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The SARS-CoV-2 virus has spread worldwide, leading governments to implement mitigation measures. Understanding the reluctance to adhere to non-pharmacological interventions might help promote adherence to these measures. This study aimed to identify factors associated with non-adherence to the first lockdown in Portugal.Cross-sectional study.This study used data from a Portuguese community-based survey entitled 'COVID-19 Barometer: Social Opinion'. Data were collected on risk perception, health status and social experiences using a snowball sampling technique. The event of interest corresponded to participants who reported not staying home during the lockdown period, serving as a proxy for non-adherence to lockdown. Logistic regression was used to identify factors associated with non-adherence to the first lockdown.Responses from 133,601 individual questionnaires that were completed during the first week of the first lockdown in 2020 were analysed. A minority of participants (5.6%) reported non-adherence to lockdown (i.e. leaving home for reasons other than essential situations). Working in the workplace was the factor with the strongest association of non-adherence to the lockdown. Several other factors were also associated with non-adherence to the first lockdown; namely, being a man, being a student, having a low level of education, having a low income, living alone or with a high-infection-risk professional (e.g. doctor, nurse, pharmaceutical, health technician, firefighter, police officer, military, essential services worker), perceiving the risk of getting COVID-19 to be high, not having social support in case of infection, feeling agitated, sad or anxious every day, and considering the preventive measures to be unimportant or inadequate.Non-adherence to lockdown was associated with socio-economic, trust and perception factors. Future research should investigate the mechanisms underlying these associations to help identify the population groups who are most at risk of non-adherence.

As Earth's climate has varied strongly through geological time, studying the impacts of past climate change on biodiversity helps to understand the risks from future climate change. However, it remains unclear how paleo-climate shapes spatial variation in biodiversity. Here, we assessed the influence of Quaternary climate change on spatial dissimilarity in taxonomic, phylogenetic, and functional composition among neighboring 200-kilometer cells (beta-diversity) for angiosperm trees worldwide. We found that larger glacial-interglacial temperature change was strongly associated with lower spatial turnover (species replacements) and higher nestedness (rich-ness changes) components of beta-diversity across all three biodiversity facets. Moreover, phylogenetic and functional turnover was lower and nestedness higher than random expectations based on taxonomic beta -di-versity in regions that experienced large temperature change, reflecting phylogenetically and functionally se-lective processes in species replacement, extinction, and colonization during glacial-interglacial oscillations. Our results suggest that future human-driven climate change could cause local homogenization and reduction in taxonomic, phylogenetic, and functional diversity of angiosperm trees worldwide. W.-B.X. and A.O. acknowledge support from the Aarhus University Research Foundation (AUFF) Starting Grant (AUFF-F-2018-7-8). J.-C.S. acknowledges support from the Danish Council for Independent Research|Natural Sciences (grant 6108-00078B) to the TREECHANGE Project. J.-C.S. also considers this work a contribution to the Center for Ecological Dynamics in a Novel Biosphere (ECONOVO) funded by Danish National Research Foundation (grant DNRF173) and the VILLUM Investigator project “Biodiversity Dynamics in a Changing World” funded by VILLUM FONDEN (grant 16549). W.L.E. was supported by the VILLUM FONDEN (grant 00025354). M.A. was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grants program. C.B. was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2022R1A2C1003504). A.G.G. was supported by the ANID PIA/BASAL (grant FB210006) and FONDECYT (grant 1200468). R.E.O. was supported by the German Research Foundation to German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig (DFG-FZT 118, 202548816). J.Pe. was supported by the Fundación Ramón Areces project (CIVP20A6621) and Spanish Government project (PID2019-110521GB-I00). J.Pi. was supported by the Estonian Research Council Grants (PUT1355, PRG 1405) and Mobilitas Pluss (MOBERC11). V.D.P. was supported by the National Council of Scientific and Technological Development (CNPq) of Brazil (grant 307689/2014-0).

Background Breast cancer (BC) is the most frequently diagnosed cancer and a leading cause of death among women worldwide. Early BC is potentially curable, but the mortality rates still observed among BC patients demonstrate the urgent need of novel and more effective diagnostic and therapeutic options. Limitless self-renewal is a hallmark of cancer, governed by telomere maintenance. In around 95% of BC cases, this process is achieved by telomerase reactivation through upregulation of the human telomerase reverse transcriptase (hTERT). The hypermethylation of a specific region within the hTERT promoter, termed TERT hypermethylated oncological region (THOR) has been associated with increased hTERT expression in cancer. However, its biological role and clinical potential in BC have never been studied to the best of our knowledge. Therefore, we aimed to investigate the role of THOR as a biomarker and explore the functional impact of THOR methylation status in hTERT upregulation in BC. Results THOR methylation status in BC was assessed by pyrosequencing on discovery and validation cohorts. We found that THOR is significantly hypermethylated in malignant breast tissue when compared to benign tissue (40.23% vs. 12.81%, P TERT core promoter alone (P TERT transcription, targeted THOR demethylation was performed using novel technology based on CRISPR-dCas9 system and significant THOR demethylation was achieved. Cells previously demethylated on THOR region did not develop a histologic cancer phenotype in in vivo assays. Additional studies are required to validate these observations and to unravel the causality between THOR hypermethylation and hTERT upregulation in BC. Conclusions THOR hypermethylation is an important epigenetic mark in breast tumorigenesis, representing a promising biomarker and therapeutic target in BC. We revealed that THOR acts as a repressive regulatory element of hTERT and that its hypermethylation is a relevant mechanism for hTERT upregulation in BC.

Safeguarding Earth?s tree diversity is a conservation priority due to the importance of trees for biodiversity and ecosystem functions and services such as carbon sequestration. Here, we improve the foundation for effective conservation of global tree diversity by analyzing a recently developed database of tree species covering 46,752 species. We quantify range protection and anthropogenic pressures for each species and develop conservation priorities across taxonomic, phylogenetic, and functional diversity dimensions. We also assess the effectiveness of several influential proposed conservation prioritization frameworks to protect the top 17% and top 50% of tree priority areas. We find that an average of 50.2% of a tree species? range occurs in 110-km grid cells without any protected areas (PAs), with 6,377 small-range tree species fully unprotected, and that 83% of tree species experience nonnegligible human pressure across their range on average. Protecting highpriority areas for the top 17% and 50% priority thresholds would increase the average protected proportion of each tree species? range to 65.5% and 82.6%, respectively, leaving many fewer species (2,151 and 2,010) completely unprotected. The priority areas identified for trees match well to the Global 200 Ecoregions framework, revealing that priority areas for trees would in large part also optimize protection for terrestrial biodiversity overall. Based on range estimates for >46,000 tree species, our findings show that a large proportion of tree species receive limited protection by current PAs and are under substantial human pressure. Improved protection of biodiversity overall would also strongly benefit global tree diversity. Made available in DSpace on 2022-06-21T15:23:55Z (GMT). No. of bitstreams: 1 Guo-et-al.-2022-PNAS-High-exposure-of-global-tree-diversity-to-human-pressure.pdf: 2523289 bytes, checksum: 245be3df3fb487ed152d25bf50f4e984 (MD5) Previous issue date: 2022 Proceedings of the National Academy of Sciences of the United States of America.

BACKGROUND: Neuromuscular diseases are characterized by the compromise of respiratory muscles, thoracic ventilation, muscle strength and coughing capacity. Patients have low quality of life and increased morbidity and mortality mostly due to respiratory impairment. OBJECTIVE: To assess the benefits of adding inspiratory muscle training to neuromuscular patients’ treatment and their compliance to the approach. METHODS: We conducted a single-center prospective study with neuromuscular patients with decreased maximal inspiratory pressure. We developed an inspiratory muscle training protocol with three-month duration and once-daily training. The protocol had a progressive intensity that was individually tailored based on patients’ baseline characteristics and tolerance. We used Powerbreathe Medic Classic devices to perform the training. RESULTS: There were 21 patients who met the inclusion criteria and were enrolled in the study. Muscular dystrophy (n= 12, 57.3%) and amyotrophic lateral sclerosis (n= 4, 19%) were the most common diseases. After three months of training, patients increased their maximal inspiratory muscle pressure (p= 0.002) and peak cough flow (p= 0.011). Compliance to the protocol was 99 ± 5.5%. CONCLUSIONS: This protocol showed significant improvements on pulmonary muscles function and might be considered as an adjunct treatment to neuromuscular treatment. However, these positive results require larger further studies to validate the clinical benefits long-term.

Different behaviors are considered important factors that may influence a healthy lifestyle. Given this fact, we aim to analyze the relationship between moderate-vigorous physical activity (MVPA), sleep time, and sedentary time, with cardiometabolic outcomes in adolescents.Cross-sectional study, with 152 eutrophic and healthy adolescents. The behavioral variables were collected objectively and the arterial thickness was measured through ultrasound. Blood variables (LDL, TG, HDL, glucose, and insulin) were collected in a private laboratory. To analyze the data, the Student t test and Kruskal-Wallis test were used to compare the groups. All analyses adopted p 0.05.Girls who demonstrated better combined behaviors, presented significant results for TG (p = 0.045), BP (p = 0.016), and cardiovascular score (p = 0.049) when compared to their peers. Furthermore, the practice of physical activity combined with sufficient sleep time was associated with lower values of arterial thickening (p = 0.017).In view of the results presented, it is possible to state that the aggregation of behaviors was more consistent in females and that the practice of physical activity and adequate sleep time can reflect on cardiovascular health.

