Loss of microglial Arid1a exacerbates microglial scar formation via elevated CCL5 after traumatic brain injury.

Traumatic brain injury (TBI) is an acquired insult to the brain caused by an external mechanical force, potentially resulting in temporary or permanent impairment. Microglia, the resident immune cells of the central nervous system, are activated in response to TBI, participating in tissue repair process. However, the underlying epigenetic mechanisms in microglia during TBI remain poorly understood. ARID1A (AT-Rich Interaction Domain 1 A), a pivotal subunit of the multi-protein SWI/SNF chromatin remodeling complex, has received little attention in microglia, especially in the context of brain injury. In this study, we generated a Arid1a cKO mouse line to investigate the potential roles of ARID1A in microglia in response to TBI. We found that glial scar formation was exacerbated due to increased microglial migration and a heightened inflammatory response in Arid1a cKO mice following TBI. Mechanistically, loss of ARID1A led to an up-regulation of the chemokine CCL5 in microglia upon the injury, while the CCL5-neutralizing antibody reduced migration and inflammatory response of LPS-stimulated Arid1a cKO microglia. Importantly, administration of auraptene (AUR), an inhibitor of CCL5, repressed the microglial migration and inflammatory response, as well as the glial scar formation after TBI. These findings suggest that ARID1A is critical for microglial response to injury and that AUR has a therapeutic potential for the treatment of TBI.

Optimizing patient outcomes in severe pneumonia: the role of multiplex PCR in the treatment of critically ill patients.

Herein, we evaluated the optimal timing for implementing the BioFire® FilmArray® Pneumonia Panel (FA-PP) in the medical intensive care unit (MICU). Respiratory samples from 135 MICU-admitted patients with acute respiratory failure and severe pneumonia were examined using FA-PP. The cohort had an average age of 67.1 years, and 69.6% were male. Notably, 38.5% were smokers, and the mean acute physiology and chronic health evaluation-II (APACHE-II) score at initial MICU admission was 30.62, and the mean sequential organ failure assessment score (SOFA) was 11.23, indicating sever illness. Furthermore, 28.9, 52.6, and 43% of patients had a history of malignancy, hypertension, and diabetes mellitus, respectively. Community-acquired pneumonia accounted for 42.2% of cases, whereas hospital-acquired pneumonia accounted for 37%. The average time interval between pneumonia diagnosis and FA-PP implementation was 1.9 days, and the mean MICU length of stay was 19.42 days. The mortality rate was 50.4%. Multivariate logistic regression analysis identified two variables as significant independent predictors of mortality: APACHE-II score (p = 0.033, OR = 1.06, 95% CI 1.00-1.11), history of malignancy (OR = 3.89, 95% CI 1.64-9.26). The Kaplan-Meier survival analysis indicated that early FA-PP testing did not provide a survival benefit. The study suggested that the FA-PP test did not significantly impact the mortality rate of patients with severe pneumonia with acute respiratory failure. However, a history of cancer and a higher APACHE-II score remain important independent risk factors for mortality.

Real-world effectiveness of fidaxomicin in patients at high risk of Clostridioides difficile recurrence.

Objective: Compare the real-world impact of fidaxomicin (FDX) and vancomycin (VAN) on Clostridioides difficile infection (CDI) recurrence in a high-risk patient population. Design: A retrospective, matched-cohort study evaluating hospitalized patients with CDI from January 1, 2016, to November 1, 2022, within a tertiary academic medical center. Patients: Adult patients with at least 1 prior CDI case who received either FDX or VAN for non-fulminant CDI while admitted, and had at least 1 additional risk factor for recurrence. Risk factors included age >70, solid organ or bone marrow transplant recipients, broad-spectrum antibiotic use within 30 days, or receipt of chemotherapy/immune-modulating agents within 30 days of admission. FDX and VAN patients were matched according to risk factors. Results: A total of 415 patient admissions were identified. After the exclusion of 92 patients for fulminant CDI, diarrhea from another cause, or use of VAN taper therapy, and 15 unmatched patients, 308 patient admissions were included (68 FDX and 240 VAN patients). There were no significant differences in 4-week recurrence (26% vs 23%; OR 1.1; P = .51), 90-day CDI readmission (29% vs 23%; P = .65), or 90-day all-cause readmission (54% vs 53%; P = .91). There was a significant 17% decrease in 90-day mortality associated with the use of FDX (OR .3; P = .04). Conclusions: In a real-world high-risk patient population, the use of FDX compared to oral VAN did not result in decreased CDI recurrence within 4 weeks or fewer hospital readmissions within 90 days. Further research is needed to better assess the value of FDX in this patient population.

