Prevalence of chronic cough, its risk factors and population attributable risk in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study.

Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors. Funding: Wellcome Trust.

Comparison of important factors to patients recovering from pulmonary embolism and items covered in patient-reported outcome measures: A mixed-methods systematic review.

OBJECTIVE: Up to 50 % of patients recovering from pulmonary embolism (PE) experience negative long-term outcomes. Patient-reported outcome measures (PROMs) are important in identifying what matters to patients. We aimed to identify PROMs used in clinical studies and recommended by the International Consortium of Health Outcomes (ICHOM) and compare individual items with factors considered important by patients recovering from PE. METHODS: This was a convergent mixed-methods systematic review, including quantitative studies, using PROMs and qualitative studies with non-cancer-related PE patients. Items from each PROM and qualitative findings were categorised using an International Classification of Function linking process to allow for integrated synthesis. RESULTS: A total of 68 studies using 34 different PROMs with 657 items and 13 qualitative studies with 408 findings were included. A total of 104 individual ICF codes were used, and subsequently sorted into 20 distinct categories representing patient concerns. Identified PROMs were found to adequately cover 17/20 categories, including anxiety, fear of bleeding, stress, depression, dizziness/nausea, sleep disturbance, pain, dyspnea, fatigue, activity levels, family and friends, socializing, outlook on life, and medical treatment. PROMs from the ICHOM core set covered the same categories, except for dizziness/nausea. CONCLUSIONS: No single PROM covered all aspects assessed as important by the PE population. PROMs recommended in the ICHOM core set cover 16/20 aspects. However, worrisome thoughts, hypervigilance around symptoms, and uncertainty of illness were experienced by patients with PE but were not covered by PROMS.

Astrocytoma Mimicking Herpetic Meningoencephalitis: The Role of Non-Invasive Multimodal Monitoring in Neurointensivism.

Neuromonitoring is a critical tool for emergency rooms and intensive care units to promptly identify and treat brain injuries. The case report of a patient with status epilepticus necessitating orotracheal intubation and intravenous lorazepam administration is presented. A pattern of epileptiform activity was detected in the left temporal region, and intravenous Acyclovir was administered based on the diagnostic hypothesis of herpetic meningoencephalitis. The neurointensivist opted for multimodal non-invasive bedside neuromonitoring due to the complexity of the patient's condition. A Brain4care (B4C) non-invasive intracranial compliance monitor was utilized alongside the assessment of an optic nerve sheath diameter (ONSD) and transcranial Doppler (TCD). Based on the collected data, a diagnosis of intracranial hypertension (ICH) was made and a treatment plan was developed. After the neurosurgery team's evaluation, a stereotaxic biopsy of the temporal lesion revealed a grade 2 diffuse astrocytoma, and an urgent total resection was performed. Research suggests that monitoring patients in a dedicated neurologic intensive care unit (Neuro ICU) can lead to improved outcomes and shorter hospital stays. In addition to being useful for patients with a primary brain injury, neuromonitoring may also be advantageous for those at risk of cerebral hemodynamic impairment. Lastly, it is essential to note that neuromonitoring technologies are non-invasive, less expensive, safe, and bedside-accessible approaches with significant diagnostic and monitoring potential for patients at risk of brain abnormalities. Multimodal neuromonitoring is a vital tool in critical care units for the identification and management of acute brain trauma as well as for patients at risk of cerebral hemodynamic impairment.

Exercise-based real-time telerehabilitation for older patients recently discharged after transcatheter aortic valve implantation: An extended feasibility study.

OBJECTIVES: To assess the extended feasibility of a telerehabilitation program and its effects on physical performance in older adults who have recently undergone transcatheter aortic valve implantation (TAVI). METHODS: In this single-center feasibility study, patients underwent an eight-week telerehabilitation program, involving web-based home exercise training twice weekly, an activity tracker, access to an informative website, and one online session with a nurse, starting one-week postoperative. Data collection was performed before surgery and three months postoperative. The feasibility of the intervention was based on recruitment and adherence to the program. As a secondary outcome, we evaluated the change in six-minute walk distance from before surgery to three months postoperative. RESULTS: Forty-one patients scheduled for TAVI were assessed for eligibility; 15 patients (37%) were enrolled. Of these, eight were excluded after surgery due to tiredness (n = 2), non-cardiac related hospital readmission (n = 2), fluctuating health (n = 1), death during hospital stay (n = 1), and reduced cognition (n = 2). Seven patients completed the eight-week web-based intervention and were evaluated three months postoperative. Their median (IQR) age was 83 [81, 87] years, and the sample comprised three men and four women. Their walked distance improved from median (IQR) 262 [199, 463] before surgery, to 381 [267, 521] meters three months postoperative. No adverse events were reported. CONCLUSION: Web-based telerehabilitation, including supervised exercise training, in older adults who have recently undergone TAVI was feasible for a small number of patients who completed the eight-week intervention. This was reflected in an improvement in their walked distance three months after the surgery. However, the low recruitment and retention rates do question the overall feasibility of this intervention in a frail, older population of post-TAVI patients.

