Characterization and quantification of epilepsy patients with hospital episodes in Portugal: A multicenter retrospective study from Liga Portuguesa Contra a Epilepsia.

INTRODUCTION: Epilepsy affects around 50 million people worldwide and is associated with lower quality of life scores, an increased risk of premature death, and significant socio-economic implications. The lack of updated evidence on current epidemiology and patient characterization creates considerable uncertainty regarding the epilepsy burden in Portugal. The study aims to characterize and quantify the epilepsy patients who have been hospitalized, with medical or surgical procedures involved, and to analyze their associated comorbidities and mortality rates. METHODS: A multicenter retrospective study was conducted using hospital production data of epilepsy patients. The study included all patients diagnosed with epilepsy-related International Classification of Diseases-9/10 codes between 2015 and 2018 in 57 Portuguese National Health Service (NHS) hospitals (n = 57 institutions). Patient characterization and quantification were done for all patients with an epilepsy diagnosis, with specific analyses focusing on those whose primary diagnosis was epilepsy. Baseline, demographic, and clinical characteristics were analyzed using descriptive statistics. RESULTS: Between 2015 and 2018, a total of 80,494 hospital episodes (i.e., patient visit that generates hospitalization and procedures) were recorded, with 18 % to 19 % directly related to epilepsy. Among these epilepsy-related hospital episodes, 13.0 % led to short term hospitalizations (less than 24 h). Additionally, the average length of stay for all these epilepsy-related episodes was 8 days. A total of 49,481 patients were identified with epilepsy based on ICD-9/10 codes. The median age of patients was 64 years (min: 0; max: 104), with a distribution of 4.8 patients per 1,000 inhabitants. From the total of deaths (9,606) between 2015 and 2018, 14% were associated with patients whose primary diagnosis was epilepsy, with 545 of these being epilepsy-related deaths. Among patients with a primary diagnosis of epilepsy, the most common comorbidities were hypertension (24%) and psychiatric-related or similar comorbidities (15%), such as alcohol dependance, depressive and major depressive disorders, dementia and other convulsions. CONCLUSION: This study showed similar results to other European countries. However, due to methodological limitations, a prospective epidemiological study is needed to support this observation. Furthermore, the present study provides a comprehensive picture of hospitalized epilepsy patients in Portugal, their comorbidities, mortality, and hospital procedures.

Bringing up to date the toolkit for the catabolism of aromatic compounds in fungi: The unexpected 1,2,3,5-tetrahydroxybenzene central pathway.

Saprophytic fungi are able to catabolize many plant-derived aromatics, including, for example, gallate. The catabolism of gallate in fungi is assumed to depend on the five main central pathways, i.e., of the central intermediates' catechol, protocatechuate, hydroxyquinol, homogentisate and gentisate, but a definitive demonstration is lacking. To shed light on this process, we analysed the transcriptional reprogramming of the growth of Aspergillus terreus on gallate compared with acetate as the control condition. Surprisingly, the results revealed that the five main central pathways did not exhibit significant positive regulation. Instead, an in-depth analysis identified four highly expressed and upregulated genes that are part of a conserved gene cluster found in numerous species of fungi, though not in Aspergilli. The cluster comprises a monooxygenase gene and a fumarylacetoacetate hydrolase-like gene, which are recognized as key components of catabolic pathways responsible for aromatic compound degradation. The other two genes encode proteins with no reported enzymatic activities. Through functional analyses of gene deletion mutants in Aspergillus nidulans, the conserved short protein with no known domains could be linked to the conversion of the novel metabolite 5-hydroxydienelatone, whereas the DUF3500 gene likely encodes a ring-cleavage enzyme for 1,2,3,5-tetrahydroxybenzene. These significant findings establish the existence of a new 1,2,3,5-tetrahydroxybenzene central pathway for the catabolism of gallate and related compounds (e.g. 2,4,6-trihydroxybenzoate) in numerous fungi where this catabolic gene cluster was observed.

Elevated neutrophil-lymphocyte ratio is associated with high rates of ICU mortality, length of stay, and invasive mechanical ventilation in critically ill patients with COVID-19 : NRL and severe COVID-19.

