Novel insights on the positive correlation between sense and antisense pairs on gene expression.

A considerable proportion of the eukaryotic genome undergoes transcription, leading to the generation of noncoding RNA molecules that lack protein-coding information and are not subjected to translation. These noncoding RNAs (ncRNAs) are well recognized to have essential roles in several biological processes. Long noncoding RNAs (lncRNAs) represent the most extensive category of ncRNAs found in the human genome. Much research has focused on investigating the roles of cis-acting lncRNAs in the regulation of specific target gene expression. In the majority of instances, the regulation of sense gene expression by its corresponding antisense pair occurs in a negative (discordant) manner, resulting in the suppression of the target genes. The notion that a negative correlation exists between sense and antisense pairings is, however, not universally valid. In fact, several recent studies have reported a positive relationship between corresponding cis antisense pairs within plants, budding yeast, and mammalian cancer cells. The positive (concordant) correlation between anti-sense and sense transcripts leads to an increase in the level of the sense transcript within the same genomic loci. In addition, mechanisms such as altering chromatin structure, the formation of R loops, and the recruitment of transcription factors can either enhance transcription or stabilize sense transcripts through their antisense pairs. The primary objective of this work is to provide a comprehensive understanding of both aspects of antisense regulation, specifically focusing on the positive correlation between sense and antisense transcripts in the context of eukaryotic gene expression, including its implications towards cancer progression. This article is categorized under: RNA Processing > 3' End Processing Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.

GRADE Guidance 39: Using GRADE-ADOLOPMENT to adopt, adapt or create contextualized recommendations from source guidelines and evidence syntheses.

INTRODUCTION: The GRADE-ADOLOPMENT methodology has been widely used to adopt, adapt or de novo develop recommendations from existing or new guideline and evidence synthesis efforts. This guidance refines the operationalization for applying GRADE-ADOLOPMENT. METHODS: Through iterative discussions, online meetings and email communications, the GRADE-ADOLOPMENT Project Group drafted the updated guidance. We then conducted a review of handbooks of guideline-producing organizations, and a scoping review of published and planned Adolopment guideline projects. The lead authors refined the existing approach based on the scoping review findings and feedback from members of the GRADE Working Group. We presented the revised approach to the group in November 2022 (approximately 115 people), in May 2023 (approximately 100 people) and twice in September 2023 (approximately 60 and 90 people) for approval. RESULTS: This GRADE guidance shows how to effectively and efficiently contextualize recommendations using the GRADE-ADOLOPMENT approach by: (1) showcasing alternative pathways for starting an adolopment effort; (2) elaborating on the different essential steps of this approach, such as building on existing EtDs when available or developing new EtDs if necessary; and (3) providing examples from adolopment case studies to facilitate the application of the approach. We demonstrate how to use contextual evidence to make judgments about EtD criteria, and highlight the importance of making the resulting EtDs available to facilitate adolopment efforts by others. CONCLUSION: This updated GRADE guidance further operationalizes the application of GRADE-ADOLOPMENT based on over six years of experience. It serves to support uptake and application by end users interested in contextualizing recommendations to a local setting or specific reality in a short period of time or with limited resources.

Post-pulmonary embolism syndrome: A reminder for clinicians.

Acute pulmonary embolism (APE) is one of the leading causes of cardiovascular emergencies and the third leading cause of death. Although efforts focus on treating the acute event, patients who survive APE may develop long-term sequelae. Research reveals that approximately half of patients who have suffered an APE do not regain their previous level of function and experience a reduction in their quality of life for several years after the episode. Acute pulmonary embolism can be classified according to the risk of short-term mortality, with most mortality and morbidity concentrated in high-risk and intermediate-risk cases. The first-line treatment for APE is systemic anticoagulation. However, identifying and more aggressively treating people with intermediate to high risk, who have a more favorable risk profile for reperfusion treatments, could reduce short-term mortality and mitigate post-pulmonary embolism syndrome (PPES). Post-pulmonary embolism syndrome refers to a variety of persistent symptoms and functional limitations that occur after an APE. The presence of persistent dyspnea, functional limitations, and/or decreased quality of life after an APE has been recently termed "PPES," although this entity encompasses different manifestations. The most severe cause of persistent dyspnea is chronic thromboembolic pulmonary hypertension, where increased pulmonary artery pressure is due to the fibrotic organization of unresolved APE. Post-PE Syndrome is not always systematically addressed in management guidelines, and its prevalence may be underestimated. More research is needed to fully understand its causes and risk factors. Interventions such as cardiopulmonary rehabilitation have been suggested to improve the quality of life of patients with PPES. A comprehensive, evidence-based approach is essential to effectively prevent and manage PPES and improve the long-term outcomes and well-being of affected patients.

Early Development of the Thalamo-Pallial Stage of the Tectofugal Visual Pathway in the Chicken (Gallus gallus).

The tectofugal pathway is a highly conserved visual pathway in all amniotes. In birds and mammals, retinorecipient neurons located in the midbrain roof (optic tectum/superior colliculus) are the source of ascending projections to thalamic relays (nucleus rotundus/caudal pulvinar), which in turn project to specific pallial regions (visual dorsal ventricular ridge [vDVR]/temporal cortex) organized according to a columnar recurrent arrangement of interlaminar circuits. Whether or to which extent these striking hodological correspondences arise from comparable developmental processes is at present an open question, mainly due to the scarcity of data about the ontogeny of the avian tectofugal system. Most of the previous developmental studies of this system in birds have focused on the establishment of the retino-tecto-thalamic connectivity, overlooking the development of the thalamo-pallial-intrapallial circuit. In this work, we studied the latter in chicken embryos by means of immunohistochemical assays and precise ex vivo crystalline injections of biocytin and DiI. We found that the layered organization of the vDVR as well as the system of homotopic reciprocal connections between vDVR layers were present as early as E8. A highly organized thalamo-vDVR projection was also present at this stage. Our immunohistochemical assays suggest that both systems of projections emerge simultaneously even earlier. Combined with previous findings, these results reveal that, in striking contrast with mammals, the peripheral and central stages of the avian tectofugal pathway develop along different timelines, with a tecto-thalamo-intrapallial organization arising before and possibly independently of the retino-isthmo-tectal circuit.

Breslow density ability to predict melanoma survival: should it be used in clinical practice?

BACKGROUND: Breslow density (BD) is an estimation of melanoma volume, which has emerged as a novel histopathological prognostic biomarker. OBJECTIVES: Our aim was to evaluate the role of BD as predictor of patients´ survival and assess its prognostic value in relation to overall survival (OS), disease-free survival (DFS), melanoma-specific survival (MSS) and metastasis-free survival (MFS). METHODS: A retrospective observational study in a cohort of 107 patients with invasive melanoma was conducted. Kaplan-Meier and Log-rank tests were used for 10-year survival analysis. The ability of BD and Breslow thickness (BT) to predict survival was assessed using receiver operating characteristic curves. RESULTS: The average follow-up was 115 months excluding deaths. BD ≥65% showed lower survival rates compared with the BD<65% group (log-rank test p<0.001). Area under the curve (AUC) of BD ≥65% was higher than BT's for all studied survival rates except for melanoma-specific survival, in which absolute BD showed the highest value. CONCLUSIONS: BD is proposed as a simple, valuable and inexpensive histopathological feature that could provide with valuable information to current melanoma staging, since it has proved a statistically significant prognostic value in relation to survival in melanoma patients, and comparable 10-year survival prediction ability to BT.

An all-out assault on a dominant resistance gene: Local emergence, establishment, and spread of strains of tomato spotted wilt orthotospovirus (TSWV) that overcome Sw-5b-mediated resistance in fresh market and processing tomatoes in California.

