Background: Consensus guidelines on the definition, investigation, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been previously published in European ...Journal of Neurology and Journal of the Peripheral Nervous System.
Objectives: To revise these guidelines.
Methods: Disease experts, including a representative of patients, considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed in an iterative fashion.
Recommendations: The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (i) intravenous immunoglobulin (IVIg) (Recommendation Level A) or corticosteroids (Recommendation Level C) should be considered in sensory and motor CIDP; (ii) IVIg should be considered as the initial treatment in pure motor CIDP (Good Practice Point); (iii) if IVIg and corticosteroids are ineffective, plasma exchange (PE) should be considered (Recommendation Level A); (iv) if the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (Good Practice Point); (v) symptomatic treatment and multidisciplinary management should be considered (Good Practice Point).
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Clozapine (CLZ), the sole antipsychotic with superior efficacy for ultra-treatment resistant schizophrenia (TRS), is limited by adverse effects, including metabolic dysregulation. Clozapine's main ...metabolite, N-desmethylclozapine (NDMC), has potent 5-HT2C antagonist properties which may explain this metabolic dysfunction, thus the CLZ:NDMC ratio is of particular interest. High insulin resistance states could be associated with CYP1A2 induction and lower CLZ:NDMC ratios. Additionally, lower CLZ:NDMC ratios have been associated with better cognitive, but worse metabolic functioning. This study investigated associations between metabolic and cognitive parameters with the CLZ/NDMC ratio. Primary outcomes included relationships between the CLZ:NDMC ratio to the homeostatic model assessment for insulin resistance (HOMA-IR) and Brief Assessment of Cognition in Schizophrenia (BACS) composite z-scores. Secondary outcomes assessed relationships between CLZ:NDMC ratios to fasting insulin, BMI, weight, fasting glucose, and BACS digit sequencing z-scores. 38 patients who were overweight or obese with schizophrenia or schizoaffective disorder completed fasting bloodwork, anthropometric, psychopathological, and cognitive assessments. Multivariate regressions found a statistically significant inverse association between the CLZ/NDMC ratio and HOMA-IR (B = - 1.028, SE B = .473, β = - 0.348 p = 0.037), which may have been driven by fasting insulin levels (B = - 27.124, SE B = 12.081, β = - 0.351 p = 0.031). The CLZ/NDMC ratio may predict insulin resistance/metabolic comorbidity among patients with TRS receiving clozapine.
Eleutherococcus senticosus somatic embryos were cultured in Murashiage and Skoog medium in balloon type bubble bioreactor (working volume 2-l) to investigate the effect of light on biomass, secondary ...metabolites, stress levels (lipid peroxidation and hydrogen peroxide (H
2O
2) and changes of antioxidant enzymes. Among the different light sources, biomass accumulation was found optimum under fluorescent (Fl) and mixed blue plus far-red (Bl
+
Fr) irradiation. Accumulation of eleutheroside E (51%) and E
1 (21%) was highest at red light while fluorescent light produced highest amount of total phenolic (2.7%), total flavonoid (34%) and chlorogenic acid (14%) contents compared to dark (control) grown mature embryos. Higher H
2O
2 content, malondialdehyde (MDA) content and lipoxygenase (LOX) activities was observed at red light treated embryos compared to dark (control) grown embryos. Antioxidant enzymes, monodehydroascorbate reductase (MDHAR), catalase (CAT), glutathione
S transferase (GST) and superoxide dismutase (SOD) which are playing important role for the detoxification of harmful substances were also induced in red light irradiated embryos. However, ascorbate peroxidase (APX) took a little part in detoxification of H
2O
2 due to its sensitivity to red light. Therefore, reduced APX activity in red light treated embryos was observed. While APX activity was maximum in fluorescent light treated embryos compared to other light sources. This reflects the sensitivity of the enzyme to the different light. The study concludes that embryo could grow under different light irradiation and protect themselves from toxicity of light sources by altering various phenolic compounds and antioxidant enzymes.
Military sexual trauma (MST), defined as sexual assault or repeated, threatening sexual harassment while in the military, is associated with increased risk of long-term mental and physical health ...problems, with the most common being symptoms of post-traumatic stress disorder (PTSD) and depression. In addition to PTSD and depression, MST is linked to difficulties in emotion regulation as well as poor treatment engagement. Thus, it is important to examine these correlates, and how they affect postintervention symptom reduction in this vulnerable population. The current study presents secondary data analyses from a randomized clinical trial comparing the efficacy of in-person versus telemedicine delivery of prolonged exposure therapy for female veterans with MST-related PTSD (n = 151). Results of the study found that changes in difficulties with emotion regulation predicted postintervention depressive symptoms but not postintervention PTSD symptoms. Neither postintervention depressive nor PTSD symptoms were affected by treatment dosing (i.e., number of sessions attended) nor treatment condition (i.e., in-person vs. telemedicine). Findings from the current study provide preliminary evidence that decreases in difficulties with emotion regulation during PTSD treatment are associated with decreases in depressive symptom severity.
