Necrotizing enterocolitis: a potential protective role for intestinal alkaline phosphatase as lipopolysaccharide detoxifying enzyme.

Introduction: Necrotizing enterocolitis (NEC) is a life-threatening inflammatory disease. Its onset might be triggered by Toll-Like Receptor 4 (TLR4) activation via bacterial lipopolysaccharide (LPS). We hypothesize that a deficiency of intestinal alkaline phosphatase (IAP), an enzyme secreted by enterocytes that dephosphorylates LPS, may contribute to NEC development. Methods: In this prospective pilot study, we analyzed intestinal resection specimens from surgical NEC patients, and from patients undergoing Roux-Y reconstruction for hepatobiliary disease as controls. We assessed IAP activity via enzymatic stainings and assays and explored IAP and TLR4 co-localization through immunofluorescence. Results: The study population consisted of five NEC patients (two Bell's stage IIb and three-stage IIIb, median (IQR) gestational age 25 (24-28) weeks, postmenstrual age at diagnosis 28 (26-31) weeks) and 11 controls (unknown age). There was significantly lower IAP staining in NEC resection specimens [49 (41-50) U/g of protein] compared to controls [115 (76-144), P = 0.03]. LPS-dephosphorylating activity was also lower in NEC patients [0.06 (0-0.1)] than in controls [0.3 (0.2-0.5), P = 0.003]. Furthermore, we observed colocalization of IAP and TLR4 in NEC resection specimens. Conclusion: This study suggests a significantly lower IAP level in resection specimens of NEC patients compared to controls. This lower IAP activity suggests a potential role of IAP as a protective agent in the gut, which needs further confirmation in larger cohorts.

Algae-Based Supplements Claiming Weight Loss Properties: Authenticity Control and Scientific-Based Evidence on Their Effectiveness.

The worldwide prevalence of obesity impacts more than 600 million adults. Successfully managing weight is effective in reducing the risk of chronic diseases, but sustaining long-term weight loss remains a challenge. Although there are supplements based on algae that claim to aid in weight loss, there is a notable scarcity of scientific evidence supporting their effectiveness, and their regular consumption safety remains inadequately addressed. In this work, commercially available Arthrospira (Spirulina) platensis Gomont and/or Fucus vesiculosus L. supplements showed moderate capacity to inhibit the activity of carbohydrate-metabolizing enzymes, and to scavenge biologically relevant reactive species. IC25 values varying between 4.54 ± 0.81 and 66.73 ± 5.91 µg of dry extract/mL and between 53.74 ± 8.42 and 1737.96 ± 98.26 µg of dry extract/mL were obtained for α-glucosidase and aldose reductase, respectively. A weaker effect towards α-amylase activity was observed, with a maximum activity of the extracts not going beyond 33%, at the highest concentrations tested. Spirulina extracts showed generally better effects than those from F. vesiculosus. Similar results were observed concerning the antiradical capacity. In a general way, the extracts were able to intercept the in vitro-generated reactive species nitric oxide (•NO) and superoxide anion (O2•-) radicals, with better results for O2•-scavenging with the spirulina samples (IC25 values of 67.16 and 122.84 µg of dry extract/mL). Chemically, similar pigment profiles were observed between spirulina supplements and the authenticated counterpart. However, fucoxanthin, the chemotaxonomic marker of brown seaweeds, was not found in F. vesiculosus samples, pointing to the occurrence of a degradation phenomenon before, during, or after raw material processing. Our findings can contribute to providing data to allow regulatory entities (e.g., EFSA and FDA) to better rule these products in a way that can benefit society.

Low-Temperature Solution-Based Molybdenum Oxide Memristors.

Solution-based memristors have gained significant attention in recent years due to their potential for the low-cost, scalable, and environmentally friendly fabrication of resistive switching devices. This study is focused on the fabrication and characterization of solution-based molybdenum trioxide (MoO3) memristors under different annealing temperatures (200 to 400 °C). A MoO3 ink recipe is developed using water as the main solvent, enabling a simplified and cost-effective fabrication process. Material analysis reveals the presence of a Mo6+ oxidation state and an amorphous structure in the films annealed up to 250 °C. Electrical tests confirm a bipolar resistive switching behavior in the memristors according to the valence change mechanism (VCM). Endurance tests demonstrate stable memristors, indicating their robust nature after multiple cycles. Memristors annealed at 250 °C exhibit a nonvolatile behavior with a retention time up to 105 s under ambient air conditions. The high reproducibility observed in these memristors highlights their potential for practical applications and scalability.

Carcass Yields and Meat Composition of Roosters of the Portuguese Autochthonous Poultry Breeds: "Branca", "Amarela", "Pedrês Portuguesa", and "Preta Lusitânica".

