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Background: It is estimated that 10% or more of patients older than 65 years are affected by frailty, a mental and physical state of vulnerability to adverse surgical outcomes. Frailty can be assessed using the Edmonton Frailty Scale: a reliable and convenient multidimensional assessment before surgery. The correlation between frailty score, presurgical optimization, and surgical outcomes was investigated in this preliminary pilot study., Study Design: A retrospective study was performed on patients referred to the surgical optimization clinic and assessed for frailty from September 2020 to May 2023. Patients received presurgical optimization for reasons including diabetes, smoking cessation, prehabilitation and nutrition, and/or cardiopulmonary issues. Outcomes were evaluated whether they proceeded to surgery, were referred to the High-Risk Surgical Committee, surgical case canceled, or not scheduled. For those who proceeded to surgery, infection rates, complications, and 30-day emergency department (ED) and readmission rates were evaluated., Results: Of 143 unique patients, 138 (men = 61, women = 77) were evaluated for this study. The average Edmonton frailty score for patients who proceeded to surgery was 7.013 (n = 78) vs 9.389 with cancelation and 9.600 for not scheduled or not optimized for surgery. Postoperative infection rates were <3%. However, 30-day ED and readmission rate was 21% (16 of 78)., Conclusions: Patients with lower average Edmonton frailty scores were more likely to proceed to surgery, whereas those with higher average Edmonton frailty scores were more likely to have surgery canceled or delayed. Frail patients cleared for surgery were found to have a high 30-day ED and readmission rate., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: True seven day a week acute care physical therapy (PT) coverage is rare. Our facility is one of a few in Canada that has increased weekend PT coverage on medicine units to seven days of full PT staffing levels., Objective: This article investigates the perspectives of physical therapists involved in the change with the focus on the emotional experiences of those therapists., Methods: Thematic analysis of interview and focus group transcripts with 18 physical therapist and 2 manager participants were aligned with four themes of: 1) optimism, hope and excitement; 2) frustration, guilt, and resentment; 3) fear, anxiety, uncertainty, and vulnerability; and 4) ambivalence, neutrality, and impartiality., Results: Although there were several perceived benefits to quality of care and work/life balance, participants' comments also reflected: frustration, guilt, and resentment related to the rapid implementation of the change and the impact of altered work schedules., Conclusions: Participants emphasized the need to discuss large changes with staff prior to implementation in order to prevent frustration and resentment. Participants also felt that increased acute care PT coverage over seven days is valuable, but other allied health professions also need a proportional increase in staffing to improve hospital flow.

Background: Primary ciliary dyskinesia (PCD) is typically an autosomal recessive disease characterized by recurrent infections of the lower respiratory tract, frequent and severe otitis media, chronic rhinosinusitis, neonatal respiratory distress, and organ laterality defects. While severe lower respiratory tract infections and bronchiectasis are common in Inuit, PCD has not been recognized in this population., Methods: We report a case series of seven Inuit patients with PCD identified by genetic testing in three Canadian PCD centers., Results: Patients ranged from 4 to 59 years of age (at time of last evaluation) and originated in the Qikiqtaaluk region (Baffin Island, n = 5), Nunavut, or Nunavik (northern Quebec, n = 2), Canada. They had typical features of PCD, including neonatal respiratory distress (five patients), situs inversus totalis (four patients), bronchiectasis (four patients), chronic atelectasis (six patients), and chronic otitis media (six patients). Most had chronic rhinitis. Genetic evaluation demonstrated that all had homozygous pathogenic variants in DNAH11 at NM&#95;001277115.1:c.4095+2C>A., Conclusions: The discovery of this homozygous DNAH11 variant in widely disparate parts of the Nunangat (Inuit homelands) suggests this is a founder mutation that may be widespread in Inuit. Thus, PCD may be an important cause of chronic lung, sinus, and middle ear disease in this population. Inuit with chronic lung disease, including bronchiectasis or laterality defects, should undergo genetic testing for PCD. Consideration of including PCD genetic analysis in routine newborn screening should be considered in Inuit regions., (© 2023 Wiley Periodicals LLC.)

