Pro-inflammatory cytokines and chemokines initiate multiple prostate cancer biologic pathways of cellular proliferation,heterogeneity and metastasis in a racially diverse population and underlie the genetic/biologic mechanism of racial disparity: Update

Pro-inflammatory cytokine and chemokines genes drive prostate cancer progression and metastasis: molecular mechanism update and the science that underlies racial disparity. comprehensive review article.Isaac J. Powell, S. Chinni, S.S. Reddy, Alexander Zaslavsky, Navnath Gavande Introduction: In 2013 we reported that with the use of bioinformatics and ingenuity pathway network analysis we were able to identify functional driver genes that were differentially expressed among a large population of African American men (AAM) and European American men (EAM). Pro-inflammatory cytokine genes were found to be more interactive and more expressed among AAM and have been found to be functional drivers of aggressive prostate cancer (CaP) and aggressiveness in other solid tumors. We examined these genes and biological pathways initiated by these cytokines in primary CaP tissue.Method We unravel the gene network and identified biologic pathways that impacted activation of the androgen receptor, mesenchymal epithelial transition (invasion) and chemokines associated with metastasis in the CaP tissue from 639 radical prostatectomy specimens.Results Biologic pathways identified by unraveling pro-inflammatory genes from our network, more expressed among AAM compared to EAM, were tumor necrosis factor (TNF), IL1b, IL6, and IL8. IL6 and IL8 are downstream of TNF activity and are known activators of androgen receptor and through mediators promote CaP cell proliferation. TNF and IL1b mediate tumor cell invasiveness through the activation of MMP (matrix metalloproteinase) which down regulates E-Cadherin to initiate epithelial mesenchymal transition which allows cells to become invasive in the microenvironment. Ultimately our network analysis indicates that TNF and IL1b activate CXCR4 receptor on CaP cells, which facilitates metastatic progression reportedly by binding to CXCL12 on lipid rafts and tumor implantation in the bone marrow.Conclusion Our retrospective biologic mechanistic model reveals a set of pro-inflammatory cytokines and chemokines that drive CaP aggressiveness, tumor heterogeneity, progression and metastasis. A prospective multi-institutional study needs to be conducted for clinical validation as well consideration of targeted therapy.     

Development of a composite indicator to prioritize districts for implementation of human immunodeficiency virus programmes in Maharashtra,India

A key recommendation of the National AIDS Control Programme‐IV of India was to develop new strategies for geo‐prioritization of the human immunodeficiency virus (HIV) epidemic. We conducted this study to categorize the districts in Maharashtra (India) based on a multidimensional framework for geo‐prioritization of services. Programmatic data on trends of HIV prevalence, coverage of marginalized populations and vulnerability factors were included. A composite indicator based on these was developed, and the cumulative score was calculated for each district. HIV prevalence among general population has declined steadily from 0.60% in 2007 to 0.33% in 2017. The programme coverage was stable but inadequate for men who have sex with men (MSM). The coverage for female sex workers (FSWs) was inadequate and reduced over time. Nine districts were categorized as high priority, 13 as moderate priority and 11 were classified as low‐priority districts based on burden and vulnerability for HIV. The high‐priority districts were Pune, Solapur and Yavatmal for FSW interventions and Pune, Thane and Latur for MSM interventions. This multidimensional indicator is based on existing programmatic data, dynamic and can be made state‐specific. It is useful to categorize and prioritize districts for allocation of resources and geo‐prioritization of services in resource limited settings.     

Vesicular and bullous eruptions in tropical (filarial) eosinophilia

A case of tropical (filarial) eosinophilia (TE) presented with vesicular and bullous eruptions. The patient had skin and mucosal blistering. Histopathological changes were that of bullous pemphigoid. The patient had very high eosinophilia with abnormal vacuoles in the cytoplasm. ELISA test was positive for filarial antibodies. There were no pulmonary signs or symptoms. X-ray chest was normal. The patient responded well to diethylcarbamazine.     

