A cross-sectional assessment of frailty, falls and perceptions of ageing in people living with HIV using an mHealth platform.

OBJECTIVE: To evaluate frailty, falls and perceptions of ageing among clinically stable individuals with HIV, engaged with remote healthcare delivered via a novel smartphone application. METHODS: This was a multi-centre European cross-sectional, questionnaire-based sub-study of EmERGE participants. Frailty was assessed using the five-item FRAIL scale. Present criteria were summed and categorized as follows: 0, robust; 1-2, pre-frail; 3-5, frail. Falls history and EQ-5D-5L quality of life measure were completed. Participants were asked their felt age and personal satisfaction with ageing. RESULTS: A total of 1373 participated, with a mean age of 45 (± 9.8) years. Frailty was uncommon at 2%; 12.4% fell in the previous year, 58.8% of these recurrently. Mood symptoms and pain were prevalent, at 43.3% and 31.8%, respectively. Ageing satisfaction was high at 76.4%, with 74.6% feeling younger than their chronological age; the mean felt age was 39.3 years. In multivariable analysis, mood symptoms and pain were positively associated with frailty, falls and ageing dissatisfaction. An increase in pain severity and mood symptoms were respectively associated with 34% and 63% increased odds of pre-frailty/frailty. An increment in pain symptoms was associated with a 71% increase in odds of falling. Pain was associated with ageing poorly, as were mood symptoms, with odds of dissatisfaction increasing by 34% per increment in severity. CONCLUSIONS: Although uncommon, frailty, falls and ageing dissatisfaction were seen in a younger cohort with medically stable HIV infection using a remote care model, promoting screening as advocated by European guidelines. These were more common in those with pain or mood symptoms, which should be proactively managed in clinical care and explored further in future research.

TNF-Mediated Compensatory Immunity to Mycobacterium avium in the Absence of Macrophage Activation by IFN-γ.

Granuloma formation is a hallmark of several infectious diseases, including those caused by Mycobacterium sp These structures are composed of accumulations of inflammatory cells, and it has been shown that cytokines such as IFN-γ and TNF-α are required for granuloma assembly during M. avium infections in mice. Macrophages (MΦs) insensitive to IFN-γ (MIIG) mice have MΦs, monocytes, and dendritic cells that are unresponsive to IFN-γ. We observed that although IFN-γ-/- mice present an exacerbated infection, the same is not true for MIIG animals, where the same levels of protection as the wild-type animals were observed in the liver and partial protection in the spleen. Unlike IFN-γ-/- mice, MIIG mice still develop well-defined granulomas, suggesting that IFN-γ-mediated MΦ activation is not required for granuloma assembly. This work also shows that MIIG animals exhibit increased cell recruitment with higher CD4+ T cells numbers as well as increased IFN-γ and TNF-α expression, suggesting that TNF-α may have a role in protection and may compensate the lack of MΦ response to IFN-γ in the MIIG model. TNF-α-deficient MIIG mice (MIIG.TNF-α-/-) exhibited increased bacterial burdens when compared with MIIG mice. These results suggest that in the absence of IFN-γ signaling in MΦs, TNF-α has a protective role against M. avium.

Toxoplasma gondii infection reduces serum progesterone levels and adverse effects at the maternal-foetal interface.

AIMS: Pregnant BALB/c mice infected with a Toxoplasma gondii type II strain were used to determine how pregnancy interferes with the development of maternal immunity to T gondii and how infection disrupts pregnancy and foetal development. METHODS: Maternal and foetal parasite loads were assessed by amplification of T gondii SAG1 using qPCR. Adverse effects of infection were evaluated on foetal-placental development by quantification of implantation units undergoing resorption and by histopathological analyses. Serum progesterone levels were quantified by immunoassay. The effect of T gondii infection on maternal immunity was determined by assessing the cellular composition of spleens by flow cytometry. RESULTS: Infected pregnant mice exhibited clinical signs of infection, inflammation and necrosis at the maternal-foetal interface and decreased serum progesterone levels. In infected mice, there was a clear effect of pregnancy and infection on macrophage cell numbers. However, no differences in the parasite load were detected between non-pregnant and pregnant mice. CONCLUSIONS: Maternal T gondii infection induced adverse effects at the maternal-foetal interface. Alterations were found in immune spleen cells, dependent on the day of pregnancy, relative to nonpregnant animals. The results obtained suggest a pregnancy-dependent mechanism during T gondii infection able to interfere with macrophage numbers.

