Modulation of the tumor microenvironment in non-muscle-invasive bladder cancer by OncoTherad® (MRB-CFI-1) nanoimmunotherapy: effects on tumor-associated macrophages, tumor-infiltrating lymphocytes, and monoamine oxidases.

Non-muscle-invasive bladder cancer (NMIBC) presents management challenges due to its high recurrence rate and a complex tumor microenvironment (TME). This study investigated the effects of OncoTherad® (MRB-CFI1) nanoimmunotherapy on the TME of BCG-unresponsive NMIBC, focusing on alterations in monoamine oxidases (MAO-A and MAO-B) and immune markers: CD163, FOXP3, CD8, and CX3CR1. A comparative analysis of immunoreactivities was made before and after OncoTherad® treatment and an immune score (IS) was established to evaluate the correlation between immunological changes and clinical outcomes. Forty bladder biopsies of twenty patients were divided into 2 groups (n = 20/group): 1 (pre-treatment biopsies); and 2 (post-treatment biopsies). Our results showed stable MAO-A levels but a significant (p < 0.05) decrease in MAO-B immunoreactivity after treatment, suggesting OncoTherad®'s efficacy in targeting the tumor-promoting and immunosuppressive functions of MAO-B. Significant (p < 0.05) reductions in CD163 and FOXP3 immunoreactivities were seen in post-treatment biopsies, indicating a decreased presence of M2 macrophages and Tregs. Corroborating with these results, we observed reductions in tumor histological grading, focality and size, factors that collectively enhanced recurrence-free survival (RFS) and pathological complete response (PCR). Moreover, elevated IFN-γ immunoreactivities in treated biopsies correlated with increased counts of CD8+ T cells and higher CX3CR1 expression, underscoring OncoTherad®'s enhancement of cytotoxic T cell functionality and overall antitumor immunity. The IS revealed improvements in immune responses post-treatment, with higher scores associated with better RFS and PCR outcomes. These findings validate OncoTherad®'s capability to modify the bladder cancer microenvironment favorably, promoting effective immune surveillance and response.

Impact of Preoperative Counseling and Education on Decreasing Anxiety in Patients With Gynecologic Tumors: A Randomized Clinical Trial.

OBJECTIVE: To evaluate the impact of counseling and preoperative education on reducing anxiety in patients undergoing surgery for gynecologic cancer. METHODS: In this randomized clinical trial, patients with gynecological tumors undergoing surgical treatment between 15 and 60 days preoperatively, were included. The group was randomized to receive preoperative routine orientation plus preoperative counseling and education by nursing (experimental group [EG]) or receive preoperative routine orientation only (control group [CG]). We stratified the groups by surgical approach: open, laparoscopy, and robotic. We excluded patients treated in another service and with the need for an intensive care unit after surgery. We used the Hospital Anxiety and Depression Scale (HADS) to evaluate symptoms of anxiety and depression. The severity of symptoms was evaluated using the Edmonton Symptom Assessment System (ESAS-Br). RESULTS: We analyzed 54 women (CG 27, EG 27). No significant differences were observed regarding ESAS scores (total, physical, emotional, well-being, and anxiety) between preoperative and postoperative evaluation. However, in the EG, comparing the preoperative versus postoperative moments, there was a significant reduction in total, emotional, and anxiety scores of ESAS (p = 0.012; p = 0.003; p = 0.001). No difference in anxiety symptoms by HADS scale was noted between the two groups, comparing preoperative and postoperative moments, CG (40.7% and 22.2%) and EG (37.0% and 25.9%) (p = 0.78; p = 0.75), respectively. Also, in depression symptoms (HADS scale), we found no difference comparing preoperative and postoperative moments (p = 0.34; p > 0.99). When we stratified by surgical approach or time between intervention and surgery ( ≤ 15, > 15 to ≤ 30, and > 30 days), no difference was observed in the anxiety and depression symptoms evaluation, in both groups. CONCLUSIONS: The preoperative education by nurse orientation reduced the total, emotional, and anxiety symptoms of ESAS score between preoperative and postoperative moments. However, by the HADS scale, there was no difference in anxiety and depression symptoms.

Orexin mechanisms in the prelimbic cortex modulate the expression of contextual conditioned fear.

