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Optimizing oncolytic virus design:a“Swiss army knife”approach to create a systemically delivered therapeutic

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1791-1792页

作者： Carolina S.Ilkow john Cameron bell Ottawa Hospital Research Institute 501 Smyth RoadOttawaONK1H 8L6Canada

In a recent paper published in Nature Biotechnology,Chen et al.1 describe a multiplex oncolytic virus platform that coupled with adoptive T cell therapy could solve the problem of repeat,systemic delivery of virus based *** is widely accepted that multi-targeted therapeutic approaches attacking several facets of cancer biology are necessary to effectively deal with the tumor heterogeneity that exists within and between patients.

关键词： therapeutic al. targeted

Associations between health-related fitness and patient-reported symptoms in newly diagnosed breast cancer patients

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journal of Sport and Health Science 2024年第6期13卷 851-862页

作者： Ki-Yong An Fernanda Z.Arthuso Myriam Filion Spencer j.Allen Stephanie M.Ntoukas Gordon j.bell jessica McNeil Qinggang Wang Margaret l.McNeely jeff K.Vallance lin Yang S.Nicole Culos-Reed leanne Dickau john R.Mackey Christine M.Friedenreich Kerry S.Courneya Faculty of Kinesiology Sportand RecreationCollege of Health SciencesUniversity of AlbertaEdmonton T6G 2H9Canada Department of Kinesiology School of Health and Human SciencesUniversity of North Carolina at GreensboroGreensboroNC 27412USA Department of Cancer Epidemiology and Prevention Research Cancer Care AlbertaAlberta Health ServicesCalgary T2S 3C3Canada Faculty of Rehabilitation Medicine University of AlbertaEdmonton T6G 2H9Canada Faculty of Health Disciplines Athabasca UniversityAthabasca T9S 3A3Canada Department of Oncology Cumming School of MedicineUniversity of CalgaryCalgary T2N 4N1Canada Faculty of Kinesiology University of CalgaryCalgary T2N 1N4Canada Faculty of Medicine and Dentistry University of AlbertaEdmonton T6G 2H9Canada

Background:Newly diagnosed breast cancer patients experience symptoms that may affect their quality of life,treatment outcomes,and *** and managing breast cancer-related symptoms soon after diagnosis is *** purpose of this study was to investigate the associations between health-related fitness(HRF)and patient-reported symptoms in newly diagnosed breast cancer ***:This study utilized baseline data from the Alberta Moving Beyond Breast Cancer Cohort Study that were collected within 90 days of *** measures included peak cardiopulmonary fitness(peak volume of oxygen consumption(VO_(2peak))),maximal muscular strength and endurance,flexibility,and body *** measures included depression,sleep quality,and *** multivariable logistic regression was performed for ***:Of 1458 participants,51.5%reported poor sleep quality,26.5%reported significant fatigue,and 10.4%reported moderate *** multivariable-adjusted models,lower relative VO_(2peak)was independently associated with a greater likelihood of all symptom measures,including moderate depression(pleep quality(p=0.009),significant fatigue(p=0.008),any symptom(pltiple symptoms(pld associations with all symptom measures such that all 3 lower quartiles exhibited similar elevated risk compared to the highest *** strength of the threshold associations varied by the symptom measure with odds ratios ranging from-1.5 for poor sleep quality to-3.0 for moderate depression and multiple ***,lower relative upper body muscular endurance was also independently associated with fatigue in a dose-response manner(p=0.001),and higher body weight was independently associated with poor sleep quality in an inverted U pattern(p=0.021).Conclusion:Relative VO_(2peak)appears to be a critical HRF component associated with multiple patient-reported symptoms in newly diag

关键词： Breast cancer Fatigue Depression Sleep quality Cardiorespiratory fitness

Choledocholithiasis: Evolving standards for diagnosis and management

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World journal of Gastroenterology 2006年第20期12卷 3162-3167页

作者： Marilee l Freitas Robert l bell Andrew j Duffy Department of Surgery Yale University School of Medicine 40 Temple StreetSuite 3 ANew HavenCT 06510United States

Cholelithiasis, one of the most common medical conditions leading to surgical intervention, affects approximately 10 % of the adult population in the United States. Choledocholithiasis develops in about 10%-20% of patients with gallbladder stones and the literature suggests that at least 3%-10% of patients undergoing cholecystectomy will have common bile duct （CBD） stones. CBD stones may be discovered preoperatively, intraoperatively or postoperatively Multiple modalities are available for assessing patients for choledocholithiasis including laboratory tests, ultrasound, computed tomography scans （CT）, and magnetic resonance cholangiopancreatography （MRCP）. Intraoperative cholangiography during cholecystectomy can be used routinely or selectively to diagnose CBD stones. The most common intervention for CBD stones is ERCP. Other commonly used interventions include intraoperative bile duct exploration, either laparoscopic or open. Percutaneous, transhepatic stone removal other novel techniques of biliary clearance have been devised. The availability, of equipment and skilled practitioners who are facile with these techniques varies among institutions. The timing of the intervention is olden dictated by the clinical situation.

