Clear Evidence Of Association Research Articles

Associations of blood lipids and LDL cholesterol lowering drug-targets with colorectal cancer risk: a Mendelian randomisation study

BackgroundWhether blood lipids are causally associated with colorectal cancer (CRC) risk remains unclear.MethodsUsing two-sample Mendelian randomisation (MR), our study examined the associations of genetically-predicted blood concentrations of lipids and lipoproteins (primary: LDL-C, HDL-C, triglycerides, and total cholesterol), and genetically-proxied inhibition of HMGCR, NPC1L1, and PCSK9 (which mimic therapeutic effects of LDL-lowering drugs), with risks of CRC and its subsites. Genetic associations with lipids were obtained from the Global Lipids Genetics Consortium (n = 1,320,016), while genetic associations with CRC were obtained from the largest existing CRC consortium (n = 58,221 cases and 67,694 controls). Our main analysis was a multivariable MR (MVMR) with mutual adjustments for LDL-C, HDL-C, and triglycerides. Secondary analyses, including MVMR additionally-adjusting for BMI or diabetes, were also performed.ResultsGenetically-predicted LDL-C was positively associated with CRC risk in the MVMR adjusted for HDL-C and triglycerides (OR = 1.09; 95%CI 1.02–1.16 per SD increase) and additionally-adjusted for BMI (OR = 1.12; 95%CI 1.05–1.21) or diabetes (OR = 1.09; 95%CI 1.02–1.17). Associations were generally consistent across anatomical subsites. No clear evidence of association was found for other lipids, lipoproteins, or LDL-lowering drug-targets.ConclusionsWe found evidence of a weak positive association between LDL-C and CRC that did not appear to be explained by potential pleiotropic pathways such as via HDL-C, triglycerides, BMI, or diabetes.

Consensus statement on Singapore Perinatal Mental Health Guidelines on Depression and Anxiety.

Perinatal depression and anxiety are public health concerns affecting approximately 1 in 10 women in Singapore, with clear evidence of association with various adverse outcomes in mother and child, including low birthweight, preterm birth and negative impact on infant neurodevelopment, temperament and behaviour. A workgroup was formed to develop recommendations to address the perinatal mental health needs of women with depression and anxiety. The approach was broad-based and aimed to incorporate holistic methods that would be readily applicable to the network of care providers supporting childbearing women. The Grading and Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision framework was employed to draw these guidelines. Workgroup members-comprising experts in the field of perinatal mental health and obstetric medicine-deliberated on the public health needs of the target population, and reviewed literature published from 2001 to 2022 that were relevant to improve the well-being of women with depression and anxiety during the preconception and perinatal periods. A consensus meeting was held involving a wider professional network, including family physicians, paediatricians, psychiatrists, social services and the Health Promotion Board in Singapore. Ten consensus statements were developed, focusing on the overall aim of achieving optimal perinatal mental health for women with depression and anxiety. They relate to awareness and advice on preconception mental health, screening and assessment, optimising care and treatment. Special considerations were recommended for women who suffered severe maternal events, tailoring care for adolescents and women with special needs, and addressing infant mental health needs.

PS-C15-10: ASSOCIATION OF BODY MASS INDEX, WAIST-TO-HEIGHT RATIO AND DURATION OF TYPE 2 DIABETES MELLITUS WITH DIABETIC RETINOPATHY IN WOMEN

