Investigating local relationships between trace elements in soils and cancer data

Medical geology research has recognised a number of potentially toxic elements (PTEs), such as arsenic, cobalt, chromium, copper, nickel, lead, vanadium, uranium and zinc, known to influence human disease by their respective deficiency or toxicity. As the impact of infectious diseases has decreased and the population ages, so cancer has become the most common cause of death in developed countries including Northern Ireland. This research explores the relationship between environmental exposure to potentially toxic elements in soil and cancer disease data across Northern Ireland. The incidence of twelve different cancer types (lung, stomach, leukaemia, oesophagus, colorectal, bladder, kidney, breast, mesothelioma, melanoma and non melanoma(NM) both basal and squamous, were examined in the form of twenty-five coded datasets comprising aggregates over the 12 year period from 1993 to 2006. A local modelling technique,geographically weighted regression (GWR) is usedto explore the relationship between environmental exposure and cancer disease data. The results show comparisons of the geographical incidence of certain cancers (stomach and NM squamous skin cancer) in relation to concentrations of certain PTEs (arsenic levels in soils and radon were identified). Findings from the research have implications for regional human health risk assessments.

Role of histone deacetylases in vascular cell homeostasis and arteriosclerosis

Histone deacetylases (HDACs) are a family of enzymes that remove acetyl groups from lysine residues of histone proteins, a modification that results in epigenetic modulation of gene expression. Although originally shown to be involved in cancer and neurological disease, HDACs are also found to play crucial roles in arteriosclerosis. This review summarizes the effects of HDACs and HDAC inhibitors on proliferation, migration, and apoptosis of endothelial and smooth muscle cells. In addition, an updated discussion of HDACs' recently discovered effects on stem cell differentiation and atherosclerosis is provided. Overall, HDACs appear to be promising therapeutic targets for the treatment of arteriosclerosis and other cardiovascular diseases.

Predictors of PTSD Symptoms in Response to Psychosis and Psychiatric Admission

The experiences of psychosis and psychiatric admission have the potential to act as events precipitating posttraumatic stress disorder (PTSD) symptoms. Known risk factors for the development of PTSD symptoms in adults were identified. These included childhood trauma, current psychiatric symptoms, perceived coercion, and relationships with mental health service providers. These factors were analyzed to determine if they were important in the development of PTSD symptoms in response to psychosis and admission. We used a cross-sectional design with a sample of 47 participants recruited from a service in Northern Ireland who had experienced psychosis and been discharged from inpatient treatment within 12 months of data collection. The main outcome measure was the impact of events scale-revised. Data was subject to correlation analyses. A cut-off point of r = +/- 0.25 was used to select variables for inclusion in hierarchical regression analyses. Forty-five percent and 31% of the sample had moderate to severe PTSD symptoms related to psychosis and admission, respectively. The majority of participants identified positive symptoms and the first admission as the most distressing aspects of psychosis and admission. Childhood sexual and physical traumas were significant predictors of some PTSD symptoms. Strong association was found between current affective symptoms and PTSD symptoms. A reduced sense of availability of mental health service providers was also associated with PTSD symptoms and depression. Awareness of risk factors for the development of PTSD symptoms in response to admission and psychosis raises important issues for services and has implications for interventions provided.

Transpupillary thermotherapy for choroidal melanoma:Tumor control and visual results in 100 consecutive cases

