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Much research has been done on bone cells, but only a few studies deal with biomaterial-induced effects on human osteoclasts, which may take on an important role in the successful regeneration of bone. In order to highlight such effects, human peripheral blood mononuclear cells (PBMCs) were extracted from venous blood, differentiated to osteoclasts and then cultured in, the presence of five particulate hydroxyapatite (HA)/ß-tricalcium phosphate (TCP) biomaterials, on bovine bone slices and glass cover slips. The biomaterials, AlgOSS 50/50 (50 % HA/50 % TCP), AlgOSS 20/80 (20 % HA/80 % TCP), Algipore (98 % HA), Cerasorb (100 % TCP) and Bio-Oss (100 % HA) were chosen to assess their influence on cell morphology and numbers. Light microscopic evaluation was performed during ongoing cell culture. After 21 d of cultivation, the biomaterial-induced effects on osteoclastic resorption of the bone slices were evaluated by scanning electron microscopy (SEM). Osteoclast-like cells were identified by TRAP staining. All five biomaterials showed larger area fractions of resorbed bone than the control (5.6 ± 6.8 %), as measured on SEM images. The purely hydroxyapatite-based Algipore (9.8 ± 9.7 %) and Bio-Oss (7.9 ± 8.8 %) showed significantly elevated area fraction rates (p ≤ 0.05) of bone resorption. Light microscope evaluation revealed a significant, but inhibiting effect of Cerasorb (p = 0.05). These data indicated that introducing of small biomaterial hydroxyapatite particles may have improved the performance of bone substitute materials.

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BACKGROUND: Cytomegalovirus (CMV)-seronegative kidney transplant (KTx) recipients of organs from CMV-seropositive donors (D+/R-) are at increased risk for CMV infection. Despite valganciclovir (VGCV) prophylaxis (900 mg daily for 200 days), late-onset CMV (LO-CMV) occurs at excessive rates. VGCV-associated cost and toxicities remain problematic. METHODS: We retrospectively evaluated 50 D+/R- adult KTx recipients from August 2008 to August 2014 who received low-dose VGCV (450 mg daily) prophylaxis for an extended duration. The primary outcome was occurrence of CMV disease. RESULTS: All patients received depletion induction and underwent ABO-compatible KTx. Mean prophylaxis and follow-up durations were 22.8 and 40.7 months, respectively. Eight patients developed CMV: 5 breakthrough cases (1 case of colitis [2%] and 4 cases of infection [8%]) and 3 cases of LO-CMV (1 syndrome [2.9%] and 2 cases of infection [5.7%]). On logistic regression, longer duration of VGCV prophylaxis was protective against CMV infection or disease (P = .044; odds ratio, 1.12 [95% confidence interval, 1.03-1.29]). None of 19 recipients with prophylaxis for ≥12 months developed LO-CMV compared with 3 of 16 recipients with prophylaxis for <12 months (18.8%) (P = .086). Four patients had recurrence of CMV, and 1 patient developed resistance. CMV was not responsible for graft or patient loss and did not affect survival. CONCLUSIONS: Low-dose VGCV is an effective prophylaxis for D+/R- KTx recipients despite depleting induction. Longer prophylaxis is more protective, and receiving VGCV for ≥12 months nearly eradicated LO-CMV without increasing antiviral resistance.

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Tendon transfers frequently require coaptation of two mismatched tendons. In this cadaver study, ultimate load, stiffness, and Young's modulus were measured in tendon-to-tendon attachments with mismatched donor and recipient tendons, using pronator teres (PT) to extensor carpi radialis brevis (ECRB) and flexor carpi ulnaris (FCU) to extensor digitorum communis (EDC). FCU-to-EDC attachments failed at higher loads than PT-to-ECRB attachments, but they had similar modulus and stiffness values. Ultimate tensile strength of the tendon attachments exceeded the maximum predicted contraction force of any of the transferred muscles, with safety factors of four-fold for the FCU-to-EDC and two-fold for the PT-to-ECRB transfers. This implies that size and shape mismatches should not be contraindications to tendon attachment in transfers. The strength safety factors suggest that postoperative immobilization of these transfers is unnecessary.

