[Association between birth conditions and bone mineral density in adults from the 1982 and 1993 birth cohorts in Pelotas, Rio Grande do Sul State, Brazil]. / Associação entre as condições de nascimento e a densidade mineral óssea de adultos das coortes de nascimentos de 1982 e 1993 de Pelotas, Rio Grande do Sul, Brasil.

This study assessed the association of birth weight, gestational age, and intrauterine growth with bone mineral density (BMD) at 22 and 30 years of age in the 1982 and 1993 birth cohorts in Pelotas, Rio Grande do Sul State, Brazil. BMD was measured by dual-energy X-ray absorptiometry (DXA) and the association was assessed using analysis of variance. Multiple linear regression was used to control for confounding factors: sex; household income at birth; maternal smoking during pregnancy; maternal schooling; maternal ethnicity/skin color; and pre-pregnancy body mass index. The study tested whether body fat in adulthood was a mediator of the association analyzed, using the G-computation Formula. A total of 6,803 participants from the 1982 and 1993 cohorts were evaluated at 30 and 22 years of age, respectively. Birth weight was associated with BMD at all sites, with a greater difference at the femoral neck. Individuals born weighing less than 2,000g had on average -0.036g/cm2 (95%CI: -0.064; -0.008) of BMD in the femoral neck than individuals weighing more than 3,500g. Individuals with an intrauterine growth z-score at least 1.28 standard deviation below the mean had an average of -0.013g/cm2 (95%CI: -0.024; -0.002) of BMD in the lumbar spine compared with individuals with an above-average z-score. The mediation analysis showed that body fat in adulthood did not mediate the association. Birth conditions have been associated with BMD in adulthood and the identification of early factors related to bone loss is essential due to the demographic inversion that has been taking place in low- and middle-income countries.

Este estudo avaliou a associação do peso ao nascer, idade gestacional e crescimento intrauterino com a densidade mineral óssea (DMO) aos 22 e 30 anos, nas coortes de nascimentos de 1982 e 1993 de Pelotas, Rio Grande do Sul, Brasil. A DMO foi medida por absorciometria por raios X com dupla energia (DXA), a associação foi avaliada usando análise de variância e a regressão linear múltipla para o controle de confundimento por: sexo, renda familiar ao nascer, tabagismo materno na gestação, escolaridade materna, cor da pele materna e índice de massa corporal pré-gestacional. Foi testado se a gordura corporal na vida adulta era mediadora da associação analisada, por meio da G-computation Formula. Foram avaliados 6.803 participantes das coortes de 1982 e 1993, aos 30 e 22 anos, respectivamente. O peso ao nascer teve associação com a DMO em todos os sítios, com maior diferença no colo femoral. Os nascidos com menos de 2.000g apresentaram, em média, -0,036g/cm2 (IC95%: -0,064; -0,008) de DMO no colo femoral em comparação àqueles com mais de 3.500g. Aqueles com escore-z de crescimento intrauterino com pelo menos 1,28 desvio padrão abaixo da média apresentaram, em média, -0,013g/cm2 (IC95%: -0,024; -0,002) de DMO na coluna lombar, em relação aos com escore-z acima da média. A análise de mediação mostrou que gordura corporal na idade adulta não mediou a associação. As condições de nascimento foram associadas com a densidade mineral óssea na vida adulta, e a identificação dos fatores precoces relacionados à perda de DMO é essencial devido à inversão demográfica em progresso em países de média e baixa renda.

Este estudio evaluó la asociación del peso al nacer, la edad gestacional y el crecimiento intrauterino con la densidad mineral ósea (DMO) a los 22 y 30 años de edad, en las Cohortes de Nacimiento de 1982 y 1993 de Pelotas, Rio Grande do Sul, Brasil. La DMO se midió mediante absorciometría de rayos X de doble emisión (DXA), y la asociación se evaluó mediante ANOVA y regresión lineal múltiple para controlar la confusión por sexo, ingresos familiares al nacer, tabaquismo materno durante el embarazo, escolaridad materna, color de piel materno e índice de masa corporal antes del embarazo. Se comprobó si la grasa corporal en la edad adulta era un mediador de la asociación analizada, utilizando G-computation Formula. Se evaluaron 6.803 participantes de las cohortes 82 y 93, de 30 y 22 años, respectivamente. El peso al nacer se asoció con la DMO en todos los sitios, con la mayor diferencia en el cuello femoral. Los nacidos con un peso inferior a 2.000g tuvieron una media de -0,036g/cm2 (IC95%: -0,064; -0,008) de DMO en el cuello femoral, que aquellos con más de 3.500g. Aquellos con una puntuación z de crecimiento intrauterino de al menos 1,28 desviaciones estándar por debajo de la media presentaron un promedio de -0,013g/cm2 (IC95%: -0,024; -0,002) de DMO en la columna lumbar, con relación a aquellos con un puntaje z superior a la media. El análisis de mediación mostró que la grasa corporal en la edad adulta no medió la asociación. Las condiciones de nacimiento se asociaron con la DMO en la edad adulta, y la identificación temprana de factores relacionados con la pérdida de DMO es esencial debido a la inversión demográfica que ha estado ocurriendo en los países de ingresos medios y bajos.

