Abstract Mitochondria are dynamic organelles essential for vital cellular functions, including ATP production, apoptosis regulation, and calcium homeostasis. Increasing research has highlighted the significance of mitochondrial DNA (mtDNA) content and alterations in the development and progression of various diseases, including cancer. The high mutation rate and vulnerability of mtDNA to damage make these alterations valuable biomarkers for cancer diagnosis, monitoring disease progression, detecting metastasis, and predicting treatment resistance across different tumor types. This review explores the emerging roles of mtDNA alterations in precision oncology, emphasizing their potential in theranostics. The authors explore the mechanisms by which mtDNA mutations contribute to tumorigenesis and therapy resistance, the impact of heteroplasmy in cancer biology, and the integration of mtDNA-based diagnostics with current therapeutic strategies. Additionally, the authors highlight the experimental tools and models currently used to investigate mtDNA alterations in cancer, including advanced sequencing technologies and animal models.

Abstract Objectives Mild Traumatic Brain Injury (mTBI) is quite prevalent in the elderly population, and the authors performed a retrospective analysis regarding the predictive value of frailty assessing tools regarding the prognosis of elderly mTBI patients. Methods All the patients underwent assessment of frailty upon admission using five tools including Frailty Phenotype (FP), FRAIL Scale (FS), Edmonton Frailty Scale (EFS), Groningen Frailty Indicator (GFI), and Clinical Frailty Scale (CFS). The predicting potential of tools was analyzed against the prognosis defined by the extended Glasgow Outcome Scale (GOSE). Results The incidence of frailty in elderly patients varies widely among the tools. Multivariate logistic regression analysis showed that only frail conditions defined by FP (p-value = 0.014) and FS (p-value = 0.004) could be employed for predicting unfavorable prognosis defined by GOSE, while frailty defined by CFS (p-value = 0.683), EFS (p-value = 0.301) and GFI (p-value = 0.925) could not. The ROC further showed that FP (AUC = 73.2 %) and FS (AUC = 76.2 %) had moderate power in predicting unfavorable conditions, while CFS (AUC = 46.1 %), EFS (AUC = 55.6 %), and GFI (AUC = 51.5 %) only had low or even no power. Conclusions FP and FS could be used to predict the unfavorable prognosis associated with mTBI in the elderly population.

Abstract Introduction One of the parameters observed in functional capacity over the years is the decrease in neuromuscular responses, a fact that is attributed to the contemporary lifestyle. Thus, there is a need to carry out interventions that induce the improvement of functional capacity. Some studies have associated electrostimulation (NMES) with Strength Training (ST) to enhance the results in improving neuromuscular function. However, little is known about the effects of this association due to the numerous protocols to be manipulated. Furthermore, adaptive responses to strength training are dependent on volume and intensity manipulation. Objective To investigate the influence of ST, concomitant with NMES (NMES+) on functional capacity. Methods This is a systematic review with meta-analysis. For the search of the articles, descriptors associated with functional capacity and NMES+ were selected in the Cochrane, PubMed, Embase and VHL meta-searcher databases. Inclusion criteria were articles that presented neuromuscular electrostimulation superimposed on voluntary contraction and ST intensity control; and that did not have a therapeutic purpose. The analysis of titles, abstracts and data extraction were performed by trios of reviewers. To assess the qualities of scientific evidence, the risk of bias was analyzed through the ROB2 tool, meta- analysis and evaluation of the quality of evidence (GRADE). Results This meta-analysis selected 3 studies. The main outcomes observed in the studies were agility, balance, cardiorespiratory capacity and strength and power. A significant improvement in effect estimates for cardiorespiratory capacity alone was observed between the two studies. Conclusion Despite the significant effect of the use of NMES+, in relation to ST in isolation, the quality of the evidence was considered low, probably due to the limited number of scientific evidence found, requiring further studies to identify the real effect of this association.