Animal Welfare in Radiation Research: The Importance of Animal Monitoring System.

Long-term research into radiation exposure significantly expanded following World War II, driven by the increasing number of individuals falling ill after the detonation of two atomic bombs in Japan. Consequently, researchers intensified their efforts to investigate radiation's effects using animal models and to study disease models that emerged post-catastrophe. As a result, several parameters have been established as essential in these models, encompassing radiation doses, regimens involving single or multiple irradiations, the injection site for transplantation, and the quantity of cells to be injected. Nonetheless, researchers have observed numerous side effects in irradiated animals, prompting the development of scoring systems to monitor these animals' well-being. The aim of this review is to delve into the historical context of using animals in radiation research and explore the ethical considerations related to animal welfare, which has become an increasingly relevant topic in recent years. These concerns have prompted research groups to adopt measures aimed at reducing animal suffering. Consequently, for animal welfare, the implementation of a scoring system for clinical and behavioral monitoring is essential. This represents one of the primary challenges and hurdles in radiation studies. It is concluded that implementing standardized criteria across all institutions is aimed at ensuring result reproducibility and fostering collaboration within the scientific community.

Lectin-based carbohydrate profile of megakaryocytes in murine fetal liver during development.

Hematopoiesis is the process by which blood cells are generated. During embryonic development, these cells migrate through different organs until they reach the bone marrow, their definitive place in adulthood. Around E10.5, the fetal liver starts budding from the gut, where first hematopoietic cells arrive and expand. Hematopoietic cell migration occurs through cytokine stimulation, receptor expression, and glycosylation patterns on the cell surface. In addition, carbohydrates can modulate different cell activation states. For this reason, we aimed to characterize and quantify fetal megakaryocytic cells in mouse fetal liver according to their glycan residues at different gestational ages through lectins. Mouse fetuses between E11.5 and E18.5 were formalin-fixed and, paraffin-embedded, for immunofluorescence analysis using confocal microscopy. The results showed that the following sugar residues were expressed in proliferating and differentiating megakaryocytes in the fetal liver at different gestational ages: α-mannose, α-glucose, galactose, GlcNAc, and two types of complex oligosaccharides. Megakaryocytes also showed three proliferation waves during liver development at E12.5, E14.5, and E18.5. Additionally, the lectins that exhibited high and specific pattern intensities at liver capsules and vessels were shown to be a less time-consuming and robust alternative alternative to conventional antibodies for displaying liver structures such as capsules and vessels, as well as for megakaryocyte differentiation in the fetal liver.

Long-Term Outcomes Following Bipolar Transurethral Plasma Enucleation of the Prostate: 10-Year Follow-Up.

Background and Purpose: The aim of our study is to assess the long-term outcomes and safety of bipolar transurethral plasma enucleation of the prostate (B-TUEP) in patients with lower urinary tract symptoms (LUTS) in a single-center cohort study. Our focus is to evaluate the impact on outcomes after 10 years of follow-up (FUP) in terms of recurrence, LUTS, and patients' quality of life after B-TUEP in prostates between 30 and 80 cc. Materials and Methods: Between May 2010 and December 2011, all consecutive patients with benign prostatic hyperplasia undergoing B-TUEP were prospectively enrolled in our study. Data on patients' history, physical examination, prostate volumes, erectile function, prostate-specific antigen levels, International Prostate Symptoms Score (IPSS), and uroflowmetry were collected at 0, 1, 3, 6, 12, 24, 36, 60, and 120 months. Early and long-term complications were recorded. Results: A total of 50 consecutive patients underwent B-TUEP in our facility, all performed by a single surgeon (R.G.). Twelve patients were excluded during the 10 years. No patients had persistent bladder outlet obstruction (BOO) requiring reoperation. In terms of results, the improvement in IPSS was sustained throughout 5 years, and the mean difference from baseline at 5 years was 17 points, with similar results at 10 years. Erectile function was also slightly improved after surgery and maintained for the next 5 years, with a slight age-related decrease at 10 years. Furthermore, the improvements in maximum urine flow rate (Qmax) were maintained at 5 years, with a mean improvement of 16 mL/s, while at 10 years, it settled on a mean improvement from baseline of 12 mL/s. Conclusions: In our 10 years' experience, B-TUEP is a safe and highly effective technique for relieving BOO, with excellent outcomes and no recurrence at 10 years of FUP. Further multicenter studies should confirm our results.

