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In mammals, the central circadian oscillator is located in the suprachiasmatic nucleus (SCN). Hypothalamus-pituitary-thyroid axis components exhibit circadian oscillation, regulated by both central clock innervation and intrinsic circadian clocks in the anterior pituitary and thyroid glands. Thyroid disorders alter the rhythmicity of peripheral clocks in a tissue-dependent response; however, whether these effects are influenced by alterations in the master clock remains unknown. This study aimed to characterize the effects of hypothyroidism on the rhythmicity of SCN, body temperature (BT) and metabolism, and the possible mechanisms involved in this signalling. C57BL/6J adult male mice were divided into Control and Hypothyroid groups. Profiles of spontaneous locomotor activity (SLA), BT, oxygen consumption ( V Ì O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ) and respiratory quotient (RQ) were determined under free-running conditions. Clock gene expression, and neuronal activity of the SCN and medial preoptic nucleus (MPOM) area were investigated in light-dark (LD) conditions. Triiodothyronine (T3) transcriptional regulation of Bmal1 promoter activity was evaluated in GH3-transfected cells. Hypothyroidism delayed the rhythmicity of SLA and BT, and altered the expression of core clock components in the SCN. The activity of SCN neurons and their outputs were also affected, as evidenced by the loss of circadian rhythmicity in V Ì O 2 ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ and RQ and alterations in the neuronal activity pattern of MPOM. In GH3 cells, T3 increased Bmal1 promoter activity in a time-dependent manner. Thyroid hormone may act as a temporal cue for the central circadian clock, and the uncoupling of central and peripheral clocks might contribute to a wide range of metabolic and thermoregulatory impairments observed in hypothyroidism. KEY POINTS: Hypothyroidism alters clock gene expression in the suprachiasmatic nucleus (SCN). Thyroid hypofunction alters the phase of spontaneous locomotor activity and body temperature rhythms. Thyroid hormone deficiency alters the daily pattern of SCN and medial preoptic nucleus neuronal activities. Hypothyroidism alterations are extended to daily oscillations of oxygen consumption and metabolism, which might contribute to the development of metabolic syndrome. Triiodothyronine increases Bmal1 promoter activity acting as temporal cue for the central circadian clock.
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Fatores de Transcrição ARNTL , Hipotireoidismo , Camundongos Endogâmicos C57BL , Núcleo Supraquiasmático , Tri-Iodotironina , Animais , Masculino , Hipotireoidismo/fisiopatologia , Hipotireoidismo/metabolismo , Hipotireoidismo/genética , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Camundongos , Núcleo Supraquiasmático/metabolismo , Núcleo Supraquiasmático/fisiologia , Ritmo Circadiano/fisiologia , Temperatura Corporal/fisiologia , Relógios Circadianos/genética , Relógios Circadianos/fisiologia , Regulação da Expressão GênicaRESUMO
Paracoccidioidomycosis (PCM) is a systemic granulomatous mycosis prevalent in individuals who carry out rural activities. Its etiological agent is a thermodimorphic fungus belonging to the genus; Paracoccidioides spp. Seven species of this fungus are known: Paracoccidioides brasiliensis, Paracoccidioides lutzii, Paracoccidioides americana, Paracoccidioides restrepiensis, Paracoccidioides venezuelensis, Paracoccidioides loboi and Paracoccidioides ceti. For a long time, Paracoccidioides brasiliensis was attributed as the only causal agent of this mycosis. What is known about adhesins, virulence, escape mechanisms and fungal involvement with the host's immune system is correlated with the species Paracoccidioides brasiliensis. Interactions between Paracoccidioides spp. and the host are complex and dynamic. The fungus needs nutrients for its needs and must adapt to a hostile environment, evading the host's immune system, thus enabling the development of the infectious process. On the other hand, the host's immune system recognizes Paracoccidioides spp. and employs all protective mechanisms to prevent fungal growth and consequently tissue invasion. Knowing this, understanding how Paracoccidioides spp. escapes the host's immune system, can help to understand the pathogenic mechanisms related to the development of the disease and, therefore, in the design of new specific treatment strategies. In this review we discuss these mechanisms and what are the adhesion molecules of Paracoccidioides spp. uses to escape the hostile environment imposed by the host's defense mechanisms; finally, we suggest how to neutralize them with new antifungal therapies.
