Cardiac Manifestations of Hemochromatosis.

Cardiac hemochromatosis, a consequence of primary or secondary iron-overload conditions, poses a threat to patient health, leading to cardiomyopathy and heart failure. This review aims to compile comprehensive information on cardiac hemochromatosis, elucidating its pathophysiology, clinical presentation, diagnosis, and management strategies. Primary and secondary hemochromatosis, genetic and acquired forms, can result in cardiotoxicity by means of iron dysregulation. Diagnostic tools, including biochemical markers, electrocardiography, echocardiography, and magnetic resonance imaging (MRI), are utilized for early detection as well as long-term monitoring post-treatment. For treatment options, phlebotomy is the standard, but for some patients (such as those with anemia), chelation therapy is an alternative option. Other potential therapies include erythrocytapheresis, calcium channel blockers, and hepcidin-targeted approaches, for which more research is needed to understand cardiac function benefits. With the onset of cardiac symptoms, patient health rapidly deteriorates. Thus, timely intervention to mitigate associated morbidity and mortality by means of screening can promote and prolong patient survival.

Aqueous PM2.5 promotes lipid accumulation, classical macrophage polarisation and heat shock response.

Fine particulate matter (PM2.5) is an air pollutant that enhances susceptibility to cardiovascular diseases. Macrophages are the first immune cells to encounter the inhaled particles and orchestrate an inflammatory response. Given their role in atherosclerosis development, we investigated whether aqueous PM2.5 could elicit atherogenic effects by polarising macrophages to a pro-oxidative and pro-inflammatory phenotype and enhancing foam cell formation. The RAW264.7 macrophage cell line was exposed to PM2.5 for 48 h, with PBS as the control. Aqueous PM2.5 induced apoptosis and reduced cell proliferation. In surviving cells, we observed morphological, phagocytic, oxidative, and inflammatory features (i.e. enhanced iNOS, Integrin-1ß, IL-6 expression), indicative of classical macrophage activation. We also detected an increase in total and surface HSP70 levels, suggesting macrophage activation. Further, exposure of high-cholesterol diet-fed mice to PM2.5 resulted in aortic wall enlargement, indicating vascular lesions. Macrophages exposed to PM2.5 and non-modified low-density lipoprotein (LDL) showed exacerbated lipid accumulation. Given the non-oxidised LDL used and the evidence linking inflammation to disrupted cholesterol negative feedback, we hypothesise that PM2.5-induced inflammation in macrophages enhances their susceptibility to transforming into foam cells. Finally, our results indicate that exposure to aqueous PM2.5 promotes classical macrophage activation, marked by increased HSP70 expression and that it potentially contributes to atherosclerosis.

Select Dietary Components Are Associated With Better Global Cognition in U.S. Adults With HIV: A Pilot Study.

ABSTRACT: People with HIV (PWH) are at an increased risk for cognitive impairment. Lifestyle factors can have protective effects on cognition; little work has examined diet and cognitive function in PWH. In this cross-sectional pilot study, 86 PWH (mean age 56 years) completed diet recalls and a neurocognitive assessment. Correlations were conducted between diet and cognitive function, adjusting for total calories, sex, and education (multiple comparison correction p values are reported). Diet quality of the sample was poor. Greater calories per day ( r = 0.28, p =.08) and greater percentage of calories from saturated fatty acids (SFAs; r = 0.26, p = 0.08) were associated with better cognition. Higher intake of SFAs ( r s 0.30-0.31, p s = 0.07), amino acids ( r s = 0.27, p s = 0.08), and phosphorus ( r = 0.29, p = .07) and magnesium ( r = 0.25, p = .08) were associated with better cognition. A diet reflecting higher protein and fat relative to carbohydrates was associated with better cognition. Targeting individual nutrients, improving diet quality, and adequate caloric intake may preserve cognition in PWH.

Real-life intrinsic capacity screening data from the ICOPE-Care program.

