Leishmania Ribosomal Protein (RP) paralogous genes compensate each other's expression maintaining protein native levels.

In the protozoan parasite Leishmania, most genes encoding for ribosomal proteins (RPs) are present as two or more copies in the genome. However, their untranslated regions (UTRs) are predominantly divergent and might be associated with a distinct regulation of the expression of paralogous genes. Herein, we investigated the expression profiles of two RPs (S16 and L13a) encoded by duplicated genes in Leishmania major. The genes encoding for the S16 protein possess identical coding sequences (CDSs) and divergent UTRs, whereas the CDSs of L13a diverge by two amino acids and by their UTRs. Using CRISPR/Cas9 genome editing, we generated knockout (Δ) and endogenously tagged transfectants for each paralog of L13a and S16 genes. Combining tagged and Δ cell lines we found evidence of differential expression of both RPS16 and RPL13a isoforms throughout parasite development, with one isoform consistently more abundant than its respective copy. In addition, compensatory expression was observed for each paralog upon deletion of the corresponding isoform, suggesting functional conservation between these proteins. This differential expression pattern relates to post-translational processes, given compensation occurs at the level of the protein, with no alterations detected at transcript level. Ribosomal profiles for RPL13a indicate a standard behavior for these paralogues suggestive of interaction with heavy RNA-protein complexes, as already reported for other RPs in trypanosomatids. We identified paralog-specific bound to their 3'UTRs which may be influential in regulating paralog expression. In support, we identified conserved cis-elements within the 3'UTRs of RPS16 and RPL13a; cis-elements exclusive to the UTR of the more abundant paralog or to the less abundant ones were identified.

Survival and Lung Function Changes in Hypersensitivity Pneumonitis According to Radiological Phenotypes Compared With Idiopathic Pulmonary Fibrosis.

INTRODUCTION: The main objective of this study was to estimate survival and changes in lung function in patients with chronic hypersensitivity pneumonitis (HP), both fibrotic (f-HP) and nonfibrotic (nf-HP), and to compare them with those in patients with idiopathic pulmonary fibrosis (IPF). METHODS: HP was diagnosed based on antigen exposure, HRCT (high-resolution CT scan), BAL (bronchoalveolar lavage), and histology. According to HRCT, HP was classified into fibrotic and non-fibrotic phenotypes. In most cases, IPF was diagnosed based on HRCT findings. RESULTS: We identified 84 patients: 46 with IPF, 18 with f-HP, and 20 with nf-HP. Five-year survival was 23.9% in IPF, 72% in f-HP, and 100% in nf-HP (p <0.0001). Honeycombing was associated with decreased survival in IPF (p <0.001) and in f-HP (p <0.0001). The mean loss of FVC (forced vital capacity) % pred. (percent predicted) was -18.3% in IPF (p =0.001), -4.8% in f-HP, and -6.0% in nf-HP. The mean change in DLCO (diffusion capacity for carbon monoxide) % pred. was -10.2% in IPF (p <0.002), -0.5% in f-HP, and +1.9% in nf-HP. The agreement between radiological phenotypes and histology in HP was 89.6%. CONCLUSIONS: We found shorter survival in IPF, followed by f-HP, and nf-HP. Over time, we did not find significant changes in FVC% pred. or DLCO% pred. in HP, while a significant decline in IPF was noted. In HP, we found strong agreement between radiological phenotypes and histology. Radiological signs suggestive of lung fibrosis in HP were reliable for the diagnosis of f-HP and seem to have intrinsic prognostic value.

Prevalence of Oropharyngeal Dysphagia and Its Value as a Prognostic Factor in Community-Acquired Pneumonia: A Prospective Case-Control Study.

