Choosing non-pharmacological treatments for neuropathic pain in spinal cord injury: a qualitative study.

Purpose: The aims of this study were to explore (1) the considerations of people with spinal cord injury (SCI) in choosing to use non-pharmacological treatments (N-PTs) for neuropathic pain (NP), (2) which factors influence their decision and who is involved in this choice.

Materials And Methods: Eleven individuals with SCI and NP were interviewed. Interviews were transcribed verbatim, transcripts were analysed through thematic coding, following an inductive content analysis approach.

Use and experienced effectiveness of non-pharmacological treatments for chronic spinal cord injury related pain in The Netherlands: A cross-sectional survey.

Context/objective: Chronic pain is a common secondary condition in spinal cord injury (SCI). Pharmacological interventions to reduce pain are associated with side effects. The reported effects of non-pharmacological treatments are unclear.

Thiopurines impair the apical plasma membrane expression of CFTR in pancreatic ductal cells via RAC1 inhibition.

Background And Aims: Thiopurine-induced acute pancreatitis (TIP) is one of the most common adverse events among inflammatory bowel disease patients treated with azathioprine (AZA), representing a significant clinical burden. Previous studies focused on immune-mediated processes, however, the exact pathomechanism of TIP is essentially unclear.

Methods: To model TIP in vivo, we triggered cerulein-induced experimental pancreatitis in mice receiving a daily oral dose of 1.

Prevalence and Determinants of Pain in Spinal Cord Injury During Initial Inpatient Rehabilitation: Data From the Dutch Spinal Cord Injury Database.

Objective: To describe the prevalence and characteristics of spinal cord injury (SCI)-related pain during initial inpatient rehabilitation and to investigate relationships with demographic and lesion characteristics.

Design: Cohort during inpatient rehabilitation.

Setting: Eight specialized SCI rehabilitation centers in the Netherlands.

Bile acid- and ethanol-mediated activation of Orai1 damages pancreatic ductal secretion in acute pancreatitis.

Regardless of its aetiology, sustained intracellular Ca overload is a well-known hallmark of acute pancreatitis (AP). Toxic Ca elevation induces pancreatic ductal cell damage characterized by impaired ion and fluid secretion - essential to wash out the protein-rich fluid secreted by acinar cells while maintaining the alkaline intra-ductal pH under physiological conditions - and mitochondrial dysfunction. While prevention of ductal cell injury decreases the severity of AP, no specific drug target has yet been identified in the ductal cells.

Endoplasmic Reticulum-Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling.

In eukaryotic cells, ultimate specificity in activation and action-for example, by means of second messengers-of the myriad of signaling cascades is primordial. In fact, versatile and ubiquitous second messengers, such as calcium (Ca) and cyclic adenosine monophosphate (cAMP), regulate multiple-sometimes opposite-cellular functions in a specific spatiotemporal manner. Cells achieve this through segregation of the initiators and modulators to specific plasma membrane (PM) subdomains, such as lipid rafts and caveolae, as well as by dynamic close contacts between the endoplasmic reticulum (ER) membrane and other intracellular organelles, including the PM.

Neuropathic pain in spinal cord injury: topical analgesics as a possible treatment.

Study Design: Review of the literature and semi-structured interviews.

Objective: To explore the possible use of topical analgesics for the treatment of neuropathic pain (NP) in spinal cord injury (SCI).

Setting: Institute for Neuropathic Pain, Soest, The Netherlands.

Modulation of Plasma Membrane Composition and Microdomain Organization Impairs Heat Shock Protein Expression in B16-F10 Mouse Melanoma Cells.

The heat shock response (HSR) regulates induction of stress/heat shock proteins (HSPs) to preserve proteostasis during cellular stress. Earlier, our group established that the plasma membrane (PM) acts as a sensor and regulator of HSR through changes in its microdomain organization. PM microdomains such as lipid rafts, dynamic nanoscale assemblies enriched in cholesterol and sphingomyelin, and caveolae, cholesterol-rich PM invaginations, constitute clustering platforms for proteins functional in signaling cascades.

The Role of Lipids and Membranes in the Pathogenesis of Alzheimer's Disease: A Comprehensive View.

