No abstract available.
Child, Preschool ; Chromosome Disorders/diagnosis/*genetics ; *Chromosomes, Human, Pair 8/genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Intellectual Disability ; Karyotyping ; Mexico ; Oligonucleotide Array Sequence Analysis

Objectives: Digital health (DH) is a revolution driven by digital technologies to improve health. Despite the importance of DH, curricular updates in healthcare university programs are scarce, and DH remains undervalued. Therefore, this report describes the first Junior Scientific Committee (JSC) focusing on DH at a nationwide congress, with the aim of affirming its importance for promoting DH in universities. Methods: The scientific committee of the Brazilian Congress of Health Informatics (CBIS) extended invitations to students engaged in health-related fields, who were tasked with organizing a warm-up event and a 4-hour session at CBIS. Additionally, they were encouraged to take an active role in a workshop alongside distinguished experts to map out the current state of DH in Brazil. Results: The warm-up event focused on the topic “Artificial intelligence in healthcare: is a new concept of health about to arise?” and featured remote discussions by three professionals from diverse disciplines. At CBIS, the JSC’s inaugural presentation concentrated on delineating the present state of DH education in Brazil, while the second presentation offered strategies to advance DH, incorporating viewpoints from within and beyond the academic sphere. During the workshop, participants deliberated on the most crucial competencies for future professionals in the DH domain. Conclusions Forming a JSC proved to be a valuable tool to foster DH, particularly due to the valuable interactions it facilitated between esteemed professionals and students. It also supports the cultivation of leadership skills in DH, a field that has not yet received the recognition it deserves.

Background: Extended-spectrum beta-lactamases (ESBLs), which allow bacteria to become resistant to commonly used antibiotics against common pathogens such as Klebsiella pneumoniae, are a significant public health concern as their presence severely limits treatment options. Discovery and development of new drug entities are critical to effectively combat infections with these increasingly common antibiotic-resistant variants. Objective: Computational approaches can accelerate and reduce the cost of the discovery phase by screening for inhibitors of “druggable” pathogen enzyme targets in silico. In this study, protein structures of the ESBL enzymes SHV-1 and CTX-M-15 were used as targets in molecular docking experiments to identify potential inhibitors for K. pneumoniae. Methodology: 5000 compounds from the Enamine Real HTS compound database were screened in silico for binding to SHV-1 and CTX-M-15. Twenty-six (26) compounds that were identified to have more favorable interactions compared to Avibactam, a known inhibitor of the target proteins, were tested for cytotoxic activities in vivo using Resazurin Microtiter Assay (REMA) against a K. pneumoniae clinical isolate containing both SHV-1 and CTX-M-15 resistance genes. Results and Conclusion Despite favorable binding energies in in silico screening, most of the compounds exhibited negligible inhibition on the growth of the K. pneumoniae clinical isolate in in vitro assays. This may be attributed to the fact that a phenotypic whole-cell assay, instead of an enzyme-targeted assay, was used for validation. Cell permeability requires a different set of molecular parameters which were not part of the study. Doxorubicin exhibited the highest in vitro bactericidal activity against this strain, which agrees with its known activity against many other bacterial pathogens and may be a promising compound for further lead optimization.
Drug Resistance, Microbial

Background: Six-pyruvoyl-tetrahydrobiopterin synthase (6-PTPS) deficiency is an inherited metabolic disorder which results in tetrahydrobiopterin (BH4) deficiency causing hyperphenylalaninemia. Objective: This study aimed to describe the clinical, biochemical, and radiologic profiles, and neurologic and developmental outcomes of patients diagnosed with 6-pyruvoyl tetrahydrobiopterin (PTPS) deficiency through newborn screening and confirmed by BH4 loading test, pterin analysis, and gene sequencing who were following-up with the metabolic team. Methods: The research was a single-center descriptive case series study design that was done at the Philippine General Hospital, a tertiary government hospital. The clinical, biochemical, radiologic profiles and neurodevelopmental evaluation of each patient were described. Results: Nine patients from 1 year 2 months to 14 years 5 months of age were enrolled in the study. Clinical manifestations before treatment were hypotonia, poor suck, and seizure. The most common clinical manifestation even after treatment initiation was seizure. The mean phenylalanine level on newborn screening was 990.68 umol/L, but after treatment was started, mean levels ranged from 75.69 to 385.09 umol/L. Two of the patients had focal atrophy of the posterior lobe on brain imaging. Pathogenic variants on molecular analysis were all missense, with two predominant variants, c.155A>G and c.58T>C. Eight of the nine patients had varying degrees of developmental delay or intellectual disability, while the remaining patient had signs of a learning disorder. Conclusion Newborn screening has played a crucial role in the early identification and management of patients with hyperphenylalaninemia due to 6-PTPS deficiency. Confirmation of diagnosis through determination of DHPR activity, urine pterins and/or molecular analysis is necessary for appropriate management. However, despite early initiation of treatment, neurodevelopmental findings of patients with 6-PTPS deficiency were still unsatisfactory.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.