BACKGROUND: Although oropharyngeal dysphagia (OD) is a common finding in patients with community-acquired pneumonia (CAP), specific recommendations are not provided in the current clinical guidelines. OBJECTIVES: To estimate the prevalence of OD and its associated factors among patients hospitalized for CAP and to assess one-year outcomes according to the presence or absence of OD. METHODS: We studied 226 patients hospitalized for CAP and 226 patients hospitalized for respiratory conditions other than CAP. We screened the risk of OD using the Eating Assessment Tool-10 (EAT-10), followed by the volume-viscosity swallow test (V-VST). RESULTS: A total of 122 (53.9%) patients with CAP had confirmed OD compared with 44 (19.4%) patients without CAP. Patients with CAP and OD were older (p < 0.001; 1.02-1.07) and had less familial/institutional support (p = 0.036; 0.12-0.91) compared to patients with CAP and no OD. OD was more prevalent as the CURB-65 score increased (p < 0.001). Patients with OD spent more time in the hospital (14.5 vs. 11.0 days; p = 0.038) and required more visits to the emergency room (ER). Twenty (16.4%) patients with CAP and OD died after discharge vs. one (0.8%) patient with CAP and no OD (p < 0.001; CI = 2.24-42.60). CONCLUSIONS: The prevalence of OD in hospitalized patients with CAP is higher than in patients hospitalized for other respiratory diagnoses. Advanced age, lower familial/institutional support, and increased CAP severity are associated with OD. Patients with CAP and OD are more frequent ER visitors after discharge and have a higher mortality. In patients with CAP and OD, aspiration pneumonia is likely underestimated.

[Human resources in the National Health System. Medical education. SESPAS Report 2024]. / Recursos humanos del Sistema Nacional de Salud. Formación. Informe SESPAS 2024.

The problems posed by medical education in Spain are diverse. This paper analyzes the system currently used to select candidates who will be admitted to a public faculty of medicine in Spain and some issues arising from the unprecedented increase in both public and private medical schools in our country. The importance of generic competencies in today's medicine and the need to return to a core design in specialist training are other aspects that are discussed. The degree of development of advanced accreditation diplomas and areas of specific competence is also subject to analysis. Finally, the authors emphasize the importance of continuous professional development and the idea of professional recertification as a system that guarantees patients the quality of the care they receive.

A Randomized Trial Comparing Quality of Life After Low-Dose Rate or High-Dose Rate Prostate Brachytherapy Boost With Pelvic External Beam Radiation Therapy.

PURPOSE: To compare health-related quality of life (QoL) in urinary, bowel, and sexual domains after combined external beam radiation therapy (EBRT) and either low-dose rate (LDR) or high-dose rate (HDR) prostate brachytherapy (BT). METHODS AND MATERIALS: Eligible men with intermediate or high-risk prostate cancer treated with combined pelvic EBRT and BT were randomly assigned to either HDR (15 Gy) or LDR (110 Gy) boost. International Prostate Symptom Score, Index of Erectile Function, and Expanded Prostate Cancer Composite were collected at baseline, 1, 3, 6, and 12 months, every 6 months to 3 years and then annually along with prostate-specific antigen/testosterone. Fisher's exact test compared categorical variables and the Mann-Whitney U test Expanded Prostate Cancer Index Composite (EPIC) domain scores. RESULTS: From January 2014 to December 2019, a random number generator assigned 195 men: 108 to HDR and 87 to LDR. Median age was 71 years. Risk group was high in 57% and unfavorable intermediate in 43%. Androgen deprivation (used in 74%) began with 3 months neoadjuvant and continued for median 12 months. Baseline EPIC scores were similar for the LDR/HDR cohorts: 89 and 88 respectively for Genito-urinary; 92 and 93 for Gastro-intestinal. EPIC urinary scores decreased at 1 month for HDR but recovered promptly to a steady state by 6 months. LDR scores reached a nadir at 3 months with slow recovery to 18 months, after which urinary QoL was similar for HDR and LDR. Bowel QOL scores fell in both cohorts reaching respective nadirs at 12 months. HDR patients recovered close to baseline and maintained higher scores than LDR patients to 5 years. The decline for LDR patients remained more than the minimum clinically important difference out to 5 years. CONCLUSIONS: The patient experience for combined EBRT and prostate BT is improved with HDR BT. Urinary QoL improves over time to be equivalent between the 2 modalities after 18 months, but LDR patients report lasting bowel symptoms.

Efficacy of Oral Furosemide Test for Primary Aldosteronism Diagnosis.

