DMAPT AS A POTENTIAL RADIOSENSITIZER FOR PANCREATIC CANCER CELLS

poster abstractPancreatic cancer is the fourth leading cause of cancer-related death in the United States with an estimated 37, 390 deaths expected to occur in 2012. The prognosis is very poor due to the recurrence and metastasis of the cancer with a 6% five-year survival rate for all stages combined. This study examined the effectiveness of dimethylamino-parthenolide (DMAPT) as a radiosensitizer to the human pancreatic cancer PaCa2 cell line. It is hypothe-sized that DMAPT, a bioavailable drug derived from parthenolide, will inhibit the activation of NF-κB and enhance radiation-induced cell killing of PaCa2 cells. NF-κB is a transcription factor that promotes cell survival, tumor pro-gression, and angiogenesis and reduces susceptibility to apoptosis. The re-sults show that DMAPT was toxic to the PaCa2 cell line. As a result, DMAPT suppressed cell growth and increased the doubling time of PaCa2 cells. The combination of 4μM DMAPT and radiation decreased cell survival. The PaCa2 cell line is radiosensitized by DMAPT but further investigation is required to determine the mechanism through which DMAPT works

Improving safety in care homes:protocol for evaluation of the Walsall and Wolverhampton care home improvement programme

Abstract Background Improving safety in care homes is becoming increasingly important. Care home residents typically have multiple physical and/or cognitive impairments, and adverse events like falls often lead to hospital attendance or admission. Developing a safety culture is associated with beneficial impacts on safety outcomes, but the complex needs of care home residents, coupled with staffing pressures in the sector, pose challenges for positive safety practices to become embedded at the individual and organisational levels. Staff training and education can positively enforce safety culture and reduce the incidence of harms, but improvement initiatives are often short lived and thorough evaluation is uncommon. This protocol outlines an evaluation of a large-scale care home improvement programme in the West Midlands. Methods The programme will run in 35 care homes across Walsall and Wolverhampton over 24\ua0months, and we anticipate that 30 care homes will participate in the evaluation ( n \u2009=\u20091500 staff). The programme will train staff and managers in service improvement techniques, with the aim of strengthening safety culture and reducing adverse safety event rates. The evaluation will use a pre-post design with mixed methods. Quantitative data will focus on: care home manager and staff surveys administered at several time points and analysis of adverse event rates. Data on hospital activity by residents at participating care homes will be compared to matched controls. Qualitative data on experience of training and the application of learning to practice will be collected via semi-structured interviews with staff ( n \u2009=\u200948 to 64) and programme facilitators ( n \u2009=\u20096), and staff focus groups ( n \u2009=\u200936 to 48 staff). The primary outcome measure is the change in mean score on the safety climate domain of the Safety Attitudes Questionnaire between baseline and programme end. Discussion This mixed methods evaluation of a large-scale care home improvement programme will allow a substantial amount of qualitative and quantitative data to be collected. This will enable an assessment of the extent to which care home staff training can effectively improve safety culture, lower the incidence of adverse safety events such as falls and pressure ulcers, and potentially reduce care home resident\u2019s use of acute services

Prognostic Significance of Blood Glucose Levels and Alterations Among Patients with Aluminium Phosphide Poisoning

Objectives: This study aimed to assess the prognostic significance of blood glucose levels and blood glucose alterations (i.e. hyper- or hypoglycaemia) among patients with aluminium phosphide (AlP) poisoning. Methods: This prospective observational study was conducted at the Postgraduate Institute of Medical Education & Research, Chandigarh, India, between January 2010 and June 2011. All patients presenting to the emergency department with a definitive history of AlP ingestion or symptoms compatible with AlP poisoning were included in the study. Blood glucose levels were recorded at presentation and every six hours thereafter. Alterations in blood glucose levels and other clinical and laboratory variables were subsequently compared between survivors and non-survivors. Results: A total of 116 patients with AlP poisoning were identified. Of these, 57 patients (49%) survived and 59 patients (51%) died. At presentation, the mean blood glucose levels of survivors and non-survivors were 119.9 ± 35.7 mg/dL and 159.7 ± 92.5 mg/dL, respectively (P <0.001). In comparison to the survivors, non-survivors had significantly higher heart rates, total leukocyte counts, blood glucose level alterations and serum creatinine levels (P <0.050). In addition, systolic blood pressure, Glasgow coma scale scores, arterial blood gas pH and bicarbonate values and duration of hospital stay was significantly lower compared to survivors (P <0.001). However, neither blood glucose levels at admission nor blood glucose alterations correlated independently with mortality in a multivariate analysis. Conclusion: The role of blood glucose level alterations in predicting patient outcomes in AlP poisoning cases remains inconclusive. Further studies with larger sample sizes are required.Keywords: Aluminum Phosphide; Poisoning; Blood Glucose; Hyperglycemia; Hypoglycemia; Mortality; Prognostic Factors; India

siRNA against presenilin 1 (PS1) down regulates amyloid β42 production in IMR-32 cells

