Sex Differences in Profile and In-Hospital Death for Acute Stroke in Chile: Data From a Nationwide Hospital Registry.

BACKGROUND: Knowledge of local contextual sex differences in the profile and outcome for stroke can improve service delivery. We aimed to determine sex differences in the profile of patients with acute stroke and their associations with in-hospital death in the national hospital database of Chile. METHODS AND RESULTS: We present a retrospective cohort based on the analysis of the 2019 Chilean database of Diagnosis-Related Groups, which represents 70% of the operational expenditure of the public health system. Random-effects multiple logistic regression models were used to determine independent associations of acute stroke (defined by main diagnosis International Classification of Diseases, Tenth Revision [ICD-10] codes) and in-hospital death, and reported with odds ratios (ORs) and 95% CIs. Of 1 048 575 hospital discharges, 15 535 were for patients with acute stroke (7074 [45.5%] in women), and 2438 (15.6%) of them died during hospitalization. Differences by sex in sociodemographic and clinical characteristics were identified for stroke and main subtypes. After fully adjusted model, women with ischemic stroke had lower in-hospital death (OR, 0.79 [95% CI, 0.69-0.91]) compared with men; other independent predictors included age per year increase (OR, 1.03 [95% CI, 1.03-1.04]), chronic kidney disease (OR, 1.47 [95% CI, 1.20-1.80]), atrial fibrillation (OR, 1.50 [95% CI, 1.26-1.80]), and other risk factors. Conversely, for intracerebral hemorrhage, women had a higher in-hospital mortality rate than men (OR, 1.19 [95% CI, 1.02-1.40]); other independent predictors included age per year increase (OR, 1.009 [95% CI, 1.003-1.01]), chronic kidney disease (OR, 1.55 [95% CI, 1.23-1.97]), oral anticoagulant use (OR, 1.88 [95% CI, 1.37-2.58]), and other risk factors. CONCLUSIONS: Sex differences in characteristics and in-hospital death of hospitalized patients exist for acute stroke in Chile. In-hospital death is higher for acute ischemic stroke in men and higher for intracerebral hemorrhage in women. Future research is needed to better identify contributing factors.

Recommendations for implementing the INTERACT3 care bundle for intracerebral hemorrhage in Latin America: results of a Delphi method.

INTRODUCTION: The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT3) showed that the implementation of a care bundle improves outcomes after acute intracerebral hemorrhage (ICH). We aimed to establish consensus-based recommendations for the broader integration of the care bundle across Latin American countries (LAC). METHODS: A 3-phase Delphi study allowed a panel of 32 healthcare workers from 14 LAC to sequentially rank statements relevant to 7 domains (training, resources/infrastructure, patient education, blood pressure, temperature, glycemic control, and anticoagulation reversal). Pre-defined consensus threshold was 75%. RESULTS: A total of 43 statements reached consensus by the third round, with 12 new statements emerging through rounds. The highest-ranked statements in each domain emphasized critical aspects but successful implementation requires appropriate resourcing. Key priorities were continuous training of all healthcare workers in ICH management, establishing protocols aligned with available resources, and collaborative interdisciplinary care supported by institutional networks. Statements related to anticoagulation reversal had the highest priority. CONCLUSIONS: Consensus statements are provided to facilitate integration of the INTERACT3 care bundle to reduce disparities in ICH outcomes in LAC.

Variants in both the N- or C-terminal domains of IHH lead to defective secretion causing short stature and skeletal defects.

BACKGROUND: Heterozygous Indian Hedgehog gene (IHH) variants are associated with brachydactyly type A1 (BDA1). However, in recent years, numerous variants have been identified in patients with short stature and more variable forms of brachydactyly. Many are located in the C-terminal domain of IHH (IHH-C), which lacks signaling activity but is critical for auto-cleavage and activation of the N-terminal (IHH-N) peptide. The absence of functional studies of IHH variants, particularly for those located in IHH-C, has led to these variants being classified as variants of uncertain significance (VUS). OBJECTIVE: To establish a simple functional assay to determine the pathogenicity of IHH VUS and confirm that variants in the C-terminal domain affect protein function. DESIGN/METHODS: In vitro studies were performed for 9 IHH heterozygous variants, to test their effect on secretion and IHH intracellular processing by western blot of cells expressing each variant. RESULTS: IHH secretion was significantly reduced in all mutants, regardless of the location. Similarly, intracellular levels of N-terminal and C-terminal IHH peptides were severely reduced in comparison with the control. Two variants present at a relatively high frequency in the general population also reduced secretion but to a lesser degree in the heterozygous state. CONCLUSIONS: These studies provide the first evidence that variants in the C-terminal domain affect the secretion capacity of IHH and thus, reduce availability of IHH ligand, resulting in short stature and mild skeletal defects. The secretion assay permits a relatively easy test to determine the pathogenicity of IHH variants. All studied variants affected secretion and interestingly, more frequent population variants appear to have a deleterious effect and thus contribute to height variation.

