Photoprotective potential of Passiflora cincinnata Mast. (Passifloraceae) hydro-alcoholic extracts.

Passiflora cincinnata is a Passifloraceae typical of the Caatinga, a biome unique to Brazil. It has various pharmacological properties associated with its high flavonoid content. Vitexin, isovitexin, orientin, isoorientin and derivatives are the main chemical and pharmacological markers for this plant. Although flavonoids enriched-extracts have been widely applied in phytocosmetics, especially in sunscreen formulations, the use of P. cincinnata as a photoprotective ingredient remains unexplored. Different hydro-alcoholic extracts were prepared and their antioxidant and photoprotective activities were evaluated by in vitro assays. The most promising extract (Pc-1) was analyzed by HPLC-DAD-ESI-MS/MS. Nine flavonoids were identified as major compounds: isovitexin-7-O-glucoside, isoorientin-2"O-hexoside, orientin, isoorientin, isovitexin-2"-O-glucoside, isovitexin-6"-O-glucoside, isoscoparin and isoquercitrin. Finally, Pc-1 (5 and 10%, v/v) was incorporated into gel formulations, alone or combined to commercial chemical filters (benzophenone-3 and octyl methoxycinnamate). Formulations containing Pc-1 showed high SPFspectrophotometric values. When combined to commercial filters, Pc-1 (5%) potentiated their photoprotective efficacy (p<0.05). A physicochemical characterization indicated no incompatibility or signs of instability after extract incorporation. Altogether, these findings encourage the use of Pc-1 as a photoprotective ingredient or co-adjuvant in sunscreens formulations.

Magnesium, selenium and zinc deficiency compromises antioxidant defense in women with obesity.

Studies have shown that deficiencies in magnesium, selenium, and zinc in individuals with obesity compromise the endogenous antioxidant defense system. This study aimed to evaluate the impact of mineral deficiency on enzymatic antioxidant defense in women with obesity. The study involved 63 women with obesity (BMI ≥ 35 kg/m2) and 77 eutrophic women (BMI between 18.5 and 24.9 kg/m2). Variables such as fasting glucose, glycated hemoglobin, fasting insulin, and serum lipids were analyzed. Insulin resistance was measured using the homeostasis assessment model (HOMA-IR) and beta cell function using the homeostasis assessment model (HOMA-ß). Dietary intake of energy, macronutrients (including magnesium, zinc, and selenium), and plasma, erythrocyte, and urinary concentrations of these minerals were measured and analyzed. Serum cortisol, plasma leptin, plasma thiobarbituric acid reactive substances, and the activity of erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPX), and erythrocyte catalase were also analyzed. Women with obesity had reduced plasma and erythrocyte concentrations and greater urinary excretion of all minerals compared to normal weight women (p < 0.05). There was a positive association between erythrocyte concentrations of zinc and selenium and the activity of the GPX and SOD enzymes in erythrocytes in women with obesity (p < 0.05), in addition to a positive association between serum insulin and the enzyme GPX, which is dependent on dietary selenium (p < 0.05). Individuals with obesity are deficient in magnesium, selenium, and zinc, which appears to impair the antioxidant defense system and contribute to important metabolic disorders such as oxidative stress in these patients.

Repeated saline injections reduce the pulmonary allergic inflammatory response in rats by inducing short-term stress.

