Prussian blue nanozymes coated with Pluronic attenuate inflammatory osteoarthritis by blocking c-Jun N-terminal kinase phosphorylation.

Osteoarthritis (OA) is a degenerative joint disorder associated with inflammation, functional disability, and high socioeconomic costs. The development of effective therapies against inflammatory OA has been limited owing to its complex and multifactorial nature. The efficacy of Prussian blue nanozymes coated with Pluronic (PPBzymes), US Food and Drug Administration-approved components, and their mechanisms of action have been described in this study, and PPBzymes have been characterized as a new OA therapeutic. Spherical PPBzymes were developed via nucleation and stabilization of Prussian blue inside Pluronic micelles. A uniformly distributed diameter of approximately 204 nm was obtained, which was maintained after storage in an aqueous solution and biological buffer. This indicates that PPBzymes are stable and could have biomedical applications. In vitro data revealed that PPBzymes promote cartilage generation and reduce cartilage degradation. Moreover, intra-articular injections with PPBzymes into mouse joints revealed their long-term stability and effective uptake into the cartilage matrix. Furthermore, intra-articular PPBzymes injections attenuated cartilage degradation without exhibiting cytotoxicity toward the synovial membrane, lungs, and liver. Notably, based on proteome microarray data, PPBzymes specifically block the JNK phosphorylation, which modulates inflammatory OA pathogenesis. These findings indicate that PPBzymes might represent a biocompatible and effective nanotherapeutic for obstructing JNK phosphorylation.

Chemosensory deficits are best predictor of serologic response among individuals infected with SARS-CoV-2.

OBJECTIVE: Smell and taste alteration are closely linked to infection with SARS-CoV-2 and may be associated with a more indolent disease course. Serologic response rates among individuals with mild disease remains limited. We sought to identify whether chemosensory changes associated with COVID-19 were predictive of a serologic response. STUDY DESIGN: Cross-sectional study. METHODS: The sample consisted of 306 adults (≥18 years old) volunteering for convalescent plasma donation following perceived COVID-19 illness from April-June 2020. Documentation of COVID-19 PCR status, clinical symptoms at time of illness, and treatment course occurred at the time of serologic analysis, where we assessed chemosensory function using patient-perceived deficits. We implemented previously validated ELISA screening to determine serologic status regarding anti-Spike immunoglobulins. Statistical analysis using stepwise logistic models were employed to identify predictive factors of serologic response. RESULTS: Of 306 patients undergoing serologic and chemosensory evaluation, 196 (64.1%) and 195 (63.7%) reported subjective olfactory and taste dysfunction, respectively, during the first two weeks of COVID-19 infection. In unadjusted models, the odds of developing suprathreshold IgG antibody titers were 1.98 times higher among those who reported altered smell (95% CI 1.14-3.42, p = 0.014) and 2.02 times higher among those with altered taste (95% CI 1.17-3.48, p = 0.011) compared to those with normal smell and taste. Multivariable logistic models adjusting for sex, age, race/ethnicity, symptom duration, smoking status and comorbidities index demonstrated that altered smell and taste remained significant predictors of positive anti-spike IgG response (smell OR = 1.90, 95% CI 1.05-3.44, p = 0.033; taste OR = 2.01, 95% CI = 1.12-3.61, p = 0.019). CONCLUSION: Subjective chemosensory dysfunction, as self-reported smell or taste deficiency, is highly predictive of serologic response following SARS-CoV-2 infection. This information may be useful for patient counseling. Additional longitudinal research should be performed to better understand the onset and duration of the serologic response in these patients.

Prussian blue nanozymes coated with pluronic attenuate inflammatory osteoarthritis by blocking c-Jun N-terminal kinase phosphorylation.

Osteoarthritis (OA) is a degenerative joint disorder associated with inflammation, functional disability, and high socioeconomic costs. The development of effective therapies against inflammatory OA has been limited owing to its complex and multifactorial nature. The efficacy of Prussian blue nanozymes coated with Pluronic (PPBzymes), US Food and Drug Administration-approved components, and their mechanisms of action have been described in this study, and PPBzymes have been characterized as a new OA therapeutic. Spherical PPBzymes were developed via nucleation and stabilization of Prussian blue inside Pluronic micelles. A uniformly distributed diameter of approximately 204 nm was obtained, which was maintained after storage in an aqueous solution and biological buffer. This indicates that PPBzymes are stable and could have biomedical applications. In vitro data revealed that PPBzymes promote cartilage generation and reduce cartilage degradation. Moreover, intra-articular injections with PPBzymes into mouse joints revealed their long-term stability and effective uptake into the cartilage matrix. Furthermore, intra-articular PPBzymes injections attenuated cartilage degradation without exhibiting cytotoxicity toward the synovial membrane, lungs, and liver. Notably, based on proteome microarray data, PPBzymes specifically block the JNK phosphorylation, which modulates inflammatory OA pathogenesis. These findings indicate that PPBzymes might represent a biocompatible and effective nanotherapeutic for obstructing JNK phosphorylation.

