Combined whole-body vibration, resistance exercise, and sustained vascular occlusion increases PGC-1α and VEGF mRNA abundances

We previously reported that high load resistance exercise with superimposed whole-body vibration and sustained vascular occlusion (vibroX) markedly improves cycling endurance capacity, increases capillary-to-fibre ratio and skeletal muscle oxidative enzyme activity in untrained young women. These findings are intriguing, since increases in oxidative muscle phenotype and endurance capacity are typically induced by endurance but not heavy resistance exercise. Here, we tested the hypothesis that vibroX activates genes associated with mitochondrial biogenesis and angiogenesis. Eight healthy, recreationally resistance-trained young men performed either vibroX or resistance exercise (RES) in a randomised, cross-over design. Needle biopsies (M. vastus lateralis) were obtained at rest and 3h post-exercise. Changes in relative gene expression levels were assessed by real-time quantitative PCR. After vibroX, vascular endothelial growth factor and peroxisome proliferator-activated receptor-γ coactivator 1α mRNA abundances increased to 2- and 4.4-fold, respectively, but did not significantly change above resting values after RES. Other genes involved in mitochondrial biogenesis were not affected by either exercise modality. While vibroX increased the expression of hexokinase II, xanthine dehydrogenase, and manganese superoxide dismutase mRNA, there were no changes in these transcripts after RES. This study demonstrates that high load resistance exercise with superimposed whole-body vibration and sustained vascular occlusion activates metabolic and angiogenic gene programs, which are usually activated after endurance but not resistance exercise. Thus, targeted modification of high load resistance exercise by vibration and vascular occlusion might represent a novel strategy to induce endurance-type muscle adaptation

Transformación en regadío de 42 ha. en el término municipal de Luna (Zaragoza)orientada a la alimentación de una explotación ovina ya existente de 1300 cabezas

El cambio climático está afectando al mundo en que vivimos y lo podemos ver en el aumento de épocas de sequía y enla concentración de lluvias en algunas épocas del año. Esto lo vienen observando los agricultores y ganaderos de nuestras regiones y ante ello intentan buscar soluciones técnicas que aumneten la rentabilidad de sus explotaciones. Este es el caso del promotor de este proyecto, agricultor y ganadero de una zona semiárida que ante la posibilidad de transformar en regadío y asegurarse las producciones a lo largo de los años en una parte de su explotación encarga el proyecto de transformar en regadío sus parcelas. La finalidad de la transformación en riego es la de aumnetar las producciones de los cultivos aumentado su rentabilidad y proporcionar al ganado de la explotación alimento durante todo el año. Tras unas condiciones que propone el promotor se realizan los direntes cálculos para la transformación de una parcela de secano a regadío mediante aspersión en cobertura total. Para ello se han tenido en cuenta los cultivos más apropiados para la zona, con sus necesidades y buscando que estos cultivos sean aprovechados, tanto las producciones como los restos, por la ganadería. Para calcular las necesidades ganaderas de la explotación se han tenido en cuenta los gastos en alimento durante todo el año. Como todo proyecto técnico se ha calculado la viabilidad de este y se observa que la inversión es viable y rentable

Prospective randomized controlled trial of simulator-based versus traditional in-surgery laparoscopic camera navigation training

Background: Surgical residents often use a laparoscopic camera in minimally invasive surgery for the first time in the operating room (OR) with no previous education or experience. Computer-based simulator training is increasingly used in residency programs. However, no randomized controlled study has compared the effect of simulator-based versus the traditional OR-based training of camera navigation skills. Methods: This prospective randomized controlled study included 24 pregraduation medical students without any experience in camera navigation or simulators. After a baseline camera navigation test in the OR, participants were randomized to six structured simulator-based training sessions in the skills lab (SL group) or to the traditional training in the OR navigating the camera during six laparoscopic interventions (OR group). After training, the camera test was repeated. Videos of all tests (including of 14 experts) were rated by five blinded, independent experts according to a structured protocol. Results: The groups were well randomized and comparable. Both training groups significantly improved their camera navigational skills in regard to time to completion of the camera test (SL P=0.049; OR P=0.02) and correct organ visualization (P=0.04; P=0.03). Horizon alignment improved without reaching statistical significance (P=0.20; P=0.09). Although both groups spent an equal amount of actual time on camera navigation training (217 vs. 272min, P=0.20), the SL group spent significantly less overall time in the skill lab than the OR group spent in the operating room (302 vs. 1002min, P<0.01). Conclusion: This is the first prospective randomized controlled study indicating that simulator-based training of camera navigation can be transferred to the OR using the traditional hands-on training as controls. In addition, simulator camera navigation training for laparoscopic surgery is as effective but more time efficient than traditional teachin

Management of Anastomotic Ulcers After Roux-en-Y Gastric Bypass: Results of an International Survey