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Interações Hospedeiro-Patógeno , Paracoccidioides , Paracoccidioidomicose , Paracoccidioides/patogenicidade , Paracoccidioides/imunologia , Paracoccidioidomicose/microbiologia , Paracoccidioidomicose/imunologia , Humanos , Virulência , Evasão da Resposta Imune , AnimaisRESUMO
It is estimated that there are over 500 species of arboviruses worldwide, with more than 150 of them directly associated with human diseases, the majority of which are zoonotic. Among the main arboviruses circulating in Brazil, dengue, Zika, and chikungunya stand out, all transmitted through a common vector, Aedes aegypti. Given this scenario, the development and implementation of more efficient surveillance strategies become urgent. This study aims to compare and evaluate the efficiency of beetroot peel, Beta vulgaris, as an attractant for Ae. aegypti oviposition under field conditions in the municipality of Agrestina, State of Pernambuco, Brazil. Beetroot peel extract is a cheap and accessible source of geosmin, which holds significant potential as an attractant for mosquitoes due to its resemblance to microbial volatiles found in water bodies rich in organic material. During the study period (November 2023 to April 2024), 40 traps were set in each neighborhood, with 20 of each attractant. Two traps were used per property, one following the traditionally used model (beer yeast infusion) and another containing beetroot peel. Overall, in both analyzed neighborhoods (Campo Novo and Cohab), beetroot peel appeared to be a more efficient attractant for the oviposition of culicids. Beetroot peel showed the highest values in egg abundance and in the analyzed indices.
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Aedes , Beta vulgaris , Controle de Mosquitos , Mosquitos Vetores , Oviposição , Animais , Brasil , Beta vulgaris/química , Feminino , ArbovírusRESUMO
PURPOSE: To assess the test-retest and inter-rater reliability of goniometry and fleximetry in measuring cervical range of motion in individuals with chronic neck pain. METHODS: A reliability study. Thirty individuals with chronic neck pain were selected. Cervical range of motion was measured by goniometry and fleximetry at two time points 7 days apart. To characterize the sample, we used the numerical pain rating scale, Pain-Related Catastrophizing Thoughts Scale, and Neck Disability Index. Intraclass correlation coefficient (ICC), standard error of measurement (SEM) and minimum detectable change (MDC) were calculated. Correlations between goniometry and fleximetry measurements were performed using Spearman's correlation coefficient (rho). RESULTS: For goniometry, we found excellent test-retest reliability (ICC ≥ 0.986, SEM ≤ 1.89%, MDC ≤ 5.23%) and inter-rater reliability (ICC ≥ 0.947, SEM ≤ 3.91%, MDC ≤ 10.84%). Similarly, we found excellent test-retest reliability (ICC ≥ 0.969, SEM ≤ 2.71%, MDC ≤ 7.52%) and inter-rater reliability (ICC ≥ 0.981, SEM ≤ 1.88%, MDC ≤ 5.20%) for fleximetry. Finally, we observed a strong correlation between the goniometry and the fleximetry for all cervical movements (rho ≥ 0.993). CONCLUSION: Goniometry and fleximetry measurements are reliable for assessing cervical range of motion in individuals with chronic neck pain.
