Folate deficiency increases the incidence of dolutegravir-associated foetal defects in a mouse pregnancy model.

BACKGROUND: Dolutegravir (DTG) is a recommended first-line regimen for all people with Human Immunodeficiency Virus (HIV) infection. Initial findings from Botswana, a country with no folate fortification program, showed an elevated prevalence of neural tube defects (NTDs) with peri-conceptional exposure to DTG. Here we explore whether a low folate diet influences the risk of DTG-associated foetal anomalies in a mouse model. METHODS: C57BL/6 mice fed a folate-deficient diet for 2 weeks, were mated and then randomly allocated to control (water), or 1xDTG (2.5 mg/kg), or 5xDTG (12.5 mg/kg) both administered orally with 50 mg/kg tenofovir disoproxil fumarate 33.3 mg/kg emtricitabine. Treatment was administered once daily from gestational day (GD) 0.5 to sacrifice (GD15.5). Foetuses were assessed for gross anomalies. Maternal and foetal folate levels were quantified. FINDINGS: 313 litters (103 control, 106 1xDTG, 104 5xDTG) were assessed. Viability, placental weight, and foetal weight did not differ between groups. NTDs were only observed in the DTG groups (litter rate: 0% control; 1.0% 1xDTG; 1.3% 5xDTG). Tail, abdominal wall, limb, craniofacial, and bleeding defects all occurred at higher rates in the DTG groups versus control. Compared with our previous findings on DTG usage in folate-replete mouse pregnancies, folate deficiency was associated with higher rates of several defects, including NTDs, but in the DTG groups only. We observed a severe left-right asymmetry phenotype that was more frequent in DTG groups than controls. INTERPRETATION: Maternal folate deficiency may increase the risk for DTG-associated foetal defects. Periconceptional folic acid supplementation could be considered for women with HIV taking DTG during pregnancy, particularly in countries lacking folate fortification programs. FUNDING: This project has been funded by Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN275201800001I and award #R01HD104553. LS is supported by a Tier 1 Canada Research Chair in Maternal-Child Health and HIV. HM is supported by a Junior Investigator award from the Ontario HIV Treatment Network.

Identification of Dietary Supplements Associated with Blood Metabolites in the Hispanic Community Health Study/Study of Latinos Cohort Study.

BACKGROUND: Metabolomics approaches have been widely used to define the consumption of foods but have less often been used to study exposure to dietary supplements. OBJECTIVES: This study aimed to identify dietary supplements associated with metabolite levels and to examine whether these metabolites predicted incident diabetes risk. METHODS: We studied 3972 participants from a prospective cohort study of 18-74-y-old Hispanic/Latino adults. At a baseline examination, we ascertained use of dietary supplements using recall methods and concurrently, a serum metabolomic panel. After adjustment for potential confounders, we identified dietary supplements associated with metabolites. We then examined the association of these metabolites with incident diabetes at the 6-y study examination. RESULTS: We observed a total of 110 dietary supplement-metabolite associations that met the criteria for statistical significance adjusted for age, sex, field center, Hispanic/Latino background, body mass index, diet, smoking, physical activity, and number of medications (adjusted P < 0.05). This included 13 metabolites uniquely associated with only one dietary supplement ingredient. Vitamin C had the most associated metabolites (n = 15), including positive associations with oxalate, tartronate, threonate, and isocitrate, which were each in turn protective for the risk of incident diabetes. Vitamin C was also associated with higher N-acetylvaline level, which was an unfavorable diabetes risk factor. Other findings related to branched chain amino acid related compounds including α-hydroxyisovalerate and 2-hydroxy-3-methylvalerate, which were inversely associated with thiamine or riboflavin intake and also predicted higher diabetes risk. Vitamin B12 had an inverse association with γ-glutamylvaline, levels of which were positively associated with the risk of diabetes. CONCLUSIONS: Our data point to potential metabolite changes associated with vitamin C and B vitamins, which may have favorable metabolic effects. Knowledge of blood metabolites that can be modified by dietary supplement intake may aid understanding the health effects of dietary supplements and identify potential biological mediators.

Nature-Based Guided Imagery as an Intervention for State Anxiety.

Anxiety is a significant mental health issue in modern society and empirical research into effective interventions to address anxiety has been extensive. Spending time in nature is one approach that has demonstrated anxiolytic effects. However, in some situations and contexts spending time in nature in order to reduce anxiety symptoms may not be possible. For example, in therapeutic settings delivered in a space with no access or exposure to any nature stimuli in the immediate surrounding environment. Guided imagery (GI) has also proven to be effective for reducing anxiety symptoms. Thus, nature-based GI might help to overcome the limitation of access to nature and strengthen the impact of GI interventions. The current study investigated the effectiveness of nature-based GI on anxiety reduction. Participants (n = 48, 18 males, 30 females, M age = 34.54, SD age = 12.91, age range = 19 - 71 years) with moderate levels of either trait or state anxiety as measured by the state-trait anxiety inventory (STAI) were recruited. Participants undertook both a nature-based GI session and a traditional non-nature-based GI session and their pre- and post- state anxiety levels were measured in each GI session. It was anticipated that post state anxiety scores would be significantly lower for both GI conditions and that a significantly greater anxiety reduction would be found in the nature-based GI than the urban-based GI. A two-way analysis of variance for repeated measures revealed results that supported both hypotheses. This study was the first to compare a nature based GI intervention with a traditional (non-nature based) GI intervention. Findings indicate that nature-based GI interventions are effective anxiety management interventions that have the added benefit of being cost-effective and easily accessible.

Photophysics and aggregation effects of a triphenylamine-based dye sensitizer on metal-oxide nanoparticles suspended in an ion trap.

The photophysical behaviour of a triphenylamine-based organic dye sensitizer (Carbz-PAHTDTT) attached to alumina and titania nanoparticles (labelled Carbz-Al and Carbz-Ti, respectively) is examined in the absence and presence of the chenodeoxycholic acid (CDCA) coadsorber. The experiments are conducted in vacuo by suspending the target dye-sensitized nanoparticles within a quadrupole ion trap, where they are probed with laser radiation to obtain emission spectra and time-resolved excited state decay curves. For Carbz-Al, the dye's emission band is blue-shifted and the excited state lifetime is increased upon the coabsorption of CDCA, effects attributed to reduced dye aggregation. Compared to Carbz-Al, the Carbz-Ti excited state lifetimes are significantly shorter due to excited dye molecules injecting electrons into the titania conduction band. For Carbz-Ti, the electron injection quantum yields for the surfaces with CDCA (CDCA : dye = 25 : 1) and without CDCA are estimated to be 0.87 and 0.71, respectively. The gas-phase results demonstrate that Carbz-PAHTDTT dye aggregates are detrimental to the performance of a dye-sensitized solar cell.