Prostate carcinoma (PCa) displays a wide variety of genetic alterations, versatile expression profiles as well as cell surface markers. Despite this heterogeneity, a common treatment for advanced PCa is androgen deprivation therapy (ADT). ADT targets the androgen receptor-a member of the nuclear receptor superfamily-which is required for development and function of the prostate and critical for PCa growth and survival. After an initial regression of the tumor during ADT, a large fraction of tumors progress to so-called castration-resistant prostate carcinoma (CRPca) which is highly resistant toward chemotherapy. The ensuing high mortality rates illustrate the importance of novel therapeutic targets for CRPCa. The transcription factor NF-κB was recently proposed as such a potential target for therapeutic intervention in CRPCa. Although NF-κB is essential for the regulation of innate and adaptive immunity recent data suggest a role of NF-κB in cancer initiation and progression. However, the exact function of NF-κB signaling in PCa is still a matter of debate. Here, we review known roles of NF-κB signaling in PCa and emphasize the crosstalk of NF-κB and androgen receptor signaling. Finally, we discuss potential therapeutic relevance of blocking NF-κB in PCa.

Introduction:Type 2 diabetes mellitus is a significant health problem and imposes great physical, financial and psychological burden among the affected population. Among people with diabetes, fatigue is a pervasive and distressing complaint, which is further accentuated by presence of depression.Objective:To assess the prevalence of fatigue and depression and associated clinical and socio demographic correlates in type 2diabetes.Materials and Methods:This cross sectional study included 100 patients of diabetes type 2 and equal number of healthy controls between the ages of 18 to 70 years. A detailed evaluation of socio demographic and clinical parameters was made. Participants were also assessed for presence of depression and fatigue using PHQ-9 and Fatigue Severity Scale(FSS)respectively.Results:Fatigue and depression was found in 68 % and 53 % of diabetic participants. Diabetic patients were 10.37 times and 4.80 times more likely to suffer from fatigue and depression respectively. Both fatigue and depression were found to be significantly associated with duration of illness, fasting and post prandial blood glucose level, diabetic complications and Body Mass Index (BMI). Fatigue was also strongly correlated with depression in study sample.Conclusions:Fatigue and depression are reasonably correlated with type 2 diabetes. Various clinical parameters of diabetes are strongly associated with both fatigue and depression. Fatigue itself has significant correlation with depression in type 2 diabetes. Regular monitoring of biochemical parameters are paramount to predict the development of fatigue and depression in type 2 diabetes.

Objectives:This is a recent study conducted during 15th September 2013 to 15th December 2013 at the community health centre (CHC), Muradnagar, distt Ghaziabad, among the victims of dog/animal bite attending the daily OPD services of CHC. To identify the level of general awareness and knowledge of wound management and rabies among the cases of dog bite and to study the awareness of people about antirabies vaccines and health service utilization.Methods:The study population composed of 250 victims of dog or animal bite, Patients were selected and approached after proper briefing, with well-prepared two page structured questionnaire designed in local language to assess their knowledge about the wound management, information about the epidemiology of dog bite.Results and conclusion:The result of the study reflect the very low level of awareness about the postdog bite management of wounds as well as about the disease rabies group of people questioned and also reveals serious gaps in understanding of wound severity, classification and correct application of PEP with ARV vaccine and RIG. There is definitely a gap in people's knowledge, attitude, and practices about dog bite and its management and there is need of taking serious measures for the control of stray dog population at the block level.

Enhanced nuclear localization of nuclear factor κB (NF-κB) in prostate cancer (PCa) samples and constitutive NF-κB signaling in a class of PCa cell lines with low androgen receptor (AR) expression (PC3 and DU-145) imply an important role of the IκB kinase (IKK)/NF-κB system in PCa. However, most PCa and PCa cell lines depend on the activity of the AR, and the role of NF-κB in these AR-expressing PCa remains unclear. Here, we demonstrate that inhibition of NF-κB signaling by the IKK inhibitor BMS345541 reduced proliferation and increased apoptosis in AR-expressing PCa cell lines. Furthermore, AR activity and target gene expression were distinctively reduced, whereas AR protein levels remained unaltered on BMS345541 treatment. Similar effects were observed particularly after small interfering RNA (siRNA)-mediated knockdown of IKK1, but not by siRNA-mediated suppression of IKK2. Moreover, IKK1 overexpression augmented 5α-dihydrotestosterone-induced nuclear AR translocation, whereas nuclear AR was reduced by IKK1 knockdown or BMS345541. However, because IKK1 also enhances the activity of a chronically nuclear AR mutant, modulation of the subcellular distribution seems not to be the only mechanism by which IKK1 enhances AR activity. Finally, reduced in vivo AR phosphorylation after BMS345541 treatment and in vitro AR phosphorylation by IKK1 or IKK2 imply that AR constitutes a novel IKK target. Taken together, our data identify IKK1 as a potentially target structure for future therapeutic intervention in PCa.

No abstract