Treatment of inclusion body myositis: is low-dose intravenous immunoglobulin the solution?

Inclusion body myositis (IBM), the most common inflammatory myopathy in the elderly, is often resistant to various forms of therapy. Placebo-controlled treatment trials with high dose intravenous immunoglobulins (IVIG) have shown disease amelioration in some but not all patients. Here, we present the informative case of a 70-year-old woman with diagnosed inclusion body myositis that showed progressive muscle weakness without treatment and following immuno-suppressive treatment with corticosteroids and azathioprine. A trial with low-dose intravenous immunoglobulins was started at that time. The patient responded rapidly to low dose IVIG treatment with amelioration of muscle strength and normalization of CK serum activities. Our results demonstrate that IBM patients may respond to low-dose IVIG treatment which has important clinical and economic consequence

Quality of Postoperative Pain Management After Maxillofacial Fracture Repair

Background: Effective pain management is an essential component in the perioperative care of surgical patients. However, post-operative pain after maxillofacial fracture repair and its optimal therapy has not been described in detail. Materials and Methods: In a prospective cohort study, 95 adults rated their pain on the first postoperative day after maxillofacial fracture repair using the questionnaire of the Quality Improvement in Postoperative Pain Management (QUIPS) project. Quality Improvement in Postoperative Pain Management allowed for a standardized assessment of patients’ characteristics and pain- related parameters. Results: Overall, the mean maximal pain and pain on activity (numeric rating scales) were significantly higher in patients with mandibular fractures than in patients with midface fractures (P = 0.002 and P = 0.045, respectively). In patients with mandibular fractures, a longer duration of surgery was significantly associated with higher satisfaction with pain intensity (P = 0.015), but was more frequently associated with postoperative vomiting (P = 0.023). A shorter duration of surgery and an absence of preoperative pain counseling in these patients were significantly correlated to desire for more pain medication (P = 0.049 and P = 0.004, respectively). Patients with mandibular fractures that received opioids in the recovery room had significantly higher strain-related pain (P = 0.017). In patients with midface fractures, a longer duration of surgery showed significantly higher levels of decreased mobility (P = 0.003). Patients receiving midazolam for premedication had significantly less minimal pain (P = 0.021). Conclusions: Patients with mandibular fractures seem to have more postoperative pain than patients with midface fractures. Monitoring of postsurgical pain and a procedure-specific pain-treatment protocol should be performed in clinical routine

Feeling Political

Historicizing both emotions and politics, this open access book argues that the historical work of emotion is most clearly understood in terms of the dynamics of institutionalization. This is shown in twelve case studies that focus on decisive moments in European and US history from 1800 until today. Each case study clarifies how emotions were central to people’s political engagement and its effects. The sources range from parliamentary buildings and social movements, to images and speeches of presidents, from fascist cemeteries to the International Criminal Court. Both the timeframe and the geographical focus have been chosen to highlight the increasingly participatory character of nineteenth- and twentieth-century politics, which is inconceivable without the work of emotions

Serological responses to koi herpesvirus (KHV) in a non-cyprinid reservoir host

Koi herpesvirus (KHV) is a highly contagious virus that causes KHV disease (KHVD) inducing high mortality in carp and koi (Cyprinus carpio L.). In the late stage, latency occurs with very low, often non-detectable virus concentrations, which represents a challenge for virus detection. After validation according to OIE recommendations, an antibody ELISA was established to recognize antibodies of C. carpio against KHV infection. In this study, the ELISA was modified to detect anti-KHV antibodies from a non-cyprinid fish. Experimentally infected rainbow trout (Oncorhynchus mykiss) were able to transmit KHV to naïve carp at two different temperatures, demonstrating their potential as a reservoir host. At 20°C, KHVD was induced in carp but not at 15°C. Unexpectedly, rainbow trout developed humoral response against KHV at both temperatures. In contrast to carp, at 15°C trout produced neutralizing antibodies but not at 20°C. While antibodies obtained from infected carp sera reacted in a similar way against all KHV, antibodies from rainbow trout sera reacted differently to the same isolates by ELISA. The data show that even when non-cyprinid fish species are infected with KHV, they can produce antibodies that differ from those observed in carp

