Basin-wide variation in tree hydraulic safety margins predicts the carbon balance of Amazon forests.

Tropical forests face increasing climate risk1,2, yet our ability to predict their response to climate change is limited by poor understanding of their resistance to water stress. Although xylem embolism resistance thresholds (for example, [Formula: see text]50) and hydraulic safety margins (for example, HSM50) are important predictors of drought-induced mortality risk3-5, little is known about how these vary across Earth's largest tropical forest. Here, we present a pan-Amazon, fully standardized hydraulic traits dataset and use it to assess regional variation in drought sensitivity and hydraulic trait ability to predict species distributions and long-term forest biomass accumulation. Parameters [Formula: see text]50 and HSM50 vary markedly across the Amazon and are related to average long-term rainfall characteristics. Both [Formula: see text]50 and HSM50 influence the biogeographical distribution of Amazon tree species. However, HSM50 was the only significant predictor of observed decadal-scale changes in forest biomass. Old-growth forests with wide HSM50 are gaining more biomass than are low HSM50 forests. We propose that this may be associated with a growth-mortality trade-off whereby trees in forests consisting of fast-growing species take greater hydraulic risks and face greater mortality risk. Moreover, in regions of more pronounced climatic change, we find evidence that forests are losing biomass, suggesting that species in these regions may be operating beyond their hydraulic limits. Continued climate change is likely to further reduce HSM50 in the Amazon6,7, with strong implications for the Amazon carbon sink.

Overcoming effector T cell exhaustion in ovarian cancer ascites with a novel adenovirus encoding for a MUC1 bispecific antibody engager and IL-2 cytokine.

T cell-focused cancer immunotherapy including checkpoint inhibitors and cell therapies has been rapidly evolving over the past decade. Nevertheless, there remains a major unmet medical need in oncology generally and immuno-oncology specifically. We have constructed an oncolytic adenovirus, Ad5/3-E2F-d24-aMUC1aCD3-IL-2 (TILT-322), which is armed with a human aMUC1aCD3 T cell engager and IL-2. TILT-322 treatment stimulated T cell cytotoxicity through the increased presence of granzyme B, perforin, and interferon-gamma. Additional immune profiling indicated TILT-322 increased gamma delta T cell activation and impacted other cell types such as natural killer cells and natural killer-like T cells that are traditionally involved in cancer immunotherapy. TILT-322 treatment also decreased the proportion of exhausted CD8+ T cells as demarked by immune checkpoint expression in ovarian ascites samples. Overall, our data showed that TILT-322 treatment led to an enhanced T cell activation and reversed T cell exhaustion translating into high antitumor efficacy when given locally or intravenously. The analysis of blood and tumors isolated from an in vivo patient-derived ovarian cancer xenograft model suggested TILT-322 mediated tumor control through improved T cell functions. Therefore, TILT-322 is a promising novel anti-tumor agent for clinical translation.

Neurological aspects of HTLV-1 infection: symptoms in apparently asymptomatic carriers.

Human T-lymphotropic virus type 1 (HTLV-1) is classically associated with the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although the mechanisms of this neurological disorder remain unclear. In addition, some patients who develop "minor" neurological signs that do not meet diagnostic criteria for HAM/TSP are classified as asymptomatic carriers. This study aims to demonstrate the neurological symptoms of Brazilian patients living with HTLV-1 classified as not-HAM.TSP. This observational study evaluated patients treated in an HTLV reference center in Bahia, Brazil, between February 2022 and July 2023. The data were obtained through the analysis of medical records and neurological consultation. Those individuals classified as HAM/ TSP were excluded from this study. 74 patients were submitted to a careful neurological evaluation: 23 HAM/TSP, 22 were classified with intermediate syndrome (IS), and 29 were oligosymptomatic. Self-reported symptoms were significantly more common in the IS group, including urinary symptoms such as nocturia, urgency, incontinence, dysuria, weakness, paresthesia, lumbar pain, xerostomia, and xerophthalmia. Physical examination findings consistent with reduced vibratory and tactile sensitivity were more common in the IS group (p = 0.017 and p = 0.013). Alterations in the V and VIII cranial nerves were present in both groups. HTLV-1 can lead to the development of important neurological signs and symptoms in apparently asymptomatic individuals. This data highlights the need for more research into the neurological aspects of HTLV-1 infection and emphasizes the importance of early diagnosis, treatment, and support for individuals living with this virus.

