Sense-antisense gene-pairs in breast cancer and associated pathological pathways

More than 30% of human protein-coding genes form hereditary complex genome architectures composed of sense-antisense (SA) gene pairs (SAGPs) transcribing their RNAs from both strands of a given locus. Such architectures represent important novel components of genome complexity contributing to gene expression deregulation in cancer cells. Therefore, the architectures might be involved in cancer pathways and, in turn, be used for novel drug targets discovery. However, the global roles of SAGPs in cancer pathways has not been studied. Here we investigated SAGPs associated with breast cancer (BC)-related pathways using systems biology, prognostic survival and experimental methods. Gene expression analysis identified 73 BC-relevant SAGPs that are highly correlated in BC. Survival modelling and metadata analysis of the 1161 BC patients allowed us to develop a novel patient prognostic grouping method selecting the 12 survival-significant SAGPs. The qRT-PCR-validated 12-SAGP prognostic signature reproducibly stratified BC patients into low- and high-risk prognostic subgroups. The 1381 SAGP-defined differentially expressed genes common across three studied cohorts were identified. The functional enrichment analysis of these genes revealed the GABPA gene network, including BC-relevant SAGPs, specific gene sets involved in cell cycle, spliceosomal and proteasomal pathways. The co-regulatory function of GABPA in BC cells was supported using siRNA knockdown studies. Thus, we demonstrated SAGPs as the synergistically functional genome architectures interconnected with cancer-related pathways and associated with BC patient clinical outcomes. Taken together, SAGPs represent an important component of genome complexity which can be used to identify novel aspects of coordinated pathological gene networks in cancers.     

Chertsey Outcome Score for Trauma: Development and validation of a newunifying patient reported outcome measure for orthopaedic trauma

Purpose: Lately there is an increasing tendency of using Patient Reported Outcome Measures (PROMs) as a final indicator of the outcome of many surgical treatments in orthopaedics and in other medical specialties. Currently there are many outcome scores in orthopaedics and most of them are site specific. In the contrary there is a lack of trauma specific outcome scores. Methods: We have designed a new PROM especially for orthopaedic trauma patients, in order to measure in what extent the patients manage to return to their pre-injury state. This score uses as baseline the preinjury status of the patient and has the aim to determine the percentage of rehabilitation after treatment for any injury. Results: A total of 60 Chertsey Outcome Score for Trauma (COST) questionnaires were gathered in our outpatients department. The participants were 57% male (aged 46.81 years ± 18.5 years) and the questionnaires collected at mean 10 months post-injury. A Cronbach''s Alpha value of 0.89 was identified for the whole construct. The three dimensions of the scale had good internal consistency as well (Cronbach''s Alpha test values 0.74, 0.84 and 0.81 for symptoms, function and mental status respectively). Strong/moderate correlation (Spearman''s Rho test 0.43e0.65) was observed between the respective physical/mental dimensions of the COST and SF-12v2 questionnaires. Conclusion: There is a need among the orthopaedic trauma society for a specific PROM of trauma. COST is a useful and easy to use tool for every trauma surgeon.     

Pharmacokinetic and pharmacodynamic profiles of a novel phospholipid-aspirin complex liquid formulation and low dose enteric-coated aspirin: results from a prospective,randomized, crossover study

Journal of Thrombosis and Thrombolysis - Low dose enteric-coated aspirin (EC-ASA) is routinely used for secondary cardiovascular event prevention. However, absorption of EC tablets is poor, which...     

Endoscopic management of gastrocutaneous fistula after bariatric surgery by using a fibrin sealant

BACKGROUND: Gastrocutaneous fistula is an uncommon and difficult to treat complication that occurs in 0.5% to 3.9% of patients who undergo gastric surgery. Sepsis usually follows, and, when it is not managed effectively, the associated mortality rate can be as high as 85%. A fibrin sealant was used to endoscopically manage gastrocutaneous fistulas that developed in 3 morbidly obese patients after bariatric surgery. METHODS: Two of 14 (14.29%) patients who underwent vertical gastroplasty (MacLean procedure) developed a non-healing gastrocutaneous fistula. In addition, one of 24 (4.17%) patients who had a biliopancreatic diversion with preservation of pylorus developed a gastrocutaneous fistula. Endoscopic application of a fibrin sealant was performed under direct vision via a double-lumen catheter passed through a forward-viewing endoscope. OBSERVATIONS: Treatment was successful in all patients after one or more endoscopic sessions in which the fibrin sealant was applied; no evidence of fistula was found at follow-up endoscopy. CONCLUSIONS: Endoscopic closure of gastrocutaneous fistula with human fibrin tissue sealant is simple, safe, and effective, and, in some cases, can be life-saving. Endoscopic application of fibrin sealant should be considered a therapeutic option for treatment of gastrocutaneous fistula that develops after bariatric surgery.     

