Adolescents' Perceptions About Healthy and Sustainable Diets: A Qualitative School-Based Study in Portugal.

In this qualitative study, we explored Portuguese adolescents' perceptions of diet, sustainability, and health through six focus group discussions (FGDs). Fifty-five adolescents (10-18 years) participated. FGDs focused on sustainability in food choices and its health impact, with our primary interest in their perceptions. Results showed a limited comprehension of "sustainable/sustainability," especially among younger participants. Those aware of sustainability recognized its diverse aspects, including health, economic, and ecological domains. Some adolescents recognized the link between health and sustainability in their diets, emphasizing the need for food literacy. These findings emphasize the importance of public health and sustainable policies among Portuguese adolescents.

Association of adverse childhood experiences with dietary patterns of school-age children: evidence from the birth cohort Generation XXI.

BACKGROUND: Adverse Childhood Experiences (ACEs) have been associated with health-risk behaviors and several chronic diseases in adulthood. However, the relationship between the exposure to ACEs and dietary patterns at school-age is unknown. OBJECTIVE: To investigate the association between ACEs and dietary patterns of 10-year-olds. METHODS: The study included 5034 children from the Generation XXI cohort, recruited in 2005/2006 in Porto, Portugal. ACEs were assessed through a self-administered questionnaire covering the first 10 years of life, quantified and grouped into 5 dimensions: "abuse", "school problems", "death/severe disease", "life changes", and "household dysfunction". Dietary patterns were identified by latent class analysis using data collected with a validated food frequency questionnaire. Five dietary patterns were studied: "low consumption", "energy-dense foods", "snacking", "intermediate consumption", and "healthier" (used as reference). Multinomial regression analyses were conducted, adjusted for child's sex, household income, family structure and mothers' age (odds ratio (OR), and 99% confidence intervals (99%CI). RESULTS: Most children were exposed to at least one ACE (96%), and approximately 27% had reported 6 or more ACEs throughout life. Those reporting 4-5 and ≥ 6 ACEs were more likely to follow the "Energy-dense foods" dietary pattern compared with those with no ACEs (OR=2.41, 99%CI = 1.00-5.77 and OR=2.65, 99%CI = 1.10-6.39, respectively). Children exposed to "abuse" in the first 10 years showed 28% higher odds of following the "low consumption" dietary pattern than following the "healthier" dietary pattern (OR=1.28, 99%CI = 1.00-1.63). CONCLUSIONS: Exposure to ACEs was associated with less healthy dietary patterns in school-aged children. Results suggest a cumulative effect of the adverse experiences resulting in a dietary pattern higher in energy-dense foods. Children with ACEs reported under the dimension of "abuse" seemed to have a reduced food consumption.

Effects of glyphosate herbicide ingestion on kidney function in rats on a balanced diet / Efeitos da ingestão do herbicida glifosato na função renal de ratos em uma dieta balanceada

Abstract Introduction: Glyphosate is the most widely used herbicide worldwide and in Brazil. There is currently increasing concern about the effects of glyphosate on human health. The Brazilian Institute for Consumer Protection showed data on the presence of glyphosate in some of Brazil's most consumed ultra-processed products. Currently, regulations on the upper limit for these residues in ultra-processed foods have yet to be established by the National Health Surveillance, and ultra-processed food consumption is independently associated with an increased risk of incident chronic kidney disease. Methods: Since an unbalanced diet can interfere with kidney function, this study aims to investigate the effect of daily intake of 5 mg/kg bw glyphosate in conjunction with a balanced diet and the possible impact on renal function in rats. Kidney function, kidney weight, markers of renal injury, and oxidative stress were evaluated. Results: There was a decrease in kidney weight. The main histopathological alterations in renal tissues were vacuolation in the initial stage and upregulation of the kidney injury marker KIM-1. Renal injury is associated with increased production of reactive oxygen species in mitochondria. Conclusion: This study showed changes in the kidney of rats exposed to a balanced diet with glyphosate, suggesting a potential risk to human kidney. Presumably, ultra-processed food that contain glyphosate can potentiate this risk. The relevance of these results lies in drawing attention to the need to regulate glyphosate concentration in ultra-processed foods in the future.