Descriptive epidemiology of acute respiratory infections among under five children in an urban slum area

A study was conducted in Sunderpur, Varanasi to study the magnitude of the problem of acute Respiratory Infections among under five children in an urban slum and the clinical profile of it in order to understand the pattern of disease presentation for identifying methods of early diagnosis and timely intervention. 150 under five children were selected by stratified random sampling method and were observed for 52 weeks at weekly interval to record the illnesses. In total 661 episodes were observed in 5623 child-weeks of observation giving an episode rate of 6.11 per child per year. ARI accounted for 67% of all morbidities. Mean duration of all the episodes taken together was 8.15 + 5.44 days. Majority of the episodes (88.96%) were confined to the Upper Respiratory Tract only. Most commonly occurring clinical features were rhinorrhea, nasal stuffiness and cough. 61.4% of all the episodes terminated within seven days, and only 26.2% continued for two weeks.     

Medulloblastoma

The utilization of multi-modal therapy in the treatment of medulloblastoma has improved survival rates and overall outcome. Recent large clinical trials have supported the use of radiation and chemotherapy as adjuvant treatment. Treatment advances have been made despite a poor understanding of the biological underpinnings of medulloblastoma. Current laboratory investigations are shedding light on the oncogenesis of medulloblastoma and may lead to improved treatments.     

Early results of the extracardiac conduit Fontan operation

BACKGROUND: Among the modifications of the Fontan operation, the extracardiac approach may offer the greatest potential for optimizing early postoperative ventricular and pulmonary vascular function, insofar as it can be performed with short periods of normothermic partial cardiopulmonary bypass and without cardioplegic arrest in most cases. In this study, we reviewed our experience with the extracardiac conduit Fontan operation, with a focus on early postoperative outcomes. METHODS AND RESULTS: Between July 1992 and April 1997, 51 patients (median age 4.9 years) underwent an extracardiac conduit Fontan operation. Median cardiopulmonary bypass time was 92 minutes and has decreased significantly over the course of our experience. Intracardiac procedures were performed in only 5 patients (10%), and the aorta was crossclamped in only 11 (22%). Intraoperative fenestration was performed in 24 patients (47%). There were no early deaths. Fontan failure occurred in 1 patient who was a poor candidate for the Fontan procedure. Transient supraventricular tachyarrhythmias occurred in 5 patients (10%). Median duration of chest tube drainage was 8 days. Factors significantly associated with prolonged resource use (mechanical ventilation, inotropic support, intensive care unit stay, and hospital stay) included longer bypass time and higher Fontan pressure. At a median follow-up of 1.9 years, there was 1 death from bleeding at reoperation. CONCLUSIONS: The extracardiac conduit Fontan procedure can be performed with minimal mortality and morbidity. Improved results may be related to advantages of the extracardiac approach and improved preservation of ventricular and pulmonary vascular function.     

Predictors of return to work after anterior cervical discectomy

Return to previous level of employment after surgery is important to patients. Predictors of return to work have been well described in lumbar disc surgery. However, this information cannot be generalized to the population undergoing cervical discectomy. The authors retrospectively reviewed 67 consecutive patients who underwent anterior cervical discectomy. Strict inclusion criteria were used. Baseline demographics were recorded as well as other potential predictors of postoperative return to work such as number of levels of disease, smoking history, and disability claims. Follow-up information about work status was reviewed with each patient at office visit. Forty-five patients were found eligible for the study. At a mean follow-up of 2.8 years (SD 1.4), 38% had not returned to work by 1 year. Preoperative sick leave in this group was significantly greater than for those patients who returned to work within the year (p = 0.0014). Postoperative neck pain was more common in individuals who did not return to work after surgery (p = 0.01). Increasing age and disability claims also appeared to negatively impact the ability to return to work. Gender, type of work, smoking history, and number of levels of disc disease did not appear to have any association with postoperative return to work. The authors conclude that the duration preoperative sick leave and postoperative neck pain negatively impact postoperative work status in patients undergoing anterior cervical discectomy. Age and disability claims also influence return to work.     

Acute transverse myelitis: MR characteristics

Magnetic resonance imaging findings in 13 patients with acute transverse myelitis are reviewed. In 12 cases centrally located high intensity signal extending over few spinal segments was noted. The lesion occupied more than two thirds of the cord's cross-sectional area in 8 patients. Central dot sign was noted in 7 patients. Variable cord enlargement was seen in 5 patients. Contrast study in one patient showed peripheral enhancement. The MR characteristics that help in differentiating transverse myelitis from spinal form of multiple sclerosis are discussed.