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We tested whether explosive resistance training with partial range of motion (ROM) would be as effective as full ROM training using a noninferiority trial design. Fifteen subjects with strength training experience took part in an explosive-concentric only-leg press training program, three times per week for 10 weeks. One leg was randomly assigned to exercise with partial ROM (ie, 9o) and the other leg to full ROM. Before and after training, we assessed leg press performance, isokinetic concentric and isometric knee extension torque, and vastus lateralis muscle architecture. Overall, both training modalities increased maximal strength and rate of force development. Training with partial ROM yielded noninferior results compared to full ROM for leg press peak power (+69 ± 47% vs. +61 ± 64%), isokinetic strength (4-6 ± 6%-12% vs. 1-6 ± 6%-10% at 30, 60, and 180˚s-1 ), and explosive torque after 100 (47 ± 24 vs. 35 ± 22) and 150 ms (57 ± 22% vs. 42 ± 25%). The comparison was inconclusive for other functional parameters (ie, isokinetic peak torque (300˚s-1 ), joint angle at isokinetic peak torque, explosive torque after 50 ms, and electrically evoked torque) and for muscle fascicle length and thickness, although noninferiority was established for pennation angle. However, partial ROM was not found statistically inferior to full ROM for any measured variable. Under the present conditions, the effects of explosive heavy resistance training were independent of joint ROM. Instead, these data suggest that the distinct timing of muscle work in explosive contractions confers more influence to the starting joint angle than ROM on adaptations to this type of training.

Background Nonresected, nonmetastatic (NR‐M0) pancreatic cancer involves both locally advanced pancreatic cancer and patients who did not undergo resection due to poor health status or patient preference. This study investigates nationwide trends of characteristics, treatment, and survival of patients with NR‐M0 pancreatic cancer. Methods From the Netherlands Cancer Registry, all patients diagnosed with pancreatic cancer between 2006 and 2014 were selected. Chemotherapy and overall survival (OS) of NR‐M0 patients were evaluated for 3‐year time periods and 2 age groups using chi‐square tests for trend and Cox proportional hazard regression analysis. Results Of 18 234 patients, 33% had NR‐M0 pancreatic cancer, which decreased over time (in consecutive 3‐year periods: 38%‐33%‐28%, P

The convenient preparation of 1,4-dideoxy-1,4-imino-L-arabinitol derivatives carrying a propargyl group by way of the addition of TMS-propargyl Grignard reagent to a N-sulfinylglycosylamine is reported. This compound was coupled via a triazole-tether to various aromatic and heteroaromatic groups, thus providing structures that can be considered as simplified mimics of UDP-Galf, the substrate of GlfT2, a galactofuranosyltransferase present in mycobacteria. These new compounds were evaluated as inhibitors of this enzyme and found to have significant activity (IC50 values in the high M to low mM range) in spite of the absence of the diphospho linkage present in the parent sugar nucleotide.

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous = 2.07 (1.55-2.77, ptrend = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.

Contradictory results have been reported on the impact of ageing on structure and functions of skeletal muscle fibres likely due to complex interplay between ageing and other phenomena such as disuse and diseases. Here we recruited healthy, physically and socially active young (YO) and elderly (EL) men in order to study aging per se without the confounding effects of impaired physical function. In vivo analyses of quadriceps and in vitro analyses of vastus lateralis muscle biopsies were performed. In EL subjects, our results show that: (i) quadriceps volume, maximum voluntary torque (MVC), and patellar tendon force (Ft) were significantly lower; (ii) muscle fibres went through significant atrophy and impairment of specific force (Po/CSA) and unloaded shortening velocity (Vo); (iii) myosin/actin ratio and myosin content in individual muscle fibres were not altered; (iv) muscle proteome went through quantitative adaptations, namely an up-regulation of the content of several groups of proteins among which myofibrillar proteins and antioxidant defence systems; (v) muscle proteome went through qualitative adaptations, namely phosphorylation of several proteins, including Myosin Light Chain-2 slow and Troponin T and carbonylation of Myosin Heavy Chains. The present results indicate that impairment of individual muscle fibres structure and function is a major feature of ageing per se and that qualitative adaptations of muscle proteome are likely more involved than quantitative adaptations in determining such phenomenon. This article is protected by copyright. All rights reserved.