Objectives Tuberculosis (TB) is the most common opportunistic infection and cause of mortality among people living with HIV, and it is possible that it may also influence the evolution of the HIV infection. We assessed the differences between HIV-positive and -negative people infected with TB. Methods The present study is a cross-sectional retrospective study by electronic record revision. We included patients admitted to a tertiary hospital with a diagnosis of TB between 2011 and 2016, comparing those with HIV coinfection with non-HIV patients, according to demographic and clinical characteristics. Results This study included 591 patients, of whom 32% were HIV-coinfected. HIV-TB patients were younger, with a predominance of male gender. Considering TB risk factors, there was a higher prevalence of homelessness and intravenous drug use in the HIV group. In the non-HIV group, direct contact with other patients with TB and immunosuppression were more prevalent. Relative to TB characteristics, the HIV-coinfected group presents with a higher prevalence of disseminated disease and a higher occurrence of previous TB infection. Cancer was the most frequent cause of immunosuppression in the HIV group and the number testing positive for TB via microbiological culture was lower. Assessment of microbiological resistance and in-hospital mortality showed similar numbers in both groups. Conclusions There are few papers comparing clinical course of TB between HIV-infected and non-infected patients. Our study differs from others in the literature as we focused on a country with middling incidence of TB and further characterized the differences between HIV-infected and non-infected patients which can contribute to the management of these patients.

IntroductionImmigrants carry an extra burden of morbidities and mortalities since the beginning of the coronavirus disease 2019 (COVID-19) pandemic. Pre-existing inequalities among immigrants may threaten their economic wellbeing during the pandemic. This study analyzed the socioeconomic impact of COVID-19 on immigrants and natives living in Amadora, Metropolitan Region of Lisbon and the extent to which preexisting inequalities had been exacerbated during the pandemic.Materials and methodsThis cross-sectional study was conducted in Amadora Municipality, Lisbon Region, through phone interviews and using a structured questionnaire. Data collected in July 2020, included information on a cohort of 420 households, of which 51% were immigrants. To evaluate the socioeconomic position and economic wellbeing changes occurring during the pandemic we estimate crude and adjusted odds ratio (OR) and 95% CI, using Portuguese natives as the reference group.ResultsOverall, 287 (70%) participants responded to the questionnaire, of which 47% are immigrants. Preexisting socioeconomic inequalities were exacerbated during the pandemic. Compared with natives, immigrants were more likely to experience job loss, temporary lay-off, and income loss during the COVID-19 pandemic. Immigrants were also more likely to face several kinds of financial hardship during the pandemic, such as difficulties in buying food, hygiene products, and paying bills.ConclusionTo the best of our knowledge, this study is the first to capture the direct socioeconomic impact of COVID-19 among immigrants and natives in Portugal. It highlights the bidirectional relation between inequalities deeply rooted among immigrants and COVID-19. Socioeconomic inequalities affect local patterns of COVID-19 burden, as confirmed in previous studies, but COVID-19 also has an impact on the economic wellbeing of Amadora immigrants during the pandemic. Urgent policies must be implemented to mitigate the economic burden of COVID-19 among immigrants, namely in Amadora, Lisbon Region.

Aim: Quality of life (QoL) is one of the most important patient-reported outcomes in chronic diseases. Using a population-based cohort, our objective was to assess health-related QoL in individuals with a previous myocardial infarction (MI). Methods: This study was conducted on a large database representative of the adult Portuguese population aged 18 years or over, living in the community. Participants were assessed through telephone interview. A standardized questionnaire was applied to every individual about self-reported chronic diseases, including previous MI. QoL was assessed with the EQ-5D-3L version of EuroQol. The prevalence of previous MI was calculated and linear regression analysis was performed. Results: The estimated prevalence of previous MI in the adult Portuguese population was 1.1%. These patients were older and more often male, had lower income and lower education levels, and were more often from urban areas. Respondents with self-reported MI assigned a lower self-perception to their health status in all domains, particularly in mobility and anxiety/depression. The mean EQ-5D-3L score in patients with MI was 0.73±0.34, significantly lower than in patients without MI (0.78±0.29). Also, the number of chronic diseases was significantly higher in patients with MI (5.0±2.2 vs. 1.7±1.8). Previous MI was not independently associated with QoL, which was related to age, gender and number of comorbidities. Conclusions: Adults with previous MI have a worse self-perceived health status and QoL. Previous MI was not an independent predictor of health-related QoL after controlling for age, gender and associated chronic diseases. Resumo: Introdução: A qualidade de vida (QOL) é um dos mais importantes resultados reportados por doentes em doenças crónicas. Utilizando uma coorte baseada na população, foi nosso objetivo avaliar a qualidade de vida relacionada com a saúde em doentes com enfarte do miocárdio (EM) prévio. Métodos: Estudo realizado numa grande base de dados representativa da população portuguesa adulta com ≥ 18 anos, a viver na comunidade. Os participantes foram avaliados por entrevista telefónica e foi aplicado um questionário estandardizado a cada indivíduo sobre doenças crónicas autotreportadas, incluindo EM no passado. A QOL foi avaliada com a ferramenta EuroQol (EQ-5D-3L). Resultados: A prevalência estimada de EM prévio foi de 1,1%. Estes doentes são mais idosos e mais homens, com menor rendimento e nível de educação e mais frequentemente de áreas urbanas. Os indivíduos com EM prévio têm pior perceção do seu estado de saúde em todos os domínios, em particular na mobilidade e ansiedade/depressão. O índice EQ-5D-3L médio foi 0,73±0,34, significativamente inferior quando comparado com doentes sem EM (0,78±0,29). O número de doenças crónicas é significativamente superior em doentes com EM (5,6±2,2 versus 1,7±1,8). O EM prévio não se associa de forma independente à QOL, estando esta relacionada com idade, género e número de comorbilidades associadas. Conclusões: Adultos com EM prévio apresentam uma pior percepção da sua saúde e QOL. O EM prévio não é preditor independente de QOL após controlo para idade, género e doenças crónicas associadas.

Funding Information: This research was funded by the Portuguese Science and Technology Foundation (FCT) with the grant number CEECIND/04266/2017. Acknowledgments: The authors would like to thank Eunice Silva for technical support. Funding Information: Funding: This research was funded by the Portuguese Science and Technology Foundation (FCT) with the grant number CEECIND/04266/2017. Daytime hypersomnolence, the prime feature of obstructive sleep apnea (OSA), frequently leads to high coffee consumption. Nevertheless, some clinicians ask for patients’ caffeine avoidance. Caffeinated drinks are sometimes associated with more severe OSA. However, these effects are not consensual. Here we investigated the effect of caffeine consumption on sleep architecture and apnea/hypopnea index in OSA. Also, the impact of caffeine on variables related with dysmetabolism, dyslipidemia, and sympathetic nervous system (SNS) dysfunction were investigated. A total of 65 patients diagnosed with OSA and 32 without OSA were included after given written informed consent. Polysomnographic studies were performed. Blood was collected to quantify caffeine and its metabolites in plasma and biochemical parameters. 24 h urine samples were collected for catecholamines measurement. Statistical analyses were performed by SPSS: (1) non-parametric Mann-Whitney test to compare variables between controls and OSA; (2) multivariate logistic regression testing the effect of caffeine on sets of variables in the 2 groups; and (3) Spearmans’ correlation between caffeine levels and comorbidities in patients with OSA. As expected OSA development is associated with dyslipidemia, dysmetabolism, SNS dysfunction, and sleep fragmentation. There was also a significant increase in plasma caffeine levels in the OSA group. However, the higher consumption of caffeine by OSA patients do not alter any of these associations. These results showed that there is no apparent rationale for caffeine avoidance in chronic consumers with OSA. publishersversion published

The diagnosis of visceral leishmaniasis (VL) has improved with the search of novel antigens; however, their performance is limited when samples from VL/human immunodeficiency virus (HIV)-coinfected patients are tested. In this context, studies conducted to identify more suitable antigens to detect both VL and VL/HIC coinfection cases should be performed. In the current study, phage display was performed using serum samples from healthy subjects and VL, HIV-infected and VL/HIV-coinfected patients; aiming to identify novel phage-exposed epitopes to be evaluated with this diagnostic purpose. Nine non-repetitive and valid sequences were identified, synthetized and tested as peptides in enzyme-linked immunosorbent assay experiments. Results showed that three (Pep2, Pep3 and Pep4) peptides showed excellent performance to diagnose VL and VL/HIV coinfection, with 100% sensitivity and specificity values. The other peptides showed sensitivity varying from 50.9 to 80.0%, as well as specificity ranging from 60.0 to 95.6%. Pep2, Pep3 and Pep4 also showed a potential prognostic effect, since specific serological reactivity was significantly decreased after patient treatment. Bioinformatics assays indicated that Leishmania trypanothione reductase protein was predicted to contain these three conformational epitopes. In conclusion, data suggest that Pep2, Pep3 and Pep4 could be tested for the diagnosis of VL and VL/HIV coinfection.