关键词： Choledocholithiasis laparoscopy Diagnosis Treatment Cholangiogram

Update on obesity surgery

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World journal of Gastroenterology 2006年第20期12卷 3196-3203页

作者： Dan Eisenberg Andrew j Duffy Robert l bell Department of Surgery Yale University School of Medicine 40 Temple St. Suite 3A New HavenCT 06510United States

The prevalence of obesity in the United States has reached epidemic proportions. With more than 30 million Americans clinically obese, the younger population has also been affected. Surgical therapy should be offered to the severely obese patient who is refractory to nonsurgical therapy, as established by the 1991 NIH Consensus Conference on Gastrointestinal Surgery for Severe Obesity. Surgery is currently the most effective therapy for weight loss. It is far more effective than any other treatment modality, both in terms of the amount of weight loss and in terms of durability in maintaining weight loss.

关键词： Obesity Gastrointestinal surgery Roux-Y gastric bypass

Soil Water Hysteresis at low Potential

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Pedosphere 2007年第4期17卷 436-444页

作者： l.PRUNTY j.bell Department of Soil Science North Dakota State University FargoND 58105 (USA)

Knowledge of the soil water characteristic curve is fundamental for understanding unsaturated *** objective of this work was to find scanning hysteresis loops of two fine textured soils at water potentials below wilting *** was done by equilibration over NaCl solutions with water potentials of-6.6 to-18.8 MPa at 25℃.When cycled repeatedly through a series of potentials in the range noted previously both soils exhibited a hysteresis *** experimental differences in water content between the drying and wetting soils at the same water potential were much too large to be accounted for by failure to allow sufficient time to attain equilibrium as predicted by the exponential decay *** wetting versus drying differences were relatively small,however,at only 4 mg g-1 or less in absolute terms and about 3% of the mean of wetting and drying,in relative *** should be a consideration when modeling biological and physical soil processes at water contents below the wilting point,where small differences in water content result in large potential energy changes.

关键词： adsorption dry soil equilibration matric potential soil water characteristic

Controversies in the treatment of gastroesophageal reflux and achalasia

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World journal of Gastroenterology 2006年第20期12卷 3155-3161页

作者： Kurt E Roberts Andrew j Duffy Robert l bell Department of Surgery Yale University School of Medicine 40 Temple St. Suite 3 ANew HavenCT 06510United States

The immense success of laparoscopic surgery as an effective treatment of gastroesophageal reflux disease （GERD） and achalasia has established minimal invasive surgery as the gold standard for these two conditions with lower morbidity and mortality, shorter hospital stay, faster convalescence, and less postoperative pain. One controversy in the treatment of GERD evolves around laparoscopic antireflux surgery （lAP, S） as the preferred treatmerit for Barrett＇s esophagus and the procedure＇s potential to reduce the risk of adenocarcinoma of the esophagus. GERD has also been associated with respiratory symptoms, asthma and laryngeal injury, and a second controversy prompts discussions about whether total or partial fundoplication is the more appropriate treatment for GERD. A new and promising alternative in the treatment of GERD is endoluminal therapy. Three types of this new treatment option will be discussed： radiofrequency energy delivered to the lower esophageal sphincter, the creation of a mechanical barrier at the gastroesophageal junction, and the direct endoscopic tightening of the lower esophageal sphincter. laparoscopic surgery is discussed not only as a very effective treatment for GERD but also as permanent cure for achalasia. This review analyzes the three most important treatment options for achalasia： medications, pneumatic dilatation, and surgical therapy. Medications as the only true non-invasive option in the treatment of achalasia are not as effective as lAPS because of their short half-life and variable absorption due to the poor esophageal emptying. The second treatment option, pneumatic dilatation, involves the stretching of the lower esophagus and is still considered the most effective nonsurgical treatment for achalasia. Finally, surgical therapy for achalasia and the two major controversies concerning this laparoscopic treatment are discussed. The first involves the extent to which the myotomy is extended onto the stomach, and the second concer

关键词： Gastroesophageal reflux disease Nissen Toupet Fundoplication Achalasia Heller myotomy