Evaluating the antimicrobial and anti-biofilm activity of three synthetic antimicrobial Citropin analogs and their ability to fight against Staphylococcus aureus and Staphylococcus pseudintermedius.

AIMS: We developed three new analogs of the antimicrobial peptide (AMP) Citropin 1.1: DAN-1-13, AJP-1-1, and HHX-2-28, and tested their potential antimicrobial and antibiofilm activities against Staphylococcus aureus and S. pseudintermedius. Potential cytotoxic or hemolytic effects were determined using cultured human keratinocytes and erythrocytes to determine their safety. METHODS AND RESULTS: To assess the antimicrobial activity of each compound, minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined against methicillin-resistant and methicillin-susceptible strains of S. aureus and S. pseudintermedius. Activity against newly formed and mature biofilms was determined in two clinical isolates using spectrophotometry and scanning electron microscopy (SEM). All three compounds exhibited antimicrobial and bactericidal activity against all studied S. aureus and S. pseudintermedius strains, with MICs ranging from 4-32 µg ml-1 and MBCs ranging from 8-128 µg ml-1. Subinhibitory concentrations of all compounds also showed ant-biofilm activity in the two tested isolates. All compounds exhibited limited cytotoxic and hemolytic activity. CONCLUSIONS: Novel analogs of Citropin 1.1 exhibit antimicrobial and bactericidal activities against S. aureus and S. pseudintermedius isolates and inhibit the biofilm formation of these bacteria.

Atrioventricular block secondary to transient causes and long-term recurrence after an index event.

BACKGROUND: Atrioventricular block (AVB) secondary to transient causes can recover with its correction. However, studies assessing predictors of recovery and long-term recurrence are lacking. METHODS: Patients with advanced or complete AVB who had a reversible cause admitted in a single expert center were retrospectively studied. Patients with AVB secondary to acute coronary syndromes were excluded from analysis. RESULTS: In a population of 162 patients, the main factors associated with recovery of rhythm without a permanent pacemaker (PPM) implantation were the presence of chronic kidney disease (CKD) on dialysis (OR 7.6; CI 95% 1.2-47.5 (p = .03)); greater serum potassium levels (OR 2.3; CI 95% 1.28-4.0 (p < .01)), higher dosage of bradycardic drugs (OR 2.2; CI 95% 1.13-4.4 (p = .02)), the association between different bradycardic drugs (OR 9.0; CI 95% 2.02-40.3 (p < .01)) and between drug therapy and hyperkaliemia (OR 5.2; CI 95% 1.8-15.1 (p < .01)). There was an overall high burden of conductions abnormalities which did not correlate with recovery of rhythm (OR 0.5; CI 95% 0.19-1.5 (p = .23)). In 29 patients (17.9%) there was a correction of the AVB. During a maximum follow-up of 130 months, 24 patients (82.8%) had a recurrence which warranted a PPM. In the overall cohort only five patients (3%) had sustained recovery of rhythm. CONCLUSIONS: Recovery of AVB was mainly observed with higher doses of drug therapy, higher serum potassium levels or a combination of factors and regardless of baseline conduction abnormalities. The high rate of recurrence during follow-up warrants a close follow-up or PPM implantation at index admission.

The state of health in the European Union (EU-27) in 2019: a systematic analysis for the Global Burden of Disease study 2019.

BACKGROUND: The European Union (EU) faces many health-related challenges. Burden of diseases information and the resulting trends over time are essential for health planning. This paper reports estimates of disease burden in the EU and individual 27 EU countries in 2019, and compares them with those in 2010. METHODS: We used the Global Burden of Disease 2019 study estimates and 95% uncertainty intervals for the whole EU and each country to evaluate age-standardised death, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) rates for Level 2 causes, as well as life expectancy and healthy life expectancy (HALE). RESULTS: In 2019, the age-standardised death and DALY rates in the EU were 465.8 deaths and 20,251.0 DALYs per 100,000 inhabitants, respectively. Between 2010 and 2019, there were significant decreases in age-standardised death and YLL rates across EU countries. However, YLD rates remained mainly unchanged. The largest decreases in age-standardised DALY rates were observed for "HIV/AIDS and sexually transmitted diseases" and "transport injuries" (each -19%). "Diabetes and kidney diseases" showed a significant increase for age-standardised DALY rates across the EU (3.5%). In addition, "mental disorders" showed an increasing age-standardised YLL rate (14.5%). CONCLUSIONS: There was a clear trend towards improvement in the overall health status of the EU but with differences between countries. EU health policymakers need to address the burden of diseases, paying specific attention to causes such as mental disorders. There are many opportunities for mutual learning among otherwise similar countries with different patterns of disease.

