Expression analysis of genes involved in collagen cross‐linking and its regulation in traumatic anterior shoulder instability

The molecular alterations involved in the capsule deformation presented in shoulder instability patients are poorly understood. Increased TGFβ1 acts as a signal for production of matrix macromolecules by fibrogenic cells at joint injury sites. TGFβ1, through its receptor TGFβR1, regulates genes involved in collagen cross‐linking, such as LOX, PLOD1, and PLOD2. We evaluated TGFβ1, TGFβR1, LOX, PLOD1, and PLOD2 gene expression in the antero‐inferior (macroscopically injured region), antero‐superior and posterior regions of the glenohumeral capsule of 29 shoulder instability patients and eight controls. We observed that PLOD2 expression was increased in the anterior‐inferior capsule region of the patients compared to controls. LOX expression tended to be increased in the posterior portion of patients. Patients with recurrent shoulder dislocation presented upregulation of TGFβR1 in the antero‐inferior capsule portion and of PLOD2 in the posterior region. Conversely, LOX was increased in the posterior portion of the capsule of patients with a single shoulder dislocation episode. In the antero‐inferior, LOX expression was inversely correlated and TGFβR1 was directly correlated with the duration of symptoms. In the posterior region, PLOD2, TGFβ1, and TGFβR1 were directly correlated with the duration of symptoms. In conclusion, PLOD2 expression was increased in the macroscopically injured region of the capsule of patients. Upregulation of TGFβ1, TGFβR1, and PLOD2 seems to be related with the maintenance of disease symptoms, especially in the posterior region. LOX upregulation seems to occur only in the initial phase of the affection. Therefore, TGFβ1, TGFβR1, LOX, and PLOD2 may play a role in shoulder instability. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:510–517, 2016.     

Kinematic changes after fusion and total replacement of the ankle: part 3: Talar movement

INTRODUCTION: The purpose of this study was to determine talar movement (e.g., talar rotation and talar shift during (dorsiflexion/plantarflexion) with respect to the tibia in the normal ankle, in the fused ankle, and in the replaced ankle by currently used prosthetic designs. METHODS: A 6-df device with an axial load of 200 N and a four-camera high-speed video system were used for the measurement of the range of motion in six fresh-frozen cadaveri leg specimens. While moving the foot through the whole range of motion for plantarflexion/dorsiflexion, segmental motion of the marked bones of the foot and shank were measured dynamically. Rotation and medial-lateral shift of the talus were then calculated with regard to flexion position of the foot. RESULTS: In the normal ankle, plantarflexion movement was coupled with talar inversion of 3.5 degrees, and dorsiflexion movement with talar eversion of 1.0 degree, in totally accounting for 4.5 degrees of talar rotation. While both the HINTEGRA and the S.T.A.R. prostheses did not show changes to the normal condition during the dorsiflexion/plantarflexion cycle (p < .05), talar rotation had a 60% decrease (p < .05) for the AGILITY prosthesis. In the normal ankle joint, a lateral talar shift of 1.4 mm was found to occur during dorsiflexion, and a lateral talar shift of 5.2 mm during plantarflexion. In both, the HINTEGRA and S.T.A.R. ankles, talar shift was converted into medial direction during dorsiflexion of the foot (difference to normal: p < .05), whereas talar shift in the lateral direction was found to occur during plantarflexion of the foot which was comparable to the normal ankle. The AGILITY ankle evidenced an 80% decrease of talar shift (p < .05) during the whole dorsiflexion/plantarflexion cycle. DISCUSSION: The two-component ankle (AGILITY) obviously tends to restrict tremendously talar motion within the ankle mortise, whereas the three-component ankles (HINTEGRA, S.T.A.R.) seem to allow talar range of motion comparable to that in the normal ankle. It is suggested that such a restriction of talar motion results in an increase of stress forces within and around the prosthesis, leading to polyethylene wear and potential loosening at the bone-implant interfaces. Therefore, a successful prosthetic design for the ankle should consist of three components that are shaped as anatomically as possible to provide a normal range of motion and to allow the full transmission of movement transfer between foot and shank and unconstrained movement of the talus within the ankle mortise.     

The Cerebellum Is Involved in Reward-based Reversal Learning

The cerebellum has recently been discussed in terms of a possible involvement in reward-based associative learning. To clarify the cerebellar contribution, eight patients with focal vascular lesions of the cerebellum and a group of 24 healthy subjects matched for age and IQ were compared on a range of different probabilistic outcome-based associative learning tasks, assessing acquisition, reversal, cognitive transfer, and generalization as well as the effect of reward magnitude. Cerebellar patients showed intact acquisition of stimulus contingencies, while reward-based reversal learning was significantly impaired. In addition, the patients showed slower acquisition of new stimulus contingencies in a second reward-based learning task, which might reflect reduced carry-over effects. Reward magnitude affected learning only during initial acquisition, with better learning on trials with high rewards in patients and control subjects. Overall, the findings suggest that the cerebellum is implicated in reversal learning as a dissociable component of reward-based learning.     

Circulating leucocyte subpopulations in sedentary subjects following graded maximal exercise with hypoxia

Summary Ten healthy sedentary subjects [age, 27.5 (SD 3.5) years; height, 180 (SD 5) cm; mass, 69.3 (SD 6.3) kg] performed two periods of maximal incremental graded cycle ergometer exercise in a supine position. Randomly ordered and using an open spirometric system, one exercise was carried out during normoxia [maximal oxygen consumption ( O_2max)=38.6 (SD 3.5) ml·min^–1·kg^–1; maximal blood lactate concentration, 9.86 (SD 1.85) mmol·l^–1; test duration, 22.6 (SD 2.7) min], the other during hypoxia [ O_2max=33.2 (SD 3.2) ml·min^–1· kg^–1; maximal blood lactate concentration, 10.38 (SD 2.02) mmol·l^–1; test duration, 19.7 (SD 2.8) min]. At rest, immediately (0 p) and 60 min (60 p) after exercise, counts of leucocyte subpopulations (flow cytometry), cortisol and catecholamine concentrations were determined. At 0 p in contrast to normoxia, during hypoxia there was no significant increase of granulocytes. There were no significant differences between normoxia and hypoxia in the increases from rest to 0 p in counts of monocytes, total lymphocytes and lymphocyte subpopulations [clusters of differentiation (CD), CD3⁺, CD4⁺CD45RO^–, CD4⁺CD45RO⁺, CD8⁺CD45RO^–, CD8⁺CD45RO⁺, CD3⁺HLA-DR⁺, CD3^–CD16/CD56⁺, CD3⁺CD16/CD56⁺, CD 19⁺] as well as adrenaline, noradrenaline and cortisol concentrations. The counts of CD3 ^–CD16/CD56⁺-and CD8 ⁺CD45RO⁺-cells increased most. At 60 p, CD3^–CD16/CD56⁺ and CD3⁺CD16/CD56⁺-cell counts were below pre-exercise levels and under hypoxia slightly but significantly lower than under normoxia. We concluded that the exercise-induced mobilization and redistribution of most leucocyte and lymphocyte subpopulations were unimpaired under acute hypoxia at sea level. Reduced increases of granulocyte counts during the study and reduced cell numbers of natural killer cells and cytotoxic, not major histocompatibility complex-restricted T-cells, only indicated marginal effects on the immune system.     

The faster the better: anastomosis time influences patient survival after deceased donor kidney transplantation

Despite a continuously growing knowledge of the impact of factors on kidney graft function, such as donor age, body mass index, and cold ischemia time, few data are available regarding anastomosis time (AT) and its impact on long‐term results. We investigated whether surgical AT correlates with patient and graft survival after kidney transplantation performing a retrospective analysis of 1245 consecutive deceased donor kidney transplantations between 01/2000 and 12/2010 at Innsbruck Medical University. Kaplan–Meier and log‐rank analyses were carried out for 1‐ and 5‐year patient and graft survival. AT was defined as time from anastomosis start until reperfusion. Median AT was 30 min. Five‐year survival of allografts with an AT >30 min was 76.6% compared with 80.6% in the group with AT <30 min (P = 0.027). Patient survival in the group with higher AT similarly was inferior with 85.7% after 5 years compared with 89.6% (P < 0.0001) [Correction added on February 18, 2015, after first online publication: the percentage value for patient survival was previously incorrect and have now been changed to 89.6%]. Cox regression analysis revealed AT as an independent significant factor for patient survival (HR 1.021 per minute; 95% CI 1.006–1.037; P = 0.006). As longer AT closely correlates with inferior long‐term patient survival, it has to be considered as a major risk factor for inferior long‐term results after deceased donor kidney transplantation.     

