High sodium, rather than high blood pressure, induces immune cell activation and renal infiltration in ovariectomized adult Wistar rats.

We used an animal model of salt-sensitive hypertension (SSH) in which ovariectomized (oVx) rats developed hypertension with high salt (HS) intake. Hypertension is accompanied by changes in the percentage of CD4+ T lymphocytes, immune CD45+ cell infiltration into renal tissue, and changes in Na+, K+- ATPase (NKA) expression in both renal tissue and peripheral blood mononuclear cells (PBMCs). To determine whether the observed changes resulted from HS intake, high blood pressure, or both, hydralazine (HDZ) was used to lower blood pressure. The oVx HS rats received two HDZ schedules either to prevent or to treat hypertension. NKA was overexpressed in the kidneys of all oVx groups and in PBMCs of oVx HS rats. This pattern was not altered with HDZ treatment. Changes in CD4+ T lymphocytes and renal infiltration of CD45+ cells were not reversed either. High salt, but not high blood pressure, induces immune cell activation and renal infiltration. Overexpressed NKA is the primary event, and HS is the perturbation to the system in this model of SSH, which resembles the postmenopausal state.

Risk factors for falls in older adults with diabetes mellitus: systematic review and meta-analysis.

AIM: To identify risk factors for falls in older adults with Type 2 Diabetes Mellitus (T2DM). METHODS: The eligible studies identified factors associated with the risk of falls in older adults with T2DM. We searched PubMed, Cinahl, Web of Science, Scopus, and the Cochrane Library databases. The review has been updated and the last review date was November 30, 2023 (CRD42020193461). RESULTS: Twelve studies met the inclusion criteria, and eight studies were included in the meta-analysis. These studies included a total of 40,778 older adults with T2DM, aged 60 to 101 years. The risk of developing the outcome falls in older adults with T2DM is 63% higher compared to the risk in older adults without T2DM (HR 1.63; 95% CI [1.30 - 2.05]). The overall chance of falling in older adults with T2DM is 59% higher than that of non-diabetic older adults (OR 1.59; 95% CI [1.36 -1.87]), and in older adults with T2DM who take insulin the chance of falling is 162% higher (OR 2.62; 95% CI [1.87 - 3.65]). No results on diabetic polyneuropathy were found in the studies. CONCLUSION: Older adults with T2DM present a higher risk of falls compared to non-diabetics. Among the included older adults with T2DM, the most important factor associated with a higher risk of falls was insulin use. TRIAL REGISTRATION: Registered in the International Prospective Register of Systematic Reviews (CRD42020193461).

Extract from Aloysia polystachya Induces the Cell Death of Colorectal Cancer Stem Cells.

Cancer stem cells (CSCs) are an important player in the resistance of cancers to therapy. In this work, we determined the flavonoids composition and biological action of Aloysia polystachya (AP) extracts in colorectal cancer. The chemical characterization of extracts was performed by HPLC. Assays of cytotoxicity, apoptosis, migration and invasion, metalloproteases activity, clonogenic growth, tumorspheres formation, Hoechts efflux, pluripotency marker expression and sensitization to chemotherapeutic drugs were performed in vitro in human HCT116 and murine CT26 colorectal cancer cells. The AP toxicity and effect in tumor growth administered alone or in combination with 5- Fluorouracile was analyzed in vivo, including histopathological studies. We found that AP extracts induced in vitro the apoptosis of colorectal cancer cell lines decreasing the CSC proportion. Moreover, they were capable to kill 5-Fluorouracile resistant side population cells. At not toxic doses in vivo, AP extracts inhibited tumor growth. Regarding the ability to reduce the CSC population, AP extracts deserves to be investigated as a useful therapy for colorectal cancer treatment.

The Novel N,N-bis-2-Hydroxyethyl-2-Aminoethanesulfonic Acid-Gluconate-Polyethylene Glycol-Hypothermic Machine Perfusion Solution Improves Static Cold Storage and Reduces Ischemia/Reperfusion Injury in Rat Liver Transplant.