Background: Anastomotic ulcers (AUs) after Roux-en-Y gastric bypass (RYGB) occur in up to 16% of patients. In an international survey among members of the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO), current preventative and therapeutic strategies in AU were analyzed. Methods: An Internet-based survey was performed. Results: One hundred eighty-nine surgeons completed the survey. Preoperative screening for Helicobacter pylori is performed by 65%. Eighty-eight percent of them prophylactically prescribe antacids for 3months after surgery (interquartile range (IQR) 1-6). In case of AU, 99% of participants opt for proton pump inhibitors (PPIs) either alone (60%) or in combination with sucralfate (39%). After ulcer resolution, 52% continue PPI for 6 (3-6) months. In case of AU recurrence, 56% continue with conservative treatment. In contrast, 41% of them favor a renewal of the gastrojejunal anastomosis either combined with truncal vagotomy (18%) or with gastric remnant resection (13%), and only 2% choose to resect both gastric pouch and gastric remnant with subsequent reconstruction by esophagojejunostomy. In case of recurrence after surgical revision, 46% of participants opt again for a conservative approach, while 36% chose to redo the gastrojejunostomy once again. Conclusions: The majority of bariatric surgeons recommend preoperative screening and eradication of H. pylori as well as prophylactic use of PPI. If an AU is diagnosed, the role of PPI as a first-line treatment seems to be undisputed. However, dosage and duration of therapy remain unclear. In refractory AU, there is no consensus among bariatric surgeons whether conservative treatment or surgical revision should be performed

Management of anastomotic ulcers after Roux-en-Y gastric bypass: results of an international survey

BACKGROUND: Anastomotic ulcers (AUs) after Roux-en-Y gastric bypass (RYGB) occur in up to 16% of patients. In an international survey among members of the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO), current preventative and therapeutic strategies in AU were analyzed. METHODS: An Internet-based survey was performed. RESULTS: One hundred eighty-nine surgeons completed the survey. Preoperative screening for Helicobacter pylori is performed by 65%. Eighty-eight percent of them prophylactically prescribe antacids for 3 months after surgery (interquartile range (IQR) 1-6). In case of AU, 99% of participants opt for proton pump inhibitors (PPIs) either alone (60%) or in combination with sucralfate (39%). After ulcer resolution, 52% continue PPI for 6 (3-6) months. In case of AU recurrence, 56% continue with conservative treatment. In contrast, 41% of them favor a renewal of the gastrojejunal anastomosis either combined with truncal vagotomy (18%) or with gastric remnant resection (13%), and only 2% choose to resect both gastric pouch and gastric remnant with subsequent reconstruction by esophagojejunostomy. In case of recurrence after surgical revision, 46% of participants opt again for a conservative approach, while 36% chose to redo the gastrojejunostomy once again. CONCLUSIONS: The majority of bariatric surgeons recommend preoperative screening and eradication of H. pylori as well as prophylactic use of PPI. If an AU is diagnosed, the role of PPI as a first-line treatment seems to be undisputed. However, dosage and duration of therapy remain unclear. In refractory AU, there is no consensus among bariatric surgeons whether conservative treatment or surgical revision should be performed

Efficacy and Safety of Rivaroxaban for Postoperative Thromboprophylaxis in Patients After Bariatric Surgery: A Randomized Clinical Trial.

IMPORTANCE Venous thromboembolism (VTE) is a leading cause of morbidity and mortality after bariatric surgery. Clinical end point studies on thromboprophylaxis with direct oral anticoagulants in patients undergoing bariatric surgery are lacking. OBJECTIVE To assess the efficacy and safety of a prophylactic dose of 10 mg/d of rivaroxaban for both 7 and 28 days after bariatric surgery. DESIGN, SETTING, AND PARTICIPANTS This assessor-blinded, phase 2, multicenter randomized clinical trial was conducted from July 1, 2018, through June 30, 2021, with participants from 3 academic and nonacademic hospitals in Switzerland. INTERVENTION Patients were randomized 1 day after bariatric surgery to 10 mg of oral rivaroxaban for either 7 days (short prophylaxis) or 28 days (long prophylaxis). MAIN OUTCOMES AND MEASURES The primary efficacy outcome was the composite of deep vein thrombosis (symptomatic or asymptomatic) and pulmonary embolism within 28 days after bariatric surgery. Main safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and mortality. RESULTS Of 300 patients, 272 (mean [SD] age, 40.0 [12.1] years; 216 women [80.3%]; mean body mass index, 42.2) were randomized; 134 received a 7-day and 135 a 28-day VTE prophylaxis course with rivaroxaban. Only 1 thromboembolic event (0.4%) occurred (asymptomatic thrombosis in a patient undergoing sleeve gastrectomy with extended prophylaxis). Major or clinically relevant nonmajor bleeding events were observed in 5 patients (1.9%): 2 in the short prophylaxis group and 3 in the long prophylaxis group. Clinically nonsignificant bleeding events were observed in 10 patients (3.7%): 3 in the short prophylaxis arm and 7 in the long prophylaxis arm. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, once-daily VTE prophylaxis with 10 mg of rivaroxaban was effective and safe in the early postoperative phase after bariatric surgery in both the short and long prophylaxis groups. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03522259

Patterns of HER-2/neu Amplification and Overexpression in Primary and Metastatic Breast Cancer

