Clinical supervision in medical education: A citation analysis.

PURPOSE: Medical education relies on clinical supervision for critical functions, including trainee assessment and ensuring patient safety. Yet, there is substantial variance in supervision, which has led to calls for a shared definition of the concept and guidelines to inform practice. AMEE Guide No. 27 provided these desired elements and is highly cited, suggesting that translation and utilization of the Guide's knowledge is suboptimal. This study investigates utilization by systematically characterizing citations to the Guide and by describing translation of its recommendations in relation to supervision. MATERIALS AND METHODS: Citations were identified using Web of Science, Scopus, and Google Scholar. The authors coded all citations and conducted a subanalysis of studies specific to supervision. RESULTS: 583 studies were identified; 268 met inclusion criteria for general analysis of which 167 studies were further analyzed. Most studies reiterated the Guide's characterization of effective supervision, but few demonstrate how these recommendations inform innovations in supervisory practice. CONCLUSION: Translation of the Guide's recommendations regarding clinical supervision appears limited. Future research should consider the extent of knowledge translation occurring in clinical supervision literature as well as AMEE Guides. Increased attention to knowledge translation in medical education may benefit the distribution of similar knowledge products.

Vibrational spectroscopic analysis of blood for diagnosis of infections and sepsis: a review of requirements for a rapid diagnostic test.

Infections and sepsis represent a growing global burden. There is a widespread clinical need for a rapid, high-throughput and sensitive technique for the diagnosis of infections and detection of invading pathogens and the presence of sepsis. Current diagnostic methods primarily consist of laboratory-based haematology, biochemistry and microbiology that are time consuming, labour- and resource-intensive, and prone to both false positive and false negative results. Current methods are insufficient for the increasing demands on healthcare systems, causing delays in diagnosis and initiation of treatment, due to the intrinsic time delay in sample preparation, measurement, and analysis. Vibrational spectroscopic techniques can overcome these limitations by providing a rapid, label-free and low-cost method for blood analysis, with limited sample preparation required, potentially revolutionising clinical diagnostics by producing actionable results that enable early diagnosis, leading to improved patient outcomes. This review will discuss the challenges associated with the diagnosis of infections and sepsis, primarily within the UK healthcare system. We will consider the clinical potential of spectroscopic point-of-care technologies to enable blood analysis in the primary-care setting.

Liquid biopsy for cancer diagnosis using vibrational spectroscopy: systematic review.

BACKGROUND: Vibrational spectroscopy (VS) is a minimally invasive tool for analysing biological material to detect disease. This study aimed to review its application to human blood for cancer diagnosis. METHODS: A systematic review was undertaken using a keyword electronic database search (MEDLINE, Embase, PubMed, TRIP and Cochrane Library), with all original English-language manuscripts examining the use of vibrational spectral analysis of human blood for cancer detection. Studies involving fewer than 75 patients in the cancer or control group, animal studies, or where the primary analyte was not blood were excluded. RESULTS: From 1446 results, six studies (published in 2010-2018) examining brain, bladder, oral, breast, oesophageal and hepatic cancer met the criteria for inclusion, with a total population of 2392 (1316 cancer, 1076 control; 1476 men, 916 women). For cancer detection, reported mean sensitivities in each included study ranged from 79·3 to 98 per cent, with specificities of 82·8-95 per cent and accuracies between 81·1 and 97·1 per cent. Heterogeneity in reporting strategies, methods and outcome measures made meta-analysis inappropriate. CONCLUSION: VS shows high potential for cancer diagnosis, but until there is agreement on uniform standard reporting methods and studies with adequate sample size for valid classification models have been performed, its value in clinical practice will remain uncertain.

