Early Type Research Articles

Mental health among bereaved youth in the ALSPAC birth cohort: Consideration of early sociodemographic precursors, cognitive ability, and type of loss.

Bereaved youth are at greater risk for adverse mental health outcomes, yet less is known about how social context shapes health for bereaved children. Ecosocial theory is employed to conceptualize bereavement in the context of sociodemographic factors. This longitudinal study used data from the Avon Longitudinal Study of Parents and Children. Of the 15,454 pregnancies enrolled, 5050 youth were still enrolled at age 16.5 and completed self-report questionnaires on life events and emotional/behavioral symptoms. Sociodemographic precursors associated with parent, sibling, or close friend bereavement included maternal smoking, parental education levels, and financial difficulties. The significant yet small main effect of higher cognitive ability, assessed at age 8, on reduced emotional/behavioral symptoms at age 16.5 (β = -0.01, SE = 0.00, p < 0.001) did not interact with bereavement. Bereavement of a parent, sibling, or close friend was associated with a 0.19 point higher emotional/behavioral symptom log score compared to non-bereaved youth (95% CI: 0.10-0.28), across emotional, conduct, and hyperactivity subscales. Descriptive findings suggest sociodemographic precursors are associated with bereavement. While there was an association between the bereavement of a parent, sibling, or close friend and elevated emotional/behavioral symptoms, cognitive ability did not moderate that effect.

The genetic and clinical characteristics of WFS1 related diabetes in Chinese early onset type 2 diabetes

Diabetes is one of the most common phenotypes of Wolfram syndrome owing to the presence of the variants of the WFS1 gene and is often misdiagnosed as other types of diabetes. We aimed to explore the prevalence of WFS1-related diabetes (WFS1-DM) and its clinical characteristics in a Chinese population with early-onset type 2 diabetes (EOD). We sequenced all exons of the WFS1 gene in 690 patients with EOD (age at diagnosis ≤ 40 years) for rare variants. Pathogenicity was defined according to the standards and guidelines of the American College of Medical Genetics and Genomics. We identified 33 rare variants predicted to be deleterious in 39 patients. The fasting [1.57(1.06–2.22) ng/ml] and postprandial C-peptide levels [2.8(1.75–4.46) ng/ml] of the patients with such WFS1 variations were lower than those of the patients without WFS1 variation [2.09(1.43–3.05) and 4.29(2.76–6.07) respectively, ng/ml]. Six (0.9%) patients carried pathogenic or likely pathogenic variants; they met the diagnostic criteria for WFS1-DM according to the latest guidelines, but typical phenotypes of Wolfram syndrome were seldom observed. They were diagnosed at an earlier age and usually presented with an absence of obesity, impaired beta cell function, and the need for insulin treatment. WFS1-DM is usually mistakenly diagnosed as type 2 diabetes, and genetic testing is helpful for individualized treatment.

STING is redundant for host defense and pathology of COVID-19-like disease in mice.

Critical COVID-19 is characterized by lack of early type I interferon-mediated host defense and subsequent hyper-inflammation in the lungs. Aberrant activation of macrophages and neutrophils has been reported to lead to excessive activation of innate immunological pathways. It has recently been suggested that the DNA-sensing cGAS-STING pathway drives pathology in the SARS-CoV-2-infected lungs, but mechanistic understanding from in vivo models is needed. Here, we tested whether STING is involved in COVID-19-like disease using the K18-hACE2 mouse model. We report that disease development after SARS-CoV-2 infection is unaltered in STING-deficient K18-hACE2 mice. In agreement with this, STING deficiency did not affect control of viral replication or production of interferons and inflammatory cytokines. This was accompanied by comparable profiles of infiltrating immune cells into the lungs of infected mice. These data do not support a role for STING in COVID-19 pathology and calls for further investigation into the pathogenesis of critical COVID-19.