An analysis of the relevance and proximity between maxillary posterior root apices to the maxillary sinus and the buccal cortical bone plate.

Background/purpose: Understanding the relationship between maxillary sinus and posterior root apices is critical in preventing dental treatment complications. This study aimed to analyze and showcase the relationship between the posterior root apices and the maxillary sinus floor, the distance to the buccal cortical bone, and their correlation with age, gender, and sides. Materials and methods: Cone-beam computed tomography images were collected from 94 patients with a total of 478 maxillary posterior teeth and 997 roots. The shortest distance from root apices to the closest border of maxillary sinus and the outer buccal cortical bone margin were measured and grouped for statistical analysis for the differences (P < 0.05). Results: The root apices of maxillary molars and single-rooted second premolars were located closer to the maxillary sinus compared to first premolars (P < 0.01). The buccal root of two-rooted first premolar had the shortest horizontal distance to the buccal cortical bone among all roots (P < 0.01). The lowest position of the maxillary sinus floor was mostly located at the palatal side (P < 0.01) and between the buccal and palatal root apices (P < 0.01) in the maxillary premolars and molars, respectively. Increasing age would lead to longer distances between the root apices and the maxillary sinus (P < 0.01). Additionally, male patients had thicker buccal cortical bone than female patients (P < 0.01). Conclusion: Different tooth positions, age, and gender significantly impact the relationships between root apices and the maxillary sinus and buccal cortical plates, informing patient-centered and individually tailored approaches for more effective and safer surgical endodontic treatment.

Predictors of Functional Cure of Chronic Hepatitis B Virus Infection: A Long-Term Follow-Up Study.

BACKGROUND & AIMS: A functional cure is an essential endpoint in the management of patients with chronic hepatitis B virus (HBV) infection. We evaluated the cumulative probability and predictors of functional cure in patients with chronic HBV infection after hepatitis B e antigen (HBeAg) seroconversion. METHODS: We retrospectively analyzed 413 (249 males and 164 females) initially HBeAg-positive chronic HBV-infected patients who were followed up for a mean of 26.36 ± 0.53 years. All underwent HBeAg seroconversion during follow-up. A functional cure was defined as durable HBsAg and HBV DNA loss without antiviral treatment for more than 24 weeks. RESULTS: After 10,888 person-years of follow-up, the cumulative probability of functional cure was 14.53% (n = 60). There were 24 (40%) subjects with functional cure after antiviral therapy. The annual functional cure rate was 0.55% per person-year, and increased to 0.96% per person-year after HBeAg seroconversion. In subjects with functional cure, the HBsAg and HBV DNA titers after HBeAg seroconversion were positively correlated with the time to functional cure (P < .001 and < .001, respectively). Multivariate Cox proportional hazards analysis of the cohort revealed that HBeAg seroconversion at <18 years of age, high-genetic-barrier nucleos(t)ide analogue(s) therapy before HBeAg seroconversion, and a serum HBsAg titer <1000 IU/mL at 18 months after HBeAg seroconversion were significant predictors of functional cure (P < .001, .001, and .001, respectively). CONCLUSIONS: In a cohort of chronic HBV-infected patients with long-term follow-up, HBeAg seroconversion in childhood, high-genetic-barrier nucleos(t)ide analogue(s) therapy, and low HBsAg titers after HBeAg seroconversion were significant predictors of functional cure.

Evaluating health literacy from an organizational perspective: A cross-sectional study of community health centers.

