Quality of life in heart failure patients undergoing hybrid comprehensive telerehabilitation versus usual care – results of the Telerehabilitation in Heart Failure Patients (TELEREH-HF) Randomized Clinical Trial

IntroductionHybrid comprehensive telerehabilitation (HCTR) consisting of telecare (with psychological telesupport), telerehabilitation and remote monitoring of implantable devices might be an innovative option improving heart failure (HF) patients’ quality of life (QoL) and emotional health. The aim of the study was to investigate the influence of HCTR on various facets of QoL in HF patients in comparison with usual care (UC) alone.Material and methodsThe present analysis formed part of a multicenter, randomized trial that enrolled 850 HF patients (NYHA I–III, LVEF ≤ 40%). Patients were randomized 1 : 1 to HCTR plus UC or UC only. Patients underwent either an HCTR program or UC with observation. The psychological intervention in the HCTR group included supportive psychological counseling via mobile phone. The Medical Outcome Survey Short Form 36 Questionnaire was used to assess QoL. Measurements were made before and after a 9-week intervention (HCTR group)/observation (UC group).ResultsAfter the intervention, the HCTR group showed significant improvement in overall QoL, physical domain (PD) of QoL, and 4 areas of QoL (physical functioning (PhF), role functioning related to physical state (RF), general health (GH), vitality (VI)). A significant positive change in QoL in the UC group was observed only in VI and social functioning. There were also significant differences in QoL after 9-week intervention/observation between the two groups. The results showed greater improvement in HCTR for overall QoL (p = 0.009), PD of QoL (p = 0.0003) and three specific areas of QoL: PhF (p = 0.001), RF (p = 0.003), bodily pain (BP) (p = 0.015).ConclusionsIn comparison to UC, HCTR resulted in improvement in overall QoL, PD of QoL and 3 specific areas of QoL: PhF, RF and BP.     

Histamine H3 receptor ligands modulate L-dopa-evoked behavioral responses and L-dopa-derived extracellular dopamine in dopamine-denervated rat striatum

To explore a recently established association between histaminergic and dopaminergic neuronal phenotypic systems in brain, we determined the effect of the respective histaminergic H(3) receptor agonist and antagonist/inverse agonist, imetit and thioperamide, on L-DOPA - derived tissue and extracellular DA and metabolite levels in the striatum of 6-hydroxydopamine (6-OHDA) - lesioned rats (i.e., parkinsonian rats). We also examined the influence of histamine H(3) ligands on L-DOPA evoked behavioral responses (locomotor activity, number of rearings, stereotyped behavior and motor coordination). Using HPLC/ED and in vivo microdialysis technique imetit (5 mg/kg, i.p.) but not thioperamide (5 mg/kg, i.p.) was shown to attenuate an L-DOPA-evoked (15 mg/kg, i.p.; carbidopa, 30 min pretreatment) increase in extracellular DA in the neostriatum of 6-OHDA-lesioned rats. However, both imetit and thioperamide increased microdialysate levels of DOPAC and HVA, probably by enhancing intraneuronal DA utilization. As indicated by neurochemical analysis of the striatum imetit produced a decrease in tissue DA content. These findings support the hypothesis that central H(3) histaminergic receptors have a modulatory role in the storage, metabolism and release of DA derived from exogenous L-DOPA challenge. Furthermore, evidence from behavioral studies indicate that histamine H3 receptor blockade markedly improved motor coordination. Conversely, histamine H(3) receptor stimulation, being without effect on motor coordination, enhanced vertical activity in rats. From the above we conclude that the histamine H(3) agonism may augment motor dyskinesia in Parkinson's disease (PD) patients and presumably worsen L-DOPA therapy. Consequently, the histaminergic system represents a viable target for modulating the effectiveness of L-DOPA therapy in Parkinson's disease.     

