Investigating the role of CNAG_05113 in the carnitine biosynthesis pathway in \u3ci\u3eCryptococcus neoformans.\u3c/i\u3e

Cryptococcus neoformans, the leading cause of fungal meningitis, is a fungal pathogen that causes severe infection of the central nervous system in patients with compromised immune systems, typically caused by HIV/AIDS. C. neoformans infections are present in developed countries including the United States, but most fatalities occur in sub-Saharan Africa where antiretroviral therapy, the treatment for HIV/AIDS, is less accessible. Current treatments for severe cryptococcal infections are extensive and outdated. There is a critical need for an improved understanding of the fungus and new targeted therapies. Our goal is to identify metabolic pathways important to the survival of C. neoformans in the human host that can then be targeted for the development of new antifungal reagents. Lung alveolar macrophages, which present a first line of host defense against C. neoformans infection, provide a glucose- and amino acid-poor environment, and nonpreferred carbon sources such as lactate and acetate are likely important early in establishment of a pulmonary infection. Utilizing a genetic screen performed by a graduated PhD student in my lab to identify genes necessary for growth on acetate, we have discovered that the last step of carnitine biosynthesis is required. Our goal was to identify other steps of the carnitine biosynthetic pathway. Using the amino acid sequence of the fungal Candida albicans 4-trimethylaminobutyraldehyde dehydrogenase (TMABADH), the third enzyme of the carnitine biosynthesis pathway which converts 4-trimethylaminobutyraldehyde (TMABA) to gamma-butyrobetaine (γBB), we identified CNAG_05113 as the encoding gene in C. neoformans. Using a strain in which the CNAG_05113 gene was deleted, the mutant was tested for growth and virulence deficiencies. CNAG_05113 cells have inhibited growth in conditions with acetate as the sole carbon source. When reintroduced to carnitine and carnitine pathway intermediates, growth of mutant cells was restored. These results indicate that CNAG_05113 encodes the third step in carnitine biosynthesis. Future research is to identify the genes encoding other steps of the carnitine biosynthesis pathway and to biochemically characterize the encoded enzymes

Physical properties of seven binary and higher-order multiple OB systems

Analyses of multi-epoch, high-resolution (~ 50000) optical spectra of seven early-type systems provided various important new insights with respect to their multiplicity. First determinations of orbital periods were made for HD 92206C (2.022 d), HD 112244 (27.665 d), HD 164438 (10.25 d), HD 123056A (~ 1314 d) and HD 123056B (< 2 d); the orbital period of HD 318015 could be improved (23.445975 d). Concerning multiplicity, a third component was discovered for HD 92206C by means of He I line profiles. For HD 93146A, which was hitherto assumed to be SB1, lines of a secondary component could be discerned. HD 123056 turns out to be a multiple system consisting of a high-mass component A (~ O8.5) displaying a broad He II 5411 A feature with variable radial velocity, and of an inner pair B (~ B0) with double He I lines. The binary HD 164816 was revisited and some of its system parameters were improved. In particular, we determined its systemic velocity to be -7 km/s, which coincides with the radial velocity of the cluster NGC 6530. This fact, together with its distance, suggests the cluster membership of HD 164816. The OB system HD 318015 (V1082 Sco) belongs to the rare class of eclipsing binaries with a supergiant primary (B0.5/0.7). Our combined orbital and light-curve analysis suggests that the secondary resembles an O9.5III star. Our results for a limited sample corroborate the findings that many O stars are actually massive multiple systems.Comment: 16 pages, 16 figures, to appear in Astronomy and Astrophysic

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien\u2013Dindo classification system. Results: A total of 3288 patients were included in the analysis, of whom 301 (9\ub72 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4\u20137) and 7 (6\u20138) days respectively (P &lt; 0\ub7001). There were no significant differences in rates of readmission between these groups (6\ub76 versus 8\ub70 per cent; P = 0\ub7499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0\ub790, 95 per cent c.i. 0\ub755 to 1\ub746; P = 0\ub7659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34\ub77 versus 39\ub75 per cent; major 3\ub73 versus 3\ub74 per cent; P = 0\ub7110). Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien–Dindo classification system. Results: A total of 3288 patients were included in the analysis, of whom 301 (9·2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4–7) and 7 (6–8) days respectively (P &lt; 0·001). There were no significant differences in rates of readmission between these groups (6·6 versus 8·0 per cent; P = 0·499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0·90, 95 per cent c.i. 0·55 to 1·46; P = 0·659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34·7 versus 39·5 per cent; major 3·3 versus 3·4 per cent; P = 0·110). Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients

Timing of nasogastric tube insertion and the risk of postoperative pneumonia: an international, prospective cohort study

Aim: Aspiration is a common cause of pneumonia in patients with postoperative ileus. Insertion of a nasogastric tube (NGT) is often performed, but this can be distressing. The aim of this study was to determine whether the timing of NGT insertion after surgery (before versus after vomiting) was associated with reduced rates of pneumonia in patients undergoing elective colorectal surgery. Method: This was a preplanned secondary analysis of a multicentre, prospective cohort study. Patients undergoing elective colorectal surgery between January 2018 and April 2018 were eligible. Those receiving a NGT were divided into three groups, based on the timing of the insertion: routine NGT (inserted at the time of surgery), prophylactic NGT (inserted after surgery but before vomiting) and reactive NGT (inserted after surgery and after vomiting). The primary outcome was the development of pneumonia within 30&nbsp;days of surgery, which was compared between the prophylactic and reactive NGT groups using multivariable regression analysis. Results: A total of 4715 patients were included in the analysis and 1536 (32.6%) received a NGT. These were classified as routine in 926 (60.3%), reactive in 461 (30.0%) and prophylactic in 149 (9.7%). Two hundred patients (4.2%) developed pneumonia (no NGT 2.7%; routine NGT 5.2%; reactive NGT 10.6%; prophylactic NGT 11.4%). After adjustment for confounding factors, no significant difference in pneumonia rates was detected between the prophylactic and reactive NGT groups (odds ratio 1.03, 95% CI 0.56\u20131.87, P&nbsp;=&nbsp;0.932). Conclusion: In patients who required the insertion of a NGT after surgery, prophylactic insertion was not associated with fewer cases of pneumonia within 30&nbsp;days of surgery compared with reactive insertion