To compare the operative time and presence of air voids on Class II restorations fabricated by dental practitioners with 1 to 5 years of experience using incremental and bulk-filling techniques.Four techniques were evaluated: incremental, bulk-filling, bulk-filling with heated composite, and snowplow technique. Standardized mandibular first molars with a MOD (mesial, occlusal, and distal) cavity were used. Voluntary operators made two restorations using each technique and the time required for each restoration was recorded. The restorations were scanned by micro-computed tomography to calculate the volume of the restoration occupied by air voids. The "operative time" and "volume of air voids" were analyzed individually by two-way ANOVA and Tukey HSD post hoc (α = .05) for the factors operator and insertion technique. A correlation between "operative time" and "volume of air voids" was evaluated using Pearson coefficient (α = .05).The incremental technique required significantly longer time, yet no differences were observed between the bulk-filling techniques. There were no significant differences between techniques regarding the volume of air voids. A significant, but weak, and inverse linear correlation (P = .0059; r = -.29; r2 = 8.41%) was found between the operative time and volume of air voids.There were no significant differences in the volume of air voids among the evaluated techniques, although bulk-filling techniques required a shorter operative time. Hence, implementing bulk-filling techniques by dental schools and restorative dental practitioners with different levels of expertise may reduce chair time and produce a volume of air voids similar to the incremental technique.

Background Brazil lacks data from syphilis in its border areas. We aimed to describe the spatial and temporal distribution of acquired syphilis (AS), in pregnancy (SP) and congenital syphilis (CS) in Brazilian municipalities in the arches border contexts. Methods An ecological, cross-sectional study was conducted from 2010 to 2020. The study was based on the cases of syphilis available in the Notifiable Diseases Information System (SINAN), and on the Primary Health Care Information System. The detection rates of AS and SP, and the incidence of CS were estimated, and the time series was analyzed. Data between the border arches were compared. Results In 2020, data showed 7,603 cases of AS (detection rate 64.8/100,000 inhabitants), 3,960 cases of SP (detection rate of 21.6/1,000 live births) and 836 cases of CS (incidence of 4.6/1,000 live births) in the border region. Between 2010 and 2020, the mean annual increase of detection rate of SP was 53.4% in Brazil, 48.0% in the border region, 59.6% in the North Arch, 28.8% in the Central and 67.2% in the South. Annual variation on the incidence of CS for the same period was 31.0% in Brazil 38.4% at the border, in the North and South Arcs 18.3% and 65.7% respectively. The Central Arch showed an increase only between 2010 and 2018 (62.7%). A total of 427 (72.6%) municipalities has primary health care coverage ≥ 95% of the population. In 2019, 538 (91.8%) municipalities reported using rapid tests for syphilis, which decreased to 492 (84%) in 2020. In 2019, 441 (75.3%) municipalities reported administering penicillin, and 422 (72%) in 2020. Conclusion Our data show syphilis reman problem at the Brazilian border, rates in pregnant are high. It was observed a reduction in the detection rates, SP and the incidence of CS between 2018 and 2020. Syphilis should be included on the agenda of all management levels, aiming at expanding access and quality care.

Reproductive sterility is the basis of the sterile insect technique (SIT) and essential for its success in the field. Numerous factors that influence dose–response in insects have been identified. However, historically the radiation dose administered has been considered a constant. Efforts aiming to standardize protocols for mosquito irradiation found that, despite carefully controlling many variable factors, there was still an unknown element responsible for differences in expected sterility levels of insects irradiated with the same dose and handling protocols. Thus, together with previous inconclusive investigations, the question arose whether dose really equals dose in terms of biological response, no matter the rate at which the dose is administered. Interestingly, the dose rate effects studied in human nuclear medicine indicated that dose rate could alter dose–response in mammalian cells. Here, we conducted experiments to better understand the interaction of dose and dose rate to assess the effects in irradiated mosquitoes. Our findings suggest that not only does dose rate alter irradiation-induced effects, but that the interaction is not linear and may change with dose. We speculate that the recombination of reactive oxygen species (ROS) in treatments with moderate to high dose rates might minimize indirect radiation-induced effects in mosquitoes and decrease sterility levels, unless dose along with its direct effects is increased. Together with further studies to identify an optimum match of dose and dose rate, these results could assist in the development of improved methods for the production of high-quality sterile mosquitoes to enhance the efficiency of SIT programs.

Phagocytosis is an orchestrated process that involves distinct steps: recognition, binding, and internalization. Professional phagocytes take up Leishmania parasites by phagocytosis, consisting of recognizing ligands on parasite surfaces by multiple host cell receptors. Binding of Leishmania to macrophage membranes occurs through complement receptor type 1 (CR1) and complement receptor type 3 (CR3) and Pattern Recognition Receptors. Lipophosphoglycan (LPG) and 63 kDa glycoprotein (gp63) are the main ligands involved in macrophage-Leishmania interactions. Following the initial recognition of parasite ligands by host cell receptors, parasites become internalized, survive, and multiply within parasitophorous vacuoles. The maturation process of Leishmania-induced vacuoles involves the acquisition of molecules from intracellular vesicles, including monomeric G protein Rab 5 and Rab 7, lysosomal associated membrane protein 1 (LAMP-1), lysosomal associated membrane protein 2 (LAMP-2), and microtubule-associated protein 1A/1B-light chain 3 (LC3). Here, we describe methods to evaluate the early events occurring during Leishmania interaction with the host cells using confocal microscopy, including (i) binding (ii) internalization, and (iii) phagosome maturation. By adding to the body of knowledge surrounding these determinants of infection outcome, we hope to improve the understanding of the pathogenesis of Leishmania infection and support the eventual search for novel chemotherapeutic targets.

We aimed to assess the proportion of the population in 133 Brazilian municipalities who - from March to August 2020 - had a health problem but failed to seek care or failed to attend to a health service for routine appointment or examination. We conducted a household survey from August 24-27 in 133 Brazilian cities by asking the subjects if, since the beginning of the COVID-19 pandemic in March 2020, they had suffered from a health problem but did not seek care or failed to attend to a routine or screening examination. Poisson regression was used for the analyses. We interviewed 33,250 subjects and 11.8% (95%CI: 11.4-12.1) reported that, since March 2020, they failed to seek care despite being ill, 17.3% (95%CI: 16.9-17.7) failed to attend to a routine or screening examination and 23.9% (95%CI: 23.4-24.4) reported one or both outcomes. Health service closure and fear of the COVID-19 infection were the main reasons for not seeking care. Women and the poorest were more likely to not look for a health service, despite having a health problem or a scheduled routine appointment. On the other hand, those subjects who self-identified as white were less likely to not look for a health service. The COVID-19 pandemic is more critical for the indigenous people and the poorest, and these people are also more likely to not seek care for other health conditions during the pandemic.

Background The global financial crisis and the economic and financial adjustment programme (EFAP) forced the Portuguese government to adopt austerity measures, which also included the health sector. The aim of this study was to analyse factors associated with HIV/AIDS patients’ length of stay (LOS) among Portuguese hospitals, and the potential impact of the EFAP measures on hospitalizations among HIV/AIDS patients. Methods Data used in this analysis were collected from the Portuguese database of Diagnosis Related Groups (DRG). We considered only discharges classified under MCD 24 created for patients with HIV infection. A total of 20,361 hospitalizations occurring between 2009 and 2014 in 41 public hospitals were included in the analysis. The outcome was the number of days between hospital admission and discharge dates (LOS). Hierarchical Poisson regression model with random effects was used to analyse the relation between LOS and patient, treatment and setting characteristics. To more effectively analyse the impact of the EFAP implementation on HIV/AIDS hospitalizations, yearly variables, as well as a variable measuring hospitals’ financial situation (current ratio) was included. Results For the 5% level, having HIV/AIDS as the principal diagnosis, the number of secondary diagnoses, the number of procedures, and having tuberculosis have a positive impact in HIV/AIDS LOS; while being female, urgent admission, in-hospital mortality, pneumocystis pneumonia, hepatitis C, and hospital’s current ratio contribute to the decrease of LOS. Additionally, LOS between 2010 and 2014 was significantly shorter in comparison to 2009. Differences in LOS across hospitals are significant after controlling for these variables. Conclusion Following the EFAP, a number of cost-containment measures in the health sector were implemented. Results from our analysis suggest that the implementation of these measures contributed to a significant decrease is LOS among HIV/AIDS patients in Portuguese hospitals.

Tympanostomy with ventilation tube insertion is the most common otologic surgery. Many surgeons recommend water precautions, although its utility is questioned. We aimed to investigate if water precautions reduce the rate of otorrhea after transtympanic tube insertion.Multicenter randomized controlled trial.A total of 244 children aged 2 to 10 years undergoing their first set of Shepard tubes for otitis media with effusion and concomitant adenoidectomy were randomized to 2 groups: 1 with ear protection during water exposure (ear plugs and headbands, n = 130) and 1 without (n = 114). Bathing or swimming with unprotected ears was considered the exposure event and incidence of otorrhea, the primary outcome. Outcomes were assessed during the 6-month follow-up period.In the water precaution group, 32% had at least 1 episode of otorrhea as compared with 22% in the unprotected group, which was not statistically significant (The incidence of otorrhea was not different with or without prescription of ear protection during water exposure among children with tympanostomy tubes, which supports current guideline recommendations that routine water precautions are unnecessary in this population.