Purpose: Asthma is characterized by pulmonary cell infiltration and hyper-responsiveness of the airways. Short-term stress reduces airway inflammation. Thus, in the present study, we examined the effects of short-term stress induced by repeated treatment with saline injections on the pulmonary allergic inflammatory response in rats. Methods: Adult male rats were divided into three groups: Naïve group (non-sensitized, challenged, or treated rats), Control group (rats sensitized with ovalbumin (OVA) to induce lung inflammation), and Saline group (rats treated for five days with saline before OVA sensitization). Inhalation challenges were performed one week after the booster with aerosolized OVA. On day 18, the effect of saline injections on total and differential leukocytes in bronchoalveolar lavage (BAL), femoral marrow lavage (FML), and blood was evaluated. The percentage of mucus, serum corticosterone, collagen, cytokines in lung explants, and norepinephrine levels were also measured. Results: OVA sensitization increased the circulating leukocytes and their migration to the lung, decreasing the bone marrow leukocytes. The repeated saline injections prevented this migration by decreasing the number of leukocytes in BAL and blood in the control group. Cytokine Interleukin-4 (IL-4) was higher in the control group than in the naive and saline groups; cytokines Interleukin-6 (IL-6), Interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNFα) were higher in the control and saline groups than in the naïve group; Interferon gamma (IFNγ) was higher in the saline group than in the naive and control groups; norepinephrine increased in animals sensitized with OVA and was higher only in the saline group relative to the naïve group. Conclusions: These results suggest that short-term stress could contribute to the anti-allergic airway inflammation effects of a given treatment.

Effect of photobiomodulation with different wavelengths on periodontal repair in non-hyperglycemic and hyperglycemic rats.

BACKGROUND: Hyperglycemic conditions is associated with more severe periodontitis and poorer outcomes after nonsurgical periodontal treatment (NPT). Then, these patients are candidates for adjunctive therapy associated with NPT. This study evaluates the effect of photobiomodulation (PBMT) at different wavelengths on periodontal repair in non-hyperglycemic/hyperglycemic animals. MATERIALS AND METHODS: Sixty-four rats were submitted to induction of periodontitis by ligatures. Hyperglycemia was induced in half of these animals, whereas the other half remained non-hyperglycemic. The animals were subdivided into 4 groups according to the PBMT protocol applied at the time of ligature removal (n = 8): CTR: Without PBMT; IRL: PBMT with infrared laser (808 nm); RL: PBMT with red laser (660 nm); and RL-IRL: PBMT with red (660 nm) and infrared laser (808 nm). After a period of 7 days, the animals were euthanized. The parameters assessed by microtomography were the bone volume relative to total tissue volume (BV/TV%), distance from the cemento-enamel junction to the top of the bone crest (CEJ-CB), trabecular thickness, space between trabeculae, and number of trabeculae. Additionally, the percentage of inflammatory cells, blood vessels, and connective tissue matrix were assessed by histomorphometric analysis. RESULTS: PBMT reduced bone loss and increased trabecular density in hyperglycemic animals (p < .05), with RL being more effective in reducing linear bone loss (CEJ-CB), whereas RL-IRL was more effective in maintaining BV/TV%. PBMT reduced blood vessels and increased the connective tissue component in hyperglycemic animals (p < .05). RL-IRL reduced inflammatory cells regardless of the systemic condition of the animal (p < .05). CONCLUSION: PBMT (RL, RL-IRL) improves the repair of periodontal tissues in hyperglycemic animals.

Effect of photobiomodulation in an experimental in vitro model of asthma-Copd overlap.

The objective of the study was to evaluate the effect of photobiomodulation (PBM) with laser on the inflammatory process in an experimental in vitro model of ACO. The groups were: (1) human bronchial epithelial cells (BEAS-2B); (2) BEAS-2B cells treated with dexamethasone; (3) BEAS-2B cells irradiated with laser; (4) BEAS-2B cells stimulated with cigarette smoke extract (CSE) + House Dust Mite (HDM); (5) BEAS-2B cells stimulated with CSE + HDM and treated with dexamethasone; (6) BEAS-2B cells incubated with CSE + HDM and irradiated with laser. After 24 h, cytokines were quantified. There was a reduction in TNF-α, IL-1ß, IL-6, IL-4, IL-5, IL-13, IL-17, IL-21, IL-23, and an increase in IL-10 and IFN-γ in cells from the laser-irradiated ACO group compared to only ACO group. With these results, we can suggest that photobiomodulation acts in the modulation of inflammation observed in ACO, and may be a treatment option.

