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Objectives Antihypertensives reduce the risk of myocardial infarction and stroke. Restrictions during the COVID-19 pandemic limited access to healthcare, which may have had a negative impact on drug prescribing. This study aimed to assess the effect of the COVID-19 pandemic on the initiation of antihypertensive drugs.Design Interrupted time series study using a segmented linear regression model.Setting Swedish population assessed through linked national healthcare registers.Participants 720 300 new users of antihypertensives.Intervention March 2020, COVID-19 pandemic onset.Main outcomes measures The change in the initiation of antihypertensives expressed as monthly cumulative incidence, stratified by age and sex. Data on dispensed prescriptions of diuretics, beta-blockers, calcium channel blockers, ACE inhibitors (ACEi) and angiotensin receptor blockers were extracted from the Swedish Prescribed Drug Register, from March 2018 to November 2021. Initiation (new use) was defined as having no previous dispensations before March 2019. Monthly cumulative incidence in March 2019–November 2021 was calculated as the number of patients initiating each drug class in each month divided by the population.Results The start of the pandemic was associated with an immediate drop in the initiation of any antihypertensive, but no sustained effects were observed, as the incidence continued to increase in the postinterruption period by +0.02% each month in both sexes. The immediate drop was statistically significant for ACEi in both sexes and all antihypertensive classes except diuretics in patients >65 years. А significant postintervention trend change was observed for initiation of diuretics (+0.013% overall), driven mainly by a significant increase in patients >65 years. Similar findings were also observed for diuretics in females (+0.02%) and ACEi (+0.03%) in patients >65 years.Conclusions The pandemic had an immediate negative short-term effect, but we found no major long-term negative influence of the COVID-19 pandemic on initiation of any type of antihypertensive drugs.

One Health, as a multi-disciplinary approach, considers animal, human, and environmental health. Serbia continuously records high rates of antimicrobial resistance, with a knowledge gap on practices regarding veterinary antibiotic use, as no standardized data regarding veterinary consumption of antibiotics that would allow for temporal or spatial comparison are available in Serbia. This study aimed to describe the sales of veterinary antibiotics in Serbia. Aggregated wholesale data on veterinary drug sales were retrieved from the annual reports available from the Medicines and Medical Devices Agency of the Republic of Serbia for a period between 2017 and 2020. Veterinary use was analyzed using standard European Medicines Agency proposed methodology and expressed in milligrams of active substance per population correction unit (mg/PCU). Overall, there has been a 13% increase in aggregated sales, in mg/PCU, of antibiotic veterinary medicinal products (VMPs) for food-producing animals in Serbia between 2017 and 2020. With sales of around 110 mg/PCU in 2020, Serbia would have ranked ninth in Europe. In 2020, the overall highest-selling antibiotic classes were penicillins (27.62 mg/PCU), tetracyclines (27.54 mg/PCU), and aminoglycosides (12.8 mg/PCU), accounting for 61.9% of the total sales of antibiotic VMPs for food-producing animals, in mg/PCU. An increase in the use of macrolides and lincosamides and a decrease in the use of penicillins and the group classified as “other antibacterials” was noted. The current study identified an increase in the sales of veterinary antibiotics in Serbia and pointed out several potential problem areas.

Textile based sensors have gained tremendous attention in moisture sensing. Moisture monitoring is crucial in wound healing. To promote the healing process, it is essential to maintain an optimal level of moisture while limiting unnecessary dressing changes. The objective of this research was to test how well a textile moisture sensor can detect moisture from the body and wound fluid when attached to the dressing. To this end, a 3D interdigitated capacitive structure was embroidered with silver conductive threads on the textile substrate, and a bandage was placed in the centre of the multilayer structure. When compared to traditional planar interdigitated structures, the main innovation of the proposed 3D capacitive structure lies in a larger surface area for interaction with the surrounding environment, leading to enhanced sensitivity to changes in capacitance with the respect to the moisture. The 3D structure of the bandage increased the ratio between electrodes and surface area to impact the surface charge sensitivity towards the adsorbed charges of the wound and body fluid. To observe the performance of the sensor, the bandage was exposed to simulated body fluid and wound fluid. Between dry and wet conditions, the sensor can detect capacitance differences of several orders of magnitude. The threshold volume for the 3D bandage was 30 μL to 50 μL, depending on the type of biofluids. The capacitive bandage integration with the inductor was tested at high frequencies (1–400 MHz). The shift in impedance was observed for the tested fluids. Finally, to compare sensing properties of the proposed structure against the previously reported designs, a bandage sensitivity was checked for three different configurations: (a) the proposed 3D bandage, (b) a 2D bandage, composed of textile substrate with both electrodes embroidered on top of bandage, and (c) classical interdigital structure without bandage composed of textile with embroidered electrodes on the top of it. The sensitivity of the 3D bandage for simulated body fluid and wound fluid is >6.6% and 7.4%, respectively, higher than the other two structures. The integration of the proposed textile-based sensor into a bandage could facilitate wound care and have a significant impact on efficacy for patients.

