20260 research outputs found
Sort by
Impact of COVID-19 lockdown on blood glucose levels in pediatric patients with type 1 diabetes mellitus
No full textPURPOSE: The coronavirus disease 2019 (COVID-19) pandemic brought stringent social distancing measures, resulting in changes to daily routines such as increased time at home, remote learning, altered meal schedules, and reduced physical activity. Therefore, we aimed to investigate the impact of the COVID-19 lockdown on glycemic control among pediatric patients with type 1 diabetes. METHODS: This study retrospectively analyzed the medical records of 47 pediatric patients with type 1 diabetes who visited Ajou University Hospital before and after the lockdown. To analyze the effects of the lockdown on glycemic control, we examined the change in glycated hemoglobin (HbA1c) levels before and after the lockdown. RESULTS: Among 47 patients, 23 (49%) were female and the average age before the lockdown as of March 2020 was 11.65+/-3.03 years. The mean HbA1c levels were 8.22%+/-1.69% and 7.86%+/-1.57% before and after the lockdown, respectively, showing better glycemic control during the lockdown (P=0.001). The decrease in HbA1c was more significant in subjects with higher pre-lockdown HbA1c levels, older patients, and individuals not using continuous glucose monitoring or continuous subcutaneous insulin infusion. However, from a long-term perspective, HbA1c levels at 3 years and 1 year before and after the lockdown were not significantly different. CONCLUSION: This study demonstrated the beneficial effect of intensive social distancing for COVID-19 on blood glucose control in pediatric patients with type 1 diabetes mellitus. Furthermore, changes due to the lockdown had a more pronounced effect on patients with existing poor glycemic control
Long-term treatment outcomes of popliteal artery entrapment syndrome by the Korean Rare Vascular Ailment Research Experts
No full textOBJECTIVE: Popliteal artery entrapment syndrome (PAES) results from an anomalous relationship between the popliteal artery and the myofascial structures of the popliteal fossa. The long-term treatment outcomes are not well-known because of the rarity of the disease. This study aimed to establish a nationwide collective dataset and analyze treatment outcomes. MATERIALS AND METHODS: The Korean Rare Vascular Ailment Research Experts performed nationwide retrospective data collection on PAES from 2003 to 2023. Fourteen tertiary medical centers participated, and data from 111 limbs of 96 patients who received invasive treatment with sufficient baseline and follow-up data were used for statistical analysis. RESULTS: The median age was 37.5 years (range, 14-82 years), and 92.8% were male. Eighty-one percent of the patients presented with claudication, and 13.5% with rest pain. The popliteal arteries were stenotic in 24.3% and occluded in 75.6%. A total of 109 open surgeries and two endovascular treatments were performed. The primary patency rates at 1, 5, and 9 years were compared according to the surgery type: musculotendinous section (MTS) only group (n = 25), 94.7%, 94.7%, and 94.7%; MTS with in situ revascularization group (n = 55), 90.1%, 77.0%, and 77.0%; and bypass surgery group (n = 29), 88.6%, 82.7%, and 68.9%, respectively. In multivariate analysis for the loss of primary patency, bypass using PTFE graft (hazard ratio, 9.676; 95% confidence interval, 1.032-90.736; P = .047) was a statistically significant risk factor. CONCLUSION: Patients with early-stage PAES treated with MTS alone showed excellent long-term primary patency. When arterial reconstruction was needed in PAES, MTS with in situ revascularization and bypass surgery showed comparable long-term primary patency. However, bypass surgery using PTFE graft should be avoided due to the high risk of occlusion
GDF15 inhibits early-stage adipocyte differentiation by enhancing HOP2 expression and suppressing C/EBPα expression
No full textExcessive adipocyte differentiation and accumulation contribute to the development of metabolic disorders. Growth differentiation factor 15 (GDF15) plays an essential role in energy homeostasis and is considered an anti-obesity factor; however, elevated serum levels of endogenous GDF15 have been reported in certain individuals with obesity. In this study, to gain a better understanding of this complex relationship between GDF15 levels and obesity, we investigated GDF15 expression and function during adipogenesis. Compared with mice fed a normal diet, those fed a short-term high-fat diet exhibited a reduction in epididymal white adipose tissue and serum GDF15 expression. These results were confirmed in human adipose-derived stem cells that showed reduced GDF15 expression during adipogenesis differentiation. During adipogenesis, GDF15 was primarily degraded via the autophagy lysosomal pathway, and GDF15 overexpression in pre-adipocytes inhibited adipogenesis by suppressing CCAAT enhancer binding protein alpha (C/EBPα). Furthermore, whereas we detected a reduction in homologous-pairing protein 2 (HOP2) expression during adipogenesis, expression increased in response to an overexpression of GDF15. Furthermore, following knockdown of HOP2 during GDF15 overexpression, there was no suppression of C/EBPα expression. These findings indicate that GDF15 undergoes lysosomal degradation via an autophagic pathway and suppresses adipocyte differentiation via the HOP2-mediated inhibition of C/EBPα expression. Collectively, our findings indicate that GDF15 could serve as a potential therapeutic target for the treatment of metabolic disorders
