Female Mice Exposed to Pyriproxyfen Since Prepuberty Showed Reproductive Impairment During Sexual Maturity and Increased Fetal Death in Their Offspring.

Pyriproxyfen (PPF) is an insecticide used in agriculture, which is approved for use in drinking water tanks for human consumption. However, some studies indicate that it may act as an endocrine disruptor and affect nontarget organisms. This study aimed to evaluate the effects of PPF on reproduction and general health status in female mice exposed from pre-puberty to adulthood. In the first experiment, females were treated by gavage from postnatal day (PND) 23 to (PND) 75 and were distributed into three experimental groups: control (vehicle), PPF 0.1 mg/kg, and PPF 1 mg/kg. Female mice were assessed for the age of puberty onset, body mass, water and food consumption, and the estrous cycle. On PDN 75, a subgroup was euthanized, when vital and reproductive organs were collected and weighed. The thyroid, ovary, and uterus were evaluated for histomorphometry. The other subgroup was assessed in relation to reproductive performance and fetal parameters. In a second experiment, the uterotrophic assay was performed with juvenile females (PND 18) using doses of 0.01, 0.1, or 1 mg/kg of PPF. PPF treatment reduced thyroid mass and increased liver mass. Furthermore, there was an increase in ovarian interstitial tissue and, in the uterus, a decrease in the thickness of the endometrial stroma with reduced content of collagen fibers. There was also a reduction of 30% in pregnancy rate in the treated groups and an increase in the frequency of fetal death. This study suggests that, based on this experimental model, the insecticide may pose a reproductive risk for females chronically exposed to the substance from the pre-pubertal period until adulthood. These results raise concerns about prolonged exposure of women to the same compound.

Leveraging Social Networks to Integrate Depression Treatment into Primary Health and Tuberculosis Care in Brazil.

Background: Tuberculosis (TB) and depression are highly comorbid and linked to higher rates of death and disability. Several evidence-based treatments for depression have been successfully implemented in low- and middle-income countries, but more knowledge is needed on how to bring these innovations to scale within complex 'real world' public health systems. Objective: To explore whether the principles of social network analysis could be used to enhance receptivity to integrating depression treatment into primary care for individuals with and without TB in Brazil. Methods: We used existing scales to identify settings and providers with high receptivity and connectivity within the primary care network. We trained and supervised existing staff in three primary care sites to deliver a brief evidence-based intervention over one year, coupled with active dissemination activities. Afterwards, we reassessed receptivity among individuals involved, and not involved, in the pilot. Results: Highly significant changes were observed in mental health literacy, attitudes towards evidence-based practices, work self-efficacy, and implementation leadership supporting our hypothesis. Limited social connections between primary care clinics precluded the examination of the hypothesis that targeting settings with high connectivity could capitalize on the information flow between and transcend the decentralized structure of the network, but leveraging the centralized nature of the TB program to integrate mental health services emerged as a promising alternative. Conclusions: The findings of this study strongly suggest that social networks may be leveraged to change individual providers' attitudes, thereby contributing to the enhanced dissemination of evidence-based interventions.

Impact of Serum Amyloid A Protein in the Human Breast: An In Vitro Study.

The mammary gland is an exocrine gland whose main function is to produce milk. Breast morphogenesis begins in the embryonic period; however, its greatest development takes place during the lactation period. Studies have found the expression of serum amyloid A protein (SAA) in both breast cells and breast milk, yet the function of this protein in these contexts remains unknown. Insufficient milk production is one of the most frequent reasons for early weaning, a problem that can be related to the mother, the newborn, or both. This study aims to investigate the relationship between lactogenesis II (the onset of milk secretion) and the role of SAA in the human breast. To this end, mammary epithelial cell cultures were evaluated for the expression of SAA and the influence of various cytokines. Additionally, we sought to assess the activation pathway through which SAA acts in the breast, its glucose uptake capacity, and the morphological changes induced by SAA treatment. SAA expression was observed in mammary epithelial cells; however, it was not possible to establish its activation pathway, as treatments with inhibitors of the ERK1/2, p38MAPK, and PI3K pathways did not alter its expression. This study demonstrated that SAA can stimulate IL-6 expression, inhibit glucose uptake, and cause morphological changes in the cells, indicative of cellular stress. These mechanisms could potentially contribute to early breastfeeding cessation due to reduced milk production and breast involution.