Evaluation of the genetic damage to workers in a Greek shipyard

Shipyards are industrial areas where workers are likely exposed to environmental pollutants such as welding fumes, fine organic solvent and dye dust, that render the occupational environment a high risk one. Assessing the risk that workers are exposed to is a high critical factor in improving their working conditions. The present study aims to investigate the potential genetic damage to workers exposed to a harsh environment in a Greek shipyard. It is focused on assessing the percentage of induced micronuclei, as well as on changes in the various cell types of shipyard workers’ oral mucosa epithelium by implementing the buccal micronucleus cytome assay. Exposed workers appeared with statistically significant induced micronuclei as compared to office employees. Statistically, significant cell lesions were detected and are related to workers’ exposure to environmental conditions. The workers’ smoking habit contributed as well to the observed buccal epithelial cell alterations. The observed data signify the high-risk workers are exposed; resulting in the shipyard’s management the need to implement measures improving the working environment conditions and to reevaluate the workers’ personal protective equipment requirements.     

Intramuscular Administration of Very High Dose of a-Tocopherol Protects Liver from Severe Ischemia/Reperfusion Injury

The effect of intramuscular administration of high (30 mg/kg body weight for 3 days) or very high (300 mg/kg body weight for 3 days) doses of a-tocopherol to Wistar rats subjected to total severe warm hepatic ischemia and reperfusion was investigated. After a 60-minute period of total hepatic ischemia and 120 minutes of reperfusion, animals were killed, and liver samples were taken for determination of malondialdehyde (MDA) and histological examinations. Blood samples were also taken for assay of serum a-tocopherol, alanine transaminase (ALT), aspartate transaminase (AST), and lactic dehydrogenase (LDH). Additional animals were followed for a 7-day survival rate determination. Results showed that ischemia and reperfusion decreased the survival rate to 10%, whereas the levels of AST, ALT, and LDH in serum were increased compared with levels in animals that were sham operated. The MDA concentrations in liver were also increased, from 1.142 to 1.567 nmoles/g, whereas the levels of a-tocopherol in serum were decreased from 10.20 to 1.80 mmol/L. Pretreatment with a-tocopherol increased the viability to 50% and 70%, for the high and very high doses, respectively, and decreased the levels of AST, ALT, and LDH in serum. It also decreased the MDA concentrations in liver to 0.975 and 0.774 nmoles/g for the high and very high doses of a-tocopherol, respectively, whereas it increased the level of a-tocopherol in serum to 11.25 and 13.02 mmol/L for the high and very high doses, respectively. Histological examinations showed protection of the liver parenchyma in the animals treated with a-tocopherol.     

Parents' causal attributions about attention deficit/hyperactivity disorder: the effect of child and parent sex

BACKGROUND: Boys with attention deficit/hyperactivity disorder (AD/HD) demonstrate disruptive behaviour at significantly higher rates compared to girls. Disruptive behaviour often develops as a result of negative interaction patterns within the caregiving relationship. Given the importance of parental cognitions as mediators of parental behaviour, the consideration of parent and child sex in the investigation of causal attributions regarding AD/HD may, at least partially, explain sex differences in the prevalence of disruptive behaviour among children with AD/HD. AIM: To examine the effect of parent and child sex on parental causal attributions and reactions about AD/HD and to investigate the interrelationships between these variables. SAMPLE: Three hundred and seventeen mothers and 317 fathers of boys and girls aged 4-6 years and enrolled in kindergartens in Athens. METHOD: A Greek version of the Parental Account of the Causes of Childhood Problems Questionnaire was used, which followed a vignette about a hypothetical child displaying symptoms of AD/HD. Half of the participants received a male and another half received a female version of the vignette. RESULTS: The child's sex greatly influenced parents' causal attributions about AD/HD. Higher ratings of intentionality were conferred to boys with AD/HD than girls and these attributions were related to stricter responses towards boys. In contrast, parents who considered biological dysfunction as underlying AD/HD, they mostly did so in the case of girls. Minimal effect of parent sex on causal attributions was found. CONCLUSIONS: Because causal attributions of intentionality relate to the response of more strictness and such attributions are more prevalent for boys than girls, then these perceptions about the aetiology of AD/HD in boys may be at the basis of negative interaction patterns. The increase of such interaction patterns may place boys at a more vulnerable position towards the development of secondary behaviour problems.