermamoeba spp., heterolobosean amoeboflagellates and fan-shaped amoebae of the family Vannellidae. Sequence analysis of the PCR products revealed that the suspected amoebae are highly homologous (99% identity and 100% query coverage) with Acanthamoeba T4 genotype and Vermamoeba vermiformis amoebae. The results showed a great diversity of amoebae in the non-human primate's microbiome, which may pose a potential risk to the health of NHPs. To our knowledge, this is the first report of free-living amoebae in non-human primates that are naturally infected. However, it is unknown whether gut-borne amoebae exploit a viable ecological niche or are simply transient residents in the gut.

Socioeconomic and gender inequalities in mental disorders among adolescents and young adults.

BACKGROUND: Socioeconomic status (SES) and gender play a key role in mental health. The objective of this study was to assess socioeconomic and gender mental health inequalities in adolescents and young adults using a population-based registry. MATERIALS AND METHODS: We conducted a lifetime follow-up study of all residents in the Basque Country between 1 and 30 years old (n=609,381) as of 31 December 2018. Primary care, specialized outpatient, and hospital care records were searched for diagnoses. SES was assessed based on household income. We estimated disaggregated lifetime prevalence of substance use, behaviour, anxiety, depression, psychosis, and attention deficit hyperactivity disorder. The local Institute of Statistics validated the mortality data. The likelihood of risks was estimated using logistic regression. RESULTS: Overall, 96,671 individuals (15.9%) had a diagnosed mental disorder, with clear gradients by gender and SES. Females of medium-to-high SES had the lowest prevalence of all mental disorders, except anxiety and depression. This group was followed by males of the same SES and females of low SES, while the highest prevalence of mental disorders was observed in low-SES males. The lower income categories had higher risks of psychiatric admission (adjusted odds ratio [AOR]: 3.64 for females; 6.66 for males) and death (AOR: 5.42). People with a mental health diagnosis had higher mortality (AOR: 2.38). CONCLUSIONS: Our work evidenced important SES and gender inequalities in the mental health and premature mortality of adolescents and young adults, findings that should drive the development and implementation of early preventive interventions.

Comparing the Efficacy of Two Cognitive Screening Tools in Identifying Gray and White Matter Brain Damage among Older Adults.

Background: Ageing is associated with structural changes in brain regions and functional decline in cognitive domains. Noninvasive tools for identifying structural damage in the brains of older adults are relevant for early treatment. Aims: This study aims to evaluate and compare the accuracy of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA©) in identifying gray and white matter brain damage in older individuals with varying degrees of cognitive impairment. Methods: Ninety older adults (62 women) with an average age of 69 ± 7 years were enrolled and categorized as having no cognitive impairment (NCI), mild cognitive impairment (MCI), or moderate cognitive impairment (MoCI). Magnetic resonance imaging (MRI) was utilized to assess the number, volume, and distribution of brain damage. The Fazekas and Scheltens scales were applied to the brain MRIs, and inferential statistics were employed to compare variables among the groups. Results: Cognitive impairment was observed in 56.7% of the participants (95% confidence interval (CI): 46.4-66.4%), with thirty-six older adults (40%) classified as MCI and 15 (17%) as MoCI. Cognitive impairment and medial temporal lobe (MTL) atrophy were found to be associated (p=0.001), exhibiting higher mean volume scales of the MTL atrophied area in the MoCI group (p < 0.001). The MMSE accurately revealed MTL atrophy based on the Scheltens (p < 0.05) and Fazekas (p < 0.05) scales. At the same time, the MoCA accurately identified periventricular white matter (PWM) abnormalities according to the Fazekas scale (p < 0.05). Conclusions: The MMSE and MoCA screening tools effectively identified gray and white matter brain damage in older adults with varying degrees of cognitive impairment. Lower MMSE scores are associated with MTL atrophy and lesions, and lower MoCA scores are related to PWM lesions. The concurrent use of MMSE and MoCA is recommended for assessing structural changes in distinct brain regions.

Analysis of health services use and clinical profiles in the year prior to suicide between 2010 and 2018: An opportunity to improve its prevention.