Small airways obstruction and its risk factors in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study.

BACKGROUND: Small airways obstruction is a common feature of obstructive lung diseases. Research is scarce on small airways obstruction, its global prevalence, and risk factors. We aimed to estimate the prevalence of small airways obstruction, examine the associated risk factors, and compare the findings for two different spirometry parameters. METHODS: The Burden of Obstructive Lung Disease study is a multinational cross-sectional study of 41 municipalities in 34 countries across all WHO regions. Adults aged 40 years or older who were not living in an institution were eligible to participate. To ensure a representative sample, participants were selected from a random sample of the population according to a predefined site-specific sampling strategy. We included participants' data in this study if they completed the core study questionnaire and had acceptable spirometry according to predefined quality criteria. We excluded participants with a contraindication for lung function testing. We defined small airways obstruction as either mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FEF25-75) less than the lower limit of normal or forced expiratory volume in 3 s to forced vital capacity ratio (FEV3/FVC ratio) less than the lower limit of normal. We estimated the prevalence of pre-bronchodilator (ie, before administration of 200 µg salbutamol) and post-bronchodilator (ie, after administration of 200 µg salbutamol) small airways obstruction for each site. To identify risk factors for small airways obstruction, we performed multivariable regression analyses within each site and pooled estimates using random-effects meta-analysis. FINDINGS: 36 618 participants were recruited between Jan 2, 2003, and Dec 26, 2016. Data were collected from participants at recruitment. Of the recruited participants, 28 604 participants had acceptable spirometry and completed the core study questionnaire. Data were available for 26 443 participants for FEV3/FVC ratio and 25 961 participants for FEF25-75. Of the 26 443 participants included, 12 490 were men and 13 953 were women. Prevalence of pre-bronchodilator small airways obstruction ranged from 5% (34 of 624 participants) in Tartu, Estonia, to 34% (189 of 555 participants) in Mysore, India, for FEF25-75, and for FEV3/FVC ratio it ranged from 5% (31 of 684) in Riyadh, Saudi Arabia, to 31% (287 of 924) in Salzburg, Austria. Prevalence of post-bronchodilator small airways obstruction was universally lower. Risk factors significantly associated with FEV3/FVC ratio less than the lower limit of normal included increasing age, low BMI, active and passive smoking, low level of education, working in a dusty job for more than 10 years, previous tuberculosis, and family history of chronic obstructive pulmonary disease. Results were similar for FEF25-75, except for increasing age, which was associated with reduced odds of small airways obstruction. INTERPRETATION: Despite the wide geographical variation, small airways obstruction is common and more prevalent than chronic airflow obstruction worldwide. Small airways obstruction shows the same risk factors as chronic airflow obstruction. However, further research is required to investigate whether small airways obstruction is also associated with respiratory symptoms and lung function decline. FUNDING: National Heart and Lung Institute and Wellcome Trust. TRANSLATIONS: For the Dutch, Estonian, French, Icelandic, Malay, Marathi, Norwegian, Portuguese, Swedish and Urdu translations of the abstract see Supplementary Materials section.

Intranasally Delivered Adenoviral Vector Protects Chickens against Newcastle Disease Virus: Vaccine Manufacturing and Stability Assessments for Liquid and Lyophilized Formulations.