The Integrated Care for Older People (ICOPE) program is a healthcare pathway that uses a screening test for intrinsic capacity (IC) as its entry point. However, real-life data informing on how IC domains cluster and change over time, as well as their clinical utility, are lacking. Using primary healthcare screening data from more than 20,000 French adults 60 years of age or older, this study identified four clusters of IC impairment: 'Low impairment' (most prevalent), 'Cognition+Locomotion+Hearing+Vision', 'All IC impaired' and 'Psychology+Vitality+Vision'. Compared to individuals with 'Low impairment', those in the other clusters had higher likelihood of having frailty and limitations in both activities of daily living (ADL) and instrumental activities of daily living (IADL), with the strongest associations being observed for 'All IC impaired'. This study found that ICOPE screening might be a useful tool for patient risk stratification in clinical practice, with a higher number of IC domains impaired at screening indicating a higher probability of functional decline.

Clinical and immunological features of laryngeal cryptococcosis.

The literature holds few descriptions on immune response findings for laryngeal cryptococcosis. Immunology has been more extensively described in cases involving the central nervous system and the lungs, although many of these studies were conducted in animal models. We aimed to analyze the clinical and immunological characteristics of three patients with laryngeal cryptococcosis. We observed a weak participation of the innate immune response, whereas adaptive immunity showed the predominance of a Th2-type response over a Th1-type response. Most cases occur in male older adults with immunosuppressive conditions, of which HIV infection was absent. Hoarseness configured the main symptom. We found a disease that was restricted to the larynx and possibly the lungs by contiguity. Patients with hoarseness and lesions in nasal endoscopy should be investigated for cryptococcosis by a biopsy of the larynx, including with negative serum cryptococcal antigen. The immunological aspects of our findings of laryngeal involvement resembled those in the most commonly affected systems.

A multicentre study of amphotericin B treatment for histoplasmosis: assessing mortality rates and adverse events.

BACKGROUND: Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates. OBJECTIVES: Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality. METHODS: This multicentre retrospective cohort study (January 2014-December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses. RESULTS: The study included 215 patients, mostly male (n = 158, 73%) with HIV infection (n = 187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (n = 19, 90%), acute kidney injury (n = 96, 59%), hypokalaemia (n = 73, 55%) and infusion reactions (n = 44, 20%) during treatment. CONCLUSIONS: We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis.

Infection by zika virus increase angiotensin I-converting enzyme activity in mouse brain.

Congenital zika virus syndrome (CZS) has become a significant worldwide concern since the sudden rise of microcephaly related to zika virus (ZIKV) in Brazil. Primarily transmitted by Aedes mosquitoes, ZIKV shares serologic similarities with dengue virus (DENV), complicating the diagnosis and/or clinical management. The Angiotensin I-Converting Enzyme (ACE) was associated with either neuroprotective or anti-inflammatory properties in the central nervous system (CNS). The possible role(s) of ACE in these two flaviviruses infection remain largely unexplored. In this study, we evaluate ACE activity in the brain of ZIKV- or DENV-infected mice, both compared to MOCK, showing about 30 % increased ACE activity only in ZIKV-infected mice (p = 0.024), while no change was noticed in brain from DENV-infected animals (p = 0.888). In addition, the treatment with interferon beta (IFNß), under conditions previously demonstrated to rescue the normal size of microcephalic brains determined by ZIKV infection, also restored ACE activity in ZIKV-infected animals to levels close to that of the MOCK control group. Although inflammatory responses expected for either ZIKV or DENV infections, only ZIKV was associated with microcephaly, as well as with increased ACE activity and reversion by treatment with IFNß. Furthermore, this increase in ACE activity was observed only after intracerebroventricular (ICV) injection (F (2, 16) = 7.907, p = 0.004), but not for intraperitoneal (IP) administration of ZIKV (F (2, 26) = 1.996, p = 0.156), suggesting that the observed central ACE activity modulation may be associated with the presence of this specific flavivirus in the brain.

Histoplasmosis in a fingolimod-treated patient: case report and scoping review.