Introduction: Surgical training traditionally adheres to the apprenticeship paradigm, potentially exposing trainees to an increased risk of complications stemming from their limited experience. To mitigate this risk, augmented and virtual reality have been considered, though their effectiveness is difficult to assess. Research question: The PASSION study seeks to investigate the improvement of manual dexterity following intensive training with neurosurgical simulators and to discern how surgeons' psychometric characteristics may influence their learning process and surgical performance. Material and methods: Seventy-two residents were randomized into the simulation group (SG) and control group (CG). The course spanned five days, commencing with assessment of technical skills in basic procedures within a wet-lab setting on day 1. Over the subsequent core days, the SG engaged in simulated procedures, while the CG carried out routine activities in an OR. On day 5, all residents' technical competencies were evaluated. Psychometric measures of all participants were subjected to analysis. Results: The SG demonstrated superior performance (p

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Dyslipidemia and obesity are recognized as two of the major global health issues and main risk factors for coronary heart disease and cerebrovascular disease. In recent years, carob has shown certain antioxidant and anti-dyslipidemic potential. In this study, Wistar rats were fed with a standard and cholesterol-enriched diet and treated orally with carob extract and simvastatin for four weeks. After sacrifice, blood samples were collected for biochemical analysis, and liver tissue was taken for histological and immunohistochemical assessment. Weight gain was significantly higher in groups fed with cholesterol-fortified granules; total cholesterol was found to be significantly lower in the hypercholesterolemic groups treated with simvastatin and simvastatin/carob combined regimens compared with hypercholesterolemic animals treated with saline (p < 0.05). The same was true for low-density lipoprotein cholesterol and the LDL/HDL ratio (p < 0.05). Adiponectin was remarkably higher in animals treated with simvastatin compared to all other groups (p < 0.05). Leptin was significantly lower in groups treated with carob and simvastatin compared to the hypercholesterolemic group treated with saline (p < 0.05). Carob/simvastatin co-administration reduced hepatocyte damage and improved liver morphology. A study confirmed the anti-dyslipidemic, anti-obesity, and hepatoprotective potential of carob pulp alone or in combination with simvastatin in the treatment of high-fat diet-fed rats.

Background and Objectives: This study aimed to examine the efficacy of tapentadol immediate release (IR) and morphine hydrochloride in the treatment of acute postoperative pain after total abdominal hysterectomy, as well as to examine the frequency of opioid-related side effects in observed patients. Materials and Methods: The prospective observational study was conducted over five months, and it included a total number of 100 patients. The two cohorts had different types of postoperative analgesia, and the effects were observed for 24 h postoperatively, by following the pain scores on NRS (Numerical Pain Scale), contentment with analgesia, and opioid-related side effects. Results: Statistical significance was found when assessing pain 24 h after surgery while coughing, where patients in the tapentadol IR group had significantly higher mean pain scores (p < 0.01). The subjective feeling of satisfaction with postoperative analgesia was statistically significant in the tapentadol IR group (p = 0.005). Vertigo appeared significantly more in patients from the morphine group (p = 0.03). Conclusions: Tapentadol IR (immediate release) and morphine hydrochloride are both effective analgesics used in the first 24 h after total transabdominal hysterectomy. Overall satisfaction of patients with analgesia was good. The frequency of side effects was higher in the morphine group, with statistical significance regarding the vertigo.

IntroductionThere is limited data on the awareness and use of synthetic cannabinoids (SCs) in high-risk population in Serbia, despite SCs becoming more and more common at illicit drug market.AimThis pilot study aimed to examine the awareness and prevalence of use of SCs in patients with an opioid-use disorder and to identify patient characteristics and other factors associated with SCs use.Patients and methodsThis cross-sectional study was conducted at the Clinic for Psychiatry, Clinical Center Vojvodina, Serbia, the largest tertiary health care institution in this region of the country. All patients hospitalized due to the treatment of opioid dependence during November and December 2017 were included (response rate 100%), and filled-out an anonymous questionnaire specifically developed for the purpose of this study. Differences between patients reporting SCs use and those who did not were compared using chi-square test with values of p