Costs and consequences of the Portuguese needle-exchange program in community pharmacies.

BACKGROUND: Needle-exchange programs (NEPs) reduce infections in people who inject drugs. This study assesses the impact community pharmacies have had in the Needle-Exchange Program in Portugal since 2015. METHODS: Health gains were measured by the number of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections averted, which were estimated, in each scenario, based on a standard model in the literature, calibrated to national data. The costs per infection were taken from national literature; costs of manufacturing, logistics and incineration of injection materials were also considered. The results were presented as net costs (i.e., incremental costs of the program with community pharmacies less the costs of additional infections avoided). RESULTS: Considering a 5-year horizon, the Needle Exchange Program with community pharmacies would account for a 6.8% (n = 25) and a 6.5% reduction (n = 22) of HCV and HIV infections, respectively. The present value of net savings generated by the participation of community pharmacies in the program was estimated at €2,073,347. The average discounted net benefit per syringe exchanged is €3.01, already taking into account a payment to community pharmacies per needle exchanged. INTERPRETATION: We estimate that the participation of community pharmacies in the Needle Exchange Program will lead to a reduction of HIV and HCV infections and will generate over €2 million in savings for the health system. CONCLUSIONS: The intervention is estimated to generate better health outcomes at lower costs, contributing to improving the efficiency of the public health system in Portugal.

How does toxoplasmosis affect the maternal-foetal immune interface and pregnancy?

Toxoplasma gondii is a zoonotic parasite which, depending on the geographical location, can infect between 10% and 90% of humans. Infection during pregnancy may result in congenital toxoplasmosis. The effects on the foetus vary depending on the stage of gestation in which primary maternal infection arises. A large body of research has focused on understanding immune response to toxoplasmosis, although few studies have addressed how it is affected by pregnancy or the pathological consequences of infection at the maternal-foetal interface. There is a lack of knowledge about how maternal immune cells, specifically macrophages, are modulated during infection and the resulting consequences for parasite control and pathology. Herein, we discuss the potential of T. gondii infection to affect the maternal-foetal interface and the potential of pregnancy to disrupt maternal immunity to T. gondii infection.

Innate IFN-γ-Producing Cells Developing in the Absence of IL-2 Receptor Common γ-Chain.

IFN-γ is known to be predominantly produced by lymphoid cells such as certain subsets of T cells, NK cells, and other group 1 innate lymphoid cells. In this study, we used IFN-γ reporter mouse models to search for additional cells capable of secreting this cytokine. We identified a novel and rare population of nonconventional IFN-γ-producing cells of hematopoietic origin that were characterized by the expression of Thy1.2 and the lack of lymphoid, myeloid, and NK lineage markers. The expression of IFN-γ by this population was higher in the liver and lower in the spleen. Furthermore, these cells were present in mice lacking both the Rag2 and the common γ-chain (γc) genes (Rag2-/-γc-/-), indicating their innate nature and their γc cytokine independence. Rag2-/-γc-/- mice are as resistant to Mycobacterium avium as Rag2-/- mice, whereas Rag2-/- mice lacking IFN-γ are more susceptible than either Rag2-/- or Rag2-/-γc-/- These lineage-negative CD45+/Thy1.2+ cells are found within the mycobacterially induced granulomatous structure in the livers of infected Rag2-/-γc-/- animals and are adjacent to macrophages that expressed inducible NO synthase, suggesting a potential protective role for these IFN-γ-producing cells. Accordingly, Thy1.2-specific mAb administration to infected Rag2-/-γc-/- animals increased M. avium growth in the liver. Overall, our results demonstrate that a population of Thy1.2+ non-NK innate-like cells present in the liver expresses IFN-γ and can confer protection against M. avium infection in immunocompromised mice.

Lack of the Transcription Factor Hypoxia-Inducible Factor 1α (HIF-1α) in Macrophages Accelerates the Necrosis of Mycobacterium avium-Induced Granulomas.

