A randomized controlled trial of an app-based intervention on physical activity and glycemic control in people with type 2 diabetes.

BACKGROUND: We investigated the effects of a physical activity encouragement intervention based on a smartphone personal health record (PHR) application (app) on step count increases, glycemic control, and body weight in patients with type 2 diabetes (T2D). METHODS: In this 12-week, single-center, randomized controlled, 12-week extension study, patients with T2D who were overweight or obese were randomized using ratio 1:2 to a group using a smartphone PHR app (control group) or group using the app and received individualized motivational text messages (intervention group) for 12 weeks. During the extension period, the sending of the encouraging text messages to the intervention group was discontinued. The primary outcome was a change in daily step count after 12 weeks and analyzed by independent t-test. The secondary outcomes included HbA1c, fasting glucose, and body weight analyzed by paired or independent t-test. RESULTS: Of 200 participants, 62 (93.9%) and 118 (88.1%) in the control and intervention group, respectively, completed the 12-week main study. The change in daily step count from baseline to week 12 was not significantly different between the two groups (P = 0.365). Among participants with baseline step counts < 7,500 steps per day, the change in the mean daily step count at week 12 in the intervention group (1,319 ± 3,020) was significantly larger than that in control group (-139 ± 2,309) (P = 0.009). At week 12, HbA1c in the intervention group (6.7 ± 0.5%) was significantly lower than that in control group (6.9 ± 0.6%, P = 0.041) and at week 24, changes in HbA1c from baseline were significant in both groups but, comparable between groups. Decrease in HbA1c from baseline to week 12 of intervention group was greater in participants with baseline HbA1c ≥ 7.5% (-0.81 ± 0.84%) compared with those with baseline HbA1c < 7.5% (-0.22 ± 0.39%) (P for interaction = 0.014). A significant reduction in body weight from baseline to week 24 was observed in both groups without significant between-group differences (P = 0.370). CONCLUSIONS: App-based individualized motivational intervention for physical activity did not increase daily step count from baseline to week 12, and the changes in HbA1c levels from baseline to week 12 were comparable. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03407222).

Novel Personalized Cancer Vaccine Using Tumor Extracellular Vesicles with Attenuated Tumorigenicity and Enhanced Immunogenicity.

Cancer vaccines offer a promising avenue in cancer immunotherapy by inducing systemic, tumor-specific immune responses. Tumor extracellular vesicles (TEVs) are nanoparticles naturally laden with tumor antigens, making them appealing for vaccine development. However, their inherent malignant properties from the original tumor cells limit their direct therapeutic use. This study introduces a novel approach to repurpose TEVs as potent personalized cancer vaccines. The study shows that inhibition of both YAP and autophagy not only diminishes the malignancy-associated traits of TEVs but also enhances their immunogenic attributes by enriching their load of tumor antigens and adjuvants. These revamped TEVs, termed attenuated yet immunogenically potentiated TEVs (AI-TEVs), showcase potential in inhibiting tumor growth, both as a preventive measure and a possible treatment for recurrent cancers. They prompt a tumor-specific and enduring immune memory. In addition, by showing that AI-TEVs can counteract cancer growth in a personalized vaccine approach, a potential strategy is presented for developing postoperative cancer immunotherapy that's enduring and tailored to individual patients.

Prior pneumococcal vaccination improves in-hospital mortality among elderly population hospitalized due to community-acquired pneumonia.

BACKGROUND: Pneumococcal vaccination is a preventive method to reduce pneumonia related mortality. However, real-world data on efficacy of the pneumococcal vaccine in reducing mortality is lacking, especially in elderly patients. This study was conducted to assess the effects of prior pneumococcal vaccination in elderly pneumonia patients. METHODS: The data was procured from the Health Insurance Review and Assessment and Quality Assessment database. Hospitalized patients who met the criteria of community-acquired pneumonia (CAP) were included and they were grouped according to vaccination state. Patients were aged ≥ 65 years and treated with beta-lactam, quinolone, or macrolide. Patients were excluded when treatment outcomes were unknown. RESULTS: A total of 4515 patients were evaluated, and 1609 (35.6%) of them were vaccinated prior to hospitalization. Mean age was 77.0 [71.0;82.0], 54.2% of them were male, and mean Charlson comorbidity index (CCI) was 3.0. The patients in the vaccinated group were younger than those in the unvaccinated group (76.0 vs. 78.0 years; P < 0.001), and showed higher in-hospital improvement (97.6 vs. 95.0%; P < 0.001) and lower 30-day mortality (2.6 vs. 5.3%; P < 0.001). After adjusting confounding factors such as age, gender, CURB score and CCI score, the vaccinated group demonstrated a significant reduction in 30-day mortality (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.41-0.81; P < 0.01) and in-hospital mortality (HR 0.53, 95% CI0.37-0.78; P < 0.001) compared to the unvaccinated group in multivariate analysis. Vaccinated group showed better 30-day survival than those in non-vaccinated group (log-rank test < 0.05). CONCLUSIONS: Among elderly hospitalized CAP patients, prior pneumococcal vaccination was associated with improved in-hospital mortality and 30-day mortality.