Neutrophil and lymphocyte ratio (NLR) has emerged as a complementary marker in intensive care. This study aimed to associate high NLR values with mortality as the primary outcome, and length of stay and need for invasive mechanical ventilation as secondary outcomes, in critically ill patients with COVID-19. A cross-sectional study encompassing 189 critically ill patients with COVID-19 was performed. The receiver operating characteristic curve was used to identify the best NLR cutoff value for ICU mortality (≥ 10.6). An NLR ≥ 10.6, compared with an NLR < 10.6, was associated with higher odds of ICU mortality (odds ratio [OR], 2.77; 95% confidence interval [CI], 1.24-6.18), ICU length of stay ≥ 14 days (OR, 3.56; 95% CI, 1.01-12.5), and need for invasive mechanical ventilation (OR, 5.39; 95% CI, 1.96-14.81) in the fully adjusted model (age, sex, kidney dysfunction, diabetes, obesity, hypertension, deep vein thrombosis, antibiotics, anticoagulants, antivirals, corticoids, neuromuscular blockers, and vasoactive drugs). In conclusion, elevated NLR is associated with high rates of mortality, length of stay, and need for invasive mechanical ventilation in critically ill patients with COVID-19.

Osteosarcopenia later in life: Prevalence and associated risk factors.

BACKGROUND AND AIMS: The identification of risk factors for osteosarcopenia in older adults is important for planning preventative strategies in clinical practice. Therefore, our study aimed to investigate the prevalence and risk factors associated with osteosarcopenia in older adults using different diagnostic criteria. METHODS: The sample included 171 community-dwelling older adults with a mean age of 79.4 ± 5.9 years and mean body mass index of 25.67 ± 4.70 kg/m2. We analyzed sociodemographic, biomarkers, lifestyle, and health condition data from participants of the "Projeto Idosos - Goiânia" cohort study. The outcome osteosarcopenia was defined as the simultaneous occurrence of sarcopenia and osteopenia. Osteopenia was diagnosed by low lumbar spine bone mineral density (BMD) using dual-energy X-ray absorptiometry (DEXA). Sarcopenia was diagnosed using handgrip dynamometry and appendicular skeletal mass index assessed by DEXA following the criteria of the two European consensuses on sarcopenia (2010 and 2018). Two osteosarcopenia outcome variables were evaluated: OsteoSarc1 and OsteoSarc2 using the 2010 and 2018 European sarcopenia consensus criteria, respectively. Multivariate Poisson regression analysis was used to calculate the prevalence ratios (PRs). RESULTS: The prevalence of OsteoSarc1 and OsteoSarc2 were 12.8% and 7.2%, respectively, with no significant gender differences. OsteoSarc1 was associated with low potassium (PR: 3.39, 95% confidence interval [CI]: 1.10-10.43) and malnutrition (PR: 3.84, 95% CI: 1.78-8.30). OsteoSarc2 was associated with being ≥80 years (PR: 7.64, 95% CI: 1.57-37.07), >4 years of education (PR: 3.25, 95% CI: 1.03-10.22), alcohol consumption (PR: 2.41, 95% CI: 1.01-5.77), low potassium (PR: 2.22, 95% CI: 1.45-6.87), low serum vitamin D (PR: 4.47, 95% CI: 1.68-11.88), and malnutrition (PR: 5.00, 95% CI: 1.06-23.51). CONCLUSIONS: OsteoSarc1 had a higher prevalence. The risk factors associated with the two outcomes were malnutrition and potassium level, as well as other risk factors, such as alcohol consumption and low vitamin D level. These findings may contribute to the prevention or treatment of this health condition in older adults.

Pharmacogenetic Variants Can Influence Optical Medication Use.