The establishment of mycobacterial infection is characterized by the formation of granulomas, which are well-organized aggregates of immune cells, namely, infected macrophages. The granuloma's main function is to constrain and prevent dissemination of the mycobacteria while focusing the immune response to a limited area. In some cases these lesions can grow progressively into large granulomas which can undergo central necrosis, thereby leading to their caseation. Macrophages are the most abundant cells present in the granuloma and are known to adapt under hypoxic conditions in order to avoid cell death. Our laboratory has developed a granuloma necrosis model that mimics the human pathology of Mycobacterium tuberculosis, using C57BL/6 mice infected intravenously with a low dose of a highly virulent strain of Mycobacterium avium. In this work, a mouse strain deleted of the hypoxia inducible factor 1α (HIF-1α) under the Cre-lox system regulated by the lysozyme M gene promoter was used to determine the relevance of HIF-1α in the caseation of granulomas. The genetic ablation of HIF-1α in the myeloid lineage causes the earlier emergence of granuloma necrosis and clearly induces an impairment of the resistance against M. avium infection coincident with the emergence of necrosis. The data provide evidence that granulomas become hypoxic before undergoing necrosis through the analysis of vascularization and quantification of HIF-1α in a necrotizing mouse model. Our results show that interfering with macrophage adaptation to hypoxia, such as through HIF-1α inactivation, accelerates granuloma necrosis.

The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ.

Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-γ (IFN-γ). Mycobacterium avium-infected mice lacking IFN-γ signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN-γ signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN-γ reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN-γ displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN-γ is responsible for the Warburg effect observed in organs infected with M. avium.

Molecular and cellular mechanisms of Mycobacterium avium-induced thymic atrophy.

Thymic atrophy has been described as a consequence of infection by several pathogens and shown to be induced through diverse mechanisms. Using the mouse model of Mycobacterium avium infection, we show in this study that the production of NO from IFN-γ-activated macrophages plays a major role in mycobacterial infection-induced thymic atrophy. Our results show that disseminated infection with a highly virulent strain of M. avium, but not with a low-virulence strain, led to a progressive thymic atrophy. Thymic involution was prevented in genetically manipulated mice unable to produce IFN-γ or the inducible NO synthase. In addition, mice with a selective impairment of IFN-γ signaling in macrophages were similarly protected from infection-induced thymic atrophy. A slight increase in the concentration of corticosterone was found in mice infected with the highly virulent strain, and thymocytes presented an increased susceptibility to dexamethasone-induced death during disseminated infection. The administration of an antagonist of glucocorticoid receptors partially reverted the infection-induced thymic atrophy. We observed a reduction in all thymocyte populations analyzed, including the earliest thymic precursors, suggesting a defect during thymic colonization by T cell precursors and/or during the differentiation of these cells in the bone marrow in addition to local demise of thymic cells. Our data suggest a complex picture underlying thymic atrophy during infection by M. avium with the participation of locally produced NO, endogenous corticosteroid activity, and reduced bone marrow seeding.

Stone Pine (Pinus pinea L.) High-Added-Value Genetics: An Overview.

Stone pine (Pinus pinea L.) has received limited attention in terms of genetic research. However, genomic techniques hold promise for decoding the stone pine genome and contributing to developing a more resilient bioeconomy. Retrotransposon and specific genetic markers are effective tools for determining population-specific genomic diversity. Studies on the transcriptome and proteome have identified differentially expressed genes PAS1, CLV1, ATAF1, and ACBF involved in shoot bud formation. The stone pine proteome shows variation among populations and shows the industrial potential of the enzyme pinosylvin. Microsatellite studies have revealed low levels of polymorphism and a unique genetic diversity in stone pine, which may contribute to its environmental adaptation. Transcriptomic and proteomic analyses uncover the genetic and molecular responses of stone pine to fungal infections and nematode infestations, elucidating the defense activation, gene regulation, and the potential role of terpenes in pathogen resistance. Transcriptomics associated with carbohydrate metabolism, dehydrins, and transcription factors show promise as targets for improving stone pine's drought stress response and water retention capabilities. Stone pine presents itself as an important model tree for studying climate change adaptation due to its characteristics. While knowledge gaps exist, stone pine's genetic resources hold significant potential, and ongoing advancements in techniques offer prospects for future exploration.

Measuring the value of solidarity: The abem financial assistance program for out-of-pocket payments on pharmacy medicines in Portugal.