la espectroscopia vibracional (vibrational spectroscopy, VS) es un dispositivo mínimamente invasivo para analizar material biológico y detectar enfermedad. Este estudio se propuso revisar su aplicación en la sangre humana para el diagnóstico de cáncer. MÉTODOS: Se llevó a cabo una revisión sistemática utilizando una búsqueda con palabras claves en bases de datos electrónicas (MEDLINE, EMBASE, PubMed, TRIP, Cochrane Library), de todos los manuscritos originales publicados en inglés que examinaban la utilización del análisis espectral vibracional de la sangre humana para la detección del cáncer. Se excluyeron estudios que incluían menos de 75 pacientes en los grupos cáncer/control, estudios en animales o cuando la muestra principal no fuera la sangre. RESULTADOS: De los 1.446 resultados, 6 estudios publicados en 2010-2018, y que examinaban cánceres del cerebro, vejiga, oral, mama, esófago e hígado cumplieron los criterios de inclusión, con una población total de 2.506 casos (1.316 cánceres, 1.076 controles; 1.476 varones, 915 mujeres). Para la detección del cáncer, las sensibilidades medias descritas en cada uno de los estudios incluidos variaron entre 79,3-98,0%, con especificidades entre 82,8-95,0%, y exactitudes diagnósticas entre 81,1% y 97,1%. La heterogeneidad en las estrategias descritas, métodos y medidas de resultados hicieron que el metaanálisis fuera inapropiado. CONCLUSIÓN: La VS muestra un alto potencial para el diagnóstico del cáncer, pero hasta que no se llegue a un acuerdo en los métodos para informar de los resultados y se hayan efectuado estudios con un tamaño muestral adecuado para una clasificación válida de los modelos, su valor en la práctica clínica sigue siendo incierto.

Evaluating the ORSIM® simulator for assessment of anaesthetists' skills in flexible bronchoscopy: aspects of validity and reliability.

BACKGROUND: Developing expertise in flexible bronchoscopy is limited by inadequate opportunities to train on difficult airways. The new ORSIM bronchoscopy simulator aims to address this by creating virtual patients with difficult airways. This study aims to provide evidence on the validity and reliability of the ORSIM for assessment of subjects on both normal and abnormal airway simulations. METHODS: Novice, trainee, and expert subjects performed seven simulations of varying difficulty and scored the perceived difficulty for each. Time to completion was measured. Three blinded raters independently scored videos of each subject's performance. We measured inter-rater agreement and the difference in raters' scores between subject groups. RESULTS: We recruited 28 study subjects, generating 196 videos for analysis. Expert subjects consistently completed the scenarios faster than novices. Overall performance scores showed significant differences between subject groups (P<0.0001). Inter-rater reliability of scores was >0.8. CONCLUSIONS: Our results provide initial evidence on the validity and reliability of the ORSIM bronchoscopy simulator, supporting its potential value in training and assessment.

Biofluid infrared spectro-diagnostics: pre-analytical considerations for clinical applications.

Several proof-of-concept studies on the vibrational spectroscopy of biofluids have demonstrated that the methodology has promising potential as a clinical diagnostic tool. However, these studies also show that there is a lack of a standardised protocol in sample handling and preparation prior to spectroscopic analysis. One of the most important sources of analytical errors is the pre-analytical phase. For the technique to be translated into clinics, it is clear that a very strict protocol needs to be established for such biological samples. This study focuses on some of the aspects of the pre-analytical phase in the development of the high-throughput Fourier Transform Infrared (FTIR) spectroscopy of some of the most common biofluids such as serum, plasma and bile. Pre-analytical considerations that can impact either the samples (solvents, anti-coagulants, freeze-thaw cycles…) and/or spectroscopic analysis (sample preparation such as drying, deposit methods, volumes, substrates, operators dependence…) and consequently the quality and the reproducibility of spectral data will be discussed in this report.

The regulation of mitochondrial DNA copy number in glioblastoma cells.

