PURPOSE: Genetic testing in consanguineous families advances the general comprehension of pathophysiological pathways. However, short stature (SS) genetics remain unexplored in a defined consanguineous cohort. This study examines a unique pediatric cohort from Sulaimani, Iraq, aiming to inspire a genetic testing algorithm for similar populations. METHODS: Among 280 SS referrals from 2018-2020, 64 children met inclusion criteria (from consanguineous families; height ≤ -2.25 SD), 51 provided informed consent (30 females; 31 syndromic SS) and underwent investigation, primarily via exome sequencing. Prioritized variants were evaluated by the American College of Medical Genetics and Genomics standards. A comparative analysis was conducted by juxtaposing our findings against published gene panels for SS. RESULTS: A genetic cause of SS was elucidated in 31 of 51 (61%) participants. Pathogenic variants were found in genes involved in the GH-IGF-1 axis (GHR and SOX3), thyroid axis (TSHR), growth plate (CTSK, COL1A2, COL10A1, DYM, FN1, LTBP3, MMP13, NPR2, and SHOX), signal transduction (PTPN11), DNA/RNA replication (DNAJC21, GZF1, and LIG4), cytoskeletal structure (CCDC8, FLNA, and PCNT), transmembrane transport (SLC34A3 and SLC7A7), enzyme coding (CYP27B1, GALNS, and GNPTG), and ciliogenesis (CFAP410). Two additional participants had Silver-Russell syndrome and 1 had del22q.11.21. Syndromic SS was predictive in identifying a monogenic condition. Using a gene panel would yield positive results in only 10% to 33% of cases. CONCLUSION: A tailored testing strategy is essential to increase diagnostic yield in children with SS from consanguineous populations.
- MeSH
- Algorithms MeSH
- Child MeSH
- Genetic Testing * methods MeSH
- Humans MeSH
- Adolescent MeSH
- Mutation genetics MeSH
- Dwarfism genetics diagnosis MeSH
- Consanguinity * MeSH
- Growth Disorders genetics diagnosis MeSH
- Child, Preschool MeSH
- Pedigree MeSH
- Exome Sequencing methods MeSH
- Body Height genetics MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Iraq MeSH
Necrotizing enterocolitis (NEC) is a severe intestinal condition primarily affecting preterm neonates. It has a high mortality rate, particularly in infants with a birthweight of below 1,500 g or for those requiring surgical intervention. The European Reference Network for Inherited and Congenital Anomalies (ERNICA) has developed a clinical practice guideline to aid clinical decision-making pertaining to the surgical treatment and management of NEC in preterm neonates. This guideline was developed in accordance with the Guidelines 2.0 checklist and GRADE methodology. A multidisciplinary group of Europe's top experts collaborated with patient representatives to develop this guideline. After selecting critical points in care for which recommendations are required, a systematic review of the literature and critical appraisal of the evidence was performed. The Evidence to Decision framework was used as a guide to structure the consensus meetings and draft the recommendations. The panel developed seven recommendations and three good practice statements on the following topics: indications for surgery, peritoneal drainage, surgical technique, management of extensive NEC, enteral feeding, and neurodevelopmental outcomes in premature neonates with NEC. The certainty of evidence was graded as (very) low for most recommendations. However, the panel weighed up the benefits and harms in light of all relevant arguments and expert opinion. This guideline provides recommendations on caring for premature neonates with NEC. These recommendations can assist clinicians in their care decisions and can inform families on treatment options and relevant considerations. This guideline will be revised every 5 years to ensure it remains up to date.