Objective: Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM). It is a leading cause of visual impairment and blindness worldwide, reducing the quality of life of patients. Clear evidence of association between anthropometric measurements and DR risk is lacking in Nigerian females with type 2 DM (T2DM). Design and Methods: A cross-sectional study of 57 female participants with physician-diagnosed T2DM with or without systemic hypertension. Anthropometric measurements were taken. Fasting blood samples were drawn for laboratory analysis. All patients underwent dilated fundoscopy by a single Ophthalmologist and diabetic retinopathy was graded based on the worse eye. Results: The mean age of the participants was 60.8 ± 11.0 years with no significant age difference between the DR and Non-DR groups. Of the 57 participants, 36 had varying degrees of DR while 21 had no features of DR. Among the patients with DR, 26 were hypertensive diabetic while 10 were only diabetic. The hypertensive diabetic were older than the diabetic. The mean weight and body mass index (BMI) were higher in the non-DR group compared to the DR group. The DR group had significantly longer disease duration for both diabetes and hypertension. The hypertensive diabetic had significantly higher systolic blood pressure (SBP), pulse pressure (PP), total cholesterol-high density lipid ratio (TC:HDL) and serum triglyceride (TG) than the diabetic. BMI was negatively correlated with presence of DR, while weight, TyG-BMI, weight-height ratio (WHt), hip circumference (HC) and DM duration were positively correlated. BMI, WHt and TyG-BMI were negatively correlated with severity of DR while DM duration showed positive correlation. Linear regression showed that the independent determinant of the presence of DR in hypertensive diabetic were WHt and DM duration, while for severity of DR, DM duration, neutrophil-lymphocyte ratio (NLR) and HbA1c status were predictors. When adjusted for DM duration, presence of DR was predicted by WHt while severity was predicted by BMI. The curve of the receiver operating characteristic was also plotted to establish the relevance of each of the factors predicting DR and their area under the curve (AUC) was compared. The results showed that DM duration, HbA1c status, NLR, HTN duration, BMI, WHt were predictors. Conclusions: BMI, waist-to-height ratio and DM duration and neutrophil-to-lymphocyte ratio are associated with the occurrence and severity of DR in female hypertensive diabetic.

Personal exposure to PM2.5 oxidative potential and its association to birth outcomes.

Prenatal exposure to fine particulate matter (PM2.5) assessed through its mass concentration has been associated with foetal growth restriction in studies based on outdoor levels. Oxidative potential of PM2.5 (OP) is an emerging metric a priori relevant to mechanisms of action of PM on health, with very limited evidence to indicate its role on birth outcomes. We investigated the association of OP with birth outcomes and compared it with that of PM2.5 mass concentration. 405 pregnant women from SEPAGES cohort (Grenoble area) carried PM2.5 personal dosimeters for one or two one-week periods. OP was measured using dithiothreitol (DTT) and ascorbic acid (AA) assays from the collected filters. Associations of each exposure metric with offspring weight, height, and head circumference at birth were estimated adjusting for potential confounders. The correlation between PM2.5 mass concentration and [Formula: see text] was 0.7. An interquartile range increase in .. was associated with reduced weight (adjusted change, -64 g, -166 to -11, p = 0.02) and height (-4 mm, -6 to -1, p = 0.01) at birth. PM2.5 mass concentration showed similar associations with weight (-53 g, -99 to -8, p = 0.02) and height (-2 mm, -5 to 0, p = 0.05). In birth height models mutually adjusted for the two exposure metrics, the association with [Formula: see text] was less attenuated than that with mass concentration, while for weight both effect sizes attenuated similarly. There was no clear evidence of associations with head circumference for any metric, nor for [Formula: see text] with any growth parameter. PM2.5 pregnancy exposure assessed from personal dosimeters was associated with altered foetal growth. Personal OP exposure was associated with foetal growth restrictions, specifically decreased weight and height at birth, possibly to a larger extent than PM2.5 mass concentration alone. These results support OP assessed from DTT as being a health-relevant metric. Larger scale cohort studies are recommended to support our findings.

Dominant Cone Rod Dystrophy, Previously Assigned to a Missense Variant in RIMS1, Is Fully Explained by Co-Inheritance of a Dominant Allele of PROM1.

