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.

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.

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.

"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.

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.

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.

Are beliefs and attitudes about COVID-19 associated with self-perceived changes in food consumption? Results from a nationwide survey during lockdown.

This study aimed to understand how beliefs and attitudes regarding COVID-19 are associated with self-perceived changes in food consumption during lockdown between March 19 and May 2, 2020. We conducted a cross-sectional study with a non-probabilistic weighted sample of the Portuguese population. Data were collected using an online survey and telephone interviews. The association between agreement with sentences about food and COVID-19 and perceived changes in food consumption were assessed by multinomial logistic regression models. Overall, 5858 citizens were included, with a mean age of 38.2 (17.3) years. Exclusive agreement with the belief "SARS-CoV-2 can be transmitted by food" (27.5%) was associated with decreased odds of perceived positive changes (e.g., increased consumption of fruit and vegetables). Agreement only with the attitudinal sentence "I started to consume foods that may protect against COVID-19" (11.9%) was associated with positive perceived consumption changes (e.g., increasing fruit and vegetables, and decreasing soft drinks and snacks). Cumulative agreement (with both sentences; 10.6%) was also associated with mostly positive food consumption changes. Specific beliefs and attitudes regarding COVID-19 and food are associated with self-perceived changes in food consumption. Longitudinal research is needed to understand how beliefs and/or attitudes about the role of food in infectious diseases act as determinants of eating behavior modification.

Genetic testing for pheochromocytoma and paraganglioma: SDHx carriers' experiences.

Pheochromocytoma and paraganglioma are frequently hereditary tumors commonly associated with succinate dehydrogenase (SDHx) pathogenic variants (PV). Genetic testing is recommended to relatives of patients carrying SDHx PV. This study aims to explore the experiences associated with genetic testing for this hereditary condition. Semi-structured interviews with 38 SDHx PV (tumor-affected and non-affected) carriers were transcribed and content-analyzed. Four ways of living with this genetic alteration emerged from the interviews: 'living as if not knowing', 'preventing others from going through this', 'feeling privileged', and 'still suffering'. Within each, negative, neutral, and positive reactions to the actual test result emerged initially, in addition to blame and guilt. Recognition of the importance of the genetic test and of the follow-up occurred in all four, but views on fecundity were divided between having and not having children. Consideration for the four different meanings of carrying an SDHx PV can improve participants' experiences and clinical practice.

Surveillance of succinate dehydrogenase gene mutation carriers: Insights from a nationwide cohort.

OBJECTIVE: Mutations in the genes coding for succinate dehydrogenase (SDHx) are the most frequent germline alterations in pheochromocytomas and paragangliomas. Evidence for the advantages associated with presymptomatic screening for SDHx mutation carriers is scarce. This study describes a nationwide cohort of these mutation carriers and aims to compare patients with clinical manifestations of the disease and those diagnosed through genetic screening. DESIGN: Cross-sectional study. PATIENTS: SDHx mutation carriers (n = 118) followed through the Portuguese Oncology referral centres: 41 probands and 77 nonprobands. MEASUREMENTS: All participants were subjected to biochemical and body imaging examinations for a complete assessment of the extent and spread of disease. Clinical data obtained this way were further analysed. RESULTS: The mean age of this cohort was 44.5 ± 17.4 years, and more than half carried the same founder SDHB mutation. About 50.8% of the mutation carriers developed pheochromocytomas or paragangliomas. Compared to patients diagnosed through genetic screening, those diagnosed clinically were characterized by larger tumours (P < .001), more frequent metastases (P = .024), were more frequently subjected to surgery (P = .011) and radiotherapy (P = .013), and had worse outcomes, such as macroscopic positive margins (P = .034). Persistent and/or unresectable disease and disease-related mortality were also more frequent in symptomatic patients compared to those diagnosed through genetic screening (P = .014). CONCLUSIONS: In this nationwide cohort study, a large proportion of mutation carriers were found to develop SDHx-related neoplasia. Genetic testing and subsequent follow-up resulted in the diagnosis of smaller and nonmetastatic tumours, fewer treatment procedures, fewer complications and greater number of disease-free patients.

Psychometric Properties of the MICRA Questionnaire in Portuguese Individuals Carrying SDHx Mutations.