Newcastle disease (ND) remains a critical disease affecting poultry in sub-Saharan Africa. In some countries, repeated outbreaks have a major impact on local economies and food security. Recently, we developed an adenovirus-vectored vaccine encoding the Fusion protein from an Ethiopian isolate of Newcastle disease virus (NDV). The adenoviral vector was designed, and a manufacturing process was developed in the context of the Livestock Vaccine Innovation Fund initiative funded by the International Development Research Centre (IDRC) of Canada. The industrially relevant recombinant vaccine technology platform is being transferred to the National Veterinary Institute (Ethiopia) for veterinary applications. Here, a manufacturing process using HEK293SF suspension cells cultured in stirred-tank bioreactors for the vaccine production is proposed. Taking into consideration supply chain limitations, options for serum-free media selection were evaluated. A streamlined downstream process including a filtration, an ultrafiltration, and a concentration step was developed. With high volumetric yields (infectious titers up to 5 × 109 TCID50/mL) in the culture supernatant, the final formulations were prepared at 1010 TCID50/mL, either in liquid or lyophilized forms. The liquid formulation was suitable and safe for mucosal vaccination and was stable for 1 week at 37 °C. Both the liquid and lyophilized formulations were stable after 6 months of storage at 4 °C. We demonstrate that the instillation of the adenoviral vector through the nasal cavity can confer protection to chickens against a lethal challenge with NDV. Overall, a manufacturing process for the adenovirus-vectored vaccine was developed, and protective doses were determined using a convenient route of delivery. Formulation and storage conditions were established, and quality control protocols were implemented.

The relationship between burden and caregiver's sleep disturbances in dementia: a systematic review / A relação entre sobrecarga e sono do cuidador na demência: um estudo de revisão sistemática

ABSTRACT Caregivers of people living with dementia (PLwD) have a high burden degree that leads to health issues, including sleep. Objective: This study aimed to analyze the impacts of the caregiving burden on caregiver's sleep disturbances. Methods: This systematic review involved a qualitative analysis of publications on Web of Science and Pubmed/Medline databases published between February 2018 and August 2022. Results: A total of 27 studies were identified and analyzed. Caregiver's sleep presents impairments in sleep latency, sleep fragmentation, sleep duration, subjective sleep quality, daytime dysfunction, and insomnia. Caregiver's distress and depressive symptoms have a dual relationship with sleep problems. Conclusion: Sleep disturbances presented by caregivers are correlated with higher burden levels and lead to more vulnerability to psychiatric symptoms and health issues.

RESUMO Cuidadores de pessoas com demência possuem alto grau de sobrecarga que impacta de forma objetiva o sono e suas dimensões. Objetivo: Este estudo teve o objetivo de analisar o impacto da sobrecarga nas alterações do sono do cuidador. Métodos: Esta revisão sistemática envolveu a análise de resultados quantitativos e qualitativos de publicações das bases de dados Web of Science e PubMed/ Medical Literature Analysis and Retrieval System Online (Medline) publicadas entre fevereiro de 2018 e agosto de 2022. Resultados: O total de 27 estudos foi identificado e analisado. Cuidadores apresentam prejuízos na latência, fragmentação, duração e qualidade subjetiva do sono, disfunção diurna e insônia. O estresse e sintomas depressivos apresentados pelo cuidador possuem com o sono uma relação bidirecional. Conclusão: Os distúrbios do sono apresentados pelos cuidadores estão correlacionados com o alto nível de sobrecarga e geram maior vulnerabilidade para sintomas psiquiátricos e problemas de saúde.

Impacto da protetização auditiva na qualidade de vida do adulto com deficiência auditiva: revisão de escopo / Impact of hearing aids on the quality of life of adults with adult disabilities: scope review

RESUMO Objetivo Verificar os benefícios da protetização auditiva na qualidade de vida do adulto com deficiência auditiva. Estratégia de pesquisa Revisão de escopo, guiada pelas recomendações PRISMA. Critérios de seleção A busca foi realizada com o auxílio dos unitermos "auxiliares de audição", "aparelho auditivo", "implante coclear", "fonoaudiologia", "deficiência auditiva", "perda auditiva", "qualidade de vida", e seus respectivos em inglês e espanhol, nos bancos virtuais de dados: LILACS, SciELO, PubMed, Scopus, Web of Science e OpenGrey. Os dados foram analisados qualitativamente. Resultados Foram identificados 1.312 registros e selecionados 6 artigos, com população protetizada auditivamente, dos 18 aos 92 anos, de ambos os gêneros, usuários de implante coclear e aparelho de amplificação sonora individual. Foram utilizados os seguintes instrumentos: Questionário de avaliação das expectativas do adulto/idoso novo usuário de próteses auditivas, International Outcome Inventory For Hearing Aids, Questionário Nijmegen de Implantes Cocleares, Questionário de Satisfação do Cliente, Caregiver Strain Questionnaire, Formulário de Questionário Relativo ao Índice, World Health Organization Quality of Life-bref, Glasgow Health Status Inventory, Abbreviated Profile of Hearing Aid Benefit, Cochlear Implant Quality of Life, Caregiver Burden Scale, Escala Quantificada de Denver e Escala Visual Analógica. Os resultados indicaram melhor qualidade de vida nos domínios testados, tanto na visão dos adultos surdos quanto na de seus parceiros. Conclusão Apesar da heterogeneidade dos protocolos de qualidade de vida utilizados nos estudos selecionados, foi possível verificar que a protetização auditiva melhora a qualidade de vida do adulto com deficiência auditiva.