Implementation of low-intensity thrombolysis monitoring care in routine practice: process evaluation of the Optimal Post rtPA-IV Monitoring in Acute Ischemic Stroke (OPTIMISTmain) study in the United States.

INTRODUCTION: The ongoing OPTIMISTmain study, an international, multicenter, stepped-wedge cluster randomized trial, aims to determine effectiveness and safety of low-intensity versus standard monitoring in thrombolysis-treated patients with mild-to-moderate acute ischemic stroke (AIS). An embedded process evaluation explored integration and impact of the intervention on care processes at participating US sites. METHODS: A mixed-methods approach with quantitative and qualitative data were collected between September 2021 and November 2022. Implementer surveys were undertaken at pre- and post-intervention phases to understand the perceptions of low-intensity monitoring strategy. A sample of stroke care nurses were invited to participate in semi-structured interviews at an early stage of post-intervention. Qualitative data were analyzed deductively using the normalization process theory; quantitative data were tabulated. RESULTS: Interviews with 21 nurses at 8 hospitals have shown low-intensity monitoring was well accepted, as there were less time constraints and reduced workload for each patient. There were initial safety concerns over missing deteriorating patients and difficulties in changing established routines. Proper training, education, and communication, and changing the habits and culture of care, were key elements to successfully adopting the new monitoring care into routine practice. Similar results were found in the post-intervention survey (42 nurses from 13 hospitals). Nurses reported time being freed up to provide patient education (56%), daily living care (50%), early mobilization (26%), mood/cognition assessment (44%), and other aspects (i.e. communication, family support). CONCLUSIONS: Low-intensity monitoring for patients with mild-to-moderate acute ischemic stroke, facilitated by appropriate education and organizational support, appears feasible and acceptable at US hospitals.

The effect of a cognitive training therapy based on stimulation of brain oscillations in patients with mild cognitive impairment in a Chilean sample: study protocol for a phase IIb, 2 × 3 mixed factorial, double-blind randomised controlled trial.

BACKGROUND: The ageing population has increased the prevalence of disabling and high-cost diseases, such as dementia and mild cognitive impairment (MCI). The latter can be considered a prodromal phase of some dementias and a critical stage for interventions to postpone the impairment of functionality. Working memory (WM) is a pivotal cognitive function, representing the fundamental element of executive functions. This project proposes an intervention protocol to enhance WM in these users, combining cognitive training with transcranial electrical stimulation of alternating current (tACS). This technique has been suggested to enhance the neuronal plasticity needed for cognitive processes involving oscillatory patterns. WM stands to benefit significantly from this approach, given its well-defined electrophysiological oscillations. Therefore, tACS could potentially boost WM in patients with neurodegenerative diseases. METHODS: This study is a phase IIb randomised, double-blind clinical trial with a 3-month follow-up period. The study participants will be 62 participants diagnosed with MCI, aged over 60, from Valparaíso, Chile. Participants will receive an intervention combining twelve cognitive training sessions with tACS. Participants will receive either tACS or placebo stimulation in eight out of twelve training sessions. Sessions will occur twice weekly over 6 weeks. The primary outcomes will be electroencephalographic measurements through the prefrontal theta oscillatory activity, while the secondary effects will be cognitive assessments of WM. The participants will be evaluated before, immediately after, and 3 months after the end of the intervention. DISCUSSION: The outcomes of this trial will add empirical evidence about the benefits and feasibility of an intervention that combines cognitive training with non-invasive brain stimulation. The objective is to contribute tools for optimal cognitive treatment in patients with MCI. To enhance WM capacity, postpone the impairment of functionality, and obtain a better quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05291208. Registered on 28 February 2022. ISRCTN87597719 retrospectively registered on 15 September 2023.

The main Optimal Post rTpa-Iv Monitoring in Ischemic Stroke Trial (OPTIMISTmain): protocol for a pragmatic, stepped wedge, cluster randomized controlled trial.

Introduction Careful monitoring of patients who receive intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is resource-intensive, and potentially less relevant in those with mild degrees of neurological impairment who are at low-risk of symptomatic intracerebral hemorrhage (sICH) and other complications. \ Methods OPTIMISTmain is an international, multicenter, prospective, stepped wedge, cluster randomized, blinded outcome assessed trial aims to determine whether a less-intensity monitoring protocol is at least as effective, safe and efficient as standard post-IVT monitoring in patients with mild deficits post-AIS. Clinically-stable adult patients with mild AIS (defined by a NIHSS <10) who do not require intensive care within 2 hours post-IVT are recruited at hospitals in Australia, Chile, China, Malaysia, Mexico, UK, US and Vietnam. An average of 15 patients recruited per period (overall 60 patient participants) at 120 sites for a total of 7200 IVT-treated AIS patients will provide 90% power (one-sided α 0.025). The initiation of eligible hospitals is based on a rolling process whenever ready, stratified by country. Hospitals are randomly allocated using permuted blocks into 3 sequences of implementation, stratified by country and the projected number of patients to be recruited over 12 months. These sequences have four periods that dictate the order in which they are to switch from control (usual care) to intervention (implementation of low intensity monitoring protocol) to different clusters of patients in a stepped manner. Compared to standard monitoring, the low-intensity monitoring protocol includes assessments of neurological and vital signs every 15 minutes for 2 hours, 2 hourly (versus every 30 minutes) for 8 hours, and 4 hourly (versus every 1 hour) until 24 hours, post-IVT. The primary outcome measure is functional recovery, defined by the modified Rankin scale (mRS) at 90 days, a seven-point ordinal scale (0 [no residual symptom] to 6 [death]). Secondary outcomes include death or dependency, length of hospital stay, and health-related quality of life, sICH and serious adverse events. Conclusion OPTIMISTmain will provide Level I evidence for the safety and effectiveness of a low-intensity post-IVT monitoring protocol in patients with mild severity of AIS.

Two new patients with acromesomelic dysplasia, PRKG2 type-identification and characterization of the first missense variant.

Acromesomelic dysplasia, PRKG2 type (AMDP, MIM 619636), is an extremely rare autosomal recessive skeletal dysplasia characterized by severe disproportionate short stature presenting with acromesomelia, mild metaphyseal widening of the long bones and mild spondylar dysplasia. To date, only four variants have been reported; one nonsense, one splice-site, and two frameshifts in five AMDP families. Here, we report the first missense variant and a second splice-site variant in PRKG2 in two patients with clinical and radiological features of acromesomelic dysplasia. Furthermore, functional studies of the novel missense variant, p.Val470Gly, revealed that it was unable to down-regulate FGF2-induced MAPK signaling and, thus, would be predicted to cause growth delay. Hence, this report expands the mutational spectrum in skeletal dysplasias associated with PRKG2 variants. In addition, we propose recognizable facial features with acromesomelic dysplasia, PRKG2 type.

Characterization of three adults and an adolescent with Osteogenesis Imperfecta type VI and a novel founder SERPINF1 variant.

Osteogenesis imperfecta (OI) type VI is an extremely rare form of OI caused by biallelic variants in the SERPINF1 gene, which codes for the pigment-epithelium derived factor (PEDF). We report on four patients (three adults and one adolescent) with a severe deforming form of OI. All patients presented no abnormalities at birth, frequent long bone and vertebrae fractures (mainly during childhood), marked short stature, severe bone deformities, chronic mild to moderate pain, and severe limitation of mobility, with three being completely wheelchair bound. Blue sclera and dentinogenesis imperfecta were absent, although some patients presented tooth, ophthalmological, and/or cardiac features. Radiographic findings included, among others, thin diaphysis and popcorn calcifications, both of which are non-specific to this type of OI. The novel homozygous variants c.816_819del (p.Met272Ilefs*8) and c.283+2T > G in SERPINF1 were identified in three and one patient, respectively. The three patients carrying the frameshift variant were born in nearby regions suggesting a founder effect. Describing the long-term outcomes of four patients with OI type VI, this cohort adds relevant data on the clinical features and prognosis of this type of OI.

[Developing tools to study the health impact of urban transformations in high vulnerability contexts: the RUCAS study]. / Desarrollo de instrumentos para estudiar el impacto en salud de las transformaciones urbanas en contextos de elevada vulnerabilidad: el estudio RUCAS.

This article describes the design and characteristics of a questionnaire and an intradomiciliary observation tool developed to assess the housing-neighborhood-health relationship both cross-sectionally and longitudinally in the context of urban transformations carried out in populations of high socio-territorial vulnerability. The instruments were developed for the multi-method longitudinal study RUCAS (Urban Regeneration, Quality of Life and Health), a natural experiment aiming to assess the quality of life and health impact of a comprehensive Urban Regeneration Program in two social housing complexes in Chile. The design of the instruments followed four main stages: (1) narrative review of the literature to define the dimensions of the study, and of existing measurement instruments to identify appropriate items for measuring them; (2) content validation with experts; (3) pre-test; and (4) pilot study. The resulting questionnaire, composed of 262 items, considers the different stages of the life course and gender issues. The intradomiciliary observation tool (77 items) is applied by the interviewer. The instruments assess (i) characteristics of the current residential situation that are known to affect health and will be intervened by the program; (ii) dimensions of health potentially affected by the residential situation and/or by the intervention within the time frame of the study (4 years); (iii) other health and health-related conditions that are relevant, even if changes will not be modified within the time frame of the study; and (iv) relevant socioeconomic, occupational and demographic dimensions. The instruments have shown to be capable of addressing the multidimensionality of urban transformation processes in contexts of urban poverty in formal housing.

Este artículo describe el proceso de diseño y las características de un cuestionario y una pauta de observación intradomiciliaria desarrollados para evaluar tanto transversal como longitudinalmente la relación vivienda-barrio-salud en el marco de transformaciones urbanas llevadas a cabo en poblaciones de elevada vulnerabilidad socio-territorial. Los instrumentos se desarrollaron para el estudio longitudinal multimétodos RUCAS (Regeneración Urbana, Calidad de Vida y Salud), un experimento natural cuyo objetivo principal es evaluar el impacto en salud y calidad de vida de un programa de Regeneración de Conjuntos Habitacionales en dos conjuntos de vivienda social en Chile. El diseño de los instrumentos siguió cuatro etapas principales: (1) revisión narrativa de la literatura para definir las dimensiones del estudio, y de instrumentos existentes para identificar ítems apropiados para su medición; (2) validación de contenido con expertos; (3) pre-test; y (4) estudio piloto. El cuestionario resultante, compuesto de 262 ítems, tiene en cuenta las distintas etapas del ciclo vital y cuestiones de género. La pauta de observación intradomiciliaria (77 ítems) es aplicada por el/la encuestadora. Los instrumentos abordan (i) características de la situación residencial actual que sabidamente afectan la salud y serán intervenidas por el programa; (ii) dimensiones de la salud potencialmente afectadas por la situación residencial y/o por la intervención dentro de los plazos del estudio (4 años); (iii) otras condiciones de salud y relacionadas con la salud que sean relevantes, aun cuando no se verán modificadas dentro de los plazos del estudio, y (iv) dimensiones socioeconómicas, ocupacionales y demográficas relevantes. Los instrumentos han mostrado ser una herramienta capaz de abordar la multidimensionalidad de los procesos de transformación urbana en contextos de pobreza urbana en vivienda formal.

Este artigo descreve o processo de desenho e as características de um questionário e uma diretriz de observação intradomiciliar desenvolvida para avaliar, tanto transversal quanto longitudinalmente, a relação moradia-vizinhança-saúde no âmbito das transformações urbanas realizadas em populações de alta vulnerabilidade sócio-territorial. Os instrumentos foram desenvolvidos para o estudo longitudinal multimétodo RUCAS (Regeneração Urbana, Qualidade de Vida e Saúde), uma experiência natural destinada a avaliar a relação moradia-vizinhança-saúde e o impacto na saúde de um programa de regeneração habitacional em dois conjuntos habitacionais sociais no Chile. A concepção dos instrumentos seguiu quatro etapas principais: (1) revisão narrativa da literatura para definir as dimensões do estudo, e dos instrumentos existentes para identificar itens apropriados para a medição; (2) validação do conteúdo com especialistas; (3) pré-teste; e (4) estudo piloto. O questionário resultante, composto de 262 itens, leva em conta diferentes estágios do ciclo de vida e questões de gênero. A diretriz de observação intradomiciliar (77 itens) é aplicada pelo entrevistador. Os instrumentos abordam (i) características da situação atual da moradia que são conhecidas por afetar a saúde e serão intervencionadas pelo programa; (ii) dimensões da saúde potencialmente afetadas pela moradia e/ou pela intervenção dentro do prazo do estudo (4 anos); (iii) outras condições de saúde e relacionadas à saúde que são relevantes, mesmo que não sejam modificadas dentro do prazo do estudo; e (iv) dimensões sócioeconômicas, ocupacionais e demográficas relevantes. Os instrumentos projetados demonstraram ser uma ferramenta capaz de abordar a multidimensionalidade dos processos de transformação urbana em contextos de pobreza urbana na habitação formal.

Evolution of clinical and radiological presentations of spondyloepimetaphyseal dysplasia, RPL13-related: Description of 11 further cases.

Spondyloepimetaphyseal dysplasia (SEMD), RPL13-related is caused by heterozygous variants in RPL13, which encodes the ribosomal protein eL13, a component of the 60S human ribosomal subunit. Here, we describe the clinical and radiological evolution of 11 individuals, 7 children and 4 adults, from 6 families. Some of the skeletal features improved during the course of this condition, whilst others worsened. We describe for the first time "corner fractures" as a feature of this dysplasia which as with other dysplasias disappear with age. In addition, we review the heights and skeletal anomalies of these reported here and previously in a total of 25 individuals from 15 families. In this study, six different RPL13 variants were identified, five of which were novel. All were located in the apparently hotspot region, located in intron 5 and exon 6. Splicing assays were performed for two of the three previously undescribed splicing variants. Until now, all splice variants have occurred in the intron 5 splice donor site, incorporating an additional 18 amino acids to the mutant protein. Here, we report the first variant in intron 5 splice acceptor site which generates two aberrant transcripts, deleting the first three and four amino acids encoded by exon 6. Thus, this study doubles the number of SEMD-RPL13-related cases and variants reported to date and describes unreported age-related clinical and radiological features.

Stroke in Latin America: Systematic review of incidence, prevalence, and case-fatality in 1997-2021.

BACKGROUND: Stroke is a major global cause of death and disability. Most strokes occur in populations of low-middle-income country (LMIC); therefore, the subsequent disease burden is greater than in populations of high-income countries. Few epidemiological data exist for stroke in Latin America, composed primarily of LMIC. AIMS: To determine epidemiological measures of incidence, prevalence, and 1-month case-fatality for stroke in Latin America/Caribbean (LAC) during 1997-2021. SUMMARY OF REVIEW: A structured search was conducted to identify relevant references from MEDLINE, WOS, and LILACS databases for prospective observational and cross-sectional studies in LAC populations from January 1997 to December 2021. A total of 9242 records were screened and 12 selected for analysis, seven incidence studies and five prevalence studies. Case-fatality was reported in six articles. Sub-group analysis by age, sex, and income countries was performed. A narrative synthesis of the findings was performed. Meta-analysis was performed using random-effect model to obtain pooled estimates with 95% confidence intervals (CIs). Studies quality was assessed according to the risk of bias criteria described in the Joanna Briggs Institute's guide. The overall crude annual incidence rate of first-ever stroke in LAC was 119.0 (95% CI = 95.9-142.1)/100,000 people (with high heterogeneity between studies (I2 = 98.1%)). The overall crude prevalence was 3060 (95% CI: 95.9-142.1)/100,000 people (with high heterogeneity between studies (I2 = 98.8%)). The overall case-fatality at 1 month after the first stroke was 21.1% (95% CI = 18.6-23.7) (I2 = 49.40%). CONCLUSION: This review contributes to our understanding regarding the burden caused by stroke in LAC. More studies with comparable designs are needed to generate reliable data and should include both standardized criteria, such as the World Health Organization clinical criteria and updated standard methods of case assurance, data collection, and reporting.