RATIONALE: Despite the existing anatomical and physiological evidence pointing to the involvement of orexinergic projections from the lateral hypothalamus (LH) in regulating fear-related responses, little is known regarding the contribution of the orexin system in the prelimbic cortex (PL) on contextual fear. OBJECTIVES: We investigated the role of orexin-A (OrxA) and orexin type 1 receptors (Orx1R) in the PL during the expression of contextual conditioned fear in mice. METHODS: Neural tract tracing of the LH-PL pathway and Orx1R immunoreactivity in the PL of C57BL/6 male mice were performed. In a pharmacological approach, the animals were treated with either the Orx1R selective antagonist SB 334,867 (3, 30, and 300 nM/0.1 µL) or OrxA (28, 70, and 140 pmol/0.1 µL) in the PL before the test session of contextual fear conditioning. RESULTS: Neural tract tracing deposits in the LH showed some perikarya, mainly axons and terminal buttons in the PL, suggesting LH-PL reciprocate pathways. Furthermore, we showed a profuse network comprised of Orx1R-labeled thin varicose fibers widely distributed in the same field of LH-PL pathways projection. The selective blockade of Orx1R with SB 334,867 at 30 and 300 nM in the PL caused a decrease in freezing response, whereas the treatment with OrxA at 140 pmol promoted an increase in freezing response. CONCLUSION: In summary, these data confirmed an anatomical link between LH and PL, established the presence of Orx1R in the PL, and a modulatory role of the orexin system in such structure, possibly mainly via Orx1R, during contextual fear conditioning.

Advancing insights in critical COVID-19: unraveling lymphopenia through propensity score matching - Findings from the Multicenter LYMPH-COVID Study.

OBJECTIVE: To elucidate the impact of lymphopenia on critical COVID-19 patient outcomes. METHODS: We conducted a multicenter prospective cohort study across five hospitals in Portugal and Brazil from 2020 to 2021. The study included adult patients admitted to the intensive care unit with SARS-CoV-2 pneumonia. Patients were categorized into two groups based on their lymphocyte counts within 48 hours of intensive care unit admission: the Lymphopenia Group (lymphocyte serum count < 1 × 109/L) and the Nonlymphopenia Group. Multivariate logistic regression, propensity score matching, Kaplan‒Meier survival curve analysis and Cox proportional hazards regression analysis were used. RESULTS: A total of 912 patients were enrolled, with 191 (20.9%) in the Nonlymphopenia Group and 721 (79.1%) in the Lymphopenia Group. Lymphopenia patients displayed significantly elevated disease severity indices, including Sequential Organ Failure Assessment and Simplified Acute Physiology Score 3 scores, at intensive care unit admission (p = 0.001 and p < 0.001, respectively). Additionally, they presented heightened requirements for vasopressor support (p = 0.045) and prolonged intensive care unit and in-hospital stays (both p < 0.001). Multivariate logistic regression analysis after propensity score matching revealed a significant contribution of lymphopenia to mortality, with an odds ratio of 1,621 (95%CI: 1,275 - 2,048; p < 0.001). Interaction models revealed an increase of 8% in mortality for each decade of longevity in patients with concomitant lymphopenia. In the subanalysis utilizing three-group stratification, the Severe Lymphopenia Group had the highest mortality rate, not only in direct comparisons but also in Kaplan‒Meier survival analysis (log-rank test p = 0.0048). CONCLUSION: Lymphopenia in COVID-19 patients is associated with increased disease severity and an increased risk of mortality, underscoring the need for prompt support for critically ill high-risk patients. These findings offer important insights into improving patient care strategies for COVID-19 patients.

Pitaya (Hylocereus polyrhizus) extract rich in betanin encapsulated in electrospun sweet potato starch nanofibers.