OBJECTIVE: Out-of-pocket payments for prescribed medicines are still comparatively high in Portugal. The abem program was launched in Portugal in May 2016 to aid vulnerable groups by completely covering out-of-pocket costs of prescribed medicines in community pharmacies. This study assesses the impact of the program on poverty and catastrophic health expenditures. METHODS: A longitudinal study was carried out with the analysis of several program databases (from the beginning of the program in May 2016 to September 2018) covering the cohorts of beneficiaries, daily data on medicines dispensed, social referencing entities, and solidarity pharmacies. The study provides estimates of standard poverty measures (intensity and severity) as well as the incidence of catastrophic health expenditures. RESULTS: More than 6000 beneficiaries were supported (56.8% female, 34.7% aged 65 or over), encompassing 127,510 medicines (mainly nervous system and cardiovascular system) with an average 26.9% co-payment (payments totalling €1.5 million). The program achieved substantial reductions in poverty (3.4% in intensity, 5.6% in severity), and eliminated cases with catastrophic health expenditures in medicines that would have affected 7.5% of the beneficiaries. CONCLUSIONS: Findings confirm a continuous increase in the number of beneficiaries, enabling access to medicines especially for the vulnerable elderly, and a sizable impact on eliminating out-of-pocket payments for medicines in the target population.

Cost-effectiveness of semaglutide 2.4 mg in chronic weight management in Portugal.

BACKGROUND: Obesity and overweight are a significant public health concern. Subcutaneous semaglutide 2.4 mg injection is a glucagon-like peptide-1 (GLP-1) analogue approved by the European Medicines Agency as an adjunct to a reduced calorie diet and increased physical activity (diet and exercise, D&E) for the treatment obesity and overweight in the presence of at least one weight related comorbidity. This study aimed to assess the cost-effectiveness of semaglutide 2.4 mg in combination with D&E compared to D&E alone for the Portuguese setting. METHODS: Analysis were conducted using the Core Obesity Model (COM) version 18, a Markov state transition cohort model, to predict the health outcomes and costs of weight related complications based on changes in surrogate endpoints. Efficacy and safety data were sourced from the STEP trials (Body Mass Index, systolic blood pressure and glycemic status) from a cohort of adults aged on average 48 years with obesity (BMI ≥ 30 kg/m2) and ≥ 1 obesity-related comorbidities, over a time horizon of 40 years. Costs were estimated from the perspective of the Portuguese National Health Service. Sensitivity analyses were conducted to test the robustness of results across a range of assumptions. RESULTS: On a patient level, Semaglutide 2.4 mg in addition to D&E compared to D&E alone, improved QALYs by 0.098 and yielded higher costs by 1,325 EUR over a 40-year time horizon, with an ICER of 13,459 EUR per QALY gained and 100% probability of cost-effectiveness at the given WTP. Semaglutide 2.4 mg remained cost-effective across all different scenarios and sensitivity analysis at a WTP of 20,000 EUR per QALY. Among the subpopulations examined, Semaglutide 2.4 mg yielded ICERs of 18,459 EUR for patients with BMI ≥ 30 kg/m2 and of 22,657 EUR for patients with BMI ≥ 35 kg/m2. CONCLUSIONS: Semaglutide 2.4 mg was cost-effective compared to D&E alone for patients with obesity (BMI ≥ 30 kg/m2) and weight related comorbidities in Portugal, over a 40-year time horizon.

Steroidal aromatase inhibitors inhibit growth of hormone-dependent breast cancer cells by inducing cell cycle arrest and apoptosis.

Different hormonal therapies are used for estrogen receptor positive (ER(+)) breast cancers, being the third-generation of aromatase inhibitors (AIs), an effective alternative to the classical tamoxifen. AIs inhibit the enzyme aromatase, which is responsible for catalyzing the conversion of androgens to estrogens. In this study, it was evaluated the effects of several steroidal AIs, namely 3ß-hydroxyandrost-4-en-17-one (1), androst-4-en-17-one (12), 4α,5α-epoxyandrostan-17-one (13a) and 5α-androst-2-en-17-one (16), on cell proliferation, cell cycle progression and cell death in an ER(+) aromatase-overexpressing human breast cancer cell line (MCF-7aro). All AIs induced a decrease in cell proliferation and these anti-proliferative effects were due to a disruption in cell cycle progression and cell death, by apoptosis. AIs 1 and 16 caused cell cycle arrest in G0/G1, while AIs 12 and 13a induced an arrest in G2/M. Moreover, it was observed that these AIs induced apoptosis by different pathways, since AIs 1, 12 and 13a activated the apoptotic mitochondrial pathway, while AI 16 induced apoptosis through activation of caspase-8. These results are important for the elucidation of the cellular effects of steroidal AIs on breast cancer cells and will also highlight the importance of AIs as inducers of apoptosis in hormone-dependent breast cancers.