Evolution of surgical skills training

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World journal of Gastroenterology 2006年第20期12卷 3219-3224页

作者： Kurt E Roberts Robert l bell Andrew j Duffy Department of Surgery Yale University School of Medicine 40 Temple StreetSuite 3ANew HavenCT 06510United Staets

Surgical training is changing： one hundred years of tradition is being challenged by legal and ethical concerns for patient safety, work hours restrictions, the cost of operating room time, and complications. Surgical simulation and skills training offers an opportunity to teach and practice advanced skills outside of the operating room environment before attempting them on living patients. Simulation training can be as straight forward as using real instruments and video equipment to manipulate simulated ＂tissue＂ in a box trainer. More advanced, virtual reality simulators are now available and ready for widespread use. Early systems have demonstrated their effectiveness and discriminative ability. Newer systems enable the development of comprehensive curricula and full procedural simulations. The Accreditation Council of Graduate Medical Education＇s （ACGME） has mandated the development of novel methods of training and evaluation. Surgical organizations are calling for methods to ensure the maintenance of skills, advance surgical training, and to credential surgeons as technically competent. Simulators in their current form have been demonstrated to improve the operating room performance of surgical residents. Development of standardized training curricula remains an urgent and important agenda, particularly for minimal invasive surgery. An innovative and progressive approach, borrowing experiences from the field of aviation, can provide the foundation for the next century of surgical training, ensuring the quality of the product. As the technology develops, the way we practice will continue to evolve, to the benefit of physicians and patients.

关键词： Surgery Training Certification Skills Simulation Curriculum

RhoA/ROCK activation in major pelvic ganglion mediates caspase-3 dependent nitrergic neuronal apoptosis following cavernous nerve injury

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Neural Regeneration Research 2017年第4期12卷 572-573页

作者： Michael bell Nikolai A. Sopko Hotaka Matsui johanna l. Hannan Trinity j. Bivalacqua The james Buchannan Brady Urological Institute and Department of Urology The Johns Hopkins School of Medicine

Severe erectile dysfunction （ED） remains a significant side effect among men following surgical intervention for treatment of clinically localized prostate cancer, despite development of nerve-sparing techniques （Weyne et al., 2015a; Sopko and Burnett, 2016）. The type of axonal injury due to prostatectomy is a classic peripheral neuropathy with an acute inflammatory phase that leads to Wallerian degeneration of the canvernous nerve （CN）, which can be followed by a regenerative phase characterized by enhanced neu- rotrophic factor activation and reduction in neuroinflam- mation （Weyne et al., 2015b）.

关键词： ROCK MPG CNI

Cost-effectiveness of Crohn's disease post-operative care

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World journal of Gastroenterology 2016年第14期22卷 3860-3868页

作者： Emily K Wright Michael A Kamm Peter Dr Cruz Amy l Hamilton Kathryn j Ritchie Sally j bell Steven j Brown William R Connell Paul V Desmond Danny liew Department of Gastroenterology St Vincent's Hospital University of Melbourne Fitzroy VIC 3065 Melbourne Australia Imperial College London SW7 2AZ United Kingdom Melbourne EpiCentre University of Melbourne and Melbourne Health Parkville VIC 3010 Melbourne Australia

AIM: To define the cost-effectiveness of strategies, including endoscopy and immunosuppression, to prevent endoscopic recurrence of Crohn’s disease following intestinal ***: In the “POCER” study patients undergoing intestinal resection were treated with post-operative drug therapy. Two thirds were randomized to active care (6 mo colonoscopy and drug intensification for endoscopic recurrence) and one third to drug therapy without early endoscopy. Colonoscopy at 18 mo and faecal calprotectin (FC) measurement were used to assess disease recurrence. Administrative data, chart review and patient questionnaires were collected prospectively over 18 ***: Sixty patients (active care n = 43, standard care n = 17) were included from one health service. Median total health care cost was $6440 per patient. Active care cost $4824 more than standard care over 18 mo. Medication accounted for 78% of total cost, of which 90% was for adalimumab. Median health care cost was higher for those with endoscopic recurrence compared to those in remission [$26347 (IQR 25045-27485) vs $2729 (IQR 1182-5215), P lect patients for colonoscopy could reduce cost by $1010 per patient over 18 mo. Active care was associated with 18% decreased endoscopic recurrence, costing $861 for each recurrence ***: Post-operative management strategies are associated with high cost, primarily medication related. Calprotectin use reduces costs. The long term cost-benefit of these strategies remains to be evaluated.

关键词： Crohn’ s disease Post-operative Health economics Health care cost Biologics