Assuntos
Artrometria Articular , Vértebras Cervicais , Dor Crônica , Cervicalgia , Amplitude de Movimento Articular , Humanos , Cervicalgia/fisiopatologia , Cervicalgia/diagnóstico , Amplitude de Movimento Articular/fisiologia , Feminino , Reprodutibilidade dos Testes , Masculino , Dor Crônica/fisiopatologia , Dor Crônica/diagnóstico , Artrometria Articular/métodos , Adulto , Pessoa de Meia-Idade , Vértebras Cervicais/fisiopatologia , Medição da Dor/métodos , Variações Dependentes do ObservadorRESUMO
BACKGROUND: Celecoxib, an anti-inflammatory drug, combined therapies using antimicrobials and immune modulator drugs are being studied. OBJECTIVE: To assess whether Celecoxib has direct in vitro antifungal effect against the Paracoccidioides brasiliensis, the causative agent of Paracoccidioidomycosis-(PCM) and also if it improves the in vivo activity of neutrophils-(PMN) in an experimental murine subcutaneous-(air pouch) model of the disease. METHODS: The antifungal activity of Celecoxib(6 mg/mL) on P. brasiliensis-(Pb18) was evaluated using the microdilution technique. Splenocytes co-cultured with Pb18 and treated with Celecoxib(6 mg/mL) were co-cultured for 24, 48 and 72-hours. Swiss mice were inoculated with Pb18 and treated with Celecoxib(6 mg/kg) in the subcutaneous air pouch. Neutrophils were collected from the air pouch. Mitochondrial activity, reactive oxygen production, catalase, peroxidase, cytokines and chemokines, nitrogen species, total protein, microbicidal activity of PMNs and viable Pb18 cells numbers were analyzed. RESULTS: Celecoxib had no cytotoxic effect on splenocytes co-cultured with Pb18, but had a marked direct antifungal effect, inhibiting fungal growth both in vitro and in vivo. Celecoxib interaction with immune system cells in the air pouch, it leads to activation of PMNs, as confirmed by several parameters (mitochondrial activity, reactive oxygen species, peroxidase, KC and IL-6 increase, killing constant and phagocytosis). Celecoxib was able to reduce IL-4, IL-10 and IL-12 cytokine production. The number of recovered viable Pb18 decreased dramatically. CONCLUSIONS: This is the first report of the direct antifungal activity of Celecoxib against P. brasiliensis. The use of Celecoxib opens a new possibility for future treatment of PCM.
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Antifúngicos , Celecoxib , Neutrófilos , Paracoccidioides , Paracoccidioidomicose , Animais , Paracoccidioides/efeitos dos fármacos , Paracoccidioides/imunologia , Camundongos , Celecoxib/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Paracoccidioidomicose/tratamento farmacológico , Paracoccidioidomicose/imunologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Citocinas/metabolismo , Células Cultivadas , Masculino , Baço/imunologia , Baço/citologia , Baço/efeitos dos fármacos , Modelos Animais de Doenças , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Risk stratification is an important step in perioperative evaluation. However, the main risk scores do not incorporate biomarkers in their set of variables. OBJECTIVE: Evaluate the incremental power of troponin to the usual risk stratification. METHODS: A total of 2,230 patients admitted to the intensive care unit after non-cardiac surgery were classified according to three types of risk: cardiovascular risk (CVR), Revised Cardiac Risk Index (RCRI); and inherent risk of surgery (IRS). The main outcome was all-cause mortality. Cox regression was used as well as c-statistics before and after addition of high-sensitivity troponin (at least one measurement up to three days after surgery). Finally, net reclassification index and integrated discrimination improvement were used to assess the incremental power of troponin for risk stratification. Significance level was set at 0.05. RESULTS: Mean age of patients was 63.8 years and 55.6% were women. The prevalence of myocardial injury after non-cardiac surgery (MINS) was 9.4%. High CVR-patients had a higher occurrence of MINS (40.1 x 24.8%, p<0.001), as well as high IRS-patients (21.3 x 13.9%, p=0.004) and those with a RCRI≥3 (3.0 x 0.7%, p=0.009). Patients without MINS, regardless of the assessed risk, had similar mortality rate. The addition of troponin to the risk assessment improved the predictive ability of death at 30 days and at 1 year in all risk assessments. CONCLUSION: The prevalence of MINS is higher in the high-risk population. However, its prevalence in lower-risk population is not negligible and causes a higher risk of death. The addition of high-sensitivity troponin increased the predictive ability of risk assessment in all groups.
