Aerobic Exercise and Pharmacological Treatments Counteract Cachexia by Modulating Autophagy in Colon Cancer

Recent studies have correlated physical activity with a better prognosis in cachectic patients, although the underlying mechanisms are not yet understood. In order to identify the pathways involved in the physical activity-mediated rescue of skeletal muscle mass and function, we investigated the effects of voluntary exercise on cachexia in colon carcinoma (C26)-bearing mice. Voluntary exercise prevented loss of muscle mass and function, ultimately increasing survival of C26-bearing mice. We found that the autophagic flux is overloaded in skeletal muscle of both colon carcinoma murine models and patients, but not in running C26-bearing mice, thus suggesting that exercise may release the autophagic flux and ultimately rescue muscle homeostasis. Treatment of C26-bearing mice with either AICAR or rapamycin, two drugs that trigger the autophagic flux, also rescued muscle mass and prevented atrogene induction. Similar effects were reproduced on myotubes in vitro, which displayed atrophy following exposure to C26-conditioned medium, a phenomenon that was rescued by AICAR or rapamycin treatment and relies on autophagosome-lysosome fusion (inhibited by chloroquine). Since AICAR, rapamycin and exercise equally affect the autophagic system and counteract cachexia, we believe autophagy-triggering drugs may be exploited to treat cachexia in conditions in which exercise cannot be prescribed

Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes

Growing evidence shows that improper intake of vitamin B6 increases cancer risk and several studies indicate that diabetic patients have a higher risk of developing tumors. We previously demonstrated that in Drosophila the deficiency of Pyridoxal 5' phosphate (PLP), the active form of vitamin B6, causes chromosome aberrations (CABs), one of cancer prerequisites, and increases hemolymph glucose content. Starting from these data we asked if it was possible to provide a link between the aforementioned studies. Thus, we tested the effect of low PLP levels on DNA integrity in diabetic cells. To this aim we generated two Drosophila models of type 2 diabetes, the first by impairing insulin signaling and the second by rearing flies in high sugar diet. We showed that glucose treatment induced CABs in diabetic individuals but not in controls. More interestingly, PLP deficiency caused high frequencies of CABs in both diabetic models demonstrating that hyperglycemia, combined to reduced PLP level, impairs DNA integrity. PLP-depleted diabetic cells accumulated Advanced Glycation End products (AGEs) that largely contribute to CABs as α-lipoic acid, an AGE inhibitor, rescued not only AGEs but also CABs. These data, extrapolated to humans, indicate that low PLP levels, impacting on DNA integrity, may be considered one of the possible links between diabetes and cancer

Has Selection for Improved Agronomic Traits Made Reed Canarygrass Invasive?

Plant breeders have played an essential role in improving agricultural crops, and their efforts will be critical to meet the increasing demand for cellulosic bioenergy feedstocks. However, a major concern is the potential development of novel invasive species that result from breeders' efforts to improve agronomic traits in a crop. We use reed canarygrass as a case study to evaluate the potential of plant breeding to give rise to invasive species. Reed canarygrass has been improved by breeders for use as a forage crop, but it is unclear whether breeding efforts have given rise to more vigorous populations of the species. We evaluated cultivars, European wild, and North American invader populations in upland and wetland environments to identify differences in vigor between the groups of populations. While cultivars were among the most vigorous populations in an agricultural environment (upland soils with nitrogen addition), there were no differences in above- or below-ground production between any populations in wetland environments. These results suggest that breeding has only marginally increased vigor in upland environments and that these gains are not maintained in wetland environments. Breeding focuses on selection for improvements of a specific target population of environments, and stability across a wide range of environments has proved elusive for even the most intensively bred crops. We conclude that breeding efforts are not responsible for wetland invasion by reed canarygrass and offer guidelines that will help reduce the possibility of breeding programs releasing cultivars that will become invasive

Postoperative outcomes in oesophagectomy with trainee involvement

BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. RESULTS: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). CONCLUSION: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery

Prosthetic mesh "slim-cigarette like" for laparoscopic repair of ventral hernias: a new technique without transabdominal fixation sutures

Prosthetic mesh rolled up and fixed with stitches like a slim cigarette ("slim-mesh") for laparoscopic ventral hernia (VH) repair is an new technique which allows an easy intraperitoneally introduction, distension and circumferential fixation of a prosthetic mesh without transabdominal fixation sutures even for meshes larger than 16\ua0cm up to 30\ua0cm for the "slim-mesh" repair of wide ventral hernias. We report the technique of laparoscopic repair of VH with "slim-mesh". This technique enables an easy intra-peritoneally introduction of the mesh through the trocar because it reduces consistently its size, it allows a rapid intra-abdominal handling of the mesh and a fast and easy fixation for VH repair. The average time of surgery with "slim-mesh" for treatment of all 28 VH was 97\ua0min ranging from 57 to 160\ua0min. The average time for the repair of the 24 VH smaller than 10\ua0cm was 91 and 135\ua0min for the four VH larger than 10-22\ua0cm. This new surgical technique leads to a reduction of surgical risks avoiding the use of transfascial sutures with the associated complications. This new surgical procedure in our experience is fast, safe, simple and also easily reproducible by surgeons in laparoscopic training. This technique may be used in wide VH (larger than 10-22\ua0cm) that generally require open surgery

Stapled haemorrhoidopexy in fourth degree haemorrhoidal prolapse: is it worthwhile?

Introduction Ten years after the introduction of stapled haemorrhoidopexy few studies have stratified patients by degree of haemorrhoidal disease when analysing results. Objective The aim of this study was prospectively to evaluate 116 patients who underwent stapled anopexy conducted by the same surgeon for III or IV degree haemorrhoidal prolapse. Materials and methods One hundred and sixteen consecutive patients affected by symptomatic haemorrhoids of III or IV degree underwent stapled anopexy using the technique described by Longo in the period January 2001 to October 2003. Mean follow-up was 28.1 months. Fischer's exact test was used for statistical analysis. Results, in terms of morbidity and recurrence rates, were stratified according to degree of haemorrhoidal disease. Results There was no statistically significant difference between the results for third degree compared with fourth degree prolapse although there was a trend towards increased incidence of postoperative bleeding and recurrence. Conclusion Third degree haemorrhoidal prolapse remains the best indication for stapled haemorrhoidopexy. This procedure may also be indicated in fourth degree haemorrhoidal prolapse. Patients with fourth degree haemorrhoids may be subjected to this procedure following adequate discussion of the outcome