Association between total cholesterol levels and all-cause mortality among newly diagnosed patients with cancer.

We aimed to determine the association between cholesterol values and the risk of all-cause mortality in newly diagnosed patients with cancer in a large-scale longitudinal cohort. Newly diagnosed patients with cancer were reviewed retrospectively. Cox proportional hazards regression models determined the association between baseline levels of total cholesterol (TC), triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol and the risk of all-cause mortality. A restricted cubic spline curve was used to identify the association between total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol with the risk of death on a continuous scale and to present the lowest values of lipid measurements associated with death. The median follow-up duration of the study was 5.77 years. Of the 59,217 patients with cancer, 12,624 patients were expired. The multivariable adjusted hazard ratio (aHR) for all-cause mortality in patients with cancer with 1st-5th (≤ 97 mg/dL) and 96th-100th (> 233 mg/dL) in TC levels was 1.54 (95% CI 1.43-1.66) and 1.28 (95% CI 1.16-1.41), respectively, compared to 61st-80th (172-196 mg/dL). The TC level associated with the lowest mortality risk in the multivariable model was 181 mg/dL. In comparison with LDL-C levels in the 61st-80th (115-136 mg/dL), the multivariable aHR for all-cause mortality in cancer patients with LDL-C levels in the 1st-5th (≤ 57 mg/dL) and 96th-100th (> 167 mg/dL) was 1.38 (95% CI 1.14-1.68) and 0.94 (95% CI 0.69-1.28), respectively. The 142 mg/dL of LDL cholesterol showed the lowest mortality risk. We demonstrated a U-shaped relationship between TC levels at baseline and risk of mortality in newly diagnosed patients with cancer. Low LDL levels corresponded to an increased risk of all-cause death.

Unusual Base Pair between Two 2-Thiouridines and Its Implication for Nonenzymatic RNA Copying.

2-Thiouridine (s2U) is a nucleobase modification that confers enhanced efficiency and fidelity both on modern tRNA codon translation and on nonenzymatic and ribozyme-catalyzed RNA copying. We have discovered an unusual base pair between two 2-thiouridines that stabilizes an RNA duplex to a degree that is comparable to that of a native A:U base pair. High-resolution crystal structures indicate similar base-pairing geometry and stacking interactions in duplexes containing s2U:s2U compared to those with U:U pairs. Notably, the C═O···H-N hydrogen bond in the U:U pair is replaced with a C═S···H-N hydrogen bond in the s2U:s2U base pair. The thermodynamic stability of the s2U:s2U base pair suggested that this self-pairing might lead to an increased error frequency during nonenzymatic RNA copying. However, competition experiments show that s2U:s2U base-pairing induces only a low level of misincorporation during nonenzymatic RNA template copying because the correct A:s2U base pair outcompetes the slightly weaker s2U:s2U base pair. In addition, even if an s2U is incorrectly incorporated, the addition of the next base is greatly hindered. This strong stalling effect would further increase the effective fidelity of nonenzymatic RNA copying with s2U. Our findings suggest that s2U may enhance the rate and extent of nonenzymatic copying with only a minimal cost in fidelity.

Autoimmune disorders reported following COVID-19 vaccination: A disproportionality analysis using the WHO database.

