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Retroviruses can be detected by the innate immune sensor cyclic GMP-AMP synthase (cGAS), which recognizes reverse-transcribed DNA and activates an antiviral response. However, the extent to which HIV-1 shields its genome from cGAS recognition remains unclear. To study this process in mechanistic detail, we reconstituted reverse transcription, genome release, and innate immune sensing of HIV-1 in a cell-free system. We found that wild-type HIV-1 capsids protect viral genomes from cGAS even after completing reverse transcription. Viral DNA could be "deprotected" by thermal stress, capsid mutations, or reduced concentrations of inositol hexakisphosphate (IP6) that destabilize the capsid. Strikingly, the capsid inhibitor lenacapavir also disrupted viral cores and dramatically potentiated cGAS activity, both in vitro and in cellular infections. Our results provide biochemical evidence that the HIV-1 capsid lattice conceals the genome from cGAS and that chemical or physical disruption of the viral core can expose HIV-1 DNA and activate innate immune signaling. Author summary: Human Immunodeficiency Virus type 1 (HIV-1) remains a global health threat. Drug therapies can help manage HIV-1 infection and prevent its spread, but without treatment, the immune system fails to control the virus. In part, this is because HIV-1 is thought to avoid detection by immune cells during entry. Once inside a target cell, the virus copies its RNA genome into double-stranded DNA within a viral protein shell called the capsid. In this study, we developed a novel cell-free method to study how the HIV-1 capsid shields viral DNA from detection. We found that the capsid normally functions as a molecular cloak that hides the viral DNA from innate immune sensors. We also identified experimental conditions and drug treatments that can "break" the capsid and allow the viral DNA to be detected, both in vitro and in cells. We anticipate that future work using cell-free systems will reveal how host factors regulate innate detection of HIV-1, possibly guiding new therapeutic strategies that block infection and engage antiviral immune responses simultaneously. [ABSTRACT FROM AUTHOR]

Background Current methods for assessing children's dietary intake, such as interviewer-administered 24-h dietary recall (24-h DR), are time consuming and resource intensive. Self-administered instruments offer a low-cost diet assessment method for use with children. The present study assessed the validity of the Portuguese self-administered, computerised, 24-h DR ( PAC24) against the observation of school lunch. Methods Forty-one, 7-10-year-old children from two elementary schools, in Lisbon, were observed during school lunch followed by completion of the PAC24 the next day. Accuracy for reporting items was measured in terms of matches, intrusions and omissions; accuracy for reporting amounts was measured in terms of arithmetic and absolute differences for matches and amounts for omissions and intrusions; and accuracy for reporting items and amounts combined was measured in terms of total inaccuracy. The ratio of the estimated weight of food consumed with the actual weight consumed was calculated along with the limits of agreement using the method of Bland and Altman. Results Comparison of PAC24 against observations at the food level resulted in values of 67.0% for matches, 11.5% for intrusions and 21.5% for omissions. The mean for total inaccuracy was 3.44 servings. For amounts, accuracy was high for matches (−0.17 and 0.23 servings for arithmetic and absolute differences, respectively) and lower for omissions (0.61 servings) and intrusions (0.55 servings). PAC24 was found to under-estimate the weight of food on average by 32% of actual intake. Conclusions PAC24 is a lower-burden procedure for both respondents and researchers and, with slight modification, comprises a promising method for assessing diet among children. [ABSTRACT FROM AUTHOR]

Retroviruses can be detected by the innate immune sensor cyclic GMP-AMP synthase (cGAS), which recognizes reverse-transcribed DNA and activates an antiviral response. However, the extent to which HIV-1 shields its genome from cGAS recognition remains unclear. To study this process in mechanistic detail, we reconstituted reverse transcription, genome release, and innate immune sensing of HIV-1 in a cell-free system. We found that wild-type HIV-1 capsids protect viral genomes from cGAS even after completing reverse transcription. Viral DNA could be "deprotected" by thermal stress, capsid mutations, or reduced concentrations of inositol hexakisphosphate (IP6) that destabilize the capsid. Strikingly, the capsid inhibitor lenacapavir also disrupted viral cores and dramatically potentiated cGAS activity, both in vitro and in cellular infections. Our results provide biochemical evidence that the HIV-1 capsid lattice conceals the genome from cGAS and that chemical or physical disruption of the viral core can expose HIV-1 DNA and activate innate immune signaling., Competing Interests: Competing interests: The authors declare no competing interests.

