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Objective In this study, we hypothesized that standing and supine X‐rays lead to different preoperative planning results. Methods The present study included 168 pictures from 81 patients who were treated surgically with high tibial osteotomy (HTO) for varus deformity between January 2017 and February 2018. Each patient underwent whole leg X‐ray examinations in both standing and supine position. On both images, the following parameters were measured: degree of axis deviation (DAD), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), width of medial (MJS) and lateral joint space (LJS), and the correction angle (CA). The results were correlated with the patients’ age and body mass index (BMI). To analyze intra‐observer reliability, the same researcher, blinded to the previous measurements, remeasured all X‐rays from 10 patients 8 weeks after the initial measurements were carried out. Results While mLDFA (P = 0.075), mMPTA (P = 0.435), and MJS (P = 0.119) did not show any differences between the two modalities, LJS (P = 0.016) and DAD (P, In this study, we hypothesized that standing and supine X‐rays lead to different preoperative planning results in high tibial osteotomies. Indeed, we did find an influence of the imaging modality on planning results; however, these results were not influenced by body mass and age.

Focal Outerbridge grade IV cartilage defects of the proximal humerus may lead to pain and an impaired shoulder function. In cases of failed operative or conservative treatment options such as intraarticular injections or arthroscopic microfracturing of the subchondral bone, partial arthroplasty of the humeral may restore the articular surface of the humeral head without altering the anatomy. This study evaluates mid-term results of open and arthroscopic partial resurfacing of the humeral head in the context of focal grade IV cartilage defects. Eighteen patients (f = 3, m = 15, mean age = 57.7 years) out of 22 patients were available for follow-up after 65 (24–116) months. Thirteen patients were treated with a partial humeral head prosthesis in an open technique and five patients received a partial humeral head prosthesis in an arthroscopic technique. The patients were followed-up clinically using the Constant-Score, the ASES Score as well as the range of motion. Plain radiographs (anterior–posterior and axial view) were carried out for radiologic assessment. At follow-up the mean CS rated 79.5. The mean ASES Score was 85.8 points. Mean active forward flexion measured 163.8°, while mean active abduction was 160.0°. The average pain level on a visual analogue scale (VAS) made out 0.7 out of 10. Patients treated with an arthroscopically implanted prosthesis achieved a mean CS of 88.8 points and a mean ASES Score of 92.6 points. The patients with openly implanted prosthesis had a CS of 75.3 points and an ASES Score of 83 points. There were no intraoperative or immediate postoperative complications. Until the final follow-up one patient needed to be converted to total shoulder arthroplasty due to progressive glenohumeral osteoarthritis. Nine patients (50%) showed progressive glenohumeral osteoarthritis. Aseptic loosening of the implants was not observed. Partial arthroscopic or open arthroplasty of the humeral head is related to good functional results after mid-term follow-up. Resurfacing of the humeral head is a safe procedure without any implant-related complications. There is a risk for progression of glenohumeral osteoarthritis, which may require surgical revision with conversion to anatomic shoulder arthroplasty. Level IV (retrospective study).

Humans can be infected by zoonotic avian, pandemic and seasonal influenza A viruses (IAVs), which differ by receptor specificity and conformational stability of their envelope glycoprotein hemagglutinin (HA). It was shown that receptor specificity of the HA determines the tropism of IAVs to human airway epithelial cells, the primary target of IAVs in humans. Less is known about potential effects of the HA properties on viral attachment, infection and activation of human immune cells. To address this question, we studied the infection of total human peripheral blood mononuclear cells (PBMCs) and subpopulations of human PBMCs with well characterized recombinant IAVs differing by the HA and the neuraminidase (NA) but sharing all other viral proteins. Monocytes and all subpopulations of lymphocytes were significantly less susceptible to infection by IAVs with avian-like receptor specificity as compared to human-like IAVs, whereas plasmacytoid dendritic cells (pDCs) and myeloid dendritic cells were equally susceptible to IAVs with avian-like and human-like receptor specificity. This tropism correlated with the surface expression of 2-3-linked sialic acids (avian-type receptors) and 2-6-linked sialic acids (human-type receptors). Despite a reduced infectivity of avian-like IAVs for PBMCs, these viruses were not less efficient than human-like IAVs in terms of cell activation as judged by the induction of cellular mRNA of IFN-α, CCL5, RIG-I, and IL-6. Elevated levels of IFN-α mRNA were accompanied by elevated IFN-α protein secretion in primary human pDC. We found that high basal expression in monocytes of antiviral interferon-induced transmembrane protein 3 (IFITM3) limited viral infection in these cells. siRNA-mediated knockdown of IFITM3 in monocytes demonstrated that viral sensitivity to inhibition by IFITM3 correlated with the conformational stability of the HA. Our study provides new insights into the role of host- and strain-specific differences of HA in the interaction of IAVs with human immune cells and advances current understanding of the mechanisms of viral cell tropism, pathogenesis and markers of virulence.

Rationale: Although depression has been widely researched, findings characterizing how brain regions influence each other remains scarce, yet this is critical for research on antidepressant treatments and individual responses to particular treatments. Objectives: To identify pre-treatment resting state effective connectivity (rsEC) patterns in patients with major depressive disorder (MDD) and explore their relationship with treatment response. Methods: Thirty-four drug-free MDD patients had an MRI scan and were subsequently treated for 6 weeks with an SSRI escitalopram 10 mg daily; the response was defined as ≥50% decrease in Hamilton Depression Rating Scale (HAMD) score. Results: rsEC networks in default mode, central executive, and salience networks were identified for patients with depression. Exploratory analyses indicated higher connectivity strength related to baseline depression severity and response to treatment. Conclusions: Preliminary analyses revealed widespread dysfunction of rsEC in depression. Functional rsEC may be useful as a predictive tool for antidepressant treatment response. A primary limitation of the current study was the small size; however, the group was carefully chosen, well-characterized, and included only medication-free patients. Further research in large samples of placebo-controlled studies would be required to confirm the results.

Fetal pain has long been a contentious issue, in large part because fetal pain is often cited as a reason to restrict access to termination of pregnancy or abortion. We have divergent views regarding the morality of abortion, but have come together to address the evidence for fetal pain. Most reports on the possibility of fetal pain have focused on developmental neuroscience. Reports often suggest that the cortex and intact thalamocortical tracts are necessary for pain experience. Given that the cortex only becomes functional and the tracts only develop after 24 weeks, many reports rule out fetal pain until the final trimester. Here, more recent evidence calling into question the necessity of the cortex for pain and demonstrating functional thalamic connectivity into the subplate is used to argue that the neuroscience cannot definitively rule out fetal pain before 24 weeks. We consider the possibility that the mere experience of pain, without the capacity for self reflection, is morally significant. We believe that fetal pain does not have to be equivalent to a mature adult human experience to matter morally, and so fetal pain might be considered as part of a humane approach to abortion.

The subscapularis muscle is an important active stabilizer of the glenohumeral joint. For this radiological study, we investigated if its radiological integrity is affected after arthroscopic glenoid reconstruction. In the technique used, an autologous iliac crest graft is transported through the rotator interval, and the graft is fixed via an antero-inferior portal with compression screws. 3 women and 6 men (mean age 31 ± 9 years, min 21, max 46 years) who had a preoperative glenoid deficit of 23% ± 6% (min 13%, max 29%) were included. In a follow-up after an interval of 34 months (min 19, max 50), MRI scans were performed on both shoulders. With ITK-SNAP, a 3D reconstruction software, the volume of the subscapularis muscle in the injured and contralateral shoulder was measured. In addition, signal intensity ratios (PSI) (infraspinatus muscle / cranial subscapularis muscle and infraspinatus muscle / caudal subscapularis muscle) were analyzed and the width of the cranial and caudal portions as well as the length of the subscapularis muscle in the parasagittal plane were determined. The 3D volume showed no difference between operated and healthy shoulders (p = 0.07), neither did PSI ratios (infraspinatus muscle / cranial subscapularis muscle: p = 1.00, infraspinatus muscle / caudal subscapularis muscle: p = 1.00). In the parasagittal plane, length (p = 0.09) and cranial width (p = 0.23) did not differ. However, the width of the lower muscle was increased in injured shoulders (p = 0.02). In this cohort, no relevant volume loss could be found after arthroscopic glenoid reconstruction. However, a greater width of the lower muscle portion could be identified in the parasagittal plane as a possible indication of scarring.

