Mutational signatures in tumours induced by high and low energy radiation in Trp53 deficient mice.

Ionising radiation (IR) is a recognised carcinogen responsible for cancer development in patients previously treated using radiotherapy, and in individuals exposed as a result of accidents at nuclear energy plants. However, the mutational signatures induced by distinct types and doses of radiation are unknown. Here, we analyse the genetic architecture of mammary tumours, lymphomas and sarcomas induced by high (56Fe-ions) or low (gamma) energy radiation in mice carrying Trp53 loss of function alleles. In mammary tumours, high-energy radiation is associated with induction of focal structural variants, leading to genomic instability and Met amplification. Gamma-radiation is linked to large-scale structural variants and a point mutation signature associated with oxidative stress. The genomic architecture of carcinomas, sarcomas and lymphomas arising in the same animals are significantly different. Our study illustrates the complex interactions between radiation quality, germline Trp53 deficiency and tissue/cell of origin in shaping the genomic landscape of IR-induced tumours

Continuous and accumulated bouts of cycling matched by intensity and energy expenditure elicit similar acute blood pressure reductions in prehypertensive men

The present study investigated differences in postexercise hypotension (PEH) after continuous versus accumulated isocaloric bouts of cycling. Ten pre-hypertensive men, aged 23 to 34 yrs, performed two bouts of cycling at 75% oxygen uptake reserve, with total energy expenditures of 400 kcal per bout. One exercise bout was performed continuously (CONTIN) and the other as two smaller bouts each expending 200 kcal (INTER1 and INTER2). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and cardiac autonomic control were monitored in a supine position for 10 min before and 60 min after each exercise bout, and during a control session. Compared to control, blood pressure was significantly reduced after CONTIN (SBP: ∆-3.4 mmHg, P < 0.001; MAP: ∆-2.5 mmHg, P = 0.001), INTER1 (SBP: ∆-2.2 mmHg, P = 0.045) and INTER2 (SBP: ∆-4.4 mmHg, P < 0.001; DBP: ∆-2.7 mmHg, P = 0.045; MAP: ∆-3.3 mmHg, P = 0.001). The PEH was similar in CONTIN and INTER2, while INTER2 elicited greater PEH than INTER1 (SBP and MAP: ∆-2.0 and ∆-1.8 mmHg, respectively, P < 0.05). Increases in sympathovagal balance from baseline were inversely related to changes in SBP and DBP after CONTIN and INTER2 (r = -0.64 to -0.71; P = 0.021 to P = 0.047). These findings indicate similar amounts of PEH are observed when exercise is performed as a single 400 kcal exercise bout or 2 x 200 kcal bouts and that the exercise recovery pattern of cardiac autonomic activity may be important in eliciting PEH

Impact of sympathetic nervous system activity on post-exercise flow-mediated dilatation in humans

Transient reduction in vascular function following systemic large muscle group exercise has previously been reported in humans. The mechanisms responsible are currently unknown. We hypothesised that sympathetic nervous system activation, induced by cycle ergometer exercise, would contribute to post-exercise reductions in flow-mediated dilatation (FMD). Ten healthy male subjects (28 ± 5 years) undertook two 30 min sessions of cycle exercise at 75% HRmax. Prior to exercise, individuals ingested either a placebo or an α1-adrenoreceptor blocker (prazosin; 0.05 mg kg−1). Central haemodynamics, brachial artery shear rate (SR) and blood flow profiles were assessed throughout each exercise bout and in response to brachial artery FMD, measured prior to, immediately after and 60 min after exercise. Cycle exercise increased both mean and antegrade SR (P < 0.001) with retrograde SR also elevated under both conditions (P < 0.001). Pre-exercise FMD was similar on both occasions, and was significantly reduced (27%) immediately following exercise in the placebo condition (t-test, P = 0.03). In contrast, FMD increased (37%) immediately following exercise in the prazosin condition (t-test, P = 0.004, interaction effect P = 0.01). Post-exercise FMD remained different between conditions after correction for baseline diameters preceding cuff deflation and also post-deflation SR. No differences in FMD or other variables were evident 60 min following recovery. Our results indicate that sympathetic vasoconstriction competes with endothelium-dependent dilator activity to determine post-exercise arterial function. These findings have implications for understanding the chronic impacts of interventions, such as exercise training, which affect both sympathetic activity and arterial shear stress

Project #68: A Collaborative Approach to Enhance the Radiology Scheduling and Access Experience

The Northwest Territory has grown exponentially in last the 5 years with the opening of 3 major medical centers(Bloomfield Twp, Royal Oak and Plymouth). As a result, there has been an influx in need for scheduling and access for our patients. The previous departmental and technical set up (phone system)was unable to accommodate such increases which resulted in higher queue totals and patient dissatisfaction. Utilizing a collaborative approach our team identifiedopportunities for enhancement and access to our patients that not only improved the patient experience but supported a more cohesive department andimproving moral.https://scholarlycommons.henryford.com/qualityexpo2024/1003/thumbnail.jp

Identifying Grasp and Pinch Patterns in Ceramic Interventions: Video Analysis of Adults Completing Ceramic Activities