As stem cells undergo differentiation, mitochondrial DNA (mtDNA) copy number is strictly regulated in order that specialized cells can generate appropriate levels of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS) to undertake their specific functions. It is not understood whether tumor-initiating cells regulate their mtDNA in a similar manner or whether mtDNA is essential for tumorigenesis. We show that human neural stem cells (hNSCs) increased their mtDNA content during differentiation in a process that was mediated by a synergistic relationship between the nuclear and mitochondrial genomes and results in increased respiratory capacity. Differentiating multipotent glioblastoma cells failed to match the expansion in mtDNA copy number, patterns of gene expression and increased respiratory capacity observed in hNSCs. Partial depletion of glioblastoma cell mtDNA rescued mtDNA replication events and enhanced cell differentiation. However, prolonged depletion resulted in impaired mtDNA replication, reduced proliferation and induced the expression of early developmental and pro-survival markers including POU class 5 homeobox 1 (OCT4) and sonic hedgehog (SHH). The transfer of glioblastoma cells depleted to varying degrees of their mtDNA content into immunocompromised mice resulted in tumors requiring significantly longer to form compared with non-depleted cells. The number of tumors formed and the time to tumor formation was relative to the degree of mtDNA depletion. The tumors derived from mtDNA depleted glioblastoma cells recovered their mtDNA copy number as part of the tumor formation process. These outcomes demonstrate the importance of mtDNA to the initiation and maintenance of tumorigenesis in glioblastoma multiforme.

An investigation of the RWPE prostate derived family of cell lines using FTIR spectroscopy.

Interest in developing robust, quicker and easier diagnostic tests for cancer has lead to an increased use of Fourier transform infrared (FTIR) spectroscopy to meet that need. In this study we present the use of different experimental modes of infrared spectroscopy to investigate the RWPE human prostate epithelial cell line family which are derived from the same source but differ in their mode of transformation and their mode of invasive phenotype. Importantly, analysis of the infrared spectra obtained using different experimental modes of infrared spectroscopy produces similar results. The RWPE family of cell lines can be separated into groups based upon the method of cell transformation rather than the resulting invasiveness/aggressiveness of the cell line. The study also demonstrates the possibility of using a genetic algorithm as a possible standardised pre-processing step and raises the important question of the usefulness of cell lines to create a biochemical model of prostate cancer progression.

FTIR-based spectroscopic analysis in the identification of clinically aggressive prostate cancer.

Fourier transform infrared (FTIR) spectroscopy is a vibrational spectroscopic technique that uses infrared radiation to vibrate molecular bonds within the sample that absorbs it. As different samples contain different molecular bonds or different configurations of molecular bonds, FTIR allows us to obtain chemical information on molecules within the sample. Fourier transform infrared microspectroscopy in conjunction with a principal component-discriminant function analysis (PC-DFA) algorithm was applied to the grading of prostate cancer (CaP) tissue specimens. The PC-DFA algorithm is used alongside the established diagnostic measures of Gleason grading and the tumour/node/metastasis system. Principal component-discriminant function analysis improved the sensitivity and specificity of a three-band Gleason score criterion diagnosis previously reported by attaining an overall sensitivity of 92.3% and specificity of 99.4%. For the first time, we present the use of a two-band criterion showing an association of FTIR-based spectral characteristics with clinically aggressive behaviour in CaP manifest as local and/or distal spread. This paper shows the potential for the use of spectroscopic analysis for the evaluation of the biopotential of CaP in an accurate and reproducible manner.

Investigating lipid-lipid and lipid-protein interactions in model membranes by ToF-SIMS.

With the chemical imaging capability of ToF-SIMS, biological molecules are identified and localized in membranes without any chemical labels. We have developed a model membrane system made with supported Langmuir-Blodgett (LB) monolayers. This simplified model can be used with different combinations of molecules to form a membrane, and thus represents a bottom-up approach to study individual lipid-lipid or lipid-protein interactions. We have used ternary mixtures of sphingomyelin (SM), phosphatidylcholine (PC), and cholesterol (CH) in the model membrane to study the mechanism of domain formation and interactions between phospholipids and cholesterol. Domain structures are observed only when the acyl chain saturation is different for SM and PC in the mixture. The saturated lipid, whether it is SM or PC, is found to be localized with cholesterol, while the unsaturated one is excluded from the domain area. More complicated model membranes which involve a functional membrane protein glycophorin are also investigated and different membrane properties are observed compared to the systems without glycophorin.