Legacy genetics of Arachis cardenasii in the peanut crop shows the profound benefits of international seed exchange.

The narrow genetics of most crops is a fundamental vulnerability to food security. This makes wild crop relatives a strategic resource of genetic diversity that can be used for crop improvement and adaptation to new agricultural challenges. Here, we uncover the contribution of one wild species accession, Arachis cardenasii GKP 10017, to the peanut crop (Arachis hypogaea) that was initiated by complex hybridizations in the 1960s and propagated by international seed exchange. However, until this study, the global scale of the dispersal of genetic contributions from this wild accession had been obscured by the multiple germplasm transfers, breeding cycles, and unrecorded genetic mixing between lineages that had occurred over the years. By genetic analysis and pedigree research, we identified A. cardenasii-enhanced, disease-resistant cultivars in Africa, Asia, Oceania, and the Americas. These cultivars provide widespread improved food security and environmental and economic benefits. This study emphasizes the importance of wild species and collaborative networks of international expertise for crop improvement. However, it also highlights the consequences of the implementation of a patchwork of restrictive national laws and sea changes in attitudes regarding germplasm that followed in the wake of the Convention on Biological Diversity. Today, the botanical collections and multiple seed exchanges which enable benefits such as those revealed by this study are drastically reduced. The research reported here underscores the vital importance of ready access to germplasm in ensuring long-term world food security.

Chemical reversion of age-related oocyte dysfunction fails to enhance embryo development in a bovine model of postovulatory aging.

PURPOSE: There are no clinical treatments to prevent/revert age-related alterations associated with oocyte competence decline in the context of advanced maternal age. Those alterations have been attributed to oxidative stress and mitochondrial dysfunction. Our study aimed to test the hypothesis that in vitro maturation (IVM) medium supplementation with antioxidants (resveratrol or phloretin) may revert age-related oocyte competence decline. METHODS: Bovine immature oocytes were matured in vitro for 23 h (young) and 30 h (aged). Postovulatory aged oocytes (control group) and embryos obtained after fertilization were examined and compared with oocytes supplemented with either 2 µM of resveratrol or 6 µM phloretin (treatment groups) during IVM. RESULTS: Aged oocytes had a significantly lower mitochondrial mass and proportion of mitochondrial clustered pattern, lower ooplasmic volume, higher ROS, lower sirtuin-1 protein level, and a lower blastocyst rate in comparison to young oocytes, indicating that postovulatory oocytes have a lower quality and developmental competence, thus validating our experimental model. Supplementation of IVM medium with antioxidants prevented the generation of ROS and restored the active mitochondrial mass and pattern characteristic of younger oocytes. Moreover, sirtuin-1 protein levels were also restored but only following incubation with resveratrol. Despite these findings, the blastocyst rate of treatment groups was not significantly different from the control group, indicating that resveratrol and phloretin could not restore the oocyte competence of postovulatory aged oocytes. CONCLUSION: Resveratrol and phloretin can both revert the age-related oxidative stress and mitochondrial dysfunction during postovulatory aging but were insufficient to enhance embryo developmental rates under our experimental conditions.

Effects of endodontic irrigation solutions on structural, chemical, and mechanical properties of coronal dentin: A scoping review.

OBJECTIVE: This review aims to assess structural, chemical, and mechanical properties of coronal dentin after endodontic irrigation. MATERIALS AND METHODS: Reporting followed the PRISMA extension for scoping reviews. An electronic search was carried out in PubMed, Embase, and Cochrane Library. Records filtered by language and published up to November 4, 2022 were independently screened by two researchers. Studies evaluating structural, chemical, or mechanical properties of human permanent coronal dentin after irrigation within the scope of nonsurgical root canal treatment were included. Data were extracted regarding study type, sample description and size, experimental groups, outcome, evaluation method, and main findings. RESULTS: From the initial 1916 studies, and by adding 2 cross-references, 11 in vitro studies were included. Seven studies provide ultrastructural and/or chemical characterization, and six assessed microhardness and/or flexural strength. One percent to 8% sodium hypochlorite (NaOCl) and 1%-17% ethylenediaminetetraacetic acid (EDTA) were the most commonly tested solutions, with contact times of 2-240 min (NaOCl) and 1-1440 min (EDTA) being evaluated. CONCLUSIONS: Overall, the literature is consensual regarding the inevitable impact of NaOCl and chelating agents on coronal dentin, with both deproteinizing and decalcifying effects being concentration- and time-dependent. The alteration of mechanical parameters further confirmed the surface and subsurface ultrastructural and chemical changes. CLINICAL SIGNIFICANCE: Endodontic treatment success highly depends on restorative sealing. Understanding the result of exposing coronal dentin, the main substrate for bonding, to irrigants' action is crucial. The deproteinizing and decalcifying effects of NaOCl and chelating agents are both concentration- and time-dependent, causing surface and subsurface ultrastructural, chemical, and mechanical alterations.

