Phase 1 Trials of Gatralimab, a Next-Generation Humanized Anti-CD52 Monoclonal Antibody, in Participants with Progressive Multiple Sclerosis.

Introduction: Lymphocyte depletion via anti-CD52 monoclonal antibody (mAb) therapy is an effective treatment strategy for relapsing-remitting multiple sclerosis (MS) but is associated with infusion/injection-associated reactions (IARs) and autoimmune-related adverse events (AEs). Gatralimab is a next-generation humanized anti-CD52 mAb.

Methods: Two first-in-human trials were conducted in participants with progressive MS to assess the pharmacodynamics, pharmacokinetics, and safety of gatralimab administered via subcutaneous (SC) and intravenous (IV) routes, and to determine the effect of different comedication regimes on IARs to SC gatralimab.

Negative emotionality shapes the modulatory effects of ketamine and lamotrigine in subregions of the anterior cingulate cortex.

Neuroimaging studies have identified the anterior cingulate cortex (ACC) as one of the major targets of ketamine in the human brain, which may be related to ketamine's antidepressant (AD) mechanisms of action. However, due to different methodological approaches, different investigated populations, and varying measurement timepoints, results are not consistent, and the functional significance of the observed brain changes remains a matter of open debate. Inhibition of glutamate release during acute ketamine administration by lamotrigine provides the opportunity to gain additional insight into the functional significance of ketamine-induced brain changes.

Effects of a single dose of amisulpride on functional brain changes during reward- and motivation-related processing using task-based fMRI in healthy subjects and patients with major depressive disorder - study protocol for a randomized clinical trial.

Background: Anhedonia and other deficits in reward- and motivation-related processing in psychiatric patients, including patients with major depressive disorder (MDD), represent a high unmet medical need. Neurobiologically, these deficits in MDD patients are mainly associated with low dopamine function in a frontostriatal network. In this study, alterations in brain activation changes during reward processing and at rest in MDD patients compared with healthy subjects are explored and the effects of a single low dose of the dopamine D2 receptor antagonist amisulpride are investigated.

Region- and time- specific effects of ketamine on cerebral blood flow: a randomized controlled trial.

There is intriguing evidence suggesting that ketamine might have distinct acute and delayed neurofunctional effects, as its acute administration transiently induces schizophrenia-like symptoms, while antidepressant effects slowly emerge and are most pronounced 24 h after administration. Studies attempting to characterize ketamine's mechanism of action by using blood oxygen level dependent (BOLD) imaging have yielded inconsistent results regarding implicated brain regions and direction of effects. This may be due to intrinsic properties of the BOLD contrast, while cerebral blood flow (CBF), as measured with arterial spin labeling, is a single physiological marker more directly related to neural activity.

Modulatory Effects of Ketamine and Lamotrigine on Cognition: Emotion Interaction in the Brain.

Introduction: Cognition and emotion are fundamentally integrated in the brain and mutually contribute to behavior. The relation between working memory (WM) and emotion is particularly suited to investigate cognition-emotion interaction since WM is an essential component of many higher cognitive functions. Ketamine affects not only WM but also has a profound impact on emotional processing.

The effects of transient receptor potential cation channel inhibition by BI 1358894 on cortico-limbic brain reactivity to negative emotional stimuli in major depressive disorder.

Abnormal emotional processing in major depressive disorder (MDD) has been associated with increased activation to negative stimuli in cortico-limbic brain regions. The authors investigated whether treatment with BI 1358894, a small-molecule inhibitor of the transient receptor potential cation channel subfamily C leads to attenuated activity in these areas in MDD patients. 73 MDD patients were randomized to receive a single oral dose of BI 1358894 (100 mg), citalopram (20 mg), or matching placebo.

Single Oral Doses of MK-8507, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor, Suppress HIV-1 RNA for a Week.

Background: MK-8507 is a novel HIV-1 non-nucleoside reverse transcriptase inhibitor being developed for treatment of HIV-1 infection. MK-8507 has high antiviral potency in vitro and pharmacokinetic (PK) properties that support once-weekly dosing.

Setting: A phase 1, open-label, proof-of-concept study was conducted in treatment-naive adults with HIV-1 infection to assess monotherapy antiviral activity.

A Randomised, Controlled Trial: Effect of a Multi-Strain Fermented Milk on the Gut Microbiota Recovery after Therapy.

() eradication therapy alters gut microbiota, provoking gastrointestinal (GI) symptoms that could be improved by probiotics. The study aim was to assess the effect in patients of a Test fermented milk containing yogurt and ( CNCM I-1518 and I-3689, CNCM I-3690) strains on antibiotic associated diarrhea (AAD) (primary aim), GI-symptoms, gut microbiota, and metabolites. A randomised, double-blind, controlled trial was performed on 136 adults under 14-day treatment, receiving the Test or Control product for 28 days.

Psychological Effects of Whole-body Electromyostimulation Training: a Controlled Pilot Study in Healthy Volunteers.

Background: Whole-body electromyostimulation (WB-EMS) training is used in popular and health sports to improve muscular performance. Little is known about the possible psychological effects of WB-EMS training. The aim of the study is therefore to investigate the possible psychological effects of WB-EMS training on subjective well-being, relaxation, mood, and perceived stress.

Comparison of Four fMRI Paradigms Probing Emotion Processing.

