This study presents the initial results of carbon-14 dating after performing sample preparation and graphite production processes at the Federal University of Bahia (UFBA) in an intercomparison with the same processes performed at the Radiocarbon Laboratory of the Fluminense Federal University (LAC-UFF). Both laboratories are located in Brazil. The accelerator mass spectrometry (AMS) system at LAC-UFF was used for radiocarbon measurements. To verify any possible contamination sources during sample preparation, we initially performed swipe tests at UFBA, which were subsequently processed and the graphite samples were produced at LAC-UFF. After UFBA, several reference materials (IAEA-C1, -C2, -C6, -C9, and OXII standards) were prepared and converted into graphite. In addition, the sample material was first partially prepared at UFF and UFBA and then analyzed with the AMS system at LAC-UFF. Subsamples were prepared for additional measurements of the δ13C composition with an elemental analyzer coupled to an isotope ratio mass spectrometer (EA–IRMS) in LFNA-UFBA to study the isotopic fractionation and yield of the graphitization reaction. The obtained values closely aligned with the reference values, demonstrating reproducibility and quality and indicating minimal contamination during chemical and graphitization processes. In the future, samples from different matrices will be prepared at UFBA for application in paleoenvironmental and archaeological studies.

Cestodiases, like echinococcoses and cysticercoses, represent a global health problem. Currently available anthelmintics, as benzimidazoles and praziquantel, have limited effectiveness against these cestodiases, creating a demand for the identification of new and more effective drugs. Here, the potential of statins (simvastatin and fluvastatin), for repositioning as novel anthelmintic is explored. Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a main enzyme in the mevalonate pathway, which is vital for the synthesis of non-steroidal isoprenoids and the maintenance of normal cell functioning. A survey for HMG-CoA reductase encoding genes showed that they are present in a single copy in the genomes of parasitic helminths and their mammal hosts. Sequence alignments and phylogenetic analyses showed 20–95% overall identities among ortholog HMG-CoA reductases, with special conservation of their catalytic domains. The HMG-CoA reductase 3D-structure was predicted for orthologs from 3 cestodes of medical importance (Echinococcus multilocularis, Echinococcus granulosus sensu lato, and Taenia solium), and from a model cestode species (Mesocestoides corti). Molecular docking between cestode HMG-CoA reductase orthologs with simvastatin demonstrated that the Arg, Ser, Lys, and Glu residues in conserved positions of the active site interact with this drug, similarly to the interactions predicted for the human reference ortholog enzyme. Furthermore, in vitro assays demonstrated that simvastatin produced a significant reduction of M. corti viability, being able to reduce 100% of parasite viability at 150 μm. Fluvastatin was also assessed showing a lower, although significant anthelmintic effect. The predicted overall structures and interactions together with in vitro assays suggest that cestodes HMG-CoA reductases are inhibited by simvastatin, being a potential therapeutic target for the repurposing of simvastatin as anthelmintic drug. Furthermore, these results pave the way for the in vivo evaluation of the potential effects of simvastatin on cestode larvae.

Social engagement is considered a relevant modifiable factor for older adults’ wellbeing. Theory and policies highlight its importance for ageing well. Empirical evidence shows that social activities are associated with positive psychological outcomes and might buffer wellbeing declines in late life. Despite growing research, social engagement lacks conceptual clarity, it is difficult to adopt standardised measures and findings are sometimes inconsistent. Previous systematic reviews either take a different approach to this topic or were published over a decade ago. Therefore, the present study aimed to review the literature systematically regarding the relationship between social engagement and wellbeing in community-dwelling older adults. Papers published from 2000 to 2021 were searched in five databases using a combination of terms. The reviewers screened the records according to predefined inclusion and exclusion criteria. After identifying eligible articles, the authors extracted data and produced a narrative synthesis covering conceptualisation, measurement and main findings. The review includes 42 papers. Despite great conceptual and methodological diversity, research supports that older adults with higher participation in social activities have improved wellbeing. Findings also suggest that these associations are stronger for individuals with disadvantages and have a cumulative nature whereby the greater the social engagement, the higher the wellbeing. Conversely, for more demanding activities, there might be optimal participation levels. Regardless of accumulating knowledge, social engagement remains diffuse and difficult to measure. This paper summarises the current state of research on this topic, showing encouraging evidence of social engagement benefits, but also questions that deserve further inquiry. Future studies should be anchored in a clear conceptual framework, use robust measures, and explore hedonic and eudaimonic wellbeing. Social engagement can be an important developmental resource for social interventions and policies aimed at improving people’s lives.

