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.     

Burnout Evaluation and Potential Predictors in a Greek Cohort of Mental Health Nurses

Background

Job burnout is one of the most serious occupational health hazards, especially, among mental health nurses. It has been attributed among others to staff shortages, health service changes, poor morale and insufficient employee participation in decision-making.

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.