Nanoparticles as a Delivery System of Antigens for the Development of an Effective Vaccine against Toxoplasma gondii.

Nanoparticles include particles ranging in size from nanometers to micrometers, whose physicochemical characteristics are optimized to make them appropriate delivery vehicles for drugs or immunogens important in the fight and/or prevention of infectious diseases. There has been a rise in the use of nanoparticles in preventive vaccine formulations as immunostimulatory adjuvants, and as vehicles for immunogen delivery to target immune cells. Toxoplasma is important worldwide, and may cause human toxoplasmosis. In immunocompetent hosts, infection is usually asymptomatic, but in immunocompromised patients it can cause serious neurological and ocular consequences, such as encephalitis and retinochoroiditis. Primary infection during pregnancy may cause abortion or congenital toxoplasmosis. Currently, there is no effective human vaccine against this disease. Evidence has emerged from several experimental studies testing nanovaccines showing them to be promising tools in the prevention of experimental toxoplasmosis. For the present study, a literature review was carried out on articles published over the last 10 years through the PubMed database, pertaining to in vivo experimental models of T. gondii infection where nanovaccines were tested and protection and immune responses evaluated. This review aims to highlight the way forward in the search for an effective vaccine for toxoplasmosis.

Microbiological Assessment of White Button Mushrooms with an Edible Film Coating.

The development of edible coatings incorporating bioextracts from mushrooms native to Portuguese forests aims to enhance the value of the endogenous forest and mycological resources by harnessing their potential as a source of antimicrobial and antioxidant compounds. Edible coatings represent an important pathway to decreasing food waste and contributing to implementing a circular bioeconomy. The coating should result in product valorization through improved preservation/conservation, increased shelf life, as well as enhancement of its antioxidant and enzymatic properties. To evaluate the effectiveness of an edible coating on fungal food matrices, a 14-day shelf-life study was conducted, wherein both coated and untreated mushrooms were examined under controlled storage temperatures of 4 °C and 9.3 °C. Agaricus bisporus was chosen as the food matrix for its bioeconomy significance, and Pleurotus eryngii was selected for the preparation of the food-based coating due to its profile of bioactive compounds. Microbiological analysis and physicochemical monitoring were conducted on the food matrices and the coating. Coated mushrooms had less mass loss and color change, and had better texture after 14 days. Microbiological analysis revealed that the coating had no antimicrobial activity. Overall, the coating improved the shelf life of the coated mushrooms but had less effect on the microbial community.

Itchy Skin: A Challenging Differential Diagnosis Between Mycosis Fungoides and Sézary Syndrome.

Primary cutaneous lymphomas represent a diverse spectrum of T-cell and B-cell lymphomas with their primary skin manifestation. Among these, mycosis fungoides (MF) and Sézary syndrome (SS) represent classic forms of cutaneous T-cell lymphomas (CTCLs). This report details the case of a 67-year-old female who presented with longstanding pruritic skin lesions, initially misdiagnosed and managed as eczema. The diagnostic process ultimately revealed the presence of Sézary cells in the peripheral blood smear (PBS). The SS diagnosis was confirmed based on CD4 positivity and CD7 negativity as determined by flow cytometry. The disease was staged as IVA1 (T2N0M1B2). The patient exhibited partial improvement with oral corticosteroid therapy. This report underscores the critical importance of integrating clinical evaluation and blood findings to distinguish between MF and SS. The progression of a circulating clone signals a poor prognosis, requiring surveillance and consideration of targeted therapies to enhance patient outcomes and improve their quality of life. Early detection remains paramount in the management of these rare cutaneous lymphomas, which are associated with unique therapeutic challenges.

[Oral Anticoagulation and the Incidence of Stroke Associated with Atrial Fibrillation in Mainland Portugal: A Modelling Study]. / Anticoagulação Oral e Incidência de Acidente Vascular Cerebral Associado a Fibrilhação Auricular em Portugal Continental: Um Estudo de Modelação.