Abstract The objective of the present study was to evaluate biochemical quantitative metabolites in peripheral blood serum samples of Juvenile Idiopathic Arthritis (JIA) patients and healthy controls. A cross-sectional study included 33 post-pubertal JIA (21 without and 12 with Methotrexate (MTX) women and 28 age-matched healthy controls. Metabolomic analyses based on targeted electrospray ionization tandem mass spectrometry were used to identify possible biochemical pathway modifications in serum from JIA patients. The mean current age (p = 0.065) was similar in JIA patients and healthy controls. Current MTX use in all subtypes of JIA patients was associated with an increase in concentrations of free carnitine [21.74 (12.7‒35.2) vs. 27.49 (14.5‒41.3) µM/L, p = 0.02], suggesting an enhanced mitochondrial metabolism and intestinal absorptive function. In contrast, a decreased mitochondrial metabolism was observed in polyarticular and systemic JIA subtypes, with a decrease of several acylcarnitines’ concentrations (p < 0.05). In conclusion, the present study identified a distinctive pattern of serum metabolic signatures in JIA patients under MTX therapy. Our findings indicate that MTX use is associated with a more efficient mitochondrial function.

Abstract Background and objective Colon Cancer (CC) is a common malignant tumor. The aim of this study was to investigate the role and regulatory mechanism of circular RNA pappalysin-1 (circ-PAPPA; hsa_circ_0088233) in CC. Methods In cancer tissues from CC patients, circ-PAPPA expression was measured and its relationship with patients’ clinical features was analyzed. Plasmid vectors or oligonucleotides interfering with the expression of circ-PAPPA, microRNA (miR)-656-3p or G-protein subunit Gamma-5 (GNG5) were transfected into CC cells. Cell viability was detected by MTT and colony formation assay; apoptosis was detected by flow cytometry; and cell migration and invasion were detected by wound healing assay and Transwell. Glycolytic capacity of CC cells was assessed by measuring glucose uptake and lactate production using commercial kits. The targeting relationship between miR-656-3p and circ-PAPPA or GNG5 was verified by bioinformatics website starBase and dual luciferase reporter gene assay assays. Results Circ-PAPPA was upregulated in CC and was negatively correlated with benign pathological features and 5-year survival rates of CC patients. Circ-PAPPA silencing inhibited the growth and glycolysis of CC cells through upregulating miR-656-3p. GNG5, a target of miR-656-3p, could reverse the impacts of silencing circ-PAPPA on CC cells. Conclusion Circ-PAPPA may play an oncogenic role in CC by promoting cell growth and glycolysis through the miR-656-3p/GNG5 axis.

Abstract Purpose A random home visit search investigated the prevalence and predictors of Dry Eye (DE) symptoms in Brazil. Methods Through home visits to 420 urban and 180 rural residences in the countryside of Southeast Brazil, the Dry Eye Disease Short Questionnaire (DEDSQ) was applied to volunteers 40 years and older. The predictive value of the DEDSQ and the risk factors were investigated. Results DE is more frequent in the urban population (38.1 % vs. 20 %; p < 0.0001) and was higher in females (37.5 % and 21.5 %; p < 0.0001). In the urban area, DE is associated with dyslipidemia (p < 0.0001), visual display terminal use > 2 h/day (p < 0.0001), and pterygium (p < 0.001), and in the rural area with dyslipidemia (p < 0.01) and prior ocular surgery (p < 0.05). In women, the predictors are antiallergics, chronic pelvic pain, fibromyalgia, and visual display terminal use > 2h/day. Aging was associated with distinct risk factors. DEDSQ showed 78.5 % of sensitivity and 71.1 % specificity. Conclusion This first domiciliary study in Brazil reveals that DE symptoms were more prevalent in the urban area and among women. DE has distinct risk factors and a high prevalence in Brazil.