FUNDAMENTO: A estratificação ode risco é uma importante etapa na avaliação perioperatória. No entanto, os principais escores de risco não incorporam biomarcadores em seus conjuntos de variáveis. OBJETIVO: Avaliar o poder incremental da troponina à estratificação de risco tradicional. MÉTODOS: Um total de 2230 pacientes admitidos na unidade de terapia intensiva após cirurgia não cardíaca foram classificados de acordo com três tipos de risco: Risco Cardiovascular (RCV), Índice de Risco Cardíaco Revisado (IRCR), e Risco Inerente da Cirurgia (RIC). O principal desfecho foi mortalidade por todas as causas. A regressão de Cox foi usada, assim como a estatística C antes e após a adição de troponina ultrassensível (pelo menos uma medida até três dias após a cirurgia). Finalmente, o índice de reclassificação líquida e a melhoria de discriminação integrada foram usadas para avaliar o poder incremental da troponina para a estratificação de risco. O nível de significância usado foi de 0,05. RESULTADOS: A idade média dos pacientes foi 63,8 anos e 55,6% eram do sexo feminino. A prevalência de lesão miocárdica após cirurgia não cardíaca (MINS) foi 9,4%. Pacientes com um RCV elevado apresentaram uma maior ocorrência de MINS (40,1% x 24,8%, p<0,001), bem como pacientes com alto RIC (21,3 x 13,9%, p=0,004) e aqueles com IRCR≥3 (3,0 x 0,7%, p=0,009). Pacientes sem MINS, independentemente do risco avaliado, apresentaram taxa de mortalidade similar. A adição de troponina à avaliação de risco melhorou a capacidade preditiva de mortalidade em 30 dias e de mortalidade em um ano em todas as avaliações de risco. CONCLUSÃO: A prevalência de MINS é mais alta na população de alto risco. No entanto, sua prevalência na população de risco mais baixo não é desprezível e causa um maior risco de morte. A adição da troponina ultrassensível melhorou a capacidade preditiva da avaliação de risco em todos os grupos.
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Biomarcadores , Troponina , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Biomarcadores/sangue , Idoso , Troponina/sangue , Fatores de Risco , Período Perioperatório , Valor Preditivo dos Testes , Procedimentos Cirúrgicos Operatórios/mortalidade , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Fatores de Tempo , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/sangueRESUMO
The yeast-encapsulated orange oil (YEOO) is a novel larvicide under development against vector mosquitoes. Despite its efficiency against Aedes aegypti (L.) in small scale experiments, its applicability in vector control can be influenced by other effects on mosquito behaviour or physiology. For this reason, the impact of YEOO particles in mosquito oviposition was evaluated in laboratory and semi-field conditions. Oviposition assays with one gravid Aedes aegypti female were carried under laboratory and semi-field conditions with natural light and temperature fluctuation. For all ovitraps, the number of eggs was manually counted in the wooden paddle and in the solution of each ovitrap. The proportion of eggs between substrates (wooden paddle and solution) varied between conditions, with females in laboratory presenting a lower preference to lay eggs in paddles when compared with studies in semi-field. This behaviour shifts in laboratory can create challenges to extrapolate results from laboratory to the field. Here, studies in both conditions indicate a similar impact of YEOO particles in Aedes aegypti oviposition. The potential treatment concentration of YEOO particles presents a strong repellent/deterrent effect (-0.559 > OAI > -0.760) within the initial 72h of application when compared with water, and weak repellent/deterrent signal (OAI = -0.220) when compared against inactivated yeast. Control ovitraps with water were more positive for egg presence than treated ovitraps, while ovitraps with YEOO particles and inactivated yeast present similar number of positive ovitraps. It is possible that the repellent/deterrent action is partially driven by the delivery system, since most times Citrus sinensis EO oviposition repellent/deterrent signal is weak, and it seem influenced by solvent/delivery used. However, it is unclear how the yeast wall that protect/surrounds the orange oil will negatively affect oviposition since live yeast are normally consider an attractant for mosquito oviposition.