Background: Implant-based submuscular breast reconstruction (SBR) can be performed with the aid of acellular dermal matrices (ADM) for implant coverage on their inferolateral pole, aiming at providing a biological interface for hiding the implant and therefore reducing the risk of complications. The purpose of this study is to assess the long-term post-operative outcomes obtained using the SBR-specific Native® ADM (DECO med s.r.l., Marcon, Venice, Italy)., Methods: All cases of Native®-assisted immediate SBR performed at our institution between October 2016 and March 2020 were retrospectively analysed. Demographic and surgical data were collected, and post-operative outcomes, including minor and major complications, were evaluated. Particular attention was paid to complications emerging before and after patient discharge. Dependence analyses were performed to uncover statistically significant relationships between risk factors and reconstructive outcomes., Results: Data on 100 patients were collected, for a total of 128 breasts. The mean age of the cohort was 49.5 years, the mean BMI was 23.4 kg/m2, and the mean follow-up was 24 months. Out of this, 14.1% of patients received pre-operative radiotherapy, while 16.4% underwent post-mastectomy radiotherapy. Breasts appeared to develop short-term minor complications more likely during hospitalisation (11.7% vs. 7.8%), while short-term major complications occurred more often after discharge (7.8% vs. 15.6%). The most frequent long-term complications were capsular contracture and contour defects (both 9.4%). Risk factors that showed a statistically significant relationship with complications were pre- and post-mastectomy radiotherapy and post-operative chemotherapy., Conclusions: The retrospective analysis showed results in line with clinical outcomes reported in the literature for the same reconstructive technique. The use of Native® ADM in SBR is safe and effective in the long term., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Martins et al.)

Introduction: Sao Tome and Principe is an African low-and-middle-income country, where extreme poverty causes major health inequalities. No systematic research has been done on the consumption of alcohol and drugs in Sao Tome and Principe, and only overall statistics are available based on the importation of alcoholic drinks and their distribution among the population. There are also no studies on consumption of alcohol and illicit substances in children and youth and no preventive measures being undertaken. Besides that, manual databases present significant limitations, considering the lack of causes associated with mortality rates (0 - 5 years and > 5), and the difficulty to establish a cause/effect relation between diseases, deaths and life expectancy. No relevant data with burden of life was found in the reports of Centro Nacional de Endemias or the non-governmental, organization Instituto Marques de Valle Flor, a facilitator on healthcare clinical specialties selected on a voluntary basis by doctors from Portuguese hospitals. So, we proposed to provide a first overview of family and housing conditions, and above all, the consumption of alcohol and illegal drugs in young people. Thus, a project, the National Survey on Harmful Consumption of Alcohol and Drugs in Schools of Sao Tome and Principe, will be realized in order to better characterize the situation among children and young students and test public health communication strategies and preventive interventions aimed at this target-population. Interventions were designed taking into consideration local sociocultural realities of target audiences. We considered dialect language, single-parent families (matriarchal structure) and polygamy (mostly) in men and a country and governments led by men (patriarchal structure) and, in which the woman's role, as Food and Agriculture Organization of the United Nations reports, remains overlooked. Subsequently, we will collect traditional alcohols samples from the two main islands for analysis (at Laboratório de Estudos Farmacêuticos and Laboratório Nacional de Engenharia Civil - Portugal) and to determine heavy metals in the production process and impact on burden of life., Material and Methods: In order to characterise the country's situation in terms of alcohol and illicit substances consumption a literature review was carried out through a search in several international electronic databases, such as those of the World Health Organization, World Health Organization Africa, United Nation, The Lancet and Lancet Global Health, etc. Available data of the following institutions of Sao Tome and Príncipe was also analyzed: National Institute of Statistics, Ministry of Education, Culture and Training and Ministry of Health and Social Affairs. Several interviews with community and church leaders as well as with members of catholic missions were carried out to better understand the local situation. Following this, a nationwide cross-sectional survey of a sample of 2064 students will be carried out. This will include a questionnaire on socio-demographic characteristics, lifestyles, health behaviors/attitudes, alcohol and illicit substances consumption. Finally, based on the overall diagnosis obtained, some edutainment health communication preventive interventions will be tested in the primary schools of three districts (EDUCA_TURTLE) and on the radio journalists (EDUCA_PRESS). These were evaluated by primary school teachers and by radio journalists.

