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BackgroundEvidence indicates that criminal behaviour in youth is linked with a range of negative physical, mental, and social health consequences. Despite a global decrease over the last 30 years, youth crime remains prevalent. Identifying and mapping the most robust risk and protective factors, and intervention strategies for youth crime could offer important keys for predicting future offense outcomes and assist in developing effective preventive and early intervention strategies. Current reviews in the area do not include literature discussing at risk populations such as First Nations groups from countries such as Australia, Canada and New Zealand. This is a critical gap given the disproportionally high rates of incarceration and youth detention among First Nations people globally, particularly in countries with a colonial past. The aim of this scoping review is to identify and map the key risk and protective factors, along with intervention strategies, that are essential for recognizing adolescents and young adults at risk of crime.MethodsThis scoping review protocol has been developed in line with the Arksey and O'Malley framework and the Joanna Briggs Institute (JBI) Reviewers' Manual. The review protocol was preregistered with Open Science Framework (https://osf.io/kg4q3). ProQuest, PubMed, Web of Science, Scopus, and PsycInfo were used to retrieve relevant articles. Grey literature was searched using Google searches and ProQuest dissertations databases. Original research articles examining protective factors, risk factors, and intervention strategies for prevention and reduction of crime in 12-24-year-olds were included. Two independent reviewers conducted eligibility decisions and data extraction. Findings has been reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews.ConclusionAnticipated findings suggest that current research has extensively examined factors across all levels of the socioecological model, from individual to community levels, revealing a predominant focus on individual-level predictors such as substance use, prior criminal history, and moral development. The review is expected to identify effective interventions that address critical factors within each domain, including Multisystemic Therapy (MST) and Multidimensional Treatment Foster Care (MTFC), which have shown promise in reducing youth crime. Additionally, it will likely highlight significant trends in risk and protective factors, such as the dual role of academic achievement-both as a risk and protective factor-and the impact of family-based interventions. The review will also address gaps in research, particularly regarding Indigenous youth, underscoring the need for targeted studies to better understand their unique challenges. These findings will guide future research and inform the development of comprehensive prevention and early intervention programs tailored to diverse youth populations.

ObjectivesThis systematic review aimed to assess the prevalence and incidence of diabetic retinopathy in patients with diabetes of Latin America and the Caribbean.MethodsWe searched Web of Science (WoS)/Core Collection, WoS/MEDLINE, WoS/Scielo, Scopus, PubMed/Medline and Embase databases until January 16, 2023. We meta-analyzed prevalences according to type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).ResultsForty-three prevalence studies (47 585 participants) and one incidence study (436 participants) were included. The overall prevalence of retinopathy in patients with T1DM was 40.6% (95% CI: 34.7 to 46.6; I2: 92.1%) and in T2DM was 37.3% (95% CI: 31.0 to 43.8; I2: 97.7), but the evidence is very uncertain (very low certainty of evidence). In meta-regression, we found that age (T1DM) and time in diabetes (T2DM) were factors associated with the prevalence. On the other hand, one study found a cumulative incidence of diabetic retinopathy of 39.6% at 9 years of follow-up.ConclusionsTwo out of five patients with T1DM or T2DM may present diabetic retinopathy in Latin America and the Caribbean, but the evidence is very uncertain. This is a major public health problem, and policies and strategies for early detection and opportunely treatment should be proposed.

Microbes have central roles in the development and health of animals, being the introduction of specific microbial species a potential conservation strategy to protect animals from emerging diseases. Thus, insight into the microbiota of the species and their habitats is essential. In this manuscript, we report for the first time the bacterial composition of all the components (eggshells of hatched and unhatched eggs, internal content of unhatched eggs, intestinal content of hatchling and pipping sea turtles, and sand) of three nesting beaches of Caretta caretta along the Italian coasts of the Mediterranean Sea. The analysis of 26 amplicon samples was carried out using next-generation sequencing analysis, targeting V3-V4 regions of the bacterial 16S rRNA gene. Samples featured mainly Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes, whose percentages depended on the sample type. Our results showed that, although from different sampling sites, the internal content of the unhatched eggs, intestinal content of hatchling and pipping sea turtles share the microbiota, which was yet different from that of eggshells and sand of the same nesting beach. This study suggests the maternal and environmental influence alongside a protective role of eggshells in shaping the egg microbiota of Caretta caretta sea turtles.

