Maternal genetics and diet modulate vitamin A homeostasis of the offspring and affect the susceptibility to obesity in adulthood in mice.

Perinatal nutrition exerts a profound influence on adult metabolic health. This study aimed to investigate whether increased maternal vitamin A (VA) supply can lead to beneficial metabolic phenotypes in the offspring. The researchers utilized mice deficient in the intestine-specific homeobox (ISX) transcription factor, which exhibit increased intestinal VA retinoid production from dietary ß-carotene (BC). ISX-deficient dams were fed a VA-sufficient or a BC-enriched diet during the last week of gestation and the whole lactation period. Total retinol levels in milk and weanling livers were 2 to 2.5-fold higher in the offspring of BC-fed dams (BC offspring), indicating increased VA supplies during late gestation and lactation. The corresponding VAS and BC offspring (males and females) were compared at weaning and adulthood after being fed either a standard or high-fat diet (HFD) with regular VA content for 13 weeks from weaning. HFD-induced increases in adiposity metrics, such as fat depot mass and adipocyte diameter, were more pronounced in males than females and were attenuated or suppressed in the BC offspring. Notably, the BC offspring were protected from HFD-induced increases in circulating triacylglycerol levels and hepatic steatosis. These protective effects were associated with reduced food efficiency, enhanced capacity for thermogenesis and mitochondrial oxidative metabolism in adipose tissues, and increased adipocyte hyperplasia rather than hypertrophy in the BC offspring. In conclusion, maternal VA nutrition influenced by genetics may confer metabolic benefits to the offspring, with mild increases in late gestation and lactation protecting against obesity and metabolic dysregulation in adulthood.

A Review of the Epigenetic Clock: Emerging Biomarkers for Asthma and Allergic Disease.

DNA methylation (DNAm) is a dynamic, age-dependent epigenetic modification that can be used to study interactions between genetic and environmental factors. Environmental exposures during critical periods of growth and development may alter DNAm patterns, leading to increased susceptibility to diseases such as asthma and allergies. One method to study the role of DNAm is the epigenetic clock-an algorithm that uses DNAm levels at select age-informative Cytosine-phosphate-Guanine (CpG) dinucleotides to predict epigenetic age (EA). The difference between EA and calendar age (CA) is termed epigenetic age acceleration (EAA) and reveals information about the biological capacity of an individual. Associations between EAA and disease susceptibility have been demonstrated for a variety of age-related conditions and, more recently, phenotypes such as asthma and allergic diseases, which often begin in childhood and progress throughout the lifespan. In this review, we explore different epigenetic clocks and how they have been applied, particularly as related to childhood asthma. We delve into how in utero and early life exposures (e.g., smoking, air pollution, maternal BMI) result in methylation changes. Furthermore, we explore the potential for EAA to be used as a biomarker for asthma and allergic diseases and identify areas for further study.

Comparative profile for COVID-19 cases from China and North America: Clinical symptoms, comorbidities and disease biomarkers.

BACKGROUND: Large inter-individual and inter-population differences in the susceptibility to and outcome of severe acute respiratory syndrome coronavirus 2 or coronavirus disease 2019 (COVID-19) have been noted. Understanding these differences and how they influence vulnerability to infection and disease severity is critical to public health intervention. AIM: To analyze and compare the profile of COVID-19 cases between China and North America as two regions that differ in many environmental, host and healthcare factors related to disease risk. METHODS: We conducted a meta-analysis to examine and compare demographic information, clinical symptoms, comorbidities, disease severity and levels of disease biomarkers of COVID-19 cases from clinical studies and data from China (105 studies) and North America (19 studies). RESULTS: COVID-19 patients from North America were older than their Chinese counterparts and with higher male: Female ratio. Fever, cough, fatigue and dyspnea were the most common clinical symptoms in both study regions (present in about 30% to 75% of the cases in both regions). Meta-analysis for the prevalence of comorbidities (such as obesity, hypertension, diabetes, cardiovascular diseases, chronic obstructive pulmonary disease, cancer, and chronic kidney diseases) in COVID-19 patients were all significantly more prevalent in North America compared to China. Comorbidities were positively correlated with age but at a significantly younger age range in China compared to North American. The most prevalent infection outcome was acute respiratory distress syndrome which was 2-fold more frequent in North America than in China. Levels of C-reactive protein were 4.5-fold higher in the North American cases than in cases from China. CONCLUSION: The differences in the profile of COVID-19 cases from China and North America may relate to differences in environmental-, host- and healthcare-related factors between the two regions. Such inter-population differences-together with intra-population variability-underline the need to characterize the effect of health inequities and inequalities on public health response to COVID-19 and can assist in preparing for the re-emergence of the epidemic.