Electrokinetically enhanced label-free plasmonic sensing for rapid detection of tumor-derived extracellular vesicles

Analysisof rare circulating extracellular vesicles (EV) from early cancers or different types of host cells requires extremely sensitive EV sensing technologies. Nanoplasmonic EV sensing technologies have demonstrated good analytical performances, but their sensitivity is often limited by EVs’ diffusion to the active sensor surface for specific target EV capture. Here, we developed an advanced plasmonic EV platform with electrokinetically enhanced yields (KeyPLEX). The KeyPLEX system effectively overcomes diffusion-limited reactions with applied electroosmosis and dielectrophoresis forces. These forces bring EVs toward the sensor surface and concentrate them in specific areas. Using the keyPLEX, we showed significant improvements in detection sensitivity by ∼100-fold, leading to the sensitive detection of rare cancer EVs from human plasma samples in 10 min. The keyPLEX system could become a valuable tool for point-of-care rapid EV analysis.

Noblesse oblige? Job position and early childhood leadership in China: the moderating role of school type

ABSTRACT This paper addresses the roles of job position in relation to early childhood leadership (ECL) and school type as a potential moderator of this relationship in China. A sample of 918 research participants, including 149 principals/vice-principals, 108 middle leaders and 661 teachers, was investigated. A three-factor model of ECL including staff management and development (SMD), peer learning and support (PLS) and communication with parents (CP) was used. By conducting linear regression analyses, it was found that the higher the job position an individual held, the more ECL practices he or she performed. The interaction terms (job position × school type) were statistically significant related to SMD and CP but not statistically significant related to PLS. In the case of public school type, the relationship between job position and CP became slightly negative. For private school type, however, it showed a curve-linear relationship. This paper indicates that teachers rarely participates in school-level decision-making due to the top-down management structure, especially in public preschools. It also suggests that the traditional preschool management system leads to preschool teachers in China are socialized as followers with no responsibilities outside classrooms.

Bacterial Microorganisms in Definitive Neonatal Sepsis

Background The proper diagnosis and treatment of neonatal sepsis is done depends on the understanding of its causative organisms. Objective The present study aimed to investigate the types of microorganisms in definitive neonatal sepsis. Methods Neonatal sepsis is a serious infectious disease with high mortality. And its diagnosed by blood culture. It includes early (appearance of clinical symptoms from birth to the third-seventh day) and late (from the third day to the twenty-eighth day) types with specific and sometimes common clinical symptoms. This cross-sectional study was performed on 266 neonates hospitalized with definitive sepsis in Ghaem Hospital in Mashhad from 2010 to 2020 using available sampling method. Infants suspected of bacterial infection who had positive blood cultures were included in the study. Type of bacterial organism, time of sepsis, main causes of death and need for mechanical ventilation were evaluated. Results Eighty eight neonates had early sepsis and 197 neonates had late sepsis. The bacterial organism of early sepsis was gram negative as 70.1% and in late sepsis was gram negative as 77.1%. The most common causes of early sepsis were Klebsiella pneumonia 21 cases (23.9%), Staphylococcus epidermis 16 cases (18.2%) and 10 cases (11.4%) E. coli . And the most common causes of late sepsis were K. pneumonia 35 cases (25.4%), Enterobacter aeroginosa 25(18.1%), S. epidermis 12(8.7%) and E. coli 11(8%). Conclusion K. pneumonia, S. epidermis and E. coli were three most common organisms in early neonatal sepsis and K. pneumonia, S. epidermis and Enterobacter were the most common organisms in late neonatal sepsis.

Macrophage phagocytosis of SARS-CoV-2-infected cells mediates potent plasmacytoid dendritic cell activation

Early and strong interferon type I (IFN-I) responses are usually associated with mild COVID-19 disease, whereas persistent or unregulated proinflammatory cytokine responses are associated with severe disease outcomes. Previous work suggested that monocyte-derived macrophages (MDMs) are resistant and unresponsive to SARS-CoV-2 infection. Here, we demonstrate that upon phagocytosis of SARS-CoV-2-infected cells, MDMs are activated and secrete IL-6 and TNF. Importantly, activated MDMs in turn mediate strong activation of plasmacytoid dendritic cells (pDCs), leading to the secretion of high levels of IFN-α and TNF. Furthermore, pDC activation promoted IL-6 production by MDMs. This kind of pDC activation was dependent on direct integrin-mediated cell‒cell contacts and involved stimulation of the TLR7 and STING signaling pathways. Overall, the present study describes a novel and potent pathway of pDC activation that is linked to the macrophage-mediated clearance of infected cells. These findings suggest that a high infection rate by SARS-CoV-2 may lead to exaggerated cytokine responses, which may contribute to tissue damage and severe disease.