INTRODUCTION: Single Nucleotide Polymorphisms (SNPs) are used as drug susceptibility biomarkers in metabolic diseases. Alterations in the gene encoding triggers the enzyme flavin monooxygenase 3 (FMO3), involved in the Sulindac metabolization, which also is responsible for the inherited metabolic disorder. Trimethylaminuria (TMAu, OMIM: 602079). DPYD gene variants are associated with the enzyme dihydropyrimidine dehydrogenase deficiency (DPD; OMIM: 274270). This autosomal recessive metabolic disorder, ultimately leads to the inability to metabolize fluoropyrimidines, which causes severe toxicity in individuals treated with these drugs. METHODS: Variants in genes responsible for the expression of enzymes that encode transporters or receptors involved in the metabolization pathways of certain drugs may condition the individuals response to certain drugs, compromising the therapeutic response and clinical prognosis. Thus the sequencing and identification of variants become relevant, not only gain knowledge on effects of these variants' on disease causality but also in terms of its side effects resulting from the coding enzymes responsible for drug metabolization. RESULTS: It was found that patients with the c.472G>A (p.Glu158Lys) and c.923A>G (p.Glu308Gly) polymorphisms, in homozygosity, in FMO3 gene did not develop polyps, thus have a protective effect in the treatment of Familial Adenomatous Polyposis (PAF). However, in the case of the DPYD gene, c.1905+1G>A (IVS14+1G>A), c.1679T>G (p.Ile560Ser), c.2846A>T (p.Asp949Val) e c.1236G>A/HapB3 variants can be lethal in cancer patients indicated for fluoropyrimidine-based chemotherapy. CONCLUSION: Knowledge on the drug mechanisms will affect the therapeutic response of patients treated with a given drug. Thus, pharmacogenetics is an essential tool in personalized medicine, since molecular studies allows the clinician to predict the probability of efficacy and toxicity of certain drugs, resulting higher efficiency in individualizing treatment and also improving the safety of the patient. From a personalized medicine perspective, the study of the characteristics of the drug and its metabolization site, the genes involved in the encoding of enzymes responsible for its metabolization will be of great interest.

Rosin from Pinus pinaster Portuguese forests shows a regular profile of resin acids.

Pinus pinaster forestry occupies >20% of the forest ecosystem area in the continental territory of Portugal with a high impact on the national economy. This species' major derived non-wood product is oleoresin, the raw material for rosin production. Rosin comprises mainly a blend of resin acids and has broad industrial and pharmaceutical applications. Oleoresin production in Portugal has been progressively reduced due to low-cost producers in other countries; currently, it reaches only 2% of the existing P. pinaster trees. To support this value chain, the chemical fingerprint of rosin derived from the national forest requires focused analysis. In the present study, we collected oleoresin within seven geographically distinct pure P. pinaster forests in two consecutive collection years. A high-resolution nuclear magnetic resonance (NMR) method was used to quantify the diversity of resin acids in the corresponding rosin samples. Overall, the acquired data highlighted that the profile of resin acids in P. pinaster rosin produced in Portugal is highly regular, regardless of the forest location, having as the major constituents abietic acid and dehydroabietic acid. The diversity of resin acids is possibly influenced, to a minor extent, by some edaphoclimatic factors.

Methylmalonyl Coenzyme A (CoA) Epimerase Deficiency, an Ultra-Rare Cause of Isolated Methylmalonic Aciduria With Predominant Neurological Features.

Methylmalonyl coenzyme A (CoA) epimerase (MCE) converts D-methylmalonyl-CoA into L-methylmalonyl CoA in the final common degradation pathway of valine, isoleucine, methionine, threonine, odd-chain fatty acids, and cholesterol side chains. Methylmalonyl-CoA epimerase deficiency is an ultra-rare autosomal recessive disorder where methylmalonic acid, methylcitrate, 3-hydroxypropionate, and propionylcarnitine are accumulated. We describe two novel pediatric patients and review the previously reported cases of MCE deficiency. Including our two novel patients, at least 24 cases of MCE deficiency have been described, with a broad clinical spectrum ranging from asymptomatic to severely neurologically impaired patients. Our patients are siblings of Arabic origin who presented with metabolic decompensation with coma and epilepsy during infancy. Methylmalonic aciduria was disclosed, L-methylmalonyl-CoA mutase deficiency was assumed, and they were treated accordingly. When first seen in our country, aged 10 and four years, respectively, both presented severe intellectual disability and spasticity. The younger had an ataxic gait, and the older was wheelchair-ridden. The study of the MMUT, MMAA, MMAB, and MMADHC genes was normal. Subsequently, the pathogenic variant c.139C>T (p.Arg47*) in the MCEE gene was identified in homozygosity in both patients, leading to the diagnosis of MCE deficiency (Online Mendelian Inheritance in Man (OMIM®) 251120, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, MD, USA). Most patients were homozygous for that variant (83% of the alleles). Correct diagnosis allowed treatment adequacy and genetic counseling. Methylmalonyl-CoA epimerase deficiency shares a similar biochemical profile with other rare genetic disorders. Patients present with overlapping clinical features with predominant neurological manifestations; genetic testing is indispensable for diagnosis. We found no association between genotype and biochemical and clinical phenotypes.