Ethical issues associated with solid organ transplantation and substance use: a scoping review.

While solid organ transplantation for patients with substance use issues has attracted ethical discussion, a typology of the ethics themes has not been articulated in the literature. We conducted a scoping review of peer-reviewed literature on solid organ transplantation and substance use published between January 1997 and April 2016. We aimed to identify and develop a typology of the main ethical themes discussed in this literature and to identify gaps worthy of future research. Seventy articles met inclusion criteria and underwent inductive content analysis. Four main ethical themes were identified: (1) personal responsibility; (2) utility; (3) moral character; and (4) fairness. Each theme had multiple sub-themes and there was substantial overlap between themes. This scoping review identified a disproportionate emphasis in the literature regarding personal responsibility, which was referenced by each of the other themes, and a narrow focus on alcohol and liver. We recommend future research further investigate these connections between ethical themes and focus on ethical issues associated with transplants from organ groups other than liver for patients who use substances other than alcohol.

Ambiguous identities of drugs and people: A scoping review of opioid-related stigma.

BACKGROUND: Human beings have long consumed opiates and opioids for pleasure and as a treatment for numerous ailments, most notably pain. North America is currently in the grips of a crisis of opioid-related overdoses, and stigma is considered a major driver of the harms. While it is well established that substance use in general is highly stigmatized, stigma is a complex concept and opioid-related stigma is not well understood. A lack of clarity on opioid-related stigma has practice and policy implications in terms of understanding the sources of opioid stigma, how it manifests in various contexts, its impact on affected groups, and the development of effective strategies to redress it. METHODS: We performed a scoping review of the academic literature to develop a typology of opioid-related stigma. A charting process identified the type, agent, and recipient of stigma as well as the methodology and substances considered. RESULTS: Our search yielded 8,543 articles, from which 49 were included in the analysis. Based on the findings, we developed a typology of four main themes: (1) interpersonal and structural stigma toward people accessing opioid agonist therapy (OAT); (2) stigma related to opioids for the treatment of chronic pain; (3) stigma in healthcare settings; and (4) self-stigma. CONCLUSION: How opioid-stigma is (re)produced depends on the context of opioid use, the social identity and networks of the person who is consuming the opioid, and what type of opioid is being consumed, including medically-sanctioned forms of treatment. Opioid-related stigma permeates intrapersonal, interpersonal, structural, and societal levels, and people who consume opioids are marginalized at all levels. Our review describes our typology of stigma and illuminates multi-level considerations for reducing opioid-related stigma in healthcare settings.

C-reactive protein as a biomarker of severe H1N1 influenza.

BACKGROUND: C-reactive protein (CRP) is an acute-phase reactant downstream of the pro-inflammatory cytokines released during influenza infection. However, the role of this inflammatory marker in influenza severity and complications is yet to be elucidated. OBJECTIVES: We aim to systematically review and evaluate the levels of CRP in severe and non-severe H1N1 influenza cases and assess its utility as a biomarker in predicting the severity of infection. METHODS: We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of Print, Embase and Embase Classic to identify human studies reporting measurements of CRP levels in patients infected with H1N1 influenza at various levels of disease severity. RESULTS: Our search identified ten studies eligible for inclusion in this systematic review. The results of the data analysis show that the average CRP levels upon diagnosis were significantly higher (P < 0.05) in patients who developed severe H1N1 influenza compared to their counterparts with a no severe disease. Furthermore, levels of CRP were associated with the degree of H1N1 severity. Subjects with H1N1-related pneumonia and patients who were hospitalized or died of the disease complications, respectively, had 1.4- and 2.5-fold significantly higher CRP levels (P < 0.05) than those with no severe disease outcome. CONCLUSION: CRP levels have been consistently shown to be significantly higher in H1N1 influenza patients who develop a severe disease outcome. The resuts of the present study suggest that serum CRP can be employed-in combination with other biomarkers-to predict the complications of H1N1 influenza.

Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis.

BACKGROUND: Flavivirus diseases such as dengue fever (DENV), West Nile virus (WNV), Zika and yellow fever represent a substantial global public health concern. Preexisting chronic conditions such as cardiovascular diseases, diabetes, obesity, and asthma were thought to predict risk of progression to severe infections. OBJECTIVE: We aimed to quantify the frequency of chronic comorbidities in flavivirus diseases to provide an estimate for their prevalence in severe and non-severe infections and examine whether chronic diseases contribute to the increased risk of severe viral expression. METHODS: We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic and grey literature databases to identify studies reporting prevalence estimates of comorbidities in flavivirus diseases. Study quality was assessed with the risk of bias tool. Age-adjusted odds ratios (ORs) were estimated for severe infection in the presence of chronic comorbidities. RESULTS: We identified 65 studies as eligible for inclusion for DENV (47 studies) and WNV (18 studies). Obesity and overweight (i.e., BMI> 25 kg/m2, prevalence: 24.5%, 95% CI: 18.6-31.6%), hypertension (17.1%, 13.3-21.8%) and diabetes (13.3%, 9.3-18.8%) were the most prevalent comorbidities in DENV. However, hypertension (45.0%, 39.1-51.0%), diabetes (24.7%, 20.2-29.8%) and heart diseases (25.6%, 19.5-32.7%) were the most prevalent in WNV. ORs of severe flavivirus diseases were about 2 to 4 in infected patients with comorbidities such as diabetes, hypertension and heart diseases. The small number of studies in JEV, YFV and Zika did not permit estimating the prevalence of comorbidities in these infections. CONCLUSION: Higher prevalence of chronic comorbidities was found in severe cases of flavivirus diseases compared to non-severe cases. Findings of the present study may guide public health practitioners and clinicians to evaluate infection severity based on the presence of comorbidity, a critical public health measure that may avert severe disease outcome given the current dearth of clear prevention practices for some flavivirus diseases.

Prevalence of chronic comorbidities in chikungunya: A systematic review and meta-analysis.

BACKGROUND: Epidemiologic evidence suggests that patients with chikungunya virus (CHIKV) infection may be at risk of severe disease complications when they also have comorbidities such as obesity, diabetes, cardiac diseases, and/or asthma. However, the prevalence of these co-existing medical conditions in severe CHIKV cases has not been systematically reported. OBJECTIVE: The aim of the present study is to conduct a systematic review and meta-analysis to describe the prevalence of chronic comorbidities in CHIKV and evaluate their possible contributions to disease severity. METHODS: A search strategy was developed for online databases. Search terms used were "Chikungunya" AND "Diabetes, Hypertension, Stroke, Cardiovascular Diseases, Coronary Artery Diseases, Obesity, OR Asthma". Only 11 articles documenting the frequency of comorbidities in CHIKV were included. Meta-analyses were conducted to evaluate the overall prevalence of comorbidities in the CHIKV infection and stratify the estimates by severity. RESULTS: Among 2,773 CHIKV patients, hypertension was the most prevalent comorbidity (31.3%; 95%CI: 17.9-48.8%) followed by diabetes (20.5%; 95%CI: 12.7-31.3%), cardiac diseases (14.8%; 95%CI: 8.1-25.5%) and asthma (7.9%; 95%CI: 3.3-17.7). There was 4- to 5-fold significant increased prevalence of diabetes, hypertension and cardiac diseases in CHIKV patients over 50 years of age compared to their younger counterparts. Severe CHIKV cases had a significantly higher proportion of diabetes than non-severe cases (p<0.05). CHIKV patients with diabetes had OR of 1.2 (95%CI: 1.05-1.48; p=0.0135) for developing severe infection outcome compared to those with no diabetes. CONCLUSION: Hypertension, diabetes and cardiac diseases may contribute to the severe outcome of CHIKV. Diabetic subjects may be at higher risk of severe infection. These findings may be relevant in developing public health measures and practices targeting CHIKV patients with comorbidities to avert the severe outcome of the infectious disease.