Tungsten mineralization in the Caojiaba tungsten deposit, southern China: Constraints from scheelite in-situ trace elements and Sr isotope evidence

The Caojiaba tungsten deposit (19.03 Mt@ 0.37 wt% WO3) is hosted in skarn within clastic and carbonate rocks in the Xiangzhong metallogenic province (XZMP), southern China. The genesis of the Caojiaba tungsten deposit remains to be determined, and the role of trace element enrichment and precipitation in scheelite has received little study to date. The deposit is characterized by early prograde skarn overprinted by retrograde skarn assemblage, and then by quartz–scheelite–sulfide veins. Scheelite (CaWO4) across the mineralization stages can be divided into four generations, i.e., scheelite type–1 (Sch1) in the prograde skarn, early scheelite type–2 (Sch2) and late scheelite type–3 (Sch3) grains in the retrograde skarn, and scheelite type–4 (Sch4) in the quartz–scheelite–sulfide vein. In the cathodoluminescence (CL) images, Sch1, Sch2, and Sch3 have core–to–rim textures displaying CL–dark core and CL–bright rims, whereas Sch4 is homogeneous in the CL response across the grains. Sch1 contains high REE + Y and Ta concentrations, and has negative Eu anomalies relative to the other three types of scheelite grains, consistent with the contribution from magmatic fluids related to the tungsten granites. The increasing fluid–rock interaction intensity, precipitation of REE–rich minerals, and pH change in ore–forming fluids increase positive Eu anomalies and LREE/HREE fractionation of scheelite from Sch2 to Sch4. The in-situ initial 87Sr/86Sr ratios of Sch2 range from 0.71727 to 0.72142, which are within or slightly higher than those of the exposed Late Triassic tungsten granites in the XZMP. The broadly increasing initial 87Sr/86Sr ratios of Sch3 (0.72070 to 0.72764) suggest a source derived from magmatic fluids and contribution of the Neoproterozoic Banxi Group slate. This study highlights that the variations in trace element and Sr isotope compositions of scheelite can be used to reveal the source of ore–forming fluids and metal, and constrain the ore–forming processes.