Organ transplantation is the treatment of choice against terminal and irreversible organ failure. Optimal preservation of the graft is crucial to counteract cold ischemia effects. As we developed an N,N-bis-2-hydroxyethyl-2-aminoethanesulfonic acid-gluconate-polyethylene glycol (BGP)-based solution (hypothermic machine perfusion [HMP]), we aimed to analyze the use of this solution on static cold storage (SCS) of rat livers for transplantation as compared with the histidine tryptophan ketoglutarate (HTK) preservation solution. Livers procured from adult male Sprague Dawley rats were preserved with BGP-HMP or HTK solutions. Liver total water content and metabolites were measured during the SCS at 0°C for 24 hours. The function and viability of the preserved rat livers were first assessed ex vivo after rewarming (90 minutes at 37°C) and in vivo using the experimental model of reduced-size heterotopic liver transplantation. After SCS, the water and glycogen content in both groups remained unchanged as well as the tissue glutathione concentration. In the ex vivo studies, livers preserved with the BGP-HMP solution were hemodynamically more efficient and the O2 consumption rate was higher than in livers from the HTK group. Bile production and glycogen content after 90 minutes of normothermic reperfusion was diminished in both groups compared with the control group. Cellular integrity of the BGP-HMP group was better, and the histological damage was reversible. In the in vivo model, HTK-preserved livers showed a greater degree of histological injury and higher apoptosis compared with the BGP-HMP group. In conclusion, our results suggest a better role of the BGP-HMP solution compared with HTK in preventing ischemia/reperfusion injury in the rat liver model.

Cryopreservation by slow cooling of rat neuronal cells.

Although primary neuronal cells are routinely used for neuroscience research, with potential clinical applications such as neuronal transplantation and tissue engineering, a gold standard protocol for preservation has not been yet developed. In the present work, a slow cooling methodology without ice seeding was studied and optimized for cryopreservation of rat cerebellar granular cells. Parameters such as cooling rate, plunge temperature and cryoprotective agent concentration were assessed using a custom built device based on Pye's freezer idea. Cryopreservation outcome was evaluated by post thawing cell viability/viable cell yield and in culture viability over a period of 14 days. The best outcome was achieved when 10% of Me2SO as cryoprotective agent, a cooling rate of 3.1 ± 0.2 °C/min and a plunge temperature of -48.2 ± 1.5 °C were applied. The granular cells cryopreserved under these conditions exhibited a cell viability of 82.7 ± 2.7% and a viable cell yield of 28.6 ± 2.2%. Moreover, cell viability in culture remained above 50%, very similar to not cryopreserved cells (control). Our results also suggest that post-thaw viability (based on membrane integrity assays) not necessarily reflects the quality of the cryopreservation procedure and proper functionality tests must be carried out in order to optimize both post thaw viability/cell yield and in culture performance.

DESIGN OF A SIMPLE SLOW COOLING DEVICE FOR CRYOPRESERVATION OF SMALL BIOLOGICAL SAMPLES.

BACKGROUND: Slow cooling is a cryopreservation methodology where samples are cooled to its storage temperature at controlled cooling rates. OBJECTIVE: Design, construction and evaluation of a simple and low cost device for slow cooling of small biological samples. MATERIALS AND METHODS: The device was constructed based on Pye's freezer idea. A Dewar flask filled with liquid nitrogen was used as heat sink and a methanol bath containing the sample was cooled at constant rates using copper bars as heat conductor. RESULTS: Sample temperature may be lowered at controlled cooling rate (ranging from 0.4°C/min to 6.0°C/min) down to ~-60°C, where it could be conserved at lower temperatures. An example involving the cryopreservation of Neuro-2A cell line showed a marked influence of cooling rate over post preservation cell viability with optimal values between 2.6 and 4.6°C/min. CONCLUSION: The cooling device proved to be a valuable alternative to more expensive systems allowing the assessment of different cooling rates to evaluate the optimal condition for cryopreservation of such samples.

[Small bowel intussusception and Vanek's tumor in an elderly woman]. / Intususcepción intestinal por pólipo fibroide inflamatorio en una anciana.