PurposeAutosomal dominant cone rod dystrophy 7 (CORD7) was initially linked to the gene RIMS1 and reported in a 4-generation British family in 1998. The purpose of this study was to investigate the legitimacy of this association, and to correctly characterize the genetic cause of this condition.MethodsThe allele frequency of RIMS1 c.2459G>A, p.Arg820His, was investigated in the Genomes Aggregation Dataset (gnomAD) datasets and whole genome sequencing (WGS) was performed for 4 members of the CORD7 family with filtering of rare pathogenic variants in a virtual gene panel comprising all genes known to be associated with inherited retinal dystrophy (IRD). Cytogenetic analysis was performed to rule out interchromosomal translocation.Results RIMS1 p.Arg820His has a maximal carrier frequency of >1:5000 in Europeans. A previously well-characterized PROM1 variant: c.1118C>T, p.Arg373Cys, was detected in 9 affected members of the CORD7 family who underwent WGS or direct sequencing. One affected family member is now known to have macular dystrophy in the absence of RIMS1 p.Arg820His. Clinical analysis of affected family members and 27 individuals with retinopathy associated with the same – PROM1 – variant showed consistent phenotypes.ConclusionsThe case for pathogenicity of RIMS1 p.Arg820His is not strong based on its presence on 10 alleles in the gnomAD dataset and absence from additional CORD affected individuals. The finding of a known pathogenic variant in PROM1 correlates well with the phenotypic characteristics of the affected individuals, and is likely to account for the condition. Clear evidence of association between RIMS1 and a retinal dystrophy is yet to be described.

Alcohol consumption patterns and growth differentiation factor 15 among life-time drinkers aged 65+ years in Spain: a cross-sectional study.

To examine the association of alcohol consumption patterns with growth differentiation factor 15 (GDF-15) in older drinkers, separately among individuals with cardiovascular disease (CVD)/diabetes and those without them, as GDF-15 is a strong biomarker of chronic disease burden. Cross-sectional study. Population-based study in Madrid (Spain). A total of 2051 life-time drinkers aged 65+ years included in the Seniors-ENRICA-2 study in 2015-17. Participants' mean age was 71.4years and 55.4% were men. According to their average life-time alcohol intake, participants were classified as occasional (≤ 1.43 g/day), low-risk (men: > 1.43-20 g/day; women: > 1.43-10g/day), moderate-risk (men: > 20-40 g/day; women: > 10-20 g/day) and high-risk drinkers (men: > 40 g/day; women: > 20 g/day; or binge drinkers). We also ascertained wine preference (> 80% of alcohol derived from wine), drinking with meals and adherence to a Mediterranean drinking pattern (MDP) defined as low-risk drinking, wine preference and one of the following: drinking only with meals; higher adherence to the Mediterranean diet; or any of these. In participants without CVD/diabetes, GDF-15 increased by 0.27% [95% confidence interval (CI) = 0.06%, 0.48%] per 1g/day increment in alcohol among high-risk drinkers, but there was no clear evidence of association in those with lower intakes or in the overall group, or across categories of alcohol consumption status. Conversely, among those with CVD/diabetes, GDF-15 rose by 0.19% (95% CI = 0.05%, 0.33%) per 1g/day increment in the overall group and GDF-15 was 26.89% (95% CI = 12.93%, 42.58%) higher in high-risk versus low-risk drinkers. Drinking with meals did not appear to be related to GDF-15, but among those without CVD/diabetes, wine preference and adherence to the MDP were associated with lower GDF-15, especially when combined with high adherence to the Mediterranean diet. Among older life-time drinkers in Madrid, Spain, high-risk drinking was positively associated with growth differentiation factor 15 (a biomarker of chronic disease burden). There was inconclusive evidence of a beneficial association for low-risk consumption.

Endogenous Circulating Sex Hormone Concentrations and Colon Cancer Risk in Postmenopausal Women: A Prospective Study and Meta-Analysis.

BackgroundObservational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results.MethodsWe investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone–binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided.ResultsIn the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log2 1-unit increment = 1.17 [95% confidence interval = 1.00 to 1.38]; odds ratioquartile4-quartile1 = 1.33 [95% confidence interval = 0.89 to 1.97], Ptrend = .20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk.ConclusionOur observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women.