Single vs Multibranched/Fenestrated Endovascular Aortic Arch Repair

To evaluate results of single vs multibranched/fenestrated endovascular aortic arch repair at a single institution. A retrospective review was performed of all endovascular aortic arch endografts at a single institution. Demographics, clinical records, and imaging were evaluated. Outcomes reviewed included debranching complications and early (within 30 days) and late (>30 days) procedural complications including death, stroke, myocardial infarction, spinal cord ischemia, endoleak, infection, and any return to the operating room. Patient were divided into two cohorts based on number of cervical vessel branches/fenestrations: group A (0 or 1 branch/fenestration) and group B (2 or 3 branches/fenestrations). Between March 2014 and May 2022, 24 patients underwent endovascular aortic arch repair. All procedures were elective. Technical success was achieved in 23 (95.8%) patients; one patient in group A had migration of the ascending Nexus module. Indications for surgery were arch aneurysm (58.3%) and proximal landing zone creation for descending thoracic aortic aneurysm repair (41.2%). The Cook CMD endograft was most commonly use overall (group A 53.8%, group B 100%), while the Nexus arch endograft was used in nearly one-half of all group A procedures (46.2%). The majority of grafts were landed in zone 0 (group A 69.2%, group B 100%) (Table). Debranching procedures were most frequently performed in group A; in particular, carotid-carotid bypass was necessary in all group A patients with proximal landing in zone 0 (53.8%). This led to graft infection in two patients requiring explant. Additional debranching complications included one carotid-subclavian bypass graft explant and one Amplatzer plug migration in a subclavian artery resulting in false lumen expansion (all group A). Overall 30-day mortality was 8.3% and stroke rate was 12.5% with no significant difference between the two groups. There were no instances of spinal cord ischemia. Early type Ia endoleaks were noted in three (12.5%) patients. There were two retrograde type A dissections on postoperative imaging; one required ascending/hemiarch replacement and partial graft explant at 3 months (group A); the other was managed nonoperatively (group B). One type III endoleak at 3 years required TEVAR (group A). Median follow-up was 6 months (interquartile range, 4-18). Endovascular aortic arch grafts have high technical success rate with acceptable morbidity and mortality. Single-branched/fenestrated grafts designed to land in zone 0 are more likely to require more in-hospital days and are prone to debranching complications without any added mortality or stroke benefit. Multibranched grafts are preferable for zone 0 landings when anatomically feasible.TableSingle vs multibranched/fenestrated endovascular aortic arch repairGroup A (n = 13) (0-1 branched/fenestrated)Group B (n = 11) (2-3 branched/fenestrated)P valueAge72 (65-77)79 (73-82).08Female sex6 (46.2)4 (36.4).95Indication for surgery.08 Arch aneurysm5 (38.5)9 (81.8) Create proximal landing zone8 (61.5)2 (18.2)Proximal landing zone.131 09 (69.2)11 12 (15.4)0 22 (15.4)0Endograft.03 Nexus6 (46.2)0 Cook CMD7 (53.8)11 (100)Technical success12 (92.3)11 (100)1Total hospital days (including debranching)7 (2-15)8 (7.5-9.5).43Debranching Carotid-carotid bypass7 (53.8)0.02 Carotid-to-subclavian bypass7 (53.8)3 (27.3).37 Carotid-to-subclavian transp1 (7.7)1 (9.1)1 Subclavian-to-carotid bypass2 (15.4)3 (27.3).83Debranching complications Infection requiring explant2 (15.4)0.54Complications (<30 days) Death1 (7.7)1 (9.1)1 StrokeDisabling02 (18.2).39Nondisabling01 (9.1).93Myocardial infarct01 (9.1).93Spinal cord ischemia00Reintervention Access-related1 (7.7)3 (27.3).46 Other01 (9.1).93Early endoleak IA2 (15.4)1 (9.1)1 IB00 III00Retrograde type A1 (7.7)1 (9.1)1Values are median (interquartile range) or number (%). Open table in a new tab

Early Sac Behavior Can Help Predict Endoleak Resolution or Persistence in Patients With Early Type II Endoleak

