This article sheds new light on the development of complementary currencies. Based on a comprehensive survey of the literature, the study questions conventional interpretations of these social ...innovations. The article challenges the view that money is the only feature that complementary currencies have in common. The author argues that in addition to the ways in which connectivity takes place, a characteristic feature of these systems is that they operate within boundaries. Territoriality, limits to convertibility and other features distinguish them from other unofficial currencies such as Bitcoin. Short case studies illustrate that these boundaries are interdependent. This theoretical framework offers a tool for the analysis of complementary currencies and a perspective on the creation of new types of such systems.
Purpose
– The purpose of this paper is to provide an overview of the Tausch- or barter-centers that existed in Germany during the 1940s. These small but unique platforms for the exchange of consumer ...durables represent an almost unknown chapter in economic history. This contribution aims to describe the major characteristics of these organizations and to investigate the implications of these findings for community currencies in general.
Design/methodology/approach
– An analysis is conducted of primary sources, which bring to light different types of these alternative markets. This is complemented by a comprehensive study of secondary sources.
Findings
– Theoretically, these exchange systems are interpreted as operating within boundaries. The results of this research project are not only relevant for our understanding of the war and post-war economy in Germany, at a time when the market mechanism was suppressed, this peculiar case also sheds some light on the functioning of markets. Furthermore, a better knowledge of the structure of the Tausch- or barter-centers is relevant with regard to our understanding of the functioning of community currencies in general.
Originality/value
– This paper provides the first survey of these organizations.
Desminopathies: pathology and mechanisms Clemen, Christoph S.; Herrmann, Harald; Strelkov, Sergei V. ...
Acta neuropathologica,
01/2013, Letnik:
125, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The intermediate filament protein desmin is an essential component of the extra-sarcomeric cytoskeleton in muscle cells. This three-dimensional filamentous framework exerts central roles in the ...structural and functional alignment and anchorage of myofibrils, the positioning of cell organelles and signaling events. Mutations of the human desmin gene on chromosome 2q35 cause autosomal dominant, autosomal recessive, and sporadic myopathies and/or cardiomyopathies with marked phenotypic variability. The disease onset ranges from childhood to late adulthood. The clinical course is progressive and no specific treatment is currently available for this severely disabling disease. The muscle pathology is characterized by desmin-positive protein aggregates and degenerative changes of the myofibrillar apparatus. The molecular pathophysiology of desminopathies is a complex, multilevel issue. In addition to direct effects on the formation and maintenance of the extra-sarcomeric intermediate filament network, mutant desmin affects essential protein interactions, cell signaling cascades, mitochondrial functions, and protein quality control mechanisms. This review summarizes the currently available data on the epidemiology, clinical phenotypes, myopathology, and genetics of desminopathies. In addition, this work provides an overview on the expression, filament formation processes, biomechanical properties, post-translational modifications, interaction partners, subcellular localization, and functions of wild-type and mutant desmin as well as desmin-related cell and animal models.
The Praeorbitolina/Palorbitolinoides Association characterizes a Lower Cretaceous biostratigraphic interval, which is marked by the common occurrence of these two foraminiferal genera. The base of ...this interval is defined by the inception of Palorbitolinoides cf. orbiculata, whereas the top is marked by the disappearance of the genus Praeorbitolina. The Praeorbitolina/Palorbitolinoides Association is evident in the uppermost part of the Lower Aptian of the Apulian and Adriatic Carbonate Platforms, as well as of the eastern Arabian Plate, all located at the southern margin of the Neo-Tethys.
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► Aptian biostratigraphic key – interval. ► Early Cretaceous Orbitolinids of the Apulian Carbonate Platform. ► Early Cretaceous Orbitolinids of the Adriatic Carbonate Platform. ► Early Cretaceous Orbitolinids of the eastern Arabian Plate.