INTRODUCTION: Atrial fibrillation is the most prevalent persistent dysrhythmia, contributing to a significant social and economic burden. The main objective of this study was to evaluate the association between oral anticoagulant use and the incidence of stroke associated with atrial fibrillation, in mainland Portugal. METHODS: The number of episodes of inpatient care with a main diagnosis of stroke and an additional diagnosis of atrial fibrillation, occurring monthly between January 2012 and December 2018, in individuals aged 18 years or over, was extracted from the hospital morbidity database. The number of patients with an atrial fibrillation code documented in this database was used as a proxy for the prevalence of known atrial fibrillation. The number of anticoagulated patients was estimated from total medicine sales of vitamin K antagonists and novel oral anticoagulants (apixaban, dabigatran, edoxaban and rivaroxaban) in mainland Portugal. Descriptive analyses were performed, and seasonal autoregressive integrated moving average (SARIMA) models were built using the R software. RESULTS: The mean number of episodes of stroke per month was 522 (± 57). The number of anticoagulated patients increased gradually from 68 943 to 180 389 per month. The decreasing trend in the number of episodes has been observed since 2016, along with the increased use of new oral anticoagulants compared to vitamin K antagonists. The final model indicated that the increase in oral anticoagulation use between 2012 and 2018, in mainland Portugal, was associated with a decrease in the number of episodes of stroke associated with atrial fibrillation. It was estimated that the shift in the type of anticoagulation used, between 2016 and 2018, was associated with a reduction of 833 episodes of stroke in patients with atrial fibrillation (4.2%). CONCLUSION: The use of oral anticoagulation was associated with a reduced incidence of stroke in patients with atrial fibrillation in mainland Portugal. This reduction was more relevant in the period between 2016 and 2018, and is probably related with the introduction of the novel oral anticoagulants.

Introdução: A fibrilhação auricular é a disritmia persistente mais prevalente, tendo um importante impacto social e económico. O objetivo principal deste estudo foi avaliar a associação entre a utilização de anticoagulantes orais e a incidência de acidente vascular cerebral associado a fibrilhação auricular, em Portugal continental. Métodos: A base de dados de morbilidade hospitalar foi utilizada para a contabilização dos episódios de internamento com um diagnóstico principal de acidente vascular cerebral e um diagnóstico adicional de fibrilhação auricular, ocorridos durante cada mês do período em análise (janeiro de 2012 a dezembro de 2018), em indivíduos com idade igual ou superior a 18 anos. O número de doentes com registo de fibrilhação auricular presentes nesta base de dados foi utilizado como um proxy da prevalência de fibrilhação auricular conhecida. O número de doentes anticoagulados foi estimado a partir das estatísticas das vendas de antagonistas da vitamina K e novos anticoagulantes orais (apixabano, dabigatrano, edoxabano e rivaroxabano) em Portugal continental. Foi realizada uma análise descritiva das variáveis, construindo-se depois modelos auto-regressivos integrados de médias móveis sazonais (seasonal autoregressive integrated moving average, SARIMA), com recurso ao software R. Resultados: Ocorreram, em média, 522 (± 57) episódios de acidente vascular cerebral por mês. Verificou-se um aumento gradual do número de doentes anticoagulados, passando de 68 943 para 180 389, por mês. A tendência decrescente no número de episódios verificou-se a partir de 2016, a par da maior utilização dos novos anticoagulantes orais, comparativamente aos antagonistas da vitamina K. O modelo final estimado indicou que o aumento do consumo de anticoagulação oral entre 2012 e 2018 em Portugal continental foi associado a um decréscimo do número de acidentes vasculares cerebrais associados a fibrilhação auricular. Estimou-se que, entre 2016 e 2018, a mudança no tipo de anticoagulação se associou a uma redução de 833 episódios de acidentes vascular cerebrais em doentes com fibrilhação auricular (4,2%). Conclusão: A anticoagulação oral associou-se à redução da incidência de acidente vascular cerebral em doentes com fibrilhação auricular, em Portugal continental. Esta redução foi mais relevante no período 2016 a 2018, em provável relação com a introdução dos novos anticoagulantes orais.

A biomechanical study of the birth position: a natural struggle between mother and fetus.