- MeSH
- Enteral Nutrition MeSH
- Clinical Decision-Making MeSH
- Humans MeSH
- Evidence-Based Medicine MeSH
- Enterocolitis, Necrotizing * surgery diagnosis MeSH
- Infant, Premature MeSH
- Infant, Newborn MeSH
- Check Tag
- Humans MeSH
- Infant, Newborn MeSH
- Publication type
- Journal Article MeSH
- Practice Guideline MeSH
- Systematic Review MeSH
- Geographicals
- Europe MeSH
The COVID-19 Pandemic contributed to accelerating the process of using information and communication technologies and digital technologies in healthcare management and delivery within healthcare systems. At that time, the Czech healthcare system faced the same problems as other European systems and struggled with a temporary limitation of direct provision of healthcare services. It was solved by switching to telemedicine. The Czech healthcare system used telemedicine to a minimal extent until then. Despite adopting the law on healthcare digitisation, it is still one of the countries with a lower level of digitisation of healthcare processes. The article presents the results of an exploratory expert investigation focused on the implementation and development of telemedicine in the Czech Republic. The conducted research aimed to identify problems related to the implementation of telemedicine in practice, place them in the broader framework of the healthcare system and structure them, propose possible solutions, and identify the future challenges of telemedicine in the Czech Republic. We based our study on the results of a three-phase QUAL-QUAN-QUAL research. Data collection in the first phase took the form of individual semi-structured interviews with patients (25) with practical experience in the field of telemedicine, followed by the second quantitative phase of the questionnaire survey with patients (650). The third qualitative phase included semi-structured interviews with experts (17) with practical experience in telemedicine. The introduction and expansion of telemedicine require several fundamental changes. These include adjustments to the legislative environment and changes to the technological infrastructure, organisation of care and work. Several barriers have been identified at the healthcare system level, healthcare providers, healthcare professionals and patients.
- MeSH
- COVID-19 * epidemiology MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Pandemics * MeSH
- Delivery of Health Care organization & administration MeSH
- Surveys and Questionnaires MeSH
- Interviews as Topic MeSH
- SARS-CoV-2 MeSH
- Aged MeSH
- Telemedicine * organization & administration MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
OBJECTIVE: To evaluate the role of clinical exchange programs in postgraduate obgyn training using the International Federation of Gynecology and Obstetrics (FIGO)-World Association of Trainees in Obstetrics and Gynecology (WATOG) One World Exchange (OWE), a clinical exchange program held in France in October 2023, as a case-study. METHODS: This was a cross-sectional study. A 31-item structured questionnaire designed with Google Forms was electronically distributed to the 51 obgyn postgraduate trainees (OWE fellows) who participated in the OWE, to collect information about the exchange. Collected data was analyzed using IBM Statistical Product and Service Solutions (SPSS) Statistics for Windows. RESULTS: The survey response rate was 68.6%. The mean age of the respondents was 33.0 ± 4.0 years. Majority of the them were females (26, 74.3%), married (19, 54.3%), at least in their third year of training (30, 85.7%) and from Africa (11, 31.4%). During the period of the exchange program, fellows observed various obstetric and gynecologic procedures, including open and minimal access procedures, with more than one-fifth (8, 22.9%) of them reporting that they were allowed to assist in some of these procedures. The fellows noted salient differences in practice between their exchange hospitals and their home countries. An overwhelming majority (30, 85.7%) of the fellows believed the OWE was beneficial and would positively impact their clinical practices back in their home countries. CONCLUSION: Clinical exchange programs like the OWE provide valuable benefits in improving the clinical knowledge and skills of postgraduate obgyn trainees.