Introduction: In Sao Tome and Principe there are no studies on alcohol and drug use among students, who could be potential allies in preventive interventions. The objectives of the present study are 1) to determine the frequency of alcohol and drug consumption in the school population, and 2) to identify the main characteristics associated with this behaviour., Material and Methods: We applied a biographical, demographic and socioeconomic questionnaire on the use of licit and illicit substances to a sample of 2064 students. Demographic and social characteristics are presented based on observed frequencies and comparisons between groups were made using chi-square tests. Significance was assessed at α = 0.05., Results: More than half of the students reported consumed alcohol at least once in their lifetime, and 32% consumed in the last 30 days. Older students were more likely to consume alcohol (p < 0.0001), but even in students under 16 years, 17% consumed in the last 30 days. We also found that 7% consumed one or more times per week in the last 30 days. The reasons presented for frequent consumption were different for boys ("participation in their group of friends") and girls ("decrease anxiety") (p = 0.005). Less than 1% of respondents admitted to having used marijuana, cocaine, crack or ecstasy., Discussion: Despite some limitations, such as self-reporting, we provide a first overview showing high consumption of alcohol by young people and the existence of illegal drugs circulating in the schools., Conclusion: It is urgent to implement preventive interventions, namely in the context of public health communication.

Objective: The main objective of this work was to translate the English version of ASSET (A Shortened Stress Evaluation Tool) into the Portuguese version and to validate its psychometric properties. Additionally, this work tested the convergent validity of the instrument., Methods: The translation and retroversion were conducted by experts and submitted to the authors for approval. Within an observational, cross-sectional study, regarding mental health at the workplace, ASSET together with other scales was applied to a sample of 405 participants. The psychometric validity of the subscales was studied using confirmatory factorial analysis., Results: The factorial structure of ASSET is globally supported by the results, with the Perceptions of Your Job and Attitudes Towards your Organisation subscales requiring slight adjustments in the item structure and the Your Health subscales replicating the original structure. The convergent validity also supports the ASSET, showing that all subscales are significantly correlated with variables used to test convergence., Conclusions: Globally, the results constitute an important contribution to ASSET and open the possibility of its usage among Portuguese-speaking countries. The results provide an evidence on the validity of the instrument and, in particular, of the mental and physical health subscales., Competing Interests: Competing interests: ASSET is a psychometric measure developed by the University of Manchester spin-off company Robertson Cooper, a company of which the author CC is a director, with the University being the largest shareholder. ASSET has been published widely in the scholarly literature., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To compare healthcare in acute myocardial infarction (AMI) treatment between contrasting health systems using comparable representative data from Europe and USA., Design: Repeated cross-sectional retrospective cohort study., Setting: Acute care hospitals in Portugal and USA during 2000-2010., Participants: Adults discharged with AMI., Interventions: Coronary revascularizations procedures (percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) surgery)., Main Outcome Measures: In-hospital mortality and length of stay., Results: We identified 1 566 601 AMI hospitalizations. Relative to the USA, more hospitalizations in Portugal presented with elevated ST-segment, and fewer had documented comorbidities. Age-sex-adjusted AMI hospitalization rates decreased in USA but increased in Portugal. Crude procedure rates were generally lower in Portugal (PCI: 44% vs. 47%; CABG: 2% vs. 9%, 2010) but only CABG rates differed significantly after standardization. PCI use increased annually in both countries but CABG decreased only in the USA (USA: 0.95 [0.94, 0.95], Portugal: 1.04 [1.02, 1.07], odds ratios). Both countries observed annual decreases in risk-adjusted mortality (USA: 0.97 [0.965, 0.969]; Portugal: 0.99 [0.979, 0.991], hazard ratios). While between-hospital variability in procedure use was larger in USA, the risk of dying in a high relative to a low mortality hospital (hospitals in percentiles 95 and 5) was 2.65 in Portugal when in USA was only 1.03., Conclusions: Although in-hospital mortality due to an AMI improved in both countries, patient management in USA seems more effective and alarming disparities in quality of care across hospitals are more likely to exist in Portugal., (© The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Introduction and Objectives: We aimed to compare access to new health technologies to treat coronary heart disease (CHD) in the health systems of Portugal and the US, characterizing the needs of the populations and the resources available., Methods: We reviewed data for 2000 and 2010 on epidemiologic profiles of CHD and on health care available to patients. Thirty health technologies (16 medical devices and 14 drugs) introduced during the period 1980-2015 were identified by interventional cardiologists. Approval and marketing dates were compared between countries., Results: Relative to the US, Portugal has lower risk profiles and less than half the hospitalizations per capita, but fewer centers per capita provide catheterization and cardiothoracic surgery services. More than 70% of drugs were available sooner in the US, whereas 12 out of 16 medical devices were approved earlier in Portugal. Nevertheless, at least five of these devices were adopted first or diffused faster in the US. Mortality due to CHD and myocardial infarction (MI) was lower in Portugal (CHD: 72.8 vs. 168 and MI: 48.7 vs. 54.1 in Portugal and the US, respectively; age- and gender-adjusted deaths per 100000 population, 2010); but only CHD deaths exhibited a statistically significant difference between the countries., Conclusions: Differences in regulatory mechanisms and price regulations have a significant impact on the types of health technologies available in the two countries. However, other factors may influence their adoption and diffusion, and this appears to have a greater impact on mortality, due to acute conditions., (Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: The development of work-family conflict over time was analyzed using Conservation of Resources Theory., Method: The reciprocal effect between work-family conflict and employee well-being was tested with cross-lagged analyses on the basis of three waves. The sample comprised 713 employees of a Portuguese service organization., Results: Structural equation modeling analyses, with sex, age, and parental demand controlled, indicated that the work-family conflict at T1 and T2 decreases the employee psychological well-being at T2 and T3, respectively. Furthermore, employee psychological well-being at T2 had a longitudinal cross-lagged effect on work-family at T3. We concluded that employee psychological well-being at T2 predicted work-family at T3, which was a subsequent outcome of work-family conflict on T1., Conclusions: This paper highlighted the importance of organizations to consider work-family conflict to ensure employees' well-being because they develop reciprocal relationship with a loss spiral effect.