Tomato spotted wilt orthotospovirus (TSWV) causes substantial economic loss to tomato production, and the Sw-5b resistance gene is widely deployed for management. Here, we show (i) the emergence of resistance-breaking (RB) TSWV strains in processing and fresh market tomato production in California over the past ten years, and (ii) evolutionary relationships with RB strains from other areas. A specific RT-PCR test was used to show the C118Y RB strain that emerged in Fresno County in 2016 quickly became predominant in the central production area and remained so through this study. In 2021, the C118Y strain was detected in the Northern production area, and was predominant in 2022. However, in 2023, the C118Y strain was unexpectedly detected in fewer spotted wilt samples from resistant varieties. This was due to emergence of the T120N RB strain, previously known to occur in Spain. A specific RT-PCR test was developed and used to show that the T120N RB strain was predominant in Colusa and Sutter counties (detected in 75-80% of samples), and detected in ~50% of samples from Yolo County. Pathogenicity tests confirmed California isolates of the T120N strain infected Sw-5b tomato varieties and induced severe symptoms. Another RB strain, C118F, was associated with spotted wilt samples of Sw-5 varieties from fresh market tomato production in southern California. Phylogenetic analyses with complete NSm sequences revealed that the C118Y and T120N RB strains infecting resistant processing tomato in California emerged locally, whereas those from fresh market production were more closely related to isolates from Mexico. Thus, widespread deployment of this single dominant resistance gene in California has driven the local emergence of multiple RB strains in different tomato production areas and types. These results further emphasize the need for ongoing monitoring for RB strains, and identification of sources of resistance to these strains.

Nivel de Conocimiento sobre Cáncer Oral que Presentan los Estudiantes de Pregrado de Estomatología de una Universidad Privada de Lima, Perú

Determinar el nivel de conocimiento sobre cáncer oral (CO) que presentaron los estudiantes de pregrado de estomatología. Estudio observacional transversal aplicado a una muestra poblacional de 184 estudiantes (24±3,09 años y 72,8 % mujeres) de una universidad privada de Lima del sexto a décimo ciclo que estuvieron matriculados en un curso de clínica (14,1 % de clínica V). Un cuestionario virtual y presencial con 24 preguntas sobre CO fue aplicado. El instrumento fue validado por juicio de expertos, tuvo un índice de validez de 0,96 (V de Aiken) y una confiabilidad (KR-20) DE 0,856 y ≥0,837 por ítem. La frecuencia de respuestas correctas del total de preguntas fue de 56,6 % siendo similar por sexo y curso de clínica, pero mayor en los >30 años (60 %). Las preguntas mejor contestadas fueron el tipo más frecuente (epidemiología), el factor relacionado (diagnóstico) y factores pronósticos (prevención). Las dimensiones mejor contestadas fueron en tratamientos y complicaciones (72,2 %) y diagnóstico (70,3 %) sobre CO. El nivel de conocimiento sobre CO fue regular (78,8 %). Ni las dimensiones, niveles o puntajes se asociaron a edad, sexo o clínica (P>0,05). Los estudiantes presentaron un nivel de conocimiento regular sobre cáncer oral, indistintamente del sexo, edad o la clínica que cursan.

The objective of this study was to determine the level of knowledge about oral cancer (OC) presented by undergraduate stomatology students. A cross-sectional observational study applied to a population sample of 184 students (24±3.09 years and 72.8 % women) from a private university in Lima from the sixth to tenth cycle who were enrolled in a clinical course (14.1 % of clinic V). A virtual and in-person questionnaire with 24 questions about OC was applied. The instrument was validated by expert judgment, it had a validity index of 0.96 (Aiken's V) and reliability (KR-20) of 0.856 and ≥0.837 per item. The frequency of correct answers to the total number of questions was 56.6 %, being similar by sex and clinical course, but higher in those >30 years of age (60 %). The best-answered questions were the most frequent type (epidemiology), the related factor (diagnosis), and the prognostic factors (prevention). The dimensions best answered were in treatments and complications (72.2 %) and diagnosis (70.3 %) of CO. The level of knowledge about OC was regular (78.8 %). Neither dimensions, levels, nor scores were associated with age, sex, or clinical features (P>0.05). The students presented a regular level of knowledge about oral cancer, regardless of sex, age or the clinical course they studied.

Health Care Delays and Social Suffering Among Indigenous People with Diabetic Foot Complications in Mexico.

Diabetic foot (DF) is a leading cause of nontraumatic lower-extremity amputations, premature death, and a sign of social inequality in diabetes treatment. In Mexico, the incidence of DF is on the rise yet little is known about its impact among indigenous people, a disadvantaged group. Based on ethnographic research conducted in Oaxaca and analysis of institutional health-data, in this article we show the health care delays that rural indigenous people face when dealing with DF. Indigenous people's uncertainty regarding their right to health and the structural barriers to medical care favor DF complications, a phenomenon that should be read as social suffering. Since health data concerning indigenous health care service users is patchy and imprecise, indigenous people's social suffering is invisibilized. This omission or partiality in the official records limits public health decision-making and undermines the human rights of the population.