The possible role of geothermal areas, such as volcanoes, in fostering biodiversity in Antarctica has received considerable recent attention. Under a geothermal refugia hypothesis, diverse life could be supported near or at geothermal sites, and we should see decreasing diversity and/or patterns of nestedness moving away from ‘hotspots’. Although there is evidence that geothermal areas have played a role in the persistence of some terrestrial species through glacial periods in Antarctica, the spatial scales at which such refugia operate is not clear. We sampled sediment from a range of locations across volcanic Deception Island in the Maritime Antarctic and used eDNA metabarcoding approaches (targeting a region of the 28S marker) to assess patterns of diversity in relation to thermal gradients. We found that although colder sites harboured significantly greater taxonomic richness than warmer sites, phylogenetic diversity was lower at colder sites (i.e. taxa at colder sites tend to be more evolutionary close to each other). We infer that increased selective processes in low-temperature environments have reduced phylogenetic diversity, supporting a hypothesis of geothermal locations acting as refugia for diverse taxa, even on fine spatial scales, in cold-climate regions such as Antarctica.

Fe-deficiency anaemia is a major public health concern in children under 5 years of age. TMPRSS6 gene, encoding matriptase-2 protein, is implicated in Fe homoeostasis and has been associated with anaemia and Fe status in various populations. The aim of this cross-sectional study was to investigate the associations between the single nucleotide polymorphism (SNP) TMPRSS6 rs855791 and biomarkers of anaemia and Fe deficiency in Brazilian children attending day care centres. A total of 163 children aged 6–42 months were evaluated. Socio-economic, demographic, biochemical, haematological, immunological and genotype data were collected. Multiple logistic and linear regressions with hierarchical selection were used to assess the effects of independent variables on categorised outcomes and blood marker concentrations. Minor allele (T) frequency of rs855791 was 0·399. Each copy of the T allele was associated with a 4·49-fold increased risk of developing anaemia (P = 0·005) and a 4·23-fold increased risk of Fe deficiency assessed by serum soluble transferrin receptor (sTfR) (P < 0·001). The dose of the T allele was associated with an increase of 0·18 mg/l in sTfR concentrations and reductions of 1·41 fl and 0·52 pg in mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH), respectively. In conclusion, the T allele of SNP TMPRSS6 rs855791 was significantly associated with anaemia and Fe deficiency assessed by sTfR in Brazilian children attending day care centres. The effect was dose dependent, with each copy of the T allele being associated with lower MCV and MCH and higher concentrations of sTfR.

Induction of puberty in cattle breeds that attain puberty in later stages, such as Gir, allows the earlier beginning of reproductive life and it might increase oocyte quality. Here, the ovulatory capacity of prepuberal Gir heifers was studied and its relationship to follicular growth, luteinizing hormone (LH) secretion and oocyte quality was evaluated. Peripubertal Gir heifers were treated with a progesterone-based protocol and according to ovulatory response were separated into groups: not-ovulated (N-OV) and ovulated (OV). Serial blood samples were taken 24 h after estradiol treatment on day 12 to evaluate LH secretion. Cumulus–oocyte complexes (COCs) were collected using ovum pick-up and assessed for brilliant cresyl blue (BCB) staining rate, IVF-grade oocytes rate, and mean oocyte diameter, in comparison with cow oocytes. Gene expression of developmental competence markers (ZAR1, MATER, and IGF2R) was also analyzed. The largest follicle diameters were similar between N-OV and OV groups on the day of estradiol treatment (d12) and the next day and decreased (P = 0.04) in the N-OV group thereafter. LH pulse secretion was different between groups (N-OV = 3.61 ± 0.34 vs OV = 2.83 ± 0.21 ng/ ml; P = 0.04). COC assessment showed that the number of recovered oocytes, BCB+ rate, IVF-grade oocytes and oocyte size was similar (P > 0.05) among groups, resembling adult cow patterns. ZAR1, MATER and IGF2R gene expression in oocytes were also similar (P > 0.05) in N-OV and OV groups. In conclusion, our results demonstrate a lower LH secretion profile in peripubertal Gir heifers prone to ovulate after induction protocol, and that oocyte quality is not affected on a short-term basis by ovulation itself.