This study aims to present the translation and cultural adaptation, as well as the psychometric characteristics of the Portuguese version of the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire in individuals with SDHx mutations. The questionnaire was translated and culturally adapted in accordance with the process recommended by the World Health Organization. As per suggestion of the authors of the original instrument, a joint, universal European and Brazilian Portuguese version of the MICRA was created. Ninety-six (asymptomatic or affected) patients with SDHx mutations nationwide completed the adapted version of the MICRA in Portugal. Analyses consisted of confirmatory factor analysis, reliability estimation (alphas), and correlations with two other distress and quality of life instruments. The Portuguese adaptation of the MICRA was understandable to patients from various socioeconomic backgrounds. All items and factor structure of the original version were retained, yielding a good model fit. The MICRA's three subscales and total score showed good internal consistency, and the correlations found between the Portuguese version of the MICRA and the other instruments assessing similar constructs further supported its validity. The adapted version of the MICRA showed good psychometric properties with a representative population of SDHx mutation carriers. This instrument can now be used to study the multidimensional impact of taking a genetic test for these mutations. It can also be used in future studies with other Portuguese populations of patients submitted to genetic tests for cancer risk assessment.

Assessment on hereditary angioedema burden of illness in Brazil: A patient perspective.

Background: Hereditary angioedema (HAE) is an autosomal dominant disorder that affects ∼1 in 50,000 individuals. The disorder is characterized by spontaneous and gradual episodes of edema in subcutaneous tissues or mucosal membrane that may endanger the patient's life. Previous studies that concern HAE treatment and burden of illness in the United States and Europe suggest an improvement in the control of HAE. However, no similar data are available in South American patients. The purpose of the present study was to evaluate the burden of disease and compliance to therapy of patients with HAE in Brazil. Methods: We developed a structured questionnaire to assess the variables that influence the diagnosis and treatment of Brazilian patients with HAE. The questionnaire was evaluated by allergists with expertise in HAE and was reformatted before applying it. The consent form was included before survey access; approval from the ethic committee of Faculdade de Medicina do ABC (Santo André, São Paulo, Brazil) was ensured. The Brazilian association of patients with HAE distributed the survey by e-mail to associated patients all over the country, and responses were accepted within a period of 3 months after signing a consent form. Results: Ninety patients (67 women, 23 men; average age, 36.5 years) responded; the main findings were the following: 53 of 90 (64%) had no need of visiting emergency departments in the past 6 months; 71 of 90 (79%) reported life-threatening fear due to their diagnosis; 73 of 90 (83%) had other family members affected, but 54 of 73 of these affected relatives did not look for specific HAE treatment; and 26 of 90 (29%) reported death due to asphyxia or throat swelling in family members. Conclusion: Patients with HAE report understanding how severe their diagnosis represent, but they did not ponder how important their commitment to treatment may decrease the constant fear brought by the disease in its possible swelling crisis. Family data supported this conclusion.

Teaching communication skills in clinical settings: comparing two applications of a comprehensive program with standardized and real patients.

BACKGROUND: Communication is important for the quality of clinical practice, and programs have been implemented to improve healthcare providers' communication skills. However, the consistency of programs teaching communication skills has received little attention, and debate exists about the application of acquired skills to real patients. This study inspects whether (1) results from a communication program are replicated with different samples, and (2) results with standardized patients apply to interviews with real patients. METHODS: A structured, nine-month communication program was applied in two consecutive years to two different samples of healthcare professionals (25 in the first year, 20 in the second year). Results were assessed at four different points in time, each year, regarding participants' confidence levels (self-rated), basic communication skills in interviews with standardized patients, and basic communication skills in interviews with real patients. Data were analyzed using GLM Repeated-Measures procedures. RESULTS: Improvements were statistically significant in both years in all measures except in simulated patients' assessment of the 2008 group. Differences between the two samples were non-significant. Differences between interviews with standardized and with real patients were also non-significant. CONCLUSIONS: The program's positive outcomes were replicated in different samples, and acquired skills were successfully applied to real-patient interviews. This reinforces this type of program structure as a valuable training tool, with results translating into real situations. It also adds to the reliability of the assessment instruments employed, though these may need adaptation in the case of real patients.

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.

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.

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.

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.

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.

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.

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.