Tralokinumab Treatment in Adult Atopic Dermatitis Patients: 28-Week Evaluation of Clinical Effectiveness, Safety, Serum Proteins and Total IgE Levels.

Introduction And Objectives: Tralokinumab-a biological that specifically targets interleukin-13-is one of the newer advanced systemic treatments for patients with moderate-to-severe atopic dermatitis (AD). Although safety and efficacy have been shown in phase-III clinical trials, daily practice data are needed. Therefore, the aim of this study was to evaluate 28-week safety and effectiveness, serum proteins and total IgE levels in adult AD patients treated with tralokinumab in daily practice.

The Role of Insulin Within the Socio-Psycho-Biological Framework in Type 2 Diabetes-A Perspective from Psychoneuroimmunology.

The interplay between socio-psychological factors and biological systems is pivotal in defining human health and disease, particularly in chronic non-communicable diseases. Recent advancements in psychoneuroimmunology and mitochondrial psychobiology have emphasized the significance of psychological factors as critical determinants of disease onset, progression, recurrence, and severity. These insights align with evolutionary biology, psychology, and psychiatry, highlighting the inherent social nature of humans.

Mitochondria: It is all about energy.

Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron and calcium homeostasis to the production of hormones and neurotransmitters, such as melatonin. They enable and influence communication at all physical levels through interaction with other organelles, the nucleus, and the outside environment.

Progression-free survival in patients with Ga-PSMA-PET-directed SBRT for lymph node oligometastases.

Background: Prostate cancer oligometastatic disease can be treated using stereotactic body radiotherapy (SBRT) in order to postpone start of systemic treatments such as androgen deprivation therapy (ADT). 68Ga-PSMA-PET/CT imaging allows for diagnosis of oligometastases at lower PSA values. We analysed a cohort of patients with prostate cancer lymph node oligometastases detected on PSMA-PET/CT.

Increasing first-time blood donation of newly registered donors using implementation intentions and explicit commitment techniques.

Background And Objectives: Most blood donors stop donating blood at the beginning of their donor career. This intervention study aims to increase first-time return behaviour of newly registered donors using implementation intentions and explicit commitment techniques.

Materials And Methods: Newly registered donors (N = 937) received an extra information sheet during their medical check-up wherein implementation intentions and explicit commitment techniques were tested.

Return behavior of occasional and multigallon blood donors: the role of theory of planned behavior, self-identity, and organizational variables.

Background: For blood establishments it is important that blood donors return for a donation. Past research has stressed the importance of theory of planned behavior (TPB) on return behavior, but self-identity (SI) and organizational variables (OVs) might play a role as well. This study added SI and OVs to the TPB to identify the determinants for return behavior.

Characteristics of donors who do or do not return to give blood and barriers to their return.

Background: In the Netherlands about 50% of whole blood donors return to give blood after an invitation to donate. This study aimed to investigate the characteristics of donor return behaviour and to gain insight into the barriers to blood donation reported by the donors themselves.

Materials And Methods: A total of 4,901 whole blood donors were invited to donate in week 39 of 2009.

Poor effect of guideline based treatment of restless legs syndrome in clinical practice.

Background: Numerous randomised controlled trials have proved the efficacy of dopaminergic and non-dopaminergic drugs in the treatment of restless legs syndrome (RLS). In contrast, epidemiological data demonstrate generally insufficient RLS treatment in clinical practice.

Objective: To prospectively assess the success of RLS treatment in the clinical setting and to evaluate potential demographic factors and comorbidities that may influence the response to therapy.

Localisation of pre- and postsynaptic cholinergic markers in the human brain.

The cholinergic neurotransmission in the central nervous system plays an important role in modulating cognitive processes such as learning, memory, arousal and sleep as well as in modulating locomotor activity. Dysfunction of the central cholinergic system is involved in numerous neuropsychiatric diseases. This review will provide a synopsis on the regional localisation of cholinergic and cholinoceptive structures within the adult human brain.

Sonographic substantia nigra hypoechogenicity in polyneuropathy and restless legs syndrome.

Substantia nigra (SN) hypoechogenicity assessed by transcranial B-mode sonography (TCS) is typical for idiopathic restless legs syndrome (RLS). Here, we investigated whether SN hypoechogenicity may differentiate between polyneuropathy (PNP) patients with and without RLS. Seventy-five patients with PNP, 65 healthy controls, and 75 patients with idiopathic RLS were investigated.

