Hepatic Vitamin A Concentrations and Association with Infectious Causes of Child Death.

OBJECTIVES: To assess postmortem vitamin A (VA) concentrations in children under 5 years of age and evaluate the association between VA deficiency (VAD) and infectious causes of death (CoD). STUDY DESIGN: In this cross-sectional study from the Child Health and Mortality Prevention Surveillance (CHAMPS) Network, liver biopsies collected within 72 hours of death were analyzed from 405 stillbirths and children under 5 years in Kenya and South Africa. Total liver VA (TLVA) concentrations were quantified using ultra-performance liquid chromatography, and cutoffs of ≤0.1 µmol/g, >0.1 to <0.7 µmol/g, ≥0.7 to <1.0 µmol/g, and ≥1.0 µmol/g were used to define VAD, adequate VA status, high VA, and hypervitaminosis A, respectively. CoD were determined by expert panel review. RESULTS: Among 366 liver samples with viable extraction, pooled prevalences of VAD, adequacy, high VA, and hypervitaminosis were 34.2%, 51.1%, 6.0%, and 8.7%, respectively. VAD was more common among neonates compared with stillbirths, infants, or children, and among those with low birthweight (LBW), underweight, or stunting (P < .05). When adjusting for site, age, and sex, there was no significant association of VAD with increased infectious CoD (OR 1.9, 95% confidence interval [CI] 0.9, 3.8, P = .073). In stratified analyses, VA deficient boys, but not girls, had an increased risk of infectious CoD (OR 3.4, 95% CI 1.3, 10.3, P = .013). CONCLUSIONS: Definitive postmortem assessment of VA status identified both VAD and VA excess among children under 5 years of age in Kenya and South Africa. VAD in boys was associated with increased risk of infectious mortality. Our findings may inform a transition from universal VA supplementation (VAS) to targeted strategies in certain countries.

Cannabis Sativa in Phytotherapy: Reappraisal of Therapeutic Potential and Regulatory Aspects.

Cannabis sativa is widely used as a folk medicine in many parts of the globe and has been reported to be a treasure trove of phytoconstituents, including cannabinoids, terpenoids, and flavonoids. Accumulating evidence from various pre-clinical and clinical studies revealed the therapeutic potential of these constituents in various pathological conditions, including chronic pain, inflammation, neurological disorders, and cancer. However, the psychoactive effect and addiction potential associated with cannabis use limited its clinical application. In the past two decades, extensive research on cannabis has led to a resurgence of interest in the clinical application of its constituents, particularly cannabinoids. This review summarizes the therapeutic effect and molecular mechanism of various phytoconstituents of cannabis. Furthermore, recently developed nanoformulations of cannabis constituents have also been reviewed. Since cannabis is often associated with illicit use, regulatory aspects are of vital importance and this review therefore also documented the regulatory aspects of cannabis use along with clinical data and commercial products of cannabis.

WITHDRAWN: Cannabis Sativa In Phytotherapy : Reappraisal Of Therapeutic Potential And Regulatory Aspects

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Prevalence of Cannabis Use and Cannabis Route of Administration among Massachusetts Adults in Buprenorphine Treatment for Opioid Use Disorder.

BACKGROUND: Recent prevalence estimates of cannabis use among individuals receiving medication treatment for OUD (MOUD) are lacking, and no study has characterized cannabis route of administration (cROA) in this population. These knowledge gaps are relevant because cannabis' effects and health outcomes vary by cROA and the availability and perceptions of cROA (e.g., vaping devices) are changing. METHODS: The Vaping In Buprenorphine-treated patients Evaluation (VIBE) cross-sectional survey assessed the prevalence and correlates of cannabis use and cROA among adults receiving buprenorphine MOUD from 02/20 to 07/20 at five community health centers in Massachusetts, a state with legal recreational and medical cannabis use. RESULTS: Among the 92/222 (41%) respondents reporting past 30-day cannabis use, smoking was the most common cROA (75%), followed by vaping (38%), and eating (26%). Smoking was more often used as a single cROA vs. in combination others (p = 0.01), whereas vaping, eating, and dabbing were more often used in combination with another cROA (all p < 0.05). Of the 39% of participants reporting multiple cROA, smoking and vaping (61%), and smoking and eating (50%), were the most prevalent combinations. Nonwhite race (vs. white) and current cigarette smoking (vs. no nicotine use) were associated with past 30-day cannabis use in multiple logistic regression. CONCLUSIONS: Prevalence of past 30-day cannabis use among individuals receiving buprenorphine MOUD in Massachusetts in 2020 was nearly double the prevalence of cannabis use in Massachusetts' adult general population in 2019 (21%). Our data are consistent with state and national data showing smoking as the most common cROA.