Background and Aim: Data on non-surgical treatment of groove pancreatitis (GP) and the risk of cancer are lacking. We aimed to determine the prevalence and predictors of cancer in patients in whom the diagnosis GP was considered, and to evaluate symptom improvement after treatment. Study: Patients referred with possible GP (2001-2014) were retrospectively included. An experienced radiologist reassessed imaging. GP patients received questionnaires evaluating their symptoms. Results: From the 38 possible GP patients, 10 had cancer (26%) and 28 GP (74%). Compared with cancer patients, GP patients more frequently had cysts (2/10 vs. 18/28, P = 0.03), less often jaundice (6/10 vs 3/27, P

The poor survival of patients with resectable pancreatic cancer might be related to the presence of occult peritoneal tumor cells (OPTC). This systematic review studies the prognostic value of cytology and carcinoembryonic antigen (CEA) by real-time polymerase chain reaction in peritoneal fluid. The results suggest that presence of OPTC is related to a worse survival in patients with resectable pancreatic cancer. Future studies should investigate its possible role in selecting patients for specific treatment strategies. J. Surg. Oncol. 2016;114:743-751. © 2016 Wiley Periodicals, Inc.

Background: Patients with resectable perihilar cholangiocarcinoma (PHC) on imaging have a substantial risk of metastatic or locally advanced disease, incomplete (R1) resection, and 90-day mortality. Our aim was to develop a preoperative prognostic model to predict surgical success, defined as a complete (R0) resection without 90-day mortality, in patients with resectable PHC on imaging. Study Design: Patients with PHC who underwent exploratory laparotomy in three tertiary referral centers were identified. Multivariable logistic regression was performed to identify preoperatively available prognostic factors. A prognostic model was developed using data from two European centers and validated in one American center. Results: In total, 671 patients with PHC underwent exploratory laparotomy. In the derivation cohort, surgical success was achieved in 102 of 331 patients (30.8%). No resection was performed in 176 patients (53.2%) because of metastatic or locally advanced disease. Of the 155 patients (46.8%) who underwent a resection, 38 (24.5%) had an R1-resection. Of the remaining 117 (35.3%), 15 (12.8%) had 90-day mortality. Independent poor prognostic factors for surgical success were identified, and a preoperative prognostic model was developed with a concordance index of 0.71. External validation showed good concordance (0.70). Conclusion: Surgical success was achieved in only 30% of patients with PHC undergoing exploratory laparotomy and could be predicted by age, cholangitis, hepatic artery involvement, lymph node metastases, and Blumgart stage.

Key points It is generally assumed that muscle fibres go through atrophy following disuse with a loss of specific force and an increase in unloaded shortening velocity. However, the underlying mechanisms remain to be clarified. Most studies have focused on events taking place during the development of disuse, whereas the subsequent recovery phase, which is equally important, has received little attention. Our findings support the hypotheses that the specific force of muscle fibres decreased following unilateral lower limb suspension (ULLS) and returned to normal after 3 weeks of active recovery as a result of a loss and recovery of myosin and actin content. Furthermore, muscle fibres went through extensive qualitative changes in muscle protein pattern following ULLS, and these were reversed by active recovery. Resistance training was very effective in restoring both muscle mass and qualitative muscle changes, indicating that long-term ULLS did not prevent the positive effect of exercise on human muscle. Abstract Following disuse, muscle fibre function goes through adaptations such as a loss of specific force (PO/CSA) and an increase in unloaded shortening velocity, which could be a result of both quantitative changes (i.e. atrophy) and qualitative changes in protein pattern. The underlying mechanisms remain to be clarified. In addition, little is known about the recovery of muscle mass and strength following disuse. In the present study, we report an extensive dataset describing, in detail,the functional and protein content adaptations of skeletal muscle in response to both disuse and re-training. Eight young healthy subjects were subjected to 3 weeks of unilateral lower limb suspension (ULLS), a widely used human model of disuse skeletal muscle atrophy. Needle biopsies samples were taken from the vastus lateralis muscle Pre-ULLS, Post-ULLS and after 3 weeks of recovery during which heavy resistance training was performed. After disuse, cross-sectional area (CSA), PO/CSA and myosin concentration (MC) decreased in both type 1 and 2A skinned muscle fibres. After recovery, CSA and MC returned to levels comparable to those observed before disuse, whereas Po/CSA and unloaded shortening velocity reached a higher level. Myosin heavy chain isoform composition of muscle samples did not differ among the experimental groups. To study the mechanisms underlying such adaptations, a two-dimensional proteomic analysis was performed. ULLS induced a reduction of myofibrillar, metabolic (glycolytic and oxidative) and anti-oxidant defence system protein content. Resistance training was very effective in counteracting ULLS-induced alterations, indicating that long-term ULLS did not prevent the positive effect of exercise on human muscle.