The potential of Human Biomonitoring (HBM) in exposure characterisation and risk assessment is well established in the scientific HBM community and regulatory arena by many publications. The European Environment and Health Strategy as well as the Environment and Health Action Plan 2004-2010 of the European Commission recognised the value of HBM and the relevance and importance of coordination of HBM programmes in Europe. Based on existing and planned HBM projects and programmes of work and capabilities in Europe the Seventh Framework Programme (FP 7) funded COPHES (COnsortium to Perform Human Biomonitoring on a European Scale) to advance and improve comparability of HBM data across Europe. The pilot study protocol was tested in 17 European countries in the DEMOCOPHES feasibility study (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) cofunded (50%) under the LIFE+ programme of the European Commission. The potential of HBM in supporting and evaluating policy making (including e.g. REACH) and in awareness raising on environmental health, should significantly advance the process towards a fully operational, continuous, sustainable and scientifically based EU HBM programme. From a number of stakeholder activities during the past 10 years and the national engagement, a framework for sustainable HBM structure in Europe is recommended involving national institutions within environment, health and food as well as European institutions such as ECHA, EEA, and EFSA. An economic frame with shared cost implications for national and European institutions is suggested benefitting from the capacity building set up by COPHES/DEMOCOPHES., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Non-coding RNAs of complex tertiary structure are involved in numerous aspects of the replication and processing of genetic information in many organisms; however, an understanding of the complex relationship between their structural dynamics and function is only slowly emerging. The Neurospora Varkud Satellite (VS) ribozyme provides a model system to address this relationship. First, it adopts a tertiary structure assembled from common elements, a kissing loop and two three-way junctions. Second, catalytic activity of the ribozyme is essential for replication of VS RNA in vivo and can be readily assayed in vitro. Here we exploit single molecule FRET to show that the VS ribozyme exhibits previously unobserved dynamic and heterogeneous hierarchical folding into an active structure. Readily reversible kissing loop formation combined with slow cleavage of the upstream substrate helix suggests a model whereby the structural dynamics of the VS ribozyme favor cleavage of the substrate downstream of the ribozyme core instead. This preference is expected to facilitate processing of the multimeric RNA replication intermediate into circular VS RNA, which is the predominant form observed in vivo.

