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Melanoides tuberculatus is an Afro-Asiatic thiarid, common in freshwater environments, now present in a wide portion of the tropical and subtropical regions of the New World. The present study had as its objective to register the occurrence of M. tuberculatus in the area of mangrove of the estuary of the Ceará River, verifying its density and the salinity which the specimens were submitted to verify its euryhalinity. Specimens of M. tuberculatus were collected in mangrove areas of the estuary of the Ceará River, located on the boundary of Caucaia and Fortaleza. Some specimens collected by hand in February 2006 were kept in an aquarium for a month. The abundance of M. tuberculatus in the studied areas varied from 0.76–10.22 individual/cm2. The salinity of the areas varied from 0–30 in the studied months. The presence of M. tuberculatus in these mangrove areas, whose salinity reached a peak of 30, and their survival in the laboratory, under a salinity of up to 35, prove the adaptation of this limnetic gastropod to euryhalinity. [ABSTRACT FROM PUBLISHER]

Gulosibacter molinativorax ON4T is the only known organism to produce molinate hydrolase (MolA), which catalyses the breakdown of the thiocarbamate herbicide into azepane-1-carboxylic acid (ACA) and ethanethiol. A combined genomic and transcriptomic strategy was used to fully characterize the strain ON4T genome, particularly the molA genetic environment, to identify the potential genes encoding ACA degradation enzymes. Genomic data revealed that molA is the only catabolic gene of a novel composite transposon (Tn6311), located in a novel low copy number plasmid (pARLON1) harbouring a putative T4SS of the class FATA. pARLON1 had an ANI value of 88.2% with contig 18 from Agrococcus casei LMG 22410T draft genome. Such results suggest that pARLON1 is related to genomic elements of other Actinobacteria, although Tn6311 was observed only in strain ON4T. Furthermore, genomic and transcriptomic data demonstrated that the genes involved in ACA degradation are chromosomal. Based on their overexpression when growing in the presence of molinate, the enzymes potentially involved in the heterocyclic ring breakdown were predicted. Among these, the activity of a protein related to caprolactone hydrolase was demonstrated using heterologous expression. However, further studies are needed to confirm the role of the other putative enzymes. [ABSTRACT FROM AUTHOR]

Behavioral journalism influences audiences by presenting peer modeling for cognitive processes that lead to behavior change. This technique was used in student newsletters promoting intergroup tolerance and moral engagement in a Houston high school with a diverse ethnic composition. Pretest (N = 393) and posttest (N = 363) cross-sectional comparisons of the student population in that school provided evidence of short-term (6 month) communication effects on attitudes and behavior. Tolerance and moral engagement increased among students in the school where behavioral journalism newsletters were distributed, and there was a corresponding reduction in hostile behavioral intentions and in reports of verbal aggression. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the nutritional composition and technological properties of meat from turkeys produced under organic conditions and compare them with those of turkeys produced under conventional conditions. Twenty carcasses of female B.U.T. Premium turkeys (Aviagen Turkeys) were obtained directly from the abattoir ten h after slaughter time of animals. Ten carcasses originated from female turkeys reared under conventional intensive husbandry conditions for meat-type turkeys (on average, 5611.8 ± 196.2 g of carcass weight) and the other ten carcasses corresponded to female turkeys raised under certified organic free-range conditions (PavosBio, Ávila, Spain) (on average, 5528.5 ± 354.4 g of carcass weight). Breast, thigh and wing meat samples were analyzed from each turkey: Chemical composition, fatty acid profile, free amino acids, mineral and vitamins content, color, and texture. Meat from female turkeys reared under organic conditions presented higher fat content in breast (1.90 vs. 1.01%, P = 0.032), thigh (3.79 vs. 2.68%, P = 0.022) and wing (12.0 vs. 8.91%, P = 0.012) than meat of female turkeys reared under intensive conventional conditions. The proportion of saturated fatty acids was higher in the meat of intensively reared female turkeys than in those reared under organic conditions (42.8 vs. 38.1%, P = 0.017 in breast; 38.8 vs. 33.6%, P = 0.0053 in thigh and 40.2 vs. 33.9%, P < 0.001 in wing). On the contrary, the proportion of monounsaturated fatty acids was higher in meat of organic turkeys (41.4 vs. 35.6%, P = 0.012 in breast; 42.3 vs. 35.6%, P < 0.001 in thigh and 46.9 vs. 39.3%, P = 0.011 in wing). Concentration of riboflavin and pyridoxine was higher by 21.1% (P = 0.010) and by 154% (P = 0.006), respectively, in meat from organically raised female turkeys than in that of female turkeys reared under intensive conditions. The organic turkey meat analyzed contained a higher proportion B2 and B6, lipids and monounsaturated fatty acids, and a lower content of omega-3 polyunsaturated fatty acids., Competing Interests: DISCLOSURES The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/purpose: Testicular torsion(TT) with unsalvageable testis has a significant psychosocial impact. Orchiectomy can be performed with optional testicular prosthesis(TP) placement, commonly deferred(dTP). Orchiectomy and simultaneous testicular prosthesis placement(sTP) may be a feasible and safe option and has been implemented in our department since 2018., Aim: The authors aim to perform a reflective analysis of the patient's experience and assess the feasibility, safety, and satisfaction of the sTP, by comparing it with the dTP., Methods: All patients with TT and unsalvageable testis submitted to orchiectomy were included in the study. An anonymous questionnaire assessed the patients' experience. Those submitted to orchiectomy and TP placement were divided in sTP and dTP groups and their clinical details, satisfaction and quality-of-life were analyzed and compared., Results: Scrotal exploration due to TT was performed in 185 patients, 54 were submitted to orchiectomy and 37 placed a TP(17 sTP, 20 dTP). All dTP patients and 66.7% of those without TP, would prefer having a prosthesis placed at the time of the orchiectomy. No significant differences in clinical details and outcomes were found, except prosthesis position (higher in dTP, p = 0.011) and operative time (13 min longer in sTP, p = 0.015). Both groups reported being satisfied with the prosthesis. Only one patient regretted placing a prosthesis(in dTP)., Conclusion: The sTP approach is as safe and effective as dTP. The patients preferred the sTP, as it avoids a second operation and possibly by having a lower psychological impact., Levels of Evidence: Level III., Competing Interests: Conflict of interest None., (Copyright © 2024 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Brucella spp. are small aerobes non-motile Gram-negative coccobacilli that act as facultative intracellular pathogens responsible for zoonotic infections. B. melitensis can survive and replicate within host macrophages, the molecular phenomena of this host: pathogen interaction remain totally unknown. The aim of this work was to evaluate the differences in the response between human macrophages infected with different B. melitensis strains. Comparison of transcriptome data was carried out for identifying differentially expressed genes among different strain infection. We evaluated the THP-1 macrophage molecular response at early stages of infection to different strains of Brucella melitensis (B. melitensis wild- type 133 (BM133), B. melitensis ATCC 23456 (BM16M) and a B. melitensis 133 omp31 mutant (LVM31)). Our analysis revealed intriguing differences in the host cell response to two virulent strains (BM16M and BM133), infection with BM16M led to an over-expression of anti-inflammatory pathways, such as cAMP signaling and PI3K-Akt pathway, and down regulation of inflammatory pathways involving IL1A and IL10 compared to BM133. Mutant strain BMLVM31 induced an activation of the apoptotic process and the absence of Omp31, impaired the inhibition of CASP1 and CASP9 expression. Additionally, the mutation of BMLV31 impairs the evasion of cathepsin D in early stages of the infection. These findings shed light on the intricate molecular interactions between B. melitensis strains and human macrophages, providing valuable insights for understanding the pathogenesis of brucellosis.

We report the genome sequence of Lentilitoribacter sp. strain EG35 isolated from the octocoral Eunicella gazella sampled off the coast of Portugal. We reveal the coding potential for the biosynthesis of polyhydroxyalkanoates - biodegradable polyesters that may serve bioplastics production, diverse homoserine lactone-like communication signals, and four putatively novel natural products., Competing Interests: The authors declare no conflict of interest.

Locally produced fish hydrolysate and oil from the agrifood sector comprises a sustainable solution both to the problem of fish waste disposal and to the petfood sector with potential benefits for the animal's health. This study evaluated the effects of the dietary replacement of mainly imported shrimp hydrolysate (5%) and salmon oil (3%; control diet) with locally produced fish hydrolysate (5%) and oil (3.2%) obtained from fish waste (experimental diet) on systemic inflammation markers, adipokines levels, cardiac function and fecal microbiota of adult dogs. Samples and measurements were taken from a feeding trial conducted according to a crossover design with two diets (control and experimental diets), six adult Beagle dogs per diet and two periods of 6 weeks each. The experimental diet, with higher docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids contents, decreased plasmatic triglycerides and the activity of angiotensin converting enzyme, also tending to decrease total cholesterol. No effects of diet were observed on serum levels of the pro-inflammatory cytokines interleukin (IL)-1β, IL-8, and IL-12/IL-23 p40, and of the serum levels of the anti-inflammatory adipokine adiponectin. Blood pressure, heart rate and echocardiographic measurements were similar between diets with the only exception of left atrial to aorta diameter ratio that was higher in dogs fed the experimental diet, but without clinical relevance. Diet did not significantly affect fecal immunoglobulin A concentration. Regarding fecal microbiome, Megasphaera was the most abundant genus, followed by Bifidobacterium , Fusobacterium , and Prevotella , being the relative abundances of Fusobacterium and Ileibacterium genera positively affected by the experimental diet. Overall, results from the performed short term trial suggest that shrimp hydrolysate and salmon oil can be replaced by protein hydrolysate and oil from fish by-products without affecting systemic inflammatory markers, cardiac structure and function, but potentially benefiting bacterial genera associated with healthy microbiome. Considering the high DHA and EPA contents and the antioxidant properties of fish oil and hydrolysate, it would be worthwhile in the future to assess their long-term effects on inflammatory markers and their role in spontaneous canine cardiac diseases and to perform metabolomic and metagenomics analysis to elucidate the relevance of microbiota changes in the gut., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cabrita, Barroso, Fontes-Sousa, Correia, Teixeira, Maia, Vilanova, Yergaliyev, Camarinha-Silva and Fonseca.)

One hundred and sixty-three extreme halophiles were recovered from a single sample collected from an inland solar saltern in Rio Maior. Based on random amplified polymorphic DNA (RAPD) profiles and partial 16S rRNA gene sequencing 125 isolates were identified as members of the Archaea domain within the genus Halorubrum. Two strains, RMP-11 T and RMP-47, showed 99.1 % sequence similarity with the species Halorubrum californiense based on phylogenetic analysis of the 16S rRNA gene sequence. However, phylogenetic analysis based on five housekeeping genes, atpB, EF-2, glnA, ppsA and rpoB', showed Halorubrum coriense as the closest related species with 96.7 % similarity. The average nucleotide identity (ANI) of strains RMP-11 T , RMP-47 and species Hrr. coriense were within the range of 90.0-90.5 %, supporting that strains RMP-11 T and RMP-47 represent a novel species of the genus Halorubrum. These strains formed red-pigmented colonies that were able to grow in a temperature range of 25-50 °C. Polyhydroxyalkanoate (PHA) granules were detected in both strains. The polar lipid profile was identical to the neutrophilic species of the genus Halorubrum. The Rio Maior sample from which both strains were isolated was metagenome sequenced. We identified five metagenome-assembled genomes representing novel Halorubrum species but distinct from the species represented by strains RMP-11 T and RMP-47. Based on phylogenetic, phylogenomic, comparative genomics, physiological and chemotaxonomic parameters, we describe a new species of the genus Halorubrum represented by strains RMP-11 T (=CECT 30760 T  = DSM 115521 T ) and RMP-47 (=CECT 30761 = DSM 115541) for which we propose the name Halorubrum miltondacostae sp. nov., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: The presence of potato cyst nematodes (PCN) causes a significant risk to potato crops globally, leading to reduced yields and economic losses. While the plant Solanum sisymbriifolium is known for its resistance to PCN and can be used as a trap crop, the molecular mechanisms behind this resistance remain poorly understood. In this study, genes differentially expressed were identified in control and infected plants during the early stages of the S. sisymbriifolium - G. pallida interaction., Results: Gene expression profiles were characterized for two S. sisymbriifolium cultivars, Melody and Sis6001, uninfected and infected by G. pallida. The comparative transcriptome analysis revealed a total of 4,087 and 2,043 differentially expressed genes (DEGs) in response to nematode infection in the cultivars Melody and Sis6001, respectively. Gene ontology (GO) enrichment analysis provided insights into the response of the plant to nematode infection, indicating an activation of the plant metabolism, oxidative stress leading to defence mechanism activation, and modification of the plant cell wall. Genes associated with the jasmonic and salicylic acid pathways were also found to be differentially expressed, suggesting their involvement in the plant's defence response. In addition, the analysis of NBS-LRR domain-containing transcripts that play an important role in hypersensitive response and programmed cell death led to the identification of ten transcripts that had no annotations from the databases, with emphasis on TRINITY&#95;DN52667&#95;C1&#95;G1, found to be upregulated in both cultivars., Conclusions: These findings represent an important step towards understanding the molecular basis underlying plant resistance to nematodes and facilitating the development of more effective control strategies against PCN., (© 2024. The Author(s).)

