Peripheral biomarkers as a predictor of poor prognosis in severe cases of COVID-19.

We evaluated glycemia and triglyceride, hepatic, muscular, and renal damage markers, redox profile, and leptin and ghrelin hormone levels of COVID-19 patients. We also realized statistical analysis to verify the potential of biomarkers to predict poor prognosis and the correlation between them in severe cases. We assessed glycemia and the levels of triglycerides, hepatic, muscular, and renal markers in automatized biochemical analyzer. The leptin and ghrelin hormones were assessed by the ELISA assay. Severe cases presented high glycemia and triglyceride levels. Hepatic, muscular, and renal biomarkers were altered in severe patients. An oxidative stress status was found in severe COVID-19 patients. Severe cases also had increased levels of leptin. The ROC curves indicated many biomarkers as poor prognosis predictors in severe cases. The Spearman analysis showed that biomarkers correlate between themselves. Patients with COVID-19 showed significant dysregulation in the levels of several peripheral biomarkers. We bring to light that a robust panel of peripheral biomarkers and hormones predict poor prognosis in severe cases of COVID-19, as well as correlates between them. Early monitoring of these biomarkers may conduct the correct clinical intervention associated with the clinical symptoms for treating patients infected by SARS-CoV-2.

Toxicological assessment of photoactivated tetra-cationic porphyrin molecules under white light exposure in a Caenorhabditis elegans model.

Photodynamic therapy (PDT) utilizes the potential of photosensitizing substances to absorb light energy and produce reactive oxygen species. Tetra-cationic porphyrins, which have organic or coordination compounds attached to their periphery, are heterocyclic derivatives with well-described antimicrobial and antitumoral properties. This is due to their ability to produce reactive oxygen species and their photobiological properties in solution. Consequently, these molecules are promising candidates as new and more effective photosensitizers with biomedical, environmental, and other biomedical applications. Prior to human exposure, it is essential to establish the toxicological profile of these molecules using in vivo models. In this study, we used Caenorhabditis elegans, a small free-living nematode, as a model for assessing toxic effects and predicting toxicity in preclinical research. We evaluated the toxic effects of porphyrins (neutral and tetra-cationic) on nematodes under dark/light conditions. Our findings demonstrate that tetra-methylated porphyrins (3TMeP and 4TMeP) at a concentration of 3.3 µg/mL (1.36 and 0.93 µM) exhibit high toxicity (as evidenced by reduced survival, development, and locomotion) under dark conditions. Moreover, photoactivated tetra-methylated porphyrins induce higher ROS levels compared to neutral (3TPyP and 4TPyP), tetra-palladated (3PdTPyP and 4PdTPyP), and tetra-platinated (3PtTPyP and 4PtTPyP) porphyrins, which may be responsible for the observed toxic effects.

Combination therapy of itraconazole and an acylhydrazone derivative (D13) for the treatment of sporotrichosis in cats.

Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against Sporothrix sp., both in vitro and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-N'-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by Sporothrix brasiliensis. In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis. IMPORTANCE: This paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.

Puberty Blocker, Leuprolide, Reduces Sex Differences in Rough-and-Tumble Play and Anxiety-like Behavior in Juvenile Rats.

We examined the effect of the puberty blocker, leuprolide acetate, on sex differences in juvenile rough-and-tumble play behavior and anxiety-like behavior in adolescent male and female rats. We also evaluated leuprolide treatment on gonadal and pituitary hormone levels and activity-regulated cytoskeleton-protein messenger RNA levels within the adolescent amygdala, a region important both for rough-and-tumble play and anxiety-like behavior. Our findings suggest that leuprolide treatment lowered anxiety-like behavior during adolescent development, suggesting that the maturation of gonadotropin-releasing hormone systems may be linked to increased anxiety. These data provide a potential new model to understand the emergence of increased anxiety triggered around puberty. Leuprolide also reduced masculinized levels of rough-and-tumble play behavior, lowered follicle-stimulating hormone, and produced a consistent pattern of reducing or halting sex differences of hormone levels, including testosterone, growth hormone, thyrotropin, and corticosterone levels. Therefore, leuprolide treatment not only pauses sexual development of peripheral tissues, but also reduces sex differences in hormones, brain, and behavior, allowing for better harmonization of these systems following gender-affirming hormone treatment. These data contribute to the intended use of puberty blockers in stopping sex differences from developing further with the potential benefit of lowering anxiety-like behavior.