Neutrophil Oxidative Burst Profile Is Related to a Satisfactory Response to Itraconazole and Clinical Cure in Feline Sporotrichosis.

Despite the central role of cats in the transmission and amplification of Sporothrix, studies regarding immune response in feline sporotrichosis are scarce. In cats with sporotrichosis, neutrophil-rich lesions are usually associated to good general condition and lower fungal burden. However, the role of neutrophils in anti-Sporothrix immunity has been little explored in cats. Thus, the aim of this study was to evaluate the neutrophil oxidative burst in the blood of cats with sporotrichosis. Cats with sporotrichosis included in the study were treated with itraconazole (ITZ) alone or combined with potassium iodide (KI). The neutrophil oxidative burst was evaluated through a flow-cytometry-based assay using dihydrorhodamine 123 (background) and stimulation with Zymosan and heat-killed Sporothrix yeasts. The cure rate was 50.0% in cats under treatment with ITZ monotherapy and 90.9% in cats treated with ITZ + KI (p = 0.014), endorsing the combination therapy as an excellent alternative for the treatment of feline sporotrichosis. Higher percentages of Sporothrix-stimulated neutrophils were associated with good general condition (p = 0.003). Higher percentages of Sporothrix- (p = 0.05) and Zymosan-activated (p = 0.014) neutrophils before and early in the treatment were related to clinical cure in ITZ-treated cats. The correlation between oxidative burst and successful use of KI could not be properly assessed given the low number of failures (n = 2) in this treatment group. Nasal mucosa involvement, typically linked to treatment failure, was related to lower percentages of activated neutrophils in the background at the treatment outcome (p = 0.02). Our results suggest a beneficial role of neutrophils in feline sporotrichosis and a positive correlation between neutrophil activation and the cure process in ITZ-treated cats.

Antidiabetic Effect of Passiflora ligularis Leaves in High Fat-Diet/Streptozotocin-Induced Diabetic Mice.

Type 2 diabetes mellitus (T2DM) is a major global public health concern, prompting the ongoing search for new treatment options. Medicinal plants have emerged as one such alternative. Our objective was to evaluate the antidiabetic effect of an extract from the leaves of Passiflora ligularis (P. ligularis). For this purpose, T2DM was first induced in mice using a high-fat diet and low doses of streptozotocin. Subsequently, an aqueous extract or an ethanolic extract of P. ligularis leaves was administered for 21 days. The following relevant results were found: fasting blood glucose levels were reduced by up to 41%, and by 29% after an oral glucose overload. The homeostasis model assessment of insulin resistance (HOMA-IR) was reduced by 59%. Histopathologically, better preservation of pancreatic tissue was observed. Regarding oxidative stress parameters, there was an increase of up to 48% in superoxide dismutase (SOD), an increase in catalase (CAT) activity by 35% to 80%, and a decrease in lipid peroxidation (MDA) by 35% to 80% in the liver, kidney, or pancreas. Lastly, regarding the lipid profile, triglycerides (TG) were reduced by up to 30%, total cholesterol (TC) by 35%, and low-density lipoproteins (LDL) by up to 32%, while treatments increased high-density lipoproteins (HDL) by up to 35%. With all the above, we can conclude that P. ligularis leaves showed antihyperglycemic, hypolipidemic, and antioxidant effects, making this species promising for the treatment of T2DM.

Multifaceted Hydrogel Scaffolds: Bridging the Gap between Biomedical Needs and Environmental Sustainability.

Hydrogels are dynamically evolving 3D networks composed of hydrophilic polymer scaffolds with significant applications in the healthcare and environmental sectors. Notably, protein-based hydrogels mimic the extracellular matrix, promoting cell adhesion. Further enhancing cell proliferation within these scaffolds are matrix-metalloproteinase-triggered amino acid motifs. Integration of cell-friendly modules like peptides and proteins expands hydrogel functionality. These exceptional properties position hydrogels for diverse applications, including biomedicine, biosensors, environmental remediation, and the food industry. Despite significant progress, there is ongoing research to optimize hydrogels for biomedical and environmental applications further. Engineering novel hydrogels with favorable characteristics is crucial for regulating tissue architecture and facilitating ecological remediation. This review explores the synthesis, physicochemical properties, and biological implications of various hydrogel types and their extensive applications in biomedicine and environmental sectors. It elaborates on their potential applications, bridging the gap between advancements in the healthcare sector and solutions for environmental issues.

