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
• algoritmy MeSH
• dítě MeSH
• genetické testování * metody   MeSH
• lidé MeSH
• mladiství MeSH
• mutace genetika   MeSH
• nanismus genetika   diagnóza   MeSH
• pokrevní příbuzenství * MeSH
• poruchy růstu genetika   diagnóza   MeSH
• předškolní dítě MeSH
• rodokmen MeSH
• sekvenování exomu metody   MeSH
• tělesná výška genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Irák MeSH

BACKGROUND: The knowledge and proficiency of primary care practitioners (PCPs) in diagnosing and managing irritable bowel syndrome (IBS) remain generally low and variable internationally. This variability is partly due to a lack of familiarity with the Rome Foundation diagnostic criteria and treatment guidelines for this condition. METHODS: We conducted an electronic survey of PCPs in the United States and nine European countries to assess their understanding of IBS pathophysiology; the use of Rome IV criteria in diagnosis, knowledge of and frequency in prescribing various recommended treatments; and the likelihood of referring patients with suspected IBS to subspecialists. RESULTS: Most PCPs in the United States and Europe perceive IBS as a diagnosis of exclusion rather than a definitive diagnosis. They also believe IBS is underdiagnosed in primary care and challenging to diagnose confidently. The majority of PCPs consider diet as a crucial component of IBS management. Notably, US PCPs reported greater confidence than their European counterparts in recommending dietary interventions such as increased dietary fiber, a low FODMAP diet, and gluten restriction. Conversely, both groups exhibited moderate to high confidence in recommending over-the-counter treatments. European PCPs showed greater confidence in treating IBS with antispasmodics and secretagogues, while US PCPs expressed greater confidence in prescribing neuromodulators. Additionally, US PCPs were more likely to refer patients with suspected IBS to a gastroenterologist, whereas both US and European PCPs showed similar referral patterns to dietitians and referred very few patients to mental health providers. Both US and European PCPs reported that IBS is moderately to extremely difficult to treat effectively and emphasized the importance of a strong and longitudinal doctor-patient relationship in managing the condition. CONCLUSION: Despite the Rome Foundation recommendations and criteria to support a positive diagnosis of IBS, most PCPs still rely on exclusionary investigations such as endoscopy and a serologic workup, while a significant percentage suggest referring patients to gastroenterologists.

• MeSH
• lékaři primární péče MeSH
• lékařská praxe - způsoby provádění * statistika a číselné údaje   MeSH
• lidé MeSH
• postoj zdravotnického personálu MeSH
• primární zdravotní péče MeSH
• průzkumy a dotazníky MeSH
• syndrom dráždivého tračníku * diagnóza   terapie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH

BACKGROUND: A third of endovascularly treated patients with stroke experience incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction [eTICI] <3), and the natural evolution of this incomplete reperfusion remains unknown. We systematically reviewed the literature and performed a meta-analysis on the natural evolution of incomplete reperfusion after endovascular therapy. METHODS: A systematic review of MEDLINE, Embase, and PubMed up until March 1, 2024, using a predefined strategy. Only full-text English-written articles reporting rates of either favorable (ie, delayed reperfusion (DR) or no new infarct) or unfavorable progression (ie, persistent perfusion deficit or new infarct) of incompletely reperfused tissue were included. The primary outcome was the rate of DR and its association with functional independence (modified Rankin Scale score, 0-2) at 90 days postintervention. Pooled odds ratios with 95% CIs were calculated using a random-effects model. RESULTS: Six studies involving 950 patients (50.7% female; median age, 71 years; interquartile range, 60-79) were included. Four studies assessed the evolution of incomplete reperfusion on magnetic resonance imaging perfusion imaging, while 2 studies used diffusion-weighted imaging and noncontrast computed tomography imaging, where new infarct was used to denote unfavorable progression. Five studies defined incomplete reperfusion as eTICI 2b50 or 2c. DR occurred in 41% (interquartile range, 33%-51%) of cases 24 hours postintervention. Achieving DR was associated with a higher likelihood of functional independence at 90 days (odds ratio, 2.5 [95% CI, 1.9-3.4]). CONCLUSIONS: Nearly half of eTICI <3 patients achieve DR, leading to favorable clinical outcomes. This subgroup may derive limited or potentially harmful effects from pursuing additional reperfusion strategies (eg, intra-arterial lytics or secondary thrombectomy). Accurately predicting the evolution of incomplete reperfusion could optimize patient selection for adjunctive reperfusion strategies at the end of an intervention. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT05499832.