RESUMO Introdução: O glifosato é o herbicida mais utilizado no mundo e no Brasil. Atualmente, há uma preocupação crescente com os efeitos do glifosato na saúde humana. O Instituto Brasileiro de Defesa do Consumidor apresentou dados sobre a presença de glifosato em alguns dos produtos ultraprocessados mais consumidos no Brasil. Atualmente, as regulamentações sobre o limite máximo desses resíduos em alimentos ultraprocessados ainda não foram estabelecidas pela Vigilância Sanitária Nacional, e o consumo de alimentos ultraprocessados está indepen­dentemente associado a um risco maior de doença renal crônica incidente. Métodos: Como uma dieta desbalanceada pode interferir na função renal, este estudo tem como objetivo investigar o efeito da ingestão diária de 5 mg/kg pc de glifosato em conjunto com uma dieta equilibrada e o possível impacto na função renal em ratos. Foram avaliados função renal, peso dos rins, marcadores de lesão renal e estresse oxidativo. Resultados: Houve redução no peso dos rins. As principais alterações histopatológicas nos tecidos renais foram vacuolização no estágio inicial e regulação positiva do marcador de lesão renal KIM-1. A lesão renal está associada à produção aumentada de espécies reativas de oxigênio nas mitocôndrias. Conclusão: Esse estudo mostrou alterações nos rins de ratos expostos a uma dieta balanceada com glifosato, sugerindo um risco potencial ao rim humano. Presumivelmente, alimentos ultraprocessados que contenham glifosato podem potencializar esse risco. A relevância desses resultados está no fato de chamar a atenção para a necessidade de regulamentar a concentração de glifosato em alimentos ultraprocessados no futuro.

A high-resolution large-area detector for quality assurance in radiotherapy.

Hadron therapy is an advanced radiation modality for treating cancer, which currently uses protons and carbon ions. Hadrons allow for a highly conformal dose distribution to the tumour, minimising the detrimental side-effects due to radiation received by healthy tissues. Treatment with hadrons requires sub-millimetre spatial resolution and high dosimetric accuracy. This paper discusses the design, fabrication and performance tests of a detector based on Gas Electron Multipliers (GEM) coupled to a matrix of thin-film transistors (TFT), with an active area of 60 × 80 mm2 and 200 ppi resolution. The experimental results show that this novel detector is able to detect low-energy (40 kVp X-rays), high-energy (6 MeV) photons used in conventional radiation therapy and protons and carbon ions of clinical energies used in hadron therapy. The GEM-TFT is a compact, fully scalable, radiation-hard detector that measures secondary electrons produced by the GEMs with sub-millimetre spatial resolution and a linear response for proton currents from 18 pA to 0.7 nA. Correcting known detector defects may aid in future studies on dose uniformity, LET dependence, and different gas mixture evaluation, improving the accuracy of QA in radiotherapy.

An Innovative Approach for Tailoring Molecularly Imprinted Polymers for Biosensors-Application to Cancer Antigen 15-3.

This work presents a novel approach for tailoring molecularly imprinted polymers (MIPs) with a preliminary stage of atom transfer radical polymerization (ATRP), for a more precise definition of the imprinted cavity. A well-defined copolymer of acrylamide and N,N'-methylenebisacrylamide (PAAm-co-PMBAm) was synthesized by ATRP and applied to gold electrodes with the template, followed by a crosslinking reaction. The template was removed from the polymer matrix by enzymatic/chemical action. The surface modifications were monitored via electrochemical impedance spectroscopy (EIS), having the MIP polymer as a non-conducting film designed with affinity sites for CA15-3. The resulting biosensor exhibited a linear response to CA15-3 log concentrations from 0.001 to 100 U/mL in PBS or in diluted fetal bovine serum (1000×) in PBS. Compared to the polyacrylamide (PAAm) MIP from conventional free-radical polymerization, the ATRP-based MIP extended the biosensor's dynamic linear range 10-fold, improving low concentration detection, and enhanced the signal reproducibility across units. The biosensor demonstrated good sensitivity and selectivity. Overall, the work described confirmed that the process of radical polymerization to build an MIP material influences the detection capacity for the target substance and the reproducibility among different biosensor units. Extending this approach to other cancer biomarkers, the methodology presented could open doors to a new generation of MIP-based biosensors for point-of-care disease diagnosis.