Background: Sickle Cell Disease (SCD) is a genetic progressive vascular disease that impacts patients overall health and quality of life. Sickle-cell pain crises (SCPCs) are a hallmark clinical presentation of SCD and have been associated with increased morbidity and mortality. The Sickle Cell Pain Diary- Self Report (SCPD-S) was developed as a daily patient-reported outcome (PRO) measure primarily intended to capture the frequency and severity of SCD-related pain during and outside of a SCPC. The SCPD-S also examines the impact of the pain associated with an SCPC on other health-related quality of life concepts. The objective of this study was to investigate the content validity of the SCPD-S., Methods: The content validation testing included 18 in-depth hybrid concept elicitation and cognitive debriefing interviews conducted with SCD patients in the US aged 12 years and older. Interviewers used a semi-structured interview guide and a think-aloud approach for the cognitive debriefing portion. All interviews were recorded, transcribed, coded and analyzed., Results: Eighteen interviews across two rounds were conducted. Round 1 hybrid interviews (n = 12) resulted in the expansion of the SCPD-S from 13 to 19 items. Items on the impact of an SCPC on social and recreational activities, sleep, and emotional well-being were added. Five items were significantly revised, as were three response choice sets. Round 2 hybrid interviews (n = 6) confirmed the comprehensiveness of the revised diary, understandability of the wording, and appropriateness of the recall period and response sets. Saturation analyses specific to concept elicitation revealed that no additional interviews were needed., Conclusions: This study provided evidence to support the content validity of the SCPD-S, a self-report daily diary. Data gathered during patient interviews indicated that the SCPD-S is a fit for purpose measure of SCD and SCPC-related pain frequency and severity and the impact of this pain on other health-related quality of life concepts including fatigue and emotional health. The numerous changes to the SCPD-S as a result of the study findings highlight the importance of the content validation process when developing a PRO measure., (© 2021. The Author(s).)

Objectives: Neutrophil to lymphocyte ratio (NLR) has been shown to be a promising biomarker in several cancers. Prognostic biomarkers are still needed to define good candidates for lung metastasectomy for colorectal cancer. We aimed to evaluate the role of NLR., Methods: Data from 574 patients who underwent lung metastasectomy for colorectal cancer in 3 departments of thoracic surgery from 2004 to 2014 were retrospectively reviewed. Overall survival (OS) and the time to pulmonary recurrence (TTPR) were the main end points., Results: Correlations between NLR and OS (R2 = 0.53), and NLR and TTPR (R2 = 0.389) were significant (P < 0.0001 for both), with corresponding Pearson R of -0.728 (P < 0.0001) and -0.624 (P < 0.0001), respectively. A receiver operating characteristic curve analysis highlighted an NLR cut-off value of 4.05 as the best predictor of OS and TTPR. NLR ≤4.05 was observed in 238 patients (41.4%). In the univariable analysis, the median OS was 117 months for patients with NLR ≤4.05 and decreased to 40 months for patients with NLR >4.05 (P < 0.0001). The median TTPR reached 52 months in case of NLR ≤4.05 and decreased to 12 months in patients with NLR >4.05. In the multivariable analysis, NLR ≤4.05 remained an independent favourable prognostic factor on both OS [hazard ratio [HR] 0.29, 95% confidence interval (CI) 0.167-0.503; P < 0.0001] and TTPR (HR 0.346, 95% CI 0.221-0.54; P < 0.0001). Significant correlations between NLR >4.05 and KRAS (Cramer's V = 0.241, P < 0.0001) and BRAF (Cramer's V = 0.153, P = 0.003) mutations were observed., Conclusions: NLR is a simple and powerful predictor of outcomes in patients undergoing pulmonary metastasectomy for colorectal cancer., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