Context: Confirmatory tests represent a fundamental step in primary aldosteronism (PA) diagnosis, but they are laborious and often require a hospital environment due to the risks involved. Objective: To evaluate the efficacy of oral furosemide as a new confirmatory test for PA diagnosis. Methods: We prospectively evaluated the diagnostic performance of 80 mg of oral furosemide in 64 patients with PA and 22 with primary hypertension (controls). Direct renin concentration (DRC) was measured before, and 2 hours and 3 hours after the oral furosemide. In addition, the oral furosemide test was compared with 2 other confirmatory tests: the furosemide upright test (FUT) and saline infusion test (SIT) or captopril challenge test (CCT) in all patients with PA. Results: The cut-off of 7.6 µU/mL for DRC at 2 hours after oral furosemide had a sensitivity of 92%, specificity of 82%, and accuracy of 90% for PA diagnosis. In 5 out of 6 controls with low-renin hypertension, which might represent a PA spectrum, renin remained suppressed. Excluding these 6 controls with low-renin hypertension, the DRC cut-off of 10 µU/mL at 2 hours after oral furosemide had a sensitivity of 95.3%, specificity of 93.7% and accuracy of 95% for PA diagnosis. DRC after 3 hours of oral furosemide did not improve diagnostic performance. Using the cut-off of 10 µU/mL, the oral furosemide test and the FUT were concordant in 62 out of 64 (97%) patients with PA. Only 4 out of 64 cases with PA (6.4%) ended the oral furosemide test with potassium <3.5 mEq/L. Hypotension was not evidenced in any patient with PA during the test. Conclusion: The oral furosemide test was safe, well-tolerated and represents an effective strategy for PA investigation.

Three Cases of Carney-Stratakis Syndrome: A Genetically Heterogeneous Disease.

Carney-Stratakis syndrome (CSS) is an autosomal dominant rare syndrome, with incomplete penetrance, characterized by the association of paragangliomas and/or pheochromocytomas and gastrointestinal stromal tumors (GISTs). CSS is caused by germline heterozygous loss-of-function pathogenic variants (PVs) in the succinate dehydrogenase subunit genes (SDHB, SDHC, SDHD), with SDHB and SDHD being the most frequent. To date, only 2 germline SDHC PVs (c.43 C > T; c.405 + 1G > A) have been described in 3 patients with CSS. Three patients with CSS and very distinct clinical presentations are reported here: 1 caused by a germline SDHC large deletion and the others with metastatic GIST and negative genetic investigation for SDHx defects. Two cases (1 and 2) presented with pheochromocytoma (case 1 also with abdominal paraganglioma) and metastatic GIST. Although these 2 cases fulfilled the diagnostic criteria for CSS, the genetic investigation for SDHx PVs by next-generation sequencing and multiplex ligation-dependent probe amplification was negative. Case 3 had a large abdominal paraganglioma and a small low-grade GIST not associated with recurrence or metastasis. This case harbored a germline SDHC exon 3 deletion, not previously reported. In conclusion, CSS is a rare and morbid disease with distinct clinical presentations and genetic heterogeneity, which can contribute to underdiagnosis.

V-Y Flap Over Moberg's Flap to Cover the Thumb's Fingertip Injury: Technique and Cases.

The Moberg flap has been used to achieve coverage of amputations of the thumb's fingertip. However, it has been associated with flexion contractures of the interphalangeal (IP) joint of the thumb. A modification of the surgical technique is presented, adding a distal V-Y flap to allow greater advancement, and avoiding IP joint contractures. The proposed surgical technique is presented, and a case series of patients treated with this modification is introduced. A total of 5 patients underwent this surgical technique. All the flaps healed without complications. No patient presented stiffness or flexion contracture of the thumb´s IP joint. There were no cases of neuropathic pain and the 2-point discrimination over the flap was 6.8 mm on average. In conclusion, the proposed variation to the Moberg's flap allows adequate coverage of injuries to the thumb's fingertip with a low rate of complications, adequate sensitivity of the reconstructed digit and avoiding flexion contractures of the IP joint.

Ethnic Discrimination and Self-rated Health among Hispanic Emerging Adults: Examining the Moderating Effects of Self-esteem and Resilience.

Exposure to ethnic discrimination has been conceptualized as a sociocultural stressor that is associated with lower self-rated health. However, this association remains understudied among Hispanics and less is known about constructs that may mitigate the effects of ethnic discrimination on self-rated health. Accordingly, this study aimed to (a) examine the association between ethnic discrimination and self-rated health among Hispanic emerging adults (ages 18-25), and (b) examine the extent to which self-esteem and resilience may moderate this association. A convenience sample of 200 Hispanic emerging adults from Arizona (n=99) and Florida (n=101) was recruited to complete a cross-sectional survey. Data were analyzed using hierarchical multiple regression and moderation analyses. Results indicate that higher ethnic discrimination was associated with lower self-rated health. Moderation analyses indicated that self-esteem functioned as a moderator that weakened the association between ethnic discrimination and self-rated health; however, resilience did not function similarly as a moderator. This study adds to the limited literature on ethnic discrimination and self-rated health among Hispanics and highlights that psychological factors, such as enhancing self-esteem, may help buffer the adverse effects of ethnic discrimination on health outcomes.

Fabrication and Arc Erosion Behavior of Ag-SnO2-ZnO Electrical Contact Materials.

This study investigated the synthesis of Ag-SnO2-ZnO by powder metallurgy methods and their subsequent electrical contact behavior. The pieces of Ag-SnO2-ZnO were prepared by ball milling and hot pressing. The arc erosion behavior of the material was evaluated using homemade equipment. The microstructure and phase evolution of the materials were investigated through X-ray diffraction, energy-dispersive spectroscopy and scanning electron microscopy. The results showed that, although the mass loss of the Ag-SnO2-ZnO composite (9.08 mg) during the electrical contact test was higher than that of the commercial Ag-CdO (1.42 mg), its electrical conductivity remained constant (26.9 ± 1.5% IACS). This fact would be related to the reaction of Zn2SnO4's formation on the material's surface via electric arc. This reaction would play an important role in controlling the surface segregation and subsequent loss of electrical conductivity of this type of composite, thus enabling the development of a new electrical contact material to replace the non-environmentally friendly Ag-CdO composite.

Cultural adaptations and cultural factors in EBI implementation with Latinx communities.

Introduction: Cultural factors are constructs that capture important life experiences of Latinx/Hispanic individuals, families, and communities. Despite their importance for Latinx communities, Latinx cultural factors have yet to be fully incorporated into the literature of many social, behavioral science, and health service fields, including implementation science. This significant gap in the literature has limited in-depth assessments and a more complete understanding of the cultural life experiences of diverse Latinx community residents. This gap has also stifled the cultural adaptation, dissemination, and implementation of evidence based interventions (EBIs). Addressing this gap can inform the design, dissemination, adoption, implementation, and sustainability of EBIs developed to serve Latinx and other ethnocultural groups. Methods: Based on a prior Framework Synthesis systematic review of Latinx stress-coping research for the years 2000-2020, our research team conducted a thematic analysis to identify salient Latinx cultural factors in this research field. This thematic analysis examined the Discussion sections of 60 quality empirical journal articles previously included into this prior Framework Synthesis literature review. In Part 1, our team conducted an exploratory analysis of potential Latinx cultural factors mentioned in these Discussion sections. In Part 2 we conducted a confirmatory analysis using NVivo 12 for a rigorous confirmatory thematic analysis. Results: This procedure identified 13 salient Latinx cultural factors mentioned frequently in quality empirical research within the field of Latinx stress-coping research during the years 2000-2020. Discussion: We defined and examined how these salient Latinx cultural factors can be incorporated into intervention implementation strategies and can be expanded to facilitate EBI implementation within diverse Latinx community settings.

Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia.

X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4-dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8-207.8, P < 0.001). The patients' susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.

Gasdermin-D activation promotes NLRP3 activation and host resistance to Leishmania infection.