Gastrointestinal Issues in Depression, Anxiety, and Neurodegenerative Diseases: A Systematic Review on Pathways and Clinical Targets Implications.

INTRODUCTION: Multiple illnesses commonly involve both the Central Nervous System (CNS) and the Gastrointestinal Tract (GI) simultaneously. Consistent evidence suggests that neurological disorders impair GI tract function and worsen the symptomatology and pathophysiology of digestive disorders. On the other hand, it has been proposed that early functional changes in the GI tract contribute to the genesis of several CNS illnesses. Additionally, the role played by the gut in these diseases can be seen as a paradigm for how the gut and the brain interact. METHODS: We mentioned significant GI symptoms and discussed how the GI tract affects central nervous system illnesses, including depression, anxiety, Alzheimer's disease, and Parkinson's disease in this study. We also explored potential pathophysiological underpinnings and novel targets for the creation of future therapies targeted at gut-brain connections. RESULTS & DISCUSSION: In this situation, modulating the gut microbiota through the administration of fecal microbiota transplants or probiotics may represent a new therapeutic option for this population, not only to treat GI problems but also behavioral problems, given the role that dysbiosis and leaky gut play in many neurological disorders. CONCLUSION: Accurate diagnosis and treatment of co-existing illnesses also require coordination between psychiatrists, neurologists, gastroenterologists, and other specialties, as well as a thorough history and thorough physical examination.

Perspectives About Ascorbic Acid to Treat Inflammatory Bowel Diseases.

It is known that reactive oxygen species cause abnormal immune responses in the gut during inflammatory bowel diseases (IBD). Therefore, oxidative stress has been theorized as an agent of IBD development and antioxidant compounds such as vitamin C (L-ascorbic acid) have been studied as a new tool to treat IBD. Therefore, the potential of vitamin C to treat IBD was reviewed here as a critical discussion about this field and guide future research. Indeed, some preclinical studies have shown the beneficial effects of vitamin C in models of ulcerative colitis in mice and clinical and experimental findings have shown that deficiency in this vitamin is associated with the development of IBD and its worsening. The main mechanisms that may be involved in the activity of ascorbic acid in IBD include its well-established role as an antioxidant, but also others diversified actions. However, some experimental studies employed high doses of vitamin C and most of them did not perform dose-response curves and neither determined the minimum effective dose nor the ED50. Allometric extrapolations were also not made. Also, clinical studies on the subject are still in their infancy. Therefore, it is suggested that the research agenda in this matter covers experimental studies that assess the effective, safe, and translational doses, as well as the appropriate administration route and its action mechanism. After that, robust clinical trials to increase knowledge about the role of ascorbic acid deficiency in IBD patients and the effects of their supplementation in these patients can be encouraged.

Characterization of Diclofenac-induced Renal Damage in Normotensive and Hypertensive Rats: A Comparative Analysis.

BACKGROUND: Diclofenac is the non-steroidal anti-inflammatory drug (NSAID) mostly prescribed worldwide, but it is highly associated with hypertension and acute kidney injury. Despite that, little information is available about the renal effects of diclofenac in hypertensive individuals, which led us to carry out this comparative study between the renal effects of this NSAID in normotensive (NTR) and spontaneously hypertensive rats (SHR). METHODS: Male Wistar NTR and SHR were orally treated with vehicle (V: 10 mL/kg) or diclofenac sodium (D: 100 mg/kg) once a day for 3 days. Urine volume, electrolytes excretion (Na+, K+, Cl-, and Ca2+), urea, creatinine, pH, and osmolarity were evaluated. Furthermore, blood samples and renal tissue were collected to perform biochemical and histological analysis. RESULTS: Diclofenac increased the renal corpuscle and bowman's space in the SHR, while no microscopic changes were observed in the renal tissue of NTR. Regarding the urinary parameters, diclofenac reduced urine volume, pH, osmolarity, and all electrolytes excretion, followed by decreased urea and creatinine levels in both lineages. Moreover, it also induced hyponatremia, hypokalemia, and hypocalcemia in SHR, while reduced glutathione-S-transferase activity, lipid hydroperoxides, and nitrite levels in renal tissue. CONCLUSIONS: The data presented herein demonstrated that diclofenac induces renal damage and impaired renal function in both NTR and SHR, but those effects are exacerbated in SHR, as seen by the histological changes and electrolytes balance disturbance, therefore, reinforcing that diclofenac may increase the risks of cardiovascular events in hypertensive patients.

Cisplatin Toxicity Causes Neutrophil-Mediated Inflammation in Zebrafish Larvae.