Impact of Microbiota: A Paradigm for Evolving Herd Immunity against Viral Diseases.

Herd immunity is the most critical and essential prophylactic intervention that delivers protection against infectious diseases at both the individual and community level. This process of natural vaccination is immensely pertinent to the current context of a pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection around the globe. The conventional idea of herd immunity is based on efficient transmission of pathogens and developing natural immunity within a population. This is entirely encouraging while fighting against any disease in pandemic circumstances. A spatial community is occupied by people having variable resistance capacity against a pathogen. Protection efficacy against once very common diseases like smallpox, poliovirus or measles has been possible only because of either natural vaccination through contagious infections or expanded immunization programs among communities. This has led to achieving herd immunity in some cohorts. The microbiome plays an essential role in developing the body's immune cells for the emerging competent vaccination process, ensuring herd immunity. Frequency of interaction among microbiota, metabolic nutrients and individual immunity preserve the degree of vaccine effectiveness against several pathogens. Microbiome symbiosis regulates pathogen transmissibility and the success of vaccination among different age groups. Imbalance of nutrients perturbs microbiota and abrogates immunity. Thus, a particular population can become vulnerable to the infection. Intestinal dysbiosis leads to environmental enteropathy (EE). As a consequence, the generation of herd immunity can either be delayed or not start in a particular cohort. Moreover, disparities of the protective response of many vaccines in developing countries outside of developed countries are due to inconsistencies of healthy microbiota among the individuals. We suggested that pan-India poliovirus vaccination program, capable of inducing herd immunity among communities for the last 30 years, may also influence the inception of natural course of heterologous immunity against SARS-CoV-2 infection. Nonetheless, this anamnestic recall is somewhat counterintuitive, as antibody generation against original antigens of SARS-CoV-2 will be subdued due to original antigenic sin.

Iron Content of Commercially Available Infant and Toddler Foods in the United States, 2015.

OBJECTIVES: To describe the iron content of commercially available infant and toddler foods. METHODS: Nutrition Facts label data were used from a 2015 database of 1037 commercial infant and toddler food and drink products. Products were grouped into food categories on the basis of name, ingredients, target age, and reference amounts customarily consumed (RACC). Mean and median iron content per 100 g and per RACC were calculated. The proportion of products considered good and excellent sources of iron were determined on the basis of percent daily value (% DV) thresholds. RESULTS: Among products marketed for infants (aged 4-12 months), infant cereals had the highest mean (6.19 mg iron per RACC; 41.25 iron mg per 100 g) iron content. Among products marketed for toddlers (aged 12-36 months), vegetable-based mixtures or meals contained the highest mean iron in mg per RACC (mean: 2.97 mg) and dry, grain-based desserts had the highest mean iron in mg per 100 g (mean: 6.45 mg). Juice and drink products had the lowest mean iron contents in both infant and toddler products. CONCLUSIONS: Most commercially available infant cereals are considered to be an excellent source of iron, likely from fortification, but wide variability was observed in iron content by food category. Products that are considered good or excellent sources of iron (≥10% DV) can help consumers identify products with higher iron content, such as infant cereals or toddler vegetable-based mixtures/meals.

Standardized Xylocarpus moluccensis fruit fraction mitigates collagen-induced arthritis in mice by regulating immune response.