Intracellular parasites from the Leishmania genus cause Leishmaniasis, a disease affecting millions of people worldwide. NLRP3 inflammasome is key for disease outcome, but the molecular mechanisms upstream of the inflammasome activation are still unclear. Here, we demonstrate that despite the absence of pyroptosis, Gasdermin-D (GSDMD) is active at the early stages of Leishmania infection in macrophages, allowing transient cell permeabilization, potassium efflux, and NLRP3 inflammasome activation. Further, GSDMD is processed into a non-canonical 25 kDa fragment. Gsdmd-/- macrophages and mice exhibit less NLRP3 inflammasome activation and are highly susceptible to infection by several Leishmania species, confirming the role of GSDMD for inflammasome-mediated host resistance. Active NLRP3 inflammasome and GSDMD are present in skin biopsies of patients, demonstrating activation of this pathway in human leishmaniasis. Altogether, our findings reveal that Leishmania subverts the normal functions of GSDMD, an important molecule to promote inflammasome activation and immunity in Leishmaniasis.

Evidence for a Founder Effect of SDHB Exon 1 Deletion in Brazilian Patients With Paraganglioma.

CONTEXT: Limited information is available concerning the genetic spectrum of pheochromocytoma and paraganglioma (PPGL) patients in South America. Germline SDHB large deletions are very rare worldwide, but most of the individuals harboring the SDHB exon 1 deletion originated from the Iberian Peninsula. OBJECTIVE: Our aim was to investigate the spectrum of SDHB genetic defects in a large cohort of Brazilian patients with PPGLs. METHODS: Genetic investigation of 155 index PPGL patients was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification, and/or target next-generation sequencing panel. Common ancestrality was investigated by microsatellite genotyping with haplotype reconstruction, and analysis of deletion breakpoint. RESULTS: Among 155 index patients, heterozygous germline SDHB pathogenic or likely pathogenic variants were identified in 22 cases (14.2%). The heterozygous SDHB exon 1 complete deletion was the most frequent genetic defect in SDHB, identified in 8 out of 22 (36%) of patients. Haplotype analysis of 5 SDHB flanking microsatellite markers demonstrated a significant difference in haplotype frequencies in a case-control permutation test (P = 0.03). More precisely, 3 closer/informative microsatellites were shared by 6 out of 8 apparently unrelated cases (75%) (SDHB-GATA29A05-D1S2826-D1S2644 | SDHB-186-130-213), which was observed in only 1 chromosome (1/42) without SDHB exon 1 deletion (X2 = 29.43; P < 0.001). Moreover, all cases with SDHB exon 1 deletion had the same gene breakpoint pattern of a 15 678 bp deletion previously described in the Iberian Peninsula, indicating a common origin. CONCLUSION: The germline heterozygous SDHB exon 1 deletion was the most frequent genetic defect in the Brazilian PPGL cohort. Our findings demonstrated a founder effect for the SDHB exon 1 deletion in Brazilian patients with paragangliomas.

Strategic Directions in Preventive Intervention Research to Advance Health Equity.

As commissioned by the Society for Prevention Research, this paper describes and illustrates strategic approaches for reducing health inequities and advancing health equity when adopting an equity-focused approach for applying prevention science evidence-based theory, methodologies, and practices. We introduce an ecosystemic framework as a guide for analyzing, designing, and planning innovative equity-focused evidence-based preventive interventions designed to attain intended health equity outcomes. To advance this process, we introduce a health equity statement for conducting integrative analyses of ecosystemic framework pathways, by describing the role of social determinants, mechanisms, and interventions as factors directly linked to specific health equity outcomes. As background, we present health equity constructs, theories, and research evidence which can inform the design and development of equity-focused intervention approaches. We also describe multi-level interventions that when coordinated can produce synergistic intervention effects across macro, meso, and micro ecological levels. Under this approach, we encourage prevention and implementation scientists to apply and extend these strategic directions in future research to increase our evidence-based knowledge and theory building. A general goal is to apply prevention science knowledge to design, widely disseminate, and implement culturally grounded interventions that incrementally attain specific HE outcomes and an intended HE goal. We conclude with recommendations for conducting equity-focused prevention science research, interventions, and training.

Family support during childhood as a predictor of mate retention and kin care in adults during the COVID-19 pandemic in Brazil: an exploratory study.