Corrigendum: Evaluation of PIK3CA mutations in advanced ER+/HER2-breast cancer in Portugal - U-PIK Project.

[This corrects the article DOI: 10.3389/fmolb.2023.1082915.].

Atenção à saúde da mulher na atenção primária: percepções sobre as práticas de enfermagem / Women's health care in primary care: perceptions about nursing practices / El cuidado de la salud de la mujer en la atención primaria: percepciones sobre las prácticas de enfermería

Objetivo: Identificar práticas de enfermagem direcionadas ao atendimento à saúde da mulher no âmbito da Atenção Primária à Saúde (APS), caracterizando-as pelo modo como ocorrem e lugar que ocupam no processo de trabalho dos Enfermeiros. Métodos: Trata-se de um estudo descritivo, exploratório e de natureza qualitativa. O material consta de 27 entrevistas com enfermeiros realizadas entre os meses de novembro de 2020 a março de 2021. Resultados: As ações de enfermagem direcionadas à saúde da mulher ocupam espaço representativo na agenda dos enfermeiros. As principais ações identificadas são voltadas à saúde materno-infantil. O planejamento familiar também foi identificado como medida educativa recorrente. Assistência às violências e ao climatério não foram mencionadas. Destacouse a autonomia dos enfermeiros na área de atuação em foco neste estudo como positiva no processo de trabalho. Conclusão: A prática do enfermeiro na APS privilegia a saúde no ciclo reprodutivo da mulher, principalmente no período pré-natal. Contudo, observam-se encaminhamentos na busca por uma prática integral, por meio da inclusão de ações mais humanizadas nos serviços. Ainda há a necessidade de se ampliar os focos de assistência à saúde da mulher na APS, e para isso é preciso fortalecer as discussões e estudos acerca dessas temáticas negligenciadas. (AU)

Objective: To identify nursing practices aimed at women's health care within the scope of Primary Health Care (PHC), characterizing them by the way they occur and the place they occupy in the nurses' work process. Methods: This is a descriptive, exploratory and qualitative study. The material consists of 27 interviews with nurses carried out between November 2020 and March 2021. Results: Nursing actions aimed at women's health occupy a representative space in the nurses' routine. The main actions identified are aimed at maternal and child health. Family planning was also identified as a recurrent educational action. Assistance to violence and climacteric were not mentioned. The nurses' autonomy in the area of expertise in focus in this study was highlighted as positive in the work process. Conclusion: The practice of nurses in PHC privileges health in the reproductive cycle of women, especially in the prenatal period. However, referrals are observed in the search for an integral practice, through the inclusion of more humanized actions in the services. There is still a need to expand the focus of women's health care in PHC, and for that it is necessary to strengthen the discussions and studies on these neglected themes. (AU)

Objetivo: Identificar las prácticas de enfermería dirigidas al cuidado de la salud de la mujer en el ámbito de la Atención Primaria de Salud (APS), caracterizándolos por la forma en que ocurren y el lugar que ocupan en el proceso de trabajo del enfermero. Métodos: Se trata de un estudio descriptivo, exploratorio y cualitativo. El material consta de 27 entrevistas a enfermeras realizadas entre noviembre de 2020 y marzo de 2021. Resultados: Las acciones de enfermería dirigidas a la salud de la mujer ocupan un espacio representativo en la agenda de los enfermeros. Las principales acciones identificadas están dirigidas a la salud maternoinfantil. La planificación familiar también fue identificada como una acción educativa recurrente. No se mencionaron la asistencia a la violencia y el climaterio. La autonomía de los enfermeros en el área de especialización en foco de este estudio fue destacada como positiva en el proceso de trabajo. Conclusión: La práctica del enfermero en la APS privilegia la salud en el ciclo reproductivo de la mujer, especialmente en el período prenatal. Sin embargo, se observan derivaciones en la búsqueda de una práctica integral, a través de la inclusión de acciones más humanizadas en los servicios. Aún existe la necesidad de ampliar el enfoque de la atención a la salud de la mujer en la APS, y para eso es necesario fortalecer las discusiones y estudios sobre estos temas desatendidos. (AU)

Oral and oropharyngeal mucosal lesions: clinical-epidemiological study of patients attended at a reference center for infectious diseases.