We have measured the muon flux and production rate of muon-induced neutrons at a depth of 611 m water equivalent. Our apparatus comprises three layers of crossed plastic scintillator hodoscopes for ...tracking the incident cosmic-ray muons and 760 L of a gadolinium-doped liquid scintillator for producing and detecting neutrons. The vertical muon intensity was measured to be I sub(mu)=(5.7+ or -0.6)x10 super(-6)cm super(- 2)s super(-1)sr super(-1). The yield of muon-induced neutrons in the liquid scintillator was determined to be Y sub(n)=(1.19+ or -0.08(stat)+ or -0.21(syst))x10 super(-4)neutrons/(mumiddotgmiddotcm super(-2)). A fit to the recently measured neutron yields at different depths gave a mean muon energy dependence of <E sub(mu)> super(0.76+ or -0.03) for liquid-scintillator targets.
The karyotypic chaos exhibited by human epithelial cancers complicates efforts to identify mutations critical for malignant transformation. Here we integrate complementary genomic approaches to ...identify human oncogenes. We show that activation of the ERK and phosphatidylinositol 3-kinase (PI3K) signaling pathways cooperate to transform human cells. Using a library of activated kinases, we identify several kinases that replace PI3K signaling and render cells tumorigenic. Whole genome structural analyses reveal that one of these kinases, IKBKE (IKKɛ), is amplified and overexpressed in breast cancer cell lines and patient-derived tumors. Suppression of IKKɛ expression in breast cancer cell lines that harbor IKBKE amplifications induces cell death. IKKɛ activates the nuclear factor-kappaB (NF-κB) pathway in both cell lines and breast cancers. These observations suggest a mechanism for NF-κB activation in breast cancer, implicate the NF-κB pathway as a downstream mediator of PI3K, and provide a framework for integrated genomic approaches in oncogene discovery.
Cognitive impairment is a core symptom domain of schizophrenia. The effect of antipsychotics, the cornerstone of treatment in schizophrenia, on this domain is not fully clear. There is some evidence ...suggesting that antipsychotics may partially improve cognitive function, and that this improvement may vary depending on the specific cognitive domain. However, this research is confounded by various factors, such as age, duration/stage of illness, medication adherence, and extrapyramidal side effects that complicate the relationship between antipsychotics and cognitive improvement. Furthermore, antipsychotics-particularly the second generation, or "atypical" antipsychotics-can induce serious metabolic side effects, such as obesity, dyslipidemia and type 2 diabetes, illnesses which themselves have been linked to impairments in cognition. Thus, the inter-relationships between cognition and metabolic side effects are complex, and this review aims to examine them in the context of schizophrenia and antipsychotic treatment. The review also speculates on potential mechanisms underlying cognitive functioning and metabolic risk in schizophrenia. We conclude that the available literature examining the inter-section of antipsychotics, cognition, and metabolic effects in schizophrenia is sparse, but suggests a relationship between metabolic comorbidity and worse cognitive function in patients with schizophrenia. Further research is required to determine if there is a causal connection between the well-recognized metabolic adverse effects of antipsychotics and cognitive deficits over the course of the illness of schizophrenia, as well as, to determine underlying mechanisms. In addition, findings from this review highlight the importance of monitoring metabolic disturbances in parallel with cognition, as well as, the importance of interventions to minimize metabolic abnormalities for both physical and cognitive health.
Right ventricular pressure-volume (PV) analysis characterizes ventricular systolic and diastolic properties independent of loading conditions like volume status and afterload. While long-considered ...the gold-standard method for quantifying myocardial chamber performance, it was traditionally only performed in highly specialized research settings. With recent advances in catheter technology and more sophisticated approaches to analyze PV data, it is now more commonly used in a variety of clinical and research settings. Herein, we review the basic techniques for PV loop measurement, analysis, and interpretation with the aim of providing readers with a deeper understanding of the strengths and limitations of PV analysis. In the second half of the review, we detail key scenarios in which right ventricular PV analysis has influenced our understanding of clinically relevant topics and where the technique can be applied to resolve additional areas of uncertainty. All told, PV analysis has an important role in advancing our understanding of right ventricular physiology and its contribution to cardiovascular function in health and disease.
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