Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogota, Colombia.
Ontology highlight
ABSTRACT:
SUBMITTER: Lago J
PROVIDER: S-EPMC8625804 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundUltra-rare inherited bleeding disorders (BDs) present important challenges for generating a strong evidence foundation for optimal diagnosis and management. Without disorder-appropriate treatment, affected individuals potentially face life-threatening bleeding, delayed diagnosis, suboptimal management of invasive procedures, psychosocial distress, pain, and decreased quality-of-life.Research design and methodsThe National Hemophilia Foundation (NHF) and the American Thrombosis and Hemostasis Network identified the priorities of people with inherited BDs and their caregivers, through extensive inclusive community consultations, to inform a blueprint for future decades of research. Multidisciplinary expert Working Group (WG) 3 distilled highly feasible transformative ultra-rare inherited BD research opportunities from the community-identified priorities.ResultsWG3 identified three focus areas with the potential to advance the needs of all people with ultra-rare inherited BDs and scored the feasibility, impact, and risk of priority initiatives, including 13 in systems biology and mechanistic science; 2 in clinical research, data collection, and research infrastructure; and 5 in the regulatory process for novel therapeutics and required data collection.ConclusionsCentralization and expansion of expertise and resources, flexible innovative research and regulatory approaches, and inclusion of all people with ultra-rare inherited BDs and their health care professionals will be essential to capitalize on the opportunities outlined herein.
| S-EPMC10020868 | biostudies-literature
Project description:BackgroundIn recent years, more awareness is raised about sex-specific dilemmas in inherited bleeding disorders. However, no large studies have been performed to assess differences in diagnosis, bleeding phenotype and management of men and women with bleeding disorders. Therefore, we investigated sex differences in a large cohort of well-defined patients with autosomal inherited bleeding disorders (von Willebrand disease (VWD), rare bleeding disorders (RBDs) and congenital platelet defects (CPDs)).MethodsWe included patients from three nationwide cross-sectional studies on VWD, RBDs and CPDs in the Netherlands, respectively the WiN, RBiN and TiN study. In all studies a bleeding score (BS) was obtained, and patients filled in an extensive questionnaire on the management and burden of their disorder.FindingsWe included 1092 patients (834 VWD; 196 RBD; 62 CPD), of whom 665 (60.9%) were women. Women were more often referred because of a bleeding diathesis than men (47.9% vs 36.6%, p = 0.002). Age of first bleeding was similar between men and women, respectively 8.9 ± 13.6 (mean ±sd) years and 10.6 ± 11.3 years (p = 0.075). However, the diagnostic delay, which was defined as time from first bleeding to diagnosis, was longer in women (11.6 ± 16.4 years) than men (7.7 ± 16.6 years, p = 0.002). Similar results were found when patients referred for bleeding were analyzed separately. Of women aging 12 years or older, 469 (77.1%) had received treatment because of sex-specific bleeding.InterpretationWomen with autosomal inherited bleeding disorders are more often referred for bleeding, have a longer diagnostic delay, and often require treatment because of sex-specific bleeding.FundingThe WiN study was supported (in part) by research funding from the Dutch Hemophilia Foundation (Stichting Haemophilia), Shire (Takeda), and CSL Behring (unrestricted grant).
| S-EPMC7848767 | biostudies-literature
Project description:Objective: To investigate transplantation of rat Schwann cells or human iPSC-derived neural crest cells and derivatives into models of acquired and inherited peripheral myelin damage. Methods: Primary cultured rat Schwann cells labeled with a fluorescent protein for monitoring at various times after transplantation. Human induced pluripotent stem cells (iPSCs) were differentiated into neural crest stem cells (NCSC), and subsequently toward a Schwann cell lineage via two different protocols. Protocol 1 = treated with MesenPRO with Heregulin. Protocol 2 = coculture with iPSC-derived Motor Neurons. Cell types were characterized using flow cytometry, immunocytochemistry and transcriptomics. Rat Schwann cells and human iPSC-derivatives were transplanted into (i) nude rats pretreated with lysolecithin to induce demyelination or (ii) a transgenic rat model of dysmyelination due to PMP22 overexpression. Results: Rat Schwann cells transplanted into sciatic nerves with either toxic demyelination or genetic dysmyelination engrafted successfully, and migrated longitudinally for relatively long distances, with more limited axial migration. Transplanted Schwann cells engaged existing axons and displaced dysfunctional Schwann cells to form normal appearing myelin. Human iPSC-derived neural crest stem cells and their derivatives shared similar engraftment and migration characteristics to rat Schwann cells after transplantation, but did not further differentiate into Schwann cells or form myelin. Interpretation: These results indicate that cultured Schwann cells surgically delivered to peripheral nerve can engraft and form myelin in either acquired or inherited myelin injury, as proof of concept for pursuing cell therapy for diseases of peripheral nerve. However, lack of reliable technology for generating human iPSC-derived Schwann cells for transplantation therapy remains a barrier in the field.