Myofibrillar myopathies (MFMs) are histopathologically characterized by desmin‐positive protein aggregates and myofibrillar degeneration. Because of the marked phenotypic and pathomorphological ...variability, establishing the diagnosis of MFM can be a challenging task. While MFMs are partly caused by mutations in genes encoding for extramyofibrillar proteins (desmin, αB‐crystallin, plectin) or myofibrillar proteins (myotilin, Z‐band alternatively spliced PDZ‐containing protein, filamin C, Bcl‐2‐associated athanogene‐3, four‐and‐a‐half LIM domain 1), a large number of these diseases are caused by still unresolved gene defects. Although recent years have brought new insight into the pathogenesis of MFMs, the precise molecular pathways and sequential steps that lead from an individual gene defect to progressive muscle damage are still unclear. This review focuses on the clinical and myopathological aspects of genetically defined MFMs, and shall provide a diagnostic guide for this numerically significant group of protein aggregate myopathies.
To characterise clinical presentation, laboratory and histopathologic characteristics and assess the treatment and outcome of neuromuscular side-effects of checkpoint therapy.
The side-effect ...registry and the institutional database from ten skin cancer centres were queried for reports on myositis and neuromuscular side-effects induced by checkpoint inhibitors. In total, 38 patients treated with ipilimumab, tremelimumab, nivolumab and pembrolizumab for metastatic skin cancer were evaluated and characterised.
Myositis was the most frequent neuromuscular adverse event. In 32% of cases, myositis was complicated by concomitant myocarditis. Furthermore, cases of isolated myocarditis, myasthenia gravis, polymyalgia rheumatica, radiculoneuropathy and asymptomatic creatine kinase elevation were reported. The onset of side-effects ranged from the first week of treatment to 115 weeks after the start of therapy. Most of the cases were severe (49% grade III–IV Common Terminology Criteria for Adverse Events), and there were two fatalities (5%) due to myositis and myositis with concomitant myocarditis. Only half of the cases (50%) completely resolved, whereas the rest was either ongoing or had sequelae. Steroids were given in 80% of the resolved cases and in 40% of the unresolved cases.
Immune-mediated neuromuscular side-effects of checkpoint inhibitors greatly vary in presentation and differ from their idiopathic counterparts. These side-effects can be life threatening and may result in permanent sequelae. Occurrence of these side-effects must be taken into consideration for patient information, especially when considering adjuvant immunotherapy with anti–programmed cell-death protein 1 (PD-1) antibodies and monitoring, which should include regular surveillance of creatine kinase.
•Neuromuscular side-effects of checkpoint inhibitors are underdetected, which delays proper treatment.•Clinical presentation of immune-related myopathies differs from that of their idiopathic counterparts.•Harmonised approach for detection, diagnostic and treatment is essential.
Idiopathic inflammatory myopathies are a group of rare, immune-mediated diseases that primarily affect the skeletal muscle but can also involve other organs such as the lungs, skin, and joints.1 ...Antisynthetase syndrome comprises a major cluster of such diseases and is characterised by the development of adaptive immune responses against various tRNA synthetases, including those for histidine (forming anti-Jo-1 antibodies), tyrosine (anti-PL7), alanine (anti-PL12), glycine (anti-EJ), isoleucine (anti-OJ), asparagine (anti-KS), phenylalanine (anti-Zo), and threonine (anti-HA).2 Histopathology studies of patients with antisynthetase syndrome have shown the presence of B cells and plasmablasts located adjacent to T cells in the affected muscles,3 and the condition is also associated with changes in the profile of peripheral B cells.3 In accordance with these findings, B-cell-depleting therapy with rituximab was efficacious in a subset of patients with antisynthetase syndrome, supporting the pathogenic role of autoreactive B cells.4 Antisynthetase syndrome can be refractory despite several treatment options—including glucocorticoids, intravenous immunoglobulins, T-cell-targeting drugs, and B-cell-targeting drugs—and is therefore associated with increased mortality.5 Considering the pathophysiology of antisynthetase syndrome, treatment with chimeric antigen receptor (CAR) T cells that recognise CD19⁺ B cells might be useful in refractory forms of the disease. Increased creatinine kinase concentrations and myalgia have been reported as part of cytokine release syndrome.8 After this short worsening, the patient markedly improved in physical function according to all International Myositis Assessment and Clinical Studies Group core set measures (figure F, appendix p 1). Regarding safety, the patient developed a fever (38–39°C, with no effect on blood pressure) 1–3 days after CAR T-cell treatment, which was treated with paracetamol and 3 × 720 mg tocilizumab.
