Prospective Analysis of Safety and Efficacy of Tenofovir Alafenamide Fumarate (TAF) in European Real-World Patients with Chronic Hepatitis B: A Single-Centre Real-Word Cohort Study.

Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir for the treatment of chronic hepatitis B (CHB) that has shown a favourable renal safety profile while offering suppression of HBV DNA similar to tenofovir disoproxil fumarate (TDF). We aimed to study changes in markers of HBV replication and renal function in a real-world setting in European patients. In our prospective single-arm, non-interventional observational study, HBeAg-positive and HBeAg-negative patients with chronic HBV mono-infection receiving TAF as their first or following line treatment were enrolled.

A Test of the Self-Medication Hypothesis Using a Latent Measurement Model: Are Stress and Impaired Control over Alcohol Mediating Mechanisms of Parenting Styles on Heavy Episodic Drinking and Alcohol-Related Problems among University Students?

Introduction: The self-medication hypothesis (SMH) suggests that individuals consume alcohol to alleviate stressful emotions. Still, the underlying mechanisms between stress and heavy episodic drinking remain to be explored. Impaired control over drinking (IC) reflects a failure of self-regulation specific to the drinking context, with individuals exceeding self-prescribed limits.

Hemokinin-1 is a mediator of chronic restraint stress-induced pain.

The Tac4 gene-derived hemokinin-1 (HK-1) binds to the NK1 receptor, similarly to Substance P, and plays a role in acute stress reactions and pain transmission in mice. Here we investigated Tac4 mRNA expression in stress and pain-related regions and its involvement in chronic restraint stress-evoked behavioral changes and pain using Tac4 gene-deleted (Tac4) mice compared to C57Bl/6 wildtypes (WT). Tac4 mRNA was detected by in situ hybridization RNAscope technique.

IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice.

Chronic stress causes several pain conditions including fibromyalgia. Its pathophysiological mechanisms are unknown, and the therapy is unresolved. Since the involvement of interleukin-1 (IL-1) has been described in stress and inflammatory pain but no data are available regarding stress-induced pain, we studied its role in a chronic restraint stress (CRS) mouse model.

Examination of pituitary adenylate cyclase-activating polypeptide in Parkinson's disease focusing on correlations with motor symptoms.

The neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) have been shown in numerous in vitro and in vivo models of Parkinson's disease (PD) supporting the theory that PACAP could have an important role in the pathomechanism of the disorder affecting mostly older patients. Earlier studies found changes in PACAP levels in neurological disorders; therefore, the aim of our study was to examine PACAP in plasma samples of PD patients. Peptide levels were measured with ELISA and correlated with clinical parameters, age, stage of the disorder based on the Hoehn and Yahr (HY) scale, subtype of the disease, treatment, and specific scores measuring motor and non-motor symptoms, such as movement disorder society-unified Parkinson's disease rating scale (MDS-UPDRS), Epworth sleepiness scale (ESS), Parkinson's disease sleep scale (PDSS-2), and Beck depression inventory (BDI).

Tailoring the Band Structure of Twisted Double Bilayer Graphene with Pressure.

Twisted two-dimensional structures open new possibilities in band structure engineering. At magic twist angles, flat bands emerge, which gave a new drive to the field of strongly correlated physics. In twisted double bilayer graphene dual gating allows changing of the Fermi level and hence the electron density and also allows tuning of the interlayer potential, giving further control over band gaps.

Combined Simultaneous Multiportal Approach via Minimally Invasive Transciliary and Endoscopic Endonasal Approaches for Tumors Invading Both the Skull Base and the Sinonasal Area.

Background: A combined transcranial and transfacial approach has long been the gold standard for surgical management of large tumors with sinonasal and skull base involvement. The extended endoscopic endonasal approach for such pathologies has its advantages, but it has flaws as well, such as anatomic limitations and more ponderous skull base reconstruction and thus higher risk of postoperative complications. Our primary technique for surgical treatment of these pathologies has been a combination of transfacial and minimally invasive transciliary supraorbital keyhole approaches.

Roadsides provide refuge for orchids: characteristic of the surrounding landscape.

