mTOR Signaling Cascade in Psoriatic Disease: Double Kinase mTOR Inhibitor a Novel Therapeutic Target

In this short communication we are providing insight about the regulatory role of the phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) kinase system in psoriatic disease. This is an upcoming active research field in respect to elucidating the inflammatory and proliferative cascades of psoriatic disease. To provide a new dimension to the understandings of the molecular principles of the pathogenesis of autoimmune diseases, we hypothesized that (i) dysregulation of cytokines and growth factors in autoimmune diseases activate the mTOR signaling system and (ii) the activated mTOR kinase system is a key regulator of the inflammatory/proliferative cascades of the disease process. In support of this hypothesis we have earlier reported that growth factors (nerve growth factor (NGF) and platelet-derived growth factor (PDGF)) and relevant cytokines (interleukin (IL)-17, IL-22) known to be critical for psoriasis, psoriatic arthritis, and rheumatoid arthritis activate the mTOR signaling system. Here, we are providing our latest observations that the mTOR signaling proteins are upregulated in psoriatic skin and further we observed that proliferation of keratinocytes (KC) and synovial cells (synovial fibroblasts (FLS)) of psoriatic arthritis are dependent on the PI3K-AKT-mTOR kinase system. To our knowledge, we are the first to explore whether a double kinase inhibitor of mTOR signal proteins has a therapeutic potential for psoriatic disease. Here we will be sharing our views, our research work in this field and as well we will provide evidences how a double kinase inhibitor of mTOR signal proteins can be an effective therapeutic agent for psoriatic disease.     

Percutaneous endoscopic cecostomy (introducer method) in chronic intestinal pseudo‐obstruction: Report of two cases and literature review

We report on two patients with recurrent episodes of chronic intestinal pseudo‐obstruction (CIPO). A 50‐year‐old woman with severe multiple sclerosis and an 84‐year‐old man with Parkinson's disease and dementia had multiple hospital admissions because of pain and distended abdomen. Radiographic and endoscopic findings showed massive dilation of the colon without any evidence of obstruction. Conservative management resolved symptoms only for a short period of time. As these patients were poor candidates for any surgical treatment we carried out percutaneous endoscopic colostomy by placing a 20‐Fr tube in the cecum with the introducer method. The procedure led to durable symptom relief without complications. We present these two cases and give a review through the existing literature of the procedure in CIPO.     

Altered DNA methylation of glucose transporter 1 and glucose transporter 4 in patients with major depressive disorder

Alterations in brain glucose metabolism and in peripheral glucose metabolism have frequently been observed in major depressive disorder (MDD). The insulin independent glucose transporter 1 (GLUT1) plays a key role in brain metabolism while the insulin-dependent GLUT4 is the major glucose transporter for skeletal and cardiac muscle. We therefore examined methylation of GLUT1 and GLUT4 in fifty-two depressed inpatients and compared data to eighteen healthy comparison subjects. DNA methylation of the core promoter regions of GLUT1 and GLUT4 was assessed by bisulfite sequencing. Further factors determined were fasting glucose, cortisol, insulin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). We found significantly increased methylation of the GLUT1 in depressed inpatients compared to healthy comparison subjects (CG). Further findings comprise increased concentrations of fasting cortisol, glucose, insulin, and increased IL-6 and TNF-α. After six weeks of inpatient treatment, significantly lower GLUT1 methylation was observed in remitted patients compared to non-remitters. GLUT4 methylation was not different between depressed patients and CG, and did not differ between remitted and non-remitted patients. Although preliminary we conclude from our results that the acute phase of major depressive disorder is associated with increased GLUT1 methylation and mild insulin resistance. The successful treatment of depression is associated with normalization of GLUT1 methylation in remitters, indicating that this condition may be reversible. Failure of normalization of GLUT1 methylation in non-remitters may point to a possible role of impeded brain glucose metabolism in the maintenance of MDD.     

The evolution and value of bleeding assessment tools

Summary. A personal history of excessive mucocutaneous bleeding is a key component in the diagnosis of a number of mild bleeding disorders, including von Willebrand disease (VWD), platelet function disorders (PFD), and coagulation factor deficiencies. However, the evaluation of hemorrhagic symptoms is a well‐recognized challenge for both patients and physicians, because the reporting and interpretation of bleeding symptoms is subjective. As a result, bleeding assessment tools (BATs) have been developed and studied in a variety of clinical settings. This work has been pioneered by a group of Italian researchers, and the resultant ‘Vicenza Bleeding Questionnaire’ stands as the original BAT. In this review, we will discuss the modifications of the Vicenza Bleeding Questionnaire that have taken place over the years, as well as the validation studies that have been published. Other BATs that have been developed and published will be reviewed, as will the special situations of assessing pediatric bleeding as well as menorrhagia. Lastly, the clinical utility of BATs will be discussed including remaining challenges and future directions for the field.     

The Role of Culture in Eating Disorders

A comprehensive understanding of eating disorders should include engagement with the role of contemporary cultural trends. Feminists and critical social theorists have made significant contributions in this regard. Using two clinical cases, this paper contemplates the relationship between culture and psyche in eating disorder, proposing a psychoanalytic conceptualization underpinned by John Steiner's (1982, 1987, 1993, 2011) theory of pathological organizations and psychic retreats. Two conceptual terms will be introduced, namely ‘the normalized body order’ and ‘the abject body object’ to develop the argument. One of the clinical cases will be used to explore a particular kind of therapeutic impasse that can occur when therapist and patient are both female. In this particular case, the normalized body order emerged temporarily obstructing therapeutic progress; the impasse was understood to be an example of the so‐called anti‐analytic third (Straker, 2006 ).     

Relationship between coping,rumination and posttraumatic growth in mothers of children with autism spectrum disorders

This study examined the relationship between coping, rumination and posttraumatic growth in mothers of children with autism spectrum disorders (ASD). One hundred and two mothers of autistic children in China were surveyed using Post-traumatic Growth Inventory, Trait Coping Style Questionnaire, and Event Related Rumination Inventory. Mothers reported mediate level of PTG, mostly on the growth of personal strength. Hierarchal regression analysis indicated that positive coping positively predicted PTG and growth on “relating to others”; deliberate rumination was positively correlated with growth on “appreciation of life”; and intrusive rumination negatively predicted growth on “personal strength”, “new possibilities” and “spiritual change”. No statistically significant relationship between negative coping and PTG was found. The results may be used to provide mothers with a better understanding of the underlying growth process and assist service providers in facilitating this progress.