Negative impact of high cumulative glucocorticoid dose on bone metabolism of patients with myasthenia gravis

This current study aimed to evaluate the frequency of low bone mass, osteopenia, and osteoporosis in patients with myasthenia gravis (MG) and to investigate the possible association between bone mineral density (BMD) and plasma levels of bone metabolism markers. Eighty patients with MG and 62 controls BMD were measured in the right femoral neck and lumbar spine by dual-energy X-ray absorptiometry. Plasma concentrations of osteocalcin, osteopontin, osteoprotegerin, tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, dickkopf (DKK-1), sclerostin, insulin, leptin, adrenocorticotropic hormone, parathyroid hormone, and fibroblast growth factor (FGF-23) were analyzed by Luminex®. The mean age of patients was 41.9 years, with 13.5 years of length of illness, and a mean cumulative dose of glucocorticoids 38,123 mg. Patients had significant reduction in BMD of the lumbar, the femoral neck, and in the whole body when compared with controls. Fourteen percent MG patients had osteoporosis at the lumbar spine and 2.5% at the femoral neck. In comparison with controls, patients with MG presented lower levels of osteocalcin, adrenocorticotropic hormone, parathyroid hormone, sclerostin, TNF-α, and DKK-1 and higher levels of FGF-23, leptin, and IL-6. There was a significant negative correlation between cumulative glucocorticoid dose and serum calcium, lumbar spine T-score, femoral neck BMD, T-score, and Z-score. After multivariate analysis, higher TNF-α levels increased the likelihood of presenting low bone mass by 2.62. MG patients under corticotherapy presented low BMD and altered levels of bone markers.     

Increased BDNF Levels in Long-term Bipolar Disorder Patients

IntroductionBipolar disorder (BD) is a prevalent, chronic and progressive illness. There is a growing body of evidence indicating that brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of BD.ObjectiveThe aim of this study was to evaluate BDNF plasma levels in BD patients with long term illness in comparison with controls.Methods87 BD type I patients and 58 controls matched by age, gender and education level were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview and the patients by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. The plasma levels of BDNF were measured by ELISA.ResultsOn average, patients had suffered from BD for 23.4 years. In comparison with controls, BD patients with mania presented a 1.90-fold increase in BDNF plasma levels (p = .001), while BD patients in remission presented a 1.64-fold increase in BDNF plasma levels (p = .03). BDNF plasma levels were not influenced by age, length of illness or current medications.ConclusionsThe present study suggests that long-term BD patients exhibit increased circulating levels of BDNF.     

The Myasthenia Gravis-specific Activities of Daily Living scale as a useful outcome measure and in routine clinical management in Polish patients

Introduction

The Myasthenia Gravis-Activities of Daily Living scale (MG-ADL) is a short, and easy to use disease-specific quality of life during daily routine tool in myasthenia gravis.

Ca²(+) /calmodulin-dependent protein kinase II mediates the octopamine-induced increase in sensitivity in spider VS-3 mechanosensory neurons

G-protein-coupled octopamine (OA) receptors mediate their effects by Ca2(+) signaling or adjusting intracellular cAMP levels. Depending on OA concentration and cell type, activation of OA receptors in excitable cells triggers excitatory or inhibitory effects, but the mechanisms by which Ca2(+) or cAMP mediates these effects are not well understood. We investigated signaling mechanisms that are potentially activated by OA, and OA effects on excitability and frequency sensitivity in mechanosensory neurons innervating the VS-3 slit sensilla on the patella of the spider Cupiennius salei. These neurons are directly innervated by octopaminergic efferents, and possess OA receptors that were immunoreactive to an antibody against an OA receptor highly expressed in mushroom bodies. OA application enhanced VS-3 neuron sensitivity, especially at high stimulation frequencies. This enhancement lasted for at least 1 h after OA application. Changes in sensitivity were also detected when the Ca2(+) ionophore ionomycin or the cAMP analog 8-Br-cAMP was applied. However, the cAMP pathway was unlikely to mediate the OA effect, as the protein kinase A inhibitor RP-cAMPS did not diminish this effect. In contrast, the OA-induced sensitivity enhancement was significantly reduced by KN-62, an inhibitor of Ca2(+) /calmodulin-dependent protein kinase II (CaMKII), and by the Ca2(+) chelator BAPTA-AM. OA depolarized the neurons by 3.8 mV from resting potential, well below the threshold for opening of voltage-activated Ca2(+) channels. OA also reduced the amplitudes of voltage-activated K(+) currents. We propose that OA receptors in VS-3 neurons activate inositol 1,4,5-trisphosphate, leading to Ca2(+) release from intracellular stores. The Ca2(+) surge switches on CaMKII, which modulates voltage-activated K(+) channels, resulting in persistent enhancement in excitability.     

Application of Screening Methods,Shape Signatures and Engineered Biosensors in Early Drug Discovery Process

Purpose  

In this study, two unreported estrogen antagonists were identified using a combination of computational screening and a simple bacterial estrogen sensor.