[Inactivation of Ras1 in Fission Yeast Aggravates the Oxidative Stress Response Induced by Tert Butyl Hydroperoxide (tBHP)].

Ras proteins are small GTPases and function as molecular switches to regulate cellular homeostasis. Ras-dependent signalling pathways regulate several essential processes such as cell cycle progression, growth, migration, apoptosis, and senescence. The dysregulation of Ras signaling pathway has been linked to several pathological outcomes. A potential role of RAS in regulating the redox signalling pathway has been established that includes the manipulation of ROS levels to provide a redox milieu that might be conducive to carcinogenesis. Reactive oxygen species (ROS) and mitochondrial impairment have been proposed as major factors affecting the physiology of cells and implicated in several pathologies. The present study was conducted to evaluate the role of Ras1, tert Butyl hydroperoxide (tBHP), and antimycin A in oxidative stress response in Schizosaccharomyces pombe cells. We observed decreased cell survival, higher levels of ROS, and mitochondrial dysfunctionality in ras1Δ cells and tBHP as well as respiratory inhibitor, antimycin A treated wild type cells. Furthermore, these defects were more profound in ras1Δ cells treated with tBHP or antimycin A. Additionally, Ras1 also has been shown to regulate the expression and activity of several antioxidant enzymes like glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), and catalase. Together, these results suggest the potential role of S. pombe Ras1 in mitigating oxidative stress response.

Impact of a Computerized Antithrombotic Risk Assessment Tool on the Prescription of Thromboprophylaxis in Atrial Fibrillation: Hospital Setting.

The computerized antithrombotic risk assessment tool (CARAT) is an online decision-support algorithm that facilitates a systematic review of a patient's stroke risk, bleeding risk, and pertinent medication safety considerations, to generate an individualized treatment recommendation. The CARAT was prospectively applied across 2 hospitals in the greater Sydney area. Its impact on antithrombotics utilization for thromboprophylaxis in patients with nonvalvular atrial fibrillation was evaluated. Factors influencing prescribers' treatment selection were identified. The CARAT recommended a change in baseline therapy for 51.8% of patients. Among anticoagulant-eligible patients (ie, where the risk of stroke outweighed the risk of bleeding) using "nil therapy" or antiplatelet therapy at baseline, the CARAT recommended an upgrade to warfarin in 60 (30.8%) patients. For those in whom the bleeding risk outweighed the stroke risk, the CARAT recommended a downgrade from warfarin to safer alternatives (eg, aspirin) in 37 (19%) patients. Among the "most eligible" (ie, high stroke risk, low bleeding risk, no contraindications; n = 75), the CARAT recommended warfarin for all cases. Discharge therapy observed a marginal increase in anticoagulation prescription in eligible patients (n = 116; 57.8% vs 64.7%, P = .35) compared to baseline. Predictors of warfarin use (vs antiplatelets) included congestive cardiac failure, diabetes mellitus, and polypharmacy. The CARAT was able to optimize the selection of therapy, increasing anticoagulant use among eligible patients. With the increasing complexity of decision-making, such tools may be useful adjuncts in therapy selection in atrial fibrillation. Future studies should explore the utility of such tools in selecting therapies from within an expanded treatment armamentarium comprising the non-vitamin K antagonist oral anticoagulants.

Presenting features, treatment patterns and outcomes of patients with breast cancer in Pakistan: Experience at a university hospital.

BACKGROUND: Breast cancer is the most common cancer in Pakistani women. We report the presenting features, treatment patterns and survival of breast cancer from a University Hospital in Southern Pakistan and compare the data with international population based studies. MATERIALS AND METHODS: Medical records of patients diagnosed to have breast cancer between January 1999 and November 2008 were reviewed retrospectively. RESULTS: A total of 845 patients were identified. Median age of diagnosis was 48 years (range 18-92). Clinical stage was as follows: Stage I 9.9%; Stage II 48.5%; Stage III 26.2%; Stage IV 13.8%; data not available 1.5%. Approximately, half (51.6%) were estrogen receptor (ER) positive and 17.5% over-expressed Her2/neu. Nearly 23% patients received neo-adjuvant chemotherapy while 68.9% received adjuvant chemotherapy. Anthracycline based treatment was the most common treatment until 2003 while later on, patients also received taxanes and trastuzumab based therapy. Age, stage, tumor size, lymph node status, tumor grade, ER status, treatment with hormonal therapy and radiation were the major predictive factors for overall survival (OS). We report an impressive 5 year OS of 75%, stage specific survival was 100%, 88% and 58% for Stages I, II and III respectively. CONCLUSION: The majority of patients present at a younger age and with locally advanced disease. However, short term follow-up reveals that the outcomes are comparable with the published literature from developed countries. Long-term follow-up and inclusion of data from population-based registries are required for accurate comparison.

Association of NOTCH with different microRNAs in head and neck cancer.

Head and neck cancer is the sixth most common cancer worldwide with an alarming increase in Asian countries. Overwhelmingly increasing cell culture and preclinical studies are identifying wide ranging mechanisms which are instrumental in disease development, progression and resistance against different therapeutics. The scientists are unable to differentiate whether expressional mutation is a cause or a consequence of some other alterations occurring in the body. We partition this review into how NOTCH1 and p16 contribute in cancer development and how microRNAs quantitatively control NOTCH1 expression. Future studies must converge on identification of miRNAs which negatively regulate p16 and targeted inhibition of p16 targeting miRNAs will be helpful in inhibiting tumor growth, cell proliferation and induction of apoptosis. Detailed mechanistic insights related to miRNA mediated Notch regulation will also be useful in delivery of tumor suppressor miRNAs or mimics to effectively inhibit cancer.

