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OBJECTIVE: To explore the impact of telemedicine on access to gender-affirming care for rural transgender and gender diverse youth. STUDY DESIGN: A retrospective analysis of data drawn from the electronic medical records of a clinic that provides approximately 10â000 adolescent and young adult visits per year and serves patients seeking gender health care. The no-show rate was examined as a proxy for access to care due to anticipated challenges with recruiting a representative sample of a historically marginalized population. Logistic regression with generalized estimating equations was conducted to model the association between the odds of a no-show visit and covariates of interest. RESULTS: Telemedicine visits, rural home address, gender health visits, longer travel time, and being younger than 18 years old were associated with lower odds of a no-show in univariate models (n = 17â928 visits). In the adjusted model, the OR of no-shows for gender health visits was 0.56 (95% CI 0.42-0.74), adjusting for rurality, telemedicine, age (< or >18 years), and travel time to the clinic. CONCLUSIONS: In this study, telemedicine was associated with reduced no-shows overall, and especially for rural, transgender and gender diverse youth, and patients who hold both identities. Although the no-show rate does not fully capture barriers to access, these findings provide insight into how this vulnerable population may benefit from expanded access to telemedicine for rural individuals whose communities may lack providers with the skills to serve this population.
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Telemedicina , Personas Transgénero , Adulto Joven , Humanos , Adolescente , Estudios Retrospectivos , Identidad de Género , Accesibilidad a los Servicios de SaludRESUMEN
BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) and progeroid laminopathies (PL) are extremely rare genetic diseases with extremely poor prognoses. This study aims to investigate the epidemiological and genotypic characteristics of patients with HGPS/PL in China. METHODS: Using a cross-sectional study design, general characteristics and genotypic data of 46 patients with HGPS/PL from 17 provinces in China were analyzed. RESULTS: Among the 46 patients with HGPS/PL, 20 patients are HGPS, and the rest are PL; the identified total prevalence of HGPS/PL is 1/23 million. Among 42 patients with gene reports, 3 carried compound heterozygous mutations in the ZMPSTE24 while the other 39 carried LMNA mutations. Among PL, LMNA c.1579 C > T homozygous mutation was the most common. The onset of classic genotype HGPS is skin sclerosis in the first month after birth. The primary clinical manifestations of PL patients include skin abnormalities, growth retardation, and joint stiffness. The median age of onset for PL was 12 (6,12) months. CONCLUSIONS: In China, the identified total prevalence of HGPS/PL is 1/23 million. 92.8% of the genetic mutations of HGPS/PL were located in LMNA, and the rest in ZMPSTE24. Most patients of HGPS/PL have skin abnormalities as the earliest manifestation. Compared to PL, the classic genotype HGPS starts earlier. IMPACT STATEMENT: Hutchinson-Gilford progeria syndrome (HGPS) and progeroid laminopathies (PL) are extremely rare genetic diseases with extremely poor prognoses. To date, there is a paucity of epidemiological data related to HGPS/PL in China. This study first examined the genotypic, phenotypic, and prevalence characteristics of 40-50% of the cases of HGPS/PL in mainland China through a collaborative international registry effort. In China, the identified total prevalence of HGPS/PL is 1/23 million. 92.8% of the genetic mutations of HGPS/PL are located in LMNA. LMNA c.1579 C > T homozygous mutations are the most common form of gene mutations among the Chinese PL population.