Desarrollo de instrumentos para estudiar el impacto en salud de las transformaciones urbanas en contextos de elevada vulnerabilidad: el estudio RUCAS / Developing tools to study the health impact of urban transformations in high vulnerability contexts: the RUCAS study / Desenvolvimento de instrumentos para estudar o impacto na saúde das transformações urbanas em contextos de alta vulnerabilidade: o estudo RUCAS

Este artículo describe el proceso de diseño y las características de un cuestionario y una pauta de observación intradomiciliaria desarrollados para evaluar tanto transversal como longitudinalmente la relación vivienda-barrio-salud en el marco de transformaciones urbanas llevadas a cabo en poblaciones de elevada vulnerabilidad socio-territorial. Los instrumentos se desarrollaron para el estudio longitudinal multimétodos RUCAS (Regeneración Urbana, Calidad de Vida y Salud), un experimento natural cuyo objetivo principal es evaluar el impacto en salud y calidad de vida de un programa de Regeneración de Conjuntos Habitacionales en dos conjuntos de vivienda social en Chile. El diseño de los instrumentos siguió cuatro etapas principales: (1) revisión narrativa de la literatura para definir las dimensiones del estudio, y de instrumentos existentes para identificar ítems apropiados para su medición; (2) validación de contenido con expertos; (3) pre-test; y (4) estudio piloto. El cuestionario resultante, compuesto de 262 ítems, tiene en cuenta las distintas etapas del ciclo vital y cuestiones de género. La pauta de observación intradomiciliaria (77 ítems) es aplicada por el/la encuestadora. Los instrumentos abordan (i) características de la situación residencial actual que sabidamente afectan la salud y serán intervenidas por el programa; (ii) dimensiones de la salud potencialmente afectadas por la situación residencial y/o por la intervención dentro de los plazos del estudio (4 años); (iii) otras condiciones de salud y relacionadas con la salud que sean relevantes, aun cuando no se verán modificadas dentro de los plazos del estudio, y (iv) dimensiones socioeconómicas, ocupacionales y demográficas relevantes. Los instrumentos han mostrado ser una herramienta capaz de abordar la multidimensionalidad de los procesos de transformación urbana en contextos de pobreza urbana en vivienda formal.

This article describes the design and characteristics of a questionnaire and an intradomiciliary observation tool developed to assess the housing-neighborhood-health relationship both cross-sectionally and longitudinally in the context of urban transformations carried out in populations of high socio-territorial vulnerability. The instruments were developed for the multi-method longitudinal study RUCAS (Urban Regeneration, Quality of Life and Health), a natural experiment aiming to assess the quality of life and health impact of a comprehensive Urban Regeneration Program in two social housing complexes in Chile. The design of the instruments followed four main stages: (1) narrative review of the literature to define the dimensions of the study, and of existing measurement instruments to identify appropriate items for measuring them; (2) content validation with experts; (3) pre-test; and (4) pilot study. The resulting questionnaire, composed of 262 items, considers the different stages of the life course and gender issues. The intradomiciliary observation tool (77 items) is applied by the interviewer. The instruments assess (i) characteristics of the current residential situation that are known to affect health and will be intervened by the program; (ii) dimensions of health potentially affected by the residential situation and/or by the intervention within the time frame of the study (4 years); (iii) other health and health-related conditions that are relevant, even if changes will not be modified within the time frame of the study; and (iv) relevant socioeconomic, occupational and demographic dimensions. The instruments have shown to be capable of addressing the multidimensionality of urban transformation processes in contexts of urban poverty in formal housing.

Este artigo descreve o processo de desenho e as características de um questionário e uma diretriz de observação intradomiciliar desenvolvida para avaliar, tanto transversal quanto longitudinalmente, a relação moradia-vizinhança-saúde no âmbito das transformações urbanas realizadas em populações de alta vulnerabilidade sócio-territorial. Os instrumentos foram desenvolvidos para o estudo longitudinal multimétodo RUCAS (Regeneração Urbana, Qualidade de Vida e Saúde), uma experiência natural destinada a avaliar a relação moradia-vizinhança-saúde e o impacto na saúde de um programa de regeneração habitacional em dois conjuntos habitacionais sociais no Chile. A concepção dos instrumentos seguiu quatro etapas principais: (1) revisão narrativa da literatura para definir as dimensões do estudo, e dos instrumentos existentes para identificar itens apropriados para a medição; (2) validação do conteúdo com especialistas; (3) pré-teste; e (4) estudo piloto. O questionário resultante, composto de 262 itens, leva em conta diferentes estágios do ciclo de vida e questões de gênero. A diretriz de observação intradomiciliar (77 itens) é aplicada pelo entrevistador. Os instrumentos abordam (i) características da situação atual da moradia que são conhecidas por afetar a saúde e serão intervencionadas pelo programa; (ii) dimensões da saúde potencialmente afetadas pela moradia e/ou pela intervenção dentro do prazo do estudo (4 anos); (iii) outras condições de saúde e relacionadas à saúde que são relevantes, mesmo que não sejam modificadas dentro do prazo do estudo; e (iv) dimensões sócioeconômicas, ocupacionais e demográficas relevantes. Os instrumentos projetados demonstraram ser uma ferramenta capaz de abordar a multidimensionalidade dos processos de transformação urbana em contextos de pobreza urbana na habitação formal.