OBJECTIVES: To investigate community health centers' (CHCs) health literacy. DESIGN: A cross-sectional study. SAMPLE: A total of 374 CHCs were surveyed and 258 CHCs responded, with an effective questionnaire response rate of 69.0%. MEASUREMENTS: Data were collected by using a self-developed health literacy assessment tool to survey CHCs' health literacy throughout Taiwan from January to December 2019. RESULTS: The item of organizational health literacy (OHL) with the highest proportion of CHCs not implementing them was "Design of easy-to-use computer applications and new media" (47.3% not yet achieved), followed by "Involving target audiences in document and service development" (34.9% not yet achieved). CHCs located in northern Taiwan had higher health literacy achievement scores than those in other regions, and those in urban areas had higher health literacy achievement scores than those in general and remote areas. CONCLUSIONS: This study identified items with poor implementation of OHL and found regional differences in health literacy among CHCs. The findings can inform the development of targeted interventions to improve health literacy in underperforming CHCs and guide policymakers in allocating resources to regions and areas in need of.

Interplay between diabetes mellitus and periodontal/pulpal-periapical diseases.

This longevity of life expectancy has indirectly led to an increase in the number of chronic diseases such as periodontitis, apical periodontitis (AP), and diabetes mellitus (DM) in the aging society, thus affecting people's quality of life. There is an interaction between periodontitis/AP and DM with a two-way relationship. Although type 1 and 2 diabetes (T1DM, T2DM) have different etiologies, glycemic control may affect the infection, inflammation and tissue healing of periodontitis and AP. Non-surgical periodontal treatment may influence the glycemic control as shown by decrease of HbA1c level in T2DM patient. However, the effect of periodontal treatment on glycemic control in T1DM and root canal treatment/apical surgery on T1DM and T2DM patients awaits investigation. DM may affect the periodontal and periapical tissues possibly via altered oral microbiota, impairment of neutrophils' activity and host immune responses and cytokine production, induction of oxidative stress etc. While periodontitis associated systemic inflammation and hyperlipidemia is suggested to contribute to the control of T2DM, more intricate studies are necessary to clarify the detailed mechanisms. The interactions between DM (T1DM and T2DM) and periodontitis and AP are therefore reviewed to provide a basis for the treatment of subsequent patients with pulpal/periodontal disease and diabetes. A two-pronged approach of medical and dental treatment is needed for the management of these patients, with emphasis on blood glucose control and improving oral hygiene and periodontal maintenance care, to ensure the best treatment outcome.

Gut Bifidobacterium longum is associated with better native liver survival in patients with biliary atresia.

Background & Aims: The gut microbiome plays an important role in liver diseases, but its specific impact on biliary atresia (BA) remains to be explored. We aimed to investigate the microbial signature in the early life of patients with BA and to analyze its influence on long-term outcomes. Methods: Fecal samples (n = 42) were collected from infants with BA before and after Kasai portoenterostomy (KPE). The stool microbiota was analyzed using 16S rRNA next-generation sequencing and compared with that of age-matched healthy controls (HCs). Shotgun metagenomic sequencing analysis was employed to confirm the bacterial composition in 10 fecal samples before KPE. The correlation of the microbiome signature with liver function and long-term outcomes was assessed. Results: In the 16S rRNA next-generation sequencing analysis of fecal microbiota, the alpha and beta diversity analyses revealed significant differences between HCs and patients with BA before and after KPE. The difference in microbial composition analyzed by linear discriminant analysis and random forest classification revealed that the abundance of Bifidobacterium longum (B. longum) was significantly lower in patients before and after KPE than in HCs. The abundance of B. longum was negatively correlated with the gamma-glutamyltransferase level after KPE (p <0.05). Patients with early detectable B. longum had significantly lower total and direct bilirubin 3 months after KPE (p <0.005) and had a significantly lower liver transplantation rate (hazard ratio: 0.16, 95% CI 0.03-0.83, p = 0.029). Shotgun metagenomic sequencing also revealed that patients with BA and detectable B. longum had reduced total and direct bilirubin after KPE. Conclusion: The gut microbiome of patients with BA differed from that of HCs, with a notable abundance of B. longum in early infancy correlating with better long-term outcomes. Impact and implications: Bifidobacterium longum (B. longum) is a beneficial bacterium commonly found in the human gut. It has been studied for its potential impacts on various health conditions. In patients with biliary atresia, we found that a greater abundance of B. longum in the fecal microbiome is associated with improved clinical outcomes. This suggests that early colonization and increasing B. longum levels in the gut could be a therapeutic strategy to improve the prognosis of patients with biliary atresia.