Purpose: To assess the clinical outcome of patients with recurrent glioblastoma treated with salvage reirradiation., Methods: Between 2005 and 2022, data from adult patients with glioblastoma treated with surgery and radio-chemotherapy Stupp regimen who developed a local in-field relapse and received stereotactic radiotherapy (SRT) were retrospectively reviewed., Results: The study population included 44 patients with recurrent glioblastoma (median of 9.5 months after the first radiotherapy). Reirradiation alone was given to 47.7% of patients. The median maximum diameter of the recurrence was 13.5 mm. The most common SRT regimen (52.3%) was 35 Gy in 10 fractions. Acute toxicity was mild, with transient worsening of previous neurological symptoms in only 15% of patients. After a median follow-up of 15 months, 40% presented radiological response, but a remarkable number of early distant progressions were recorded (32.5%). The median time to progression was 4.8 months, being the dose, the scheme, the size of the recurrence or the strategy (exclusive RT vs. combined) unrelated factors. The median overall survival (OS) was 14.9 months. Karnofsky index < 70 and the size of the recurrence (maximum diameter < 25 mm) were significant factors associated with OS. Radiological changes after reirradiation were commonly seen (> 50% of patients) hindering the response assessment., Conclusions: Reirradiation is a feasible and safe therapeutic option to treat localized glioblastoma recurrences, able to control the disease for a few months in selected patients, especially those with good functional status and small lesions. Hypofractionated schemes provided a suitable toxicity profile. Radiological changes were common., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Ichthyoplankton monitoring is crucial for stock assessments, offering insights into spawning grounds, stock size, seasons, recruitment, and changes in regional ichthyofauna. This study evaluates the efficiency of multi-marker DNA metabarcoding using mitochondrial cytochrome c oxidase subunit I (COI), 12S rRNA and 16S rRNA gene markers, in comparison to morphology-based methods for fish species identification in ichthyoplankton samples. Two transects with four coastal distance categories were sampled along the southern coast of Portugal, being each sample divided for molecular and morphological analyses. A total of 76 fish species were identified by both approaches, with DNA metabarcoding overperforming morphology-75 versus 11 species-level identifications. Linking species-level DNA identifications with higher taxonomic morphological identifications resolved several uncertainties associated with traditional methods. Multi-marker DNA metabarcoding improved fish species detection by 20-36% compared to using a single marker/amplicon, and identified 38 species in common, reinforcing the validity of our results. PERMANOVA analysis revealed significant differences in species communities based on the primer set employed, transect location, and distance from the coast. Our findings underscore the potential of DNA metabarcoding to assess ichthyoplankton diversity and suggest that its integration into routine surveys could enhance the accuracy and comprehensiveness of fish stock assessments., (© 2024. The Author(s).)

The global promotion of decarbonisation through the circular solutions and (re)use of bio-based resources (BBR), i.e. waste streams, notably from the agricultural, forest and municipal sectors has steadily increased in recent decades. Among the transformative solutions offered by BBR, biosolids (BS), biochars (BC), and bioashes (BA) specifically attract scientific attention due to their highly complex organo-mineral matrices, which present significant potential for recovery in the agro-/forest-ecosystems. These materials enhance various soil (i) chemical (pH, macro/micro nutrient concentrations, organic matter content), (ii) physical (porosity, water-air relations, compaction) or (iii) microbial (diversity, activity) properties. Furthermore, some of transformed BBR contribute to a multitude of environmental services such as the remediation of contaminated sites and wastewater treatment, employing cost-effective and eco-friendly approaches that align with circular economy/waste management principles, ultimately contributing to climate change mitigation. However, several challenges impede the widespread utilization/transformation of BBR, including technological limitations in processing and application, concerns about contamination ( e.g. , PAHs, PCBs, micro/nano plastics present in BS), toxicity issues ( e.g. , heavy metals in BA or nanoparticles in BC), and regulatory constraints ( e.g. , non-uniform regulations governing the reuse of BA and BS). Addressing these challenges demands an interdisciplinary and intersectoral approach to fully unlock the potential of BBR in sustainable decarbonisation efforts., Competing Interests: The authors declare no competing interest., (This journal is © The Royal Society of Chemistry.)

The Social Survey of Andalusia is an instrument for monitoring the Andalusian reality developed by the regional government of Andalusia, whose dataset is open access to the citizens. The 2022 edition included questions related to happiness, social relations as well as socio-demographic factors. Based on this dataset, the present study aimed to analyse the relationship between socio-demographic factors and people's experiences of happiness. It also set out to explore which factors might be indispensable for experiencing moments of happiness as measured in the survey. A sample of 4,968 cases was gotten, conducting a descriptive analysis, a logit regression in complex samples, and a Necessary Conditions Analysis. The results found two very different social profiles in terms of the experience of happiness, determined by age, sex, educational level and economic status. However, neither factor proved to be a necessary condition for happiness. Both conclusions should be taken into consideration in any socio-community intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Matas-Terrón, Sánchez Barroso and Matas-Terrón.)