PURPOSE: Owing to adverse event following immunization (AEFI) related to autoimmune disorders and coronavirus disease 2019 (COVID-19) vaccines sharing common biological mechanisms, identifying the risk of AEFIs associated with COVID-19 vaccines remains a critical unmet need. We aimed to assess the potential safety signals for 16 AEFIs and explore co-reported adverse events (AEs) and drugs using the global database of the World Health Organization, VigiBase. METHODS: We assessed the occurrence of 16 AEFIs following COVID-19 vaccination through the Standardized MedDRA Queries group "Immune-mediated/Autoimmune Disorders" from MedDRA and performed a disproportionality analysis using reporting odds ratio (ROR) and information component (IC) with 95% confidence intervals (CIs). RESULTS: We identified 25,219 events associated with COVID-19 vaccines in VigiBase. Although rare, we detected four potential safety signals related to autoimmune disorders following COVID-19 vaccination, including ankylosing spondylitis or psoriatic arthritis (ROR 1.86; 95% CI 1.53-2.27), inflammatory bowel disease (ROR 1.77; 95% CI 1.60-1.96), polymyalgia rheumatica (ROR 1.42; 95% CI 1.30-1.55), and thyroiditis (ROR 1.40; 95% CI 1.30-1.50), with positive IC025 values. The top co-reported AEs were musculoskeletal disorders, and immunosuppressants were the most representative co-reported drugs. CONCLUSION: In addressing the imperative to comprehend AEFI related to autoimmune disorders following COVID-19 vaccination, our study identified four potential safety signals. Thus, our research underscores the importance of proactive safety monitoring for the identification of the four AEFIs following COVID-19 vaccination, considering the associated advantages.

COVID-19 and Adolescent Outpatient Mental Health Service Utilization.

OBJECTIVE: The COVID-19 pandemic created challenges in accessing mental health (MH) services when adolescent well-being declined. Still, little is known about how the COVID-19 pandemic affected outpatient MH service utilization for adolescents. METHODS: Retrospective data were collected from electronic medical records of adolescents aged 12-17 years at Kaiser Permanente Mid-Atlantic States, an integrated health care system from January 2019 to December 2021. MH diagnoses included anxiety, mood disorder/depression, anxiety and mood disorder/depression, attention-deficit/hyperactivity disorder, or psychosis. We used interrupted time series analysis to compare MH visits and psychopharmaceutical prescribing before and after the COVID-19 onset. Analyses were stratified by demographics and visit modality. RESULTS: The study population of 8121 adolescents with MH visits resulted in a total of 61,971 (28.1%) of the 220,271 outpatient visits associated with an MH diagnosis. During 15,771 (7.2%) adolescent outpatient visits psychotropic medications were prescribed. The increasing rate of MH visits prior to COVID-19 was unaffected by COVID-19 onset; however, in-person visits declined by 230.5 visits per week (P < .001) from 274.5 visits per week coupled with a rise in virtual modalities. Rates of MH visits during the COVID-19 pandemic differed by sex, mental health diagnosis, and racial and ethnic identity. Psychopharmaceutical prescribing during MH visits declined beyond expected values by a mean of 32.8 visits per week (P < .001) at the start of the COVID-19 pandemic. CONCLUSIONS: A sustained switch to virtual visits highlights a new paradigm in care modalities for adolescents. Psychopharmaceutical prescribing declined requiring further qualitative assessments to improve the quality of access for adolescent MH.

Exploring examinees' responses to constructed response items with a supervised topic model.

Textual data are increasingly common in test data as many assessments include constructed response (CR) items as indicators of participants' understanding. The development of techniques based on natural language processing has made it possible for researchers to rapidly analyse large sets of textual data. One family of statistical techniques for this purpose are probabilistic topic models. Topic modelling is a technique for detecting the latent topic structure in a collection of documents and has been widely used to analyse texts in a variety of areas. The detected topics can reveal primary themes in the documents, and the relative use of topics can be useful in investigating the variability of the documents. Supervised latent Dirichlet allocation (SLDA) is a popular topic model in that family that jointly models textual data and paired responses such as could occur with participants' textual answers to CR items and their rubric-based scores. SLDA has an assumption of a homogeneous relationship between textual data and paired responses across all documents. This approach, while useful for some purposes, may not be satisfied for situations in which a population has subgroups that have different relationships. In this study, we introduce a new supervised topic model that incorporates finite-mixture modelling into the SLDA. This new model can detect latent groups of participants that have different relationships between their textual responses and associated scores. The model is illustrated with an example from an analysis of a set of textual responses and paired scores from a middle grades assessment of science inquiry knowledge. A simulation study is presented to investigate the performance of the proposed model under practical testing conditions.

Safety and efficacy of tenalisib in combination with romidepsin in patients with relapsed/refractory T-cell lymphoma: results from a phase I/II open-label multicenter study.

Tenalisib, a selective phosphoinositide-3-kinase δ/γ, and salt-inducible-kinase-3 inhibitor has shown efficacy and was well-tolerated in patients with T-cell lymphoma (TCL). In vitro studies suggest a synergistic anti-tumor potential for the combination of tenalisib with the histone-deacetylase inhibitor, romidepsin. This multicenter, open-label, phase I/II study was designed to characterize the safety, efficacy and pharmacokinetics of oral tenalisib twice-daily and intravenous romidepsin administered on days 1, 8 and 15 in 28-day cycles in adults with relapsed/refractory TCL. Phase I/dose escalation determined the maximum tolerated dose (MTD)/optimal doses of tenalisib and romidepsin. The phase II/dose expansion assessed the safety and anti-tumor activity of the combination at MTD/optimal dose. Overall, 33 patients were enrolled. In dose escalation, no dose-limiting toxicity was identified. Hence, the recommended doses for dose expansion were tenalisib 800 mg twice daily orally, and romidepsin 14 mg/m2 intravenous. Overall treatment-emergent adverse events of any grade reported in >15% of patients were nausea, thrombocytopenia, increased aspartate aminotransferase, increased alanine aminotransferase, decreased appetite, neutropenia, vomiting, fatigue, anemia, dysgeusia, weight loss, diarrhea, and hypokalemia. Twenty-three patients (69.7%) had related grade ≥3 treatment-emergent adverse events. The overall objective response rate in evaluable patients was 63.0% (peripheral TCL: 75% and cutaneous TCL: 53.3%), with a complete response and partial response of 25.9% and 37.0% respectively. The median duration of response was 5.03 months. Co-administration of tenalisib and romidepsin did not significantly alter the pharmacokinetics of romidepsin. Overall, tenalisib and romidepsin combination demonstrated a favorable safety and efficacy profile supporting its further development for relapsed/refractory TCL (clinicaltrials gov. Identifier: NCT03770000).

Increased risk of incident mental disorders in adults with new-onset type 1 diabetes diagnosed after the age of 19: A nationwide cohort study.

AIM: This population-based study aimed to investigate the risk of mental disorders in adults with new-onset type 1 diabetes mellitus compared to the general population without diabetes. METHODS: We selected 10,391 adults with new-onset type 1 diabetes and 51,995 adults in the general population without diabetes with a median follow-up of 7.94 years using the National Health Insurance Database in South Korea between January 2009 and December 2020. The adjusted hazard ratios (aHRs) were estimated for the occurrence of mental disorders. RESULTS: The incidence of mental disorders was more than twice as high in patients with new-onset type 1 diabetes (66 per 1000 person-years) than in those without diabetes (29 per 1000 person-years). The aHR [95 % confidence interval] comparing adults with new-onset type 1 diabetes with those without diabetes were 2.20 [2.12.2.29] for mental disorders, 3.16 [2.99.3.35], for depression, 2.55 [2.32.2.80] for mood disorders, 1.89 [1.80.1.97] for anxiety and stress related disorders, 2.50 [1.48.4.22] for eating disorders, 2.62 [1.45.4.73] for personality and behavior disorders and 4.39 [3.55.5.43] for alcohol and drug misuse disorders. When new-onset type 1 diabetes occurred at the age of 41 to 50, the aHR of developing mental illness was 2.43 [2.19.2.70], compared to those without diabetes. CONCLUSIONS: In this nationwide prospective study, new-onset type 1 diabetes in adulthood was significantly associated with a higher risk of mental disorders than in the general population without diabetes.

Association between lipid variability and the risk of mortality in cancer patients not receiving lipid-lowering agents.