Fingolimod is a sphingosine-1-phosphate receptor modulator used to treat multiple sclerosis. While fingolimod has been associated with an increased risk of cryptococcal meningitis, its correlation with other deep mycoses remains unclear. In this study, we conducted a scoping review of fingolimod associated with histoplasmosis, based on a case report, a literature review, and data from the FDA Adverse Events Reporting System (FAERS) as of January 24th, 2023. A 30-year-old Brazilian woman diagnosed with relapsing-remitting multiple sclerosis, receiving a daily dose of 0.5 mg of fingolimod, presented with a two-month history of fever and unintended weight loss, accompanied by lymphadenopathy, splenomegaly, and lung involvement was investigated. Biopsy of a lung nodule revealed fungal structures suggestive of Histoplasma sp. Additionally, serological testing yielded positive for Histoplasma capsulatum. Disseminated histoplasmosis should be considered in the differential diagnosis of febrile syndromes in patients undergoing fingolimod therapy for multiple sclerosis, particularly in the Americas, where this mycosis is endemic. Treatment with itraconazole and modification of immunotherapy can achieve excellent clinical outcomes.

Validity of equations for estimating fat-free mass in people living with the human immunodeficiency virus.

BACKGROUND & AIMS: Equations estimating fat-free mass (FFM) in people living with the human immunodeficiency virus (HIV) show differences in the validation process. The current study aimed to verify the validity of FFM estimation equations derived from bioelectrical impedance (BIA) in people living with HIV aged 40 years and older. METHODS: A cross-sectional study was conducted with 68 participants evaluated using dual-energy X-ray absorptiometry (DXA) and by two BIA devices (Analyzer and Biodynamics). The study aimed to determine the validity of six different FFM equations from four different studies by Lukaski and Bolonchuk (1987), Kotler et al. (1996), Beraldo et al. (2015) and Hegelund et al. (2017). Comparisons were made using the t-test or Wilcoxon test. To verify the validity between DXA and two BIA devices, the following statistical analyses were performed: Lin's concordance correlation coefficient, intraclass correlation coefficient, coefficient of determination, standard error of the estimate, differences in the limits of agreement by Bland and Altman analysis, correlation between the average and the differences of the methods by Pearson or Spearman correlation. RESULTS: Only equation 2 of Kotler et al. (1996) for males by Biodynamics BIA showed no difference in FFM. The Lin's concordance correlation coefficient was excellent (0.96), irrespective of sex, for Equation 2 of Kotler et al. (1996) by BIA Analyzer. All equations were reproducible (>0.85). The coefficient of determination ranged from 68% to 92%, and the standard error of the estimates ranged from 1.8 kg to 5.0 kg. The differences between the limits of agreement ranged from 7.2 kg to 14.9 kg, and the correlations between the average and the differences of the methods showed differences in FFM for three equations (p < 0.01). CONCLUSION: The choice of equations must consider the equipment used and the sex of the sample investigated. Only Equation 2 of Kotler et al. (1996) was considered valid, irrespective of sex, to estimate the FFM by BIA Analyzer.

Association between neuroimaging and clinical outcomes in individuals with central nervous system cryptococcosis.

BACKGROUND: The radiological manifestations of central nervous system (CNS) cryptococcosis are diverse and often subtle. There is heterogeneity on how different neuroimaging patterns impact prognosis. This study aims to assess the association between the neuroimaging and clinical outcomes of CNS cryptococcosis. METHODS: All patients with CNS cryptococcosis between July 2017 and April 2023 who underwent brain magnetic resonance imaging (MRI) were included. The primary outcome was mortality during hospitalisation. Secondary outcomes were readmission, ventricular shunting, duration of hospitalisation and time to the first negative cerebrospinal fluid culture. We compared the outcomes for each of the five main radiological findings on the brain MRI scan. RESULTS: We included 46 proven CNS cryptococcosis cases. The two main comorbidity groups were HIV infection (20, 43%) and solid organ transplantation (10, 22%), respectively. Thirty-nine patients exhibited at least one radiological abnormality (85%), with the most common being meningeal enhancement (34, 74%). The mortality rates occurred at 11% (5/46) during hospitalisation. We found no significant disparities in mortality related to distinct radiological patterns. The presence of pseudocysts was significantly associated with the need for readmission (p = .027). The ventricular shunting was significantly associated with the presence of pseudocysts (p = .005) and hydrocephalus (p = .044). CONCLUSION: In this study, there is no association between brain MRI findings and mortality. Larger studies are needed to evaluate this important issue.