Objective: The authors evaluated the results of primary transpupillary thermotherapy for choroidal melanoma in 100 cases. Design: Prospective nonrandomized analysis of treatment method. Participants: One hundred patients with choroidal melanoma were studied. Main Outcome Measures: Tumor response, ocular side effects, and visual results. Results: Of 100 consecutive patients with choroidal melanoma treated with transpupillary thermotherapy, the mean tumor basal diameter was 7.1 mm and tumor thickness was 2.8 mm. The tumor margin touched the optic disc in 34 eyes (34%) and was beneath the fovea in 42 eyes (42%). Documented growth was present in 64 eyes (64%), and known clinical risks for growth were present in all of the remaining 36 eyes (36%), with an average of 4 of 5 statistical risk factors for growth per tumor. After a mean of three treatment sessions and 14 months of follow-up, the mean tumor thickness was reduced to 1.4 mm. Treatment was successful in 94 eyes (94%) and failed in 6 eyes (6%). Three patients with amelanotic tumors showed no initial response to thermotherapy, but subsequent intravenous indocyanine green administration during thermotherapy resulted in improved heat absorption and tumor regression to a flat scar. The six eyes classified as treatment failures included four eyes with tumors that showed partial or no response to thermotherapy, thus requiring plaque radiotherapy or enucleation, and two eyes with recurrence, subsequently controlled with additional thermotherapy. After treatment, the visual acuity was the same (within 1 line) or better than the pretreatment visual acuity in 58 eyes (58%) and worse in 42 eyes (42%). The main reasons for poorer vision included treatment through the foveola for subfoveal tumor (25 eyes), retinal traction (10 eyes), retinal vascular obstruction (5 eyes), optic disc edema (1 eye), and unrelated ocular ischemia (1 eye). Temporal location (versus nasal and superior, P = 0.02) and greater distance from the optic disc (P = 0.04) were risks for retinal traction. Conclusions: Transpupillary thermotherapy may be an effective treatment for small posterior choroidal melanoma, especially those near the optic disc and fovea. Despite satisfactory local tumor control, ocular side effects can result in decreased vision. Longer follow- up will be necessary to assess the impact of thermotherapy on ultimate local tumor control and metastatic disease.

Biomarkers in diabetes:hemoglobin A1c, vascular and tissue markers

Biomarkers are conventionally defined as "biological molecules that represent health and disease states." They typically are measured in readily available body fluids (blood or urine), lie outside the causal pathway, are able to detect subclinical disease, and are used to monitor clinical and subclinical disease burden and response to treatments. Biomarkers can be "direct" endpoints of the disease itself, or "indirect" or surrogate endpoints. New technologies (such as metabolomics, proteomics, genomics) bring a wealth of opportunity to develop new biomarkers. Other new technologies enable the development of nonmolecular, functional, or biophysical tissue-based biomarkers. Diabetes mellitus is a complex disease affecting almost every tissue and organ system, with metabolic ramifications extending far beyond impaired glucose metabolism. Biomarkers may reflect the presence and severity of hyperglycemia (ie, diabetes itself) or the presence and severity of the vascular complications of diabetes. Illustrative examples are considered in this brief review. In blood, hemoglobin A1c (HbA1c) may be considered as a biomarker for the presence and severity of hyperglycemia, implying diabetes or prediabetes, or, over time, as a "biomarker for a risk factor," ie, hyperglycemia as a risk factor for diabetic retinopathy, nephropathy, and other vascular complications of diabetes. In tissues, glycation and oxidative stress resulting from hyperglycemia and dyslipidemia lead to widespread modification of biomolecules by advanced glycation end products (AGEs). Some of these altered species may serve as biomarkers, whereas others may lie in the causal pathway for vascular damage. New noninvasive technologies can detect tissue damage mediated by AGE formation: these include indirect measures such as pulse wave analysis (a marker of vascular dysfunction) and more direct markers such as skin autofluorescence (a marker of long-term accumulation of AGEs). In the future, we can be optimistic that new blood and tissue-based biomarkers will enable the detection, prevention, and treatment of diabetes and its complications long before overt disease develops.

A lethal tetrad in diabetes:hyperglycemia, dyslipidemia, oxidative stress, and endothelial dysfunction

This paper addresses the consequences of diabetes and obesity, diseases that have become epidemic in our society, particularly in the past 20 years. Specifically, it summarizes current knowledge about some of the risk factors and mechanisms for the vascular complications of diabetes. These complications can be broadly divided into microvascular disease, such as diabetic retinopathy and diabetic nephropathy, and macrovascular disease, such as accelerated atherosclerosis, and they are the main cause for morbidity and premature mortality among diabetic patients. The roles of hyperglycemia, dyslipidemia and dyslipoproteinemia, oxidative stress, and endothelial dysfunction will be considered. Finally, the "treatment gap" will be addressed. This gap refers to our failure to achieve currently accepted goals to reduce established risk factors for complications in the clinical management of diabetic patients.