The influence of different spontaneous breathing trials on regional ventilation distribution in patients with prolonged mechanical ventilation.

OBJECTIVE: This study aimed to explore the influence of different spontaneous breathing trials (SBTs) on regional ventilation distribution in patients with prolonged mechanical ventilation (PMV). METHODS: A total of 24 patients with PMV were analyzed retrospectively. They received three different SBT modes which are automatic tube compensation (ATC), continuous positive airway pressure (CPAP), and T-piece (TP), over three days, and every SBT lasted two hours. Electrical impedance tomography (EIT) was used to monitor the SBT process and five-minute EIT data from five periods (pre-SBT which is t0, at the beginning and the end of the first hour SBT are t1 and t2, at the beginning and the end of the second hour SBT are t3 and t4) were analyzed. RESULTS: In all PMV patients, the temporal skew of aeration (TSA) values at t3 were significantly different in three SBTs (ATC: 18.18±22.97; CPAP: 20.42±17.01; TP:11.26±11.79; p=0.05). In the weaning success group, TSA (t1) values were significantly different too (ATC: 11.11±13.88; CPAP: 19.09±15.77; TP: 9.09±12.74; p=0.04). In the weaning failure group, TSA (t4) values were significantly different in three SBTs (ATC: 36.67±18.46; CPAP: 15.38±11.69; TP: 17.65±17.93; p=0.04). The patient's inspiratory effort (Global flow index at t1) in patients with weaning failure under CPAP (3.51±4.31) was significantly higher than that in the ATC (1.15±1.47) and TP (0.89±1.28). The SBT mode with the best ventilation uniformity may be the one that activates the respiratory muscles the most which may be the optimal SBT. The SBT mode of most uniform ventilation distribution settings varies from patient to patient. CONCLUSION: The regional ventilation distribution was different for each individual, making the SBT with the best ventilation distribution of patients need to be personalized. EIT is a tool that can be considered for real-time assessment.

Self-efficacy and autonomous motivation are associated with lower sugar-sweetened beverage consumption in low-income overweight and obese mothers of young children.

Sugar-sweetened beverage (SSB) consumption is strongly associated with obesity. Autonomous motivation and self-efficacy, key concepts of self-determination theory, may influence SSB consumption. Low-income mothers of young children experience disproportionate rates of obesity. Whether autonomous motivation and self-efficacy are associated with SSB consumption in low-income mothers of young children is unknown. This exploratory secondary data analysis explored whether autonomous motivation or self-efficacy were associated with SBB consumption using data from a lifestyle intervention for low-income, overweight or obese mothers with young children. Participants (N = 311) completed surveys assessing autonomous motivation, self-efficacy, and SSB consumption at baseline, after the 16-week intervention, and at 3-month follow-up. Using baseline data, we performed linear regression models to explore associations of self-efficacy and autonomous motivation with SSB consumption. We also performed mixed effects models to explore whether autonomous motivation or self-efficacy were associated with SSB consumption over time. At baseline, a one-point increase in autonomous motivation and self-efficacy were associated with 4.36 (p < 0.001) and 6.43 (p = 0.025) fewer ounces of SSB consumption per day, respectively. In longitudinal models, SSB consumption decreased over time. Change in SSB consumption was associated with self-efficacy (B = -4.88; p = 0.015) and autonomous motivation (B = -2.29; p = 0.008). Our findings suggest self-efficacy and autonomous motivation may influence SSB consumption among mothers of young children with overweight and obesity. Further investigation should explore if self-efficacy and autonomous motivation have long-term effects on SSB consumption.

