R Engine Cell: integrating R into the i2b2 software infrastructure

Informatics for Integrating Biology and the Bedside (i2b2) is an initiative funded by the NIH that aims at building an informatics infrastructure to support biomedical research. The University of Pavia has recently integrated i2b2 infrastructure with a registry of inherited arrhythmogenic diseases. Within this project, the authors created a novel i2b2 cell, named R Engine Cell, which allows the communication between i2b2 and the R statistical software. As survival analyses are routinely performed by cardiology researchers, the authors have first concentrated on making Kaplan–Meier analyses available within the i2b2 web interface. To this aim, the authors developed a web-client plug-in to select the patient set on which to perform the analysis and to display the results in a graphical, intuitive way. R Engine Cell has been designed to easily support the integration of other R-based statistical analyses into i2b2.     

The relationship among sperm global DNA methylation,telomere length,and DNA fragmentation in varicocele: a cross-sectional study of 20 cases

Varicocele pathophysiology is related to increased oxidative stress, which might result in loss sperm DNA integrity as well as in genomic instability. Sperm telomere shortening and loss of global DNA methylation are the main features of genomic instability, leading to cell senescence and death, whereas sperm DNA fragmentation (SDF) characterizes the loss of chromatin integrity. We hypothesize that sperm genomic stability and DNA integrity is reduced in infertile men with moderate and large-sized varicoceles, thus being candidate markers of sperm quality in varicocele-related infertility. Here, we assessed the sperm global DNA methylation, telomere length, and SDF in men with and without clinically palpable varicoceles. While the rates of SDF and telomere length were not statistically different between varicocele patients and controls, global sperm DNA methylation seems to be lower in men with varicocele (49.7% ± 20.7%) than controls (64.7% ± 17.1%). A negative correlation between SDF and sperm motility and a positive correlation between sperm morphology and telomere length were observed. Our results suggest that varicocele may result in genomic instability, in particular, global DNA hypomethylation. However, a large sample size may confirm these findings. The understanding of the molecular mechanisms involved in the pathophysiology of varicocele-related infertility may help to better select candidates for varicocele repair.     

Takotsubo Syndrome (Stress Cardiomyopathy): An Intriguing Clinical Condition in Search of Its Identity

Takotsubo syndrome is a relatively frequent clinical entity presenting typically as an acute coronary syndrome in the absence of obstructive coronary artery disease and characterized angiographically by transient left ventricular systolic dysfunction, sparing the basal segments of the left ventricle (“apical ballooning”). Takotsubo syndrome characteristically affects peri- or postmenopausal women, albeit recent series show that men also are at risk. Takotsubo syndrome is characteristically triggered by severe emotional or physical stress, which suggests a pathogenic role for increased sympathetic activity leading to myocardial perfusion abnormalities and ventricular dysfunction. The reasons why severe emotional and physical stress result in the development of takotsubo syndrome in certain individuals but not others is still a matter of speculation, but strongly suggests the existence of predisposing factors/mechanisms in certain subjects. The present article reviews the different factors that can play a role in the development of takotsubo syndrome in different patients. We propose that triggers (ie, emotional stressors, physical stressors, iatrogenic stressors, and neurologic triggers), pathogenic mechanisms (ie, increased catecholamine levels, coronary vasomotor abnormalities leading to myocardial ischemia), and predisposing factors (ie, cardiovascular risk factors, endothelial dysfunction, comorbidities) all interact in a complex fashion and possibly differently in different patients to cause takotsubo syndrome. Identifying these factors may help in preventing and managing the condition more effectively.     

Burnout in health care providers of dialysis service in Northern Italy--a multicentre study.

BACKGROUND: Few data are available regarding the prevalence of burnout among dialysis health care workers. Aims of the present study were to assess and compare burnout levels in a sample of nurses and physicians working in dialysis units, and to investigate their relationships with quality of life, in a cross-sectional observational study. METHODS: A total of 344 workers from 10 dialysis centres in Northern Italy completed a battery of questionnaires including the Maslach Burnout Inventory, the MOS-36 Item Short Form Health Survey [SF36: physical (PCS) and mental (MCS) component scores] and the 30-item General Health Questionnaire (GHQ30). Data on social and demographic characteristics and working conditions were also collected. General Estimating Equations models were used for the analysis. RESULTS: Overall, burnout scores were lower than the Italian normative sample, with no significant differences between physicians and nurses. However, 30% of nurses had high emotional exhaustion vs 18% of physicians (adjusted OR 2.38, P = 0.003). Emotional exhaustion was also predicted by number of worked hours and months worked in dialysis in the previous 2 years. Depersonalisation was predicted by male gender and bad relationship with coworkers. Having no children and having a permanent hospital position predicted low personal accomplishment. PCS was lower in nurses (50.0 vs 53.3, P < 0.001), while no significant difference was found for MCS and GHQ30. Lower PCS was associated with emotional exhaustion (P = 0.007) and GHQ30 > 5 with depersonalization (P = 0.032). CONCLUSIONS: Although burnout is not a general problem in dialysis health care providers, a subgroup of them may be identified, who would benefit from supportive measures to prevent this condition. Nurses appeared more burned-out in the emotional exhaustion scale than physicians.     