Poultry meat is an important part of the human diet, and the valorisation of autochthonous breeds is a determinant for the sustainability of the rural areas. The increasing demand for niche products demands for better knowledge of the carcass characteristics and meat quality of these local populations. The present study aims to characterise the roosters' meat from the "Branca" (BR), "Amarela" (AM), "Pedrês Portuguesa" (PP), and "Preta Lusitânica" (PL) breeds. A total of 80 birds (n = 20 per breed) between 38 and 42 weeks old were slaughtered. The physicochemical and nutritional composition were determined in the breast and drumstick meat. The meat of the PL breed had a higher (p ≤ 0.05) pH value, the AM meat revealed a water-holding capacity (WHC) of superior value and moisture content (p ≤ 0.05), while the BR breed had the highest (p ≤ 0.05) ash content. On the other hand, it was observed that the PP meat had a higher (p ≤ 0.05) yellowness index (b*). The breast meat exhibited, in all breeds, a lower pH value, WHC, redness (a*), and lipid content and greater (p ≤ 0.05) lightness (L*), b*, moisture, and ash and protein contents compared to the drumstick. Furthermore, it presented higher (p ≤ 0.05) K, P, and Mg contents and a superior proportion of total and sensorial relevant amino acids. Regarding the fatty acid profile, the breed differences were more significant in the drumstick, with the AM breed lipids presenting a higher (p ≤ 0.05) percentage of MUFAs in the fat, a lower atherogenic index, and a higher (p ≤ 0.05) value for the hypocholesterolemic/hypercholesterolemic fatty acids ratio, while the BR breed lipids presented a higher (p ≤ 0.05) percentage of PUFAs and PUFAs/SFAs ratio and a lower n-6/n-3 ratio. Considering the results obtained, it can be concluded that the meat from these breeds is a wholesome dietary option, distinguished by a favourable overall nutritional composition marked by elevated protein content, reduced lipid amounts, and amino and fatty acid profiles with desirable nutritional indices.

"Help Me Control My Impulses!": Adolescent Impulsivity and Its Negative Individual, Family, Peer, and Community Explanatory Factors.

The literature shows that impulsivity, prevalent in adolescence, is negatively linked with a variety of psychosocial factors (e.g., positive interpersonal relationships, emotion regulation); however, there is limited research examining the relative contribution of multiple factors for this trait nor exploring how these factors influence the associations between impulsivity and risk-related outcomes. Drawing on multiple components of the unified theory of development (i.e., psychological variables, peers subsystem, community subsystem, family processes subsystem), this cross-sectional study aims to identify explanatory psychosocial variables (i.e., early memories of warmth and safeness, rational decision-making style, resilience, emotion regulation, coping, parental attachment, social group attachment, satisfaction with school and family-related variables) that are negatively related with impulsivity, in younger (13-15) and older (16-19 years) adolescents, and explore their moderating role in the associations between this trait and some risk-related outcomes (i.e., verbal aggression, anger, self-harm, other high-risk behaviors). A representative sample of 6894 adolescents (52.9% female) living in the Azores (Portugal), with ages ranging from 13 to 19 (M = 15.4), was used. Two stepwise multiple regressions, one for each age group, revealed that only emotion regulation, parental attachment, and social group attachment had a negative effect on impulsivity in both age groups; additionally, satisfaction with teachers also had this effect in younger adolescents. The first three variables weakened the positive associations between impulsivity and the risk-related outcomes. These results suggest that the psychological system and all subsystems of the social context measured play a relevant role in explaining adolescent impulsivity and that it may be reduced by promoting emotion regulation, positive parenting practices, healthier relationships with peers, and healthier relationships with teachers.

The role of intestinal alkaline phosphatase in the development of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a devastating neonatal disease that affects neonates worldwide and often leads to high morbidity and mortality rates. Despite extensive research, the cause of NEC remains unclear, and current treatment options are limited. An important novel finding is the potential role of intestinal Alkaline Phosphatase (IAP) in both pathogenesis and treatment of NEC. IAP can play a vital role in detoxifying liposaccharides (LPS), a key mediator of many pathological processes, thereby reducing the inflammatory response associated with NEC. Furthermore, IAP can help prevent dysbiosis, improve intestinal perfusion, and promote autophagy. In this comprehensive review, we present evidence of the possible connection between IAP and the LPS/Toll-like receptor 4 (TLR4) pathway, impaired gut immunity, and dysbiosis in the preterm gut. Based on these findings, the administration of exogenous IAP might provide promising preventive and therapeutic avenues for the management of NEC.

Unearthing of the Antidiabetic Potential of Aqueous Extract of Solanum betaceum Cav. Leaves.