Cisplatin is an antineoplastic agent used to treat various tumors. In mammals, it can cause nephrotoxicity, tissue damage, and inflammation. The release of inflammatory mediators leads to the recruitment and infiltration of immune cells, particularly neutrophils, at the site of inflammation. Cisplatin is often used as an inducer of acute kidney injury (AKI) in experimental models, including zebrafish (Danio rerio), due to its accumulation in kidney cells. Current protocols in larval zebrafish focus on studying its effect as an AKI inducer but ignore other systematic outcomes. In this study, cisplatin was added directly to the embryonic medium to assess its toxicity and impact on systemic inflammation using locomotor activity analysis, qPCR, microscopy, and flow cytometry. Our data showed that larvae exposed to cisplatin at 7 days post-fertilization (dpf) displayed dose-dependent mortality and morphological changes, leading to a decrease in locomotion speed at 9 dpf. The expression of pro-inflammatory cytokines such as interleukin (il)-12, il6, and il8 increased after 48 h of cisplatin exposure. Furthermore, while a decrease in the number of neutrophils was observed in the glomerular region of the pronephros, there was an increase in neutrophils throughout the entire animal after 48 h of cisplatin exposure. We demonstrate that cisplatin can have systemic effects in zebrafish larvae, including morphological and locomotory defects, increased inflammatory cytokines, and migration of neutrophils from the hematopoietic niche to other parts of the body. Therefore, this protocol can be used to induce systemic inflammation in zebrafish larvae for studying new therapies or mechanisms of action involving neutrophils.

Immunology of Kidney Disease.

The immune system and the kidneys are closely related. Immune components mediate acute kidney disease and are crucial to the progression of chronic kidney disease. Beyond its pathogenic functions, the immune system supports immunological homeostasis in healthy kidneys. The kidneys help maintain immune equilibrium by removing metabolic waste products and toxins, thereby limiting local and systemic inflammation. In this review, we describe the close relationship between the immune system and the kidneys. We discuss how the imbalance in the immune response can be deleterious to the kidneys and how immunomodulation can be important in preventing end-stage renal disease. In addition, recent tools such as in silico platforms and kidney organoids can help unveil the relationship between immune cells and kidney homeostasis. Expected final online publication date for the Annual Review of Immunology, Volume 42 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

3-Demethyl-2-geranyl-4-prenylbellidifoline, a natural xanthone with diuretic and kidney protective properties.

OBJECTIVES: The diuretic and kidney protective effect of the 3-demethyl-2-geranyl-4-prenylbellidifoline (DGP) were evaluated in rats. METHODS: The normotensive (NTR) and spontaneously hypertensive rats (SHR) received, once a day for 7 days, oral treatment with DGP (0.1 mg/kg), hydrochlorothiazide (10 mg/kg), or vehicle (10 ml/kg). Urine, blood, and kidney samples were collected for further analysis. KEY FINDINGS: The urine and Na+ elimination content were significantly higher in the groups that received DGP. Furthermore, a Ca2+-sparing action was detected in the urine of DGP-treated groups, which was consistent with the reduction in calcium oxalate crystal formation. Relevantly, the treatment did not change the parameters examined in the blood. Concerning the renal analyses, DGP treatment recovered the morphological damages of the kidney corpuscle area of SHR. In addition to the differences observed between the NTR and SHR vehicle groups, DGP augmented the amount of reduced glutathione and the activity of glutathione S-transferase GST while reducing the catalase and N-acetyl-ß-D-glucosaminidase activity and nitrite levels. CONCLUSION: Together, this study displayed the prolonged diuretic action of DGP and its natriuretic, Ca2+-sparing, and antiurolytic effects. The antioxidative and anti-inflammatory effects of DGP were evidenced in SHR kidneys, opening perspectives for further studies regarding the benefits of this xanthone.

Enhancing functional recovery following postpartum femoral neuropathy: early neurorehabilitation and multidisciplinary obstetric care.

Postpartum femoral neuropathy has a reported incidence of less than 1% and its total recovery time extends up to 6 months to a year. A multidisciplinary approach is vital to rule out permanent disability and to assure a correct diagnosis and earlier rehabilitation. We report a case of a 37-year-old puerperal woman with a history of intrapartum epidural analgesia, who presented post-labor unilateral lower-limb motor weakness and sensory loss, with functional compromise on independent gait. A multidisciplinary team consisting of an anesthesiologist, a physiatrist, a neurologist, and an obstetrician was then established. In the initial physiatry and neurology assessment, the patient reported pain (numerical rating scale 7/10) over the inguinal ligament, lower limb hypoesthesia, and muscle weakness. Femoral neuropathy was suspected. Magnetic resonance imaging ruled out potential complications related to the anesthetic procedure. The patient was then enrolled in a supervised rehabilitation program and, 3 weeks later, electrodiagnostic studies confirmed the initial suspicion. Two months later, the patient had regained lower-limb active range of motion and no pain nor paresthesia was reported. Our case report describes how an early multimodal rehabilitation program within a multidisciplinary framework allows for sooner neuromotor function improvement and activities of daily living independence.

Aqueous extract of the bark of Uncaria tomentosa, an amazonian medicinal plant, promotes gastroprotection and accelerates gastric healing in rats.