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Lamina Tipo A , Proteínas de la Membrana , Mutación , Progeria , Humanos , Progeria/genética , Progeria/epidemiología , China/epidemiología , Masculino , Femenino , Lamina Tipo A/genética , Estudios Transversales , Preescolar , Lactante , Prevalencia , Niño , Proteínas de la Membrana/genética , Metaloendopeptidasas/genética , Genotipo , Adolescente , Laminopatías/genética , Laminopatías/epidemiología , FenotipoRESUMEN
BACKGROUND: Adolescent suicidal ideation are associated with factors including psychological abuse/neglect, sleep problems, and depressed mood, but the systematic effects of these factors on suicidal ideation remain unclear, which is a research gap this work aims to fill. METHODS: A multi-center, the cluster sampling method was employed to collect general demographic data, such as age, gender, the experience of being left behind, and parents' marital status, from 12,192 students across 17 secondary schools in China. The Child Psychological Abuse and Neglect Scale (CPANS), Pittsburgh Sleep Quality Index (PSQI), the Chinese version of the Depressed mood, Anxiety and Stress Scale - 21 Items (DASS-21) and Chinese version of Positive and Negative Suicide Ideation Inventory (PANSI) were utilized. Data were analyzed using t-tests, chi-square tests, correlation analyses, and structural equation modeling mediation analyses. RESULTS: The prevalence of psychological abuse/neglect and adolescent suicidal ideation was 34.8% and 13%, respectively. This mediation analysis suggests that, in the relationship between psychological abuse/neglect and suicidal ideation, sleep problems and depressed mood play both parallel and sequential mediating roles. CONCLUSION: Sleep problems and depressed mood play a mediating role in the development of suicidal ideation in adolescents. Good sleep habits and depressed mood interventions help reduce the risk of suicidal ideation in adolescents who experience psychological neglect/abuse.
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Trastornos del Sueño-Vigilia , Ideación Suicida , Niño , Humanos , Adolescente , Abuso Emocional , Ansiedad , ChinaRESUMEN
BACKGROUND: Peer victimization (PV) is one of the major causes of non-suicidal self-injury. Non-suicidal self-injury (NSSI), peer victimization, social anxiety, and mobile phone addiction are significantly related; however, the interaction mechanism and effect of sex differences remain to be determined. OBJECTIVE: Herein, we investigated the relationship between peer victimization and NSSI among Chinese high school students. We also explored the chain mediating roles of social anxiety and mobile phone addiction and the regulatory role of sex. The findings of this study provide insights for theoretical interventions based on internal mechanisms. METHOD: A self-reported survey of 14,666 high school students from Sichuan County was conducted using a peer victimization scale, NSSI scale, social anxiety scale, and mobile phone addiction scale. A self-administered questionnaire was used to capture sociodemographic information. RESULTS: Peer victimization, social anxiety, and mobile phone addiction were positively correlated with NSSI. Peer victimization had significant direct predictive effects on NSSI (95% CI: 0.341, 0.385) and significant indirect predictive effects on NSSI through social anxiety (95% CI: 0.008, 0.019) or mobile phone addiction (95% CI: 0.036, 0.053). Peer victimization had significant indirect predictive effects on NSSI through social anxiety as well as mobile phone addiction (95% CI: 0.009, 0.014). The first stage (predicting the effect of peer victimization on NSSI) and the third stage (predicting the effect of mobile phone addiction on NSSI) were both moderated by sex. CONCLUSIONS: Peer victimization could directly predict NSSI and indirectly predict NSSI through social anxiety and mobile phone addiction. Thus, social anxiety and mobile phone addiction exhibited chain mediating effects between peer victimization and NSSI in high school students; moreover, sex might be involved in the regulation of the mediation process.