Models for predicting the risk of illness in leprosy contacts in Brazil: Leprosy prediction models in Brazilian contacts.

OBJECTIVE: This study aims to develop and validate predictive models that assess the risk of leprosy development among contacts, contributing to an enhanced understanding of disease occurrence in this population. METHODS: A cohort of 600 contacts of people with leprosy treated at the National Reference Center for Leprosy and Health Dermatology at the Federal University of Uberlândia (CREDESH/HC-UFU) was followed up between 2002 and 2022. The database was divided into two parts: two-third to construct the disease risk score and one-third to validate this score. Multivariate logistic regression models were used to construct the disease score. RESULTS: Of the four models constructed, model 3, which included the variables anti-phenolic glycolipid I immunoglobulin M positive, absence of Bacillus Calmette-Guérin vaccine scar and age ≥60 years, was considered the best for identifying a higher risk of illness, with a specificity of 89.2%, a positive predictive value of 60% and an accuracy of 78%. CONCLUSIONS: Risk prediction models can contribute to the management of leprosy contacts and the systematisation of contact surveillance protocols.

Imiquimod-Loaded Nanosystem for Treatment Human Papillomavirus-Induced Lesions.

Human papillomavirus (HPV)-associated cervical cancer is the most common cancer among women worldwide. The treatment options are strongly related to increased infertility in women. Imiquimod (IQ) is an imidazoquinoline, which has proven antiviral effects against persistent HPV infection by activating immune cells via Toll-like receptors 7/8 when formulated in carriers, like nanogels, for topical use. An effective alternative to conventional therapies is the nanoparticle drug delivery system. We studied lipidic nanoparticles with IQ (Lipo IQ) and functionalized them with a DNA aptamer, AT11 (Lipo IQ AT11), to improve the selectivity for cervical cancer cells combined with the efficacy of essential oils. The formulations showed that the physicochemical properties are adequate for vaginal drug delivery and have antimicrobial activity at higher concentrations (with MIC50 starting from 0.625%). The final formulations exhibited cytotoxicity in cancer cells, enhanced by essential oils without affecting healthy cells, resulting in less than 10% cell viability in HeLa cells and over 60% in NHDF cells. Essential oils potentiate Lipo IQ's effectiveness, while AT11 increases the selectivity for cervical cancer cells. As suggested by the results of the permeation assay, the formulations were internalized by the cancer cells. Overall, the obtained results suggested that the synergistic effect of the essential oils and the nanosystem potentiate the cytotoxic effect of Lipo IQ and that Lipo IQ AT11 promotes selectivity towards cancer cells.

Guillain-Barré Syndrome and Encephalitis Following a Cytomegalovirus Infection in an Immunocompetent Adult: A Case Report.

BACKGROUND Cytomegalovirus (CMV) is a common herpesvirus that often causes asymptomatic or mild infections. In immunocompromised patients, CMV can lead to severe complications, including Guillain-Barre syndrome (GBS) and encephalitis. While these conditions have been described in the immunocompetent population, simultaneous presentation of CMV-associated GBS and encephalitis in such individuals has not been previously reported. CASE REPORT We present a case of a 58-year-old woman with poorly controlled diabetes who developed concurrent GBS and encephalitis following a CMV infection. The patient experienced bilateral ascending paraparesis 1 week after self-limited gastrointestinal symptoms. Despite initial treatment with plasma exchange therapy, her condition deteriorated with altered mental status and generalized tonic-clonic seizures, necessitating orotracheal intubation. Laboratory analysis revealed the presence of CMV in her cerebrospinal fluid. After treatment with further sessions of plasma exchange therapy and ganciclovir, her muscular strength in the extremities improved. However, she developed acute lung edema and failed extubation, leading to cardiorespiratory arrest with neurological sequelae. Palliative care was institutionalized, and she died 2 weeks later due to pneumonia. CONCLUSIONS This case highlights an unusual clinical presentation of overlapping CMV-associated GBS and encephalitis in an immunocompetent individual, with diabetes as the only identified risk factor. It underscores the importance of considering CMV as a potential etiological factor in such complex cases and the need for prompt diagnosis to improve patient outcomes. Further research is warranted to explore the underlying mechanisms and implications of this rare overlapping neurological manifestation.