Abstract Objective The authors explored differentially expressed circRNAs in Acute Ischemic Stroke (AIS) and revealed the role and potential downstream molecular mechanisms of circLOC375190. Methods circLOC375190 expression was modulated by lentiviral injection in the brain of transient Middle Cerebral Artery Occlusion (tMCAO) mice. Neurological dysfunction was assessed, as well as infarction size, histopathological changes, and neuronal apoptosis in tMCAO mice. An in vitro Oxygen-Glucose Deprivation/Reoxygenation (OGD/R) PC-12 cell model was established. PC-12 cells were transfected and evaluated for viability, cytotoxicity, apoptosis, and autophagy. Inflammatory factors in mouse brain tissues and PC-12 cells were examined via enzyme-linked immunosorbent assay, and related genes were measured via real-time reverse transcriptase-polymerase chain reaction and Western blot. The ring structure of circLOC375190 was assessed by actinomycin-D and RNase-R assays. circRNA targeting to downstream factors was assessed by Fluorescence in situ hybridization assay, dual luciferase reporter assay, and RNA immunoprecipitation assay. Results circLOC375190 level was increased in tMCAO mice. Knocking down circLOC375190 reduced infarct size, attenuated cerebral pathological injury and neuronal apoptosis, and inhibited inflammatory damage and autophagy in tMCAO mice. circLOC375190 knockdown enhanced neuronal viability and reduced cytotoxicity, apoptosis, and autophagy in OGD/R-treated PC12 cells. Mechanistically, circLOC375190 acted as a sponge for miR-93-5p to upregulate MAP kinase interacting serine/threonine kinase 2 expression and activate the mechanistic target of rapamycin complex 1/transcription factor EB pathway. Conclusion circLOC375190 exacerbates tMCAO-mediated neurological injury by regulating neuronal autophagy.

Abstract Background Post-acute COVID-19 Syndrome (PACS) occurs in some COVID-19 patients long after acute infection and significantly affects patients’ health. However, the mechanism by which PACS develops is unknown. Myosin light chain 9 (Myl9), produced by activated platelets, plays a role in immune dysregulation and microthrombi formation during acute COVID-19. However, in the PACS phase, the association between Myl9 and residual symptoms remains unclear, and further investigation is needed. Methods In this prospective cohort study, serum Myl9 concentrations were measured in 195 COVID-19 patients during hospitalization and at 3- and 6-month follow-up visits. Gaussian mixture modeling was used to identify groups on the basis of Myl9 levels. Relationships between Myl9 levels and residual symptoms were evaluated. Clinical characteristics influencing Myl9 levels were analyzed via logistic regression. Results A total of 304 serum samples from 195 patients were collected. Two distinct groups were identified in the Myl9 distribution with a cutoff of 386 ng/mL by Gaussian mixture modeling in this cohort. The high-Myl9 group presented significant residual respiratory symptoms at 6 months post-infection (p < 0.05). Elevated Myl9 levels at 6 months were correlated with increased neutrophil counts (p < 0.01) and respiratory comorbidities at diagnosis (p < 0.05) according to univariate regression analysis. Multivariate regression analysis confirmed the relationship between the neutrophil count and high Myl9 levels. Conclusion Prolonged high Myl9 levels are associated with respiratory symptoms, suggesting the potential involvement of prolonged inflammation or endothelial damage in PACS.

Abstract Objectives To evaluate the efficacy and safety of pulmonary rehabilitation under the supervision of health professionals at the institute versus conventional exercise-based pulmonary rehabilitation at home in Chronic Obstructive Pulmonary Disease (COPD) patients. Methods Patients of COPD received pulmonary rehabilitation under the supervision of a professional at the institute (PI cohort, n = 115) or self-driven traditional Chinese methods-based pulmonary rehabilitation at home (CE cohort, n = 127) or did not receive any type of pulmonary rehabilitation (ME cohort, n = 155). All patients received inhaled pharmacological treatment for COPD. Results Before commencing inhaled pharmacological treatment with or without pulmonary rehabilitation (BT) COPD patients had 5 (5-4) / patient BODE (body-mass index, airflow obstruction, dyspnea, and exercise capacity) index score and 12 (13-12) / patient exacerbations (in 6-months) reported. After 6 months of inhaled pharmacological treatment for COPD with or without pulmonary rehabilitation (AT), a six-minute walking test was improved and the BODE index score and exacerbations during 6 months were decreased for patients of the PI cohort as compared to BT conditions and compared to those of the CE and ME cohorts in AT conditions (p < 0.05 for all). Patients of PI, CE, and ME cohorts had the risk of under treatment for <0.01 BODE index score, <1.32 BODE index score, and <3.14 BODE index score, respectively. Conclusions Chinese patients with COPD have worse clinical conditions. After 6 months of inhaled pharmacological treatment for COPD with pulmonary rehabilitations at institutes improves the conditions of COPD patients.

Abstract Background Communication barriers make it difficult for deaf women to access information about contraceptive methods, making them vulnerable to unplanned pregnancies. Objective To identify knowledge and attitudes of deaf women in relation to contraceptive methods. Method The authors conducted a systematic review of the literature, PROSPERO registry (CRD42021277635), conducted from August 2021 to April 2024. The included studies focused on knowledge and attitudes about contraception among women with deafness. Results Twelve articles were included, with a total of 2,641 participants and those reported low knowledge about contraceptive methods. Nine studies showed withdrawal, condoms, and oral contraceptives as the best methods that deaf women know. Five studies showed low knowledge about intrauterine devices and subdermal implants. The main reasons given for abandoning the method were reproductive desire and fear of side effects. The use of hormonal contraceptives was higher among adult women and, two studies showed that among teenagers the practice of withdrawal was higher than the use of condoms. The barriers most mentioned in the eight articles for the use of contraceptives were those of communication. Conclusion Knowledge of contraceptives among deaf women was low; however, the attitude of acceptance of the use of contraceptive methods was favorable, despite the little access to more effective methods, especially among adolescents. The factor associated with low knowledge evidenced in the systematic review was communication barriers.

Abstract Background The common drugs used for the treatment of Newly Diagnosed Multiple Myeloma (NDMM) include bortezomib and lenalidomide, but the adverse effects of lenalidomide cannot be ignored, especially when it is used in the initial therapy. Methods This retrospective study evaluated the efficacy and safety of a modified DVD regimen (pegylated liposomal doxorubicin, bortezomib, and dexamethasone) followed by lenalidomide in the treatment of NDMM. A total of 40 NDMM patients were treated with a reduced dose of pegylated liposomal doxorubicin (20 mg/m2) on day 1, subcutaneous bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11, and dexamethasone (20 mg) on days 1, 2, 3, 4, 8, 9, 11, and 12 (20 days for each course). When patients failed to achieve partial or better response after 2 courses of treatment, a regimen containing lenalidomide was administered. After the induction therapy, 15 eligible patients received Peripheral Blood Stem Cells (PBSC) mobilization and transplantation followed by maintenance therapy with lenalidomide. Results The response rate (≥ very good partial response) was 55% and 80% after 2 and 4 courses, respectively. The 18-month Progression Free Survival (PFS) and Overall Survival (OS) were 78.6% and 83.4%, respectively. Grade 3 or 4 hematologic toxicity occurred in less than 10% of patients. In addition, all 15 transplant-eligible patients successfully mobilized PBSC (median CD34+cells = 4.59 × 106/kg) and underwent autologous PSBC transplantation. Conclusions This study suggests that the modified DVD regimen followed by lenalidomide is an effective and well-tolerated regimen, and has little influence on the PBSC collection and transplantation for patients with NDMM.

Abstract Introduction Inflammation is hypothesized to be a pivotal factor influencing muscle function, with C-Reactive Protein (CRP) serving as a common biomarker of inflammation. However, the literature pertaining to the relationship between CRP and muscle mass remains scant, particularly among representative adult populations in the United States. The present study aimed to delve into the association between serum CRP levels and muscle mass among American adults, leveraging data from the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2006. Methods A cohort of 13,518 participants, representative of the US adult population, underwent dual-energy X-Ray Absorptiometry (DXA) to assess Appendicular Skeletal Muscle Mass (ASM) and had their CRP levels measured. Muscle mass was defined using ASM adjusted by Body Mass Index (ASM/BMI) criteria. Employing weighted logistic regression models, restricted cubic spline analysis, and subgroup analyses, the authors examined the association between serum CRP and low muscle mass. Results After meticulously adjusting for various covariates, the present findings revealed a positive association between serum CRP levels and the risk of low muscle mass in American adults (OR = 1.07, 95 % CI 1.01‒1.14, p = 0.016). Notably, an inverse J-shaped relationship was observed, with serum CRP inflection points of 0.273 mg/dL for the overall population, 0.172 mg/dL for males, and 0.296 mg/dL for females. Subgroup analysis further demonstrated that factors such as gender, race, educational level, smoking status, congestive heart failure, stroke, renal weakness/failure, coronary heart disease, diabetes, hypertension, vigorous physical activity, moderate physical activity, and muscle strengthening activities did not significantly impact this positive correlation (all p for interaction values > 0.05). Conclusions This nationally representative cross-sectional study provides robust evidence of an inverse J-shaped association between serum CRP levels and the risk of low muscle mass in adults in the United States, with a critical inflection point of 0.273 mg/dL. These findings may inform future research and clinical strategies aimed at mitigating the negative effects of inflammation on muscle mass and function in the adult population.