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Víctimas de Crimen , Conducta Autodestructiva , Humanos , Masculino , Femenino , Caracteres Sexuales , Adicción a la Tecnología , Estudiantes , AnsiedadRESUMEN
OBJECTIVE: To establish the reference range of serum concentration of vitamin A (VA) and vitamin E (VE) in Southern Sichuan area of China. METHODS: From August 1, 2021, to May 31, 2023, 9482 blood tablets were received for the screening of VA and VE. The information was divided into four different age groups: ≤1 year old, 1< to ≤6 years, 6< to ≤17 years, and 17< to ≤59 years. In each age group, the four seasons were further subdivided into spring, summer, autumn, and winter, as well as male and female genders. The serum concentration of VA and VE was detected by liquid chromatography-tandem mass spectrometry (HPLC-MS), and the reference range was established for verification. RESULTS: The concentration of VA and VE in 9482 cases showed skewed distribution. When comparing between different age groups, the serum concentration of VA and VE was statistically significant (p < 0.05). While comparing different seasons, the serum VA levels in different seasons were significantly different (p < 0.05) except in summer and autumn. There was statistical significance in VE level in different seasons (p < 0.05). And while comparing different genders, there was no statistical significance in VA concentration levels (p > 0.05). The VE concentration levels were statistically significant (p < 0.05). The established reference range was established and verified, and the results were in accordance with the standard. CONCLUSION: The reference range of VA and VE should be set according to different ages, different seasons, and different genders.
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Estaciones del Año , Vitamina A , Vitamina E , Humanos , Masculino , Femenino , Valores de Referencia , Persona de Mediana Edad , China , Adulto , Vitamina A/sangre , Adulto Joven , Adolescente , Vitamina E/sangre , Preescolar , Niño , Lactante , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta PresiónRESUMEN
The amygdala, known for its functional heterogeneity, plays a critical role in the neural mechanism of adolescent major depressive disorder (aMDD). However, changes in its subregional functional networks in relation to stressful factors remain unclear. We recruited 78 comorbidity-free, medication-naive aMDD patients and 40 matched healthy controls (HC) to explore changes in resting-state functional connectivity (FC) across four amygdala subregions: the centromedial nucleus (CM), the basolateral nucleus (LB), the superficial nucleus (SF), and the amygdalostriatal transition area (Astr). Then, we performed partial correlation analysis to investigate the relationship between amygdala subregional FC and stressful factors as measured by the Chinese Version of Family Environment Scale (FES-CV) and the Adolescent Self-Rated Life Events Scale (ASLEC). Compared to HC, aMDD patients demonstrated significantly decreased functional connectivity between the left CM and left precentral gyrus, as well as between left SF and left precentral gyrus, and between left LB and posterior cingulate gyrus (PCC)/precuneus. In aMDD group, left CM-precentral gyrus FC exhibited negative correlation with interpersonal relationship and punishment, and positive correlation with family cohesion and expressiveness. This study reveals distinct patterns of abnormal functional connectivity among amygdala subregions in aMDD. Our findings suggest that the CM network, in particular, may be involved in stress-related factors in aMDD, which provide a potential target for the prevention and treatment of adolescent depression.
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Pursuing a more efficient signal amplification strategy is highly demanded for improving the performance of the promising cathodic photoelectrochemical (PEC) sensors. In this work, we present an extremely effective dual signal amplification strategy by the integration of a Z-scheme nanohybrids-based photocathode with the effective signal modulation of an organic photoelectrochemical transistor (OPECT) device. Specifically, photocathodic gate material of CdTe-BiOBr nanohybrids with a Z-scheme electron-transfer route was designed and synthesized for preliminary improvement of the activity of the photogate; afterward, signal modulation of the OPECT system by the photocathodic gate of CdTe-BiOBr was then accomplished for further signal amplification by 2 orders of magnitude. As a result, the output PEC signal of CdTe-BiOBr was enhanced by 17.5-fold as compared to BiOBr, and the channel current (IDS) of the OPECT device was 117-fold magnified than its gate current (IG) response. Exemplified by tetracycline (TC) as a model target and aptamer as the specific recognition element, a versatile cathodic aptasensing platform was constructed based on the proposed OPECT device. The introduced OPECT aptasensor merits advantages, including a good linear range (1.0 × 10-12 to 1.0 × 10-6 M), a low limit of detection (4.2 × 10-13 M), and superior sensitivity than the traditional PEC methods for TC detection, which represents a universal protocol for developing the innovative photocathodic OPECT sensing platform toward accurate analysis.