Caretta caretta is the most common sea turtle species in the Mediterranean Sea. The species is threatened by anthropomorphic activity that causes thousands of deaths and hundreds of strandings along the Mediterranean coast. Stranded turtles are often cared for in rehabilitation centres until they recover or die. The objective of this study was to characterize the gut microbiome of nine sea turtles stranded along the Sicilian coast of the Mediterranean Sea using high-throughput sequencing analysis targeting V3-V4 regions of the bacterial 16S rRNA gene. Stool samples were collected from eight specimens hosted in the recovery centre after a few days of hospitalization (under 7) and from one hosted for many weeks (78 days). To better explore the role of bacterial communities in loggerhead sea turtles, we compared our data with published fecal microbiomes from specimens stranded along the Tuscan and Ligurian coast. Our results highlight that, despite the different origin, size and health conditions of the animals, Firmicutes, Bacteroidetes and Proteobacteria constitute the main components of the microbiota. This study widens our knowledge on the gut microbiome of sea turtles and could be helpful for the set up of rehabilitation therapies of stranded animals after recovery in specialized centres.

Children exposed to family poverty have been found to have higher morbidity and mortality rates, poorer mental health and cognitive outcomes and reduced life chances across a wide range of life domains. There is, however, very little known about the extent to which poverty is experienced by children over their early life course, particularly in community samples. This study tracks changes in family poverty and the main factors that predict family poverty (adverse life experiences) over a 30-year period since the birth of the study child.Data are from a prospective, longitudinal, birth cohort study conducted in Brisbane, Australia. Consecutive families were recruited at the mothers' first obstetrical visit at one of two major obstetrical hospitals in Brisbane. Data are available for 2087 families with complete data at the 30-year follow-up. Poverty was measured using family income at each time point (adjusted for inflation).Poverty affects about 20% of families at any time point. It is common for families to move in and out of poverty, as their circumstances are affected by such adversities as unemployment and marital breakdown. Over the period of the study about half the families in the study experienced poverty on at least one occasion. Only a very small minority of families experienced persistent poverty over the 30-year duration of the study. Logistic regressions with time lag show that family poverty predicts subsequent adversities and adverse events predict subsequent poverty.Experiences of poverty and adversity are common and may vary greatly over the child's early life course. In assessing the health consequences of poverty, it is important to distinguish the timing and chronicity of early life course experiences of poverty and adversity.

The protein p27Kip1 (p27), a member of the Cip-Kip family of cyclin-dependent kinase inhibitors, is involved in tumorigenesis and a correlation between reduced levels of this protein in human tumours and a worse prognosis has been established. Recent reports revealed that p27 also behaves as a transcriptional regulator. Thus, it has been postulated that the development of tumours with low amounts of p27 could be propitiated by deregulation of transcriptional programs under the control of p27. However, these programs still remain mostly unknown. The aim of this study has been to define the transcriptional programs regulated by p27 by first identifying the p27-binding sites (p27-BSs) on the whole chromatin of quiescent mouse embryonic fibroblasts. The chromatin regions associated to p27 have been annotated to the most proximal genes and it has been considered that the expression of these genes could by regulated by p27. The identification of the chromatin p27-BSs has been performed by Chromatin Immunoprecipitation Sequencing (ChIP-seq). Results revealed that p27 associated with 1839 sites that were annotated to 1417 different genes being 852 of them protein coding genes. Interestingly, most of the p27-BSs were in distal intergenic regions and introns whereas, in contrast, its association with promoter regions was very low. Gene ontology analysis of the protein coding genes revealed a number of relevant transcriptional programs regulated by p27 as cell adhesion, intracellular signalling and neuron differentiation among others. We validated the interaction of p27 with different chromatin regions by ChIP followed by qPCR and demonstrated that the expressions of several genes belonging to these programs are actually regulated by p27. Finally, cell adhesion assays revealed that the adhesion of p27-/- cells to the plates was much higher that controls, revealing a role of p27 in the regulation of a transcriptional program involved in cell adhesion.

Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is required for diverse cellular functions. Mammalian CaMKK activates CaMKs and also the evolutionarily-conserved AMP-activated protein kinase (AMPK). The fission yeast Schizosaccharomyces pombe CaMKK, Ssp1, is required for tolerance to limited glucose through the AMPK, Ssp2, and for the integration of cell growth and division through the SAD kinase Cdr2.Here we report that Ssp1 controls the G2/M transition by regulating the activity of the CaMK Srk1. We show that inhibition of Cdc25 by Srk1 is regulated by Ssp1; and also that restoring growth polarity and actin localization of ssp1-deleted cells by removing the actin-monomer-binding protein, twinfilin, is sufficient to suppress the ssp1 phenotype.These findings demonstrate that entry into mitosis is mediated by a network of proteins, including the Ssp1 and Srk1 kinases. Ssp1 connects the network of components that ensures proper polarity and cell size with the network of proteins that regulates Cdk1-cyclin B activity, in which Srk1 plays an inhibitory role.

BACKGROUND:The HIV-Brazil Cohort Study was established to analyze the effectiveness of combination antiretroviral therapy (cART) and the impact of this treatment on morbidity, quality of life (QOL) and mortality. The study design, patients' profiles and characteristics of cART initiation between 2003 and 2010 were described. METHODOLOGY/PRINCIPAL FINDINGS:Since 2003, the HIV-Brazil Cohort has been following HIV-infected adults receiving cART at 26 public health care facilities, using routine clinical care data and self-reported QOL questionnaires. When not otherwise available, data are obtained from national information systems. The main outcomes of interest are diseases related or unrelated to HIV; suppression of viral replication; adverse events; virological, clinical and immunological failures; changes in the cART; and mortality. For the 5,061 patients who started cART between 2003 and 2010, the median follow-up time was 4.1 years (IQR 2.2-5.9 years) with an 83.4% retention rate. Patient profiles were characterized by a predominance of men (male/female ratio 1.7∶1), with a mean age of 36.9 years (SD 9.9 years); 55.2% had been infected with HIV via heterosexual contact. The majority of patients (53.4%) initiated cART with a CD4+ T-cell count ≤200 cells/mm3. The medications most often used in the various treatment regimens were efavirenz (59.7%) and lopinavir/ritonavir (18.2%). The proportion of individuals achieving viral suppression within the first 12 months of cART use was 77.4% (95% CI 76.1-78.6). Nearly half (45.4%) of the patients presented HIV-related clinical manifestations after starting cART, and the AIDS mortality rate was 13.9 per 1,000 person-years. CONCLUSIONS/SIGNIFICANCE:Results from cART use in the daily practice of health services remain relatively unknown in low- and middle-income countries, and studies with the characteristics of the HIV-Brazil Cohort contribute to minimizing these shortcomings, given its scope and patient profile, which is similar to that of the AIDS epidemic in the country.

The impact of low-to-moderate levels of alcohol consumption during pregnancy on child cognitive outcomes has been of recent concern. This study has tested the hypothesis that low-to-moderate maternal alcohol use in pregnancy is associated with lower school test scores at age 11 in the offspring via intrauterine mechanisms.We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort study based in the South West of England. Analyses were conducted on 7062 participants who had complete data on: maternal and paternal patterns of alcohol use in the first trimester and at 18 weeks' gestation, child's academic outcomes measured at age 11, gender, maternal age, parity, marital status, ethnicity, household crowding, home ownership status and parental education. We contrasted the association of mother's alcohol consumption during pregnancy with child's National Curriculum Key Stage 2 (KS2) test scores with the association for father's alcohol consumption (during the time the mother was pregnant) with child's National Curriculum Key Stage 2 (KS2) test scores. We used multivariate linear regression to estimate mean differences and 95% confidence intervals [CI] in KS2 scores across the exposure categories and computed f statistics to compare maternal and paternal associations.Drinking up to 1 unit of alcohol a day during pregnancy was not associated with lower test scores. However, frequent prenatal consumption of 4 units (equivalent to 32 grams of alcohol) on each single drinking occasion was associated with reduced educational attainment [Mean change in offspring KS2 score was -0.68 (-1.03, -0.33) for maternal alcohol categories compared to 0.27 (0.07, 0.46) for paternal alcohol categories]. Frequent consumption of 4 units of alcohol during pregnancy may adversely affect childhood academic outcomes via intrauterine mechanisms.

