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Alpine ski racing is known as a high-risk sport; however, little is known on the health problems occurring at youth level. The purpose of this study was to investigate the prevalence of health problems in youth competitive alpine skiers with respect to sex, age, and season differences, to describe their severity and location and to assess the influence of biological maturation. Over a 12-month period, 155 youth competitive alpine skiers around the growth spurt were prospectively monitored for health problems using the Oslo Sports Trauma Research Centre (OSTRC) questionnaire. These data were verified by supplemental interviews at the end. Biological maturation was estimated by a non-invasive, anthropometric-based assessment method. During competition season, 42.2% of the skiers suffered from health problems and 19.8% reported their problem being substantial. Females had significantly higher rates of acute and overuse injuries compared to males, while there was no sex difference in duration, severity, and time loss. Skiers of the category U15 showed higher prevalence of acute and overuse injuries than U14 skiers. During preparation season, health problem prevalence was substantially lower. The knee was found to be the most affected body part for both acute and overuse injuries. There was a direct association between the offset to the age at peak height velocity (APHV) and the occurrence and severity of acute injuries. In conclusion, youth competitive alpine skiers suffer from a large number of health problems. Since sex, age, and biological maturation are important, effective injury prevention should already start before reaching the APHV.

INTRODUCTION We evaluated the contribution of denervation-related molecular processes to rotator cuff muscle degeneration after tendon release. METHODS We assessed the levels of myogenic (myogenin and myogenic differentiation factor [myoD]) and pro-adipogenic (peroxisome proliferator-activated receptor gamma) transcription factors; the denervation-associated proteins tenascin-C, laminin-2, and calcium/calmodulin dependent kinase II (CaMKII); and cellular alterations in sheep after infraspinatus tenotomy (TEN), suprascapular neurectomy (NEU), or both (TEN-NEU). RESULTS Extracellular ground substance increased at the expense of contractile tissue 16 weeks after surgery, correlating with CaMKII isoform levels. Sheep undergoing NEU and TEN-NEU had exaggerated infraspinatus atrophy and increased fast fibers compared with TEN sheep. The βMCaMKII isoform levels increased with tenotomy, and myoD levels tripled after denervation and were associated with slow fibers. DISCUSSION In sheep, denervation did not affect muscle-to-fat conversion after tenotomy of the infraspinatus. Furthermore, concurrent neurectomy mitigated the loss of fast fibers after tenotomy by inducing a fast-contractile phenotype. This article is protected by copyright. All rights reserved.

Osteoarthritis (OA) of the glenohumeral joint constitutes the most frequent indication for nontraumatic shoulder joint replacement. Recently, a small critical shoulder angle (CSA) was found to be associated with a high prevalence of OA. This study aims to verify the hypothesis that a small CSA leads to higher glenohumeral joint reaction forces during activities of daily living than a normal CSA. A shoulder simulator with simulated deltoid (DLT), supraspinatus (SSP), infraspinatus/teres minor (ISP/TM), and subscapularis (SSC) musculotendinous units was constructed. The DLT wrapping on the humerus was simulated using a pulley that could be horizontally adjusted to simulate the 28° CSA found in OA or the 33° CSA found in disease-free shoulders. Over a range of motion between 6° and 82° of thoracohumeral abduction joint forces were measured using a six-axis load cell. An OA-associated CSA yielded higher net joint reaction forces than a normal CSA over the entire range of motion. The maximum difference of 26.4 N (8.5%) was found at 55° of thoracohumeral abduction. Our model thus suggests that a CSA typical for OA predisposes the glenohumeral joint to higher joint reaction forces and could plausibly play a role in joint overloading and development of OA. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1047-1052, 2016.