OBJECTIVES/GOALS: Aiming to better understand the molecular pathogenesis of familial partial lipodystrophy (PL), we initiated whole-exome sequencing for our patients with PL syndromes. A novel variant of early B cell factor 2 (EBF2) was identified. Here we report the biological impact of a novel truncating EBF2 variant. METHODS/STUDY POPULATION: Using 3T3-L1 and human primary subcutaneous preadipocytes, we performed loss-of-function and gene rescue experiments. All cells were cultured in DMEM with 10% bovine calf serum (Invitrogen) at 5% CO2. After lentivirus transfection, cells were grown to confluence and then exposed to adipogenesis induction media containing dexamethasone (0.25µM), insulin (1µg/ml) and isobutyl methylxanthine (0.5 mM). Total RNA was extracted using RNeasy Mini Kit (Qiagen) and cDNA was synthesized using IScript (Bio-Rad). Real-time qPCR was performed using TaqMan probes for Pparg and Fabp4, two key adipogenesis markers. RESULTS/ANTICIPATED RESULTS: Patient was found to carry a heterozygous nonsense mutation in exon 6 of EBF2, causing the premature termination of the protein at amino acid position 165. Adipogenesis was significantly suppressed in 3T3L1 cells when endogenous Ebf2 was suppressed with siRNA and lentiviral shRNA. Adipocytes with suppressed Ebf2 expression showed marked reduction of intracellular lipid content and Pparg and Fabp4 expression (>80% reduction). With lentiviral gene transfer, EBF2 fully rescued adipogenic potential, whereas the truncated variant EBF2 did not. Of note, 3T3-L1 cells transfected with the EBF2 variant displayed impaired adipogenesis, suggesting a dominant-negative effect of the EBF2 variant on adipogenesis. We confirmed the dominant effect of the EBF2 variant in human adipocyte differentiation. DISCUSSION/SIGNIFICANCE: Our data suggest that EBF2 is indispensable for adipogenesis. The loss of function and dominant-negative effect of the truncating variant of EBF2 likely plays a pathogenic role in PL. Whole exome sequencing of PL patients and ex-vivo functional analysis help identify novel gene variants and better understand the molecular pathogenesis of PL.

Although morphological plasticity has been widely known in various cactus genera, few studies have investigated the origin and molecular relationship between morphological variants from cacti. Morphological variants are relevant specimens because atypical, exotic and generally unique forms are preferred by cactus traders and collectors. The current study investigates the molecular relationship between the tortuosus and monstruosus ornamental variants of Cereus peruvianus used in landscapes. Polymorphisms in loci of simple-sequence repeats in DNA were used as molecular markers. The variants tortuosus and monstruosus, and plants with typically columnar and erect shoots cultivated in southern Brazil were retrieved from public parks and home gardens. High polymorphism, an indicative of vegetative propagation, and a moderate genetic divergence were detected at the molecular level in monstruosus and tortuosus plants. Artificial selection and vegetative propagation of the ornamental variants of Cereus may be inducing a moderate genetic divergence and formation of two heterologous groups with conservative genetic diversity. Polymorphism in Cereus variants revealed groups with contrasting genes among the variants tortuosus and monstruosus which may be useful for breeding to generate new and different new variants.