BACKGROUND: Pitaya fruit (Hylocereus spp.) is rich in bioactive compounds such as betanin. This study aimed to extract betanin-rich pitaya fruit and encapsulate it in electrospun nanofibers produced with sweet potato starch. The influence of different concentrations of this bioactive compound on the morphology, functional groups, hydrophilicity, load capacity, color, thermal properties, and contact angle of the electrospun nanofibers with water and milk was assessed. The potential antioxidant and stability of nanofibers during gastrointestinal digestion in vitro were demonstrated. RESULTS: The nanofibers presented average diameters ranging from 134 to 204 nm and displayed homogeneous morphology. The load capacity of the extract in the nanofibers was 43% to 83%. The encapsulation increased the thermal resistance of betanins (197-297 °C). The static contact angle with water and milk showed that these materials presented greater affinity with milk. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) showed that the nanofibers with 5%, 25%, and 45% pitaya extract presented unique characteristics. They showed resistance in delivering betanins to the stomach, with 12% inhibition of the 2,2-diphenyl-1-picrylhydrazyl (DPPH˙) radical. However, only the 45% concentration reached the intestine with 9.83% inhibition of the DPPH˙ radical. CONCLUSIONS: Pattern recognition from multivariate analyses indicated that nanofibers containing 5%, 25%, and 45% of the extract presented distinct characteristics, with the ability to preserve betanins against thermal degradation and perform the controlled delivery of these bioactives in the stomach and intestine to produce antioxidant activity. © 2024 Society of Chemical Industry.

Evaluation of Anti-Inflammatory Activity of the New Cardiotonic Steroid γ-Benzylidene Digoxin 8 (BD-8) in Mice.

Cardiotonic steroids are known to bind to Na+/K+-ATPase and regulate several biological processes, including the immune response. The synthetic cardiotonic steroid γ-Benzylidene Digoxin 8 (BD-8) is emerging as a promising immunomodulatory molecule, although it has remained largely unexplored. Therefore, we tested the immunomodulatory potential of BD-8 both in vitro and in vivo. Hence, primary mouse macrophages were incubated with combinations of BD-8 and the pro-inflammatory fungal protein zymosan (ZYM). Nitric oxide (NO) production was determined by Griess reagent and cytokines production was assessed by enzyme-linked immunosorbent assay. Inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS), p-nuclear factor kappa B p65 (NF-κB p65), p-extracellular signal-regulated kinase (p-ERK), and p-p38 were evaluated by flow cytometry. Macrophages exposed to BD-8 displayed reduced phagocytic activity, NO levels, and production of the proinflammatory cytokine IL-1ß induced by ZYM. Furthermore, BD-8 diminished the expression of iNOS and phosphorylation of NF-κB p65, ERK, and p38. Additionally, BD-8 exhibited anti-inflammatory capacity in vivo in a carrageenan-induced mouse paw edema model. Taken together, these findings demonstrate the anti-inflammatory activity of BD-8 and further reinforce the potential of cardiotonic steroids and their derivatives as immunomodulatory molecules.

Is terbinafine an effective treatment for feline sporotrichosis?

BACKGROUND: Terbinafine has been successfully used in the treatment of human sporotrichosis; however, its effectiveness in the treatment of feline sporotrichosis is unknown. Therefore, this study aimed to describe the use of terbinafine in the treatment of feline sporotrichosis. METHODS: A cohort study was conducted in cats with sporotrichosis to assess the effectiveness and safety of terbinafine (30‒60 mg/kg/day). Clinical examination and analysis of laboratory parameters were performed monthly until clinical signs resolved or terbinafine treatment was discontinued. RESULTS: Of the 54 cats with sporotrichosis included in the study, 19 were lost during follow-up and five were withdrawn from the study due to switching to treatment with another prescription drug. Of the remaining 30 cats, 10 achieved clinical cure, with a median treatment time of 18.5 weeks. Treatment failed in 18 cases, and two cats died. Twenty-two cats had adverse reactions to terbinafine treatment, and 10 cats showed elevation of serum transaminases. LIMITATION: Loss during follow-up was high, which makes it difficult to draw accurate conclusions regarding clinical outcomes. CONCLUSION: The low rate of clinical cure observed suggests that terbinafine does not represent an effective treatment option for cases of feline sporotrichosis.

Impact of streptozotocin-induced diabetes on experimental masseter pain in rats.