Solanum betaceum Cav., commonly known as tamarillo or Brazilian tomato, belongs to the Solanaceae family. Its fruit is used in traditional medicine and food crops due to its health benefits. Despite the numerous studies involving the fruit, there is no scientific knowledge about the tamarillo tree leaves. In this work, the phenolic profile of aqueous extract obtained from S. betaceum leaves was unveiled for the first time. Five hydroxycinnamic phenolic acids were identified and quantified, including 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, chlorogenic acid, caffeic acid and rosmarinic acid. While the extract displayed no effect on α-amylase, the extract inhibited the activity of α-glucosidase (IC50 = 1617 mg/mL), and it was particularly effective for human aldose reductase (IC50 = 0.236 mg/mL): a key enzyme in glucose metabolism. Moreover, the extract exhibited interesting antioxidant properties, such as a potent capacity to intercept the in vitro-generated reactive species O2•- (IC50 = 0.119 mg/mL) and •NO (IC50 = 0.299 mg/mL), as well as to inhibit the first stages of lipid peroxidation (IC50 = 0.080 mg/mL). This study highlights the biological potential of S. betaceum leaves. The scarcity of research on this natural resource underscores the need for additional studies in order to fully explore its antidiabetic properties and to promote the value of a species currently at risk of extinction.

Nutritional counselling in adults promoting adherence to the Mediterranean diet as adjuvant in the treatment of major depressive disorder (INDEPT): a randomized open controlled trial study protocol.

BACKGROUND: Major Depressive Disorder (MDD) is a leading cause of disability worldwide. Approximately one-third of patients with MDD do not respond to treatment, and often exhibit elevated inflammation biomarkers, which are associated with worse prognosis. Previous research has linked healthier dietary patterns, such as the Mediterranean Diet (MedDiet), with a lower risk of MDD and symptoms of depression, potentially due to their anti-inflammatory properties. The aim of this study is to evaluate the effectiveness of a nutritional counselling intervention promoting MedDiet to alleviate symptoms of depression in adults recently diagnosed with MDD and presenting with elevated inflammation biomarkers. METHODS: This study is a randomized controlled trial (RCT) that will recruit adults from outpatient clinics, between the ages of 18 and 70 years who have been diagnosed with MDD and are currently receiving treatment with the first prescribed antidepressant, and who exhibit elevated inflammation biomarkers (interleukin-6 and/or C-reactive protein). The control group will receive treatment-as-usual (TAU) only. The primary outcome of the study will be the change in symptoms of depression, as measured by the Beck Depression Inventory 2 (BDI-II), after 12 weeks of intervention. Data analysis will follow an intention-to-treat approach. Secondary outcomes will include changes in inflammation biomarkers, quality of life, adherence to the MedDiet, and cost-effectiveness of nutritional counselling. All outcomes will be assessed at baseline, after the 12-week intervention, and at 6- and 12-months post-baseline. DISCUSSION: This study will be the first RCT to evaluate the effect of a nutritional intervention with anti-inflammatory properties, as an adjuvant in the treatment of MDD, in individuals diagnosed with MDD and elevated inflammation biomarkers. The results of this study may contribute to the development of more effective and personalized interventions for MDD patients with elevated inflammation biomarkers.

Cap-Assisted Endoscopic Mucosal Resection for Rectal Neuroendocrine Tumors: An Effective Option.

Introduction: The incidence of rectal neuroendocrine tumors (r-NETs) is increasing, and most small r-NETs can be treated endoscopically. The optimal endoscopic approach is still debatable. Conventional endoscopic mucosal resection (EMR) leads to frequent incomplete resection. Endoscopic submucosal dissection (ESD) allows higher complete resection rates but is also associated with higher complication rates. According to some studies, cap-assisted EMR (EMR-C) is an effective and safe alternative for endoscopic resection of r-NETs. Aims: This study aimed to evaluate the efficacy and safety of EMR-C for r-NETs ≤10 mm without muscularis propria invasion or lymphovascular infiltration. Methods: Single-center prospective study including consecutive patients with r-NETs ≤10 mm without muscularis propria invasion or lymphovascular invasion confirmed by endoscopic ultrasound (EUS), submitted to EMR-C between January 2017 and September 2021. Demographic, endoscopic, histopathologic, and follow-up data were retrieved from medical records. Results: A total of 13 patients (male: 54%; n = 7) with a median age of 64 (interquartile range: 54-76) years were included. Most lesions were located at the lower rectum (69.2%, n = 9), and median lesion size was 6 (interquartile range: 4.5-7.5) mm. On EUS evaluation, 69.2% (n = 9) of tumors were limited to muscularis mucosa. EUS accuracy for the depth of invasion was 84.6%. We found a strong correlation between size measurements by histology and EUS (r = 0.83, p < 0.01). Overall, 15.4% (n = 2) were recurrent r-NETs and had been pretreated by conventional EMR. Resection was histologically complete in 92% (n = 12) of cases. Histologic analysis revealed grade 1 tumor in 76.9% (n = 10) of cases. Ki-67 index was inferior to 3% in 84.6% (n = 11) of cases. The median procedure time was 5 (interquartile range: 4-8) min. Only 1 case of intraprocedural bleeding was reported and was successfully controlled endoscopically. Follow-up was available in 92% (n = 12) of cases with a median follow-up of 6 (interquartile range: 12-24) months with no evidence of residual or recurrent lesion on endoscopic or EUS evaluation. Conclusion: EMR-C is fast, safe, and effective for resection of small r-NETs without high-risk features. EUS accurately assesses risk factors. Prospective comparative trials are needed to define the best endoscopic approach.

