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The neurovascular unit (NVU) consists of cells intrinsic to the vessel wall, the endothelial cells and pericytes, and astrocyte endfeet that surround the vessel but are separated from it by basement membrane. Endothelial cells are primarily responsible for creating and maintaining blood–brain-barrier (BBB) tightness, but astrocytes contribute to the barrier through paracrine signaling to the endothelial cells and by forming the glia limitans. Gap junctions (GJs) between astrocyte endfeet are composed of connexin 43 (Cx43) and Cx30, which form plaques between cells. GJ plaques formed of Cx43 do not diffuse laterally in the plasma membrane and thus potentially provide stable organizational features to the endfoot domain, whereas GJ plaques formed of other connexins and of Cx43 lacking a large portion of its cytoplasmic carboxyl terminus are quite mobile. In order to examine the organizational features that immobile GJs impose on the endfoot, we have used super-resolution confocal microscopy to map number and sizes of GJ plaques and aquaporin (AQP)-4 channel clusters in the perivascular endfeet of mice in which astrocyte GJs (Cx30, Cx43) were deleted or the carboxyl terminus of Cx43 was truncated. To determine if BBB integrity was compromised in these transgenic mice, we conducted perfusion studies under elevated hydrostatic pressure using horseradish peroxide as a molecular probe enabling detection of micro-hemorrhages in brain sections. These studies revealed that microhemorrhages were more numerous in mice lacking Cx43 or its carboxyl terminus. In perivascular domains of cerebral vessels, we found that density of Cx43 GJs was higher in the truncation mutant, while GJ size was smaller. Density of perivascular particles formed by AQP4 and its extended isoform AQP4ex was inversely related to the presence of full length Cx43, whereas the ratio of sizes of the particles of the AQP4ex isoform to total AQP4 was directly related to the presence of full length Cx43. Confocal analysis showed that Cx43 and Cx30 were substantially colocalized in astrocyte domains near vasculature of truncation mutant mice. These results showing altered distribution of some astrocyte nexus components (AQP4 and Cx30) in Cx43 null mice and in a truncation mutant, together with leakier cerebral vasculature, support the hypothesis that localization and mobility of gap junction proteins and their binding partners influences organization of astrocyte endfeet which in turn impacts BBB integrity of the NVU.

Introduction: The analysis of movement quality is important for better exercise prescription. This study tested the reproducibility of a protocol for remote assessment of dynamic knee alignment using images taken by patients. Methods: Thirteen women filmed themselves performing single-leg squats on two days at a 15-day interval. Three raters measured the knee frontal plane projection angle using the resultant images. Results: Two participants (15.4%) were excluded for not performing the protocol correctly. The intraclass correlation coefficient was between 0.880 and 0.999 for the intra-rater comparison, and between 0.817 and 0.987 for the inter-rater comparison. Discussion: The success of the protocol in 84.6% of participants and the excellent reproducibility suggest that the methodology of analyzing patient-captured cell phone images might be a plausible alternative for remote evaluation of dynamic knee alignment.

Agro-industrial residues rich in carbohydrates represent low-cost and sustainable feedstock for enzyme production. This study demonstrates that green Arabica coffee press cake, a mannan-rich coproduct of oil extraction, is an efficient carbon source for Aspergillus niger (CFAM 1234) cultivation and for inducing mannanase production. Furthermore, the enzymes obtained were tested for mannose recovery in the enzymatic hydrolysis of healthy and defective coffee beans to investigate their hydrolytic potential. Mannanase production was investigated using various carbon sources—including ground coffee beans; coffee press cake; different particle sizes of coffee press cake; aqueous coffee cake extract (prepared at 30 g·L[sup.−1] under constant stirring (300 rpm) at 80 °C for 2 h, followed by filtration.); and a commercial galactomannan, locust bean gum (LBG). CNHSO analysis was performed in the best carbon source (coffee press cake) and LBG. Statistical optimization (Plackett–Burman and Central Composite Rotatable Design) simplified the culture medium composition to coffee press cake (48.78 g·L[sup.−1]), yeast extract (4 g·L[sup.−1]), and potassium phosphate (0.25 g·L[sup.−1], pH 5.5) and increased mannanases productivity to 22.4 ± 0.6 U·mL[sup.−1] within only 3 days (a 42.9% improvement compared to non-optimized conditions, which were 30 g·L[sup.−1], carbon source, 4 g·L[sup.−1] yeast extract, 1 g·L[sup.−1] Al[sub.2]O[sub.3], 0.5 g·L[sup.−1] potassium phosphate buffer (pH 5.5), 0.5 g·L[sup.−1] of MgSO[sub.4]·7H[sub.2]O, and 0.05 g·L[sup.−1] of CaCl[sub.2]·2H[sub.2]O, which resulted in a maximum of ~20 U·mL[sup.−1] in 7 days). The crude extract also exhibited β-mannosidase activity (1.39 ± 0.06 U·mL[sup.−1]). When applied to the hydrolysis of untreated healthy and defective coffee beans, the enzyme preparation enabled ~25% mannose recovery (considering the value obtained through acid hydrolysis as 100%), highlighting its potential as a mannose resource. The results demonstrate that coproducts from the coffee production chain can be used as an efficient carbon source (coffee cake) for mannanase production, as well as sugar recovery (defective coffee beans), offering an integrated strategy to strengthen the circular bioeconomy and generate carbohydrates with potential industrial and nutritional applications.