ETHNOPHARMACOLOGICAL IMPORTANCE: Uncaria tomentosa Willd. DC., is used in the Amazonian region of South America, wherein ethnic groups use the plant to treat diseases, including gastric disorders. However, despite its widespread popular use, this species has yet to be assessed for its anti-ulcer effects. AIM OF THE STUDY: In this study, we aimed to evaluate the in vivo gastroprotective and gastric healing activities of an aqueous extract of the bark of Uncaria tomentosa (AEUt) and sought to gain an understanding of the pharmacological mechanisms underlying these biological effects. MATERIALS AND METHODS: To verify the gastroprotective properties rats were treated with AEUt (30, 60, or 120 mg/kg) prior to inducing gastric ulceration with ethanol or piroxicam. Additionally, the involvement of nitric oxide, non-protein sulfhydryl compounds (NP-SH), α-2 adrenergic receptors, and prostaglandins was investigated. Furthermore, a pylorus ligature model was employed to investigate the antisecretory activity of AEUt. The gastric healing effects of AEUt (60 mg/kg) were examined in rats in which ulceration had been induced with 80% acetic acid, whereas the quality of healing was evaluated in mice with interleukin-induced recurrent ulcers. We also evaluated the in vivo thickness of the gastric wall using ultrasonography. Moreover, the levels of reduced glutathione (GSH) and malondialdehyde (MDA) were evaluated in ulcerated mucosa, and we determined the activities of the enzymes myeloperoxidase (MPO), N-acetyl-ß-D-glycosaminidase, superoxide dismutase, catalase, and glutathione S-transferase. In addition, we assessed the effects of AEUt on cell viability and subjected the AEUt to phytochemical analyses. RESULTS: Administration of the AEUt (60 or 120 mg/kg) prevented ethanol- and piroxicam-induced ulceration, which was also confirmed histologically. Moreover, we observed that pre-treatment with NEM and indomethacin abolished the gastroprotective effects of AEUt, thereby indicating the involvement of NP-SH and prostaglandins in these protective effects. In addition, we found that the administration of AEUt had no appreciable effects on the volume, acidity, or peptic activity of gastric juice. Furthermore, the AEUt (60 mg/kg) accelerated the gastric healing of acetic acid-induced ulcers by 46.2% and ultrasonographic findings revealed a reduction in the gastric wall thickness in this group. The gastric healing effect of AEUt was also accompanied by a reduction in MPO activity. The AEUt (60 mg/kg) also minimized ulcer recurrence in mice exposed to IL-1ß and was associated with the maintenance of GSH levels and a reduction in MDA contents. We deduce that the biological effects of AEUt could be associated with the activities of polyphenols and the alkaloids isomitraphylline and mitraphylline, identified as predominant constituents of the AEUt. Furthermore, we found no evidence to indicate that AEUt would have any cytotoxic effects. CONCLUSION: Collectively, our findings provide compelling evidence indicating the therapeutic efficacy of U. tomentosa. Our data indicate that compounds in AEUt confer gastroprotection and that this preventive effect of AEUt was accompanied by gastric healing and a reduction in gastric ulcer recurrence. Moreover, we provide evidence to indicate that the gastroprotective and gastric healing effects involve the antioxidant system and anti-inflammatory responses that contribute to preserving the gastric mucosa.

Are silymarin and N-acetylcysteine able to prevent liver damage mediated by multiple factors? Findings against ethanol plus LPS-induced liver injury in mice.

This study investigated the effect of N-acetylcysteine (NAC) and silymarin (SIL) in the liver of mice exposed to ethanol and lipopolysaccharides (LPS). Mice were divided into four groups (n = 6): naive, vehicle, NAC (200 mg/kg), and SIL (200 mg/kg). Treatments were given orally (po) once daily for 10 days. Liver injury was induced by administration of ethanol (30%, po) for 10 days, once daily, followed by a single administration of LPS (2 mg/kg, ip) 24 h before euthanasia. After the treatment period, animals were euthanized, and liver and blood samples were collected. NAC, but not SIL, prevented the increase in oxalacetic glutamic transaminase (OGT) and pyruvic glutamic transaminase (PGT) serum levels. NAC and SIL did not restore levels of reduced glutathione or hepatic malonaldehyde. The treatments with NAC or SIL showed no difference in the activity of glutathione S-transferase, superoxide dismutase, and catalase compared to vehicle group. Myeloperoxidase and N-acetylglucosaminidase activities are increased, as well as the IL-6 and IL-10 levels in the liver. The treatment with NAC, but not SIL, reduced the N-acetylglucosamines activity and the IL-6 and IL-10 amount in the liver. Histological findings revealed microsteatosis in the vehicle group, which was not prevented by SIL but was partially reduced in animals receiving NAC. Unlike other liver injury models, NAC (200 mg/kg) or SIL (200 mg/kg) did not positively affect antioxidant patterns in liver tissue of animals exposed to ethanol plus LPS, but NAC treatment displays anti-inflammatory properties in this model.