This work aimed to evaluate the in vitro anthelmintic effect of carvone nanoemulsions on Haemonchus contortus. Three R-carvone nanoemulsions were prepared: uncoated R-carvone nanoemulsions homogenized in a sonicator (UNAlg-son) and homogenized in an ultrahomogenizer (UNAlg-ultra) and sodium alginate-coated R-carvone (CNAlg-ultra). The physicochemical characterizations of the nanoemulsions were carried out. The anthelmintic activity was evaluated using egg hatch test (EHT), larval development test (LDT) and adult worm motility test (AWMT). Changes in cuticle induced in adult H. contortus were evaluated by scanning electron microscopy (SEM). The results were subjected to analysis of variance and compared using the Tukey test (P < 0.05). The effective concentration to inhibit 50% (EC50) of egg hatching and larval development was calculated. The particle sizes were 281.1 nm (UNAlg-son), 152.7 nm (UNAlg-ultra) and 557.8 nm (CNAlg-ultra), and the zeta potentials were −15 mV (UNAlg-son), −10.8 mV (UNAlg-ultra) and −24.2 mV (CNAlg-ultra). The encapsulation efficiency was 99.84 ± 0.01%. SEM of the nanoemulsions showed an increase in size. In EHT, the EC50 values of UNAlg-son, UNAlg-ultra and CNAlg-ultra were 0.19, 0.02 and 0.17 mg mL−1, respectively. In LDT, they were 0.29, 0.31 and 0.95 mg mL−1 for UNAlg-son, UNAlg-ultra and CNAlg-ultra, respectively. The adult motility inhibition was 100% after 12 h of exposure to UNAlg-ultra and CNAlg-ultra, while for UNAlg-son, it was 79.16%. SEM showed changes in the buccal capsule and cuticular damage. It was concluded that R-carvone nanoemulsions showed antiparasitic action demonstrating promise for the control of infections caused by gastrointestinal nematodes in small ruminants.

Vitamin E is an important nutrient from the earliest stages of life. It plays key roles as an antioxidant and in the maintenance of the immune system, among others. Vitamin E deficiency (VED), which occurs more frequently in children, is rarely addressed in the literature. This narrative review aims to summarise the chemistry, biology, serum indicators and clinical trials that have evaluated the impact of fortification and other relevant aspects of vitamin E, in addition to the prevalence of its deficiency, in children worldwide. Vitamin E intake in recommended amounts is essential for this nutrient to perform its functions in the body. Serum α-tocopherol is the most widely used biochemical indicator to assess the prevalence of VED. VED has been associated with symptoms secondary to fat malabsorption and may lead to peripheral neuropathy and increased erythrocyte haemolysis. Reduced concentrations of α-tocopherol may be caused by the combination of diets with low amounts of vitamin E and inadequate consumption of fats, proteins and calories. The lowest prevalence of VED was found in Asia and the highest in North America and Brazil. High proportions of VED provide evidence that this nutritional deficiency is a public health problem in children and still little addressed in the international scientific literature. The planning, evaluation and implementation of health policies aimed at combatting VED in the paediatric population are extremely important.

Portugal has high fish/seafood consumption, which may have both risks and benefits. This study aims to quantify the net health impact of hypothetical scenarios of fish/seafood consumption in the Portuguese population using a risk–benefit assessment methodology. Consumption data from the National Food, Nutrition and Physical Activity Survey 2015–2016 (n 5811) were used to estimate the mean exposure to methylmercury and EPA + DHA in the current and the alternative scenarios considered. Alternative scenarios (alt) were modelled using probabilistic approaches to reflect substitutions from the current consumption in the type of fish/seafood (alt1: excluding predatory fishes; alt2: including only methylmercury low-level fishes) or in the frequency of weekly fish/seafood consumption (alt3 to alt6: 1, 3, 5 or 7 times a week, replacing fish/seafood meals with meat or others). The overall health impact of these scenarios was quantified using disability-adjusted life years (DALY). In the Portuguese population, about 11 450 DALY could be prevented each year if the fish/seafood consumption increased to a daily basis. However, such a scenario would result in 1398 extra DALY considering the consumption by pregnant women and the respective risk on fetal neurodevelopment. Our findings support a recommendation to increase fish/seafood consumption up to 7 times/week. However, for pregnant women and children, special considerations must be proposed to avoid potential risks on fetal neurodevelopment due to methylmercury exposure.

