Bioequivalence and Safety of Generic Glecaprevir/Pibrentasvir Compared to a Branded Product: A Randomized, Crossover Study in Healthy Volunteers.

This was an open-label, randomized, single-dose, 2-period, crossover clinical trial with an adaptive design to evaluate the bioequivalence and comparative pharmacokinetics of generic glecaprevir/pibrentasvir versus the brand name product in healthy White male and female volunteers under fed conditions. Safety profiles were also assessed. A total of 56 healthy adult volunteers were enrolled and randomly assigned in a 1:1 ratio to receive a single dose of either the generic or reference formulation.

Clinical Pharmacology of GP40321 (Insulin Glulisine Biosimilar): Pharmacokinetic and Pharmacodynamic Comparability in a Hyperinsulinemic-Euglycemic Clamp Procedure.

The aim of the study was to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of T-glu (GP40321, test drug), and reference insulin glulisine in a hyperinsulinemic-euglycemic clamp procedure. During this study, 34 healthy male volunteers underwent the hyperinsulinemic-euglycemic clamp procedure following subcutaneous 0.3 U/kg injection of T-glu or reference insulin glulisine in a randomized, double-blind, crossover study.

Bioequivalence of Reference and Biosimilar Preparations of Premixed Biphasic Insulin Aspart: A Comparative Clamp Study.

Biphasic insulin aspart 30 is a premixed formulation containing a soluble fraction of insulin aspart (30%) and a protamine-crystallized fraction (70%) that was developed to combine the rapid-acting and prolonged advantages of commercially available insulins. The aim of this bioequivalence study was to compare the pharmacokinetics (PKs) of GP-bi-asp and Novo-bi-asp, and evaluate the pharmacodynamic (PD) properties as well as the safety of these drugs in the hyperinsulinemic euglycemic clamp (HEC) procedure. This was a phase 1, randomized, double-blind, 2-sequence, 2-period crossover study.

Meta-analysis of the effects of anti-migraine therapeutics in the rat trigeminovascular nociception model as a tool for design optimization.

The main reasons for the low reliability of results from preclinical studies are the lack of prior sample size calculations and poor experimental design. Here, we demonstrate how the tools of meta-analysis can be implemented to tackle these issues. We conducted a systematic search to identify controlled studies testing established migraine treatments in the electrophysiological model of trigeminovascular nociception (EMTVN).

Associations of stress and stress-related psychiatric disorders with GrimAge acceleration: review and suggestions for future work.

The notion of "biological aging" as distinct from chronological aging has been of increasing interest in psychiatry, and many studies have explored associations of stress and psychiatric illness with accelerated biological aging. The "epigenetic clocks" are one avenue of this research, wherein "biological age" is estimated using DNA methylation data from specific CpG dinucleotide sites within the human genome. Many iterations of the epigenetic clocks have been developed, but the GrimAge clock continues to stand out for its ability to predict morbidity and mortality.

Dimensions of childhood adversity differentially affect biological aging in major depression.

Adverse childhood experiences have been consistently linked with physical and mental health disorders in adulthood that may be mediated, in part, via the effects of such exposures on biological aging. Using recently developed "epigenetic clocks", which provide an estimate of biological age, several studies have demonstrated a link between the cumulative exposure to childhood adversities and accelerated epigenetic aging. However, not all childhood adversities are equivalent and less is known about how distinct dimensions of childhood adversity relate to epigenetic aging metrics.

[Morphopathology of myocardial hypoxic-ischemic injuries in newborns at 22-27 weeks' gestation].

Objective: To determine the parameters of myocardial structural injuries developed in chronic intrauterine hypoxia conditions in newborns at 22-27 weeks' gestation.

Material And Methods: A battery of morphological techniques, including organometry studies and separate weighing of the heart; 3D histology; morphometry with the determination of the area of cardiomyocyte nuclei, the specific area of the muscular and interstitial components of the right ventricular myocardium; immunohistochemistry with monoclonal antibodies to transforming growth factor βı (TGF-βı), cardiac troponin T (cTnT), and transmission electron microscopy, was used to examine heart samples from 30 deceased newborns at 22-27 weeks' gestation who developed in chronic intrauterine hypoxia conditions. A control group consisted of hearts from 20 extremely low body weight (ELBW) newborns, the main cause of whose death was asphyxia caused by the premature detachment of a normally positioned placenta.