Associação entre as condições de nascimento e a densidade mineral óssea de adultos das coortes de nascimentos de 1982 e 1993 de Pelotas, Rio Grande do Sul, Brasil / Association between birth conditions and bone mineral density in adults from the 1982 and 1993 birth cohorts in Pelotas, Rio Grande do Sul State, Brazil / Asociación entre las condiciones de nacimiento y la densidad mineral ósea de adultos de las cohortes de nacimiento de 1982 y 1993 en Pelotas, Rio Grande do Sul, Brasil

Resumo: Este estudo avaliou a associação do peso ao nascer, idade gestacional e crescimento intrauterino com a densidade mineral óssea (DMO) aos 22 e 30 anos, nas coortes de nascimentos de 1982 e 1993 de Pelotas, Rio Grande do Sul, Brasil. A DMO foi medida por absorciometria por raios X com dupla energia (DXA), a associação foi avaliada usando análise de variância e a regressão linear múltipla para o controle de confundimento por: sexo, renda familiar ao nascer, tabagismo materno na gestação, escolaridade materna, cor da pele materna e índice de massa corporal pré-gestacional. Foi testado se a gordura corporal na vida adulta era mediadora da associação analisada, por meio da G-computation Formula. Foram avaliados 6.803 participantes das coortes de 1982 e 1993, aos 30 e 22 anos, respectivamente. O peso ao nascer teve associação com a DMO em todos os sítios, com maior diferença no colo femoral. Os nascidos com menos de 2.000g apresentaram, em média, -0,036g/cm2 (IC95%: -0,064; -0,008) de DMO no colo femoral em comparação àqueles com mais de 3.500g. Aqueles com escore-z de crescimento intrauterino com pelo menos 1,28 desvio padrão abaixo da média apresentaram, em média, -0,013g/cm2 (IC95%: -0,024; -0,002) de DMO na coluna lombar, em relação aos com escore-z acima da média. A análise de mediação mostrou que gordura corporal na idade adulta não mediou a associação. As condições de nascimento foram associadas com a densidade mineral óssea na vida adulta, e a identificação dos fatores precoces relacionados à perda de DMO é essencial devido à inversão demográfica em progresso em países de média e baixa renda.

Abstract: This study assessed the association of birth weight, gestational age, and intrauterine growth with bone mineral density (BMD) at 22 and 30 years of age in the 1982 and 1993 birth cohorts in Pelotas, Rio Grande do Sul State, Brazil. BMD was measured by dual-energy X-ray absorptiometry (DXA) and the association was assessed using analysis of variance. Multiple linear regression was used to control for confounding factors: sex; household income at birth; maternal smoking during pregnancy; maternal schooling; maternal ethnicity/skin color; and pre-pregnancy body mass index. The study tested whether body fat in adulthood was a mediator of the association analyzed, using the G-computation Formula. A total of 6,803 participants from the 1982 and 1993 cohorts were evaluated at 30 and 22 years of age, respectively. Birth weight was associated with BMD at all sites, with a greater difference at the femoral neck. Individuals born weighing less than 2,000g had on average -0.036g/cm2 (95%CI: -0.064; -0.008) of BMD in the femoral neck than individuals weighing more than 3,500g. Individuals with an intrauterine growth z-score at least 1.28 standard deviation below the mean had an average of -0.013g/cm2 (95%CI: -0.024; -0.002) of BMD in the lumbar spine compared with individuals with an above-average z-score. The mediation analysis showed that body fat in adulthood did not mediate the association. Birth conditions have been associated with BMD in adulthood and the identification of early factors related to bone loss is essential due to the demographic inversion that has been taking place in low- and middle-income countries.

Resumen: Este estudio evaluó la asociación del peso al nacer, la edad gestacional y el crecimiento intrauterino con la densidad mineral ósea (DMO) a los 22 y 30 años de edad, en las Cohortes de Nacimiento de 1982 y 1993 de Pelotas, Rio Grande do Sul, Brasil. La DMO se midió mediante absorciometría de rayos X de doble emisión (DXA), y la asociación se evaluó mediante ANOVA y regresión lineal múltiple para controlar la confusión por sexo, ingresos familiares al nacer, tabaquismo materno durante el embarazo, escolaridad materna, color de piel materno e índice de masa corporal antes del embarazo. Se comprobó si la grasa corporal en la edad adulta era un mediador de la asociación analizada, utilizando G-computation Formula. Se evaluaron 6.803 participantes de las cohortes 82 y 93, de 30 y 22 años, respectivamente. El peso al nacer se asoció con la DMO en todos los sitios, con la mayor diferencia en el cuello femoral. Los nacidos con un peso inferior a 2.000g tuvieron una media de -0,036g/cm2 (IC95%: -0,064; -0,008) de DMO en el cuello femoral, que aquellos con más de 3.500g. Aquellos con una puntuación z de crecimiento intrauterino de al menos 1,28 desviaciones estándar por debajo de la media presentaron un promedio de -0,013g/cm2 (IC95%: -0,024; -0,002) de DMO en la columna lumbar, con relación a aquellos con un puntaje z superior a la media. El análisis de mediación mostró que la grasa corporal en la edad adulta no medió la asociación. Las condiciones de nacimiento se asociaron con la DMO en la edad adulta, y la identificación temprana de factores relacionados con la pérdida de DMO es esencial debido a la inversión demográfica que ha estado ocurriendo en los países de ingresos medios y bajos.