• MeSH
• endovaskulární výkony * metody   MeSH
• ischemická cévní mozková příhoda * chirurgie   diagnostické zobrazování   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• reperfuze metody   MeSH
• senioři MeSH
• trombolytická terapie metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

INTRODUCTION: Alopecia areata is a common autoimmune disease which results in reversible hair loss. Janus kinase inhibitors are prescribed for severe alopecia areata with encouraging results. There are no studies comparing the efficacy and safety of Janus kinase inhibitors to traditional treatment options, such as topical immunomodulators and traditional immunosuppressants. AIMS: To retrospectively compare the efficacy and safety of baricitinib, an approved Janus kinase inhibitor, to other treatments for severe AA during a 6-month treatment period. MATERIALS/METHODS: We included patients with newly presenting, relapsing or treatment-resistant alopecia areata with Severity of Alopecia Tool (SALT) score ≥ 50, for the period between July 2021 and July 2023. Medical histories were reviewed and possible side effects were recorded. Primary endpoints were SALT ≤ 20 and SALT ≤ 10 after 6 months of treatment. RESULTS: Seventy-five patients (53 females) were divided into three groups: topical immunomodulators (51 patients); baricitinib (19 patients); and a group receiving pulsed intramuscular corticosteroids or traditional immunosuppressants (11 patients). Twenty-one patients received more than one treatment options within 2 years. After 6 months, the baricitinib group showed superior efficacy with 32% and 26% of patients achieving SALT ≤ 20 and SALT ≤ 10, compared to 12% and 9% in both other groups. Baricitinib demonstrated better secondary outcomes (50% and 90% reduction from initial SALT scores). All treatments exhibited mild-to-moderate and expected side effects. Weight gain, which had not been reported in clinical trials for alopecia areata, was observed in three baricitinib-treated patients. CONCLUSION: Baricitinib was superior to traditional treatments for severe alopecia areata after 6 months. Weight gain concerned 16% of patients receiving baricitinib.

• MeSH
• alopecia areata * farmakoterapie   MeSH
• azetidiny * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• dospělí MeSH
• hormony kůry nadledvin terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• imunologické faktory aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• imunosupresiva * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• inhibitory Janus kinas * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• puriny * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• pyrazoly * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• retrospektivní studie MeSH
• stupeň závažnosti nemoci * MeSH
• sulfonamidy * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Heavy metals are naturally occurring components of the Earth's crust and persistent environmental pollutants. Human exposure to heavy metals occurs via various pathways, including inhalation of air/dust particles, ingesting contaminated water or soil, or through the food chain. Their bioaccumulation may lead to diverse toxic effects affecting different body tissues and organ systems. The toxicity of heavy metals depends on the properties of the given metal, dose, route, duration of exposure (acute or chronic), and extent of bioaccumulation. The detrimental impacts of heavy metals on human health are largely linked to their capacity to interfere with antioxidant defense mechanisms, primarily through their interaction with intracellular glutathione (GSH) or sulfhydryl groups (R-SH) of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and other enzyme systems. Although arsenic (As) is believed to bind directly to critical thiols, alternative hydrogen peroxide production processes have also been postulated. Heavy metals are known to interfere with signaling pathways and affect a variety of cellular processes, including cell growth, proliferation, survival, metabolism, and apoptosis. For example, cadmium can affect the BLC-2 family of proteins involved in mitochondrial death via the overexpression of antiapoptotic Bcl-2 and the suppression of proapoptotic (BAX, BAK) mechanisms, thus increasing the resistance of various cells to undergo malignant transformation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of antioxidant enzymes, the level of oxidative stress, and cellular resistance to oxidants and has been shown to act as a double-edged sword in response to arsenic-induced oxidative stress. Another mechanism of significant health threats and heavy metal (e.g., Pb) toxicity involves the substitution of essential metals (e.g., calcium (Ca), copper (Cu), and iron (Fe)) with structurally similar heavy metals (e.g., cadmium (Cd) and lead (Pb)) in the metal-binding sites of proteins. Displaced essential redox metals (copper, iron, manganese) from their natural metal-binding sites can catalyze the decomposition of hydrogen peroxide via the Fenton reaction and generate damaging ROS such as hydroxyl radicals, causing damage to lipids, proteins, and DNA. Conversely, some heavy metals, such as cadmium, can suppress the synthesis of nitric oxide radical (NO·), manifested by altered vasorelaxation and, consequently, blood pressure regulation. Pb-induced oxidative stress has been shown to be indirectly responsible for the depletion of nitric oxide due to its interaction with superoxide radical (O2·-), resulting in the formation of a potent biological oxidant, peroxynitrite (ONOO-). This review comprehensively discusses the mechanisms of heavy metal toxicity and their health effects. Aluminum (Al), cadmium (Cd), arsenic (As), mercury (Hg), lead (Pb), and chromium (Cr) and their roles in the development of gastrointestinal, pulmonary, kidney, reproductive, neurodegenerative (Alzheimer's and Parkinson's diseases), cardiovascular, and cancer (e.g. renal, lung, skin, stomach) diseases are discussed. A short account is devoted to the detoxification of heavy metals by chelation via the use of ethylenediaminetetraacetic acid (EDTA), dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propane sulfonic acid (DMPS), and penicillamine chelators.