Risk Perception and Fatigue in Port Workers: A Pilot Study.

INTRODUCTION AND OBJECTIVES: The aims of this study were to assess fatigue in port workers; analyze the association between fatigue and levels of trust in organizations, as well as the association between authorities and risk perception; and examine the official documents governing the studied port, along with the current health and communication status of the port workers. MATERIALS AND METHODS: This was a descriptive and cross-sectional pilot study, which presented quantitative and qualitative data, and it was carried out among port workers in the city of Pelotas, Rio Grande do Sul, Brazil. Thirty-nine port workers responded to quantitative questionnaires, which collected their socio-demographic data, as well as a risk perception questionnaire, the Chalder Fatigue Scale, and the Checklist of Individual Strength. Five documents from the port regiment were studied and qualitatively analyzed. The health communications consisted of presenting infographics with research data and providing information for reducing fatigue. RESULTS: Fifteen workers (38.5%) were considered fatigued. There was a reduction in fatigue associated with trust in the unions and the labor management body, and there was an agreement that the precarious environment was completely unacceptable. The qualitative data in the documents indicated that it was possible to identify the infrastructure of the port environment, the legislation, the strategies to be adopted in cases of natural disasters, emergency plans, plans for the protection and promotion of workers' health, individual and collective protection plans, the division of the sectors and those responsible for them, and documents detailing the hierarchy within the ports. The qualitative analysis culminated in graphic representations (infographics) created to communicate the research results to port workers, specifically in relation to fatigue, and we presented the ways to prevent fatigue at work. Discussion/Limitations: Studying the risk perceptions and fatigue levels of port workers through research with the active participation of these workers presented their lived experiences, which promoted discussion and perhaps more effective proposals to change their work conditions.

Intra- and inter-rater reliability of muscle and fat thickness measurements obtained using portable ultrasonography in older adults.

BACKGROUND & AIMS: Ultrasonography (US) is a promising tool for assessing body composition, offering accuracy and accessibility. However, technician skills and equipment characteristics can impact measurement reliability. We aimed to evaluate the intra- and inter-rater reliability of two evaluators using A-mode Portable Ultrasound to measure muscle and fat thickness in Brazilian older adults. METHODS: Quantitative cross-sectional study carried out with 150 community-dwelling older adults of Campinas-SP-Brazil, recruited in a retirement preparation program and a geriatric outpatient care unit. Scans of nine anatomical points were performed using the portable ultrasound in A-mode (BodyMetrix Pro System BX2000; Livermore, CA), with 6 scans per location and 3 measurements taken by each evaluator. After the selection and analysis of the generated images, muscle and fat thickness were measured. Reliability estimates between measures of the same evaluator (intra-rater) and between evaluators (inter-rater) were assessed using intraclass correlation coefficients (ICC), and differences within and between technicians were assessed using one-way ANOVA. Analyses were carried out for the overall sample and stratified by sex and by nutritional status. RESULTS: Excellent ICC values (>0.90) were found for subcutaneous fat thickness in intra- and inter-rater reliability analyses. The lowest ICC values were observed for deep abdominal fat thickness measured by evaluator 1 (ICC = 0.90) and evaluator 2 (ICC = 0.87), as well as in the inter-rater analysis (ICC = 0.85). Muscle thickness measurements had satisfactory ICC values for triceps, biceps, anterior thigh, and calf, ranging from moderate to good (ICC 0.50-0.90). CONCLUSION: A portable A-mode ultrasound demonstrates excellent reliability among both intra- and inter-raters for assessing fat thickness but only moderate for muscle thickness in older adults. Hence, this could prompt inquiries regarding the sole reliance on this tool for quantifying muscle mass and examining sarcopenia in older adults. To our knowledge, this study represents the first assessment of reliability for a portable A-mode ultrasound device conducted with older adults.