Impacts of industrial actions, protests, strikes and lockouts by health and care workers during COVID-19 and other pandemic contexts: a systematic review.

BACKGROUND: Public health emergencies of international concern (PHEICs) as the COVID-19 pandemic and others that have occurred since the early 2000s put enormous pressure on health and care systems. This is being a context for protests by health and care workers (HCWs) because of additional workload, working conditions and effects on mental and physical health. In this paper, we intended to analyze the demands of HCWs associated with industrial actions, protests, strikes and lockouts (IAPSLs) which occurred during COVID-19 pandemic and other PHEICs; to identify the impact of these grievances; and describe the relevant interventions to address these IAPSLs. METHODS: We included studies published between January 2000 and March 2022 in PubMed, Embase, Scopus, BVS/LILACS, WHO's COVID-19 Research Database, ILO, OECD, HSRM, and Google Scholar for grey literature. Eligibility criteria were HCWs as participants, IAPSLs as phenomenon of interest occurring in the context of COVID-19 and other PHEICs. GRADE CERQual was used to assess risk of bias and confidence of evidence. RESULTS: 1656 records were retrieved, and 91 were selected for full-text screening. We included 18 publications. A system-wide approach, rather than a limited approach to institutions on strike, makes it possible to understand the full impact of the strike on health and care services. PHEICs tend to aggravate already adverse working conditions of HCWs, acting as drivers for HCWs strikes, leading to staff shortages, and financial issues, both in the North and in the Global South, particularly evident in Asia and Africa. In addition, issues related to deficiencies in leadership and governance in heath sector and lack of medical products and technologies (e.g., lack of personal protective equipment) were the main drivers of strikes, each contributing 25% of the total drivers identified. CONCLUSIONS: It is necessary to focus on the preparedness of health and care systems to respond adequately to PHEICs, and this includes being prepared for HCWs' IAPSLs, talked much in the context of COVID-19 pandemic. Evidence to assist policymakers in defining strategies to respond adequately to the health and care needs of the population during IAPSLs is crucial. The main impact of strikes is on the disruption of health care services' provision. Gender inequality being a major issue among HCWs, a proper understanding of the full impact of the strike on health and care services will only be possible if gender lens is combined with a systemic approach, rather than gender-undifferentiated approaches limited to the institutions on strike.

An engineered POSS drug delivery system for copper(II) anticancer metallodrugs in a selective application toward melanoma cells.

In this work, a polyhedral silsesquioxane (POSS) was used as an engineered drug delivery system for two oxindolimine-copper(II) anticancer complexes, [Cu(isaepy)]+ and [Cu(isapn)]+. The interest in hybrid POSS comes from the necessity of developing materials that can act as adjuvants to improve the cytotoxicity of non-soluble metallodrugs. Functionalization of POSS with a triazole ligand (POSS-atzac) permitted the anchorage of such copper complexes, producing hybrid materials with efficient cytotoxic effects. Structural and morphological characterizations of these copper-POSS systems were performed by using different techniques (IR, NMR, thermogravimetric analysis). A combination of continuous-wave (CW) and pulsed EPR (HYSCORE) spectroscopies conducted at the X-band have enabled the complete characterization of the coordination environment of the copper ion in the POSS-atzac matrix. Additionally, the cytotoxic effects of the loaded materials, [Cu(isapn)]@POSS-atzac and [Cu(isaepy)]@POSS-atzac, were assessed toward melanomas (SK-MEL), in comparison to non-tumorigenic cells (fibroblast P4). Evaluation of their nuclease activity or ability to facilitate cleavage of DNA indicated concentrations as low as 0.6 µg mL-1, while complete DNA fragmentation was observed at 25 µg mL-1. By using adequate scavengers, investigations on active intermediates responsible for their cytotoxicity were performed, both in the absence and in the presence of ascorbate as a reducing agent. Based on the observed selective cytotoxicity of these materials toward melanomas, investigations on the reactivity of these complexes and corresponding POSS-materials with melanin, a molecule that contributes to melanoma resistance to chemotherapy, were carried out. Results indicated the main role of the binuclear copper species, formed at the surface of the silica matrix, in the observed reactivity and selectivity of these copper-POSS systems.