Objectively measured physical activity among people with and without HIV in Uganda: associations with cardiovascular risk and coronary artery disease.

Background: Africa has a disproportionate burden of HIV-related cardiovascular disease. We aimed to describe physical activity in people living with HIV (PLHIV) and people without HIV (PWOH) in Uganda and characterize its relationship with the presence of computed tomography angiography-detected (CCTA) coronary artery disease (CAD). Methods: We performed a cross-sectional analysis of the Ugandan Study of HIV Effects on the Myocardium and Atherosclerosis using Computed Tomography (mUTIMA-CT) cohort. From 2017-2019, physical activity in PLHIV and PWOH was assessed by accelerometry over seven days. Participants additionally underwent CCTA. Univariable and multivariable modified Poisson regression was used to analyze the relationship between physical activity and CAD presence. Results: 168 participants were analyzed. The median (IQR) age was 57 (53-58) years old and 64% were female. Males had more moderate-to-vigorous physical activity per week [68 minutes (12-144) vs 15 minutes (0-50), P<0.001] and less light physical activity [788 minutes (497-1,202) vs [1,059 (730-1490), P=0.001] compared to females, but there was no difference by HIV status. After adjusting for age, which accounted for 10% of the variation in steps taken, and sex, no significant associations were found between physical activity and coronary plaque. Conclusion: Objectively measured physical activity was low compared to guideline recommendations, with males being somewhat more active than females and without significant differences by HIV status. Physical activity was not associated with the presence of CAD independently of age and sex.

Analysis of epidemiological and clinical aspects in cases of fungal osteomyelitis caused by non-Candida species.

Osteomyelitis caused by non-Candida species is rare and often neglected, and current recommendations are based on primarily clinical experience and expert opinion. The objective of this study was to describe a case series of non-Candida fungal osteomyelitis. This retrospective study included 10 patients with non-Candida fungal osteomyelitis. Patients with osteomyelitis and microbiologically confirmed non-Candida species from bone fragment cultures were selected from the institution Infection Control Board database. Fusarium spp. were the most commonly isolated fungus from bone fragment cultures in five patients (50%). The majority did not present immunosuppression. The most common etiology was post-traumatic (n = 7, 70%), particularly open fractures. All patients were treated with antifungals associated with surgery. The antifungals used were itraconazole in five patients (50%), and voriconazole in another five patients (50%), with a median duration of antifungal therapy of four weeks (range: 3-25). There were no observed deaths within 30 days and one year. An antifungal approach combined with surgical treatment demonstrated favorable clinical outcomes, including low mortality rates and effective remission.

Fatal hepatic mucormycosis in an allogeneic hematopoietic-stem cell transplanted patient: Case report of a rare presentation and review of the literature.

Hepatic mucormycosis is a rare condition. Our objective is to report a case in a HSCT patient and to perform a review of the literature. A 36-year-old man with acute myeloid leukemia, performed a haploidentical HSCT. In D+132, when treating acute GVHD with methylprednisolone and etanercept, a hepatic abscess was diagnosed. Puncture of the abscess was performed, and fungal hyphae were visualized. The culture of the aspirate identified Mucor sp. Sequencing confirmed the isolate as Mucor indicus. The patient died despite the use of Amphotericin B. Our search identified 24 hepatic mucormycosis reports. Fifteen (62.5 %) were male and 79.1 % were immunocompromised. Fever accompanied with abdominal pain was present in 41.6 %. Twelve (50.0 %) had multiple hepatic lesions. Mortality rate was 45.8 % (n = 11/24). In conclusion, the most common clinical presentation of hepatic mucormycosis in immunocompromised patients might be abdominal pain and fever, along with hepatic abscess findings in abdominal imaging exams.