- MeSH
- Adult MeSH
- Gynecology * education MeSH
- Humans MeSH
- International Educational Exchange * MeSH
- Obstetrics * education MeSH
- Cross-Sectional Studies MeSH
- Surveys and Questionnaires MeSH
- Societies, Medical MeSH
- Education, Medical, Graduate * methods MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- France MeSH
Super-resolution (SR) microscopy is a cutting-edge method that can provide detailed structural information with high resolution. However, the thickness of the specimen has been a major limitation for SR methods, and large biological structures have posed a challenge. To overcome this, the key step is to optimise sample preparation to ensure optical homogeneity and clarity, which can enhance the capabilities of SR methods for the acquisition of thicker structures. Oocytes are the largest cells in the mammalian body and are crucial objects in reproductive biology. They are especially useful for studying membrane proteins. However, oocytes are extremely fragile and sensitive to mechanical manipulation and osmotic shocks, making sample preparation a critical and challenging step. We present an innovative, simple and sensitive approach to oocyte sample preparation for 3D STED acquisition. This involves alcohol dehydration and mounting into a high refractive index medium. This extended preparation procedure allowed us to successfully obtain a unique two-channel 3D STED SR image of an entire mouse oocyte. By optimising sample preparation, it is possible to overcome current limitations of SR methods and obtain high-resolution images of large biological structures, such as oocytes, in order to study fundamental biological processes. Lay Abstract: Super-resolution (SR) microscopy is a cutting-edge tool that allows scientists to view incredibly fine details in biological samples. However, it struggles with larger, thicker specimens, as they need to be optically clear and uniform for the best imaging results. In this study, we refined the sample preparation process to make it more suitable for SR microscopy. Our method includes carefully dehydrating biological samples with alcohol and then transferring them into a mounting medium that enhances optical clarity. This improved protocol enables high-resolution imaging of thick biological structures, which was previously challenging. By optimizing this preparation method, we hope to expand the use of SR microscopy for studying large biological samples, helping scientists better understand complex biological structures.
The Global Alliance for Genomics and Health (GA4GH) Phenopacket Schema was released in 2022 and approved by ISO as a standard for sharing clinical and genomic information about an individual, including phenotypic descriptions, numerical measurements, genetic information, diagnoses, and treatments. A phenopacket can be used as an input file for software that supports phenotype-driven genomic diagnostics and for algorithms that facilitate patient classification and stratification for identifying new diseases and treatments. There has been a great need for a collection of phenopackets to test software pipelines and algorithms. Here, we present Phenopacket Store. Phenopacket Store v.0.1.19 includes 6,668 phenopackets representing 475 Mendelian and chromosomal diseases associated with 423 genes and 3,834 unique pathogenic alleles curated from 959 different publications. This represents the first large-scale collection of case-level, standardized phenotypic information derived from case reports in the literature with detailed descriptions of the clinical data and will be useful for many purposes, including the development and testing of software for prioritizing genes and diseases in diagnostic genomics, machine learning analysis of clinical phenotype data, patient stratification, and genotype-phenotype correlations. This corpus also provides best-practice examples for curating literature-derived data using the GA4GH Phenopacket Schema.
- MeSH
- Algorithms MeSH
- Databases, Genetic MeSH
- Phenotype * MeSH
- Genomics * methods MeSH
- Humans MeSH
- Software * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Farmakogenetické (PGx) vyšetření představuje slibný nástroj pro optimalizaci psychiatrické farmakoterapie. Svým potenciálem může přispět ke zvýšení její účinnosti a snížení rizika vzniku nežádoucích účinků. Ekonomická limitace v podobě vyšší ceny vyšetření vyžaduje cílenější výběr pacientů, tento přístup však v praxi zatím chybí. Za tím účelem byl klinickými farmaceutkami v Psychiatrické nemocnici Bohnice vyvinut skórovací systém CYPRI (CYP pharmacogenetic risk score) identifikující pacienty, kteří by mohli mít z PGx vyšetření největší prospěch. Cílem pilotní studie bylo pak zhodnotit účinnost a efektivitu skórovacího systému CYPRI při výběru pacientů pro PGx vyšetření v kontextu následně uskutečněných a klinicky významných změn v jejich medikaci. Do pilotní studie, která probíhala mezi lednem 2024 a březnem 2025, bylo zařazeno 23 pacientů (průměrný věk 38 let, 74 % mužů). Vzorek zahrnoval hospitalizované pacienty s širokým spektrem psychiatrických diagnóz, včetně schizofrenie, bipolární a schizoafektivní poruchy, deprese i úzkostných poruch. Pacienti, u kterých bylo PGx indikováno lékařem a/nebo klinickým farmaceutem a kteří v CYPRI skórovali alespoň jedním bodem, podstoupili po souhlasu PGx vyšetření. Následně u nich byla provedena analýza dopadu výsledku tohoto vyšetření na úpravy v medikaci. Byla zjištěna statisticky významná korelace (t = 2,733; p = 0,0063) mezi hodnotami CYPRI skóre a následnými klinicky významnými změnami v medikaci. Pacienti s vysokým CYPRI skóre (> 3) také vyžadovali statisticky významně více úprav medikace a monitorace než pacienti s nízkým skóre (≤ 3) (p < 0,05). Tyto výsledky potvrzují, že CYPRI skóre by mohlo v budoucnu sloužit jako strukturovaný a nákladově efektivní nástroj pro výběr vhodných kandidátů na PGx vyšetření, zejména v oboru psychiatrie. Širší použití CYPRI skóre v praxi prozatím limituje, i přes slibné výsledky z pilotní studie, relativně malá velikost vzorku. Pro potvrzení těchto výstupů je zapotřebí další výzkum na větších kohortách.