The hard-shelled seed industry plays an important role in the global agricultural economy. In fact, only considering hazelnut and walnut, the global nut supply is over 5.6 tons. As a result considerable amounts are produced year by year, burnt or discarded as waste, bypassing a potential source of valuable compounds or features. This review deals with the recent scientific literature on their chemical composition as well as functional applications as an approach to sustain the utilization of the main byproduct derived from industry. Indeed, nutshells have received great interest due to their lignin, antioxidant, physical and mechanical features. It was found that these properties vary among cultivars and localities of plantation, influencing physical and structural features. The inconsistencies regarding the above-mentioned properties of nutshells lead to exploring the status of hazelnut and walnut shell applications in sustainable bio-economy chains. In fact, in terms of potential applications, the state of the art links their use to the construction industry and the manufacture of materials, such as resin or plastic composites, particleboards or construction panels, or vital infrastructure and as a filler in cement pavements. However, their current use continues bypassing their great antioxidant potential and their interesting chemical and mechanical features.

The global population over 60 years old is projected to reach 1.5 billion by 2050. Understanding age-related disorders and gender-specificities is crucial for a healthy aging. Reliable age-related biomarkers are needed, preferentially obtained through non-invasive methods. Urine-derived stem cells (UDSCs) can be easily obtained, although a detailed bioenergetic characterization, according to the donor aging, remain unexplored. UDSCs were isolated from young and elderly adult women (22-35 and 70-94 years old, respectively). Surprisingly, UDSCs from elderly subjects exhibited significantly higher maximal oxygen consumption and bioenergetic health index than those from younger individuals, evaluated through oxygen consumption rate. Exploratory data analysis methods were applied to engineer a minimal subset of features for the classification and stratification of UDSCs. Additionally, RNAseq of UDSCs was performed to identify age-related transcriptional changes. Transcriptional analysis revealed downregulation of genes related to glucuronidation and estrogen metabolism, and upregulation of inflammation-related genes in UDSCs from elderly individuals. This study demonstrates unexpected differences in the UDSCs' OCR between young and elderly individuals, revealing improved bioenergetics in concurrent with an aged-like transcriptome signature. UDSCs offer a non-invasive model for studying age-related changes, holding promise for aging research and therapeutic studies., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Spatial skills are key predictors of achievement in science, technology, engineering, and mathematics disciplines, despite being acquired through everyday life and not formally taught in schools. Spatial skills include a diverse group of abilities broadly related to reasoning about properties of space such as distance and direction. Recently, more research has investigated the link between spatial skills and spatial anxiety, defined as a fear or apprehension felt when engaged in spatial thinking. There has yet to be a meta-analytic review summarizing these findings. Thus, the goal of this preregistered meta-analytic review is to provide an estimate of the size of the relation between spatial anxiety and spatial skills while considering several moderators (grade/age group, sex, spatial skills measure/subtype, spatial anxiety measure/subtype, geographical region of sample, publication type/year, and risk of bias). Analyzing 283 effect sizes accumulated from research conducted between 1994 and 2020, we found a small, negative, and statistically significant ( r = -.14) correlation between spatial anxiety and spatial skills. Results showed that effect sizes including mental manipulation anxiety, scalar comparison anxiety, and navigation skill were often significantly stronger than effect sizes including measures of other subtypes. The magnitude of the relation was not significantly different in children and adults, though effect sizes tended to be weaker for younger samples ( r = -.08). Our results are consistent with previous findings of a significant relation between spatial anxiety and skills, and this work bridges a gap in the existing research, lending support to future research efforts investigating spatial cognition. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: When health-related research funding agencies choose to fund research, they balance a number of competing issues: costs, stakeholder views and potential benefits. The REWARD Alliance, and the related Lancet-REWARD Campaign, question whether those decisions are yielding all the value they could. Methods: A group of health-related research funding agencies, organisations that represent health-related research funding agencies and those that inform and set health-related-research funding policy from around the world have come together since 2016 to share, learn, collaborate and influence emerging practice. This group meets under the name of the Ensuring Value in Research Funders' Forum (EViR Funders' Forum). The EViR Funders' Forum worked together to develop a set of ten Guiding Principles, that if funders adhered to would reduce research waste and ensure value in research. Results: The EViR Funders' Forum has previously agreed and published a Consensus Statement. The Forum has agreed on a set of ten Guiding Principles to help health-research funders to maximise the value of research by ensuring that: research priorities are justifiable; the design, conduct and analysis of research minimise bias; regulation and management are proportionate to risks; methods and findings are accessible in full; and findings are appropriately and effectively disseminated and used. Conclusions: When setting research funding policy, we must balance multiple stakeholders' needs and expectations. When funders do this well, they maximise the probability of benefits to society from the research they support - when funders do this badly, they passively allow or actively contribute to research waste. These challenges must be resolved by funders either working together or in conjunction with other actors in the research ecosystem., Competing Interests: Competing interests: Kelly Dunham is employed by the Patient-Centered Outcomes Research Institute (PCORI) and Evelyn Whitlock was previously employed by PCORI. The views presented in this article are solely the responsibility of the authors and do not necessarily represent the views of PCORI, its Board of Governors, or its Methodology Committee., (Copyright: © 2023 Westmore M et al.)

