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Background and Objectives: Neurodevelopmental disorders (NDDs), including developmental delay (DD), autism spectrum disorder (ASD), intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), and specific learning disorders, affect 15% of children and adolescents worldwide. Advances in next-generation sequencing, particularly whole exome sequencing (WES), have improved the understanding of NDD genetics. Methodology: This study analyzed 3244 patients undergoing WES (single, duo, trio analyses), with 1028 meeting inclusion criteria (67% male; aged 0–50 years). Results: Pathogenic (P) or likely pathogenic (LP) variants were identified in 190 patients, achieving a diagnostic yield of 13.4% (singleton), 14% (duo), and 21.2% (trio). A total of 207 P/LP variants were identified in NDD-associated genes: 38% were missense (48 de novo), 29% frameshift (26 de novo), 21% nonsense (14 de novo), 11% splicing site (14 de novo), and 1% inframe (1 de novo). De novo variants accounted for 49.8% of cases, with 86 novels de novo variants and 27 novel non de novo variants unreported in databases like ClinVar or scientific literature. Conclusions: This is the largest study on WES in Colombian children with NDDs and one of the largest in Latino populations. It highlights WES as a cost-effective first-tier diagnostic tool in low-income settings, reducing diagnostic timelines and improving clinical care. These findings underscore the feasibility of implementing WES in underserved populations and contribute significantly to understanding NDD genetics, identifying novel variants with potential for further research and clinical applications.

BackgroundOf the 1.6 million transgender and gender-diverse (TGD) people in the United States, approximately 700,000 are youth aged 13-24 years. Many factors make it difficult for TGD young people to identify resources for support and information related to gender identity and medical transition. These range from lack of knowledge to concerns about personal safety in the setting of increased antitransgender violence and legislative limitations on transgender rights. Web-based resources may be able to address some of the barriers to finding information and support, but youth may have difficulty finding relevant content or have concerns about the quality and content of information they find on the internet. ObjectiveWe aim to understand ways TGD young adults look for web-based information about gender and health. MethodsIn August 2022, 102 young adults completed a 1-time survey including closed- and open-ended responses. Individuals were recruited through the Prolific platform. Eligibility was restricted to people between the ages of 18-25 years who identified as transgender and were residents of the United States. The initial goal was to recruit 50 White individuals and 50 individuals who identified as Black, indigenous, or people of color. In total, 102 people were eventually enrolled. ResultsYoung adults reported looking on the internet for information about a broad range of topics related to both medical- and social-gender affirmation. Most participants preferred to obtain information via personal stories. Participants expressed a strong preference for obtaining information from other trans people. ConclusionsThere is a need for accessible, expert-informed information for TGD youth, particularly more information generated for the transgender community by members of the community.

Introducción Los protocolos de manejo de anemia perioperatoria mejoran el cuidado del paciente y disminuyen los costos en salud. El objetivo de este estudio fue identificar el efecto de dicho programa en pacientes sometidos a reemplazo total de cadera (RTC) o rodilla (RTR), en la tasa de transfusiones, tiempo de estadía hospitalaria y eventos adversos. Métodos Se realizó un estudio observacional retrospectivo, incluyendo pacientes sometidos a RTC o RTR primarios. El programa abarcó la valoración preoperatoria, el uso de 2 dosis de ácido tranexámico, la aplicación de transfusiones restringidas, y el uso de hierro suplementario. Se compararon los resultados entre pacientes pre y post implementación del protocolo. Resultados Se incluyeron 179 pacientes (80 RTR y 99 RTC) pre protocolo entre enero y diciembre 2014 (grupo A) y 187 casos (103 RTR y 84 RTC) post protocolo entre enero y noviembre 2016 (grupo B). En el grupo A, la caida de hemoglobina fue mayor que en el grupo B en RTR (5,1±1,2 vs. 4,2±1,2 g/dl; p

A whole-exome capture and next-generation sequencing was applied to an 11 y/o patient with a clinical history of congenital hypotonia, generalized motor and cognitive neurodevelopmental delay, and severe cognitive deficit, and without any identifiable Syndromic pattern, and to her parents, we disclosed a de novo heterozygous pathogenic mutation, c.697_699del p.Phe233del (rs786204835)(ACMG classification PS2, PM1, PM2, PP5), harbored in the PURA gene (MIM*600473) (5q31.3), associated with Autosomal Dominant Mental Retardation 31 (MIM # 616158). We used the significant improvement in the accuracy of protein structure prediction recently implemented in AlphaFold that incorporates novel neural network architectures and training procedures based on the evolutionary, physical, and geometric constraints of protein structures. The wild-type (WT) sequence and the mutated sequence, missing the Phe233, were reconstructed. The predicted local Distance Difference Test (lDDT) for the PURAwt and the PURA–Phe233del showed that the occurrence of the Phe233del affects between 220–320 amino acids. The distortion in the PURA structural conformation in the ~5 Å surrounding area after the p.Phe233del produces a conspicuous disruption of the repeat III, where the DNA and RNA helix unwinding capability occurs. PURA Protein–DNA docking corroborated these results in an in silico analysis that showed a loss of the contact of the PURA–Phe233del III repeat domain model with the DNA. Together, (i) the energetic and stereochemical, (ii) the hydropathic indexes and polarity surfaces, and (iii) the hybrid Quantum Mechanics–Molecular Mechanics (QM–MM) analyses of the PURA molecular models demarcate, at the atomic resolution, the specific surrounding region affected by these mutations and pave the way for future cell-based functional analysis. To the best of our knowledge, this is the first report of a de novo mutation underpinning a PURA syndrome in a Latin American patient and highlights the importance of predicting the molecular effects in protein structure using artificial intelligence algorithms and molecular and atomic resolution stereochemical analyses.

