Search

Previous studies have suggested a variation in the incidence of acute promyelocytic leukemia (APL) among the geographic regions with relatively higher percentages in the Latin American population. We aimed to explore the population burden of pediatric APL, gathering information from the population-based cancer registry (PBCR) and the diagnosis of APL obtained through incident cases from a hospital-based cohort. The homozygous deletion in glutathione S-transferases (GSTs) leads to a loss of enzyme detoxification activity, possibly affecting the treatment response. Mutations in the RAS pathway genes are also considered to be a key component of the disease both in the pathogenesis and in the outcomes. We have assessed mutations in a RAS-MAP kinase pathway (FLT3, PTPN11, and K-/NRAS) and GST variant predisposition risk in the outcome. Out of the 805 children and adolescents with acute myeloid leukemia (AML) who are registered in the PBCR, 35 (4.3%) were APL cases. The age-adjusted incidence rate (AAIR) was 0.03 per 100,000 person-years. One-hundred and sixty-three patients with APL were studied out of 931 AML cases (17.5%) from a hospital-based cohort. Mutations in FLT3, KRAS, and NRAS accounted for 52.1% of the cases. Patients with APL presented a 5-year probability of the overall survival (OS) of 67.3 ± 5.8%. A GST-theta 1 (GSTT1) null genotype conferred adverse prognosis, with an estimated hazard ratio of 2.8, 95% confidence interval (CI) 1.2-6.9. We speculate that the GSTT1 polymorphism is associated with therapeutics and would allow better OS of patients with APL with a GSTT1 null genotype.

Decision support tools in agriculture help farmers make science-informed decisions rather than experience-dependent ones, which is increasingly important in the context of climate change. However, these tools often fail to accommodate diverse users in terms of their contents, ease of use, and dissemination strategies. The objectives of this study are 1) to understand gender roles in potato production, 2) to understand men and women's knowledge and perceptions of pesticide application, and 3) assess the usability of a handheld decision support tool for potato late blight control from the perspective of gender in Peru. A qualitative participatory assessment was carried out in two communities in the Andes to explore not only the technical usability of the tool for men and women farmers, but also gender roles, knowledge, and perceptions of pest and disease management that determine household decisions on pesticide use. The findings confirmed that women farmers face challenges to using the tool, based on both technical and socio-cultural aspects. Furthermore, women farmers play a significant role in potato production in general, and their involvement in late blight management is likely to contribute to making appropriate household decisions on the use of pesticides, thereby mitigating overall health and environmental risks. The study concludes with recommendations for modifying the tool for women users as well as incorporating women's perspectives at the design stage. [ABSTRACT FROM AUTHOR]

Simple Summary: The bone healing process involves the local development and resolution of an inflammatory process, which theoretically contributes to healing by mediating the migration of cells associated with the repair process, and to promote the local production of growth factors associated with osteogenic cellular differentiation. Using mice strains previously described to present distinct inflammatory behavior, namely AIRmin and AIRmax, which also present distinct alleles of the Slc11a1 gene that also modulate inflammatory responsiveness, it is possible to investigate the association between inflammatory responsiveness and the bone healing outcome. After tooth extraction, it was observed that AIRmaxSS and AIRminRR presented the highest and lowest inflammatory readouts, respectively, associated with lowest repair levels in both strains. Conversely, the intermediate inflammatory phenotypes observed in AIRminSS and AIRmaxRR was associated with higher repair levels in such strains, supporting the idea that extreme high and low inflammatory responses are not ideal for a proper bone repair outcome, while an intermediate and transitory inflammation presented by AIRminSS and AIRmaxRR is associated with proper alveolar bone healing outcome. Alveolar bone healing is influenced by various local and systemic factors, including the local inflammatory response. This study aimed to evaluate the role of inflammatory responsiveness in alveolar bone healing using 8-week-old male and female mice (N = 5/time/group) strains selected for maximum (AIRmax) or minimum (AIRmin) acute inflammatory response carrying distinct homozygous RR/SS Slc11a1 genotypes, namely AIRminRR, AIRminSS, AIRmaxRR, and AIRmaxSS mice. After upper right incisor extraction, bone healing was analyzed at 0, 3, 7, and 14 days using micro-computed tomography, histomorphometry, birefringence, immunohistochemistry, and PCRArray analysis. AIRmaxSS and AIRminRR presented the highest and lowest inflammatory readouts, respectively, associated with lowest repair levels in both strains, while intermediate inflammatory phenotypes observed in AIRminSS and AIRmaxRR were associated with higher repair levels in such strains. The better healing outcomes are associated with intermediate inflammatory cell counts, a balanced expression of pro- and anti-inflammatory cytokines and chemokines, increased expression of growth and osteogenic factors and MSCs markers. Our results demonstrate that extreme high and low inflammatory responses are not ideal for a proper bone repair outcome, while an intermediate and transitory inflammation is associated with a proper alveolar bone healing outcome. [ABSTRACT FROM AUTHOR]