Seminatural habitats are declining throughout the world; thus, the role of small anthropogenic habitats in the preservation of plants is becoming increasingly appreciated. Here, we surveyed the orchid flora of roadside verges in five Central European countries (Austria, Hungary, Romania, Slovakia, and Slovenia) and tested how the surrounding landscape matrix affects the overall number of species and individuals, and also different functional groups of orchids. We found more than 2,000 individuals of 27 orchid species during our surveys.

Electrically Controlled Spin Injection from Giant Rashba Spin-Orbit Conductor BiTeBr.

Ferromagnetic materials are the widely used source of spin-polarized electrons in spintronic devices, which are controlled by external magnetic fields or spin-transfer torque methods. However, with increasing demand for smaller and faster spintronic components utilization of spin-orbit phenomena provides promising alternatives. New materials with unique spin textures are highly desirable since all-electric creation and control of spin polarization is expected where the strength, as well as an arbitrary orientation of the polarization, can be defined without the use of a magnetic field.

Possible effects of pituitary adenylate cyclase activating polypeptide (PACAP) on early embryo implantation marker HB-EGF in mouse.

Pituitary adenylate cyclase activating polypeptide (PACAP) was originally isolated as a hypothalamic neuropeptide stimulating adenylate cyclase activity. Besides its neuroprotective effects, numerous data proved its role in reproductive processes. However, there are limited data on its role in preimplantation embryo development and implantation.

Lack of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Disturbs Callus Formation.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a naturally secreted signaling peptide and has important regulatory roles in the differentiation of the central nervous system and its absence results in disorders in femur development. PACAP has an important function in prevention of oxidative stress or mechanical stress in chondrogenesis but little is known about its function in bone regeneration. A new callus formation model was set to investigate its role in bone remodeling.

Phenotypic characterization of testicular immune cells expressing immune checkpoint molecules in wild-type and pituitary adenylate cyclase-activating polypeptide-deficient mice.

Problem: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide having several regulatory functions in the nervous system and in peripheral organs including those of the reproductive system. PACAP-deficient male mice have several morphological, biochemical, behavioral defects and show disturbed signaling in spermatogenesis affecting fertility in PACAP KO mice. Reproductive functions such as fertility, mating, and maternal behaviors have been widely investigated, but no immune analyses are available regarding the testicular immune-privileged environment in male PACAP-deficient mice.

Age-related alterations of articular cartilage in pituitary adenylate cyclase-activating polypeptide (PACAP) gene-deficient mice.

Pituitary adenylate cyclase activating polypeptide (PACAP) is an evolutionarly conserved neuropeptide which is produced by various neuronal and non-neuronal cells, including cartilage and bone cells. PACAP has trophic functions in tissue development, and it also plays a role in cellular and tissue aging. PACAP takes part in the regulation of chondrogenesis, which prevents insufficient cartilage formation caused by oxidative and mechanical stress.

Risk factors for resistance development against lamivudine during long-term treatment of chronic hepatitis B virus infections.

Background/aim: The use of lamivudine for the treatment of chronic hepatitis B (CHB) is limited by high rates of lamivudine resistance. However, it is still in use in many regions. Factors associated with lamivudine resistance development have been studied in only a few European cohorts.

VPAC1 receptors play a dominant role in PACAP-induced vasorelaxation in female mice.

Background: PACAP and VIP are closely related neuropeptides with wide distribution and potent effect in the vasculature. We previously reported vasomotor activity in peripheral vasculature of male wild type (WT) and PACAP-deficient (KO) mice. However, female vascular responses are still unexplored.

Association of HLA-DPA1 and HLA-DPB1 polymorphisms with spontaneous HBsAg seroclearance in Caucasians.

Background & Aims: Acute hepatitis B virus (HBV) infections may clear spontaneously or become chronic and run through different phases. The single nucleotide polymorphisms (SNPs) rs3077, rs9277535 and rs9277534 within the human leucocyte antigen (HLA)-DP gene have been found to be associated with HBV susceptibility and persistence in Asians. However, evidence for the influence of these variants in Caucasians has been limited so far.