Lipoprotein glycation and its metabolic consequences

Glycation of lipoproteins is implicated in the development of the macro- and microvascular complications of diabetes, atherosclerosis in general, and other disease processes including aging. Enhanced glycation may have direct effects, and may also amplify the effects of oxidative stress on lipoproteins. Most studies have examined the effects of glycation of LDL, particularly with respect to its atherogenicity. Other lipoproteins are more difficult to study because their several apolipoproteins, being of varying age, are not uniformly exposed to glucose. Inhibition of the combined stresses of glycation and oxidation towards lipoproteins may have beneficial effects on health.

α-Tocopherol induces proatherogenic changes to HDL2 & HDL3: An in vitro and ex vivo investigation

Introduction: High density lipoproteins (HDL) have considerable potential for improving cardiovascular health. Additionally, epidemiological studies have identified an inverse relationship between a-tocopherol intake and cardiovascular disease, which has not been translated in randomised controlled trials. Objectives: This study assessed if increased α-tocopherol within HDL2 and HDL3 (HDL2&3) influenced their antiatherogenic potential. In the first of two in vitro investigations, the oxidation potential of HDL2&3 was assessed when α-tocopherol was added following their isolation. In the second, their oxidation potential was assessed when HDL2&3 were isolated from serum pre-incubated with α-tocopherol. Additionally, a 6-week placebo-controlled intervention with α-tocopherol assessed if α-tocopherol influenced the oxidation potential and activities of HDL2&3-associated enzymes, paraoxonase-1 (PON-1) and lecithin cholesteryl acyltransferase (LCAT). Results: Conflicting results arose from the in vitro investigations, whereby increasing concentrations of α-tocopherol protected HDL2&3 against oxidation in the post-incubated HDL2&3, and promoted HDL2&3-oxidation when they were isolated from serum pre-incubated with α-tocopherol. Following the 6-week placebo-controlled investigation, α-tocopherol increased in HDL2&3, while HDL2&3 became more susceptible to oxidation, additionally the activities of HDL2&3-PON-1 and HDL2-LCAT decreased. Conclusion: These results have shown for the first time that α-tocopherol induces changes to HDL2&3, which could contribute to the pathophysiology of cardiovascular disease.

Pioglitazone protects HDL(2&3) against oxidation in overweight and obese men

The worldwide epidemic of obesity is a major public health concern and is persuasively linked to the rising prevalence of diabetes and cardiovascular disease. Obesity is often associated with an abnormal lipoprotein profile, which may be partly negated by pioglitazone intervention, as this can influence the composition and oxidation characteristics of low-density lipoprotein (LDL). However, as pioglitazone's impact on these parameters within high-density lipoprotein (HDL), specifically HDL(2&3), is absent from the literature, this study was performed to address this shortcoming.

Validation study to compare effects of processing protocols on measured Nε_(carboxymethyl)lysine and Nε_(carboxyethyl)lysine in blood.

Epidemiological studies show that elevated plasma levels of advanced glycation end products (AGEs) are associated with diabetes, kidney disease, and heart disease. Thus AGEs have been used as disease progression markers. However, the effects of variations in biological sample processing procedures on the level of AGEs in plasma/serum samples have not been investigated. The objective of this investigation was to assess the effect of variations in blood sample collection on measured Ne_(carboxy-methyl)lysine (CML), the best characterised AGE, and its homolog, Ne_(carboxyethyl)lysine (CEL). The investigation examined the effect on CML and CEL of different blood collection tubes, inclusion of a stabilising cocktail, effect of freeze thaw cycles, different storage times and temperatures, and effects of delaying centrifugation on a pooled sample from healthy volunteers. CML and CEL were measured in extracted samples by ultra_performance liquid chromatography-tandem mass spectrometry. Median CML and CEL ranged from 0.132 to 0.140 mM/M lys and from 0.053 to 0.060 mM/M lys, respectively. No significant difference was shown CML or CEL in plasma/serum samples. Therefore samples collected as part of epidemiological studies that do not undergo specific sample treatment at collection are suitable for measuring CML and CEL.

Shame, intimacy and self-definition: An assessment of the emotional foundation and intimate relationship consequences of an introjective personality orientation.