Brain insulin resistance and Alzheimer's disease: a systematic review.

The disability of cells to react to insulin, causing glucose intolerance and hyperglycemia, is referred to as insulin resistance. This clinical condition, which has been well-researched in organs such as adipose tissue, muscle, and liver, has been linked to neurodegenerative diseases like Alzheimer's disease (AD) when it occurs in the brain. Objective: The authors aimed to gather data from the current literature on brain insulin resistance (BIR) and its likely repercussions on neurodegenerative disorders, more specifically AD, through a systematic review. Methods: A comprehensive search was conducted in multiple medical databases, including the Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline), and PubMed®, employing the descriptors: "insulin resistance", "brain insulin resistance", "Alzheimer's disease", "neurodegeneration", and "cognition". The authors focused their search on English-language studies published between 2000 and 2023 that investigated the influence of BIR on neurodegenerative disorders or offered insights into BIR's underlying mechanisms. Seventeen studies that met the inclusion criteria were selected. Results: The results indicate that BIR is a phenomenon observed in a variety of neurodegenerative disorders, including AD. Studies suggest that impaired glucose utilization and uptake, reduced adenosine triphosphate (ATP) production, and synaptic plasticity changes caused by BIR are linked to cognitive problems. However, conflicting results were observed regarding the association between AD and BIR, with some studies suggesting no association. Conclusion: Based on the evaluated studies, it can be concluded that the association between AD and BIR remains inconclusive, and additional research is needed to elucidate this relationship.

A incapacidade das células de reagir à insulina, ocasionando intolerância à glicose e hiperglicemia, é chamada de resistência à insulina. Essa condição clínica, que tem sido bem pesquisada em órgãos como tecido adiposo, músculo e fígado, tem sido associada às doenças neurodegenerativas como a doença de Alzheimer (DA) quando ocorre no cérebro. Objetivo: O objetivo dos autores foi reunir os dados da literatura atual sobre a resistência insulínica cerebral (RIC) e sua provável repercussão em doenças neurodegenerativas, mais especificamente na DA, por meio de uma revisão sistemática da literatura. Métodos: Foi realizada uma pesquisa abrangente em vários bancos de dados médicos, incluindo o Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline) e PubMed, empregando os descritores: "resistência à insulina", "resistência insulínica cerebral", "doença de Alzheimer", "neurodegeneração" e "cognição". Os autores concentraram sua busca em estudos no idioma inglês publicados entre 2000 e 2023 que investigaram a influência da RIC em distúrbios neurodegenerativos ou ofereceram insights sobre os mecanismos subjacentes da RIC. Dezessete estudos que atenderam aos critérios de inclusão foram selecionados. Resultados: Os resultados demonstram que a RIC é um fenômeno observado em uma variedade de doenças neurodegenerativas, incluindo a DA. Estudos sugerem que a utilização e captação prejudicadas de glicose, a produção reduzida de trifosfato de adenosina (ATP) e as alterações na plasticidade sinápticas causadas pela RIC estão ligadas a problemas cognitivos. No entanto, foram observados resultados conflitantes com relação à associação entre DA e RIC, com alguns estudos sugerindo nenhuma associação. Conclusão: Com base nos estudos avaliados, pode-se concluir que a associação entre DA e RIC ainda é inconclusiva, e pesquisas adicionais são necessárias para elucidar essa relação.

Delivery of hereditary cancer genetics services to patients newly diagnosed with ovarian and endometrial cancers at three gynecologic oncology clinics in the USA, Brazil, and Mexico.