ABSTRACT Purpose To verify the benefits of hearing aids in the quality of life of adults with hearing loss. Research strategy Scoping review guided by PRISMA recommendations. Selection criteria with the help of the keywords "hearing aids", "hearing aid", "cochlear implant", "speech therapy", "hearing impairment", "hearing loss", "quality of life", and their respective in English and Spanish in the virtual databases: LILACS, SciELO, PubMed, SCOPUS, Web of Science and Open Grey. Qualitatively analyzed. Results 1,312 records were identified and six articles were selected, with a hearing aided population from 18 to 92 years old, from both genders, cochlear implant and individual sound amplification device users. Questionnaires were used (assessment of expectations of adults/elderly users of hearing aids, International Outcome Inventory For Hearing Aids, Nijmegen Cochlear Implant, Satisfaction, Caregiver Strain Questionnaire, Relative to the Index, World Health Organization Quality of Life-bref, Glasgow Health Status Inventory, Abbreviated Profile of Hearing Aid Benefit, Cochlear Implant Quality of Life and scales (Care Giving Burden Scale), Denver Quantified and visual analog). The results indicated a better quality of life in the domains tested, both in the view of deaf adults and their partners. Conclusion Despite the heterogeneity of the quality of life protocols used in the selected studies, it was possible to verify that hearing aids increase the quality of life of adults with hearing loss.

Breastfeeding duration and eating behavior in early childhood: a systematic review / Duração da amamentação e comportamentos alimentares na primeira infância: uma revisão sistemática

Abstract Objectives: to analyze the influence of breastfeeding duration on eating behavior in children aged two to six years. Methods: this review was conducted by PRISMA guidelines. SciELO, Lilacs, Embase, and PubMed databases were researched by using a specific syntax, for studies published from 2000 to 2020. The Joanna Briggs Institute Critical Appraisal checklist was used to assess the risk of study bias. Results: a total of 26,211 articles were identified, of which seven were included in the study. The results showed a significant association in four studies. All authors used their own questionnaires to assess breastfeeding exposure; there was no standard classification of exclusive and total breastfeeding duration. The breastfeeding duration was associated with reduced food neophobia, lower scores on the food responsiveness subscale, and lower 'picky eating' behavior. Validated instruments were predominantly used to assess the outcome of eating behavior; however, this assessment was not similar between studies. Conclusion: a significant association was observed between breastfeeding duration and eating behavior in children aged two to six years. Further research should be conducted to describe the mechanisms involved in this association.

Resumo Objetivos: analisar a influência da duração do aleitamento materno no comportamento alimentar em crianças de dois a seis anos. Métodos: esta revisão foi conduzida de acordo com as diretrizes PRISMA. As bases de dados SciELO, Lilacs, Embase e PubMed foram pesquisadas usando uma sintaxe específica, para estudos publicados de 2000 a 2020. O Joanna Briggs Institute Critical Appraisal checklist foi utilizado para avaliar o risco de viés do estudo. Resultados: foram identificados 26.211 artigos, dos quais sete foram incluídos no estudo. Os resultados mostraram associação significativa em quatro estudos. Todos os autores usaram seus próprios questionários para avaliar a exposição à amamentação; não havia uma classificação padrão de duração do aleitamento materno exclusivo e total. A duração do aleitamento materno foi associada à redução da neofobia alimentar, menores escores na subescala de responsividade alimentar e menor comportamento alimentar exigente. Instrumentos validados foram usados predominantemente para avaliar o resultado do comportamento alimentar, no entanto, essa avaliação não foi semelhante entre os estudos. Conclusão: observou-se associação significativa entre a duração da amamentação e o comportamento alimentar em crianças de dois a seis anos. Mais pesquisas devem ser realizadas para descrever os mecanismos envolvidos nesta associação.