INTRODUCTION: Suicide is the first cause of external death in Spain. International studies show frequent and varied health contacts in the months prior to suicide. There are hardly any studies on that phenomenon in this country. OBJECTIVE: To analyze health care use in the year prior to suicide between 2010 and 2018 in the Basque Country, as well as pharmacological prescriptions and psychiatric diagnoses received. METHODS: Retrospective descriptive study with all suicides registered by the Basque Institute of Legal Medicine (BILM) between 2010 and 2018. The records of the BILM and the Basque Health Service (Osakidetza) were cross-checked. RESULTS: 1526 suicides were analyzed. 74% had health contacts in the previous year. The use was higher in women (p<0.05) and in older ages (p<0001). Primary care was the most used specialty (58.8% the previous year and 7.1% the previous week), followed by Hospital Emergencies (50.3% and 10.2%) and Outpatient Medical Specialties (49% and 11.6%), especially Radiology. Outpatient psychiatry only contacted 29.6% that year, although it had the highest average number of visits (15.1 SD22.6). The most frequent diagnostic category among psychiatric patients was F30-39 (26.7%), with differences between sexes and ages. 49.7% received psychotropic drugs. CONCLUSIONS: The results are aligned with international evidence, which they also extend, and reinforce the need to extend prevention beyond psychiatric services. It seems advisable to increase proactivity in the search for risk by sensitizing and training different professional profiles, but also to work from non-health settings to improve assistance to highly vulnerable profiles (young men) with low health links.

Risk factors for suicide reattempt: a systematic review and meta-analysis.

BACKGROUND: Suicide is one of the main external causes of death worldwide. People who have already attempted suicide are at high risk of new suicidal behavior. However, there is a lack of information on the risk factors that facilitate the appearance of reattempts. The aim of this study was to calculate the risk of suicide reattempt in the presence of suicidal history and psychosocial risk factors and to estimate the effect of each individual risk factor. METHODS: This systematic review and meta-analysis were conducted following the PRISMA-2020 guidelines. Studies on suicide reattempt that measured risk factors were searched from inception to 2022. The risk factors studied were those directly related to suicide history: history of suicide prior to the index attempt, and those that mediate the transition from suicidal ideation to attempt (alcohol or drug misuse, impulsivity, trauma, and non-suicidal self-injury). RESULTS: The initial search resulted in 11 905 articles. Of these, 34 articles were selected for this meta-analysis, jointly presenting 52 different effect sizes. The pooled effect size across the risk factors was significant (OR 2.16). Reattempt risk may be increased in presence of any of the following risk factors: previous history, active suicidal ideation, trauma, alcohol misuse, and drug misuse. However, impulsivity, and non-suicidal self-injury did not show a significant effect on reattempt. CONCLUSION: Most of the risk factors traditionally associated with suicide are also relevant when talking about suicide reattempts. Knowing the traits that define reattempters can help develop better preventive and intervention plans.

SESSAMO, follow-up of secondary students to assess mental health and obesity: a cohort study.

During last decades, a departure from health-related lifestyles has been observed among adolescents. Evidence reports that healthy lifestyles could be predictors of better mental health status. The aims of the SESSAMO Project are: 1) to assess the association between lifestyles and physical and mental health; 2) to assess how self-concept and stressful life events can modulate these associations; and 3) to establish the role of social determinants in the lifestyle and in adolescents' health. The SESSAMO Project is a prospective cohort carried out in Spain. Students aged 14-16 years (2nd-4th ESO) and their parents are invited to participate. Baseline data are collected through on-line, validated, self-administered questionnaires through a digital platform. Information on lifestyles, stressful life events and self-concept are collected. Screening of depression, anxiety, eating disorders, suicide risk, psychotic experiences and COVID impact is assessed. Every three years, up to age of 25, participants will be contacted again to update relevant information.

Is Incentive Spirometry Superior to Standard Care in Postoperative Cardiac Surgery on Clinical Outcomes and Length of Hospital and Intensive Care Unit Stay? A Systematic Review with Meta-Analysis.

INTRODUCTION: Cardiac surgery is a frequent surgical procedure and may present a high risk of complications. Among the prophylactic strategies studied to decrease the rates of negative outcomes, respiratory care seems to reduce pulmonary complications. Incentive spirometry (IS) is a low-cost, respiratory exercise technique, used for the prevention and treatment of postoperative pulmonary complications (PPC). The aim of this review was to evaluate whether IS is superior to respiratory care, mobilization exercises, and noninvasive ventilation on PPC, and clinical outcomes. METHODS: Systematic review. Medical Literature Analysis and Retrieval System Online (or MEDLINE®), Embase®, Cochrane Central Register of Controlled Trials (or CENTRAL), Physiotherapy Evidence Database (or PEDro), Cumulative Index of Nursing and Allied Health (or CINAHL®), Latin American and Caribbean Health Sciences Literature (or LILACS), Scientific Electronic Library Online (or SciELO), Allied, Scopus®, and OpenGrey databases, clinical trial registration sites, conferences, congresses, and symposiums were searched. RESULTS: Twenty-one randomized trials and one quasi-randomized trial (1,677 participants) were included. For partial pressure of oxygen (PaO2), IS was inferior to respiratory care (mean difference [MD] -4.48; 95% confidence interval [CI] -8.32 to -0.63). Flow-oriented IS was inferior to respiratory care on PaO2 (MD -4.53; 95% CI -8.88 to -0.18). However, compared to respiratory care, flow-oriented IS was superior on recovery vital capacity. CONCLUSIONS: This meta-analysis revealed that IS was not superior to standard respiratory care for PPCs and clinical outcomes, therefore its use should not be widely recommended until further studies with high quality be performed to ensure this clinical guidance.