OBJECTIVE: Three gynecologic oncology clinics located in the USA, Brazil, and Mexico collaborated to evaluate their delivery of hereditary cancer genetics services. This descriptive retrospective review study aimed to establish baseline rates and timeliness of guideline-recommended genetics service delivery to patients with ovarian, fallopian tube, primary peritoneal (ovarian), and endometrial cancers at each clinic. METHODS: Patients who were newly diagnosed with ovarian and endometrial cancers between September 1, 2018 and December 31, 2020 were identified from the medical records of the clinics. Genetics service delivery metrics included the rates of mismatch repair deficiency tumor testing for patients with endometrial cancer (microsatellite instability/immunohistochemistry, MSI/IHC), referral to genetics services for patients with ovarian cancer, completed genetics consultations, and germline genetic testing for patients with ovarian and endometrial cancers. Timeliness was calculated as the average number of days between diagnosis and the relevant delivery metric. Descriptive statistics were used to analyze data. RESULTS: In total, 1195 patients (596 with ovarian cancer, 599 with endometrial cancer) were included in the analysis, and rates of genetics service delivery varied by clinic. For patients with ovarian cancer, referral rates ranged by clinic from 32.6% to 89.5%; 30.4-65.1% of patients completed genetics consultation and 32.6-68.7% completed genetic testing. The timeliness to genetic testing for patients with ovarian cancer ranged by clinic from 107 to 595 days. A smaller proportion of patients with endometrial cancer completed MSI/IHC testing (10.0-69.2%), with the average time to MSI/IHC ranging from 15 to 282 days. Rates of genetics consultation among patients with endometrial cancer ranged by clinic from 10.8% to 26.0% and 12.5-16.6% completed genetic testing. CONCLUSIONS: All clinics successfully established baseline rates and timeliness of delivering hereditary cancer genetics services to patients with ovarian and endometrial cancers. Lower rates of delivering genetics services to patients with endometrial cancer warrant additional research and quality improvement efforts.

Effects of upper limbs' neuromuscular electrical stimulation (NMES) superimposed to voluntary contraction added to a protocol of intradialytic leg cycle ergometer exercise, in muscle strength, functional capacity and quality of life of adult patients with CKD: a randomized clinical trial protocol.

OBJECTIVE: To investigate the effects of unilateral upper limbs' (ULM) neuromuscular electrical stimulation (NMES) superimposed on a voluntary contraction added to a protocol of intradialytic leg cycle ergometer exercise on muscle strength, functional capacity and quality of life of adult patients with chronic kidney disease (CKD). METHODS: This randomized controlled clinical trial will be carried out at a Brazilian University Hospital. The patients will be evaluated and randomly allocated to an intervention group (i.e., unilateral NMES on the upper limb without hemodialysis fistula for 20 min and leg cycle ergometer for 30 min) or a control group (i.e., unilateral NMES-Sham on the upper limb without hemodialysis fistula for 20 min and leg cycle ergometer for 30 min). The patients will be treated for 8 weeks, with three weekly treatment sessions totaling 24 sessions. MEASUREMENTS: ULM muscle strength, functional capacity, quality of life and also the feasibility, safety and patient adherence to the exercise protocol. All physical measurements will be collected by trained researchers before treatment (week 0) and at the end of treatment (week 9), always in the second hemodialysis session of the week. It will be used in an intention-to-treat analysis. RESULTS/CONCLUSIONS: The outcomes of this clinical trial protocol may help to know the possible benefits of unilateral ULM' NMES superimposed on a voluntary contraction added to a protocol of leg cycle ergometer for patients with CKD and to aid clinical decisions about future implementation or not of this technique (NMES) in intradialytic physical training programs.

Phosphate buffering in mangrove sediment pore water under eutrophication and deforestation influences.