This study aimed to assess the influence of streptozotocin (STZ)-induced diabetes on the nociceptive behavior evoked by the injection of hypertonic saline (HS) into the masseter muscle of rats. Forty male rats were equally divided into four groups: a) isotonic saline control, which received 0.9% isotonic saline (IS), (Ctrl-IS); b) hypertonic saline control, which received 5% HS (Ctrl-HS); c) STZ-induced diabetic, which received IS, (STZ-IS); d) STZ-induced diabetic, which received HS (STZ-HS). Experimental diabetes was induced by a single intraperitoneal injection of STZ at dose of 60 mg/kg dissolved in 0.1 M citrate buffer, and 100 µL of HS or IS were injected into the left masseter to measure the nociceptive behavior. Later on, muscle RNA was extracted to measure the relative expression of the following cytokines: cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and interleukins (IL)-1ß, -2, -6, and -10. One-way analysis of variance (ANOVA) was applied to the data (p < 0.050). We observed a main effect of group on the nociceptive response (ANOVA: F = 11.60, p < 0.001), where the Ctrl-HS group presented the highest response (p < 0.001). However, nociceptive response was similar among the Ctrl-IS, STZ-IS, and STZ-HS group (p > 0.050). In addition, the highest relative gene expression of TNF-α and IL-6 was found in the masseter of control rats following experimental muscle pain (p < 0.050). In conclusion, the loss of somatosensory function can be observed in deep orofacial tissues of STZ-induced diabetic rats.

Biological screening for congenital toxoplasmosis in newborns from Jataí, Goiás, Brazil: a cross-sectional study.

OBJECTIVE: To conduct a serological screening for toxoplasmosis in the heel prick test and to evaluate its epidemiological aspects in newborns and postpartum women in Jataí, Goiás. METHOD: Cross-sectional epidemiological study for the biological screening of newborns in Jataí, Goiás. RESULTS: The study participants amounted to 228 newborns, whose samples were collected between the third and seventh day of life. IgG antibodies against Toxoplasma gondii were detected in 40.79% (93/228) of the samples; out of these, 23.6% (22/93) had high IgG antibody titers, leading to the collection of two other peripheral blood samples and the detection of a decrease in these titers. CONCLUSION: The findings show the importance of strengthening actions in primary health care to prevent infection and training health professionals in this area to equip them with information regarding cases of reinfection and reactivation of infection in pregnant women, minimizing risks for babies.

Plasma itraconazole concentrations during treatment of feline sporotrichosis.

Itraconazole (ITZ) is the most used drug to treat feline sporotrichosis; however, little is known about its pharmacokinetics in cats with this mycosis. The aim of this study was to determine plasma ITZ concentrations in cats with sporotrichosis treated with ITZ as monotherapy or in combination with potassium iodide (KI). Cats diagnosed with sporotrichosis received orally ITZ (100 mg/cat/day) or combination therapy with ITZ (100 mg/cat/day) and KI (2.5-5 mg/kg/day) in the case of worsening or stagnation of the clinical condition. At each monthly visit, blood samples were collected at an interval of 4 h for analysis of trough and peak plasma ITZ concentrations by HPLC. Clinical features and laboratory parameters were evaluated during follow-up. Sixteen cats were included in the study. The median plasma ITZ concentration of all cats was 0.75 µg/mL. The median plasma ITZ concentration was 0.5 µg/mL in cats that received ITZ monotherapy (n = 12) and 1.0 µg/mL in those treated with ITZ + KI (n = 4). The clinical cure rate was 56.3% (n = 9) and the median treatment duration was 8 weeks. Nine cats (56.3%) developed adverse clinical reactions, and hyporexia was the most frequent (n = 8; 88.9%). Serum alanine aminotransferase was elevated in four cats (25%). The median plasma ITZ concentration detected in cats was considered to be therapeutic (>0.5 µg/mL) and was reached after 4 weeks of treatment. Plasma ITZ concentrations were higher in cats that received ITZ + KI compared to those treated only with ITZ, suggesting pharmacokinetic synergism between these drugs.

Itraconazole is the most common therapy for feline sporotrichosis, and combination therapy with potassium iodide is used in nonresponsive cases. Our study showed that all cats achieved a therapeutic plasma concentration of itraconazole, with higher levels in cats treated with the combination therapy.

Extracellular vesicles derived from bovine adipose-derived mesenchymal stromal cells enhance in vitro embryo production from lesioned ovaries.