Using ultrasound measurements to predict body composition of yearling bulls.

Carcass traits have been successfully used to determine body composition of steers. Body composition, in turn, has been used to predict energy content of ADG to compute feed requirements of individual animals fed in groups. This information is used in the Cornell value discovery system (CVDS) to predict DM required (DMR) for the observed animal performance. In this experiment, the prediction of individual DMR for the observed performance of group-fed yearling bulls was evaluated using energy content of gain, which was based on ultrasound measurements to estimate carcass traits and energy content of ADG. One hundred eighteen spring-born purebred and crossbred bulls (BW = 288 +/- 4.3 kg) were sorted visually into 3 marketing groups based on estimated days to reach USDA low Choice quality grade. The bulls were fed a common high-concentrate diet in 12 slatted-floor pens (9 to 10 head/pen). Ultrasound measurements including back-fat (uBF), rump fat, LM area (uLMA), and intramuscular fat were taken at approximately 1 yr of age. Carcass measurements including HCW, backfat over the 12th to 13th rib (BF), marbling score (MRB), and LM area (LMA) were collected for comparison with ultrasound data for predicting carcass composition. The 9th to 11th-rib section was removed and dissected into soft tissue and bone for determination of chemical composition, which was used to predict carcass fat and empty body fat (EBF). The predicted EBF averaged 23.7 +/- 4.0%. Multiple regression analysis indicated that carcass traits explained 72% of the variation in predicted EBF (EBF = 16.0583 + 5.6352 x BF + 0.01781 x HCW + 1.0486 x MRB - 0.1239 x LMA). Because carcass traits are not available on bulls intended for use as herd sires, another equation using predicted HCW (pHCW) and ultrasound measurements was developed (EBF = 39.9535 x uBF - 0.1384 x uLMA + 0.0867 x pHCW - 0.0897 x uBF x pHCW - 1.3690). This equation accounted for 62% of the variation in EBF. The use of an equation to predict EBF developed with steer composition data overpredicted the EBF predicted in these experiments (28.7 vs. 23.7%, respectively). In a validation study with 37 individually fed bulls, the use of the ultrasound-based equation in the CVDS to predict energy content of gain accounted for 60% of the variation in the observed efficiency of gain, with 1.5% bias, and identified 3 of the 4 most efficient bulls.

Identifying differences in feed efficiency among group-fed cattle.

Identification of efficient animals in the postweaning growth phase for use in selection for improved feed efficiency is important to improve the economic and environmental sustainability of the beef cattle industry. Progeny testing using group-fed animals in commercial feedlots is the most common and practical method used to evaluate postweaning growth on large numbers of animals. We developed the Cornell Value Discovery System (CVDS) to dynamically predict growth rate, accumulated weight, days required to reach target body composition, carcass weight, and composition of individual beef cattle fed in group pens. Observed BW, ADG, BW at 28% empty body fat (EBF), breed type, environmental conditions, and dietary ME concentration are used by the CVDS to predict, for each animal in a pen, the feed DM required for maintenance (FFM), the feed DM required for gain, and the total DM required for maintenance and gain (DMR). The CVDS then computes DMR-to-ADG ratio (DMR:ADG), which is a feed conversion measure, and ADG-to-DMR ratio (ADG:DMR), which is a feed efficiency measure, for each animal. This study used the observed F:G ratio of 362 individually fed steers to evaluate CVDS-predicted indicators of feed efficiency and the Kleiber ratio. A subset of 37 data points was used to evaluate residual feed intake (RFI) as an indicator of feed efficiency. The database included 4 published studies, each with detailed individual animal description, environment, diet, and body composition information. The CVDS-predicted DMR:ADG accounted for 84% of the variation in the actual F:G ratio with a mean bias of 1.94% (P = 0.20). The predicted FFM to actual DMI ratio had a high correlation with actual ADG (R2 = 0.76), and indicated a decay-type nonlinear dilution of FFM as ADG increased. The CVDS-predicted ADG:DMR and the Kleiber ratio had a significant (R2 = 0.88) logarithmic relationship. In an analysis of a contemporary group within the database, RFI was highly correlated with the F:G ratio (r = 0.71). There was a positive relationship between RFI and EBF. The RFIM (DMI - DMR) was moderately correlated with DMI and ADG (0.37 and -0.38; respectively), suggesting that selecting for low RFI(M) would decrease DMI and increase ADG in this database. We conclude that the CVDS model can be used to identify differences in the F:G and G:F ratios by predicting DMR for individual growing cattle fed in groups.