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This study clinically assessed the concept that both thumb flexion and forearm pronation can be restored by brachioradialis (BR)-to-flexor pollicis longus (FPL) tendon transfer if the BR is passed dorsal to the radius. Six patients [two women and four men, mean age 32.3 years (SD 4.9, range 23-56)] underwent BR-to-FPL transfer dorsal to the radius and through the interosseous membrane (IOM). Lateral key pinch strength and pronation range of motion (ROM) were measured 1 year after surgery. A group of six patients [two women and four men, mean age 31.2 years (SD 5.0, range 19-52)] who underwent traditional palmar BR-to-FPL was included for comparison. Postoperative active pronation was significantly greater in the dorsal transfer group compared to the palmar group [149 (SD 6) and 75 (SD 3), respectively] and pinch strength was similar in the two groups [1.28 (SD 0.16) kg and 1.20 (SD0.21) kg, respectively]. We conclude that it is feasible to reconstruct lateral key pinch and forearm pronation simultaneously using only the BR motor.

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The material properties of passive skeletal muscle are critical to proper function and are frequently a target for therapeutic and interventional strategies. Investigations into the passive viscoelasticity of muscle have primarily focused on characterizing the elastic behavior, largely neglecting the viscous component. However, viscosity is a sizeable contributor to muscle stress and extensibility during passive stretch and thus there is a need for characterization of the viscous as well as the elastic components of muscle viscoelasticity. Single mouse muscle fibers were subjected to incremental stress relaxation tests to characterize the dependence of passive muscle stress on time, strain and strain rate. A model was then developed to describe fiber viscoelasticity incorporating the observed nonlinearities. The results of this model were compared with two commonly used linear viscoelastic models in their ability to represent fiber stress relaxation and strain rate sensitivity. The viscous component of mouse muscle fiber stress was not linear as is typically assumed, but rather a more complex function of time, strain and strain rate. The model developed here, which incorporates these nonlinearities, was better able to represent the stress relaxation behavior of fibers under the conditions tested than commonly used models with linear viscosity. It presents a new tool to investigate the changes in muscle viscous stresses with age, injury and disuse.

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BACKGROUND: The length at which a muscle/sarcomere operates in vivo (operational length) and the length at which it generates maximal stress (optimal length) can be quite different. In a previous study, we found that the rabbit external anal sphincter (EAS) operates on the ascending limb of the length-tension curve, in other words at lengths shorter than its optimal length (short sarcomere length). In this study, we tested whether the human EAS muscle also operates at a short sarcomere length. METHODS: The length-tension relationship of the EAS muscle was studied in vivo in 10 healthy nullipara women. EAS muscle length was altered by anal distension using custom-designed probes of 5, 10, 15, and 20mm diameter. Probes were equipped with a sleeve sensor to measure anal canal pressure. The EAS muscle electromyograph (EMG) was recorded using wire electrodes. Ultrasound images of anal canal were obtained to measure EAS muscle thickness and anal canal diameter. EAS muscle stress was calculated from the anal canal pressure, inner radius, and thickness of the EAS muscle. KEY RESULTS: Rest and squeeze stress of the anal canal increased with the increase in probe size. Similarly, the change in anal canal stress, i.e. the difference between the rest and the squeeze, which represents the active contribution of EAS to the anal canal stress, increased with the increase in probe size. However, increase in probe size was not associated with an increase in the external anal sphincter EMG activity. CONCLUSIONS & INFERENCES: Increase in EAS muscle stress with the increase in probe size, in the presence of constant EMG (neural input), demonstrates that the human EAS muscle operates on the ascending limb of the length-tension curve or at low sarcomere lengths. We propose that surgically adjusting EAS sarcomere length may represent a novel strategy to treat fecal incontinence in humans.

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BACKGROUND: Our recent studies show that the external anal sphincter muscle (EAS) operates at a sarcomere length range which is below optimal. In this study, we tested the hypothesis that by surgically increasing sarcomere length and bringing it close to the optimal length, EAS muscle function and anal canal pressure can be enhanced. METHODS: Rabbits (n = 25) were anesthetized and subjected to either a sham or an EAS plication of different length by placing sutures at two locations, at a distance of 13%, 20%, 28%, or 35% of the circumferential length of the anal canal. Anal canal pressures were recorded before and after the plication. Anal canal was harvested and the EAS muscle sarcomere length was measured using laser diffraction. KEY RESULTS: Electrical stimulation of the EAS muscle resulted in a stimulus-dependent increase in the anal canal pressure (mmHg) and EAS muscle stress (mN mm(-2)). A significant increase in maximal pressure (212 ± 13 after compared with 139 ± 22 before plication) as well as stress (166 ± 10 after as compared with 88 ± 14 before plication) was recorded at 20% plication length. Passive anal canal stress at 20% plication was not significantly different compared with the sham group. The mean sarcomere lengths with sham and 20% plication were 2.11 and 2.60 µm, respectively. CONCLUSIONS & INFERENCES: EAS plication resulted in a length-dependent increase in EAS muscle sarcomere length with an optimal sarcomere length at 20% plication. These considerations may help guide repair of anal sphincter muscle defects in the humans.

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STUDY DESIGN: Secure, web-based survey. OBJECTIVES: To determine how quadriplegics in the US view tendon transfer surgeries (TTS) and what activities of daily living (ADL) involving arm/hand function are important in improving quality of life (QoL). SETTING: World wide web. METHODS: Individuals >or=18 years of age living with a cervical spinal cord injury (SCI). Participants obtained a pass code to enter a secure website and answered survey questions. A total of 137 participants completed the survey. RESULTS: Two-thirds of participants had injury levels between C4/5 and C5/6. Over 90% felt that improving their arm/hand function would improve their QoL. ADL that were ranked most important to regain were dressing, feeding, transferring in/out of bed, and handwriting. Less than half of the participants had never been told about TTS and only 9% had ever had TTS. Nearly 80% reported that they would be willing to spend 2-3 months being less independent, while recovering from surgery, to ultimately become more independent. Over 75% reported that the ideal time preferred to have TTS, if chosen, would be within 5 years post-injury. CONCLUSION: Regaining arm and hand function is of primary importance to individuals with cervical SCI, in particular, to increase independence in multiple ADL. There is a critical need in the US to improve awareness of TTS as a viable option for improving arm/hand function in some people. This information needs to be provided early after injury so that informed choices can be made within the first 5 years.

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This study explored the effects of environmental and organizational stressors on the health of shiftworkers in a printing company (n = 124). A questionnaire was used to gather data on work history, organizational factors, psychosocial characteristics, medical history, present health, occupational and non-occupational exposures, and lifestyle factors. The perception of environmental and organizational conditions was associated (P < 0.05) with chronic back pain (odds ratio [OR], 1.29), varicose veins (OR, 1.35), allergic rhinitis (OR, 1.27), depression (OR, 1.45), and gastritis (OR, 1.15). Anxiety scores were associated with allergic rhinitis (OR, 1.14) and skin allergy (OR, 1.09). Shiftwork was a significantly risk factor for conjunctivitis (OR, 3.68), depression (OR, 0.23), cardiac arrhythmia (OR, 7.13), and gastritis (OR, 4.38). Other associations included tenure and chronic back pain (OR, 4.89), toluene exposure and skin allergy (OR, 3.76), worksite and conjunctivitis (OR, 7.0), and worksite and dermatitis (OR, 1.24 to 4.95). The number of hours of exercise per week was associated with varicose veins (OR, 4.33), and alcohol intake was associated with cardiac arrhythmia (OR, 6.74).

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Exercise involving lengthening of an activated muscle can cause injury. Recent reports documented the mechanics of exercise-induced muscle injury as well as physiological and cellular events and manifestations of injury. Loss of the cytoskeletal protein desmin and loss of cellular integrity as evidenced by sarcolemmal damage occur early during heavy eccentric exercise. These studies indicate that the earliest events in muscle injury are mechanical in nature, while later events indicate that it may be more appropriate to conclude that intense exercise initiates a muscle remodeling process. We conclude that muscle injury after eccentric exercise is differently severe in muscles with different architecture, is fibre type-specific, primarily because of fibre strain in the acute phase, and is exacerbated by inflammation after the initial injury.

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The serial sarcomere number of skeletal muscle changes in response to chronic length perturbation. The role of the intermediate filament desmin in regulating these changes was investigated by comparing the architectural adaptations of the tibialis anterior, extensor digitorum longus (EDL) and soleus from wild-type mice with those of homozygous desmin knockout mice after hindlimb immobilization. After 28 days, serial sarcomere number increased significantly in the lengthened wild-type tibialis anterior (by approximately 9%) and EDL (by approximately 17%). Surprisingly, muscles from desmin knockout mice also experienced significant serial remodeling, with the serial sarcomere number of the tibialis anterior increasing by approximately 10% and that of the EDL by approximately 27%. A consistent result was observed in the shortened soleus: a significant decrease in sarcomere number was observed in the muscles from both wild-type (approximately 26%) and knockout (approximately 12%) mice. Thus, although desmin is not essential for sarcomerogenesis or sarcomere subtraction in mouse hindlimb muscles, the results do suggest subtle differences in the nature of sarcomere number adaptation. We speculate that desmin may play a role in regulating the optimal arrangement of sarcomeres within the muscle or in sensing the magnitude of the immobilization effect itself.

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The force generated by skeletal muscle varies with sarcomere length and velocity. An understanding of the sarcomere length changes that occur during movement provides insights into the physiological importance of this relationship and may provide insights into the design of certain muscle/joint combinations. The purpose of this review is to summarize and analyze the available literature regarding published sarcomere length operating ranges reported for various species. Our secondary purpose is to apply analytical techniques to determine whether generalizations can be made regarding the "normal" sarcomere length operating range of skeletal muscle. The analysis suggests that many muscles operate over a narrow range of sarcomere lengths, covering 94+/-13 % of optimal sarcomere length. Sarcomere length measurements are found to be systematically influenced by the rigor state and methods used to make these measurements.

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Serum creatine kinase and dorsiflexion torque levels were measured in New Zealand White rabbits 1, 2, 7, 14, or 28 days after a single bout of eccentric exercise (n=26). No significant correlation was observed between creatine kinase activity and torque across time periods (P>0.15) and the regression relationship described only about 8% of the experimental variability. These data demonstrate that there exists a poor correlation between serum creatine kinase levels and skeletal muscle function after eccentric exercise.

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Skeletal muscle architecture is one of the most important properties that determines a muscle's force and excursion capability. In the current review, basic architectural terms first are reviewed and then specific examples relevant to upper extremity anatomy are presented. Specific examples of anatomic considerations required for surgical reconstruction after radial nerve palsy also are detailed. Together, these data show not only the wide variety of architectural designs in human muscles, but the importance of considering architectural design when making surgical decisions.