Background: Occupation-based interventions are effective in hand rehabilitation. The purpose of this study was to identify the grasp and pinch patterns used during specific ceramic activities for rehabilitative interventions. Method: A convenience sample of 59 videos with 38 subjects were taken of adults without hand dysfunction completing various ceramic activities. Elementary Grasp Actions (EGA’s) were analyzed to identify the different grasps and pinch patterns. Results: The EGA’s occurred 279 times across 12 ceramics activities. The EGA’s with the highest frequencies include nonprehensile, pinch, and lateral pinch. Nonprehensile was the most frequently used grasp used by the left hand. The EGA’s with the most prolonged durations were nonprehensile, special pinch, and oblique. The mean frequency and duration of each grasp and pinch pattern for specific ceramic activities are presented. Conclusion: Therapists can use the results of this study to help individuals with hand dysfunction through specific ceramic activity interventions

The Case for Coordinating Efforts to Establish Program Guidelines and Strengthen Physiology Undergraduate Degree Programs

Undergraduate degree programs named “Physiology” have existed for over 50 yr. The number of programs and enrolled students have been growing since ~2005 (5, 9). There are many thousands of students currently enrolled in physiology pro- grams across the United States and indeed across the world. Despite the long history and current popularity of the physiol- ogy major, there is no coordinated plan articulated for the design, administration, or assessment of degree programs in physiology at the undergraduate level. Although several professional societies have invested in under- graduate physiology education in various ways, none has under- taken the task of developing programmatic guidelines at the level of a degree program. This paper outlines the work being done by multiple stakeholders in physiology undergraduate education in the hopes of building a collaboration among interested parties. A large-scale collaboration could result in establishing consensus national programmatic guidelines. Through coordinated efforts, we ensure that entities with common educational interests are working together, and we collectively strengthen our programs to help our students succeed. The goals of this paper are to: 1) draw attention to the lack of national, program-level guidelines for physiology under- graduate degree programs; 2) share ongoing efforts by stake- holders in physiology undergraduate education; 3) suggest a mechanism for coordination among stakeholders; and 4) dis- cuss challenges and considerations for development of pro- grammatic guidelines for physiology programs

Recommendations in Post-exercise Hypotension: Concerns, Best Practices and Interpretation

Post-exercise hypotension (PEH) is a clinically relevant phenomenon that has been widely investigated. However, the characteristics of study designs, such as familiarization to blood pressure measurements, duration of PEH assessments or strategies to analyze PEH present discrepancies across studies. Thus identifying key points to standardize across PEH studies is necessary to help researchers to build stronger study designs, to facilitate comparisons across studies, and to avoid misinterpretations of results. The goal of this narrative review of methods used in PEH studies was therefore to gather and find possible influencers in the characteristics of study design and strategies to analyze blood pressure. Data found in this review suggest that PEH studies should have at least two familiarization screening visits, and should assess blood pressure for at least 20 min, but preferably for 120 min, during recovery from exercise. Another important aspect is the strategy to analyze PEH, which may lead to different interpretations. This information should guide a priori study design decisions

Differential Post-Exercise Blood Pressure Responses between Blacks and Caucasians

Post-exercise hypotension (PEH) is widely observed in Caucasians (CA) and is associated with histamine receptors 1- and 2- (H1R and H2R) mediated post-exercise vasodilation. However, it appears that blacks (BL) may not exhibit PEH following aerobic exercise. Hence, this study sought to determine the extent to which BL develop PEH, and the contri- bution of histamine receptors to PEH (or lack thereof) in this population. Forty-nine (22 BL, 27 CA) young and healthy subjects completed the study. Subjects were randomly assigned to take either a combined H1R and H2R antagonist (fexofenadine and ranitidine) or a con- trol placebo. Supine blood pressure (BP), cardiac output and peripheral vascular resistance measurements were obtained at baseline, as well as at 30 min, 60 min and 90 min after 45 min of treadmill exercise at 70% heart rate reserve. Exercise increased diastolic BP in young BL but not in CA. Post-exercise diastolic BP was also elevated in BL after exercise with histamine receptor blockade. Moreover, H1R and H2R blockade elicited differential responses in stroke volume between BL and CA at rest, and the difference remained follow- ing exercise. Our findings show differential BP responses following exercise in BL and CA, and a potential role of histamine receptors in mediating basal and post-exercise stroke vol- ume in BL. The heightened BP and vascular responses to exercise stimulus is consistent with the greater CVD risk in BL

Postexercise hypotension as a clinical tool: a “single brick” in the wall

After an exercise session, a reduction of blood pressure (BP) is expected, a phenomenon called postexercise hypotension (PEH). PEH as a predictor of chronic training responses for BP has been broadly explored. It suggests that when PEH occurs after each exercise sessions, its benefits may summate over time, contributing to the chronic adaptation. Thus, PEH is an important clinical tool, acting as a “single brick” in the wall, and building the chronic effect of decreasing BP. However, there is large variation in the literature regarding methodology and results, creating barriers for understanding comparisons among PEH studies. Thus, the differences among subjects' and exercise protocols’ characteristics observed in the studies investigating PEH must be considered when readers interpret the results. Furthermore, understanding of these factors of influence might be useful for avoiding misinterpretations in future comparisons and how the subjacent mechanisms contribute to the BP reduction after exercise