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Aedes , Controle de Mosquitos , Oviposição , Óleos de Plantas , Aedes/fisiologia , Aedes/efeitos dos fármacos , Animais , Oviposição/efeitos dos fármacos , Feminino , Óleos de Plantas/farmacologia , Controle de Mosquitos/métodos , Mosquitos Vetores/fisiologia , Mosquitos Vetores/efeitos dos fármacos , Saccharomyces cerevisiae/fisiologia , Repelentes de Insetos/farmacologiaRESUMO
Resumo Fundamento A estratificação ode risco é uma importante etapa na avaliação perioperatória. No entanto, os principais escores de risco não incorporam biomarcadores em seus conjuntos de variáveis. Objetivo Avaliar o poder incremental da troponina à estratificação de risco tradicional. Métodos Um total de 2230 pacientes admitidos na unidade de terapia intensiva após cirurgia não cardíaca foram classificados de acordo com três tipos de risco: Risco Cardiovascular (RCV), Índice de Risco Cardíaco Revisado (IRCR), e Risco Inerente da Cirurgia (RIC). O principal desfecho foi mortalidade por todas as causas. A regressão de Cox foi usada, assim como a estatística C antes e após a adição de troponina ultrassensível (pelo menos uma medida até três dias após a cirurgia). Finalmente, o índice de reclassificação líquida e a melhoria de discriminação integrada foram usadas para avaliar o poder incremental da troponina para a estratificação de risco. O nível de significância usado foi de 0,05. Resultados A idade média dos pacientes foi 63,8 anos e 55,6% eram do sexo feminino. A prevalência de lesão miocárdica após cirurgia não cardíaca (MINS) foi 9,4%. Pacientes com um RCV elevado apresentaram uma maior ocorrência de MINS (40,1% x 24,8%, p<0,001), bem como pacientes com alto RIC (21,3 x 13,9%, p=0,004) e aqueles com IRCR≥3 (3,0 x 0,7%, p=0,009). Pacientes sem MINS, independentemente do risco avaliado, apresentaram taxa de mortalidade similar. A adição de troponina à avaliação de risco melhorou a capacidade preditiva de mortalidade em 30 dias e de mortalidade em um ano em todas as avaliações de risco. Conclusão A prevalência de MINS é mais alta na população de alto risco. No entanto, sua prevalência na população de risco mais baixo não é desprezível e causa um maior risco de morte. A adição da troponina ultrassensível melhorou a capacidade preditiva da avaliação de risco em todos os grupos.
Abstract Background Risk stratification is an important step in perioperative evaluation. However, the main risk scores do not incorporate biomarkers in their set of variables. Objective Evaluate the incremental power of troponin to the usual risk stratification Methods A total of 2,230 patients admitted to the intensive care unit after non-cardiac surgery were classified according to three types of risk: cardiovascular risk (CVR), Revised Cardiac Risk Index (RCRI); and inherent risk of surgery (IRS). The main outcome was all-cause mortality. Cox regression was used as well as c-statistics before and after addition of high-sensitivity troponin (at least one measurement up to three days after surgery). Finally, net reclassification index and integrated discrimination improvement were used to assess the incremental power of troponin for risk stratification. Significance level was set at 0.05. Results Mean age of patients was 63.8 years and 55.6% were women. The prevalence of myocardial injury after non-cardiac surgery (MINS) was 9.4%. High CVR-patients had a higher occurrence of MINS (40.1 x 24.8%, p<0.001), as well as high IRS-patients (21.3 x 13.9%, p=0.004) and those with a RCRI≥3 (3.0 x 0.7%, p=0.009). Patients without MINS, regardless of the assessed risk, had similar mortality rate. The addition of troponin to the risk assessment improved the predictive ability of death at 30 days and at 1 year in all risk assessments. Conclusion The prevalence of MINS is higher in the high-risk population. However, its prevalence in lower-risk population is not negligible and causes a higher risk of death. The addition of high-sensitivity troponin increased the predictive ability of risk assessment in all groups.
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The capuchin monkey (Sapajus apella), a New World monkey species, exhibits prominent characteristics that make it an ideal model for neuroscience research. These characteristics include its phylogenetic traits, telencephalization coefficient, anatomical structures and pathways, genetic profile, immune responses, cognitive abilities, and complex behavioral repertoires. Traditionally, methodologies for stereotactic neurosurgery in research models have relied on the use of brain atlases. However, this approach can lead to errors due to the considerable variation in brain size and shape among individual monkeys. To address this issue, we developed a protocol for deriving individual coordinates for each monkey using a straightforward and relatively inexpensive method involving MRI imaging. Our protocol utilizes a specially designed, 3D-printed stereotactic head-holder that is safe to use with an MR magnet, non-invasive placement of fiducial markers, and post-processing with open-source software. This approach enhances MRI data visualization, improves anatomical targeting, and refines the design of neurosurgical experiments. Our technique could also prove beneficial in other areas of neuroscience research that require accurate calculation of stereotaxic coordinates. Furthermore, it could be useful for other nonhuman primate species for which brain atlases are typically unavailable.