The hepatic extramedullary hematopoiesis during experimental murine Schistosomiasis mansoni.

Many years ago, our research group has demonstrated extramedullary hematopoiesis in the peripheral zone of murine hepatic schistosomal granulomas. In the present study, we revisit this phenomenon using new technical and conceptual approaches. Therefore, newborn mice were percutaneously infected by Schistosoma mansoni cercariae and euthanized between 35- and 60-days post infection. Liver samples were submitted to histopathology and immunohistochemical analyses. Cells under mitosis and/or expressing Ki67 demonstrated the proliferation of hematopoietic cells both around the parasite's eggs trapped in the liver and around hepatic vessels. After 50 days post infection, proliferating cells at different levels on differentiation were located preferentially in the peripheral zone of the granulomas, around the vessels and inside the sinusoids. The presence of acidic and sulfated glycoconjugates, reticular fibers and the absence of fibronectin characterized the microenvironment for attraction and maintenance of hematopoiesis. Some neutrophils secreted MMP9 from the earliest points of infection, indicating degradation of the extracellular matrix in regions of histolysis and a possible chemoattraction of hematopoietic stem cells to the liver. Fall-3+ cells and Sca-1+ cells indicated that early hematopoietic progenitors could be mobilized to the liver. Groups of vWF+ megakaryocytes suggest chemoattraction of these cells and/or migration, proliferation, and differentiation of very immature progenitors to this organ. The increase of blood vessels and extramedullary hematopoiesis in this environment, where markers of immature hematopoietic and endothelial cells have been identified, points to the possibility of the presence of progenitors for endothelial and hematopoietic cells in the liver during the infection. There is also the possibility of concomitant migration of more differentiated hematopoietic progenitors, that proliferate and differentiate in the liver, and the occurrence of angiogenesis caused by inflammation or release of ovular antigens that stimulate the activation and proliferation of endothelial cells. Altogether, these data increase knowledge about a murine model that is of interest for investigating the pathology of the schistosomiasis and also the dynamics of hematopoiesis.

Impact of collaborative actions of Leishmania (Viannia) braziliensis subpopulations on the infection profile.

This study focuses on the role of the population structure of Leishmania spp. on the adaptive capacity of the parasite. Herein, we investigate the contribution of subpopulations of the L. (V.) braziliensis Thor strain (Thor03, Thor10 and Thor22) in the profile of murine macrophages infection. Infection assays were performed with binary combinations of these subpopulations at stationary phases. The initial interaction time showed major effects on the combination assays, as demonstrated by the significant increase in the infection rate at 5 h. Based on the endocytic index (EI), Thor10 (EI = 563.6) and Thor03 (EI = 497) showed a higher infection load compared to Thor22 (EI = 227.3). However, the EI decreased in Thor03 after 48 h (EI = 447) and 72 h (EI = 388.3) of infection, and showed changes in the infection level in all Thor10/Thor22 combinations. Assays with CellTrace CFSE-labelled Thor22 promastigotes indicated an increase (~1.5 fold) in infection by this subpopulation in the presence of Thor10 when compared to the infection profile of Thor03/Thor22 combinations in the same proportions. In addition, the potential of these subpopulations, alone or in binary combinations, to modulate the expression of cytokines and nitric oxide (NO) in vitro was investigated. Lower NO and tumour necrosis factor-α production levels were observed for all Thor10/Thor22 combinations at 24 h compared to these subpopulations alone. In contrast, Thor03/Thor22 combination assays increased IL-10 production at this time. Collectively, these results provide in vitro evidence on the potential of L. (V.) braziliensis population structure to play a relevant role in a host infection by this parasite.

Exercise-Based Real-time Telerehabilitation for Older Adult Patients Recently Discharged After Transcatheter Aortic Valve Implantation: Mixed Methods Feasibility Study.