The association between COVID-19 vaccination and Bell's palsy

In the past 100 days, more than 3 billion doses of SARS-CoV-2 vaccines have been administered globally.1 With 20 vaccines currently authorised in at least one country and 108 under clinical development as of July 20, 2021,2 there is ongoing public concern regarding the possible adverse effects of SARS-CoV-2 immunisation. An adverse event reported in the product information of two vaccines developed with a novel mRNA technology is Bell's palsy, a form of acute facial nerve paralysis.3 So far there has been no clear evidence of association between COVID-19 vaccination and facial paralysis.

Association of Prenatal Alcohol Exposure and Offspring Depression: A Negative Control Analysis of Maternal and Partner Consumption.

BackgroundPrevious research has suggested that intrauterine alcohol exposure is associated with a variety of adverse outcomes in offspring. However, few studies have investigated its association with offspring internalizing disorders in late adolescence.MethodsUsing data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the associations of maternal drinking in pregnancy with offspring depression at age 18 and 24 (n = 13,480). We also examined partner drinking as a negative control for intrauterine exposure for comparison.ResultsOffspring of mothers that consumed any alcohol at 18 weeks gestation were at increased risk of having a diagnosis of depression (fully adjusted model: OR 1.17, 95% CI 1.02 to 1.34), but there was no clear evidence of association between partners’ alcohol consumption at 18 weeks gestation during pregnancy and increased risk of offspring depression (fully adjusted model: OR 0.87, 95% CI 0.74 to 1.01). Postestimation tests found a positive difference between the association of maternal and partner alcohol use on offspring depression, showing a stronger association for maternal compared with partner alcohol use (OR 1.41, CI 1.07 to 1.84).ConclusionsMaternal drinking in pregnancy was associated with increased risk of offspring depression at age 18. Residual confounding may explain this association, but the negative control comparison of paternal drinking provides some evidence that it may be causal, and this warrants further investigation.

Hip morphology and its relationship with hip strength, mobility and lower limb biomechanics: a systematic review in adults

Abstract This systematic review (PROSPERO registration n.43640) aimed to summarise and determine the quality of evidence relating hip bone morphology to (i) hip strength, (ii) mobility and (iii) lower limb biomechanics during functional activities. A standardized search on MEDLINE/PubMed, Web of Science, ScienceDirect and Scopus resulted in 17 papers that met inclusion criteria: i) original investigations with a minimal sample of n=10, ii) studies on humans and iii) presence of at least one quantitative hip morphological parameter and one hip functional (i.e. strength and mobility) and/or one lower limb biomechanical parameter. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool with adaptations. Sixteen out of the 17 included studies showed high risk of bias. We observed that primary evidence pointed to the influence of hip morphology on hip mobility in the transverse plane. Specifically, positive correlations between femoral anteversion angle and range of internal hip rotation in physical examination were observed. Regarding biomechanical parameters, no clear evidence of association between hip morphology, and kinematic and kinetic parameters were found. Our results point to a field that is currently under explored and future studies with low risk of bias addressing these relationships are required.

Cellular, humoral and molecular responses in rainbow trout (Oncorhynchus mykiss) exposed to a herbicide and subsequently infected with infectious hematopoietic necrosis virus

Aquatic ecosystems are now chronically polluted by a cocktail of many chemical substances. There is now clear evidence of associations between exposure to pollutants and greater susceptibility to pathogens. The aim of the present study was to characterize the defense capacities of rainbow trout (Oncorhynchus mykiss), chronically exposed to pendimethalin (PD), to subsequent experimental challenge with the infectious hematopoietic necrosis virus (IHNV). Immunological responses were examined at different organizational levels, from individuals to gene expression. No negative effects of PD were noted on the Fulton index nor on the liver or spleen somatic indices (LSI; SSI) before viral infection, but the infectious stress seems to generate a weak but significant decrease in Fulton and LSI values, which could be associated with consumption of energy reserves. During the viral challenges, the distribution of cumulative mortality was slightly different between infected groups. The impact of the virus on fish previously contaminated by PD started earlier and lasted longer than controls. The proportion of seropositive fish was lower in the fish group exposed to PD than in the control group, with similar quantities of anti-IHNV antibodies secreted in positive fish, regardless of the treatment. While no significant differences in C3-1 expression levels were detected throughout the experiment, TNF1&2, TLR3, Il-1β and IFN expression levels were increased in all infected fish, but the difference was more significant in fish groups previously exposed to herbicide. On the other hand, β-def expression was decreased in the pendimethalin-IHNV group compared to that in fish only infected by the virus (control-IHNV group).