Bridging Genetic Insights with Neuroimaging in Autism Spectrum Disorder-A Systematic Review.

Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive patterns of behavior. Family studies show that ASD is highly heritable, and hundreds of genes have previously been implicated in the disorder; however, the etiology is still not fully clear. Brain imaging and electroencephalography (EEG) are key techniques that study alterations in brain structure and function. Combined with genetic analysis, these techniques have the potential to help in the clarification of the neurobiological mechanisms contributing to ASD and help in defining novel therapeutic targets. To further understand what is known today regarding the impact of genetic variants in the brain alterations observed in individuals with ASD, a systematic review was carried out using Pubmed and EBSCO databases and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review shows that specific genetic variants and altered patterns of gene expression in individuals with ASD may have an effect on brain circuits associated with face processing and social cognition, and contribute to excitation-inhibition imbalances and to anomalies in brain volumes.

Fire suppression and land-use strategies drive future dynamics of an invasive plant in a fire-prone mountain area under climate change.

Woody invasive alien species can have profound impacts on ecosystem processes and functions, including fire regulation, which can significantly affect landscape resilience. Acacia dealbata, a widespread invasive alien plant in the Iberian Peninsula, holds well-known fire-adaptation traits (e.g., massive soil seed banks and heat-stimulated seed germination). In this study, we assess to what extent fire suppression and land-use strategies could affect the potential distribution of A. dealbata in a fire-prone transboundary protected mountain area of Portugal and Spain, using Habitat Suitability Models. Specifically, we predicted changes in habitat suitability for A. dealbata between years 2010 and 2050. We explored the potential impacts of two land-use strategies ('Business-as-usual' or 'High Nature Value farmlands') combined with three levels of fire suppression effectiveness using the biomod2 package in R. We also considered the potential effects of two climate change scenarios (RCP4.5 and RCP8.5). Our modeling approach demonstrated a strong capacity to predict habitat suitability using either climate or land-cover information alone (AUC climate = 0.947; AUC LC = 0.957). According to climate-based models, A. dealbata thrives under conditions characterized by higher precipitation seasonality, higher precipitation in the warmest month, and higher minimum temperature in the coldest month. Regarding land cover, A. dealbata thrives mainly in landscapes dominated by urban areas and evergreen forest plantations. Our models forecasted that habitat suitability by 2050 could either increase or decrease depending on the specific combinations of fire suppression, land-use, and climate scenarios. Thus, a combination of business-as-usual and fire-exclusion strategies would enhance habitat suitability for the species. Conversely, management promoting High Nature Value farmlands would decrease the available suitable habitat, particularly under low fire suppression efforts. These findings suggest that promoting sustainable farming activities could impede the spread of A. dealbata by reducing habitat availability, while strategies aiming at fire-exclusion could facilitate its expansion, likely by enabling establishment and large seed production. This study highlights the complex interplay between fire-prone invasive species, fire and land-use strategies, and climate change; and thus the need to consider the interactions between land-use and fire management to promote invasive species control and landscape resilience.

PEGylation versus glycosylation: effect on the thermodynamics and thermostability of crisantaspase.

Thermostability is an important and desired feature of therapeutic proteins and is critical for the success or failure of protein drugs development. It can be increased by PEGylation-binding of poly(ethylene glycol) moieties-or glycosylation-post-translational modification to add glycans. Here, the thermostability and thermodynamic parameters of native, PEGylated, and glycosylated versions of the antileukemic enzyme crisantaspase were investigated. First-order kinetics was found to describe the irreversible deactivation process. Activation energy of the enzyme-catalyzed reaction (E*) was estimated for native, PEGylated, and glycosylated enzyme (10.2, 14.8, and 18.8 kJ mol-1 respectively). Half-life decreased progressively with increasing temperature, and longer half-life was observed for PEG-crisantaspase (87.74 min) at 50 °C compared to the native form (9.79 min). The activation energy of denaturation of PEG-crisantaspase (307.1 kJ mol-1) was higher than for crisantaspase (218.1 kJ mol-1) and Glyco-crisantaspase (120.0 kJ mol-1), which means that more energy is required to overcome the energy barrier of the unfolding process. According to our results, PEG-crisantaspase is more thermostable than its native form, while Glyco-crisantaspase is more thermosensitive.