Introdução: Os tumores neuroendócrinos do reto (r-NETs) apresentam incidência crescente. A maioria dos tumores de pequenas dimensões pode ser excisada endoscopicamente, no entanto, a abordagem ótima é controversa. A mucosectomia convencional associa-se, frequentemente, a resseção endoscópica incompleta. A disseção endoscópica submucosa (ESD) permite elevadas taxas de resseção completa, mas é tecnicamente complexa e associa-se a maior número de complicações. Alguns estudos sugerem a mucosectomia assistida por cap (EMR-C) como uma alternativa eficaz e segura. Objetivo: Este estudo pretendeu avaliar a eficácia e segurança da mucosectomia com cap na resseção de r-NETs com dimensões ≤10 mm, sem invasão da muscularis própria nem infiltração linfovascular. Material e Métodos: Estudo prospetivo unicêntrico incluindo consecutivamente r-NETs com ≤10 mm, sem invasão da muscularis própria ou linfovascular confirmada em ultrassonografia endoscópica (EUS), submetidos a mucosectomia assistida cap entre janeiro de 2017 e setembro de 2021. Colheita de dados demográficos, clínicos e histopatológicos através de registos médicos eletrónicos. Resultados: Incluídos 13 doentes (género masculino: 54%; n = 7) com idade mediana de 64 (intervalo interquartil [IIQ]: 54­76) anos. A maioria das lesões localizava-se no reto inferior (69.2%; n = 9) e apresentava tamanho mediano de 6 (IIQ: 4.5­7.5) mm. Na avaliação por EUS, 69.2% (n = 9) encontravam-se limitados à muscularis mucosa. A acuidade da EUS na avaliação do envolvimento das camadas da parede retal foi de 84.6% e o tamanho avaliado por EUS correlacionou-se fortemente com o medido na histologia (r = 0.83, p < 0.01). Dois casos (15.4%) corresponderam a recorrências de mucosectomias convencionais prévias. A resseção foi macroscópica e histologicamente completa em 92% (n = 12) dos casos. A análise histológica revelou 76.9% (n = 10) tumores de grau 1. O índice Ki-67 foi inferior a 3% em 84.6% (n = 11) dos casos. O tempo mediano de procedimento foi 5 (IIQ: 4­8) minutos. Verificou-se apenas um caso de hemorragia intraprocedimento resolvida endoscopicamente. O seguimento de 92% dos casos (n = 12) com mediana de 6 (IIQ:12­24) meses não revelou lesão residual ou recorrência em avaliações endoscópica e ultrassonográfica. Discussão/Conclusão: A EMR-C é uma técnica endoscópica segura, rápida e efetiva para a resseção de r-TNEs pequenos sem fatores de alto risco. A EUS apresenta elevada acuidade na avaliação dos fatores de risco. Estudos comparativos prospetivos são necessários para estabelecimento da abordagem endoscópica mais profícua.

A cell-penetrant peptide blocking C9ORF72-repeat RNA nuclear export reduces the neurotoxic effects of dipeptide repeat proteins.

Hexanucleotide repeat expansions in C9ORF72 are the most common genetic cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Studies have shown that the hexanucleotide expansions cause the noncanonical translation of C9ORF72 transcripts into neurotoxic dipeptide repeat proteins (DPRs) that contribute to neurodegeneration. We show that a cell-penetrant peptide blocked the nuclear export of C9ORF72-repeat transcripts in HEK293T cells by competing with the interaction between SR-rich splicing factor 1 (SRSF1) and nuclear export factor 1 (NXF1). The cell-penetrant peptide also blocked the translation of toxic DPRs in neurons differentiated from induced neural progenitor cells (iNPCs), which were derived from individuals carrying C9ORF72-linked ALS mutations. This peptide also increased survival of iNPC-differentiated C9ORF72-ALS motor neurons cocultured with astrocytes. Oral administration of the cell-penetrant peptide reduced DPR translation and rescued locomotor deficits in a Drosophila model of mutant C9ORF72-mediated ALS/FTD. Intrathecal injection of this peptide into the brains of ALS/FTD mice carrying a C9ORF72 mutation resulted in reduced expression of DPRs in mouse brains. These findings demonstrate that disrupting the production of DPRs in cellular and animal models of ALS/FTD might be a strategy to ameliorate neurodegeneration in these diseases.