Long-Term Effectiveness and Safety of Dutasteride versus Finasteride in Patients with Male Androgenic Alopecia in South Korea: A Multicentre Chart Review Study.

BACKGROUND: Dutasteride improves hair growth compared with finasteride in male androgenic alopecia (AGA) and is well tolerated. However, real-world evidence for long-term dutasteride use in AGA is lacking. OBJECTIVE: To describe baseline characteristics, treatment patterns and long-term safety and effectiveness of dutasteride versus finasteride. METHODS: This was a multicentre, retrospective medical chart review study conducted in South Korea. The index date was the first prescription of dutasteride or finasteride. Baseline characteristics were assessed 6 months prior to index. Safety and effectiveness (improvements in basic and specific [BASP] classification) data were collected from index throughout the observation period. RESULTS: Overall, 600 male adult patients were included (dutasteride, n=295; finasteride, n=305). Dutasteride-treated patients were older (p<0.001) and more likely to have moderate/severe BASP classification at baseline (p=0.010) compared with finasteride-treated patients. Among patients treated with recommended, on-label dosing exclusively (n=535: dutasteride, n=250; finasteride, n=285), dutasteride-treated patients showed greater improvement in hair growth than finasteride-treated patients, as measured by the BASP basic M classification (adjusted incidence rate ratio [95% confidence interval]: 2.06 [1.08, 3.95]; p=0.029). Among this same subset, overall occurrence of adverse events (AEs) during the observation period were not statistically equivalent between groups (dutasteride 7.6%, finasteride 10.5%; p=0.201), although reports of AEs of special interest were equivalent (p<0.001). CONCLUSION: Dutasteride showed greater effectiveness than finasteride in improving BASP classification in treating male AGA and had a similar or possibly lower occurrence of overall AEs. Dutasteride may provide an effective and safe treatment option for male patients with AGA.

Neoadjuvant chemoradiation alters the immune microenvironment in pancreatic ductal adenocarcinoma.

Patients with pancreatic ductal adenocarcinoma (PDAC) have a grim prognosis despite complete surgical resection and intense systemic therapies. While immunotherapies have been beneficial with many different types of solid tumors, they have almost uniformly failed in the treatment of PDAC. Understanding how therapies affect the tumor immune microenvironment (TIME) can provide insights for the development of strategies to treat PDAC. We used quantitative multiplexed immunofluorescence (qmIF) quantitative spatial analysis (qSA), and immunogenomic (IG) analysis to analyze formalin-fixed paraffin embedded (FFPE) primary tumor specimens from 44 patients with PDAC including 18 treated with neoadjuvant chemoradiation (CRT) and 26 patients receiving no treatment (NT) and compared them with tissues from 40 treatment-naïve melanoma patients. We find that relative to NT tumors, CD3+ T cell infiltration was increased in CRT treated tumors (p = .0006), including increases in CD3+CD8+ cytotoxic T cells (CTLs, p = .0079), CD3+CD4+FOXP3- T helper cells (Th, p = .0010), and CD3+CD4+FOXP3+ regulatory T cells (Tregs, p = .0089) with no difference in CD68+ macrophages. IG analysis from micro-dissected tissues indicated overexpression of genes involved in antigen presentation, T cell activation, and inflammation in CRT treated tumors. Among treated patients, a higher ratio of Tregs to total T cells was associated with shorter survival time (p = .0121). Despite comparable levels of infiltrating T cells in CRT PDACs to melanoma, PDACs displayed distinct spatial profiles with less T cell clustering as defined by nearest neighbor analysis (p < .001). These findings demonstrate that, while CRT can achieve high T cell densities in PDAC compared to melanoma, phenotype and spatial organization of T cells may limit benefit of T cell infiltration in this immunotherapy-resistant tumor.

Impact of Treatment Parameters on Racial Survival Differences in Oropharyngeal Cancer: National Cancer Database Study.