First-degree atrioventricular block in hypertrophic cardiomyopathy patients: an easy and worthy prognostic marker?

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Recently, a connection has been observed between the presence of first-degree atrioventricular block (FDAVB) and cardiovascular outcomes, although the pathophysiology of this association remains poorly understood. Considering the period 2000-2023, we retrospectively included HCM patients at sinus rhythm at the first appointment and sought possible interactions of FDAVB (defined as PR interval >200 ms) with different clinical and imaging variables and with the occurrence of cardiovascular events, including atrial fibrillation (AF). A total of 97 patients were included, of whom 57 (58.8%) were men, with a mean age of 51±19 years, and 14 (14.4%) had FDAVB. During a median of 4.29 (P25 1.92, P75 7.67) years of follow-up, 35 cardiovascular events occurred, including 13 de novo diagnoses of AF, 8 hospitalizations due to heart failure, 8 new-onset strokes, 4 myocardial infarctions, and 2 implantations of cardio defibrillators in secondary prevention; no HCM-related death occurred. We did not find any association between outcomes and the presence of FDAVB. The role of FDAVB as a prognostic marker in HCM patients requires further investigation. We found that FDAVB patients were older, more frequently reported dyspnea, had a larger QRS duration, a higher E/e' ratio, and lower maximal left ventricle wall thickness by magnetic resonance (p<0.05). After multivariable analysis, FDAVB was independently associated with a higher echocardiographic E/e' ratio (p=0.039) (odds ratio=1.588). This is the first paper to document an independent association between FGAVB and a higher E/e' ratio in HCM patients.

Percutaneous distal bicortical proximal phalanx osteotomy for second toe deformities - A two-year prospective cohort study.

PURPOSE: The main purpose of our study was to evaluate satisfaction, recurrence, bone union and other complications after a minimum of two years follow-up in patients who had percutaneous claw and hammer (CHT) second toe correction utilizing a novel distal and bicortical proximal phalanx osteotomy (DBPPO). METHODS: A minimum two-year follow-up prospective cohort study was conducted on consecutive patients with symptomatic CHT deformities of the second toe corrected with percutaneous surgery. Primary outcomes included satisfaction, recurrence, bony union, and other complication rates specific to the second toe deformity correction. Secondary outcomes included Metatarsophalangeal-Interphalangeal AOFAS scale and Visual Analogue Scale (VAS). RESULTS: Between January and October 2020, 34 patients (43 feet) were clinically and radiologically evaluated pre and postoperatively at a mean of 26.6 months. Thirty-eight feet (88.4 %) were satisfied or very satisfied with their second toe deformity correction and 41 feet (95.3 %) would undergo surgery on this toe again. No deformity recurrence requiring revision was found. There were two complications (4.7 %): one toe (2.3 %) with persistent numbness and one (2.3 %) had a simple infection that resolved with oral antibiotics. All 43 s toe osteotomies demonstrated bony consolidation. Stiffness was reported in nine second toes (20.9 %), seven of them (77.8 %) having a rigid pre-operative deformity. Secondary outcomes demonstrated significant improvement in the mean ( ± standard deviation) AOFAS score which increased from 47.5 ± 17.9 preoperatively to 95.7 ± 7.7 postoperatively (p < .001). Mean VAS significantly improved from 4.9 ± 2.5 preoperatively to 0.3 ± 1.3 postoperatively (p < .001). CONCLUSION: Percutaneous treatment of claw and hammer second toe deformities utilizing a DBPPO resulted in high levels of satisfaction with bony consolidation, no recurrence and low complication rates at two years follow-up. LEVEL OF EVIDENCE: Level II - Prospective cohort study.

Seroprevalence of Specific SARS-CoV-2 Antibodies during Omicron BA.5 Wave, Portugal, April-June 2022.

After the rapid spread of SARS-CoV-2 BA.5 Omicron lineage in Portugal, we developed a seroepidemiologic survey based on a sample of 3,825 residents. Results indicated that from April 27 through June 8, 2022, the estimated seroprevalence of SARS-CoV-2 nucleocapsid or spike IgG was 95.8%, which indicates a high level of protection.

Burden of infectious disease studies in Europe and the United Kingdom: a review of methodological design choices.