OBJECTIVE: To determine the prevalence, epidemiological profile, and clinical characteristics of Oral or Oropharyngeal Mucosal Lesions (OOPML) in patients attended at the Otorhinolaryngology Service of the Evandro Chagas National Institute of Infectious Diseases (INI-FIOCRUZ) from 2005 to 2017. METHODS: Statistical analysis of descriptive data from medical records (gender, age, education level, skin color, origin, smoking, alcoholism, HIV co-infection, time of disease evolution, first symptom, and OOPML location) was performed. RESULTS: Of 7551 patients attended at the service, 620 (8.2%) were included in the study. OOPML were classified into developmental anomalies (n = 3), infectious diseases (non-granulomatous n = 220; granulomatous n = 155), autoimmune diseases (n = 24), neoplasms (benign n = 13; malignant, n = 103), and unclassified epithelial/soft tissue diseases (n = 102). OOPML of infectious diseases (60.5%) and neoplasms (18.7%) were the most frequent. The predominant demographics of patients with OOPML were: males (63.5%), white (53.5%), and those in the fifth to sixth decades of life (43.3%). Local pain (18.1%) and odynophagia (15%) were the most reported first symptoms, and the most frequent OOPML sites were the palatine tonsil (28.5%), hard palate (22.7%), and tongue (20.3%). The median evolution time was three months. CONCLUSIONS: Infectious OOPML were the most frequent, as expected in a reference center for infectious diseases, and thus, they are likely to be less frequent in general care and/or dental services. Underreporting of OOPML is possible, as oral/oropharyngeal examination is often not included in the routine medical examination. Oral cavity/oropharynx examination should be performed by specialists, such as dentists and otorhinolaryngologists, who have the expertise in identifying OOPML, even in incipient/asymptomatic cases. Given the numerous diseases in which OOPML can present, diagnosis could be facilitated by multidisciplinary teams, potentially enabling the early treatment of diseases, and thus, reduce morbidity and improve prognosis. The use of standardized medical records for oral/oropharyngeal systematic examination could provide relevant tools for differential diagnoses and information for new clinical-epidemiological studies. LEVEL OF EVIDENCE: Level 3.

Measurement properties of the incremental step test for people with chronic obstructive pulmonary disease: a cross-sectional study.

OBJECTIVES: The new incremental step test (IST) is a field test that was developed for people with chronic obstructive pulmonary disease (COPD), based on the characteristics of the incremental shuttle walk test (ISWT); however, its measurement properties still need to be determined. We aimed, first, to assess the construct validity (through the comparison with the ISWT), within-day reliability and measurement error of the IST in people with COPD; and, second, to identify whether the participants have a learning effect in the IST. DESIGN: Cross-sectional study, conducted according to COnsensus-based Standards for the selection of health status Measurement INstruments guidelines. SETTING: A family health unit in Portugal, April 2022 to June 2023. PARTICIPANTS AND ANALYSIS: 63 participants (67.5±10.5 years) attended two sessions to perform two IST and two ISWT, separately. Spearman's correlations were used to compare the best performances between the IST and the ISWT. Intraclass correlation coefficient (ICC2,1) was used for reliability, and the SE of measurement (SEM), minimal detectable change at 95% CI (MDC95) and Bland and Altman 95% limits of agreement (LoA) were used for measurement error. The learning effect was explored with the Wilcoxon signed-rank test. RESULTS: The IST was significant and strongly correlated with the ISWT (0.72<ρ<0.74, p<0.001), presented an ICC2,1 of 0.95 (95% CI 0.92 to 0.97), SEM=11.7 (18.9%), MDC95=32.4 (52.2%) and the LoA were -33.61 to 31.48 for the number of steps. No difference was observed between the number of steps of the two attempts of the IST (p>0.05). CONCLUSIONS: The IST can be suggested as a valid and reliable test to assess exercise capacity in people with COPD, with no learning effect when two IST are performed on the same day. The measurement error of the IST is considered indeterminate. TRIAL REGISTRATION NUMBER: NCT04715659.

Severe primary hypothyroidism and ovarian hyperstimulation syndrome in a spontaneous pregnancy: a case report.