UV light and adaptive divergence of leaf physiology, anatomy, and ultrastructure drive heat stress tolerance in genetically distant grapevines.

The genetic basis of plant response to light and heat stresses had been unveiled, and different molecular mechanisms of leaf cell homeostasis to keep high physiological performances were recognized in grapevine varieties. However, the ability to develop heat stress tolerance strategies must be further elucidated since the morpho-anatomical and physiological traits involved may vary with genotype × environment combination, stress intensity, and duration. A 3-year experiment was conducted on potted plants of Sardinian red grapevine cultivars Cannonau (syn. Grenache) and Carignano (syn. Carignan), exposed to prolonged heat stress inside a UV-blocking greenhouse, either submitted to low daily UV-B doses of 4.63 kJ m-2 d-1 (+UV) or to 0 kJ m-2 d-1 (-UV), and compared to a control (C) exposed to solar radiation (4.05 kJ m-2 d-1 average UV-B dose). Irrigation was supplied to avoid water stress, and canopy light and thermal microclimate were monitored continuously. Heat stress exceeded one-third of the duration inside the greenhouse and 6% in C. In vivo spectroscopy, including leaf reflectance and fluorescence, allowed for characterizing different patterns of leaf traits and metabolites involved in oxidative stress protection. Cannonau showed lower stomatal conductance under C (200 mmol m-2 s-1) but more than twice the values inside the greenhouse (400 to 900 mmol m-2 s-1), where water use efficiency was reduced similarly in both varieties. Under severe heat stress and -UV, Cannonau showed a sharper decrease in primary photochemical activity and higher leaf pigment reflectance indexes and leaf mass area. UV-B increased the leaf pigments, especially in Carignano, and different leaf cell regulatory traits to prevent oxidative damage were observed in leaf cross-sections. Heat stress induced chloroplast swelling, plastoglobule diffusion, and the accumulation of secretion deposits in both varieties, aggravated in Cannonau -UV by cell vacuolation, membrane dilation, and diffused leaf blade spot swelling. Conversely, in Carignano UV-B, cell wall barriers and calcium oxalate crystals proliferated in mesophyll cells. These responses suggest an adaptive divergence among cultivars to prolonged heat stress and UV-B light. Further research on grapevine biodiversity, heat, and UV-B light interactions may give new insights on the extent of stress tolerance to improve viticulture adaptive strategies in climate change hotspots.

IgG seroprevalence of Toxoplasma gondii and Leishmania infantum in leprosy patients: Implications for screening and management of co-infections.

Parasitic co-infections are common in developing countries and can interfere with leprosy treatment, leading to an increased risk of inflammatory leprosy reactions. This study assessed serum immunoglobulin G (IgG) levels against Toxoplasma gondii and Visceral Leishmaniasis (VL) antigens in 270 leprosy patients from Brazilian states. Regarding the respective cut-offs, the prevalence of IgG seropositivity for T. gondii and VL were 21.05 % and 47.36 % in the leprosy-negative group, and 77.7 % and 52.6 % in the leprosy-positive group. Of the 270 leprosy patients, 158 (58.5 %) presented with inflammatory leprosy reactions. Of those, 72 (59.5 %) had neuritis, 35 (48.6 %) had reverse reactions, and 28 (38.9 %) had ENL in both Brazilian states. Leprosy patients with anti-Leishmania IgG seropositivity were 3.25 times more likely to develop neuritis (95 % C.I.: 1.187 - 9.154; p = 0.019). These findings are particularly relevant for clinical settings where both leprosy and parasitic diseases are prevalent and could provide essential guidance for detecting and addressing complications arising from parasitic co-infections in leprosy patients, thereby improving clinical management strategies.