Phosphorus (P) behavior was evaluated in mangrove wetlands impacted by urban sewage, including a deforested site. Sediment cores were analyzed for grain size, organic carbon, total nitrogen, stable isotopes (δ13C and δ15N), P contents, and pore water PO43- concentrations and net consumption/production rates. Under stronger eutrophication influence, significantly higher P (1390 vs. <1000 µg/g), δ15N (8.9 vs. <6.7 ‰) and algal material contents (with lower C/N ratio and heavier δ13C) occurred. Depth-integrated PO43- consumption rates in eutrophicated sites were up to two orders of magnitude higher (at the deforested site) than in a moderately preserved mangrove. The whole core of the moderately preserved site presented no saturation of PO43- buffering capacity, while more eutrophicated sites developed buffering zones saturated at ∼18-26 cm depth. Contrasting to nearby subtidal environments, eutrophication did not cause larger pore water PO43- concentration, evidencing the role of PO43- buffering on P filtering by mangrove wetlands.

A Randomized Clinical Trial Comparing Itraconazole and a Combination Therapy with Itraconazole and Potassium Iodide for the Treatment of Feline Sporotrichosis.

Feline sporotrichosis is an endemic disease with high occurrence in Brazil. Itraconazole (ITZ) remains the drug of choice for treating this disease in cats, despite the increasing reports of therapeutic failure. A controlled, randomized clinical trial was performed on 166 naive cats with sporotrichosis to assess the effectiveness and safety of the combination therapy with ITZ and potassium iodide (KI) compared with ITZ monotherapy. Cats were randomly allocated into two treatment groups: G1-ITZ 100 mg/cat/day-and G2-ITZ 100 mg/cat/day + KI 2.5-20 mg/kg/day. Cats treated in G2 presented 77% more risk of reaching a clinical cure (a positive effect) than those treated in G1, even when controlled by negative predictors. The survival curves of the two treatment protocols indicate that a clinical cure was achieved faster in G2. An increase in the KI dose was necessary in 28 cats due to the persistence of clinical signs. Adverse reactions were equally frequent in both groups and manageable with a temporary drug suspension and/or a hepatoprotective therapy. The combination therapy was associated with a higher cure rate and a shorter treatment time, suggesting that ITZ+KI arises as a better option for treating feline sporotrichosis and should be considered the first-line treatment, especially in the presence of negative predictors.

Shih-Tzu dogs show alterations in ocular surface homeostasis despite adequate aqueous tear production.

BACKGROUND: Shih-Tzu dogs are frequently affected by ocular surface disorders such as corneal ulceration and dry eye disease (DED). The aim of this study was to evaluate ocular surface homeostasis in Shih-Tzu dogs that have adequate aqueous production. Twenty-eight dogs were subjected to eyelid blink counting, Schirmer tear test (STT-1), ophthalmic evaluation, tear film break-up time (TBUT), fluorescein test and Masmali tear ferning (TF) grading scale. RESULTS: Of the 28 animals evaluated, the median value of incomplete eyelid blinks/min (median = 15.0 blinks/min; Interquartil interval - IQR = 8.7 blinks/min - 19.5 blinks/min) was higher than the complete blinks/min (median = 2.5 blinks/min; IQR = 1.6 blinks/min - 4.3 blinks/min), with statistically significant difference. The Schirmer tear test had a median value of 25.0 mm/min (IQR = 22.7 mm/min - 27.5 mm/min), considered within the normal range for the species. On ophthalmic examination, all dogs had trichiasis of the caruncle and medial lower eyelid entropion. Lagophthalmos was the third most common alteration observed (71.4%; 20/28). The median of TBUT was 4.0 s; (IQR = 3.0 - 6.0 s). All the animals were negative to the fluorescein test and the TFT indicated that the majority of the eyes (51.8%; 29/56) were classified in abnormal grades 3 and 4 according to the Masmali tear ferning (TF) grading scale. CONCLUSIONS: Although the Shith-Tzu dogs had STT-1 values within the normal range for the species there was high prevalence of abnormal TFT grades and low TBUT in all dogs, showing that despite adequate aqueous production, these dogs have poor precorneal tear film quality. In addition, the dogs showed few complete eyelid blinks and ophthalmic alterations, promoting poor tear film diffusion. All these findings, isolated or together, can result in DED.

Biocontrol capacity of bacteria isolated from sawdust of the dairy cattle production environment.