Background: Ovarian hyperstimulation syndrome (OHSS) is a rare ovulation induction therapy side effect. Nevertheless, it can occur in spontaneous ovulation cycles linked to multiple gestation, molar pregnancy, polycystic ovarian syndrome, and hypothyroidism. The pathogenesis of OHSS remains poorly understood. However, in recent studies, it has been observed that increased concentrations of thyroid-stimulating hormone (TSH) can potentially have stimulatory effects on the ovaries due to the homologous structure shared between TSH and gonadotropins. It is recommended to delay pregnancies until euthyroidism is achieved with replacement therapy to reduce potentially fatal problems. Case Description: We describe the case of a 22-year-old female patient who sought medical attention due to a 4-week history of abdominal discomfort and amenorrhea. Upon evaluation, it was determined that she was in the 9th week of pregnancy and experiencing OHSS due to severe primary hypothyroidism. The diagnosis was confirmed through laboratory and imaging data, enabling timely care and preventing complications arising from unwarranted surgical intervention. Administration of levothyroxine led to total regression of the ovarian cysts. Even so, the patient decided to terminate her pregnancy. Conclusions: This case illustrates the occurrence of OHSS in a woman with untreated hypothyroidism. Notably, this syndrome is relatively uncommon, and the patient's ability to conceive while having unviable thyroid hormone levels further adds to this case's exceptional nature.

Oral and oropharyngeal mucosal lesions: clinical-epidemiological study of patients attended at a reference center for infectious diseases

Abstract Objective To determine the prevalence, epidemiological profile, and clinical characteristics of Oral or Oropharyngeal Mucosal Lesions (OOPML) in patients attended at the Otorhinolaryngology Service of the Evandro Chagas National Institute of Infectious Diseases (INI-FIOCRUZ) from 2005 to 2017. Methods Statistical analysis of descriptive data from medical records (gender, age, education level, skin color, origin, smoking, alcoholism, HIV co-infection, time of disease evolution, first symptom, and OOPML location) was performed. Results Of 7551 patients attended at the service, 620 (8.2%) were included in the study. OOPML were classified into developmental anomalies (n = 3), infectious diseases (non-granulomatous n = 220; granulomatous n = 155), autoimmune diseases (n = 24), neoplasms (benign n = 13; malignant, n = 103), and unclassified epithelial/soft tissue diseases (n = 102). OOPML of infectious diseases (60.5%) and neoplasms (18.7%) were the most frequent. The predominant demographics of patients with OOPML were: males (63.5%), white (53.5%), and those in the fifth to sixth decades of life (43.3%). Local pain (18.1%) and odynophagia (15%) were the most reported first symptoms, and the most frequent OOPML sites were the palatine tonsil (28.5%), hard palate (22.7%), and tongue (20.3%). The median evolution time was three months. Conclusions Infectious OOPML were the most frequent, as expected in a reference center for infectious diseases, and thus, they are likely to be less frequent in general care and/or dental services. Underreporting of OOPML is possible, as oral/oropharyngeal examination is often not included in the routine medical examination. Oral cavity/oropharynx examination should be performed by specialists, such as dentists and otorhinolaryngologists, who have the expertise in identifying OOPML, even in incipient/asymptomatic cases. Given the numerous diseases in which OOPML can present, diagnosis could be facilitated by multidisciplinary teams, potentially enabling the early treatment of diseases, and thus, reduce morbidity and improve prognosis. The use of standardized medical records for oral/oropharyngeal systematic examination could provide relevant tools for differential diagnoses and information for new clinical-epidemiological studies. Level of evidence: Level 3.

Cancer related fatigue measurement scales: A systematic review.

Cancer-related fatigue (CRF) is a common symptom experienced by all the cancer patients at all stages of the disease and in survivors. Fatigue from cancer is one of the understated, underestimated, and least managed. Several scales have been developed to measure CRF, but they vary in the quality of psychometric properties, ease of administration, and dimensions of CRF. This systematic review explores the validity and reliability of the different CRF measurement scales. A systematic review methodology was followed to identify the scales that have been validated to measure CRF. Three separate databases PubMed, CINAHL, and Google Scholar searches were performed using different medical subject heading terms. Articles were analyzed for validity and reliability. A total of 1294 articles from three different searches identified 15 scales (unidimensional and multidimensional). Each scale varied by its psychometric properties, items, scale type, dimension, site of cancer, and population in which it is validated. Most of the scales had been validated in mixed cancer populations. Some scales are insensitive to differences in fatigue to cancer stages. Few scales are burdensome for the advanced cancer patients. In this study, 15 CRF scales were identified. Validity and reliability are varied by each questionnaire. The ideal and accepted item numbers, scale, and domains are not established. The psychometric properties of each measure require further consideration. More studies are needed to explore fatigue scales with many populations.