Lipids participate in Amyloid Precursor Protein (APP) trafficking and processing - important factors in the initiation of Alzheimer's disease (AD) pathogenesis and influence the formation of neurotoxic β-amyloid (Aβ) peptides. An important risk factor, the presence of ApoE4 protein in AD brain cells binds the lipids to AD. In addition, lipid signaling pathways have a crucial role in the cellular homeostasis and depend on specific protein-lipid interactions.

Heat Shock Proteins and Autophagy Pathways in Neuroprotection: from Molecular Bases to Pharmacological Interventions.

Neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease and Huntington's disease (HD), amyotrophic lateral sclerosis, and prion diseases are all characterized by the accumulation of protein aggregates (amyloids) into inclusions and/or plaques. The ubiquitous presence of amyloids in NDDs suggests the involvement of disturbed protein homeostasis (proteostasis) in the underlying pathomechanisms. This review summarizes specific mechanisms that maintain proteostasis, including molecular chaperons, the ubiquitin-proteasome system (UPS), endoplasmic reticulum associated degradation (ERAD), and different autophagic pathways (chaperon mediated-, micro-, and macro-autophagy).

Chaperone co-inducer BGP-15 inhibits histone deacetylases and enhances the heat shock response through increased chromatin accessibility.

Defects in cellular protein homeostasis are associated with many severe and prevalent pathological conditions such as neurodegenerative diseases, muscle dystrophies, and metabolic disorders. One way to counteract these defects is to improve the protein homeostasis capacity through induction of the heat shock response. Despite numerous attempts to develop strategies for chemical activation of the heat shock response by heat shock transcription factor 1 (HSF1), the underlying mechanisms of drug candidates' mode of action are poorly understood.

Associations Between Self-Efficacy and Secondary Health Conditions in People Living With Spinal Cord Injury: A Systematic Review and Meta-Analysis.

Objective: To describe the association between self-efficacy and secondary health conditions (SHCs) in people living with spinal cord injury (SCI).

Data Sources: PubMed, EMBASE, the Cochrane Library, and CINAHL were systematically searched from database inception to September 2016.

Study Selection: Studies describing patients living with SCI in which self-efficacy was measured by a standardized questionnaire and an association was made with somatic or psychological SHCs.

The central role of heat shock factor 1 in synaptic fidelity and memory consolidation.

Networks of neuronal synapses are the fundamental basis for making and retaining memory. Reduced synapse number and quality correlates with loss of memory in dementia. Heat shock factor 1 (HSF1), the major transcription factor regulating expression of heat shock genes, plays a central role in proteostasis, in establishing and sustaining synaptic fidelity and function, and in memory consolidation.

Rac1 participates in thermally induced alterations of the cytoskeleton, cell morphology and lipid rafts, and regulates the expression of heat shock proteins in B16F10 melanoma cells.

Eukaryotic cells exhibit a characteristic response to hyperthermic treatment, involving morphological and cytoskeletal alterations and the induction of heat shock protein synthesis. Small GTPases of the Ras superfamily are known to serve as molecular switches which mediate responses to extracellular stimuli. We addressed here how small GTPase Rac1 integrates signals from heat stress and simultaneously induces various cellular changes in mammalian cells.

Plasma membranes as heat stress sensors: from lipid-controlled molecular switches to therapeutic applications.

The classic heat shock (stress) response (HSR) was originally attributed to protein denaturation. However, heat shock protein (Hsp) induction occurs in many circumstances where no protein denaturation is observed. Recently considerable evidence has been accumulated to the favor of the "Membrane Sensor Hypothesis" which predicts that the level of Hsps can be changed as a result of alterations to the plasma membrane.

Membrane fluidity matters: hyperthermia from the aspects of lipids and membranes.

Hyperthermia is a promising treatment modality for cancer in combination both with radio- and chemotherapy. In spite of its great therapeutic potential, the underlying molecular mechanisms still remain to be clarified. Due to lipid imbalances and 'membrane defects' most of the tumour cells possess elevated membrane fluidity.

Hydroximic acid derivatives: pleiotropic HSP co-inducers restoring homeostasis and robustness.