Nutrición enteral en pacientes críticos con COVID-19 ventilados en decúbito prono

Introducción: el SARS-CoV-2 desde el 2020 generó innumerables desafíos. El decúbito prono se utilizó para mejorar la oxigenación, y la terapia nutricional se adaptó para cubrir los requerimientos y reducir complicaciones. Objetivos: evaluar la tolerancia de la nutrición enteral y su adecuación energética en pacientes ventilados en decúbito prono con infección por SARS-CoV-2, en sala respiratoria del Departamento de Cuidados Intensivos Adultos del Hospital de Clínicas-Facultad de Ciencias Médicas - Universidad Nacional de Asunción, de marzo a julio 2021. Metodología: estudio observacional, descriptivo, retrospectivo, de corte transversal, de casos consecutivos, con información obtenida de fichas de pacientes de terapia intensiva, que recibieron soporte nutricional en posición prona. Se tomaron datos demográficos, clínicos y nutricionales. Se evaluó la tolerancia nutricional durante la posición prona, definiéndola como la presencia de un volumen de residuo gástrico < 500 mL cada 6 h.. La adecuación energética fue determinada teniendo en cuenta el porcentaje cumplido de la prescripción nutricional. Resultados: se reclutaron 41 pacientes. El 60,9 % eran hombres; la mediana de edad fue 55 años (RIC=23). Las principales comorbilidades fueron obesidad (57,3 %) e hipertensión arterial (43,9 %). El 85,4 % presentó buena tolerancia gástrica en posición prono, con residuo gástrico menor a 500 ml. El porcentaje de adecuación energética fue de 84 %. Conclusión: la terapia nutricional enteral en decúbito prono fue bien tolerada por la mayoría de nuestros pacientes, posibilitando alcanzar los requerimientos nutricionales indicados.

Introduction: SARS-CoV-2 since 2020 has generated countless challenges. Prone position was used to improve oxygenation, and nutritional therapy was adapted to meet requirements and reduce complications. Objectives: evaluate the tolerance of enteral nutrition and its energetic adequacy in ventilated patients in the prone position with SARS-CoV-2 infection, in the respiratory room of the Adult Intensive Care Department of the Hospital de Clínicas - Facultad de Ciencias Médicas - Universidad Nacional de Asunción, from March to July 2021. Methodology: observational, descriptive, retrospective, cross-sectional study of consecutive cases, with information obtained from records of intensive care patients, who received nutritional support in a prone position. Demographic, clinical and nutritional data were taken. Nutritional tolerance was evaluated during the prone position, defining it as the presence of a volume of gastric residue < 500 mL every 6 h. Energy adequacy was determined taking into account the percentage fulfilled of the nutritional prescription. Results: 41 patients were recruited. 60.9 % were men; the median age was 55 years (IQR=23). The main comorbidities were obesity (57.3 %) and high blood pressure (43.9 %). 85.4 % had good gastric tolerance in the prone position, with gastric residue less than 500 ml. The percentage of energy adequacy was 84 %. Conclusion: enteral nutritional therapy in the prone position was well tolerated by the majority of our patients, making it possible to achieve the indicated nutritional requirements.

Síndrome de Wells: presentación con un gran polimorfismo clínico

El síndrome de Wells es una afección dérmica que presenta un gran polimorfismo clínico. Es una patología autolimitada, recurrente y su origen es incierto. Reportamos el caso de una paciente de 29 años, procedente del área Central de Paraguay, comerciante, sin patología de base que consultó por edema de manos y piel. El tratamiento indicado fue corticoide vía oral y desparasitación con buena evolución y sin recidivas.

Wells syndrome is a dermal condition with a high clinical polymorphism. It is a self-limited, recurrent pathology and its origin is uncertain. We report the case of a 29-year-old female patient from the central area of Paraguay, a shopkeeper, with no underlying pathology, who consulted for hand and skin edema. The indicated treatment was oral corticosteroid and deworming with good evolution and no recurrences.

Validation of a synthetic simulation model of endoscopic rectus sheath plication.

