Generalized, predominantly proximal weakness and a greatly elevated creatine kinase level developed in a man with Covid-19. Immunohistochemical analysis of a muscle-biopsy specimen revealed abnormal ...expression of MHC-1 and myxovirus resistance protein A on muscle fibers, suggesting type I interferonopathy.
Coffee consumption is associated with reduced risk of conditions that share low-grade inflammation as their physiopathological basis. We therefore summarized the effects of coffee or coffee ...components on serum levels of inflammatory markers. Clinical trials assessing the effect of coffee, caffeine or other coffee components on inflammatory markers were searched without restriction to publication date. Fifteen studies (8 involving coffee and 7 caffeine) were included. Increased adiponectin levels were found in four of seven trials comparing filtered coffee/caffeinated coffee with placebo or comparing its levels at baseline and after consumption of medium or dark roasted coffee, but no change was seen in caffeine trials. None of the five studies assessing the effects of coffee found changes in C-reactive protein (CPR), but one out of three trials found decreased CPR levels in response to caffeine. Interleukin (IL)-6 was increased by caffeinated coffee compared with placebo in one of four coffee trials, and by caffeine in three out of five studies. Caffeine increased IL-10 levels in two of three trials. These data suggest a predominant anti-inflammatory action of coffee but not of caffeine consumption. Moreover, the proinflammatory and anti-inflammatory responses to caffeine point to its complex effects on the inflammatory response.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Inclusion body myositis (IBM) is the most common idiopathic inflammatory myopathy occurring in patients over the age of 50 years and probably accounts for about 30% of all inflammatory myopathies. ...Muscle biopsy characteristically reveals endomysial inflammation, small groups of atrophic fibres, eosinophilic cytoplasmic inclusions and muscle fibres with one or more rimmed vacuoles. However, any given biopsy may lack these histopathological abnormalities; the clinical examination is often the key to diagnosis. Early and often asymmetrical weakness and atrophy of the quadriceps and flexor forearm muscles (ie, wrist and finger flexors) are the clinical hallmarks of IBM. The pathogenesis of IBM is unknown. It may be autoimmune inflammatory myopathy or a primary degenerative myopathy with a secondary inflammatory. A prevailing theory is that there is an overproduction of beta-amyloid precursor protein in muscle fibres that is somehow cleaved into abnormal beta-amyloid, and the accumulation of the latter is somehow toxic to muscle fibres. However, there are many problems with this theory and more work needs to be done. Unfortunately, IBM is generally refractory to therapy. Further research into the pathogenesis, along with both preliminary small pilot trials and larger double blind, placebo controlled efficacy trials, are needed to make progress in our understanding and therapeutic approach for this disorder.
The major types of idiopathic inflammatory myopathy include dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and immune mediated necrotising myopathy (NM). These myositides ...appear clinically, histologically and pathogenically distinct. DM, PM and immune mediated NM are responsive to immunosuppressive therapy, in contrast with IBM which is generally refractory to therapy. Greater understanding of the pathogenic bases of these disorders should hopefully lead to better treatment. We need well designed, prospective, double blind, placebo controlled trials in order to determine the best therapeutic options for these different disorders.
Magnetic topological phases of quantum matter are an emerging frontier in physics and material science. Along these lines, several kagome magnets have appeared as the most promising platforms. Here, ...we explore magnetic correlations in the kagome magnet Co
Sn
S
. Using muon spin-rotation, we present evidence for competing magnetic orders in the kagome lattice of this compound. Our results show that while the sample exhibits an out-of-plane ferromagnetic ground state, an in-plane antiferromagnetic state appears at temperatures above 90 K, eventually attaining a volume fraction of 80% around 170 K, before reaching a non-magnetic state. Strikingly, the reduction of the anomalous Hall conductivity (AHC) above 90 K linearly follows the disappearance of the volume fraction of the ferromagnetic state. We further show that the competition of these magnetic phases is tunable through applying either an external magnetic field or hydrostatic pressure. Our results taken together suggest the thermal and quantum tuning of Berry curvature induced AHC via external tuning of magnetic order.
The criticality of raw materials has become an important issue in recent years. As the supply of certain raw materials is essential for technologically-advanced economies, the European Commission and ...other international counterparts have started several initiatives to secure reliable and unhindered access to raw materials. Such efforts include the EU Raw Materials Initiative, European Innovation Partnership on Raw Materials, US Critical Materials Institute, and others. In this paper, the authors present a multi-faceted and multi-national review of the essentials for the critical raw materials (CRMs) Co, Nb, W, and rare earth elements (REEs). The selected CRMs are of specific interest as they are considered relevant for emerging technologies and will thus continue to be of increasing major economic importance. This paper presents a 'sustainability evaluation' for each element, including essential data about markets, applications and recycling, and possibilities for substitution have been summarized and analysed. All the presented elements are vital for the advanced materials and processes upon which modern societies rely. These elements exhibit superior importance in 'green' applications and products subject to severe conditions. The annual production quantities are quite low compared to common industrial metals. Of the considered CRMs, only Co and REE gross production exceed 100 000 t. At the same time, the prices are quite high, with W and Nb being in the range of 60 USD kg−1 and some rare earth compounds costing almost 4000 USD kg−1. Despite valiant effort, in practice some of the considered elements are de facto irreplaceable for many specialized applications, at today's technological level. Often, substitution causes a significant loss of quality and performance. Furthermore, possible candidates for substitution may be critical themselves or available in considerably low quantities. It can be concluded that one preferred approach for the investigated elements could be the use of secondary resources derived from recycling. W exhibits the highest recycling rate (37%), whereas Co (16%), Nb (11%) and rare earths (~0%) lag behind. In order to promote recycling of these essential elements, financial incentives as well as an improvement of recycling technologies would be required.