G protein coupled receptors (GPCRs) produce pleiotropic effects by their capacity to engage numerous signaling pathways once activated. Functional selectivity (also called biased signaling), where specific compounds can bring GPCRs to adopt conformations that enable selective receptor coupling to distinct signaling pathways, continues to be significantly investigated. However, an important but often overlooked aspect of functional selectivity is the capability of ligands such as angiotensin II (AngII) to adopt specific conformations that may preferentially bind to selective GPCRs structures. Understanding both receptor and ligand conformation is of the utmost importance for the design of new drugs targeting GPCRs. In this study, we examined the properties of AngII cyclic analogs to impart biased agonism on the angiotensin type 1 receptor (AT 1 R). Positions 3 and 5 of AngII were substituted for cysteine and homocysteine residues ([Sar 1 Hcy 3,5 ]AngII, [Sar 1 Cys 3 Hcy 5 ]AngII and [Sar 1 Cys 3,5 ]AngII) and the resulting analogs were evaluated for their capacity to activate the Gq/11, G12, Gi2, Gi3, Gz, ERK and β-arrestin (βarr) signaling pathways via AT 1 R. Interestingly, [Sar 1 Hcy 3,5 ]AngII exhibited potency and full efficacy on all pathways tested with the exception of the Gq pathway. Molecular dynamic simulations showed that the energy barrier associated with the insertion of residue Phe 8 of AngII within the hydrophobic core of AT 1 R, associated with Gq/11 activation, is increased with [Sar 1 Hcy 3,5 ]AngII. These results suggest that constraining the movements of molecular determinants within a given ligand by introducing cyclic structures may lead to the generation of novel ligands providing more efficient biased agonism., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Inflammatory bowel diseases (IBDs) are multifaceted and relapsing immune disorders, which necessitate long-term dependence on powerful drugs. As the use of natural product-based therapies has emerged as a promising intervention, the present study aimed to further characterize dried apple peel powder (DAPP) mechanisms of action and evaluate the preventive and curative effects of DAPP on mitochondrial functions in a murine model. Induction of intestinal inflammation in mice is performed by oral administration of the dextran sodium sulfate (DSS) at 2.5% for 10 days. Doses of DAPP (200 or 400 mg/kg/day) were administered by gavage for 10 days pre- and 1 day after colitis induction simultaneously with DSS treatment for a period of 10 days. The preventive (200 mg/kg/day) and therapeutic (400 mg/kg/day) doses of DAPP limited DSS-induced histological lesions, improved macroscopic parameters and attenuated clinical signs. DAPP at the same conditions reduced massive infiltration of inflammatory cells and concomitantly displayed a robust potential of counteracting inflammation and oxidative stress in DSS mice. Moreover, DAPP partially restored mitochondrial abnormalities related to size, density, redox homeostasis, fatty acid β-oxidation, ATP synthesis, apoptosis and regulatory mitochondrial transcription factors. Our findings demonstrate the preventive and therapeutic impact of DAPP on experimental colitis while underlying the role of mitochondria. They also suggest that this natural DAPP product may represent an interesting candidate for further studies on the prevention/treatment of IBD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Although most parents carrying a BRCA1/2 genetic mutation share their test result with their underage children, they report needing support to decide if, when, and how to share risk information and what reactions to expect from their children. We developed a tool to guide parents carrying a BRCA1/2 mutation share their genetic result with underage children. Here, we report on the development of this tool using a qualitative methodology. A tool prototype was developed based on the International Patient Decision Aids Standards Collaboration framework. Content was assessed using feedback from focus groups, individual interviews, and a 12-item reading grid. Participants were nine BRCA1/2 mutation carriers with underage children and three cancer genetics health professionals. Thematic content analysis was conducted on interview transcripts. The tool was developed using an iterative process until saturation of data. An independent advisory committee was involved in all steps of tool development until reaching consensus. Rather than a decision aid per se (to communicate or not), the parents wanted a more comprehensive tool to help them communicate genetic test result to their children. To meet parents' needs, a communication guidance booklet was developed, setting out the pros and cons of communication, steps to prepare sharing the test result, communication tips, and parents' testimonies. This communication tool responds to a significant unmet need faced by parents carrying a genetic predisposition to cancer. Future studies are needed to assess how the information from the parent's genetic test result impacts the child's development, health behaviors, and relationship with the parent.

Cytoplasmic lipid droplets (CLD) are considered as neutral lipid reservoirs, which protect cells from lipotoxicity. It became clear that these fascinating dynamic organelles play a role not only in energy storage and metabolism, but also in cellular lipid and protein handling, inter-organelle communication, and signaling among diverse functions. Their dysregulation is associated with multiple disorders, including obesity, liver steatosis and cardiovascular diseases. The central aim of this review is to highlight the link between intra-enterocyte CLD dynamics and the formation of chylomicrons, the main intestinal dietary lipid vehicle, after overviewing the morphology, molecular composition, biogenesis and functions of CLD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To determine the modifiable factors affecting glucose variability in people with cystic fibrosis (CF). CF-related diabetes (CFRD) is the most common complication of CF, and its presence increases morbidity and mortality in patients. Patients with CF (with and without CFRD) have potentially harmful glucose fluctuations and glucose excursions when compared to healthy adults. Carbohydrate intake and exercise have been shown to affect glycemia. Therefore, our hypothesis was that the proportion of energy from carbohydrates and total energy expenditure (TEE) would influence glucose fluctuations in adults with CF., Methods: A cross-sectional study involved 36 patients with CF, in whom continuous glucose monitoring systems were installed. Glucose fluctuations were then quantified using 3 indexes: mean amplitude of glucose excursions, standard deviation and coefficient of variation. Patients filled out a 3-day food diary to quantify energy intake and the proportions of calories from carbohydrates, fats and proteins, and they wore Sensewear Armbands to estimate spontaneous TEE and footsteps walked. Glucose tolerance status was determined using oral glucose tolerance tests., Results: Patients with CF with normal and impaired glucose tolerance had fewer glucose fluctuations than patients with CFRD (p<0.05). However, linear regression models used to determine whether nutrition or energy expenditure affects glucose fluctuations demonstrated that energy, the proportion of carbohydrates, of fat and of protein, TEE or the number of footsteps walked did not affect glucose fluctuation indexes (p>0.05)., Conclusions: TEE and the proportion of energy from carbohydrates did not affect glucose fluctuations in adults with CF., (Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

The aim of this study is to describe a potential modulatory effect of acute acylated ghrelin (AG) administration on the glucose, insulin, and free fatty acids (FFA) responses to salbutamol (SALBU). Six healthy young male volunteers underwent the following four testing sessions in random order at least 7 days apart: (a) acute AG administration (1.0 μg/kg i.v. as bolus at 0'); (b) SALBU infusion (0.06 μg/kg/min i.v. from -15' to +45'); (c) SALBU infusion+AG; and (d) isotonic saline infusion. Blood samples for glucose, insulin, and FFA levels were collected every 15 min. As expected, with respect to saline, SALBU infusion induced a remarkable increase in glucose (10.8±5.6 mmol/l×min; P<0.05), insulin (2436.8±556.9 pmol/l×min; P<0.05), and FFA (18.9±4.5 mmol/l×min; P<0.01) levels. A significant increase in glucose (7.4±3.9 mmol/l×min; P<0.05) and FFA levels (10.0±2.8 mmol/l×min; P<0.01) without significant variations in insulin levels were recorded after AG administration. Interestingly, the hyperglycemic effect of AG appeared to be significantly potentiated during SALBU infusion (26.7±4.8 mmol/l×min; P<0.05). On the other hand, the stimulatory effect of SALBU on insulin and FFA was not significantly modified by AG administration. The results of this study show that acute AG administration has a synergic effect with β2-adrenergic receptor activation by SALBU on blood glucose increase, suggesting that their pharmacological hyperglycemic action takes place via different mechanisms. On the other hand, AG has a negligible influence on the other pharmacological metabolic effects of SALBU infusion.

Acyl-ghrelin (AG), desacyl-ghrelin (DAG) and obestatin are all derived from the same gene transcript; however their plasma levels do not necessarily change in parallel. The influence of these peptides towards the development of obesity and their direct effects on adipocyte physiology has not been thoroughly investigated. This study was designed to evaluate the direct effects of peptides of the ghrelin family on preadipocyte proliferation, differentiation and adipocyte lipid and glucose metabolism in 3T3-L1 cells. 3T3 cells were treated with physiological peptide concentrations for 1 h to 9 days, and the relevant assays measured. In preadipocytes, AG, GHRP-6 and DAG stimulated proliferation, measured as (3)H-thymidine incorporation (up to 200%, P < 0.05), while all peptides stimulated differentiation (up to 300%, P < 0.01) as compared to standard differentiation conditions. In adipocytes, FA uptake was increased in a concentration-dependent manner especially with obestatin (three- to fourfold, P < 0.001) and DAG (three- to fivefold, P < 0.001). By contrast, glucose transport was unchanged. DAG and obestatin significantly decreased lipolysis measured as non-esterified fatty acid and glycerol release by 50%, P < 0.05-0.01 and 51%, P < 0.01, respectively. Interestingly, DAG stimulation of FA uptake was blocked with GHSR1 antagonist (D-lys(3))-GHRP-6 (P < 0.05), phospholipase C inhibitor U73122 and phosphatidylinositol-3-kinase inhibitor wortmannin (P < 0.001). Finally, in omental but not subcutaneous human adipose tissue, GHSR1 correlated with BMI (r = 0.549, P < 0.05) and insulin (r = 0.681, P < 0.01). Taken together, these results suggest that ghrelin-related peptides may directly affect adipose tissue metabolism., (Copyright © 2010 Wiley-Liss, Inc.)

