ENDEAVORS TOWARD NOVEL SYNTHETIC ROADMAPS IN THE SYNTHESIS OF PERTINENT PHARMACOLOGICAL MOLECULAR SCAFFOLD MOIETIES

One of the main goals in the GML lab group is the development of novel, economical, and environmentally friendly organic methods for the synthesis of pharmacologically relevant molecular moieties. The most salient pieces of data to the GML lab group members, reading dependable organic journals, are finding organic moieties that are largely unexplored, finding organic moieties which various research groups are having difficulty synthesizing, and finding complex organic procedures to key organic structures that can be easily reduced, or reconstructed, into novel methods that are more economical and environmentally friendly. By looking at these unexplored molecules, as well as hard to reach organic moieties, the GML lab group employs various organic methods to break down the target moiety at hand in order to recreate these compounds using superior novel methodologies. In my time working within the GML lab group , I successfully introduced a novel synthesis route for the Lewis acid catalyzed synthesis of hexahydrobenzofuranones, a selective synthesis of pyrrolidines, pyrrolines, and azepines from haloaziridines, and a photoisomerization reaction of vinyl oxaziridines from vinyl nitrones. It is the hope of the GML lab to use these synthetic strategies, and the respective synthesis routes developed from them, to improve on existing synthetic organic chemistry through reactions which rely on mild conditions to afford crucial organic moieties

Optimising child accident research outcomes: An action research project on maximising the dissemination and implementation of the Summer Research Scholarship Project reports and recommendations of the Child Accident Prevention Foundation of New Zealand

A key objective of the Child Accident Prevention Foundation of New Zealand (hereafter referred to as "CAPFNZ" or "the Foundation") is to reduce the incidence and severity of child accidents. The reports and recommendations that arise from the Foundation's Summer Research Scholarship (SRS) projects have the potential to be a major means to achieving this end. The purpose of this research was to investigate the extent to which the SRS projects were achieving that objective, by assessing the degree to which CAPFNZ SRS reports and especially their recommendations are currently in the public domain. The research also identified the current barriers or obstacles to dissemination, and determined cost-effective ways in which dissemination and implementation of these reports and their findings could be enhanced. Our proposal foreshadowed the prospect of this project yielding a demonstration website as one approach to achieving a more effective distribution of CAPFNZ SRS reports and related material

Combination antidepressants : use by GPs and psychiatrists

Background : Current treatment of depression fails to achieve remission in 50% of patients. Combinations of two antidepressants are used by some Australian psychiatrists.Objective : This article investigates the pros and cons of combination antidepressant therapy and provides suggestions for when to consider their use, which combinations to choose, and how to introduce combination antidepressant therapies.Discussion : Combining two antidepressants is a controversial strategy, with supporters and critics arguing its efficacy and safety from opposing perspectives. The use of combination antidepressant therapies may facilitate remission from depression. However, there is limited evidence supporting these treatments, and safety concerns are often cited. There is some support for combination therapies in selected cases from international bodies. After considering risks and benefits on a case-by-case basis, careful use of selected combination antidepressant therapy may be one of a range of effective treatments for some individuals suffering from depression.<br /

Enhanced recovery after surgery

Enhanced Recovery or Fast Track Recovery after Surgery protocols (ERAS) have significantly changed perioperative care following colorectal surgery and are promoted as reducing the stress response to surgery. The present systematic review aimed to examine the impact on the magnitude of the systemic inflammatory response (SIR) for each ERAS component following colorectal surgery using objective markers such as C-reactive protein (CRP) and interleukin-6 (IL-6). A literature search was performed of the US National Library of Medicine (MEDLINE), EMBASE, PubMed, and the Cochrane Database of Systematic Reviews using appropriate keywords and subject headings to February 2015. Included studies had to assess the impact of the selected ERAS component on the SIR using either CRP or IL-6. Nineteen studies, including 1898 patients, were included. Fourteen studies (1246 patients) examined the impact of laparoscopic surgery on the postoperative markers of SIR. Ten of these studies (1040 patients) reported that laparoscopic surgery reduced postoperative CRP. One study (53 patients) reported reduced postoperative CRP using opioid-minimising analgesia. One study (142 patients) reported no change in postoperative CRP following preoperative carbohydrate loading. Two studies (108 patients) reported conflicting results with respect to the impact of goal-directed fluid therapy on postoperative IL-6. No studies examined the effect of other ERAS components, including mechanical bowel preparation, antibiotic prophylaxis, thromboprophylaxis, and avoidance of nasogastric tubes and peritoneal drains on markers of the postoperative SIR following colorectal surgery. The present systematic review shows that, with the exception of laparoscopic surgery, objective evidence of the effect of individual components of ERAS protocols in reducing the stress response following colorectal surgery is limited