PURPOSE: Literature reviews outline minimally invasive approaches for abdominal diastasis in patients without skin excess. However, few surgeons are trained in endoscopic rectus sheath plication, and no simulated training programs exist for this method. This study aimed to develop and validate a synthetic simulation model for the training of skills in this approach under the Messick validity framework. METHODS: A cross-sectional study was carried out to assess the participants' previous level of laparoscopic/endoscopic skills by a questionnaire. Participants performed an endoscopic plication on the model and their performance was evaluated by one blinded observer using the global rating scale OSATS and a procedure specific checklist (PSC) scale. A 5-level Likert survey was applied to 5 experts and 4 plastic surgeons to assess Face and Content validity. RESULTS: Fifteen non-experts and 5 experts in abdominal wall endoscopic surgery were recruited. A median OSATS score [25 (range 24-25) vs 14 (range 5-22); p < 0.05 of maximum 25 points] and a median PSC score [11 (range 10-11) vs 8 (range 3-10); p < 0.05 of maximum 11 points] was significantly higher for experts compared with nonexperts. All experts agreed or strongly agreed that the model simulates a real scenario of endoscopic plication of the rectus sheath. CONCLUSION: Our simulation model met all validation criteria outlined in the Messick framework, demonstrating its ability to differentiate between experts and non-experts based on their baseline endoscopic surgical skills. This model stands as a valuable tool for evaluating skills in endoscopic rectus sheath plication.

Links between booksharing and early vocabulary development in Costa Rica.

Early vocabulary development is crucial for future cognitive and academic outcomes, and parent-child booksharing has been recognized as a powerful home literacy practice to promote word learning. However, evidence about the link between booksharing and language development in diverse cultural and socioeconomic settings is currently limited, hindering the formulation of a broadly applicable framework to understand the favorable conditions for early vocabulary development. This study explores the relationship between booksharing and early receptive and expressive vocabulary in a sample of 183 mothers and their toddlers in Costa Rica, a context where reading is not a common practice and children have limited access to books. Mothers completed an interview about their booksharing practices and reported children's receptive and expressive vocabulary. Results demonstrated a positive link between maternal booksharing and children's expressive vocabulary. Child gender moderated the link between booksharing and receptive vocabulary, exhibiting a stronger association in girls than in boys. Mothers with lower education levels reported higher expressive vocabulary scores for their children than mothers with higher education levels. These findings underscore the significance of booksharing in the home literacy environment, even in cultural contexts with distinct reading practices. Moreover, they highlight the need to incorporate sociocultural factors into comprehensive accounts concerning the role of booksharing in early word learning.

[Tissue perfusion monitoring in children with acute circulatory dysfunction: narrative review]. / Monitorización de la perfusión tisular en el niño con disfunción circulatoria aguda: revisión narrativa.

Sepsis is one of the main causes of admission to Intensive Care Units (ICU). The hemodynamic objectives usually sought during the resuscitation of the patient in septic shock correspond to macrohemodynamic parameters (heart rate, blood pressure, central venous pressure). However, persistent alterations in microcirculation, despite the restoration of macrohemodynamic parameters, can cause organ failure. This dissociation between the macrocirculation and microcirculation originates the need to evaluate organ tissue perfusion, the most commonly used being urinary output, lactatemia, central venous oxygen saturation (ScvO2), and veno-arterial pCO2 gap. Because peripheral tissues, such as the skin, are sensitive to disturbances in perfusion, noninvasive monitoring of peripheral circulation, such as skin temperature gradient, capillary refill time, mottling score, and peripheral perfusion index may be helpful as early markers of the existence of systemic hemodynamic alterations. Peripheral circulation monitoring techniques are relatively easy to interpret and can be used directly at the patient's bedside. This approach can be quickly applied in the intra- or extra-ICU setting. The objective of this narrative review is to analyze the various existing tissue perfusion markers and to update the evidence that allows guiding hemodynamic support in a more individualized therapy for each patient.

Understanding the factors associated with COVID-19 vaccine hesitancy in Venezuela.