Background: Acylated ghrelin (AG) is a physiological GH secretion amplifier, in part stimulating GHRH neurones and antagonizing somatostatin activity. In humans, AG is one of the most potent pharmacological stimuli of GH secretion and, unlike GHRH, is refractory to the inhibitory effect of glucose, free fatty acids (FFA) and somatostatin. Somatotroph secretion is also profoundly modulated by the adrenergic system. Indeed, beta-adrenergic agonists abolish spontaneous and GHRH-stimulated GH secretion. Based on these data, the aim of the present study was to investigate the effects of beta adrenergic agonism on the GH response to AG., Subjects and Measurements: Six young healthy male volunteers underwent: (a) acute AG intravenous (iv) administration (1.0 microg/kg); (b) salbutamol infusion (SLB; 0.06 microg/kg/min iv); (c) AG + SLB; and (d) saline infusion. In all sessions GH levels were assayed every 15 min from time -30 to +210 min., Results: SLB induced a significant (P < 0.05) inhibition of spontaneous GH secretion that persisted up to 75 min after SLB withdrawal. AG induced a marked increase (P < 0.01) in GH that was not modified by SLB., Conclusions: The GH-releasing effect of AG is refractory to the inhibitory effect of SLB-induced beta-adrenergic receptor activation. Although further studies are needed to confirm these results during the lifespan and particularly during prolonged exposure to beta agonists, the present data clearly suggest that, among GH stimulatory tests, AG administration might be the most suitable in clinical conditions of chronic treatment with beta-2 agonists, such as in asthmatic disease.

The renewed interest in home dialysis therapies makes it pertinent to address the essentials of establishing and running a successful home dialysis program. The success of a home program depends on a clear understanding of the structure of the home program team, the physical plant, educational tool requirements, reimbursement sources and a business plan. A good command of the technical and economic aspects is important, but the primary drivers for the creation and growth of a home dialysis program are the confidence and commitment of the nephrological team., (Copyright 2006 S. Karger AG, Basel.)

Objectives: Our goals were to determine whether selection bias occurred in a prehospital study comparing an esophageal detector device (EDD) to a disposable capnometer for detecting esophageal intubation, and to determine whether such a bias would have changed the study's conclusions about EDD effectiveness., Methods: In a study of patients requiring prehospital intubation, we determined the sensitivity, specificity and predictive values of the EDD for detecting esophageal intubation. We then compared intubation success rate in patients who were enrolled in the study (n = 129) to that in eligible patients who were excluded from it (n = 107). After finding that the incidence of failed intubation was higher in the "excluded" group, we used sensitivity and specificity parameters derived from the study population to assess whether EDD test characteristics would differ in studied vs. excluded patients., Results: The first intubation attempt was successful in 125 of 129 study patients and 76 of 107 excluded patients (97% vs. 71%, p = 0.03), confirming the presence of selection bias. The negative predictive value of the EDD for esophageal intubation was 98% in the study cohort and would have been 77% in patients like those excluded (i.e., difficult intubation cases)., Conclusions: The high "first attempt" intubation success rate seen in this study was due to selective exclusion of failed intubations. This selection bias led to a clinically important overestimation of the EDD's negative predictive value. Bias may substantially alter the estimations of test accuracy reported in scientific studies. To reduce the chance of unrecognized selection bias in studies of diagnostic tests, investigators must determine whether recruited subjects resemble patients in whom the test will ultimately be used.