BACKGROUND AND AIMS: Ovum pick-up (OPU) is an intrinsic step of in vitro fertilization procedures. Nevertheless, it can cause ovarian lesions and compromise female fertility in bovines. Recently, we have shown that intraovarian injection of adipose-derived mesenchymal stromal cells (AD-MSCs) effectively preserves ovarian function in bovines. Given that MSC-derived extracellular vesicles (MSC-EVs) have been shown to recapitulate several therapeutic effects attributed to AD-MSCs and that they present logistic and regulatory advantages compared to AD-MSCs, we tested whether MSC-EVs would also be useful to treat OPU-induced lesions. METHODS: MSC-EVs were isolated from the secretome of bovine AD-MSCs, using ultrafiltration (UF) and ultracentrifugation methods. The MSC-EVs were characterized according to concentration and mean particle size, morphology, protein concentration and EV markers, miRNA, mRNA, long noncoding RNA profile, total RNA yield and potential for induction of the proliferation and migration of bovine ovarian stromal cells. We then investigated whether intraovarian injection of MSC-EVs obtained by UF would reduce the negative effects of acute OPU-induced ovarian lesions in bovines. To do so, 20 animals were divided into 4 experimental groups (n = 5), submitted to 4 OPU cycles and different experimental treatments including vehicle only (G1), MSC-EVs produced by 7.5 × 106 AD-MSCs (G2), MSC-EVs produced by 2.5 × 106 AD-MSCs (G3) or 3 doses of MSC-EVs produced by 2.5 × 106 AD-MSCs, injected after OPU sessions 1, 2 and 3 (G4). RESULTS: Characterization of the MSC-EVs revealed that the size of the particles was similar in the different isolation methods; however, the UF method generated a greater MSC-EV yield. MSC-EVs processed by both methods demonstrated a similar ability to promote cell migration and proliferation in ovarian stromal cells. Considering the higher yield and lower complexity of the UF method, UF-MSC-EVs were used in the in vivo experiment. We evaluated three therapeutic regimens for cows subjected to OPU, noting that the group treated with three MSC-EV injections (G4) maintained oocyte production and increased in vitro embryo production, compared to G1, which presented compromised embryo production following the OPU-induced lesions. CONCLUSIONS: MSC-EVs have beneficial effects both on the migration and proliferation of ovarian stromal cells and on the fertility of bovines with follicular puncture injury in vivo.

Correction: Prevalence and factors associated with self-reported anxiety in adults during the COVID-19 pandemic in Argentina, Brazil, Peru, Mexico, and Spain: A cross-sectional Ibero-American study.

[This corrects the article DOI: 10.1371/journal.pone.0280528.].

Tecnologias utilizadas para assistência de enfermagem às pessoas com hipertensão arterial sistêmica / Technologies used for nursing care of people with systemic arterial hypertension / Tecnologías utilizadas para los cuidados de enfermería a personas con hipertensión arterial sistémica

Objetivo: Analisar as evidências científicas a respeito da utilização de tecnologias em saúde para a assistência de enfermagem às pessoas com hipertensão arterial sistêmica. Métodos: Revisão integrativa, realizada nas bases de dados Literatura Latino-Americana e do Caribe em Ciências da Saúde, National Library of Medicine, Scopus, Cumulative Index to Nursing and Allied Health Literature, Web of Science e Excerpta Medica Database, em julho de 2020, com o corpus de 21 artigos. Resultados: A maioria das tecnologias foi desenvolvida em formato digital e utilizada, principalmente, para a realização de orientações, envolvendo comportamentos saudáveis para o controle dos níveis pressóricos, além de tecnologias direcionadas para a verificação da pressão arterial e para o atendimento do enfermeiro às pessoas com hipertensão arterial sistêmica. Conclusão: As tecnologias utilizadas consideraram o âmbito educacional ou assistencial e contribuíram para a assistência de enfermagem à pessoa com hipertensão arterial sistêmica. (AU)