Background: This study sought to examine the relationship between rural residence and physical activity levels among US myocardial infarction (MI) survivors., Methods: We conducted a cross-sectional study using nationally representative Behavioral Risk Factor Surveillance System surveys from 2017 and 2019. We determined the survey-weighted percentage of rural and urban MI survivors meeting US physical activity guidelines. Logistic regression models were used to examine the relationship between rural/urban residence and meeting physical activity guidelines, accounting for sociodemographic factors., Results: Our study included 22,732 MI survivors (37.3% rural residents). The percentage of rural MI survivors meeting physical activity guidelines (37.4%, 95% CI: 35.1%-39.7%) was significantly less than their urban counterparts (45.6%, 95% CI: 44.0%-47.2%). Rural residence was associated with a 28.8% (95% CI: 20.0%-36.7%) lower odds of meeting physical activity guidelines, with this changing to a 19.3% (95% CI: 9.3%-28.3%) lower odds after adjustment for sociodemographic factors., Conclusions: A significant rural/urban disparity in physical activity levels exists among US MI survivors. Our findings support the need for further efforts to improve physical activity levels among rural MI survivors as part of successful secondary prevention in US high-MI burden rural areas., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Understanding factors that promote resilience in pediatric ADHD is important though highly understudied., Aims: The current study sought to provide a preliminary 'shortlist' of key individual, family, and social-community assets among children with ADHD., Methods and Procedures: The study included well-characterized, clinically-evaluated samples of children with (n=108) and without ADHD (n=98) ages 8-13 years (M=10.31; 41.3% girls; 66.5% White/Non-Hispanic). All subsets regression and dominance analysis identified the subset of predictors that accounted for the most variance in broad-based resilience for children with ADHD and their relative importance. Findings were compared for children with versus without ADHD as preliminary evidence regarding the extent to which identified assets are promotive, protective, or conditionally helpful., Outcomes and Results: Higher levels of peer acceptance, social skills, and academic performance were top predictors of resilience among children with ADHD. Better child working memory, attention, higher levels of hyperactivity, older age, and fewer parent self-reported mental health concerns were also identified as predictors of resilience in ADHD. Both overlapping and unique factors were associated with resilience for children with versus without ADHD. Conclusions and Results: These results, if replicated, provide a strong preliminary basis for strength-based basic/applied research on key assets that promote resilience in ADHD., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The cohesin complex plays essential roles in chromosome segregation, 3D genome organisation, and DNA damage repair through its ability to modify DNA topology. In higher eukaryotes, meiotic chromosome function, and therefore fertility, requires cohesin complexes containing meiosis-specific kleisin subunits: REC8 and RAD21L in mammals and REC-8 and COH-3/4 in Caenorhabditis elegans . How these complexes perform the multiple functions of cohesin during meiosis and whether this involves different modes of DNA binding or dynamic association with chromosomes is poorly understood. Combining time-resolved methods of protein removal with live imaging and exploiting the temporospatial organisation of the C. elegans germline, we show that REC-8 complexes provide sister chromatid cohesion (SCC) and DNA repair, while COH-3/4 complexes control higher-order chromosome structure. High-abundance COH-3/4 complexes associate dynamically with individual chromatids in a manner dependent on cohesin loading (SCC-2) and removal (WAPL-1) factors. In contrast, low-abundance REC-8 complexes associate stably with chromosomes, tethering sister chromatids from S-phase until the meiotic divisions. Our results reveal that kleisin identity determines the function of meiotic cohesin by controlling the mode and regulation of cohesin-DNA association, and are consistent with a model in which SCC and DNA looping are performed by variant cohesin complexes that coexist on chromosomes., Competing Interests: MC, GS, CB, JP, PL, JD, AJ, OC, NS, JP, EM No competing interests declared, (© 2023, Castellano-Pozo et al.)

Summary: We present an adolescent with X-linked hypophosphatemic rickets (XLH) with bone age advancement and its response to aromatase inhibitors (AIs). A male with XLH, confirmed with a deletion on the PHEX gene, received regular treatment since the first year of life with average growth velocity and height. He had bone age compatible with chronological age until 13 when he had a bone age advancement and a decrease in the predicted final height thought to be due to initiation of oral isotretinoin, which has been previously reported. Then, anastrozole was initiated and maintained concomitant to the rickets treatment for 2 years with bone age stabilization. He had no adverse effects or worsening of bone health markers. As a result, he maintained his height gain and improved his final height Z score compared with the predicted final height at initiating anastrozole. In conclusion, although AIs was a reasonable strategy to stabilize bone age and minimize height impairment, careful monitoring is mandatory to understand its benefits and effects on XLH patients., Learning Points: Although X-linked hypophosphatemic rickets patients have normal puberty, they can be affected by metabolic and environmental factors that may advance their bone age and impair the predicted final height, similar to the general population. Isotretinoin may accelerate skeletal maturation during puberty in an adolescent with X-linked hypophosphatemic rickets. Aromatase inhibitors showed to be a reasonable strategy to stabilize bone age and minimize height impairment in an adolescent with X-linked hypophosphatemic rickets.

Describing diet-related effects on the gut microbiome is essential for understanding its interactions with fat and/or sugar-rich diets to promote obesity-related metabolic diseases. Here, we sequenced the V3-V4 hypervariable region of the bacterial 16S rRNA gene to study the composition and dynamics of the gut microbiome of adult mice fed diets rich in fat and/or sugar, at 9 and 18 weeks of diet. Under high-fat, high-sugar diet, the abundances of Tuzzerella and Anaerovorax were transiently increased at 9 weeks, while Lactobacillus remained elevated at 9 and 18 weeks. The same diet decreased the abundances of Akkermansia , Paludicola , Eisenbergiella , and Butyricicoccus at 9 and 18 weeks, while Intestinimonas and UCG-009 of the Butyricicoccaceae family responded only at 18 weeks. The high-fat diet decreased the abundances of UBA1819 at 9 weeks, and Gastranaerophilales , Clostridia UCG-014, and ASF356 at 9 and 18 weeks. Those of Marvinbryantia , Harryflintia , Alistipes , Blautia , Lachnospiraceae A2, Eubacterium coprostanoligenes group, and Eubacterium brachy group were lowered only at 18 weeks. Interestingly, these genera were not sensitive to the high-sugar diet. The mouse gut microbiome was differentially affected by diets rich in fat or fat and sugar. The differences observed at 9 and 18 weeks indicate a progressive microbiome response.

Baricitinib and imatinib are considered therapies for coronavirus disease 2019 (COVID-19), but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID-19 patients. Phase-2, open-label, randomized trial with a pick-the-winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID-19 pneumonia and a symptom duration ≤10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard-care, baricitinib (4 mg qd, 7 days) plus standard-care, or standard-care alone. Primary outcome was time to clinical improvement (discharge alive or a reduction of 2 points in an ordinal scale of clinical status) compared on a day-by-day basis to identify differences ≥15% between the most and least favorable groups. Secondary outcomes included oxygenation and ventilatory support requirements, additional therapies administered, all-cause mortality, and safety. One hundred and sixty-five patients analyzed. Predefined criteria for selection of the most advantageous arm were met for baricitinib, but not for imatinib. However, no statistically significant differences were observed in formal analysis, but a trend toward better results in patients receiving baricitinib was found compared to standard care alone (hazard ratio [HR] for clinical improvement: 1.41, 95% confidence intervals [CI]: 0.96-2.06; HR for discontinuing oxygen: 1.46, 95% CI: 0.94-2.28). No differences were found regarding additional therapies administered or safety. Baricitinib plus standard care showed better results for hospitalized COVID-19 patients, being the most advantageous therapeutic strategy among those proposed in this exploratory clinical trial., (© 2023 Wiley Periodicals LLC.)