Is the near coming xenotransplantation era relieving us from needing to look for more non-living organ donors?

Despite organ transplantation being the most successful treatment for end-stage organ dysfunction, the number of annual solid organ transplantations is much lower than that required to satisfy the demand of patients on waiting lists. The explanation for this phenomenon is the relative scarcity of non-living organ donors due to several factors, such as: (1) Late arrival of patients with a neurocritical condition to an emergency service; (2) lack of detection of those patients as possible organ donors by health professionals dedicated to pro curement or by clinicians at emergency and intensive care units, for instance; (3) late transfer of the patient to an intensive care unit to try to recover their health and to provide hemodynamic, ventilatory, and metabolic support; (4) lack of confirmation of the physiological status of the possible donor; (5) late or incorrect positive diagnosis of the subject's death, either due to brain or cardiac death; (6) difficulty in obtaining legal authorization, either by direct relatives or by the authority, for the extraction of organs; and (7) deficient retrieval surgery of the organs actually donated. The recent reports of relatively successful xenotransplants from genetically modified pigs open the possibility to fix this mismatch between supply and demand, but some technical (organ rejection and opp ortunistic infections), and economic issues, still remain before accepting a progressive replacement of the organ sources for transplantation. An approximate economic cost analysis suggests that the hypothetical acquisition cost of any genetically modified pig derived organ is high and would not even satisfy the solid organ demand of the wealthiest countries.

Stroke care and collaborative academic research in Latin America.

OBJECTIVE: A narrative overview of regional academic research collaborations to address the increasing burden and gaps in care for patients at risk of, and who suffer from, stroke in Latin America (LA). MATERIALS AND METHODS: A summary of experiences and knowledge of the local situation is presented. No systematic literature review was performed. RESULTS: The rapidly increasing burden of stroke poses immense challenges in LA, where prevention and manage-ment strategies are highly uneven and inadequate. Clinical research is increasing through various academic consortia and networks formed to overcome structural, funding and skill barriers. However, strengthening the ability to generate, analyze and interpret randomized evidence is central to further develop effective therapies and healthcare systems in LA. CONCLUSIONS: Regional networks foster the conduct of multicenter studies -particularly randomized controlled trials-, even in resource-poor regions. They also contribute to the external validity of international studies and strengthen systems of care, clinical skills, critical thinking, and international knowledge exchange.

Biallelic cGMP-dependent type II protein kinase gene (PRKG2) variants cause a novel acromesomelic dysplasia.

BACKGROUND: C-type natriuretic peptide (CNP), its endogenous receptor, natriuretic peptide receptor-B (NPR-B), as well as its downstream mediator, cyclic guanosine monophosphate (cGMP) dependent protein kinase II (cGKII), have been shown to play a pivotal role in chondrogenic differentiation and endochondral bone growth. In humans, biallelic variants in NPR2, encoding NPR-B, cause acromesomelic dysplasia, type Maroteaux, while heterozygous variants in NPR2 (natriuretic peptide receptor 2) and NPPC (natriuretic peptide precursor C), encoding CNP, cause milder phenotypes. In contrast, no variants in cGKII, encoded by the protein kinase cGMP-dependent type II gene (PRKG2), have been reported in humans to date, although its role in longitudinal growth has been clearly demonstrated in several animal models. METHODS: Exome sequencing was performed in two girls with severe short stature due to acromesomelic limb shortening, brachydactyly, mild to moderate platyspondyly and progressively increasing metaphyseal alterations of the long bones. Functional characterisation was undertaken for the identified variants. RESULTS: Two homozygous PRKG2 variants, a nonsense and a frameshift, were identified. The mutant transcripts are exposed to nonsense-mediated decay and the truncated mutant cGKII proteins, partially or completely lacking the kinase domain, alter the downstream mitogen activation protein kinase signalling pathway by failing to phosphorylate c-Raf 1 at Ser43 and subsequently reduce ERK1/2 activation in response to fibroblast growth factor 2. They also downregulate COL10A1 and upregulate COL2A1 expression through SOX9. CONCLUSION: In conclusion, we have clinically and molecularly characterised a new acromesomelic dysplasia, acromesomelic dysplasia, PRKG2 type (AMDP).