Endoleak is a known complication of endovascular aortic repair (EVAR). The purpose of this study was to investigate the natural behavior of endoleaks based on initial aneurysm sac behavior. We analyzed 1631 patients who underwent EVAR for abdominal aortic aneurysm at a single center between 2001 and 2020. Patients were stratified into “No Leak” or “Leak” groups and then further grouped by sac behavior: “expansion,” “stabilization,” or “regression.” Endoleaks were confirmed on computed tomography, magnetic resonance imaging, or angiography. Statistical analysis was performed using χ2 tests and odds ratios. Among 1631 patients who underwent EVAR, 296 (18.2%) had type II endoleak at first follow-up. Of these 296, 125 (42.2%) had sac regression, 121 (40.9%) had sac expansion, and 50 (16.9%) had stable sacs. At a mean follow-up of 52.9 months (standard deviation [SD] ± 46.9 months), the regression group demonstrated 50 (54.9%) endoleak resolution, whereas 27 (29.6%) showed persistent type II, 2 (2.2%) developed late type I, and 12 (13.2%) had an unspecified leak. The expansion group at a mean follow-up of 58.7 months (SD ±42.3 months) had 24 (19.8%) with endoleak resolution, 64 (52.9%) with persistent type II endoleak, 10 (8.3%) develop late type I endoleak, and 23 (19.0%) had unspecified endoleaks. The stable group at a mean follow-up of 27.9 months (SD ±34.0 months) showed 12 (24%) with leak resolution, 32 (64%) with persistent type II leak, 2 (4%) late type I, and 4 (8%) with a late unspecified leak. Regression was associated with fewer developments of late endoleak than the nonregression group (45% vs 76%; P < .001). Nonregression was 8.33-fold more likely to develop late type I endoleak, 4.94 fold more likely to have persistent type II endoleak, and 3.13-fold more likely to develop late unspecified endoleak compared with regression (Table). Regression was 4.59-fold more likely to experience spontaneous endoleak resolution compared with nonregression (Table). EVAR patients with early type II endoleak and sac regression were less likely to develop late type I or unspecified endoleaks and were more likely to undergo spontaneous endoleak resolution. This study confirms that sac regression is the most important prognostic metric for successful EVAR even in patients with early type II endoleak.TableOdds ratio analysis of the presence of late type I-III endoleak across sac behavior groupsNo leak, regressionNo leak, stabilizationNo leak, expansionOdds ratio (95% CI)P valueType I late endoleak21028.33 (1.76-39.54).008Type II late endoleak2764324.94 (2.70-9.04)<.0001Unspecified late endoleak122343.13 (1.40-6.98).006Resolution of endoleak5024120.22 (0.13-0.38)<.0001CI, Confidence interval.Boldface P values represent significance P < .05. Open table in a new tab

Adverse events with risankizumab in the real world: postmarketing pharmacovigilance assessment of the FDA adverse event reporting system.

Risankizumab, a humanized IgG1 monoclonal antibody that selectively inhibits IL-23, is currently approved for the treatment of moderate-to-severe plaque psoriasis and Crohn's disease. The real-world safety study of risankizumab in a large- sample population is currently lacking. The aim of this study was to evaluate risankizumab-associated adverse events (AEs) and characterize the clinical priority through the data mining of the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Disproportionality analyses were performed by calculating the reporting odds ratios (RORs), deemed significant when the lower limit of the 95% confidence interval was greater than 1, to quantify the signals of risankizumab-related AEs from the second quarter (Q2) of 2019 to 2022 Q3. Serious and non-serious cases were compared, and signals were prioritized using a rating scale. Risankizumab was recorded in 10,235 reports, with 161 AEs associated with significant disproportionality. Of note, 37 PTs in at least 30 cases were classified as unexpected AEs, which were uncovered in the drug label, such as myocardial infarction, cataract, pancreatitis, diabetes mellitus, stress, and nephrolithiasis. 74.68%, 25.32%, and 0% PTs were graded as weak, moderate, and strong clinical priorities, respectively. A total of 48 risankizumab-related AEs such as pneumonia, cerebrovascular accident, cataract, loss of consciousness, cardiac disorder, hepatic cirrhosis, and thrombosis, were more likely to be reported as serious AEs. The median TTO of moderate and weak signals related to risankizumab was 115 (IQR 16.75-305) and 124 (IQR 29-301) days, respectively. All of the disproportionality signals had early failure type features, indicating that risankizumab-associated AEs gradually decreased over time. Our study found potential new AE signals and provided valuable evidence for clinicians to mitigate the risk of risankizumab-associated AEs based on an extensive analysis of a large-scale postmarketing international safety database.

