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Background: Based on emerging evidence that brief periods of cessation from resistance training (RT) may re-sensitize muscle to anabolic stimuli, we aimed to investigate the effects of a 1-week deload interval at the midpoint of a 9-week RT program on muscular adaptations in resistance-trained individuals., Methods: Thirty-nine young men ( n  = 29) and women ( n  = 10) were randomly assigned to 1 of 2 experimental, parallel groups: An experimental group that abstained from RT for 1 week at the midpoint of a 9-week, high-volume RT program (DELOAD) or a traditional training group that performed the same RT program continuously over the study period (TRAD). The lower body routines were directly supervised by the research staff while upper body training was carried out in an unsupervised fashion. Muscle growth outcomes included assessments of muscle thickness along proximal, mid and distal regions of the middle and lateral quadriceps femoris as well as the mid-region of the triceps surae. Adaptions in lower body isometric and dynamic strength, local muscular endurance of the quadriceps, and lower body muscle power were also assessed., Results: Results indicated no appreciable differences in increases of lower body muscle size, local endurance, and power between groups. Alternatively, TRAD showed greater improvements in both isometric and dynamic lower body strength compared to DELOAD. Additionally, TRAD showed some slight psychological benefits as assessed by the readiness to train questionnaire over DELOAD., Conclusion: In conclusion, our findings suggest that a 1-week deload period at the midpoint of a 9-week RT program appears to negatively influence measures of lower body muscle strength but has no effect on lower body hypertrophy, power or local muscular endurance., Competing Interests: Brad J Schoenfeld serves on the scientific advisory board of Tonal Corporation, a manufacturer of fitness equipment. Michael Israetel is a cofounder of Renaissaince Periodization. The other authors declare that they have no competing interests., (©2024 Coleman et al.)

Purpose: Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk., Experimental Design: This is a multicenter case-control study using banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or urothelial carcinoma surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmp platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting urothelial carcinoma tumor presence, grade, and recurrence risk were compared with cytology, cystoscopy, and pathology., Results: uCGP algorithms had a validation sensitivity/specificity of 95%/90% for initial cancer diagnosis in patients with hematuria and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary urothelial carcinoma classification demonstrated an NPV of 91%. uCGP recurrence-risk prediction significantly prognosticated future recurrence (hazard ratio, 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable with cytology (45% vs. 42%) with much higher sensitivity (79% vs. 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%., Conclusions: uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients., (©2023 The Authors; Published by the American Association for Cancer Research.)

The purpose of this study was to compare the effects of electromagnetic resistance alone, as well as in combination with variable resistance or accentuated eccentric methods, with traditional dynamic constant external resistance exercise on myoelectric activity during elbow flexion. The study employed a within-participant randomized, cross-over design whereby 16 young, resistance-trained male and female volunteers performed elbow flexion exercise under each of the following conditions: using a dumbbell (DB); using a commercial electromagnetic resistance device (ELECTRO); variable resistance (VR) using a setting on the device that attempts to match the level of resistance to the human strength curve, and; eccentric overload (EO) using a setting on the device that increases the load by 50% on the eccentric portion of each repetition. Surface electromyography (sEMG) was obtained for the biceps brachii, brachioradialis and anterior deltoid on each of the conditions. Participants performed the conditions at their predetermined 10 repetition maximum. " The order of performance for the conditions was counterbalanced, with trials separated by a 10-min recovery period. The sEMG was synced to a motion capture system to assess sEMG amplitude at elbow joint angles of 30°, 50°, 70°, 90°, 110°, with amplitude normalized to the maximal activation. The anterior deltoid showed the largest differences in amplitude between conditions, where median estimates indicated greater concentric sEMG amplitude (~ 7-10%) with EO, ELECTRO and VR compared with DB. Concentric biceps brachii sEMG amplitude was similar between conditions. In contrast, results indicated a greater eccentric amplitude with DB compared to ELECTRO and VR, but unlikely to exceed a 5% difference. Data indicated a greater concentric and eccentric brachioradialis sEMG amplitude with DB compared to all other conditions, but differences were unlikely to exceed 5%. The electromagnetic device tended to produce greater amplitudes in the anterior deltoid, while DB tended to produce greater amplitudes in the brachioradialis; amplitude for the biceps brachii was relatively similar between conditions. Overall, any observed differences were relatively modest, equating to magnitudes of ~ 5% and not likely greater than 10%. These differences would seem to be of minimal practical significance., (© 2023. The Author(s).)

