Clancyploug6990

BACKGROUND Clinical guidance on the symptomatic treatment of behavioral variant frontotemporal dementia (bvFTD) is limited. OBJECTIVE To provide a systematic review of pharmacological interventions for symptomatic treatment of bvFTD, based on the International bvFTD Criteria Consortium clinical diagnostic criteria apathy, disinhibition, lack of empathy or sympathy, hyperorality, stereotypical behavior, and executive dysfunction. METHODS We systematically searched the PubMed, Embase, and PsycINFO databases for reports on pharmacological interventions for individuals with bvFTD, published between 1970 and 2018, using key indicators and relevant terms. BTK inhibitor concentration Studies were included if the efficacy of the intervention in alleviating bvFTD symptoms was provided as an outcome. Due to the high prevalence of depressive symptoms in individuals with bvFTD, we also evaluated the effect of the interventions on depression. RESULTS We included 23 studies-11 randomized controlled trials, eight open-label studies, one proof-of-concept study, and three case series-reporting on a total of 573 individuals. Of the 23 studies, 16 used pharmacological interventions that improved bvFTD symptoms. Based on the Neuropsychiatric Inventory, trazodone had the greatest significant reductive effect on the symptoms of bvFTD. Overall, citalopram, rivastigmine, paroxetine, and trazodone all reduced multiple symptoms, including disinhibition, hyperorality, and depression. CONCLUSIONS This review provides an overview of the pharmacological interventions that can be used to treat the main bvFTD symptoms as well as a guideline for managing bvFTD. More research is needed to investigate the efficacy of pharmacological interventions for bvFTD through use of a validated outcome and a focus on the specific behavioral problems associated with bvFTD.Endometriosis is an estrogen-dependent inflammatory disease that affects approximately 10% of women. Debilitating pelvic or abdominal pain is one of its major clinical features. Current animal models of endometriosis-associated pain require surgery either to implant tissue or to remove the ovaries. Moreover, existing models do not induce spontaneous pain, which is the primary symptom of patients with chronic pain, including endometriosis. A lack of models that accurately recapitulate the disease phenotype must contribute to the high failure rate of clinical trials for analgesic drugs directed at chronic pain, including those for endometriosis. We set out to establish a murine model of endometriosis-associated pain. Endometriosis was induced non-surgically by injecting a dissociated uterine horn into a recipient mouse. The induced lesions exhibited histological features that resemble human lesions along with an increase in pro-inflammatory cytokines and recruitment of immune cells. We also observed the presence of CGRP-, TRPA1-, and TRPV1-expressing nerve fibers in the lesions. This model induced mechanical allodynia, spontaneous abdominal pain, and changes in thermal selection behavior that indicate discomfort. These behavioral changes were reduced by drugs used clinically for endometriosis, specifically letrozole (aromatase inhibitor) and danazol (androgen). Endometriosis also induced neuronal changes as evidenced by activation of the NF-κB signaling pathway in TRPA1- and TRPV1-expressing DRG neurons. In conclusion, we have established a model of endometriosis-associated pain that responds to clinically active drugs and can, therefore, be used to identify novel therapies.Previous studies have demonstrated that parental cognitive, behavioral, and emotional factors are related to child functioning in children and adolescents with chronic pain. This is particularly important to understand how to potentially enhance the efficacy of psychological interventions for children by incorporating interventions targeting parents. We conducted a systematic review and meta-analysis to identify the specific parent factors that have been examined in the literature and to quantify the associations observed between parent factors and child pain and disability. A search of the electronic databases EMBASE, PsychINFO, Medline, and PubMed was conducted, using search terms related to chronic pain, pediatric population, and parents. Fifty-four studies met criteria and were included in the review. Parent pain catastrophizing and protective behavior were the most commonly assessed parental constructs in the literature. Meta-analyses were conducted for associations between parent pain catastrophizing, parent protective behaviors, parent anxiety and depression, and parent stress associated with parenting a child with chronic pain with child pain, disability, school functioning, and emotional functioning. Correlation coefficients were pooled using the random-effects model. A medium relationship was observed between higher protective behavior and poorer school functioning (r = -0.39), and small relationships were found between higher parent pain catastrophizing and increased child disability (r = 0.29); higher protective behaviors and increased child disability (r = 0.25); and increased parent depression and anxiety with increased child disability (r = 0.23 and r = 0.24, respectively). Future research is needed to investigate broader parent variables and overcome methodological weaknesses in this field.Mutations in Nav1.9 encoded by SCN11A have been associated with episodic pain, small-fiber neuropathy and congenital insensitivity to pain. In this study, we collected and characterized one Chinese family with episodic pain. The SCN11A mutation (c.664C>A/p.Arg222Ser) was identified and cosegregated with the episodic pain phenotype. In addition, we found that alcohol intake triggered intense pain attacks and detected the ALDH2 polymorphism (c.1510G>A/p.Glu504Lys) in three patients with episodic pain. The alcohol-aggravated pain symptom and this ALDH2 polymorphism were also reconfirmed in our previously reported episodic pain patient with the Nav1.9 mutation (p.Ala808Gly, patient III-2 in HBBJ family). To assess the pathogenicity of the Nav1.9 mutation and the new trigger, we introduced a mutation (p.Ala796Gly) into the mouse (orthologous mutation in human is p.Ala808Gly). The alteration hyperpolarized channel activation, increased the residual current through non-inactivating channels, and induced hyperexcitability of dorsal root ganglion (DRG) neurons in Scn11a mice.