We report our results of 1000 diagnostic WES cases based on 2819 sequenced samples from 54 countries with a wide phenotypic spectrum. Clinical information given by the requesting physicians was ...translated to HPO terms. WES processes were performed according to standardized settings. We identified the underlying pathogenic or likely pathogenic variants in 307 families (30.7%). In further 253 families (25.3%) a variant of unknown significance, possibly explaining the clinical symptoms of the index patient was identified. WES enabled timely diagnosing of genetic diseases, validation of causality of specific genetic disorders of PTPN23, KCTD3, SCN3A, PPOX, FRMPD4, and SCN1B, and setting dual diagnoses by detecting two causative variants in distinct genes in the same patient. We observed a better diagnostic yield in consanguineous families, in severe and in syndromic phenotypes. Our results suggest that WES has a better yield in patients that present with several symptoms, rather than an isolated abnormality. We also validate the clinical benefit of WES as an effective diagnostic tool, particularly in nonspecific or heterogeneous phenotypes. We recommend WES as a first-line diagnostic in all cases without a clear differential diagnosis, to facilitate personal medical care.
Little is known about electrocardiographic (ECG) characteristics of menopausal women with or at increased risk of coronary heart disease (CHD). Data from 10,101 participants in the Raloxifene Use for ...The Heart (RUTH) trial were used to correlate baseline ECG abnormalities with clinical characteristics. Baseline characteristics that were statistically significantly associated (p ≤0.05) with ECG findings in univariate analyses were used to derive multivariate model selection. Of 59% normal electrocardiograms, 50% were from women with CHD and 69% from women at increased risk of CHD. In the women with CHD, 59% reported a previous myocardial infarction (MI); 43% had a normal electrocardiogram, and 49% had a definite ECG Q-wave MI. Women in the increased-risk group had not reported a previous MI, yet 11% had a definite ECG Q-wave MI. Of women reporting hypertension, 35% had ECG evidence of left ventricular hypertrophy, but 58% did not have an abnormal electrocardiogram. Significantly more women with diabetes in the increased-risk and documented CHD cohorts had abnormal electrocardiograms (p <0.01 for the 2 cohorts). Percent abnormal electrocardiograms increased with increasing age (55 to 64, 65 to 74, and ≥75 years, p <0.01) in all cohorts. Angina and coronary artery bypass graft surgery, but not percutaneous coronary intervention, predicted an abnormal electrocardiogram. In conclusion, there were high percentages of normal electrocardiograms in the increased-risk and documented CHD groups of RUTH participants, with substantial discrepancy between MI history and ECG MI documentation, and increasing age was the predominant correlate with an abnormal electrocardiogram in all 3 cohorts.
New aspects of myofibrillar myopathies Kley, Rudolf A; Olivé, Montse; Schröder, Rolf
Current opinion in neurology,
10/2016, Letnik:
29, Številka:
5
Journal Article
Recenzirano
Myofibrillar myopathies (MFMs) are hereditary muscle disorders characterized by distinct histopathological features. This review provides an overview of recent research with respect to new disease ...genes, clinical phenotypes, insights into pathomechanisms and therapeutic strategies.
Beyond the known disease genes DES, FLNC, MYOT, CRYAB, ZASP, BAG3, FHL1 and TTN, mutations in PLEC, ACTA1, HSPB8 and DNAJB6 have also been associated with a MFM phenotype. Proteomic analysis revealed new information about the composition of protein aggregates in myotilinopathy and identified a new diagnostic marker. New animal models mirror central aspects of MFM pathology and novel therapeutic strategies for treatment of MFM were evaluated in cell and animal models.
MFMs are an expanding and numerically significant group of protein aggregate diseases with marked clinical and genetic heterogeneity. Though no specific therapy is currently available, the generation of patient-mimicking cell and animal models now paves the way for the preclinical evaluation of novel therapeutic strategies.
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