The Brazilian Atlantic Forest (BAF) is one of the most important biodiversity hotspots and species-rich ecosystems globally. Due to human activities, it has been significantly reduced and fragmented. This study examined both biotic (floristic composition, diversity, and structure) and abiotic (topographic and soil) factors in BAF fragments undergoing varying levels and durations of human disturbance cessation: approximately 20 years (20 y), ~30 years (30 y), and over 40 years (>40 y). We aimed to understand the recovery dynamics of floristic composition, diversity, and structure in BAF fragments in relation to abiotic factors. Several statistical tools were employed to examine similarities/differences and relationships. Forests of the 30 y group exhibit significantly greater homogeneity in terms of floristic composition, while forests of the 20 y group are characterized by lower species abundance and diversity. The floristic composition was primarily influenced by soil features and the time of disturbance. Under "Environmental Protection Areas", soil–vegetation recovery can occur more swiftly than usually observed for BAF. A significant BAF recovery was observed approximately 40 years after the end of human disturbance. A partial recovery featured 30 y disturbed areas, while in 20 y forests, recovery is in its early stages. Human-disturbed BAF can gradually rebound when effective management practices are implemented. [ABSTRACT FROM AUTHOR]

Background: Brazil is one of the countries with the highest rates of caesarean sections (CS), reaching almost 90% of births in the private sector. A quality improvement project called "Adequate Childbirth Project (PPA)" was conceived to reduce CS in the private sector. This project consisted of four primary components: "Governance", "Participation of Women", "Reorganization of Care" and "Monitoring". This paper aims to evaluate: (1) which specific activities of the PPA had the largest effect on the probability of a woman having a vaginal delivery; (2) which primary component of the PPA had the largest effect on the probability of vaginal delivery and (3) which scenarios combining the implementation of different activities planned in the PPA had a higher effect on the probability of vaginal delivery. Methods: A sample of 12 private hospitals participating in the PPA was evaluated. We used a Bayesian Network (BN) to capture both non-linearities and complex cause-effect relations. The BN integrated knowledge from experts and data from women to estimate 26 model parameters. The PPA was evaluated in 2473 women belonging to groups 1–4 of the Robson classification, who were divided into two groups: those participating or not participating in the PPA. Results: The probability of a woman having a vaginal delivery was 37.7% higher in women participating in the PPA. The most important component of the project that led to an increase in the probability of vaginal delivery was "Reorganization of Care", leading to a 73% probability of vaginal delivery among women in labor. The activity that had the greatest effect on the type of delivery was access to best practices during labor, with a 72% probability of vaginal delivery. Considering the 12 scenarios combining the different activities of the PPA, the best scenarios included: a non-scheduled delivery, access to information about best practices, access to at least 4 best practices during labor and respect of the birth plan, with an 80% probability of vaginal delivery in the best combinations. Conclusion: PPA has been shown to be an effective quality improvement program, increasing the likelihood of vaginal delivery in private Brazilian hospitals. Plain English Summary: Introduction: Brazil boasts one of the highest rates of caesarean sections (CS) globally, with nearly 90% of births in private facilities being delivered via CS. In response, the 'Adequate Childbirth Project – PPA' was launched as a quality improvement initiative aimed at curbing CS rates in private healthcare. Its goal is to improve the quality of childbirth and reduce the number of CS in private healthcare. The project has four main parts: 'Governance', 'Participation of Women', 'Reorganization of Care', and 'Monitoring'. Method: an evaluative study was conducted across 12 private hospitals involved in the PPA, involving 2473 women who were categorized into PPA participants and non-participants. They used a method called a cause-effect network to see which parts of the PPA helped more women have vaginal deliveries. Results: They found that women in the PPA were 37.7% more likely to have a vaginal delivery. Giving women access to good practices during labor and birth was really important. Also, 'Reorganization of Care' was the most important part of the project. It led to a 73% chance of vaginal delivery for women in labor. Conclusion: The PPA is effective in helping more women in private hospitals have vaginal deliveries. This means it's a good program for improving childbirth in Brazil's private hospitals. [ABSTRACT FROM AUTHOR]

Indomethacin (IND) as a non-selective cyclooxygenase 1 and 2 inhibitor administered orally causes numerous adverse effects, mostly related to the gastrointestinal tract. Moreover, when applied exogenously in topical preparations, there are obstacles to its permeation through the stratum corneum due to its low water solubility and susceptibility to photodegradation. In this work, solid dispersions (SDs) of IND with low-substituted hydroxypropyl cellulose (LHPC) were developed. The IND—SDs were incorporated into a hydroxypropyl guar (HPG) hydrogel to enhance drug solubility on the skin. The hydrogels were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR), viscosity, drug release, and unspecific cytotoxicity in mammalian cells. SEM showed a highly porous structure for SD hydrogels. DSC and XRPD studies showed that amorphous IND species were formed; therefore, these hydrogels exhibited superior drug release in comparison with IND raw material hydrogels. FTIR evidenced the presence of the hydrogen bond in the SD hydrogel. The rheology parameter viscosity increased across gels formulated with SDs in comparison with hydrogels with pure IND. In addition, IND—SD hydrogels combine the advantages of a suitable viscosity for dermal use and no potentially hazardous skin irritation. This study suggests that the formulated IND—SD hydrogels represent a suitable candidate for topical administration. [ABSTRACT FROM AUTHOR]