Sonographic abnormalities of brainstem structures in restless legs syndrome.

Background And Purpose: Using transcranial B-mode sonography (TCS), the first morphological marker for restless legs syndrome (RLS), hypoechogenicity of the substantia nigra (SN) has been found. The aim of this study was to validate SN hypoechogenicity as a morphological marker for RLS in a large patient cohort and to investigate further RLS-associated brain abnormalities using TCS.

Methods: One hundred forty-three RLS patients (37 with symptomatic RLS) and 45 controls, matched for age and gender, underwent TCS by an experienced and independent rater who was blinded to clinical data.

Evaluating the suitability of nicotinic acetylcholine receptor antibodies for standard immunodetection procedures.

Nicotinic acetylcholine receptors play important roles in numerous cognitive processes as well as in several debilitating central nervous system (CNS) disorders. In order to fully elucidate the diverse roles of nicotinic acetylcholine receptors in CNS function and dysfunction, a detailed knowledge of their cellular and subcellular localizations is essential. To date, methods to precisely localize nicotinic acetylcholine receptors in the CNS have predominantly relied on the use of anti-receptor subunit antibodies.

Autoradiography of 2-[18F]F-A-85380 on nicotinic acetylcholine receptors in the porcine brain in vitro.

Noninvasive molecular imaging of subtypes of neuronal nicotinic acetylcholine receptors (nAChRs) will provide information on the role of these receptors in neurodegenerative diseases. The binding of the positron emission tomography ligand 2-[18F]F-A-85380 to nAChRs was investigated in the porcine brain by quantitative autoradiography in vitro. The high-affinity binding of 2-[18F]F-A-85380 to each of the investigated 12 brain areas was saturable and apparently monophasic (e.

Nicotinic acetylcholine receptors in Alzheimer's disease.

Nicotinic cholinoceptive dysfunction associated with cognitive impairment is a leading neurochemical feature of Alzheimer's disease. There-fore, nicotinic acetylcholine receptors have attracted considerable interest as potential therapeutic targets. The deficit of nicotine binding sites in Alzheimer's disease may be related to alterations of nicotinic receptor synthesis on the levels of (i) transcription, (ii) translation and post-translational modifications, (iii) receptor transport and turnover, including membrane insertion.

The LGI1 gene involved in lateral temporal lobe epilepsy belongs to a new subfamily of leucine-rich repeat proteins.

Recently mutations in the LGI1 (leucine-rich, glioma-inactivated 1) gene have been found in human temporal lobe epilepsy. We have now identified three formerly unknown LGI-like genes. Hydropathy plots and pattern analysis showed that LGI genes encode proteins with large extra- and intracellular domains connected by a single transmembrane region.

Focal application of neutralizing antibodies to soluble neurotrophic factors reduces collateral axonal branching after peripheral nerve lesion.

A major reason for the insufficient recovery of function after motor nerve injury are the numerous axonal branches which often re-innervate muscles with completely different functions. We hypothesized that a neutralization of diffusable neurotrophic factors at the lesion site in rats could reduce the branching of transected axons. Following analysis of local protein expression by immunocytochemistry and by in situ hybridization, we transected the facial nerve trunk of adult rats and inserted both ends into a silicon tube containing (i) collagen gel with neutralizing concentrations of antibodies to NGF, BDNF, bFGF, IGF-I, CNTF and GDNF; (ii) five-fold higher concentrations of the antibodies and (iii) combination of antibodies.

Expression of the alpha4 isoform of the nicotinic acetylcholine receptor in the fetal human cerebral cortex.

Nicotinic acetylcholine receptors are likely to play an important role in neuronal migration during development. Furthermore, the alpha4 receptor subunit gene is related to a hereditary juvenile form of epilepsy. Only little information is available, however, on the expression of cerebrocortical nicotinic acetylcholine receptors during human fetal development.

Parvalbumin-containing interneurons of the human cerebral cortex express nicotinic acetylcholine receptor proteins.