<p>Abstract</p> <p>Background</p> <p>One of the pathological hallmarks of Alzheimer's disease (AD) is the deposition of the ~4 kDa amyloid β protein (Aβ) within lesions known as senile plaques. Aβ is also deposited in the walls of cerebral blood vessels in many cases of AD. A substantial proportion of the Aβ that accumulates in the AD brain is deposited as Amyloid, which is highly insoluble, proteinaceous material with a β-pleated-sheet conformation and deposited extracellularly in the form of 5-10 nm wide straight fibrils. As γ-secretase catalyzes the final cleavage that releases the Aβ42 or 40 from amyloid β -protein precursor (APP), therefore, it is a potential therapeutic target for the treatment of AD. γ-Secretase cleavage is performed by a high molecular weight protein complex containing presenilins (PSs), nicastrin, Aph-1 and Pen-2. Previous studies have demonstrated that the presenilins (PS1 and PS2) are critical components of a large enzyme complex that performs γ-secretase cleavage.</p> <p>Methods</p> <p>In this study we used RNA interference (RNAi) technology to examine the effects of small-interfering RNA (siRNA) against PS1 on expression levels of PS1 and Aβ42 in IMR-32 Cells using RTPCR, western blotting and immunofluorescence techniques.</p> <p>Results</p> <p>The results of the present study showed down regulation of PS1 and Aβ42 in IMR32 cells transfected with siRNA against PS1.</p> <p>Conclusion</p> <p>Our results substantiate the concept that PS1 is involved in γ-secretase activity and provides the rationale for therapeutic strategies aimed at influencing Aβ42 production.</p

Study of Photoluminescence Behaviour of Porous Silicon Samples Prepared at 20 mA Current Density

The paper presents a study on a series of porous silicon films of various thicknesses, prepared at 20 mA current density using a photoluminescence fitting model to determine the average crystallite size of sphe-rical shaped interconnected silicon quantum dots. Discrepancy in photoluminescence behavior of the samples is well explained with this model. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/3097

Sleep Disordered Breathing, Obesity and Atrial Fibrillation: A Mendelian Randomisation Study.

Funder: National Institute for Health Research (NIHR)It remains unclear whether the association between obstructive sleep apnoea (OSA), a form of sleep-disordered breathing (SDB), and atrial fibrillation (AF) is causal or mediated by shared co-morbidities such as obesity. Existing observational studies are conflicting and limited by confounding and reverse causality. We performed Mendelian randomisation (MR) to investigate the causal relationships between SDB, body mass index (BMI) and AF. Single-nucleotide polymorphisms associated with SDB (n = 29) and BMI (n = 453) were selected as instrumental variables to investigate the effects of SDB and BMI on AF, using genetic association data on 55,114 AF cases and 482,295 controls. Primary analysis was conducted using inverse-variance weighted MR. Higher genetically predicted SDB and BMI were associated with increased risk of AF (OR per log OR increase in snoring liability 2.09 (95% CI 1.10-3.98), p = 0.03; OR per 1-SD increase in BMI 1.33 (95% CI 1.24-1.42), p < 0.001). The association between SDB and AF was not observed in sensitivity analyses, whilst associations between BMI and AF remained consistent. Similarly, in multivariable MR, SDB was not associated with AF after adjusting for BMI (OR 0.68 (95% CI 0.42-1.10), p = 0.12). Higher BMI remained associated with increased risk of AF after adjusting for OSA (OR 1.40 (95% CI 1.30-1.51), p < 0.001). Elevated BMI appears causal for AF, independent of SDB. Our data suggest that the association between SDB, in general, and AF is attributable to mediation or confounding from obesity, though we cannot exclude that more severe SDB phenotypes (i.e., OSA) are causal for AF

Provision of ECPR during COVID-19: evidence, equity, and ethical dilemmas

The use of extracorporeal cardiopulmonary resuscitation (ECPR) to restore circulation during cardiac arrest is a time-critical, resource-intensive intervention of unproven efficacy. The current COVID-19 pandemic has brought additional complexity and significant barriers to the ongoing provision and implementation of ECPR services. The logistics of patient selection, expedient cannulation, healthcare worker safety, and post-resuscitation care must be weighed against the ethical considerations of providing an intervention of contentious benefit at a time when critical care resources are being overwhelmed by pandemic demand