Objective: To study the patterns and determinants of psychoactive drug use by Lisbon University students., Materials and Methods: A cross-sectional survey was conducted, from January to April 2000, in a probabilistic sample of 1,147 students. Information about use of psychoactive drugs and co-variates was collected by a questionnaire administered by trained interviewers. Psychoactive drugs were considered to be all medicines classified in group N (nervous system) of the ATC system except the anesthetics (subgroup N01) and the analgesics (subgroup N02)., Results: 91 students (7.9%) had taken psychoactive drugs during the fortnight before the interview, 39 of whom (42.8%) mentioned continuous use. The prevalence of use was significantly higher in females (9.6%), older than 25 years (13.1%), married (16%), who considered themselves to have a weak health status (21.7%), as under intense stress (15.5%). After adjustment by multivariate analysis the variables sex, self-evaluation of health status and daily stress retained a higher significant association with psychoactive drug use. A total of 132 drugs were reported as being used in that period. Tranquilizers (ATC = N05B or N05C) were used by 82 students (7.2%), while 22 (1.9%) consumed psychoactive stimulants (N06B) and 19 (1.7%) antidepressants (N06A). In all of these therapeutical subgroups, females had higher consumption prevalence than males, but the difference was statistically significant only for tranquilizers (P < 0.001). Anxiety, depression and insomnia were the most frequently stated health problems. More than 90% of drug consumers considered they had a compliant attitude and about 60% considered themselves well-informed about adverse effects of the drug used. The reported prevalence of self-medication for psychoactive drugs used was 12.8%., Conclusions: The prevalence of psychoactive drug use among students of Lisbon University was higher than expected, considering age group and the usual health status of this population. The administration of a questionnaire was a very useful tool to characterise the pattern of use and the consumer's knowledge about the drugs consumed.

The hepatitis delta virus (HDV), an infectious human pathogen and satellite of hepatitis B virus, leads to intensified disease symptoms, including progression to liver cirrhosis. Both the circular RNA genome of HDV and its complementary antigenome contain the same cis-cleaving catalytic RNA motif that plays a crucial role in virus replication. Previously, the high-resolution crystal structure of the product form of a cis-acting genomic HDV ribozyme has been determined, while a trans-acting version of the ribozyme was used to dissect the cleavage reaction pathway. Using fluorescence resonance energy transfer (FRET) on a synthetic trans-cleaving form of the ribozyme, we are able to directly observe substrate binding (at a rate constant k(on) of 7.8 x 10(6) M(-1) min(-1) at pH 7.5, 11 mM MgCl(2), and 25 degrees C) and dissociation (at 0.34 min(-1)). Steady-state and time-resolved FRET experiments in solution and in nondenaturing gels reveal that the substrate (precursor) complex is slightly more compact (by approximately 3 A) than the free ribozyme, yet becomes significantly extended (by approximately 15 A) upon cleavage and product complex formation. We also find that trans cleavage is characterized by a high transition-state entropy (-26 eu). We propose that the significant global conformational change that we observe between the precursor and product structures occurs on the reaction trajectory into a constrained product complex-like transition state. Our observations may present the structural basis of the recently described utilization of intrinsic substrate binding energy to the overall catalytic rate enhancement by the trans-acting HDV ribozyme.

A number of studies have shown the benefit of hypertensive treatment even though the most common forms of the disease are mild-to-moderate in severity. Considering the overall aging of the world's population, it is of particular interest to study hypertension and its treatment in geriatric patients. A short-term study of isradipine was conducted to assess its effectiveness and tolerability in patients with mild-to-moderate hypertension. The study was carried out by general practitioners and involved 3343 patients, aged > or = 18 years, with diastolic blood pressures (DBPs) ranging from 95 to 114 mm Hg. A 4-week wash-out and placebo run-in phase was followed by a 12-week active treatment period with isradipine at 1.25 or 2.5 mg/day, depending on the blood pressure response. Posttreatment results in a subgroup of 1092 patients (444 men and 648 women), aged > or = 60 years, showed decreases in systolic blood pressure (SBP) from 173.1 to 149.2 mm Hg (mean decrease, 20.9 mm Hg) and, in DBP, from 102.0 to 85.0 mm Hg (mean decrease, 16.9 mm Hg). The majority (84.6%) of these patients showed DBP reductions of > 10 mm Hg, and 82.3% achieved normalization (DBP < 90 mm Hg) at the end of treatment. The mean dosage was 1.74 +/- 0.69 mg twice daily, and 37% of patients doubled their initial 1.25 mg twice daily dosages. There were no significant changes in either heart rate or major metabolic parameters. Adverse events were reported by 3.1% of the patients, and 90% of both patients and physicians expressed satisfaction with the therapy. There were no differences between men and women with regard to adverse events or efficacy, nor were the results in patients > or = 60 years different from those in younger patients. Thus, isradipine was effective and well tolerated in these geriatric patients.