Myiasis as a risk factor for prion diseases in humans

Prion diseases are transmissible spongiform encephalopathies of humans and animals. The oral route is clearly associated with some prion diseases, according to the dissemination of bovine spongiform encephalopathy (BSE or mad cow disease) in cattle and kuru in humans. However, other prion diseases such as scrapie (in sheep) and chronic wasting disease (CWD) (in cervids) cannot be explained in this way and are probably more associated with a pattern of horizontal transmission in both domestic and wild animals. The skin and mucous membranes are a potential target for prion infections because keratinocytes and lymphocytes are susceptible to the abnormal infective isoform of the prion protein. Iatrogenic transmission of Creutzfeldt-Jakob disease (CJD) was also recognized after corneal transplants in humans and scrapie was successfully transmitted to mice after ocular instillation of infected brain tissue, confirming that these new routes could also be important in prion infections. Some ectoparasites have been proven to harbour prion rods in laboratory experiments. Prion rods were identified in both fly larvae and pupae; adult flies are also able to express prion proteins. The most common causes of myiasis in cattle and sheep, closely related animals with previous prion infections, are Hypoderma bovis and Oestrus ovis, respectively. Both species of flies present a life cycle very different from human myiasis, as they have a long contact with neurological structures, such as spinal canal and epidural fat, which are potentially rich in prion rods. Ophthalmomyiases in humans is commonly caused by both species of fly larvae worldwide, providing almost direct contact with the central nervous system (CNS). The high expression of the prion protein on the skin and mucosa and the severity of the inflammatory response to the larvae could readily increase the efficiency of transmission of prions in both animals and humans.     

Sexual dimorphism in [3H]histamine binding sites of rat cerebral cortex

[3H]Histamine binding sites, identified on rat brain homogenate membranes, displayed sexual dimorphism with higher density and lower affinity in preparations from adult female compared to the males. The ontogenetic development of [3H]histamine binding sites was studied in male and female brain cortex neural membranes. Histamine binding sites were detectable in newborn-10 day old rats. Density increased with age, reaching adult levels at 37-45 days. No significant differences between sexes were observed in the binding constants until 37 days after birth, when the [3H]histamine binding characteristics began to differentiate according to sex. Sexual dimorphism in brain histamine binding site development appeared to depend on ovarian steroids. Binding patterns in immature female rats which were ovariectomized at 21 days and killed at 37+ were similar to those found in males. On the other hand, when oestradiol replacement was administered for 10 days to ovariectomized rats a total recovery of [3H]histamine binding pattern was obtained, which was comparable to that observed in intact female rats of the same age.     

Effects of glibenclamide and metformin (alone or in combination) on insulin release from isolated human pancreatic islets

Isolated human pancreatic islets were prepared by collagenase digestion and density gradient purification, and the effects of glibenclamide (0.5 and 5.0 µmol/l) and metformin (20 and 200 µmol/l), alone or in combination, on insulin release were evaluated at varying glucose concentrations. At 3.3 mmol/l glucose level, the addition of 5.0 µmol/l glibenclamide or 5.0 µmol/l glibenclamide plus 200 µmol/l metformin caused a significant increase of insulin release, compared with glucose alone. At 16.7 mmol/l glucose concentration, a significant increase of insulin secretion, compared with glucose alone, was produced by the addition of either 5.0 µmol/l glibenclamide, 200 µmol/l metformin, or both 5.0 µmol/l glibenclamide and 200 µmol/l metformin. The effect of the combination of the two drugs was significantly higher than that with either drug used alone. Thus, glibenclamide was shown to have an insulinotropic effect on human islets at both low and high glucose concentrations, and metformin at high glucose concentrations. A possible synergistic effect of glibenclamide and metformin at high glucose concentrations is also suggested.