Cd99l2 regulates excitatory synapse development and restrains immediate-early gene activation
No full textCd99 molecule-like 2 (Cd99l2) is a type I transmembrane protein that plays a role in the transmigration of leukocytes across vascular endothelial cells. Despite its high expression in the brain, the role of Cd99l2 remains elusive. We find that Cd99l2 is expressed primarily in neurons and positively regulates neurite outgrowth and the development of excitatory synapses. We demonstrate that Cd99l2 inversely regulates the expression of immediate-early genes (IEGs), including Arc, Egr1, and c-Fos, by inhibiting the activity of the transcription factors CREB and SRF. Neuronal inactivation increases the transport of Cd99l2 to the cell surface from recycling endosomes, thereby enhancing Cd99l2-mediated inhibitory signaling. Additionally, Cd99l2 knockout mice exhibit impaired excitatory synaptic transmission and plasticity in the hippocampus, along with deficits in spatial memory and contextual fear conditioning. Based on these findings, we propose that neuronal Cd99l2 functions as a synaptic cell adhesion molecule that inversely controls neuronal activation
Concurrence of Subacute Combined Degeneration and Deep Vein Thrombosis After Chronic Nitrous Oxide Abuse
No full textPrognostic Value of Postpercutaneous Coronary Intervention Murray-Law-Based Quantitative Flow Ratio: Post Hoc Analysis From FLAVOUR Trial
No full textBackground: Coronary physiology measured by fractional flow reserve (FFR) is superior to angiography for assessing the efficacy of percutaneous coronary intervention (PCI). Yet, the clinical adoption of post-PCI FFR is limited. Murray law-based quantitative flow ratio (μQFR) may represent a promising alternative, as it can quickly compute FFR from a single angiographic view. Objectives: The authors aimed to investigate the potential role of post-PCI μQFR in predicting clinical outcomes. Methods: This was a post hoc blinded analysis of the FLAVOUR trial. Patients with angiographically intermediate lesions randomized 1:1 to receive FFR or intravascular ultrasound-guided PCI were included. Post-PCI μQFR was assessed in successfully stented vessels, blinded to clinical outcomes. Suboptimal physiological outcome post-PCI was defined a priori as post-PCI μQFR <0.90. The primary endpoint was 2-year target vessel failure, including cardiac death, target vessel myocardial infarction, and target vessel revascularization. Secondary endpoints included the diagnostic concordance of pre-PCI μQFR with FFR in the FFR-guidance arm. Results: Post-PCI μQFR was successfully analyzed in 806 vessels from 777 participants (feasibility 97.0% [806 of 831]). Suboptimal physiological outcome post-PCI was identified in 24.7% (199 of 806) of vessels and post-PCI μQFR <0.90 was associated with higher risk of 2-year target vessel failure (6.1% [12 of 199] vs 2.7% [16 of 607]; HR: 2.45 [95% CI: 1.14-5.26]; P = 0.022). Pre-PCI μQFR was obtained in 877 of 919 vessels (feasibility 95.4%), showing 90% accuracy, 82% sensitivity, and 94% specificity for identifying physiologically significant stenosis defined by pre-PCI FFR ≤0.80. Conclusions: In patients with intermediate lesions who underwent PCI with contemporary imaging or physiology guidance, lower post-PCI μQFR values predict subsequent adverse events. (Fractional FLow Reserve And IVUS for Clinical OUtcomes in Patients With InteRmediate Stenosis [FLAVOUR]; NCT02673424
Internal Structure of the Patient Health Questionnaire-9: A Systematic Review and Meta-analysis
No full textPURPOSE: This review aimed to evaluate the internal structure (structural validity, internal consistency, and measurement invariance) of the Patient Health Questionnaire-9 (PHQ-9), which is one of the most widely used self-administered instruments for assessing and screening depression. METHODS: The updated COnsensus-based Standards for the selection of health Measurement Instruments methodology for a systematic review of self-reported instruments was used. PubMed, Embase, CINAHL, PsycINFO, and the Cochrane Library databases were searched from their inception up to February 28, 2023. RESULTS: This study reviewed 98 psychometric studies reported on in 90 reports conducted in 40 countries. Various versions of the PHQ-9 were identified: one-factor structures (8 types), two-factor structures (10 types), bifactor structures (4 types), three-factor structure (1 type), and second-order three-factor structure (1 type). There was sufficient high-quality evidence for structural validity of the one-factor structure with nine items scored using a four-point Likert scale based on confirmatory factor analysis, for internal consistency with a quantitatively pooled Cronbach alpha of .85, and for measurement invariance across sex, age, education level, marital status, and income groups. There was sufficient high-quality evidence for structural validity, internal consistency (Cronbach's alpha = .76- .92, omega = 0.83- .92), and measurement invariance across sex for the PHQ-8 (which excluded item 9: "suicidality or self-harm thoughts"). CONCLUSION: The one-factor PHQ-9 and PHQ-8 (excluding item 9) scored using a four-point Likert scale have the best internal structure based on the current evidence. The one-factor PHQ-9 and PHQ-8 justify the use of aggregated total scores in both practice and research. The total score of the PHQ-9 using a four-point Likert scale can be used to compare depression levels across sex, age, education level, marital status, and income groups due to the availability of sufficient evidence for measurement invariance across these demographic groups