Validity, reliability, and responsiveness of the Brazilian version of the instrument World Health Organization Disability Assessment Schedule (WHODAS 2.0) for individuals with obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is a disabling health condition, and there is no disease-specific patient-reported outcome instrument to assess individuals with OSA. OBJECTIVES: To evaluate the psychometric properties of the Brazilian version of the World Health Organization Disability Assessment Schedule (WHODAS 2.0) in individuals with OSA. METHODS: One hundred individuals with OSA responded to the WHODAS 2.0 version of 36 items, the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and the 12-item health survey (SF-12). Internal consistency, convergent and discriminative validity, and responsiveness to continuous positive airway pressure (CPAP) were the psychometric properties tested. RESULTS: Cronbach's α values indicate good internal consistency (0.91 - 0.73), except for the self-care domain (α = 0.52). Convergent validity indicated an excellent correlation (r = -0.80) between the domains of functioning and quality of life. Discriminative validity showed no association between OSA severity and functioning (p = 0.90). The responsiveness to CPAP treatment showed a large effect size (r = 0.82; p < 0.05) CONCLUSIONS: The WHODAS 2.0 instrument is valid, reliable, and responsive for assessing individuals with OSA.

Effect of photobiomodulation in the balance between effector and regulatory T cells in an experimental model of COPD.

Introduction: Currently, Chronic Obstructive Pulmonary Disease (COPD) has a high impact on morbidity and mortality worldwide. The increase of CD4+, CD8+ cells expressing NF-κB, STAT4, IFN-γ and perforin are related to smoking habit, smoking history, airflow rate, obstruction and pulmonary emphysema. Furthermore, a deficiency in CD4+CD25+Foxp3+ regulatory T cells (Tregs) may impair the normal function of the immune system and lead to respiratory immune disease. On the other hand, the anti-inflammatory cytokine IL-10, produced by Treg cells and macrophages, inhibits the synthesis of several pro-inflammatory cytokines that are expressed in COPD. Therefore, immunotherapeutic strategies, such as Photobiomodulation (PBM), aim to regulate the levels of cytokines, chemokines and transcription factors in COPD. Consequently, the objective of this study was to evaluate CD4+STAT4 and CD4+CD25+Foxp3+ cells as well as the production of CD4+IFN- γ and CD4+CD25+IL-10 in the lung after PBM therapy in a COPD mice model. Methods: We induced COPD in C57BL/6 mice through an orotracheal application of cigarette smoke extract. PMB treatment was applied for the entire 7 weeks and Bronchoalveolar lavage (BAL) and lungs were collected to study production of IFN- γ and IL-10 in the lung. After the last administration with cigarette smoke extract (end of 7 weeks), 24 h later, the animals were euthanized. One-way ANOVA followed by NewmanKeuls test were used for statistical analysis with significance levels adjusted to 5% (p < 0.05). Results: This result showed that PBM improves COPD symptomatology, reducing the number of inflammatory cells (macrophages, neutrophils and lymphocytes), the levels of IFN-γ among others, and increased IL-10. We also observed a decrease of collagen, mucus, bronchoconstriction index, alveolar enlargement, CD4+, CD8+, CD4+STAT4+, and CD4+IFN-γ+ cells. In addition, in the treated group, we found an increase in CD4+CD25+Foxp3+ and CD4+IL-10+ T cells. Conclusion: This study suggests that PBM treatment could be applied as an immunotherapeutic strategy for COPD.