Clinical predictors of NEDA-3 one year after diagnosis of pediatric multiple sclerosis: an exploratory single-center study.

Introduction: Multiple sclerosis (MS) is an inflammatory and demyelinating disorder of central nervous system that can be diagnosed in pediatric age (<18 years) in 3-5% of the cases. This early onset is associated with higher relapse rates and earlier progression to neurological disability. By using NEDA-3 (No Evidence of Disease Activity-3) criteria, we aimed to identify clinical predictors associated with absence of disease activity and control of disease progression 12 months after the diagnosis, in a cohort of pediatric-onset MS (POMS) patients regularly followed-up in our center. Methods: We analyzed demographic, clinical, laboratorial and imaging variables of patients with POMS identified in our center, between 2010 and 2021, in two moments: at the diagnosis and 12 months after it. Statistical tests were applied to compare the distribution of those variables between groups defined by NEDA-3 status and by each one of its three variable components. Results: We included 27 patients in the study (18 female), with a mean age of 14.8 years (± 2.8), being all diagnosed with relapsing-remitting MS and with a median score of 1.5 at the Expanded Disability Status Scale (EDSS). The use of natalizumab (p = 0.017) and the negativity for anti-EBV IgG antibodies (p = 0.018) at diagnosis were associated with a higher achievement of NEDA-3 status 12 months after, in our cohort. Prescribed treatment was also associated with statistically significant differences in the "absence of MRI activity" component of NEDA-3 (p = 0.006): patients under treatment with natalizumab had a higher probability of achieving this status, and the opposite was observed in glatiramer acetate-treated children. Discussion and conclusion: Our exploratory results underline the pivotal importance that an early and more effective therapeutical approach may have in the control of disease activity, in POMS. Additionally, they also seem to suggest that the presence of anti-EBV antibodies is not innocent, as it can be related to a less favorable evolution of the disease, even at a very early stage. Further studies are needed to confirm the applicability of these variables as prognostic and personalized tools in this clinical setting.

Magnitude of risk factors for chronic noncommunicable diseases in adolescents and young adults in Brazil: A population-based study.

AIM OF THE STUDY: Estimate the magnitude and factors associated with risk factors for chronic noncommunicable diseases in adolescents and young adults in Brazil. METHODS: Cross-sectional study that analyzed data from the 2019 National Health Survey. The population of interest was adolescents and young adults aged 15 to 24 years. Data were collected through individual interviews during home visits. Dependent variables included major risk factors for chronic noncommunicable diseases. Demographic and socioeconomic characteristics were used as independent variables. Multiple Poisson regression models were used to assess the relationship between independent variables and risk factors. RESULTS: A total of 10,460 individuals (5,001 men and 5,459 women) were included. Regardless of sex, the most prevalent risk factors were insufficient fruit and vegetable consumption (92.6%) and leisure-time physical inactivity (43.3%). The prevalence rates of tobacco smokers, alcohol consumption once a month or more, and alcohol abuse were 8.9%, 28.7%, and 18.5%, respectively. Regular consumption of soft drinks and/or artificial juices was described by 17.2%. The prevalence of overweight was 32.5%. Young adults, males, and individuals with lower educational levels, of black race/skin color, with lower household income, and residents of urban areas had a higher prevalence for most risk factors. Differences in the determinants were found for some factors. Inequalities between Brazilian regions were recorded for seven of the nine factors analyzed. The most socioeconomically developed regions had the highest prevalence of most risk factors. The high magnitude of risk factors indicates a potential increase in the burden of chronic noncommunicable diseases in a future scenario for Brazil.

Nascent Aß42 Fibrillization in Synaptic Endosomes Precedes Plaque Formation in a Mouse Model of Alzheimer's-like ß-Amyloidosis.

