Control4Life: A randomized controlled trial protocol examining the feasibility and efficacy of a combined pelvic health rehabilitation and exercise fitness program for individuals undergoing prostatectomy.

BACKGROUND: Urinary incontinence (UI), erectile dysfunction and cardiometabolic conditions are common after prostatectomy for prostate cancer (PCa). Although physical activity could improve overall survival and quality of survivorship, fear of UI can restrict participation in exercise. Individuals with PCa could benefit from therapeutic exercise programming to support continence recovery and cardiometabolic health. AIM: The main objective of this study is to determine the feasibility and the effects of a combined pelvic health rehabilitation and exercise fitness program on UI after prostatectomy. The combined exercise program will be delivered both in-person and virtually. METHODS: This study follows a modified Zelen, two-arm parallel randomized controlled trial design. A total of 106 individuals with PCa will be recruited before prostatectomy surgery. Participants will be randomized between two groups: one receiving usual care and one receiving a combined exercise fitness and intensive pelvic floor muscle training program. Exercise programming will begin 6-8 weeks after prostatectomy and will last 12 weeks. Outcomes include: the 24-h pad test (primary outcome for UI); physical fitness, metabolic indicators, and patient-reported outcomes on erectile function, self-efficacy, severity of cancer symptoms and quality of life. Important timepoints for assessments include before surgery (T0), after surgery (T1), after intervention (T3) and at one-year after surgery (T4). CONCLUSION: This study will inform the feasibility of offering comprehensive exercise programming that has the potential to positively impact urinary continence, erectile function and cardiometabolic health of individuals undergoing prostatectomy for prostate cancer. CLINICALTRIALS REGISTRATION NUMBER: NCT06072911.

Fast adaptation of pre-operative patient specific models to real-time intra-operative volumetric data streams.

Image-guided catheter ablation therapy is becoming an increasingly popular treatment option for atrial fibrillation. Successful treatment relies on accurate guidance of the treatment catheter. Integration of high-resolution, pre-operative data with electrophysiology data and positional data from tracked catheters improves targeting, but lacks the means to monitor changes in the atrial wall. Intra-operative ultrasound provides a method for imaging the atrial wall, but the real-time, dynamic nature of the data makes it difficult to seamlessly integrate with the static pre-operative patient-specific model. In this work, we propose a technique which uses a self-organizing map (SOM) for dynamically adapting a pre-operative model to surface patch data. The surface patch would be derived from a segmentation of the anatomy in a real-time, intra-operative ultrasound data stream. The method is demonstrated on two regular geometric shapes as well as data simulated from a real, patient computed tomography dataset.

Nitration of the mitochondrial complex I subunit NDUFB8 elicits RIP1- and RIP3-mediated necrosis.

Nitric oxide (NO) and other reactive nitrogen species target multiple sites in the mitochondria to influence cellular bioenergetics and survival. Kinetic imaging studies revealed that NO from either activated macrophages or donor compounds rapidly diffuses to the mitochondria, causing a dose-dependent progressive increase in NO-dependent DAF fluorescence, which corresponded to mitochondrial membrane potential loss and initiated alterations in cellular bioenergetics that ultimately led to necrotic cell death. Cellular dysfunction is mediated by an elevated 3-nitrotyrosine signature of the mitochondrial complex I subunit NDUFB8, which is vital for normal mitochondrial function as evidenced by selective knockdown via siRNA. Overexpression of mitochondrial superoxide dismutase substantially decreased NDUFB8 nitration and restored mitochondrial homeostasis. Further, treatment of cells with either necrostatin-1 or siRNA knockdown of RIP1 and RIP3 prevented NO-mediated necrosis. This work demonstrates that the interaction between NO and mitochondrially derived superoxide alters mitochondrial bioenergetics and cell function, thus providing a molecular mechanism for reactive oxygen and nitrogen species-mediated alterations in mitochondrial homeostasis.

Risk factors for venous gas emboli after decompression from prolonged hyperbaric exposures.

INTRODUCTION: The physical forces governing gas phase nucleation and growth in a liquid would predict less variation in the development of decompression sickness (DCS) than is known to occur in people. METHODS: In order to gain insight into the causes of biological susceptibility to DCS, we analyzed a dataset containing 250 human steady-state hyperbaric exposures using multivariate ordinal and linear regression analysis for relationships between venous gas emboli (VGE) and exposure parameters and subject characteristics. RESULTS: In both previously published data and new chamber exposure data, we found that the strongest predictor of VGE magnitude after decompression was the duration and depth of the hyperbaric exposure, as predicted. Of the subject factors, only age was significantly associated with VGE; body mass index (BMI) and gender were not. The relationship between age and VGE strengthened with decompression magnitude. DISCUSSION: These results suggest that the physiology of aging interacts with the mechanism of VGE generation, altering the risk of DCS after decompression.

Evaluation of platelet transfusion triggers in a tertiary-care hospital.

BACKGROUND: Our 1100-bed referral hospital uses approximately 12,000 units of random-donor platelets (PLTs) and 1,900 units of single-donor apheresis PLTs per year with a mean of 23 percent outdating. An analysis of patterns of utilization has been undertaken to evaluate practice. STUDY DESIGN AND METHODS: Over a 9-month period, data were collected on a total of 1682 transfusion episodes in 464 patients. When the pretransfusion count was greater than 10 x 10(9) per L an attempt was made to identify the specific indications for PLT transfusions such as bleeding. RESULTS: The majority (78%) of PLTs were transfused when the counts were above 10 x 10(9) per L. The mean pretransfusion counts for different services were: bone marrow transplant (BMT) 17.4 x 10(9) per L, hematology-oncology 14.6 x 10(9) per L, the Heart Institute 3 x 10(9) per L, and other services 36 x 10(9) per L. The percentage of transfusions given to patients with a count greater than 10 x 10(9) per L varied by service with 79 percent in BMT, 60 percent in hematology and oncology, 98 percent at the Heart Institute, and 81 percent in other services. Routine monitoring of counts shows a mean increment of 10.2 x 10(9) per L per transfusion. One hour posttransfusion counts, 24-hour posttransfustion counts, and documentation of clinical justification for transfusions was often not available. CONCLUSIONS: The data show that most patients who receive PLTs have pretransfusion counts of more than 10 x 10(9) per L and more than one-third have pretransfusion counts of greater than 20 x 10(9) per L. The medical literature supports prophylactic PLT transfusion based solely on the count when the PLT number is 10 x 10(9) per L or less. Above this level additional justification is needed although there are different points of view concerning the appropriate triggers. Our data suggest that there is a need for clear hospital transfusion guidelines and ongoing monitoring of PLT use.