Vaccine Development against Infectious Diseases: State of the Art, New Insights, and Future Directions.

In the 18th century, English physician Edward Jenner laid the foundation for modern vaccination by achieving protection against variola [...].

Predictions from a mathematical approach to model ionic signaling for rapid responses of Sertoli cells exhibit similarities to pharmacological approaches.

Sertoli cells are essential for the male reproduction system as they provide morphological support and nutrients for germ cells to guarantee ongoing spermatogenesis. The aim of this work was to predict the electrical properties at the plasma membrane that trigger Sertoli cell rapid responses by involving ionic channels. The rapid responses of Sertoli cells in culture were monitored using patch clamp electrical measurement and compared to data obtained using pharmacological tools (from intact seminiferous tubules). A mathematical model was used to define the roles of potassium channels and the ATP-dependent Na+/K+pump in these responses. Mathematical data verification was also performed to determine the resting and hormonal stimulated membrane potentials of Sertoli cells in the intact seminiferous tubules and of Sertoli cells in culture (patch clamp measurements). The prediction of these data based on mathematical modeling demonstrated, for the first time, the involvement of potassium channels and the activation of Na+/K+pump in the hyperpolarization of Sertoli cells and their consequent rapid responses. Moreover, the mathematical analysis showing the involvement of ionic balance in the rapid responses of these cells to hormones, such as follicle-stimulating hormone, is consistent with previous reports obtained using pharmacological techniques in Sertoli cells. Thus, the validation of such data is reliable and represents a first step in the proposition for a mathematical model to predict rapid responses of Sertoli cells to hormonal stimuli.

Oral Manifestations: A Warning-Sign in Children with Hematological Disease Acute Lymphocytic Leukemia.

Acute lymphocytic leukemia (ALL) is the most frequent form of all childhood leukemias, mostly affecting children between 2 and 4 years old. Oral symptoms, such as mouth ulcers, mucositis, xerostomia, Herpes or Candidiasis, gingival enlargement and bleeding, petechiae, erythema, mucosal pallor and atrophic glossitis, are very common symptoms of ALL and can be early signs of the disease. Secondary and tertiary complications, a direct effect of chemo and radiotherapy, are associated with more severe bleeding, higher susceptibility to infections, ulcerations, inflammation of the mucous membranes, osteoradionecrosis, xerostomia, taste alterations, trismus, carious lesions and dental abnormalities. Immunotherapy, though less toxic, causes oral dysesthesia and pain. Overall, the effects in the oral cavity are transient but there are long-term consequences like caries, periodontal disease and tooth loss that impair endodontic and orthodontic treatments. Also, dental abnormalities resulting from disturbed odontogenesis are known to affect a child's quality of life. The medical dentist should identify these complications and perform appropriate oral care in tandem with other health professionals. Thus, poor oral hygiene can lead to systemic ALL complications. The aim of this review is to describe the oral complications in children with ALL who are undergoing chemo, radio or immunotherapy.

Electrophilic Agonists Modulate the Transient Receptor Potential Ankyrin-1 Channels Mediated by Insulin and Glucagon-like Peptide-1 Secretion for Glucose Homeostasis.

This pre-clinical study investigated the transient receptor potential ankyrin-1 (TRPA1) channels on modulating targets for glucose homeostasis using agonists: the electrophilic agonists, cinnamaldehyde (CIN) and allyl isothiocyanate (AITC), and the non-electrophilic agonist, carvacrol (CRV). A glucose tolerance test was performed on rats. CIN and AITC (5, 10 and 20 mg/kg) or CRV (25, 100, 300, and 600 mg/kg) were administered intraperitoneally (i.p.), and glycemia was measured. In the intestine, Glucagon-like peptide-1 (GLP-1) and disaccharidase activity were evaluated (in vivo and in vitro, respectively). Furthermore, in vivo and in vitro insulin secretion was determined. Islets were used to measure insulin secretion and calcium influx. CIN and AITC improved glucose tolerance and increased insulin secretion in vivo and in vitro. CRV was unable to reduce glycemia. Electrophilic agonists, CIN and AITC, inhibited disaccharidases and acted as secretagogues in the intestine by inducing GLP-1 release in vivo and in vitro and contributed to insulin secretion and glycemia. The effect of CIN on calcium influx in pancreatic islets (insulin secretion) involves voltage-dependent calcium channels and calcium from stores. TRPA1 triggers calcium influx and potentiates intracellular calcium release to induce insulin secretion, suggesting that electrophilic agonists mediate this signaling transduction for the control of glycemia.

