Brighton & Sussex Medical School

Sussex, United States

Brighton & Sussex Medical School

Sussex, United States
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Ghezzi P.,Brighton & Sussex Medical School | Jaquet V.,University of Geneva | Marcucci F.,University of Milan | Schmidt H.H.H.W.,Maastricht University
British Journal of Pharmacology | Year: 2017

The theory that oxidative stress (OS) is at the root of several diseases is extremely popular. However, so far, no antioxidant has been recommended or offered by healthcare systems neither has any been approved as therapy by regulatory agencies that base their decisions on evidence-based medicine. This is simply because, so far, despite many preclinical and clinical studies indicating a beneficial effect of antioxidants in many disease conditions, randomised clinical trials have failed to provide the evidence of efficacy required for drug approval. In this review, we discuss the levels of evidence required to claim causality in preclinical research on OS, the weakness of the oversimplification associated with OS theory of disease and the importance of the narrative in its popularity. Finally, from a more translational perspective, we discuss the reasons why antioxidants acting by scavenging ROS might not only prevent their detrimental effects but also interfere with essential signalling roles. We propose that ROS have a complex metabolism and are generated by different enzymes at diverse sites and at different times. Aggregating this plurality of systems into a single theory of disease may not be the best way to develop new drugs, and future research may need to focus on specific oxygen-toxifying pathways rather than on non-specific ROS scavengers. Finally, similarly to what is nowadays required for clinical trials, we recommend making unpublished data available in repositories (open data), as this will allow big data approaches or meta-analyses, without the drawbacks of publication bias. Linked Articles: This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit © 2016 The British Pharmacological Society

Keramida G.,University of Sussex | Potts J.,University of Sussex | Bush J.,University of Sussex | Verma S.,Brighton Sussex Medical School | And 2 more authors.
American Journal of Roentgenology | Year: 2014

OBJECTIVE. Nonalcoholic Tatty liver disease is associated with hepatic inflammation, An emerging technique to image inflammation is PET using the glucose tracer, l8F-FDG, The purpose of this study was to determine whether in hepatic steatosis the liver accumulates FDG in excess of FDG physiologically exchanging between blood and hepatocyte, MATERIALS AND METHODS. Hepatic FDG uptake, as SUV = [voxel counts I administered activity] × body weight), and CT density were measured in a liver region in images obtained 60 minutes after injection of FDG in 304 patients referred for routine PET/CT. Maximum SUV (region voxel with the highest count rate. SUVmax) and average SUV (SUVave) were measured. Blood FDG concentration was measured as the maximum SUV over the left ventricular cavity (SUVLv). SUVave was adjusted for hepatic fat using a formula equating percentage fat to CT density. Patients were divided in subgroups on the basis of blood glucose (< 4, 4 to < 5, 5 to < 6, 6 to < 8, 8 to < 10, and > 10 mmol/L). Hepatic steatosis was defined as CT density less than 40 HU (n = 71). RESULTS. The percentage of hepatic fat increased exponentially with blood glucose. SUVmax / SUVLv anil fat-adjusted SUVave. / SUVLV but not SUVave / SUVLV correlated with blood glucose. Fat-adjusted SUVave was higher in patients with hepatic steatosis (p < 0.001) by ~0.4 in all blood glucose groups. There was a similar difference (~0.3) in SUVmax (p < 0.005) but no difference in SUV.avc. SUVmax / SUVLV and fat-adjusted SUV ave / SUVLV correlated with blood glucose in patients with hepatic steatosis but not in those without. SUVave / SUVLV correlated with blood glucose in neither group. CONCLUSION. FDG uptake is increased in hepatic steatosis, probably resulting from irreversible uptake in inflammatory cells superimposed on reversible hepatocyte uptake. ©American Roentgen Ray Society.