According to the "membrane sensor" hypothesis, the membrane's physical properties and microdomain organization play an initiating role in the heat shock response. Clinical conditions such as cancer, diabetes and neurodegenerative diseases are all coupled with specific changes in the physical state and lipid composition of cellular membranes and characterized by altered heat shock protein levels in cells suggesting that these "membrane defects" can cause suboptimal hsp-gene expression. Such observations provide a new rationale for the introduction of novel, heat shock protein modulating drug candidates.

Membrane-lipid therapy in operation: the HSP co-inducer BGP-15 activates stress signal transduction pathways by remodeling plasma membrane rafts.

Aging and pathophysiological conditions are linked to membrane changes which modulate membrane-controlled molecular switches, causing dysregulated heat shock protein (HSP) expression. HSP co-inducer hydroxylamines such as BGP-15 provide advanced therapeutic candidates for many diseases since they preferentially affect stressed cells and are unlikely have major side effects. In the present study in vitro molecular dynamic simulation, experiments with lipid monolayers and in vivo ultrasensitive fluorescence microscopy showed that BGP-15 alters the organization of cholesterol-rich membrane domains.

Gene expression profiling in vastus lateralis muscle during an acute exacerbation of COPD.

Background/aims: The molecular mechanisms leading to loss in muscle force during an acute exacerbation in COPD patients are unknown. A cross-sectional study was designed to compare the gene expression profile of the vastus lateralis muscle in patients with an acute COPD exacerbation and in stable COPD patients.

Methods: Muscle biopsies were taken in 9 COPD patients with an exacerbation on day 4 of hospitalization and in 15 stable COPD patients.

Resistance training prevents deterioration in quadriceps muscle function during acute exacerbations of chronic obstructive pulmonary disease.

Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) acutely reduce skeletal muscle strength and result in long-term loss of functional capacity.

Objectives: To investigate whether resistance training is feasible and safe and can prevent deteriorating muscle function during exacerbations of COPD.

Methods: Forty patients (FEV(1) 49 +/- 17% predicted) hospitalized with a severe COPD exacerbation were randomized to receive usual care or an additional resistance training program during the hospital admission.

Atrophy and hypertrophy signalling in the diaphragm of patients with COPD.

We investigated whether atrophy and hypertrophy signalling were altered in the diaphragm of chronic obstructive pulmonary disease (COPD) patients. We studied diaphragm fibre dimensions and proportion, expression of markers of the ubiquitin-proteasome pathway, nuclear factor (NF)-kappaB pathways, muscle regulatory factors and myostatin in diaphragm biopsies from 19 patients with severe COPD and 13 patients without COPD. Type I proportion was significantly increased in the diaphragm of COPD patients while type II proportion was decreased.

Markers of inflammation and disuse in vastus lateralis of chronic obstructive pulmonary disease patients.

Background: Disuse and/or local inflammation in the muscle cannot be excluded as potential influences for the decreased muscle force in patients hospitalised due to an acute chronic obstructive pulmonary disease (COPD) exacerbation. This study aims to compare expression levels of markers of disuse (insulin-like growth factor-1 (IGF-I), MyoD and myogenin) and inflammation [interleukin-6 (IL-6), IL-8 and tumour necrosis factor-alpha (TNF-alpha)] in the muscle of hospitalised and stable COPD patients and healthy elderly.

Material And Methods: Muscle biopsies (m.

Auditory and phonetic perception of vowels in children with apraxic speech disorders.

The aim of this study was to assess auditory and phonetic perceptual processing of vowels in children with apraxic disorders, who demonstrated clinically with only a speech output deficit. Two experiments were conducted. In the preparatory Experiment 1 series of vowels were constructed by moving formant frequencies away from the extreme values in the vowel space in the direction of a 'neutral-vowel position'.

Formant transition duration and place perception in misarticulating children and adolescents.

The explanation of articulatory problems as an output speech disorder does not preclude the possibility that auditory processing problems are associated. Identification of brief auditory spectral cues in a place-of-articulation continuum was studied in children with articulation problems. First, it was shown that formant transition durations smaller than 20·0 ms dramatically decreased phonemic identification rates for alveolar stop consonants in control subjects.