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BACKGROUND: Central Illustration : Predictive Model of All-Cause Death in Patients with Heart Failure using Heart Rate Variability. BACKGROUND: Short and long-duration heart rate variability (HRV) data from Holter monitoring could identify predictors of all-cause death in heart failure (HF) patients. OBJECTIVES: To build a predictive model of all-cause death in patients with HF using HRV. METHODS: Retrospective study including patients with suspected or confirmed HF who were admitted for decompensated HF or syncope that underwent Holter monitoring. In analysis of augmented sympathetic tonus, we evaluated the lowest HRV in nonoverlapping 10-minutes periods throughout 24h continuous electrocardiographic signal recording (short HRV variables). Variables with p<0.01 were included in a multivariate Cox regression model to determine the occurrence of the all-cause death. Variables with statistical significance in Cox regression were chosen to build the predictive model. P<0.05 was considered significant. RESULTS: A total of 116 patients were included, mean age of 71.9±16.3 years, 45.7% men, mean follow-up of 2.83±1.27 years. Thirty-nine deaths occurred (33.6%). By comparing survivors vs. non-survivors, the variables that showed statistical significance were lowest SDNN, lowest rMSSD, age and left ventricular ejection fraction (LVEF). In Cox regression, independent predictors of all-cause death were: age>69 years (HR 3.95, 95%CI 1.64-9.52); LVEF≤57% (HR 4.70, 95%CI 2.38-9.28) and lowest rMSSD≤12ms (HR 5.54, 95%CI 2.04-15.08). An integer value was assigned to each variable. Score<3 showed AUC=0.802 (95%CI 0.72-0.87). CONCLUSION: In HF patients hospitalized for decompensated HF or syncope, independent long-term predictors of all-cause death were age, LVEF, and 10-minutes rMSSD. These findings indicate that even brief moments of high sympathetic tone can impact survival, specifically in the elderly and patients with HF with reduced ejection fraction.
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Insuficiência Cardíaca , Função Ventricular Esquerda , Masculino , Humanos , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Feminino , Frequência Cardíaca/fisiologia , Volume Sistólico , Função Ventricular Esquerda/fisiologia , Estudos Retrospectivos , SíncopeRESUMO
OBJECTIVE: To analyze the association between municipal rates of ambulatory care sensitive conditions (ACSC) hospitalization and the quality of primary health care (PHC), socioeconomic, and demographic variables and those related to local characteristics of the health system from 2010 to 2019. METHOD: Ecological time series study in Brazilian municipalities analyzing the correlation of ACSC hospitalization rates with PHC quality measured by the three cycles of the Primary Care Access and Program for improving primary care access and quality (PMAQ-AB). The study included municipalities whose teams participated in 80% or more of at least two PMAQ-AB cycles. The correlation between standardized ACSC hospitalization rates and PHC quality and other variables was analyzed. Spearman's test was used between the response variable and numerical explanatory variables. Generalized equations estimation was used as a multivariate model associating ACSC hospitalization rates with the other variables over the years. RESULTS: A total of 3,500 municipalities were included in the models. The quality of PHC (PMAQ-AB score) showed an inverse association with the variation in ACSC hospitalization rates. Hospitalization rates fell by -2% per year every ten-point increase in the PMAQ-AB score, adjusted by the remaining variables. A one-unit increase in the beds per 1,000 inhabitants variable had an impact of approximately +6.4% on ACSC hospitalization rates. Regarding population size, larger municipalities had lower ACSC hospitalization rates. Increased PHC coverage and lower socioeconomic inequality were also associated with the reduction in hospitalizations. CONCLUSIONS: The reduction in ACSC hospitalization rates over time was associated with an increase in the quality of PHC. It was also associated with a reduction in the number of hospital beds and municipalities with better socioeconomic indicators.