• MeSH
• antioxidancia metabolismus   MeSH
• bioakumulace MeSH
• látky znečišťující životní prostředí toxicita   MeSH
• lidé MeSH
• oxidační stres * účinky léků   MeSH
• těžké kovy * toxicita   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The diversity of cultivable endophytic fungi in native subshrubs of the Brazilian Cerrado is largely unknown. This study investigated the cultivable endophytic mycobiome of stems, leaves, and flowers of Peltaea polymorpha (Malvaceae). In total, 208 endophytic fungi were isolated, 95 from stems, 65 from leaves, and 48 from flowers. The isolates were classified as ascomycetes belonging to three classes, eight orders, ten families, 12 genera, and 31 species. Diaporthe, Nigrospora, and Colletotrichum were the dominant genera in the three analyzed organs. The richness estimators suggested that the number of species might be slightly higher than observed. The highest values for the Shannon and Simpson diversity indices were observed in stems. Beta diversity showed overlapping of fungal communities in different organs, with a high rate of sharing of taxa. Furthermore, the dominant primary fungal lifestyles were plant pathogens and saprobes. Our findings show that the cultivable endophytic fungal community of P. polymorpha is species-rich and that communities in different organs share genera and species.

• MeSH
• Ascomycota izolace a purifikace   klasifikace   genetika   MeSH
• biodiverzita * MeSH
• endofyty * klasifikace   izolace a purifikace   genetika   růst a vývoj   MeSH
• fylogeneze MeSH
• houby * klasifikace   izolace a purifikace   genetika   růst a vývoj   MeSH
• květy mikrobiologie   MeSH
• listy rostlin mikrobiologie   MeSH
• mykobiom MeSH
• pastviny MeSH
• stonky rostlin mikrobiologie   MeSH
• tropické klima MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Brazílie MeSH

BACKGROUND: Postoperative nausea and vomiting (PONV) in pediatric patients is a common and clinically significant postoperative complication. The incidence of PONV has not been extensively studied in large pediatric cohorts. Furthermore, in 2020, the Fourth Consensus Guidelines for the management of PONV were published. However, the association between perioperative factors and adherence to these guidelines remains unclear. This study aims to assess both the incidence of PONV and guideline adherence within a large and diverse pediatric population. METHODS: We conducted a retrospective observational study at a large tertiary medical center, including pediatric patients (≤18 years) who underwent surgery between September 2020 and March 2023. We conducted a retrospective analysis of data from our electronic health records, focusing on patient demographics, surgical details, anesthesia details, and prophylaxis for PONV. We calculated the incidence of PONV and used multivariable logistic regression to identify the predictors of guideline adherence. RESULTS: The cohort included 3772 patients with a median (interquartile range [IQR]) age of 9.21 (3.55-14.68) years. The incidence (95% confidence intervals) of early PONV was 1.0% (0.7-1.4) and 3.8% (3.2-4.5) for delayed PONV. Adherence to the fourth consensus guidelines for PONV management was observed in 32.5% (31.0-34.0) of cases. A high risk of PONV was identified in 55.9% (54.3-57.5) of the patients. The most common number of PONV risk factors was 3, observed in 1151 patients (30.5% [29.1-32.0]). Significant predictors of guideline adherence included the intraoperative use of long-acting opioids (odds ratio [OR], 2.711, P < .001) and age ≥3 years (OR, 2.074, P < .001). Nonadherence was associated with a higher incidence of PONV at 24 hours postsurgery (4.4% (3.6-5.2) vs 2.7% (1.9-3.8), P = .012). Factors such as specific high PONV risk surgeries ( P = .001), maintenance with inhalational agents solely ( P = .017), and neostigmine use ( P < .001) were also all statistically significant. CONCLUSIONS: Our study revealed a lower-than-expected incidence of PONV in pediatric patients, highlighting the need for standardized definitions and improved reporting. Adherence to PONV guidelines was suboptimal, emphasizing the need for better implementation strategies.