Abstract Introduction The Transverse Rectus Abdominis Myocutaneous (TRAM) flap is used for breast reconstruction, but involves the risk of necrosis. Adipose tissue-derived mesenchymal Stem Cells (ADSCs) can be used to stimulate neovascularization and reduce the risk of TRAM flap necrosis. Aim Determine the effect of ADSCs on TRAM flap viability in rats. Methods Twenty-four Wistar-EPM rats were distributed into three groups (n = 8). A right caudal pedicled TRAM flap was performed in all the animals and was the only procedure performed in Group TRAM. The additional procedures of intradermal injection of α-MEM culture medium and intradermal injection of α-MEM containing ADSCs labeled with a fluorescent marker were performed in Groups α-MEM and α-MEM-SC, respectively. The percentage of flap necrosis was determined, and the level of neovascularization and distribution of stem cells in the TRAM flap was assessed using immunohistochemical analysis and fluorescence microscopy, respectively. Results The percentage of necrosis observed in Group α-MEM-SC was lower than that observed in Groups TRAM and α-MEM, namely 23.36 % vs. 50.42 % and 53.57 %, respectively (p < 0.05). In Zone IV of the flap, the number of vessels was greater in Group α-MEM-SC than in the other groups (p < 0.05). Multiple stem cells were observed in the four zones of the flap in Group α-MEM-SC. No stem cells were observed in Groups TRAM or α-MEM. Conclusion ADSCs increased TRAM flap viability and the number of vessels in Zone IV of the flap in rats.

Abstract Purpose This study aimed to evaluate the accuracy and quality of healing of main corneal incisions in femtosecond laser procedures in cataract surgery. Methods It was a prospective, non-randomized, investigator-masked study. A total of 37 eyes of 37 patients with indication for cataract surgery were separated into two groups in this prospective, nonrandomized study: Femto group, with incisions automated by femtosecond laser (18 eyes), and Phaco group, with incisions made using a keratome (19 eyes). The planned incisions were 2.2 mm wide and 1.65 mm long. The length of the incision and prevalence of endothelial gap, endothelial misalignment, and localized Descemet Membrane Detachment (DMD) were compared. Results The mean incision length was statistically higher in the Femto group in two examinations: 1.64 mm ± 0.16 vs. 1.43 mm ± 0.30 (p = 0.001) in Exam 1 (between 2 and 4 days) and 1.58 mm ± 0.22 vs. 1.27 mm ± 0.34 (p < 0.0001) in Exam 2 (between 1 and 3 months). No eye presented an endothelial gap in Exam 2. The endothelial gap was higher in the Femto group in Exam 1. In the two examinations, endothelial misalignment was lower in the Femto group, whereas the incidence of DMD was lower in the Femto group in the two examinations. Conclusions Automated incisions with femtolaser presented a higher mean length and lower DMD prevalence compared to manual incisions with a keratome.

Abstract Quilombola women are primarily responsible for maintaining ethnopharmacological knowledge. Their knowledge is transmitted orally to their descendants, preserving cultural identity and ensuring the survival of Quilombola communities. Was conducting a scoping review on the use of medicinal plants by Quilombola women. Based on the PPC strategy (population, concept, and context) and the “Joanna Briggs Institute Reviewer's Manual”, this systematic scoping review sought to answer the guiding question: which medicinal plants are used for diseases that compromise women's health in Brazilian communities of African descent? The article has registered this research in the Open Science Framework available at osf.io/eb2nc, at identifier DOI https://doi.org/10.17605/OSF.IO/5N24Y. Using the search keys, 888 studies were found. After reading the titles and abstracts, 38 studies moved on to the next stage. During the reading of the texts in full, 32 were excluded for not meeting all the inclusion criteria and six studies were included in the research. In all, 44 plants, belonging to 23 families, were mentioned in the studies. The plants reported by the study have a plurality in their therapeutic use, the form of preparation, and part of the plant used. Regarding women's health, plants were recorded for sexual, menstrual, and postpartum care. The appreciation and recognition of this ancestral knowledge contribute not only to Women's health but also to strengthening the identity and rescuing the cultural roots of these communities.