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Assistência Ambulatorial , Hospitalização , Humanos , Brasil , Fatores Socioeconômicos , Atenção Primária à SaúdeRESUMO
Bio-based materials, such as wood bio-concrete (WBC), hold promise in reducing energy consumption and carbon footprint of the construction industry. However, the durability of these materials is not well understood and can be negatively affected by the high water absorption capacity of wood bio-aggregates. In the field of cement composites, for example, silane-siloxane-based water repellent has been used to protect such materials from natural environmental attack. Nevertheless, there is still a limited understanding of various aspects related to this type of treatment, including its performance when applied to the bio-concrete substrate. This research aimed to investigate the influence of silane-siloxane on the rheology and hydration of cementitious paste through isothermal calorimetry and thermogravimetric analysis. Additionally, the impact of silane-siloxane on the physical and mechanical properties of WBCs was examined by conducting tests at fresh state (flow table and entrained air content) and hardened state (compressive strength and capillary water absorption). The composites were produced with a volumetric fraction of 45% of wood shavings while the cement matrix consisted of a combination of cement, rice husk ash, and fly ash. Silane-siloxane was applied in three ways: as coating, incorporated as an admixture, and in a combination of both methods. The results indicated that by incorporating silane in the cementitious pastethe viscosity increased by 40% and the hydration was delayed by approximately 6 h when compared to the reference. In addition, silane improved the compressive strength of WBCs by 24% when incorporated into the mixture, expressively reduced the water sorptivity of WBCs (93%), and was more effective if used as coating.
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Primary familial brain calcification (PFBC), often called Fahr's disease, is a condition in which calcium phosphate accumulates in the brain, mainly in the basal ganglia, thalamus, and cerebellum, and without the association of any metabolic or infectious cause. Patients present a variety of neurological and psychiatric disorders, usually during adulthood. The disease is caused by autosomal dominant pathogenic variants in genes such as SLC20A2, PDGFRB, PDGFB, and XPR1. MYORG and JAM2 are the other genes linked to homozygous patterns of inheritance. Here, we briefly discuss the recent cases reported by Ceylan et al. (2022) and Al-Kasbi et al. (2022), which challenge the current association with two previous genes and a clear pattern of inheritance. Ceylan et al. report a new biallelic variant related to a pathogenic variant in the SLC20A2 gene, which is typically associated with a heterozygous mutation pattern. The affected siblings displayed a severe and early onset of the disease, revealing a phenotype similar to that seen in CMV infections, often named as pseudo-TORCH. Furthermore, a study of genes related to intellectual disability conducted by Al-Kasbi et al. demonstrated that the biallelic manifestation of the XPR1 gene was associated with early symptoms, leading to the belief that the homozygous pattern of genes responsible for causing PFBC with an autosomal dominant pattern may also be linked to early-onset manifestations of PFBC. Further studies might explore the variety of clinical presentations linked to PFBC genes, especially if we pay attention to complex patterns of inheritance, reinforcing the need for a more detailed bioinformatic analysis.
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Doenças dos Gânglios da Base , Encefalopatias , Humanos , Adulto , Encefalopatias/metabolismo , Receptor do Retrovírus Politrópico e Xenotrópico , Encéfalo/metabolismo , Mutação , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/metabolismoRESUMO
The potential of fluoride (F) as a neurotoxicant in humans is still controversial in the literature. However, recent studies have raised the debate by showing different mechanism of F-induced neurotoxicity, as oxidative stress, energy metabolism and inflammation in the central nervous system (CNS). In the present study, we investigated the mechanistic action of two F concentration (0.095 and 0.22 µg/ml) on gene and protein profile network using a human glial cell in vitro model over 10 days of exposure. A total of 823 genes and 2,084 genes were modulated after exposure to 0.095 and 0.22 µg/ml F, respectively. Among them, 168 were found to be modulated by both concentrations. The number of changes in protein expression induced by F were 20 and 10, respectively. Gene ontology annotations showed that the main terms were related to cellular metabolism, protein modification and cell death regulation pathways, such as the MAP kinase (MAPK) cascade, in a concentration independent manner. Proteomics confirmed the changes in energy metabolism and also provided evidence of F-induced changes in cytoskeleton components of glial cells. Our results not only reveal that F has the potential to modulate gene and protein profiles in human U87 glial-like cells overexposed to F, but also identify a possible role of this ion in cytoskeleton disorganization.