Tight correlation between expression of the Forkhead transcription factor FOXM1 and HER2 in human breast cancer

BACKGROUND: FOXM1 regulates expression of cell cycle related genes that are essential for progression into DNA replication and mitosis. Consistent with its role in proliferation, elevated expression of FOXM1 has been reported in a variety of human tumour entities. FOXM1 is a gene of interest because recently chemical inhibitors of FOXM1 were described to limit proliferation and induce apoptosis in cancer cells in vitro, indicating that FOXM1 inhibitors could represent useful anticancer therapeutics. METHODS: Using immunohistochemistry (IHC) we systematically analysed FOXM1 expression in human invasive breast carcinomas (n = 204) and normal breast tissues (n = 46) on a tissue microarray. Additionally, using semiquantitative realtime PCR, a collection of paraffin embedded normal (n = 12) and cancerous (n = 25) breast tissue specimens as well as benign (n = 3) and malignant mammary cell lines (n = 8) were investigated for FOXM1 expression. SPSS version 14.0 was used for statistical analysis. RESULTS: FOXM1 was found to be overexpressed in breast cancer in comparison to normal breast tissue both on the RNA and protein level (e.g. 8.7 fold as measured by realtime PCR). We found a significant correlation between FOXM1 expression and the HER2 status determined by HER2 immunohistochemistry (P < 0.05). Univariate survival analysis showed a tendency between FOXM1 protein expression and unfavourable prognosis (P = 0.110). CONCLUSION: FOXM1 may represent a novel breast tumour marker with prognostic significance that could be included into multi-marker panels for breast cancer. Interestingly, we found a positive correlation between FOXM1 expression and HER2 status, pointing to a potential role of FOXM1 as a new drug target in HER2 resistant breast tumour, as FOXM1 inhibitors for cancer treatment were described recently. Further studies are underway to analyse the potential interaction between FOXM1 and HER2, especially whether FOXM1 directly activates the HER2 promoter

Berufliche Stabilitäts- und Flexibilitätsorientierungen in Ostdeutschland: Ergebnisse eines Forschungspraktikums

Das im folgenden vorgestellte Projekt Stabilitäts- und Flexibilitätsorientierungen in ostdeutschen Lebensverläufen wurde am Institut für Soziologie der Universität Leipzig im Rahmen eines Lehrpraktikums durchgeführt. In dem Projekt wurden berufliche Stabilitäts- und Flexibilitätsorientierungen ostdeutscher Beschäftigter vor dem Hintergrund individueller Ressourcen und Gelegenheitsstrukturen untersucht. Anhand von 68 biographischen Interviews älterer und jüngerer Kohorten sollte gezeigt werden, in welchem Maße individuelle Merkmale sowie familiäre, arbeitsmarktliche, sozialpolitische und betriebliche Gelegenheitsstrukturen die individuellen Handlungsorientierungen beeinflussen. Vor dem Hintergrund der \"Entstandardisierung\" von Lebenslaufmustern und der \"Flexibilisierung\" von Erwerbsverläufen wurde dabei nach den Ursachen und Veränderungen kohortenspezifischer Unterscheidungen berufsbiographischer Entwürfe gefragt.:Vorbemerkung; Stabilität und Flexibilität im Lebensverlauf; Analytisches Modell und methodisches Vorgehen; Ergebnisse; Bewältigungsstrategien – Eine Zusammenfassung; Literatur, Anhan

LIPAD (LRRK2/Luebeck International Parkinson's Disease) Study Protocol:Deep Phenotyping of an International Genetic Cohort

Background: Pathogenic variants in the Leucine-rich repeat kinase 2 (LRRK2) gene are the most common known monogenic cause of Parkinson's disease (PD). LRRK2-linked PD is clinically indistinguishable from idiopathic PD and inherited in an autosomal dominant fashion with reduced penetrance and variable expressivity that differ across ethnicities and geographic regions.Objective: To systematically assess clinical signs and symptoms including non-motor features, comorbidities, medication and environmental factors in PD patients, unaffected LRRK2 pathogenic variant carriers, and controls. A further focus is to enable the investigation of modifiers of penetrance and expressivity of LRRK2 pathogenic variants using genetic and environmental data.Methods: Eligible participants are invited for a personal or online examination which comprises completion of a detailed eCRF and collection of blood samples (to obtain DNA, RNA, serum/plasma, immune cells), urine as well as household dust. We plan to enroll 1,000 participants internationally: 300 with LRRK2-linked PD, 200 with LRRK2 pathogenic variants but without PD, 100 PD patients with pathogenic variants in the GBA or PRKN genes, 200 patients with idiopathic PD, and 200 healthy persons without pathogenic variants.Results: The eCRF consists of an investigator-rated (1 h) and a self-rated (1.5 h) part. The first part includes the Movement Disorder Society Unified Parkinson's Disease Rating, Hoehn &amp;Yahr, and Schwab &amp; England Scales, the Brief Smell Identification Test, and Montreal Cognitive Assessment. The self-rating part consists of a PD risk factor, food frequency, autonomic dysfunction, and quality of life questionnaires, the Pittsburgh Sleep Quality Inventory, and the Epworth Sleepiness as well as the Hospital Anxiety and Depression Scales. The first 15 centers have been initiated and the first 150 participants enrolled (as of March 25th, 2021).Conclusions: LIPAD is a large-scale international scientific effort focusing on deep phenotyping of LRRK2-linked PD and healthy pathogenic variant carriers, including the comparison with additional relatively frequent genetic forms of PD, with a future perspective to identify genetic and environmental modifiers of penetrance and expressivityClinical Trial Registration:ClinicalTrials.gov, NCT04214509

Hsp40 Couples with the CSPα Chaperone Complex upon Induction of the Heat Shock Response

In response to a conditioning stress, the expression of a set of molecular chaperones called heat shock proteins is increased. In neurons, stress-induced and constitutively expressed molecular chaperones protect against damage induced by ischemia and neurodegenerative diseases, however the molecular basis of this protection is not known. Here we have investigated the crosstalk between stress-induced chaperones and cysteine string protein (CSPα). CSPα is a constitutively expressed synaptic vesicle protein bearing a J domain and a cysteine rich “string” region that has been implicated in the long term functional integrity of synaptic transmission and the defense against neurodegeneration. We have shown previously that the CSPα chaperone complex increases isoproterenol-mediated signaling by stimulating GDP/GTP exchange of Gαs. In this report we demonstrate that in response to heat shock or treatment with the Hsp90 inhibitor geldanamycin, the J protein Hsp40 becomes a major component of the CSPα complex. Association of Hsp40 with CSPα decreases CSPα-CSPα dimerization and enhances the CSPα-induced increase in steady state GTP hydrolysis of Gαs. This newly identified CSPα-Hsp40 association reveals a previously undescribed coupling of J proteins. In view of the crucial importance of stress-induced chaperones in the protection against cell death, our data attribute a role for Hsp40 crosstalk with CSPα in neuroprotection

Neuroendocrine carcinoma of the breast, a rare entity - differentiation between primary lesion and metastasis, a diagnostic pitfall

Eine Differenzierung zwischen Primarius oder Metastase einer neuroendokrinen Läsion der Mamma ist anhand von herkömmlichen klinischen, radiologischen oder histopathologischen Aspekten nicht möglich und bedarf einer weiterführenden immunhistochemischen Nachweismethodik unter Einbeziehung spezifischer Marker. Mit positivem Nachweis von GCDFP-15 und/oder Mammaglobin ist die eindeutige Zuordnung zur primären Läsion in der Brust möglich. In Folge dessen sollte dieser spezifische Markernachweis in der Diagnostik des neuroendokrinen Karzinoms der Mamma aufgenommen werden und ermöglicht so ein tumorspezifisches therapeutisches Management.A differentiation between the primarius and the metastasis of a neuroendocrine lesion in the breast is not workable based on conventional clinical, radiological and histopathological facts. Therefore it needs supplementary specific immunhistochemical methods. With a positive result for GCDFP-15 and/or mammaglobin is it possible to assign the tumor to a primary origin of the breast. Therefore these specific markers should be proofed in the conventional immunhistochemical setting. Afterwards it is possible to differentiate these two types of neuroendocrine malignancy in the breast and to decide which therapeutic regime is necessary