Dishonesty in scientific research

Fraudulent business practices, such as those leading to the Enron scandal and the conviction of Bernard Madoff, evoke a strong sense of public outrage. But fraudulent or dishonest actions are not exclusive to the realm of big corporations or to evil individuals without consciences. Dishonest actions are all too prevalent in everyone’s daily lives, because people are constantly encountering situations in which they can gain advantages by cutting corners. Whether it’s adding a few dollars in value to the stolen items reported on an insurance claim form or dropping outlier data points from a figure to make a paper sound more interesting, dishonesty is part of the human condition. Here, we explore how people rationalize dishonesty, the implications for scientific research, and what can be done to foster a culture of research integrity.     

An optimized technique of endoscopic third ventriculocisternostomy (ETV) for children with occlusive hydrocephalus

In this article, we present an optimized minimally invasive technique of ETV for children with occlusive hydrocephalus. The study comprises of 64 consecutive pediatric cases (34 boys and 30 girls aged from 1 month to 5 years) of occlusive hydrocephalus from various etiologies, which were treated with a modified technique of ETV. Mean clinical follow-up period after ETV was 24.2?±?3.8 months. Application of the new technique made it possible to significantly reduce the length of the soft tissue incision for access, and the use of upgraded instruments allowed to perform a twist drill hole in the skull to less than half a usual size. Access to the brain and lateral ventricle was performed by blunt trephination of the dura without the need for significant corticectomy or coagulation, and yielded minimal damage to the brain, which is very important in patients of young age. Continued endoscopic control during the approach down to the lateral ventricle increases safety and decreases risk of injury, and can be performed in cases of pathologies affecting the anatomical relationships of the lateral and third ventricle. Mortality in our cohort was 0%, and there were no postoperative neurological, endocrinological, or infectious complications. Patency rates of the first ETV performed was 78%, with the remaining patients requiring additional surgical procedures for complicated settings. This new technique of minimally invasive ETV placement in pediatric patients is an effective and safe method to treat occlusive hydrocephalus and can be recommended for extensive clinical use.     

Group cognitive behavioral treatment in female soldiers diagnosed with binge/purge eating disorders

ABSTRACT

Cognitive behavioral treatment (CBT) is the recommended intervention in bulimia nervosa (BN) and eating disorders not otherwise specified with binge/purge (EDNOS-B/P) symptoms. There are fewer data on its application in a group format. We sought to investigate the effect of group CBT in female soldiers with B/P symptomatology in an open trial design. For this purpose we assessed 64 female soldiers serving in the Israeli Defense Force diagnosed with BN and EDNOS-B/P who participated in a group CBT format of 16 weekly sessions and one follow-up session. In this study, 42 participants (65.6%) completed treatment and 22 participants (34.4%) did not. A total of 39 treatment completers (92.8% of treatment completers) and 19 non-completers (86.4% of treatment non-completers) were assessed around 12 months after treatment. Participants completed at baseline and following treatment questionnaires assessing eating-related symptoms, depression, anxiety, and overall functioning. At follow-up they were assessed for eating-related symptoms. Our findings show only minimal baseline differences between treatment completers and non-completers. Significant improvement from baseline to post-treatment was shown for B/P and restrictive symptoms, depression, anxiety, and overall functioning. At that time, more than a third of treatment completers were abstinent from binging and more than a half from vomiting. The improvement in B/P and restricting symptoms was maintained at 1 year follow-up for treatment completers. At that time around 60% were abstinent from binging and more than 70% from vomiting. Participants not completing treatment were also improved at follow-up but to a lesser extent. The findings of the present study suggest that group CBT may be effective for the treatment of female soldiers with BN and EDNOS-B/P.     

Effect of A2B adenosine receptor gene ablation on adenosine-dependent regulation of proinflammatory cytokines