OBJECTIVE: To investigate how differences in treatment parameters account for survival differences between races of patients with oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Database. METHODS: Data of patients with OPSCC undergoing radiation therapy (RT) or concurrent chemoradiation therapy as primary treatment were obtained from the National Cancer Database from 2004 to 2016. We analyzed 4 treatment-related time intervals to determine their impact on survival between races when controlling for human papilloma virus (HPV) status. Cox proportional hazards models, stepwise logistic regressions, covariate adjustments, and propensity score matching were performed. RESULTS: A total of 3152 patients were identified (2877 White, 275 Black). In HPV- cases, Black patients with prolonged radiation duration had a significantly worse overall survival as compared with White patients (hazard ratio, 1.77; 95% CI, 1.03-3.05; P = .039). In a logistic regression model, the only covariate that was significantly associated with prolonged RT was facility type. When further adjusted for facility type, the survival difference between Black and White patients with HPV- status and prolonged RT times was no longer significant (hazard ratio, 1.55; 95% CI, 0.90-2.69; P = .116). CONCLUSIONS: There is a significant disparity in overall survival between Black and White patients with HPV- OPSCC when RT duration is prolonged. Clinicians should be aware of the negative impact of prolonged RT, especially in Black patients, so that they can attempt to decrease treatment-related time intervals. Facility type was also found to affect the outcomes of patients with OPSCC, and efforts should be made to improve patient access to well-equipped, high-volume facilities.

Two-Stage Approaches to Accounting for Patient Heterogeneity in Machine Learning Risk Prediction Models in Oncology.

PURPOSE: Machine learning models developed from electronic health records data have been increasingly used to predict risk of mortality for general oncology patients. But these models may have suboptimal performance because of patient heterogeneity. The objective of this work is to develop a new modeling approach to predicting short-term mortality that accounts for heterogeneity across multiple subgroups in the presence of a large number of electronic health record predictors. METHODS: We proposed a two-stage approach to addressing heterogeneity among oncology patients of different cancer types for predicting their risk of mortality. Structured data were extracted from the University of Pennsylvania Health System for 20,723 patients of 11 cancer types, where 1,340 (6.5%) patients were deceased. We first modeled the overall risk for all patients without differentiating cancer types, as is done in the current practice. We then developed cancer type-specific models using the overall risk score as a predictor along with preselected type-specific predictors. The overall and type-specific models were compared with respect to discrimination using the area under the precision-recall curve (AUPRC) and calibration using the calibration slope. We also proposed metrics that characterize the degree of risk heterogeneity by comparing risk predictors in the overall and type-specific models. RESULTS: The two-stage modeling resulted in improved calibration and discrimination across all 11 cancer types. The improvement in AUPRC was significant for hematologic malignancies including leukemia, lymphoma, and myeloma. For instance, the AUPRC increased from 0.358 to 0.519 (∆ = 0.161; 95% CI, 0.102 to 0.224) and from 0.299 to 0.354 (∆ = 0.055; 95% CI, 0.009 to 0.107) for leukemia and lymphoma, respectively. For all 11 cancer types, the two-stage approach generated well-calibrated risks. A high degree of heterogeneity between type-specific and overall risk predictors was observed for most cancer types. CONCLUSION: Our two-stage modeling approach that accounts for cancer type-specific risk heterogeneity has improved calibration and discrimination than a model agnostic to cancer types.

The frequency of gastroesophageal reflux when radiofrequency catheter ablation procedures for atrial fibrillation under general anesthesia with a supraglottic device: Observational pilot study.

ABSTRACT: Gastroesophageal reflux (GER) in radiofrequency catheter ablation (RFCA) occurs due to vagal plexus damage during pulmonary vein isolation. We hypothesized that the frequency of GER in the oropharynx will be less compared to other areas (low-esophagus, mid-esophagus). We confirmed the frequency of GER before and after RFCA in 3 areas.We studied 30 patients who were scheduled for RFCA under general anesthesia. Anesthesia was performed using supraglottic devices (SGD) with a suction port. Two esophageal temperature probes capable of suction and measuring temperature were inserted through the suction port. The pH of the 3 areas was measured before and after the RFCA at 3 areas (mid-esophagus, low-esophagus, and oropharynx).GER was observed in 13 of 30 patients (43%). In one patient, it was observed in the oropharynx, in 4 patients it was observed in the mid-esophagus, and in 13 patients, it was observed in the low-esophagus. For patients with GER at the oropharynx and mid-esophagus, it was also observed at the low-esophagus. The difference in the pH before and after the RFCA was not significant at the oropharynx and mid-esophagus (P = .726 and P = .424, respectively), but it was significantly different at the low-esophagus (P < .001). The total ablation time was longer in the GER group compared to the non-GER group (P = .021).GER after RFCA occurred in 43% of patients, only 1 patient in the oropharynx. And aspiration pneumonia after SGD extubation did not occur. Therefore, the use of SGDs in RFCA does not completely eliminate the possibility of aspiration, so care should be taken.