BACKGROUND: Despite nearly a quarter of Venezuelans remaining unvaccinated against coronavirus disease 2019 (COVID-19), the factors contributing to vaccine hesitancy in the country have not been thoroughly investigated. METHODS: A cross-sectional study was conducted from October 15th to 30th, 2022, using a knowledge, attitudes, and practices (KAP) survey to identify factors associated with COVID-19 vaccine hesitancy. RESULTS: The study analyzed data from 1,930 participants from all 24 states of Venezuela. The majority (93.4%) were vaccinated. The mean age was 40 years, predominantly female (67.3%), and held a university degree (70.6%). The mean KAP score was significantly higher among vaccinated individuals compared to unvaccinated ones (7.79 vs. 3.94 points for knowledge, 40 vs. 24 points for attitudes, and 16 vs. 10 points for practices, all p < 0.001). Increases in the scores for KAP were associated with increased odds of being vaccinated (84.6%, 25.6%, and 33% respectively for each one-point increase, all p < 0.001). Certain demographic factors such as marital status, occupation, religious beliefs, monthly income, and location influence COVID-19 vaccine knowledge. Higher income and certain occupations decrease the odds of low knowledge, while residing in specific states increases it. Attitudes towards the COVID-19 vaccine are influenced by age, health status, vaccination status, and location. Higher income and absence of certain health conditions decrease the odds of negative attitudes. Lastly, age, occupation, monthly income, and location affect vaccine practices. Advanced age and higher income decrease the odds of inappropriate practices, while residing in La Guaira state increases them. CONCLUSION: Factors such as age, education level, occupation, monthly income, and location were found to be associated with knowledge and attitudes towards COVID-19 vaccine among the surveyed Venezuelans.

Movement Disorder Perspectives on Monocarboxylate 8 Deficiency: A Case Series of 3 Colombian Patients with Allan-Herndon-Dudley Syndrome.

BACKGROUND: Deficiencies in the thyroid hormone transporter monocarboxylate 8 (MCT8) due to pathogenic variants in the SLC16A2 gene (OMIM 300095) result in a complex phenotype with main endocrine and neurologic symptoms. This rare disorder, named Allan-Herndon-Dudley syndrome (AHDS) (OMIM 300523), is inherited in an X-linked trait. One of the prominent features of AHDS is the presence of movement disorders (MD), which are complex and carry a significant burden of the disease. CASES: Patient 1: male with hypotonia since birth, developmental delay, dystonic posturing at 4 months and at 15 months, and startle reaction developed with sensory stimuli. Patient 2: male, at 2 months, shows hypotonia and developmental delay, paroxysmal episodes triggered by a stimulus with sudden blush, tonic asymmetric posture, and no epileptiform activity. At 10 months, generalized dystonic posturing. Patient 3: typical neurodevelopmental milestones until 6 months; at 24 months, dystonia, startle reaction, and upper motoneuron signs. CONCLUSIONS: We aim to describe our patients diagnosed with AHDS, focusing on MD phenomenology and strengthening the phenotype-genotype correlations for this rare condition.

Severe pulmonary hypertension in pulmonary alveolar microlithiasis: A comprehensive literature review.

This review focuses on Pulmonary Alveolar Microlithiasis (PAM), an autosomal recessive genetic disorder characterized by calcium crystal deposits (microliths) resulting from loss of function of the SLC34A2 gene. PAM is a rare disease with approximately 1100 reported cases globally. The historical context of its discovery and the genetic, epidemiological, and pathophysiological aspects are discussed. PAM falls under interstitial lung diseases and is associated with pulmonary hypertension (PH), primarily categorized as Group 3 PH. The clinical manifestations, diagnostic approaches, and challenging aspects of treatment are explored. A clinical case of PAM with severe pulmonary hypertension is presented, emphasizing the importance of comprehensive evaluation and the potential benefits of phosphodiesterase-5 inhibitors (PDE5i) therapy. Despite limited therapeutic options and challenging diagnosis, this review sheds light on recent developments and emerging treatments for PAM and associated pulmonary hypertension.

Unpacking participation in healthcare governance: Lessons from two local health councils in Brazil and Spain.