Objective: To analyze the scientific evidence regarding the use of health technologies for nursing care for people with systemic arterial hypertension. Methods: Integrative review, carried out in the databases of Latin American and Caribbean Literature in Health Sciences, National Library of Medicine, Scopus, Cumulative Index to Nursing and Allied Health Literature, Web of Science e Excerpta Medica Database, in July 2020, with a corpus of 21 articles. Results: Most of the technologies were developed in digital format and used mainly to carry out guidelines, involving healthy behaviors for the control of blood pressure levels, in addition to technologies aimed at checking blood pressure and, for the attendance of nurses to people with systemic arterial hypertension. Conclusion: The technologies used considered the educational or care scope and contributed to nursing care to people with systemic arterial hypertension. (AU)

Objetivo: Analizar la evidencia científica sobre el uso de tecnologías de la salud para el cuidado de enfermería con personas con hipertensión arterial sistémica. Métodos: Revisión integrativa, realizada en las bases de datos de Literatura Latinoamericana y del Caribe en Ciencias de la Salud, National Library of Medicine, Scopus, CINAHL, Web of Science y Embase, en julio de 2020, con um corpus de 21 artículos. Resultados: La mayoría de las tecnologías fue desarrollado en formato digital y se utilizaron principalmente para la realización de orientación, involucrando comportamientos saludables para el control de los niveles de presión arterial, además de tecnologías dirigidas al control de la presión arterial y, para la atención de enfermeros a personas con hipertensión arterial sistémica. Conclusión: Las tecnologías utilizadas consideraron el alcance educativo o asistenciales y contribuyeron a la atención de enfermería a personas con hipertensión arterial sistémica. (AU)

Genetic variants in miR-146a and miR-196a2 in endometriosis: a Brazilian study.

OBJECTIVE: The aim of this study was to determine the allelic and genotypic frequencies of the polymorphisms, rs2910164 miR-146a and rs11614913 miR-196a2, by investigating their association with endometriosis. METHODS: This is a case-control study performed with approximately 120 women. The polymorphisms were determined by real-time polymerase chain reaction. For the statistical analysis, the chi-square and logistic regression tests were used. RESULTS: There were no significant differences in the genotype and allele frequencies of rs2910164 and rs11614913 between cases and controls. The frequencies in both polymorphisms are in accordance with Hardy-Weinberg equilibrium regarding miR-146a (patients: χ2=1.64, p=0.20; controls: χ2=0.25, p=0.62) and miR-196a2 (patients: χ2=0.58, p=0.44; controls: χ2=2.78, p=0.10). No relationship was observed between rs2910164 and rs11614913 and endometriosis in the inheritance models analyzed. CONCLUSION: In this study, our results show that the studied polymorphisms are not implicated in the development of endometriosis.

Body Condition Scores in Cats and Associations with Systolic Blood Pressure, Glucose Homeostasis, and Systemic Inflammation.

BACKGROUND: Feline obesity is the most common nutritional disease in cats. This study aimed to investigate the differences between systolic blood pressure (SBP) and circulating concentrations of glucose, fructosamine, and serum amyloid-A (SAA) in ideal-weight, overweight, and obese cats. METHODS: The animals were divided into three groups: ideal-weight (BCS 5, N = 20), overweight (BCS 6, N = 20), and obese cats (BCS ≥ 7, N = 20). SBP, circulating concentrations of glucose, fructosamine, and SAA were evaluated. RESULTS: The SBP values of the ideal-weight, overweight, and obese cats were 140.0 mmHg, 160.0 mmHg, and 160.0 mmHg, respectively. The blood glucose and fructosamine levels for the ideal, overweight, and obese cats were 104.0 mg/dL and 245.0 µmol/L, 123.0 mg/dL and 289.0 µmol/L, and 133.0 mg/dL and 275.0 µmol/L, respectively, for each group. The SAA values were <5 ug/mL in all the groups. The SBP values of the cats with ideal BCS were significantly lower compared to overweight (p = 0.019) and obese (p = 0.001) cats. The blood glucose values of obese cats were higher than those of ideal-weight cats (p = 0.029). There was no statistical difference between the groups for fructosamine and SAA. CONCLUSIONS: Obese cats had significantly higher SBP and blood glucose concentrations than ideal-weight cats, showing the effect of BSC on these parameters.

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.

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 in COVID-19 patients. We also conducted 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. 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 and biomarkers correlate with each other. Early monitoring of these biomarkers may lead to appropriate clinical interventions in patients infected by SARS-CoV2.

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.

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.

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.