Background Evidence-based, patient-specific estimates of abusive head trauma probability can inform physicians’ decisions to evaluate, confirm, exclude, and/or report suspected child abuse. Objective To derive a clinical prediction rule for pediatric abusive head trauma that incorporates the (positive or negative) predictive contributions of patients’ completed skeletal surveys and retinal exams. Participants and Setting 500 acutely head-injured children under three years of age hospitalized for intensive care at one of 18 sites between 2010 and 2013. Methods Secondary analysis of an existing, cross-sectional, prospective dataset, including (1) multivariable logistic regression to impute the results of abuse evaluations never ordered or completed, (2) regularized logistic regression to derive a novel clinical prediction rule that incorporates the results of completed abuse evaluations, and (3) application of the new prediction rule to calculate patient-specific estimates of abusive head trauma probability for observed combinations of its predictor variables. Results Applying a mean probability threshold of >0.5 to classify patients as abused, the 7-variable clinical prediction rule derived in this study demonstrated sensitivity 0.73 (95% CI: 0.66-0.79) and specificity 0.87 (95% CI: 0.82-0.90). The area under the receiver operating characteristics curve was 0.88 (95% CI: 0.85-0.92). Patient-specific estimates of abusive head trauma probability for 72 observed combinations of its seven predictor variables ranged from 0.04 (95% CI: 0.02-0.08) to 0.98 (95% CI: 0.96-0.99). Conclusions Seven variables facilitate patient-specific estimation of abusive head trauma probability after abuse evaluation in intensive care settings.

Aims: Clinical risk factors and bone mineral densitometry underestimate low-energy fracture (LEF) risk in people with diabetes. We aim to estimate the prevalence of LEF in diabetics, compare with nondiabetics; and evaluate possible predictors of LEF in people with diabetes. Methods: Cross-sectional, population-based study in Portuguese subjects over 40 years-old. Estimates computed as weighted proportions/means, considering sample design. Multivariate logistic regression models to evaluate the association of diabetes and LEF; and predictors of LEF in diabetics. Results: 7675 subjects were analysed, of which 1173 reported diabetes. Diabetics were older (mean age 66.0 ± 11.49y), more frequently reported osteoporosis and falls in the previous 12 months (32.4% vs. 22.9%). Prevalence of self-reported LEF was 16.2% (95% CI:13.68-19.13) among diabetics (vs. 13.3%, 95% CI:12.14-14.57, in nondiabetics); OR for the association diabetes and LEF:1.26, 95% CI:1.01-1.58, p = 0.045 (in women, adjusted OR:1.41, 95% CI:1.05-1.89, p = 0.02). Thirty percent of diabetics reported at least one major LEF and 70% in other sites. In diabetics, LEF was independently associated with self-reported osteoporosis and falls in the previous 12 months. Conclusion: People with diabetes reported more falls and had higher prevalence of self-reported LEF. Self-reported osteoporosis and falls were associated with LEF in diabetics. Our findings emphasize the need for fracture and falls preventive measures in diabetics. info:eu-repo/semantics/publishedVersion

Mycotoxins are toxic secondary metabolites produced by a variety of fungi, which when ingested can cause several deleterious effects to the health of humans and animals. In this work, the detection and quantification of six major mycotoxins (aflatoxins—AFLA, deoxynivalenol—DON, fumonisins—FUMO, ochratoxin A—OTA, T-2 toxin—T-2 and zearalenone—ZON) in 1749 samples of feed and feed ingredients for cattle, collected in Brazil between 2017 and 2021, was carried out using enzyme-linked immunosorbent assay (ELISA). In total, 97% of samples were contaminated with at least one mycotoxin, yet, very few samples exceeded the lowest European Union guidance values for cattle, and the estimated daily intake also showed a low risk for the animals. However, co-occurrences were widely observed, as 87% of samples contained two or more mycotoxins at the same time, and the presence of more than one mycotoxin at the same time in feed can lead to interactions. In conclusion, the contamination of feed and feed ingredients for cattle with mycotoxins in Brazil is very common. Hence, the monitoring of these mycotoxins is of significant importance for food safety.

The aim of this study was to evaluate the performance of the new classification of urinary tract dilatation (UTD) to predict long-term clinical outcomes in infants with isolated antenatal hydronephrosis (ANH).Between 1989 and 2019, 447 infants diagnosed with isolated severe ANH and were prospectively followed. The main predictive variable for the analysis was the new UTD classification system. The events of interest were surgical interventions, urinary tract infections, chronic kidney disease stage II or higher, hypertension and proteinuria. The primary end-point was time until the occurrence of a composite event of renal injury, including proteinuria, hypertension and chronic kidney disease.Among 447 infants with ANH included in the analysis, 255 (57%) had UTD P1, 93 (20.8%) UTD P2 and 99 (22.2%) UTD P3. Median followup time was 9 years (IQR 7-12 years). Of 447 patients included in the analysis, 11 (2.5%) had hypertension, 13 (2.9%) exhibited persistent mild proteinuria, 14 (3%) developed chronic kidney disease Stage 2 and 26 (5.8%) had the composite outcome of renal injury. By survival analysis, the UTD system predicted accurately all events of interest. According to the Kaplan-Meier survival analysis, the probability of renal injury at 20 years of age was estimated at about 0%, 14% and 56% for patients assigned to UTD P1, UTD P2 and UTD P3, respectively (p0.001).Our findings provide insights that the new UTD classification has a good performance for discriminating not only mid-term, but also long-term clinical outcomes, including renal injury.

The tumor microenvironment (TME) is a heterogenous assemblage of malignant and non-malignant cells, including infiltrating immune cells and other stromal cells, together with extracellular matrix and a variety of soluble factors. This complex and dynamic milieu strongly affects tumor differentiation, progression, immune evasion, and response to therapy, thus being an important therapeutic target. The phenotypic and functional features of the various cell types present in the TME are largely dependent on their ability to adopt different metabolic programs. Hence, modulating the metabolism of the cells in the TME, and their metabolic crosstalk, has emerged as a promising strategy in the context of anticancer therapies. Natural compounds offer an attractive tool in this respect as their multiple biological activities can potentially be harnessed to ‘(re)-educate’ TME cells towards antitumoral roles. The present review discusses how natural compounds shape the metabolism of stromal cells in the TME and how this may impact tumor development and progression.

Interactions of glycan-specific epitopes to human lectin receptors represent novel immune checkpoints for investigating cancer and infection diseases. By employing a multidisciplinary approach that combines isothermal titration calorimetry, NMR spectroscopy, molecular dynamics simulations, and X-ray crystallography, we investigated the molecular determinants that govern the recognition of the tumour and pathogenic glycobiomarker LacdiNAc (GalNAcβ1-4GlcNAc, LDN), including their comparison with the ubiquitous LacNAc epitope (Galβ1-4GlcNAc, LN), by two human immune-related lectins, galectin-3 (hGal-3) and the macrophage galactose C-type lectin (hMGL). A different mechanism of binding and interactions was observed for the hGal-3/LDN and hMGL/LDN complexes, which explains the remarkable difference in the binding specificity of LDN and LN by these two lectins. The new structural clues reported herein are fundamental for the chemical design of mimetics targeting hGal-3/hMGL recognition process.

Aims: Chronic heart failure (HF) is a major comorbidity accounting for an increased severity and mortality related to coronavirus disease 2019 (COVID-19). To reduce the risk of COVID-19 in HF patients, telemedicine has been encouraged. Methods and results: During the COVID-19 pandemic, telemedical management with mainly over-the-phone appointments became a major strategy of follow-up of our HF clinic patients. Previously, the large majority of patients have been seen in the hospital with direct patient-provider contact. We compared both strategies of follow-up, in pre-pandemic (PPP) and pandemic (PP) periods, regarding total mortality and hospitalizations/emergency department (ED) visits due to HF exacerbation. We prospectively studied a cohort of 196 patients. The mean follow-up time in PPP was 1.4 years. In this period, 20 patients died. In PP (follow-up of 71 days), there was one additional death. Total mortality in the first year of follow-up was 12.0%, matching the mortality predicted by the Meta-Analysis Global Group in Chronic Heart Failure score. Considering hospitalizations/ED visits due to decompensated HF, there was no statistically significant difference between PPP and PP. Only one patient was diagnosed with COVID-19. Conclusions: In the light of an increase in telemedical management of this cohort of HF patients, we were able to maintain a low rate of admissions due to HF decompensation, without an increment in mortality. Regarding these results, we encourage the incremental use of telemedicine in HF patients in the context of this or future pandemics and also in situations in which physical consultation might not be possible due to logistic issues. publishersversion published

To estimate the impact of the PediBIRN (Pediatric Brain Injury Research Network) 4-variable clinical decision rule (CDR) on abuse evaluations and missed abusive head trauma in pediatric intensive care settings.This was a cluster randomized trial. Participants included 8 pediatric intensive care units (PICUs) in US academic medical centers; PICU and child abuse physicians; and consecutive patients with acute head injures3 years (n = 183 and n = 237, intervention vs control). PICUs were stratified by patient volumes, pair-matched, and randomized equally to intervention or control conditions. Randomization was concealed from the biostatistician. Physician-directed, cluster-level interventions included initial and booster training, access to an abusive head trauma probability calculator, and information sessions. Outcomes included "higher risk" patients evaluated thoroughly for abuse (with skeletal survey and retinal examination), potential cases of missed abusive head trauma (patients lacking either evaluation), and estimates of missed abusive head trauma (among potential cases). Group comparisons were performed using generalized linear mixed-effects models.Intervention physicians evaluated a greater proportion of higher risk patients thoroughly (81% vs 73%, P = .11) and had fewer potential cases of missed abusive head trauma (21% vs 32%, P = .05), although estimated cases of missed abusive head trauma did not differ (7% vs 13%, P = .22). From baseline (in previous studies) to trial, the change in higher risk patients evaluated thoroughly (67%→81% vs 78%→73%, P = .01), and potential cases of missed abusive head trauma (40%→21% vs 29%→32%, P = .003), diverged significantly. We did not identify a significant divergence in the number of estimated cases of missed abusive head trauma (15%→7% vs 11%→13%, P = .22).PediBIRN-4 CDR application facilitated changes in abuse evaluations that reduced potential cases of missed abusive head trauma in PICU settings.ClinicalTrials.gov: NCT03162354.