Repeated doses of captopril induce airway hyperresponsiveness by modulating the TRPV1 receptor in rats.

Although TRPV1 receptors play an essential role in the adverse effects on the airways following captopril treatment, there is no available evidence of their involvement in treatment regimens involving repeated doses of captopril. Comparing the difference in these two treatment regimens is essential since captopril is a continuous-use medication. Thus, this study explored the role of the transient receptor potential vanilloid 1 (TRPV1) in the effects of captopril on rat airways using two treatment regimens. Airway resistance, bronchoalveolar lavage (BAL), and histological and immunohistochemical analyses were conducted in rats administered with single or repeated doses of captopril. This study showed that the hyperresponsiveness to bradykinin and capsaicin in captopril-treated rats was acute. Treatment with the selective B2 antagonist, HOE140 reduced bradykinin hyperresponsiveness and abolished capsaicin exacerbation in single-dose captopril-treated rats. Likewise, degeneration of TRPV1-positive neurones also reduced hyperresponsiveness to bradykinin. Single-dose captopril treatment increased leukocyte infiltration in the BAL when compared with the vehicle and this increase was reduced by TRPV1-positive neurone degeneration. However, when compared with the vehicle treatment, animals treated with repeated doses of captopril showed an increase in leukocyte influx as early as 1 h after the last captopril treatment, but this effect disappeared after 24 h. Additionally, an increase in TRPV1 expression occurred only in animals who received repeated captopril doses and the degeneration of TRPV1-positive neurones attenuated TRPV1 upregulation. In conclusion, these data strongly indicate that a treatment regimen involving multiple doses of captopril not only enhances sensitisation but also upregulates TRPV1 expression. Consequently, targeting TRPV1 could serve as a promising strategy to reduce the negative impact of captopril on the airways.

Role of TRPA1 in the pharmacological effect triggered by the topical application of trans-anethole in mice.

PURPOSE: This study investigated the pharmacological effects of topical trans-anethole, a natural compound found in anise, star anise, and fennel essential oils, and its relationship with the transient receptor potential of ankyrin 1 (TRPA1). METHODS: The effects of topical anethole were assessed by eye wiping, nociceptive behaviour, and ear oedema in mice. Histological evaluations were performed on the ears of the animals topically treated with anethole. RESULTS: Anethole caused less eye irritation than capsaicin (a TRPV1 agonist) and allyl isothiocyanate (a TRPA1 agonist). Anethole (250 and 500 nmol/20 µL/paw) promoted neurogenic nociception in the paw (20.89 ± 3.53 s and 47.56 ± 8.46 s, respectively) compared with the vehicle (0.88 ± 0.38 s). HC030031 (56.1 nmol/20 µL/paw), a TRPA1 antagonist, abolished this nociceptive response. Anethole (4, 10, and 20 µmol/20 µL/ear) induced ear oedema (30.25 ± 4.78 µm, 78.00 ± 3.74 µm, and 127.50 ± 27.19 µm, respectively) compared with the vehicle (5.00 ± 0.5 µm). HC030031 (56.1 nmol/20 µL/ear) inhibited the oedema induced by anethole (10 µmol/20 µL/ear). Ears pre-treated with anethole or allyl isothiocyanate on the first day and re-exposed to these compounds on the third day showed a reduction in oedema (68.16 ± 6.04% and 38.81 ± 8.98.9%, respectively). Cross-desensitisation between anethole and allyl isothiocyanate was observed. Histological analysis confirmed the beneficial effects of anethol. CONCLUSION: As repeated topical applications of anethole induce the desensitisation of TRPA1, we suggest its clinical application as a topical formulation for treating skin diseases or managing pain associated with this receptor. Anethole may also have advantages over capsaicin and allyl isothiocyanate because of its low pungency and pleasant aroma.