Accumulation of amyloid-ß peptide (Aß) aggregates in synapses may contribute to the profound synaptic loss characteristic of Alzheimer's disease (AD). The origin of synaptic Aß aggregates remains elusive, but loss of endosomal proteostasis may trigger their formation. In this study, we identified the synaptic compartments where Aß accumulates, and performed a longitudinal analysis of synaptosomes isolated from brains of TgCRND8 APP transgenic mice of either sex. To evaluate the specific contribution of Aß-degrading protease endothelin-converting enzyme (ECE-1) to synaptic/endosomal Aß homeostasis, we analyzed the effect of partial Ece1 KO in brain and complete ECE1 KO in SH-SY5Y cells. Global inhibition of ECE family members was used to further assess their role in preventing synaptic Aß accumulation. Results showed that, before extracellular amyloid deposition, synapses were burdened with detergent-soluble Aß monomers, oligomers, and fibrils. Levels of all soluble Aß species declined thereafter, as Aß42 turned progressively insoluble and accumulated in Aß-producing synaptic endosomal vesicles with characteristics of multivesicular bodies. Accordingly, fibrillar Aß was detected in brain exosomes. ECE-1-deficient mice had significantly increased endogenous synaptosomal Aß42 levels, and protease inhibitor experiments showed that, in TgCRND8 mice, synaptic Aß42 became nearly resistant to degradation by ECE-related proteases. Our study supports that Aß accumulating in synapses is produced locally, within endosomes, and does not require the presence of amyloid plaques. ECE-1 is a determinant factor controlling the accumulation and fibrillization of nascent Aß in endosomes and, in TgCRND8 mice, Aß overproduction causes rapid loss of Aß42 solubility that curtails ECE-mediated degradation.SIGNIFICANCE STATEMENT Deposition of aggregated Aß in extracellular plaques is a defining feature of AD. Aß aggregates also accumulate in synapses and may contribute to the profound synaptic loss and cognitive dysfunction typical of the disease. However, it is not clear whether synaptotoxic Aß is mainly derived from plaques or if it is produced and aggregated locally, within affected synaptic compartments. Filling this knowledge gap is important for the development of an effective treatment for AD, as extracellular and intrasynaptic pools of Aß may not be equally modulated by immunotherapies or other therapeutic approaches. In this manuscript, we provide evidence that Aß aggregates building up in synapses are formed locally, within synaptic endosomes, because of disruptions in nascent Aß proteostasis.

CD8+ tissue-resident memory T-cell development depends on infection-matching regulatory T-cell types.

Immunological memory is critical for immune protection, particularly at epithelial sites, which are under constant risk of pathogen invasions. To counter invading pathogens, CD8+ memory T cells develop at the location of infection: tissue-resident memory T cells (TRM). CD8+ T-cell responses are associated with type-1 infections and type-1 regulatory T cells (TREG) are important for CD8+ T-cell development, however, if CD8+ TRM cells develop under other infection types and require immune type-specific TREG cells is unknown. We used three distinct lung infection models, to show that type-2 helminth infection does not establish CD8+ TRM cells. Intracellular (type-1) and extracellular (type-3) infections do and rely on the recruitment of response type-matching TREG population contributing transforming growth factor-ß. Nevertheless, type-1 TREG cells remain the most important population for TRM cell development. Once established, TRM cells maintain their immune type profile. These results may have implications in the development of vaccines inducing CD8+ TRM cells.

Leigh Syndrome Spectrum: A Portuguese Population Cohort in an Evolutionary Genetic Era.

Mitochondrial diseases are the most common inherited inborn error of metabolism resulting in deficient ATP generation, due to failure in homeostasis and proper bioenergetics. The most frequent mitochondrial disease manifestation in children is Leigh syndrome (LS), encompassing clinical, neuroradiological, biochemical, and molecular features. It typically affects infants but occurs anytime in life. Considering recent updates, LS clinical presentation has been stretched, and is now named LS spectrum (LSS), including classical LS and Leigh-like presentations. Apart from clinical diagnosis challenges, the molecular characterization also progressed from Sanger techniques to NGS (next-generation sequencing), encompassing analysis of nuclear (nDNA) and mitochondrial DNA (mtDNA). This upgrade resumed steps and favored diagnosis. Hereby, our paper presents molecular and clinical data on a Portuguese cohort of 40 positive cases of LSS. A total of 28 patients presented mutation in mtDNA and 12 in nDNA, with novel mutations identified in a heterogeneous group of genes. The present results contribute to the better knowledge of the molecular basis of LS and expand the clinical spectrum associated with this syndrome.

Purification of archetypal soybean root suberin mostly comprising alka(e)noic acids using an ionic liquid catalyst.