This paper analyses the environment of open data and its perception by Mexicans based on the National Survey on Access to Public Information and Protection of Personal Data (ENAID 2016), and the Survey on Public Perception of Science and Technology (ENPECYT 2015). The literature review was focused on how the open data age represents a new social paradigm that has revolutionized the way that people and organizations obtain, analyse and use large amounts of information to make decisions. Mexico has mechanisms and platforms for access to open data, however, its use and contribution to real innovation is unknown. This work focuses on this problem, the data reflect important weaknesses in the perception of open data implementation as well as little interest in innovation and ignorance about it.

Objective. To determine the prevalence of dry eye symp­toms (DES) and associated risk factors among adults in Tlax­cala, Mexico. Materials and methods. A cross-sectional population-based study that included 1 508 individuals aged ≥50 years who answered the Dry Eye Questionnaire (DEQ- 5), with a score ranging between 0 and 22; the following categories were defined: no DES (

Objective. To evaluate cardiovascular risk, metabolic profile, low urinary tract symptoms (LUTS), and sexual function in patients with nonfunctional pituitary macroadenoma (NFPMA) and hypogonadotropic hypogonadism with testosterone therapy (TTh). Methods. A retrospective clinical study at a tertiary care center was performed in 101 men with NFPMA, HH, and TTh; metabolic profile, cardiovascular risk, International Prostate Symptoms Score (IPSS), and International Index of Erectile Function 5 (IIEF-5) scores were evaluated before initiation of TTh and at the last checkup with TTh. Results. Age was 49.3 ± 8.8 years; T before TTh was 195 ng/mL (101–259) vs. 574 (423–774) at the last checkup. The time of TTh administration was 34 months (12–72). An increase in triglyceride levels (200 (153–294) vs. 174 (134–233) mg/dL; p=0.03), dyslipidemia (40% vs. 52%; p=0.03), and MetS (25% vs. 34%; p=0.05) was corroborated. A statistical difference in the Globorisk score and cardiovascular (CV) risk stratification was not found. IIEF-5 score was 15.5 ± 6.5 vs. 17.8 ± 5.3 (p=0.11). An improvement in penetration quality (2.0 ± 1.5 vs. 2.6 ± 1.3; p=0.05), erection after penetration (1.8 ± 1.2 vs. 2.5 ± 1.6; p=0.02), completion of intercourse (1.8 ± 1.2 vs. 2.4 ± 1.3; p=0.03), and satisfaction of sexual intercourse (1.8 ± 1.3 vs. 2.5 ± 1.5; p=0.01) was evidenced. IPSS score was 6 (IQR 2–10) vs. 7 (IQR 4–12); p=0.30. A lower rate of intermittency (14% vs. 3%; p=0.02), urgency (39% vs. 16%; p=0.01), and episodes of nocturia (18% vs. 4%; p=0.02) was found. An increase of hematocrit (44.1 ± 4.4 vs. 47.3 ± 4.4%; p=0.001), hemoglobin (14.9 ± 1.4 vs. 15.9 ± 1.4 g/dL; p=0.001), and prostatic specific antigen (0.59 (0.43–1.19) vs. 0.82 (0.45–1.4) ng/mL; p=0.02) was evidenced during TTh. Conclusion. TTh in young men with NFPMA improves LUTS, sexual function, and some metabolic parameters, and it is relatively safe in the prostatic context.

Background: Cultural competence training in residency is important to improve learners’ confidence in cross-cultural encounters. Recognition of cultural diversity and avoidance of cultural stereotypes are essential for health care providers. Methods: We developed a multimethod approach for cross-cultural training of Internal Medicine residents and evaluated participants’ preparedness for cultural encounters. The multimethod approach included (1) a conference series, (2) a webinar with a national expert, (3) small group sessions, (4) a multicultural social gathering, (5) a Grand Rounds presentation on cross-cultural training, and (6) an interactive, online case-based program. Results: The program had 35 participants, 28 of whom responded to the survey. Of those, 16 were white (62%), and residents comprised 71% of respondents (n=25). Following training, 89% of participants were more comfortable obtaining a social history. However, prior to the course only 27% were comfortable caring for patients who distrust the US system and 35% could identify religious beliefs and customs which impact care. Most (71%) believed that the training would help them give better care for patients from different cultures, and 63% felt more comfortable negotiating a treatment plan following the course. Conclusions: Multimethod training may improve learners’ confidence and comfort with cross-cultural encounters, as well as lay the foundation for ongoing learning. Follow-up is needed to assess whether residents’ perceived comfort will translate into improved patient outcomes.