Sleep duration is associated with appetitive traits in school-age years - results from the Generation XXI birth cohort.

Sleep may influence appetite regulation through physiological and neurocognitive pathways. However, the association between sleep and appetite in childhood has been scarcely reported, particularly using a prospective design. We aimed to test associations between sleep duration at 7 years of age (y) and appetitive traits at both 7 and 10 y. Participants are from the population-based birth cohort Generation XXI (Porto, Portugal), at 7 (n = 2437) and 10 y (n = 1938) follow-ups. Data on sleep was gathered at 7 y and, considering bedtime and get-up time, total mean sleep duration was calculated and further categorized according to the 10th and 90th percentiles. Appetitive traits were assessed at 7 and 10 y using the parent-reported Children's Eating Behaviour Questionnaire. Associations were tested through Generalized Linear Models (co-variates: child's sex; maternal age, education and pre-pregnancy body mass index at 7 y). At 10 y, associations were further adjusted for the respective appetitive trait at 7 y. Children slept a mean of 10.2 h/night, and 13% and 9% slept ≤9.5 and ≥ 11.0 h/night at 7 y, respectively. For each additional hour in sleep duration, children scored 0.078 (99%CI: -0.145; -0.011) lower on Food Responsiveness, 0.065 (99%CI: -0.129; -0.002) lower on Emotional Undereating and 0.096 (99%CI: -0.161; -0.032) lower on Food Fussiness. Lastly, children sleeping ≤9.5 h/night scored higher on Food Responsiveness (ß = 0.145 99%CI: 0.020; 0.271); while those sleeping ≥11.0 h/night scored lower on Food Fussiness (ß = -0.255 99%CI: -0.370; -0.079). No significant prospective associations were found. In conclusion, in 7 y children, sleep duration was cross-sectionally associated with lower scores on food approach (Food Responsiveness) and avoidant traits (Emotional Undereating and Food Fussiness). However, the magnitude of the associations was small and further studies are warranted.

Interaction of the antifungal ketoconazole and its diphenylphosphine derivatives with lipid bilayers: Insights into their antifungal action.

Ketoconazole (Ke) is an important antifungal drug, and two of its diphenylphosphinemethyl derivatives (KeP: Ph2PCH2-Ke and KeOP: Ph2P(O)CH2-Ke) have shown improved antifungal activity, namely against a yeast strain lacking ergosterol, suggesting alternative modes of action for azole compounds. In this context, the interactions of these compounds with a model of the cell membrane were investigated, using POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) large unilamellar vesicles and taking advantage of the intrinsic fluorescence of Ke, KeP and KeOP. Steady-state fluorescence spectra and anisotropy, including partition and aggregation studies, as well as fluorescence lifetime measurements, were carried out. In addition, the ability of the compounds to increase membrane permeability was assessed through carboxyfluorescein leakage. The membrane/water mole fraction partition coefficients (Kp,x): (3.31 ± 0.36) x105, (8.31 ± 1.60) x105 and (4.66 ± 0.72) x106, for Ke, KeP and KeOP, respectively, show that all three compounds have moderate to high affinity for the lipid bilayer. Moreover, KeP, and particularly KeOP interact more efficiently with POPC bilayers than Ke, which correlates well with their in vitro antifungal activity. Furthermore, although the three compounds disturb the lipid bilayer, KeOP is the quickest and most efficient one. Hence, the higher affinity and ability to permeabilize the membrane of KeOP when compared to that of KeP, despite the higher lipophilicity of the latter, points to an important role of Ph2P(O)CH2- oxygen. Overall, this work suggests that membrane interactions are important for the antifungal activity of these azoles and should be considered in the design of new therapeutic agents.

Sleep timing behaviour, sleep duration and adherence to obesogenic dietary patterns from pre-school to school age: results from the Portuguese birth cohort Generation XXI.

In an obesogenic environment, short sleeping may increase opportunistic eating. The timing of sleep might also influence the drive to eat. This study investigated the prospective association of sleep timing and duration with diet in 5286 children from the Portuguese birth cohort Generation XXI, evaluated at 4 and 7 years of age. At 4 years, sleep duration was categorised into ≤10 and >10 h. Four sleep timing categories were generated based on the median split for sleep-onset and -offset times: 'Early Sleep-Early Wake'; 'Early Sleep-Late Wake'; 'Late Sleep-Early Wake'; 'Late Sleep-Late Wake'. At 7 years, diet was obtained by a food frequency questionnaire and three dietary patterns were included: 'Healthier', 'Energy-Dense Foods (EDF)' and 'Snacking'. The Healthy Eating Index was used to evaluate diet quality. Multinomial logistic regression models and generalised linear models were performed. Children who had a late sleep, independently of the time of waking up, had higher odds of following the 'EDF' pattern, compared with the 'Healthier'. Boys who had late sleep and/or late wake had also higher odds of following the 'Snacking' pattern and had poorer diet quality. In both sexes, a late sleep or late wake were associated with a lower diet quality, compared to the group 'Early Sleep-Early Wake', and independently of nap behaviour. In boys, shorter sleep duration was associated with a poorer diet. In conclusion, pre-schoolers with late bedtimes or wake-up times have worse dietary patterns and poorer diet quality at the age of 7 years, which seems to be independent of sleep duration.

Onion (Allium cepa L.) Skin Waste Valorization: Unveiling the Phenolic Profile and Biological Potential for the Creation of Bioactive Agents through Subcritical Water Extraction.

Onion skin waste (OSW), the primary non-edible byproduct from onion processing, offers a renewable source of bioactive compounds. This study aims to valorize OSW through subcritical water extraction (SWE), aligning with a circular economy and biorefinery principles. SWE was carried out at 145 °C and 50 bar for 50 min in a discontinuous reactor, producing a phenolic-rich extract (32.3 ± 2.6 mg/g) dominated by protocatechuic acid (20.3 ± 2.5 mg/g), quercetin-4'-O-glucoside (7.5 ± 0.2 mg/g), and quercetin (3.2 ± 0.6 mg/g). Additionally, the extract contains sugars (207.1 ± 20.3 mg sucrose-Eq/g), proteins (22.8 ± 1.6 mg BSA-Eq/g), and free amino acids (20.4 ± 1.2 mg arginine-Eq/g). Its phenolic richness determines its scavenging activity against ●NO and O2●- radicals and its α-glucosidase and aldose-reductase inhibition without affecting α-amylase. Notably, the extract demonstrates significant α-glucosidase inhibition (IC50 = 75.6 ± 43.5 µg/mL), surpassing acarbose (IC50 = 129.5 ± 1.0 µg/mL) in both pure enzyme and cell culture tests without showing cytotoxicity to AGS, HepG2, and Caco-2 human cell lines. The extract's bioactivity and nutritional content make it suitable for developing antioxidant and antidiabetic nutraceutical/food components, highlighting SWE's potential for OSW valorization without using organic solvents.

Appetitive traits from childhood to adolescence: Analysis of their stability, derivation of trajectory profiles, and associated characteristics.