75 Effect of Atmospheric Aging on Soot Particle Toxicity in Airway Epithelial-Endothelial Co-Culture Models at the Air–Liquid Interface

Abstract Secondary organic aerosols (SOAs) formed from anthropogenic or biogenic volatile precursors in the atmosphere substantially contribute to the ambient fine particulate matter (PM2.5) burden, which has been associated with adverse human health effects. However, there is only limited evidence of their differential toxicological impact. To study those effects, we generated different aerosols by atmospheric aging of volatile biogenic (β-pinene) or anthropogenic (naphthalene) precursors of SOA that condensed on soot particles (SPs). In-depth, physicochemical aerosol characterization revealed very similar physical properties for SOAβPIN-SP and SOANAP-SP, but distinct differences in chemical composition. For example, SOANAP-SP was associated with the formation of more oxidized and more aromatic SOAs with a higher oxidative potential compared to β-pinene. By exposing a co-culture model system consisting of lung epithelial cells (A549) and endothelial cells (EA.hy926) at the air-liquid interface to different aerosol concentrations, we aimed to discriminate toxicological effects. Integrated transcriptomic and metabolomics analysis revealed induction of stress-related airways remodeling and an early type I immune response, for the A549 cells, especially after the exposure to SOANAP-SP. The underlying EA.hy926 cells showed similar transcriptomic changes in early response genes and genes related to cardiovascular pathologies after exposure to both SOA types, however to a greater extent after SOANAP-SP. While fresh SP without coating by SOA evinced only minor changes in both cell lines. Altogether, this supports the assumption of a pivotal role of atmospheric chemistry and the chemical PM composition on the toxicological outcomes and highlights the importance of organic compounds on cellular effects.

The Impact of Resveratrol-Enriched Bread on Cardiac Remodeling in a Preclinical Model of Diabetes.

The World Health Organization aims to stop the rise of diabetes by 2025, and diet is one of the most efficient non-pharmacological strategies used to prevent it. Resveratrol (RSV) is a natural compound with anti-diabetic properties, and incorporating it into bread is a suitable way to make it more accessible to consumers as it can be included as part of their daily diet. This study aimed to evaluate the effect of RSV-enriched bread in preventing early type 2 diabetes cardiomyopathy in vivo. Male Sprague Dawley rats (3 weeks old) were divided into four groups: controls with plain bread (CB) and RSV bread (CBR), and diabetics with plain bread (DB) and RSV bread (DBR). Type 2 diabetes was induced by adding fructose to the drinking water for two weeks followed by an injection of streptozotocin (STZ) (40 mg/kg). Then, plain bread and RSV bread (10 mg RSV/kg body weight) were included in the rats' diet for four weeks. Cardiac function, anthropometric, and systemic biochemical parameters were monitored, as well as the histology of the heart and molecular markers of regeneration, metabolism, and oxidative stress. Data showed that an RSV bread diet decreased the polydipsia and body weight loss observed in the early stages of the disease. At the cardiac level, an RSV bread diet diminished fibrosis but did not counteract the dysfunction and metabolic changes seen in fructose-fed STZ-injected rats.

Uncovering alterations in the murine interferon response due to dsRNA mycovirus during Aspergillus fumigatus infection

Abstract Aspergillus fumigatus is a mold that causes an array of diseases, the most severe form being invasive aspergillosis which occurs in highly immunocompromised individuals. We demonstrated that tissue-resident alveolar macrophages are critical for maintaining host resistance against Aspergillus fumigatus due to their role in the early type I/III interferon response. Specifically, CD11c-Cre x Mavs fl/flmice have a decreased interferon response and survival outcomes when challenged with A. fumigatus, which can be functionally restored via adoptive transfer of wild-type SiglecF +alveolar macrophages. Why alveolar macrophages are potent inducers of the type I/III interferon response after Aspergillus fumigatus challenge remains elusive. Here, we demonstrate that TGF-beta metabolically programs alveolar macrophages to be potent interferon inducers via enhanced dependency on oxidative phosphorylation and peroxisome biogenesis. The type I/III interferon responses were partially related to the inability of alveolar macrophages to recognize mycoviral double-stranded RNA (dsRNA). Aspergillus fumigatus strains infected with polymycovirus 1 (PmV1) are shown to induce a robust type I/III interferon responses both in vitro and in vivo. Critically, Mda5/MAVS-dependent interferon response can still be induced in a fungal dsRNA independent manner, which warrant further explorations. In this study we identified key metabolic traits of alveolar macrophages which enable robust Mda5/MAVS signaling necessary for initiating the Aspergillus fumigatus induced interferon response, which maintains host resistance against this ubiquitous mold, through both fungal dsRNA-dependent and -independent mechanisms.