Pharmacogenetic (PGx) testing is a promising tool for optimizing psychiatric pharmacotherapy by improving its effectiveness and reducing the risk of adverse effects. However, its higher cost necessitates a more selective approach to patient screening, which is currently lacking in clinical practice. To address this gap, clinical pharmacists at Bohnice Psychiatric Hospital developed a CYPRI (CYP Pharmacogenetic Risk Score) scoring system to identify patients who would benefit the most from PGx testing. This pilot study aimed to assess the effectiveness and efficiency of the CYPRI scoring system in selecting patients for PGx testing, focusing on clinically significant medication adjustments that followed. Our study was conducted from January 2024 to March 2025 and included 23 hospitalized patients (mean age: 38 years; 74% male) with a range of psychiatric diagnoses, including schizophrenia, bipolar disorder, schizoaffective disorder, depression, and anxiety disorders. Pharmacogenetic testing was offered to patients following an initial indication by a psychiatrist and/or clinical pharmacist, provided they scored at least one point on the CYPRI scale. Upon providing an informed consent, they underwent the PGx testing. The resulting impact on medication adjustments was analyzed. A statistically significant correlation was found between the CYPRI scores and clinically significant medication changes (t = 2.733; p = 0.0063). Additionally, patients with high CYPRI scores (> 3) required significantly more medication adjustments and monitoring than those with low scores (≤ 3) (p < 0.05). These findings suggest that the CYPRI score could serve as a structured and cost-effective tool for identifying suitable candidates for PGx testing, especially in psychiatry. Despite these promising results, the relatively small sample size remains a limitation for the broader implementation of the CYPRI score. Further research with larger cohorts is needed to validate these findings.
BACKGROUND: The role of primary healthcare (PHC) during a pandemic varies across European countries. The coronavirus disease 2019 (COVID-19) pandemic has altered the working practices of family medicine doctors and impacted the resilience of healthcare systems. OBJECTIVES: This study aimed to examine European healthcare system responses to the pandemic, focusing on rural and urban differences. MATERIAL AND METHODS: This cross-sectional, mixed-methods study used a semi-structured online questionnaire with 68 questions, including 21 free-text comments. Data were collected from May 2020 to January 2021. Key informants from 16 European Rural and Isolated Practitioners Association (EURIPA) member countries distributed questionnaires to 406 PHC doctors. Data were analyzed using descriptive statistics and nonparametric tests (χ2, Kruskal-Wallis, Mann-Whitney U) with a significance threshold of 0.05. RESULTS: A statistically significant difference was found between rural (36.4%, 55/151), semirural (19.4%, 24/124) and urban populations (29.8%, 39/131) regarding medicine shortages (χ2 = 9.91, degrees of freedom (df) = 4, p = 0.042). The semirural setting showed a statistically significant difference from the other settings (p = 0.004 in post hoc χ2 test). Significant differences were found between countries in resilience features including, effectiveness of triage, adapting to the rapidly changing requirements, government help, existence of a community resilience group, improved interprofessional collaboration, medicine shortage, and general practitioners (GPs) involvement in palliative care. CONCLUSIONS: Medicine shortage was more prevalent in rural and urban areas compared to semirural areas. Differences were observed between countries in their responses to the pandemic, particularly in adapting to the rapidly changing requirements, effectiveness of triage, government help, and the existence of a community resilience group. These differences were confirmed with qualitative analysis. The results emphasize the need for tailored approaches considering diverse contexts in shaping effective healthcare system resilience.