Cholinergic fibers from the basal forebrain are known to contact cholinoceptive cortical pyramidal neurons. Recent electrophysiological studies have revealed that nicotinic acetylcholine receptors are also present in human cerebrocortical interneurons. A direct visualization of nicotinic receptor subunits in cortical interneurons has, however, not yet been performed.

Classical Alzheimer features and cholinergic dysfunction: towards a unifying hypothesis?

Objective: Our autopsy studies show possible links between classical Alzheimer pathology and decreased expression of nicotinic acetylcholine receptors. For further elucidation we are now using in vitro models. We report preliminary evidence for the impact of beta-amyloid on nicotinic receptor expression in hippocampal dissociation culture.

Cellular expression of alpha7 nicotinic acetylcholine receptor protein in the temporal cortex in Alzheimer's and Parkinson's disease--a stereological approach.

Cognitive deficits in Alzheimer's and Parkinson's disease are closely related to disturbed cholinergic transmission. The decrease of nicotinic acetylcholine receptor protein has been assessed by Western blotting and immunohistochemistry. Stereology, however, has not been used to assess numbers of receptor-expressing human cerebrocortical neurons.

Expression of nicotinic acetylcholine receptors in Alzheimer's disease: postmortem investigations and experimental approaches.

Nicotinic ligand binding studies have shown rather early that the cholinoceptive system is affected in Alzheimer's disease (AD). Today, molecular histochemistry enables one to study the nicotinic acetylcholine receptor (nAChR) subunit expression on the cellular level in human autopsy brains, in animal models and in in vitro approaches, thus deciphering the distribution of nAChRs and their role as potential therapeutic targets. The studies on the nAChR expression in the frontal and temporal cortex of AD patients and age-matched controls could demonstrate that both, the numbers of alpha4- and alpha7-immunoreactive neurons and the quantitative amount, in particular of the alpha4 protein, were markedly decreased in AD.

Quantitative assessment of nicotinic acetylcholine receptor proteins in the cerebral cortex of Alzheimer patients.

Cholinergic transmission has for long been known to be one of the most severely affected systems in Alzheimer's disease (AD), resulting clinically in massive cognitive deficits. The molecular basis of this dysfunction--on both the pre- and the postsynaptic sites--is still a matter of ongoing investigations. Here, we report on the quantitative assessment of nicotinic acetylcholine receptor isoform expression in AD vs.

Mutation screening of the CHRNA4 and CHRNB2 nicotinic cholinergic receptor genes in Alzheimer's disease.

Potential genomic changes leading to decreased nicotine binding, crucial for cognitive dysfunction in Alzheimer's disease (AD), have not yet been studied. A search for mutations of the genes coding for the most widely distributed nicotinic receptor subtype alpha4beta2 (CHRNA4/CHRNB2) has been performed in AD patients by screening the coding regions of both genes by single strand conformation analysis and heteroduplex analysis of fibroblast-derived genomic DNA. Polymorphisms in CHRNA4, none of which led to amino acid changes in the predicted sequence, were found in three patients.

Expression of nicotinic acetylcholine receptor subunits in the cerebral cortex in Alzheimer's disease: histotopographical correlation with amyloid plaques and hyperphosphorylated-tau protein.

Impairment of cholinergic transmission and decreased numbers of nicotinic binding sites are well-known features accompanying the cognitive dysfunction seen in Alzheimer's disease (AD). In order to elucidate the underlying cause of this cholinoceptive dysfunction, the expression of two pharmacologically different nicotinic acetylcholine receptor (nAChR) subunits (alpha4, alpha7) was studied in the cerebral cortex of Alzheimer patients as compared to controls. Patch-clamp recordings of 14 dissociated neurons of control cortices showed responses suggesting the existence of alpha4- and alpha7-containing functional nAChRs in the human cortex.

Expression of alpha 4-1 and alpha 5 nicotinic cholinoceptor mRNA in the aging rat cerebral cortex.

Although important in neurodegeneration, systematic studies of nicotinic acetylcholine receptor expression in normal aging human brains are difficult to perform. We have studied the expression of nicotinic receptor alpha 4-1 and alpha 5 mRNA in the frontal and parietal isocortex of 3- (young adult), 24- (late middle aged), and 33-month-old (old) rats by nonisotopic in situ hybridization. In all groups transcripts were mainly present in layer II/III and V pyramidal neurons.