Enhancing Opiorphin's Metabolic Stability and Preserving its Potent Analgesic Effect: A Systematic Review.

BACKGROUND: Opiorphin has been reported to show a stronger analgesic effect than morphine without causing side effects brought about by morphine-like drugs. Functional opiorphin analogs have been created to enhance its metabolic stability and preserve its potent analgesic effect. OBJECTIVE: We conducted a systematic review to summarize all opiorphin analogs and identify those with the strongest metabolic stability and antinociceptive effect. METHODS: From a total of 122 articles, 11 made it to the quantitative synthesis phase. The included articles were categorized into the type of modifications used to improve the metabolic stability of the peptide, metabolism and toxicity profile, drug absorption and in vitro cytotoxicity, anti-nociceptive effect, the opiorphin analogs' administration in animals or humans, and the type of the test used to test the antinociceptive effect. RESULTS: The substitution of natural amino acid with a non-natural amino acid, side-chain modifications, or D-aminoacid substitution were the most used type of peptide modification to create opiorphin analogs. STR-324 and PEGylated liposomes loaded with opiorphin showed the best metabolism and toxicity performance. [C]-[(CH2)6]-QRF-[S-O-(CH2)8]-R showed high stability in human plasma and stronger inhibitory potency. YQRFSR and PEGylated liposomes loaded with opiorphin showed a stronger antinociceptive effect than the parent opiorphin or morphine, with an analgesic effect of PEGylated liposomes lasting more than 50%. Intravenous administration was the preferred method of opiorphin analog administration, and different tests were used to test the antinociceptive effect. CONCLUSION: This paper presents the first systematic review discussing opiorphin and opiorphin analogs and identifies the most promising candidates for future research.

A Pharmacoepidemiological Study of Myocarditis and Pericarditis Following the First Dose of mRNA COVID-19 Vaccine in Europe.

This study assessed the myocarditis and pericarditis reporting rate of the first dose of mRNA COVID-19 vaccines in Europe. Myocarditis and pericarditis data pertinent to mRNA COVID-19 vaccines (1 January 2021-11 February 2022) from EudraVigilance database were combined with European Centre for Disease Prevention and Control (ECDC)'s vaccination tracker data. The reporting rate was expressed as events (occurring within 28 days of the first dose) per 1 million individuals vaccinated. An observed-to-expected (OE) analysis quantified excess risk for myocarditis or pericarditis following the first mRNA COVID-19 vaccination. The reporting rate of myocarditis per 1 million individuals vaccinated was 17.27 (95% CI, 16.34-18.26) for CX-024414 and 8.44 (95% CI, 8.18-8.70) for TOZINAMERAN; and of pericarditis, 9.76 (95% CI, 9.06-10.51) for CX-024414 and 5.79 (95% CI, 5.56-6.01) for TOZINAMERAN. Both vaccines produced a myocarditis standardized morbidity ratio (SMR) > 1, with the CX-024414 vaccine having a greater SMR than TOZINAMERAN. Regarding TOZINAMERAN, SMR for pericarditis was >1 when considering the lowest background incidence, but <1 when considering the highest background incidence. Our results suggest an excess risk of myocarditis following the first dose of the mRNA COVID-19 vaccine, but the relationship between pericarditis and the mRNA COVID-19 vaccine remains unclear.

The Diverging Trend in Exposure to Environmental Tobacco Smoke Among US Children.

OBJECTIVE: Environmental tobacco smoke exposure (ETSE) was race/ethnicity-specific, but how the race/ethnicity-specific ETSE has changed over time, diverging or converging, remains unclear. We examined ETSE trends by race/ethnicity in US children aged 3-11 years. METHODS: We analyzed the data of 9678 children who participated in the biennial National Health and Nutrition Examination Surveys, 1999-2018. ETSE was defined as serum cotinine ≥ 0.05 ng/ml, with ≥ 1 ng/ml as heavy exposure. For trend description, adjusted biennial prevalence ratios (abiPR: the ratio associated with a 2-year increase in time) were estimated by race/ethnicity. The prevalence ratios between races/ethnicities were used to quantify ethnoracial differences in different survey periods. Analyses were performed in 2021. RESULTS: The overall ETSE prevalence was cut by almost half, from 61.59% (95% confidence interval = 56.55%, 66.62%) in the 1999-2004 survey to 37.61% (33.90%, 41.31%) in 2013-2018, exceeding the national 2020 health target (47.0%). However, the decrease occurred unequally between races/ethnicities. Heavy ETSE declined significantly in white [abiPR = 0.80 (0.74, 0.86)] and Hispanic children [0.83 (0.74, 0.93)], but insignificantly in black children [0.97 (0.92, 1.03)]. Consequently, the adjusted prevalence ratio between black children and white children increased from 0.82 (0.47, 1.44) in 1999-2004 to 2.73 (1.51, 4.92) in 2013-2018 for heavy ETSE. Hispanic children remained at the lowest risk throughout the study period. CONCLUSION: Overall ETSE prevalence was cut by half between 1999 and 2018. However, due to uneven declines, the gaps between black children and others have expanded in heavy ETSE. Special vigilance is needed in preventive medicine practice with black children.

Changes in physical activity and risk of ischemic stroke: The ARIC study.