Abstract
Unconventional superconductors often feature competing orders, small superfluid density, and nodal electronic pairing. While unusual superconductivity has been proposed in the kagome metals
...A
V
3
Sb
5
, key spectroscopic evidence has remained elusive. Here we utilize pressure-tuned and ultra-low temperature muon spin spectroscopy to uncover the unconventional nature of superconductivity in RbV
3
Sb
5
and KV
3
Sb
5
. At ambient pressure, we observed time-reversal symmetry breaking charge order below
$${T}_{{{\rm{1}}}^{*}\simeq$$
T
1
*
≃
110 K in RbV
3
Sb
5
with an additional transition at
$${T}_{{{\rm{2}}}^{*}\simeq$$
T
2
*
≃
50 K. Remarkably, the superconducting state displays a nodal energy gap and a reduced superfluid density, which can be attributed to the competition with the charge order. Upon applying pressure, the charge-order transitions are suppressed, the superfluid density increases, and the superconducting state progressively evolves from nodal to nodeless. Once optimal superconductivity is achieved, we find a superconducting pairing state that is not only fully gapped, but also spontaneously breaks time-reversal symmetry. Our results point to unprecedented tunable nodal kagome superconductivity competing with time-reversal symmetry-breaking charge order and offer unique insights into the nature of the pairing state.
Abstract
In its orthorhombic
T
d
polymorph, MoTe
2
is a type-II Weyl semimetal, where the Weyl fermions emerge at the boundary between electron and hole pockets. Non-saturating magnetoresistance and ...superconductivity were also observed in
T
d
-MoTe
2
. Understanding the superconductivity in
T
d
-MoTe
2
, which was proposed to be topologically non-trivial, is of eminent interest. Here, we report high-pressure muon-spin rotation experiments probing the temperature-dependent magnetic penetration depth in
T
d
-MoTe
2
. A substantial increase of the superfluid density and a linear scaling with the superconducting critical temperature
T
c
is observed under pressure. Moreover, the superconducting order parameter in
T
d
-MoTe
2
is determined to have 2-gap
s
-wave symmetry. We also exclude time-reversal symmetry breaking in the superconducting state with zero-field μSR experiments. Considering the strong suppression of
T
c
in MoTe
2
by disorder, we suggest that topologically non-trivial
s
+−
state is more likely to be realized in MoTe
2
than the topologically trivial
s
++
state.
The non-dystrophic myotonias are an important group of skeletal muscle channelopathies electrophysiologically characterized by altered membrane excitability. Many distinct clinical phenotypes are now ...recognized and range in severity from severe neonatal myotonia with respiratory compromise through to milder late-onset myotonic muscle stiffness. Specific genetic mutations in the major skeletal muscle voltage gated chloride channel gene and in the voltage gated sodium channel gene are causative in most patients. Recent work has allowed more precise correlations between the genotype and the electrophysiological and clinical phenotype. The majority of patients with myotonia have either a primary or secondary loss of membrane chloride conductance predicted to result in reduction of the resting membrane potential. Causative mutations in the sodium channel gene result in an abnormal gain of sodium channel function that may show marked temperature dependence. Despite significant advances in the clinical, genetic and molecular pathophysiological understanding of these disorders, which we review here, there are important unresolved issues we address: (i) recent work suggests that specialized clinical neurophysiology can identify channel specific patterns and aid genetic diagnosis in many cases however, it is not yet clear if such techniques can be refined to predict the causative gene in all cases or even predict the precise genotype; (ii) although clinical experience indicates these patients can have significant progressive morbidity, the detailed natural history and determinants of morbidity have not been specifically studied in a prospective fashion; (iii) some patients develop myopathy, but its frequency, severity and possible response to treatment remains undetermined, furthermore, the pathophysiogical link between ion channel dysfunction and muscle degeneration is unknown; (iv) there is currently insufficient clinical trial evidence to recommend a standard treatment. Limited data suggest that sodium channel blocking agents have some efficacy. However, establishing the effectiveness of a therapy requires completion of multi-centre randomized controlled trials employing accurate outcome measures including reliable quantitation of myotonia. More specific pharmacological approaches are required and could include those which might preferentially reduce persistent muscle sodium currents or enhance the conductance of mutant chloride channels. Alternative strategies may be directed at preventing premature mutant channel degradation or correcting the mis-targeting of the mutant channels.
The major forms of autoimmune myopathies include dermatomyositis (DM), polymyositis (PM), myositis associated with antisynthetase syndrome (ASS), immune-mediated necrotizing myopathy (IMNM), and ...inclusion body myositis (IBM). While each of these conditions has unique clinical and histopathological features, they all share an immune-mediated component. These conditions can occur in isolation or can be associated with systemic malignancies or connective tissue disorders (overlap syndromes). As more has been learned about these conditions, it has become clear that traditional classification schemes do not adequately group patients according to shared clinical features and prognosis. Newer classifications are now utilizing myositis-specific autoantibodies which correlate with clinical and histopathological phenotypes and risk of malignancy, and help in offering prognostic information with regard to treatment response. Based on observational data and expert opinion, corticosteroids are considered first-line therapy for DM, PM, ASS, and IMNM, although intravenous immunoglobulin (IVIG) is increasingly being used as initial therapy in IMNM related to statin use. Second-line agents are often required, but further prospective investigation is required regarding the optimal choice and timing of these agents.
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