Inflammatory fibroid polyps are non-frequent benign lesions, described by Vanek in 1949, originated in the sub mucosa of the gastrointestinal tract. They have an uncertain origin and they are formed of fibroblastic and mesenchymal proliferations with an important eosinophilic proportion. Depending on where are they localized, could present different type of symptoms. The inflammatory fibroid polyps are one of the rare benign conditions causing intestinal intussusception in adults. We present the case of a 82 years old woman, who presented an intestinal intussusception due to an inflammatory fibroid polyp localized in the small bowel.

[Pituitary cryptococcoma: a strange case of secondary granulomatous hypophysitis]. / Cryptococcoma hipofisiario: un extraño caso de hipofisitis granulomatosa secundaria.

Hypophysitis is a pathology with low incidence and prevalence. Likewise, deep fungal infections in immunocompetent patients also represent a rare phenomenon. Even rarer is the case described below, where these two mentioned elements are combined, namely: pituitary cryptococcoma or granulomatous hypophysitis caused by said pathogen in a host without altered immune response. After research in PubMed, there are limited cases in the medical literature of granulomatous hypophysitis caused by Cryptococcus spp., which simulated a pituitary macroadenoma by clinical and imaging manifestations. We did not find reports in which there is no evidence of involvement of the meningeal tissue. The fungal etiology is scarcely described in the reference guidelines for hypophysitis and we believe that Cryptococcus spp. it should be taken into account in the differential diagnosis of secondary granulomatous hypophysitis since it is a ubiquitous pathogen and the treatment is substantially different from other entities. It becomes more relevant given the current trend towards the use of high-dose systemic glucocorticoids for the treatment of hypophysitis, which could have generated greater damage if the correct diagnosis had not been made.

La hipofisitis es una afección con baja incidencia y prevalencia. Asimismo, las infecciones profundas por hongos en pacientes inmunocompetentes también representan un fenómeno infrecuente. Más raro aún es el caso que se describe a continuación, en donde se conjugan estos dos elementos mencionados, a saber: cryptococcoma hipofisario o hipofisitis granulomatosa causado por dicho patógeno en un huésped sin alteración de la respuesta inmune. Luego de una búsqueda realizada en PubMed, existen limitados casos en la literatura médica de hipofisitis granulomatosa por Cryptococcus spp., que simuló por manifestaciones clínicas e imagenológicas un macroadenoma hipofisario. No encontramos informes en los que no haya evidencia de afectación del tejido meníngeo. La etiología micótica está escasamente descrita en las guías de referencia para hipofisitis y creemos que Cryptococcus spp. debe ser tenido en cuenta en el diagnóstico diferencial de las hipofisitis granulomatosas secundarias dado que es un patógeno ubicuo y el tratamiento es sustancialmente diferente a otras entidades. Cobra mayor relevancia ante la tendencia actual al uso de glucocorticoides sistémicos a altas dosis para el tratamiento de la hipofisitis, que podría haber generado mayor daño de no haberse hecho el diagnóstico correcto.

NCoA3 upregulation in breast cancer­associated adipocytes elicits an inflammatory profile.

Nuclear receptor coactivator 3 (NCoA3) is a transcriptional coactivator of NF­κB and other factors, which is expressed at relatively low levels in normal cells and is amplified or overexpressed in several types of cancer, including breast tumors. NCoA3 levels have been shown to be decreased during adipogenesis; however, its role in tumor­surrounding adipose tissue (AT) remains unknown. Therefore, the present study assessed the modulation of NCoA3 in breast cancer­associated adipocytes and evaluated its association with the expression of inflammatory markers. 3T3­L1 adipocytes were stimulated with conditioned medium from human breast cancer cell lines and the expression levels of NCoA3 were evaluated by reverse transcription­quantitative (q)PCR. NF­κB activation was measured by immunofluorescence, and tumor necrosis factor and monocyte chemoattractant protein 1 levels were analyzed by qPCR and dot blot assays. The results obtained from the in vitro model were supported using mammary AT (MAT) from female mice, MAT adjacent to tumors from patients with breast cancer and bioinformatics analysis. The results revealed that adipocytes expressing high levels of NCoA3 were mainly associated with a pro­inflammatory profile. In 3T3­L1 adipocytes, NCoA3 downregulation or NF­κB inhibition reversed the expression of inflammatory molecules. In addition, MAT from patients with a worse prognosis exhibited high levels of this coactivator. Notably, adipocyte NCoA3 levels could be modulated by inflammatory signals from tumors. The modulation of NCoA3 levels in synergy with NF­κB activity in MAT in a tumor context could be factors required to establish breast cancer­associated inflammation. As adipocytes are involved in the development and progression of breast cancer, this signaling network deserves to be further investigated to improve future tumor treatments.