Affordable Care Act State-Specific Medicaid Expansion: Impact on Health Insurance Coverage and Breast Cancer Screening Rate.

BACKGROUND: Under the Affordable Care Act, states were given the option to expand Medicaid in 2014. By the end of 2014, 32 states had opted to expand Medicaid and 19 did not. Previous quasi-experimental studies took advantage of this state-specific policy implementation and found increased insurance coverage in expansion compared with nonexpansion states. With longer-term data now available, we studied the effect of Medicaid expansion on changes in insurance coverage and mammography rates in expansion and nonexpansion states. STUDY DESIGN: Seven states that expanded Medicaid eligibility in 2014 and 6 nonexpansion states were selected based on available data. The US Census American Community Survey was queried for insurance coverage from 2011 to 2016 and the CDC Behavioral Risk Factor Surveillance System from 2010 to 2018. Difference-in-difference linear mixed models were used to estimate and compare insurance coverage and screening mammogram rates between expansion and nonexpansion states before and after 2014. RESULTS: The increase in insurance rates for all persons covered by some type of health insurance after Medicaid expansion was significantly different in expansion than nonexpansion states (p = 0.001). The increase in Medicaid coverage was significant in expansion compared with nonexpansion states (p < 0.001). A similar trend was seen in screening mammogram rates in women from low-income households in expansion vs nonexpansion states (p = 0.049). CONCLUSIONS: Medicaid expansion states saw greater improvement in total insurance and Medicaid coverage, and in mammogram rates in lower-income women compared with nonexpansion states after Medicaid legislation was passed. Our study demonstrates that people do take advantage of expanded eligibility by acquiring insurance and this can improve access to preventive measures, such as screening mammography.

Affordable Care Act State-Specific Medicaid Expansion: Impact on Health Insurance Coverage and Breast Cancer Screening Rates.

BACKGROUND: Under the Affordable Care Act, states were given the option to expand Medicaid in 2014. By the end of 2014, 32 states had opted to expand Medicaid while 19 did not. Previous quasi-experimental studies took advantage of this state-specific policy implementation and found increased insurance coverage in expansion compared to non-expansion states. With longer-term data now available, we studied the effect of Medicaid expansion on changes in insurance coverage and mammography rates in expansion and non-expansion states. STUDY DESIGN: Seven states which expanded Medicaid eligibility in 2014 and six non-expansion states were selected based on available data. The U.S. Census American Community Survey was queried for insurance coverage from 2011-2016 and the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System from 2010-2018. Difference-in-difference linear mixed models were used to estimate and compare insurance coverage and screening mammogram rates between expansion and non-expansion states before and after 2014. RESULTS: The increase in insurance rates for all persons covered by some type of health insurance after Medicaid expansion was significantly different in expansion than non-expansion states (p=0.001). The increase in Medicaid coverage was significant in expansion compared to non-expansion states (p<0.001). A similar trend was seen in screening mammogram rates in women from low income households in expansion versus non-expansion states (p=0.049). CONCLUSION: Medicaid expansion states saw greater improvement in total insurance and Medicaid coverage, and in mammogram rates in lower income women, when compared to non-expansion states after Medicaid legislation was passed. Our study demonstrates that people do take advantage of expanded eligibility by acquiring insurance and this may improve access to preventive measures such as screening mammography.

HPV status in patients with nasopharyngeal carcinoma in the United States: A SEER database study.

PURPOSE: To investigate the etiologic and prognostic role of Human Papilloma Virus (HPV) in Nasopharyngeal Carcinoma (NPC). MATERIALS AND METHODS: Patients diagnosed with NPC were identified with the Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was used to investigate the effect of clinicopathologic predictors on HPV positivity in NPC. Survival analyses were performed with Kaplan-Meier curves and Cox regression models. RESULTS: 180/517 patients (34.8%) with known HPV testing were positive for HPV-associated NPC. East Asians and individuals over 25 were less likely to have HPV-associated NPC, while controlling for AJCC-7 stage and AJCC-7 M stage. According to the survival analysis, cause-specific survival (CSS) did not differ significantly by HPV status throughout the study period, but did differ significantly by HPV ethnicity group. CONCLUSIONS: The clinical implications of HPV in NPC are further elucidated but require more investigation. LEVEL OF EVIDENCE: IV.

Factors Influencing Unmarried Mothers' Parenting Stress: Based on Depression, Social Support, and Health Perception.