• MeSH
• antiemetika terapeutické užití   MeSH
• dítě MeSH
• dodržování směrnic * normy   MeSH
• incidence MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• pooperační nevolnost a zvracení * epidemiologie   diagnóza   prevence a kontrola   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• směrnice pro lékařskou praxi jako téma normy   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

OBJECTIVES: Mindfulness-based interventions (MBIs) for persons with dementia (PwD) have yielded mixed results, possibly attributable to the fact that little is known about the validity and reliability of trait mindfulness self-report measures in PwD. This narrative review sought to identify studies involving self-reported trait mindfulness and other clinical measures that may hold information on the convergent validity and reliability of these measures in PwD. METHODS: Scientific databases were searched for studies involving PwD and mindfulness assessments. RESULTS: N = 426 studies from PubMed and N = 156 from PsychInfo databases were reviewed. Four cross-sectional studies were identified that allowed inferences about the validity of mindfulness measures. A qualitative review indicated that convergent validity with other measures varied with sample heterogeneity and cognitive impairment. Merely one MBI included self-reported trait mindfulness, however without reporting sample-specific validity or reliability. CONCLUSIONS: Despite efforts to implement MBIs in PwD, information on basic methodological psychometric issues is minimal. Future studies ought to address the validity and reliability of self-reported mindfulness in detail across different stages of dementia. CLINICAL IMPLICATIONS: Results of MBIs need to be considered cautiously. Basic information about psychometric properties of mindfulness self-report measures is required and these measures need to be included systematically in MBIs.

• MeSH
• demence * psychologie   terapie   MeSH
• lidé MeSH
• psychometrie metody   MeSH
• reprodukovatelnost výsledků MeSH
• senioři MeSH
• všímavost * metody   MeSH
• zpráva o sobě * normy   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVE: Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing of interoceptive signals in patients with FND. METHODS: The authors examined univariate and multivariate functional MRI neural responses of 38 patients with mixed FND and 38 healthy control individuals (HCs) during a task exploring goal-directed attention to cardiac interoception-versus-control (exteroception or rest) conditions. The relationships between interoception-related neural responses, heartbeat-counting accuracy, and interoceptive trait prediction error (ITPE) were also investigated for FND patients. RESULTS: When attention was directed to heartbeat signals versus exteroception or rest tasks, FND patients showed decreased neural activations (and reduced coactivations) in the right anterior insula and bilateral dorsal anterior cingulate cortices (among other areas), compared with HCs. For FND patients, heartbeat-counting accuracy was positively correlated with right anterior insula and ventromedial prefrontal activations during interoception versus rest. Cardiac interoceptive accuracy was also correlated with bilateral dorsal anterior cingulate activations in the interoception-versus-exteroception contrast, and neural activations were correlated with ITPE scores, showing inverse relationships to those observed for heartbeat-counting accuracy. CONCLUSIONS: This study identified state and trait interoceptive disruptions in FND patients. Convergent between- and within-group findings contextualize the pathophysiological role of cingulo-insular (salience network) areas across the spectrum of functional seizures and functional movement disorder. These findings provide a starting point for the future development of comprehensive neurophysiological assessments of interoception for FND patients, features that also warrant research as potential prognostic and monitoring biomarkers.

• MeSH
• dospělí MeSH
• interocepce * fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku MeSH
• mladý dospělý MeSH
• mozek * patofyziologie   diagnostické zobrazování   MeSH
• nemoci nervového systému * patofyziologie   diagnostické zobrazování   MeSH
• pozornost fyziologie   MeSH
• srdeční frekvence fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články 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
• enterální výživa MeSH
• klinické rozhodování MeSH
• lidé MeSH
• medicína založená na důkazech MeSH
• nekrotizující enterokolitida * chirurgie   diagnóza   MeSH
• novorozenec nedonošený MeSH
• novorozenec MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• směrnice pro lékařskou praxi MeSH
• systematický přehled MeSH
• Geografické názvy
• Evropa MeSH