Previous fMRI research has applied a variety of tasks to examine brain activity underlying emotion processing. While task characteristics are known to have a substantial influence on the elicited activations, direct comparisons of tasks that could guide study planning are scarce. We aimed to provide a comparison of four common emotion processing tasks based on the same analysis pipeline to suggest tasks best suited for the study of certain target brain regions.

Safety, pharmacokinetics, and antiretroviral activity of islatravir (ISL, MK-8591), a novel nucleoside reverse transcriptase translocation inhibitor, following single-dose administration to treatment-naive adults infected with HIV-1: an open-label, phase 1b, consecutive-panel trial.

Background: Islatravir (also known as ISL and MK-8591) is a unique nucleoside reverse transcriptase translocation inhibitor in clinical development for treatment of people with HIV-1 infection. In preclinical studies, intracellular islatravir-triphosphate exhibits a long half-life and prolonged virological effects. In this study, we aimed to assess islatravir safety, pharmacokinetics, and antiretroviral activity in treatment-naive adults with HIV-1 infection.

A randomized Phase 2 study to evaluate the orexin-2 receptor antagonist seltorexant in individuals with insomnia without psychiatric comorbidity.

Background: Seltorexant is a potent and selective antagonist of the orexin-2 receptor that is being developed for the treatment of insomnia and major depressive disorder.

Aims: The primary objective was to investigate the effect of seltorexant on sleep efficiency after single and multiple dose administration in subjects with insomnia disorder without psychiatric comorbidity. Secondary objectives included evaluation of total sleep time, latency to persistent sleep, and wake after sleep onset.

The effect of sacubitril/valsartan compared to olmesartan on cardiovascular remodelling in subjects with essential hypertension: the results of a randomized, double-blind, active-controlled study.

Aims: Progressive aortic stiffening eventually leads to left ventricular (LV) hypertrophy and heart failure if left untreated. Anti-hypertensive agents have been shown to reverse this to some extent. The effects of sacubitril/valsartan (LCZ696), a dual-action angiotensin receptor blocker (ARB), and neprilysin inhibitor, on arterial stiffness and LV remodelling have not been investigated.

Antiviral Activity, Safety, and Exposure-Response Relationships of GSK3532795, a Second-Generation Human Immunodeficiency Virus Type 1 Maturation Inhibitor, Administered as Monotherapy or in Combination With Atazanavir With or Without Ritonavir in a Phase 2a Randomized, Dose-Ranging, Controlled Trial (AI468002).

Background: GSK3532795 is a second-generation human immunodeficiency virus type 1 (HIV-1) maturation inhibitor that targets HIV-1 Gag, inhibiting the final protease cleavage between capsid protein p24 and spacer protein-1, producing immature, noninfectious virions.

Methods: This was a phase 2a, randomized, dose-ranging multipart trial. In part A, subtype B-infected subjects received 5-120 mg GSK3532795 (or placebo) once daily for 10 days.

The effect of a low-fat spread with added plant sterols on vascular function markers: results of the Investigating Vascular Function Effects of Plant Sterols (INVEST) study.

Background: Plant sterols (PSs) lower LDL cholesterol, an established risk factor for coronary artery disease (CAD). No direct evidence is available supporting a reduced risk of CAD for foods with added PSs. Endothelial dysfunction is seen as an early indicator of atherosclerotic damage.

Improvement of neurocognitive function in responders to an antiviral therapy for chronic hepatitis C.

Unlabelled: Earlier studies have suggested neurocognitive impairment in patients with chronic hepatitis C virus (HCV) infection even before liver cirrhosis has developed. Since these deficits might be reversible after successful antiviral therapy, we analyzed the long-term course of neurocognitive parameters in HCV patients with and without successful virus elimination by an interferon-based antiviral treatment. In a multicenter study including 168 HCV patients receiving antiviral therapy (peginterferon alpha-2b and ribavirin) we performed a long-term follow-up of neurocognitive performance before and after treatment.

Platelet serotonin (5-HT) levels in interferon-treated patients with hepatitis C and its possible association with interferon-induced depression.

Background & Aims: Interferon-associated depression is a frequent side effect of antiviral therapy for chronic hepatitis C. The aim of the present study was to investigate the correlation between platelet serotonin (5-hydroxytryptamine, 5-HT) concentrations and IFN-induced depression.

Methods: The study represents a secondary analysis of a previously published trial on the efficacy of SSRI medication in HCV patients on IFN therapy.

Deterioration of health-related quality of life and fatigue in patients with chronic hepatitis C: Association with demographic factors, inflammatory activity, and degree of fibrosis.

Background/aims: Health-related quality of life (HRQoL) is impaired in patients with chronic hepatitis C. We investigated HRQoL and fatigue in patients with chronic hepatitis C virus (HCV) infection in relation to the degree of fibrosis and inflammation, and controlled for the influence of relevant demographic and medical variables.

Methods: We conducted a cross-sectional two-center study including 215 outpatients with chronic hepatitis C applying the Short-Form Health Survey (SF-36) and the Fatigue Impact Scale (FIS-D).

Phosphorylation of mouse LASP-1 on threonine 156 by cAMP- and cGMP-dependent protein kinase.

LIM and SH3 domain protein (LASP-1) is a specific focal adhesion protein involved in cell migration. Overlay studies demonstrate that LASP-1 directly binds to the proline-rich domains of zyxin, lipoma preferred partner (LPP), and vasodilator-stimulated phosphoprotein (VASP), with zyxin being the most prominent interacting partner. Despite the LIM/zinc-finger domain, hypothesized to be involved in homodimerization, LASP-1 exists as a monomer.