Background: Progressive overload is a principle of resistance training exercise program design that typically relies on increasing load to increase neuromuscular demand to facilitate further adaptations. However, little attention has been given to another way of increasing demand-increasing the number of repetitions., Objective: This study aimed to compare the effects of two resistance training programs: (1) increasing load while keeping repetition range constant vs (2) increasing repetitions while keeping load constant. We aimed to compare the effects of these programs on lower body muscle hypertrophy, muscle strength, and muscle endurance in resistance-trained individuals over an 8-week study period., Methods: Forty-three participants with at least 1 year of consistent lower body resistance training experience were randomly assigned to one of two experimental, parallel groups: A group that aimed to increase load while keeping repetitions constant (LOAD: n = 22; 13 men, nine women) or a group that aimed to increase repetitions while keeping load constant (REPS: n = 21; 14 men, seven women). Subjects performed four sets of four lower body exercises (back squat, leg extension, straight-leg calf raise, and seated calf raise) twice per week. We assessed one repetition maximum (1RM) in the Smith machine squat, muscular endurance in the leg extension, countermovement jump height, and muscle thickness along the quadriceps and calf muscles. Between-group effects were estimated using analyses of covariance, adjusted for pre-intervention scores and sex., Results: Rectus femoris growth modestly favored REPS (adjusted effect estimate (CI 90% ), sum of sites: 2.8 mm [-0.5, 5.8]). Alternatively, dynamic strength increases slightly favored LOAD (2.0 kg [-2.4, 7.8]), with differences of questionable practical significance. No other notable between-group differences were found across outcomes (muscle thicknesses, <1 mm; endurance, <1%; countermovement jump, 0.1 cm; body fat, <1%; leg segmental lean mass, 0.1 kg), with narrow CIs for most outcomes., Conclusion: Both progressions of repetitions and load appear to be viable strategies for enhancing muscular adaptations over an 8-week training cycle, which provides trainers and trainees with another promising approach to programming resistance training., Competing Interests: Brad J Schoenfeld serves on the scientific advisory board of Tonal Corporation, a manufacturer of exercise equipment. Mike Israetel and Jared Feather are employed by Renaissance Periodization. The other authors declare no competing interests., (© 2022 Plotkin et al.)

Insulin is a key regulator of adipose tissue lipolysis, and impaired adipose tissue insulin action results in unrestrained lipolysis and lipotoxicity, which are hallmarks of the metabolic syndrome and diabetes. Insulin regulates adipose tissue metabolism through direct effects on adipocytes and through signaling in the central nervous system by dampening sympathetic outflow to the adipose tissue. Here we examined the role of insulin signaling in agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) neurons in regulating hepatic and adipose tissue insulin action. Mice lacking the insulin receptor in AgRP neurons (AgRP IR KO) exhibited impaired hepatic insulin action because the ability of insulin to suppress hepatic glucose production (hGP) was reduced, but the ability of insulin to suppress lipolysis was unaltered. To the contrary, in POMC IR KO mice, insulin lowered hGP but failed to suppress adipose tissue lipolysis. High-fat diet equally worsened glucose tolerance in AgRP and POMC IR KO mice and their respective controls but increased hepatic triglyceride levels only in POMC IR KO mice, consistent with impaired lipolytic regulation resulting in fatty liver. These data suggest that although insulin signaling in AgRP neurons is important in regulating glucose metabolism, insulin signaling in POMC neurons controls adipose tissue lipolysis and prevents high-fat diet-induced hepatic steatosis., (© 2017 by the American Diabetes Association.)

Insulin replacement is the cornerstone of type 1 diabetes (T1D) treatment; however, glycemic control remains a challenge. Leptin has been shown to effectively restore euglycemia in rodent models of T1D; however, the mechanism or mechanisms by which leptin exerts glycemic control are unclear. In this issue of the JCI, Perry and colleagues provide evidence that suppression of lipolysis is a key facet of leptin-mediated restoration of euglycemia. However, more work remains to be done to fully understand the antidiabetic mechanisms of leptin., Competing Interests: The authors have declared that no conflict of interest exists.

Insulin-like growth factor I (IGF-I) is a potent hormone that stimulates growth and differentiation and inhibits apoptosis in numerous tissues. Preliminary evidence suggests that IGF-I exerts differentiating, mitogenic and restoring activities in the immune system but the sites of synthesis of local IGF-I are unknown. Identification of these sites would allow the functional role of local IGF-I to be clarified. The presence of IGF-I in non-immune cells suggests that it acts as a trophic factor, while its occurrence in subtypes of lymphocytes or antigen-presenting cells indicates paracrine/autocrine direct regulatory involvement of IGF-I in the human immune response. The present study investigated the location of IGF-I messenger RNA and protein on archival human lymph node samples by in situ hybridization, immunohistochemistry and double immunofluorescence staining using an IGF-I probe and antisera specific for human IGF-I and CD3 (T lymphocytes), CD20 (B lymphocytes), CD68 (macrophages), CD21 (follicular dendritic cells), S100 (interdigitating dendritic cells) and podoplanin (fibroblastic reticular cells). Numerous cells within the B- and T-cell compartments expressed the IGF-I gene, and the majority of these cells were identified as macrophages. Solitary follicular dendritic cells exhibited IGF-I. A few T lymphocytes, and no B lymphocytes, contained IGF-I immunoreactive material. Furthermore, IGF-I immunoreactive cells outside the follicles that did not react with CD3, CD20, S100 or podoplanin markers were identified as high-endothelial venule (HEV) cells. From this we conclude that the main task of IGF-I in human non-tumoral lymph node may be autocrine and paracrine regulation of the differentiation, stimulation and survival of lymphocytes, antigen-presenting cells and macrophages and the differentiation and maintenance of HEV cells.