This study aimed to assess the potential stability of appetitive traits from childhood to early adolescence, identify groups of individuals with distinct trajectories for these traits, and explore their association with other child and family characteristics. Participants were 5040 children from the Generation XXI cohort. Appetitive traits were assessed with the Children's Eating Behaviour Questionnaire (CEBQ) at ages seven, 10, and 13 (eight subscales). Mixed-effect models estimated individual trajectories of appetitive traits and Gaussian mixture models identified groups following different trajectories (appetitive trait trajectory profiles). Appetitive traits showed moderate-to-high stability across the three ages (intra-class correlation coefficients:0.66-0.83); most of the variance observed across time were due to persistent individual differences rather than age-related changes. Six appetitive trait trajectory profiles were identified: 'Moderate appetite' (scores close to the average) (29% of children), 'Small to moderate appetite' (lowest food approach and emotional eating) (26%), 'Increasing appetite' (increasing food approach) (15%), 'Avid appetite' (highest food approach and lowest food avoidance) (12%), 'Smallest appetite' (highest food avoidance and low food approach) (10%), and 'Small appetite but increasing' (decreasing high food avoidance and Desire to Drink) (8%). In multinomial logistic regression, these profiles were associated with different child and family characteristics. Compared to children with a 'Moderate appetite' profile, those with higher BMI, who desired a thinner body, whose mothers were younger, had lower education, higher pre-pregnancy BMI (OR = 1.07; 95%CI:1.04,1.09), smoked during pregnancy (OR = 1.51; 95%CI:1.21,1.90), and used more restrictive feeding practices (OR = 1.79; 95%CI:1.57,2.03) had increased odds of belonging to the 'Avid Appetite'. In conclusion, distinct appetitive trait trajectory profiles emerged, differentiating individuals with avid and small appetites. These findings have implications for identifying children at higher risk for obesogenic profiles.

Effects of glyphosate herbicide ingestion on kidney function in rats on a balanced diet.

INTRODUCTION: Glyphosate is the most widely used herbicide worldwide and in Brazil. There is currently increasing concern about the effects of glyphosate on human health. The Brazilian Institute for Consumer Protection showed data on the presence of glyphosate in some of Brazil's most consumed ultra-processed products. Currently, regulations on the upper limit for these residues in ultra-processed foods have yet to be established by the National Health Surveillance, and ultra-processed food consumption is independently associated with an increased risk of incident chronic kidney disease. METHODS: Since an unbalanced diet can interfere with kidney function, this study aims to investigate the effect of daily intake of 5 mg/kg bw glyphosate in conjunction with a balanced diet and the possible impact on renal function in rats. Kidney function, kidney weight, markers of renal injury, and oxidative stress were evaluated. RESULTS: There was a decrease in kidney weight. The main histopathological alterations in renal tissues were vacuolation in the initial stage and upregulation of the kidney injury marker KIM-1. Renal injury is associated with increased production of reactive oxygen species in mitochondria. CONCLUSION: This study showed changes in the kidney of rats exposed to a balanced diet with glyphosate, suggesting a potential risk to human kidney. Presumably, ultra-processed food that contain glyphosate can potentiate this risk. The relevance of these results lies in drawing attention to the need to regulate glyphosate concentration in ultra-processed foods in the future.

Evaluation of the Antiproliferative Properties of CpRu Complexes Containing N-Methylated Triazaphosphaadamantane Derivatives.

Piano-stool-{CpRu} complexes containing 1,3,5-triaza-7-phosphaadamantane (PTA), N-methyl-1,3,5-triaza-7-phosphaadamantane (mPTA), and 3,7-dimethyl-1,3,7-triaza-5-phosphabyciclo[3.3.1]nonane (dmoPTA) were evaluated as drugs against breast cancer. The evaluated compounds include two new examples of this family, the complexes [RuCp(DMSO-κS)(HdmoPTA)(PPh3)](CF3SO3)2 (8) and [RuCp(PPh3)2-µ-dmoPTA-1κP-2κ2N,N'-PdCl2](CF3SO3) (11), which have been synthesized and characterized by NMR, IR, and single-crystal X-ray diffraction. The cytotoxic activity of compounds was evaluated against MDA-MB-231 breast cancer cells, and the three most active complexes were further tested against the hormone-dependent MCF-7 breast cancer cell line. Their cell death mechanism and ruthenium uptake were also evaluated, as well as their binding ability to human serum albumin.