This research paper aimed to find endemic bacteria from the cattle production system to control the growth of mastitis pathogens. Bacteria were isolated from compost barn sawdust of two dairy cattle systems and later tested to verify their ability to control the growth of Staphylococcus aureus isolates obtained from cattle with mastitis. Bacterial isolates from these systems were tested to verify biocontrol capacity using the double-layer method. A total of 189 isolates were obtained from all samples by considering the morphology of the different bacterial colonies, with 30 isolates showing positive results for the growth control of at least one S. aureus strain and 19 isolates showing the ability to control more than one pathogen strain. The ability to control more than one pathogen and present a significant halo of inhibition in our isolates represents positive traits in the search for cattle mastitis biocontrol microorganisms. Thus, the results obtained represent the range of bacteria capable of controlling the pathogens without the use of antibiotics.

Menadione and protocatechuic acid: A drug combination with antitumor effects in murine osteosarcoma cells.

Osteosarcoma (OS) is a primary malignant bone tumor that has an abnormal expression of oncogenesis and tumor suppressors and causes dysregulation of various signaling pathways. Thus, novel therapeutic strategies for OS are needed to overcome the resistance of traditional treatments. This study evaluated the cytotoxic and anticancer effects of the association between menadione (MEN) and protocatechuic acid (PCA) in murine OS cells (UMR-106). The concentrations were 3.12 µM of isolated MEN, 500 µM of isolated PCA, and their associations. We performed cell viability assays, morphology modification analysis, cell migration by the wound-healing method, apoptosis by flow cytometry, reactive oxygen species (ROS) production, gene expression of NOX by RT-qPCR, and degradation of MMP-2 and 9 by zymography. Our results showed that the association of MEN+PCA was more effective in OS cells than the compounds alone. The association decreased cell viability, delayed cell migration, and decreased the expression of NOX-2 and ROS. In addition, the MEN+PCA association induced a slight increase in the apoptotic process. In summary, the association can enhance the compound's antitumor effects and establish a higher selectivity for tumor cells, possibly caused by significant mitochondrial damage and antioxidant properties.

Brain insulin resistance and Alzheimer's disease: a systematic review / Resistência insulínica cerebral e a doença de Alzheimer: uma revisão sistemática

ABSTRACT. The disability of cells to react to insulin, causing glucose intolerance and hyperglycemia, is referred to as insulin resistance. This clinical condition, which has been well-researched in organs such as adipose tissue, muscle, and liver, has been linked to neurodegenerative diseases like Alzheimer's disease (AD) when it occurs in the brain. Objective: The authors aimed to gather data from the current literature on brain insulin resistance (BIR) and its likely repercussions on neurodegenerative disorders, more specifically AD, through a systematic review. Methods: A comprehensive search was conducted in multiple medical databases, including the Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline), and PubMed®, employing the descriptors: "insulin resistance", "brain insulin resistance", "Alzheimer's disease", "neurodegeneration", and "cognition". The authors focused their search on English-language studies published between 2000 and 2023 that investigated the influence of BIR on neurodegenerative disorders or offered insights into BIR's underlying mechanisms. Seventeen studies that met the inclusion criteria were selected. Results: The results indicate that BIR is a phenomenon observed in a variety of neurodegenerative disorders, including AD. Studies suggest that impaired glucose utilization and uptake, reduced adenosine triphosphate (ATP) production, and synaptic plasticity changes caused by BIR are linked to cognitive problems. However, conflicting results were observed regarding the association between AD and BIR, with some studies suggesting no association. Conclusion: Based on the evaluated studies, it can be concluded that the association between AD and BIR remains inconclusive, and additional research is needed to elucidate this relationship.