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results.

Evidence for an association of prenatal exposure to particulate matter with clinical severity of Autism Spectrum Disorder.

Early-life exposure to air pollutants, including ozone (O3), particulate matter (PM2.5 or PM10, depending on diameter of particles), nitrogen dioxide (NO2) and sulfur dioxide (SO2) has been suggested to contribute to the etiology of Autism Spectrum Disorder (ASD). In this study, we used air quality monitoring data to examine whether mothers of children with ASD were exposed to high levels of air pollutants during critical periods of pregnancy, and if higher exposure levels may lead to a higher clinical severity in their offspring. We used public data from the Portuguese Environment Agency to estimate exposure to these pollutants during the first, second and third trimesters of pregnancy, full pregnancy and first year of life of the child, for 217 subjects with ASD born between 2003 and 2016. These subjects were stratified in two subgroups according to clinical severity, as defined by the Autism Diagnostic Observational Schedule (ADOS). For all time periods, the average levels of PM2.5, PM10 and NO2 to which the subjects were exposed were within the admissible levels defined by the European Union. However, a fraction of these subjects showed exposure to levels of PM2.5 and PM10 above the admissible threshold. A higher clinical severity was associated with higher exposure to PM2.5 (p = 0.001), NO2 (p = 0.011) and PM10 (p = 0.041) during the first trimester of pregnancy, when compared with milder clinical severity. After logistic regression, associations with higher clinical severity were identified for PM2.5 exposure during the first trimester (p = 0.002; OR = 1.14, 95%CI: 1.05-1.23) and full pregnancy (p = 0.04; OR = 1.07, 95%CI: 1.00-1.15) and for PM10 (p = 0.02; OR = 1.07, 95%CI: 1.01-1.14) exposure during the third trimester. Exposure to PM is known to elicit neuropathological mechanisms associated with ASD, including neuroinflammation, mitochondrial disruptions, oxidative stress and epigenetic changes. These results offer new insights on the impact of early-life exposure to PM in ASD clinical severity.

Factors associated with non-pharmaceutical interventions compliance during COVID-19 pandemic: a Portuguese cross-sectional survey.

BACKGROUND: The use of non-pharmaceutical interventions (NPI) is one of the main tools used in the coronavirus disease 2019 (COVID-19) pandemic response, including physical distancing, frequent hand washing, face mask use, respiratory hygiene and use of contact tracing apps. Literature on compliance with NPI during the COVID-19 pandemic is limited. METHODS: We studied this compliance and associated factors in Portugal, between 28th October 2020 and 11th January 2021 (Portuguese second and third waves of the pandemic), using logistic regressions. Data were collected through a web-based survey and included questions regarding NPI compliance, COVID-19-related concerns, perception of institutions' performance, agreement with the measures implemented and socio-demographic characteristics. RESULTS: From the 1263 eligible responses, we found high levels of compliance among all COVID-19 related NPI, except for the contact tracing app. Females and older participants showed the highest compliance levels, whereas the opposite was observed for previously infected participants. There was heterogeneity of COVID-19 NPI compliance across Portuguese regions and a clear gradient between concern, government performance's perception or agreement and compliance. CONCLUSIONS: Results suggested areas for further study with important implications for pandemic management and communication, for future preparedness, highlighting other factors to be accounted for when recommending policy measures during public health threats.

The increasing significance of disease severity in a burden of disease framework.

Recent estimates have reiterated that non-fatal causes of disease, such as low back pain, headaches and depressive disorders, are amongst the leading causes of disability-adjusted life years (DALYs). For these causes, the contribution of years lived with disability (YLD) - put simply, ill-health - is what drives DALYs, not mortality. Being able to monitor trends in YLD closely is particularly relevant for countries that sit high on the socio-demographic spectrum of development, as it contributes more than half of all DALYs. There is a paucity of data on how the population-level occurrence of disease is distributed according to severity, and as such, the majority of global and national efforts in monitoring YLD lack the ability to differentiate changes in severity across time and location. This raises uncertainties in interpreting these findings without triangulation with other relevant data sources. Our commentary aims to bring this issue to the forefront for users of burden of disease estimates, as its impact is often easily overlooked as part of the fundamental process of generating DALY estimates. Moreover, the wider health harms of the COVID-19 pandemic have underlined the likelihood of latent and delayed demand in accessing vital health and care services that will ultimately lead to exacerbated disease severity and health outcomes. This places increased importance on attempts to be able to differentiate by both the occurrence and severity of disease.