PubMed | Brighton & Sussex Medical School, University of Sussex and University College London
Type: Journal Article | Journal: BMC public health | Year: 2017

Contraceptive advice and supply (CAS) and sexually transmitted infection (STI) testing are increasingly provided in primary care. Most risk assessment tools are based on sexual risk behaviours and socio-demographics, for use online or in specialist services. Combining socio-demographic and psychosocial questions (e.g. religious belief and formative experience) may generate an acceptable tool for targeting women in primary care who would benefit from intervention. We aimed to identify psychosocial and socio-demographic factors associated with reporting key sexual risk behaviours among women in the British general population.We undertook complex survey analysis of data from 4911 hetero-sexually active women aged 16-44 years, who participated in Britains third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a national probability sample survey undertaken 2010-2012. We used multivariable regression to examine associations between the available psychosocial and socio-demographic variables in Natsal-3 and reports of three key sexual behaviours: a) 2+ partners in the last year (2PP); b) non-use of condoms with 2+ partners in the last year (2PPNC); c) non-use of condoms at first sex with most recent sexual partner (FSNC). We adjusted for key socio-demographic factors: age, ethnicity and socio-economic status (measured by housing tenure).Weekly binge drinking (6+ units on one occasion), and first sex before age 16 were each positively associated with all three sexual behaviours after adjustment. Current relationship status, reporting drug use (ever), younger age and living in rented accommodation were also associated with 2+ partners and 2+partners without condoms after adjustment. Currently being a smoker, older age and respondent ethnicity were associated with FSNC after adjustment for all other variables. Current smoking status, treatment for depression (last year), and living at home with both parents until the age of 14 were each associated with one or more of the behaviours.Reported weekly binge drinking, early sexual debut, and age group may help target STI testing and/or CAS among women. Further research is needed to examine the proportion of sexual risk explained by these factors, the acceptability of these questions to women in primary care and the need to customise them for community and other settings.

Tomczyk S.,Institute of Tropical Medicine | Deribe K.,Brighton & Sussex Medical School | Deribe K.,Addis Ababa Institute of Technology | Brooker S.J.,London School of Hygiene and Tropical Medicine | And 8 more authors.
PLoS Neglected Tropical Diseases | Year: 2014

The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs.We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses.Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR=0.15; 95% CI: 0.08–0.29), CLM (OR=0.24; 95% CI: 0.06–0.96), tungiasis (OR=0.42; 95% CI: 0.26–0.70), hookworm infection (OR=0.48; 95% CI: 0.37–0.61), any STH infection (OR=0.57; 95% CI: 0.39–0.84), strongyloidiasis (OR=0.56; 95% CI: 0.38–0.83), and leptospirosis (OR=0.59; 95% CI: 0.37–0.94). No significant association between footwear use and podoconiosis (OR=0.63; 95% CI: 0.38–1.05) was found and no data were available for mycetoma, myiasis, and snakebite. The main limitations were evidence of heterogeneity and poor study quality inherent to the observational studies included.Our results show that footwear use was associated with a lower odds of several different NTDs. Access to footwear should be prioritized alongside existing NTD interventions to ensure a lasting reduction of multiple NTDs and to accelerate their control and elimination.PROSPERO International prospective register of systematic reviews CRD42012003338. © 2014 Tomczyk et al.

PubMed | Isfahan University of Medical Sciences, Neyshabur University of Medical science, Mashhad University of Medical Sciences, Payame Noor University and Brighton & Sussex Medical School
Type: Journal Article | Journal: Clinical biochemistry | Year: 2016

Hypertriglyceridemia is an established risk factor for coronary-heart-disease. Inflammatory cytokines are known to be important mediators of atherogenesis; however, the relationship between the concentrations of specific inflammatory cytokines and the presence of hypertriglyceridemia has not been well established. The purpose of this study was to investigate the relationship between the serum levels of several pro- and anti-inflammatory cytokines and the presence of hypertriglyceridemia.Four hundred and eighty-four subjects with/without established hypertriglyceridemia were recruited. Anthropometric parameters and biochemical analysis (including a full fasting lipid profile) were determined. The serum levels of several cytokines and growth factors including IL-1, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-, MCP-1, IFN-, EGF, and VEGF were measured followed by univariate and multivariate analyses.Individuals with hypertriglyceridemia had a significantly higher body mass index, total-cholesterol and triglyceride, compared to the group without hypertriglyceridemia. Serum levels of MCP-1, TNF- and IL-8 were significantly higher in subjects with hypertriglyceridemia [e.g., IL-8 from 7.8ng/L (95% CI: 4.6-18.9) versus 5.7ng/L (95% CI: 3.6-11.9), P<0.05]. The multivariate analysis showed that the increased serum concentration of TNF- was independently associated with high-density lipoprotein cholesterol (HDL-C), while the serum levels of IL-8 and MCP-1 were associated with hypertriglyceridemia.Subjects with serum triglycerides of 2.25mmol/L had an altered cytokine-profile, particularly with respect to serum IL-8, MCP-1 and TNF-, which might partially account for its adverse clinical-consequences. Further-investigations in a large multi-center setting are warranted to unravel the potential functional-importance of these cytokines in individuals with hypertriglyceridemia.

