Pharmacological Intervention in Children with Autism Spectrum Disorder with Standard Supportive Therapies Significantly Improves Core Signs and Symptoms: A Single-Center, Retrospective Case Series

Purpose: Autism spectrum disorder (ASD) is a debilitating neurodevelopmental disorder with high heterogeneity and no clear common cause. Several drugs, in particular risperidone and aripiprazole, are used to treat comorbid challenging behaviors in children with ASD. Treatment with risperidone and aripiprazole is currently recommended by the Food and Drug Administration (FDA) in the USA for children aged 5 and 6 years and older, respectively. Here, we investigated the use of these medications in younger patients aged 4 years and older. Patients and Methods: This retrospective case series included 18 children (mean age, 5.7 years) with ASD treated at the Kids Neuro Clinic and Rehab Center in Dubai. These patients began treatment with risperidone or aripiprazole at the age of 4 years and older, and all patients presented with comorbid challenging behaviors that warranted pharmacological intervention with either risperidone or aripiprazole. Results: All 18 children showed objective improvement in their ASD core signs and symptoms. Significant improvement was observed in 44% of the cases, and complete resolution (minimal-to-no-symptoms) was observed in 56% of the cases as per the Childhood Autism Rating Scale 2-Standard Test (CARS2-ST) and the Clinical Global Impression (CGI) scales. Conclusion: Our findings indicate that the chronic administration of antipsychotic medications with or without ADHD medications is well tolerated and efficacious in the treatment of ASD core and comorbid symptoms in younger children when combined with standard supportive therapies. This is the first report to suggest a treatment approach that may completely resolve the core signs and symptoms of ASD. While the reported outcomes indicate significant improvement to complete resolution of ASD, pharmacological intervention should continue to be considered as part of a multi-component intervention in combination with standard supportive therapies. Furthermore, the findings support the critical need for double-blind, placebo-controlled studies to validate the outcomes

Multimodal perioperative pain protocol for Gynecologic Oncology laparotomy reduces length of hospital stay

Our primary objective was to evaluate the impact of a multimodal perioperative pain regimen on length of hospital stay for patients undergoing laparotomy with a gynecologic oncologist

Evaluating implementation of LEAPS, a youth-led early childhood care and education intervention in rural Pakistan: Protocol for a stepped wedge cluster-randomized trial

Background: The Sustainable Development Goals (SDGs) highlight the importance of investments in early childhood care and education (ECCE) and youth development. Given Pakistan\u27s large young population, and gender and urban-rural inequalities in access to education, training, and employment, such investments offer opportunities. LEAPS is a youth-led ECCE program that trains female youth, 18-24 years, as Community Youth Leaders (CYLs) to deliver high-quality ECCE for children, 3.5-5.5 years, in rural Sindh, Pakistan.Methods: We use a stepped wedge cluster-randomized trial to evaluate implementation of LEAPS. Ninety-nine clusters will be randomized to receive the intervention in one of three 7-month steps (33 clusters/step). The primary outcome is children\u27s school readiness (indexed by the total score on the International Development and Early Learning Assessment (IDELA)). Secondary child outcomes are children\u27s IDELA domain scores and executive functions. Data are collected in cross-sectional surveys of 1089 children (11 children/cluster from 99 clusters) aged 4.5-5.5 years at four timepoints (baseline and at the end of each step). Additionally, we will enroll three non-randomized youth participant open cohorts, one per step (33 CYLs: 66 comparison youth per cohort; 99:198 in total). Youth cohorts will be assessed at enrollment and every 7 months thereafter to measure secondary outcomes of youth personal and professional development, depressive symptoms, and executive functions. A non-randomized school cohort of 330 LEAPS students (10 students/cluster from 33 clusters) will also be enrolled and assessed during Step 1 after intervention rollout and at endline. The quality of the learning environment will be assessed in each LEAPS ECCE center and in a comparison center at two timepoints midway following rollout and at endline. A concurrent mixed-methods implementation evaluation will assess program fidelity and quality, and the extent to which a technical support strategy is successful in strengthening systems for program expansion. A cost evaluation will assess cost per beneficiary. Data collection for implementation and cost evaluations will occur in Step 3.Discussion: Youth-led models for ECCE offer a promising approach to support young children and youth. This study will contribute to the evidence as a means to promote sustainable human development across multiple SDG targets.Trial registration: ClinicalTrials.gov NCT03764436 . Registered on December 5, 2018