The Nephroprotective Effects of the Allogeneic Transplantation with Mesenchymal Stromal Cells Were Potentiated by ω3 Stimulating Up-Regulation of the PPAR-γ.

Mesenchymal stromal cells (MSCs) obtained from bone marrow are a promising tool for regenerative medicine, including kidney diseases. A step forward in MSCs studies is cellular conditioning through specific minerals and vitamins. The Omega-3 fatty acids (ω3) are essential in regulating MSCs self-renewal, cell cycle, and survival. The ω3 could act as a ligand for peroxisome proliferator-activated receptor gamma (PPAR-γ). This study aimed to demonstrate that ω3 supplementation in rats could lead to the up-regulation of PPAR-γ in the MSCs. The next step was to compare the effects of these MSCs through allogeneic transplantation in rats subjected to unilateral ureteral obstruction (UUO). Independent of ω3 supplementation in the diet of the rats, the MSCs in vitro conserved differentiation capability and phenotypic characteristics. Nevertheless, MSCs obtained from the rats supplemented with ω3 stimulated an increase in the expression of PPAR-γ. After allogeneic transplantation in rats subjected to UUO, the ω3 supplementation in the rats enhanced some nephroprotective effects of the MSCs through a higher expression of antioxidant enzyme (SOD-1), anti-inflammatory marker (IL-10), and lower expression of the inflammatory marker (IL-6), and proteinuria.

Long COVID Symptoms in Non-Hospitalised Patients: A Retrospective Study.

INTRODUCTION: The COVID-19 pandemic has presented numerous challenges to healthcare systems. As the number of affected individuals continues to rise, it is crucial to find preventive, diagnostic, and therapeutic approaches. This study aims to describe different COVID-19 sequelae within a Primary Health Care population. METHODS: A retrospective cohort study was conducted in adults diagnosed with COVID-19 from March 2020 to April 2022, excluding pregnant women, minors, nursing home residents, hospitalizations, and deaths. Data was gathered from surveillance records on the Trace COVID-19® platform, a pre-set original questionnaire (which included the Portuguese version of the World Health Organization's Quality of Life Assessment Instrument), and, if needed, patient electronic health records. Information on sociodemographic and clinical characteristics of acute COVID-19 was collected along with long COVID symptoms. RESULTS: This study included 284 patients, aged 19 to 99 years old. The five most prevalent acute COVID-19 symptoms were fever (50.0%), tiredness (48.2%), myalgias (44.7%), dry cough (37.7%) and odynophagia (36.3%). Symptoms related to the neurological system (23.2%) and tiredness (22.9%) were the most prevalent in long COVID symptoms. Acute tiredness and arthralgia were associated with all long COVID outcomes. The associations between acute COVID-19 symptoms with long COVID outcomes were stronger for anosmia [OR = 5.07, 95% confidence interval (CI) 2.49 - 10.36, p < 0.001] on a neurological chapter, acute tiredness for long lasting tiredness (OR = 4.07, 95% CI 2.07 - 8.02, p = 0.041), fatigue for muscles and/or bones chapter (OR = 7.55, 95% CI 3.06 - 18.66, p < 0.001), tiredness on an endocrine/hormonal chapter (OR = 6.54, 95% CI 2.37 - 18.04, p < 0.001), dyspnea for respiratory symptoms (OR = 5.67, 95% CI 1.92 - 16.74, p = 0.002) and fever for stomach or intestine symptoms (OR = 8.06, 95% CI 2.55 - 25.47, p < 0.001). Almost all quality of life dimensions were negatively associated with the number of long COVID symptoms. CONCLUSION: A higher number of acute symptoms, as well as the presence of specific COVID-19 symptoms were associated with reported symptoms ≥ 12 weeks after infection. In the studied population, an increased number of symptoms in both acute and long COVID had a significant negative impact on the perception of overall quality of life. The identification of these relationships could provide a new perspective for post-COVID care.