Cytokine production by bovine adipose tissue stromal vascular fraction cells upon Neospora caninum stimulation.

In bovines few studies addressed the contribution of adipose tissue to the host immune response to infection. Here we evaluated the in vitro response of bovine adipose tissue stromal vascular fraction (SVF) cells to the protozoan parasite Neospora caninum, using live and freeze-killed tachyzoites. Live N. caninum induced the production of IL-6, IL-1ß and IL-10 by SVF cells isolated from subcutaneous adipose tissue (SAT), while in mesenteric adipose tissue (MAT) SVF cell cultures only IL-1ß and IL-10 production was increased, showing slight distinct responses between adipose tissue depots. Whereas a clear IL-8 increase was detected in peripheral blood leucocytes (PBL) culture supernatants in response to live N. caninum, no such increase was observed in SAT or MAT SVF cell cultures. Nevertheless, in response to LPS, increased IL-8 levels were detected in all cell cultures. IL-10 levels were always increased in response to stimulation (live, freeze-killed N. caninum and LPS). Overall, our results show that bovine adipose tissue SVF cells produce cytokines in response to N. caninum and can therefore be putative contributors to the host immune response against this parasite.

Sickle Cell Disease in Brazil: Current Management.

Sickle cell disease (SCD) comprises inherited red blood cell disorders due to a mutation in the ß-globin gene (c20A > T, pGlu6Val) and is characterized by the presence of abnormal hemoglobin, hemoglobin S, hemolysis, and vaso-occlusion. This mutation, either in a homozygous configuration or in compound states with other ß-globin mutations, leads to polymerization of hemoglobin S in deoxygenated conditions, causing modifications in red blood cell shape, particularly sickling. Vaso-occlusive crisis (VOC) is the hallmark of the disease, but other severe complications may arise from repeated bouts of VOCs. SCD is considered a global health problem, and its incidence has increased in some areas of the world, particularly the Americas and Africa. Management of the disease varies according to the region of the world, mainly due to local resources and socioeconomic status. This review aimed to describe more recent data on SCD regarding available treatment options, especially in Brazil. New treatment options are expected to be available to all patients, particularly crizanlizumab, which is already approved in the country.

Designing an antimicrobial film for wound applications incorporating bacteriophages and ε-poly-l-lysine.

Alginate-based dressings have been shown to promote wound healing, leveraging the unique properties of alginate. This work aimed to develop and characterize flexible individual and bilayered films to deliver bacteriophages (phages) and ε-Poly-l-lysine (ε-PLL). Films varied in different properties. The moisture content, swelling and solubility increased with higher alginate concentrations. The water vapour permeability, crucial in biomedical films to balance moisture levels for effective wound healing, reached optimal levels in bilayer films, indicating these will be able to sustain an ideal moist environment. The bilayer films showed improved ductility (lower tensile strength and increased elongation at break) compared to individual films. The incorporated phages maintained viability for 12 weeks under vacuum and refrigerated conditions, and their release was sustained and gradual. Antibacterial immersion tests showed that films with phages and ε-PLL significantly inhibited Pseudomonas aeruginosa PAO1 growth (>3.1 Log CFU/cm2). Particle release was influenced by the swelling degree and diffusional processes within the polymer network, providing insights into controlled release mechanisms for particles of varying size (50 nm to 6 µm) and charge. The films developed, demonstrated modulated release capabilities for active agents, and may show potential as controlled delivery systems for phages and wound healing adjuvants.

Exploiting the therapeutic potential of contracting skeletal muscle-released extracellular vesicles in cancer: Current insights and future directions.

