Predictors of successful anti-inflammatory drug trials in patients with schizophrenia: A meta-regression and critical commentary.

Given evidence pointing toward a role for immune dysregulation in the pathogenesis of schizophrenia, anti-inflammatory agents are promising adjunctive treatments that have potential to support a causal relationship for inflammation and psychopathology and lead to novel treatments for individuals. Indeed, previous meta-analyses have demonstrated small-to-medium effect sizes (ES) in favor of various anti-inflammatory agents, though there is significant heterogeneity and challenges in the interpretation of this literature. Identifying predictors, including sociodemographic variables, trial duration, and/or symptoms themselves, of successful anti-inflammatory trials may help identify which patients who might benefit from these compounds. We performed a meta-regression analysis of 63 adjunctive anti-inflammatory trial arms (2232 patients randomized to adjunctive anti-inflammatory agents and 2207 patients randomized to placebo).Potential predictors of effect size estimates for changes in psychopathology scores from baseline to endpoint included geography, trial duration, sample size, age, sex, race, smoking, body mass index, illness duration, age of onset of psychosis, study quality score and psychopathology scores (total and subscale) at baseline. Geography (ß = 0.31, p = 0.011), smaller sample size (ß = 0.33, p = 0.009), and higher study quality score (ß = 0.44, p < 0.001) were significant predictors of larger ES estimates for change in total psychopathology in favor of anti-inflammatory agents. Smaller sample size (ß = 0.37, p = 0.034) and higher study quality score (ß = 0.55, p = 0.003) were significant predictors of larger ES estimates for change in negative psychopathology in favor of anti-inflammatory agents. Higher study quality score (ß = 0.46, p = 0.019) was a significant predictor of larger ES estimates for change in general psychopathology in favor of anti-inflammatory agents. These findings should be interpreted with caution given concerns of publication bias regarding the geographic differences and small study effects. The lack of an association with other demographic variables should be seen as a primary limitation of the literature that needs to be considered in future studies. The association with study quality score suggests that future anti-inflammatory trials must consider demographic variables known to be associated with inflammation (e.g., BMI and smoking) and evidence of increased baseline inflammation should be incorporated in study design. Moreover, evidence of target engagement and endpoints thoughts to be associated with increased inflammation should be considered as well.

Associations of deep sleep and obstructive sleep apnea with family relationships, life satisfaction, and physical stress experience in children: a caregiver perspective.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and poor quality of sleep negatively impacts health-related quality of life in adults, but few studies have evaluated the association between sleep disturbance (eg, OSA, inadequate sleep) and health-related quality of life domains (eg, family relations, life satisfaction) in children. METHODS: Children ages 8-17 years referred to a sleep center for routine polysomnography from April 2022 to August 2022 were approached to participate in the study, and children visiting the department of pediatrics for their wellness visit were recruited for comparisons. Statistical analysis was conducted using R 3.6.0. RESULTS: Ninety-nine children were recruited from the sleep clinic, and 23 children were recruited from the primary care clinic. Of these children, 62 were diagnosed with obstructive sleep apnea (31 mild, 12 moderate, 19 severe), and 37 did not meet criteria for a diagnosis. Health-related quality of life domains did not differ across OSA severity levels. Children in general had lower life satisfaction and higher physical stress experience compared to children visiting for their wellness examination (well-child visitors, P = .05 and P = .005, respectively). Children with severe OSA had significantly lower life satisfaction and significantly higher physical stress experience when compared with well-child visitors (P = .008 and P = .009, respectively). Correlation analysis showed that N3 (deep) sleep was positively associated with family relations and life satisfaction, while it was negatively associated with anger. CONCLUSIONS: Based on caregiver response, N3 sleep is positively associated with family relations and life satisfaction and negatively associated with anger. Severe OSA is associated with lower life satisfaction and higher physical stress experience. CITATION: Bhushan B, Zee PC, Grandner MA, et al. Associations of deep sleep and obstructive sleep apnea with family relationships, life satisfaction, and physical stress experience in children: a caregiver perspective. J Clin Sleep Med. 2023;19(12):2087-2095.

A cross-sectional survey of prevalence and correlates of sunscreen use among a rural Tri-State Appalachian population.