The grading of urinary tract dilatation (UTD) on postnatal sonography is a fundamental step to establish rational management for infants with antenatal hydronephrosis (ANH). The aim of this study was to compare the prediction accuracy of UTD grading systems for relevant clinical outcomes. In addition, we propose a refinement of the UTD classification by adding quantitative measurements and evaluate its impact on accuracy.Between 1989 and 2019, 447 infants diagnosed with isolated AHN were prospectively followed. The events of interest were surgical interventions and kidney injury. Comparison of performance of the grading systems and the impact on the accuracy of a modified UTD classification (including the size of the kidney parenchyma) was assessed by the area under the receiver-operating characteristic curve (AUC).Of 447 infants, 131 (29%) underwent surgical intervention and 26 (5.8%) had developed kidney injury. The median follow-up time was 9 years (IQ range, 7-12 years). The performance for detecting the need for surgical intervention was excellent for all grading systems (AUC 0.90). However, for predicting kidney injury, the modified UTD classification exhibited significant improvement in accuracy (AUC = 0.913, 95%CI, 0.883-0.937) as compared with UTD classification (AUC = 0.887, 95%CI, 0.854-0.915) (P = 0.027).Our study confirms that the hydronephrosis grading systems provide excellent accuracy in discriminating patients who need surgical intervention among infants with AHN. Our findings suggest that the inclusion of kidney parenchymal thickness to UTD classification might increase the accuracy for predicting infants who may develop kidney injury. A higher resolution version of the Graphical abstract is available as Supplementary information.

Here, we describe 4-dimethylaminoantipyrine (4-DMAA)-mediated interfacing as a broad biochemical indicator to stabilize and promote the higher response of electrodes for immunological detection. We hypothesized that the improved biological interactions of 4-DMAA with electrodes and biological samples may be due to the interaction properties of the benzene and pyrazole chemical groups with graphite and proteins, respectively. In order to demonstrate that 4-DMAA could be used as a general indicator in electrochemical immunoassays, we used peptides as probes for the diagnosis of four neglected tropical infectious diseases Tegumentary leishmaniasis, Visceral leishmaniasis, Strongyloidiasis, and Leprosy on commercial graphite screen-printed electrodes. 4-DMAA oxidation was used to indicate specific biological recognition between the epitope-based peptide and serum immunoglobulin G (IgG) from infected patients. We demonstrated that 4-DMAA should be incorporated into the electrodes prior to serum application, which avoids interference with its sensitivity and specificity. In addition, 4-DMAA oxidizes at a low anodic potential, and the oxidation peak is useful for detecting proteins in biological fluids. In summary, we have successfully demonstrated the broad application of 4-DMAA as a general indicator for the specific diagnosis of four infectious diseases in electrochemical immunosensors. Such a strategy is quite advantageous for indirect detection of proteins that lack electrochemical activities or are spatially inaccessible on the electrode surface. This new indicator opens a new avenue for monitoring biological recognition, especially for immunosensors.

Cardiovascular diseases represent the first cause of death globally. Inflammatory rheumatic disease (IRMD) patients, due to their lifelong inflammatory status, are at increased risk of developing premature cardiovascular disease. We aimed to assess the risk for cardiovascular events (CVE) in a population-based study. We followed 10,153 adults from the EpiDoC Cohort, a large Portuguese population-based prospective study (2011-2016). IRMD patients were identified at baseline and followed during 5 years. CVE were defined as a composite of self-reported myocardial infarction or angina pectoris, arrhythmias, valvular disease, stroke or transient ischemic attack and peripheral artery disease. Statistical analysis was performed by utilizing multivariate logistic regression and goodness-of-fit and area under ROC curve. At baseline, IRMD patients had similar age as the non-IRMD participants (mean age 55 vs 53 years-old; 72.1% female); dyslipidaemia and sedentary lifestyle were more common (40.7% vs 31.4%, p = 0.033; 87.3% vs 67%, p = 0.016, respectively). During an average follow-up of 2.6 years, 26 CVE were reported among IRMD patients. IRMD patients had higher odd of CVE (OR 1.64, 95% CI 1.04-2.58; p = 0.03), despite comparable mortality rates (1.7% vs 0.7%, p = 0.806). A stepwise approach attained that gender, age, history of hypertension, body mass index, IRMD and follow-up time are the most important predictive variables of CVE (AUC 0.80). IRMD patients, at community level, have an increased short-term risk of major CVE when compared to non-IRMD, and that highlights the potential benefit of a systematic screening and more aggressive cardiovascular risk assessment and management of these patients.

Pediatric care providers, pediatricians, pediatric subspecialty physicians, and other health care providers should be able to recognize children with abnormal head shapes that occur as a result of both synostotic and deformational processes. The purpose of this clinical report is to review the characteristic head shape changes, as well as secondary craniofacial characteristics, that occur in the setting of the various primary craniosynostoses and deformations. As an introduction, the physiology and genetics of skull growth as well as the pathophysiology underlying craniosynostosis are reviewed. This is followed by a description of each type of primary craniosynostosis (metopic, unicoronal, bicoronal, sagittal, lambdoid, and frontosphenoidal) and their resultant head shape changes, with an emphasis on differentiating conditions that require surgical correction from those (bathrocephaly, deformational plagiocephaly/brachycephaly, and neonatal intensive care unit-associated skill deformation, known as NICUcephaly) that do not. The report ends with a brief discussion of microcephaly as it relates to craniosynostosis as well as fontanelle closure. The intent is to improve pediatric care providers’ recognition and timely referral for craniosynostosis and their differentiation of synostotic from deformational and other nonoperative head shape changes.

Pediatric radiologists are frequently summoned to testify in court regarding the imaging of child abuse. This essay provides guidance on how to prepare for trial and what to expect in court. Preparation is paramount and includes meeting with the attorney and reviewing imaging studies, medical records and pertinent reports in anticipation of questioning in court. We also provide guidance to aid in testimony in court. Legal standards for testimony are discussed herein.

Zika virus (ZIKV), a member of the Flaviviridae family, was brought into the spotlight due to its widespread and increased pathogenicity, including Guillain-Barre syndrome and microcephaly. Neural progenitor cells (NPCs), which are multipotent cells capable of differentiating into the major neural phenotypes, are very susceptible to ZIKV infection. Given the complications of ZIKV infection and potential harm to public health, effective treatment options are urgently needed. Betulinic acid (BA), an abundant terpenoid of the lupane group, displays several biological activities, including neuroprotective effects. Here we demonstrate that Sox2+ NPCs, which are highly susceptible to ZIKV when compared to their neuronal counterparts, are protected against ZIKV-induced cell death when treated with BA. Similarly, the population of Sox2+ and Casp3+ NPCs found in ZIKV-infected cerebral organoids was significantly higher in the presence of BA than in untreated controls. Moreover, well-preserved structures were found in BA-treated organoids in contrast to ZIKV-infected controls. Bioinformatics analysis indicated Akt pathway activation by BA treatment. This was confirmed by phosphorylated Akt analysis, both in BA-treated NPCs and brain organoids, as shown by immunoblotting and immunofluorescence analyses, respectively. Taken together, these data suggest a neuroprotective role of BA in ZIKV-infected NPCs.

A 14-Item Mediterranean Diet Adherence Screener (MEDAS) questionnaire was developed and validated in face-to-face interviews, but not via telephone. The aims of this study were to evaluate the validity and reliability of a telephone-administered version of the MEDAS as well as to validate the Portuguese version of the MEDAS questionnaire. A convenience community-based sample of adults (n = 224) participated in a three-stage survey. First, trained researchers administered MEDAS via a telephone. Second, the Portuguese version of Food Frequency Questionnaire (FFQ), and MEDAS were administered in a semi-structured face-to-face interview. Finally, MEDAS was again administered via telephone. The telephone-administered MEDAS questionnaire was compared with the face-to-face-version using several metrics. The telephone-administered MEDAS was significantly correlated with the face-to-face-administered MEDAS [r = 0.805, p &lt, 0.001, interclass correlation coefficient (ICC) = 0.803, p &lt, 0.001] and showed strong agreement (k = 0.60). The MEDAS scores that were obtained in the first and second telephone interviews were significantly correlated (r = 0.661, p &lt, ICC = 0.639, p &lt, 0.001). The overall agreement between the Portuguese version of MEDAS and the FFQ-derived Mediterranean diet adherence score had a Cohen&rsquo, s k = 0.39. The telephone-administered version of MEDAS is a valid tool for assessing the adherence to the Mediterranean diet and acquiring data for large population-based studies.