Clinical experience of infantile hepatic hemangioma.

PURPOSE: To describe the clinical presentation, treatment preference, and relevant complications of infantile hepatic hemangioma (IHH) in propranolol era. METHODS: The National Taiwan University Hospital integrated Medical Database (NTUH-iMD) was used to enroll twenty-one cases of IHH diagnosed from 2006 to 2020. Medical charts were retrospectively reviewed. RESULTS: In nine patients (42.9%), IHH was found incidentally, and in seven patients (33%), it was detected during postnatal self-paid ultrasonography. Focal disease was determined in 17 patients, multifocal disease in 1 patient, and diffuse disease in 3 patients. Patients with diffuse disease had a lower hemoglobulin level than patients with focal IHH (9.38 vs. 12.6 mg/dL, p = 0.045). Two patients had Kasabach-Merritt phenomenon (KMP), one had hypothyroidism, and one had both. All patients with KMP had focal hepatic hemangiomas. Among the 17 patients with focal IHH, nine were prescribed propranolol, one was treated by surgical resection of the tumor, and the others had expectant management. All patients with multifocal and diffuse IHH were administered propranolol. One infant (7.7%) treated with propranolol had bradycardia initially but it subsided after dose adjustment. CONCLUSIONS: Most IHH is found incidentally or detected during postnatal ultrasonography screening. Patients with large focal lesions should also be screened for associated complications. Propranolol is the drug of choice and a safe therapeutic option for IHH, especially for focal tumors >5 cm as well as multifocal and diffuse lesions.

Antiretroviral Stewardship: Top 10 Questions Encountered by Stewardship Teams and Solutions to Optimize Therapy.

PURPOSE: Infectious disease pharmacists and physicians overseeing antimicrobial stewardship programs possess expertise and often advanced certification in management of antiretrovirals to treat HIV. Stewardship programs are responsible for managing facility formularies and must stay up to date with the latest antiretrovirals, including once daily formulations and depot injectables. Furthermore, stewardship program members need to understand drug-interactions, short-, and long-term toxicities of these regimens, including dyslipidemia and cardiovascular effects. Patients receiving chronic antiretroviral therapy may present to the acute care, ambulatory care, and long-term care settings. Like other antimicrobials, audit-and-feedback, drug monitoring, and dose-optimization are often required to prevent antiretroviral associated medication errors and minimize resistance. METHODS: A narrative review was conducted on antiretroviral stewardship, addressing common clinical questions encountered by stewardship teams and best practices to optimize antiretroviral therapy and reduce the risk for treatment interruptions, resistance, drug interactions, long term toxicities, and other adverse effects. FINDINGS: People living with HIV are often hospitalized and treated by medical teams without formal HIV training. For this reason, these patients are at greater risk for medication errors during hospitalization and between transitions of care. Many opportunities are present for antiretroviral stewardship to mitigate these errors. Frequent updates to simplify HIV regimen, maintain select patients on fixed-dose combination tablets, and strategies to minimize drug interactions make it difficult for even the seasoned clinician to keep up regularly. IMPLICATIONS: Despite the availability of free online HIV resources and progress made in HIV management, significant opportunities for antiretroviral stewardship remain. Implementing electronic order entry updates, formulary upgrades, and formal pharmacy renal dose adjustments to optimize antiretroviral therapy will help clinicians harness these opportunities. Dedicated time and expertise for antiretroviral stewardship as part of local antimicrobial stewardship programs are needed.