Objectives To determine rate of blood pressure (BP) control and to analyse patient-related, medication-related and healthcare system-related factors associated with poor BP control in outpatients with hypertension (HT).Design Cross-sectional study.Setting Two study sites with different levels of healthcare (primary healthcare (PHC) and secondary level of healthcare (SHC)) in Vojvodina, Northern Serbia.Participants A total of 581 patients (response rate 96.8%) visiting their primary care physician between July 2019 and June 2020 filled out a pretested semistructured questionnaire and had a BP reading during their regular appointments.Primary and secondary outcome measures Data on demographics, medication, BP control (target systolic BP≤140 mm Hg and∕ or diastolic BP≤90 mm Hg) and knowledge on HT was collected. Based on the median of knowledge score, patients were classified as having poor, average and adequate knowledge.Results Majority of the respondents (74.9%) had poorly controlled BP and had HT longer than 10 years. Larger number of patients at PHC site was managed with monotherapy while at the SHC majority received three or more antihypertensive drugs. Respondents from SHC showed a significantly lower knowledge score (9, 2–15) compared with the respondents from PHC (11, 4–15, p=0.001). The share of respondents with adequate knowledge on HT was significantly higher in the group with good BP control (26% and 9.2%, respectively). In a multivariate regression analysis, factors associated with poor BP control were knowledge (B=−1.091; p

IntroductionOne of the most common oral diseases affecting children is early childhood caries (ECC). The link between oxidative stress and ECC has been proven in numerous clinical studies. Technical and biological variability were so high in most of the studies that none of the markers have yet been proven suitable for routine clinical use. This study aimed to evaluate the antioxidant status and the levels of leptin and adiponectin in saliva of children with severe early childhood caries (S-ECC).MethodsMorning unstimulated saliva samples were collected from children (n = 40, 0–6 years old) for the evaluation of oxidative stress which were measured by total antioxidant capacity (TAC), and by the ferric reducing antioxidant power (FRAP) assays, as well as to assess the salivary levels of leptin and adiponectin. FRAP, TAC, leptin and adiponectin concentrations were evaluated in S-ECC group (n = 31) and caries free group CF (n = 9). All results were analyzed based on age and sex.ResultsOverall median salivary leptin and adiponectin levels were 5.59 pg/mL and 24.86 ng/mL, respectively. Significantly lower leptin levels were observed in saliva of caries free children (4.66 pg/mL) than in the S-ECC group (6.64 pg/mL, p < 0.01). No significant difference was observed for adiponectin levels (S-ECC and CF, 25.31 and 23.2 ng/mL, respectively, p = 0.961). TAC and FRAP values of saliva had similar values in children with S-ECC and caries free children. TAC and FRAP values also remained stable with the age of the children, without significant differences with respect to sex.ConclusionThe increased concentrations of leptin in saliva of children with S-ECC suggests that leptin may play a role in inflammatory and immune responses in the development of early childhood caries.

The global prevalence of dyslipidemia (elevated plasma levels of total cholesterol, LDL-Cholesterol, triglycerides, and lower plasma levels of HDL-Cholesterol) is constantly on the rise. Lately, carob pulp has been recognized as an effective natural product for the treatment of dyslipidemia. The two main components of the carob pulp, polyphenols, and insoluble fiber are believed to have beneficial effects on lipid metabolism. Studies on humans and animals confirmed its lipid-lowering effects. Several mechanisms have been proposed to explain this phenomenon, namely by affecting three organ systems: 1) gastrointestinal tract, 2) liver and 3) adipose tissue. Also, carob products have antioxidative, anti-inflammatory, and vascular-protective activity.

The framework of this study was a comprehensive investigation of Morus nigra L. extracts, with the aim to establish the correlation between chemical composition and antioxidant/hepatoprotective activity of a series of black mulberry extracts obtained from aerial parts of the plant. Black mulberry leaf (MLEE), bark (MBEE), juice (MJ) and fresh fruit (MFEE) extracts were obtained using the conventional Soxhlet extraction, while the supercritical CO2 extraction procedure was employed for preparation of the seed oil (MSO). Analysis of the chemical composition was performed using spectrophotometric, HPLC and GC methods. For the evaluation of antioxidant activity, in vitro FRAP and DPPH assays were applied. In Haan strain NMRI mice with streptozotocin-induced oxidative stress, in vivo antioxidant activity and liver tissue integrity were examined. The content of polyphenolic compounds was the highest in MBEE (68.3 ± 0.7 mgGAE/g) with the most abundant compounds being polyphenolic acids, followed by MLEE (23.4 ± 0.5 mgGAE/g) with the flavonoids isoquercetin and rutin being present in a significant amount. An analysis of MSO revealed a high content of γ-linoleic acid. The highest antioxidant activity in vitro (FRAP and DPPH) was observed for MLEE, MBEE and MSO. Beneficial effects were confirmed in vivo, with lower values of hepatosomatic index, potentiation of the activity of the enzymes superoxide dismutase and catalase, a lower rate of lipid peroxidation and reduced positivity for the P450 enzyme in animals treated with MLEE, MBEE and MSO. Black mulberry leaf and bark extracts as well as seed oil exhibited significant antioxidant activity. Apart from the confirmed biological properties of the fruit and leaf extracts, the observed activities of black mulberry seed oil and bark extract imply its importance as a sustainable source of phytochemicals.