Soybean (Glycine max) is an increasingly relevant crop due to its economic importance and also a model plant for the study of root symbiotic associations with nodule forming rhizobia. Plant polyesters mediate plant-microbe interactions with both pathogenic and beneficial microbes; suberin has been hypothesized to play a key role during the early steps of rhizobia attachment to the root. The downside is that suberin chemistry in soybean root is still scarcely studied. This study addresses this outstanding question by reporting a straightforward workflow for a speedy purification of suberin from soybean root and for its subsequent detailed chemical analysis. To purify suberin, cholinium hexanoate (an ionic liquid) was used as the catalyst. The ensuing suberin is highly esterified as observed by a precise Nuclear Magnetic Resonance quantification of each ester type, discriminating between primary and acylglycerol esters. Moreover, the composing hydrolysable monomers detected through GC-MS revealed that hexadecanoic acid is the most abundant monomer, similar to that reported before by others. Overall, this study highlights the adequacy of the ionic liquid catalyst for the isolation of suberin from soybean roots, where the polymer natural abundance is low, and builds new knowledge on the specificities of its chemistry; essential to better understand the biological roles of suberin in roots.

Sex distinctions regarding serum zinc levels in critically ill COVID-19 patients.

PURPOSE: Men and women exhibit different presentations in COVID-19. In X chromosome, changes in zinc finger domains cause disorders of sex development. So, we aimed to evaluate sex distinctions regarding serum zinc in severe COVID-19. METHOD: Data from electronic records of severe COVID-19 patients were correlated with serum zinc. Logistic regression investigated predictors and protectors of hypozincemia in men and women. RESULTS: We assessed 188 medical records (men = 114, women = 74). In men, low zinc was correlated with hypertension (cc = 0.303, p < 0.001), diabetes (cc = 0.198, p = 0.031), hemoglobin (cc = -0.258, p = 0.005), and albumin (cc = -0.219, p = 0.027). Low lymphocyte count (cc = 0.315, p = 0.005), C-reactive protein (cc = -0.248, p = 0.037), and enteral nutrition (cc = 0.269, p = 0.016) were correlated with hypozincemia in women. Age correlated with low zinc in men (c = -0.304, p = 0.001) and women (cc = -0.298, p = 0.010). In men, hypertension (OR = 4.905, p = 0.005) and lymphopenia (OR = -0.999, p = 0.019) were low zinc predictors, while lung injury > 50% was a protective factor (OR = -0.280, p = 0.025). Lymphopenia (OR = -0.999, p = 0.005) and difficult weaning from mechanical ventilation (MV) (OR = 4.359, p = 0.036) were predictors of hypozincemia in women. Difficult weaning from MV (OR = 3.012, p = 0.003) and age (OR = 1.038, p = 0.002) were hypozincemia predictors regardless sex. CONCLUSION: Hypertension, diabetes, hemoglobin and albumin were correlated with low zinc in men. Lymphopenia, reactive-C protein and enteral nutrition were correlated with low zinc in women. In men, hypertension and low lymphocytes were predictors of hypozincemia. Lymphopenia and difficult weaning from MV were predictors of low zinc in women.

Increased Production of Pathogenic, Airborne Fungal Spores upon Exposure of a Soil Mycobiota to Chlorinated Aromatic Hydrocarbon Pollutants.

Organic pollutants are omnipresent and can penetrate all environmental niches. We evaluated the hypothesis that short-term (acute) exposure to aromatic hydrocarbon pollutants could increase the potential for fungal virulence. Specifically, we analyzed whether pentachlorophenol and triclosan pollution results in the production of airborne fungal spores with greater virulence than those derived from an unpolluted (Control) condition. Each pollutant altered the composition of the community of airborne spores compared to the control, favoring an increase in strains with in vivo infection capacity (the wax moth Galleria mellonella was used as an infection model). Fungi subsisting inside larvae at 72 h postinjection with airborne spore inocula collected in polluted and unpolluted conditions exhibited comparable diversity (mainly within Aspergillus fumigatus). Several virulent Aspergillus strains were isolated from larvae infected with the airborne spores produced in a polluted environment. Meanwhile, strains isolated from larvae injected with spores from the control, including one A. fumigatus strain, showed no virulence. Potential pathogenicity increased when two Aspergillus virulent strains were assembled, suggesting the existence of synergisms that impact pathogenicity. None of the observed taxonomic or functional traits could separate the virulent from the avirulent strains. Our study emphasizes pollution stress as a possible driver of phenotypic adaptations that increase Aspergillus pathogenicity, as well as the need to better understand the interplay between pollution and fungal virulence. IMPORTANCE Fungi colonizing soil and organic pollutants often meet. The consequences of this encounter constitute an outstanding question. We scrutinized the potential for virulence of airborne fungal spores produced under unpolluted and polluted scenarios. The airborne spores showed increased diversity of strains with higher infection capacity in Galleria mellonella whenever pollution is present. Inside the larvae injected with either airborne spore community, the surviving fungi demonstrated a similar diversity, mainly within Aspergillus fumigatus. However, the isolated Aspergillus strains greatly differ since virulence was only observed for those associated with a polluted environment. The interplay between pollution and fungal virulence still hides many unresolved questions, but the encounter is costly: pollution stress promotes phenotypic adaptations that may increase Aspergillus pathogenicity.