PURPOSE: To identify factors affecting parenting stress of unmarried mothers. METHODS: The subjects were 108 unmarried women who were parenting their children under the age of six. The data was collected from December 15, 2016 to March 5, 2017. The instruments consisted of self-reported questionnaires that included93 items: 21 on depression, 16 on social support, 20 on health perception, and 36 on parenting stress. The collected data were analyzed by t-test, ANOVA, Pearson correlations, and hierarchical multiple regression. RESULTS: The factors influencing parenting stress were health perception (ß=-.55, p < .001), evaluative support (ß=-.42, p=.005), informative support (ß=-.35, p=.040), emotional support (ß=-.24, p=.045), partner support (ß=-.20, p=.048), and depression (ß=.14, p=.033), and the explanatory power was 57%. CONCLUSION: In order to alleviate the parenting stress of unmarried mothers, it is necessary to develop programs considering the physical, psychological, and social factors of unmarried mothers. Their subjective assessment of their health can increase or decrease their parenting stress, so it is necessary to develop parenting-stress intervention focusing on health perception.

Long-term Recovery From Hurricane Sandy: Evidence From a Survey in New York City.

OBJECTIVES: This study aimed to examine a range of factors influencing the long-term recovery of New York City residents affected by Hurricane Sandy. METHODS: In a series of logistic regressions, we analyzed data from a survey of New York City residents to assess self-reported recovery status from Hurricane Sandy. RESULTS: General health, displacement from home, and household income had substantial influences on recovery. Individuals with excellent or fair health were more likely to have recovered than were individuals with poor health. Those with high and middle income were more likely to have recovered than were those with low income. Also, individuals who had not experienced a decrease in household income following Hurricane Sandy had higher odds of recovery than the odds for those with decreased income. Additionally, displacement from the home decreased the odds of recovery. Individuals who applied for assistance from the Build it Back program and the Federal Emergency Management Agency had lower odds of recovering than did those who did not apply. CONCLUSIONS: The study outlines the critical importance of health and socioeconomic factors in long-term disaster recovery and highlights the need for increased consideration of those factors in post-disaster interventions and recovery monitoring. More research is needed to assess the effectiveness of state and federal assistance programs, particularly among disadvantaged populations. (Disaster Med Public Health Preparedness. 2018;12:172-175).

Active pulmonary tuberculosis and latent tuberculosis infection among homeless people in Seoul, South Korea: a cross-sectional study.

BACKGROUND: The aim of this study was to determine the prevalence rate of latent TB infection (LTBI) and active TB among homeless in Seoul metropolitan city, South Korea, and to compare the TB burden among homeless people with that of a control group. METHODS: The homeless participants were recruited from five sites between October 30, 2009 and April 12, 2010. LTBI was diagnosed through the QuantiFERON(R) TB Gold In-Tube(QFT-GIT) assay and a tuberculin skin test(TST) and, and active PTB was diagnosed based on chest radiography. RESULTS: Among 313 participants, the prevalence of LTBI was 75.9% (95% CI, 71.1-80.8%) and 79.8% (95% CI, 74.9-84.7%) based on a QFT-GIT assay and the TST, respectively, and that of active PTB was 5.8% (95% CI, 3.2-8.3%). The prevalence of LTBI among homeless participants was about five times higher than controls. Also, the age-specific prevalence rate ratio of active PTB was as high as 24.86. CONCLUSIONS: The prevalence rate of LTBI as well as active PTB among homeless people was much higher than that of the general population in South Korea. Thus, adequate strategies to reduce the TB burden among homeless people are needed.

Establishment and maintenance of human embryonic stem cells on STO, a permanently growing cell line.

Human embryonic stem (hES) cells have been traditionally cultured on primary mouse embryonic fibroblasts (PMEFs). However, though STO cells have some advantages over PMEFs and human embryonic fibroblasts (hEFs) as feeder cells, they have never been used as feeder cells to establish hES cell lines. In this study, three hES cell lines (Miz-hES1, Miz-hES2, and Miz-hES3) were established from inner cell masses (ICM), using STO as feeder cells. The three hES cell lines had normal karyotypes and expressed high levels of alkaline phosphatase (AP), cell surface markers (SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81), and transcription factor Oct-4. After culture on STO cells for 2 yr, hES cells maintained the potential to form derivatives of all three embryonic germ layers. Our results show that STO feeder cells have the potential to support the establishment and maintenance of hES cell lines. In addition, our results suggest that laminin may play an important role in maintaining the undifferentiated proliferation of hES cells.