The dose-response relationship of sildenafil effects on cardiac function is not completely elucidated. The aim of this study was to assess the effects of different doses of sildenafil on coronary flow and oxidative stress in isolated rat hearts. Coronary flow and markers of oxidative stress, including nitrite outflow, and superoxide anion production in coronary effluent, were determined for isolated rat hearts. The experiments were performed during control conditions and in the presence of sildenafil (10, 20, 50, 200 nM) alone or with Nω-nitro-L-arginine monomethyl ester (L-NAME) (30 μM). Sildenafil was shown to result in a significant increase in coronary flow at lower coronary perfusion pressure (CPP) values at all administered doses, whereas, with an increase in CPP, a reduction in coronary flow was observed. An increase in nitric oxide (NO) was most pronounced in the group treated with the lowest dose of sildenafil at the highest CPP value. After the inhibition of the NO-cyclic guanosine monophosphate (cGMP) signaling (NOS) system by L-NAME, only a dose of 200 nM sildenafil was high enough to overcome the inhibition and to boost release of O2−. That effect was CPP-dependent, with statistical significance reached at 80, 100 and 120 mmHg. Our findings indicate that sildenafil causes changes in heart vasculature in a dose-dependent manner, with a shift from a vasodilatation effect to vasoconstriction with a pressure increase. The highest dose administered is capable of producing superoxide anion radicals in terms of NOS system inhibition.

This research aimed to examine the effects of pre-treatment with basil extract, prepared as an infusion, on acetaminophen-induced acute liver injury in rats. In vitro analysis of total phenolic, flavonoid content, and antioxidant activity was performed by spectrophotometric methods. Effects of basil extract on oxidative stress parameters, biochemical markers of liver injury, and liver morphology were determined in an in vivo model of acetaminophen-induced liver injury in Wistar rats. Total phenolic content was 52.61 ± 1.35 mg GAE/g of DE, and flavonoid content was 0.5 ± 0.2 mg QE/g of DE. IC50 values ranged from 0.22 to 45.76 μg/ml for DPPH radical, OH radical, H2O2 and lipid peroxidation. Ascorbic acid was used as a positive control. The extract lowered the intensity of lipid peroxidation and potentiated the activity of antioxidant enzymes. In addition, serum levels of aspartate aminotransferase and alanine aminotransferase were significantly lower in basil extract-treated animals in comparison to respective controls.

The complex issue of antibacterial resistance (ABR) requires actions taken with the One Health approach, involving both human and veterinarian medicine. It can spread from animals to humans through the food chain or through direct contact. Health profession students, as the future antibiotic providers, can greatly impact antibiotic-related issues in the future. The study was conducted to evaluate knowledge, attitudes and practice of future antibiotic prescribers in relation to judicious use of antibiotics. This cross-sectional, questionnaire-based study was performed on 400 students of health professions who were allowed to prescribe antibiotics of the University of Novi Sad, Serbia. Students of medicine and students of dentistry showed a significantly higher knowledge score compared to students of veterinary medicine (p = 0.001). Multivariate regression identified predictors of adequate antibiotic knowledge: being a female student (B = 0.571; p = 0.020), higher grade average (B = 1.204; p = 0.001), students of medicine (B = 0.802; p = 0.006) and dentistry (B = 0.769; p = 0.026), and students who used a complete package of antibiotics during the last infection (B = 0.974; p = 0.001) or for the period recommended by the doctor (B = 1.964; p = 0.001). Out of the total sample, self-medication was reported among 42.8% of students. The identified predictors of self-medication were: more frequent (B = 0.587; p = 0.001) and irregular (B = 0.719; p = 0.007) antibiotic use, taking antibiotics until symptoms disappeared (B = 2.142; p = 0.001) or until the bottle was finished (B = 1.010; p = 0.001) during the last infection. It seems prudent to reevaluate the educational curricula regarding antibiotic use and ABR of prospective prescribers in Serbia.