Secondary Metabolites Diversity of Aspergillus unguis and Their Bioactivities: A Potential Target to Be Explored.

Aspergillus unguis belongs to the Aspergillus section Nidulantes. This species is found in soils and organisms from marine environments, such as jellyfishes and sponges. The first chemical study reported in the literature dates from 1970, with depsidones nidulin (1), nornidulin (2), and unguinol (3) being the first isolated compounds. Fifty-two years since this first study, the isolation and characterization of ninety-seven (97) compounds have been reported. These compounds are from different classes, such as depsides, depsidones, phthalides, cyclopeptides, indanones, diarylethers, pyrones, benzoic acid derivatives, orcinol/orsenillate derivatives, and sesterpenoids. In terms of biological activities, the first studies on isolated compounds from A. unguis came only in the 1990s. Considering the tendency for antiparasitic and antibiotics to become ineffective against resistant microorganisms and larvae, A. unguis compounds have also been extensively investigated and some compounds are considered very promising. In addition to these larvicidal and antimicrobial activities, these compounds also show activity against cancer cell lines, animal growth promotion, antimalarial and antioxidant activities. Despite the diversity of these compounds and reported biological activities, A. unguis remains an interesting target for studies on metabolic induction to produce new compounds, the determination of new biological activities, medicinal chemistry, structural modification, biotechnological approaches, and molecular modeling, which have yet to be extensively explored.

Exposure to heavy metals and red blood cell parameters in children: A systematic review of observational studies.

Background: Mechanistic studies show that heavy metals interfere with the hematopoietic system by inhibiting key enzymes, which could lead to anemia. However, the link between children's exposure and red blood cell (RBC) parameters has been inconsistent. We aimed to summarize evidence on human studies exploring the association between exposure to lead, mercury, cadmium, arsenic, and chromium VI and RBC parameters in children. Methods: Following the PRISMA guidelines, we searched PubMed, Scopus, and Web of Science databases for studies published between January 2010 and April 2022. Eligible papers included human observational studies that directly assessed exposure (internal dose) to the heavy metals under study and RBC parameters in participants aged ≤ 18 years. We excluded studies using hospital-based samples. Study quality was assessed using the National Institutes of Health's Quality Assessment Tools for Cohort and Cross-Sectional Studies. We synthesized the evidence using vote counting based on the direction of the relationship. Results: Out of 6,652 retrieved papers, we included a total of 38 (33 assessing lead, four mercury, two cadmium, and two arsenic; chromium VI was not assessed in any included paper). More than half of the studies were conducted in Asia. We found evidence of a positive relationship between lead concentration and hemoglobin (proportion of studies reporting negative relationships = 0.750; 95% Confidence Interval (CI) 0.583, 0.874) and mean corpuscular hemoglobin (0.875; 95% CI 0.546, 0.986), and a positive relationship with red cell distribution width (0.000; 95%CI 0.000, 0.379). When considering only good-quality studies (24% of the Pb studies), only the relationship with hemoglobin levels remained (0.875; 95% CI: 0.546, 0.986). Conclusion: We found evidence of a negative relationship between lead concentration and hemoglobin and mean corpuscular hemoglobin and of a positive relationship with red cell distribution width in children. We also identified a need to conduct more studies in European countries. Future studies should use standardized practices and make efforts to increase study quality, namely by conducting comprehensive longitudinal studies. Our findings support the need to take further actions to limit heavy metal exposure during childhood.

Developing healthy eating promotion mass media campaigns: A qualitative study.

Background: Involving consumers in the development and assessment of mass media campaigns has been advocated, though research is still lacking. This study aimed to explore opinions and attitudes of citizens, health professionals, communication professionals, and digital influencers regarding the development and implementation of healthy eating promotion mass media campaigns. Methods: We conducted five semi-structured focus groups, where participants were exposed to the first nationwide mass media campaign promoting healthy eating in Portugal. Through criteria-based purposive sampling, 19 citizens, five health professionals, two communication professionals, and four digital influencers were included. Transcripts were analyzed using Charmaz's line-to-line open coding process. Results: Main identified themes were: considerations about informative-centered campaigns, health/nutritional issues to address, campaign formulation, target audiences, dissemination channels, and influencers' involvement. Participants favored campaigns focused on practical, transformative, and useful information with simple, innovative, activating, and exciting messages instead of strictly informative campaigns. Health and communication professionals mentioned the importance of adapting the message and dissemination channels to the target audience, addressing the most vulnerable and hard-to-reach individuals, and highlighted the importance of short video format. Conclusions: Active involvement of the health promotion target audience is crucial for the development and effectiveness of health campaigns. Campaigns need to convey health messages on simple though exciting communication materials, targeted to the most vulnerable subgroups, including deprived, less educated, younger, and older generations.