A pilot study applying the plant Anchored Hybrid Enrichment method to New World sages (Salvia subgenus Calosphace; Lamiaceae)

We conducted a pilot study using Anchored Hybrid Enrichment to resolve relationships among a mostly Neotropical sage lineage that may have undergone a recent evolutionary radiation. Conventional markers (ITS, trnL-trnF and trnH-psbA) have not been able to resolve the relationships among species nor within portions of the backbone of the lineage. We sampled 12 representative species of subgenus Calosphace and included one species of Salvia´s s.l. closest relative, Lepechinia, as outgroup. Hybrid enrichment and sequencing were successful, yielding 448 alignments of individual loci with an average length of 704. bp. The performance of the phylogenomic data in phylogenetic reconstruction was superior to that of conventional markers, increasing both support and resolution. Because the captured loci vary in the amount of net phylogenetic informativeness at different phylogenetic depths, these data are promising in phylogenetic reconstruction of this group and likely other lineages within Lamiales. However, special attention should be placed on the amount of phylogenetic noise that the data could potentially contain. A prior exploration step using phylogenetic informativeness profiles to detect loci with sites with disproportionately high substitution rates (showing "phantom" spikes) and, if required, the ensuing filtering of the problematic data is recommended. In our dataset, filtering resulted in increased support and resolution for the shallow nodes in maximum likelihood phylogenetic trees resulting from concatenated analyses of all the loci. Additionally, it is expected that an increase in sampling (loci and taxa) will aid in resolving weakly supported, short deep internal branches.Fil: Fragoso Martínez, Itzi. Universidad Nacional Autónoma de México; México. Institute Of Biology Of Unam;Fil: Salazar, Gerardo A.. Universidad Nacional Autónoma de México; MéxicoFil: Martínez Gordillo, Martha. Universidad Nacional Autónoma de México; MéxicoFil: Magallón, Susana. Universidad Nacional Autónoma de México; MéxicoFil: Sánchez-Reyes, Luna. Universidad Nacional Autónoma de México; MéxicoFil: Moriarty Lemmon, Emily. Florida State University; Estados UnidosFil: Lemmon, Alan R.. Florida State University; Estados UnidosFil: Sazatornil, Federico David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Granados Mendoza, Carolina. Instituto Potosino de Investigación Científica y Tecnológica; México. Universidad Nacional Autónoma de México; Méxic

Rehabilitación de la infraestructura cultural en el AMG

México tiene una gran infraestructura cultural, por ello creemos que las instituciones competentes deben reconocer la responsabilidad que tienen en el mantenimiento de los espacios destinados a la difusión y promoción de la cultura. ​Esta investigación pretende conocer la historia y el contexto de la infraestructura cultural del AMG, específicamente el nacimiento, esplendor y abandono de cinco espacios culturales: el Teatro Torres Bodet, la Sala Roxy, el Teatro María Teresa, el Laboratorio de Arte Larva y el Auditorio Concha Acústica, así como su condición actual en el proceso de reactivación y reinserción en el circuito cultural tanto por instituciones públicas como por iniciativas privadas.ITESO, A.C

SARS-CoV-2 Viral Load in Saliva Rises Gradually and to Moderate Levels in Some Humans