Residual renal function (RRF) is a major contributor to total solute clearance in peritoneal dialysis (PD) patients, and maintenance of RRF has been linked to decreased morbidity and mortality in PD. There have been few clinical studies examining the impact of factors that potentially affect RRF in PD. This is a prospective observational study that examines the effects of parenteral aminoglycosides, a common nephrotoxin in the general population, on RRF in a cohort of PD patients. Seventy-two patients from two Rhode Island PD units were observed over 4 years. Twenty-four-hour renal creatinine clearances and urine volumes were measured every 4 to 6 months. The patients were divided into three groups, depending on exposure to peritonitis and aminoglycoside use. Group I included patients without peritonitis who received no intravenous (IV) or intraperitoneal (IP) antibiotics. Group II included patients with peritonitis who received IV or IP penicillins, cephalosporins, vancomycin, or quinolones, but no aminoglycosides. Group III included patients with peritonitis who received IV or IP aminoglycosides for at least 3 days. Patients in group III had a more rapid decline in renal creatinine clearance (-0.66 +/- 0.58 mL/min/mon) than groups I and II (P < 0.005) and had a more rapid decline in daily urine volume (-74 +/- 62 mL/d/mon) than groups I and II (P < 0.01). We conclude that IV or IP aminoglycosides seem to increase the rapidity of decline in RRF in PD patients. In patients with solute clearance dependent on RRF, it seems reasonable to withhold aminoglycosides, especially if other antibiotics are available and appropriate.

Methanol fuel use in motor vehicles and stationary combustion has the potential to improve air quality. A modeling study of methanol fuel use in Los Angeles, California, shows that the low chemical reactivity of methanol vapor slows ozone formation and would lead to lower ozone concentrations. Predicted peak ozone levels decreased up to 16 percent, and exposure to levels above the federal standard dropped by up to 22 percent, when pure (M100) methanol fuel use was simulated for the year 2000. Similar results were obtained for 2010. Use of a gasoline-methanol blend (M85) resulted in smaller reductions. Predicted formaldehyde levels and exposure were not increased severely, and in some cases declined, in the simulations of methanol use.

The purpose of the present study was to determine whether diagonal intersegmental interactions are present during normal human gait. The demonstration of consistently synchronous phasing would indicate the feasibility of utilizing an electromyographic (EMG) signal to control functional electrical stimulation to a paralyzed lower extremity muscle during gait. The EMG activity of several muscles of the upper extremity and of the tibialis anterior (TA) were monitored with surface electrodes in 8 women. Variability in both the frequency of occurrence and duration of EMG activity was found in all muscles of the upper extremity. No single arm muscle common to all subjects was phased similarly to TA. However, 6 subjects demonstrated at least 1 muscle of the upper extremity that was working at the same time as TA. It is postulated that differences in upper limb kinematics may mask the existence of intersegmental interactions during gait.

Following a 12-week endurance training program, the SDH activities of gastrocnemius medialis muscle of streptozotocin-induced diabetic animals increased by 50%. On the other hand, a 14% decrease was observed in the same muscle of diabetic animals submitted to power training. No difference between groups, for soleus and gastrocnemius lateralis muscles following the two different training regimens was observed. It can be concluded that streptozotocin-induced diabetic animals controlled by daily insulin demonstrate a normal muscle enzyme adaptation to exercise. These data also demonstrate that regular power and/or endurance exercise can result in reduced exogenous insulin need in streptozotocin-induced diabetic rats (18% and 28% respectively), suggesting a more efficient membrane transport of glucose with induced exercise, and a decreased need for insulin supported transport.

The effect of disuse on the functional properties of fast-twitch mammalian muscle is controversial, perhaps because the various disuse models reduce activity to different degrees, and may introduce factors other than reduced activity per se. Our goal was to compare the effects of 14 days of disuse produced by neurally applied tetrodotoxin and joint fixation (knee and ankle) on several morphologic and functional characteristics of the rat gastrocnemius. Joint fixation produced a decrease in muscle wet weight and absolute tetanic tension measured in situ, and a preferential atrophy of slow-twitch fibers. The degree of atrophy was more severe with TTX-disuse and affected all fiber types to the same extent. In further contrast to joint fixation, TTX-disuse caused a preferential loss of myofibrillar protein and a decrease in tetanic tension per unit muscle wet weight. In addition, TTX-disuse resulted in an elevation of twitch:tetanic ratio, a prolonged twitch, and generated a relatively higher proportion of tetanic force at 50 Hz. The normalized maximal rate of tetanic tension development (% Po/ms) was highest in the TTX group. The fatigue index was unaffected by either intervention. The data suggest that complete disuse of mammalian fast-twitch muscle causes atrophy, prolongation of the twitch, and a loss in contractile strength per gram of tissue, and are consistent with qualitative or quantitative changes in the sarcoplasmic reticulum and a decrease in myofibrillar protein concentration with disuse.