Survey of hepatitis B virus infection status after 35 years of universal vaccination implementation in Taiwan.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) vaccination programs in Taiwan are one of the earliest programs in the world and have largely reduced the prevalence of HBV infection. We aimed to demonstrate the vaccination efficacy after 35 years and identify gaps toward HBV elimination. METHODS: A total of 4717 individuals aged 1-60 years were recruited from four administrative regions based on the proportion of population distribution. Serum levels of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels were assessed. HBV viral load, genotypes and HBsAg 'ɑ' determinant variants were evaluated if indicated. RESULTS: After 35 years of vaccination, the overall seropositivity rates for HBsAg and anti-HBc in Taiwan were 4.05% and 21.3%, respectively. The vaccinated birth cohorts exhibited significantly lower seropositivity rates for both markers compared to the unvaccinated birth cohorts (HBsAg: 0.64% vs. 9.78%; anti-HBc: 2.1% vs. 53.55%, respectively; p < 0.0001). Maternal transmission was identified as the main route of HBV infection in breakthrough cases. Additionally, increased prevalences of genotype C and HBsAg escape mutants were observed. CONCLUSION: The 35-year universal HBV vaccination program effectively reduced the burden of HBV infection, but complete eradication of HBV infection has not yet been achieved. In addition to immunization, comprehensive screening and antiviral therapy for infected individuals, especially for pregnant women, are crucial strategies to eliminate HBV.

Lhx2 promotes axon regeneration of adult retinal ganglion cells and rescues neurodegeneration in mouse models of glaucoma.

The axons of retinal ganglion cells (RGCs) form the optic nerve, transmitting visual information from the eye to the brain. Damage or loss of RGCs and their axons is the leading cause of visual functional defects in traumatic injury and degenerative diseases such as glaucoma. However, there are no effective clinical treatments for nerve damage in these neurodegenerative diseases. Here, we report that LIM homeodomain transcription factor Lhx2 promotes RGC survival and axon regeneration in multiple animal models mimicking glaucoma disease. Furthermore, following N-methyl-D-aspartate (NMDA)-induced excitotoxicity damage of RGCs, Lhx2 mitigates the loss of visual signal transduction. Mechanistic analysis revealed that overexpression of Lhx2 supports axon regeneration by systematically regulating the transcription of regeneration-related genes and inhibiting transcription of Semaphorin 3C (Sema3C). Collectively, our studies identify a critical role of Lhx2 in promoting RGC survival and axon regeneration, providing a promising neural repair strategy for glaucomatous neurodegeneration.

Transcriptome Deconvolution Reveals Absence of Cancer Cell Expression Signature in Immune Checkpoint Blockade Response.

Immune checkpoint therapy (ICB) has conferred significant and durable clinical benefit to some patients with cancer. However, most patients do not respond to ICB, and reliable biomarkers of ICB response are needed to improve patient stratification. Here, we performed a transcriptome-wide meta-analysis across 1,486 tumors from ICB-treated patients and tumors with expected ICB outcomes based on microsatellite status. Using a robust transcriptome deconvolution approach, we inferred cancer- and stroma-specific gene expression differences and identified cell-type specific features of ICB response across cancer types. Consistent with current knowledge, stromal expression of CXCL9, CXCL13, and IFNG were the top determinants of favorable ICB response. In addition, we identified a group of potential immune-suppressive genes, including FCER1A, associated with poor response to ICB. Strikingly, PD-L1 expression in stromal cells, but not cancer cells, is correlated with ICB response across cancer types. Furthermore, the unbiased transcriptome-wide analysis failed to identify cancer-cell intrinsic expression signatures of ICB response conserved across tumor types, suggesting that cancer cells lack tissue-agnostic transcriptomic features of ICB response. SIGNIFICANCE: Our results challenge the prevailing dogma that cancer cells present tissue-agnostic molecular markers that modulate immune activity and ICB response, which has implications on the development of improved ICB diagnostics and treatments.

Relationship between orofacial dysfunction and orofacial features, oral function, and eating performance among preschool children.