This study aimed to determine and describe the prevalence of combination antibiotics dispensed in outpatients with health insurance in Syria. Data on all dispensed medicines between June 2018 and May 2019 for 81,314 adults were obtained, and medicines belonging to the J01 group of the World Health Organization (WHO) anatomical therapeutic classification (ATC) were included in the analysis. Prescriptions were stratified according to the number of antibiotics, age, and sex. Antibiotic utilization was expressed as the number of prescriptions per 1000 persons per year. Out of 59,404 prescriptions for antibiotics, 14.98% contained antibiotic combinations, distributed to 22.49% of the patients. The prevalence of dispensing antibiotic combinations was higher in female patients (23.00%), and the youngest (18–30 years, 26.19%) and oldest age groups (>70 years, 25.19%). The antibiotics most commonly combined were co-amoxiclav, second- and third-generation cephalosporins, and macrolides. Over 60% of the combinations contained ceftriaxone alone or in combination with sulbactam. The present study shows an alarmingly widespread prescription of antibiotic combinations, posing a risk to global health by promoting resistance development.

La creciente preocupación por la contaminación generada por los plásticos derivados del petróleo representa uno de los desafíos ambientales más apremiantes a nivel global en la actualidad. El uso generalizado de plásticos en una amplia gama de productos, combinado con una gestión inadecuada de los residuos, ha dado lugar a una acumulación masiva de estos materiales en entornos naturales como océanos, ríos, suelos y diversos ecosistemas. Esta problemática no solo afecta la biodiversidad y la calidad de vida de las comunidades, sino que también plantea interrogantes éticos y de sostenibilidad para las generaciones presentes y futuras. En este contexto de urgencia ambiental, es necesario explorar y promover soluciones innovadoras y sostenibles que aborden de manera integral la problemática de los plásticos y fomenten una cultura de reducción, reutilización y reciclaje. Dentro de este marco, el arte emerge como una poderosa herramienta capaz de generar conciencia, transformación social y ambiental, así como de inspirar cambios significativos en las prácticas individuales y colectivas. El artículo se centra en el desarrollo de un modelo de evaluación para el Arte Público Participativo que utiliza desechos plásticos como material artístico. Este enfoque, conocido como Upcycling o Supra-reciclaje, tiene como objetivo principal la reutilización creativa de los plásticos en la creación de obras artísticas. Además de su función estética, estas obras tienen la intención de empatizar y transmitir emociones que aporten concienciación sobre sostenibilidad, consumo responsable y gestión de residuos. Este estudio analiza cómo el arte puede ser un instrumento efectivo para abordar desafíos ambientales globales al transformar desechos en recursos artísticos y educativos. Para fundamentar y enriquecer este estudio, se recurre a diversas corrientes teóricas y disciplinas, que van desde la sociología ambiental hasta la psicología social y la ecología cultural. Entre las teorías y consideraciones relevantes se encuentran la "Teoría del valor, las normas y las creencias hacia el medioambiente" de Stern et al. (2000), que proporciona un marco conceptual para comprender cómo se construyen y transforman las actitudes y comportamientos hacia el entorno natural. Asimismo, se considera la "Psicología social de los objetos" de Mead (1932), que explora la relación entre los individuos, los objetos y la identidad personal en el contexto de la sociedad contemporánea. Además, se aborda la "Teoría de la Basura" de Thompson (1979), que analiza la evolución del valor social de los objetos, incluyendo los desechos, en el contexto de la cultura material y el consumo. La metodología propuesta para la evaluación de estos proyectos artísticos participativos se sustenta en un conjunto de variables fundamentales que abarcan aspectos como el grado de participación comunitaria en la creación de las obras, la selección y uso innovador de materiales plásticos, el impacto ambiental de las instalaciones artísticas, la integración con el entorno urbano o natural, así como el mensaje temático y simbólico que transmiten las obras a la audiencia. Este modelo de evaluación no solo busca valorar la calidad estética y conceptual de las obras, sino también su impacto social, educativo y medioambiental. Desde una perspectiva más amplia, esta focalización de Arte Público Participativo orientado en la reutilización creativa de desechos plásticos representa una oportunidad única para transformar la percepción y las prácticas relacionadas con los residuos y el consumo en nuestra sociedad. En resumen, este artículo aborda el papel crucial que desempeña el arte, especialmente cuando se integra en proyectos participativos que incluyen la reutilización creativa de desechos plásticos. Se examina cómo esta guía puede ser fundamental en la sensibilización, educación y movilización de la sociedad hacia prácticas más sostenibles y conscientes. Además de su impacto en el ámbito artístico, este enfoque contribuye significativamente a la construcción de una cultura de respeto y cuidado hacia el medio ambiente y los recursos naturales