CORRELATION OF AGGREGATED BETA AMYLOID LEVEL IN PLASMA WITH MOCA AND MMSE AMONG TYPE 2 DIABETIC PATIENTS WITH DEMENTIA

Type 2 Diabetes Mellitus (DM) as a risk factor for Alzheimer's disease (AD) and decline in cognitive functions have been studied in recent years; however, no clear evidence of association has been found yet. As potential biomarker for AD, aggregated beta amyloid level in plasma is likewise under study by some medical researchers. We examined the correlation between plasma beta amyloid levels and cognitive functions of Type 2 DM patients with Dementia as indicated by their neurocognitive assessment scores with the end in view of finding a less invasive early detection of AD among diabetic patients. In this Cross Sectional study, 100 Type 2 DM patients with dementia (39% male, 68.71 ± 6.9 years) underwent plain cranial CT scan, plasma beta amyloid, Mini Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA) tests. Patients were categorized as having Vascular or Non Vascular Dementia with the use of NINDS-AIREN Criteria for Vascular Dementia. Elevated aggregated beta amyloid level in plasma (≥ 1.1 pg/ml) was used as biomarker for AD. Among Type 2 DM patients with dementia, there was an increased prevalence of AD (46.7%) as shown by the elevated beta amyloid level independent of Vascular Dementia. The prevalence of vascular dementia was 6%. Among patients with Non Vascular Dementia, majority (51.3%) had elevated beta amyloid. There was no significant correlation between MMSE score and beta amyloid (r= - 0.0192, p = 0.8557), while no significant correlation between MoCA score and beta amyloid (r=0.0939, p=0.3731) among Type 2 DM patients with Dementia. The results did not show significant correlation between both MMSE (r=−0.0664, p=0.6725) and MoCA scores (r=- 0.0877, p=0.5759) with beta amyloid level among those patients with AD. Using the beta amyloid as a biomarker, the study suggests a link between AD and Type 2 DM; however, we recommend that further researches be conducted to ascertain the use of aggregated beta amyloid level in plasma as a less invasive screening routine for AD among Type 2 DM patients with dementia.

Rescue medication use as a patient-reported outcome in COPD: a systematic review and regression analysis

BackgroundReducing rescue medication use is a guideline-defined goal of asthma treatment, however, little is known about the validity of rescue medicine use as a marker of symptoms in chronic obstructive pulmonary disease (COPD). To improve patient outcomes, greater insight is needed into the relationship between rescue medication use and alternative COPD outcomes.MethodsA systematic search of electronic databases (Embase®, MEDLINE® and Cochrane CENTRAL) was conducted from database start to 26 May, 2015. Studies of bronchodilator therapy with a duration of ≥24 weeks were included if they reported either mean change from baseline (CFB) in rescue medication use in puffs/day or % rescue-free days (%RFD), and at least one other COPD endpoint. Correlation and meta-regression analyses were undertaken to test the association between rescue medication use and other COPD outcomes using weighted means (weights proportional to the sample size of the treatment group) and unweighted means (equal weight for each treatment group). Each association was assessed at 6 months and study end.ResultsForty-six studies involving 46,531 patients provided mean data from 145 treatment groups for evaluation. Changes in both measures of rescue medication use were correlated with changes in trough forced expiratory volume in one second ([FEV1]; Pearson correlation coefficients |r| ≥ 0.63; p < 0.0001) and with St George’s Respiratory Questionnaire (SGRQ) score (|r| ≥ 0.70; p < 0.0001) at study end. Change in rescue medication use in puffs/day during the study correlated with annualized rates of moderate/severe exacerbations at 6 months and study end (both r = 0.66; p ≤ 0.0028). CFB in puffs/day was not well correlated with Transition Dyspnoea Index (TDI), but %RFD did correlate with TDI score at 6 months and study end (both r = 0.69; p < 0.0001). The values for CFB in puffs/day corresponding to the proposed minimal clinically important differences for trough FEV1 and SGRQ score were -1.3 and -0.6 puffs/day, respectively. A -1.0 puffs/day CFB in rescue use corresponded to a change of 0.26 events/patient-year in moderate/severe exacerbations.ConclusionThis analysis provides clear evidence of associations at a patient group level between rescue medication use and other clinically important COPD outcomes.