Background/purpose: Orofacial (OF) development is influenced by multiple factors. This study aimed to explore the relationship between OF dysfunction (OFD) and OF features, oral function, and eating performance among preschool children. Materials and methods: There were 243 preschool children and their parents who participated in this cross-sectional study. Participant demographic information and eating performance were obtained from questionnaires completed by their mothers. OF features and functions were assessed using oral examinations. OFD assessments were performed using Nordic Orofacial Test-Screening (NOT-S). Results: Approximately 80% of participants had at least one domain of NOT-S affected. The main OFD in a structured interview was chewing and swallowing (64.61%). Dysarthria (40.38%), weak bite force (53.85%), inability to effectively chew (45.19%), and taking longer than 30 min to eat meals (75.00%) were significantly more prevalent among participants with OFD than among those without OFD (all P < 0.05). Also, compared with participants born full-term, those born prematurely and who had OFD had higher rates of V-shaped dental arch (42.11%), high-arched palate (31.58%), small mouth opening capacity (7.89%), dysarthria (65.79%), preference to eating soft-textured food (42.11%), and weak cough strength (21.05%). Taking longer than 30 min to eat meals (adjusted odds ratio (AOR = 8.87, P < 0.001) and not effectively chewing food (AOR = 8.81, P < 0.001) were significantly associated with OFD. Conclusion: Chewing and swallowing and habits are common among preschool children and associated with OFD. OFD is associated with OF features, and presented in oral function and eating performance.

Inducing cyclooxygenase-2 expression, prostaglandin E2 and prostaglandin F2α production of human dental pulp cells by activation of toll-like receptor-3, mitogen-activated protein kinase kinase/extracellular signal-regulated kinase and p38 signaling.

Background/purpose: Bacterial infection was the major etiology for pulpal/root canal infection. This study aimed to investigate the activation of toll-like receptor-3 (TLR) on cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) and PGF2α production of human dental pulp cells (HDPCs) and associated signaling. Materials and methods: HDPCs were exposed to different concentrations of Poly (I:C) (a TLR3 activator). Cell viability was determined by 3- (4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and alkaline phosphatase (ALP) activity was evaluated by ALP staining. Activation of extracellular signal-regulated kinase (ERK) and p38 by Poly (I:C) was determined by immunofluorescent staining. The COX-2 protein expression was analyzed by Western blot. PGE2 and PGF2α production was measured by enzyme-linked immunosorbent assay. The mRNA expression was studied by real-time polymerase-chain reaction. Moreover, HDPCs were exposed to Poly(I:C) with/without U0126 or SB203580 treatment and analysis of COX-2 expression and prostanoid production were conducted. Results: Poly (I:C) showed little effect on ALP activity, but decreased viability of HDPCs. It stimulated COX-2 mRNA and protein expression. Poly (I:C) induced PGE2 and PGF2α production of HDPCs. Poly (I:C) activated p-ERK, and p-p38 protein expression. Treatment by U0126 (a mitogen-activated protein kinase kinase (MEK)/ERK inhibitor) and SB203580 (a p38 inhibitor) attenuated Poly (I:C)-induced COX-2 mRNA and protein expression as well as PGE2 and PGF2α production. Conclusion: TLR3 activation is involved in the infection and inflammatory responses of pulp tissues, via MEK/ERK, and p38 signaling to mediate COX-2 expression as well as PGE2 and PGF2α production, contributing to the pathogenesis and progression of pulpal/periapical diseases.

The incidence of Clostridium difficile infection in children with and without inflammatory bowel diseases: A single-center study in Taiwan from 2006 to 2019.

BACKGROUND: The incidence of Clostridium difficile infection (CDI) is increasing around the world, and patients with inflammatory bowel disease (IBD) have a higher risk of obtaining CDI. The data on the incidence rate of CDI in the Asian pediatric IBD population was lacking. METHODS: We retrospectively collected data from a tertiary medical center in Taipei, Taiwan. All patients aged 1-18 years old who visited the outpatient department or were admitted to our hospital between 2006 and 2019 were included. CDI was defined as positive stool C. difficile toxin or C. difficile culture results with appropriate antibiotic use within the range of 7 days prior or 14 days after the result. RESULTS: We compared the average annual incidence of CDI before and after 2013. The average incidence of community-acquired CDI (CA-CDI) increased from 0.063 to 0.564 cases per 1,000 visits, with a rate ratio (RR) of 8.82 (95% CI 5.74-14.38). In patients with IBD, the rate increased from 26.738 to 278.873 cases per 1,000 visits (RR=10.12, 95% CI: 4.57-29.02). The average incidence rate increased from 0.685 to 1.874 cases per 1,000 admissions in pediatric general patients (RR = 2.72, 95% CI 1.82-4.20) and from 14.706 to 62.500 cases per 1,000 admissions in pediatric IBD patients (RR = 3.77, 95% CI 0.71-93.53). CONCLUSIONS: Both CA-CDI and healthcare facility-onset CDI (HO-CDI) were increasing substantially in the pediatric population over the past decade in Taiwan. Compared to the general pediatric population, pediatric IBD patients had a much higher incidence of CDI.