The evaluation of food consumption in childhood is essential to help understand the effect of food choices on health. The objective of this study was to conduct a systematic review of studies that identified the dietary patterns in schoolchildren (7–10 years old) and their associated factors. Observational studies published in the last ten years were searched in the databases BVS (Virtual Health Library), Embase, PubMed, Scopus, and Web of Science. The Newcastle Ottawa Scale was adopted to evaluate the articles’ quality. The studies covered schoolchildren, children, and adolescents as part of the sample. We selected 16 studies, 75% of which were considered good/very good and seven mentioned three food patterns. A dietary pattern considered unhealthy was identified in 93.75% of the studies, having as associated factors to its consumption: higher screen time, low bone mass, gain of weight and fat in children, and meal skipping. The children who usually had breakfast showed greater adherence to the dietary pattern consisting of healthier foods. The children’s dietary patterns were related to their behavior, nutritional status, and family environment habits. Food and nutrition education’s effective actions, as well as the regularization of the marketing of ultra-processed foods, must be stimulated and inserted in public policies as a way to promote and protect children’s health.

This work explores the relationship between chemical pollutants, soil fauna, and microbial processes within the framework of Ecological Risk Assessment (ERA). Collembola have been widely studied in ecotoxicology. Folsomia candida is used as the standard species in toxicity tests to be indicative of pollutant effects on soil microarthropods; however, such single species tests ignore interactions with other species and functional endpoints. The connection between Collembola and microbial biomass remains unclear, highlighting a research gap in under- standing their interdependence. Using a microcosm test, we investigated the impact of six dif- ferent concentrations of the insecticide Teflubenzuron (0.025, 0.08, 0.25, 0.8, 2.53, and 8 mg/kg soildw), dosed to the top 2 cm soil layer, on a community of four species of Collembola (Folsomia candida, Sinella curviseta, Ceratophysella denticulata, and Protaphorura fimata) and its subsequent effects on microbial community structure. We looked at soil respiration rate and the activity of four enzymes: Phosphomonoesterase, β-glucanase, β-glucosidase and Leucine aminopepti- dase. At 4 different time points (12, 33, 54 and 78 days of), 5 replicates of each soil contaminated with the different concentrations of Teflubenzuron and the controls were destructively sam- pled and the Collembola community composition and abundance were analysed in different soil layers (A = 0 - 2 cm, B = 2 - 4 cm, C = 4 - 10 cm). At the end of the experiment, almost all adult springtails disappeared, also from the controls. When compared to the control groups, the highest concentrations of Teflubenzuron caused a lower production of juveniles, particu- larly in the later stages of the study, consistent with prior research indicating the heightened toxicity of Teflubenzuron to juvenile springtails. Soil respiration rate decreased at 8 mg/kg soildw of Teflubenzuron. Whilst springtail abundance decreased in all soil layers, enzymatic activity showed a general increasing trend until 54 days after the start of the experiment and Teflubenzuron concentration until 0.08 mg/kg soildw. We discuss the complex patterns of the interaction between springtails and microbial parameters exhibited over time and across dif- ferent concentrations of Teflubenzuron, and its consequences for risk assessment.

The neurovascular unit (NVU) consists of cells intrinsic to the vessel wall, the endothelial cells and pericytes, and astrocyte endfeet that surround the vessel but are separated from it by basement membrane. Endothelial cells are primarily responsible for creating and maintaining blood-brain-barrier (BBB) tightness, but astrocytes contribute to the barrier through paracrine signaling to the endothelial cells and by forming the glia limitans. Gap junctions (GJs) between astrocyte endfeet are composed of connexin 43 (Cx43) and Cx30, which form plaques between cells. GJ plaques formed of Cx43 do not diffuse laterally in the plasma membrane and thus potentially provide stable organizational features to the endfoot domain, whereas GJ plaques formed of other connexins and of Cx43 lacking a large portion of its cytoplasmic carboxyl terminus are quite mobile. In order to examine the organizational features that immobile GJs impose on the endfoot, we have used super-resolution confocal microscopy to map number and sizes of GJ plaques and aquaporin (AQP)-4 channel clusters in the perivascular endfeet of mice in which astrocyte GJs (Cx30, Cx43) were deleted or the carboxyl terminus of Cx43 was truncated. To determine if blood-brain-barrier integrity was compromised in these transgenic mice, we conducted perfusion studies under elevated hydrostatic pressure using horseradish peroxide as a molecular probe enabling detection of micro-hemorrhages in brain sections. These studies revealed that microhemorrhages were more numerous in mice lacking Cx43 or its carboxyl terminus. In perivascular domains of cerebral vessels, we found that density of Cx43 GJs was higher in the truncation mutant, while GJ size was smaller. Density of perivascular particles formed by AQP4 and its extended isoform AQP4ex was inversely related to the presence of full length Cx43, whereas the ratio of sizes of the particles of the AQP4ex isoform to total AQP4 was directly related to the presence of full length Cx43. Confocal analysis showed that Cx43 and Cx30 were substantially colocalized in astrocyte domains near vasculature of truncation mutant mice. These results showing altered distribution of some astrocyte nexus components (AQP4 and Cx30) in Cx43 null mice and in a truncation mutant, together with leakier cerebral vasculature, support the hypothesis that localization and mobility of gap junction proteins and their binding partners influences organization of astrocyte endfeet which in turn impacts BBB integrity of the NVU. Competing Interest Statement The authors have declared no competing interest.

The aim of this study was to describe the dietary intake of British vegetarians according to the Nova classification and to evaluate the association between the consumption of ultra-processed foods and the nutritional quality of the diet. We used data from the UK national survey (2008/2019). Food collected through a 4-d record were classified according to the Nova system. In all tertiles of the energy contribution of ultra-processed foods, differences in the average nutrient intake, as well as in the prevalence of inadequate intake, were analysed, considering the values recommended by international authorities. Ultra-processed foods had the highest dietary contribution (56·3 % of energy intake), followed by fresh or minimally processed foods (29·2 %), processed foods (9·4 %) and culinary ingredients (5 %). A positive linear trend was found between the contribution tertiles of ultra-processed foods and the content of free sugars (β 0·25, P < 0·001), while an inverse relationship was observed for dietary fibre (β –0·26, P = 0·002), potassium (β –0·38, P < 0·001), Mg (β –0·31, P < 0·001), Cu (β –0·22, P < 0·003), vitamin A (β –0·37, P < 0·001) and vitamin C (β –0·22, P < 0·001). As the contribution of ultra-processed foods to total energy intake increased (from the first to the last tertile of consumption), the prevalence of inadequate intake of free sugars increased (from 32·9 % to 60·7 %, respectively), as well as the prevalence of inadequate fibre intake (from 26·1 % to 47·5 %). The influence of ultra-processed foods on the vegetarian diet in the UK is of considerable magnitude, and the consumption of this food was associated with poorer diet quality.

Limited information is available regarding medication use in COPD patients from Latin America. This study evaluated the type of medication used and the adherence to different inhaled treatments in stable COPD patients from the Latin American region. This was an observational, cross-sectional, multinational, and multicenter study in COPD patients attended by specialist doctors from seven Latin American countries. Adherence to inhaled therapy was assessed using the Test of Adherence to Inhalers (TAI) questionnaire. The type of medication was assessed as: short-acting β-agonist (SABA) or short-acting muscarinic antagonist (SAMA) only, long-acting muscarinic antagonist (LAMA), long-acting β-agonist (LABA), LABA/LAMA, inhaled corticosteroid (ICS), ICS/LABA, ICS/LAMA/LABA, or other. In total, 795 patients were included (59.6% male), with a mean age of 69.5±8.7 years and post-bronchodilator FEV of 50.0%±18.6%. The ICS/LAMA/LABA (32.9%) and ICS/LABA (27.7%) combinations were the most common medications used, followed by LABA/LAMA (11.3%), SABA or SAMA (7.9%), LABA (6.4%), LAMA (5.8%), and ICS (4.3%). The types of medication most commonly used in each Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013 category were ICS/LABA (A: 32.7%; B: 19.8%; C: 25.7%; D: 28.2%) and ICS/LAMA/LABA (A: 17.3%; B: 30.2%; C: 33%; D: 41.1%). The use of long-acting bronchodilators showed the highest adherence (good or high adherence >50%) according to the TAI questionnaire. COPD management in specialist practice in Latin America does not follow the current guideline recommendations and there is an overuse of ICSs in patients with COPD from this region. Treatment regimens including the use of long-acting bronchodilators are associated with the highest adherence.

Over 200,000 new cases of leprosy are detected each year, of which approximately 7% are associated with grade-2 disabilities (G2Ds). For achieving leprosy elimination, one of the main challenges will be targeting higher risk groups within endemic communities. Nevertheless, the socioeconomic risk markers of leprosy remain poorly understood. To address this gap we systematically reviewed MEDLINE/PubMed, Embase, LILACS and Web of Science for original articles investigating the social determinants of leprosy in countries with > 1000 cases/year in at least five years between 2006 and 2016. Cohort, case-control, cross-sectional, and ecological studies were eligible for inclusion; qualitative studies, case reports, and reviews were excluded. Out of 1,534 non-duplicate records, 96 full-text articles were reviewed, and 39 met inclusion criteria. 17 were included in random-effects meta-analyses for sex, occupation, food shortage, household contact, crowding, and lack of clean (i.e., treated) water. The majority of studies were conducted in Brazil, India, or Bangladesh while none were undertaken in low-income countries. Descriptive synthesis indicated that increased age, poor sanitary and socioeconomic conditions, lower level of education, and food-insecurity are risk markers for leprosy. Additionally, in pooled estimates, leprosy was associated with being male (RR = 1.33, 95% CI = 1.06-1.67), performing manual labor (RR = 2.15, 95% CI = 0.97-4.74), suffering from food shortage in the past (RR = 1.39, 95% CI = 1.05-1.85), being a household contact of a leprosy patient (RR = 3.40, 95% CI = 2.24-5.18), and living in a crowded household (≥5 per household) (RR = 1.38, 95% CI = 1.14-1.67). Lack of clean water did not appear to be a risk marker of leprosy (RR = 0.94, 95% CI = 0.65-1.35). Additionally, ecological studies provided evidence that lower inequality, better human development, increased healthcare coverage, and cash transfer programs are linked with lower leprosy risks. These findings point to a consistent relationship between leprosy and unfavorable economic circumstances and, thereby, underscore the pressing need of leprosy control policies to target socially vulnerable groups in high-burden countries.

Genetic subtypes of acute lymphoblastic leukaemia (ALL) are used to determine risk and treatment in children. 25% of precursor B-ALL cases are genetically unclassified and have intermediate prognosis. We aimed to use a genome-wide study to improve prognostic classification of ALL in children. We constructed a classifier based on gene expression in 190 children with newly diagnosed ALL (German Cooperative ALL [COALL] discovery cohort) by use of double-loop cross-validation and validated this in an independent cohort of 107 newly diagnosed patients (Dutch Childhood Oncology Group [DCOG] independent validation cohort). Hierarchical cluster analysis with classifying gene-probe sets revealed a new ALL subtype, the underlying genetic abnormalities of which were characterised by comparative genomic hybridisation-arrays and molecular cytogenetics. Our classifier predicted ALL subtype with a median accuracy of 90·0% (IQR 88·3–91·7) in the discovery cohort and correctly identified 94 of 107 patients (accuracy 87·9%) in the independent validation cohort. Without our classifier, 44 children in the COALL cohort and 33 children in the DCOG cohort would have been classified as B-other. However, hierarchical clustering showed that many of these genetically unclassified cases clustered with BCR–ABL1-positive cases: 30 (19%) of 154 children with precursor B-ALL in the COALL cohort and 14 (15%) of 92 children with precursor B-ALL in the DCOG cohort had this BCR–ABL1-like disease. In the COALL cohort, these patients had unfavourable outcome (5-year disease-free survival 59·5%, 95% CI 37·1–81·9) compared with patients with other precursor B-ALL (84·4%, 76·8–92·1%; p=0·012), a prognosis similar to that of patients with BCR–ABL1-positive ALL (51·9%, 23·1–80·6%). In the DCOG cohort, the prognosis of BCR–ABL1-like disease (57·1%, 31·2–83·1%) was worse than that of other precursor B-ALL (79·2%, 70·2–88·3%; p=0.026), and similar to that of BCR–ABL1-positive ALL (32·5%, 2·3–62·7%). 36 (82%) of the patients with BCR–ABL1-like disease had deletions in genes involved in B-cell development, including IKZF1, TCF3, EBF1, PAX5, and VPREB1; only nine (36%) of 25 patients with B-other ALL had deletions in these genes (p=0·0002). Compared with other precursor B-ALL cells, BCR–ABL1-like cells were 73 times more resistant to L-asparaginase (p=0·001) and 1·6 times more resistant to daunorubicin (p=0·017), but toxicity of prednisolone and vincristine did not differ. New treatment strategies are needed to improve outcome for this newly identified high-risk subtype of ALL. Dutch Cancer Society, Sophia Foundation for Medical Research, Paediatric Oncology Foundation Rotterdam, Centre of Medical Systems Biology of the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research, American National Institute of Health, American National Cancer Institute, and American Lebanese Syrian Associated Charities.