118 research outputs found

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

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    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\u2032 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 \u3b1-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

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

    Get PDF
    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?

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    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

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    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

    Forensic Implications of Anatomical Education and Surgical Training With Cadavers

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    Anatomical education and surgical training with cadavers are usually considered an appropriate method of teaching, above all for all surgeons at various levels. Indeed, in such a way they put into practice and exercise a procedure before performing it live, reducing the learning curve in a safe environment and the risks for the patients. Really, up to now it is not clear if the nonuse of the cadavers for anatomical education and surgical training can have also forensic implications. A substantial literature research was used for this review, based on PubMed and Web of Science database. From this review, it is clear that the cadaveric training could be considered mandatory, both for surgeons and for medical students, leading to a series of questions with forensic implications. Indeed, there are many evidences that a cadaver lab can improve the learning curve of a surgeon, above all in the first part of the curve, in which frequent and severe complications are possible. Consequently, a medical responsibility for residents and surgeons which perform a procedure without adequate training could be advised, but also for hospital, that has to guarantee a sufficient training for its surgeons and other specialists through cadaver labs. Surely, this type of training could help to improve the practical skills of surgeons working in small hospitals, where some procedures are rare. Cadaver studies can permit a better evaluation of safety and efficacy of new surgical devices by surgeons, avoiding using patients as ≪guinea pigs≫. Indeed, a legal responsibility for a surgeon and other specialists could exist in the use of a new device without an apparent regulatory oversight. For a good medical practice, the surgeons should communicate to the patient the unsure procedural risks, making sure the patients' full understanding about the novelty of the procedure and that they have used this technique on few, if any, patients before. Cadaver training could represent a shortcut in the standard training process, increasing both the surgeon learning curve and patient confidence. Forensic clinical anatomy can supervise and support all these aspects of the formation and of the use of cadaver training

    Pyridoxine/pyridoxamine 5\u2032-phosphate oxidase (Sgll/PNPO) is important for DNA integrity and glucose homeostasis maintenance in Drosophila

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    Pyridoxine/pyridoxamine 5\u2032-phosphate oxidase (PNPO) and pyridoxal kinase (PDXK) cooperate to produce pyridoxal 5\u2032-phosphate (PLP), the active form of vitamin B6. PDXK phosphorylates pyridoxine, pyridoxamine, and pyridoxal by producing PNP, PMP, and PLP, whereas PNPO oxidizes PNP, PMP, into PLP. We previously demonstrated that PDXK depletion in Drosophila and human cells impacts on glucose metabolism and DNA integrity. Here we characterized sgll, the Drosophila ortholog of PNPO gene, showing that its silencing by RNA interference elicits chromosome aberrations (CABs) in brains and induces diabetic hallmarks such as hyperglycemia and small body size. We showed that in sgllRNAi neuroblasts CABs are largely produced by the genotoxic effect of the advanced glycation end products triggered by high glucose. As in sgllRNAi cells, part of PLP is still produced by PDXK activity, these data suggest that PLP dosage need to be tightly regulated to guarantee glucose homeostasis and DNA integrity

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

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    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

    Proctologia

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    CD-ROM interattivo di tecnica chirurgic
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