BACKGROUND: The use of telehealth technology to improve functional recovery following transcatheter aortic valve implantation (TAVI) has not been investigated. OBJECTIVE: In this study, we aimed to examine the feasibility of exercise-based cardiac telerehabilitation after TAVI. METHODS: This was a single-center, prospective, nonrandomized study using a mixed methods approach. Data collection included testing, researchers' observations, logbooks, and individual patient interviews, which were analyzed using a content analysis approach. The intervention lasted 3 weeks and consisted of home-based web-based exercise training, an activity tracker, a TAVI information website, and 1 web-based session with a nurse. RESULTS: Of the initially included 13 patients, 5 (40%) completed the study and were interviewed; the median age was 82 (range 74-84) years, and the sample comprised 3 men and 2 women. Easy access to supervised exercise training at home with real-time feedback and use of the activity tracker to count daily steps were emphasized by the patients who completed the intervention. Reasons for patients not completing the program included poor data coverage, participants' limited information technology skills, and a lack of functionality in the systems used. No adverse events were reported. CONCLUSIONS: Exercise-based telerehabilitation for older people after TAVI, in the population as included in this study, and delivered as a web-based intervention, does not seem feasible, as 60% (8/13) of patients did not complete the study. Those completing the intervention highly appreciated the real-time feedback during the web-based training sessions. Future studies should address aspects that support retention rates and enhance patients' information technology skills.

OBESITY AND SEVERE STEATOSIS: THE IMPORTANCE OF BIOCHEMICAL EXAMS AND SCORES. / OBESIDADE E ESTEATOSE GRAVE: A IMPORTÂNCIA DA AVALIAÇÃO BIOQUÍMICA E ESCORES.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is considered a public health problem, mainly in severely obese patients. The aim of the present study was to investigate different biochemical-based scores available and determine which one could best serve as an NAFLD predicting tool in a severely obese population. METHODS: This was a cross-sectional study involving severely obese patients. All patients were evaluated with serum laboratory parameters for 1 week before biopsy, and all patients were treated with intraoperative liver biopsy, during bariatric surgery. RESULTS: A total of 143 severely obese patients were included. The median body mass index (BMI) was 48 kg/m2 (35-65). Diabetes mellitus was present in 36%, and steatosis was present in 93% (severe steatosis in 20%). Only aspartate transaminase (AST) to platelet ratio index (APRI=0.65 (95% CI: 0.55-0.8) and homeostatic model assessment for insulin resistance (HOMA-IR=0.7 (95% CI: 0.58-0.82) showed significant capacity for the prediction of severe steatosis. Hepatic steatosis index (HSI), NAFLD fibrosis score (NAFLDS), alanine aminotransferase (ALT)/AST, and fibrosis-4 (FIB-4) were not able to correctly predict severe steatosis on liver biopsy. APRI showed high specificity of 82% and low sensitivity of 54%. In contrast, HOMA-IR showed high sensitivity of 84% and low specificity of 48%. CONCLUSIONS: NAFLDS, FIB-4, AST/ALT, and HSI have no utility for the evaluation of severe steatosis in severely obese patients. Diabetes and insulin-resistance-related biochemical assessments, such as HOMA-IR, can be used as good screening tools for severe steatosis in these patients. APRI score is the most specific biochemical diagnostic tool for steatosis in severely obese patients and can help clinicians to decide the need for bariatric or metabolic surgery.

OBJETIVOS: A doença hepática gordurosa não-alcoólica já é considerada um problema de saúde pública, principalmente em pacientes com obesidade severa. O objetivo do presente estudo foi investigar os diferentes escores de bioquímiosa disponíveis e determinar qual deles poderia servir melhor como uma ferramenta de avaliação da NAFLD em uma população de obesos. MÉTODOS: Este é um estudo transversal de pacientes obesos. Todos os pacientes foram avaliados com parâmetros laboratoriais séricos 1 semana antes da biópsia e todos os pacientes foram submetidos a biópsia hepática intra-operatória, durante a cirurgia bariátrica. RESULTADOS: Cento e quarenta e três pacientes obesos foram incluídos. Apenas APRI (0,65; IC 95%: 0,55 a 0,8) e HOMA-IR (0,7; IC 95%: 0,58 a 0,82) mostraram capacidade significativa de predição de esteatose grave. HSI, NALFDS, ALS / AST e FIB-4 não foram capazes de prever corretamente esteatose grave na biópsia hepática. APRI mostrou alta especificidade (82%) e baixa sensibilidade (54%). Em contraste, o HOMA-IR apresentou alta sensibilidade (84%) e baixa especificidade (48%). CONCLUSÃO: O NALFDS, FIB-4, AST / ALT e HSI não têm utilidade para avaliação de esteatose grave em pacientes com obesidade severa. Diabetes e avaliação bioquímica relacionada à resistência à insulina, como o HOMA-IR, podem ser empregados como boas ferramentas de rastreamento para esteatose grave em tais pacientes. O escore APRI é a ferramenta diagnóstica bioquímica mais específica para esteatose em pacientes com obesidade severa e pode ser empregado, por equipes médicas, para auxiliar na indicação de cirurgia bariátrica ou metabólica.