Predicting individual feed requirements of cattle fed in groups.

A published model designed to predict individual feed required for the observed shrunk BW and ADG of growing cattle when fed in groups was modified and evaluated to improve its accuracy. This model is needed to accurately bill feed and compute cost of gain in marketing programs based on individual animal management. Because of its importance in predicting energy required for growth, a database of 401 steers was used to develop an equation to predict percentage of empty-body fat (EBF) from carcass measurements (12th rib fat thickness, hot carcass weight, USDA quality grade, and longissimus muscle area), which accounted for 61% of the variation in EBF with no bias (P > 0.1). When tested with an independent data set of 951 steers, the equation accounted for 51% of the variation with 1% proportional bias. The large variation in the carcass measurements at a particular EBF observed in this study indicates further improvement is limited by the inability of carcass measurements to account for variation in fat distribution in the various carcass components. Because of its importance in setting the target end point, a database of 1,355 steers and heifers was used to determine the relationship between EBF and USDA quality grade. These data indicate growing and finishing cattle reach Select and low-Choice quality grades at an EBF of 26.15 +/- 0.19 and 28.61 +/- 0.20%, respectively (P < 0.05). A data set of 228 steers from different breeds from two serial slaughter studies indicated 14.26 +/- 1.52 kg of empty BW change are required to increase EBF one percentage unit for cattle fed high-energy diets; this adjustment is needed to adjust final shrunk BW to the target EBF end point. The model to predict DM required with modifications developed in this study was evaluated with data from 365 individually fed cattle and it accounted for 74% of the variation in observed DM consumed with no bias (P > 0.1). When the revised model was applied to a commercial feedlot data set containing 12,105 steers and heifers, the total observed DM consumed was predicted with a bias of less than 1%. The model presented in this study accounts for differences known to affect animal requirements (breed type, BW and ADG, and weight at the target EBF end point) and can be used to fairly allocate feed to individuals fed in a group under commercial feedlot conditions.

Factors associated with home versus institutional death among cancer patients in Connecticut.

OBJECTIVE: To assess the relationships between home death and a set of demographic, disease-related, and health-resource factors among individuals who died of cancer. DESIGN: Prospective cohort study. SETTING: All adult deaths from cancer in Connecticut during 1994. PARTICIPANTS: Six thousand eight hundred and thirteen individuals who met all of the following criteria: died of a cancer-related cause in 1994, had previously been diagnosed with cancer in Connecticut, and were age 18 and older at the time of death. MEASUREMENT: Site of death. RESULTS: Twenty-nine percent of the study sample died at home, 42% died in a hospital, 17% died in a nursing home, and 11% died in an inpatient hospice facility. Multivariate analysis indicated that demographic characteristics (being married, female, white, and residing in a higher income area), disease-related factors (type of cancer, longer survival postdiagnosis), and health-resource factors (greater availability of hospice providers, less availability of hospital beds) were associated with dying at home rather than in a hospital or inpatient hospice. CONCLUSIONS: The implications of this study for clinical practice and health planning are considerable. The findings identify groups (men, unmarried individuals, and those living in lower income areas) at higher risk for institutionalized death-groups that may be targeted for possible interventions to promote home death when home death is preferred by patients and their families. Further, the findings suggest that site of death is influenced by available health-system resources. Thus, if home death is to be supported, the relative availability of hospital beds and hospice providers may be an effective policy tool for promoting home death.