Appetitive traits and food groups consumption in school-aged children: prospective associations from the Generation XXI birth cohort.

PURPOSE: Appetite can influence children's dietary choices; however, this relationship in school-aged children is still unclear. We aimed to explore the prospective associations between child appetitive traits at age 7 and food consumption at 10 years of age. METHODS: The study included 3860 children from the Generation XXI birth cohort, recruited in 2005/2006 in Porto, Portugal. The Children's Eating Behaviour Questionnaire was used to evaluate children's appetitive traits at 7 years. Food consumption was measured at 10 years through a validated Food Frequency Questionnaire. Logistic regression models were performed and adjusted for possible confounders. RESULTS: Children with greater Enjoyment of Food at 7 years were 36% more likely to eat fruits ≥ 2 times/day and 54% more likely to eat vegetables > 2.5 times/day at 10 years compared to those with less frequent consumption. Children who ate more in response to negative emotions had higher odds of consuming energy-dense foods (OR = 1.33; 99% CI 1.13-1.58) and salty snacks (OR = 1.28; 99% CI 1.08-1.51) 3 years later. Those with less ability to adjust intake (higher Satiety Responsiveness) and more selective about foods (higher Food Fussiness) at 7 years were less likely to consume vegetables frequently, and were more likely to consume energy-dense foods and sugar-sweetened beverages. CONCLUSIONS: Children's appetitive traits at 7 years were associated with the consumption of several food groups at 10 years of age. Eating more in response to negative emotions (Emotional Eating), with less ability to adjust intake (Satiety Responsiveness) and more food selectivity (Food Fussiness) were associated with worse dietary choices (in general, lower fruit and vegetables, and higher energy-dense foods and sugar-sweetened beverages consumption). LEVEL OF EVIDENCE: Level III: Evidence obtained from well-designed cohort or case-control analytic studies.

Machine learning for adaptive deep brain stimulation in Parkinson's disease: closing the loop.

Parkinson's disease (PD) is the second most common neurodegenerative disease bearing a severe social and economic impact. So far, there is no known disease modifying therapy and the current available treatments are symptom oriented. Deep Brain Stimulation (DBS) is established as an effective treatment for PD, however current systems lag behind today's technological potential. Adaptive DBS, where stimulation parameters depend on the patient's physiological state, emerges as an important step towards "smart" DBS, a strategy that enables adaptive stimulation and personalized therapy. This new strategy is facilitated by currently available neurotechnologies allowing the simultaneous monitoring of multiple signals, providing relevant physiological information. Advanced computational models and analytical methods are an important tool to explore the richness of the available data and identify signal properties to close the loop in DBS. To tackle this challenge, machine learning (ML) methods applied to DBS have gained popularity due to their ability to make good predictions in the presence of multiple variables and subtle patterns. ML based approaches are being explored at different fronts such as the identification of electrophysiological biomarkers and the development of personalized control systems, leading to effective symptom relief. In this review, we explore how ML can help overcome the challenges in the development of closed-loop DBS, particularly its role in the search for effective electrophysiology biomarkers. Promising results demonstrate ML potential for supporting a new generation of adaptive DBS, with better management of stimulation delivery, resulting in more efficient and patient-tailored treatments.

Integrating morphological, biochemical, behavioural, and molecular approaches to investigate developmental toxicity triggered by tebuthiuron in zebrafish (Danio rerio).