Substance use, criminal behaviour and psychiatric symptoms following childhood traumatic brain injury: findings from the ALSPAC cohort

Recent research suggests a link between traumatic brain injury (TBI) in youth and later risk behaviour. We explored the association between mild TBI and psychiatric symptoms, substance use and criminal behaviour using data from a longitudinal birth cohort. Participants with mild TBI (n = 800), orthopaedic injuries (n = 2305) and no injuries (n = 8307) were identified from self and parent reports up to age 16 years. Self-report measures of substance use (alcohol, tobacco and cannabis) and criminal behaviours, and parent-reported psychiatric symptoms were collected at age 17 years. Analyses were adjusted for pre-birth and early childhood confounders. Participants with a TBI showed increased odds of hazardous alcohol use compared to those with no injury and those with an orthopaedic injury. Relative to those with no injury, participants with a TBI showed increased odds of problematic use of tobacco and cannabis, being in trouble with the police and having more parent-reported conduct problems. Sustaining either a TBI or an orthopaedic injury increased the odds of offending behaviour compared to having no injuries. There was no clear evidence of association between orthopaedic injury and the other risk outcomes. The increased odds of risk behaviour associated with TBI relative to no injury replicated previous research. However, the inclusion of a non-brain-related injury group adds evidence for a possible causal pathway between mild TBI in youth and later hazardous alcohol use only. This highlights the importance of including an additional negative control injury group in mild TBI research.

Jobs Off the Farm: Wealth, Human Capital, and Social Group in Rural Eastern India

ABSTRACTThis study examines the effects of wealth, human capital, and social group on the occupational choice and income of farm households, to gain an understanding of the mechanism underlying the recently increasing income diversification in rural eastern India. The results show that wealth and human capital have a positive impact on the choice of high-return jobs, and low caste workers are more likely to work in casual, low-paying jobs, partly due to their dependence on personal networks in finding jobs. Notably, no clear evidence of association between social group and income is found.

Childhood pneumonia and crowding, bed-sharing and nutrition: a case-control study from The Gambia.

Greater Banjul and Upper River Regions, The Gambia. To investigate tractable social, environmental and nutritional risk factors for childhood pneumonia. A case-control study examining the association of crowding, household air pollution (HAP) and nutritional factors with pneumonia was undertaken in children aged 2-59 months: 458 children with severe pneumonia, defined according to the modified WHO criteria, were compared with 322 children with non-severe pneumonia, and these groups were compared to 801 neighbourhood controls. Controls were matched by age, sex, area and season. Strong evidence was found of an association between bed-sharing with someone with a cough and severe pneumonia (adjusted OR [aOR] 5.1, 95%CI 3.2-8.2, P < 0.001) and non-severe pneumonia (aOR 7.3, 95%CI 4.1-13.1, P < 0.001), with 18% of severe cases estimated to be attributable to this risk factor. Malnutrition and pneumonia had clear evidence of association, which was strongest between severe malnutrition and severe pneumonia (aOR 8.7, 95%CI 4.2-17.8, P < 0.001). No association was found between pneumonia and individual carbon monoxide exposure as a measure of HAP. Bed-sharing with someone with a cough is an important risk factor for severe pneumonia, and potentially tractable to intervention, while malnutrition remains an important tractable determinant.