Drug hypersensitivity in drug-resistant tuberculosis

ObjectiveTo evaluate drug resıstant tuberculosis patients who developed drug hypersensitivity to antituberculosis drug. MethodsThis was a retrospective study. The primary aim of the study is to determine the demographic and clinical characteristics of patients who develop drug hypersensitivity in drug resistant tuberculosis patients. The secondary aim of the study is to examine the treatment results. Demographic features, tuberculosis diagnostic indicator, clinical signs of developing hypersensitivity reaction, reaction time, and treatment were evaluated. ResultsA total of 25 patients were included in the study. The prevalence of hypersensitivity in drug resistance patients was 11.9%. Twelve (48%) of the cases were women. Mean age (mean ± SD) was 37.24 ± 14.44 years; early type hypersensitivity reaction in 13 (52%). Three patients were isoniazid resistant; 19 patients were multidrug-resistant (MDR); 2 patients were pre-extensive drug resistant (Pre-XDR), 1 patient was extensive drug resistance (XDR) tuberculosis. The most common skin findings were maculopapular eruption and urticaria. But also we had seen ısole angıodema, urtıcarıa and angıoedema, erythema multıforme, lıchenoıd drug eruptıon and drug rash with eosinophilia and systemic symptoms. In patients who developed a hypersensitivity reaction, the responsible agent was identified in 14 cases in total. Among the drugs, pyrazinamide, ethambutol, moxifloxacin, amikacin, para amino salicylic, prothionamide, and cycloserine are the responsible agents. When evaluated in terms of treatment results, 15 (60%) patients successfully completed the treatment. ConclusionOur study is the first study in the literature that evaluated the drug hypersensitivity in drug resıstance tuberculosis patients. Drug hypersensitivity that develops with tuberculosis treatment may lead to discontinuation or change in treatment. İt can cause treatment failure, drug resistance, relapse, and even death. In resistant tuberculosis, the already existing resistance pattern may become more difficult to treat. Success can be achieved with the right management in these patients who have few treatment options, more drug side effects, and high treatment failure rates. The established regimen should be curative and prevent recurrence.

Value-added Catalog of M-giant Stars in LAMOST DR9

In this work, we update the catalog of M-giant stars from the low-resolution spectra of the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) Data Release 9. There are 58,076 M giants identified from the classification pipeline with seven temperature subtypes from M0 to M6. The 2471 misclassified non–M-giant stars are white dwarf binaries, early types, and M dwarfs. And the contamination rate is 4.2% in the M-giants sample. A total of 372 carbon stars were identified by CaH spectral indices, and were further confirmed by the LAMOST spectra. We update the correlation between the (W1 – W2)0 color and [M/H] from APOGEE DR17. We calculate the radial velocities of all M giants by applying cross-correlation to the spectra between 8000 and 8950 Å with synthetic spectra from ATLAS9. Taking star distances less than 4 kpc from Gaia EDR3 as the standard, we refitted the photometric distance relation of M giants. And based on our M-giant stars, we select a group of Sagittarius stream members, whose sky and 3D velocity distributions are well consistent with K-giant Saggitarius stream members found in Yang et al. With our M giants, we find that the disk is asymmetric out to R = 25 kpc, which is 5 kpc further out than detected using K giants.

Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19

Rhinoviruses and allergens, such as house dust mite are major agents responsible for asthma exacerbations. The influence of pre-existing airway inflammation on the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. We analyse mechanisms of response to viral infection in experimental in vivo rhinovirus infection in healthy controls and patients with asthma, and in in vitro experiments with house dust mite, rhinovirus and SARS-CoV-2 in human primary airway epithelium. Here, we show that rhinovirus infection in patients with asthma leads to an excessive RIG-I inflammasome activation, which diminishes its accessibility for type I/III interferon responses, leading to their early functional impairment, delayed resolution, prolonged viral clearance and unresolved inflammation in vitro and in vivo. Pre-exposure to house dust mite augments this phenomenon by inflammasome priming and auxiliary inhibition of early type I/III interferon responses. Prior infection with rhinovirus followed by SARS-CoV-2 infection augments RIG-I inflammasome activation and epithelial inflammation. Timely inhibition of the epithelial RIG-I inflammasome may lead to more efficient viral clearance and lower the burden of rhinovirus and SARS-CoV-2 infections.

