A multifunctional platform is presented which (a) allows determination of extracellular pH in real time, (b) detects cancer cells, down to 5 cells, and (c) enables evaluating the efficacy of glycolysis inhibiting drugs.
Ursolic acid (UA), a pentacyclic triterpenoid carboxylic acid, is the major component of many plants including apples, basil, cranberries, peppermint, rosemary, oregano and prunes and has been reported to possess antioxidant and anti-tumor properties. These properties of UA have been attributed to its ability to suppress NF-κB (nuclear factor kappa B) activation. Since NF-κB, in co-ordination with NF-AT (nuclear factor of activated T cells) and AP-1(activator protein-1), is known to regulate inflammatory genes, we hypothesized that UA might exhibit potent anti-inflammatory effects.The anti-inflammatory effects of UA were assessed in activated T cells, B cells and macrophages. Effects of UA on ERK, JNK, NF-κB, AP-1 and NF-AT were studied to elucidate its mechanism of action. In vivo efficacy of UA was studied using mouse model of graft-versus-host disease. UA inhibited activation, proliferation and cytokine secretion in T cells, B cells and macrophages. UA inhibited mitogen-induced up-regulation of activation markers and co-stimulatory molecules in T and B cells. It inhibited mitogen-induced phosphorylation of ERK and JNK and suppressed the activation of immunoregulatory transcription factors NF-κB, NF-AT and AP-1 in lymphocytes. Treatment of cells with UA prior to allogenic transplantation significantly delayed induction of acute graft-versus-host disease in mice and also significantly reduced the serum levels of pro-inflammatory cytokines IL-6 and IFN-γ. UA treatment inhibited T cell activation even when added post-mitogenic stimulation demonstrating its therapeutic utility as an anti-inflammatory agent.The present study describes the detailed mechanism of anti-inflammatory activity of UA. Further, UA may find application in the treatment of inflammatory disorders.
Aim of the study was determine health care outcomes from the patients' perspective in patients reliant on Mitrofanoff catheterisation for bladder emptying.Patients over the age of 16 dependent on Mitrofanoff catheterisation for bladder emptying were asked to complete a health care outcome questionnaire, the SF-36 (®) Health Survey v2. Quality of life measures for 8 health concepts were compared against published data for the normal population.Out of a total of 25 patients who were eligible for enrolment into our study, we were able to contact 19 patients. The norm-based score for Physical Functioning (PF=50.4), Role Physical (RP=53.8), Bodily Pain (BP=55.6), Vitality (VT=56.9), Social Functioning (SF=51.5), Role Emotional (RE=52.2), and Mental Health (MH=54.6) were all higher than those reported within the normal population (normal=50.0). Physical and mental component summary measures were higher than in the normal population. When compared against age-matched norms our patient group scored higher than the normal population for all measures except Physical Functioning (50.4 vs. 53.4) and physical component summary (51.9 vs. 53.5). The self-reported scores for Vitality, Mental Health and the mental component summary were all statistically significantly better than those seen in the age-matched control population (p<0.01).Quality of life in patients dependent on Mitrofanoff catheterisation for bladder emptying is good. The SF-36 measures 8 major health care outcomes and in our patients these measures of health were similar to those seen in the general population, rather than the poorer outcomes reported in patients with other chronic medical conditions.
Background Psychiatric comorbidity is known to impact upon use of nonpsychiatric health services. The aim of this systematic review and meta-analysis was to assess the specific impact of severe mental illness (SMI) on the use of inpatient, emergency, and primary care services for nonpsychiatric medical disorders. Methods and findings PubMed, Web of Science, PsychINFO, EMBASE, and The Cochrane Library were searched for relevant studies up to October 2018. An updated search was carried out up to the end of February 2020. Studies were included if they assessed the impact of SMI on nonpsychiatric inpatient, emergency, and primary care service use in adults. Study designs eligible for review included observational cohort and case-control studies and randomised controlled trials. Random-effects meta-analyses of the effect of SMI on inpatient admissions, length of hospital stay, 30-day hospital readmission rates, and emergency department use were performed. This review protocol is registered in PROSPERO (CRD42019119516). Seventy-four studies were eligible for review. All were observational cohort or case-control studies carried out in high-income countries. Sample sizes ranged from 27 to 10,777,210. Study quality was assessed using the Newcastle-Ottawa Scale for observational studies. The majority of studies (n = 45) were deemed to be of good quality. Narrative analysis showed that SMI led to increases in use of inpatient, emergency, and primary care services. Meta-analyses revealed that patients with SMI were more likely to be admitted as nonpsychiatric inpatients (pooled odds ratio [OR] = 1.84, 95% confidence interval [CI] 1.21–2.80, p = 0.005, I2 = 100%), had hospital stays that were increased by 0.59 days (pooled standardised mean difference = 0.59 days, 95% CI 0.36–0.83, p < 0.001, I2 = 100%), were more likely to be readmitted to hospital within 30 days (pooled OR = 1.37, 95% CI 1.28–1.47, p < 0.001, I2 = 83%), and were more likely to attend the emergency department (pooled OR = 1.97, 95% CI 1.41–2.76, p < 0.001, I2 = 99%) compared to patients without SMI. Study limitations include considerable heterogeneity across studies, meaning that results of meta-analyses should be interpreted with caution, and the fact that it was not always possible to determine whether service use outcomes definitively excluded mental health treatment. Conclusions In this study, we found that SMI impacts significantly upon the use of nonpsychiatric health services. Illustrating and quantifying this helps to build a case for and guide the delivery of system-wide integration of mental and physical health services.
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