This paper describes and compares the integration of cross-sector actors' participation into the governance of two local health councils, one located in Salvador de Bahia (Brazil) and the other in the Canary Islands (Spain). Based on the cross-national comparative research conducted as part of a doctoral thesis, a qualitative design based on secondary data analysis was proposed on the three stages of the organisational integration process of participation. We used information from individual semi-structured interviews (n = 70), situational observation, focus groups, literature review, and field notes to understand participatory processes of networking between multiple cross-sector actors and to show how such processes might be associated with innovative practices. For these innovations to be successfully implemented, stakeholders need to acquire adequate competencies in cross-sector collaboration, enabling them to learn about new organisational practices and to adapt the network of actors to the often unpredictable influences of contextual factors.

Survival of patients with chronic acid sphingomyelinase deficiency (ASMD) in the United States: A retrospective chart review study.

Background: Acid sphingomyelinase deficiency (ASMD), historically known as Niemann-Pick disease type A, A/B, and B, is a rare lysosomal storage pathology with multisystemic clinical manifestations. The aims of this study were to estimate the survival probability in patients in the United States with chronic ASMD (ASMD types B and A/B), and to describe the disease characteristics of these patients. Methods: This observational retrospective study included medical chart records of patients with chronic ASMD with retrievable data abstracted by 69 participating physicians from 25 medical centers in the United States. Included patients had a date of ASMD diagnosis or first presentation to a physician for ASMD symptoms (whichever occurred first) between January 01, 1990, and February 28, 2021. Medical chart records were excluded if patients were diagnosed with ASMD type A. Eligible medical chart records were abstracted to collect demographic, medical and developmental history, and mortality data. Survival outcomes were analyzed using Kaplan-Meier survival analyses from birth until death. Results: The overall study population (N = 110) included 69 patients with ASMD type B, nine with type A/B, and 32 with ASMD "non-type A" (ASMD subtype was unknown, but patients were confirmed as not having ASMD type A). The majority of patients were male with a median age at diagnosis of 3.8 years. Thirty-eight patients died during the study observation period, at a median age of 6.8 years. The median (95% confidence interval) survival age from birth was 21.3 (10.2; 60.4) years. At diagnosis or first presentation, 42.7% patients had ≥1 ASMD-related complication; splenic (30.0%) and hepatobiliary (20.9%) being the most common, and 40.9% required ≥1 medical visit due to complications. Conclusion: Patients with chronic ASMD in the United States have poor survival and significant burden of illness.

The impact of the COVID-19 pandemic on people living with HIV: a cross-sectional study in Caracas, Venezuela.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has disrupted multiple health services, including human immunodeficiency virus (HIV) testing, care, and treatment services, jeopardizing the achievement of the Joint United Nations Programme on HIV/AIDS 90-90-90 global target. While there are limited studies assessing the impact of the COVID-19 pandemic on people living with HIV (PLHIV) in Latin America, there are none, to our knowledge, in Venezuela. This study aims to assess the impact of the COVID-19 pandemic among PLHIV seen at the outpatient clinic of a reference hospital in Venezuela. METHODS: We conducted a cross-sectional study among PLHIV aged 18 years and over seen at the Infectious Diseases Department of the University Hospital of Caracas, Venezuela between March 2021 and February 2022. RESULTS: A total of 238 PLHIV were included in the study. The median age was 43 (IQR 31-55) years, and the majority were male (68.9%). Most patients (88.2%, n = 210) came for routine check-ups, while 28 (11.3%) were newly diagnosed. The majority of patients (96.1%) were on antiretroviral therapy (ART), but only 67.8% had a viral load test, with almost all (95.6%) being undetectable. Among those who attended regular appointments, 11.9% reported missing at least one medical consultation, and 3.3% reported an interruption in their ART refill. More than half of the patients (55.5%) had received at least one dose of the COVID-19 vaccine, while the rest expressed hesitancy to get vaccinated. Most patients with COVID-19 vaccine hesitancy were male (65.1%), younger than 44 years (57.5%), employed (47.2%), and had been diagnosed with HIV for less than one year (33%). However, no statistically significant differences were found between vaccinated patients and those with COVID-19 vaccine hesitancy. Older age was a risk factor for missing consultations, while not having an alcoholic habit was identified as a protective factor against missing consultations. CONCLUSION: This study found that the COVID-19 pandemic had a limited impact on adherence to medical consultations and interruptions in ART among PLHIV seen at the University Hospital of Caracas, Venezuela.