Abusive head trauma (AHT) is the most lethal form of child abuse; preventing AHT should be a national priority, but research into this area is woefully underfunded. Prevention programs have primarily focused on universal parent education during the neonatal period, a time when parents are a captive audience of the health care establishment whose focus is on the needs of their newborn infant, and who will soon be exposed to the frustration and anger of infant crying. Research has suggested a strong causal link between infant crying and AHT, and parents - particularly fathers and father figures - have been identified as the most common perpetrators of AHT. A number of studies have suggested that educating parents during the postnatal period about the normalcy of inconsolable infant crying and its evolution over the first several months of postnatal life improves parental knowledge about infant crying and a number of positive parenting behaviors, and decreases emergency room visits for crying. In 1998, we began a pilot program in Upstate New York near Buffalo that led to a 47% reduction in AHT incidence. Similar studies have demonstrated 35-75% reductions in incidence, which has led to enthusiasm for this approach to preventing AHT. We, as well as another group, have enacted statewide programs in Pennsylvania and North Carolina; unfortunately, these two large statewide replication trials failed to demonstrate any impact of such an intervention on AHT rates. Serial messages for parents, provided repeatedly over the period of greatest risk for AHT, might be another avenue of research.

Determining the timing of intracranial injuries in general, and abusive head trauma (AHT) in particular, is important to the care of children with traumatic brain injury. Additionally, identifying the time of the injury provides important information as to who might have, and who did not, inflict the trauma. Understanding the appearance and evolution of intracranial findings on neuroimaging has been an important factor in assessing the time of the injury. However, a number of studies in the last two decades have both suggested greater uncertainty about the reliability of this process and advanced our knowledge in this area. In this review, the authors consider the biophysical factors that contribute to the appearance and evolution of intracranial hemorrhage and, in particular, subdural hemorrhage (SDH). The traditional view of SDH is predicated largely on prior studies of intracerebral hemorrhage, although a number of variables make this comparison untenable. Moreover, more recent studies have suggested a number of factors that could alter the density (CT) or signal intensity (MRI) and produce mixed density/intensity SDH. These factors need to be considered in interpreting neuroimaging studies. A number of these recent studies evaluating serial neuroimaging in children with AHT have modified our understanding of intracranial hemorrhage and its evolution in this context. Taken together, the studies to date, having important limitations, provide only broad ranges over which to time injuries. The authors conclude that neuroimaging studies at this time are not likely, in isolation, to be able to accurately pinpoint a specific time of injury; rather, neuroimaging can only provide a range of possible times and should instead be used as a means to supplement or corroborate timing based on clinical presentation and other imaging findings.

This is the peer reviewed version of the following article: [Acoustic settings combination as a sensory crispness indicator of dry crispy food. Dias-Faceto, L.S.; Salvador, A.; Conti-Silva, A.C. Journal of Texture Studies 51 (2): 232-24 (2020), which has been published in final form a thttps://doi.org/10.1111/jtxs.12485. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.", Crispness is a critical attribute of quality for crispy products, which can be evaluated through both instrumental and sensory analyses. The aim of the study was to identify the best combination of settings of a device coupled to a texture analyzer for acoustic analysis in order to find strong correlations with the sensory texture. For that, nine commercial food products were submitted to force and acoustic (acoustic envelope detector) analyses, using two settings for acoustic data acquisition (gain 1 and gain 4), and two settings for acoustic data management (threshold 0.5 and 2.5). The products were also evaluated using texture descriptive sensory analysis. The gain changing from 1 to 4 (enhancing the test sensitivity) increased the number of acoustic peaks and reduced the sound pressure level. Changing the threshold from 0.5 to 2.5 (reducing the interference of background noise on the acquired data) reduced the number of acoustic peaks. The correlation between the instrumental and the sensory analysis showed gain 1 as the most adequate acoustic setting to obtain the acoustic parameters of products with different crispness intensities. Moreover, threshold 2.5 is the most appropriate for acoustic data collection. Therefore, sensory attributes and instrumental properties strong correlations indicate that texture analyzer in combination with the acoustic envelope detector is a good instrument to mimic human mastication and texture perception, through both force and sound stimuli. This study about dry crisp food may contribute to the literature and food industry, as well to future studies about wet crispy and crunchy foods., The authors are grateful for the financial support grant #2014/24822‐2 and #2017/06713‐0 from the São Paulo Research Foundation (FAPESP).

Background: Thirty-day hospital readmission is receiving growing attention as an indicator of the quality of hospital care. Understanding factors associated with 30-day hospital readmission among HIV patients in Portugal is essential given the high burden cost of HIV hospitalizations in Portugal, a country suffering from financial constrains for almost 10 years. Objectives: We aimed to estimate the 30-day hospital readmission rates among HIV patients in Portugal and to identify its determinants using population-based data for Portuguese public hospitals. Study Design: A multilevel longitudinal population-based study. Methods: Between January 2009 and December 2014, a total of 37,134 registered discharges in the Portuguese National Health Service (NHS) facilities with HIV/AIDS as a main or secondary cause of admission were analyzed. Logistic regression was used to compare 30-day hospital readmission categories by computing odds ratio (OR) and corresponding 95% confidence intervals (95% CIs). A normal random effects model was used to determine unmeasured factors specific to each hospital. Results: A total of 4914 (13.2%, 95% CI: 12.9%−13.6%) hospitalizations had a subsequent 30-day readmission. Hospitalizations that included exit against medical opinion (OR = 1.18, 95% CI: 1.01–1.39), scheduled admissions (OR = 1.71, 95% CI: 1.58–1.85), and tuberculosis infection (OR = 1.20, 95% CI: 1.05–1.38) exhibited a higher risk of hospitalizations with subsequent 30-day readmission. In contrast, hospitalizations that included females (OR = 0.87, 95% CI: 0.81–0.94), a transfer to another facility (OR = 0.78, 95% CI: 0.67–0.91), and having a responsible financial institution (OR = 0.63, 95% CI: 0.55–0.72) exhibited a lower risk of hospitalizations with subsequent 30-day readmission. Hospitalizations associated with higher number of diagnosis, older ages, or hospitalizations during the economic crisis showed an increasing trend of 30-day readmission, whereas an opposite trend was observed for hospitalizations with higher number of procedures. Significant differences exist between hospital quality, adjusting for other factors. Conclusion: This study analyzes the indicators of 30-day hospital readmission among HIV patients in Portugal and provides useful information for enlightening policymakers and health care providers for developing health policies that can reduce costs associated with HIV hospitalizations. This work was supported by the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education) [grant number PD/BD/128066/2016 (AS)] and the Department of Global Health and Tropical Medicine, Institute of Hygiene, and Tropical Medicine (IHMT), NOVA University of Lisbon.

Introdução: Bonanno definiu resiliência como a capacidade do indivíduo em lidar com os eventos traumáticos, nomeadamente a capacidade de manter os níveis de funcionamento físico e psicológico relativamente estáveis. O objetivo do estudo foi avaliar as propriedades psicométricas da escala de resiliência Connor-Davidson de 10 itens. A escala resumida apresenta boas qualidades psicométricas (α Cronbach – 0,85) quando comparada com a escala longa (25 itens) (α Cronbach – 0,89). Material e Métodos: Obtivemos uma amostra de conveniência de inscritos em centros de emprego que foi aleatoriamente dividida em duas subamostras (amostra 1 = 5127 e amostra 2 = 5134). Aplicámos a análise de componentes principais na amostra 1. Com a amostra 2 procedeu-se à análise fatorial confirmatória usando o método da máxima verosimilhança. Usámos a análise multigrupo para a comparação do modelo fatorial entre os géneros e a situação profissional. Efetuámos a análise convergente e divergente através da análise de correlação de Pearson. Resultados: A análise de componentes principais extraiu um fator com uma variância explicada de 53,97%. A análise fatorial confirmatória comprovou a unidimensionalidade da escala. Confirmámos a invariância entre géneros e situação profissional. A escala de resiliência Connor-Davidson de 10 itens correlacionou-se positivamente com as medidas da escala SF-36 e negativamente com a escala GHQ-12. Discussão: A análise exploratória e confirmatória corroborou a unidimensionalidade e boas propriedades psicométricas, semelhantes à escala original de 10 itens. Conclusão: Trata-se do primeiro estudo de validação desta escala na população portuguesa (Portugal), de acordo com a pesquisa efetuada. Os seus resultados são muito satisfatórios, recomendando-se o seu uso na população portuguesa. info:eu-repo/semantics/publishedVersion