The health benefits of exercise training in a cancer setting are increasingly acknowledged; however, the underlying molecular mechanisms remain poorly understood. It has been suggested that extracellular vesicles (EVs) released from contracting skeletal muscles play a key role in mediating the systemic benefits of exercise by transporting bioactive molecules, including myokines. Nevertheless, skeletal muscle-derived vesicles account for only about 5% of plasma EVs, with the immune cells making the largest contribution. Moreover, it remains unclear whether the contribution of skeletal muscle-derived EVs increases after physical exercise or how muscle contraction modulates the secretory activity of other tissues and thus influences the content and profile of circulating EVs. Furthermore, the destination of EVs after exercise is unknown, and it depends on their molecular composition, particularly adhesion proteins. The cargo of EVs is influenced by the training program, with acute training sessions having a greater impact than chronic adaptations. Indeed, there are numerous questions regarding the role of EVs in mediating the effects of exercise, the clarification of which is critical for tailoring exercise training prescriptions and designing exercise mimetics for patients unable to engage in exercise programs. This review critically analyzes the current knowledge on the effects of exercise on the content and molecular composition of circulating EVs and their impact on cancer progression.

Validity and reliability of a ruler drop test to measure dual-task reaction time, choice reaction time and discrimination reaction time.

BACKGROUND: The aim of this study was to determine the absolute and relative reliability of the Ruler Drop Test (RDT) for assessing dual-task, choice, and discrimination reaction time. In addition, the construct validity of the RDT is examined in comparison to the Deary-Liewald reaction time (DLRT). METHODS: Tests were administered by the same evaluator, one week apart. Intraclass Correlation Coefficient (ICC3.1) was used to measure relative reliability, and the standard error of measurement (SEM) and minimal detectable change (MDC95) were used to measure absolute reliability. Spearman correlation test was used to measure construct validity. RESULTS: The results showed that the relative reliability was good for the choice ruler drop (ICC = 0.81), moderate for the dual-task ruler drop test (ICC = 0.70) and discrimination ruler drop test (ICC = 0.72), and good for simple ruler drop test. However, the simple ruler drop test had poor reliability (ICC = 0.57). The RDT shows construct validity compared to the DLRT. CONCLUSION: We conclude that the RDT is a suitable instrument for measuring dual-task, choice and discrimination reaction time. Future studies should explore the reliability of these measures in other populations.

Anxious and depressive symptoms and health-related quality of life in a cohort of people who recently attempted suicide: A network analysis.

BACKGROUND: Suicide is an international health concern with immeasurable impact from the perspective of human and social suffering. Prior suicide attempts, anxious and depressive symptoms, and relatively lower health-related quality of life (HRQoL) are among the most replicated risk factors for suicide. Our goal was to visualize the distribution of these features and their interconnections with use of a network analysis approach in individuals who recently attempted suicide. METHODS: Individuals with a recent suicide attempt were recruited from nine University Hospitals across Spain as part of the SURVIVE cohort study. Anxious and depressive symptoms, and perceived HRQoL were included in the network analysis. Network structures were estimated with the EBICglasso model. Centrality measures and bridge symptoms connecting communities were explored. Subnetworks comparing younger and older individuals, and women and men were analyzed. RESULTS: A total of 1106 individuals with a recent suicide attempt were included. Depressed mood was the symptom with the greatest influence in the overall network, followed by anxiety symptoms such as feeling nervous, worrying, restless, and having difficulties to relax. Perceived general health was associated with increased suicidal ideation in the whole sample. Older people showed a specific connection between perceived general health and depressed mood. LIMITATIONS: The cross-sectional design does not allow determination of established causality. CONCLUSIONS: Depressed mood was the core network's symptom and, therefore, an important target in the management and prevention of suicide. HRQoL had more influence on the network of older populations, in which it should be a primary focus.

Leishmania and HIV co-infection: first naturally Leishmania strain presenting decreased susceptibility to miltefosine, recovered from a patient in Portugal.

BACKGROUND: In Europe, up to 70% of visceral leishmaniasis (VL) cases occurring in adults living with HIV. People living with HIV with VL co-infection often display persistent parasitemia, requiring chronic intermittent anti-Leishmania therapies. Consequently, frequent VL relapses and higher mortality rates are common in these individuals. As such, it is of paramount importance to understand the reasons for parasite persistence to improve infection management. METHODS: To outline possible causes for treatment failure in the context of HIV-VL, we followed a person living with HIV-VL co-infection for nine years in a 12-month period. We characterized: HIV-related clinicopathological alterations (CD4+ T counts and viremia) and Leishmania-specific seroreactivity, parasitemia, quantification of pro-inflammatory cytokines upon stimulation and studied a Leishmania clinical isolate recovered during this period. RESULTS: The subject presented controlled viremia and low CD4+ counts. The subject remained PCR positive for Leishmania and also seropositive. The cellular response to parasite antigens was erratic. The isolate was identified as the first Leishmania infantum case with evidence of decreased miltefosine susceptibility in Portugal. CONCLUSION: Treatment failure is a multifactorial process driven by host and parasite determinants. Still, the real-time determination of drug susceptibility profiles in clinical isolates is an unexplored resource in the monitoring of VL.