Introduction Cuff tear arthritis and complex proximal humeral fractures are common pathologies that are frequently addressed by the implantation of a reversed shoulder prosthesis. The present cadaveric study aimed to analyze the effect of cement augmentation of the glenoid component on the primary stability in geriatric patients. Hypothesis Cement augmentation of glenoid baseplate screws has an influence on primary stability in reversed shoulder arthroplasty (RSA). Materials and methods Glenoid base plates (Delta Xtend, DePuy Synthes, Westchester, USA) were implanted in 6 pairs of formalin-fixated scapulae of 4 female and 2 male donors (average age 83 years). Two angle stable screws were placed at the superior and inferior position. Cement augmentation was performed with 2 ml bone cement (Kyphon, Medtronic, Minneapolis, USA) per screw in right specimens. Afterwards, biomechanical testing with 600 to 1000 N (100 cycles) at a 65° abduction angle was performed. Finally, a load-to-failure analysis was conducted. Results No implant loosening was observed during cyclic tests from 600 N to 1000 N. In addition no difference in the plastic deformation was detected at 600 N (p = 0.301), 700 N (p = 0.522), 800 N (p = 0.480), 900 N (p = 0.521) and 1000 N (p = 0.748). Load-to-failure analyses revealed implant loosening at 3314 N (SD 823 N) in the cement-augmented implants and at 3059 N (SD 974 N) in scapulae with non-cemented screws (p = 0.522). Discussion Cement-augmented fixation of the glenoid component did not result in an increased primary stability in this study. Thus, the application of cement should be critically assessed considering associated risks and increased costs. Level of proof Basic science study, controlled laboratory study.

After decades of rising prevalence of atopic and airway-related diseases, studies showed stagnating prevalence in western industrialised countries. Objective of this study is to analyse the time trend of prevalence of atopic diseases and airway-related symptoms among Bavarian children before starting primary school.Five cross-sectional studies from 2004/2005, 2006/2007, 2012/2013, 2014/2015 and 2016/2017 took place in urban and rural regions in Bavaria, Germany. Using standardized parent questionnaires children's atopic diseases and airway-related symptoms were surveyed. Logistic regression analysis (Bonferroni correction: adjusted significance level 0.005) was performed to analyse prevalence of symptoms and diseases from 2004 to 2017 for time trends.The surveys included 27384 Bavarian children aged 5-6 years (52.6% male). In all children the calculated 12-month prevalence of symptoms '≥four episodes of wheeze' (p-value = .0880) and 'rhinoconjunctivitis' (p-value = .3994) reported by parents stagnated, whereas 'wheeze' (p-value.0001; OR = 0.97; CI = [0.96-0.98]) and 'rhinitis' (p-value = .0007; OR = 0.98; CI = [0.97-0.99]) decreased. In all children the calculated lifetime prevalence of physician-diagnosed 'asthma' (p-value = .5337), and 'hay fever' (p-value = .8206) stagnated, whereas of 'bronchitis' (p-value.0001; OR = 0.98; CI = [0.98-0.99]) decreased over time. The calculated lifetime prevalence of physician-diagnosed 'atopic eczema' (p-value = .0002; OR = 0.98; CI = [0.97-0.99]) decreased in all children, whereas the calculated 12-month prevalence of the symptom 'itchy rash' increased (p-value = .0033; OR = 1.07; CI = [1.05-1.08]) over time.Several calculated prevalence of children's atopic diseases and airway-related symptoms reported by parents stagnated in a subgroup of Bavarian children before starting primary school between 2004 and 2017. The time trend of prevalence in 'wheeze', 'rhinitis' and 'bronchitis' decreased. Prevalence of 'atopic eczema' decreased over time, whereas 'itchy rash' increased.

The employment of reverse shoulder arthroplasty for dislocated proximal humerus fractures of elderly patients becomes increasingly relevant. The standard inclination angle of the humeral component was 155°. Lately, there is a trend towards smaller inclination angles of 145° or 135°. Additionally, there has been an increased focus on the lateralization of the glenosphere. This retrospective comparative study evaluates clinical and radiological results of patients treated for proximal humerus fractures by reverse shoulder arthroplasty with different inclination angles of the humeral component, which was either 135° or 155°. Additionally, a different lateral offset of the glenosphere, which was either 0 mm or 4 mm, was used.For this retrospective comparative analysis, 58 out of 66 patients treated by reverse total shoulder arthroplasty for proximal humerus fractures were included. The minimum follow-up was 24 months. Thirty (m = 3, f = 27; mean age 78 years; mean FU 35 months, range 24-58 months) were treated with a standard 155° humeral component and a glenosphere without lateral offset (group A), while 28 patients (m = 2, f = 26; mean age 79 years; mean FU 30 months, range 24-46 months) were treated with a 135° humeral component and a glenosphere with a 4 mm lateral offset (group B). We determined range of motion, Constant score, and the American Shoulder and Elbow Surgeons Shoulder score as clinical outcomes and evaluated tuberosity healing as well as scapula notching.Neither forward flexion (A = 128°, B = 121°; p = 0.710) nor abduction (A = 111°, B = 106°; p = 0.327) revealed differences between the groups. The mean Constant Score rated 63 in group A, while it was 61 in group B (p = 0.350). There were no differences of the ASES Score between the groups (A = 74, B = 72; p = 0.270). There was an increased risk for scapula notching in group A (47%) in comparison to group B (4%, p = 0.001). Healing of the greater tuberosity was achieved in 57% of group A and in 75% of group B (p = 0.142). The healing rate of the lesser tuberosity measured 33% in group A and 71% in group B (p = 0.004).Both inclination angles of the humeral component are feasible options for the treatment of proximal humerus fractures in elderly patients. Neither the inclination angle nor the lateral offset of the glenosphere seem to have a relevant influence on the clinical outcome. The healing rate of the lesser tuberosity was higher in implants with a decreased neck-shaft angle. There is an increased risk for scapula notching, if a higher inclination angle of the humeral component is chosen.III. Retrospective comparative study.

OBJECTIVE Dynamic horizontal instability is considered to be the main reason for poor outcome after treatment for acromioclavicular (ac) joint instability. In this study, we describe a simple technique to quantify this pathology via sonography. METHODS Thirty-six shoulders from 18 patients with ac joint instabilities were examined using modified Alexander views and a standardized sonographic examination. On the Alexander views, overlap of acromion and clavicle (OLAC), glenoid center to posterior clavicle distance (GCPC), and lateral extension (LE) were measured. Afterwards, the results were analyzed and compared with sonography. Posterior translation of the clavicle and the difference of translation between healthy and injured shoulder were evaluated. RESULTS The mean age of the patients was 39 ± 14 years (range 19-61 years). We included 4 (22%) Rockwood type 3, 1 (6%) Rockwood type 4, and 13 (72%) Rockwood type 5 lesions. Four (22%) patients were female and 14 (78%) male patients. Posterior clavicle translation of the injured shoulder correlated strongly between OLAC and sonography (r = -0.514, P = .029), and the difference of translation between healthy and injured shoulder correlated very strongly between LE and sonography (r = 0.737, P

Background Monoamine oxidase inhibitors (MAOIs) were the first class of modern antidepressants; however, they are under-utilized as compared to the newer antidepressants. Methods In this systematic review, network meta-analysis was used to investigate the comparative efficacy and acceptability of MAOIs for depressive disorders. Overall, the network meta-analysis included 52 double-blind, randomized controlled trials (RCTs) that compared 14 antidepressants or placebo. Across studies, the mean arm size was n = 58 participants from a total N = 6462 (5309 active drug; 1153 placebo). Results Except fluvoxamine, all antidepressants demonstrated superior efficacy to placebo, and none demonstrated substantially better or worse all-cause dropout rates. Phenelzine demonstrated superior evidence for efficacy compared to all other treatments, and clomipramine demonstrated superior evidence for acceptability compared to all other treatments. Limitations The study is primarily limited by low estimate precision due to a relative paucity of studies for some of the included treatment conditions. Further evidence is required to study the relative efficacy of MAOIs against newer antidepressants. Conclusions The results of this analysis largely support the re-evaluation of the use of MAOIs as antidepressant agents in the treatment algorithm of depression.

