The Healthy Native Youth Implementation toolbox: Using Implementation Mapping to adapt an Online Decision Support System to Promote Culturally-Relevant Sexual Health Education For american indian and alaska Native Youth

BACKGROUND: American Indian and Alaska Native (AI/AN) youth experience serious disparities in sexual and reproductive health, including the highest teen birth rate among racial/ethnic groups, and disproportionate rates of sexually transmitted infections (STI), including HIV. A growing number of evidence-based programs (EBPs) that integrate the strengths and cultural teachings of Native communities exist. Yet, multiple factors, including lack of trained personnel, limited resources, and geographic isolation, may hinder their adoption and implementation. Innovative implementation strategies that facilitate the adoption and implementation of sexual health EBPs in Native communities may help reduce these disparities. METHODS: We applied Implementation Mapping, a systematic planning framework that utilizes theory, empirical evidence, and community input, to adapt a theory-based, online decision support system, iCHAMPSS (CHoosing And Maintaining Effective Programs for Sex Education in Schools), to support underlying dissemination and implementation processes unique to Native communities. We used an iterative design process, incorporating input from Native practitioners and academicians, to ensure that the adapted decision support system reflects cultural identification, community values, and experiences. RESULTS: Grounded in diffusion of innovations, organizational stage theory, and social cognitive theory, the CONCLUSION: There is a continued need to design, test, and evaluate D&I strategies that are relevant to Native communities. Th

Maternal Immune Response During Pregnancy and Vertical Transmission in Human Toxoplasmosis

Toxoplasmosis is a parasitic zoonosis distributed worldwide, caused by the ingestion of contaminated water/food with the parasite Toxoplasma gondii. If a pregnant woman is infected with this parasite, it may be transmitted to the fetus and produce ocular, neurological, or systemic damage with variable severity. The strength and profile of mother's immune response have been suggested as important factors involved in vertical transmission rate and severity of clinical outcome in the congenitally infected fetus. The aim of this work was to evaluate a possible relation between the mother's immune response during pregnancy and congenital transmission to the fetus. We obtained peripheral blood from T. gondii infected pregnant woman and tested it for anti T. gondii (IgG1, IgG2, IgG3, IgG4, and IgA) in serum. Peripheral blood mononuclear cells (PBMCs) were isolated to analyze the in vitro effect of soluble T. gondii antigens on proliferation and production of cytokines. We found that IgG2-4 and IgA antibodies and lymphocytes proliferation, especially CD4+, CD8+, and CD19+ were positive in a higher proportion of cases in transmitter than in non-transmitter women. Furthermore, IgG2-3 and IgA anti-Toxoplasma antibody levels were higher in those mothers who transmitted the infection than in those who did not. Interestingly, a higher proportion of positive cases to IFN-γ and negatives to the immunoregulatory cytokine TGF-β, were related to T. gondii vertical transmission. Our descriptive results are consistent with the paradoxical previous observations in murine models of congenital toxoplasmosis, which suggest that an increased immune response that protects the mothers from a disseminated or severe disease, and should protect the fetus from infection, is positively related to parasite transmission

Surgeons' perspectives on artificial intelligence to support clinical decision-making in trauma and emergency contexts: results from an international survey

Background Artificial intelligence (AI) is gaining traction in medicine and surgery. AI-based applications can offer tools to examine high-volume data to inform predictive analytics that supports complex decision-making processes. Time-sensitive trauma and emergency contexts are often challenging. The study aims to investigate trauma and emergency surgeons’ knowledge and perception of using AI-based tools in clinical decision-making processes. Methods An online survey grounded on literature regarding AI-enabled surgical decision-making aids was created by a multidisciplinary committee and endorsed by the World Society of Emergency Surgery (WSES). The survey was advertised to 917 WSES members through the society’s website and Twitter profile. Results 650 surgeons from 71 countries in five continents participated in the survey. Results depict the presence of technology enthusiasts and skeptics and surgeons' preference toward more classical decision-making aids like clinical guidelines, traditional training, and the support of their multidisciplinary colleagues. A lack of knowledge about several AI-related aspects emerges and is associated with mistrust. Discussion The trauma and emergency surgical community is divided into those who firmly believe in the potential of AI and those who do not understand or trust AI-enabled surgical decision-making aids. Academic societies and surgical training programs should promote a foundational, working knowledge of clinical AI

Structure and tree diversity of secondary dry tropical forests in the Sierra de Huautla Biosphere Reserve, Morelos