Prevalence and factors associated with long COVID in adults from Southern Brazil: findings from the PAMPA cohort.

Most COVID-19 survivors have reported experiencing persistent symptoms after the infection - these types of cases are known as long COVID. Since Brazil was an epicenter of the COVID-19 pandemic, a high burden of long COVID is expected. This study aimed to identify the prevalence and factors associated with long COVID in adults in Southern Brazil, analyzing data from the PAMPA cohort. Participants filled out a self-reported online questionnaire in June 2022. This study only included subjects who tested positive for COVID-19. Long COVID was defined by any symptoms that persisted for at least three months after the SARS-CoV-2 infection. Poisson's regression models with robust variance were used to identify factors associated with long COVID; and results were reported as prevalence ratios (PR) and respective 95% confidence intervals (95%CI). A total of 1,001 participants (77.4% women, mean age [SD] = 38.3 [11.9] years) were analyzed. The prevalence of long COVID among these patients was 77.4% (95%CI: 74.7; 79.9). The likelihood of long COVID was higher in unvaccinated participants (PR = 1.23, 95%CI: 1.06; 1.42), in those with chronic conditions (PR = 1.13, 95%CI: 1.04; 1.24), and in those who were hospitalized due to the COVID-19 infection (PR = 1.24, 95%CI: 1.16; 1.32). This prevalence was also higher in women (PR = 1.21, 95%CI: 1.09; 1.33) than in men. Physical activity was associated with a reduced likelihood of fatigue, neurological complications, coughing, and headaches as persistent symptoms after a COVID-19 infection. It was found that three out of four adults in Southern Brazil experienced long COVID. Public policies aiming to reduce the burden of long COVID must be prioritized, especially in groups that are at higher risk of developing this harmful condition.

Role of K+ and Ca2+ Channels in the Vasodilator Effects of Plectranthus barbatus (Brazilian Boldo) in Hypertensive Rats.

Plectranthus barbatus, popularly known as Brazilian boldo, is used in Brazilian folk medicine to treat cardiovascular disorders including hypertension. This study investigated the chemical profile by UFLC-DAD-MS and the relaxant effect by using an isolated organ bath of the hydroethanolic extract of P. barbatus (HEPB) leaves on the aorta of spontaneously hypertensive rats (SHR). A total of nineteen compounds were annotated from HEPB, and the main metabolite classes found were flavonoids, diterpenoids, cinnamic acid derivatives, and organic acids. The HEPB promoted an endothelium-dependent vasodilator effect (~100%; EC50 ~347.10 µg/mL). Incubation of L-NAME (a nonselective nitric oxide synthase inhibitor; EC50 ~417.20 µg/mL), ODQ (a selective inhibitor of the soluble guanylate cyclase enzyme; EC50 ~426.00 µg/mL), propranolol (a nonselective α-adrenergic receptor antagonist; EC50 ~448.90 µg/mL), or indomethacin (a nonselective cyclooxygenase enzyme inhibitor; EC50 ~398.70 µg/mL) could not significantly affect the relaxation evoked by HEPB. However, in the presence of atropine (a nonselective muscarinic receptor antagonist), there was a slight reduction in its vasorelaxant effect (EC50 ~476.40 µg/mL). The addition of tetraethylammonium (a blocker of Ca2+-activated K+ channels; EC50 ~611.60 µg/mL) or 4-aminopyridine (a voltage-dependent K+ channel blocker; EC50 ~380.50 µg/mL) significantly reduced the relaxation effect of the extract without the interference of glibenclamide (an ATP-sensitive K+ channel blocker; EC50 ~344.60 µg/mL) or barium chloride (an influx rectifying K+ channel blocker; EC50 ~360.80 µg/mL). The extract inhibited the contractile response against phenylephrine, CaCl2, KCl, or caffeine, similar to the results obtained with nifedipine (voltage-dependent calcium channel blocker). Together, the HEPB showed a vasorelaxant effect on the thoracic aorta of SHR, exclusively dependent on the endothelium with the participation of muscarinic receptors and K+ and Ca2+ channels.

Diuretic, Natriuretic, And Ca2+-Sparing Effect Of The Alkaloid Boldine In Rats.

BACKGROUND: Previous studies indicate the renal vasodilating effects of boldine, an alkaloid found in Peumus boldus. However, its potential to induce diuresis still needs to be studied. METHODS: Wistar rats were used and the urine volume was noted for 8 h and further studied. RESULTS: The acute treatment at 0.1 and 0.3 mg/kg of boldine showed a diuretic, natriuretic, and Ca2+-sparing effect in rats without changing the urinary elimination of K+and Cl-. When boldine was given in combination with hydrochlorothiazide, there was an increase in urinary volume compared to the vehicle group. However, this was not different from the treatments in its isolated form. Urine Ca2+values ​​remained low but were not enhanced by this association. The excretion of Na+and Cl- was significantly increased compared to the group that received only vehicle or boldine. On the other hand, although the association of amiloride plus boldine did not result in a diuretic effect, the increase in Na+and the reduction in K+excretion were significantly potentiated. Furthermore, in the presence of the non-selective muscarinic receptor antagonist atropine, boldine showed reduced capacity to increase urinary volume, maintaining the natriuretic and Ca2+-sparing effect, besides a very evident K+-sparing action. Similar results were obtained in the presence of the non-selective cyclooxygenase inhibitor indomethacin. Furthermore, boldine showed an ex vivo antiurolithiasis activity, reducing calcium oxalate's precipitation and crystallization. CONCLUSIONS: This study reveals the diuretic, natriuretic, Ca2+-sparing, and antiurolithiatic effects of boldine, an action possibly related to muscarinic receptor activation and prostanoid generation.

Migrants' living conditions, perceived health needs and implications for the use of antibiotics and antimicrobial resistance in the United Kingdom: A qualitative study.

Background and Aims: Antimicrobial resistance (AMR) is among the top public health concerns around the globe. Migrants, especially forced migrants, could be at higher risk of acquiring and transmitting AMR during their journeys or in host countries. There is limited understanding regarding migrants' living conditions and the wider factors contributing to their risk of acquiring infections, and behaviors around antimicrobial use, and AMR development. In this study, we aimed to explore transit experiences, living conditions, and antibiotic use of migrants living in the United Kingdom. Methods: We conducted semistructured qualitative interviews with 27 participants and identified five themes regarding migrants' journey and their living conditions during transit and after arriving in the United Kingdom, their access to water, sanitation and hygiene (WASH), and their use of antibiotics. Results: Migrants, particularly forced migrants, experienced unfavorable living conditions, poor access to WASH, and challenges in accessing healthcare, which further contributed to health conditions like urinary and skin problems. Isolation and difficulty in accessing healthcare played significant roles in migrants' perceived need for storing and using antibiotics as a safety net. Conclusion: The findings highlight the need for coordinated and multilevel interventions to address these challenges and contribute toward tackling AMR and improving the health of this population group.

Epac induces ryanodine receptor-dependent intracellular and inter-organellar calcium mobilization in mpkCCD cells.

Arginine vasopressin (AVP) induces an increase in intracellular Ca2+ concentration ([Ca2+]i) with an oscillatory pattern in isolated perfused kidney inner medullary collecting duct (IMCD). The AVP-induced Ca2+ mobilization in inner medullary collecting ducts is essential for apical exocytosis and is mediated by the exchange protein directly activated by cyclic adenosine monophosphate (Epac). Murine principal kidney cortical collecting duct cells (mpkCCD) is the cell model used for transcriptomic and phosphoproteomic studies of AVP signaling in kidney collecting duct. The present study examined the characteristics of Ca2+ mobilization in mpkCCD cells, and utilized mpkCCD as a model to investigate the Epac-induced intracellular and intra-organellar Ca2+ mobilization. Ca2+ mobilization in cytosol, endoplasmic reticulum lumen, and mitochondrial matrix were monitored with a Ca2+ sensitive fluorescent probe and site-specific Ca2+ sensitive biosensors. Fluorescence images of mpkCCD cells and isolated perfused inner medullary duct were collected with confocal microscopy. Cell permeant ligands of ryanodine receptors (RyRs) and inositol 1,4,5 trisphosphate receptors (IP3Rs) both triggered increase of [Ca2+]i and Ca2+ oscillations in mpkCCD cells as reported previously in IMCD. The cell permeant Epac-specific cAMP analog Me-cAMP/AM also caused a robust Ca2+ mobilization and oscillations in mpkCCD cells. Using biosensors to monitor endoplasmic reticulum (ER) luminal Ca2+ and mitochondrial matrix Ca2+, Me-cAMP/AM not only triggered Ca2+ release from ER into cytoplasm, but also shuttled Ca2+ from ER into mitochondria. The Epac-agonist induced synchronized Ca2+ spikes in cytosol and mitochondrial matrix, with concomitant declines in ER luminal Ca2+. Me-cAMP/AM also effectively triggered store-operated Ca2+ entry (SOCE), suggesting that Epac-agonist is capable of depleting ER Ca2+ stores. These Epac-induced intracellular and inter-organelle Ca2+ signals were mimicked by the RyR agonist 4-CMC, but they were distinctly different from IP3R activation. The present study hence demonstrated that mpkCCD cells retain all reported features of Ca2+ mobilization observed in isolated perfused IMCD. It further revealed information on the dynamics of Epac-induced RyR-dependent Ca2+ signaling and ER-mitochondrial Ca2+ transfer. ER-mitochondrial Ca2+ coupling may play a key role in the regulation of ATP and reactive oxygen species (ROS) production in the mitochondria along the nephron. Our data suggest that mpkCCD cells can serve as a renal cell model to address novel questions of how mitochondrial Ca2+ regulates cytosolic Ca2+ signals, inter-organellar Ca2+ signaling, and renal tubular functions.