Everolimus induced Pneumonitis.

Everolimus (RAD 001) is an orally administered inhibitor of mTOR (mammalian target of rapamycin), a central regulator of intracellular signaling pathways involved in cell growth and proliferation, cellular metabolism and angiogenesis. Drug is currently in use to prevent allograft rejection after solid organ transplantation and in treatment of advanced renal cell carcinoma (RCC). Noninfectious pneumonitis is rare adverse reaction associated with rapamycin and rapamycin analogues. Awareness of this toxicity and appropriate management is important to optimize patient safety. Here we report a case of everolimus induced pneumonitis in a 72 years old male with metastatic renal cell carcinoma (mRCC) after 4 months of commencement of everolimus. Drug was discontinued and patient was treated accordingly and discharged after 10 days of hospital admission.

Genotypic and phenotypic characteristics of Cronobacter species, with particular attention to the newly reclassified species Cronobacter helveticus, Cronobacter pulveris, and Cronobacter zurichensis.

In 2013, Enterobacter helveticus, Enterobacter pulveris and Enterobacter turicensis, were reclassified as Cronobacter helveticus, Cronobacter pulveris and Cronobacter zurichensis, respectively. Previously these species had been used as negative controls for some Cronobacter detection assays. This study examined cultural, biochemical and molecular Cronobacter detection and identification assays, with emphasis on the new species. Additionally, 32 Cronobacter genomes were examined for the presence of PCR target genes using the BLAST function of the online Cronobacter PubMLST facility. The results of the cultural methods varied and no single medium was able to correctly detect all Cronobacter spp. Since the supporting databases have not been updated to include the Cronobacter genus, Enterobacter sakazakii was returned for four strains of the newly reclassified species with ID32E and none with API 20E. PCR probes targeting rpoB and ompA could not correctly identify the new Cronobacter spp., due to primer specificity or absent target genes. As neonates have been identified as a high-risk group for infection, international standards require the absence of all Cronobacter species in powdered infant formula. However, many conventional detection methods cannot correctly identify the newly recognized species. Conversely, DNA sequence-based methods can adapt to taxonomic revisions and will likely become more common.

Classification of papulo-squamous skin diseases using image analysis.

INTRODUCTION: Papulo-squamous skin diseases are variable but are very close in their clinical features. They present with the same lesions, erythematous scaly lesions. Clinical evaluation of skin lesions is based on common sense and experience of the dermatologist to differentiate features of each disease. AIM: To evaluate a computer-based image analysis system as a helping tool for classification of commonly encountered diseases. MATERIALS AND METHODS: The study included 50 selected images from each of psoriasis, lichen planus, atopic dermatitis, seborrheic dermatitis, pityrasis rosea, and pitryasis rubra pilaris with a total of 300 images. The study comprised three main processes peformed on the 300 included images: segmentation, feature extraction followed by classification. RESULTS: Rough sets recorded the highest percentage of accuracy and sensitivity of segmentation for the six groups of diseases compared with the other three used techniques (topological derivative, K-means clustering, and watershed). Rule-based classifier using the concept of rough sets recorded the best percentage of classification (96.7%) for the six groups of diseases compared with the other six techniques of classification used: K-means clustering, fuzzy c-means clustering, classification and regression tree, rule-based classifier with discretization, and K-nearest neighbor technique. CONCLUSION: Rough sets approach proves its superiority for both the segmentation and the classification processes of papulo-squamous skin diseases compared with the other used segmentation and classification techniques.

The stem cell transplant program in Pakistan--the first decade.

Stem cell transplantation is curative in a number of otherwise fatal hematological diseases. In Pakistan, SCT was started in October 1995 at Dr Ziauddin Hospital by Dr Tahir Shamsi and his team. The first case was of a young man suffering from AML. In 1999, allogeneic BMT was started at Bismillah Taqee Institute of Health Sciences and Blood Diseases Centre, Karachi. In 2001, the Armed Forces Bone Marrow Transplant Centre, started functioning. Since then, over 350 allogeneic stem cell transplants have been carried out in these latter two centers. Another 50 autologous procedures were carried out in all centers. In 2004, a third center started transplants at the Aga Khan Hospital. The main indications for transplant are aplastic anemia, beta-thalassemia major and hematological malignancies. HLA-identical sibling donors provide stem cells for the recipient. In 70% of cases, a matched donor is identified. In sharp contrast to the rest of the world, the majority of transplants are allogeneic, donor-recipient pairs are CMV positive and fungal infection, tuberculosis and malaria are particular problems. The early results are promising, with transplant-related mortality reported to be 10-20%, whereas long-term survival is reported to be 78, 72 and 49% in aplastic anemia, beta-thalassemia major and leukemia, respectively. Financial constraints, poor socioeconomic status, poor transfusion services, trained human resources and difficulty in keeping pace with technological advances are major hurdles in the growth of transplant medicine. Government support is badly needed to strengthen existing facilities and to develop more centers.