Analysis of functional status and muscle strength in adults and older adults in an intensive care unit: a prospective cohort study. / Análise do estado funcional e força muscular de adultos e idosos em Unidade de Terapia Intensiva: Coorte prospectiva.

The aim of this study was to analyze and assess the association between functional status (FS) and muscle strength (MS) in young adults, adults and older adults in an intensive care unit (ICU). We conducted a prospective cohort study with 48 patients. FS was assessed using the Functional Status Score for the Intensive Care Unit (FSS-ICU) and MS was measured using the Medical Research Council Sum-Score (MRC-SS) and by testing handgrip strength (HS). The assessments were performed on awakening and ICU discharge. The data were analyzed using the Kruskall-Wallis, chi-squared, Wilcoxon and Spearman's correlation tests. FS and MRC-SS scores were higher on ICU discharge in all groups. Gains were lowest in the older adult group. HS was greater in both hands on ICU discharge in all groups except the adults. FSS-ICU on both awakening and ICU discharge was highest in the adults; HS-R was lowest in the older adults. There was a strong association between FS and MS in the young adults and adults. FS and MS showed progressive improvement during ICU stay. Gains in FS and MS on awakening and ICU discharge were lowest among the older adults. Important associations were found between these variables in all groups except the older adults. This can be explained by the multifactorial nature of illness and incapacity in this group.

Avaliar e correlacionar o estado funcional (EF) e a força muscular (FM) em adultos jovens, adultos e idosos em Unidade de Terapia Intensiva (UTI). Coorte prospectiva com 48 pacientes avaliando EF por meio do Functional Status Score for the Intensive Care Unit (FSS-ICU) e FM pelo Medical Research Council Sum-Score (MRC-SS) e força de preensão palmar (FPP), no despertar e na alta da UTI. Dados analisados pelos testes Kruskall-Wallis, Qui-quadrado, Wilcoxon e Correlação de Sperman. Na comparação do despertar em relação à alta, o EF e o MRC-SS foram maiores na alta em todos os grupos, com menor ganho nos idosos. A FPP aumentou bilateralmente na alta, exceto no grupo de adultos, pois apresentavam valores maiores no despertar. Na comparação dos grupos, o FSS-ICU foi maior nos adultos no despertar e alta, e a FPP-D menor nos idosos. O EF apresentou forte associação com a FM em adultos jovens e adultos, pois ambos apresentam progressiva melhora durante a permanência na UTI. Os idosos apresentam menor ganho do estado funcional, além de apresentarem menor força muscular desde o despertar. Estas variáveis apresentam importante associação apenas nos adultos jovens e adultos, considerando a natureza multifatorial do processo de adoecimento e incapacidade nos idosos.

Sickness absence among public workers in the healthcare sector of the Federal District, Brazil.

BACKGROUND: To describe the profile and indicators of sickness absence for civil servants allocated to the 18 public health units of a Federal District (Brasilia) Health Region, Brazil. METHODS: Cross-sectional study of all sick leaves longer than 3 days granted in 2014. Sickness absence indicators were calculated and analyzed per sex, marital status, age, educational level, professional category, length in the job, working hours and workplace. RESULTS: The analyzed population (n=2,501) was granted 2,205 sick leaves in total, corresponding to 40,755 missed work days. The prevalence of sickness absence was 39%, the leave frequency index 88%, the severity index 16 days, the average sickness absence length 42 days, and the average length of leaves 18 days. More than 85% of the missed work days corresponded to workers with recurrence of sickness absence. Mental and behavioral disorders and musculoskeletal diseases were the main causes of sick leave. CONCLUSION: Planning health actions demands accurate knowledge of the characteristics and morbidity profile of this population of workers. The results of the present study express the magnitude of sickness absence in the public health sector, and point to the need for thorough change in the organization of the work process and innovative interventions in the workplace.