The current study sought to elaborate and test a theoretical proposition that introjective personality functioning, which has been implicated in various psychological difficulties (e.g., self-critical depression, obsessive-compulsive disorder), has an emotional foundation in the self-conscious emotion of shame and is supported by dissociation. Moreover, introjective functioning was predicted to be associated with reduced interpersonal intimacy. To test the model, a Web-based survey design using path analysis was used. Three hundred and fifteen university students were assessed with measures of self-conscious emotions (i.e., shame, guilt, and embarrassment), introjective (self-definition) and anaclitic (relational) personality style, pathological dissociation, and interpersonal intimacy. Introjective personality was found to be associated with increased shame and reduced interpersonal intimacy. However, the path between pathological dissociation and introjective functioning was not significant. The results are discussed with reference to the moderating influence of introjective functioning between shame and reduced interpersonal intimacy.

Why are you tall while others are short? Agricultural production and other proximate determinants of global heights

We analyze the proximate determinants of the biological standard of living from a global perspective, namely high-quality nutrition and the disease environment during the nineteenth and twentieth centuries. Until the mid-twentieth century, the local availability of cattle, meat, and milk per capita and the local disease environment mainly determined the stature of the population – and, by implication, how long they lived and how healthy they were. During the late twentieth century, the trade of agricultural products and health-promoting technologies increased in relative importance; hence, the local availabilities became less decisive in explaining height differences.

Validation study to compare effects of processing protocols on measured N (ε)-(carboxymethyl)lysine and N (ε)-(carboxyethyl)lysine in blood

Epidemiological studies show that elevated plasma levels of advanced glycation end products (AGEs) are associated with diabetes, kidney disease, and heart disease. Thus AGEs have been used as disease progression markers. However, the effects of variations in biological sample processing procedures on the level of AGEs in plasma/serum samples have not been investigated. The objective of this investigation was to assess the effect of variations in blood sample collection on measured N (ε)-(carboxymethyl)lysine (CML), the best characterised AGE, and its homolog, N (ε)-(carboxyethyl)lysine (CEL). The investigation examined the effect on CML and CEL of different blood collection tubes, inclusion of a stabilising cocktail, effect of freeze thaw cycles, different storage times and temperatures, and effects of delaying centrifugation on a pooled sample from healthy volunteers. CML and CEL were measured in extracted samples by ultra-performance liquid chromatography-tandem mass spectrometry. Median CML and CEL ranged from 0.132 to 0.140 mM/M lys and from 0.053 to 0.060 mM/M lys, respectively. No significant difference was shown CML or CEL in plasma/serum samples. Therefore samples collected as part of epidemiological studies that do not undergo specific sample treatment at collection are suitable for measuring CML and CEL.

Comparison of 5% versus 15% sucrose intakes as part of a eucaloric diet in overweight and obese subjects:effects on insulin sensitivity, glucose metabolism, vascular compliance, body composition and lipid profile. A randomised controlled trial

AIMS: The effect of dietary sucrose on insulin resistance and the pathogenesis of diabetes and vascular disease is unclear. We assessed the effect of 5% versus 15% sucrose intakes as part of a weight maintaining, eucaloric diet in overweight/obese subjects.

METHODS: Thirteen subjects took part in a randomised controlled crossover study (M:F 9:4, median age 46 years, range 37-56 years, BMI 31.7±0.9 kg/m(2)). Subjects completed two 6 week dietary periods separated by 4 week washout. Diets were designed to have identical macronutrient profile. Insulin action was assessed using a two-step hyperinsulinaemic euglycaemic clamp; glucose tolerance, vascular compliance, body composition and lipid profiles were also assessed.

RESULTS: There was no change in weight or body composition between diets. There was no difference in peripheral glucose utilization or suppression of endogenous glucose production. Fasting glucose was significantly lower after the 5% diet. There was no demonstrated effect on lipid profiles, blood pressure or vascular compliance.

CONCLUSION: A low-sucrose diet had no beneficial effect on insulin resistance as measured by the euglycaemic glucose clamp. However, reductions in fasting glucose, one hour insulin and insulin area under the curve with the low sucrose diet on glucose tolerance testing may indicate a beneficial effect and further work is required to determine if this is the case. Clinical Trial Registration number ISRCTN50808730.