Questionnaire on parental attitudes and rearing practices (FEPS)

A positive parent-child relationship is one of the most important determinants of a healthy cognitive, emotional and social development. The relationship from parent to child is determined by parenting styles. Parenting styles are characterised by the two dimensions parental attitudes and rearing practices. The development and the psychometric properties of a questionnaire on parental attitudes and rearing practices (FEPS), which contains an extended version of the Parental Bonding Instrument by Parker et al. (PBI, 1979) and two scales on parental reinforcement and punishment behaviour, is presented. In a sample of 457 women and 159 men factorial and item analysis revealed four scales (care, autonomy, low punishment and low material reinforcement). The care dimension contained items of immaterial reinforcement on the positive pole and items of coldness and ignorance as means of punishment on the negative pole. Based on findings from its first application in a clinical study it can be assumed that the FEPS differentiates between clinical and non-clinical populations. Additionally, varying patterns of the four scales may emerge as risk factors for the development of certain psychiatric/psychological problems.     

GDF15 promotes simultaneous astrocyte remodeling and tight junction strengthening at the blood–brain barrier

Perivascular astrocyte processes (PAP) surround cerebral endothelial cells (ECs) and modulate the strengthening of tight junctions to influence blood–brain barrier (BBB) permeability. Morphologically altered astrocytes may affect barrier properties and trigger the onset of brain pathologies. However, astrocyte-dependent mediators of these events remain poorly studied. Here, we show a pharmacologically driven elevated expression and release of growth/differentiation factor 15 (GDF15) in rat primary astrocytes and cerebral PAP. GDF15 has been shown to possess trophic properties for motor neurons, prompting us to hypothesize similar effects on astrocytes. Indeed, its increased expression and release occurred simultaneously to morphological changes of astrocytes in vitro and PAP, suggesting modulatory effects of GDF15 on these cells, but also neighboring EC. Administration of recombinant GDF15 was sufficient to promote astrocyte remodeling and enhance barrier properties between ECs in vitro, whereas its pharmacogenetic abrogation prevented these effects. We validated our findings in male high anxiety-related behavior rats, an animal model of depressive-like behavior, with shrunk PAP associated with reduced expression of the junctional protein claudin-5, which were both restored by a pharmacologically induced increase in GDF15 expression. Thus, we identified GDF15 as an astrocyte-derived trigger of astrocyte process remodeling linked to enhanced tight junction strengthening at the BBB.     

Impact of duration of untreated psychosis on pre-treatment, baseline, and outcome characteristics in an epidemiological first-episode psychosis cohort

INTRODUCTION: To assess the impact of duration of untreated psychosis (DUP) on baseline and 18-month follow-up characteristics controlling for relevant confounders in an epidemiological first-episode psychosis (FEP) cohort. METHOD: The Early Psychosis Prevention and Intervention Centre (EPPIC) in Australia admitted 786 FEP patients from January 1998 to December 2000. Data were collected from medical files using a standardized questionnaire. Data from 636 patients were analyzed. RESULTS: Median DUP was 8.7 weeks. Longer DUP was associated with worse premorbid functioning (p<0.001), higher rate of schizophrenia-spectrum disorders (p<0.001), and younger age at onset of psychosis (p=0.004). Longer DUP was not associated with baseline variables but with a lower rate of remission of positive symptoms (p<0.001) and employment/occupation (p<0.001), a higher rate of persistent substance use (p=0.015), worse illness severity (p<0.001) and global functioning (p<0.001) at follow-up after controlling for relevant confounders, explaining approximately 5% of variance of remission of positive symptoms (p<0.001) in the total sample and 3% in schizophrenia-spectrum disorders excluding bipolar I disorder (p=0.002). Outcome was significantly worse when DUP exceeded 1-3 months. CONCLUSION: Avoiding pitfalls of non-epidemiological studies, DUP appears to be a modest independent predictor of prognosis in the medium-term. Results support the need for assertive early detection strategies.     

Patients' Satisfaction with Psychiatric Treatment: Comparison Between an Open and a Closed Ward

The study compared patients' satisfaction with psychiatric inpatient treatment between an open and a closed ward. During a six-month period, all voluntarily participating patients on two wards of a psychiatric University hospital were investigated anonymously at admission and/or before discharge. A self-rating questionnaire (SATQ-98) was used to assess satisfaction with several domains of psychiatric inpatient treatment. In total, 135 questionnaires were received (retrieval rate 49%). The general level of satisfaction with treatment was high. General satisfaction, satisfaction with medication, ward equipment, visiting opportunities, and regulations for going out were significantly lower at discharge on the closed ward. Dissatisfaction with medication was related to low actual mood, and to low satisfaction with the frequency of psychotherapeutic interventions, visiting opportunities, and with the treating doctor. The results thus far strongly support the need for patients' satisfaction with treatment to be taken into account in order to improve psychiatric inpatient services, particularly on closed wards.