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Compuestos de Cadmio , Puntos Cuánticos , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Límite de Detección , Telurio , Tetraciclina/análisis , Antibacterianos/análisisRESUMEN
BACKGROUND: Nephrotic syndrome is common in children and adults worldwide, and steroid-sensitive nephrotic syndrome (SSNS) accounts for 80%. Aberrant metabolism involvement in early SSNS is sparsely studied, and its pathogenesis remains unclear. Therefore, the goal of this study was to investigate the changes in initiated SSNS patients-related metabolites through serum and urine metabolomics and discover the novel potential metabolites and metabolic pathways. METHODS: Serum samples (27 SSNS and 56 controls) and urine samples (17 SSNS and 24 controls) were collected. Meanwhile, the non-targeted analyses were performed by ultra-high-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UHPLC-QTOF-MS) to determine the changes in SSNS. We applied the causal inference model, the DoWhy model, to assess the causal effects of several selected metabolites. An ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to validate hits (D-mannitol, dulcitol, D-sorbitol, XMP, NADPH, NAD, bilirubin, and α-KG-like) in 41 SSNS and 43 controls. In addition, the metabolic pathways were explored. RESULTS: Compared to urine, the metabolism analysis of serum samples was more clearly discriminated at SSNS. 194 differential serum metabolites and five metabolic pathways were obtained in the SSNS group. Eight differential metabolites were identified by establishing the diagnostic model for SSNS, and four variables had a positive causal effect. After validation by targeted MS, except XMP, others have similar trends like the untargeted metabolic analysis. CONCLUSION: With untargeted metabolomics analysis and further targeted quantitative analysis, we found seven metabolites may be new biomarkers for risk prediction and early diagnosis for SSNS.
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Síndrome Nefrótico , Adulto , Humanos , Niño , Cromatografía Liquida , Espectrometría de Masas en Tándem/métodos , Metabolómica/métodos , Cromatografía Líquida de Alta Presión/métodos , BiomarcadoresRESUMEN
BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is characterized by unrelieved proteinuria after an initial 4-8 weeks of glucocorticoid therapy. Genes in podocytes play an important role in causing SRNS. OBJECTIVE: This study aimed to report a pathogenic mutation in SRNS patients and investigate its effects on podocytes, as well as the pathogenic mechanism. METHODS: We screened out a novel mutation by using whole-exon sequencing in the SRNS cohort and verified it via Sanger sequencing. Conservative analysis and bioinformatic analysis were used to predict the pathogenicity of the mutation. In vitro, stable podocyte cell lines were constructed to detect the effect of the mutation on the function of the podocyte. Moreover, an in vivo mouse model of podocyte ANLN gene knockout (ANLNpodKO) was used to confirm clinical manifestations. Transcriptome analysis was performed to identify differential gene expression and related signaling pathways. RESULTS: ANLN E841K was screened from three unrelated families. ANLN E841K occurred in the functional domain and was predicted to be harmful. The pathological type of A-II-1 renal biopsy was minimal change disease, and the expression of ANLN was decreased. Cells in the mutation group showed disordered cytoskeleton, faster cell migration, decreased adhesion, increased endocytosis, slower proliferation, increased apoptosis, and weakened interaction with CD2 association protein. ANLNpodKO mice exhibited more obvious proteinuria, more severe mesangial proliferation, glomerular atrophy, foot process fusion, and increased tissue apoptosis levels than ANLNflox/flox mice after tail vein injection of adriamycin. Upregulated differentially expressed genes in cells of the mutation group were mainly enriched in the PI3K-AKT pathway. CONCLUSION: The novel mutation known as ANLN E841K affected the function of the ANLN protein by activating the PI3K/AKT/mTOR/apoptosis pathway, thus resulting in structural and functional changes in podocytes. Our study indicated that ANLN played a vital role in maintaining the normal function of podocytes. Video Abstract.
