Integrative Assessment of Total and Intact HIV-1 Reservoir by a 5-Region Multiplexed Rainbow DNA Digital PCR Assay.

Background: Persistent latent reservoirs of intact HIV-1 proviruses, capable of rebounding despite suppressive antiretroviral therapy (ART), hinder efforts towards an HIV-1 cure. Hence, assays specifically quantifying intact proviruses are crucial to assess the impact of curative interventions. Two recent assays have been utilized in clinical trials: intact proviral DNA assay (IPDA) and quadruplex quantitative PCR (Q4PCR).

Analysing matched continuous longitudinal data: A review.

Longitudinal data are frequently encountered in medical research, where participants are followed throughout time. Additional structure and hence complexity occurs when there is pairing between the participants (e.g.

In depth analysis of the HIV reservoir confirms effectiveness and safety of DTG/3TC in a phase 4 randomized controlled switch trial (RUMBA).

Background: Reducing the number of active compounds for lifelong HIV treatment is of interest, especially to reduce potential long-term side effects. So far, available data assessing viral control, support the robustness and safety of 2DR (2-drug regimen) ART compared to 3DR. However, further in-depth investigations of the viral reservoirs are mandatory to guarantee long-term safety of these regimens regarding stable intact HIV-1 DNA copies, HIV-1 RNA transcripts and sustained immunological control.

A joint normal-ordinal (probit) model for ordinal and continuous longitudinal data.

In biomedical studies, continuous and ordinal longitudinal variables are frequently encountered. In many of these studies it is of interest to estimate the effect of one of these longitudinal variables on the other. Time-dependent covariates have, however, several limitations; they can, for example, not be included when the data is not collected at fixed intervals.

Assessing the impact of COVID-19 passes and mandates on disease transmission, vaccination intention, and uptake: a scoping review.

Purpose: Policymakers have struggled to maintain SARS-CoV-2 transmission at levels that are manageable to contain the COVID-19 disease burden while enabling a maximum of societal and economic activities. One of the tools that have been used to facilitate this is the so-called "COVID-19 pass". We aimed to document current evidence on the effectiveness of COVID-19 passes, distinguishing their indirect effects by improving vaccination intention and uptake from their direct effects on COVID-19 transmission measured by the incidence of cases, hospitalizations, and deaths.

A longitudinal perspective on perceived vulnerability to disease during the COVID-19 pandemic in Belgium.

During the coronavirus disease 2019 pandemic, individuals relied heavily on media sources to stay informed about the disease and public health measures. However, differences exist in the type and frequency of news media consumption, which can be linked to their perceived vulnerability to disease. In this longitudinal study, 1000 Flemish (Belgium) individuals were followed from March 2020 until September 2020, focussing on the evolution in perceived vulnerability to disease (i.

Do optimism and moralization predict vaccination? A five-wave longitudinal study.

Objective: To examine if personal and comparative optimism, perceived effectiveness, and moralization of vaccination predict people's decision to get vaccinated.

Methods: We measured self-reported vaccination decisions in a five-wave longitudinal study ( ≍ 5,000/wave) in Belgium over a six months period (December 2020-May 2021) during the COVID-19 pandemic. Among the predictors were demographic factors, personal and comparative optimism for three aspects of COVID-19 (infection, severe disease, good outcome), perceived effectiveness of vaccination, and the extent to which vaccination is being viewed in prosocial terms (altruism, civic spirit) versus as instrumental in one's self-interest (common sense, concern about one's health).

Normal tension glaucoma: A dynamic optical coherence tomography angiography study.

Purpose: Vascular dysregulation seems to play a role in the pathogenesis of glaucoma, in particular normal tension glaucoma (NTG). The development of optical coherence tomography angiography (OCTA) enabled the measurement of the retinal microvasculature non-invasively and with high repeatability. Nonetheless, only a few studies transformed OCTA into a dynamic examination employing a sympathomimetic stimulus.

Self-uniqueness beliefs and adherence to recommended precautions. A 5-wave longitudinal COVID-19 study.

Rationale: Research on health-related self-uniqueness beliefs suggested that these beliefs might predict adherence to precautions against COVID-19.

Objective: We examined if comparative optimism (believing that one is less at less than others), self-superiority (believing that one already adheres better to precautions than others), and egocentric impact perception (believing that adverse events affect oneself more than others) predicted intended adherence to precautions.

Method: We measured self-reported intentions, optimism for self and others, perceived past adherence by self and others, and perceived impact of the measures and the disease on self and others in a 5-wave longitudinal study in December 2020-May 2021 (N ≈ 5000/wave).

Longitudinal Alterations in Gait Features in Growing Children With Duchenne Muscular Dystrophy.

Prolonging ambulation is an important treatment goal in children with Duchenne muscular dystrophy (DMD). Three-dimensional gait analysis (3DGA) could provide sensitive parameters to study the efficacy of clinical trials aiming to preserve ambulation. However, quantitative descriptions of the natural history of gait features in DMD are first required.

Consecutive action of two BAHD acyltransferases promotes tetracoumaroyl spermine accumulation in chicory.