Vilém Dušan Lambl in the Imperial University of Kharkiv (Charkov) (1861-1871): biography outlines.

This article focuses on the biography of the famous Czech pathologist Dušan Lambl (1824-95), especially during his period of life in Kharkiv, Sloboda Ukraine (part of the Russian Empire). At the end of the 1850s, pursued by the authorities of the Austrian Empire as a politically compromised person (being a Czech patriot and slavophile, he took an active part in the so-called Spring of Nations in 1848), Dušan Lambl was forced to seek refuge in the Russian Empire. He put forward his candidacy for the post of professor in the department of anatomy at the School of Medicine of Kharkiv University and was selected for this position.

[Congenital immature teratomas. Two case reports].

Teratomas belong to a group of germ cell tumors and consist of tissues that are derived from 3 germ layers. The localization of teratomas is extremely diverse. The main task of a morphological study is to diagnose the type of teratoma.

"GrimAge," an epigenetic predictor of mortality, is accelerated in major depressive disorder.

Major depressive disorder (MDD) is associated with premature mortality and is an independent risk factor for a broad range of diseases, especially those associated with aging, such as cardiovascular disease, diabetes, and Alzheimer's disease. However, the pathophysiology underlying increased rates of somatic disease in MDD remains unknown. It has been proposed that MDD represents a state of accelerated cellular aging, and several measures of cellular aging have been developed in recent years.

Increased Salience Network Connectivity Following Manual Therapy is Associated with Reduced Pain in Chronic Low Back Pain Patients.

Chronic low back pain (cLBP) has been associated with changes in brain plasticity. Nonpharmacological therapies such as Manual Therapy (MT) have shown promise for relieving cLBP. However, translational neuroimaging research is needed to understand potential central mechanisms supporting MT.

Are long telomeres better than short? Relative contributions of genetically predicted telomere length to neoplastic and non-neoplastic disease risk and population health burden.

Background: Mendelian Randomization (MR) studies exploiting single nucleotide polymorphisms (SNPs) predictive of leukocyte telomere length (LTL) have suggested that shorter genetically determined telomere length (gTL) is associated with increased risks of degenerative diseases, including cardiovascular and Alzheimer's diseases, while longer gTL is associated with increased cancer risks. These varying directions of disease risk have long begged the question: when it comes to telomeres, is it better to be long or short? We propose to operationalize and answer this question by considering the relative impact of long gTL vs. short gTL on disease incidence and burden in a population.

BIOMARKER SST2 AS AN EARLY PREDICTOR OF ACUTE RENAL INJURY IN PATIENTS WITH ST-SEGMENT ELEVATION ACUTE MYOCARDIAL INFARCTION.

One of the serious complications of ST-segment elevation myocardial infarction (STEMI) is acute kidney injury (AKI). Promising in this respect is the stimulating growth factor sST2. A sharp increase of ST2 level in case of injury is accompanied by inhibition of IL-33 favorable antihypertrophic effects.

Striatal hypofunction as a neural correlate of mood alterations in chronic pain patients.

Background: Chronic pain and mood disorders share common neuroanatomical substrates involving disruption of the reward system. Although increase in negative affect (NA) and decrease in positive affect (PA) are well-known factors complicating the clinical presentation of chronic pain patients, our understanding of the mechanisms underlying the interaction between pain and PA/NA remains limited. Here, we used a validated task probing behavioral and neural responses to monetary rewards and losses in conjunction with functional magnetic resonance imaging (fMRI) to test the hypothesis that dysfunction of the striatum, a key mesolimbic structure involved in the encoding of motivational salience, relates to mood alterations comorbid with chronic pain.

In-vivo imaging of neuroinflammation in veterans with Gulf War illness.

Gulf War Illness (GWI) is a chronic disorder affecting approximately 30% of the veterans who served in the 1991 Gulf War. It is characterised by a constellation of symptoms including musculoskeletal pain, cognitive problems and fatigue. The cause of GWI is not definitively known but exposure to neurotoxicants, the prophylactic use of pyridostigmine bromide (PB) pills, and/or stressors during deployment have all been suspected to play some pathogenic role.

The neuroinflammatory component of negative affect in patients with chronic pain.