PubMed | Neyshabur University of Medical science, Mashhad University of Medical Sciences and 7 Brighton & Sussex Medical School
Type: Journal Article | Journal: Annals of clinical biochemistry | Year: 2016

Background Obesity is associated with a state of systemic inflammation, mediated by adipose tissue-derived cytokines that may also have metabolic effects, including an effect on insulin resistance. The aim of this study was to compare the serum profile of pro- and anti-inflammatory cytokines in obese and non-obese subjects. Methods A total of 242 subjects who were either overweight or obese (body mass index [BMI]25kg/m

Asres A.,Health Science University | Davey G.,Brighton & Sussex Medical School
Maternal and Child Health Journal | Year: 2015

Attempts to predict pregnancy and childbirth complications before they occur have not been successful. Provision of safe delivery service for all births is considered to be a critical intervention for ensuring safe motherhood. Hence the aim of the study was to assess factors associated with safe delivery service utilization among women in Sheka Zone South West Ethiopia. A community based comparative cross sectional survey was conducted among 554 women in Sheka Zone from February to March 2008. Data were collected through structured pre-tested questionnaire and entered into Epinfo version 3.3. Analyses were done with SPSS version 13 computer software with which bivariate and multiple logistic regressions were carried out. Mothers who completed at least secondary school were more likely to give birth at health facility than those uneducated (AOR = 3.26, 95 % CI 1.51–7.06). Women with birth order above four were less likely to give birth in a health facility than those with first order births (AOR = 0.21, 95 %CI 0.10–0.43). Women who had encountered problems in their immediate birth and received prenatal care were more likely to give birth at health facilities AOR = 33.78 95 % CI 16.44–69.39) and (AOR = 2.55, 95 % CI 1.05–6.21) respectively. Factors associated with safe delivery service utilization are related to the women’s socioeconomic status and obstetric experiences. Consequently promotion of maternal education, prenatal care utilization, information education and communication on obstetric risks and general health service expansion are needed to ensure safe delivery service. © 2014, Springer Science+Business Media New York.

PubMed | Brighton & Sussex Medical School and Mashhad University of Medical Sciences
Type: | Journal: Annals of clinical biochemistry | Year: 2016

Background Metabolic syndrome is defined by a clustering of cardiovascular risk factors and is associated with a heightened inflammatory state. A raised serum high-sensitivity C-reactive protein, a marker of inflammation, is also known to associate with cardiovascular risk. We have investigated the relationship between the presence of metabolic syndrome and serum high-sensitivity C-reactive protein concentration in a large representative Persian population cohort without a history of cardiovascular disease. Methods The MASHAD study population cohort comprised 9778 subjects, who were recruited from the city of Mashhad, Iran, between 2007 and 2008. Several cardiovascular risk factors were measured in this population without cardiovascular disease. Individuals were categorized into quartiles of serum high-sensitivity C-reactive protein concentration: first quartile - 0.72 (0.59-0.85) (median [range]) mg/L, second quartile - 1.30 (1.14-1.4) mg/L, third quartile - 2.29 (1.92-2.81) mg/L and fourth quartile - 6.63 (4.61-11.95) mg/L, respectively. The prevalence of metabolic syndrome in each quartile was determined using either International Diabetes Federation or Adult Treatment Panel III criteria. Results The prevalence of metabolic syndrome was highest in the fourth quartile for serum high-sensitivity C-reactive protein (1220 subjects [50.0%]), and significantly higher than that in the first quartile (reference group) (634 subjects [25.9%]) ( P<0.001). A positive smoking habit (OR, 1.47 [1.26-1.70], P<0.001) and the presence of either metabolic syndrome-International Diabetes Federation (OR, 1.35 [1.18-1.55], P<0.001) or metabolic syndrome-ATPIII (OR, 1.40 [1.18-1.50], P<0.001) were strong predictors of a fourth quartile for serum high-sensitivity C-reactive protein concentration. Conclusions There was a significant association between high concentrations of serum high-sensitivity C-reactive protein and the presence of metabolic syndrome among individuals without a history of cardiovascular disease in our Persian cohort.