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COVID-19 , Cardiopatias , Doenças Vasculares , Humanos , Síndrome de COVID-19 Pós-Aguda , COVID-19/complicaçõesRESUMO
Introduction: Diabetes mellitus describes a metabolic disorder of multiple etiologies, characterized by chronic hyperglycemia, which induces a series of molecular events capable of leading to microvascular damage, affecting the blood vessels of the retina, causing diabetic retinopathy. Studies indicate that oxidative stress plays a central role in complications involving diabetes. Açaí (Euterpe oleracea) has attracted much attention given its antioxidant capacity and potential associated health benefits in preventing oxidative stress, one of the causes of diabetic retinopathy. The objective of this work was to evaluate the possible protective effect of açaí (E. oleracea) on the retinal function of mice with induced diabetes, based on full field electroretinogram (ffERG). Methods: We opted for mouse models with induced diabetes by administration of a 2% alloxan aqueous solution and treatment with feed enriched with açaí pulp. The animals were divided into 4 groups: CTR (received commercial ration), DM (received commercial ration), DM + açaí (E. oleracea-enriched ration) and CTR + açaí (E. oleracea-enriched ration). The ffERG was recorded three times, 30, 45 and 60 days after diabetes induction, under scotopic and photopic conditions to access rod, mixed and cone responses, in addition to monitoring the weight and blood glucose of the animals during the study period. Statistical analysis was performed using the two-way ANOVA test with Tukey's post-test. Results: Our work obtained satisfactory results with the ffERG responses in diabetic animals treated with açaí, where it was observed that there was no significant decrease in the b wave ffERG amplitude of this group over time when compared to the results of the Diabetic group not treated with açaí, which showed a significant reduction of this ffERG component. Discussion: The results of the present study show, for the first time, that treatment with an açaí-enriched diet is effective against the decrease in the amplitude of visual electrophysiological responses in animals with induced diabetes, which opens a new horizon for the prevention of retinal damage in diabetic individuals from treatment with açaí base. However, it is worth mentioning that our findings consist of a preliminary study and further researches and clinical trials are needed to examine açaí potential as an alternative therapy for diabetic retinopathy.
Assuntos
Insuficiência Cardíaca , Humanos , Nitrogênio da Ureia Sanguínea , Volume Sistólico , Prognóstico , CreatininaRESUMO
Abstract Background Literature is scarce on echocardiographic characteristics of COVID-19 patients admitted to the intensive care unit (ICU). Objectives To describe echocardiographic characteristics of ICU COVID-19 patients and associate them with clinical signals/symptoms, laboratory findings and outcomes. Methods Patients with RT-PCR-confirmed COVID-19, admitted to the ICU, who underwent echocardiography were included. Clinical characteristics associated with an abnormal echocardiogram (systolic ventricular dysfunction of any degree — left and/or right ventricle — and/or high filling pressures and/or moderate to severe pericardial effusion) were analyzed. Groups were compared using the Student's t-test, chi-square, and logistic regression. A p < 0.05 was considered statistically significant. Results A total of 140 patients met inclusion criteria, and 74 (52.9%) had an abnormal echocardiogram. A low number of left and right ventricular systolic dysfunction was observed, and 35% of the population had a normal diastolic function. In the univariate analysis, characteristics associated with abnormal echocardiogram were age, chronic kidney disease, elevated troponin, previous heart failure, and simplified acute physiology score 3 (SAPS 3). In the regression model, troponin and SAPS3 score were independent markers of abnormal echocardiogram. An abnormal echocardiogram was associated with a higher prevalence of in-hospital death (RR 2.10; 95% CI 1.04-4.24) and orotracheal intubation (RR 2.3; 95% CI 1.14-4.78). Conclusions COVID-19 has little effect on ventricular function, but it is common to find increased filling pressures. Elevated serum troponin level and SAPS3 score were the independent markers of an abnormal echocardiogram. In addition, the prevalence of in-hospital death and need for mechanical ventilation were higher in patients with abnormal echocardiogram.