Fishmeal and fish oil substitution in aquafeeds might have adverse effects on fish growth and health, mainly in carnivorous species, such as Mediterranean yellowtail (Seriola dumerili). Mediterranean yellowtail shows great potential as an alternative aquaculture species due to its fast growth and high price on the market, but the need for high-quality protein and fatty acid content in its diets is limiting its production. In order to improve the sustainability of its production, this study was conducted with 360 fish of 35 g to evaluate the effects on fish growth and health. Six diets were used: one control diet without replacement, three with FM replacement (FM66, FM33, and FM0) (33%, 66%, and 100% FM replacement), and two with FO replacement (FO50 and FO0) (50% and 100% FO replacement). The substitution of FM was with vegetable (VM) (corn gluten) and animal (AM) (krill and meat meal) meals. The reductions in FM and FO of up to 33 and 0%, respectively, did not affect the growth and survival of S. dumerili at the intestinal morphology level, except for the anterior intestine regarding the lower villi length and width and the posterior intestine regarding the lower width of the lamina propria. On the other hand, the substitution of fish ingredients in the diet affects liver morphology, indicating alterations in the major diameter of hepatocytes or their nuclei. Finally, diet did not affect the gut microbiota with respect to the control, but significant differences were found in alpha and beta diversity when FO and FM microbiota were compared. A 66% FM replacement and total FO replacement would be possible without causing major alterations in the fish.

Two novel conjugate molecules were designed: pyrene and phenanthridine-amino acid units with a different linker length between the aromatic fragments. Molecular modelling combined with spectrophotometric experiments revealed that in neutral and acidic buffered water solutions conjugates predominantly exist in intramolecularly stacked conformations because of the π–π stacking interaction between pyrene and phenanthridine moieties. The investigated systems exhibited a pH-dependent excimer formation that is significantly red-shifted relative to the pyrene and phenanthridine fluorescence. While the conjugate with a short linker showed negligible spectrophotometric changes due to the polynucleotide addition, the conjugate with a longer and more flexible linker exhibited a micromolar and submicromolar binding affinity for ds-polynucleotides and inactivated a mutant of dipeptidyl peptidase enzyme E451A. Confocal microscopy revealed that the conjugate with the longer linker entered the HeLa cell membranes and blue fluorescence was visualized as the dye accumulated in the cell membrane.

A reunificação familiar é um processo complexo que se inicia com o acolhimento residencial da criança e/ou jovem na instituição e continua após o regresso a casa, podendo contribuir para consolidação e sucesso das medidas de proteção. O presente estudo teve como objetivo analisar as dinâmicas geradoras dos processos de resiliência em famílias após implementação do Programa “Caminhar em Família” que visa a reunificação familiar por meio de promoção de competências parentais durante o acolhimento. Foi desenvolvido um estudo de caso qualitativo de caráter descritivo e retrospectivo. A amostra não probabilística foi composta por 4 famílias, sendo 5 progenitores e 6 crianças/jovens que saíram do acolhimento no ano de 2019 e estavam aptas à reunificação. A participação das famílias no programa permitiu confirmar o fortalecimento da resiliência no sistema relacional de pais e filhos graças à compreensão, capacitação e empoderamento suscitados nas diferentes etapas da medida de proteção. A associação conceitual de dois modelos teóricos da resiliência familiar das autoras Froma Walsh e Lietz e Strenght possibilitou identificar diferentes forças e recursos individuais e familiares na gestão da crise e respostas específicas às necessidades das famílias nos diferentes estádios do acolhimento e reunificação. Os resultados reforçam a importância de programas socioeducativos que privilegiam o fortalecimento das dimensões promotoras de aspectos saudáveis que compõe a resiliência em famílias. Estes elementos devem ser os norteadores das intervenções para uma reunificação familiar segura e estável.