Peningkatan Pengetahuan Orangtua melalui Kegiatan Parenting dalam Upaya Mendukung Kegiatan PAUD Holistik Integratif di Kelompok Bermain Nirwana 1 Semanding Tuban

The purpose of parenting class activities is to increase parental knowledge in supporting holistic integrative early childhood education programs. The activities carried out use an educative approach, with the method of discussion, and question and answer lectures. The material provided includes parental responsibilities in child care, understanding between educators and parents, types of Holistic Integrative Early Childhold Education services and types of parenting activities. The executors of the activities were 1 overseer from the Tuban Education Office, teachers and operators in the Nirwana 1 playgroup, and the target activities were 22 parents of students. The results of the activities that have been carried out have resulted in an increase in knowledge scores with an average pre-test score of 61 and a post-test score of 76. The results of this activity are expected to have an impact on increasing parental participation in integrative holistic PAUD activity programs

Cardiac adverse events associated with quetiapine: Disproportionality analysis of FDA adverse event reporting system.

Quetiapine, an atypical second-generation antipsychotic drug, is approved for treatment of schizophrenia, bipolar disorder, and depression. Due to the limitations of clinical trials, the association between quetiapine and rare cardiac adverse events (AEs) is still unclear. This study is to evaluate quetiapine-associated cardiac AEs through data mining of FDA Adverse Event Reporting System (FAERS). Reporting odds ratio (ROR) was used to quantify the signals of quetiapine-related cardiac AEs from the first quarter (Q1) of 2018-2022 Q1. Serious and nonserious cases were compared, and signals were prioritized using a rating scale. A total of 1004 cases of quetiapine-associated cardiac AEs were identified, with 31 signals being detected, among which 13 AEs were identified as new and unexpected signals. Besides, nine and 22 cardiac AEs were identified as moderate and weak clinical priority. The median TTO for moderate and weak clinical priority signals were 0 and 4 days, respectively. All of the cardiac AEs had early failure type characteristics, suggesting that most of the patients developed cardiac AEs in a few days after quetiapine treatment, and that the risk of cardiac AEs occurrence would be gradually decreased over time. Our study provided valuable evidence for health-care professionals to mitigate the risk of quetiapine-associated cardiac AEs based on an extensive analysis of a real-world, large-sample FAERS database, and prioritize cardiac AE signals.

Development and validation of DNA methylation scores in two European cohorts augment 10-year risk prediction of type 2 diabetes.

Type 2 diabetes mellitus (T2D) presents a major health and economic burden that could be alleviated with improved early prediction and intervention. While standard risk factors have shown good predictive performance, we show that the use of blood-based DNA methylation information leads to a significant improvement in the prediction of 10-year T2D incidence risk. Previous studies have been largely constrained by linear assumptions, the use of cytosine-guanine pairs one-at-a-time and binary outcomes. We present a flexible approach (via an R package, MethylPipeR) based on a range of linear and tree-ensemble models that incorporate time-to-event data for prediction. Using the Generation Scotland cohort (training set ncases = 374, ncontrols = 9,461; test set ncases = 252, ncontrols = 4,526) our best-performing model (area under the receiver operating characteristic curve (AUC) = 0.872, area under the precision-recall curve (PRAUC) = 0.302) showed notable improvement in 10-year onset prediction beyond standard risk factors (AUC = 0.839, precision-recall AUC = 0.227). Replication was observed in the German-based KORA study (n = 1,451, ncases = 142, P = 1.6 × 10-5).