Optimization of Mother-to-Child Hepatitis B Virus Prevention Program: Integration of Maternal Screening and Infant Post-Vaccination Serologic Testing.

BACKGROUND: Evaluation of the impact of a hepatitis B virus (HBV) prevention program that incorporates maternal antiviral prophylaxis on mother-to-child transmission (MTCT) is limited using real-world data. METHODS: We analyzed data on maternal HBV screening, neonatal immunization, and post-vaccination serologic testing (PVST) for hepatitis B surface antigen (HBsAg) among at-risk infants born to HBV carrier mothers from the National Immunization Information System during 2008-2022. Through linkage with the National Health Insurance Database, information on maternal antiviral therapy was obtained. Multivariate logistic regression was performed to explore MTCT risk in relation to infant-mother characteristics and prevention strategies. RESULTS: In total, 2 460 218 deliveries with maternal HBV status were screened. Between 2008 and 2022, the annual HBsAg and hepatitis B e antigen (HBeAg) seropositivity rates among native pregnant women decreased from 12.2% to 2.6% and from 2.7% to 0.4%, respectively (P for both trends < .0001). Among the 22 859 at-risk infants who underwent PVST, the MTCT rates differed between infants born to HBsAg-positive/HBeAg-negative and HBeAg-positive mothers (0.75% and 6.33%, respectively; P < .001). MTCT risk increased with maternal HBeAg positivity (odds ratio [OR], 9.29; 95% confidence interval [CI], 6.79-12.73) and decreased with maternal antiviral prophylaxis (OR, 0.28; 95% CI, .16-.49). For infants with maternal HBeAg positivity, MTCT risk was associated with mothers born in the immunization era (OR, 1.40; 95% CI, 1.17-1.67). CONCLUSIONS: MTCT was related to maternal HBeAg positivity and effectively prevented by maternal prophylaxis in the immunized population. At-risk infants born to maternal vaccinated cohorts might possibly pose further risk.

Optimizing analytical precision in the identification of synthetic cathinones and isomers: a comparative assessment of diverse GC-MS operating parameters.

Analyzing new psychoactive substances (NPSs) in forensic laboratories present a formidable challenge globally. Within illicit drug analysis, gas chromatography-mass spectrometry (GC-MS) emerges as a robust analytical tool. This study endeavors to assess and compare peak resolution in the analysis of illicit drugs, specifically focusing on 21 synthetic cathinones, encompassing 9 cathinone isomers. Varied GC-MS operating conditions, including distinct GC-MS columns and thermal gradients, were systematically employed for the simultaneous analysis of these synthetic cathinones. The study utilized HP-1 nonpolar and HP-5MS low-bleed columns to achieve optimal analyte resolution through modulation of GC-MS oven conditions. Mass spectra were meticulously recorded within a mass-to-charge (m/z) range spanning from 40 to 500 in full scan mode. The data showed that the cathinone isomers slightly differed in retention times and mass spectra. The GC oven conditions affected the peak resolution for chromatographic separation even with the same column. The peak resolution improved using a slower thermal gradient heat speed with a prolonged analysis time. Conclusively, the interplay of GC columns and thermal gradients emerged as pivotal factors impacting peak resolution in the analysis of illicit drugs. These empirical insights contribute to a nuanced understanding of peak resolution dynamics and facilitate the identification of synthetic cathinones, including their isomers, in seized materials through the judicious application of GC-MS methodologies.