Pulmonary biological glue embolism after endoscopic repair of gastric varices - A case report.

Cyanoacrylate injection is widely used to treat hemorrhagic gastric varices. A pulmonary glue embolism is an unusual but potentially fatal complication. We present a case of a 51-year-old man with a history of alcoholic hepatic cirrhosis Child-Pugh B, who had an acute pulmonary embolism with sudden cardiorespiratory collapse due to biological glue injection used for the emergent repair of bleeding gastric varices. After the restoration of respiratory and hemodynamic parameters, he was admitted to the intensive care unit and the pulmonary biological glue emboli were documented with computed tomography scan. A high index of suspicion for this entity is essential in patients submitted to endoscopic sclerotherapy. Some might be asymptomatic or mildly symptomatic, while others might present with cardiorespiratory collapse.

Prevalence and factors associated with multimorbidity in adults in Brazil, according to sex: a population-based cross-sectional survey.

Introduction: Multimorbidity, defined as the coexistence of two or more chronic diseases in the same individual, represents a significant health challenge. However, there is limited evidence on its prevalence and associated factors in developing countries, such as Brazil, especially stratified by sex. Thus, this study aims to estimate the prevalence and analyze the factors associated with multimorbidity in Brazilian adults according to sex. Methods: Cross-sectional population-based household survey carried out with Brazilian adults aged 18 years or older. The sampling strategy consisted of a three-stage conglomerate plan. The three stages were performed through simple random sampling. Data were collected through individual interviews. Multimorbidity was classified based on a list of 14 self-reported chronic diseases/conditions. Poisson regression analysis was performed to estimate the magnitude of the association between sociodemographic and lifestyle factors with the prevalence of multimorbidity stratified by sex. Results: A total of 88,531 individuals were included. In absolute terms, the prevalence of multimorbidity was 29.4%. The frequency in men and women was 22.7 and 35.4%, respectively. Overall, multimorbidity was more prevalent among women, the older people, residents of the South and Southeast regions, urban area residents, former smokers, current smokers, physically inactive, overweight, and obese adults. Individuals with complete high school/incomplete higher education had a lower prevalence of multimorbidity than those with higher educational level. The associations between education and multimorbidity differed between sexes. In men, multimorbidity was inversely associated with the strata of complete middle school/incomplete high school and complete high school/incomplete higher education, while in women, the association between these variables was not observed. Physical inactivity was positively associated with a higher prevalence of multimorbidity only in men. An inverse association was verified between the recommended fruit and vegetable consumption and multimorbidity for the total sample and both sexes. Conclusion: One in four adults had multimorbidity. Prevalence increased with increasing age, among women, and was associated with some lifestyles. Multimorbidity was significantly associated with educational level and physical inactivity only in men. The results suggest the need to adopt integrated strategies to reduce the magnitude of multimorbidity, specific by gender, including actions for health promotion, disease prevention, health surveillance and comprehensive health care in Brazil.

Diagnosis across a cohort of "atypical" atypical and complex parkinsonism.