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Proteínas de Microfilamentos , Síndrome Nefrótico , Podocitos , Animales , Humanos , Ratones , Mutación/genética , Síndrome Nefrótico/genética , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Podocitos/patología , Proteinuria , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas de Microfilamentos/genéticaRESUMEN
J-tip guide wire entrapment within the heart is a serious and dangerous complication that is rarely mentioned. We present a case in which the J-tip guide wire was entrapped in the right atrium during tunneled cuffed venous catheterization. We were unable to remove the guide wire using previously reported methods and concluded with surgery. Owing to the special structure of the guide wire itself, a safe removal process needs to be discussed. Patient consent for publication was obtained prior to the submission of the manuscript.
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Cateterismo Venoso Central , Humanos , Cateterismo Venoso Central/efectos adversos , Diálisis Renal , CorazónRESUMEN
Alterations in resting-state functional connectivity (rsFC) of hippocampus and orbitofrontal cortex (OFC) have been highly implicated in major depressive disorder (MDD) and the researches have penetrated to the subregional level. However, relatively little is known about the intrinsic connectivity patterns of these two regions in adolescent MDD (aMDD), especially that of their functional subregions. Therefore, in the current study, we recruited 68 first-episode drug-naive aMDD patients and 43 matched typically developing controls (TDC) to characterize the alterations of whole-brain rsFC patterns in hippocampus and OFC at both regional and subregional levels in aMDD. The definition of specific functional subregions in hippocampus and OFC were based on the prior functional clustering-analysis results. Furthermore, the relationship between rsFC alterations and clinical features was also explored. Compared to TDC group, aMDD patients showed decreased connectivity of the left whole hippocampus with bilateral OFC and right inferior temporal gyrus at the regional level and increased connectivity between one of the right hippocampal subregions and right posterior insula at the subregional level. Reduced connectivity of OFC was only found in the subregion of left OFC with left anterior insula extending to lenticula in aMDD patients relative to TDC group. Our study identifies that the aberrant hippocampal and orbitofrontal rsFC was predominantly located in the insular cortex and could be summarized as an altered hippo-orbitofrontal-insular circuit in aMDD, which may be the unique features of brain network dysfunction in depression at this particular age stage. Moreover, we observed the distinct rsFC alterations in adolescent depression at the subregional level, especially the medial and lateral OFC.
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Bronchial asthma is divided into Th2 high, Th2 low and mixed types. The Th2 high type is dominated by eosinophils while the Th2 low type is divided into neutrophilic and paucigranulocytic types. Eosinophilic asthma has gained increased attention recently, and its pathogenesis and treatment are well understood. However, severe neutrophilic asthma requires more in-depth research because its pathogenesis is not well understood, and no effective treatment exists. This review looks at the advances made in asthma research, the pathogenesis of neutrophilic asthma, the mechanisms of progression to severe asthma, risk factors for asthma exacerbations, and biomarkers and treatment of neutrophilic asthma. The pathogenesis of neutrophilic asthma is further discussed from four aspects: Th17-type inflammatory response, inflammasomes, exosomes and microRNAs. This review provides direction for the mechanistic study, diagnosis and treatment of neutrophilic asthma. The treatment of neutrophilic asthma remains a significant challenge for clinical therapists and is an important area of future clinical research.