Conserving freshwater habitats and their biodiversity in the Amazon Basin is a growing challenge in the face of rapid anthropogenic changes. We used the most comprehensive fish-occurrence database available (2355 valid species; 21,248 sampling points) and 3 ecological criteria (irreplaceability, representativeness, and vulnerability) to identify biodiversity hotspots based on 6 conservation templates (3 proactive, 1 reactive, 1 representative, and 1 balanced) to provide a set of alternative planning solutions for freshwater fish protection in the Amazon Basin. We identified empirically for each template the 17% of sub-basins that should be conserved and performed a prioritization analysis by identifying current and future (2050) threats (i.e., degree of deforestation and habitat fragmentation by dams). Two of our 3 proactive templates had around 65% of their surface covered by protected areas; high levels of irreplaceability (60% of endemics) and representativeness (71% of the Amazonian fish fauna); and low current and future vulnerability. These 2 templates, then, seemed more robust for conservation prioritization. The future of the selected sub-basins in these 2 proactive templates is not immediately threatened by human activities, and these sub-basins host the largest part of Amazonian biodiversity. They could easily be conserved if no additional threats occur between now and 2050.Puntos Calientes de Diversidad de Peces de Agua Dulce para las Prioridades de Conservación en la Cuenca del Amazonas Resumen Cada día, la conservación de los hábitats de agua dulce y su biodiversidad en la cuenca del Amazonas es un reto creciente de cara a los rápidos cambios antropogénicos. Usamos la base de datos de presencia de peces más completa que existe (2,355 especies válidas; 21,248 puntos de muestreo) y tres criterios ecológicos (carácter irremplazable, representatividad y vulnerabilidad) para identificar los puntos calientes de biodiversidad con base en seis patrones de conservación (tres proactivos, uno reactivo, uno representativo y uno balanceado) y así proporcionar un conjunto de soluciones alternativas para la planeación de la protección de peces de agua dulce en la cuenca del Amazonas. Identificamos para cada patrón de manera empírica el 17% de las subcuencas que deberían conservarse y realizamos un análisis de priorización identificando amenazas actuales y a futuro (2050) (es decir, grado de deforestación y fragmentación del hábitat causado por presas). Dos de nuestros tres patrones proactivos tuvieron alrededor del 65% de su superficie cubierta por áreas protegidas; niveles altos de carácter irremplazable (60% de especies endémicas) y de representatividad (71% de la fauna ictiológica del Amazonas); y una vulnerabilidad baja actual y a futuro. Entonces, estos dos patrones parecen estar más completos para la priorización de la conservación. El futuro de las subcuencas en estos dos patrones proactivos no está amenazado por las actividades humanas a corto plazo. Además, estas subcuencas albergan la mayor parte de la biodiversidad amazónica. Se podrían conservar fácilmente si ninguna amenaza adicional sucede entre ahora y el 2050.

γ-Hydroxybutyric acid (GHB) is an endogenous compound with a historical use, both in licit and illicit terms. Importantly, the post-mortem behavior of GHB has been studied due to the possibility of using this compound as a biomarker for estimating the post-mortem interval (PMI). However, the post-mortem behavior of the recently discovered glucuronated GHB metabolite (GHB-GLUC) has not been studied. Nevertheless, GHB-GLUC may also have potential both to assist in PMI determination and also to increase the window of detection of GHB consumption. In this work, for the first time, a reliable method using GC–MS/MS for the quantification of GHB-GLUC in whole blood samples was developed and validated, with a simple, fast and cheap sample pretreatment. The method proved to be specific, precise, linear in a work range between 200 and 5000 ng/mL, with LOD and LOQ of 52.65 ng/mL and 200 ng/mL, respectively, and an extraction recovery of 51%. Furthermore, the method was applied to a set of real post-mortem blood samples non-related with GHB intoxication and the obtained results were also discussed.

Portuguese adults have a long lifespan, but it is unclear whether they live a healthy life in their final years. We aimed to determine the prevalence of multimorbidity and characterize lifestyle and other health outcomes among older Portuguese adults.We performed a cross-sectional evaluation of 2393 adults, aged 65 and older, during the second wave of follow-up of the EpiDoC cohort, a population-based study involving long-term follow-up of a representative sample of the Portuguese population. Subjects completed a structured questionnaire during a telephone interview. Socioeconomic, demographic, lifestyle behaviours, chronic diseases, and health resources consumption were assessed. Cluster analysis was done to identify dietary patterns. Descriptive and analytic analysis was performed to estimate multimorbidity prevalence and its associated factors.Multimorbidity prevalence among older adults was 78.3%, increased with age strata (72.8% for 65 - 69 years to 83.4% for ≥ 80 years), and was highest in Azores (84.9%) and Alentejo (83.6%). The most common chronic diseases were hypertension (57.3%), rheumatic disease (51.9%), hypercholesterolemia (49.4%), and diabetes (22.7%). Depression symptoms were frequent (11.8%) and highest in the oldest strata. The mean health-related quality of life (EQ-5D-3L) score was 0.59 ± 0.38. Hospitalization in the previous 12 months was reported by 25.8% of individuals. Overall, 66.6% of older adults were physically inactive. 'Fruit and vegetables dietary pattern' was followed by 85.4% of individuals; however, regional inequalities were found (69% in Azores). Obesity prevalence was 22.3% overall and was highest among Azoreans (33%).The high prevalence of multimorbidity, combined with unhealthy lifestyle behaviours, suggests that the elderly populationconstitutes a vulnerable group warranting dedicated intervention.Introdução: A esperança de vida está a aumentar em Portugal, contudo desconhece-se o estado de saúde dos idosos. Pretende-se determinar a prevalência de multimorbilidade, caracterizar estilos de vida e outros fatores relacionados com a saúde dos idosos. Material e Métodos: Efetuou-se uma avaliação transversal a 2393 adultos com 65 ou mais anos de idade, da coorte EpiDoC que é constituída por uma amostra representativa da população portuguesa. Os inquiridos responderam a um questionário estruturado através de uma entrevista telefónica, tendo-se recolhido dados socioeconómicos demográficos, estilo de vida, doenças crónicas e consumo de recursos em saúde. Análise de clusters foi realizada para a identificação de padrões alimentares. Efetuou-se análise descritiva e analítica para estimar a prevalência de multimorbilidade e fatores associados. Resultados: A prevalência de multimorbilidade nos idosos foi de 78,3% (72,8% entre os 65 - 69 anos, 83,4% com 80 + anos) e foi superior nos Açores (84,9%) e no Alentejo (83,6%). As doenças crónicas mais prevalentes foram a hipertensão arterial (57,3%), doenças reumáticas (51,9%), hipercolesterolemia (49,4%) e diabetes (22,7%). Os sintomas de depressão (11,8%) foram frequentes, aumentando ao longo dos grupos etários. A qualidade de vida (EQ-5D-3L) foi em média de 0,59 ± 0,38 e 25,8% dos idosos reportaram ter sido hospitalizados nos 12 meses prévios à entrevista. Cerca de 66,6% dos idosos são fisicamente inativos. O padrão alimentar caracterizado por ‘+ fruta e + hortícolas’ foi reportado por 85,4% dos idosos, contudo foram encontradas iniquidades regionais (69% para os idosos açorianos). A prevalência de obesidade foi de 22,3%, sendo superior nos açorianos (33%). Conclusões: A elevada prevalência de multimorbilidade combinada com estilos de vida pouco saudáveis sugere que a população idosa constitui um grupo vulnerável que requer uma intervenção direcionada.

Background The development of a vaccine for the prevention of visceral leishmaniasis (VL) still represents a significant unmet medical need. A human vaccine can be found if one takes into consideration that many people living in endemic areas of disease are infected but do not develop active VL, including those subjects with subclinical or asymptomatic infection. Methods In this study, a phage display was used to select phage-exposed peptides that were specific to immunoglobulin G (IgG) antibodies from asymptomatic and symptomatic VL patients, separating them from non-infected subjects. Phage clones presenting valid peptide sequences were selected and used as stimuli of peripheral blood mononuclear cells (PBMCs) obtained from both patients’ groups and controls. Those with higher interferon-gamma (IFN-γ)/interleukin (IL)-10 ratios were further selected for vaccination tests. Results Among 17 evaluated clones, two were selected, B1 and D11, and used to immunize BALB/c mice in an attempt to further validate their in vivo protective efficacy against Leishmania infantum infection. Both clones induced partial protection against the parasite challenge, which was evidenced by the reduction of parasitism in the evaluated organs, a process mediated by a specific T helper (Th)1 immune response. Conclusions To the best of our knowledge, this study is the first to use a rational strategy based on in vitro stimulation of human PBMCs with selected phage-displayed clones to obtain new immunogens against VL. Electronic supplementary material The online version of this article (10.1186/s13071-017-2576-8) contains supplementary material, which is available to authorized users.

Serological methods used to diagnose visceral leishmaniasis (VL) are considered minimally invasive, but they present problems related with their sensitivity and/or specificity. In this study, a subtractive selection using the phage display technology against antibodies from healthy subjects living in endemic and non-endemic areas of disease, as well as from Chagas disease patients and those developing active VL, was developed. The aim of this study was to select bacteriophage-fused epitopes to be used in the serodiagnosis of human VL. Eight phage clones were selected after the bio-panning rounds, and their reactivity was evaluated in a phage-ELISA assay against a human serological panel. A wild-type clone and the recombinant K39-based immunochromatographic test were used as controls. In the results, it was shown that all clones showed an excellent performance to serologically identify VL patients, demonstrating the feasibility of the isolated phages for developing a specific and sensitive serodiagnosis of human VL.