The new digital panorama has enhanced the importance of the Internet, as well as Information and Communications Technology (ICT), in developing a society in which seniors play a proactive role. The main purpose of this article is to define a taxonomy of silver surfers according to the ways they use the Internet and ICT, with a special focus on e-commerce and e-government. A quantitative methodology was used, based on the study of 405 Spanish internet users between 60 and 79 years of age, which was conducted by telephone in February of 2019. Seven groups were identified through a combination of dimensionality reduction techniques and cluster analysis. The results indicate neither a consistent pattern in the specific ways older adults use the Internet nor a homogeneous level of digital knowledge among this demographic group. To some extent, this is a result of disparities in both the perception of digital security that seniors associate with e-commerce and/or e-government and the level of trust engendered by such operations. The Able and Daring are the most numerous clusters, which coincide with the categories of the most active and prepared users. The Sceptical take third place in terms of number of users, as they display limited use of the Internet and claim to have a low digital skills level. However, carrying out both online shopping and administrative procedures without the need for assistance is becoming increasingly frequent among all of those surveyed., Competing Interests: Competing interestsThe authors declare that this research has been conducted without any conflict of interest that could commercially or financially compromise the results of the study., (© The Author(s) 2023.)

To determine the effects of pre-harvest calcium (Ca), magnesium (Mg) and potassium (K) spraying on the antioxidant activity and capacity of hazelnut ( Corylus avellana L.) shells, as an approach to sustain the utilization of the main residue derived from this industry, four commercial hazelnut (Tonda di Giffoni) orchards located in Southern Chile (Cunco, Gorbea, Perquenco and Radal), during the 2018/19 season were sprayed three times with five combinations of Ca (300 and 600 mg L -1 ), Mg (300 and 600 mg L -1 ) and K (300 and 600 mg L -1 ). Yield components were determined in harvested whole nuts, whereas Ca, Mg and K concentrations, as well as total phenolic compounds, free radical scavenging antioxidant activity, and oxygen radical absorbance capacity, were determined in shells. All spray treatments with both Ca, Mg and K combinations showed a significant interaction between locality and treatment (L × T) on increased stabilized nut yield (kg ha -1 ) in comparison with the control treatments, whereas nut quality was differentially affected by treatment and orchard locality, thus confirming a significant L × T relationship regarding nut length and kernel yield. However, locality showed a major effect on kernels and shells. A significant relationship was determined between locality and the Ca, Mg and K spraying (L × T) concerning antioxidant compounds such as phenolics, whose amounts exceeded those of the control treatments by three times. Antioxidant capacity and activity in shells showed a significant L × T relationship, and nutshells collected from Cunco showed remarkably (3-4 times) higher levels of these factors than the other evaluated localities. Interactions between spray treatment and orchard location were responsible for the different values obtained in the experiments, confirming the influence of the environment on the efficacy of the treatments. Finally, these shells are worth further study as an interesting residue of the hazelnut industry due to their nutritional and antioxidant properties.

Tuberculosis (TB) is a transmissible disease listed as one of the 10 leading causes of death worldwide (10 million infected in 2019). A swift and precise diagnosis is essential to forestall its transmission, for which the discovery of effective diagnostic biomarkers is crucial. In this study, we aimed to discover molecular biomarkers for the early diagnosis of tuberculosis. Two independent cohorts comprising 29 and 34 subjects were assayed by proteomics, and 49 were included for metabolomic analysis. All subjects were arranged into three experimental groups—healthy controls (controls), latent TB infection (LTBI), and TB patients. LC-MS/MS blood serum protein and metabolite levels were submitted to univariate, multivariate, and ROC analysis. From the 149 proteins quantified in the discovery set, 25 were found to be differentially abundant between controls and TB patients. The AUC, specificity, and sensitivity, determined by ROC statistical analysis of the model composed of four of these proteins considering both proteomic sets, were 0.96, 93%, and 91%, respectively. The five metabolites (9-methyluric acid, indole-3-lactic acid, trans-3-indoleacrylic acid, hexanoylglycine, and N-acetyl-L-leucine) that better discriminate the control and TB patient groups (VIP > 1.75) from a total of 92 metabolites quantified in both ionization modes were submitted to ROC analysis. An AUC = 1 was determined, with all samples being correctly assigned to the respective experimental group. An integrated ROC analysis enrolling one protein and four metabolites was also performed for the common control and TB patients in the proteomic and metabolomic groups. This combined signature correctly assigned the 12 controls and 12 patients used only for prediction (AUC = 1, specificity = 100%, and sensitivity = 100%). This multiomics approach revealed a biomarker signature for tuberculosis diagnosis that could be potentially used for developing a point-of-care diagnosis clinical test.