PubMed | Saint Louis University, Mashhad University of Medical Sciences and Brighton & Sussex Medical School
Type: | Journal: Clinical nutrition (Edinburgh, Scotland) | Year: 2017

Several genome-wide-association-studies have identified genetic variants in a region on chromosome 9p21 that are associated with an increased risk of Cardiovascular disease (CVD) and diabetes. Here we have explored the interaction of a genetic variant of the CDKN2A/B-rs10811661 gene locus with cardiovascular risk factors and environmental-exposures (e.g., diet and physical activity) in 1165 individuals recruited from the Mashhad-Stroke and Heart-Atherosclerotic-Disorders cohort.Genotyping was carried out using TaqMan-real-time-PCR based method. The association of CDKN2A/B-rs10811661 locus and its interaction with dietary intake in association with the main determinants of dyslipidemia, and cardiovascular-risk-factors were assessed in 2 cohorts.Our data showed that obese subjects with a TT genotype had a higher level of TG, TG/HDL ratio and Hs-CRP, compared to the subjects with the wild type genotype, or individuals with a normal BMI. Moreover, the presence of a TT genotype was associated with increased risk of hypercholesterolemia, insulin resistance and CVD. These effects were more pronounced in the sub-group with low physical activity and a high dietary energy intake (e.g., the interaction between TT genotype and total energy intake on serum cholesterol was positive (RERI: 0.2, 95%CI (-0.96-1.3), AP: 0.1, 95%CI (-0.5-0.7) and SI: 1.2, 95%CI (0.3-5.1))).We have found a significant association between the CDKN2A-rs10811661 polymorphism with cardiovascular risk factors and dyslipidemia in a non-diabetic population. It is possible that a low energy diet and high physical activity could ameliorate the unfavorable effects of T allele of CDKN2A/B locus. Functional analysis is warranted to investigate the value of this genetic biomarker of CVD risk in obese people.

News Article | October 26, 2016

High levels of inflammation as a child may predict a higher risk of manic behaviour in later life, a finding that could lead to new ways of treating conditions like bipolar disorder. Hypomania involves spells of hyperactivity and is often a symptom of mood disorders, including bipolar disorder, seasonal affective disorder and some kinds of psychosis. People experiencing hypomania may take more risks, feel more confident and become impatient with others. After spells like this, they may “crash”, needing to sleep for long periods and sometimes remembering little about the previous few days. Earlier studies suggested a link between inflammation and mood disorders, prompting Joseph Hayes at University College London and his team to see if inflammation as a child might lead to mental health problems later. Analysing data from more than 1700 people, his team identified a significant link between high levels of a chemical involved in inflammation at age 9, and experiencing aspects of hypomania at age 22. The chemical, called IL-6, is normally secreted by white blood cells to stimulate an inflammatory immune response to infection or trauma. Hayes’s team says it is unclear how inflammation in childhood could induce symptoms of hypomania but IL-6 is known to affect the brain. A study that used injections to increase IL-6 in the blood of healthy volunteers found that this caused symptoms of anxiety, and reduced performance in memory tests. There is also evidence that IL-6 can affect brain activity in a region called the subgenual cingulate. This region is thought to govern a vast network of brain areas, including those that affect mood and anxiety, sleep, memory and self-esteem. The team suggests that targeting inflammatory pathways may help treat conditions such as bipolar disorder. “The study provides important new evidence in support of a role for inflammation in pathological increases in mood,” says Neil Harrison at Brighton & Sussex Medical School in the UK. “Taken together with results from earlier studies, this suggests that high levels of inflammation during childhood increase the risk of disorders of mood later in life.” Read more: Schizophrenia and inflammation link could lead to new treatments

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