Birth trauma affects millions of women and infants worldwide. Levator ani muscle avulsions can be responsible for long-term morbidity, associated with 13-36% of women who deliver vaginally. Pelvic floor injuries are enhanced by fetal malposition, namely persistent occipito-posterior (OP) position, estimated to affect 1.8-12.9% of pregnancies. Neonates delivered in persistent OP position are associated with an increased risk for adverse outcomes. The main goal of this work was to evaluate the impact of distinct fetal positions on both mother and fetus. Therefore, a finite element model of the fetal head and maternal structures was used to perform childbirth simulations with the fetus in the occipito-anterior (OA) and OP position of the vertex presentation, considering a flexible-sacrum maternal position. Results demonstrated that the pelvic floor muscles' stretch was similar in both cases. The maximum principal stresses were higher for the OP position, and the coccyx rotation reached maximums of 2.17[Formula: see text] and 0.98[Formula: see text] for the OP and OA positions, respectively. Concerning the fetal head, results showed noteworthy differences in the variation of diameters between the two positions. The molding index is higher for the OA position, with a maximum of 1.87. The main conclusions indicate that an OP position can be more harmful to the pelvic floor and pelvic bones from a biomechanical point of view. On the other side, an OP position can be favorable to the fetus since fewer deformations were verified. This study demonstrates the importance of biomechanical analyses to further understand the mechanics of labor.

The efficiency of the EmERGE platform for medically stable people living with HIV in Portugal.

Background: The aim of this study was to calculate the cost-effectiveness of the EmERGE Pathway of Care for medically stable people living with HIV in the Hospital Capuchos, Centro Hospitalar Universitário de Lisboa Central (HC-CHLC). The app enables individuals to receive HIV treatment information and communicate with caregivers. Methods: This before-and-after study collected the use of services data 1 year before implementation and after implementation of EmERGE from November 1, 2016, to October 30, 2019. Departmental unit costs were calculated and linked to mean use of outpatient services per patient-year (MPPY). Annual costs per patient-year were combined with primary (CD4 count; viral load) and secondary outcomes (PAM-13; PROQOL-HIV). Results: Five hundred eighty-six EmERGE participants used HIV outpatient services. Annual outpatient visits decreased by 35% from 3.1 MPPY (95% confidence interval [CI]: 3.0-3.3) to 2.0 (95% CI: 1.9-2.1) as did annual costs per patient-year from €301 (95% CI: €288-€316) to €193 (95% CI: €182-€204). Laboratory tests and costs increased by 2%, and radiology investigations decreased by 40% as did costs. Overall annual cost for HIV outpatient services decreased by 5% from €2093 (95% CI: €2071-€2112) to €1984 (95% CI: €1968-€2001); annual outpatient costs decreased from €12,069 (95% CI: €12,047-€12,088) to €11,960 (95% CI: €11,944-€11,977), with 83% of annual cost because of antiretroviral therapy (ART). Primary and secondary outcome measures did not differ substantially between periods. Conclusions: The EmERGE Pathway produced cost savings after implementation-extended to all people living with HIV additional savings are likely to be produced, which can be used to address other needs. Antiretroviral drugs (ARVs) were the main cost drivers and more expensive in Portugal compared with ARV costs in the other EmERGE sites.

Bisphenols A, F, S and AF trigger apoptosis and/or endoplasmic reticulum stress in human endometrial stromal cells.

Disruption of non-differentiated endometrial stromal cells could have noxious consequences in female reproduction, impairing endometrial remodelling and implantation. Following the classification of bisphenol A (BPA) as an endocrine disrupting chemical, it started to be gradually withdrawn from the market, being substituted by structural analogues, whose effects in human health are not fully understood. This work used a telomerase-immortalized human endometrial stromal cell line (St-T1b) to study the effects of BPA and its three most commercialized structural analogues (ranked: bisphenols S, F and AF) on endometrial stromal cells to understand their effects on female reproductive function. Bisphenols showed dissimilar effects. All four compounds generated endoplasmic reticulum (ER) stress. In addition, bisphenols A, F and AF induced apoptosis through different mechanisms, with bisphenol AF causing cell cycle arrest at G2/M phase. Bisphenol AF decreased mitochondrial transmembrane potential and bisphenols A, F and AF produced oxidative stress.