The use of organic ingredients as a source of protein in aquaculture diets has gained significant attention due to the growing demand for organic seafood products. This study aimed to evaluate the potential for the use of organic ingredients as protein sources in the diet of juvenile organic seabass (Dicentrarchus labrax). A total of 486 juvenile seabass with an average weight of 90 g were fed six diets containing varied organic proteins. The control group (CON) was fed a diet with conventional fishmeal from sustainable fisheries as the primary protein source. The other five groups were fed diets with different compositions: organic Iberian pig meal byproduct (IB diet), a combination of organic Iberian pig meal byproduct and insect meal (IB-IN diet), a mix of organic Iberian pig meal byproduct and organic rainbow trout meal byproduct (IB-TR diet), a blend of organic rainbow trout meal byproduct and insect meal (TR-IN), and a mixed diet containing all of these protein sources (MIX diet). Over a 125-day feeding trial, growth performance, feed utilisation, feed digestibility, and histological parameters were assessed. The results showed that the fish fed the control diet had the highest final weight and specific growth rate, followed by the fish fed the TR-IN and IB-TR diets. The IB-TR diet had the highest apparent digestibility coefficients (ADCs) for protein, while the TR-IN diet had the lowest. Histological analysis revealed that fish fed the control diet had the largest nucleus diameter and hepatocyte diameter. Use of IN seems to penalise performance in several ways. Fish fed diets containing insect meal grew less, and those diets had lower digestibility. Fish fed the TR and IB diets grew at rates near that of the control, and the feed had acceptable digestibility.

A 120-day experiment investigated the new organic raw materials for Gilthead seabream (Sparus aurata) feeding on growth, nutritional parameters, digestibility, and histology. An organic control diet (CON) and three diets with 100% organic raw materials—the rest of rainbow trout, visceral Iberian pig, and insects as a protein source (TRO, IBE, and INS)—were tested. After the experiment, growth, nutritional parameters, digestibility, and histology were measured. The CON diet-fed seabream obtained the highest weight; there was no difference between the experimental diets. The crude protein content was the highest in seabream fed the TRO and INS diets. Crude fat was the highest value observed in the CON diet. High digestibility was observed in seabream-fed IBE and INS diets. Except for EAA methionine (Met), there were no static differences in retention efficiency. The diet with the highest hydrolysis rate was IBE. Diet differences were significant but had the typical healthy liver morphology of seabream. Seabream fed on the TRO and INS diets had shorter distal gut measurements. In conclusion, the full substitution of fishmeal with organic raw materials, including rainbow trout remains, Iberian pig viscera, and insects, offers several benefits in terms of digestibility, histology, and growth performance and may help improve sustainable and healthy aquaculture practices.

Skin cancers are among the most common cancers worldwide and are increasingly prevalent. Cutaneous melanoma (CM) is characterized by the malignant transformation of melanocytes in the epidermis. Although CM shows lower incidence than other skin cancers, it is the most aggressive and responsible for the vast majority of skin cancer-related deaths. Indeed, 75% of patients present with invasive or metastatic tumors, even after surgical excision. In CM, the photoprotective pigment melanin, which is produced by melanocytes, plays a central role in the pathology of the disease. Melanin absorbs ultraviolet radiation and scavenges reactive oxygen/nitrogen species (ROS/RNS) resulting from the radiation exposure. However, the scavenged ROS/RNS modify melanin and lead to the induction of signature DNA damage in CM cells, namely cyclobutane pyrimidine dimers, which are known to promote CM immortalization and carcinogenesis. Despite triggering the malignant transformation of melanocytes and promoting initial tumor growth, the presence of melanin inside CM cells is described to negatively regulate their invasiveness by increasing cell stiffness and reducing elasticity. Emerging evidence also indicates that melanin secreted from CM cells is required for the immunomodulation of tumor microenvironment. Indeed, melanin transforms dermal fibroblasts in cancer-associated fibroblasts, suppresses the immune system and promotes tumor angiogenesis, thus sustaining CM progression and metastasis. Here, we review the current knowledge on the role of melanin secretion in CM aggressiveness and the molecular machinery involved, as well as the impact in tumor microenvironment and immune responses. A better understanding of this role and the molecular players involved could enable the modulation of melanin secretion to become a therapeutic strategy to impair CM invasion and metastasis and, hence, reduce the burden of CM-associated deaths.