Tebuthiuron (TBU), a phenylurea herbicide, is widely applied in agricultural and non-agricultural soils. Because TBU resists degradation, it can contaminate water and reach the biota once it is released into the environment. However, the potential toxic effects of TBU on aquatic developing organisms have been poorly studied. By taking advantage of the early-life stages of zebrafish (Danio rerio), we have combined morphological, biochemical, behavioural, and molecular approaches to investigate the developmental toxicity triggered by environmentally relevant concentrations (from 0.1 to 1000 µg/L) of TBU. Exposure to TBU did not elicit morphological abnormalities but it significantly delayed hatching. In addition, TBU altered the frequency of tail coils in one-day post-fertilization (dpf) old embryos. Moreover, TBU exposure during four days significantly inhibited the whole body AChE activity of larvae. At the molecular level, TBU did not significantly affect the mRNA levels of four genes (elavl3, gfap, gap43, and shha) that play key roles during the neurodevelopment of zebrafish. By assessing the motor responses to repeated light-dark stimuli, 6 dpf larvae exposed to TBU displayed hyperactivity, showing greater travelling distance during the dark periods. Our categorization of swimming speed revealed an interesting finding - after the light was turned off, the exposed larvae abandoned the freezing mode (<2 mm/s) and travelled mainly at cruising speed (2-20 mm/s), showing that the larval hyperactivity did not translate into higher swimming velocity. Overall, our results offer new insights into the TBU toxicity to developing organisms, namely effects in AChE activity and hyperactivity, providing support data for future studies considering environmental risk assessment of this herbicide.

Opposing effects of ecdysone signaling regulate neuroblast proliferation to ensure coordination of brain and organism development.

Growth regulation must be robust to ensure correct final size, but also adaptative to adjust to less favorable environmental conditions. Developmental coordination between whole-organism and the brain is particularly important, as the brain is a critical organ with little adaptability. Brain growth mainly depends on neural stem cell (NSC) proliferation to generate differentiated neural cells, it is however unclear how organism developmental progression is coordinated with NSCs. Here we demonstrate that the steroid hormone ecdysone plays a multi-step, stage specific role in regulating Drosophila NSCs, the neuroblasts. We used animals that are unable to synthesize ecdysone, to show that the developmental milestone called "critical weight peak", the peak that informs the body has reached minimum viable weight to survive metamorphosis, acts a checkpoint necessary to set neuroblast cell cycle pace during larval neurogenesis. The peaks of ecdysone that occur post-critical weight are no longer required to maintain neuroblast division rate. We additionally show that in a second stage, at the onset of pupariation, ecdysone is instead required to trigger neuroblast's proliferation exit and consequently the end of neurogenesis. We demonstrate that, without this signal from ecdysone, neuroblasts lose their ability to exit proliferation. Interestingly, although these neuroblasts proliferate for a longer period, the number of differentiated neurons is smaller compared to wild-type brains, suggesting a role for ecdysone in neuron maintenance. Our study provides insights into how neural stem cells coordinate their division rate with the pace of body growth, identifying a novel coordination mechanism between animal development and NSC proliferation.

An Antibody-Based Survey of Toxoplasma gondii and Neospora caninum Infection in Client-Owned Cats from Portugal.

Toxoplasma gondii and Neospora caninum are obligate intracellular protozoan parasites infecting a wide range of hosts worldwide. However, information on the epidemiology of toxoplasmosis and neosporosis in cats from Portugal is limited. Thus, this study aims to evaluate anti-T. gondii and anti-N. caninum seroprevalence in client-owned cats from Portugal and to identify risk factors using a panel of well-characterized sera. A total of 183 domestic cats were sampled and screened for antibodies against T. gondii and N. caninum using commercial ELISA assays, and their owners answered an online questionnaire designed to obtain background information. The overall anti-T. gondii and anti-N. caninum seroprevalences were 13.1% (CI: 8.97-18.77) and 3.8% (CI: 1.87-7.68), respectively. Univariate analysis revealed that living strictly indoors was a significant protection factor (cOR: 0.053; CI: 0.005-0.627), and the presence of a chronic disease a significant risk factor (cOR: 3.106; CI: 1.062-9.082) to T. gondii seroprevalence. When performing multivariate analysis, only chronic disease (aOR: 57.527; CI: 1.7-1976.7) and seropositivity to N. caninum (aOR: 7.929; CI:0.8-82.9) were found to be a significant risk factor to anti-T. gondii antibodies. To the best of our knowledge, this is the first report of N. caninum seropositivity in cats from Portugal.