Introduction: Experiences during development help to explain behavior expression in adulthood. Aims: In this study, we explored how unpredictability and harshness experienced during childhood may have impacted the occurrence of reproductive milestones in adulthood and the expression of fundamental motives related to self-protection, disease avoidance, mate seeking, mate retention, and kin care (children/family) during the pandemic. Methods: This was an exploratory study with 438 participants. Through the administration of online questionnaires, participants were assessed and categorized based on their childhood experiences, resulting in three groups: low unpredictability, high unpredictability with family support, and high unpredictability without family support. Results: We found that family support experienced during childhood predicts a slow life-history strategy. This involves an emphasis on growth and parenting efforts at the expense reproduction and was relevant even for participants who faced financial unpredictability. During the pandemic, we also observed that mate retention and kin care (family) motives were predominant among individuals who had greater family support during childhood. Discussion: Overall, the findings suggest that unpredictability experienced during childhood is crucial for the development of life-history strategies and the manifestation of fundamental motives in adulthood.

Autoantibodies against type I IFNs in patients with critical influenza pneumonia.

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients <70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10-5), but not >70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10-5), especially those <70 yr old (OR = 139.9, P = 3.1 × 10-10). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for ∼5% of cases of life-threatening influenza pneumonia in patients <70 yr old.

Effects of a Diabetes Prevention Program on Type 2 Diabetes Risk Factors and Quality of Life Among Latino Youths With Prediabetes: A Randomized Clinical Trial.

Importance: Latino youths are disproportionately impacted by prediabetes and type 2 diabetes (T2D). Lifestyle intervention is the first-line approach for preventing or delaying T2D among adults with prediabetes. Objective: To assess the efficacy of a diabetes prevention program among Latino youths aged 12 to 16 years with prediabetes. Design, Setting, and Participants: This 2-group parallel randomized clinical trial with 2:1 randomization assessed a lifestyle intervention against usual care among Latino youths with prediabetes and obesity with 6- and 12-month follow-up. The study was conducted at YMCA facilities in Phoenix, Arizona from May 2016 to March 2020. Intervention: Participants were randomized to lifestyle intervention (INT) or usual care control (UCC). The 6-month INT included 1 d/wk of nutrition and health education and 3 d/wk of physical activity. UCC included 2 visits with a pediatric endocrinologist and a bilingual, bicultural registered dietitian to discuss diabetes risks and healthy lifestyle changes. Main Outcomes and Measures: Insulin sensitivity, glucose tolerance, and weight-specific quality of life (YQOL-W) at 6- and 12-month follow-up. Results: A total of 117 Latino youths (mean [SD] age, 14 [1] years; 47 [40.1%] girls) were included in the analysis. Overall, 79 were randomized to INT and 38 to UCC. At 6 months, the INT led to significant decreases in mean (SE) 2-hour glucose (baseline: 144 [3] mg/dL; 6 months: 132 [3] mg/dL; P = .002) and increases in mean (SE) insulin sensitivity (baseline: 1.9 [0.2]; 6 months: 2.6 [0.3]; P = .001) and YQOL-W (baseline: 75 [2]; 6 months: 80 [2]; P = .006), but these changes were not significantly different from UCC (2-hour glucose: mean difference, -7.2 mg/dL; 95% CI, -19.7 to 5.3 mg/dL; P for interaction = .26; insulin sensitivity: mean difference, 0.1; 95% CI, -0.7 to 0.9; P for interaction = .79; YQOL-W: mean difference, 6.3; 95% CI, -1.1 to 13.7; P for interaction = .10, respectively). Both INT (mean [SE], -15 mg/dL [4.9]; P = .002) and UCC (mean [SE], -15 mg/dL [5.4]; P = .005) had significant 12-month reductions in 2-hour glucose that did not differ significantly from each other (mean difference, -0.3; 95% CI, -14.5 to 14.1 mg/dL; P for interaction = .97). At 12 months, changes in mean (SE) insulin sensitivity in INT (baseline: 1.9 [0.2]; 12 months: 2.3 [0.2]; P = .06) and UCC (baseline: 1.9 [0.3]; 12 months: 2.0 [0.2]; P = .70) were not significantly different (mean difference, 0.3; 95% CI, -0.4 to 1.0; P for interaction = .37). At 12 months, YQOL-W was significantly increased in INT (basline: 75 [2]; 12 months: 82 [2]; P < .001) vs UCC (mean difference, 8.5; 95% CI, 0.8 to 16.2; P for interaction = .03). Conclusions and Relevance: In this randomized clinical trial, both INT and UCC led to similar changes in T2D risk factors among Latino youths with diabetes; however, YQOL-W was improved in INT compared with UCC. Diabetes prevention interventions that are effective in adults also appeared to be effective in high risk youths. Trial Registration: ClinicalTrials.gov Identifier: NCT02615353.