Dibutyl phthalate disrupts energy metabolism and morphology in the gills and induces hepatotoxicity in zebrafish.

This study investigated the acute effects of dibutyl phthalate (DBP) exposure on energy metabolism and gill histology in zebrafish (Danio rerio). The in vitro incubation of gill tissue with 10 µM DBP for 60 min altered tissue energy supply, as shown by decreased lactate content and lactate dehydrogenase (LDH) activity. Higher concentrations of DBP (100 µM and 1 mM) increased lactate content and LDH activity; however, they blocked glucose uptake, depleted the glycogen content in cellular stores, and induced injury to the gills, as measured by LDH release to the extracellular medium. In addition, in vivo exposure of fish to 1 pM DBP for 12 h induced liver damage by increasing alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) activities. Gill histology indicated hyperemia, lamellar fusion, lamellar telangiectasis, and necrosis. Data indicate that acute exposure of zebrafish gills to the higher DBP concentrations studied induces anaerobic cellular activity and high lactate production, causing gill damage, diminishing cell viability, and incurring liver dysfunction.

Barriers and Facilitators to Integrating Depression Treatment Within a TB Program and Primary Care in Brazil.

Tuberculosis (TB) and depression is common and is associated with poor TB outcomes. The World Health Organization End TB Strategy explicitly calls for the integration of TB and mental health services. Interpersonal Counseling (IPC) is a brief evidence-based treatment for depression that can be delivered by non-mental health specialists with expert supervision. The goal of this study was to explore potential barriers and facilitators to training non-specialist providers to deliver IPC within the TB Control Program and primary care in Itaboraí, Rio de Janeiro state. Data collection consisted of six focus groups (n = 42) with health professionals (n = 29), program coordinators (n = 7), and persons with TB (n = 6). We used open coding to analyze the data, followed by deductive coding using the Chaudoir multi-level framework for implementation outcomes. The main structural barriers identified were poverty, limited access to treatment, political instability, violence, and social stigma. Organizational barriers included an overburdened and under-resourced health system with high staff turnover. Despite high levels of stress and burnout among health professionals, several provider-level facilitators emerged including a high receptivity to, and demand for, mental health training; strong community relationships through the community health workers; and overall acceptance of IPC delivered by any type of health provider. Patients were also receptive to IPC being delivered by any type of professional. No intervention-specific barriers or facilitators were identified. Despite many challenges, integrating depression treatment into primary care in Itaboraí using IPC was perceived as acceptable, feasible, and desirable.

Is There Any Difference in the In Situ Immune Response in Active Localized Cutaneous Leishmaniasis That Respond Well or Poorly to Meglumine Antimoniate Treatment or Spontaneously Heal?

Localized cutaneous leishmaniasis caused by Leishmania braziliensis can either respond well or poorly to the treatment or heal spontaneously; It seems to be dependent on the parasite and/or host factors, but the mechanisms are not fully understood. We evaluated the in situ immune response in eighty-two active lesions from fifty-eight patients prior to treatment classified as early spontaneous regression (SRL-n = 14); treatment responders (GRL-n = 20); and non-responders (before first treatment/relapse, PRL1/PRL2-n = 24 each). Immunohistochemistry was used to identify cell/functional markers which were correlated with the clinical characteristics. PRL showed significant differences in lesion number/size, clinical evolution, and positive parasitological examinations when compared with the other groups. SRL presented a more efficient immune response than GRL and PRL, with higher IFN-γ/NOS2 and a lower percentage of macrophages, neutrophils, NK, B cells, and Ki-67+ cells. Compared to SRL, PRL had fewer CD4+ Tcells and more CD163+ macrophages. PRL1 had more CD68+ macrophages and Ki-67+ cells but less IFN-γ than GRL. PRL present a less efficient immune profile, which could explain the poor treatment response, while SRL had a more balanced immune response profile for lesion healing. Altogether, these evaluations suggest a differentiated profile of the organization of the inflammatory process for lesions of different tegumentary leishmaniasis evolution.