Correction: de Oliveira et al. Viper Venom Phospholipase A2 Database: The Structural and Functional Anatomy of a Primary Toxin in Envenomation. Toxins 2024, 16, 71.

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Comparison between melatonin versus melatonin and photobiomodulation versus photobiomodulation in the treatment of Alopecia X in German Spitz dogs: Clinical, randomized, double-blind, parallel, non-inferiority protocol.

Canine Alopecia X is a non-inflammatory hair loss disorder of unknown etiology that predominantly affects German Spitz dogs. Treatment modalities include hormone and/or melatonin supplementation and low trauma microneedling. Melatonin influences hair growth and pigmentation in several species and presents a low risk of adverse effects when used in dogs with Alopecia X. Photobiomodulation (PBM) is frequently used in human androgenetic alopecia and alopecia areata; despite this, PBM remains unexplored in canine Alopecia X. To address this knowledge gap, sixty dogs of both sexes will be randomly assigned to three groups: (i) melatonin only group (3 mg/Kg, n = 20); (ii) PBM only group (diode laser, wavelength 660nm, 100mw power, with 3 J/point, 2 sessions/week for 3 months, n = 20); (ii) PBM + melatonin group (n = 20). The objective is to determine the potential of PBM alone or in conjunction with melatonin supplementation in promoting hair regrowth (hair density and diameter) by means of dermatoscopy and planimetry over a period of 90 days.

Low-pass whole genome sequencing as a cost-effective alternative to chromosomal microarray analysis for low- and middle-income countries.

Low-pass whole genome sequencing (LP-WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing-based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP-WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP-WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%-20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP-WGS emerges as a cost-effective alternative for investigating copy number changes in cytogenetics.

Photobiomodulation mitigates Bothrops jararacussu venom-induced damage in myoblast cells by enhancing myogenic factors and reducing cytokine production.

BACKGROUND: Photobiomodulation has exhibited promise in mitigating the local effects induced by Bothrops snakebite envenoming; however, the mechanisms underlying this protection are not yet fully understood. Herein, the effectiveness of photobiomodulation effects on regenerative response of C2C12 myoblast cells following exposure to Bothrops jararacussu venom (BjsuV), as well as the mechanisms involved was investigated. METHODOLOGY/PRINCIPAL FINDINGS: C2C12 myoblast cells were exposed to BjsuV (12.5 µg/mL) and irradiated once for 10 seconds with laser light of 660 nm (14.08 mW; 0.04 cm2; 352 mW/cm2) or 780 nm (17.6 mW; 0.04 cm2; 440 mW/ cm2) to provide energy densities of 3.52 and 4.4 J/cm2, and total energies of 0.1408 and 0.176 J, respectively. Cell migration was assessed through a wound-healing assay. The expression of MAPK p38-α, NF-Кß, Myf5, Pax-7, MyoD, and myogenin proteins were assessed by western blotting analysis. In addition, interleukin IL1-ß, IL-6, TNF-alfa and IL-10 levels were measured in the supernatant by ELISA. The PBM applied to C2C12 cells exposed to BjsuV promoted cell migration, increase the expression of myogenic factors (Pax7, MyF5, MyoD and myogenin), reduced the levels of proinflammatory cytokines, IL1-ß, IL-6, TNF-alfa, and increased the levels of anti-inflammatory cytokine IL-10. In addition, PBM downregulates the expression of NF-kB, and had no effect on p38 MAKP. CONCLUSION/SIGNIFICANCE: These data demonstrated that protection of the muscle cell by PBM seems to be related to the increase of myogenic factors as well as the modulation of inflammatory mediators. PBM therapy may offer a new therapeutic strategy to address the local effects of snakebite envenoming by promoting muscle regeneration and reducing the inflammatory process.