INTRODUÇÃO: Descrever o perfil e os indicadores de absenteísmo-doença entre servidores de 18 unidades de saúde pública de uma Regional de Saúde do Distrito Federal (Brasília), Brasil. MÉTODOS: Estudo transversal de todas as licenças médicas homologadas em 2014 superiores a três dias. Os indicadores de absenteísmo-doença foram calculados de acordo com sexo, estado civil, faixa etária, nível de escolaridade, categoria profissional, tempo de serviço, carga horária e lotação. RESULTADOS: A população de 2.501 servidores apresentou 2.205 licenças médicas que resultaram em 40.755 dias de trabalho perdidos. Os indicadores demonstraram prevalência de absenteísmo-doença de 39%, índice de frequência de licenças de 88%, índice de gravidade de 16 dias, duração média do absenteísmo-doença de 42 dias e duração média das licenças de 18 dias. Mais de 85% dos dias perdidos foram atribuídos aos servidores com recorrência de licenças médicas. Transtornos mentais e comportamentais, além das doenças osteomusculares, representaram maiores causas de afastamento. CONCLUSÃO: O planejamento das ações em saúde do servidor exige o conhecimento das características dessa população, bem como do perfil de morbidade. Os resultados apresentados expressam a magnitude do absenteísmo-doença no setor saúde do serviço público e apontam para a necessidade de mudanças profundas na organização do processo de trabalho, com intervenções inovadoras nos espaços profissionais.

USE OF DRUGS IN CHILDREN AGED ZERO TO FIVE YEARS OLD IN TUBARÃO, SANTA CATARINA, BRAZIL. / USO DE MEDICAMENTOS EM CRIANÇAS DE ZERO A CINCO ANOS DE IDADE RESIDENTES NO MUNICÍPIO DE TUBARÃO, SANTA CATARINA.

OBJECTIVE: To analyze the context of drug use in children aged zero to five years old. METHODS: Cross-sectional study based on interviews conducted at home with caregivers (parents, uncles or grandparents) of the children enrolled in ten Family Health Strategy units across different geographical points of the city of Tubarão, Santa Catarina, Brazil. RESULTS: A total of 350 caregivers were interviewed, whose children's mean age was 2.6 years. Of these, 56.9% had used at least one drug in the 15 days prior to the interview, 31.1% had been exposed to self-medication and 35.7% had used at least one medication obtained by current prescription. The use of medication was associated with the age range up to 24 months, periodic consultation with pediatricians and diagnosis of chronic and acute diseases. Among medicated children, 19.1% inappropriately had been exposed to at least one medication (considering dose, dose interval or period of treatment). Regarding medication storage, 55.2% of interviewees stored them in unsafe places that could be accessed by children and 32.0% in inappropriate places, with exposure to light, heat or humidity. Moreover, 45.2% of the interviewees stored drugs out of their packages, 38.9% without secondary packaging, and 1.6% of drugs had expired date. CONCLUSIONS: Drug use is high among children in this age range, and actions aimed at the safe and rational use of these substances in this population should be encouraged.

OBJETIVO: Analisar o perfil de utilização de medicamentos em crianças de zero a cinco anos de idade. MÉTODOS: Estudo transversal baseado em entrevistas realizadas em domicílio com cuidadores (pais, tios ou avós) das crianças cadastradas em dez unidades de Estratégia Saúde da Família (ESF), distribuídas em diferentes pontos geográficos do município de Tubarão, Santa Catarina. RESULTADOS: Foram entrevistados 350 cuidadores, cujas crianças sorteadas possuíam, em média, 2,6 anos de idade. Destas, 56,9% utilizaram, pelo menos, um medicamento nos 15 dias anteriores à entrevista, sendo que 31,1% foram expostas à automedicação e 35,7% utilizaram, pelo menos, um medicamento obtido por prescrição atual. O uso de medicamentos foi associado à faixa etária de até 24 meses, consulta periódica com pediatra e diagnóstico de doenças agudas e doenças crônicas. Entre as crianças medicadas, 19,1% foram expostas a pelo menos um medicamento de forma inadequada (considerando dose, intervalo entre doses ou período de tratamento). Quanto ao armazenamento, 55,2% dos medicamentos estavam guardados em lugar inseguro, ou seja, ao acesso das crianças, e 32,0% em locais inadequados, por estarem expostos a luz, calor ou umidade. Ainda, 45,2% estavam sem bula, 38,9% sem embalagem secundária e 1,6% fora do prazo de validade. CONCLUSÕES: As crianças estudadas apresentam uma frequência elevada de uso de medicamentos, devendo ser incentivadas ações que visem ao uso seguro e racional de fármacos nessa população.