2018-01-26 | GSE109686 | GEO
Project description:Latin America has been severely affected by the COVID-19 pandemic but estimations of rates of infections are very limited and lack the level of detail required to guide policy decisions. We implemented a COVID-19 sentinel surveillance study with 59,770 RT-PCR tests on mostly asymptomatic individuals and combine this data with administrative records on all detected cases to capture the spread and dynamics of the COVID-19 pandemic in Bogota from June 2020 to early March 2021. We describe various features of the pandemic that appear to be specific to a middle income countries. We find that, by March 2021, slightly more than half of the population in Bogota has been infected, despite only a small fraction of this population being detected. The initial buildup of immunity contributed to the containment of the pandemic in the first and second waves. We also show that the share of the population infected by March 2021 varies widely by occupation, socio-economic stratum, and location. This, in turn, has affected the dynamics of the spread with different groups being infected in the two waves.
| S-EPMC8342514 | biostudies-literature
Project description:BackgroundAccording to the 2015 National Survey of the Nutritional Situation in Colombia the prevalence of stunting in children under 5 years of age was 10.8%. In terms of region, Bogotá, presented the highest prevalence rate (13%), a figure that exceeded national records. With the collaboration of local and national government, and nongovernmental it was decided to develop a pilot study involving a public health intervention with residents of Bogotá under 1 year of age with nutritional classification by anthropometry compatible with stunting risk or stunting.MethodsPre-experimental, before and after study that sought to determine the magnitude of the change in nutritional status through a 10 months public health nutrition intervention in children under one-year-old residing in 3 prioritized territories of Bogotá.ResultsThe intervention comprised 1126 children living in the following territories in Bogotá: Kennedy, San Cristóbal, and Engativá. A total of 43.3% children presented delay in height for age, and 56.7% presented risk of short stature. In the final measurement, data were obtained from 686 children, identifying that 17% of the children progressed from stunting to a stunting risk and that 4.5% recovered their growth trajectory, achieving an adequate length for their age.ConclusionThat children classified as at risk or stunting at the beginning of the intervention showed an increased probability of approaching or being in the appropriate growth trajectory according to the length-for-age indicator after the intervention.
| S-EPMC8034142 | biostudies-literature
Project description:According to the World Health Organization, in 2016, Colombia obtained the tenth position worldwide, the third in the continent and the second in South America, according to the accident rate of 9.7 motorcycle fatalities per 100,000 populations. Between 2012 and 2021, the number of deceased and injured motorcyclists among all road users was 50%, with an annual average of 3140 fatal victims and 20,800 injured victims. Bogotá, Cali, and Medellín were the cities with the most accidents. In Bogota in 2017, the deaths of motorcyclists on the roads were around 32% of the road actors. This data article presents the dataset used to analyze and predict the severity of motorcyclist road accidents in Bogota in the article entitled "Extraction of decision rules using genetic algorithms and simulated annealing for prediction of severity of traffic accidents by motorcyclists" [1]. The data set was consolidated from the registration of 175,245 traffic accidents and the report of 337,828 road actors involved in crashes in Bogotá between January 2013 and February 2018. The data was compiled, processed, and enriched with additional information about infrastructure and weather conditions. The data corresponds to 35,693 motorcyclist traffic accidents, represented by 28 variables, and classified into five categories: road actors, motorcyclists and individuals involved, weather conditions and timing, road conditions and location and characteristics of the accident. The data on motorcyclist traffic accidents opens up a scenario to deepen and compare road safety in Latin America, where studies on vulnerable road users are limited. According to severity, the data on motorcycle traffic accidents recorded 28% with material damage, 69% with injured and 3% with fatal victims.
| S-EPMC9309645 | biostudies-literature
Project description:AimCurrently, it is unknown which patient-reported outcomes are important for patients with autosomal inherited bleeding disorders. Therefore, the purpose of this study is to systematically review the available literature assessing patient-reported outcomes and their measurement methods in autosomal inherited bleeding disorders.MethodsThe Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trails and Google Scholar databases were searched from inception until 14 August 2020. Studies on patient-reported outcomes in patients with von Willebrand disease, inherited platelet function disorders and coagulation factor deficiencies were included.ResultsTwenty-one articles met the inclusion criteria. Three studies were assessed as having poor quality, and therefore a high risk of bias. Nineteen studies had fair quality rating. Different measurements methods were used, ranging from predefined to self-developed questionnaires. The majority of included studies focused on von Willebrand disease. Patients with von Willebrand disease reported lower health-related quality of life compared to the general population. Overall, this trend was especially visible in the following domains: vitality, physical and social functioning and pain. Women with inherited bleeding disorders scored lower on health-related quality of life compared to men, especially women with heavy menstrual bleeding. Patients with joint bleeds or heavy menstrual bleeding reported an increased level of pain.ConclusionPatients with autosomal inherited bleeding disorders report lower health related quality of life, especially those with joint bleeds or heavy menstrual bleeding. Numerous measurement methods are used in patients with autosomal inherited bleeding disorders, highlighting the need for studies using established, standardized measurement methods.