Over five million people are diagnosed with skin cancers each year. With the sun's ultraviolet radiation exposure being the major risk factor for all skin cancers, sunscreen use is a vital preventative measure. However, in the US, sunscreen use remains inadequate. Furthermore, research regarding sunscreen use amongst rural populations has been particularly sparse. To identify the prevalence of sunscreen use and identify correlates thereof, a cross-sectional study was conducted on a sample of patients from rural Tri-State Appalachia. A total of 212 patients participated in this study. Findings showed that young individuals, females and those with higher educational attainment were more likely to utilize sunscreen. Furthermore, individuals with skin types prone to burning were four times as likely to utilize sunscreen. Overall, sunscreen use amongst residents in the Tri-State area was low, emphasizing the need for targeted interventions to prevent the incidence of skin cancer amongst this population.

A systemic review on the antioxidant and anti-inflammatory effects of resveratrol, curcumin, and dietary nitric oxide supplementation on human cardiovascular health.

The potential benefits of supplemental nutrients and dietary interventions against cardiovascular morbidity and mortality have been extensively investigated throughout the years. Numerous supplements claim cardioprotection and reduction of cardiovascular risk factors, but the roles of many supplements have not been determined. In the vast number of supplements on the market asserting cardioprotective effects, only 3 have been thoroughly evaluated and consistently reported as effective by our clinic patients. They have used supplements such as fish oil, multivitamins, and calcium, but many had not known of the benefits of resveratrol, curcumin, and nitric oxide as supplements for improving cardiovascular health. The cardioprotective effects of these dietary supplements in both animal models and humans have been explored with proposed mechanisms of action mostly attributed to antioxidant and anti-inflammatory properties. Resveratrol is one of the most studied polyphenols with established cardiovascular benefits. Preclinical studies have demonstrated these effects exerted via improved inflammatory markers, atherogenic profile, glucose metabolism, and endothelial function and are further supported by clinical trials. Curcumin has a well-established anti-inflammatory role by regulating numerous transcription factors and cytokines linked to inflammation. Inflammation is an underlying pathology in cardiovascular diseases, rendering curcumin a potential therapeutic compound. Similarly, nitric oxide supplementation has demonstrated cardiovascular benefits by normalizing blood pressure; enhancing blood flow; and reducing inflammation, immune dysfunction, and oxidative stress. A comprehensive review was performed evaluating the cardioprotective effects of these 3 dietary supplements with hope to provide updated information, promote further awareness of these supplements, and inspire future studies on their effects on cardiovascular health.

"Psychodermatology" knowledge, attitudes, and practice among health care professionals.

Psychiatric disorders are prevalent in dermatology patients. Psychodermatology is the body of knowledge at the intersection of psychiatry and dermatology practice. The purpose of this literature review was to assess the knowledge, attitudes, and practices of health care professionals regarding psychodermatology. A search of relevant articles was conducted in PubMed, CINAHL, ERIC, and PsychInfo databases using a comprehensive set of search terms. Studies were included if (1) study participants were health care professionals, (2) studies contained data that could be extracted, and (3) studies were published in peer-reviewed journals. A review of study findings was conducted. A total of nine studies were included in the review. Studies were conducted in several countries. Findings from the review confirmed that providers frequently reported psychocutaneous disorders in their practice. There were, however, gaps and variations in providers' knowledge base and level of comfort treating these patients. Further, providers acknowledged a lack of training in the practice of psychodermatology. The findings from this review suggest that health care professionals from multiple areas of the world may lack a full understanding, level of comfort, and proper training in psychodermatology. Improving the knowledge base and increasing level of comfort in treating psychodermatological disorders can improve the practice of psychodermatology amongst providers. Further, addressing knowledge and comfort level among providers through training and continuing education may improve outcomes for patients with psychocutaneous disorders.

O-GlcNAc modification of Sox2 regulates self-renewal in pancreatic cancer by promoting its stability.