The ICOPE-WHO and the IVCF-20: a critical view of the Handbook for Multidimensional Geriatric Assessment in Primary Care / O ICOPE-OMS e o IVCF-20: observações críticas sobre o Manual de Avaliação Multidimensional da Pessoa Idosa para a Atenção Primária à Saúde

O rápido envelhecimento populacional impulsiona iniciativas com o objetivo de otimizar a saúde da população idosa em todo o mundo. Recentemente, no Brasil, foi publicado pelo Conselho Nacional dos Secretários de Saúde (CONASS) o Manual de Avaliação Multidimensional da Pessoa Idosa, que propõe a adoção combinada e em larga escala da ferramenta de triagem do ICOPE da Organização Mundial da Saúde (OMS) e do instrumento Índice de Vulnerabilidade Clínico-Funcional-20 (IVCF-20) para definir linhas de cuidado à pessoa idosa. Embora iniciativas dessa natureza sejam prementes, os instrumentos propostos ainda não têm validação adequada na população brasileira, e a sua utilização com o objetivo de balizar diretrizes em saúde em todo o território nacional parece precipitada e arriscada. Diante disso, propõe-se um debate amplo e urgente entre os especialistas da área, com o objetivo de planejar políticas de saúde pública eficazes e seguras para a população idosa brasileira. (AU)

Rapid population aging is driving initiatives aimed at optimizing the health of older populations worldwide. In Brazil, the National Council of State Secretaries of Health (CONASS) recently published the Handbook for Multidimensional Geriatric Assessment in Primary Care, which proposes the combined, large-scale adoption of the World Health Organization (WHO) ICOPE screening tool and the Clinical-Functional Vulnerability Index-20 (IVCF-20) instrument to define care pathways for older people. Although there is a pressing need for initiatives of this nature, the proposed instruments have not yet been adequately validated in the Brazilian population, and their use for the purpose of establishing countrywide health guidelines appears hasty and risky. Therefore, we propose a broad, urgent debate among experts in the field with the aim of planning effective and safe public health policies for the Brazilian older population. (AU)

Assessment of intrinsic capacity in the Brazilian older population and the psychometric properties of the WHO/ ICOPE screening tool: a multicenter cohort study protocol / Avaliação da capacidade intrínseca da população idosa brasileira e das propriedades psicométricas do instrumento de triagem do ICOPE/OMS: protocolo de estudo de coorte multicêntrico

Introduction: The World Health Organization (WHO) has proposed to monitor intrinsic capacity (IC) in the older population as a public health strategy through the Integrated Care for Older People (ICOPE) program. Although the program has been developed based on solid concepts, scientific evidence on its practical applicability is still scarce. Objectives: To evaluate IC in Brazilian older adults, its progress over time, and its association with sociodemographic and health factors and outcomes. To evaluate the psychometric properties of the WHO/ICOPE screening tool. Methods: This is a prospective multicenter cohort study with a 36-month follow-up. We will recruit 3838 people aged ≥60 years, registered in the health care units included in the study by the participating centers. We will collect sociodemographic and health data and will administer tools to assess IC domains, both those provided for in the ICOPE screening tool and the sequence of confirmatory assessments provided for in the program. Participants will be reassessed every 6 months for 36 months. Expected results: To establish the profile of IC in the study population and to understand its progress and the variables associated with the clinical outcomes of interest. To reveal the diagnostic and psychometric properties of the WHO/ICOPE screening tool. The project is funded by the Brazilian National Council for Scientific and Technological Development (CNPq). Relevance: Understanding the potential use of the ICOPE public health strategy proposed by the WHO within the scope of the Brazilian Unified Health System (SUS) by integrating several research centers in the field of Geriatrics and Gerontology throughout Brazil. (AU)