Aim: We investigated the association between total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride (TG) variability and cancer patient mortality risk. Methods: We retrospectively analyzed 42,539 cancer patients who were not receiving lipid-lowering agents and who had at least three TC measurements within 2 years of their initial cancer diagnosis. Using a multivariable Cox regression model, the risk of mortality was evaluated. Results: In multivariable analysis, Q2 (adjusted hazard ratio [aHR]: 1.32, 95% confidence interval (CI): 1.24-1.41), Q3 (aHR: 1.66, 95% CI: 1.56-1.76), and Q4 (aHR: 1.96, 95% CI: 1.84-2.08) of coefficient of variation (CV) in TC were significantly associated with mortality risk compared to Q1, showing a linear association between higher TC variability and mortality (P for trend<0.001). Q2 (aHR: 1.34, 95% CI: 1.06-1.77), Q3 (aHR: 1.40, 95% CI: 1.06-1.85), and Q4 (aHR: 1.50, 95% CI: 1.14-1.97) were all significantly associated with a higher risk of death compared to Q1 in multivariable Cox regression for the association between CV in LDL and all-cause mortality (P for trend=0.005). Conclusion: In cancer patients who do not receive lipid-lowering agents, high variability in total cholesterol and LDL cholesterol levels was found to pose significant role in mortality risk.

Bone-modifying agents for non-small-cell lung cancer patients with bone metastases during the era of immune checkpoint inhibitors: A narrative review.

During the course of lung cancer progression, bone metastases occur in about 40% of patients. Common complications associated with bone metastases in lung cancer patients include musculoskeletal pain, pathologic fractures, spinal cord compression, and hypercalcemia. We discuss the efficacy of bone-modifying agents (BMAs) in reducing skeletal-related events (SREs) and improving cancer-related outcomes, particularly in patients with stage IV non-small-cell lung cancer with bone metastases. In addition, the combined effects of BMAs with radiotherapy or immunotherapy in reducing SREs in patients with lung cancer and bone metastases are explored.

CD1-mediated immune responses in mucosal tissues: molecular mechanisms underlying lipid antigen presentation system.

The cluster of differentiation 1 (CD1) molecule differs from major histocompatibility complex class I and II because it presents glycolipid/lipid antigens. Moreover, the CD1-restricted T cells that recognize these self and foreign antigens participate in both innate and adaptive immune responses. CD1s are constitutively expressed by professional and nonprofessional antigen-presenting cells in mucosal tissues, namely, the skin, lung, and intestine. This suggests that CD1-reactive T cells are involved in the immune responses of these tissues. Indeed, evidence suggests that these cells play important roles in diverse diseases, such as inflammation, autoimmune disease, and infection. Recent studies elucidating the molecular mechanisms by which CD1 presents lipid antigens suggest that defects in these mechanisms could contribute to the activities of CD1-reactive T cells. Thus, improving our understanding of these mechanisms could lead to new and effective therapeutic approaches to CD1-associated diseases. In this review, we discuss the CD1-mediated antigen presentation system and its roles in mucosal tissue immunity.

Clinical, Electrophysiological, and Sonographic Findings in Patients With Nerve Injury After Vessel Puncture.

BACKGROUND AND PURPOSE: This study aimed to describe the clinical, electrophysiological, and ultrasonographic findings of patients with nerve injury after vessel puncture. METHODS: Data on ten patients (three males and seven females) with nerve injury after vessel puncture were reviewed. Demographic and clinical data were analyzed retrospectively. Bilateral electrophysiological studies were performed based on clinical findings. Ultrasonographic examinations were performed on both the affected and unaffected sides of the injured nerve. RESULTS: The nerves of nine patients were injured following vein puncture, and injury occurred following arterial sampling in one patient. Seven patients had superficial radial sensory nerve injury: five medial, one lateral, and one at both branches. One patient had injury to the dorsal ulnar cutaneous nerve, one to the lateral antebrachial cutaneous nerve, and one to the median nerve. Nerve conduction studies produced abnormal findings in 80% of patients, whereas ultrasonographic examinations produced abnormal findings in all of the patients. Spearman's coefficient for the correlation between the amplitude ratio and nerve cross-sectional area ratio was not significant, at -0.127 (95% confidence interval=-0.701 to 0.546, p=0.721). CONCLUSIONS: Ultrasonography supported by electrodiagnosis was found to be a useful method for identifying the lesion location and structural abnormalities of vessel-puncture-related neuropathy.

The Differential Impact of Neglectful and Intrusive Parenting Behavior on Adolescents' Relationships with Peers and Teachers Using Longitudinal data: Mediating Effects of Depression and Social Withdrawal.

This study used longitudinal data to verify the mediating effects of depression and social withdrawal on the impacts of neglectful and intrusive parenting behavior on adolescents' interpersonal relationships with peers and teachers in school. We used data from the Korea Children and Youth Panel Survey's (KCYPS, 2010) 4-6th waves, which followed fourth graders across Korea. To analyze the data, we conducted a descriptive analysis, bivariate correlation analysis, and structural equation modeling. Specifically, the results showed that depression and social withdrawal had a greater indirect effect on the link between neglectful parenting behavior and relationships with peers and/or teachers than did intrusive parenting behavior. Based on these findings, we also highlighted the importance of parenting behavior in improving relationships with peers and teachers as well as the need for tailored interventions based on adolescents' degree of depression and social withdrawal.

Impact of continuous glucose monitoring on glycemic control and its derived metrics in type 1 diabetes: a longitudinal study.

Aim: We explored the effectiveness of continuous glucose monitoring for 1 year on glycated A1c reduction in adults with type 1 diabetes mellitus. Methods: We included type 1 diabetes mellitus adults who were either new continuous glucose monitoring users (N = 155) or non-users who were under standard care (N = 384). Glycated A1c was measured at baseline and 3, 6, 9, and 12 months. Individuals with (N = 155) or without continuous glucose monitoring use (N = 310) were matched 1:2 by propensity score. We used the linear mixed models to identify the quantitative reduction in repeated measures of glycated A1c. Results: The change in glycated A1c from baseline to 12 months was -0.5% ± 1.0% for the continuous glucose monitoring user group (N = 155, P < 0.001) and -0.01% ± 1.0% for the non-user group (N = 310, P = 0.816), with a significant difference between the two groups (P = 0.003). Changes in glycated A1c were significant at 3, 6, 9, and 12 months compared with those at baseline in patients using continuous glucose monitoring (P < 0.001), and the changes differed significantly between the groups (P < 0.001). A linear mixed model showed an adjusted treatment group difference in mean reduction in glycated A1c of -0.11% (95% confidence interval, -0.16 to -0.06) each three months. In the continuous glucose monitoring user group, those who achieved more than 70% of time in range significantly increased from 3 months (37.4%) to 12 months (48.2%) (P < 0.001). Conclusion: In this longitudinal study of type 1 diabetes mellitus adults, the use of continuous glucose monitoring for 1 year showed a significant reduction in glycated A1c in real-world practice.

Harnessing Oncolytic Extracellular Vesicles for Tumor Cell-Preferential Cytoplasmic Delivery of Misfolded Proteins for Cancer Immunotherapy.

In this study, extracellular vesicles (EVs) are reimagined as more than just a cellular waste disposal system and are repurposed for cancer immunotherapy. Potent oncolytic EVs (bRSVF-EVs) loaded with misfolded proteins (MPs) are engineered, which are typically considered cellular debris. By impairing lysosomal function using bafilomycin A1 and expressing the respiratory syncytial virus F protein, a viral fusogen, MPs are successfully loaded into the EVs expressing RSVF. bRSVF-EVs preferentially transplant a xenogeneic antigen onto cancer cell membranes in a nucleolin-dependent manner, triggering an innate immune response. Furthermore, bRSVF-EV-mediated direct delivery of MPs into the cancer cell cytoplasm initiates endoplasmic reticulum stress and immunogenic cell death (ICD). This mechanism of action leads to substantial antitumor immune responses in murine tumor models. Importantly, when combined with PD-1 blockade, bRSVF-EV treatment elicits robust antitumor immunity, resulting in prolonged survival and complete remission in some cases. Overall, the findings demonstrate that utilizing tumor-targeting oncolytic EVs for direct cytoplasmic delivery of MPs to induce ICD in cancer cells represents a promising approach for enhancing durable antitumor immunity.

Family Structure and Adolescent Mental Health Service Utilization During the COVID-19 Pandemic.