Fully substituted phenolamide accumulation in the pollen coat of Eudicotyledons is a conserved evolutionary chemical trait. Interestingly, spermidine derivatives are replaced by spermine derivatives as the main phenolamide accumulated in the Asteraceae family. Here, we show that the full substitution of spermine in chicory (Cichorium intybus) requires the successive action of two enzymes, that is spermidine hydroxycinnamoyl transferase-like proteins 1 and 2 (CiSHT1 and CiSHT2), two members of the BAHD enzyme family.

Author Correction: A GDSL lipase-like from Ipomoea batatas catalyzes efficient production of 3,5-diCQA when expressed in Pichia pastoris.

A Correction to this paper has been published: https://doi.org/10.1038/s42003-020-01488-x.

A GDSL lipase-like from Ipomoea batatas catalyzes efficient production of 3,5-diCQA when expressed in Pichia pastoris.

The synthesis of 3,5-dicaffeoylquinic acid (3,5-DiCQA) has attracted the interest of many researchers for more than 30 years. Recently, enzymes belonging to the BAHD acyltransferase family were shown to mediate its synthesis, albeit with notably low efficiency. In this study, a new enzyme belonging to the GDSL lipase-like family was identified and proven to be able to transform chlorogenic acid (5-O-caffeoylquinic acid, 5-CQA, CGA) in 3,5-DiCQA with a conversion rate of more than 60%.

A BAHD neofunctionalization promotes tetrahydroxycinnamoyl spermine accumulation in the pollen coat of the Asteraceae family.

In eudicotyledons, accumulation of trihydroxycinnamoyl spermidine that is restricted to the pollen wall constitutes an evolutionary conserved trait. However, the role of this compound, which is synthetized by the BAHD enzyme spermidine hydroxycinnamoyl transferase (SHT), is still a matter of debate. Here, we show that this particular phenolamide is replaced by tetrahydroxycinnamoyl spermine in the pollen coat of the Asteraceae.

Results and evaluation of a first-in-human study of RG7342, an mGlu5 positive allosteric modulator, utilizing Bayesian adaptive methods.

Aim: The objectives of this first-in-human study were to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics, and maximum tolerated dose (MTD) of single ascending oral doses of RG7342, a positive allosteric modulator (PAM) of the metabotropic glutamate receptor 5 (mGlu5) for the treatment of schizophrenia, in healthy male subjects.

Methods: This was a single-centre, randomized, double-blind, adaptive study of 37 subjects receiving single ascending oral doses of RG7342 (ranging from 0.06-1.

Preclinical and Early Clinical Profile of a Highly Selective and Potent Oral Inhibitor of Aldosterone Synthase (CYP11B2).

Unlabelled: Primary hyperaldosteronism is a common cause of resistant hypertension. Aldosterone is produced in the adrenal by aldosterone synthase (AS, encoded by the gene CYP11B2). AS shares 93% homology to 11β-hydroxylase (encoded by the gene CYP11B1), responsible for cortisol production.

Selection and validation of reference genes for quantitative real-time PCR analysis of gene expression in Cichorium intybus.

Plant polyphenols represent a huge reservoir of bioactive compounds. Industrial chicory, an important crop from northwestern Europe, accumulates an original combination of such compounds, i.e.

Lead optimization of thiazolo[5,4-c]piperidines: 3-cyclobutoxy linker as a key spacer for H(3)R inverse agonists.

The simpler, the better: H(3) histamine receptor (H(3)R) are of interest as therapeutic targets in cognitive and somnolence disorders. Here, lead optimization of H(3)R inverse agonists bearing a thiazolo[5,4-c]piperidine group gave rise to a clinical candidate with a much simpler unprecedented benzamide scaffold, displaying decreased hERG activity while maintaining high brain receptor occupancies.

Pharmacokinetic and technical comparison of Sandostatin® LAR® and other formulations of long-acting octreotide.

Background: Sandostatin® LAR® (Novartis Pharma AG) is a long-acting repeatable formulation of the somatostatin analogue octreotide, the safety and efficacy of which has been established through 15 years of clinical experience. Recently, other formulations of octreotide using polymer poly(lactic-co-glycolic acid) technology have been developed. This study compares the composition and pharmacokinetic (PK) profile of Sandostatin LAR with three other versions of the depot delivery system (formulations A, B and C, available in selected countries).

Benzyl prolinate derivatives as novel selective KCC2 blockers.

The discovery and optimization of a novel class of selective submicromolar KCC2 blockers is described. Details of synthesis and SAR are given together with ADME properties of selected compounds. A methylsulfone residue on the R(1) phenyl group improved the overall general profile of these prolinate derivatives.

Drug metabolism and pharmacokinetics.

In this article, aspects of absorption, distribution, metabolism, and excretion have been described bearing in mind the pathogenesis of allergic diseases and their possible therapeutic opportunities. The importance of the routes of administration of the different therapeutic groups has been emphasized. The classical aspects of drug metabolism and disposition related to oral administration have been reviewed, but special emphasis has been given to intranasal, cutaneous, transdermal, and ocular administration as well as to the absorption and the subsequent bioavailability of drugs.