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Asma , Neutrófilos , Asma/tratamiento farmacológico , Eosinófilos , Humanos , Inflamación/tratamiento farmacológico , Células Th17RESUMEN
OBJECTIVE: To explore the relationship between well-child visit (WCV) attendance during early childhood and age at autism spectrum disorder (ASD) diagnosis using data drawn from a statewide all-payer claims database. STUDY DESIGN: We used a correlational study design with longitudinal data drawn from the Virginia All-Payer Claims Database. All children born in 2011 with a diagnosis of ASD were included (n = 253). Survival analysis determined the impact of WCV attendance on ASD diagnosis at each American Academy of Pediatrics-recommended early childhood visit, and the 5-year visit. RESULTS: Survival analysis revealed a significant impact of WCV attendance at the 24-month, 3-, and 4-year visits on earlier ASD diagnosis. Children who attended the 24-month visit were diagnosed nearly 10 months earlier than those who did not. Overall, children with ASD attended fewer than 50% of visits during early childhood. CONCLUSIONS: Promoting consistent WCV attendance during early childhood is an actionable strategy for improving early identification of ASD. Further exploration is needed to determine barriers to visit attendance and the impact of patterns of early childhood WCV attendance on age of ASD diagnosis. Development and implementation of interventions to promote adherence to the American Academy of Pediatrics-recommended visits is needed.
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Trastorno del Espectro Autista/diagnóstico , Utilización de Instalaciones y Servicios/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Servicios Preventivos de Salud/estadística & datos numéricos , Preescolar , Diagnóstico Precoz , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , VirginiaRESUMEN
BACKGROUND: This study aimed to explore the impacts of COVID-19 outbreak on mental health status in general population in different affected areas in China. METHODS: This was a comparative study including two groups of participants: (1) general population in an online survey in Ya'an and Jingzhou cities during the COVID-19 outbreak from 10-20 February 2020; and (2) matching general population selected from the mental health survey in Ya'an in 2019 (from January to May 2019). General Health Questionnaire (GHQ-12), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were used. RESULTS: There were 1775 participants (Ya'an in 2019 and 2020: 537 respectively; Jingzhou in 2020: 701). Participants in Ya'an had a significantly higher rate of general health problems (GHQ scores ⩾3) in 2020 (14.7%) than in 2019 (5.2%) (p < 0.001). Compared with Ya'an (8.0%), participants in Jingzhou in 2020 had a significantly higher rate of anxiety (SAS scores ⩾50, 24.1%) (p < 0.001). Participants in Ya'an in 2020 had a significantly higher rate of depression (SDS scores ⩾53, 55.3%) than in Jingzhou (16.3%) (p < 0.001). The risk factors of anxiety symptoms included female, number of family members (⩾6 persons), and frequent outdoor activities. The risk factors of depression symptoms included participants in Ya'an and uptake self-protective measures. CONCLUSIONS: The prevalence of psychological symptoms has increased sharply in general population during the COVID-19 outbreak. People in COVID-19 severely affected areas may have higher scores of GHQ and anxiety symptoms. Culture-specific and individual-based psychosocial interventions should be developed for those in need during the COVID-19 outbreak.
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COVID-19 , Humanos , Femenino , Salud Mental , SARS-CoV-2 , Depresión/epidemiología , Ansiedad/psicología , Brotes de Enfermedades , Encuestas y Cuestionarios , China/epidemiologíaRESUMEN
BACKGROUND: The current study examined the change in local government staff's emotional distress over 7 years after the 2008 Wenchuan earthquake, and the influence of earthquake exposure and professional quality of life (ProQOL) on emotional distress. METHODS: This longitudinal study assessed 250 participants at 1 year after the earthquake; 162 (64.8%) were followed up at 7 years. Emotional distress was assessed with the Self-Reporting Questionnaire (SRQ) at both time points. We assessed ProQOL, including compassion satisfaction, burnout, and secondary traumatic stress, and earthquake exposure at 1 year. Wilcoxon signed-rank tests were performed to test longitudinal changes in emotional distress. Hierarchical multiple regression was conducted to examine the effect of earthquake exposure and ProQOL. RESULTS: The positive screening rate of emotional distress (SRQ ≥ 8) was 37.6 and 15.4% at one and 7 years, respectively. Emotional distress scores declined over time (p < 0.001). Earthquake exposure and ProQOL predicted one-year (ps < 0.05) but not seven-year emotional distress, whereas burnout predicted both one-year (p = 0.018) and seven-year (p = 0.047) emotional distress. CONCLUSIONS: Although emotional distress can recover over time, it persists even 7 years later. Actions to reduce burnout during the early stage of post-disaster rescue have long-term benefits to staff's psychological outcomes.