| S-EPMC9305757 | biostudies-literature
Project description:The bleeding phenotype of hereditary coagulation disorders is caused by the low or undetectable activity of the proteins involved in hemostasis, due to a broad spectrum of genetic alterations. Most of the affected coagulation factors are produced in the liver. Therefore, two-dimensional (2D) cultures of primary human hepatocytes and recombinant overexpression of the factors in non-human cell lines have been primarily used to mimic disease pathogenesis and as a model for innovative therapeutic strategies. However, neither human nor animal cells fully represent the hepatocellular biology and do not harbor the exact genetic background of the patient. As a result, the inability of the current in vitro models in recapitulating the in vivo situation has limited the studies of these inherited coagulation disorders. Induced Pluripotent Stem Cell (iPSC) technology offers a possible solution to overcome these limitations by reprogramming patient somatic cells into an embryonic-like pluripotent state, thus giving the possibility of generating an unlimited number of liver cells needed for modeling or therapeutic purposes. By combining this potential and the recent advances in the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology, it allows for the generation of autologous and gene corrected liver cells in the form of three-dimensional (3D) liver organoids. The organoids recapitulate cellular composition and organization of the liver, providing a more physiological model to study the biology of coagulation proteins and modeling hereditary coagulation disorders. This advanced methodology can pave the way for the development of cell-based therapeutic approaches to treat inherited coagulation disorders. In this review we will explore the use of liver organoids as a state-of-the-art methodology for modeling coagulation factors disorders and the possibilities of using organoid technology to treat the disease.
| S-EPMC9880334 | biostudies-literature
Project description:BackgroundHeavy menstrual bleeding (HMB) is a presenting symptom of an inherited bleeding disorder (BD) and results in hospitalizations, limitations of daily activities, and a reduction in quality of life. Adult women with BD report a sense of stigma, difficulties understanding their bleeding, and challenges with diagnostic labels. The experiences of adolescents with HMB and BD are unknown despite advances in medical management through the rapidly growing network of young women's hematology programs.ObjectivesThe objective of our qualitative study was to describe the experiences of adolescents with HMB with a BD and the impact on their day-to-day lives.Patients/methodsOur qualitative study utilized semistructured interviews with adolescents with HMB after a BD diagnosis. We included adolescents with a BD within a multidisciplinary Young Women's Bleeding Disorders Clinic who had achieved menarche within the preceding 3 years and conducted interviews until theme saturation. All interviews were transcribed verbatim and analyzed using qualitative thematic descriptive analysis.ResultsWe identified the following themes in nine participants: anxiety and embarrassment, especially related to school; isolation and "otherness"; increased cautiousness and planning because of HMB and BD; and empowerment and identity formation because of the diagnosis of a BD.ConclusionsOur study uncovers previously unappreciated experiences of adolescents with HMB and a BD. HMB is an isolating and stressful experience in adolescents, but a BD diagnosis results in identity formation and empowerment. Psychological support and facilitating connections to others with similar life experiences soon after diagnosis represents key areas for targeted interventions.
| S-EPMC9152438 | biostudies-literature
Project description:BackgroundThe incidence of invasive pneumococcal disease (IPD) varies depending on a number of factors, including vaccine uptake, in both children and adults, the geographic location, and local serotype prevalence. There are limited data about the burden of Streptococcus pneumoniae (Spn), serotype distribution, and clinical characteristics of adults hospitalized due to IPD in Colombia. The objectives of this study included assessment of Spn serotype distribution, clinical characteristics, mortality, ICU admission, and the need for mechanical ventilation.MethodsThis was an observational, retrospective, a citywide study conducted between 2012 and 2019 in Bogotá, Colombia. We analyzed reported positive cases of IPD from 55 hospitals in a governmental pneumococcal surveillance program. Pneumococcal strains were isolated in each hospital and typified in a centralized laboratory. This is a descriptive study stratified by age and subtypes of IPD obtained through the analysis of medical records.ResultsA total of 310 patients with IPD were included, of whom 45.5% were female. The leading cause of IPD was pneumonia (60%, 186/310), followed by meningitis. The most frequent serotypes isolated were 19A (13.87%, 43/310) and 3 (11.94%, 37/310). The overall hospital mortality rate was 30.3% (94/310). Moreover, 52.6% (163/310 patients) were admitted to the ICU, 45.5% (141/310) required invasive mechanical ventilation and 5.1% (16/310) non-invasive mechanical ventilation.ConclusionPneumococcal pneumonia is the most prevalent cause of IPD, with serotypes 19A and 3 being the leading cause of IPD in Colombian adults. Mortality due to IPD in adults continues to be very high.
| S-EPMC8507327 | biostudies-literature