What is the central question of this study? Do the contractile properties of single muscle fibres differ between body-builders, power athletes and control subjects? What is the main finding and its importance? Peak power normalized for muscle fibre volume in power athletes is higher than in control subjects. Compared with control subjects, maximal isometric tension (normalized for muscle fibre cross-sectional area) is lower in body-builders. Although this difference may be caused in part by an apparent negative effect of hypertrophy, these results indicate that the training history of power athletes may increase muscle fibre quality, whereas body-building may be detrimental. We compared muscle fibre contractile properties of biopsies taken from the vastus lateralis of 12 body-builders (BBs; low- to moderate-intensity high-volume resistance training), six power athletes (PAs; high-intensity, low-volume combined with aerobic training) and 14 control subjects (Cs). Maximal isotonic contractions were performed in single muscle fibres, typed with SDS-PAGE. Fibre cross-sectional area was 67 and 88% (P < 0.01) larger in BBs than in PAs and Cs, respectively, with no significant difference in fibre cross-sectional area between PAs and Cs. Fibres of BBs and PAs developed a higher maximal isometric tension (32 and 50%, respectively, P < 0.01) than those of Cs. The specific tension of BB fibres was 62 and 41% lower than that of PA and C fibres (P < 0.05), respectively. Irrespective of fibre type, the peak power (PP) of PA fibres was 58% higher than that of BB fibres (P < 0.05), whereas BB fibres, despite considerable hypertrophy, had similar PP to the C fibres. This work suggests that high-intensity, low-volume resistance training with aerobic exercise improves PP, while low- to moderate-intensity high-volume resistance training does not affect PP and results in a reduction in specific tension. We postulate that the decrease in specific tension is caused by differences in myofibrillar density and/or post-translational modifications of contractile proteins.

Animal studies suggest that regular exposure to whole-body vibration (WBV) induces an anabolic response in bone and tendon. However, the effects of this type of intervention on human tendon properties and its influence on the muscle-tendon unit function have never been investigated. The aim of this study was to investigate the effect of WBV training on the patellar tendon mechanical, material and morphological properties, the quadriceps muscle architecture and the knee extension torque-angle relationship. Fifty-five subjects were randomized into either a vibration, an active control, or an inactive control group. The active control subjects performed isometric squats on a vibration platform without vibration. Muscle and tendon properties were measured using ultrasonography and dynamometry. Vibration training induced an increase in proximal (6.3%) and mean (3.8%) tendon cross-sectional area, without any appreciable change in tendon stiffness and modulus or in muscle architectural parameters. Isometric torque at a knee angle of 90° increased in active controls (6.7%) only and the torque-angle relation remained globally unchanged in all groups. The present protocol did not appreciably alter knee extension torque production or the musculo-tendinous parameters underpinning this function. Nonetheless, this study shows for the first time that WBV elicits tendon hypertrophy in humans.

The aim of this study was to investigate the effects of vitamin C and E supplementation on changes in muscle mass (lean mass and muscle thickness) and strength during 12 weeks of strength training in elderly men. Thirty-four elderly males (60-81 years) were randomized to either an antioxidant group (500 mg of vitamin C and 117.5 mg vitamin E before and after training) or a placebo group following the same strength training program (three sessions per week). Body composition was assessed with dual-energy X-ray absorptiometry and muscle thickness by ultrasound imaging. Muscle strength was measured as one-repetition maximum (1RM). Total lean mass increased by 3.9% (95% confidence intervals: 3.0, 5.2) and 1.4% (0, 5.4) in the placebo and antioxidant groups, respectively, revealing larger gains in the placebo group (P = 0.04). Similarly, the thickness of m. rectus femoris increased more in the placebo group [16.2% (12.8, 24.1)] than in the antioxidant group [10.9% (9.8, 13.5); P = 0.01]. Increases of lean mass in trunk and arms, and muscle thickness of elbow flexors, did not differ significantly between groups. With no group differences, 1RM improved in the range of 15-21% (P < 0.001). In conclusion, high-dosage vitamin C and E supplementation blunted certain muscular adaptations to strength training in elderly men.

The aim of this study was to investigate the effect of alpine skiing on patellar tendon properties in patients with total knee arthroplasty (TKA). Thirty-one adults (70.4 ± 4.7 years) with unilateral TKA were recruited 2.7 ± 0.9 years after surgery and assigned to an intervention (IG) or a control group (CG). The IG underwent a 12-week guided skiing program. Tendon stiffness, Young's modulus, and cross-sectional area (CSA) were measured before and after the intervention. In both groups, mean tendon CSA was 28% (P

This study investigated the effectiveness of recreational skiing as an intervention to improve quadriceps muscle architecture, strength, and antagonistic co-activation in patients with unilateral total knee arthroplasty (TKA). Hence, patients with TKA were assigned to either an intervention group (IG) or control group (CG). The IG completed a 12-week guided skiing program whereas the CG was instructed not to change their daily routines for the same period and was not allowed to ski. Before, after the intervention/after an 8-week retention period m. rectus femoris (RF) cross-sectional area (CSA), m. vastus lateralis muscle thickness, fascicle length, and pennation angle were measured with ultrasonography, while isometric (90° knee angle) knee extension, flexion torque and m. biceps femoris co-activation were assessed on an isokinetic dynamometer in 26 patients. There were significant and stable increases in RF CSA for the operated (10%; P 0.05). There were no significant effects for other parameters (all P > 0.05). Overall, the skiing intervention was successful in increasing muscle mass in TKA older patients.

A study of the preparation and of the reactivity of N-tert-butanesulfinyl glycosylamines is reported for the first time. As they react readily as latent imine equivalents with a variety of carbon nucleophiles, these new carbohydrate derivatives constitute very useful precursors for the diastereoselective synthesis of bioactive compounds such as iminosugar-C-glycosides.

The purpose of this study was to examine whether athletes with highly flexible hamstring muscle-tendon units display different passive and contractile mechanical properties compared with controls. Flexibility, passive, and active torque-angle properties were assessed in 21 female elite rhythmic gymnasts and 16 female age-matched athletes. Passive resistance to stretch was measured during knee extension with the hip fixed at 100° of flexion. Concentric isokinetic maximal voluntary knee flexion and extension torques were measured at 60°/s in the same position. Tests of flexibility and passive resistance to stretch indicated a greater flexibility in the gymnasts. Despite no differences between groups in knee flexion and extension peak torque, gymnasts reached knee flexion peak torque at more extended positions (longer muscle lengths) and displayed significantly different torque-angle relations. When active torque was corrected for passive resistance to stretch, differences increased, gymnasts producing more work, and maintaining ≥ 70% of peak torque over a larger range of joint excursion. In conclusion, individuals with a higher flexibility of the hamstrings MTU present a different torque-angle profile, favoring the production of flexion torque toward extended knee positions, displaying larger functional range of motion and a higher mechanical work output during knee flexion.

Difluoromethylated arenes are scaffolds of great interest. We report herein a mild and general method for the introduction of the CF2PO(OEt)2 moiety into arenes. The CuCF2PO(OEt)2 species, which is generated in situ from the corresponding silylated derivatives, in combination with aryl diazonium salts furnished the highly valuable aryl difluoromethylphosphonates in moderate to good yields. This represents the first general method to introduce difluoromethylphosphonates under mild conditions.

Several families of iminosugar-based galactoside mimics were designed, synthesized, and evaluated as galactocerebrosidase (GALC) inhibitors. They were also tested as inhibitors of lysosomal β- and α-galactosidases in order to find new potent and selective pharmacological chaperones for treatment of the lysosomal storage disorder, Krabbe disease. Whereas 1-C-alkyl imino-L-arabinitols are totally inactive toward the three enzymes, 1-C-alkyl imino-D-galactitols were found to be active only toward α-galactosidase A. Finally, 1-N-iminosugars provided the best results, as 4-epi-isofagomine was found to be a good inhibitor of both lysosomal β-galactosidase and GALC. Further elaboration of this structure is required to achieve selectivity between these two galactosidases.

A series of iminoxylitol derivatives carrying a C-linked di-O-acyl or di-O-alkyl glyceryl substituent were prepared and characterized. All of these compounds, which were designed as glucosylceramide (GlcCer) mimics, were nanomolar inhibitors of lysosomal β-glucosidase (glucocerebrosidase, GCase). Two of these pseudoglycolipids were further evaluated for their ability to enhance the activity of mutant GCase in human Gaucher cells. Although the di-O-hexyl ether was surprisingly devoid of chaperoning activity on both N370S and L444P GCases, the di-O-decanoyl ester was a potent chaperone of the L444P hydrolase, capable of increasing the residual activity of the enzyme by a factor of two at a very low concentration (50 nM); such a significant effect on the L444P mutation in human fibroblasts has not yet been observed. In heat-stress studies, the diether was found to be much more effective in stabilizing the wild-type enzyme than the diester. Four representative pseudoglycolipids were also assayed as inhibitors of GlcCer synthase, because such compounds could find use in the substrate reduction therapy approach to treat lysosomal storage diseases, but these compounds revealed only moderate activity. As efficient pharmacological chaperones, new structures such as the di-C10 -ester constitute leads for the development of therapeutic agents for types 2 and 3 Gaucher disease, the most severe neuronopathic forms of this lysosomal disease.

Costameres are mechano-sensory sites of focal adhesion in the sarcolemma that provide a structural anchor for myofibrils. Their turnover is regulated by integrin-associated focal adhesion kinase (FAK). We hypothesized that changes in content of costamere components (beta 1 integrin, FAK, meta-vinculin, gamma-vinculin) with increased and reduced loading of human anti-gravity muscle would: (i) relate to changes in muscle size and molecular parameters of muscle size regulation [p70S6K, myosin heavy chain (MHC)1 and MHCIIA]; (ii) correspond to adjustments in activity and expression of FAK, and its negative regulator, FRNK; and (iii) reflect the temporal response to reduced and increased loading. Unloading induced a progressive decline in thickness of human vastus lateralis muscle after 8 and 34 days of bedrest (−4% and −14%, respectively; n = 9), contrasting the increase in muscle thickness after 10 and 27 days of resistance training (+5% and +13%; n = 6). Changes in muscle thickness were correlated with changes in cross-sectional area of type I muscle fibers (r = 0.66) and beta 1 integrin content (r = 0.76) at the mid-point of altered loading. Changes in meta-vinculin and FAK-pY397 content were correlated (r = 0.85) and differed, together with the changes of beta 1 integrin, MHCI, MHCII and p70S6K, between the mid- and end-point of resistance training. By contrast, costamere protein level changes did not differ between time points of bedrest. The findings emphasize the role of FAK-regulated costamere turnover in the load-dependent addition and removal of myofibrils, and argue for two phases of muscle remodeling with resistance training, which do not manifest at the macroscopic level.

Background Patients undergoing oesophageal surgery have a high risk for post-operative complications including pulmonary infections. Recently, physical therapy has shifted from the post-operative to the pre-operative phase to diminish post-operative complications and to shorten hospital stay. The purpose of this pilot study was to investigate the feasibility and initial effectiveness of pre-operative inspiratory muscle training (IMT) on the incidence of pneumonia in patients undergoing oesophagectomy. Methods A pragmatic non-randomized controlled trial was conducted among all patients who underwent an oesophagectomy between January 2009 and February 2010. Patients in the intervention group received IMT prior to surgery. Feasibility was assessed on the basis of the occurrence of adverse effects during testing or training and patient satisfaction. Initial effectiveness on respiratory function was evaluated by maximal inspiratory pressure (MIP) and endurance, the incidence of post-operative pneumonia and length of hospital stay. Results Eighty-three patients were included, of which 44 received pre-operative IMT. No adverse effects were observed. IMT was well tolerated and appreciated. In the intervention group, the median MIP and endurance improved significantly after IMT by 32% and 41%, respectively (p

Strain is one of the parameters determining tendon adaptation to mechanical stimuli. The aim of this study was to test whether the patellar tendon strain induced during recreational alpine skiing would affect tendon mechanical properties in older individuals. Twenty-two older males and females (67 ± 2 years) were assigned to a 12-week guided skiing programme (IG) and 20 aged-matched volunteers served as controls (CG). Patellar tendon mechanical properties and cross-sectional area (CSA) were measured before and after training, with combined dynamometry and ultrasonography scanning. None of the variables changed significantly in the CG after training. In the IG, tendon stiffness and Young's modulus were increased (respectively, 14% and 12%, P

This study investigated whether regular alpine skiing could reverse sarcopenia and muscle weakness in older individuals. Twenty-two older men and women (67 ± 2 years) underwent 12 weeks of recreational skiing, two to three times a week, each session lasting ∼ 3.5 h. An age-matched, inactive group (n=20, 67 ± 4 years) served as a control (CTRL). Before and after the training period, knee extensors muscle thickness (T(m) ), pennation angle (θ) and fascicle length (L(f) ) of the vastus lateralis muscle were measured by ultrasound. Maximum isokinetic knee extensor torque (MIT) at an angular velocity of 60°/s was measured by dynamometry. After the training, T(m) increased by 7.1% (P

We hypothesized that 12 weeks of downhill skiing mitigates the functional deficits of knee extensor muscles in elderly subjects due to the specific recruitment of fast motor units during forceful turns on the slope. Downhill skiing led to a 1.4-fold increase in the mean cross-sectional area of slow (P=0.04)- and fast (P=0.08)-type muscle fibers. Fold changes in the expression of the structural component of focal adhesions, gamma-vinculin, were correlated with alterations in concentric force (r=0.64). Hypertrophy of fast fibers was more pronounced in women than in men (1.7 vs 1.1). Gender-specific structural-functional adjustments of knee extensor muscles and attached patellar tendon were reflected by altered expression of pro- vs de-adhesive proteins and a number of correlations. The de-adhesive protein tenascin-C was selectively increased in women compared with men (1.7 vs 1.1) while the content of the adhesive collagen XII was specifically reduced in women. The pro-adhesive focal adhesion kinase showed a specific increase in men compared with women (1.9 vs 1.1). Our findings indicate that quantitatively matched adaptations in slow and fast motor units of extensor muscle underlie the preventive effect of skiing against sarcopenia and support that hypertrophy and reinforcement of fiber adhesion operate in the improvement of muscle strength.

The purpose of this study was to determine whether the gain in soleus H-reflex excitability induced by unilateral lower limb suspension (ULLS) is associated with changes in neural drive to the plantar flexor muscles. Six male subjects (23 ± 2 years, 187 ± 7 cm, 79 ± 9 kg) underwent 24 days of ULLS of the dominant limb. Plantar flexor maximal voluntary contraction (MVC) torque, activation capacity (twitch interpolation), soleus maximal electromyographic (EMG) activity, Hoffman (H)-reflex, and the first volitional (V) wave normalized to the compound muscle action potential (M-wave) were quantified before and after ULLS. Following ULLS, MVC torque decreased by 15% (P < 0.05). However, neither activation capacity nor EMG activity was significantly altered after the suspension. The V-wave remained unchanged consistently after ULLS, whereas the H-reflex increased significantly (+20%). Furthermore, there was no significant relationship between changes in H-reflex and V-wave over the ULLS period. These findings indicate that 24 days of ULLS can result in a substantial reduction of muscle strength without any apparent change in voluntary activation capacity. H-reflex and V-wave findings suggest that the spinal adaptations that underlie the unloading-induced increase in resting soleus H-reflex excitability did not significantly affect the efferent motor output to the plantar flexor muscles.

Aim: Although most partial liver resections are performed for malignant lesions, an increasing contingent of benign lesions is also considered for surgery. The aim was to assess post-operative morbidity and mortality after liver resection for benign hepatobiliary lesions in comparison with outcome after resection of malignant lesions. Methods: A total of 286 liver resections were undertaken between January 1992 and December 2004. After exclusion of resection for bile duct tumours or hepatocellular carcinoma, 205 partial liver resections were retrospectively analysed. Results: Patients with benign lesions comprised 34% of the group (n=70). Benign lesions mainly consisted of focal nodular hyperplasia (n=12; 17%) and liver haemangiomas (11; 15.7%). The malignant lesions consisted of colorectal tumour metastases (n=121; 89%). Patients with benign lesions predominantly underwent minor liver resections (66 vs. 47%; P=0.013). The overall post-operative morbidity occurred in 31% (64/205). Major morbidity occurred in 16% (22/135) in the malignant group compared with 9% (6/70) in the benign group (P=0.099). No differences were seen in major post-operative morbidity in the earlier period compared with the later period (14 vs. 14.3%, P=0.950). In multivariate analysis, only presence of comorbidity (P=0.017), prolonged surgical procedure (P=0.021) and surgical irradicality (P=0.039) maintained significance as independent risk factors for major morbidity. Conclusion: Limited liver resections for the treatment of a wide range of benign hepatobiliary lesions are associated with low morbidity and no mortality. However, the indications must be assessed with care. The presence of comorbidity, prolonged surgical time and incomplete resections were associated with major morbidity.

We investigated how myofibrillar protein synthesis (MPS) and muscle anabolic signalling were affected by resistance exercise at 20–90% of 1 repetition maximum (1 RM) in two groups (25 each) of post-absorptive, healthy, young (24 ± 6 years) and old (70 ± 5 years) men with identical body mass indices (24 ± 2 kg m−2). We hypothesized that, in response to exercise, anabolic signalling molecule phosphorylation and MPS would be modified in a dose-dependant fashion, but to a lesser extent in older men. Vastus lateralis muscle was sampled before, immediately after, and 1, 2 and 4 h post-exercise. MPS was measured by incorporation of [1,2-13C] leucine (gas chromatography–combustion–mass spectrometry using plasma [1,2-13C]α-ketoisocaparoate as surrogate precursor); the phosphorylation of p70 ribosomal S6 kinase (p70s6K) and eukaryotic initiation factor 4E binding protein 1 (4EBP1) was measured using Western analysis with anti-phosphoantibodies. In each group, there was a sigmoidal dose–response relationship between MPS at 1–2 h post-exercise and exercise intensity, which was blunted (P < 0.05) in the older men. At all intensities, MPS fell in both groups to near-basal values by 2–4 h post-exercise. The phosphorylation of p70s6K and 4EBP1 at 60–90% 1 RM was blunted in older men. At 1 h post-exercise at 60–90% 1 RM, p70s6K phosphorylation predicted the rate of MPS at 1–2 h post-exercise in the young but not in the old. The results suggest that in the post-absorptive state: (i) MPS is dose dependant on intensity rising to a plateau at 60–90% 1 RM; (ii) older men show anabolic resistance of signalling and MPS to resistance exercise.

Aim: To investigate the influence of tendinous and synaptic changes induced by unilateral lower limb suspension (ULLS) on the tendon tap reflex. Methods: Eight young men underwent a 23-day period of ULLS. Muscle cross-sectional area (CSA), torque and electromyographic (EMG) activity of the plantar flexor muscles (normalized to the M wave), Achilles tendon–aponeurosis mechanical properties, soleus (SOL) H and T reflexes and associated peak twitch torques were measured at baseline, after 14 and 23 days of ULLS, and 1 week after resuming ambulatory activity. Results: Significant decreases in muscle CSA (−9%), in maximal voluntary torque (−10%) and in the associated SOL EMG activity (−16%) were found after ULLS (P < 0.05). In addition to a 36% (P < 0.01) decrease in tendon–aponeurosis stiffness, normalized H reflex increased by 35% (P < 0.05). An increase in the slope (28%, P < 0.05) and intercept (85%, P < 0.05) of the T reflex recruitment curve pointed to an increase in the gain and to a decrease in the sensitivity of this reflex, possibly resulting from the decrease in the tendon–aponeurosis stiffness at low forces. Following ULLS, changes in tendinous stiffness correlated with changes in neuromuscular efficiency (peak twitch torque to reflex ratio) at higher tendon tap forces. Conclusion: These findings point out the dual and antagonistic influences of spinal and tendinous adaptations upon the tendon tap reflex in humans under conditions of chronic unloading. These observations have potential implications for the sensitivity of the short-latency Ia stretch response involved in rapid compensatory contractions to unexpected postural perturbations.

Passive stretching is commonly used to increase limb range of movement prior to athletic performance but it is unclear which component of the muscle-tendon unit (MTU) is affected by this procedure. Movement of the myotendinous junction (MTJ) of the gastrocnemius medialis muscle was measured by ultrasonography in eight male participants (20.5 +/- 0.9 years) during a standard stretch in which the ankle was passively dorsiflexed at 1 deg s(-1) from 0 deg (the foot at right angles to the tibia) to the participants' volitional end range of motion (ROM). Passive torque, muscle fascicle length and pennation angle were also measured. Standard stretch measurements were made before (pre-) and after (post-) five passive conditioning stretches. During each conditioning stretch the MTU was taken to the end ROM and held for 1 min. Pre-conditioning the extension of the MTU during stretch was taken up almost equally by muscle and tendon. Following conditioning, ROM increased by 4.6 +/- 1.5 deg (17%) and the passive stiffness of the MTU was reduced (between 20 and 25 deg) by 47% from 16.0 +/- 3.6 to 10.2 +/- 2.0 Nm deg(-1). Distal MTJ displacement (between 0 and 25 deg) increased from 0.92 +/- 0.06 to 1.16 +/- 0.05 cm, accounting for all the additional MTU elongation and indicating that there was no change in tendon properties. Muscle extension pre-conditioning was explicable by change in length and pennation angle of the fascicles but post-conditioning this was not the case suggesting that at least part of the change in muscle with conditioning stretches was due to altered properties of connective tissue.

We hypothesized that rates of myofibrillar and patellar tendon collagen synthesis would fall over time during disuse, the changes being accompanied in muscle by decreases in focal adhesion kinase (FAK) phosphorylation and in gene expression for proteolytic enzymes. We studied nine men (22 +/- 4 years, BMI 24 +/- 3 kg m(-2) (means +/- s.d.) who underwent unilateral lower leg suspension for 23 days; five were studied between 0 and 10 days and four between 10 and 21 days. Muscle and tendon biopsies were taken in the postabsorptive state at days 0, 10 and 21 for measurement of protein synthesis, gene expression and protein phosphorylation. Muscle cross-sectional area decreased by 5.2% at 14 days and 10.0% (both P < 0.001), at 23 days, i.e. 0.5% day(-1), whereas tendon dimensions were constant. Rates of myofibrillar protein synthesis fell (P < 0.01) from 0.047% h(-1) at day 0 to 0.022% h(-1) at 10 days without further changes. Tendon collagen synthetic rates also fell (P < 0.01), from 0.052 to 0.023% h(-1) at 10 days and then to 0.010% h(-1) at 21 days. FAK phosphorylation decreased 30% (P < 0.01) at 10 days. No changes occurred in the amounts/phosphorylation of PKB-P70s6k-mTOR pathway components. Expression of mRNA for MuRF-1 increased approximately 3-fold at 10 days without changes in MAFbx or tripeptidyl peptidase II mRNA, but all decreased between 10 and 21 days. Thus, both myofibrillar and tendon protein synthetic rates show progressive decreases during 21 days of disuse; in muscle, this is accompanied by decreased phosphorylation of FAK, with no marked increases in genes for proteolytic enzymes.

Muscles and tendons are highly adaptive to changes in chronic loading, though little is known about the adaptative time course. We tested the hypothesis that, in response to unilateral lower limb suspension (ULLS), the magnitude of tendon mechanical adaptations would match or exceed those of skeletal muscle. Seventeen men (1.79 +/- 0.05 m, 76.6 +/- 10.3 kg, 22.3 +/- 3.8 years) underwent ULLS for 23 days (n = 9) or acted as controls (n = 8). Knee extensor (KE) torque, voluntary activation (VA), cross-sectional area (CSA) (by magnetic resonance imaging), vastus lateralis fascicle length (L(f)) and pennation angle (), patellar tendon stiffness and Young's modulus (by ultrasonography) were measured before, during and at the end of ULLS. After 14 and 23 days (i) KE torque decreased by 14.8 +/- 5.5% (P < 0.001) and 21.0 +/- 7.1% (P < 0.001), respectively; (ii) VA did not change; (iii) KE CSA decreased by 5.2 +/- 0.7% (P < 0.001) and 10.0 +/- 2.0% (P < 0.001), respectively; L(f) decreased by 5.9% (n.s.) and 7.7% (P < 0.05), respectively, and by 3.2% (P < 0.05) and 7.6% (P < 0.01); (iv) tendon stiffness decreased by 9.8 +/- 8.2% (P < 0.05) and 29.3 +/- 11.5% (P < 0.005), respectively, and Young's modulus by 9.2 +/- 8.2% (P < 0.05) and 30.1 +/- 11.9% (P < 0.01), respectively, with no changes in the controls. Hence, ULLS induces rapid losses of KE muscle size, architecture and function, but not in neural drive. Significant deterioration in tendon mechanical properties also occurs within 2 weeks, exacerbating in the third week of ULLS. Rehabilitation to limit muscle and tendon deterioration should probably start within 2 weeks of unloading.

The reaction of furanose and pyranose derivatives with optically active sulfinamidine (II) gives the title compounds (III) and (VII), respectively.

Difluoromethylated arenes are scaffolds of great interest. We report herein a mild and general method for the introduction of the CF2PO(OEt)2 moiety into arenes. The CuCF2PO(OEt)2 species, which is generated in situ from the corresponding silylated derivatives, in combination with aryl diazonium salts furnished the highly valuable aryl difluoromethylphosphonates in moderate to good yields. This represents the first general method to introduce difluoromethylphosphonates under mild conditions.