14 research outputs found
Taste Perception And Food Choices
OBJECTIVES:
The extent to which variation in taste perception influences food preferences is, to date, controversial. Bitterness in food triggers an innate aversion that is responsible for dietary restriction in children. We investigated the association among genetic variations in bitter receptor TAS2R38 and food choices in healthy children in the Mediterranean area, to develop appropriate tools to evaluate the relation among genetic predisposition, dietary habits, and feeding disorders. The aims of the study were to get a first baseline picture of taste sensitivity in healthy adults and their children and to explore taste sensitivity in a preliminary sample of obese children and in samples affected by functional gastrointestinal diseases.
METHODS:
Individuals (98 children, 87 parents, 120 adults) were recruited from the general population in southern Italy. Bitterness sensitivity was assessed by means of a suprathreshold method with 6-propyl-2-thiouracil. Genomic DNA from saliva was used to genotype individuals for 3 polymorphisms of TAS2R38 receptor, A49P, A262 V, and V296I. Food intake was assessed by a food frequency questionnaire.
RESULTS:
Children's taste sensation differed from that of adults: we observed a higher frequency of supertasters among children even in the mother-child dyads with the same diplotypes. Among adults, supertaster status was related with proline-alanine-valine (taster allele) homozygous haplotype, whereas supertaster children were mainly heterozygous. Regarding the food choices, we found that a higher percentage of taster children avoided bitter vegetables or greens altogether compared with taster adults. Taster status was also associated with body mass index in boys.
CONCLUSIONS:
Greater sensitivity to 6-propyl-2-thiouracil predicts lower preferences for vegetables in children, showing an appreciable effect of the genetic predisposition on food choices. None of the obese boys was a supertaster
Characterization of novel Bovine Leukemia Virus (BLV) antisense transcripts by deep sequencing reveals constitutive expression in tumors and transcriptional interaction with viral microRNAs
The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance
INTRODUCTION
Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic.
RATIONALE
We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs).
RESULTS
Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants.
CONCLUSION
Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century
Impairment of carbamazepine-10, 11-epoxide elimination by valnoctamide, a valpromide isomer, in healthy subjects.
The effect of the valpromide isomer valnoctamide (VCD, 200 mg three times daily for 8 days), an over-the-counter tranquillizer, on the elimination kinetics of a single oral dose of carbamazepine-10, 11-epoxide (CBZ-E, 100 mg) was investigated in healthy subjects. During VCD treatment, the half-life of CBZ-E was prolonged significantly compared with control (19.7 +/- 6.7 h vs 6.9 +/- 2.0 h, means +/- s.d., P less than 0.01), and its oral clearance decreased four-fold (from 109.6 +/- 30.7 to 28.8 +/- 11.1 ml h-1 kg-1, P less than 0.01). These findings indicate that VCM, like valpromide, strongly inhibits epoxide hydrolase in vivo
Elevation of plasma phenytoin by viloxazine in epileptic patients: a clinically significant drug interaction.
The effect of viloxazine (150-300 mg daily for 21 days) on plasma phenytoin levels at steady state was examined in 10 epileptic patients stabilised on a fixed phenytoin dosage. After starting viloxazine treatment, plasma phenytoin concentrations increased by 37% on average (range 7-94%) from a mean value of 18.8 micrograms/ml at baseline to a mean value of 25.7 micrograms/ml during the last week of combined therapy. In four patients the rise in plasma phenytoin was associated with the development of signs of phenytoin toxicity. Discontinuation of viloxazine resulted in return of plasma phenytoin towards baseline values and disappearance of the clinical symptoms. The mechanism of interaction probably involves inhibition of phenytoin metabolism by viloxazine. Careful monitoring of plasma phenytoin levels is recommended in patients treated with phenytoin who need to be started on viloxazine therapy
Effects of the antidepressant drug viloxazine on oxcarbazepine and its hydroxylated metabolites in patients with epilepsy.
The effects of Viloxazine (VLX, 100 mg b.i.d. for 10 days) on the steady-state plasma concentrations of Oxcarbazepine (OXC), its active metabolite 10, 11-dihydro-10-hydroxy-carbazepine (MHD) and the corresponding diol (DHD) were studied in a randomized, double-blind cross-over placebo-controlled trial in 6 epileptic patients stabilized on a fixed dosage of OXC. Administration of VLX resulted in an 11% increase in the plasma concentration of MHD (p = 0.003) associated with a 31% fall in DHD levels (p = 0.0001). Plasma concentrations of unchanged OXC were unaffected by VLX. No changes in seizure frequency nor signs of drug toxicity were observed during the study. Although VLX may inhibit the conversion of MHD to the inactive diol, the interaction is unlikely to be of clinical significance
Carbamazepine-Valnoctamide Interaction in Epileptic Patients: In Vitro/In Vivo Correlation
Six patients stabilized with carbamazepine (CBZ) therapy received an 8-day "add-on" supplement of valnoctamide (VCD), a tranquilizer available over the counter (OTC) in several European countries that exhibits promising anticonvulsant activity in animal models. During VCD intake, serum levels of the active CBZ metabolite, carbamazepine-10,11-epoxide (CBZ-E), increased fivefold from 1.5 +/- 0.7 micrograms/ml at baseline to 7.4 +/- 4.4 micrograms/ml after 4 days of VCD therapy and 7.7 +/- 3.1 micrograms/ml after 7 days of VCD therapy (means +/- SD, p < 0.01). In 4 patients, the increase in serum CBZ-E levels was associated with clinical signs of CBZ intoxication. CBZ-E levels returned to baseline after VCD therapy was discontinued. Serum CBZ levels remained stable throughout the study. The interaction observed in this study is similar to that described in patients treated with CBZ and valpromide (VPD, an isomer of VCD). In a mechanistic study, therapeutic concentrations of VCD inhibited hydrolysis of styrene oxide in human liver microsome preparations. Thus, VCD is a potent inhibitor of microsomal epoxide hydrolase (IC50 15 microM). There was a striking similarity between in vitro and in vivo inhibition potencies. In this study, VCD clearance was higher in epileptic patients (treated with CBZ) than in healthy subjects
O9.06 * PROGNOSTIC RELEVANCE AND ONCOGENIC CORRELATES OF EPILEPSY IN GLIOBLASTOMA PATIENTS
A phylodynamic workflow to rapidly gain insights into the dispersal history and dynamics of SARS-CoV-2 lineages
Since the start of the COVID-19 pandemic, an unprecedented number of genomic sequences of SARS-CoV-2 have been generated and shared with the scientific community. The unparalleled volume of available genetic data presents a unique opportunity to gain real-time insights into the virus transmission during the pandemic, but also a daunting computational hurdle if analyzed with gold-standard phylogeographic approaches. To tackle this practical limitation, we here describe and apply a rapid analytical pipeline to analyze the spatiotemporal dispersal history and dynamics of SARS-CoV-2 lineages. As a proof of concept, we focus on the Belgian epidemic, which has had one of the highest spatial densities of available SARS-CoV-2 genomes. Our pipeline has the potential to be quickly applied to other countries or regions, with key benefits in complementing epidemiological analyses in assessing the impact of intervention measures or their progressive easement