It was investigated how many cattle become infected with Trypanosoma vivax by subcutaneous (SC), intramuscular (IM) and intravenous (IV) routes, using the same syringe and needle from an animal with acute T. vivax infection. Besides, the T. vivax viability in 109 injectable veterinary drugs (antibiotics, antiparasitics, reproductive hormones, vitamin complex and derivatives, vaccines, anaesthetics, anti-inflammatory/antipyretics, antitoxics). In the field assay, four groups were performed: T01, T02 and T03 animals that received saline solution with the same syringe and needle contaminated with T. vivax via SC, IM and IV routes, respectively, and T04 control animals that received only saline solution with the same syringe and needle IV. In the laboratory, drugs had their pH measured and T. vivax viability verified. The number of cattle infected with T. vivax via SC (3/20) was lower (P ≤ 0.05) compared to via IM (9/20), which was lower (P ≤ 0.05) compared to IV (15/20). The solution pH did not influence T. vivax viability. In 44% (48/109) of the products, T. vivax remained viable regardless of time, stooding out that in 100% of oxytocins the protozoan was verified, at some evaluation times. The mean of T. vivax quantified in foot-and-mouth and brucellosis vaccines and in doramectin-based products were higher (P ≤ 0.05) than found in blood + saline solution.

Cross-sectional nutritional survey data collected in eight countries were used to estimate saturated fatty acid intakes. Our objective was to estimate the proportion of excessive saturated fatty acid intakes (>10 % of total energy intake) that could be avoided if ultra-processed food consumption was reduced to levels observed in the first quintile of each country. Secondary analysis was performed of 24 h dietary recall or food diary/record data collected by the most recently available nationally representative cross-sectional surveys carried out in Brazil (2008–9), Chile (2010), Colombia (2005), Mexico (2012), Australia (2011–12), the UK (2008–16), Canada (2015) and the US (2015–16). Population attributable fractions estimated the impact of reducing ultra-processed food consumption on excessive saturated fatty acid intakes (above 10 % of total energy intake) in each country. Significant relative reductions in the percentage of excessive saturated fatty acid intakes would be observed in all countries if ultra-processed food consumption was reduced to levels observed in the first quintile's consumption. The reductions in excessive intakes ranged from 10⋅0 % (95 % CI 6⋅2–13⋅6 %) in Canada to 35⋅0 % (95 % CI 28⋅7–48⋅0 %) in Mexico. In all eight studied countries, all presenting more than 30 % of intakes with excessive saturated fatty acids, lowering the dietary contribution of ultra-processed foods to attainable, context-specific levels was shown to be a potentially effective way to reduce the percentage of intakes with excessive saturated fatty acids, which may play an important role in the prevention of non-communicable diseases, particularly cardiovascular diseases.

VmCT1 is an antimicrobial peptide (AMP) isolated from the venom of the scorpion Vaejovis mexicanus with antimicrobial, anticancer and antimalarial activities, which the rational design with Arg-substitution has yielded AMPs with higher antimicrobial activity than VmCT1. Chagas is a neglected tropical disease, becoming the development of new antichagasic agents is urgent. Thus, we aimed to evaluate the antichagasic effect of VmCT1 and three Arg-substituted analogues, as well their action mechanism. Peptides were tested against the epimastigote, trypomastigote, amastigote forms of Trypanossoma cruzi Y strain and against LLC-MK2 mammalian cells. The mechanism of action of these peptides was evaluated by means of flow cytometry and scanning electron microscopy. VmCT1 presented activity against all three forms of T. cruzi, with EC50 against trypomastigote forms of 1.37 μmol L−1 and selectivity index (SI) of 58. [Arg]3-VmCT1, [Arg]7-VmCT1 and [Arg]11-VmCT1 also showed trypanocidal effect, but [Arg]11-VmCT1 had the best effect, being able to decrease the EC50 against trypomastigote forms to 0.8 μmol L−1 and increase SI to 175. Necrosis was cell death pathway of VmCT1, as well [Arg]7-VmCT1 and [Arg]11-VmCT1, such as observed by membrane damage in flow cytometry analyses and scanning-electron-microscopy. In conclusion, [Arg]11-VmCT1 revealed promising as a candidate for new antichagasic therapeutics.