Hemolymph of triatomines presents fungistatic activity against Cryptococcus neoformans and improves macrophage function through MCP-I/TNF-α increase

Triatomines are blood-feeding arthropods belonging to the subfamily Triatominae (Hemiptera; Reduviidae), capable of producing immunomodulatory and water-soluble molecules in their hemolymph, such as antimicrobial peptides (AMPs). In this work, we evaluated the antifungal and immunomodulatory activity of the hemolymph of Meccus pallidipennis (MPH) and Rhodnius prolixus (RPH) against Cryptococcus neoformans. Methods: We assessed the activity of the hemolymph of both insects on fungal growth by a minimum inhibitory concentration (MIC) assay. Further, RAW 264.7 macrophages were cultivated with hemolymph and challenged with C. neoformans. Then, their phagocytic and killing activities were assessed. The cytokines MCP-1, IFN-γ, TNF-α, IL-10, IL-12, and IL-6 were measured in culture supernatants 4- and 48-hours post-infection. Results: Both hemolymph samples directly affected the growth rate of the fungus in a dose-dependent manner. Either MPH or RPH was capable of inhibiting fungal growth by at least 70%, using the lowest dilution (1:20). Treatment of RAW 264.7 macrophages with hemolymph of both insects was capable of increasing the production of MCP-I and TNF-α. In addition, when these cells were stimulated with hemolymph in the presence of C. neoformans, a 2- and a 4-fold increase in phagocytic rate was observed with MPH and RPH, respectively, when compared to untreated cells. For the macrophage killing activity, MPH decreased in approximately 30% the number of viable yeasts inside the cells compared to untreated control; however, treatment with RPH could not reduce the total number of viable yeasts. MPH was also capable of increasing MHC-II expression on macrophages. Regarding the cytokine production, MCP-I and TNF-α, were increased in the supernatant of macrophages treated with both hemolymphs, 4 and 48 hours after stimulation. Conclusion: These results suggested that hemolymph of triatomines may represent a source of molecules capable of presenting antifungal and immunomodulatory activity in macrophages during fungal infection.(AU)

A Rare Presentation of Multi-Organ Embolism in a Multifactorial Hypercoagulable State: Case Report.

Paradoxical embolism is an uncommon phenomenon, accounting for only 2% of all cases of systemic arterial embolism. This condition suggests the presence of a patent foramen ovale, present in 20% - 25% of the adult population. The authors report the case of a 63-year-old male patient with a history of lung adenocarcinoma and hereditary thrombophilia admitted to hospital with acute onset of dyspnea, diplopia, confusion and decreased motor strength of the right limbs. Cranial computed tomography scan showed acute ischemic injury in the left posterior cerebral artery and computed tomography pulmonary angiography revealed bilateral pulmonary thromboembolism. A transesophageal echocardiogram confirmed the presence of patent foramen ovale. The patient was treated with anticoagulant therapy with progressive clinical improvement. Due to a high risk of recurrent thromboembolic episodes, the percutaneous closure of patent foramen ovale was performed and anticoagulant therapy was maintained indefinitely.

A embolização paradoxal é um fenómeno incomum, correspondendo apenas a 2% de todos os casos de embolia sistémica arterial. Esta condição sugere a presença de foramen ovale patente, presente em 20% - 25% da população adulta. Os autores relatam um caso de um homem de 63 anos, com os diagnósticos prévios de adenocarcinoma do pulmão e trombofilia hereditária, admitido no hospital com quadro agudo de dispneia, diplopia, confusão e diminuição da força dos membros à direita. A tomografia computorizada crânio-encefálica mostrou uma lesão isquémica cerebral na região da artéria cerebral posterior esquerda e a angiotomografia computorizada torácica revelou tromboembolismo pulmonar bilateral. O ecocardiograma transesofágico confirmou a presença de foramen ovale patente. O doente foi tratado com terapêutica anticoagulante com melhoria clínica progressiva. Devido ao elevado risco de recorrência de eventos tromboembólicos, o doente foi submetido a encerramento percutâneo do foramen ovale patente e a anticoagulação foi mantida por tempo indeterminado.