A subset of gut leukocytes has telomerase-dependent "hyper-long" telomeres and require telomerase for function in zebrafish.

BACKGROUND: Telomerase, the enzyme capable of elongating telomeres, is usually restricted in human somatic cells, which contributes to progressive telomere shortening with cell-division and ageing. T and B-cells cells are somatic cells that can break this rule and can modulate telomerase expression in a homeostatic manner. Whereas it seems intuitive that an immune cell type that depends on regular proliferation outbursts for function may have evolved to modulate telomerase expression it is less obvious why others may also do so, as has been suggested for macrophages and neutrophils in some chronic inflammation disease settings. The gut has been highlighted as a key modulator of systemic ageing and is a key tissue where inflammation must be carefully controlled to prevent dysfunction. How telomerase may play a role in innate immune subtypes in the context of natural ageing in the gut, however, remains to be determined. RESULTS: Using the zebrafish model, we show that subsets of gut immune cells have telomerase-dependent"hyper-long" telomeres, which we identified as being predominantly macrophages and dendritics (mpeg1.1+ and cd45+mhcII+). Notably, mpeg1.1+ macrophages have much longer telomeres in the gut than in their haematopoietic tissue of origin, suggesting that there is modulation of telomerase in these cells, in the gut. Moreover, we show that a subset of gut mpeg1.1+ cells express telomerase (tert) in young WT zebrafish, but that the relative proportion of these cells decreases with ageing. Importantly, this is accompanied by telomere shortening and DNA damage responses with ageing and a telomerase-dependent decrease in expression of autophagy and immune activation markers. Finally, these telomerase-dependent molecular alterations are accompanied by impaired phagocytosis of E. coli and increased gut permeability in vivo. CONCLUSIONS: Our data show that limiting levels of telomerase lead to alterations in gut immunity, impacting on the ability to clear pathogens in vivo. These are accompanied by increased gut permeability, which, together, are likely contributors to local and systemic tissue degeneration and increased susceptibility to infection with ageing.

Emergent solution based IGZO memristor towards neuromorphic applications.

Solution-based memristors are emergent devices, due to their potential in electrical performance for neuromorphic computing combined with simple and cheap fabrication processes. However, to achieve practical application in crossbar design tens to hundreds of uniform memristors are required. Regarding this, the production step optimization should be considered as the main objective to achieve high performance devices. In this work, solution-based indium gallium zinc oxide (IGZO) memristor devices are produced using a combustion synthesis process. The performance of the device is optimized by using different annealing temperatures and active layer thicknesses to reach a higher reproducibility and stability. All IGZO memristors show a low operating voltage, good endurance, and retention up to 105 s under air conditions. The optimized devices can be programmed in a multi-level cell operation mode, with 8 different resistive states. Also, preliminary results reveal synaptic behavior by replicating the plasticity of a synaptic junction through potentiation and depression; this is a significant step towards low-cost processes and large-scale compatibility of neuromorphic computing systems.

Dietary Acrylamide Exposure and Risk of Site-Specific Cancer: A Systematic Review and Dose-Response Meta-Analysis of Epidemiological Studies.

Diet is a main source of acrylamide exposure to humans. Existing observational data on the relationship between dietary exposure to acrylamide and risk of cancer are inconsistent. We performed a systematic review and dose-response meta-analysis of epidemiological studies evaluating the association between dietary acrylamide exposure and several site-specific cancer. A systematic literature search was conducted in PubMed, Scopus, and Web of Science databases until March 7, 2022. Studies were eligible if they were carried out in non-occupationally exposed adults, assessed dietary acrylamide exposure (µg/day) and reported risk estimates of cancer incidence (all but gynecological cancers). Using a random-effects model, we performed a meta-analysis of site-specific cancer risk comparing the highest vs. lowest category of dietary acrylamide exposure. We also carried out a one-stage dose-response meta-analysis assessing the shape of the association. Out of 1,994 papers screened, 31 were eligible (total of 16 studies), which included 1,151,189 participants in total, out of whom 48,175 developed cancer during the median follow-up period of 14.9 years (range 7.3-33.9). The mean estimated dose of dietary acrylamide across studies was 23 µg/day. Pooled analysis showed no association between the highest vs. lowest dietary acrylamide exposure and each site-specific cancer investigated, with no evidence of thresholds in the dose-response meta-analysis. There were also no associations between dietary acrylamide exposure and the risk of cancers when stratifying by smoking status, except for increased risk of lung cancer in smokers. In conclusion, high dietary acrylamide exposure was not associated with an increased risk of site-specific non-gynecological cancer.