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Anatomic and biomechanical properties of the passive brachioradialis muscle were investigated to understand the limited excursion of this muscle seen during tendon transfer surgery. First, architectural measurements were performed on three fiber bundles obtained from four regions of the brachioradialis (10 specimens) chosen to represent the range of muscle fiber lengths across the brachioradialis. Next, in separate specimens (eight specimens), passive excursion was measured by securing the distal tendon stump to a servomotor. A constant load of 4.9 N was applied to the tendon, while the distal tendon was released from the surrounding tissue in 3-cm increments. Within the four regions studied, muscle fiber length varied significantly from 104.2 +/- 6.2 mm to 179.8 +/- 6.1 mm. As the brachioradialis was released, an average of 3 mm of mobility was obtained for each interval whereas for the succeeding three intervals, an average of 5.3 mm of mobility was obtained. This resulted in 22.2 +/- 2.3 mm of mobility when each specimen was fully released. These data show that there is no intrinsic muscle fiber length limitation to excursion, but that excursion is limited by other intermuscular connections to adjacent connective tissue and other muscles.

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The architectural properties of the posterior deltoid muscle and the 3 heads of the triceps were measured using microdissection techniques to determine whether substitution of triceps function by the posterior deltoid is architecturally appropriate. Muscles from 10 fresh cadaver specimens were fixed by high-pressure perfusion using buffered formaldehyde. Muscle architectural properties, including pennation angle, fiber bundle length, sarcomere length, and physiologic cross-sectional area, were determined. Fiber bundle length varied significantly among the deltoid (123.1 +/- 7.8 mm), medial (64.5 +/- 3.8 mm), lateral (66.5 +/- 5.4 mm), and long (85.3 +/- 9.5) heads of the triceps. The physiologic cross-sectional area of the posterior deltoid was significantly less than the total triceps area and was predicted to provide only approximately 20% of the maximum isometric tension of the combined triceps heads. These data demonstrate that the long fibers of the posterior deltoid render it a very suitable transfer to provide elbow extension because of its tremendous excursion and also show why useful functional results seem relatively independent of posterior deltoid tension at the time of surgery.

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Isoforms of myosin heavy chain (MHC) and myosin light chain (MLC) influence contractile kinetics of skeletal muscle. We previously showed that the four major skeletal muscle fibre types in Rana pipiens (type 1, type 2, type 3 and tonic; amphibian nomenclature) contain four unique MHC isoforms. In the present study we defined the MLCs expressed in each of these R. pipiens fibre types. The MLC composition of single MHC-typed fibres was determined from western blots using a panel of monoclonal MLC antibodies. A total of seven MLCs were identified, including four types of MLC1, two of MLC2 and a single MLC3. Twitch fibre types (types 1, 2 and 3) expressed MLC1(f) and MLC2(f), while tonic fibres contained a unique set of isoforms, MLC1(Ta), MLC1(Tb) and MLC2(T). MLC3 was expressed primarily in type 1, type 1-2 and type 2 fibres. Surprisingly, some frogs displayed a striking pattern of MLC expression where a unique isoform of MLC1 (MLC1(x)) was coexpressed along with the normal MLC1 isoform(s) in all fibre types. MLC1(x) was either expressed in all fibres of a given frog or was completely absent. The intraspecific polymorphism in MLC1 expression is likely to have a genetic basis, but is unlikely to be caused by allelic variation. The ratio of MLC3/MLC1 increased in direct proportion to the percentage of type 1 MHC, but was only weakly correlated. The variability in MLC3/MLC1 within a fibre type was extremely large. Both the MHC isoform and MLC3/MLC1 ratio varied significantly between 1 mm segments along the length of fibres. For all segments combined, MLC3/MLC1 increased with the percentage of type 1 MHC, but the correlation between segments was weaker than between fibres.

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Skeletal muscle architecture is the structural property of whole muscles that dominates their function. This review describes the basic architectural properties of human upper and lower extremity muscles. The designs of various muscle groups in humans and other species are analyzed from the point of view of optimizing function. Muscle fiber arrangement and motor unit arrangement is discussed in terms of the control of movement. Finally, the ability of muscles to change their architecture in response to immobilization, eccentric exercise, and surgical tendon transfer is reviewed. Future integrative physiological studies will provide insights into the mechanisms by which such adaptations occur. It is likely that muscle fibers transduce both stress and strain and respond by modifying sarcomere number in a way more suited to the new biomechanical environment.

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