PURPOSE: This study evaluated the relationship between sociodemographic factors including family structure and mental health service (MHS) utilization before and during the COVID-19 pandemic. We also investigated the moderation effects of the COVID-19 pandemic on MHS utilization. METHODS: Our retrospective cohort study analyzed adolescents aged 12-17 years with a mental health diagnosis as identified in the electronic medical record enrolled in Kaiser Permanente Mid-Atlantic States in Maryland and Virginia, a comprehensive integrated health system. We used logistic regression models with an interaction term for the COVID-19 pandemic year to determine the relationship between family structure and adolescent MHS utilization ≥ one outpatient behavioral health visit within the measurement year, while adjusting for age, chronic medical condition (= physical illness lasting > 12 months), mental health condition, race, sex, and state of residence. RESULTS: Among 5,420 adolescents, only those in two-parent households significantly increased MHS utilization during COVID-19 compared to the prepandemic year (McNemar's χ2 = 9.24, p < .01); however, family structure was not a significant predictor. Overall, the odds of adolescents using MHS were associated with a 12% increase during COVID-19 (odds ratio 1.12, 95% confidence interval [CI]: 1.02-1.22, p < .01). Higher odds of using MHS was associated with chronic medical condition (adjusted odds ratio = 1.15; 95% CI: 1.05-1.26, p < .01) and with White adolescents compared to all racial/ethnic minorities. The odds ratio of females using MHS compared to their male counterparts increased by 63% (ratio of adjusted odds ratio = 1.63; 95% CI: 1.39-1.91, p < .01) during the COVID-19 pandemic. DISCUSSION: Individual-level demographic factors served as predictors of MHS utilization with effects moderated by COVID-19.

Tiotropium Bromide Improves Neutrophilic Asthma by Recovering Histone Deacetylase 2 Activity.

BACKGROUND: The value of tiotropium bromide (TIO) in neutrophilic asthma was meaningful in previous study. We hypothesized that TIO's mechanism of action is associated with histone deacetylase 2 (HDAC2) activity, which is key for controlling the transcription of inflammatory cytokines and usually downregulated in neutrophilic asthma. METHODS: The effects of TIO and dexamethasone (DEX) on HDAC2 activity, nuclear factor kappa B (NF-κB), and C-X-C motif chemokine ligand 1 (CXCL1) were evaluated in neutrophilic asthma mouse model (C57BL, 6-week-old). An in-vitro study was conducted using primary human bronchial/tracheal epithelial (HBE) cells from asthma patients. Western blot analyses were performed for phospho-phospholipase Cγ-1 (PLCγ-1) and inositol trisphosphate (IP3) receptors (IP3R) with treating lipopolysaccharide (LPS) and TIO. RESULTS: Ovalbumin was used to induce eosinophilic inflammation in this study. After neutrophilic asthma was induced by LPS (O+L group), HDAC2 activity was diminished with increased NF-κB activity and CXCL1 compared to the control group. TIO significantly improved NF-κB activity, CXCL1, and HDAC2 activity compared with the O+L group in in-vivo study (P < 0.05, each). Western blot analyses showed that LPS treated HBE cells from asthma patients increased PLCγ-1 and diminished IP3 receptor levels. After TIO treatment, recovery of IP3R and improved PLCγ-1 levels were observed. CONCLUSION: These results support the hypothesis that TIO modulates inflammation by recovering HDAC2 activity from the acetylcholine-stimulated inflammation cascade in neutrophilic asthma. The detailed inflammation cascade of recovering HDAC2 activity by TIO might be associated with PLCγ-1-IP3-IP3R mediated intracellular calcium ion pathway.

EBV-positive PCNSL in older patients: incidence, characteristics, tumor pathology, and outcomes across a large multicenter cohort.

The objective of this multicenter retrospective study was to examine the incidence, patient characteristics, pathology, and outcomes associated with Epstein-Barr virus (EBV)-related CNS lymphoma (CNSL) in older patients. Among 309 CNSL patients aged ≥60, 11.7% had EBV + tumors of which 72.2% were solid organ transplant (SOT)-related post-transplant lymphoproliferative disorders (PTLD). Younger age, SOT or autoimmune disease, and immunosuppressive treatment correlated highly with EBV-positivity. EBV + tumors were associated with absent C-MYC and BCL6 expression. EBV + PTLD was more likely to be associated with the absence of CD5 expression. EBV + non-PTLD had better median OS (not reached) compared to EBV + PTLD (10.8 months) and EBV-negative patients (43 months). Multivariable Cox regression analysis showed that age, performance status, and PTLD were negative predictors of OS. EBV status and immunosuppressive treatment were not correlated with OS. Our findings merit further investigation of EBV + PCNSL tumors and EBV-directed therapies.