Malignancy risk of thyroid nodules: quality assessment of the thyroid ultrasound report.

BACKGROUND: Thyroid nodules are a challenge in clinical practice and thyroid ultrasonography is essential for assessing the risk of malignancy. The use of ultrasound-based malignancy risk classification systems has been recommended by several scientific societies but radiologist's adherence to these guidelines may vary. The authors aimed to analyze the quality of the information provided by the thyroid ultrasound report, to assess the malignancy risk of thyroid nodules, in Portugal. METHODS: Multicenter and retrospective study, conducted in three of the five Portuguese NUTS2 corresponding to about 88.3% of the mainland population. We included 344 consecutive unselected participants aged ≥ 18 years who underwent thyroid ultrasonography in 2019. The description of six features of the dominant thyroid nodule was analyzed: maximum size, shape, margins, composition, echogenicity and echogenic foci. A utility score, including these six features, was used as an indicator of the report's quality. A score of 4 was considered as a minimum value. RESULTS: Maximum diameter was reported for all nodules. Shape, margins, composition, echogenicity and echogenic foci were reported in 8.1%, 25.0%, 76.5%, 53.2% and 20.9%, respectively. Only 21.8% of the nodules had a score ≥ 4. At least one of four suspicious features, including marked hypoechogenicity, microcalcifications, irregular margins and non-oval shape, was identified in 8.7% of the nodules. Cervical lymph nodes' status was reported in 93% of the exams. The risk category was only reported in 7.8% of the participants. CONCLUSION: The adherence of Portuguese radiologists to a standardized reporting model and to an ultrasound-based malignancy risk stratification system is still low and has implications for the correct characterization of the malignancy risk of nodules and the decision to perform fine-needle aspiration biopsy.

Müller Glia maintain their regenerative potential despite degeneration in the aged zebrafish retina.

Ageing is a significant risk factor for degeneration of the retina. Müller glia cells (MG) are key for neuronal regeneration, so harnessing the regenerative capacity of MG in the retina offers great promise for the treatment of age-associated blinding conditions. Yet, the impact of ageing on MG regenerative capacity is unclear. Here, we show that the zebrafish retina undergoes telomerase-independent, age-related neurodegeneration but that this is insufficient to stimulate MG proliferation and regeneration. Instead, age-related neurodegeneration is accompanied by MG morphological aberrations and loss of vision. Mechanistically, yes-associated protein (Yap), part of the Hippo signalling, has been shown to be critical for the regenerative response in the damaged retina, and we show that Yap expression levels decline with ageing. Despite this, morphologically and molecularly altered aged MG retain the capacity to regenerate neurons after acute light damage, therefore, highlighting key differences in the MG response to high-intensity acute damage versus chronic neuronal loss in the zebrafish retina.

A Behavioural Assay to Investigate Judgment Bias in Zebrafish.

In this protocol, we describe for the first time a judgment bias paradigm to phenotype the way zebrafish assess ambiguous stimuli. We have developed and validated a protocol for a judgment bias test based on a Go/No-go task, and performed using a half radial maze. After a habituation phase, fish are trained to discriminate between two reference arms [positive (P) and negative (N)]. For this purpose, they experience a positive event (food reward in P), when presented with a specific location/color cue, and a negative event (chasing with net in N), when presented with a different location/color cue. Acquisition of the discrimination learning between P and N is revealed by the latencies to enter the experimental arms of the behavioral maze being significantly lower for the P arm than for the N arm. Once zebrafish are able to discriminate between P and N arms, their latency to enter other maze arms spatially located between P and N [(Near Positive (NP), Ambiguous (A) = half-way between P and N, and Near Negative (NN)] is analyzed. Latencies (L) to enter NP, A and NN maze arms are interpreted as indicating the individual expectancy to experience a reward/punishment on each of them. A judgment bias score (JBS) is calculated from the latencies to enter the P, N, and A arms for each fish [JBS = (LA-LP)*100/(LN-LP)], based on which fish can be classified into an optimistic/pessimistic axis. A JBS below 50 indicates that fish perceive the ambiguous stimulus as a positive one (optimistic bias), while JBS above 50 indicates that fish perceive the ambiguous stimulus as a negative one (pessimistic bias). However, for classification criteria, it could be advantageous to use the method of selecting extreme phenotypes (e.g., upper and lower quartiles of the JBS), since JBS in zebrafish falls into a bimodal distribution (unpublished data). Therefore, this protocol provides a unique, inexpensive, and effective alternative to other methods of measuring affective states in zebrafish that might be of great interest to a broad target audience and have a large number of applications. Graphic abstract: Flow chart of the judgment bias protocol in zebrafish.