Background/Aims: Androgenetic alopecia is an extremely common dermatological disorder affecting both men and women. Oral finasteride (FNS), a synthetic 4-aza-3-oxosteroid compound with poor aqueous solubility, blocks the peripheral conversion of testosterone to dihydrotestosterone (DHT) in a significant reduction in DHT concentration, achieving satisfactory results in alopecia treatment. However, its oral intake generally causes severe side effects. Considering that there is currently no scientifically proven treatment, new drug delivery systems able to improve alopecia therapy are urgently required. Methods: In this study, polymeric nanoparticles have been proposed as a new carrier for topical delivery of FNS in hair follicles. Results and Conclusions: Polymeric nanoparticles, prepared by using a modified method of the emulsification/solvent diffusion, showed a mean particle size around 300 nm, which may be sufficient for reaching the dermis and hair follicles and negative zeta potential values. Scanning electron microscope measurements showed that all the polymeric nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. A high encapsulation efficiency was achieved for FNS (79.49 ± 0.47%). In vitro release assays in physiological conditions demonstrated that nanoparticles yielded a prolonged release of FNS for 3 h. Skin assays through an in vitro permeation study demonstrated that nanoparticles had low levels of penetration of FNS, improving its time residence onto the skin. All excipients used in nanoparticle composition and in 3 different vehicles were safe. These results suggest that the proposed novel formulation presents several good characteristics indicating its suitability for dermal delivery of FNS for alopecia treatment.

To evaluate the perception of parents and children and the impact of molar and incisor hypomineralization (MIH) on the oral health-related quality of life (OHRQoL).A cross-sectional study was conducted with a group of 253 children aged 6-12 years presenting MIH and their parents or guardians who initially answered an interview containing socioeconomic and demographic questions as well as the Parental-Caregiver's Perceptions Questionnaire (P-CPQ). The children answered the Child Perceptions Questionnaire (CPQ8-10) and Child Perceptions Questionnaire (CPQ11-14) and the clinical evaluation of MIH was performed. Poisson regression with robust variance was used in the data analysis.The parent's perception showed that the impact felt by the children regarding caries leads to a higher oral symptom impact, functional limitation, emotional well-being and total PCPQ score domains, as well. For children with severe MIH, a higher prevalence of impact was felt regarding the functional limitation and emotional well-being. For CPQ8-10, the oral symptoms domain presented the highest mean score, while CPQ11-14 showed the functional limitations domain and P-CPQ the emotional well-being domain.Considering the perception of parents or guardians, it was concluded that MIH promotes a negative impact on the OHRQoL. MIH had no significant impact on OHRQoL according to children's perceptions.

To evaluate the effectiveness on lifestyle change of an mHealth intervention to promote healthy behaviours in adolescence (TeenPower) and to analyse the predictors of the mHealth intervention effectiveness.This study is designed as a non-randomized controlled trial with a two-arm structure.Adolescents of 12-16-year old were recruited from three school districts, with access to the Internet and smartphone/tablet devices. The intervention group was invited to engage in the mHealth intervention (TeenPower) for 6 months in addition to a school-based intervention. The control group only followed the school-based intervention. A repeated measures factorial ANOVA was used and the main effectiveness outcome was the lifestyle change measured by the adolescent lifestyle profile.The outcomes of the mHealth intervention (TeenPower) show a significant effect on nutrition (ƞAlthough the considerable dropout rate, the mHealth intervention presented significant impact on multiple lifestyle domains, providing support for the effectiveness of mHealth interventions for health promotion as an add-on to standard interdisciplinary interventions.Adolescents must have the necessary and appropriate knowledge for the correct and responsible decision-making regarding their health and lifestyle. Innovative strategies (mHealth intervention) were used to promote healthy behaviours. This study evaluates the effectiveness of an mHealth intervention (TeenPower) specifically designed for adolescents. We found a significant impact in several lifestyle domains such as health responsibility, nutrition, positive life perspective, and global lifestyle.目的: 评价促进青少年健康行为的移动医疗(mHealth)干预对生活方式改变的作用,并分析移动医疗(mHealth)干预有效性的相关因素。 设计: 该研究被设计为一项非随机对照试验(两组结构)。 方法: 从三个学区招募了12岁~16岁的青少年,他们可以使用互联网和智能手机/平板电脑设备。除接受学校干预外,干预组还接受为期6个月的移动医疗(mHealth)(TeenPower)。对照组仅接受学校干预。采用因素方差分析(factorial ANOVA)重复测量,并且主要影响结果是青少年生活方式发生变化。 结果: 移动医疗(mHealth)干预(TeenPower)的结果显示对营养(ƞ2 p = 0.03, p = .03)、积极生活观(ƞ2 p = 0.04, p = .01)和全球生活方式(ƞ2p = 0.02, p = .05)有显著影响,退学率为62.1%。对移动医疗(mHealth)干预有效性相关因素的分析表明,年龄稍大的青少年的心理压力管理率有显著提高的趋势(r=.40;p.05)。 结论: 尽管退学率相当高,但移动医疗(mHealth)干预对多个生活方式领域产生了重大影响,支持移动医疗(mHealth)干预作为附加的标准跨学科干预手段对促进健康的有效性。 影响: 青少年必须具备必要和适当的知识,能够作出与其健康生活方式相关的正确且负责任的决定。创新策略(mHealth干预)用于促进健康行为。该研究评估了专为青少年设计的健康干预(TeenPower)的有效性。我们发现,该等干预在诸如健康责任、营养、积极生活观和全球生活方式等生活方式领域有着重大影响。.

Vitamin D deficiency is prevalent worldwide, but its prevalence is unknown in adult Portuguese population. In Portugal, 66% of adults present Vitamin D insufficiency/deficiency. Winter, living in Azores, older age, and obesity were the most important risk factors. It highlights the need of strategies to prevent vitamin D deficiency in Portugal.To estimate the prevalence and risk factors of vitamin D deficiency in the adult Portuguese population.Adults (≥ 18 years old) from the EpiReumaPt Study (2011-2013) were included. Standardized questionnaires on socio-demographic and lifestyle features were obtained. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were evaluated using ADVIA Centaur VitD competitive immunoassay (Siemens Healthineers) in 2015-2017 as 25 (OH)D Level 0: ≤ 10 ng/mL; Level 1: 11-19 ng/mL; Level 2: 20-29 ng/mL, and Level 3: ≥ 30 ng/mL. Weighted multinomial regression analysis was conducted to evaluate the association between socio-demographic and lifestyle variables and vitamin D status.Based on weighted analysis, the estimated prevalence of levels of 25(OH)D ≤ 10, 20, and 30 ng/mL was 21.2, 66.6, and 96.4%, respectively. The strongest independent predictors of serum 25 (OH)D ≤ 10 ng/mL were living in the Azores archipelagos (OR 9.39; 95%CI 1.27-69.6) and having the blood sample collection in winter (OR 18.53; 95%CI 7.83-43.87) or spring (11.55; 95%CI 5.18-25.74). Other significant predictors included older age (OR 5.65, 95%CI 2.08-15.35), obesity (OR 2.61; 95%CI 1.35-5.08), current smoking (OR 2.33; 95%CI 1.23-4.43), and female gender (OR 1.9, 95%CI 1.1-3.28). Conversely, physical exercise (OR 0.48, 95%CI 0.28-0.81) and occasional alcohol intake (OR 0.48, 95%CI 0.29-0.81) were associated with a lower risk of 25(OH)D ≤ 10 ng/mL.Vitamin D deficiency/insufficiency [25(OH)D 20 ng/ml] is highly prevalent in Portugal, affecting 60% of all Portuguese adults, with strong geographical and seasonal variation. This study highlights the need to critically assess the relevance of vitamin D deficiency as a public health problem and the urgent need for a wide and scientifically robust debate about the most appropriate interventions at the individual and societal levels.

During tumorigenesis, breast tumour cells undergo metabolic reprogramming, which generally includes enhanced glycolysis, tricarboxylic acid cycle activity, glutaminolysis and fatty acid biosynthesis. However, the extension and functional importance of these metabolic alterations may diverge not only according to breast cancer subtypes, but also depending on the interaction of cancer cells with the complex surrounding microenvironment. This microenvironment comprises a variety of non-cancerous cells, such as immune cells (e.g. macrophages, lymphocytes, natural killer cells), fibroblasts, adipocytes and endothelial cells, together with extracellular matrix components and soluble factors, which influence cancer progression and are predictive of clinical outcome. The continuous interaction between cancer and stromal cells results in metabolic competition and symbiosis, with oncogenic-driven metabolic reprogramming of cancer cells shaping the metabolism of neighbouring cells and vice versa. This review addresses current knowledge on this metabolic crosstalk within the breast tumour microenvironment (TME). Improved understanding of how metabolism in the TME modulates cancer development and evasion of tumour-suppressive mechanisms may provide clues for novel anticancer therapeutics directed to metabolic targets.