PACAP deficiency as a model of aging.

Dysregulation of neuropeptides may play an important role in aging-induced impairments. In the long list of neuropeptides, pituitary adenylate cyclase-activating polypeptide (PACAP) represents a highly effective cytoprotective peptide that provides an endogenous control against a variety of tissue-damaging stimuli. PACAP has neuro- and general cytoprotective effects due to anti-apoptotic, anti-inflammatory, and antioxidant actions.

Protective Role of Endogenous PACAP in Inflammation-induced Retinal Degeneration.

Purpose: Pituitary adenylate Cyclase-Activating Polypeptide (PACAP) is a neuroprotective peptide that has been shown to exert protective effects in different models of neurodegenerative diseases, including retinal degenerations. Data obtained from PACAP-deficient (PACAP KO) mice provide evidence that endogenous PACAP has a neuroprotective role in different pathologies. PACAP KO mice show enhanced sensitivity to different insults, such as oxidative stress, hypoxia and inflammation.

Signalling Alterations in Bones of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Gene Deficient Mice.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with diverse developmental roles, including differentiation of skeletal elements. It is a positive regulatory factor of chondrogenesis and osteogenic differentiation in vitro, but little is known about its role in bone formation. In our experiments, diaphyses of long bones from hind limbs of PACAP gene-deficient mice showed changes in thickness and increased staining intensity.

Polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population.

Innate immunity can induce spontaneous hepatitis B surface antigen (HBsAg) seroclearance (SC) of hepatitis B virus (HBV) infection or transition towards an inactive carrier state. Toll-like receptor (TLR) 3 signalling has been linked to these processes. Alterations in the TLR3 gene might impair immune responses against HBV.

Altered Notch Signaling in Developing Molar Teeth of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)-Deficient Mice.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with neuroprotective and neurotrophic effects. This suggests its influence on the development of teeth, which are, similarly to the nervous system, ectoderm and neural crest derivatives. Our earlier studies have shown morphological differences between wild-type (WT) and PACAP-deficient mice, with upregulated sonic hedgehog (SHH) signaling in the lack of PACAP.

Comparative analysis of decidual and peripheral immune cells and immune-checkpoint molecules during pregnancy in wild-type and PACAP-deficient mice.

Problem: PACAP is a neuropeptide having a major relevance in the nervous system and in several peripheral organs including those of the reproductive system. PACAP-deficient mice have several morphological, biochemical, behavioral defects, and show reduced fertility. Female reproductive functions such as fertility, mating behavior, maternal behaviors, and implantation alterations have been widely investigated, but no comparative immune analyses are available in pregnant wild-type (WT) and PACAP knockout (KO) mice.

Accelerated pre-senile systemic amyloidosis in PACAP knockout mice - a protective role of PACAP in age-related degenerative processes.

Dysregulation of neuropeptides may play an important role in aging-induced impairments. Among them, pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent cytoprotective peptide that provides an endogenous control against a variety of tissue-damaging stimuli. We hypothesized that the progressive decline of PACAP throughout life and the well-known general cytoprotective effects of PACAP lead to age-related pathophysiological changes in PACAP deficiency, supported by the increased vulnerability to various stressors of animals partially or totally lacking PACAP.

Protective effects of pituitary adenylate cyclase activating polypeptide against neurotoxic agents.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide highly expressed in the central and peripheral nervous system, where it exerts several neuromodulatory functions and is an important trophic and protective factor. PACAP has been shown to activate several protective pathways, mainly through its specific PAC1 receptor and protein kinase A, C and MAP kinases downstream. It has been shown to have very potent neuroprotective actions against different neurotoxic agents both in vitro and in vivo.

Pituitary adenylate cyclase-activating polypeptide ameliorates vascular dysfunction induced by hyperglycaemia.

Background: Short-lasting hyperglycaemia occurs frequently in prediabetes and poorly controlled diabetes mellitus leading to vascular damage. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to play a protective role in vascular complications of diabetes; moreover, antioxidant effects of PACAP were also described. Therefore, we hypothesized that PACAP exerts protective effects in short-term hyperglycaemia-induced vascular dysfunctions.