Percepção dos estudantes sobre promoção da saúde no ensino superior e qualidade de vida / Students' perception of health promotion in higher education and quality of life / Percepción de los estudiantes sobre promoción de la salud en la educación superior y la calidad de vida

Objetivo: Avaliar a percepção dos estudantes sobre a promoção da saúde em uma instituição de ensino superior, relacionando com a qualidade de vida (QV). Métodos: Trata-se de um estudo transversal, descritivo, de natureza quantitativa, realizado em uma faculdade privada, de natureza confessional e filantrópica, localizada no Sul do Brasil, no mês de novembro de 2019. Aplicaramse questionários a 390 estudantes universitários, configurando uma amostra representativa de 62,4% dos matriculados. Para avaliação da promoção da saúde sob a percepção dos estudantes, utilizou-se o questionário IAPSU ­ Instrumento de Avaliação da Promoção da Saúde na Universidade. Para avaliação da QV dos acadêmicos, utilizou-se o instrumento de avaliação da QV - WHOQOL-bref. Analisaram-se os dados, estatisticamente, por meio de tabelas de frequências cruzadas, através dos testes de Wilcoxon, com nível de confiança de 95% (α=0,05). Resultados: Os universitários mostraram percepção positiva da instituição como promotora da saúde, alcançando escore médio superior a 90 (de 0 a 100) nos domínios atividade física, alimentação e fatores ambientais. Verificou-se que a média obtida na qualidade de vida geral do instrumento WHOQOL-bref diferiu significativamente entre os participantes que relataram praticar atividade física e recreativa (p=0,0001), e que participaram de atividades sobre alimentação saudável oferecidas pela instituição (p=0,005). Conclusão: Conclui-se que os estudantes avaliaram positivamente as ações promotoras da saúde na universidade avaliada, com melhor percepção da qualidade de vida entre os estudantes que relataram praticar atividade física e recreativa, e que participaram de atividades sobre alimentação saudável.

Objective: To assess students' perception of health promotion in a higher education institution relating it to quality of life (QoL). Methods: This is a quantitative descriptive cross-sectional study carried out in November 2019 in a private denominational and philanthropic university located in Southern Brazil. Questionnaires were applied to 390 university students in a representative sample of 62.4% of the students enrolled. To assess health promotion based on students' perception, the Health Promotion at the University Assessment Tool (Instrumento de Avaliação da Promoção da Saúde na Universidade ­ IAPSU) was used. To assess the students' QoL, the QoL assessment instrument - WHOQOL-bref was used. Data were analyzed statistically using crosstabs and Wilcoxon test with a confidence level of 95% (α=0.05). Results: The university students showed a positive perception of the institution as a promoter of health, exhibiting a mean score above 90 (from 0 to 100) in the physical activity, food and environmental factors domains. It was found that the mean scores for general quality of life in the WHOQOL-bref instrument differed significantly between participants who reported practicing physical and recreational activities (p=0.0001), and those who participated in healthy eating activities offered by the institution (p=0.005). Conclusion: The studentspositively rated the health-promoting actions at the university analyzed, with a better perception of quality of life seen among students who reported practicing physical and recreational activities, and who participated in healthy eating activities.

Objetivo: Evaluar la percepción de los estudiantes sobre la promoción de la salud en institución de educación superior relacionando con la calidad de vida (CV). Métodos: Se trata de un estudio transversal, descriptivo, de naturaleza cuantitativa realizado en una facultad privada, de naturaleza confesional y filantrópica, localizada en el Sur de Brasil en el mes de noviembre de 2019. Se aplicaron cuestionarios con 390 estudiantesuniversitarios que ha sido una muestra representativa del 62,4% de los matriculados. Para la evaluación de la promoción de la salud bajo la percepción de los estudiantes, se utilizó el cuestionario IAPSU ­ Instrumento de Evaluación de la Promoción de la Salud en la Universidad. Para la evaluación de la CV de los académicos, se utilizó el instrumento de evaluación de la CV ­ el WHOQOL-bref. Se analizaron los datos, estadísticamente, a través de tablas de frecuencias cruzadas, a través de las pruebas de Wilcoxon con el nivel de confianza del 95% (α=0,05). Resultados: Los universitarios mostraron percepción positiva de la institución como promotora de la salud alcanzando una puntuación media más de 90 (de 0 a 100) para los dominios actividad física, alimentación y factores ambientales. Se verifico que la media de la calidad de vida general del instrumento WHOQOL-bref ha sido significativamente distinta entre los participantes que relataron la práctica de actividad física y de recreación (p=0,0001) y los que participaron de actividades sobre alimentación saludable ofrecidas por la institución (p=0,005). Conclusión: Se concluye que los estudiantes evaluaron positivamente las acciones de promoción de la salud de la universidad evaluada con mejor percepción de la calidad de vida entre los estudiantes que relataron la práctica de actividad física y de recreación y los que participaron de actividades de alimentación saludable.