Introduction: PIK3CA is one of the most mutated oncogenes in solid tumors. In breast cancer (ER-positive, HER2-negative), these events represent a predictive biomarker of response to alpelisib. In glioblastomas (GBM), PIK3CA mutations were described as early constitutive events. Here, we investigated PIK3CA mutational profile across glioma molecular subgroups and its relevance during glioma recurrence. Furthermore, PIK3CA mutations’ effect in PI3K pathway, prognosis, and response to therapy was also explored. Material and Methods: Exons 10 and 21 of PIK3CA mutations were evaluated in 394 gliomas and 19 glioma recurrences from Instituto Português de Oncologia Lisboa Francisco Gentil (IPOLFG) and compared with The Cancer Genome Atlas (TCGA) data. TIMER2.0 and NetMHCpan4.1 were used to assess the immune-microenvironment contribution. Results: PIK3CA mutations were identified among all glioma subgroups, although with no impact on their stratification or prognosis. In both cohorts (IPOLFG and TCGA), PIK3CA mutation frequencies in IDH -mutant and IDH -wild-type GBM were similar (IPOLFG: 9% and 3%; TCGA: 8% and 2%). These mutations were not mutually exclusive with PTEN deletion and EGFR amplification. Despite their reduced frequency, we discovered PIK3CA mutations were maintained during glioma recurrence regardless of administered therapies. The immune microenvironment might not contribute to this phenotype as PIK3CA mutations did not influence immune cell infiltration. Conclusions: Despite the absence of a predominant effect in glioma stratification, PIK3CA mutations were maintained during glioma recurrence, possibly contributing to glioma cell survival, representing promising therapeutic targets in recurrent glioma. Nevertheless, understanding the potential synergistic effects between PIK3CA mutations, PTEN deletion, and EGFR amplification is pivotal to targeted therapies’ efficiency.

The fishmeal replacement by vegetable meals or other alternative sources, without affecting fish performance and productivity, is one of the principal challenges in aquaculture. The use of hydrolyzed porcine mucosa (HPM) and nucleotide (NT) concentrates, as feed additives in gilthead seabream (Sparus aurata L.) non-fishmeal diets was assessed in order to determine the possible effects on growth, feed efficiency, protein digestion, and gut histology when these were included in a plant-based diet (HPM 1% and 2%, P1 and P2; NT 250 and 500 ppm, N250 and N500), in comparison with two control diets, AA0 (100% plant-protein-based diet) and FM100 (100% fishmeal-protein-based diet). Diets were assayed in triplicate and the growth assay lasted 134 days. Results showed a significant improvement in all groups in terms of final weight and specific growth rate in comparison with the AA0 group. An improvement in the feed conversion ratio and the protein efficiency ratio was also observed when the additives were included in lower percentages (P1 and N250) compared to the FM100 group. Significant differences were found in hepatosomatic index, villi thickness, and goblet cells. Thus, the inclusion of NT and HPM was tested as beneficial for the improvement of efficiency of plant feed in seabream.

The binding interactions of six ligands, neutral and monocationic asymmetric monomethine cyanine dyes comprising benzoselenazolyl moiety with duplex DNA and RNA and G-quadruplex structures were evaluated using fluorescence, UV/Vis (thermal melting) and circular dichroism (CD) spectroscopy. The main objective was to assess the impact of different substituents (methyl vs. sulfopropyl vs. thiopropyl/thioethyl) on the nitrogen atom of the benzothiazolyl chromophore on various nucleic acid structures. The monomethine cyanine dyes with methyl substituents showed a 100-fold selectivity for G-quadruplex versus duplex DNA. Study results indicate that cyanines bind with G-quadruplex via end π-π stacking interactions and possible additional interactions with nucleobases/phosphate backbone of grooves or loop bases. Cyanine with thioethyl substituent distinguishes duplex DNA and RNA and G-quadruplex structures by distinctly varying ICD signals. Furthermore, cell viability assay reveals the submicromolar activity of cyanines with methyl substituents against all tested human cancer cell lines. Confocal microscopy analysis shows preferential accumulation of cyanines with sulfopropyl and thioethyl substituents in mitochondria and indicates localization of cyanines with methyl in nucleus, particularly nucleolus. This confirms the potential of examined cyanines as theranostic agents, possessing both fluorescent properties and cell viability inhibitory effect.

The aquaculture of carnivorous fish is in continuous expansion, which leads to the need to reduce the dependence on fishmeal (FM). Plant proteins (PP) represent a suitable protein alternative to FM and are increasingly used in fish feed. However, PP may lead to stunted growth and enteritis. In the current study, the effect of high FM substitution by PP sources on the growth, mortality and intestinal health of rainbow trout (Oncorhynchus mykiss) was evaluated in terms of the histological intestine parameters and expression of genes related to inflammation (IL-1β, IL-8 and TGF-β) and immune responses (Transferrin, IgT and IFN-γ). The results show that a total substitution registered lower growth and survival rates, probably due to a disruption to the animal’s health. Confirming this hypothesis, fish fed FM0 showed histological changes in the intestine and gene changes related to inflammatory responses, which in the long-term could have triggered an immunosuppression. The FM10 diet presented not only a similar expression to FM20 (control diet), but also similar growth and survival. Therefore, 90% of FM substitution was demonstrated as being feasible in this species using a PP blend of wheat gluten (WG) and soybean meal (SBM) as a protein source.