Observational studies have generated conflicting evidence on the effects of moderate maternal alcohol consumption during pregnancy on offspring cognition mainly reflecting problems of confounding. Among mothers who drink during pregnancy fetal alcohol exposure is influenced not only by mother's intake but also by genetic variants carried by both the mother and the fetus. Associations between children's cognitive function and both maternal and child genotype at these loci can shed light on the effects of maternal alcohol consumption on offspring cognitive development.We used a large population based study of women recruited during pregnancy to determine whether genetic variants in alcohol metabolising genes in this cohort of women and their children were related to the child's cognitive score (measured by the Weschler Intelligence Scale) at age 8.We found that four genetic variants in alcohol metabolising genes in 4167 children were strongly related to lower IQ at age 8, as was a risk allele score based on these 4 variants. This effect was only seen amongst the offspring of mothers who were moderate drinkers (1-6 units alcohol per week during pregnancy (per allele effect estimates were -1.80 (95% CI= -2.63 to -0.97) p=0.00002, with no effect among children whose mothers abstained during pregnancy (0.16 (95%CI= -1.05 to 1.36) p=0.80), p-value for interaction =0.009). A further genetic variant associated with alcohol metabolism in mothers was associated with their child's IQ, but again only among mothers who drank during pregnancy.

BACKGROUND: Worldwide, a high proportion of HIV-infected individuals enter into HIV care late. Here, our objective was to estimate the impact that late entry into HIV care has had on AIDS mortality rates in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed data from information systems regarding HIV-infected adults who sought treatment at public health care facilities in Brazil from 2003 to 2006. We initially estimated the prevalence of late entry into HIV care, as well as the probability of death in the first 12 months, the percentage of the risk of death attributable to late entry, and the number of avoidable deaths. We subsequently adjusted the annual AIDS mortality rate by excluding such deaths. Of the 115,369 patients evaluated, 50,358 (43.6%) had entered HIV care late, and 18,002 died in the first 12 months, representing a 16.5% probability of death in the first 12 months (95% CI: 16.3-16.7). By comparing patients who entered HIV care late with those who gained timely access, we found that the risk ratio for death was 49.5 (95% CI: 45.1-54.2). The percentage of the risk of death attributable to late entry was 95.5%, translating to 17,189 potentially avoidable deaths. Averting those deaths would have lowered the 2003-2006 AIDS mortality rate by 39.5%. Including asymptomatic patients with CD4(+) T cell counts >200 and ≤ 350 cells/mm(3) in the group who entered HIV care late increased this proportion by 1.8%. CONCLUSIONS/SIGNIFICANCE: In Brazil, antiretroviral drugs reduced AIDS mortality by 43%. Timely entry would reduce that rate by a similar proportion, as well as resulting in a 45.2% increase in the effectiveness of the program for HIV care. The World Health Organization recommendation that asymptomatic patients with CD4(+) T cell counts ≤ 350 cells/mm(3) be treated would not have a significant impact on this scenario.

DUX4 (Double Homeobox Protein 4) is a nuclear transcription factor encoded at each D4Z4 unit of a tandem-repeat array at human chromosome 4q35. DUX4 constitutes a major candidate pathogenic protein for facioscapulohumeral muscular dystrophy (FSHD), the third most common form of inherited myopathy. A low-level expression of DUX4 compromises cell differentiation in myoblasts and its overexpression induces apoptosis in cultured cells and living organisms. In this work we explore potential molecular determinants of DUX4 mediating nuclear import and cell toxicity. Deletion of the hypothetical monopartite nuclear localization sequences RRRR(23), RRKR(98) and RRAR(148) (i.e. NLS1, NLS2 and NLS3, respectively) only partially delocalizes DUX4 from the cell nuclei. Nuclear entrance guided by NLS1, NLS2 and NLS3 does not follow the classical nuclear import pathway mediated by α/β importins. NLS and homeodomain mutants from DUX4 are dramatically less cell-toxic than the wild type molecule, independently of their subcellular localization. A triple ΔNLS1-2-3 deletion mutant is still partially localized in the nuclei, indicating that additional sequences in DUX4 contribute to nuclear import. Deletion of ≥111 amino acids from the C-terminal of DUX4, on a ΔNLS1-2-3 background, almost completely re-localizes DUX4 to the cytoplasm, indicating that the C-ter tail contributes to subcellular trafficking of DUX4. Also, C-terminal deletion mutants of DUX4 on a NLS wild type background are less toxic than wild type DUX4. Results reported here indicate that DUX4 possesses redundant mechanisms to assure nuclear entrance and that its various transcription-factor associated domains play an essential role in cell toxicity.