Transmission of SARS-CoV-2 in community settings often occurs before symptom onset, therefore testing strategies that can reliably detect people in the early phase of infection are urgently needed. Early detection of SARS-CoV-2 infection is especially critical to protect vulnerable populations who require frequent interactions with caretakers. Rapid COVID-19 tests have been proposed as an attractive strategy for surveillance, however a limitation of most rapid tests is their low sensitivity. Low-sensitivity tests are comparable to high sensitivity tests in detecting early infections when two assumptions are met: (1) viral load rises quickly (within hours) after infection and (2) viral load reaches and sustains high levels (>10⁵ - 10⁶ RNA copies/mL). However, there are no human data testing these assumptions. In this study, we document a case of presymptomatic household transmission from a healthy college student to his brother and father. Participants prospectively provided twice-daily saliva samples. Samples were analyzed by RT-qPCR and RT-ddPCR and we measured the complete viral load profiles throughout the course of infection of the brother and father. This study provides evidence that in at least some human cases of SARS-CoV-2, viral load rises slowly (over days, not hours) and not to such high levels to be detectable reliably by any low-sensitivity test. Additional viral load profiles from different samples types across a broad demographic must be obtained to describe the early phase of infection and determine which testing strategies will be most effective for identifying SARS-CoV-2 infection before transmission can occur

Epidemic Leptospirosis Associated with Pulmonary Hemorrhage—Nicaragua, 1995

In October 1995, epidemic “hemorrhagic fever,” without jaundice or renal manifestations, was reported in rural Nicaragua following heavy flooding; 2259 residents were evaluated for nonmalarial febrile illnesses (cumulative incidence, 6.1%) and 15 (0.7%) died with pulmonary hemorrhage. A case-control study found that case-patients were more likely than controls to have ever walked in creeks (matched odds ratio [MOR], 15.0; 95% confidence interval [CI], 1.7–132.3), have household rodents (MOR, 10.4; 95% CI, 1.1–97.1), or own dogs with titers ≥ 400 to Leptospira species (MOR, 23.4; 95% CI, 3.6–`). Twenty-six of 51 case-patients had serologic or postmortem evidence of acute leptospirosis. Leptospira species were isolated from case-patients and potential animal reservoirs. This leptospirosis epidemic likely resulted from exposure to flood waters contaminated by urine from infected animals, particularly dogs. Leptospirosis should be included in the differential diagnosis for nonmalarial febrile illness, particularly during periods of flooding or when pulmonary hemorrhage occurs

Results From the Global Rheumatology Alliance Registry

Funding Information: We acknowledge financial support from the ACR and EULAR. The ACR and EULAR were not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: © 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.Objective: Some patients with rheumatic diseases might be at higher risk for coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). We aimed to develop a prediction model for COVID-19 ARDS in this population and to create a simple risk score calculator for use in clinical settings. Methods: Data were derived from the COVID-19 Global Rheumatology Alliance Registry from March 24, 2020, to May 12, 2021. Seven machine learning classifiers were trained on ARDS outcomes using 83 variables obtained at COVID-19 diagnosis. Predictive performance was assessed in a US test set and was validated in patients from four countries with independent registries using area under the curve (AUC), accuracy, sensitivity, and specificity. A simple risk score calculator was developed using a regression model incorporating the most influential predictors from the best performing classifier. Results: The study included 8633 patients from 74 countries, of whom 523 (6%) had ARDS. Gradient boosting had the highest mean AUC (0.78; 95% confidence interval [CI]: 0.67-0.88) and was considered the top performing classifier. Ten predictors were identified as key risk factors and were included in a regression model. The regression model that predicted ARDS with 71% (95% CI: 61%-83%) sensitivity in the test set, and with sensitivities ranging from 61% to 80% in countries with independent registries, was used to develop the risk score calculator. Conclusion: We were able to predict ARDS with good sensitivity using information readily available at COVID-19 diagnosis. The proposed risk score calculator has the potential to guide risk stratification for treatments, such as monoclonal antibodies, that have potential to reduce COVID-19 disease progression.publishersversionepub_ahead_of_prin

Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS