[Curriculum "Tracheostomy management in dysphagia therapy"]. / Curriculum "Trachealkanülenmanagement in der Dysphagietherapie".

The number of tracheotomized patients with dysphagia and their need for treatment are continuously increasing in clinical and community settings. The revised version of the directive on home care and community-based intensive care of the Federal Joint Committee (G-BA) requires that tracheotomized patients are regularly evaluated with the aim of identifying and promoting the therapeutic potential after hospital discharge. Dysphagia treatment plays a crucial role as without improvement of severe dysphagia there is practically no possibility for decannulation. Tracheotomized patients with dysphagia are treated by speech and language therapists (SLT); however, the contents of tracheostomy management (TM) are not obligatory in the speech and language therapeutic training curricula, so that there is a need for further education and treatment standards must be secured. Therefore, the German Interdisciplinary Society for Dysphagia (DGD) in cooperation with the participating German medical and therapeutic societies developed a postgraduate curriculum for TM. This should serve as the basis for contents in TM and qualification of therapists within the framework of the delegation of medical services. The goals of the TM curriculum are the definition of theoretical and practical contents of TM, the qualification to perform TM according to current standards of care and quality assurance. The curriculum defines two qualification levels (user and trainer), entry requirements, curricular contents, examination and qualification criteria as well as transitional regulations for SLTs already experienced in TM.

Pre-operative Assessment of Shoulder Pathologies on MRI by a Radiologist and an Orthopaedic Surgeon.

Introduction: Pathologies of the shoulder, i.e. rotator cuff tears and labral injuries are very common. Most patients receive MRI examination prior to surgery. A correct assessment of pathologies is significant for a detailed patient education and planning of surgery. Materials and methods: Sixty-nine patients were identified, who underwent both, a standardised shoulder MRI and following arthroscopic shoulder surgery in our hospital. For this retrospective comparative study, the MRIs were pseudonymised and evaluated separately by an orthopaedic surgeon and a radiologist. A third rater evaluated images and reports of shoulder surgery, which served as positive control. Results of all raters were then compared. The aim was an analysis of agreement rates of diagnostic accuracy of preoperative MRI by a radiologist and an orthopaedic surgeon. Results: The overall agreement with positive control of detecting transmural cuff tears was high (84% and 89%) and lower for partial tears (70-80%). Subscapularis tears were assessed with moderate rates of agreement (60 - 70%) compared to intra-operative findings. Labral pathologies were detected mostly correctly. SLAP lesions and pulley lesions of the LHB were identified with only moderate agreement (66.4% and 57.2%) and had a high inter-rater disagreement. Conclusion: This study demonstrated that tears of the rotator cuff (supraspinatus, infraspinatus) and labral pathologies can be assessed in non-contrast pre-operative shoulder MRI images with a high accuracy. This allows a detailed planning of surgery and aftercare. Pathologies of the subscapularis tendon, SLAP lesions and biceps instabilities are more challenging to detect correctly. There were only small differences between a radiologic and orthopaedic interpretation of the images.

Spontaneous playful teasing in four great ape species.

Joking draws on complex cognitive abilities: understanding social norms, theory of mind, anticipating others' responses and appreciating the violation of others' expectations. Playful teasing, which is present in preverbal infants, shares many of these cognitive features. There is some evidence that great apes can tease in structurally similar ways, but no systematic study exists. We developed a coding system to identify playful teasing and applied it to video of zoo-housed great apes. All four species engaged in intentionally provocative behaviour, frequently accompanied by characteristics of play. We found playful teasing to be characterized by attention-getting, one-sidedness, response looking, repetition and elaboration/escalation. It takes place mainly in relaxed contexts, has a wide variety of forms, and differs from play in several ways (e.g. asymmetry, low rates of play signals like the playface and absence of movement-final 'holds' characteristic of intentional gestures). As playful teasing is present in all extant great ape genera, it is likely that the cognitive prerequisites for joking evolved in the hominoid lineage at least 13 million years ago.

[Curriculum "Tracheostomy management in dysphagia therapy"]. / Curriculum "Trachealkanülenmanagement in der Dysphagietherapie".

The number of tracheotomized patients with dysphagia and their need for treatment are continuously increasing in clinical and community settings. The revised version of the directive on home care and community-based intensive care of the Federal Joint Committee (G-BA) requires that tracheotomized patients are regularly evaluated with the aim of identifying and promoting the therapeutic potential after hospital discharge. Dysphagia treatment plays a crucial role as without improvement of severe dysphagia there is practically no possibility for decannulation. Tracheotomized patients with dysphagia are treated by speech and language therapists (SLT); however, the contents of tracheostomy management (TM) are not obligatory in the speech and language therapeutic training curricula, so that there is a need for further education and treatment standards must be secured. Therefore, the German Interdisciplinary Society for Dysphagia (DGD) in cooperation with the participating German medical and therapeutic societies developed a postgraduate curriculum for TM. This should serve as the basis for contents in TM and qualification of therapists within the framework of the delegation of medical services. The goals of the TM curriculum are the definition of theoretical and practical contents of TM, the qualification to perform TM according to current standards of care and quality assurance. The curriculum defines two qualification levels (user and trainer), entry requirements, curricular contents, examination and qualification criteria as well as transitional regulations for SLTs already experienced in TM.

A case of COVID-19 vaccination-associated forme fruste purpura fulminans.

We report the case of a female, 77 year old patient with multi-localized skin infarctions following vaccination with mRNA-1273 (Moderna). This phenomenon is to our knowledge otherwise only seen in infection-associated purpura fulminans - which was thoroughly ruled out in our patient. This report demonstrates that we need to be vigilant of a wider array of vascular phenomena related to Covid vaccinations.

Position sensitive measurement of trace lithium in the brain with NIK (neutron-induced coincidence method) in suicide.

Mood disorder is the leading intrinsic risk factor for suicidal ideation. Questioning any potency of mood-stabilizers, the monovalent cation lithium still holds the throne in medical psychiatric treatment. Furthermore, lithium`s anti-aggressive and suicide-preventive capacity in clinical practice is well established. But little is still known about trace lithium distribution and any associated metabolic effects in the human body. We applied a new technique (neutron-induced coincidence method "NIK") utilizing the 6Li(n,α)3H reaction for the position sensitive, 3D spatially resolved detection of lithium traces in post-mortem human brain tissue in suicide versus control. NIK allowed, for the first time in lithium research, to collect a three dimensional high resolution map of the regional trace lithium content in the non lithium-medicated human brain. The results show an anisotropic distribution of lithium, thus indicating a homeostatic regulation under physiological conditions as a remarkable link to essentiality. In contrast to suicide we could empirically prove significantly higher endogenous lithium concentrations in white compared to gray matter as a general trend in non-suicidal individuals and lower lithium concentrations in emotion-modulating regions in suicide.

Dual redundant sequencing strategy: Full-length gene characterisation of 1056 novel and confirmatory HLA alleles.

The high-throughput department of DKMS Life Science Lab encounters novel human leukocyte antigen (HLA) alleles on a daily basis. To characterise these alleles, we have developed a system to sequence the whole gene from 5'- to 3'-UTR for the HLA loci A, B, C, DQB1 and DPB1 for submission to the European Molecular Biology Laboratory - European Nucleotide Archive (EMBL-ENA) and the IPD-IMGT/HLA Database. Our workflow is based on a dual redundant sequencing strategy. Using shotgun sequencing on an Illumina MiSeq instrument and single molecule real-time (SMRT) sequencing on a PacBio RS II instrument, we are able to achieve highly accurate HLA full-length consensus sequences. Remaining conflicts are resolved using the R package DR2S (Dual Redundant Reference Sequencing). Given the relatively high throughput of this strategy, we have developed the semi-automated web service TypeLoader, to aid in the submission of sequences to the EMBL-ENA and the IPD-IMGT/HLA Database. In the IPD-IMGT/HLA Database release 3.24.0 (April 2016; prior to the submission of the sequences described here), only 5.2% of all known HLA alleles have been fully characterised together with intronic and UTR sequences. So far, we have applied our strategy to characterise and submit 1056 HLA alleles, thereby more than doubling the number of fully characterised alleles. Given the increasing application of next generation sequencing (NGS) for full gene characterisation in clinical practice, extending the HLA database concomitantly is highly desirable. Therefore, we propose this dual redundant sequencing strategy as a workflow for submission of novel full-length alleles and characterisation of sequences that are as yet incomplete. This would help to mitigate the predominance of partially known alleles in the database.

Satellite DNA methylation status and expression of selected genes in Bos indicus blastocysts produced in vivo and in vitro.

Bovine embryos produced in vivo and in vitro differ with respect to molecular profiles, including epigenetic marks and gene expression profiles. This study investigated the CpG methylation status in bovine testis satellite I (BTS) and Bos taurus alpha satellite I (BTαS) DNA sequences, and concomitantly the relative abundance of transcripts, critically involved in DNA methylation (DNMT1 and DNMT3A), growth and development (IGF2R) and pluripotency (POU5F1) in Bos indicus embryos produced in vitro or in vivo. Results revealed that methylation of BTS were higher (P < 0.05) in embryos produced in vitro compared with their in vivo produced counterparts, while the methylation status of BTαS was similar in both groups. There were no significant differences in transcript abundance for DNMT3A, IGF2R and POU5F1 between blastocysts produced in vivo and in vitro. However, a significantly lower amount of DNMT1 transcripts was found in the in vitro cultured embryos (P < 0.05) compared with their in vivo derived counterparts. In conclusion, this study reported only minor changes in the expression of developmentally important genes and satellite DNA methylation related to the in vitro embryo production system.

First study on 236U in the Northeast Pacific Ocean using a new target preparation procedure for AMS measurements.

We succeeded in obtaining the depth profile of 236U for a sampling station in the Northeast Pacific Ocean using only one litre of seawater sample from each depth. For this purpose, a new procedure was developed that allowed for the preparation of accelerator mass spectrometry targets for trace uranium using only 100 µg of iron carrier material. The 236U concentrations in water samples from the Northeast Pacific Ocean showed large variations from (9.26 ± 0.42) × 106 atoms/kg at 60 m depth to (0.08 ± 0.02) × 106 atoms/kg at a depth of 3000 m. The high 236U concentrations in surface water reflect the input of 236U by global and local fallout from nuclear weapons tests. The low 236U concentrations in seawater from 1500 m and below are an indicator for the low vertical diffusion of surface water to deeper layers in the North Pacific Ocean. The total inventory of 236U on the water column was (8.35 ± 0.23) × 1012 atoms/m2, which is lower compared to those of other ocean regions solely affected by global fallout on comparable latitudes. This study represents the first dataset for 236U in the Pacific Ocean and shows the possibility of downsizing sample volumes which may help in future applications of 236U as tracer for large ocean areas.

Recent near-Earth supernovae probed by global deposition of interstellar radioactive (60)Fe.

The rate of supernovae in our local Galactic neighbourhood within a distance of about 100 parsecs from Earth is estimated to be one every 2-4 million years, based on the total rate in the Milky Way (2.0 ± 0.7 per century). Recent massive-star and supernova activity in Earth's vicinity may be traced by radionuclides with half-lives of up to 100 million years, if trapped in interstellar dust grains that penetrate the Solar System. One such radionuclide is (60)Fe (with a half-life of 2.6 million years), which is ejected in supernova explosions and winds from massive stars. Here we report that the (60)Fe signal observed previously in deep-sea crusts is global, extended in time and of interstellar origin from multiple events. We analysed deep-sea archives from all major oceans for (60)Fe deposition via the accretion of interstellar dust particles. Our results reveal (60)Fe interstellar influxes onto Earth at 1.5-3.2 million years ago and at 6.5-8.7 million years ago. The signal measured implies that a few per cent of fresh (60)Fe was captured in dust and deposited on Earth. Our findings indicate multiple supernova and massive-star events during the last ten million years at distances of up to 100 parsecs.

[Endoprosthetic tumor replacement : Reconstruction of the extensor mechanism and complications]. / Tumorendoprothetik : Rekonstruktion des Streckapparates und Komplikationen.

BACKGROUND: The reconstruction of the extensor mechanism around the knee is an essential part of tumorresection and tumor arthroplasty in orthopaedic oncology for functional rehabilitation of quality of life and daily activities. OBJECTIVES: Operative procedures, treatment options and management of complications with reconstruction of the extensor mechanism after tumor resection around the knee depend on the type of arthroplasty. MATERIALS AND METHODS: Description of the different treatment option for extensor deficiency divided into infra- and suprapatellar modalities. RESULTS: The operative procedure is always an individual decision depending on the size of the tumor and its localisation. The extensor mechanism is reconstructed with autogenic, allogenic or synthetic material in combination with tumor arthroplasty. CONCLUSIONS: Extensor reconstruction (supra-/infrapatellar) is an essential part of tumor resection and tumor arthroplasty around the knee. Often, low functional results and high levels of complications (arthrofibrosis, rerupture extensor mechanism, periprosthetic joint infection) are seen in these highly demanding cases in orthopaedic oncology.

[Caspase-1 regulates autoinflammation in rheumatic diseases]. / Caspase-1 als Regulator der Autoinflammation bei rheumatischen Erkrankungen.

Caspase-1 is an integral regulator of the innate immune system. Its core functions are the processing and secretion of the proinflammatory cytokines interleukin 1ß (IL-1 beta) and IL-18 and the initiation of proinflammatory cell death, which is referred to as pyroptosis. Activation of caspase-1 plays a pivotal role during immune defense mechanisms against infections by the innate immune system. Dysregulated activation of caspase-1 has been recognized to be involved in the pathophysiology of a constantly increasing number of inflammatory diseases. This article gives an overview of the regulation and function of caspase-1 and its involvement in monogenic, polygenic and/or polyetiological rheumatic diseases.

[Operative therapy for rheumatoid arthritis of the hand]. / Operative Therapie bei rheumatoider Arthritis der Hand.

The need for operative treatment of severe rheumatic deformities of the hand and wrist is decreasing due to the increased use of disease-modifying drugs; however, some patients do not tolerate or do not sufficiently respond to these drugs, which often results in the hands being affected and in advanced stages to severe deformity and loss of function. In these cases operative surgery can help to slow the progression of rheumatic destruction and restore the function of the patient's hand. This article describes the principles of surgery for rheumatoid arthritis of the hand. A meticulous synovectomy or tenosynovectomy is the first stage of treatment. With progression of rheumatic destruction various salvage procedures are necessary to preserve the best possible functional state.

Mouse white adipose tissue-derived mesenchymal stem cells gain pericentral and periportal hepatocyte features after differentiation in vitro, which are preserved in vivo after hepatic transplantation.

AIM: Mesenchymal stem cells may differentiate into hepatocyte-like cells in vitro and in vivo. Therefore, they are considered a novel cell resource for the treatment of various liver diseases. Here, the aim was to demonstrate that mesenchymal stem cells may adopt both perivenous and periportal hepatocyte-specific functions in vitro and in vivo. METHODS: Adipose tissue-derived mesenchymal stem cells were isolated from immunodeficient C57BL/6 (B6.129S6-Rag2(tm1Fwa) Prf1(tm1Clrk) ) mice and differentiated into the hepatocytic phenotype by applying a simple protocol. Their physiological and metabolic functions were analysed in vitro and after hepatic transplantation in vivo. RESULTS: Mesenchymal stem cells changed their morphology from a fibroblastoid into shapes of osteocytes, chondrocytes, adipocytes and hepatocytes. Typical for mesenchymal stem cells, hematopoietic marker genes were not expressed. CD90, which is not expressed on mature hepatocytes, decreased significantly after hepatocytic differentiation. Markers indicative for liver development like hepatic nuclear factor 4 alpha, or for perivenous hepatocyte specification like cytochrome P450 subtype 3a11, and CD26 were significantly elevated. Periportal hepatocyte-specific markers like carbamoylphosphate synthetase 1, the entry enzyme of the urea cycle, were up-regulated. Consequently, cytochrome P450 enzyme activity and urea synthesis increased significantly to values comparable to cultured primary hepatocytes. Both perivenous and periportal qualities were preserved after hepatic transplantation and integration into the host parenchyma. CONCLUSIONS: Adult mesenchymal stem cells from adipose tissue differentiated into hepatocyte-like cells featuring both periportal and perivenous functions. Hence, they are promising candidates for the treatment of region-specific liver cell damage and may support organ regeneration in acute and chronic liver diseases.

Pathogenesis and prevention strategies of heterotopic ossification in total hip arthroplasty: a narrative literature review and results of a survey in Germany.

INTRODUCTION: Heterotopic ossification (HO) after THA can lead to pain, impaired range of motion and possibly revision surgery. This article summarizes current literature on the pathogenesis of HO in THA and trauma. Second, it presents the results of a survey on prophylactic concepts for HO in Germany. MATERIALS AND METHODS: A narrative literature review was conducted by searching three databases (Pubmed, ScienceDirect, the Cochrane library) on the aetiology of HO. Between 2013 and 2014, a questionnaire was sent to 119 orthopaedic and trauma surgery departments in Germany. RESULTS: The acquired form of HO seems to develop after tissue trauma, which induces a local inflammation. A change in tissue conditions, multiple signalling pathways and involvement of several different cell types seem to promote enchondral ossification and finally HO formation. The feed back rate of the survey was 67%. Eighty-seven percent of all departments currently administer NSAIDs with a mean time span of 3 weeks after surgery for oral prophylaxis. Prophylactic perioperative irradiation is performed in 64% of trauma/orthopaedic departments if the patient is at risk for HO with a mean dosage of 7 Gy. CONCLUSIONS: Basic research detected new pathways and cell signalling mechanisms of HO pathogenesis, which could offer new treatment and prophylaxis options in the near future. So far, there is no uniform strategy for the clinical prophylaxis of HO in THA. Guidelines and new clinical trials need to be developed to further reduce HO rates in THA.

Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus.

In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of well-characterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex- and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the highest activity of systemic lupus erythematosus. Our results show that native circulating IgG complexes from active systemic lupus erythematosus patients expose fucosyl residues and their glycan core is accessible to soluble lectins. Two putative mechanisms may contribute to the increased exposure of these glycans: (1) the canonical N-glycosylation site of the IgG-CH2 domain; (2) an IgG binding non-IgG molecule, like complement or C-reactive protein. In both cases the complexed IgG may be alternatively targeted to lectin receptors of effector cells, e.g. dendritic cells.

[Wrist arthroscopy : challenging procedure of modern hand surgery]. / Handgelenksarthroskopie : Herausforderndes Verfahren der modernen Handchirurgie.

Arthroscopy of the wrist has developed in the shadow of arthroscopy of the large joints. Nowadays, wrist arthroscopy has a relevant importance in the diagnostics and therapy in hand surgery and is indispensable for serious surgery of the wrist. Special equipment and extensive knowledge of the surgeon are necessary for carrying out the procedure.

Crucial elements and technical implementation of intelligent monitoring networks.

Growing complexity of water monitoring instrumentation leads to specialized solutions in respect to sensor integration across several measurement device suppliers. Despite efforts of standardization for data interfaces and protocols, problems regarding the combination of several devices to gain the complete picture in terms of water quality remain. This assessment, especially accomplished from the perspective of a catchment area, requires a transition from sole use of data collectors toward an implementation of intelligent measurement networks. Several challenges and bottlenecks concerning distributed data collection are discussed starting with data acquisition up to the user-scope of utilizing data processing software. Finally, experiences using automated data inspection and export tools are discussed and a brief overview of expectable long-term data availability is given.

[Painful total knee arthroplasty. A treatment algorithm]. / Die schmerzhafte Knieprothese. Ein Behandlungsalgorithmus.

BACKGROUND: Persisting and newly occurring complaints after implantation of a total knee endoprosthesis (TKE) are common problems for orthopaedic surgeons in clinics and private practices. The search for the cause and the diagnostics are often difficult due to the many possible influencing factors. Painful TKE requires patience from the orthopaedic surgeon as well as from the patient. THERAPY MODALITIES: The indications for surgical revision should basically be considered with caution and conservative therapeutic procedures can contribute to a considerable improvement in complaints. The treatment algorithm presented in this article helps to adopt a therapeutic direction and if necessary in assessing the indications for revision or replacement surgery. The algorithm offers the possibility of a systematic classification according to clinical, radiological and laboratory testing aspects and assists in the decision for further procedures depending on the four differential diagnoses of limitations in movement, instability, loosening and infection. CONCLUSION: Revision operations should be performed in specialized centers and should be tailored to the individual patient. A comprehensive knowledge of knee joint biomechanics and experience with the large spectrum of modular and axis-linked revision systems are essential for revision surgeons.