Background: Only 25% of patients with HER-2/neu-positive metastatic breast tumors respond favorably to trastuzamab (Herceptin) treatment. We hypothesized that a high failure rate of patients on trastuzamab could result if some of the metastases were HER-2 negative and these metastases ultimately determine the course of the disease. Methods: We used tissue microarrays (TMAs) containing four samples each from 196 lymph node-negative primary tumors, 196 lymph node-positive primary tumors, and three different lymph node metastases from each lymph node-positive tumor to estimate HER-2 gene amplification by fluorescence in situ hybridization (FISH) and Her-2 protein overexpression by immunohistochemistry (IHC). Results: FISH and IHC analyses gave the same result with respect to HER-2 status for 93.7% of the tissues contained in the TMAs. Tissue samples were, therefore, considered to be HER-2 positive if they were positive for either HER-2 DNA amplification or Her-2 protein expression and HER-2 negative if both FISH and IHC gave a negative result. The HER-2 status of lymph node-positive primary tumors was maintained in the majority of their metastases. For HER-2-positive primary tumors, 77% (95% confidence interval [CI] = 59% to 90%) had entirely HER-2-positive metastases, 6.5% (95% CI = 8% to 21%) had entirely HER-2-negative metastases, and 16.3% (95% CI = 5% to 34%) had a mixture of HER-2-positive and HER-2-negative metastases. For HER-2-negative primary tumors, 95% (95% CI = 88% to 98%) had metastases that were entirely negative for HER-2. Conclusions: Our data suggest that differences in HER-2 expression between primary tumors and their lymph node metastases cannot explain the high fraction of nonresponders to trastuzamab therap

Combined whole-body vibration, resistance exercise, and sustained vascular occlusion increases PGC-1α and VEGF mRNA abundances

We previously reported that high load resistance exercise with superimposed whole-body vibration and sustained vascular occlusion (vibroX) markedly improves cycling endurance capacity, increases capillary-to-fibre ratio and skeletal muscle oxidative enzyme activity in untrained young women. These findings are intriguing, since increases in oxidative muscle phenotype and endurance capacity are typically induced by endurance but not heavy resistance exercise. Here, we tested the hypothesis that vibroX activates genes associated with mitochondrial biogenesis and angiogenesis. Eight healthy, recreationally resistance-trained young men performed either vibroX or resistance exercise (RES) in a randomised, cross-over design. Needle biopsies (M. vastus lateralis) were obtained at rest and 3 h post-exercise. Changes in relative gene expression levels were assessed by real-time quantitative PCR. After vibroX, vascular endothelial growth factor and peroxisome proliferator-activated receptor-γ coactivator 1α mRNA abundances increased to 2- and 4.4-fold, respectively, but did not significantly change above resting values after RES. Other genes involved in mitochondrial biogenesis were not affected by either exercise modality. While vibroX increased the expression of hexokinase II, xanthine dehydrogenase, and manganese superoxide dismutase mRNA, there were no changes in these transcripts after RES. This study demonstrates that high load resistance exercise with superimposed whole-body vibration and sustained vascular occlusion activates metabolic and angiogenic gene programs, which are usually activated after endurance but not resistance exercise. Thus, targeted modification of high load resistance exercise by vibration and vascular occlusion might represent a novel strategy to induce endurance-type muscle adaptations

Statins reduce intratumor cholesterol affecting adrenocortical cancer growth

Mitotane causes hypercholesterolemia in ACC patients. We suppose that cholesterol increases within the tumor and can be used to activate proliferative pathways. In this study, we used statins to decrease intratumor cholesterol and investigated the effects on ACC growth related to ER\u3b1 action at the nuclear and mitochondrial levels. We first used microarray to investigate mitotane effect on genes involved in cholesterol homeostasis and evaluated their relationship with patients' survival in ACC TCGA. We then blocked cholesterol synthesis with simvastatin and determined the effects on H295R cell proliferation, estradiol production and ER\u3b1 activity in vitro and in xenograft tumors. We found that mitotane increases intratumor cholesterol content and expression of genes involved in cholesterol homeostasis, among them INSIG, whose expression affects patients' survival. Treatment of H295R cells with simvastatin to block cholesterol synthesis decreased cellular cholesterol content and this affected cell viability. Simvastatin reduced estradiol production and decreased nuclear and mitochondrial ER\u3b1 function. A mitochondrial target of ER\u3b1, the respiratory complex IV (COX IV) was reduced after simvastatin treatment, which profoundly affected mitochondrial respiration activating apoptosis. In vivo experiments confirmed the ability of simvastatin to reduce tumor volume and weight of grafted H295R cells, intratumor cholesterol content, Ki-67 and ER\u3b1, COX IV expression and activity and increase TUNEL positive cells. Collectively these data demonstrate that a reduction in intratumor cholesterol content prevents estradiol production, inhibits mitochondrial respiratory chain inducing apoptosis in ACC cells. Inhibition of mitochondrial respiration by simvastatin represents a novel strategy to counteract ACC growth