- MeSH
- COVID-19 * epidemiology MeSH
- Humans MeSH
- Pandemics MeSH
- Primary Health Care * organization & administration MeSH
- Cross-Sectional Studies MeSH
- Surveys and Questionnaires MeSH
- SARS-CoV-2 MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
Zdá se, že doba, ve které jsme věřili, že naši osobnost, chování a nemoci předurčují naše geny, pomalu ale jistě končí. Výzkum na poli epigenetiky prokazuje, že informace obsažená v genech je pod významným regulačním vlivem aktuálního prostředí a gen tedy neobsahuje zdaleka tak konkrétní informaci, jak jsme se dlouho domnívali. I když prostředí nedovede ovlivnit strukturu genu, má přes chemické (epigenetické) modifikace zásadní vliv na to, jestli a jak se informace obsažená v genu vyjádří. Epigenetické modifikace nám umožňují učit se ze zkušeností a adaptovat naše těla, chování i metabolismus na aktuální prostředí a přežití. Současně jsou však tyto modifikace spojovány i s rozvojem nemocí a zkráceným přežitím. Jak tomuto zásadnímu konfliktu rozumět? Výzkum na poli sociální a behaviorální epigenomiky nabízí širší pohled na význam epigenetických modifikací nejen pro adaptaci a přežití jedince a sociální skupiny, ale i pro adaptaci jedince na jeho roli v sociální hierarchii a tím i na rovnováhu a přežití komplexních biologických systémů. Tento pohled může vnést do porozumění zdraví a nemoci dost odlišný význam.
The era of strong belief in gene influence on our personality, behavior and diseases seems to be getting to the end. Scientific evidence in the field of epigenetics suggests significant environmental regulatory influence on gene expression. Epigenetic research shows that genes do not carry such rigid information as it had been originally proposed. Though environmental stimuli do not change gene structure, they can influence gene expression by maens of chemical epigenetic modifications. Epigenetic modifications help us learn from our experience and adapt our bodies, behavior and metabolism for current environment and survival. Surprisingly are these modifications concurrently associated with disease development and shorter life expectancy. How should be this apperent conflict understood? Research in the fields of social and behavioral epigenomics brings more complex understanding of the role of epigenetic modifications for individual and social group adaptation and survival, for formation of individual personality and social status in complex hierarchies and perhaps even for balance and survival of complex biological systems. This view could bring quite different perspective to understanding of health and diseases.
Goals: This research aims to clarify the relationships between healthcare use and availability, preparation for active ageing and ageing, and involvement in the care of one's health among people aged 65 and over. Methods: Qualitative research (grounded theory) was used to achieve the goal. This study was conducted from the beginning of February to the end of April 2024. The informants were people aged 65 and over who lived in South Bohemia. Semi-structured interviews were used. Results: Health was the central category. Other categories were care availability, GP services, active ageing, alternative medicine, and hospitalisation. The connections found show that health is the key to fulfilling the idea of healthy ageing and is closely related to self-sufficiency. Self-sufficiency is essential from the point of view of active ageing. They pay attention to maintaining it from the point of view of planning the future. On the other hand, illness is a factor influencing thoughts about the future, the availability of care, and the need for information. Communication becomes an essential element, which is intertwined with the entire concept of successful ageing. Conclusion: The results suggest that paying more attention to examining the expectations of patients and healthcare professionals regarding care aimed at maintaining and restoring health, or possibly implementing changes, is going to be necessary.
- MeSH
- Health Services Accessibility MeSH
- Communication MeSH
- Qualitative Research MeSH
- Humans MeSH
- Disease psychology MeSH
- Delivery of Health Care MeSH
- General Practitioners MeSH
- Interviews as Topic MeSH
- Aged MeSH
- Healthy Aging * psychology MeSH
- Self Report MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