Reverse total shoulder arthroplasty is widely used for the treatment of cuff tear arthropathy. Standard implants consist of a humeral component with an inclination angle of 155° and a glenosphere without lateral offset. Recently, lower inclination angles of the humeral component as well as lateralized glenospheres are implanted to provide better rotation of the arm and to decrease the rate of scapular notching. This study investigates the clinical and radiological results of a standard reverse total shoulder in comparison with an implant with an inclination angle of 135° in combination with a 4 mm lateralized glenosphere in context of cuff tear arthropathy. For this retrospective comparative analysis 42 patients treated by reverse total shoulder arthroplasty for cuff tear arthropathy were included. Twenty-one patients (m = 11, f = 10; mean age 76 years; mean follow-up 42 months) were treated with a standard 155° humeral component and a standard glenosphere with caudal eccentricity (group A), while twenty-one patients (m = 5, f = 16; mean age 72 years; mean follow-up 34 months) were treated with a 135° humeral component and 4 mm lateral offset of the glenosphere (group B). At follow-up patients of both groups were assessed with plain X-rays (a.p. and axial view), Constant Score, adjusted Constant Score, the subjective shoulder value and the range of motion. The clinical results were similar in both groups concerning the Constant Score (group A = 56.3 vs. group B = 56.1; p = 0.733), the adjusted CS (group A = 70.4% vs. group B = 68.3%; p = 0.589) and the SSV (group A = 72.0% vs. group B = 75.2%; p = 0.947). The range of motion of the operated shoulders did not differ significantly between group A and group B: Abduction = 98° versus 97.9°, p = 0.655; external rotation with the arm at side = 17.9° versus 18.7°, p = 0.703; external rotation with the arm positioned in 90° of abduction = 22.3° versus 24.7°, p = 0.524; forward flexion = 116.1° versus 116.7°, p = 0.760. The rate of scapular notching was higher (p = 0.013) in group A (overall: 66%, grade 1: 29%, grade 2: 29%, grade 3: 10%, grade 4: 0%) in comparison to group B (overall: 33%, grade 1: 33%, grade 2: 0%, grade 3: 0%, grade 4: 0%). Radiolucency around the humeral component was detected in two patients of group B. Stress shielding at the proximal humerus was observed in six patients of Group A (29%; cortical thinning and osteopenia in zone M1 and L1) and two patients of group B (10%; cortical thinning and osteopenia in zone M1 and L1). Calcifications of the triceps origin were observed in both groups (group A = 48% vs. group B = 38%). Theoretically, a lower inclination angle of the humeral component and an increased lateral offset of the glenosphere lead to improved impingement-free range of motion and a decreased rate of scapular notching, when compared to a standard reverse total shoulder implant. This study compared two different designs of numerous options concerning the humeral component and the glenosphere. In comparison to a standard-fashioned implant with a humeral inclination of 155° and a standard glenosphere, implants with a humeral inclination angle of 135° and a 4 mm lateralized glenosphere lead to comparable clinical results and rotatory function, while the rate of scapular notching is decreased by almost 50%. While the different implant designs did not affect the clinical outcome, our results indicate that a combination of a lower inclination angle of the humeral component and lateralized glenosphere should be favored to reduce scapular notching. Level III, retrospective comparative study

The ectonucleotidases CD39 and CD73 regulate immune responses by balancing extracellular ATP and adenosine in inflammation and are likely to be involved in the pathophysiology of COVID-19. Here, we analyzed CD39 and CD73 on different lymphocyte populations in a small cohort of COVID-19 patients and in healthy individuals. We describe a significantly lower level of expression of CD73 on cytotoxic lymphocyte populations, including CD8+ T, natural killer T (NKT), and natural killer (NK) cells, during COVID-19. Interestingly, the decrease of CD73 on CD8+ T cells and NKT cells correlated with serum ferritin levels. Furthermore, we observed distinct functional differences between the CD73+ and CD73- subsets of CD8+ T cells and NKT cells with regard to cytokine/toxin secretion. In COVID-19 patients, the majority of the CD73-CD8+ T cells were capable of secreting granzyme B, perforin, tumor necrosis factor (TNF-α) or interferon-gamma (IFN-γ). To conclude, in this first study of CD39 and CD73 expression of lymphocytes in COVID-19, we show that CD8+ T cells and NKT cells lacking CD73 possess a significantly higher cytotoxic effector functionality compared to their CD73+ counterparts. Future studies should investigate differences of cellular CD39 and CD73 expression in patients at different disease stages and their potential as prognostic markers or targets for immunomodulatory therapies.

Humans are host to a multitude of microorganisms that rapidly populate the body at birth, subject to a complex interplay that is dependent on host genetics, lifestyle, and environment. The host-associated microbiome, including the oral microbiome, presents itself in a complex ecosystem important to health and disease. As the most common chronic disease globally, dental caries is induced by host-microbial dysbiosis in children and adults. Multiple biological and environmental factors are likely to impact disease predisposition, onset, progression, and severity, yet longitudinal studies able to capture these influences are missing. To investigate how host genetics and environment influenced the oral microbial communities over time, we profiled supragingival plaque microbiomes of dizygotic and monozygotic twins during 3 visits over 12-months. Dental plaque DNA samples were amplified by targeting the 16S rRNA gene V4 region, and microbial findings were correlated with clinical, diet and genetic metadata. We observed that the oral microbiome variances were shaped primarily by the environment when compared to host genetics. Among the environmental factors shaping microbial changes of our subjects, significant metadata included age of the subject, and the age by which subjects initiated brushing habits, and the types of actions post-brushing. Relevant heritability of the microbiome included Actinomyces and Capnocytophaga in monozygotic twins and Kingella in dizygotic twins. Corynebacterium and Veillonella abundances were associated with age, whereas Aggregatibacter was associated with younger subjects. Streptococcus abundance showed an inverse association over time, and Selenomonas abundances increased with brushing frequency per day. Unraveling the exact biological mechanisms in caries has the potential to reveal novel host-microbial biomarkers, pathways, and targets important to effective preventive measures, and early disease control in children.

Background Arthroscopic glenoid reconstruction using autografts is an advanced procedure that requires experience and preparation. Knowledge about anatomic pitfalls is therefore important to establish well-positioned portals and prevent neurovascular damage. Methods We included 43 computed tomography scans from 43 patients. The distance between the tip of the coracoid process and a perpendicular line representing the anteroinferior glenoid was measured. From these results an anteroinferior working portal was designed, and the angulation needed for screw insertion to fixate a hypothetical graft was measured. In a second step, 9 patients underwent magnetic resonance imaging scans 34 ± 10 months after glenoid reconstruction, and the distance between the screw approach path and the neurovascular bundle was measured. Results In the analyzed scans, average defect size was 23%, and the coracoid process to the anteroinferior glenoid distance was 32 ± 7 mm. We thus hypothesized that a corridor 20 to 30 mm inferior to the coracoid process would be the ideal position for a working portal. Through this portal, 85% of screws could be applied with 0° to 30° angulation. When the postoperative scans were analyzed, the distance from the neurovascular bundle showed an average of 26 ± 6 mm for the superior screw and 21 ± 5 mm for the inferior screw. Conclusions The ideal distance between the coracoid process and an anteroinferior working portal is 32 mm. Having established the portal, instruments should not be inserted pointing in a medial direction of the coracoid process due to the proximity of the neurovascular bundle.

Introduction The fixation of the coracoid process onto the glenoid is an important step of the Latarjet procedure, and implant-associated complications are a relevant and severe problem. This study compares the fixation strength and failure mode of two biodegradable materials with stainless-steel screws. Methods 24 Fresh-frozen cadaveric scapulae were divided into three groups of equal size and received a coracoid transfer. Cadavers were matched according to their bone mineral density (BMD). In group 1, small-fragment screws made of stainless steel were used. In the second group, magnesium screws were used, and in the third group, screws consisted of polylactic acid (PLLA). A continuously increasing sinusoidal cyclic compression force was applied until failure occurred, which was defined as graft displacement relative to its initial position of more than 5 mm. Results At 5-mm displacement, the axial force values showed a mean of 374 ± 92 N (range 219–479 N) in group 1 (steel). The force values in group 2 (magnesium) had a mean of 299 ± 57 N (range 190–357 N). In group 3 (PLLA), failure occurred at 231 ± 83 N (range 109–355 N). The difference between group 1 (steel) and group 2 (magnesium) was not statistically significant (P = 0.212), while the difference between group 1 (steel) and group 3 (PLLA) was significant (P = 0.005). Conclusion Stainless-Steel screws showed the highest stability. However, all three screw types showed axial force values of more than 200 N. Stainless steel screws and PLLA screws showed screw cut-out as the most common failure mode, while magnesium screws showed screw breakage in the majority of cases. Evidence Controlled laboratory study.