Negative affect (NA) is a significant cause of disability for chronic pain patients. While little is known about the mechanism underlying pain-comorbid NA, previous studies have implicated neuroinflammation in the pathophysiology of both depression and chronic pain. Here, we tested the hypothesis that NA in pain patients is linked to elevations in the brain levels of the glial marker 18 kDa translocator protein (TSPO), and changes in functional connectivity.

The cardiac diagnostic work-up in stroke patients-A subanalysis of the Find-AFRANDOMISED trial.

Background: The cardiac diagnostic workup of stroke patients, especially the value of echocardiography and enhanced and prolonged Holter-ECG monitoring, is still a matter of debate. We aimed to analyse the impact of pathologies detected by echocardiography and ECG monitoring on therapeutic decisions and prognosis.

Methods: Find-AFRANDOMISED was a prospective multicenter study which randomised 398 acute ischemic stroke patients ≥ 60 years to enhanced and prolonged Holter-ECG monitoring or usual stroke unit care.

Brain Mechanisms of Anticipated Painful Movements and Their Modulation by Manual Therapy in Chronic Low Back Pain.

Heightened anticipation and fear of movement-related pain has been linked to detrimental fear-avoidance behavior in chronic low back pain (cLBP). Spinal manipulative therapy (SMT) has been proposed to work partly by exposing patients to nonharmful but forceful mobilization of the painful joint, thereby disrupting the relationship among pain anticipation, fear, and movement. Here, we investigated the brain processes underpinning pain anticipation and fear of movement in cLBP, and their modulation by SMT, using functional magnetic resonance imaging.

Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation.

Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [C]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes.

Brain Correlates of Continuous Pain in Rheumatoid Arthritis as Measured by Pulsed Arterial Spin Labeling.

Objective: Central nervous system pathways involving pain modulation shape the pain experience in patients with chronic pain. The aims of this study were to understand the mechanisms underlying pain in patients with rheumatoid arthritis (RA) and to identify brain signals that may serve as imaging markers for developing targeted treatments for RA-related pain.

Methods: Patients with RA and matched control subjects underwent functional magnetic resonance imaging, using pulsed arterial spin labeling.

Encoding of Self-Referential Pain Catastrophizing in the Posterior Cingulate Cortex in Fibromyalgia.

Objective: Pain catastrophizing is a common feature of chronic pain, including fibromyalgia (FM), and is strongly associated with amplified pain severity and disability. While previous neuroimaging studies have focused on evoked pain response modulation by catastrophizing, the brain mechanisms supporting pain catastrophizing itself are unknown. We designed a functional magnetic resonance imaging (fMRI)-based pain catastrophizing task whereby patients with chronic pain engaged in catastrophizing-related cognitions.

[Pathomorphology of the ventricular germinal zone and neocortex in newborn infants with posthemorrhagic hydrocephalus].

Aim: Тo study the morphological features of the ventricular germinal zone and neocortex in newborns at 22-40 weeks' gestation with posthemorrhagic hydrocephalus.

Material And Methods: The brains of fetuses and newborns at 22-40 weeks' gestation with posthemorrhagic hydrocephalus (n=12) were examined; a control group included the brains with a lateral ventricle lumen width of not more than 0.5 cm (n=30).

Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AF): an open-label randomised controlled trial.

Background: Atrial fibrillation is a major risk factor for recurrent ischaemic stroke, but often remains undiagnosed in patients who have had an acute ischaemic stroke. Enhanced and prolonged Holter-electrocardiogram-monitoring might increase detection of atrial fibrillation. We therefore investigated whether enhanced and prolonged rhythm monitoring was better for detection of atrial fibrillation than standard care procedures in patients with acute ischaemic stroke.

[Specific features of reelin expression in the brain of fetuses and newborns with internal hydrocephalus].

Aim: to study reelin expression in the neocortex of fetuses and newborns with internal hydrocephalus (HC) and to reveal its features in relation to the etiology of HC.

Material And Methods: The brains of fetuses and newborn at 22-40 weeks' gestation with internal HC associated with Sylvian aqueduct malformation (n=9), post-inflammatory (n=4) and post-hemorrhagic (n=5) HC were examined. In a comparison group, the fragments of brain tissue with a slit-like lumen of the lateral ventricles were no more than 0.

Neural Plasticity in Common Forms of Chronic Headaches.

Headaches are universal experiences and among the most common disorders. While headache may be physiological in the acute setting, it can become a pathological and persistent condition. The mechanisms underlying the transition from episodic to chronic pain have been the subject of intense study.