Pancreatic adenocarcinoma (PDAC) claims more than 90% of the patients diagnosed with the disease owing to its aggressive biology that is manifested by high rate of tumor recurrence. Aberrant upregulation in the transcriptional activity of proteins involved in self-renewal like Sox2, Oct4 and Nanog is instrumental in these recurrence phenomena. In cancer, Sox2 is aberrantly "turned-on" leading to activation of downstream genes those results in relapse of the tumor. Molecular mechanisms that regulate the activity of Sox2 in PDAC are not known. In the current study, we have studied the how glycosylation of Sox2 by O-GlcNAc transferase (OGT) can affect its transcriptional activity and thus regulate self-renewal in cancer. Methods: RNA-Seq analysis of CRISPR-OGTi PDAC cells indicated a deregulation of differentiation and self-renewal pathways in PDAC. Pancreatic tumor burden following inhibition of OGT in vivo was done by using small molecule inhibitor, OSMI, on subcutaneous implantation of PDAC cells. Sox2 activity assay was performed by Dual Luciferase Reporter Assay kit. Results: Our study shows for the first time that in PDAC, glycosylation of Sox2 by OGT stabilizes it in the nucleus. Site directed mutagenesis of this site (S246A) prevents this modification. We further show that inhibition of OGT delayed initiation of pancreatic tumors by inhibition of Sox2. We also show that targeting OGT in vivo with a small molecule-inhibitor OSMI, results in decreased tumor burden in PDAC. Conclusion: Understanding this mechanism of SOX2 regulation by its glycosylation is expected to pave the way for development of novel therapy that has the potential to eradicate the cells responsible for tumor-recurrence.

Clinical experience of long-term use of dienogest after surgery for ovarian endometrioma.

OBJECTIVE: Endometriosis is a common and recurring gynecologic disease which have afflicting females of reproductive age. We investigated the efficacy of long-term, post-operative use of dienogest for ovarian endometrioma. METHODS: We studied 203 patients who had undergone laparoscopic or robotic surgery for ovarian endometrioma, and were administrated dienogest 2 mg/day beginning in July of 2013, and continuing. We evaluated side effects of dienogest and ultrasonography was performed every 6 months to detect potential recurrence of endometrioma (2 cm) in these post-surgical patients. RESULTS: The follow-up observation periods were 30.2±20.9 months from surgery. The mean age was 34.1±7.2 years old. The mean diameter of pre-operative endometrioma was 5.6±3.0 cm2. One hundred eighty-two (89.7%) women received dienogest continuously for 12.0±7.1 months. Of the subjects, 21 (10.3%) patients discontinued dienogest at 2.4±1.0 months. The most common side effect when dienogest was discontinued was abnormal uterine bleeding. The occurrence rate of vaginal bleeding was 15.8%, a number which did not differ significantly in patients with/without post-operative gonadotropin releasing hormone agonist administration. The other side effects were gastrointestinal trouble including constipation, acne, headache, depression, hot flush, weight gain, and edema. However, no serious adverse events or side effects were documented and recurrent endometriomas were diagnosed in 3 patients (1.5%). CONCLUSION: The data indicates that dienogest was both tolerable and safe for long-term use as prophylaxis in an effort to obviate the recurrence of ovarian endometrioma post-operatively, as well as potential need for surgical re-intervention.

Fluorescence properties of doxorubicin in PBS buffer and PVA films.

We studied steady-state and time-resolved fluorescence properties of an anticancer drug Doxorubicin in a saline buffer and poly-vinyl alcohol (PVA) film. Absorption of Doxorubicin, located at blue-green spectral region, allows a convenient excitation with visible light emitting diodes or laser diodes. Emission of Doxorubicin with maximum near 600nm can be easily detected with photomultipliers and CCD cameras. Both, absorption and fluorescence spectra in polymeric matrix show more pronounced vibronic structures than in solution. Also, the steady-state anisotropy in the polymer film is significantly higher than in the saline solution. In PVA film the fluorescence anisotropy is about 0.30 whereas in the saline buffer only 0.07. Quantum efficiencies of Doxorubicin were compared to a known standard Rhodamine 101 which has fluorescence emission in a similar spectral region. The quantum yield of Doxorubicin in PVA film is more than 10% and about twice higher than in the saline solution. Similarly, the lifetime of doxorubicin in PVA film is about 2ns whereas in the saline solution only about 1ns. The fluorescence anisotropy decays show that Doxorubicin molecules are freely rotating in the saline buffer with a correlation time of about 290ps, and are almost completely immobilized in the PVA film. The spectroscopic investigations presented in this manuscript are important, as they provide answers to changes in molecular properties of Doxorubicin depending changes in the local environment, which is useful when synthesizing nanoparticles for Doxorubicin entrapment.