INTRODUCTION: The diagnostic approach for adulthood parkinsonism can be challenging when atypical features hamper its classification in one of the two main parkinsonian groups: Parkinson's disease or atypical parkinsonian syndromes (APS). Atypical features are usually associated with non-sporadic neurodegenerative causes. METHODS: Retrospective analysis of patients with a working clinical diagnosis of "atypical" APS and complex parkinsonism. "Atypical" APS were classified according to the diagnostic research criteria and the "4-step diagnostic approach" (Stamelou et al. 2013). When not indicated, the final aetiological diagnosis was prospectively assessed. Brain MRI of progressive supranuclear palsy (PSP) look-alikes was reviewed by a neuroradiologist. RESULTS: Among 18 patients enrolled, ten were assigned to the "atypical" APS and eight to the complex parkinsonism group. In the "atypical" APS group, nine patients had PSP and one had corticobasal degeneration. In the PSP group the median magnetic resonance parkinsonism index was 17.1. A final aetiological diagnosis was established for 11 patients, four from the complex parkinsonism (L-2-hidroxiglutaric aciduria and DiGeorge syndrome) and seven from the "atypical" APS (Perry syndrome, postencephalitic PSP, vascular PSP, and MTP-AT6 mitochondrial disease) group. CONCLUSIONS: In this study, the identification of atypical APS features, as proposed in the "4-step diagnostic approach", successfully guided the investigation of alternative diagnoses. Distinctive non-neurodegenerative etiologies causing "atypical" atypical and complex parkinsonism were uncovered, including acquired (post-encephalitis and vascular) and genetic (MTP-AT6 mitochondrial disease mimicking PSP, described for the first time) ones. In the future, accurate clinical identification and distinction between neurodegenerative and non-neurodegenerative parkinsonism etiologies will allow for refining clinical trials.

A new class of monoclonal Aß antibodies selectively targets and triggers deposition of Aß protofibrils.

Aggregation and accumulation of amyloid-ß peptide (Aß) are a critical trigger for the onset of Alzheimer's disease (AD). While the plaques are the most outstanding Aß pathological feature, much of the recent research emphasis has been on soluble Aß species because of their diffusible, proinflammatory, and toxic properties. The focus on soluble aggregated Aß species has also increased the interest in antibodies that are selective for different Aß conformations. In the current study, we developed and characterized a new class of monoclonal antibodies (referred to as mAbSL) that are selective for Aß protofibrils. Cloning and sequencing of the heavy and light chain variable regions for multiple antibodies identified sequence characteristics that may impart the conformational selectivity by the antibodies. Transfection of FreeStyle 293F cells with the plasmids permitted in-house expression and purification of mAbSL antibodies along with non-conformation-selective Aß monoclonal antibodies (Aß mAbs). Several of the purified mAbSL antibodies demonstrated significant affinity and selectivity for Aß42 protofibrils compared with Aß42 monomers and Aß42 fibrils. Competition ELISA assays assessing the best overall antibody, mAbSL 113, yielded affinity constants of 7 nM for the antibody-Aß42 protofibril interaction, while the affinity for either Aß42 monomers or Aß42 fibrils was roughly 80 times higher. mAbSL 113 significantly inhibited Aß42 monomer aggregation by a unique mechanism compared with the inhibition displayed by Aß mAb 513. Aß42 protofibril dynamics were also markedly altered in the presence of mAbSL 113, whereby insoluble complex formation and protofibril deposition were stimulated by the antibody at low substoichiometric molar ratios. As the field contemplates the therapeutic effectiveness of Aß conformation-selective antibodies, the findings presented here demonstrate new information on a monoclonal antibody that selectively targets Aß protofibrils and impacts Aß dynamics.

Opioids and constipation therapy in the last week of life: Their impact on patients, caregivers, and the location of death.

The use of opioids to control pain at the end of life may cause constipation, a symptom that can negatively influence the well-being of patients and caregivers. The main aim of this study was to evaluate the impact of constipation on symptomatic control and patients' overall quality of life at this stage. A particular focus was placed on opioids. We also intended to investigate whether constipation and caregiver fatigue is related to the place of death (hospital vs home). The approach of 121 patients followed in 2021 in their last week of life by a home team specialized in palliative care was analyzed in an observational, retrospective, non-interventional study. The patients were followed up for an average of 39.7 days. A total of 82.6% wished to die at home, which occurred in 74% of the cases. The constipation prevention protocol reduced constipation by 55.1%. It seems that morphine is more related with constipation and tapentadol seems to reduce constipation induced by opioids. Patients tended to die in hospitals when their caregivers were exhausted; however, it was not possible to determine a cutoff point using the Zarit scale, which was used to assess caregiver burden. Constipation in the last week of life does not seem to influence the well-being of patients or their caregivers significantly and the individualization of intensive treatment of constipation is needed. Different opioids have different probabilities of causing adverse effects such as constipation. Future special support mechanisms can be created and activated for the most tired caregivers to avoid exhaustion and promote death at home, if that is the patient's will.