Early Impairment of Paracrine and Phenotypic Features in Resident Cardiac Mesenchymal Stromal Cells after Thoracic Radiotherapy.

Radiotherapy-induced cardiac toxicity and consequent diseases still represent potential severe late complications for many cancer survivors who undergo therapeutic thoracic irradiation. We aimed to assess the phenotypic and paracrine features of resident cardiac mesenchymal stromal cells (CMSCs) at early follow-up after the end of thoracic irradiation of the heart as an early sign and/or mechanism of cardiac toxicity anticipating late organ dysfunction. Resident CMSCs were isolated from a rat model of fractionated thoracic irradiation with accurate and clinically relevant heart dosimetry that developed delayed dose-dependent cardiac dysfunction after 1 year. Cells were isolated 6 and 12 weeks after the end of radiotherapy and fully characterized at the transcriptional, paracrine, and functional levels. CMSCs displayed several altered features in a dose- and time-dependent trend, with the most impaired characteristics observed in those exposed in situ to the highest radiation dose with time. In particular, altered features included impaired cell migration and 3D growth and a and significant association of transcriptomic data with GO terms related to altered cytokine and growth factor signaling. Indeed, the altered paracrine profile of CMSCs derived from the group at the highest dose at the 12-week follow-up gave significantly reduced angiogenic support to endothelial cells and polarized macrophages toward a pro-inflammatory profile. Data collected in a clinically relevant rat model of heart irradiation simulating thoracic radiotherapy suggest that early paracrine and transcriptional alterations of the cardiac stroma may represent a dose- and time-dependent biological substrate for the delayed cardiac dysfunction phenotype observed in vivo.

Effects of photobiomodulation on pain, lactate and muscle performance (ROM, torque, and EMG parameters) of paretic upper limb in patients with post-stroke spastic hemiparesis-a randomized controlled clinical trial.

The objective of the study was to investigate the impact of photobiomodulation (PBM) on the paretic upper limb in post-stroke patients with spastic hemiparesis and to understand the potential of PBM as a long-term non-invasive therapy for reducing the side effects caused by spasticity in the hemiparetic upper limb after a stroke. This is a double-blind randomized clinical trial constituted of 27 participants, being Control group (CG = 12 healthy individuals) and PBM group (PBMG = 15 post-stroke individuals). In the CG, the baseline blood lactate (BL) was evaluated, followed by the evaluation of the IC torque of the biceps and triceps muscles, with the isokinetic dynamometer associated with surface electromyography (EMG) and, subsequently, a new measurement of BL. The PBMG received 10 sessions of treatment with PBM (780 nm, Power: 100 mV, Power Density: 3.18 W/cm2, Energy: 4 J, Fluency: 127.4 J/cm2, Time: 40 s per point and 1.280 s total, Spot: 0.0314 cm2, 32 Points: 16 points (brachial biceps) and 16 points (brachial triceps) applied with contact at 90°, Total Energy: 64 J), which in the pre-treatment evaluation measured BL, the visual analogue scale (VAS) of pain; torque and EMG of the same muscles in the IC, subsequently, a new measurement of VAS and BL, and measurement of range of motion (ROM) during the reaching movement. At the conclusion of the ten sessions, all participants underwent a reassessment, wherein all tests originally administered during the initial evaluation were repeated. Subsequently, the data were analyzed using the Shapiro-Wilk normality test. For related data, the paired t-test was used for normal distributions and the Wilcoxon test for non-normal data. For unrelated data, the t test was used for normal distributions and the Mann-Whitney test for non-normal data. Muscle torque was higher for the CG, with a significant difference (CGxPBMG = p < 0.0001). There was no significant difference between the EMG values of the CG in relation to the Pre-PBM phase and with the Post-PBM phase of the PBMG (p > 0.05). On the other hand, there was a 38% reduction in pain reported by hemiparetic patients (p = 0.0127) and a decrease in BL in the PBMG. Post-PBM ROM increased by 46.1% in the elbow extension of the paretic limb. In conclusion, Photobiomodulation (PBM) demonstrated significant improvements in muscle performance, reducing fatigue and pain levels, and enhancing range of motion in post-stroke patients with spastic hemiparesis. These findings support the potential integration of PBM into rehabilitation protocols, but further research and clinical trials are needed to validate and expand upon these promising outcomes.