OBJECTIVE: This study was undertaken to evaluate the effect of Xylocarpus moluccensis fruit fraction (F018) on the pathogenesis of collagen-induced arthritis in mice. METHODS: Arthritis was induced by intradermal injection of collagen (2 mg/ml) with complete Freund's adjuvant in DBA/1J mice. F018 was administered orally at 1, 3 and 10 mg/kg for 20 days. Disease progression and mechanism were assessed by micro-CT analysis, RT-PCR, flow cytometry assay, myeloperoxidase (MPO) and MTT assay. RESULTS: F018 at 3 and 10 mg/kg significantly reduced paw thickness, clinical score, mononuclear cell infiltration and collagen layer depletion in the knee section of collagen-induced arthritis (CIA) mice when compared with collagen-induced arthritis mice alone. Furthermore, F018 treatment in collagen-induced arthritis mice significantly recovered bone volume and trabecular number and decreased the trabecular space by modulating RANKL and OPG mRNA expression in the synovial tissue. F018 treatment in collagen-induced arthritis mice significantly attenuated spleen index, lymphocyte proliferation and paw myeloperoxidase (MPO) activity, pro-inflammatory cytokine TNFα, IL1ß, and IL6 mRNA expression and enhanced IL10 mRNA expression in paw tissue. Furthermore, F018 treatment in collagen-induced arthritis mice significantly reduced splenic dendritic cell maturation and Th17 cells. In culture, F018 significantly decreased collagen-induced arthritis-FLS proliferation and promoted apoptosis. CONCLUSION: F018 may serve as a potential curative agent for arthritis.

Alteration in apoptotic rate of testicular cells and sperms following administration of Bisphenol A (BPA) in Wistar albino rats.

The aim of the study was to evaluate the effect of Bisphenol A [BPA] widely used as a plasticizer in the formation of polycarbonate plastics and epoxy resins, exposure causing alteration in apoptosis rate, and protective effect of Vitamin E when supplemented with BPA orally. Adult male Wistar albino rats aged 3 months were randomly divided into seven groups: control (olive oil treated) BPA-treated (dose 5, 50,100 µg/100gmBW) and Vitamin E intervention group (dose 5, 50, 100 µg/100gmBW BPA+ Vitamin E dose 4 mg/100gmBW). Animals were sacrificed 3 months later, and blood and tissue samples were collected. Apoptotic changes were analyzed in epididymal spermatozoa and testis tissue by binding of annexin V apoptotic biomarker. A significant decline in the weight of testis, testosterone level, and sperm count was observed. Histopathological and apoptotic changes were observed in testis tissue. In epididymal sperms, the early apoptotic cells were observed by staining of annexin V-conjugated FITC and PI green fluorescence in spermatozoa head which indicated the damage of membrane and late apoptotic cells. These changes reduced significantly in Vitamin E-treated groups though were not found to be comparable to control animals. All these changes were attributed to disrupted spermatogenesis that would interfere with sperm formation. Thus, the study infers that BPA affects the apoptosis process in the testis and epididymal sperm that would interfere with its function and contribute to infertility, whereas Vitamin E-supplemented dose has a protective effect towards these changes, indicating its role in improving male fertility.

Use of Iodine-Containing Dietary Supplements Remains Low among Women of Reproductive Age in the United States: NHANES 2011-2014.

In the United States, the American Thyroid Association recommends that women take a dietary supplement containing 150 µg of iodine 3 months prior to conception and while pregnant and lactating to support fetal growth and neurological development. We used data from the National Health and Nutrition Examination Survey 2011–2014 to describe the use of dietary supplements with and without iodine in the past 30 days among 2155 non-pregnant, non-lactating (NPNL) women; 122 pregnant women; and 61 lactating women. Among NPNL women, 45.3% (95% Confidence Interval [CI]: 42.0, 48.6) used any dietary supplement and 14.8% (95% CI: 12.7, 16.8) used a dietary supplement with iodine in the past 30 days. Non-Hispanic black and Hispanic women were less likely to use any dietary supplement as well as one with iodine, than non-Hispanic white or non-Hispanic Asian women (p < 0.05). Among pregnant women, 72.2% (95% CI: 65.8, 78.6) used any dietary supplement; however, only 17.8% (95% CI: 11.4, 24.3) used a dietary supplement with iodine. Among lactating women, 75.0% (95% CI: 63.0, 87.0) used a dietary supplement; however, only 19.0% (95% CI: 8.8, 29.2) used a dietary supplement with iodine. Among NPNL women using a supplement with iodine, median daily iodine intake was 75.0 µg. Self-reported data suggests that the use of iodine containing dietary supplements among pregnant and lactating women remains low in contrast with current recommendations.