Systematic review and meta-analysis on population attributable fraction for physical inactivity to dementia.

INTRODUCTION: The number of cases of dementia attributable to physical inactivity remains unclear due to heterogeneity in physical inactivity definitions and statistical approaches used. METHODS: Studies that used population-based samples to estimate the population attributable fraction (PAF) of physical inactivity for dementia were included in this review. Weighted PAFs were adjusted for communality among the risk factors (i.e., inactive persons may also share other risk factors) analyzed. Values were reported as percentage (%) of cases of dementia attributable to physical inactivity. RESULTS: We included 22 studies. The overall impact of physical inactivity, defined by any criteria, on dementia ranged from 6.6% (95% CI: 3.6%, 9.6%; weighted) to 16.6% (95% CI: 14.4%, 18.9%; unweighted). Studies using the WHO criterion for physical inactivity estimated a higher unweighted impact (ß = 7.3%; 95% CI: 2.0%, 12.6%) than studies using other criteria. DISCUSSION: Conservatively, one in 15 cases of dementia may be attributable to physical inactivity, defined by any criteria.

Chikungunya virus infection in the southernmost state of Brazil was characterised by self-limited transmission (2017-2019) and a larger 2021 outbreak.

BACKGROUND: Chikungunya is a mosquito-borne virus that has been causing large outbreaks in the Americas since 2014. In Brazil, Asian-Caribbean (AC) and East-Central-South-African (ECSA) genotypes have been detected and lead to large outbreaks in several Brazilian states. In Rio Grande do Sul (RS), the southernmost state of Brazil, the first cases were reported in 2016. OBJECTIVES AND METHODS: We employed genome sequencing and epidemiological investigation to characterise the Chikungunya fever (CHIKF) burden in RS between 2017-2021. FINDINGS: We detected an increasing CHIKF burden linked to travel associated introductions and communitary transmission of distinct lineages of the ECSA genotype during this period. MAIN CONCLUSIONS: Until 2020, CHIKV introductions were most travel associated and transmission was limited. Then, in 2021, the largest outbreak occurred in the state associated with the introduction of a new ECSA lineage. CHIKV outbreaks are likely to occur in the near future due to abundant competent vectors and a susceptible population, exposing more than 11 million inhabitants to an increasing infection risk.

Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling.

Junctions between the endoplasmic reticulum (ER) and the plasma membrane (PM) are specialized membrane contacts ubiquitous in eukaryotic cells. Concentration of intracellular signaling machinery near ER-PM junctions allows these domains to serve critical roles in lipid and Ca2+ signaling and homeostasis. Subcellular compartmentalization of protein kinase A (PKA) signaling also regulates essential cellular functions, however, no specific association between PKA and ER-PM junctional domains is known. Here, we show that in brain neurons type I PKA is directed to Kv2.1 channel-dependent ER-PM junctional domains via SPHKAP, a type I PKA-specific anchoring protein. SPHKAP association with type I PKA regulatory subunit RI and ER-resident VAP proteins results in the concentration of type I PKA between stacked ER cisternae associated with ER-PM junctions. This ER-associated PKA signalosome enables reciprocal regulation between PKA and Ca2+ signaling machinery to support Ca2+ influx and excitation-transcription coupling. These data reveal that neuronal ER-PM junctions support a receptor-independent form of PKA signaling driven by membrane depolarization and intracellular Ca2+, allowing conversion of information encoded in electrical signals into biochemical changes universally recognized throughout the cell.

Antiulcer mechanisms of the hydroalcoholic extract from Aztec marigolds' medicinal and edible flowers (Tagetes erecta L.).

The antiulcer mechanisms of the dry extract of T. erecta flowers (DETe) were studied here. The acute ulcers induced by acidified ethanol or indomethacin were reproduced in mice pretreated with DETe (3 - 300 mg/kg). The antiulcer activity of DETe was also verified in mice pretreated with NEM, L-NAME, indomethacin, or yohimbine. The antisecretory effect of DETe was verified in rats, and its anti-Helicobacter pylori activity was determined in vitro. DETe (300 mg/kg, p.o) reduced the ethanol- or indomethacin-induced ulcer by 49 and 93%, respectively. The pre-treatment with L-NAME, NEM or yohimbine abolished the gastroprotective effect of DETe. However, DETe did not change the volume, acidity, or peptic activity in rats and did not affect H. pylori. This study expands knowledge about the antiulcerogenic potential of DETe, evidencing the role of nitric oxide, non-protein sulfhydryl groups, α2 adrenergic receptors, and prostaglandins, but not antisecretory or anti-H. pylori properties.