RESUMO. A incapacidade das células de reagir à insulina, ocasionando intolerância à glicose e hiperglicemia, é chamada de resistência à insulina. Essa condição clínica, que tem sido bem pesquisada em órgãos como tecido adiposo, músculo e fígado, tem sido associada às doenças neurodegenerativas como a doença de Alzheimer (DA) quando ocorre no cérebro. Objetivo: O objetivo dos autores foi reunir os dados da literatura atual sobre a resistência insulínica cerebral (RIC) e sua provável repercussão em doenças neurodegenerativas, mais especificamente na DA, por meio de uma revisão sistemática da literatura. Métodos: Foi realizada uma pesquisa abrangente em vários bancos de dados médicos, incluindo o Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline) e PubMed, empregando os descritores: "resistência à insulina", "resistência insulínica cerebral", "doença de Alzheimer", "neurodegeneração" e "cognição". Os autores concentraram sua busca em estudos no idioma inglês publicados entre 2000 e 2023 que investigaram a influência da RIC em distúrbios neurodegenerativos ou ofereceram insights sobre os mecanismos subjacentes da RIC. Dezessete estudos que atenderam aos critérios de inclusão foram selecionados. Resultados: Os resultados demonstram que a RIC é um fenômeno observado em uma variedade de doenças neurodegenerativas, incluindo a DA. Estudos sugerem que a utilização e captação prejudicadas de glicose, a produção reduzida de trifosfato de adenosina (ATP) e as alterações na plasticidade sinápticas causadas pela RIC estão ligadas a problemas cognitivos. No entanto, foram observados resultados conflitantes com relação à associação entre DA e RIC, com alguns estudos sugerindo nenhuma associação. Conclusão: Com base nos estudos avaliados, pode-se concluir que a associação entre DA e RIC ainda é inconclusiva, e pesquisas adicionais são necessárias para elucidar essa relação.

COVID-19, Anxiety, and Body Mass Index Increase Leptin Levels: a Cross-sectional Multicentric Study.

Although many efforts have been made to understand the pathophysiological mechanisms of COVID-19, critical gaps remain to be explored. This study aimed to investigate potential alterations in adipokine levels (specifically adiponectin, leptin, and resistin) among individuals with COVID-19. Within this population, we further assessed the association between these markers with both, body mass index (BMI) and psychiatric symptoms. This cross-sectional study included an age- and sex-matched sample of adults with COVID-19 (cases) and without COVID-19 (controls). We evaluated the severity of psychiatric symptoms, BMI, and adipokines. Individuals with COVID-19 presented greater BMI, stress levels, and leptin levels when compared to controls. Leptin levels were greater in individuals with moderate/severe COVID-19 as compared to individuals with COVID-19 who were asymptomatic or having mild symptoms. Leptin levels were positively correlated with BMI, severity of depressive and anxiety symptoms, and stress levels in the total sample. Leptin levels were also positively correlated with BMI, severity of anxiety symptoms, and stress levels in controls. In cases, there was a positive correlation between adiponectin and the severity of depressive symptoms and stress levels and leptin/resistin with BMI. A linear regression model revealed that BMI, severity of anxiety symptoms, and the diagnosis of COVID-19 are independently associated with increased leptin levels. Thus, leptin levels seem to be impacted by the COVID-19 infection, anxiety, and BMI.

OncoTherad® (MRB-CFI-1) Nanoimmunotherapy: A Promising Strategy to Treat Bacillus Calmette-Guérin-Unresponsive Non-Muscle-Invasive Bladder Cancer: Crosstalk among T-Cell CX3CR1, Immune Checkpoints, and the Toll-Like Receptor 4 Signaling Pathway.