High throughput in silico identification and characterization of Plasmodium falciparum PRL phosphatase inhibitors.

Kinases and phosphatases are involved in many essential processes in Plasmodium lifecycle. Among the identified 67 Plasmodium falciparum phosphatases, Phosphatase of Regenerating Liver (PRL) family protein homolog, PfPRL, is an essential parasite tyrosine phosphatase. PfPRL is shown to be prenylated, secreted, and involved in the host invasion process. In the present study, a structure-based high throughput in silico screening of PfPRL binders, using ChEMBL-NTD compounds lead to the identification of nine compounds based on binding energy, Lipinski rule of five, and QED score. The most of the shortlisted compounds are known to inhibit parasite growth at a concentration (EC50) ≤2 µm in in vitro P. falciparum culture assays. MD simulations were carried out on the shortlisted nine potential enzyme-inhibitor complexes to analyze specificity, stability, and to calculate the free binding energies of the complexes. The study identifies PfPRL as one of the potential drug targets for selected ChEMBL-NTD compounds that may be exploited as a scaffold to develop novel antimalarials.

The role of spirituality in diabetes self-management in an urban, underserved population: a qualitative exploratory study.

BACKGROUND: Although many studies examine motivators for diabetes self-management, few explore the role spirituality plays in this disease, especially in low-income urban populations. METHODS: This qualitative, focus group study elicits thoughts of diabetic patients regarding spirituality in diabetes self-care, at an urban primary care practice in Rhode Island. Focus group discussions were audiotaped, transcribed verbatim, and analyzed using the immersion/crystallization technique. RESULTS: Themes included: significant impact of diabetes on daily life; fear and family as prominent self-care motivators; relationships with self, others, nature and the divine as major sources of hope and strength. Patients varied considerably regarding the role spirituality played in their illness, ranging from minimal to profound impact. All appeared comfortable discussing spirituality within the context of strength and hope. CONCLUSION: Patients in this urban, underserved population are willing to discuss spirituality related to their diabetes care. They vary in the role spirituality plays in their illness experience.

Effects of two different catheter ablation techniques on spectral characteristics of atrial fibrillation.

OBJECTIVES: The aim of this study was to determine the effects of circumferential pulmonary vein ablation (CPVA) and electrogram-guided ablation (EGA) on the spectral characteristics of atrial fibrillation (AF) and the relationship between changes in dominant frequency (DF) and clinical outcome. BACKGROUND: Circumferential pulmonary vein ablation and EGA have been used to eliminate AF. Spectral analysis may identify high-frequency sources. METHODS: In 84 consecutive patients, CPVA (n = 42) or EGA (n = 42) was performed for paroxysmal (n = 49) or persistent (n = 35) AF. During EGA, complex electrograms were targeted. Lead V1 and electrograms from the left atrium and coronary sinus were analyzed to determine the DF of AF before and after ablation. RESULTS: The left atrial DF was higher in persistent (5.83 +/- 0.86 Hz) than paroxysmal AF (5.33 +/- 0.76 Hz, p = 0.03). There was a frequency gradient from the left atrium to the coronary sinus (p = 0.02). Circumferential pulmonary vein ablation and EGA resulted in a similar decrease in DF (18 +/- 17% vs. 17 +/- 15%, p = 0.8). During a mean follow-up of 9 +/- 6 months, the change in DF after CPVA was similar among patients with and without recurrent AF. An acute decrease in DF after EGA was associated with freedom from recurrent AF only in patients with persistent AF (19 +/- 14% vs. 3 +/- 6%, p = 0.02). CONCLUSIONS: Both CPVA and EGA decrease the DF of AF, consistent with elimination of high-frequency sources. Whereas the efficacy of EGA is associated with a decrease in DF in patients with persistent AF, the efficacy of CPVA is independent of changes in DF. This suggests that CPVA and EGA eliminate different mechanisms in the genesis of persistent AF.