Validation of a modified clinical risk score to predict cancer-specific survival for stage II colon cancer

Many patients with stage II colon cancer will die of their disease despite curative surgery. Therefore, identification of patients at high risk of poor outcome after surgery for stage II colon cancer is desirable. This study aims to validate a clinical risk score to predict cancer-specific survival in patients undergoing surgery for stage II colon cancer. Patients undergoing surgery for stage II colon cancer in 16 hospitals in the West of Scotland between 2001 and 2004 were identified from a prospectively maintained regional clinical audit database. Overall and cancer-specific survival rates up to 5 years were calculated. A total of 871 patients were included. At 5 years, cancer-specific survival was 81.9% and overall survival was 65.6%. On multivariate analysis, age ≥75 years (hazard ratio (HR) 2.11, 95% confidence intervals (CI) 1.57–2.85; P&#60;0.001) and emergency presentation (HR 1.97, 95% CI 1.43–2.70; P&#60;0.001) were independently associated with cancer-specific survival. Age and mode of presentation HRs were added to form a clinical risk score of 0–2. The cancer-specific survival at 5 years for patients with a cumulative score 0 was 88.7%, 1 was 78.2% and 2 was 65.9%. These results validate a modified simple clinical risk score for patients undergoing surgery for stage II colon cancer. The combination of these two universally documented clinical factors provides a solid foundation for the examination of the impact of additional clinicopathological and treatment factors on overall and cancer-specific survival

Long-term follow-up of patients undergoing resection of tnm stage i colorectal cancer: an analysis of tumour and host determinants of outcome

Background Screening for colorectal cancer improves cancer-specific survival (CSS) through the detection of early-stage disease; however, its impact on overall survival (OS) is unclear. The present study examined tumour and host determinants of outcome in TNM Stage I disease. Methods All patients with pathologically confirmed TNM Stage I disease across 4 hospitals in the North of Glasgow between 2000 and 2008 were included. The preoperative modified Glasgow Prognostic Score (mGPS) was used as a marker of the host systemic inflammatory response (SIR). Results There were 191 patients identified, 105 (55 %) were males, 91 (48 %) were over the age of 75 years and 7 (4 %) patients underwent an emergency operation. In those with a preoperative CRP result (n = 150), 35 (24 %) patients had evidence of an elevated mGPS. Median follow-up of survivors was 116 months (minimum 72 months) during which 88 (46 %) patients died; 7 (8 %) had postoperative deaths, 15 (17 %) had cancer-related deaths and 66 (75 %) had non-cancer-related deaths. 5-year CSS was 95 % and OS was 76 %. On univariate analysis, advancing age (p &#60; 0.001), emergency presentation (p = 0.008), and an elevated mGPS (p = 0.012) were associated with reduced OS. On multivariate analysis, only age (HR = 3.611, 95 % CI 2.049–6.365, p &#60; 0.001) and the presence of an elevated mGPS (HR = 2.173, 95 % CI 1.204–3.921, p = 0.010) retained significance. Conclusions In patients undergoing resection for TNM Stage I colorectal cancer, an elevated mGPS was an objective independent marker of poorer OS. These patients may benefit from a targeted intervention

Morphology of the Esophageal Hiatus: Is It Different in 3 Types of Hiatus Hernias?

Background/aimsThe esophageal hiatus is formed by the right crus of the diaphragm in the majority of subjects. Contraction of the hiatus exerts a sphincter-like action on the lower esophageal sphincter (LES). The aim is to study the hiatal anatomy (using CT scan imaging) and function (using high-resolution manometry [HRM]), and esophageal motor function in patients with sliding and paraesophageal hiatal hernia.MethodsWe assessed normal subjects (n = 20), patients with sliding type 1 hernia (n = 18), paraesophageal type 2 hernia (n = 19), and mixed type 3 hernia (n = 19). Hernia diagnosis was confirmed on the upper gastrointestinal series. The hiatal morphology was constructed from the CT scan images. The LES pressure and relaxation, percent peristalsis, bolus pressure, and hiatal squeeze pressure were assessed by HRM.ResultsThe CT images revealed that the esophageal hiatus is formed by the right crus of the diaphragm in all normal subjects and 86% of hernia patients. The hiatus is elliptical in shape with a surface area of 1037 mm2 in normal subjects. The hiatal dimensions were larger in patients compared to normal subjects. The HRM revealed impaired LES relaxation and higher bolus pressure in patients with paraesophageal compared to the sliding hernia. The hiatal pinch on HRM was recognized in significantly higher number of patients with sliding as compared to paraesophageal hernia.ConclusionsUsing a novel approach, we provide details of the esophageal hiatus in patients with various kinds of hiatal hernia. Impaired LES relaxation in paraesophageal hernia may play a role in its pathophysiology and genesis of symptoms