Genetics of pancreatic adenocarcinoma

grantor: University of TorontoRecent evidence suggests that susceptibility to pancreatic adenocarcinoma may be inherited. This thesis examines germline and somatic mutations in pancreatic cancer patients. In the first series of experiments, 102 such patients were studied to define (i) the proportion belonging to hereditary cancer syndrome families, and (ii) the frequency of germline mutations of various cancer predisposing genes in patients with a personal or family history of cancer. Ina second related set of experiments, the role of germline 'p16' mutations in patients with both pancreatic adenocarcinoma and malignant melanoma was investigated. In the last set of experiments, the relationship between a specific type of tumor K-'ras' mutation and a history of smoking was examined. This work shows that known causes of genetic predisposition are an important risk factor only in a small proportion of pancreatic cancer patients and that there are probably, as yet unidentified genes predisposing to this disease.M.Sc

Redefining informed consent form in cell and gene therapy trials

Informed consent is a foundation of the ethical conduct of research involving human participants. Based on the ethical principle of respect for persons, the goal of informed consent is to ensure that participants are aware of the risks and potential benefits and make a voluntary decision about participating in clinical trial research. The extraordinary scientific advances happening globally, have demonstrated the potential of regenerative therapies in transforming the health of the nation by providing a therapeutic option for diseases that were previously considered incurable. These therapies, which include cells and gene therapy (GT) labeled as Advanced Therapeutic Medicinal Products globally, have complex mechanisms of action. Owing to their highly personalized and intricate nature of these therapies, developing the latter often presents unique challenges above and beyond those encountered for small molecule drugs. We recently looked through some cell and GT clinical trials and realized the lacunae in the informed consent form (ICF) provided by the investigators. Especially in a country like India, where the general understanding and perception of patients is limited regarding clinical trials, it is felt that any lapses in the consent process may jeopardize the informed decision-making and safety of the participants and tarnish the reputation of India globally. The present article highlights the need for appropriate patient and public education on the various aspects of cell and gene therapies and aims to address all the elements of ICF in light of the challenges associated with these innovative therapies

Per-Operative Kinking of a Reinforced Endotracheal Tube: An Unforeseen Complication

Reinforced tubes are routinely used in Oro-maxillary surgeries. In spite of its advantages, any intra-operative deformity in reinforced tubes can at times lead to occlusion of a patent airway. To change this tube intraoperatively with distorted oral anatomy could be an anaesthetic challenge

Mortality predictors during the third wave of COVID-19 pandemic: A multicentric retrospective analysis from tertiary care centers of Western India

Background: The COVID-19 has a varied mode of presentation in different regions of the world. This multicentric study was planned to evaluate the survival outcomes in intensive care unit-admitted patients admitted during the third wave of the COVID-19 pandemic on the basis of clinicodemographic profile and vaccination status. Methodology: Data from 299 patients admitted to three tertiary care centers in Western India were collected and analyzed. Based on survival outcomes, all patients were divided into two groups: survivors and nonsurvivors. Univariate analysis of the demographic profile, comorbidities, vaccination status, and disease severity was performed, whereas multivariate analysis was performed to predict independent factors associated with mortality. Results: Among total 299 studied patients, 208 (69.5%) patients survived and 91 (30.4%) did not. The number of elderly patients and patients with comorbidities such as diabetes, tuberculosis, chronic obstructive pulmonary disease, cardiovascular and respiratory diseases, and malignancy were more prevalent among nonsurvivors. Patients who did not receive a single dose of vaccine were higher in the nonsurvivor group (P = 0.037); however, no significant difference in survival outcome was found if patients had received the first or both doses of vaccine. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score at 24 h after admission and Sequential Organ Failure Assessment (SOFA) score at admission were significantly higher in nonsurvivors compared to survivors (P < 0.0001). On multivariate analysis, APACHE II and SOFA scores were found to be independent predictors of outcome. Conclusions: Older age, presence of comorbidities, nonvaccination and higher disease severity scores affected mortality during the third wave of COVID-19

Unravelling the synergistic interaction of Thrips tabaci and newly recorded, Thrips parvispinus with Alternaria porri (Ellis.) Cif., inciting onion purple blotch

Onion purple blotch is the most indispensable foliar disease of crop and has become a major concern for farmers and research fraternity. An attempt to investigate the role of injury in parasitism by Alternaria porri indicated that disease incidence and severity enhance considerably with injury. Thrips injured plants inoculated with A. porri presented 100% incidence and 52–72% severity while mechanically injured plants inoculated with A. porri showed 60–70% incidence and 28–34% severity. The uninjured plants showed considerably less disease incidence (30–40%) and severity (10–16%). Injured inoculated plants presented reduced leaf length and leaf area while the leaf diameter remained unaffected. The lesion number, lesion length and size was substantially enhanced with concomitant infestation of pest and pathogen. Thrips tabaci injury led to more pronounced symptoms of purple blotch compared to Thrips parvispinus injury. There was substantial decrease in photosynthetic rate and chlorophyll content with stress imposed on plant whilst the relative stress injury was enhanced. The induction of injury and inoculation of A. porri had an impact on the concentration of total phenolics, total soluble sugars, total proteins and hydrogen peroxide in onion leaves. A. porri combined with injury caused a more pronounced decrease in total soluble sugars and total protein content while enhancement in total phenolics and hydrogen peroxide content compared to uninjured plants. The dynamic nature of morpho-physiological and biochemical changes owing to stress conditions imposed on onion plant adds an extra layer of complexity in understanding the onion plant physiology and their ability to work out in response to challenging environment conditions

ECM1 silenced cells, as evaluated by western blots, showed significantly reduced cell attachment (*p<0.01) for both A375 and M21 cell lines when compared to cells transfected with NT siRNA.

<p>Attachment was measured as described in the methods section.</p