This study assessed the safety and efficacy of OncoTherad® (MRB-CFI-1) nanoimmunotherapy for non-muscle invasive bladder cancer (NMIBC) patients unresponsive to Bacillus Calmette-Guérin (BCG) and explored its mechanisms of action in a bladder cancer microenvironment. A single-arm phase I/II study was conducted with 44 patients with NMIBC who were unresponsive to BCG treatment. Primary outcomes were pathological complete response (pCR) and relapse-free survival (RFS). Secondary outcomes comprised response duration and therapy safety. Patients' mean age was 65 years; 59.1% of them were refractory, 31.8% relapsed, and 9.1% were intolerant to BCG. Moreover, the pCR rate after 24 months reached 72.7% (95% CI), whereas the mean RFS reached 21.4 months. Mean response duration in the pCR group was 14.3 months. No patient developed muscle-invasive or metastatic disease during treatment. Treatment-related adverse events occurred in 77.3% of patients, mostly grade 1-2 events. OncoTherad® activated the innate immune system through toll-like receptor 4, leading to increased interferon signaling. This activation played a crucial role in activating CX3CR1+ CD8 T cells, decreasing immune checkpoint molecules, and reversing immunosuppression in the bladder microenvironment. OncoTherad® has proved to be a safe and effective therapeutic option for patients with BCG-unresponsive NMIBC, besides showing likely advantages in tumor relapse prevention processes.

THE CONNECTION BETWEEN BILE ACIDS AND TYPE 2 DIABETES MELLITUS - A REVIEW.

BACKGROUND: Bile acids (BAs) are steroid molecules synthesized exclusively in the liver, being end products of cholesterol catabolism. BAs are known to be involved in several metabolic alterations, including metabolic syndrome and type 2 diabetes mellitus (DM2). DM2 is a chronic degenerative disease characterized by insulin resistance, insulin deficiency due to insufficient production of pancreatic ß-cells, and elevated serum glucose levels leading to multiple complications. OBJECTIVE: The objective of this study is to investigate the role of BAs in the pathophysiology of DM2, highlighting the possibilities in the development of therapeutic procedures targeting BAs as an optional pathway in the treatment of DM2. METHODS: The research was carried out through narrative review and publications on the relationship between BAs and DM2. The databases used for the search include PubMed, Scopus, and Web of Science. The keywords used for the search include bile acids, type 2 diabetes mellitus, metabolic syndrome, and metabolic disorders. RESULTS: The studies have reported the involvement of BAs in the pathophysiology of DM2. BAs act as a ligand for the nuclear farnesoid X receptor, regulating glucose metabolism, lipid metabolism, and cellular energy production. Additionally, BAs modulate the production, elimination, and mobilization of BAs through the farnesoid X receptor. BAs also act as a signaling pathway through Takeda G protein-coupled receptor 5, further contributing to metabolic regulation. These findings suggest that targeting BAs may offer a novel therapeutic approach in the treatment of DM2. CONCLUSION: This study highlights the important role of BAs in DM2, specifically through their interactions with key metabolic pathways. Targeting BAs may represent an innovative and effective approach to the treatment of DM2.

Corrigendum: Assessment of the accuracy of 11 different diagnostic tests for the detection of Schistosomiasis mansoni in individuals from a Brazilian area of low endemicity using latent class analysis.

[This corrects the article DOI: 10.3389/fmicb.2022.1048457.].

Reproductive development of dairy heifers in an integrated livestock-forest system during the summer.

This study aimed to assess the cortisol, body and reproductive development of prepubertal Holstein and Holstein-Gir ¾ heifers at 27 months of age maintained in an integrated livestock-forest (ILF) system for 60 summer days compared to the monoculture system in full sun (FS). The ILF system promoted changes (P=0.02) in the cortisol levels of Holstein-Gir ¾ heifers and did not affect weight gain in any of the breed groups studied. Animals in ILF system presented a lower (P=0.006) vulvar development for the rima height parameter and similar for the vulva width parameter. The ovarian follicular population of Holstein-Gir ¾ heifers in the ILF system was lower (P=0.004); however, for the Holstein heifers, no statistical difference was found, and numbers were higher (P=0.08) in the ILF system. None of the other ovarian parameters studied had any changes, and we also found important racial differences. Weight gain (P=0.003), vulvar development (P<0.001), and mean follicular size (P=0.008) were higher in the Holstein-Gir ¾ animals. Based on such results, the effect of the ILF system at 27 months of age on stress and reproductive parameters in the Holstein breed is considered positive, although negative effects have been detected on reproductive parameters in the Holstein-Gir ¾ breed.