Case report: A third variant in the 5' UTR of TWIST1 creates a novel upstream translation initiation site in a child with Saethre-Chotzen syndrome.

Introduction: Saethre-Chotzen syndrome, a craniosynostosis syndrome characterized by the premature closure of the coronal sutures, dysmorphic facial features and limb anomalies, is caused by haploinsufficiency of TWIST1. Although the majority of variants localize in the coding region of the gene, two variants in the 5' UTR have been recently reported to generate novel upstream initiation codons. Methods: Skeletal dysplasia Next-generation sequencing (NGS) panel was used for genetic analysis in a patient with bicoronal synostosis, facial dysmorphisms and limb anomalies. The variant pathogenicity was assessed by a luciferase reporter promoter assay. Results: Here, we describe the identification of a third ATG-creating de novo variant, c.-18C>T, in the 5' UTR of TWIST1 in the patient with a clinical diagnosis of Saethre-Chotzen syndrome. It was predicted to create an out-of-frame new upstream translation initiation codon resulting in a 40 amino acid larger functionally inactive protein. We performed luciferase reporter promoter assays to demonstrate that the variant does indeed reduce translation from the main open reading frame. Conclusion: This is the third variant identified in this region and confirms the introduction of upstream ATGs in the 5' UTR of TWIST1 as a pathogenic mechanism in Saethre-Chotzen syndrome. This case report shows the necessity for performing functional characterization of variants of unknown significance within national health services.

Comparación cesáreas de no emergencia y parto normal, en servicios públicos/privados durante los años 2016-2019 en Chile / Comparison of non-emergency cesarean section and normal childbirth, in public/private services during the years 2016-2019 in Chile

Introducción: La Organización Mundial de la Salud (OMS) propuso que el porcentaje de cesáreas debería ser entre un 10 y 15%. Sin embargo, en los últimos años, a nivel mundial, se ha visto un aumento en su realización. El objetivo de este estudio fue describir la población de embarazadas en Chile durante los años 2016-2019 que tuvieron parto vaginal (PV) o cesárea de no emergencia (CNE), y compararlos entre servicio público y privado. Material y Método: Estudio ecológico realizado en embarazadas que se sometieron a CNE o PV en Chile entre los años 2016-2019. Se obtuvieron datos del Departamento de estadística e información de Salud. No se requirió comité de ética. Resultados: Durante el periodo estudiado hubo 57,60% (339.592) de PV y 42,39% (249.925) de CNE. En el sistema público hubo una diferencia de 54,94% (187.046) de PV por sobre el sistema privado. Mientras que la diferencia de CNE en el sistema privado fue un 10,06% (25.153) por sobre el sistema público. Discusión: Durante los cuatro años, las PV superaron a las CNE, sin embargo, las CNE representaron más del 40% del total de nacimientos, superando ampliamente las recomendaciones de la OMS. Las falencias a nivel nacional en el sistema de clasificación, y en la recopilación de datos limitan el desarrollo de estudios más acabados. Conclusión: Para enfrentar las altas cifras de CNE, es necesario unificar, ampliar y regularizar un base de datos nacional que dé paso a la creación de guías y protocolos que limiten el uso mal justificado de CNE.

Introduction: The World Health Organization (WHO) proposed that the percentage of caesarean sections should be between 10 and 15%. However, in recent years, worldwide, there has been an increase in its realization. The objective of this study was to describe the population of pregnant women in Chile during the years 2016-2019 who had a vaginal delivery (VD) or non-emergency cesarean section (NECS), and to compare them between public and private services. Material and Method: Ecological study carried out in pregnant women who underwent NECS or VD in Chile between the years 2016-2019. Data were obtained from the Department of Statistics and Health Information. No ethics committee was required. Results: During the studied period there were 57.60% (339,592) of VD and 42.39% (249,925) of NECS. In the public system there was a difference of 54.94% (187,046) of VD over the private system. While the difference of NECS in the private system was 10.06% (25,153) over the public system. Discussion: During the four years, VD exceeded NECS, however, NECS represented more than 40% of all births, far exceeding the WHO recommendations. Shortcomings at the national level in the classification system and in data collection limit the development of more complete studies. Conclusion: To face the high numbers of NECS, it is necessary to unify, expand and regularize a national database that gives way to the creation of guides and protocols that limit the poorly justified use of NECS.