DNA double-strand breaks (DSBs) are deleterious lesions, which must be repaired precisely to maintain genomic stability. During meiosis, programmed DSBs are repaired via homologous recombination (HR) while repair using the nonhomologous end joining (NHEJ) pathway is inhibited, thereby ensuring crossover formation and accurate chromosome segregation. 1 How DSB repair pathway choice is implemented during meiosis is unknown. In C. elegans, meiotic DSB repair takes place in the context of the fully formed, highly dynamic zipper-like structure present between homologous chromosomes called the synaptonemal complex (SC). , The SC consists of a pair of lateral elements bridged by a central region composed of the SYP proteins in C. elegans. How the structural components of the SC are regulated to maintain the architectural integrity of the assembled SC around DSB repair sites remained unclear. Here, we show that SYP-4, a central region component of the SC, is phosphorylated at Serine 447 in a manner dependent on DSBs and the ATM/ATR DNA damage response kinases. We show that this SYP-4 phosphorylation is critical for preserving the SC structure following exogenous (γ-IR-induced) DSB formation and for promoting normal DSB repair progression and crossover patterning following SPO-11-dependent and exogenous DSBs. We propose a model in which ATM/ATR-dependent phosphorylation of SYP-4 at the S447 site plays important roles both in maintaining the architectural integrity of the SC following DSB formation and in warding off repair via the NHEJ repair pathway, thereby preventing aneuploidy.2 How DSB repair pathway choice is implemented during meiosis is unknown. In C. elegans, meiotic DSB repair takes place in the context of the fully formed, highly dynamic zipper-like structure present between homologous chromosomes called the synaptonemal complex (SC). 3 , 4 , 5 , 6 , 7 , 8 , 9 The SC consists of a pair of lateral elements bridged by a central region composed of the SYP proteins in C. elegans. How the structural components of the SC are regulated to maintain the architectural integrity of the assembled SC around DSB repair sites remained unclear. Here, we show that SYP-4, a central region component of the SC, is phosphorylated at Serine 447 in a manner dependent on DSBs and the ATM/ATR DNA damage response kinases. We show that this SYP-4 phosphorylation is critical for preserving the SC structure following exogenous (γ-IR-induced) DSB formation and for promoting normal DSB repair progression and crossover patterning following SPO-11-dependent and exogenous DSBs. We propose a model in which ATM/ATR-dependent phosphorylation of SYP-4 at the S447 site plays important roles both in maintaining the architectural integrity of the SC following DSB formation and in warding off repair via the NHEJ repair pathway, thereby preventing aneuploidy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Accurate chromosome segregation requires a cohesin-mediated physical attachment between chromosomes that are to be segregated apart, and a bipolar spindle with microtubule plus ends emanating from exactly two poles toward the paired chromosomes. We asked whether the striking bipolar structure of C. elegans meiotic chromosomes is required for bipolarity of acentriolar female meiotic spindles by time-lapse imaging of mutants that lack cohesion between chromosomes. Both a spo-11 rec-8 coh-4 coh-3 quadruple mutant and a spo-11 rec-8 double mutant entered M phase with separated sister chromatids lacking any cohesion. However, the quadruple mutant formed an apolar spindle whereas the double mutant formed a bipolar spindle that segregated chromatids into two roughly equal masses. Residual non-cohesive COH-3/4-dependent cohesin on separated sister chromatids of the double mutant was sufficient to recruit haspin-dependent Aurora B kinase, which mediated bipolar spindle assembly in the apparent absence of chromosomal bipolarity. We hypothesized that cohesin-dependent Aurora B might activate or inhibit spindle assembly factors in a manner that would affect their localization on chromosomes and found that the chromosomal localization patterns of KLP-7 and CLS-2 correlated with Aurora B loading on chromosomes. These results demonstrate that cohesin is essential for spindle assembly and chromosome segregation independent of its role in sister chromatid cohesion., Competing Interests: The authors have declared that no competing interests exist.

Gulosibacter molinativorax ON4 T is the only known organism to produce molinate hydrolase (MolA), which catalyses the breakdown of the thiocarbamate herbicide into azepane-1-carboxylic acid (ACA) and ethanethiol. A combined genomic and transcriptomic strategy was used to fully characterize the strain ON4 T genome, particularly the molA genetic environment, to identify the potential genes encoding ACA degradation enzymes. Genomic data revealed that molA is the only catabolic gene of a novel composite transposon (Tn6311), located in a novel low copy number plasmid (pARLON1) harbouring a putative T4SS of the class FATA. pARLON1 had an ANI value of 88.2% with contig 18 from Agrococcus casei LMG 22410 T draft genome. Such results suggest that pARLON1 is related to genomic elements of other Actinobacteria, although Tn6311 was observed only in strain ON4 T . Furthermore, genomic and transcriptomic data demonstrated that the genes involved in ACA degradation are chromosomal. Based on their overexpression when growing in the presence of molinate, the enzymes potentially involved in the heterocyclic ring breakdown were predicted. Among these, the activity of a protein related to caprolactone hydrolase was demonstrated using heterologous expression. However, further studies are needed to confirm the role of the other putative enzymes., (© 2022. The Author(s).)

Background: Tuberculosis (TB) is a disease with worldwide presence and a major cause of death in several developing countries. Current diagnostic methodologies often lack specificity and sensitivity, whereas a long time is needed to obtain a conclusive result., Methods: In an effort to develop better diagnostic methods, this study aimed at the discovery of a biomarker signature for TB diagnosis using a Nuclear Magnetic Resonance based metabolomics approach. In this study, we acquired 1 H NMR spectra of blood serum samples of groups of healthy subjects, individuals with latent TB and of patients with pulmonary and extra-pulmonary TB. The resulting data were treated with uni- and multivariate statistical analysis., Results: Six metabolites (inosine, hypoxanthine, mannose, asparagine, aspartate and glutamate) were validated by an independent cohort, all of them related with metabolic processes described as associated with TB infection., Conclusion: The findings of the study are according with the WHO Target Product Profile recommendations for a triage test to rule-out active TB., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Farmed salmonids show alterations in bone structure that result in skeletal deformities during formation, repair, and regeneration processes, with loss of mineralization at the level of the axial skeleton, mainly the head and spine, affecting their quality of life and even causing death. Despite improving factors, such as farming conditions, diets, and genetics, bone alterations appear more frequently in farmed fish than in wild fish. Thus, we used SEM-EDX, and TGA-DSC to study bone mineralization in farmed and wild rainbow trouts. As expected, we found significant differences in the nutritional parameters of farmed and wild fish (p < 0.05). Microstructural analyses indicated that farmed fish have a more robust mineral structure (p < 0.05), confirming the differences in mineralization and microstructure between both groups. However, the mechanisms regulating absorption and distribution in the organism and their effect on bone mineralization remain to be known. In our study, the combined use of techniques such as SEM-EDX and TGA-DSC allows a clearer assessment and detailed characterization beneficial to understanding the relationship between diet control and bone microstructure.

Erythroferrone is a recently identified erythroid regulator produced by erythroblasts in the mammalian bone marrow and extramedullary sites, known to be induced in conditions of anemia or blood loss. Iron metabolism is affected by erythroferrone through its capacity to inhibit hepcidin production, leading to the increase of iron availability required for erythropoiesis. However, little is known about erythroferrone function in other vertebrates, in particular teleost fish, that unlike mammals, present two different functional types of hepcidin, one type mostly involved in iron metabolism and the other in antimicrobial response. The study of erythroferrone evolution and its biological role in teleost fish can give us valuably new insights into its function. To address these questions, we characterized erythroferrone in the European sea bass ( Dicentrarchus labrax ), a species presenting two hepcidin types, and evaluated variations in its expression levels in response to different experimental conditions. During experimental anemia, erythroferrone responds by increasing its expression and suppressing hepcidin production, following the pattern observed in mammals, but it is not influenced by iron overload. However, during bacterial infection, erythroferrone is downregulated and hepcidin levels increase. Furthermore, administration of Hamp1 but not of Hamp2 peptides suppresses erythroferrone expression. In conclusion, in dual hepcidin teleost fish erythroferrone seems to only interact with type 1 hepcidin, known to be involved in iron homeostasis, but not with type 2, which has an almost exclusive antimicrobial role., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Neves, Barroso, Carvalho, Nunes, Gonçalves and Rodrigues.)