Pharmacological studies suggest that A(2B) adenosine receptors mediate proinflammatory effects of adenosine. This concept was recently challenged by the finding that A(2B) adenosine receptor knockout (A(2B)KO) mice had moderate inflammation due to elevated basal plasma tumor necrosis factor (TNF)-alpha and an exaggerated response to lipopolysaccharide (LPS) challenge. However, it is unclear whether this phenomenon actually reflects the loss of putative taming of proinflammatory cytokine production via activation of A(2B) receptors by endogenous adenosine. In this report, we examined adenosine receptor-dependent regulation of interleukin (IL)-6 and TNF-alpha blood plasma levels in A(2B)KO and wild-type mice in vivo and their release from peritoneal macrophages ex vivo. Stimulation of adenosine receptors with 5'-N-ethylcarboxamidoadenosine (NECA) up-regulated IL-6 and suppressed LPS-induced TNF-alpha in wild-type mice. The selective A(2B) antagonists 3-isobutyl-8-pyrrolidinoxanthine and 8-[4-[((4-cyanophenyl)carbamoylmethyl)oxy]phenyl]-1,3-di(n-propyl)xanthine (MRS 1754) inhibited NECA-induced IL-6 release but not the suppression of LPS-induced TNF-alpha secretion from macrophages. Genetic ablation of A(2B) receptors abrogated NECA-induced increases in IL-6 release from mouse peritoneal macrophages and dramatically reduced the ability of NECA to raise IL-6 plasma levels in vivo. In contrast, the absence of A(2B) adenosine receptors did not affect NECA-induced suppression of LPS-activated TNF-alpha release in macrophages, nor did it reduce the ability of NECA to suppress LPS-induced increase in TNF-alpha plasma levels in vivo. Thus, our results indicate that stimulation of A(2B) receptors up-regulates the proinflammatory cytokine IL-6 and argue against the recently suggested anti-inflammatory role of A(2B) receptors in suppression of LPS-stimulated TNF-alpha production by adenosine.     

Accelerated renal fibrosis in cardiorenal syndrome is associated with long-term increase in urine neutrophil gelatinase-associated lipocalin levels

Background: Cardiac events are the main cause of death among patients with end-stage renal failure. Even a mild renal disease is currently considered a major risk factor for cardiovascular complications following myocardial infarction (MI). The aim of the present study was to detect histological, sera and urine characteristics of kidney injury in cardiorenal syndrome (CRS) compared to chronic kidney disease (CKD) with an intact cardiac function. Methods: We employed a rat model for CRS, in which an acute MI (AMI) was induced 4 weeks after establishment of subtotal nephrectomy. Four weeks later, left ventricular function was assessed by echocardiography and changes in renal performance were examined using histological and biochemical parameters. Results: Increased interstitial fibrosis as well as renal inflammation were observed in renal sections derived from CRS rats, compared to subtotal nephrectomy (CKD)-only animals. Moreover, we found that even though AMI on the background of CKD was not associated with a further decrease in creatinine clearance or a further increase in sera BUN levels compared to CKD only, a significant long-term elevation in urine neutrophil gelatinase-associated lipocalin (Ngal) levels was detectable post-MI induction. Conclusions: AMI in the CKD setting is associated with accelerated renal fibrosis and long-term elevated urine Ngal values, suggesting that cardiac dysfunction contributes to accelerated intrinsic kidney injury in CKD. The data indicate that elevated urine Ngal may potentially serve as an early non-invasive laboratory parameter for a left ventricular dysfunction-related renal injury.     

Adenosine receptors in regulation of dendritic cell differentiation and function

Differentiation of functional dendritic cells (DCs) critically depends on the microenvironment. DCs differentiate in hypoxic tumor sites and inflamed or damaged tissue. Because local concentrations of adenosine reach high physiologically relevant levels in these conditions, we assessed the expression of adenosine receptors and the effect of their activation on differentiation of human monocytes and mouse peritoneal macrophages and hematopoietic progenitor cells (HPCs) into myeloid DCs. Stimulation of adenosine receptors skews DC differentiation toward a distinct cell population characterized by expression of both DC and monocyte/macrophage cell surface markers. Pharmacologic analysis and experiments with cells from A(2B) adenosine receptor knockout mice identified A(2B) receptor as the mediator of adenosine effects on DCs. Unlike normal myeloid DCs, adenosine-differentiated DCs have impaired allostimulatory activity and express high levels of angiogenic, pro-inflammatory, immune suppressor, and tolerogenic factors, including VEGF, IL-8, IL-6, IL-10, COX-2, TGF-beta, and IDO. They promoted tumor growth if injected into tumors implanted in mice. Using adenosine desaminase knockout animals, we showed that DCs with proangiogenic phenotype are highly abundant under conditions associated with elevated levels of extracellular adenosine in vivo. Adenosine signaling through A(2B) receptor is an important factor of aberrant DC differentiation and generation of tolerogenic, angiogenic, and proinflammatory cells.