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Terremotos , Distrés Psicológico , Trastornos por Estrés Postraumático , China/epidemiología , Humanos , Gobierno Local , Estudios Longitudinales , Calidad de Vida , Encuestas y CuestionariosRESUMEN
PURPOSE: Children should attend well child visits (WCVs) during early childhood so that developmental disorders may be identified as early as possible, so treatment can begin. The aim of this research was to determine if rurality impacts access to WCV during early childhood, and if altering rurality measurement methods impacts outcomes. DESIGN AND METHODS: We utilized a longitudinal correlational design with early childhood data gathered from the Virginia All Payer Claims Database, which contains claims data from Medicaid and the majority of Virginia commercial insurance payers (n = 6349). WCV attendance was evaluated against three rurality metrics: a traditional metric using Rural-Urban Commuting Area codes, a developed land variable, and a distance to care variable, at a zip code level. RESULTS: Two of the rurality methods revealed that rural children attend fewer WCVs than their urban counterparts, (67% vs. 50% respectively, using a traditional metric; and a 0.035 increase in WCV attendance for every percent increase in developed land). Differences were attenuated by insurance payer; children with Medicaid attend fewer WCVs than those with private insurance. CONCLUSIONS: Young children in rural Virginia attend fewer WCVs than their non-rural counterparts, placing them at higher risk for missing timely developmental disorder screenings. The coronavirus disease pandemic has been associated with an abrupt and significant reduction in vaccination rates, which likely indicates fewer WCVs and concomitant developmental screenings. Pediatric nurses should encourage families of young children to develop a plan for continued WCVs, so that early identification of developmental disorders can be achieved.
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Medicaid , Población Rural , Niño , Preescolar , Humanos , Examen Físico , Medición de Riesgo , Estados Unidos , Virginia/epidemiologíaRESUMEN
A new class of 2(1H)-pyrimidinone derivatives was identified as potential EGFR T790M inhibitors against TKI-resistant NSCLC. These novel compounds inhibited the EGFR T790M kinase activity at concentrations in the range of 85.3 to 519.9â¯nM. In particular, compound 7e exhibited the strongest activity against both EGFRWT (IC50â¯=â¯96.9â¯nM) and EGFRT790M (IC50â¯=â¯85.3â¯nM) kinases in the cells. Compared with inhibitor 7e, compound 7b displayed enhanced antiproliferative activity against gefitinib-resistant H1975 cells harboring the EGFR T790M mutation. In addition, compound 7b also has low toxicity against the normal human liver cells LO2, with an IC50 of 11.1⯵M. Moreover, both the AO/EB and DAPI staining assays also demonstrated the inhibitory efficacy of 7b against the resistant H1975 cells. This contribution provides a new scaffold 2(1H)-pyrimidinone as potential EGFR T790M inhibitor against drug-resistant NSCLC.