Shoulders with rotator cuff tears (RCT) tears are associated with significantly larger critical shoulder angles (CSA) (RCT CSA = 38.2°) than shoulders without RCT (CSA = 32.9°). We hypothesized that larger CSAs increase the ratio of glenohumeral joint shear to joint compression forces, requiring substantially increased compensatory supraspinatus loads to stabilize the arm in abduction. A previously established three dimensional (3D) finite element (FE) model was used. Two acromion shapes mimicked the mean CSA of 38.2° found in patients with RCT and that of a normal CSA (32.9°). In a first step, the moment arms for each muscle segment were obtained for 21 different thoracohumeral abduction angles to simulate a quasi-static abduction in the scapular plane. In a second step, the muscle forces were calculated by minimizing the range of muscle stresses able to compensate an external joint moment caused by the arm weight. If the joint became unstable, additional force was applied by the rotator cuff muscles to restore joint stability. The model showed a higher joint shear to joint compressive force for the RCT CSA (38.2°) for thoracohumeral abduction angles between 40° and 90° with a peak difference of 23% at 50° of abduction. To achieve stability in this case additional rotator cuff forces exceeding physiological values were required. Our results document that a higher CSA tends to destabilize the glenohumeral joint such that higher than normal supraspinatus forces are required to maintain modeled stability during active abduction. This lends strong support to the concept that a high CSA can induce supraspinatus (SSP) overload. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:961-968, 2016.

Previous studies suggested that degradation of contractile tissue requires cleavage of the costamere, a structural protein complex that holds sarcomeres in place. This study examined if costamere turnover is affected by a rotator cuff tear in a previously established ovine model. We found the activity of focal adhesion kinase (FAK), a main regulator of costamere turnover, was unchanged at 2 weeks but decreased by 27% 16 weeks after surgical release of the infraspinatus tendon. This was accompanied by cleavage of the costamere protein talin into a 190 kDa fragment while full length talin remained unchanged. At 2 weeks after tendon release, muscle volume decreased by 17 cm from an initial 185 cm(3) , the fatty tissue volume was halved, and the contractile tissue volume remained unchanged. After 16 weeks, the muscle volume decreased by 36 cm(3) , contractile tissue was quantitatively lost, and the fat content increased by 184%. Nandrolone administration mitigated the loss of contractile tissue by 26% and prevented fat accumulation, alterations in FAK activity, and talin cleavage. Taken together, these findings imply that muscle remodeling after tendon release occurs in two stages. The early decrease of muscle volume is associated with reduction of fat; while, the second stage is characterized by substantial loss of contractile tissue accompanied by massive fat accumulation. Regulation of costamere turnover is associated with the loss of contractile tissue and seems to be impacted by nandrolone treatment. Clinically, the costamere may represent a potential intervention target to mitigate muscle loss after a rotator cuff tear. © 2017 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res.

Shoulders with supraspinatus (SSP) tears are associated with significantly larger critical shoulder angles (CSA) compared to disease-free shoulders. We hypothesized that larger CSAs increase the ratio of joint shear to joint compression forces (defined as "instability ratio"), requiring substantially increased compensatory supraspinatus loads. A shoulder simulator with simulated deltoid, supraspinatus, infraspinatus/teres minor, and subscapularis musculotendinous units was constructed. The model was configured to represent either a normal CSA of 33° or a CSA characteristic of shoulders with rotator cuff tears (38°), and the components of the joint forces were measured. The instability ratio increased for the 38° CSA compared with the control CSA (33°) for a range of motion between 6° to 61° of thoracohumeral abduction with the largest differences in instability observed between 33° and 37° of elevation. In this range, SSP force had to be increased by 13-33% (15-23 N) to stabilize the arm in space. Our results support the concept that a high CSA can induce SSP overload particularly at low degrees of active abduction.

Static superior shoulder instability is associated with long-standing rotator cuff tears. Factors or mechanisms which can prevent superior migration of the humeral head, and therefore allow preservation or restoration of shoulder function despite nonanatomical cuff repair, are poorly understood. The question has therefore arisen, whether centering of the humeral head was the result of active shoulder muscle function. It was the goal of this experimental investigation to (1) determine the pattern of glenohumeral translations during active shoulder abduction measured by open-magnetic resonance imaging (MRI) techniques, and to (2) determine the influence of experimental paralysis of the infra- and supraspinatus muscles on these translations. In contrast to prior experimental investigations, the humeral head remained always centered in the glenoid fossa during active abduction. No superior migration of the humeral head could be provoked with experimental paralysis of the supra- and/or infraspinatus muscles. The hypothesis that static or dynamic superior humeral head displacement is prevented by active-supra- and/or infraspinatus muscle function must therefore be rejected, for the shoulder with a structurally intact muscle-tendon-bone unit.

Idiopathic or surgical tightening of the glenohumeral joint capsule may cause displacement of the humeral head relative to the glenoid fossa and favor the development of instability and/or osteoarthritis. In the present investigation the relative position of the humerus to the glenoid fossa was determined at the end of the ranges of eight different passive movements before and after selective capsular plication in eight cadaveric shoulders to study the effects of selective capsular plications on the kinematics of the shoulder. While the capsule was in its unaltered state, translation of the humeral head was 3.8 mm superiorly in abduction, 7.3 mm antero-superiorly in flexion. In internal rotation in 0 degrees, 45 degrees and 90 degrees of abduction the head moved 6.1, 8.0 and 12.0 mm antero-inferiorly. In external rotation at 0 degrees of abduction the translation was 0.9 mm antero-inferiorly, at 45 degrees and 90 degrees of abduction it was 4.3 and 5.6 mm postero-inferiorly, respectively. Plications of the anterior part of the capsule reproducibly and significantly either increased or decreased translations during flexion (up to 5.9 mm anteriorly and up to 3.8 mm inferiorly), external rotation (up to 2.9 mm posteriorly and 1 mm inferiorly) and internal rotation (from 5.5 mm posteriorly to 2 mm anteriorly and up to 2.2 mm superiorly). Posterior plications had only little effect on translations (mainly a decrease of anterior translation during flexion of 2.8 mm).The 'obligate' glenohumeral translations which occur towards the end of passive shoulder movements are altered in a reproducible fashion by tightening specific parts of the glenohumeral joint capsule, as often carried out in treatment of shoulder instability. These alterations of the kinematics of the glenohumeral joint may be relevant for the development of static subluxation and osteoarthitis as seen after too tight plication in the treatment of instability [Int. Orthop. (SICOT) 67-B (1985) 709; J. Bone Joint Surg. Am. 72 (1990) 1193; J. Bone Joint Surg. Am. 66-A (1984) 169; J. Bone Joint Surg. Am. 65 (1983) 456].

The purpose of this study was to determine the relationship between rotator cuff (RC) tear and the orientation of the glenoid. Ninety-six shoulders (94 patients) that underwent open RC repair were grouped according to the type of tear. We measured on MRI the acromio-glenoid angle (AG) and the supraspinatus fossa glenoid angle on the anterior-posterior (SGAP) and axial (SGAX) views. RC patients had a smaller AG angle (76+/-7 degrees vs. 86+/-10 degrees ) and a larger SGAP angle (112+/-6 degrees vs. 102+/-7 degrees ) compared to controls (p

Strong bases (lithium diisopropylamide (LDA) or BuLi) convert cyclosporin A (CS) to hexalithio derivative containing a Li alkoxide, four Li azaenolate, and one Li enolate units. The Li6 compound is solubilized in tetrahydrofuran (THF) by addition of excess LDA or LiCl. Reactions with electrophiles (alkyl halides, aldehydes, ClCO2R, CO2, (RS)2, D2O) at low temperatures give products containing new side chains in amino-acid residue 3 of the cyclic undecapeptide (see 1–13, Schemes 1, and 2, and Figs. 1 and 2) in moderate to high yields and, with Re- or Si-selectivities, depending upon the conditions of lithiation of up to 7:1, Pure CS derivatives (Scheme 2, Table 1 in the Exper. Part) can be isolated by column chromatography. N-Alkylations or cleavage of the peptide backbone by carbonyl addition occur only at higher temperatures and/or with prolonged reaction times (see 14 and 15 in Scheme 4). Very little or no epimerization of stereogenic centers occurs under the conditions employed. Possible reasons for the feasibility of these surprizing conversions of CS are discussed (Schemes 4 and 5 and Fig. 3). For comparision, [MeAla3]CS (2b) and [D-MeAla3]CS (2a) were also prepared by conventional peptide synthesis in solution (Schemes 6 and 7). Their 1H- and 13C-NMR spectra are compared with those of CS (Table 2 in the Exper. Part).

Z-Protected diphenyl (decarboxy-dipeptidyl)phosphonates 5a-c with a (decarboxysarcosinyl)phosphonate moiety are prepared from Z-L-alanine (1a). Z-L-valine (1b), and Z-L-phenylalanine (1c) by the following series of steps: coupling with methyl sarcosinate (2a–c), saponification (3a–c), Hofer-Moest oxidative decarboxyiation by electrolysis in MeOH (4a–c), and Arbuzov reaction with P(OPh)3/TiCl4 (Scheme 3). Double deprotonation and alkylation lead to non-stereoselective incorporation of side chains next to the phosphonate group (products of type 6–8, nine examples, see Scheme 4). In the cases of 6a–c and 8c, the diastereoisomers could be separated and the configuration of the newly formed stereogenic center deduced. We assign the L,D-configuration to the diastereoisomers for which the 31P-NMR signal appears at higher field.

Z-Protected diphenyl (decarboxy-dipeptidyl)phosphonates 5a-c with a (decarboxysarcosinyl)phosphonate moiety are prepared from Z-L-alanine (1a). Z-L-valine (1b), and Z-L-phenylalanine (1c) by the following series of steps: coupling with methyl sarcosinate (2a–c), saponification (3a–c), Hofer-Moest oxidative decarboxyiation by electrolysis in MeOH (4a–c), and Arbuzov reaction with P(OPh)3/TiCl4 (Scheme 3). Double deprotonation and alkylation lead to non-stereoselective incorporation of side chains next to the phosphonate group (products of type 6–8, nine examples, see Scheme 4). In the cases of 6a–c and 8c, the diastereoisomers could be separated and the configuration of the newly formed stereogenic center deduced. We assign the L,D-configuration to the diastereoisomers for which the 31P-NMR signal appears at higher field.

1. Six weeks of a dynamic heavy-resistance training of the quadriceps muscle in healthy young men resulted in a continuous increase in muscle strength, in an increase in muscle cross-sectional area (significant only in the second half of the training period) and in an increase in radiological density of the muscle tissue of 3.1% (2P less than 0.001) in the first three weeks and 1.6% (2P less than 0.01) in the second three weeks. 2. The linear distance between myosin filaments (38.7 +/- 0.3 nm before, 38.7 +/- 0.4 nm after training; mean +/- S.E.M.) as well as the ratio of actin to myosin filaments (3.94 +/- 0.03 before, 3.86 +/- 0.06 after training) did not change with training. 3. These results refute the concept that the increases in muscle strength or radiological density during short-term heavy-resistance training are caused by changes in myofilament spacing.

Electrochemical Decarboxylation of L-Threonine and Oligopeptide Derivatives with Formation of N-Acyl-N, O-acetals: Preparation of Oligopeptides with Amide or Phophonate C-Terminus Derivatives of α-amino acids with two stereogenic centers (cf.L-threonine) and of di-, tri-, and tetrapeptides are electrolyzed in MeOH or AcOH, with formation of N-acyl-N, O-acetals (1b–15b, 20b), in an anodic oxidative substitution of the COOH by an OR group. The amine ends of the oligopeptides may be benzyloxycarbonyl(Z)- or (tert-butoxy)carbonyl(Boc)-protected. With unprotected dipeptides, an electrolytic decarboxylative cyclization to imidazolidinones (18c, 19c) may also occur (in H2O/NH4OAc). The electrolyses are carried out in simple flasks with cooling jackets (‘undivided cell’), using constant current conditions and anodes of Pt or glassy C. The electrolyte is generated in situ by adding 10–20 mol-% of a tertiary amine. Mild acidic hydrolysis of electrolysis products thus obtained may lead to amino-acid amides or peptide amides (10c, 11c, 12c, 17c) with one amino acid less than the starting material. The N, O-acetals from L-threonine and the oligopeptides also react with organometallic nucleophiles such as Grignard compounds (21–26, 29), with formation of products in which the original COOH group has been replaced by alkyl or allyl (sometimes even with moderate stereoselectivity). By treatment of the peptide-derived (open-chain) N, O-acetals with trialkyl or triaryl phosphites/TiCl4 the RO group is replaced by a phosphodiester group in a (non-diastereoselective) Michaelis-Arbuzov-type reaction (1d, 1e, 2d–9d, 5e). Thus, the two-step sequence of electrolysis and phosphonation converts an oligopeptide derivative to an analogue with a phosphonic-acid end group. The diastereoisomeric N-protected dimethyl and diethyl dipeptidephosphonates (also prepared from the corresponding diaryl esters by Ti(OR)4-mediated transesterification) could be separated by preparative HPLC (SiO2, Lichrosorb Si 60, 10 μm); the dextrorotatory isomers of 1d–3d were assigned L, D-, the laevoratory ones L, L-configuration by hydrolysis to and identification of the known amino and aminophosphonic acids. The results described demonstrate a new simple route leading, from a given oligopeptide, to pure peptide analogues of known configuration.