BACKGROUND: Limited data exist regarding the impact of changes in physical activity (PA) over time on ischemic stroke risk. Exploring this understudied area could help improve stroke prevention strategies and promote PA during the lifespan. METHODS: We evaluated 11,089 Atherosclerosis Risk in Communities (ARIC) participants recruited in 1987-1989 who completed Visit 3 (1993-1995). We classified PA as meeting recommendations, not meeting recommendations, or no PA. Categories of increased, decreased, stable high, and stable low PA and a continuous PA variable were also evaluated. Crude and adjusted Cox regression models were used to characterize the association of 6-year changes in PA and ischemic stroke risk. RESULTS: Participants had a mean age of 60 years. During a median of 21 years, 762 ischemic stroke events occurred. Compared to the participants with recommended PA at both visits, those with no PA had 46% higher hazards of ischemic stroke (hazard ratio (HR) = 1.46 (95% confidence interval (CI) = 1.17, 1.82)), and those with recommended PA at Visit 1 and no PA at Visit 3 also had 37% higher hazards (HR = 1.37 (95% CI = 1.02, 1.83)). Participants who increased their PA from Visit 1 to Visit 3 had 23% lower hazard than those with stable low PA at both visits (HR = 0.77 (95% CI = 0.63, 0.94)), while those who decreased their PA had 25% higher hazards compared to those with stable high PA at both visits (HR = 1.25 (95% CI = 1.01, 1.54)). CONCLUSION: Physical inactivity during midlife increases ischemic stroke risk, while meeting PA recommendations reduces it.

Late Surges in COVID-19 Cases and Varying Transmission Potential Partially Due to Public Health Policy Changes in 5 Western States, March 10, 2020, to January 10, 2021.

OBJECTIVE: This study investigates the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission potential in North Dakota, South Dakota, Montana, Wyoming, and Idaho from March 2020 through January 2021. METHODS: Time-varying reproduction numbers, R t , of a 7-d-sliding-window and of non-overlapping-windows between policy changes were estimated using the instantaneous reproduction number method. Linear regression was performed to evaluate if per-capita cumulative case-count varied across counties with different population size or density. RESULTS: The median 7-d-sliding-window R t estimates across the studied region varied between 1 and 1.25 during September through November 2020. Between November 13 and 18, R t was reduced by 14.71% (95% credible interval, CrI, [14.41%, 14.99%]) in North Dakota following a mask mandate; Idaho saw a 1.93% (95% CrI [1.87%, 1.99%]) reduction and Montana saw a 9.63% (95% CrI [9.26%, 9.98%]) reduction following the tightening of restrictions. High-population and high-density counties had higher per-capita cumulative case-count in North Dakota on June 30, August 31, October 31, and December 31, 2020. In Idaho, North Dakota, South Dakota, and Wyoming, there were positive correlations between population size and per-capita weekly incident case-count, adjusted for calendar time and social vulnerability index variables. CONCLUSIONS: R t decreased after mask mandate during the region's case-count spike suggested reduction in SARS-CoV-2 transmission.

Climate change and health vulnerability in Nepal: A systematic review of the literature since 2010.

The Nepali population is among those most vulnerable to the health impacts of climate change. We conducted a systematic literature review to document the health effects of climate change in Nepal and identify knowledge gaps by examining vulnerability categories related to health. Three databases were searched for journal articles that addressed health and vulnerability related to climate change in Nepal from 2010 onwards. Of the 1063 articles identified, 37 were eligible for inclusion. The findings suggested the health of the population was affected mostly by food insecurity, floods, droughts, and reduced water levels. Studies revealed both morbidity and mortality increased due to climate change, with the most impacted populations being women, children, and the elderly. At greatest risk for impacts from climate change were those from poor and marginal populations, especially impoverished women. The public health sector, healthcare, and potable water sources were some of the least mentioned vulnerability subcategories, indicating more research is needed to better understand their adaptation capacities. We propose that identifying vulnerabilities and areas of limited research are critical steps in the prioritization of health policy and interventions for the most vulnerable populations in Nepal.

The Use of Penalized Regression Analysis to Identify County-Level Demographic and Socioeconomic Variables Predictive of Increased COVID-19 Cumulative Case Rates in the State of Georgia.

Systemic inequity concerning the social determinants of health has been known to affect morbidity and mortality for decades. Significant attention has focused on the individual-level demographic and co-morbid factors associated with rates and mortality of COVID-19. However, less attention has been given to the county-level social determinants of health that are the main drivers of health inequities. To identify the degree to which social determinants of health predict COVID-19 cumulative case rates at the county-level in Georgia, we performed a sequential, cross-sectional ecologic analysis using a diverse set of socioeconomic and demographic variables. Lasso regression was used to identify variables from collinear groups. Twelve variables correlated to cumulative case rates (for cases reported by 1 August 2020) with an adjusted r squared of 0.4525. As time progressed in the pandemic, correlation of demographic and socioeconomic factors to cumulative case rates increased, as did number of variables selected. Findings indicate the social determinants of health and demographic factors continue to predict case rates of COVID-19 at the county-level as the pandemic evolves. This research contributes to the growing body of evidence that health disparities continue to widen, disproportionality affecting vulnerable populations.

[Unusual cause of tetraparesis in an adult]. / Causa rara de tetraparésia no adulto.

A 61 year old male developed progressive spastic tetraparesis and paresis of the lower cranial nerves (IX, X and XI) after a minor spine-head trauma. Magnetic resonance depicted a partially cystic IV ventricular mass, extending to C1/C2 level. Neuropathology was compatible with choroids plexus papilloma (CCP). This case shows a rare clinical presentation of an infrequent adult tumour.