Introdução: A Organização Mundial da Saúde (OMS) propõe o monitoramento da capacidade intrínseca (CI) da população idosa como estratégia de saúde pública por meio do Programa ICOPE (Integrated Care for Older People). Embora construído com base em conceitos sólidos, a evidência científica sobre a aplicabilidade prática da proposta ainda é escassa. Objetivo: Avaliar a capacidade intrínseca da população idosa brasileira, sua trajetória e sua associação com variáveis sociodemográficas, de saúde e desfechos. Avaliar as propriedades psicométricas da ferramenta de triagem da estratégia ICOPE da OMS. Metodologia: Coorte multicêntrica prospectiva com seguimento de 36 meses. Serão recrutadas 3.838 pessoas com 60 anos ou mais, cadastradas nas unidades de saúde incluídas no estudo pelos centros participantes. Serão coletados dados sociodemográficos e de saúde e aplicados instrumentos para avaliação dos domínios da CI, tanto aqueles previstos no instrumento de triagem do ICOPE quanto a sequência de avaliações confirmatórias previstas no programa. Os participantes serão acompanhados semestralmente ao longo de 36 meses. Resultados esperados: Estabelecer o perfil da CI na população estudada, entender a sua trajetória e as variáveis associadas aos desfechos clínicos avaliados. Revelar as propriedades diagnósticas e o perfil psicométrico da ferramenta de triagem do ICOPE da OMS. O projeto tem financiamento do Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Relevância: Compreensão sobre o potencial de utilização da estratégia ICOPE de saúde pública proposta pela OMS no âmbito do Sistema Único de Saúde (SUS) pela integração de diversos centros de pesquisa científica na área de Geriatria e Gerontologia de todo o Brasil. (AU)

Mechanistic insights on the antibacterial action of the kyotorphin peptide derivatives revealed by in vitro studies and Galleria mellonella proteomic analysis.

OBJECTIVES: The selected kyotorphin derivatives were tested to improve their antimicrobial and antibiofilm activity. The antimicrobial screening of the KTP derivatives were ascertained in the representative strains of bacteria, including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli and Pseudomonas aeruginosa. METHODS: Kyotorphin derivatives, KTP-NH2, KTP-NH2-DL, IbKTP, IbKTP-NH2, MetKTP-DL, MetKTP-LD, were designed and synthesized to improve lipophilicity and resistance to enzymatic degradation. Peptides were synthesized by standard solution or solid-phase peptide synthesis and purified using RP-HPLC, which resulted in >95 % purity, and were fully characterized by mass spectrometry and 1H NMR. The minimum inhibitory concentrations (MIC) determined for bacterial strains were between 20 and 419 µM. The direct effect of IbKTP-NH2 on bacterial cells was imaged using scanning electron microscopy. The absence of toxicity, high survival after infection and an increase in the hemocytes count was evaluated by injections of derivatives in Galleria mellonella larvae. Proteomics analyses of G. mellonella hemolymph were performed to investigate the underlying mechanism of antibacterial activity of IbKTP-NH2 at MIC. RESULTS: IbKTP-NH2 induces morphological changes in bacterial cell, many differentially expressed proteins involved in DNA replication, synthesis of cell wall, and virulence were up-regulated after the treatment of G. mellonella with IbKTP-NH2. CONCLUSION: We suggest that this derivative, in addition to its physical activity on the bacterial membranes, can elicit a cellular and humoral immune response, therefore, it could be considered for biomedical applications.

Restoration of degraded estuarine and marine ecosystems: A systematic review of rehabilitation methods in Europe.

This article provides a comprehensive study of ecosystem rehabilitation methods widely used in the 21st century, focusing on Europe. The review covers the evolution and trends in scientific article publication, identification of European countries demonstrating high publication outputs, collaboration patterns, leading journals, and thematic areas. Additionally, it examines primary stressors in European aquatic ecosystems, and different methods and treatments commonly employed for remediation purposes. The analysis of selected articles revealed a significant increase in studies over time, driven by public awareness and financial incentives from national, European and global organizations. Italy, Portugal and Spain were the leading countries in degraded ecosystem rehabilitation studies, mainly focusing on remediating contaminated areas where metals were identified as the primary stressor (chemical pollution). Chemical remediation method emerged as the most used, closely followed by biological remediation method, which have gained prominence in recent years due to their ecological, economic, and social combined benefits. Furthermore, recent studies demonstrate a growing trend towards the combined use of more than one treatment/method to rehabilitate ecosystems, particularly with biological treatments. This combined approach has the potential for synergistic effects in achieving more effective rehabilitation and their sustainability in the long term, thus, a focus for future research.