QTOF-ESI MS Characterization and Antioxidant Activity of Physalis peruviana L. (Cape Gooseberry) Husks and Fruits from Costa Rica.

There is increasing interest in research of secondary metabolites from Physalis peruviana (Cape gooseberry) because of their potential bioactivities. In this study, the profile of compounds found in fruits and husks from Costa Rica was determined through ultra-performance liquid chromatography coupled with high-resolution mass spectrometry using a quadrupole time-of-flight analyzer (UPLC-ESI-QTOF MS) on extracts (n = 10) obtained through pressurized liquid extraction (PLE) conditions. In total, 66 different compounds were identified, comprising 34 withanolides, 23 sucrose ester derivatives and 9 flavonoids. UPLC-DAD analysis was performed to determine the ß-carotene in fruits and to quantify the flavonoids in all 10 samples, with the results showing higher contents in samples from the Dota region (58.6−60.1 µg/g of dry material versus 1.6−2.8 mg/g of dry material). The Folin−Ciocalteau total polyphenolic content (FC) and antioxidant activity using the DPPH method showed better results for the husk extracts, with the ones from the Dota region holding the best values (4.3−5.1 mg GAE/g of dry material versus IC50 = 1.6−2.3 mg of dry material/mL). In addition, a significant negative correlation was found between the RU, FC and DPPH values (r = −0.902, p < 0.05), aligning with previous reports on the role of polyphenols in antioxidant activity. Principal correlation analysis (PCoA) and hierarchical clustering (HC) analysis were performed on HRMS results, and they indicated that the D1 and D2 fruit samples from the Dota region were clustered with husks related to a higher presence of the analyzed metabolites. In turn, principal component analysis (PCA) performed on the flavonoid content and antioxidant activity yielded results indicating that the D1 and D2 husks and fruit samples from the Dota region stood out significantly, showing the highest antioxidant activity. In summation, our findings suggest that P. peruviana husks and fruits from Costa Rica constitute a substrate of interest for further studies on their potential health benefits.

VEMERS 2.0: Upgrading of an Emergency Use Ventilator from a Single Mandatory Volume Control Mode of Ventilation (VEMERS 1.0) to 8 Modes of Ventilation.

The upgrading of an emergency use ventilator from a single mandatory volume control mode of ventilation (VEMERS 1.0) to 8 modes of ventilation (VEMERS 2.0) is described. The original VEMERS 1.0 was developed in the midst of the COVID-19 crisis in Chile (April to August 2020) following special but nonetheless strict guidelines specified by local medical associations and national health and scientific ministries. The upgrade to 8 modes of ventilation in VEMERS 2.0 was made possible with minor but transcendental changes to the original architecture. The main contribution of this research is that starting from a functional block diagram of an ICU mechanical ventilator and carrying a systematic analysis, the main function blocks are implemented in such a way that combinations of standard off-the-shelf pneumatic and electronic components can be used. This approach has both economical and technical advantages. No special parts need to be fabricated at all, and because of a wider variety of options, the use of extensively field-proven off-the-shelf commercial components assures better availability and lower costs when compared to that of conventional ICU mechanical ventilators, without sacrificing reliability. Given the promising results obtained with VEMERS 2.0 in the subsequent national certification process, the production of 40 VEMERS 2.0 units was sponsored by the Ministry of Science and the Ministry of Economy. Twenty units have been distributed among hospitals along the country. The purpose of VEMERS 2.0, as a low-cost but very reliable option, is to increase the number of mechanical ventilators available (3,000 for a population of 18,000,000) in the country to eventually reach a ratio similar to that of more developed countries. VEMERS is an open-source project for others to use the knowledge gained.