Background: Laboratory skills training is an essential step before conducting minimally invasive surgery in clinical practice. Our main aim was to develop an animal model for training in clinically highly challenging laparoscopic duodenal atresia repair that could be useful in establishing a minimum number of repetitions to indicate safe performance of similar interventions on humans., Materials and Methods: A rabbit model of laparoscopic duodenum atresia surgery involving a diamond-shaped duodeno-duodenostomy was designed. This approach was tested in two groups of surgeons: in a beginner group without any previous clinical laparoscopic experience (but having undergone previous standardized dry-lab training, n = 8) and in an advanced group comprising pediatric surgery fellows with previous clinical experience of laparoscopy (n = 7). Each participant performed eight interventions. Surgical time, expert assessment using the Global Operative Assessment of Laparoscopic Skills (GOALS) score, anastomosis quality (leakage) and results from participant feedback questionnaires were analyzed., Results: Participants in both groups successfully completed all eight surgeries. The surgical time gradually improved in both groups, but it was typically shorter in the advanced group than in the beginner group. The leakage rate was significantly lower in the advanced group in the first two interventions, and it reached its optimal level after five operations in both groups. The GOALS and participant feedback scores showed gradual increases, evident even after the fifth surgery., Conclusions: Our data confirm the feasibility of this advanced pediatric laparoscopic model. Surgical time, anastomosis quality, GOALS score and self-assessment parameters adequately quantify technical improvement among the participants. Anastomosis quality reaches its optimal value after the fifth operation even in novice, but uniformly trained surgeons. A minimum number of wet-lab operations can be determined before surgery can be safely conducted in a clinical setting, where the development of further non-technical skills is also required., (© 2021. The Author(s).)

(1) Background: Evidence-based practice (EBP) informs daily clinical interventions with the purpose of seeking changes to traditional practice through scientific evidence that justifies the reasons for our actions. The objectives were to describe the barriers, beliefs, and attitudes in the application of EBP among university health professionals (not doctors) and to evaluate the influence of the COVID-19 pandemic among them. (2) Methods: This prospective study is both descriptive and observational. The individuals under study were university health professionals (not doctors) from various autonomous regions within Spain, in both public and private spheres. Sociodemographic and labor-related variables linked to the research and its completion were studied. Likewise, the survey instrument Health Sciences Evidence-Based Practice questionnaire (HS-EBP) was administered to evaluate the barriers to, beliefs in, and attitudes towards evidence-based practice. (3) Results: A total of 716 responses were gathered, of which 387 were collected during the period of confinement, and 343 in the COVID-19 post-confinement period. Possible associations that might help respond to the objectives were explored through a correlational study between the sociodemographic variables and each sub-scale of the HS-EBP 30 questionnaire ( n = 716). (4) Conclusions: Barriers to, beliefs in, and attitudes towards evidence-based practice are described. There is a leadership gap where line management provides insufficient motivation to follow work routines. The COVID-19 pandemic has caused immense stress among health professionals. The post-confinement group showed a significant change in the variables "beliefs and attitudes", and likewise in the "evaluation" block, justified by the need to update knowledge and to apply evidence.

Genotoxic stress during DNA replication constitutes a serious threat to genome integrity and causes human diseases. Defects at different steps of DNA metabolism are known to induce replication stress, but the contribution of other aspects of cellular metabolism is less understood. We show that aminopeptidase P (APP1), a metalloprotease involved in the catabolism of peptides containing proline residues near their N-terminus, prevents replication-associated genome instability. Functional analysis of C. elegans mutants lacking APP-1 demonstrates that germ cells display replication defects including reduced proliferation, cell cycle arrest, and accumulation of mitotic DSBs. Despite these defects, app-1 mutants are competent in repairing DSBs induced by gamma irradiation, as well as SPO-11-dependent DSBs that initiate meiotic recombination. Moreover, in the absence of SPO-11, spontaneous DSBs arising in app-1 mutants are repaired as inter-homologue crossover events during meiosis, confirming that APP-1 is not required for homologous recombination. Thus, APP-1 prevents replication stress without having an apparent role in DSB repair. Depletion of APP1 (XPNPEP1) also causes DSB accumulation in mitotically-proliferating human cells, suggesting that APP1's role in genome stability is evolutionarily conserved. Our findings uncover an unexpected role for APP1 in genome stability, suggesting functional connections between aminopeptidase-mediated protein catabolism and DNA replication., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a rare disorder in which astrocyte damage and/or demyelination often cause severe neurological deficits., Objective: To identify Portuguese patients with NMOSD and assess their epidemiological/clinical characteristics., Methods: This was a nationwide multicenter study. Twenty-four Portuguese adult and 3 neuropediatric centers following NMOSD patients were included., Results: A total of 180 patients met the 2015 Wingerchuk NMOSD criteria, 77 were AQP4-antibody positive (Abs+), 67 MOG-Abs+, and 36 seronegative. Point prevalence on December 31, 2018 was 1.71/100,000 for NMOSD, 0.71/100,000 for AQP4-Abs+, 0.65/100,000 for MOG-Abs+, and 0.35/100,000 for seronegative NMOSD. A total of 44 new NMOSD cases were identified during the two-year study period (11 AQP4-Abs+, 27 MOG-Abs+, and 6 seronegative). The annual incidence rate in that period was 0.21/100,000 person-years for NMOSD, 0.05/100,000 for AQP4-Abs+, 0.13/100,000 for MOG-Abs+, and 0.03/100,000 for seronegative NMOSD. AQP4-Abs+ predominated in females and was associated with autoimmune disorders. Frequently presented with myelitis. Area postrema syndrome was exclusive of this subtype, and associated with higher morbidity/mortality than other forms of NMOSD. MOG-Ab+ more often presented with optic neuritis, required less immunosuppression, and had better outcome., Conclusion: Epidemiological/clinical NMOSD profiles in the Portuguese population are similar to other European countries., (Copyright © 2021. Published by Elsevier B.V.)