Factors associated with falls in older adults with cataracts. / Fatores associados a quedas em idosos com catarata.

The aim of the present study was to evaluate factors associated with falls in community-dwelling older adults diagnosed with cataracts. An analytical, cross-sectional study was conducted with a sample of community-dwelling older adults residing in the Federal District of Brazil. Interviews and assessment tools were administered, such as the Timed Up and Go test, Short Physical Performance Battery (SPPB), Biodex Balance System, Katz Index, Lawton Scale, Minnesota Leisure Time Physical Activity Questionnaire and Mini Mental State Examination. Statistical analysis involved binary logistic regression. One hundred forty-two older adults (85 with cataracts) participated in the study (mean age: 69.39 ± 5.67 years). Falls were associated with the female sex (OR: 4.45) and sub-maximum score on the SPPB (OR: 3.53) among patients with cataracts, whereas multimorbidity (OR: 5.10) was the risk factor risk for older adults without cataracts. The data suggest different risk factors for falls among older adults diagnosed with cataracts.

O objetivo deste artigo é avaliar os fatores associados a quedas em idosos comunitários com diagnóstico de catarata. Trata-se de pesquisa transversal e analítica. A amostra se constituiu de idosos comunitários residentes no Distrito Federal, Brasil. Foram aplicados os seguintes instrumentos: questionário sociodemográfico; Timed Up and Go; Short Battery Performance Test; a Plataforma de Equilíbrio Biodex Balance System; o Índice de Katz, escala de Lawton; Mini-Exame do Estado Mental; e os critérios de fragilidade de John Hopkins Medical Institutions. Para análise empregou-se regressão logística binária. Participaram 142 idosos (85 destes com catarata), com média de idade de 69,39 anos (± 5,67). Observou-se associação das quedas com sexo feminino (OR:4,45) e pontuação submáxima no SPPB (OR:3,53) entre os pacientes com catarata, ao passo que a presença de multimorbidades (OR:5,10) foi o fator de risco para os idosos sem catarata. Os dados sugerem fatores de risco diferentes para idosos com diagnóstico de catarata.

High RAC3 expression levels are required for induction and maintaining of cancer cell stemness.

RAC3 is a transcription coactivator, usually overexpressed in several tumors and required to maintain the pluripotency in normal stem cells. In this work we studied the association between RAC3 overexpression on cancer cell stemness and the capacity of this protein to induce cancer stem properties in non tumoral cells. We performed in vitro and in vivo experiments using two strategies: by overexpressing RAC3 in the non tumoral cell line HEK293 and by silencing RAC3 in the human colorectal epithelial cell line HCT116 by transfection. Furthermore, we analysed public repository microarrays data from human colorectal tumors in different developmental stages. We found that RAC3 overexpression was mainly associated to CD133+ side-population of colon cancer cells and also to early and advanced stages of colon cancer, involving increased expression of mesenchymal and stem markers. In turn, RAC3 silencing induced diminished tumoral properties and cancer stem cells as determined by Hoechst efflux, tumorspheres and clonogenic growth, which correlated with decreased Nanog and OCT4 expression. In non tumoral cells, RAC3 overexpression induced tumoral transformation; mesenchymal phenotype and stem markers expression. Moreover, these transformed cells generated tumors in vivo. Our results demonstrate that RAC3 is required for maintaining and induction of cancer cell stemness.