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Antineoplásicos/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Receptores ErbB/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/química , Pirimidinonas/química , Antineoplásicos/química , Antineoplásicos/metabolismo , Sitios de Unión , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Receptores ErbB/genética , Receptores ErbB/metabolismo , Gefitinib/farmacología , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Simulación del Acoplamiento Molecular , Mutación , Inhibidores de Proteínas Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Estructura Terciaria de Proteína , Pirimidinonas/metabolismo , Pirimidinonas/farmacologíaRESUMEN
PURPOSE: The aim of this study was to investigate gender differences of periodic limb movements during sleep (PLMS) in patients with obstructive sleep apnea (OSA). METHODS: This was a case-control study recruiting 364 patients with OSA (182 men, 182 women) matched for age and apnea-hypopnea index (AHI). All participants underwent overnight polysomnography (PSG), followed by the multiple sleep latency test (MSLT) and the Epworth Sleepiness Scale (ESS). RESULTS: Women with OSA had a significantly higher prevalence of PLMS than men (24.2 vs. 15.9 %, p < 0.05). Women with OSA showed an increased prevalence of PLMS compared to men in the younger group aged ≤55 years (23.0 vs. 10.6 %, p < 0.05), but not in the older groups >55 years (25.3 vs. 21.6 %, p > 0.05). Binary linear regression analysis in OSA patients confirmed that women were more likely to have PLMS than men (OR 1.71, 95 % CI 1.00-2.92), particularly in patients with age ≤55 years old (OR 2.48, 95 % CI 1.06-5.79), after adjusting for age, BMI, AHI, and habits of smoking and drinking. CONCLUSIONS: The results demonstrate that, for patients with OSA, young women had significantly increased prevalence of PLMS compared to young men, but there was no difference in prevalence of PLMS between the men and women in the older age group.
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Síndrome de Mioclonía Nocturna/diagnóstico , Síndrome de Mioclonía Nocturna/epidemiología , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Adulto , Factores de Edad , Anciano , Estudios de Casos y Controles , Comorbilidad , Estudios Transversales , Trastornos de Somnolencia Excesiva/diagnóstico , Trastornos de Somnolencia Excesiva/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Factores SexualesRESUMEN
Orf101 (Bm101) of Bombyx mori nucleopolyhedrovirus (BmNPV) is a highly conserved gene in lepidopteran nucleopolyhedroviruses, but its function remains unknown. In this study, Bm101 was characterized. Transcripts of Bm101 were detected from 24 through 96 h post infection (h p.i.) by RT-PCR. The corresponding protein was also detected from 24 to 96 h p.i. in BmNPV-infected BmN cells by Western blot analysis using a polyclonal antibody against Bm101. Western blot assay of occlusion-derived virus and budded virus (BV) preparations revealed that Bm101 encodes a 28-kDa structural protein that is associated with BV and is located in the envelope fraction of budded virions. In addition, confocal analysis showed that the protein was localized in the cytosol and cytoplasmic membrane in virus-infected cells. In conclusion, the available data suggest that Bm101 is a functional ORF of BmNPV and encodes a protein expressed in the late stage of the infection cycle that is associated with the BV envelope.
Asunto(s)
Bombyx/virología , Nucleopoliedrovirus/genética , Nucleopoliedrovirus/fisiología , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/metabolismo , Ensamble de Virus , Animales , Western Blotting , Perfilación de la Expresión Génica , Peso Molecular , Proteínas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas del Envoltorio Viral/químicaRESUMEN
Bombyx mori nucleopolyhedrovirus (BmNPV) is a major viral agent that causes deadly grasserie disease in silkworms, while BmNPV DNA polymerase (BmNPV-pol), encoded by ORF53 gene, plays a central role in viral DNA replication. Efficacy studies of BmNPV-POL are limited because of poor heterologous protein expression in E. coli. Here, we redesigned the BmNPV-pol to preferentially match codon frequencies of E. coli without altering the amino acid sequence. Following de novo synthesis, codon-optimized BmNPV-pol (co-BmNPV-pol) gene was cloned into pET32a and pGEX-4T-2 vector. The expression of co-BmNPV-POL in E. coli was significantly increased when BmNPV-POL was fused with GST protein rather than a His-tag. The co-BmNPV-POL fusion proteins were isolated using GST affinity chromatography and Mono Q iron exchange chromatography. Protein purity and identity were confirmed by western blot and MALDI-TOF analyses. The biological activity of purified proteins was measured on a poly(dA)/oligo(dT) primer/template. The specific polymerasing activity of the recombinant BmNPV-POL was 6,329 units/mg at optimal conditions. Thus, a large amount of purified protein as a soluble form with high activity would provide many benefits for the functional research and application of BmNPV-POL.