Adult Chediak-Higashi parkinsonian syndrome with dystonia.

Chediak-Higashi syndrome (CHS) is a rare autosomal-recessive disorder characterized by immune deficiency, partial oculocutaneous albinism, and large eosinophilic, peroxidase-positive inclusion bodies in granule-containing cells. The adult form of CHS manifests during late childhood to early adulthood and is marked by various neurologic sequelae, including parkinsonism, dementia, spinocerebellar degeneration, and peripheral neuropathy. We report the case of a 29-year-old man with adult CHS who exhibited a progressive asymmetric parkinsonism, including rest tremor, and axial, cervical, and appendicular dystonia. The diagnosis was confirmed by the presence of characteristic large peroxidase-positive granules within leukocytes and markedly decreased natural killer cell function. Levodopa/carbidopa and amantadine provided benefit for tremor. CHS, although rare, should be considered in the differential diagnosis of young adult parkinsonism.

Single-fiber myosin heavy-chain isoform composition of rodent laryngeal muscle: modulation by thyroid hormone.

BACKGROUND: Studies have shown that canine laryngeal muscle contains a large number of muscle fibers that coexpress varying combinations of myosin heavy-chain (MyHC) isoforms. Currently, it is not clear whether this phenomenon is unique to canine laryngeal muscle or occurs in all mammals. OBJECTIVES: To examine the single-fiber MyHC isoform composition of rodent laryngeal muscle and to examine the plasticity of single-fiber MyHC isoform composition via manipulation of thyroid state. RESULTS: (1) Findings of single-fiber electrophoretic analyses clearly demonstrate that most fibers in both the posterior cricoarytenoid and thyroarytenoid muscles exhibit MyHC polymorphism. However, the proportions and patterns of polymorphism appear to be muscle specific. (2) Although the fast type IIL isoform was observed in fibers from both muscles, it was always coexpressed in combination with other MyHC isoforms (ie, no pure type IIL fibers were found), and always represented a minor proportion of the total MyHC pool. (3) Altering the thyroid state proved a useful tool for exploring the scope of MyHC isoform expression in these muscles. While the posterior cricoarytenoid muscle seemed more sensitive to the thyroid state, transitions in both muscles were primarily confined to the fast type IIX and IIB MyHC isoforms. CONCLUSION: The findings of this study support the concept that single-fiber MyHC polymorphism occurs commonly in mammalian laryngeal muscle.

Novel transitions in MHC isoforms: separate and combined effects of thyroid hormone and mechanical unloading.

Single-fiber (n = 3,818 fibers) electrophoretic analyses were used to delineate the separate and combined effects of hyperthyroidism (T3) and hindlimb suspension (HS) on the myosin heavy chain (MHC) isoform composition (1-, 2-, and 4-wk time points) of the rat soleus muscle. The key findings of this study are as follows. First, T3 and HS both altered the distribution of MHC isoforms at the single-fiber level; however, the populations of fibers produced by these two interventions were clearly different from one another. Second, T3 + HS rapidly converted the soleus into a fast muscle, producing large increases in the relative contents of the fast type IIx and IIb MHC isoforms which were primarily expressed in several populations of hybrid fibers (e.g., types I/IIa/IIx, I/IIx/IIb, I/IIa/IIx/IIb). Finally, T3 + HS produced unique populations of hybrid fibers that did not adhere to the Ileft arrow over right arrow IIaleft arrow over right arrow IIxleft arrow over right arrow IIb sequential scheme of MHC plasticity. Collectively, the findings of this study demonstrate that the intervention of T3 + HS is a powerful model for manipulating and studying MHC isoform plasticity in slow skeletal muscle.

A new concept in laryngeal muscle: multiple myosin isoform types in single muscle fibers of the lateral cricoarytenoid.

This report describes the first known investigation of canine laryngeal muscle in which single fibers were dissected and their myosin heavy chain (MHC) isoform content was analyzed. Both SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and western blot techniques were used. The data from single fiber SDS-PAGE indicate that the lateral cricoarytenoid (LCA) is predominantly a fast muscle composed of the following MHC isoforms: Type I, 16.3%; Type IIA, 71.3%; Type IIX, 10.4%; and Type IIB, 2.0%. The results reveal a phenomenon that, to our knowledge, has not been previously described for laryngeal muscle: the presence of two or more MHC isoforms in a single canine LCA muscle fiber. A large number (41%) of muscle fibers coexpressed two or more MHC isoforms. The three most common patterns of coexpression were Type IIA/IIX (72%), Type IIA/I (16%), and Type IIA/IIX/I (8%). Interestingly, the fast Type IIX MHC isoform was typically present with other isoforms and rarely found by itself in individual fibers. Additional experiments are underway to determine whether other laryngeal muscles exhibit such an unusually high ratio of MHC isoform polymorphism.

Single-fiber and whole muscle analyses of MHC isoform plasticity: interaction between T3 and unloading.

Previous data suggest that separate interventions of hyperthyroidism (T3) and hindlimb suspension (HS) act on some but not all slow type I fibers in the soleus muscle. This may be due to the presence of "refractory" fibers that are unresponsive to either of these interventions. Alternatively, T3 and HS might act on different populations of slow type I fibers in the soleus muscle. Adult female Sprague-Dawley rats were assigned to 1) control, 2) T3, 3) HS, or 4) T3+HS. Nine animals were assigned to each group. Single-fiber electrophoretic analyses (n = 40 per muscle) of the soleus muscle demonstrated that the HS reduced the percentage of slow type I fibers from approximately 80% (control) to approximately 40% (HS) of the fiber population. Although hyperthyroidism affected a greater percentage of slow type I fibers than HS, a small population (approximately 10% of the slow type I fibers) were unaffected by T3. The combined intervention, in contrast, transformed all slow type I fibers into fibers expressing various combinations of fast myosin heavy chain (MHC) isoforms. These findings demonstrate that the soleus muscle does not contain so-called refractory fibers. They further suggest that the soleus muscle contains different populations of slow type I fibers that vary in their sensitivity to altered physiological conditions.

Modulation of myosin isoform expression by mechanical loading: role of stimulation frequency.

This study tested for the hypothesis that mechanical loading, not stimulation frequency per se, plays a key role in determining the plasticity of myosin heavy chain (MHC) protein isoform expression in muscle undergoing resistance training. Female Sprague-Dawley rats were randomly assigned to resistance-training programs that employed active 1) shortening (n = 7) or 2) lengthening contractions (n = 8). The medial gastrocnemius (MG) muscles in each group trained under loading conditions that approximated 90-95% of maximum isometric tetanic tension but were stimulated at frequencies of 100 and approximately 25 Hz, respectively. Lengthening and shortening contractions were produced by using a Cambridge ergometer system. The MG muscles trained every other day, performing a total of 16 training session. Both training programs produced significant (P < 0.01) and similar reductions in the fast type IIB MHC protein isoform in the white MG muscle, reducing its relative content to approximately 50% of the total MHC protein isoform pool. These changes were accompanied by increases in the relative content of the fast type IIX MHC protein isoform that were of similar magnitude for both groups. The results of this study clearly demonstrate that stimulation frequency does not play a key role in modulating MHC isoform alterations that result from high-resistance training.