Itching Sensation and Elevated Interleukin-31 Levels as Potential Indicators of Exceptional Response to Biologics in Patients With Moderate-To-Severe Psoriasis
No full textAlthough the introduction of biologics has significantly changed the psoriasis treatment paradigm, predicting which patients will respond favourably to biologics remains a challenge. Our study aimed to retrospectively investigate the characteristics of ‘exceptional responders’ (ERs), that is, patients who achieve a Psoriasis Area and Severity Index (PASI) of 100 between weeks 16 and 28 of their initial evaluation period. We conducted a retrospective analysis of the electronic medical records and clinical photographs of 139 patients with psoriasis. Demographic and clinical characteristics of the patients were collected and analysed. Peripheral blood samples previously obtained from consenting individuals (n = 10 for each group) were used to compare the serum concentrations of interleukin-31 (IL-31), lipocalin-2 (LCN2) and chemokine ligand 2 (CCL2), between ERs and non-ERs. We observed no significant differences in nail involvement, arthralgia, mean body mass index, or baseline PASI between ERs and non-ERs. Notably, the occurrence of itching was significantly higher in the ER group than in the non-ER group. The IL-31 concentration displayed a concomitant increase with the intensity of itching and was significantly higher in ERs than in non-ERs prior to the initiation of biologics. After treatment, a significant decrease in IL-31 levels was observed in the ER group but not in the non-ER group. While both LCN2 and CCL2 levels decreased significantly after treatment in both groups, they did not exhibit clear distinctions that could differentiate between ERs and non-ERs. Baseline IL-31, combined with itch intensity, discriminated ERs from non-ERs. Clinicians should recognise that patients presenting with pruritus and high serum IL-31 levels may respond exceptionally well to biological agents, whereas those without pruritus and with lower IL-31 levels tend to have a more subtle response
A prevalent MOCS2 variant in the Roma population is associated with a novel mild form of molybdenum cofactor deficiency
No full textXanthinurias are rare inherited disorders of purine metabolism. Xanthinuria type III is caused by molybdenum cofactor deficiency (MoCD) due to pathogenic variants in MOCS1, MOCS2, MOCS3, or GEPH genes. Here, we described five Roma patients from four unrelated families with hypouricemia, accumulation of xanthine/hypoxanthine, deficiency of xanthine oxidase activity, variable age of diagnosis, and only asymptomatic or mild clinical course. Whole exome sequencing was performed on all probands, aged 3 to 43 years, due to lack of genetic confirmation for xanthinuria types I and II. The causality of the putative pathogenic variant was confirmed by analysis of sulfite and related metabolites and in vitro functional characterization of metal-binding pterin (MPT) synthesis and protein complex formation. Considering the rarity of the condition and recessive inheritance, 34 candidate variants were identified after filtering out allele frequency threshold in non-Finnish Europeans. An ultra-rare MOCS2 variant rs776441627 in two overlapping reading frames (c.244A > T (NM_176806.4; p.Ile82Phe) = c.57A > T (NM_004531.5; p.Leu19Phe)) segregated with the disease in all five patients (four homozygotes, one compound heterozygote). The variant has an allele frequency of 3.6% in a Roma population control group. Functional characterization revealed the significantly decreased MPT synthesis activity and confirmed the causality of rs776441627 in MoCD. CONCLUSION: The rs776441627 is a functional variant for MoCD with a mild to asymptomatic clinical phenotype and fully penetrant biochemical phenotype. Hypouricemia should be considered in the differential diagnostic algorithm of pediatric and adult patients with neurological symptoms, and MOCS2 should be considered in gene panels for xanthinuria screening. WHAT IS KNOWN: * Xanthinuria type III is caused by molybdenum cofactor deficiency (MoCD) due to pathogenic variants in MOCS1, MOCS2, MOCS3, or GEPH genes. * The majority of patients with xanthinuria III present with classical early-onset MoCD due to autosomal recessive variants in the MOCS1 gene, manifesting severe progressive neurological complications during the first postnatal days. * To date, approximately 40 patients with MoCD due to pathogenic MOCS2 variants have been reported; most were diagnosed during the neonatal period with intractable seizures and feeding disorders. WHAT IS NEW: * A novel ultra-rare variant, rs776441627, located in two overlapping reading frames of the MOCS2, was identified in five Roma patients presenting a mild to asymptomatic clinical MoCD phenotype and a fully penetrant biochemical phenotype. * Functional studies of p.Ile82Phe (small MOCS2A subunit) and p.Leu19Phe (large MOCS2B subunit) demonstrate a strong reduction in molydopterin synthase complex formation and activity, consistent with the changes in biomarkers of MoCD observed in affected individuals. * The rs776441627 variant shows significantly elevated frequency among the Roma population, highlighting the importance of considering ethnic background in the differential diagnosis of MoCD. * Hypouricemia may provide an initial, generally available biochemical key marker indicator of molybdenum cofactor deficiency