Multidrug-resistant tuberculosis (MDR-TB), resistance to at least isoniazid and rifampin, is a worldwide problem.To develop a clinical prediction rule to stratify risk for MDR-TB among patients with pulmonary tuberculosis.Derivation and internal validation of the rule among adult patients prospectively recruited from 37 health centers (Perú), either a) presenting with a positive acid-fast bacillus smear, or b) had failed therapy or had a relapse within the first 12 months.Among 964 patients, 82 had MDR-TB (prevalence, 8.5%). Variables included were MDR-TB contact within the family, previous tuberculosis, cavitary radiologic pattern, and abnormal lung exam. The area under the receiver-operating curve (AUROC) was 0.76. Selecting a cut-off score of one or greater resulted in a sensitivity of 72.6%, specificity of 62.8%, likelihood ratio (LR) positive of 1.95, and LR negative of 0.44. Similarly, selecting a cut-off score of two or greater resulted in a sensitivity of 60.8%, specificity of 87.5%, LR positive of 4.85, and LR negative of 0.45. Finally, selecting a cut-off score of three or greater resulted in a sensitivity of 45.1%, specificity of 95.3%, LR positive of 9.56, and LR negative of 0.58.A simple clinical prediction rule at presentation can stratify risk for MDR-TB. If further validated, the rule could be used for management decisions in resource-limited areas.

Abstract Designing a cultural competence curriculum is inherently complex. Many elements are needed, and multiple frameworks exist. We used a novel approach to identify and prioritize elements to include in a cultural competence curriculum to address disparities in cardiovascular disease. First, we used the Nominal Group Technique (NGT) to generate and prioritize a list of ideas to include in the curriculum. NGT is a structured small-group process that fosters creativity and equal participation of participants. We conducted four NGT sessions and elicited responses to the question “What sorts of things could be included in a curriculum that focuses on cultural competence training for physicians?” Participants in the NGT sessions were nine medical students, seven medicine residents, seven practicing physicians, and seven disparities researchers. To organize the ideas generated, we then asked 45 educators and researchers to group and rank the ideas based on their own perceptions of importance. Finally, to produce homogeneous groupings of elements based on the ideas grouped and ranked, we used multidimensional scaling (MDS) and hierarchical cluster analysis. The NGT sessions generated 61 ideas, 29 of which were selected by at least two participants. We observed five clusters of related issues within the multidimensional space (asterisks indicate the NGT groups' top-rated ideas): (1) patients' cultural background (provide information on cultures,∗ habits, customs, values), (2) impact on health care and health behavior (include factors influencing health services, folk remedies, diet), (3) differences in therapies and health disparities (provide pharmacological therapies, reasons for cardiovascular disparities), (4) awareness of approaches to multicultural care (increase awareness of own biases,∗ stereotype avoidance), and (5) resources to manage cultural diversity (provide resources for patients and their families to comprehend instructions,∗ provide questions to permit taking a cultural history,∗ language translation guide and available services, community resources). The MDS showed good fit of the dimensions (Stress = .074; R2 = .97). Our cognitive mapping approach allowed us to use input from various stakeholders and generate critical domains to guide the development of the new curriculum. This curriculum is composed of online cultural competence training modules. Users can learn effective cross-cultural approaches to care for African American patients with cardiovascular disease, especially hypertension. Videos with real patient scenarios and case-based modules increase learners' awareness. This project has been completely funded by a grant from the National Institutes of Health (NIH) through the National Heart Lung and Blood Institute (NHLBI).

La Inmunodeficiencia Severa Combinada (IDSC) es una enfermedadde origen genético, que se puede heredar de forma autosómicarecesiva o ligada al cromosoma X. La IDSC se caracteriza por undefecto en el número y la diferenciación de los linfocitos T y NK. Losindividuos afectados desarrollan diarrea crónica, infecciones persistentes y severas como neumonía, septicemia e infecciones fúngicas.Estos pacientes presentan retardo en el crecimiento y pueden morir atemprana edad si no se realiza una terapia de corrección genética o untrasplante de células hematopoyéticas. Las mutaciones responsablesde la IDSC comprometen principalmente el gen de la cadena gamacomún (γc) y la proteína Jak3 que son proteínas fundamentales en latransducción de señales de los receptores para varias citoquinas esenciales en la diferenciación y activación de células del sistema inmune, las cuales incluyen IL-2, IL-4, IL-7, IL-9 e IL-15 (1,2).

La respuesta inmune contra microorganismos intracelulares,como el Mycobacterium dependen de la inmunidad mediada porcélulas (IMC). El principal mecanismo efector de la IMC es la activación del macrófago infectado por medio de citoquinas producidas por células Th1, particularmente el IFNγ. Recientemente se identificó la deficiencia del receptor de IFN gama (IFNγR) en humanos como un desorden autosómico recesivo, que conduce a un defecto en la expresión o función del IFNgR. Esta deficiencia se caracteriza por aumento de la severidad y cronicidad de las infecciones intracelulares, especialmente en aquellos casos donde el macrófago es la principal célula efectora (1,2).