Background Implant anchorage in highly osteoporotic bone is challenging, since it often leads to osteosynthesis failure in geriatric patients with supracondylar femoral fractures. Cementation of screws is presumed to prevent such osteosynthesis failure. This study aimed to investigate the effect of a newly designed, cementable fenestrated condylar screw for plate fixation in a biomechanical setting. Methods Eight pairs of osteoporotic cadaver femora with an average age of 77 years, ranging between 62 and 88 years, were randomly assigned to either an augmented or a non-augmented group. In both groups an instable 33-A3 fracture according to the AO / OTA classification was fixed with an angular stable locking plate. All right samples received a cement augmentation of their fenestrated condylar screws with calcium phosphate bone cement (CPC). Mechanical testing was performed at a load to failure mode by cyclic axial loading, using a servohydraulic testing machine. Results With a mean of 2475 N (95% CI: 1727–3223 N), the pressure forces resulting in osteosynthesis failure were significantly higher in specimen with cemented condylar screws as compared to non-cemented samples (1875 N (95% CI: 1320–2430 N)) (p = 0.024). In both groups the deformation of the constructs, with the distal screws cutting through the condylar bone, were the most frequent cause for failure. Analysis of axial stiffness (p = 0.889) and irreversible deformity of the specimens revealed no differences between the both groups (p = 0.161). No cement leakage through the joint line or the medial cortex was observed. Conclusion Based on the present study results, the newly introduced, cementable condylar screw could be an encouraging feature for the fixation of supracondylar femoral fractures in patients with reduced bone quality in terms of load to failure accuracy of the cement application.

Background This study aimed to comprehensively define the breadth and specificity of the hepatitis delta virus (HDV)-specific T-cell response in patients at different stages of chronic coinfection with hepatitis B virus (HBV). Methods Following in vitro stimulation with an overlapping set of 21 HDV-specific 20mer peptides and exogenous interleukin 2, HDV-specific CD4+ and CD8+ T-cell responses of 32 HDV-infected patients were analyzed by enzyme-linked immunospot analysis and intracellular cytokine staining for interferon γ production at the single-peptide level. Additionally, HLA-binding studies were performed both in silico and in vitro. Results We were able to detect ≥1 T-cell response in >50% our patients. Interestingly, there was no significant difference between the breadth of the response in patients positive and those negative for HDV by PCR. HDV-specific T-cell responses focused on 3 distinct HDV-specific epitopes that were each detected in 12%-21% of patients-2 HLA class II-restricted epitopes (amino acids 11-30 and 41-60) and 1 major histocompatibility complex class I-restricted epitope (amino acids 191-210). In in vitro HLA-binding assays, the 2 CD4+ T-cell specificities (amino acids 11-30 and 41-60) showed promiscuous binding to multiple HLA-DR molecules. Conclusions This comprehensive characterization of HDV T-cell epitopes provides important information that will facilitate further studies of HDV immunopathogenesis.

Glenoid bone loss in recurrent anterior instability of the shoulder needs to be addressed to restore joint stability. Over the last years, several arthroscopic methods have been described to treat this condition. However, no clinical mid-term results have been presented for arthroscopic iliac crest bone grafting procedures. We included 32 patients with significant glenoid bone loss and repetitive dislocations of the shoulder who were treated in our shoulder unit with a previously described all-arthroscopic reconstruction technique. All patients filled out a questionnaire evaluating repetitive dislocations, consumption of pain medicine, Constant Score (CS, adapted to age and gender), activities of daily living (ADL), visual analogue scale for pain (VAS) as well as the Western Ontario Shoulder Instability Index (WOSI). Additionally, all complications were recorded. After a mean follow-up of 42 months, three traumatic dislocations had been observed. With an ADL of 25 points (95% CI 24–27), a WOSI of 71% (95% CI 65–76) and CS of 87 points (95% CI 82–92), our patients showed good functional results. The VAS result for pain was 2.1 (95% CI 1.5–2.6). No patient reported the regular usage of pain medicine related to the shoulder instability at final follow-up. The all-arthroscopic glenoid reconstruction using iliac crest grafts shows good functional results with a recurrence rate of 9%. At final follow-up 42 months after surgery, our patients showed low pain levels and acceptable complications.

The aim of this study was to evaluate a standardised algorithm to assess and treat impaired limb perfusion prior to surgical fixation of geriatric ankle fractures and determine the prevalence of peripheral arterial disease (PAD) in geriatric patients presenting with ankle fractures. Eighty-four patients >65 years pre-operatively diagnosed and treated according to an algorithm (study group) were compared with 84 patients diagnosed and treated before the algorithm was introduced (control group). In 14 patients of the study group, clinical noninvasive examination revealed signs of relevant PAD, which was confirmed with computed tomographic angiography (CTA) in nine patients, all of whom had successful angioplasty prior to surgical fixation of the ankle fracture. In three of these patients, PAD had previously been diagnosed. After standardised diagnostics and treatment of malperfusion, a significantly reduced overall and, particularly, wound complication rate was found. PAD is an underdiagnosed condition in geriatric patients presenting with ankle fractures. This study underlines the relevance of limb perfusion for adequate wound healing in geriatric ankle fractures. Therefore, special attention should be paid to diagnose and—if indicated—optimise limb perfusion prior to surgical fixation of geriatric ankle fractures.

Background Chronic hepatitis delta virus (HDV) infection causes severe liver disease which often leads to cirrhosis and hepatocellular carcinoma (HCC). Aim of this study was to establish the disease severity and prognostic factors for disease outcome by analysing frequencies of clinical events and their correlation with baseline virological and biochemical parameters as well as interferon and nucleos(t)ide analogue treatment choice. Methods We studied a single-centre cohort of 49 anti-HDAg-positive patients with HBsAg persistence for at least 6 months. Virological and biochemical parameters, interferon and nucleos(t)ide analogue treatment choice as well as clinical events during follow-up were analysed by retrospective chart review (mean follow-up time 3 years, range 0.25–7.67 years). Results Severe clinical events occurred in 11/49 hepatitis D patients, including HCC (8/49), death (8/49) or liver transplantation (2/49). HCCs only occurred secondary to liver cirrhosis and their event rates in this cohort of hepatitis D patients did not differ from a matched HBV mono-infected cohort with comparable frequency of liver cirrhosis. A stepwise multivariate logistic regression revealed low platelet count (p = 0. 0290) and older age (p = 0.0337) correlating most strongly with overall clinical events, while serum HDV RNA positivity at baseline did not correlate with any clinical outcome. Interferon-free but not nucleos(t)ide analogue-free patient care correlated with the occurrence of HCC at logistic regression, although only 3/18 interferon-treated patients demonstrated repeatedly negative HDV PCR results post therapy. Conclusions Our data indicate that progressive liver disease at baseline plays a major role as predictive factor for overall clinical outcome of hepatitis D patients. In particular, HCC risk may not be underestimated in hepatitis D virus RNA negative hepatitis D patients with advanced liver fibrosis.

Older patients with severe physical trauma are at high risk of developing neuropsychiatric syndromes with global impairment of cognition, attention, and consciousness. We employed a thoracic trauma (TxT) mouse model and thoroughly analyzed age-dependent spatial and temporal posttraumatic alterations in the central nervous system. Up to 5 days after trauma, we observed a transient 50% decrease in the number of excitatory synapses specifically in hippocampal pyramidal neurons accompanied by alterations in attention and motor activity and disruption of contextual memory consolidation. In parallel, hippocampal corticotropin-releasing hormone (CRH) expression was highly upregulated, and brain-derived neurotrophic factor (BDNF) levels were significantly reduced. In vitro experiments revealed that CRH application induced neuronal autophagy with rapid lysosomal degradation of BDNF via the NF-κB pathway. The subsequent synaptic loss was rescued by BDNF as well as by specific NF-κB and CRH receptor 1 (CRHR1) antagonists. In vivo, the chronic application of a CRHR1 antagonist after TxT resulted in reversal of the observed histological, molecular, and behavioral alterations. The data suggest that neuropsychiatric syndromes (i.e., delirium) after peripheral trauma might be at least in part due to the activation of the hippocampal CRH/NF-κB/BDNF pathway, which results in a dramatic loss of synaptic contacts. The successful rescue by stress hormone receptor antagonists should encourage clinical trials focusing on trauma-induced delirium and/or other posttraumatic syndromes., publishedVersion

Objective Heterozygous SHANK3 mutations or partial deletions of the long arm of chromosome 22, also known as Phelan–McDermid syndrome, result in a syndromic form of the autism spectrum as well as in global developmental delay, intellectual disability, and several neuropsychiatric comorbidities. The exact pathophysiological mechanisms underlying the disease are still far from being deciphered but studies of SHANK3 models have contributed to the understanding of how the loss of the synaptic protein SHANK3 affects neuronal function. Methods and results Diffusion tensor imaging‐based and automatic volumetric brain mapping were performed in 12 SHANK3‐deficient participants (mean age 19 ± 15 years) versus 14 age‐ and gender‐matched controls (mean age 29 ± 5 years). Using whole brain–based spatial statistics, we observed a highly significant pattern of white matter alterations in participants with SHANK3 mutations with focus on the long association fiber tracts, particularly the uncinate tract and the inferior fronto‐occipital fasciculus. In contrast, only subtle gray matter volumetric abnormalities were detectable. In a back‐translational approach, we observed similar white matter alterations in heterozygous isoform–specific Shank3 knockout (KO) mice. Here, in the baseline data sets, the comparison of Shank3 heterozygous KO vs wildtype showed significant fractional anisotropy reduction of the long fiber tract systems in the KO model. The multiparametric Magnetic Resonance Imaging (MRI) analysis by DTI and volumetry demonstrated a pathology pattern with severe white matter alterations and only subtle gray matter changes in the animal model. Interpretation In summary, these translational data provide strong evidence that the SHANK3‐deficiency–associated pathomechanism presents predominantly with a white matter disease. Further studies should concentrate on the role of SHANK3 during early axonal pathfinding/wiring and in myelin formation.

Anti-α4β7 therapy with vedolizumab (VDZ) has been suggested as possible immune intervention in HIV. Relatively little is known about the α4β7-integrin (α4β7) expression of different T-cell subsets in different anatomical compartments of healthy individuals, patients with HIV or inflammatory bowel disease (IBD). Surface expression of α4β7 as well as the frequency of activation, homing and exhaustion markers of T cells were assessed by multicolour flow cytometry in healthy volunteers (n = 15) compared to HIV infected patients (n = 52) or patients diagnosed with ulcerative colitis (UC) (n = 14), 6 of whom treated with vedolizumab. In addition, lymph nodal cells (n = 6), gut-derived cells of healthy volunteers (n = 5) and patients with UC (n = 6) were analysed. Additionally, we studied longitudinal PBMC samples of an HIV patient who was treated with vedolizumab for concomitant UC. Overall, only minor variations of the frequency of α4β7 on total CD4+ T cells were detectable regardless of the disease status or (VDZ) treatment status in peripheral blood and the studied tissues. Peripheral α4β7+ CD4+ T cells of healthy individuals and patients with UC showed a higher activation status and were more frequently CCR5+ than their α4β7- counterparts. Also, the frequency of α4β7+ cells was significantly lower in peripheral blood CD4+ effector memory T cells of HIV-infected compared to healthy individuals and this reduced frequency did not recover in HIV patients on ART. Conversely, the frequency of peripheral blood naive α4β7+ CD4+ T cells was significantly reduced under VDZ treatment. The results of the current study will contribute to the understanding of the dynamics of α4β7 expression pattern on T cells in HIV and UC and will be useful for future studies investigating VDZ as possible HIV cure strategy.

Introduction Compromised bone quality and the need for early mobilization continue to lead to implant failure in elderly patients with distal femoral fractures. The cement augmentation of screws might facilitate improving implant anchorage. The aim of this study was to analyse the impact of cement augmentation of the condylar screws on implant fixation in a human cadaveric bone model. Material and methods Ten pairs of osteoporotic femora (mean age: 90 years, range: 84–99 years) were used. A 2-cm gap osteotomy was created in the metaphyseal region to simulate an unstable AO/OTA 33-A3 fracture. All specimens were treated with a polyaxial locking plate. Specimens randomly assigned to the augmented group received an additional cement augmentation of the condylar screws using bone cement. A servohydraulic testing machine was used to perform incremental cyclic axial loading using a load-to-failure mode. Results All specimens survived at least 800 N of axial compressive force. The mean compressive forces leading to failure were 1620 N (95% CI: 1382–1858 N) in the non-augmented group and 2420 N (95% CI: 2054–2786 N) in the group with cement-augmented condylar screws ( p = 0.005). Deformation with cutting out of the condylar screws and condylar fracture were the most common reasons for failure in both groups. Whereas axial stiffness was comparable between both osteosyntheses ( p = 0.508), significant differences were observed for the plastic deformation of the constructs ( p = 0.014). Conclusion The results of the present study showed that the cement augmentation of the condylar screws might be a promising technique for the fixation of distal femoral fractures in elderly patients with osteoporotic bones.

Introduction The distal radial fracture is a common fracture and frequently seen in geriatric patients. During the last years, volar plating has become a popular treatment option. While the application of locking screws at the distal fragment is widely accepted, there is no evidence for their use at the radial shaft. Materials and methods In six osteoporotic pairs of matched human cadaver radii an extra-articular model creating an AO 23-A2.1 fracture was employed. Osteosynthesis were performed using the APTUS 2.5 Adaptive TriLock Distal Radius System (Medartis AG) with locking (LS) or non-locking screws (NLS) for proximal fixation. Biomechanical testing was performed in a staircase fashion: starting with 50 cycles at 200 N, the load was continuously increased by 50 N every 80 cycles up to a maximum force of 400 N. Finally, load to failure was analyzed with failure defined as sudden loss of force measured (20%) or major deformation of the radii (10 mm). Results At 200 N, 250 N, 300 N, 400 N and load to failure, the NLS group showed a higher degree of elastic modulus. In contrast, the LS group showed higher elastic modulus at 350 N. Maximum force was higher in the LS group without reaching statistical significance. Reasons for loss of fixation were longitudinal shaft fractures, horizontal peri-implant fractures and distal cutting out. No difference was seen between the two groups concerning the development of the above mentioned complications. Conclusion Our study did not show biomechanical superiority for distal radius fracture fixation by using locking screws in the proximal holes in an osteoporotic cadaver study. At load to failure, longitudinal shaft fractures and peri-implant fractures seemed to be a more relevant problem rather than failure of the proximal fixation.

Background Type III interferons (IFNs) (λ1–3) activate similar signaling cascades as type I IFNs (α and β) via different receptors. Since IFN-α and lymphotoxin-β activate cytosine deamination and subsequent purging of nuclear hepatitis B virus (HBV) DNA, we investigated whether IFN-β and -λ may also induce these antiviral effects in differentiated HBV-infected hepatocytes. Methods After determining the biological activity of IFN-α2, -β1, -λ1, and -λ2 in differentiated hepatocytes, their antiviral effects were analyzed in HBV-infected primary human hepatocytes and HepaRG cells. Results Type I and III IFNs reduced nuclear open-circle DNA and covalently closed circular DNA (cccDNA) levels in HBV-infected cells. IFN-β and -λ were at least as efficient as IFN-α. Differential DNA-denaturing polymerase chain reaction and sequencing analysis revealed G-to-A sequence alterations of HBV cccDNA in IFN-α, -β, and -λ–treated liver cells indicating deamination. All IFNs induced apolipoprotein B messenger RNA–editing enzyme–catalytic polypeptide-like (APOBEC) deaminases 3A and 3G within 24 hours of treatment, but IFN-β and -λ induced longer-lasting expression of APOBEC deaminases in comparison to IFN-α. Conclusions IFN-β, IFN-λ1, and IFN-λ2 induce cccDNA deamination and degradation at least as efficiently as IFN-α, indicating that these antiviral cytokines are interesting candidates for the design of new therapeutic strategies aiming at cccDNA reduction and HBV cure.

BACKGROUND & AIMS: Hepatitis D virus (HDV) superinfection in patients with hepatitis B virus (HBV) is associated with rapid progression to liver cirrhosis and hepatocellular carcinoma. Treatment options are limited, and no vaccine is available. Although HDV-specific CD8(+) T cells are thought to control the virus, little is known about which HDV epitopes are targeted by virus-specific CD8(+) T cells or why these cells ultimately fail to control the infection. We aimed to define how HDV escapes the CD8(+) T-cell–mediated response. METHODS: We collected plasma and DNA samples from 104 patients with chronic HDV and HBV infection at medical centers in Europe and the Middle East, sequenced HDV, typed human leukocyte antigen (HLA) class I alleles from patients, and searched for polymorphisms in HDV RNA associated with specific HLA class I alleles. We predicted epitopes in HDV that would be recognized by CD8(+) T cells and corresponded with the identified virus polymorphisms in patients with resolved (n = 12) or chronic (n = 13) HDV infection. RESULTS: We identified 21 polymorphisms in HDV that were significantly associated with specific HLA class I alleles (P < .005). Five of these polymorphisms were found to correspond to epitopes in HDV that are recognized by CD8(+) T cells; we confirmed that CD8(+) T cells in culture targeted these HDV epitopes. HDV variant peptides were only partially cross-recognized by CD8(+) T cells isolated from patients, indicating that the virus had escaped detection by these cells. These newly identified HDV epitopes were restricted by relatively infrequent HLA class I alleles, and they bound most frequently to HLA-B. In contrast, frequent HLA class I alleles were not associated with HDV sequence polymorphisms. CONCLUSIONS: We analyzed sequences of HDV RNA and HLA class I alleles that present epitope peptides to CD8(+) T cells in patients with persistent HDV infection. We identified polymorphisms in the HDV proteome that associate with HLA class I alleles. Some variant peptides in epitopes from HDV were only partially recognized by CD8(+) T cells isolated from patients; these could be mutations that allow HDV to escape the immune response, resulting in persistent infection. HDV escape from the immune response was associated with uncommon HLA class I alleles, indicating that HDV evolves, at the population level, to evade recognition by common HLA class I alleles.

Rap GTPase-activating proteins (RapGAPs) are essential for synaptic function as they tightly regulate synaptic Rap signaling. Among the most abundant synaptic RapGAPs in brain are the Spine-associated RapGAPs (SPARs) Sipa1l1/SPAR and Sipa1l2/SPAR2, whereas nothing has been reported on Sipa1l3/SPAR3. In this study, we show that Sipa1l3/SPAR3 is conserved across species, has a distinct expression pattern in the developing rat brain and is localized at excitatory postsynapses. We further demonstrate that the Sipa1l3/SPAR3 C-terminus is required for postsynaptic targeting and represents an interaction module for Fezzins such as ProSAPiP1/Lzts3, a binding partner of the postsynaptic scaffold protein Shank3. Taken together, our data imply that Sipa1l3/SPAR3 is a hitherto unknown synaptic RapGAP, which is targeted to postsynaptic specializations and interacts with Fezzins. Spine-associated RapGAPs (SPARs) are essential modulators of synaptic signaling. Our study is the first to characterize the SPAR family member Sipa1l3/SPAR3 in neuronal tissue. We show that Sipa1l3/SPAR3 is conserved across species, has a distinct expression pattern in brain and is localized to excitatory postsynapses via its C-terminus, which represents an interaction module for other postsynaptic proteins including the Fezzin ProSAPiP1/Lzts3.

Acute hepatic failure due to hepatitis B virus (HBV) can occur both during primary infection as well as after reactivation of chronic infection. Guidelines recommend considering antiviral therapy in both situations, although evidence supporting this recommendation is weak. Since HBV is not directly cytopathic, the mechanism leading to fulminant hepatitis B is thought to be primarily immune-mediated. Therefore, immunosuppression combined with antiviral therapy might be a preferred therapeutic intervention in acute liver failure in hepatitis B. Here we report our favourable experience in three hepatitis B patients with fulminant hepatic failure who were treated by combining high-dose steroid therapy with standard antiviral treatment, which resulted in a rapid improvement of clinical and liver parameters.

Next-Generation Sequencing is providing insights into the critical role of the oral microbiome in dental diseases. Application of this method can require the collection of dental plaque from large cohorts in field-type conditions, which necessitates a transport medium to preserve the microbiome composition. We evaluated the use of two transport media, VMG II and RNAprotect® Bacteria Reagent (Qiagen), for room temperature storage of dental plaque. VMG II has not previously been assessed for suitability to store microbiome samples intended for deep sequencing. We compared the microbiome composition of dental plaque (total n=23) stored in either VMG II or RNAprotect Bacteria at room temperature with immediately-frozen plaque. 454 sequencing of 16S gene amplicons was used to assess the plaque microbial composition. While the bacterial diversity recovered was similar between storage conditions (p>0.1), the abundance of bacteria was influenced by storage environment. Dental plaque stored in VMG II was most similar to immediately-frozen material, with only one of the 324 bacterial species being differentially abundant (Neisseria, p

The optimal treatment of isolated fractures of the greater tuberosity is an important topic of current surgical research. While non-displaced fractures are amenable to conservative treatment, displacement of the fragment can result in rotator cuff malfunction and impingement. For the present study, risk factors predicting secondary fragment displacement were analyzed.Certain risk factors determine a higher risk of secondary displacement in patients with greater tuberosity fractures.All patients diagnosed with a fracture of the greater tuberosity and initially treated non-surgically at our Level I trauma center between January 2008 and July 2015 were included in this retrospective analysis. Patients were grouped into: no secondary displacement (group 1) and secondary displacement at follow-up (group 2). The following risk factors were analyzed: age, gender, side of fracture, initial displacement, fragment/head ratio, fragment shape, dislocation, concomitant fractures and concomitant fractures to the same extremity.82 patients (42 male, 40 female) were eligible for further analyses. Median follow-up was 8.0±39.5 days. Patients with secondary displacement (group 2) were significantly older (group 1: 51.7±15.5, group 2: 68.3±14.3; p0.001) and had significantly more shoulder dislocations (p=0.024), whereas gender (p=0.299), side of fracture (p=0.189) and fragment/head ratio (p=0.660) showed no significant different distribution between both groups. Finally, split-type fractures increased the risk of secondary displacement.The present study identified age older than 65 years to be an important risk factor for secondary displacement in the conservative management of fractures of the greater tuberosity. Furthermore, fracture type and shoulder dislocations are factors associated with an increased relative risk for secondary displacement.III, Retrospective comparative study.

Recurrent anterior instability of the glenohumeral joint is a demanding condition, especially in cases of glenoid bone loss. Various treatment options have been described, such as arthroscopic grafting techniques and the Latarjet procedure. In this study, the degree to which an arthroscopically applied iliac crest graft restores the glenoid anatomy was evalutated. Nine patients (three women and six men) with an average age of 31 ± 9 years (21–46 years) who were treated with an arthroscopic iliac crest graft technique were included in this study. After a mean follow up of 34 ± 10 months (19–50 months) after the procedure, MRI scans of both shoulders were performed and the glenoid width, Glenoid Index (GI), Pixel Signal intensity (PSI), thickness of the tissue covering the articular aspect of the graft, inclination, version, concavity and balance stability angle were measured. All scans showed the cultivation of tissue on the graft, which visually resembled the cartilage of the native ipsilateral glenoid. Additionally, reshaping of the graft to repair the glenoid configuration could be observed. Glenoid width (p = 0.022) and GI (p

Host-associated microbial communities are influenced by both host genetics and environmental factors. However, factors controlling the human oral microbiome and their impact on disease remain to be investigated. To determine the combined and relative effects of host genotype and environment on oral microbiome composition and caries phenotypes, we profiled the supragingival plaque microbiome of 485 dizygotic and monozygotic twins aged five to eleven. Oral microbiome similarity always increased with shared host genotype, regardless of caries state. Additionally, although most of the variation in the oral microbiome was determined by environmental factors, highly heritable oral taxa were identified. The most heritable oral bacteria were not associated with caries state, did not tend to co-occur with other taxa, and decreased in abundance with age and sugar consumption frequency. Thus, while the human oral microbiome composition is influenced by host genetic background, potentially cariogenic taxa are likely not controlled by genetic factors.

Phelan McDermid Syndrome (PMDS) is a genetic disorder characterized by features of Autism spectrum disorders. Similar to reports of Zn deficiency in autistic children, we have previously reported high incidence of Zn deficiency in PMDS. However, the underlying mechanisms are currently not well understood. Here, using inductively coupled plasma mass-spectrometry to measure the concentration of Zinc (Zn) and Copper (Cu) in hair samples from individuals with PMDS with 22q13.3 deletion including SHANK3 (SH3 and multiple ankyrin repeat domains 3), we report a high rate of abnormally low Zn/Cu ratios. To investigate possible underlying mechanisms, we generated enterocytes from PMDS patient-derived induced pluripotent stem cells and used Caco-2 cells with knockdown of SHANK3. We detected decreased expression of Zn uptake transporters ZIP2 and ZIP4 on mRNA and protein level correlating with SHANK3 expression levels, and found reduced levels of ZIP4 protein co-localizing with SHANK3 at the plasma membrane. We demonstrated that especially ZIP4 exists in a complex with SHANK3. Furthermore, we performed immunohistochemistry on gut sections from Shank3αβ knockout mice and confirmed a link between enterocytic SHANK3, ZIP2 and ZIP4. We conclude that apart from its well-known role in the CNS, SHANK3 might play a specific role in the GI tract.

Background Glenoid bone loss in recurrent anterior shoulder instability is a challenging problem for shoulder surgeons, and knowledge about the anatomy of glenoid deficits is scarce. In this study, we tried to evaluate the pattern of this pathology. Methods Our analysis included 44 shoulders from 44 patients with recurrent anterior shoulder instability accompanied by a clinically relevant glenoid bone loss. The defect size, the localization of the inferior defect edge, and the defect angle were measured, and osseous landmarks were identified. An en face view on 2-dimensional computed tomography scans of each patient was fitted onto a template to create a deficit map for small ( 23%) defects. Results The study cohort consisted of 9 women and 35 men with a mean age of 33 ± 11 years at the date of the scan. The defect size and localization of the inferior defect edge showed significant differences between both groups, indicating a more posterior position of larger defects. The defect angle, however, showed no significant difference between small and large defects. Both groups showed a vertical defect pattern. Conclusion The osseous glenoid deficit in recurrent anterior shoulder instability shows a vertical pattern with no remarkable differences between small and large defects. This finding can influence biomechanical models as well as surgical reconstruction.

The signal-induced proliferation associated family of proteins comprises four members, SIPA1 and SIPA1L1-1L3. Mutations of the human SIPA1L3 gene result in congenital cataracts. In Xenopus, loss of Sipa1l3 function led to a severe eye phenotype that was distinguished by smaller eyes and lenses including lens fiber cell maturation defects. We found a direct interaction between Sipa1l3 and Epha4, building a functional platform for proper ocular development. Epha4 deficiency phenocopied loss of Sipa1l3 and rescue experiments demonstrated that Epha4 acts up-stream of Sipa1l3 during eye development. Both, Sipa1l3 and Epha4 are required for early eye specification. The ocular phenotype, upon loss of either Epha4 or Sipa1l3, was partially mediated by rax. We demonstrated that canonical Wnt signaling is inhibited downstream of Epha4/Sipa1l3 during normal eye development. Depletion of either Sipa1l3 or Epha4 resulted in an up-regulation of axin2 expression, a direct Wnt/β-catenin target gene. In line with this, Sipa1l3 or Epha4 depletion could be rescued by blocking Wnt/β-catenin or activating non-canonical Wnt signaling. We therefore conclude that this pathomechanism prevents proper eye development and maturation of lens fiber cells resulting in congenital cataracts.

The Craniofacial Biology Research Group in the School of Dentistry at The University of Adelaide is entering an exciting new phase of its studies of dental development and oral health in twins and their families. Studies of the teeth and faces of Australian twins have been continuing for nearly 30 years, with three major cohorts of twins recruited over that time, and currently we are working with twins aged 2 years old to adults. Cross-sectional data and records relating to teeth and faces of twins are available for around 300 pairs of teenage twins, as well as longitudinal data for 300 pairs of twins examined at three different stages of development, once with primary teeth, once at the mixed dentition stage, and then again when the permanent teeth had emerged. The third cohort of twins comprises over 600 pairs of twins recruited at around birth, together with other family members. The emphasis in this third group of twins has been to record the timing of emergence of the primary teeth and also to sample saliva and dental plaque to establish the timing of colonization of decay-forming bacteria in the mouth. Analyses have confirmed that genetic factors strongly influence variation in timing of primary tooth emergence. The research team is now beginning to carry out clinical examinations of the twins to see whether those who become colonized earlier with decay-forming bacteria develop dental decay at an earlier age. By making comparisons within and between monozygotic (MZ) and dizygotic (DZ) twin pairs and applying modern molecular approaches, we are now teasing out how genetic, epigenetic, and environmental factors interact to influence dental development and also oral health.

Utilising data derived from twins and their families, different approaches can be applied to study genetic and environmental influences on human dental variation. The different methods have advantages and limitations and special features of the twinning process are important to consider. Model-fitting approaches have shown that different combinations of additive genetic variance (A), non-additive genetic variance (D), common environmental variance (C), and unique environmental variance (E) contribute to phenotypic variation within the dentition, reflecting different ontogenetic and phylogenetic influences. Epigenetic factors are also proposed as important in explaining differences in the dentitions of monozygotic co-twins. Heritability estimates are high for most tooth size variables, for Carabelli trait and for dental arch dimensions, moderate for intercuspal distances, and low for some occlusal traits. In addition to estimating the contributions of unmeasured genetic and environmental influences to phenotypic variation, structural equation models can also be used to test the effects of measured genetic and environmental factors. Whole-genome linkage analysis, association analysis of putative candidate genes, and whole genome association approaches, now offer exciting opportunities to locate key genes involved in human dental development.

Introduction Despite the importance of rehabilitation in the treatment of patients with severe trauma or even of severely injured patients, the cooperation between acute and rehabilitation hospitals is often inadequate. The present study aims to identify factors that make it probable that a severely injured patient requires inpatient rehabilitation following the acute treatment. Material and methods A retrospective analysis of 75.357 cases from the TraumaRegister DGU ® (TR-DGU) was performed. All cases from 2002 until 2013 with an ISS≥9, who were taken to the ICU were included. Regarding the discharge destination the subgroups "at home" and "rehabilitation hospital" were analyzed in detail. Finally, we performed a multivariate regression analysis based on the parameters previously collected. Results 24.208 patients (32.1%) were transferred to a rehabilitation clinic. In the multivariate regression analysis the most relevant independent parameters for discharge in a rehabilitation hospital were age (18–54: OR 1.65; 55–74: OR 2.86 and 75 and older: OR 5.07, all p≤0.001), AIS pelvis≥2 (OD 1.94), AIS legs (OR 2.02), AIS spine (AIS 4: OR 5.78 and AIS 5–6: OR 6.36) and the AIS head (AIS 3: OR 1.88; AIS 4: OR 3.11 and AIS 5–6: OR 7.55) (all p≤0.001). The length of stay in the ICU (3–7 days: OR 1.88; 8–28 Days: OR 5.42 and 29 and more days: OR 14.7, all p≤0.001) was also a relevant parameter. The overall ISS presented no relevant influence with an OR of 1.02 (p=0.03). Discussion and conclusion Knowing independent factors for a required inpatient rehabilitation helps the treating physicians to identify the patients at an early stage in acute hospitals. So the transfer to a rehabilitation clinic can be organized faster and more selective in future.

Purpose. Incidence of geriatric fractures is increasing. Knowledge of outcome data for hip-fracture patients undergoing intensive-care unit (ICU) treatment, including invasive ventilatory management (IVM) and hemodiafiltration (CVVHDF), is sparse.Methods. Single-center prospective observational study including 402 geriatric hip-fracture patients. Age, gender, the American Society of Anesthesiologists (ASA) classification, and the Barthel index (BI) were documented. Underlying reasons for prolonged ICU stay were registered, as well as assessed procedures like IVM and CVVHDF. Outcome parameters were in-hospital, 6-month, and 1-year mortality and need for nursing care.Results. 15% were treated > 3 days and 68% < 3 days in ICU. Both cohorts had similar ASA, BI, and age. In-hospital, 6-month, and 12-month mortality of ICU > 3d cohort were significantly increased (p=0.001). Most frequent indications were cardiocirculatory pathology followed by respiratory failure, renal impairment, and infection. 18% of patients needed CVVHDF and 41% IVM. In these cohorts, 6-month mortality ranged > 80% and 12-month mortality > 90%. 100% needed nursing care after 6 and 12 months.Conclusions. ICU treatment > 3 days showed considerable difference in mortality and nursing care needed after 6 and 12 months. Particularly, patients requiring CVVHDF or IVM had disastrous long-term results. Our study may add one further element in complex decision making serving this vulnerable patient cohort.

Introduction Hemorrhagic shock remains one of the most common causes of death in severely injured patients. It is unknown to what extent the presence of a blood bank in a trauma center influences therapy and outcome in such patients. Material and Methods We retrospectively analyzed prospectively recorded data from the TraumaRegister DGU® and the TraumaNetzwerk DGU®. Inclusion criteria were Injury Severity Score (ISS) ≥ 16, primarily treated patients, and hospital admission 2 years before or after the audit process. Results Complete data sets of 18,573 patients were analyzed. Of 457 hospitals included, 33.3% had an in-house blood bank. In trauma centers with a blood bank (HospBB), packed red blood cells (PRBCs) (21.0% vs. 17.4%, p < 0.001) and fresh frozen plasma (FFP) (13.9% vs. 10.2%, p

Our understanding of tooth eruption in humans remains incomplete. We hypothesized that genetic factors contribute significantly to phenotypic variation in the emergence of primary incisors. We applied model-fitting to data from Australian twins to quantify contributions of genetic and environmental factors to variation in timing of the emergence of human primary incisors. There were no significant differences in incisor emergence times between zygosity groups or sexes. Emergence times of maxillary central incisors and mandibular lateral incisors were less variable than those of maxillary lateral incisors and mandibular central incisors. Maxillary lateral incisors displayed significant directional asymmetry, the left side emerging earlier than the right. Variation in timing of the emergence of the primary incisors was under strong genetic control, with a small but significant contribution from the external environment. Estimates of narrow-sense heritability ranged from 82 to 94% in males and 71 to 96% in females.

Background After three decades of an increase in the prevalence of asthma and allergies, new findings show a plateau in the prevalence of industrialized nations. The objective of this study was to determine whether there was a change in the parent reported prevalence of asthma and allergies among Bavarian preschool children since 2004. Methods A parent questionnaire was administered as part of the Bavarian school entrance examination in three cross-sectional studies from 2004/2005, 2006/2007 and 2012/2013. The questionnaire included items on allergy testing history, identified allergens, symptoms (e.g. wheezing, itchy eyes, rash), medically diagnosed asthma, hay fever and atopic dermatitis. Logistic regression was performed to observe time patterns and adjust for risk factors. Results Data were available for 6350 (2004/2005), 6483 (2006/2007) and 5052 (2012/2013) individuals. Symptoms and diseases were more frequent in boys, except for allergies which affect the skin. From 2004 to 2012 the parent reported prevalence of asthma (2.6% to 2.8%), hay fever (4.7% to 4.0%) and atopic dermatitis (12.4% to 11.1%) either remained quite stable or decreased not significantly. Conclusions Results from these three cross-sectional surveys of parent reports suggest that the parent reported prevalences of asthma and allergies are quite stable with small fluctuations since 2004 for Bavarian preschool children. Future research is needed to determine if this trend will continue.

Background A precise understanding of glenohumeral anatomy is required to optimize preoperative planning in shoulder joint arthroplasty, which is difficult in the presence of degenerative disease. In unilateral disease, the contralateral shoulder can be used as a representation of normal anatomy; however, intrasubject differences in shoulder morphology have not been investigated. Methods A retrospective study of all patients aged >65 years who received whole body computed tomography at our trauma center from 2010 through 2014 was conducted. Right and left shoulder computed tomography scans were examined, and the following anatomic parameters were measured: humeral head diameter in anteroposterior and axial views, glenoid diameter in anteroposterior and axial views, glenoid surface, scapula neck depth, neck-shaft angle, glenoid inclination, glenoid/head ratio, and glenoid version. Patients with inadequate scan quality, osseous lesions, pre-existing anatomic abnormality, or metallic implant at the shoulder region and significant osteoarthritis were excluded. Results The study analyzed 102 shoulders of 51 patients. Mean age was 71.4 ± 8.2 years. Humeral head and glenoid diameters, scapula neck depth (right, 36 ± 8 mm; left, 36 ± 7 mm; P = .684), glenoid/head ratio (right, 0.6 ± 0.1; left, 0.6 ± 0.0; P = .961), and glenoid surface (right, 790 ± 152 mm 2 ; left, 754 ± 134 mm 2 ; P = .215) showed no significant side-related differences. In addition, no significant difference was found regarding the neck-shaft angle ( P = .211) and glenoid anteversion or retroversion (right, 65% [n = 33] anteversion and 35% [n = 18] retroversion; left, 69% [n = 35] anteversion and 31% [n = 16] retroversion; P = .417). Conclusion There are no significant side-dependent differences in the osseous anatomy of the glenohumeral joint. In patients with unilateral shoulder degeneration, the contralateral shoulder can provide reference values during the planning of shoulder replacement surgery.

Proximal humeral fractures remain a surgical challenge, and scientific discussions are commonly focused on their ideal treatment. One possible treatment involves the use of an angle stable plate osteosynthesis. However, which material can most feasibly be used to attach the greater tuberosity to the implant remains unknown. In two prospective, non-randomized trials, we compared the results of a FiberWire® and a wire cerclage. A total of 104 patients with 3- and 4-part fractures were included in this examination. In 25 cases, the greater tuberosity was fixated with a FiberWire®, size 2, while 79 cases received a wire cerclage. Plate osteosynthesis was constantly performed via the anterolateral delta-split approach using the NCB®-PH-plate by Zimmer®. The patients were followed clinically at discharge, 6 weeks and 6 months postoperatively and were examined for relevant complications. Age and gender were equally distributed in both groups. Concerning the follow-up after 6 weeks, a significant benefit concerning shoulder function was observed in the FiberWire®-group (wire cerclage: 39.20±11.85, 95% CI 32.37-44.56, FiberWire®: 45.84±16.80, 95% CI 28.34-61.56: p=0.049). After 6 months, the difference between the groups was not significant (wire cerclage: 58.13±18.73, 95% CI 50.25-72.40, FiberWire®: 68.85±23.10, 95% CI 46.83-99.53: p=0.06).

Elastic intramedullary nailing (ESIN) has been proposed as an alternative minimal-invasive method for the operative management of mid-shaft fractures of the clavicle. However, a relevant complication rate has been reported in previous cohorts. The present retrospective single-centre study aimed to analyse the complications following ESIN in adult patients with clavicular mid-shaft fractures (Allman type I) and their impact on functional and patient-perceived outcome measures. Results were compared to a control group receiving locking plate osteosynthesis. The clinical course and outcome of operatively managed patients with clavicular mid-shaft fractures were retrospectively analysed. Patients were assigned to group A (ESIN) and group B (plate fixation). Radiological, functional (Constant Murley Shoulder Outcome Score (CS), the Disabilities of the Arm, Shoulder and Hand (DASH) Score, the Oxford Shoulder Score (OSS)), and patient perceived aesthetic and clinical outcome were measured. A total of 47 (33 male, 14 female) operatively managed patients with a mean age of 26.7 ± 14.9 years and a follow up time of 38.1 ± 19.4 months were analysed. 36 patients were treated by ESIN (Group A), whereas 11 patients received open reduction and internal plate fixation (Group B). Patients were operatively treated with a mean delay of 7.4 ± 9.3 days (group A: 6.6 ± 8.7 days, group B: 10.2 ± 11.1 days, p=0.326) between trauma and the surgical index procedure. There were no significant differences in the functional (CS: p=0.338, DASH: p=0.247, OSS: p=0.434) and patient-perceived (p=0.346) outcome measures between both groups. Surgical complications were noted in 14 patients (group A: 12, group B: 2) and non-union in 4 patients (group A: 3, group B: 1). There was no correlation between the recorded complications as assessed by the Clavien and Dindo classification and the functional as well as the patient-perceived outcome measures. Despite a relevant incidence rate of surgical complications, ESIN provides good to excellent functional and patient-perceived results in the treatment of clavicular mid-shaft fractures.

Background The optimal treatment for proximal humeral fractures remains under debate. In this article, we report the mid-term results of patients who underwent the less-invasive implantation of a polyaxial locking plate for displaced proximal humeral fractures. Methods This study included patients who were treated with a polyaxial locking plate via an anterolateral deltoid split approach from May 2008 to December 2011. We evaluated outcome parameters after a minimum follow-up period of 2.5 years (median 4.5 years, follow-up rate 62 %) including the age- and gender-dependent Constant score, the activities of daily living score, and the visual analog scale for both pain and subjective shoulder function. Results Of the 140 patients who underwent surgery, 114 were included in the follow-up and 71 completed the questionnaire. Fifteen patients (21 %) exhibited 2-fragment fractures, and 56 patients (79 %) exhibited 3- and 4-part fractures. The Constant score improved significantly (4.5 years: 70 ± 21, p