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High-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce neuropathic pain, but intermittent “theta-burst” stimulation (iTBS) could be a better alternative because of shorter duration and greater ability to induce cortical plasticity. Here we compared head-to-head the pain-relieving efficacy of the two modalities when applied daily for 5days to patients with neuropathic pain.

Forty-six patients received 20Hz-rTMS and/or iTBS protocols and 39 of them underwent the full two procedures in a random cross-over design. They rated pain intensity, sleep quality, fatigue and general health status daily during 5 consecutive weeks.

Pain relief during the month following stimulation was superior after 20Hz-rTMS relative to iTBS (F(1,38)=4.645; p=0.037). Correlation between respective levels of maximal relief showed a significant deviation toward the 20Hz-rTMS effect. A greater proportion of individuals responded to 20Hz-rTMS (52% vs 32%, 95%CI[0.095-3.27]; p=0.06), and reports of fatigue significantly improved after 20Hz-rTMS relative to iTBS (p=0.01). General health and sleep quality scores did not differentiate both techniques.

High-frequency rTMS appeared superior to iTBS for neuropathic pain relief.

Adequate matching between the oscillatory activity of motor cortex and that of rTMS may increase synaptic efficacy, thus enhancing functional connectivity of motor cortex with distant structures involved in pain regulation.

Adequate matching between the oscillatory activity of motor cortex and that of rTMS may increase synaptic efficacy, thus enhancing functional connectivity of motor cortex with distant structures involved in pain regulation.

Patients with intermittent claudication (IC) are initially treated with supervised exercise therapy (SET), as advised by national and international guidelines. Dutch health insurance companies and the Dutch National Health Care Institute suggested an 87% compliance rate with these guidelines in the Netherlands in 2017 and judged this to be undesirably low. The aim of this study was to evaluate compliance with IC guidelines and to elaborate on the reasons for deviating from them (practice variation) in a large teaching hospital.

A retrospective single centre cohort study was conducted at a large teaching hospital in the Netherlands. In total, 420 patients with newly diagnosed IC between 1 January 2017 and 31 December 2018 were analysed. Data included risk profiles and prescribed therapies.

For all 420 included patients, the compliance rate with the guidelines for SET was 80.5%. The rate of adequately motivated and defensible practice variation was 15.7%; the rate of unjustified practice variation was 3.8%. Meaningful care was seen in 96.2% of cases.

Deviation from IC guidelines was found in 19.5% of patients. Almost three quarters of this deviation can be explained by the decision to provide personalised, meaningful care.

Deviation from IC guidelines was found in 19.5% of patients. SCH-442416 Almost three quarters of this deviation can be explained by the decision to provide personalised, meaningful care.Many aspects of the mechanisms underlying the symbiosis between humans and gut microbes remain unknown and encompass some of the most intriguing questions in microbiome research. An important factor in this symbiosis is the interplay between microbes and human-produced glycans in mucin and breast milk. In this Opinion paper, I propose a synergy between the structural diversity of human mucin glycans and the enzymatic repertoire of the gut microbiome. The contribution of microbes to mucosal health is discussed, and the role of breast milk glycans in mucosal colonization by microbes is explained. The use of prebiotic mucin glycans in general, and specialized infant and medical nutrition in particular, should be considered as the field of interest to modulate the microbiota and improve mucosal health.Cytokine storm syndrome (CSS) has generally been described as a collection of clinical manifestations resulting from an overactivated immune system. Cytokine storms (CSs) are associated with various pathologies, as observed in infectious diseases, certain acquired or inherited immunodeficiencies and autoinflammatory diseases, or following therapeutic interventions. Despite the role of CS in tissue damage and multiorgan failure, a systematic understanding of its underlying molecular mechanisms is lacking. Recent studies demonstrate a positive feedback loop between cytokine release and cell death pathways; certain cytokines, pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs), can activate inflammatory cell death, leading to further cytokine secretion. Here, we discuss recent progress in innate immunity and inflammatory cell death, providing insights into the cellular and molecular mechanisms of CSs and therapeutics that might quell ensuing life-threatening effects.Cytokines control immune related events and are critically involved in a plethora of patho-physiological processes including autoimmunity and cancer development. In rare cases, single nucleotide polymorphisms (SNPs) or single nucleotide variations (SNVs) in cytokine receptors eventually cause detrimental ligand-independent, constitutive activation of signal transduction. Most SNPs have, however, no or only marginal influences on gene expression, protein stability, localization and function and thereby only slightly affecting pathogenesis probability. The SNP database (dbSNP) is an archive for a broad collection of polymorphisms in which SNPs are categorized and marked with a locus accession number “reference SNP” (rs). Here, we engineered an algorithm to directly align dbSNP information to DNA and protein sequence information to clearly illustrate a genetic SNP landscape exemplified for all tall cytokine receptors of the IL-6/IL-12 family, including IL-23R, IL-12Rβ1, IL-12Rβ2, gp130, LIFR, OSMR and WSX-1. This information was complemented by a comprehensive literature summary and structural insights of relevant disease-causing SNPs in cytokine/cytokine receptor interfaces. In summary, we present a general strategy with potential to apply to other cytokine receptor networks.