"Se estudió la recuperación en riqueza, composición, estructura y diversidad arbórea en 3 condiciones de bosque tropical caducifolio secundario con diferente tiempo de abandono (C35, C45 y C65 años) en el sureste del estado de Morelos. En cada condición se establecieron 3 unidades de muestreo de 50 × 50 m (2,500 m2) y se midieron a todos los individuos ≥ 2.5 cm de diámetro normal (DN). En total se registraron 2,791 individuos, pertenecientes a 79 especies, 53 géneros y 30 familias. Fabaceae fue la familia con el mayor número de especies e individuos. C45 presentó la mayor riqueza de especies (57), seguida de C35 (48) y C65 (43). Las condiciones fueron diferentes (p < 0.0001) en área basal, altura total, DN y cobertura de copa. Las especies con mayores índices relativos de valor de importancia (IVIR) y de valor forestal (IVFR) fueron Pachycereus grandis (IVIR = 22.6, IVFR = 28.7), Amphipterygium adstringens (IVIR = 20.9, IVFR = 17.0), Lysiloma divaricatum (IVIR = 11.2, IVFR = 18.9) y Quercus glaucoides (IVIR = 10.5, IVFR = 13.1). Se encontraron diferencias altamente significativas (p < 0.001) entre condiciones de abandono para la heterogeneidad (Shannon-Wiener: H´), y valores significativamente (p < 0.05) mayores en C65 para el recíproco de Simpson (1/D), así como en C35 y C45 para los índices de Margalef (DMG) y α de Fisher (S). La semejanza florística (Sorensen: Is) fue máxima entre condiciones con menor tiempo de abandono (72%) y mínima con la condición de mayor tiempo (54%). El procedimiento de permutación de respuesta múltiple indicó diferencias significativas (p < 0.05) en la composición de especies entre condiciones tempranas (C35 y C45) y tardías (C65). Estos resultados explican el proceso de la sucesión secundaria en los bosques tropicales caducifolios del área de estudio y dan elementos para efectuar una mejor planificación de las actividades conducentes a su conservación.""The recovery in richness, composition, structure and tree diversity was studied in three conditions of secondary tropical deciduous forest with different time of abandonment (C35, C45 and C65 years) in the southeast of the state of Morelos. In each condition, three plots of 50 × 50 m (2,500 m2) were established and all individuals ≥ 2.5 cm of normal diameter (ND) were measured. In total, 2,791 individuals belonging to 79 species, 53 genera and 30 families were registered. Fabaceae was the family with the largest number of species and individuals. C45 had the highest species richness (57), followed by C35 (48) and C65 (43). The conditions were different (p < 0.0001) in basal area, total height, ND and crown coverage. The species with the highest relative value of importance (IVIR) and forest value (IVFR) were Pachycereus grandis (IVIR = 22.6, IVFR = 28.7), Amphipterygium adstringens (IVIR = 20.9, IVFR = 17.0), Lysiloma divaricatum (IVIR =11.2, IVFR = 18.9) and Quercus glaucoides (IVIR = 10.5, IVFR = 13.1). High significant differences (p < 0.001) between abandonment conditions were found for heterogeneity (Shannon-Wiener: H’), and highest significant values (p < 0.05) for Simpson reciprocal index (1/D) in C65, as well as to Margalef (DMG) and Fisher’s α (S) indexes in C35 and C45. The floristic similarity (Sorensen: Is) was highest among conditions with less time of abandonment (72%) and minimum with the condition of greater time (54%). The multiple response permutation procedure indicated significant differences (p < 0.05) in the species composition between early (C35 and C45) and late (C65) conditions. These results explain the process of secondary succession in the tropical deciduous forests of the study area and provide elements for improve planning of the activities leading to its conservation.

The pathogenic mechanism of the Mycobacterium ulcerans virulence factor, mycolactone, depends on blockade of protein translocation into the ER.

Infection with Mycobacterium ulcerans is characterised by tissue necrosis and immunosuppression due to mycolactone, the necessary and sufficient virulence factor for Buruli ulcer disease pathology. Many of its effects are known to involve down-regulation of specific proteins implicated in important cellular processes, such as immune responses and cell adhesion. We have previously shown mycolactone completely blocks the production of LPS-dependent proinflammatory mediators post-transcriptionally. Using polysome profiling we now demonstrate conclusively that mycolactone does not prevent translation of TNF, IL-6 and Cox-2 mRNAs in macrophages. Instead, it inhibits the production of these, along with nearly all other (induced and constitutive) proteins that transit through the ER. This is due to a blockade of protein translocation and subsequent degradation of aberrantly located protein. Several lines of evidence support this transformative explanation of mycolactone function. First, cellular TNF and Cox-2 can be once more detected if the action of the 26S proteasome is inhibited concurrently. Second, restored protein is found in the cytosol, indicating an inability to translocate. Third, in vitro translation assays show mycolactone prevents the translocation of TNF and other proteins into the ER. This is specific as the insertion of tail-anchored proteins into the ER is unaffected showing that the ER remains structurally intact. Fourth, metabolic labelling reveals a near-complete loss of glycosylated and secreted proteins from treated cells, whereas cytosolic proteins are unaffected. Notably, the profound lack of glycosylated and secreted protein production is apparent in a range of different disease-relevant cell types. These studies provide a new mechanism underlying mycolactone's observed pathological activities both in vitro and in vivo. Mycolactone-dependent inhibition of protein translocation into the ER not only explains the deficit of innate cytokines, but also the loss of membrane receptors, adhesion molecules and T-cell cytokines that drive the aetiology of Buruli ulcer

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines

Background: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. Methods: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, see Supplementary data) concluded the following: Results: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50–200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. Conclusions: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed

Diversity and ethics in trauma and acute care surgery teams: results from an international survey

Background Investigating the context of trauma and acute care surgery, the article aims at understanding the factors that can enhance some ethical aspects, namely the importance of patient consent, the perceptiveness of the ethical role of the trauma leader, and the perceived importance of ethics as an educational subject. Methods The article employs an international questionnaire promoted by the World Society of Emergency Surgery. Results Through the analysis of 402 fully filled questionnaires by surgeons from 72 different countries, the three main ethical topics are investigated through the lens of gender, membership of an academic or non-academic institution, an official trauma team, and a diverse group. In general terms, results highlight greater attention paid by surgeons belonging to academic institutions, official trauma teams, and diverse groups. Conclusions Our results underline that some organizational factors (e.g., the fact that the team belongs to a university context or is more diverse) might lead to the development of a higher sensibility on ethical matters. Embracing cultural diversity forces trauma teams to deal with different mindsets. Organizations should, therefore, consider those elements in defining their organizational procedures. Level of evidence Trauma and acute care teams work under tremendous pressure and complex circumstances, with their members needing to make ethical decisions quickly. The international survey allowed to shed light on how team assembly decisions might represent an opportunity to coordinate team member actions and increase performance

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline