The neuroinflammatory component of negative affect in patients with chronic pain.

Negative affect (NA) is a significant cause of disability for chronic pain patients. While little is known about the mechanism underlying pain-comorbid NA, previous studies have implicated neuroinflammation in the pathophysiology of both depression and chronic pain. Here, we tested the hypothesis that NA in pain patients is linked to elevations in the brain levels of the glial marker 18 kDa translocator protein (TSPO), and changes in functional connectivity. 25 cLBP patients (42.4 ± 13 years old; 13F, 12M) with chronic low back pain (cLBP) and 27 healthy control subjects (48.9 ± 13 years old; 14F, 13M) received an integrated (i.e., simultaneous) positron emission tomography (PET)/magnetic resonance imaging (MRI) brain scan with the second-generation TSPO ligand [11C]PBR28. The relationship between [11C]PBR28 signal and NA was assessed first with regression analyses against Beck Depression Inventory (BDI) scores in patients, and then by comparing cLBP patients with little-to-no, or mild-to-moderate depression against healthy controls. Further, the relationship between PET signal, BDI and frontolimbic functional connectivity was evaluated in patients with mediation models. PET signal was positively associated with BDI scores in patients, and significantly elevated in patients with mild-to-moderate (but not low) depression compared with controls, in anterior middle and pregenual anterior cingulate cortices (aMCC, pgACC). In the pgACC, PET signal was also associated with this region's functional connectivity to the dorsolateral PFC (pgACC-dlPFC), and mediated of the association between pgACC-dlPFC connectivity and BDI. These observations support a role for glial activation in pain-comorbid NA, identifying in neuroinflammation a potential therapeutic target for this condition.

Determination of the occlusal vertical dimension in edentulous patients using lateral cephalograms.

The determination of the occlusal vertical dimension (OVD) in edentulous patients is based on clinical assessment with high variability. This study tested the hypothesis: The average OVD in edentulous patients with conventional dentures is too low compared to orthodontic norms, when only clinical parameters are used for the determination of the OVD. Edentulous patients with conventional full dentures were enrolled. Clinical parameters were judged by two senior prosthodontists. Digital lateral cephalograms were taken and served to calculate the OVD according to the lower face height angle (ANS-Xi-D) taking tooth-independent facial growth patterns into account. The ANS-Xi-D angle was compared with reference values by applying one-sample mean comparison tests. Thirty-six participants (17 female, 19 male; mean age 65.3 ± 10.6 years) were enrolled in this study. Clinically, the OVD of four dentures was judged too low, in one case too high, and in the other 31 cases as correct. The mean ANS-Xi-D angle was 48.28°±4.86 and statistically not different to the norm value of 49°±4 (n.s.). There was a tendency that the ANS-Xi-D angle was different between participants with different tooth-independent facial growth patterns (ANOVA, P = .0548). Predominantly, clinically sufficient prostheses show adequate ANS-Xi-D angles. Short-face type denture patients are often restored to comply with mesiofacial norms. The determination of the OVD based on lateral cephalography is not recommendable to be a standard diagnostic parameter. Orthodontic norms are derived from dentate cohorts and might not take the continuing facial growth and other confounding factors of edentulous subjects into account.

[Caregiver intervention studies : Recommendations on endpoints and outcome measures for cognitively impaired care recipients]. / Interventionsstudien zur Unterstützung häuslicher Pflege : Empfehlungen zu Endpunkten und Assessment-Instrumenten bei kognitiv eingeschränkten Pflegebedürftigen.

BACKGROUND: Even though the intervention effects on cognitively impaired care recipients are of interest, the evaluation in dementia caregiver studies on caregiver outcomes is often limited. Furthermore, the comparison of studies and interventions is difficult because of the large variance of endpoints and assessments used in this field. OBJECTIVE: The aim of this study was to give an overview on the most prevalent outcomes for cognitively impaired care recipients and expert based recommendations for assessment. MATERIAL AND METHODS: A written Delphi survey was carried out on 16 assessments from 5 dimensions with 14 experts working in different disciplines in German healthcare and research institutes. RESULTS: The most important outcomes and best rated assessments were 1) for problem behavior: revised memory and behavior problem checklist and neuropsychiatric inventory Q, 2) for depressive symptoms: geriatric depression scale, 3) for quality of life: quality of life in Alzheimer's disease, 4) for cognition: mini mental state examination and 5) for ADL/IADL: Katz activities of daily living and Lawton instrumental activities of daily living. CONCLUSION: Due to the varying experiences of the experts with particular assessments, the ratings were in some cases relatively heterogeneous. Overall previous international recommendations could be confirmed. There is particular need of German validation studies on internationally used instruments within the dimensions of problem behavior and quality of life.

[Post-treatment rehabilitation after autologous chondrocyte implantation: State of the art and recommendations of the Clinical Tissue Regeneration Study Group of the German Society for Accident Surgery and the German Society for Orthopedics and Orthopedic Surgery]. / Nachbehandlung bei der autologen Chondrozytentransplantation: Eine Bestandsaufnahme und Empfehlung der AG Klinische Geweberegeneration der DGU/DGOOC.

BACKGROUND: Over the course of the past two decades autologous chondrocyte implantation (ACI) has become an important surgical technique for treating large cartilage defects. The original method using a periostal flap has been improved by using cell-seeded scaffolds for implantation, the matrix-based autologous chondrocyte implantation (mb-ACI) procedure. MATERIAL AND METHODS: Uniform nationwide guidelines for post-ACI rehabilitation do not exist. A survey was conducted among the members of the clinical tissue regeneration study group concerning the current rehabilitation protocols and the members of the study group published recommendations for postoperative rehabilitation and treatment after ACI based on the results of this survey. RESULTS: There was agreement on fundamentals concerning a location-specific rehabilitation protocol (femoral condyle vs. patellofemoral joint). With regard to weight bearing and range of motion a variety of different protocols exist. Similar to this total agreement on the role of magnetic resonance imaging (MRI) for postsurgical care was found but again a great variety of different protocols exist. CONCLUSIONS: This manuscript summarizes the recommendations of the members of the German clinical tissue regeneration study group on postsurgical rehabilitation and MRI assessment after ACI (level IVb/EBM).

Severe posttraumatic radiocarpal cartilage damage: first report of autologous chondrocyte implantation.

STUDY DESIGN: Case report. CLINICAL QUESTION: Traumatic articular cartilage defects predispose to secondary osteoarthritis accompanied by impairment or complete loss of function in the corresponding joint. On this account, the timely and correct diagnosis as well as the selection of an appropriate therapy for reconstruction of articular cartilage defects is important. METHODS: A 22-year-old healthy male patient with history of traumatic intra-articular distal radius fracture is presented with in the course detectable 4° cartilage damage in the fovea scaphoidea and into the fovea lunata. For the first time, autologous chondrocyte implantation by the use of an in situ polymerizable albumin-hyaluronic acid gel was performed to restore the articular cartilage. RESULTS: The assessment 6 months after autologous chondrocyte implantation using the standard DASH questionnaire for upper extremity pointed out an improvement in the patient outcome (DASH score pre-operative: 10.8 and 6 months post-operative: 7.5). The clinical examination also showed an improvement in the range of movement of the wrist without pain. The radiological control investigation (MRI- examination) of the wrist 6 months after implantation also revealed a good integration of the implant. CONCLUSION: The case presented here demonstrates the first use of autologous chondrocyte implantation for cartilage reconstruction using an in situ polymerizable albumin-hyaluronic acid gel after traumatic cartilage lesion with 4° cartilage damage of the wrist in a 22-year-old non-smoking, active and healthy man. Initial results are promising in terms of mobility, pain and patient outcome. However, further clinical studies have to be performed with larger number of cases.

[Changes of patella position after closed and open wedge high tibial osteotomy: review of the literature]. / Veränderung der Patellahöhe nach "open"- und "closed wedge high tibial osteotomy" : Review der Literatur.

AIM: High tibial osteotomy (HTO) is an established treatment for varus osteoarthritis of the knee. The correction can be achieved by lateral closed wedge HTO or medial open wedge HTO techniques. Both techniques can change the patella position which influences alignment of the patella. Patella infera may compromise the result of secondary total knee prosthesis. An analysis of the current literature was carried out focusing on changes of patella position after HTO. METHOD: A literature search was performed in PubMed which identified 15 relevant publications and the Insall-Salvati-index, the Blackburne-Peel-index and the Caton-Deschamps-index were analyzed. RESULTS: Results after closed wedge HTO: the Insall-Salvati-index decreased in 7 papers, increased in 3 papers and was unchanged in 1 paper. The Blackburne-Peel-index increased in 5 papers and decreased in 2. The Caton-Deschamps-index decreased in 4 papers and increased in 2 papers. Results after open wedge HTO: the InsalI-Salvati-index decreased in 5 papers and increased in 2. The Blackburne-Peel-index decreased in all 7 papers and the Caton-Deschamps-index decreased in all 5 papers. The results of these studies vary significantly and there was a tendency to patella infera in both techniques. The Blackburne-Peel-index and the Caton-Deschamps-index may be biased by slope changes but the exact effect is not yet known. The Insall-Salvati-index seems to be independent of slope changes. The effect of different rehabilitation concepts on patella height is not known. CONCLUSION: The clinical relevance of the observed changes in patella position must be clarified by prospective studies with strict criteria.

Potential of education-based insulin therapy for achievement of good metabolic control: a real-life experience.

AIMS: Achievement of good metabolic control in Type 1 diabetes is a difficult task in routine diabetes care. Education-based flexible intensified insulin therapy has the potential to meet the therapeutic targets while limiting the risk for severe hypoglycaemia. We evaluated the metabolic control and the rate of severe hypoglycaemia in real-life clinical practice in a centre using flexible intensified insulin therapy as standard of care since 1990. METHODS: Patients followed for Type 1 diabetes (n = 206) or those with other causes of absolute insulin deficiency (n = 17) in our outpatient clinic were analysed in a cross-sectional study. Mean age (± standard deviation) was 48.9 ± 15.7 years, with diabetes duration of 21.4 ± 14.4 years. Outcome measures were HbA(1c) and frequency of severe hypoglycaemia. RESULTS: Median HbA(1c) was 7.1% (54 mmol/mol) [interquartile range 6.6-7.8 (51-62 mmol/mol)]; a good or acceptable metabolic control with HbA(1c) < 7.0% (53 mmol/mol) or 7.5% (58 mmol/mol) was reached in 43.5 and 64.6% of the patients, respectively. The frequency of severe hypoglycaemic episodes was 15 per 100 patient years: 72.3% of the patients did not experience any such episodes during the past 5 years. CONCLUSIONS: Good or acceptable metabolic control is achievable in the majority of patients with Type 1 diabetes or other causes of absolute insulin deficiency in routine diabetes care while limiting the risk for severe hypoglycaemia.

Implications of biological activated carbon filters for micropollutant removal in wastewater treatment.

Granulated Activated Carbon (GAC) filtration is a common process for advanced wastewater treatment. In such filters, the removal of organic substances results from adsorptive as well as biological processes. This work investigated the potential of biological processes and their influence on GAC-filter performance. During 32 months, the removal of micropollutants,Dissolved Organic Carbon (DOC) and the spectral absorption coefficient was monitored in six GAC-filters. The effects of pre-treatment (cloth- and/or membrane-filtration), EBCT (from 6 - 35 min) and GAC-type were evaluated. Likewise, the impact of the influent´s fluctuations in temperature, flow and concentration (ammonia, nitrate, and soluble reactive phosphorus (sRP)) were analysed. Biological processes were tracked by the frequency of backwashing, oxygen consumption, removal of poorly absorbable micropollutants and production of transformation products. Pre-treatment influenced biofilm growth significantly. Membrane filtration delayed the first backwashing event by 122 d in comparison to cloth-filtration, where the first backwash was conducted after only 21 d. Removal of poorly absorbable substances was observed early on (40 - 50 d). Parallel operation contributed to a better utilisation of the GAC-capacity and the biological removal potential. Influent nitrogen species > 0.5 mg N/L promoted biofilm growth, whereas sRP seemed to have no effect. The developed biofilm and optimal operating conditions led to longer life spans of the GAC-filters, making carbon usage rates comparable to those from PAC applications. The results suggest that biological processes accounted for about 25 - 42% of the totally removed DOC at the end of the operation.

Empty bed contact time: The key for micropollutant removal in activated carbon filters.

The removal of micropollutants from wastewater is an emerging issue that currently concerns the wastewater sector the most. Granular Activated Carbon (GAC) has gained recognition as a suitable technology for dealing with this problem. This study assesses the performance of six GAC-filters for the removal of micropollutants installed as final treatment step at a municipal wastewater treatment plant. The influence of the GAC-type and the Empty Bed Contact Time (EBCT) on the filter performance was evaluated. The breakthrough behaviour of 13 selected micropollutants as well as the removal of the Dissolved Organic Carbon (DOC) and UV absorption at 254 nm were investigated. Besides, the adsorbed DOC (qDOC) was introduced as assessment parameter (adsorbed and biodegraded DOC), instead of the commonly used treated bed volume. Finally, Size Exclusion Chromatography (SEC) with online DOC and UV254nm detection was applied for a better understanding of the influent and effluent characteristics. The results showed that the pore size distribution is a crucial feature of the activated carbon. A balanced proportion of macro-, meso­ and micropores may play a role in the better removal of micropollutants in presence of DOC. Regardless of the GAC-type, a minimum EBCT between 20 - 30 min was necessary. We proved that a short EBCT would not fully use the sorption capacity, whereas a long EBCT would increase the carbon demand without improving of the removal. Lastly, according to the SEC results, after a short operation time no difference between the influent and effluent chromatographable fractions (DOC and UV254nm) was observed.

Alterations in the jejunum of young goats caused by feeding soy protein-based diets.

This study was designed to investigate whether soy protein or soy protein supplemented with indispensable amino acids (AA) change the protein expression pattern and utilization of pre-cursors for RNA biosynthesis in jejunal mucosa in relation to casein and whether these changes affect mucosal cell growth. Kids were fed comparable diets based on cow;s milk, of which 50% of crude protein were replaced by either casein (CAS), soy protein (SP) or soy protein supplemented with indispensible AA (SPA) for 34 days (n = 4/group). Jejunal tissue was collected 5 h after adding a single dose of (15)N-RNA to the diet, in order to determine morphology, protein repertoire by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry, and RNA biosynthesis by isotope ratio-mass spectrometry. In mid-jejunum, morphological alterations induced by partial replacement of casein with soy protein were accompanied by changes in mucosal proteins related to generation of the cytoskeleton and in pathways for mucosal RNA biosynthesis, resulting in a smaller re-utilization of dietary RNA pre-cursors and in an increased activity of enzymes involved in nucleic acid breakdown. Soy protein supplemented with indispensible aminoacids tended to revise mucosal growth retardation with no impact on salvage of dietary RNA pre-cursors for mucosal RNA biosynthesis, but changes in cytoskeleton generation. Feeding soy protein with supplementation of indispensible AA does not ameliorate soy protein effects on mucosal morphology and RNA metabolism in the jejunum in a significant manner.

Semi-supervised labelling of the femur in a whole-body post-mortem CT database using deep learning.

A deep learning pipeline was developed and used to localize and classify a variety of implants in the femur contained in whole-body post-mortem computed tomography (PMCT) scans. The results provide a proof-of-principle approach for labelling content not described in medical/autopsy reports. The pipeline, which incorporated residual networks and an autoencoder, was trained and tested using n = 450 full-body PMCT scans. For the localization component, Dice scores of 0.99, 0.96, and 0.98 and mean absolute errors of 3.2, 7.1, and 4.2 mm were obtained in the axial, coronal, and sagittal views, respectively. A regression analysis found the orientation of the implant to the scanner axis and also the relative positioning of extremities to be statistically significant factors. For the classification component, test cases were properly labelled as nail (N+), hip replacement (H+), knee replacement (K+) or without-implant (I-) with an accuracy >97%. The recall for I- and H+ cases was 1.00, but fell to 0.82 and 0.65 for cases with K+ and N+. This semi-automatic approach provides a generalized structure for image-based labelling of features, without requiring time-consuming segmentation.

Visual cortical neurons: are bars or gratings the optimal stimuli?

Neurons in the visual cortex of monkeys and cats have been characterized as either (i) bar and edge detectors or (ii) cells selective for certain spatial frequencies. To assess which of these functional descriptions is more accurate, we measured (i) the selectivity and (ii) the responsivity-sensitivity of these neurons to bars of various widths and gratings of various spatial frequencies. All of the cells recorded from were considerably more selective along the dimension of spatial frequency than along the dimension of bar width. Further, most were more responsive and sensitive to the grating of optimal frequency than to the bar of optimal width.

[Regional anaesthesia as advantage in competition between hospitals. Strategic market analysis]. / Regionalanästhesie als Wettbewerbsvorteil im Krankenhaus. Strategische Umfeldanalyse.

BACKGROUND: The German Social Act V section sign 12 is aimed towards competition, efficiency and quality in healthcare. Because surgical departments are billing standard diagnosis-related group (DRG) case costs to health insurance companies, they claim best value for money for internal services. Thus, anaesthesia concepts are being closely scrutinized. The present analysis was performed to gain economic arguments for the strategic positioning of regional anaesthesia procedures into clinical pathways. METHODS: Surgical procedures, which in 2005 had a relevant caseload in Germany, were chosen in which regional anaesthesia procedures (alone or in combination with general anaesthesia) could routinely be used. The structure of costs and earnings for hospital services, split by types and centres of cost, as well as by underlying procedures are contained in the annually updated public accessible dataset (DRG browser) of the German Hospital Reimbursement Institute (InEK). For the year 2005 besides own data, national anaesthesia staffing costs are available from the German Society of Anaesthesiology (DGAI). The curve of earnings per DRG can be calculated from the 2005 InEK browser. This curve intersects by the cost curve at the point of national mean length of stay. The cost curve was calculated by process-oriented distribution of cost centres over the length of stay and allows benchmarking within the national competitive environment. For comparison of process times data from our local database were used. While the InEK browser lacks process times, the cost positions 5.1-5.3 (staffing costs anaesthesia) and the national structure adjusted anaesthesia staffing costs 2005 as published by the DGAI, were used to calculate nationwide mean available anaesthesia times which were compared with own process times. RESULTS: Within the portfolio diagram of lengths of stay for each DRG and process times most procedures are located in the economic lower left, in particular those with high case mix (length of stay and anaesthesia times below reimbursement relevant national mean). The driver of increased earnings is shortening length of stay. Our use of regional anaesthesia is 5 to 10-fold higher than national benchmarks and may contribute to our advantageous position in national competition. The annual increases in profit per DRG range between EUR 1,706 and EUR 467,359 and compensate by far the investment of regional anaesthesia derived pain management, besides the advantage of increased patient satisfaction and avoidance of complications. CONCLUSION: Regional anaesthesia is a considerable value driver in clinical pathways by shortening length of stay. The present analysis further demonstrates that time for regional block performance is covered by anaesthesia reimbursement within the DRG costing schedule.

Degenerative Cartilage Lesions of the Medial Knee Compartment. Associated Factors, Operative Options, and Preliminary Results from the CartilageRegistry DGOU. / Degenerativ bedingte Knorpelschäden im medialen Kniekompartiment. Assoziierte Faktoren, operative Optionen und präliminäre Ergebnisse aus dem KnorpelRegister (DGOU).

PURPOSE: This study was aimed to determine the impact of bioregenerative operations in case of degenerative cartilage lesions within the media knee compartment. MATERIAL AND METHODS: The CartilageRegistry DGOU was founded in 2013. At the deadline August 2016 a total of 1847 patients were included. A total of 23.3% (n = 432) was suffering from a degenerative cartilage lesion in the medial compartment. Follow-up was performed after 6, 12, and 24 months (online evaluation). The patients were asked for their subject feeling as well as the KOOS (Knee injury and Osteoarthritis Outcome Score) was determined. RESULTS: Most of the patients (n = 358) suffered from a single femoral lesion. In 25 cases single tibial and in 49 cases combined defects ("kissing lesions") were addressed by different treatment options: 39.9% autologous chondrocyte transplantation, in 8.1% in combination with a spongiosa plasty. Other treatments were drilling, microfracturing with or without matrix. In 17.9% the surgeons had chosen combined methods. The bioregenerative treatment was combined with a concomitant operation in 39.7% in patients with medial, in 56.0% in patients with a tibial, and in 67.9% in patients with combined defects. The mostly performed additional operations were osteotomies. There were no gender differences at baseline or during follow-up. The history of patients with femoral defects was shorter than in the other groups. The patients with medial defects judged the subjective outcome significant more frequently better after 6, 12, or 24 months compared with the other groups. The KOOS raised from baseline (median 52 points) to a median of 75 after 6, to 78 points after 12, and to 80 points after 24 months. Patients with femoral defects had a better KOOS-outcome in tendency. Revision operations were required in 7.1%. CONCLUSIONS: The treatment of degenerative cartilage lesions (respective early OA) by bioregenerative procedures are well-established measures. These treatments are sufficient to produce high patients' satisfaction and acceptable short/midterm results.

[Therapy of articular cartilage lesions]. / Therapie von Gelenkknorpelschäden.

Lesions of adult articular cartilage do not heal or regenerate. They give rise to the development of osteoarthritis, and surgical treatment is necessary before the initiation of joint degeneration. Various treatment modalities ranging from microfracture to autologous mosaicplasty and autologous chondrocyte transplantation are available. Commonly they are distinguished by the presence or absence of cell transplantation. The treatment choice depends on size, depth, and location of the lesion; therefore exact classification is mandatory. The surgical procedure aims to reconstruct a physiological distribution of the biomechanical forces by surface restoration. Additional joint pathologies such as mechanical axis deviation, meniscal defects, and ligament insufficiencies threaten the surgical success and must be addressed simultaneously.

The effects of angiotensin receptor neprilysin inhibition by sacubitril/valsartan on adipose tissue transcriptome and protein expression in obese hypertensive patients.

Increased activation of the renin-angiotensin system is involved in the onset and progression of cardiometabolic diseases, while natriuretic peptides (NP) may exert protective effects. We have recently demonstrated that sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, which blocks the angiotensin II type-1 receptor and augments natriuretic peptide levels, improved peripheral insulin sensitivity in obese hypertensive patients. Here, we investigated the effects of sacubitril/valsartan (400 mg QD) treatment for 8 weeks on the abdominal subcutaneous adipose tissue (AT) phenotype compared to the metabolically neutral comparator amlodipine (10 mg QD) in 70 obese hypertensive patients. Abdominal subcutaneous AT biopsies were collected before and after intervention to determine the AT transcriptome and expression of proteins involved in lipolysis, NP signaling and mitochondrial oxidative metabolism. Both sacubitril/valsartan and amlodipine treatment did not significantly induce AT transcriptional changes in pathways related to lipolysis, NP signaling and oxidative metabolism. Furthermore, protein expression of adipose triglyceride lipase (ATGL) (Ptime*group = 0.195), hormone-sensitive lipase (HSL) (Ptime*group = 0.458), HSL-ser660 phosphorylation (Ptime*group = 0.340), NP receptor-A (NPRA) (Ptime*group = 0.829) and OXPHOS complexes (Ptime*group = 0.964) remained unchanged. In conclusion, sacubitril/valsartan treatment for 8 weeks did not alter the abdominal subcutaneous AT transcriptome and expression of proteins involved in lipolysis, NP signaling and oxidative metabolism in obese hypertensive patients.

A milk diet partly containing soy protein does not change growth but regulates jejunal proteins in young goats.

Soy protein is known to alter intestinal function and structure. We determined in young goats whether a diet partly containing soy protein differently affects intestinal morphology and the jejunal and hepatic proteome as compared with a milk diet. Fourteen male 2-wk-old White German dairy goat kids were fed comparable diets based on whole cow's milk in which 35% of the crude protein was casein (milk protein group; MP) or soy protein supplemented by indispensable AA (SPAA) for 34 d (n = 7/group). Body weight gain and food efficiency were not different. Jejunal and hepatic tissue was collected to determine intestinal morphology by microscopy and protein repertoire by 2-dimensional gel electrophoresis and mass spectrometry. Jejunal crypt depth was reduced and villus height to crypt depth ratio was higher in SPAA than in milk protein. Out of 131 proteins identified, 32 proteins were found to be differently expressed in both groups. In SPAA, down-regulated jejunal proteins were involved in processes related to cytoskeleton generation, protein, lipid, and energy metabolism. Downregulated hepatic proteins were related to glycolysis and Krebs cycle. Thirteen proteins were upregulated in SPAA. Among these, 2 hepatic proteins were related to carbohydrate breakdown. The other 11 jejunal proteins were involved in cytoskeleton assembly, proteolysis, and carbohydrate breakdown. In addition, glutathione-S-transferase was found to be upregulated in the medial jejunum. In conclusion, a SPAA diet as compared with a milk diet was related to changes in jejunal morphology and jejunal proteins relevant for protein turnover, energy metabolism, and cytoskeleton assembly with no apparent impact on animal BW gain.

[Treatment of Osteochondral Lesions in the Ankle: A Guideline from the Group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU)]. / Behandlung osteochondraler Läsionen des Sprunggelenks: Empfehlungen der Arbeitsgemeinschaft Klinische Geweberegeneration der DGOU.

Background: Osteochondral lesions (OCL) of the ankle are a common cause of ankle pain. Although the precise pathophysiology has not been fully elucidated, it can be assumed that a variety of factors are responsible, mainly including traumatic events such as ankle sprains. Advances in arthroscopy and imaging techniques, in particular magnetic resonance imaging (MRI), have improved the possibilities for the diagnosis of OCLs of the ankle. Moreover, these technologies aim at developing new classification systems and modern treatment strategies. Material and Methods: This article is a review of the literature. Recommendations of the group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU) for the treatment of OCLs of the ankle are presented. The review gives a concise overview on the results of clinical studies and discusses advantages and disadvantages of different treatment strategies. Results: Non-operative treatment shows good results for selected indications in children and adolescents, especially in early stages of osteochondritis dissecans (OCD). However, surgical treatment is usually indicated in OCLs in adolescents and adults, depending on the size and location of the lesion. Various arthroscopic and open procedures are frequently employed, including reattachment of the fragment, local debridement of the lesion with fragment removal and curettage of the lesion, bone marrow-stimulation by microfracture or microdrilling (antegrade or retrograde), and autologous matrix-induced chondrogenesis (AMIC®) - with or without reconstruction of a subchondral bone defect or cyst by autologous cancellous bone grafting. Isolated subchondral cysts with an intact cartilage surface can be treated by retrograde drilling and possibly additional retrograde bone grafting. For larger defects or as salvage procedure, osteochondral cylinder transplantation (OATS® or Mosaicplasty®) or matrix-induced autologous chondrocyte transplantation (MACT) are recommended. Transplantation of so-called (osteochondral) mega grafts, such as autologous bone grafts or allografts, are used for very large osteochondral defects that cannot be reconstructed otherwise. Implantation of the so-called "small metal implants" - such as HemiCAP Talus® - is reserved for selected cases after failed primary reconstruction. Corrective osteotomies are indicated in accompanying axial malalignments. Conclusions: There are several different treatment strategies for OCLs, but clinical studies are rare and evidence is limited. Therefore, interventional studies, e.g. randomised controlled trials (RCTs), but also observational studies, e.g. based on data of the Cartilage Registry of the German Society of Orthopaedics and Traumatology (www.knorpelregister-dgou.de), are needed and are recommended by the authors.

Improved Insulin Sensitivity With Angiotensin Receptor Neprilysin Inhibition in Individuals With Obesity and Hypertension.

Natriuretic peptide (NP) deficiency and sustained renin-angiotensin system activation are associated with impaired oxidative metabolism and predispose to type-2 diabetes. We hypothesized that sacubitril/valsartan (LCZ696), which augments NP through neprilysin inhibition while blocking angiotensin II type-1 (AT1 )-receptors, improves insulin sensitivity, lipid mobilization, and oxidation. After 8 weeks of treatment of obese patients with hypertension, sacubitril/valsartan 400 mg q.d., but not amlodipine 10 mg q.d., was associated with a significant increase from baseline in the insulin sensitivity index (hyperinsulinemic-euglycemic clamp), and tended to be higher in patients treated with sacubitril/valsartan compared to amlodipine. Abdominal adipose tissue interstitial glycerol concentrations increased with sacubitril/valsartan, but decreased with amlodipine. Whole-body lipolysis and substrate oxidation did not change with either treatment. Results confirm that sacubitril/valsartan treatment leads to a metabolic benefit in the study population and supports the relevance of neprilysin inhibition along with AT1 -receptor blockade in the regulation of human glucose and lipid metabolism.

Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: A guideline by the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU).

BACKGROUND: Autologous chondrocyte implantation (ACI) is an established and well-accepted procedure for the treatment of localised full-thickness cartilage defects of the knee. METHODS: The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning therapeutic consequences of primary cartilage lesions and the suitable indication for ACI. RESULTS: Based on best available scientific evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than three to four square centimetres; in the case of young and active sports patients at 2.5cm(2), while advanced degenerative joint disease needs to be considered as the most important contraindication. CONCLUSION: The present review gives a concise overview on important scientific background and the results of clinical studies and discusses the advantages and disadvantages of ACI. LEVEL OF EVIDENCE: Non-systematic Review.