Current relevance of hypoxia in head and neck cancer.

Head and Neck cancer (HNC) is a complex mix of cancers and one of the more common cancers with a relatively poor prognosis. One of the factors that may assist us in predicting survival and allow us to adjust our treatment strategies is the presence of tumor hypoxia. In this overview we aim to evaluate the current evidence and potential clinical relevance of tumor hypoxia in head and neck cancer according to an extensive search of current literature.An abundance of evidence and often contradictory evidence is found in the literature. Even the contradictory evidence and comparisons are difficult to judge as criteria and methodologies differ greatly, furthermore few prospective observational studies exist for verification of the pre-clinical studies. Despite these discrepancies there is clear evidence of associations between prognosis and poor tumor oxygenation biomarkers such as HIF-1α, GLUT-1 and lactate, though these associations are not exclusive. The use of genetic markers is expanding and will probably lead to significantly more and complex evidence. The lack of oxygenation in head and neck tumors is of paramount importance for the prediction of treatment outcomes and prognosis. Despite the wide array of conflicting evidence, the drive towards non-invasive prediction of tumor hypoxia should continue.

P40 Penile squamous cell carcinoma in a patient treated with etanercept for psoriasis

<h3>Background</h3> Differential diagnosis of genital ulceration includes benign skin disease, infection and malignancy. An increase in sexually transmitted infections in older patients has been seen. Biologics inhibit immune system components that fuel inflammation. They are used to treat refractory chronic inflammatory conditions, including psoriasis. Concerns have been raised regarding an association between use of biologic treatments such as Etanercept and squamous cell carcinoma (SCC). We present a case of a patient taking Etanercept for psoriasis, who developed penile SCC. <h3>Case</h3> A 57 years old man, listed by Urology for biopsy of a penile ulcer of 8 week duration, was referred to Genitourinary Medicine to exclude infective causes. He had a long history of severe psoriasis which had been treated with Etanercept for more than 7 years. He had had sex with one casual female partner 3 months prior to presentation. A deep, clean, indurated ulcer was seen on the corona. Regional nodes were impalpable. Tests were negative for syphilis, HIV and herpes simplex. The biopsy showed invasive SCC. He subsequently underwent a partial penectomy. <h3>Discussion</h3> Penile cancer is uncommon in the United Kingdom. Embarrassment may cause delay in presentation. Penile SCC has been reported in patients on Etanercept. Clear evidence of association is lacking. Patients on biologics should be advised to carefully examine their skin including the genitals, reporting any skin changes promptly. Increasing awareness among patients and physicians about this possible association could prevent delay in diagnosis. The National Biologic Registers will reveal more definite evidence over time.

Moving beyond classical markers of water quality: detection of enteric viruses and genotoxicity in water of the Sinos River.

It is well recognized that the classical biological and chemical markers of environmental pollution do not necessarily indicate the presence or absence of emerging threats to public health, such as waterborne viruses and genotoxicants. The purpose of this preliminary study was to evaluate the presence of material of enteroviruses (EV), rotavirus (RV) and adenovirus (AdV) and genotoxicity in water samples from points of routine monitoring of water quality in the main course of the Sinos River. The points are classified into different levels of pollution in accordance to the Brazilian federal regulations. Viral genomes from EV, AdV were detected in two of the 4 collection points regardless of the level of urbanisation of the surrounding areas. In contrast, genotoxicity was not observed in piava (Leporinus obtusidens) fingerlings cultivated on these same water samples. Results were compared with classical physical, chemical and microbiological parameters. There was no clear evidence of association between any of the classical markers and the presence of viral genomes in the water samples tested.

399 Exposure to phthalates, perfluorinated compounds and organochlorines and pregnancy outcomes in women from Greenland, Poland and Ukraine

ObjectivesEvidence for effects of environmental contaminants on pregnancy outcomes remains inconclusive. We investigated the associations between multiple, correlated exposures and related pregnancy outcomes using Bayesian, multivariate dimension reduction, and shrinkage...