224 research outputs found
Surgical Management of Cervical Spondyloarthropathy in Hemodialysis Patients
Dialysis-related spondyloarthropathy is a rare cause of spinal deformity and cervical myelopathy. Optimal management of cervical spine spondyloarthropathy often requires circumferential reconstructive surgery, because affected patients typically have both the anterior column and the facet joints compromised. The occasional presence of noncontiguous or "skip lesions" adds an additional level of complexity to surgical management, because decompression and fusion in an isolated segment of neural compression can worsen spine deformity by applying increased stress to adjacent cervical spine segments. We report two cases of hemodialysis patients who presented with cervical myelopathy and initially had anterior cervical discectomy or corpectomy. Because symptoms recurred due to hardware failure, both patients required posterior spine fusion as well. In retrospect, because of the hardware failure, both of these patients might have benefited from a circumferential (combined anterior and posterior) cervical spine reconstruction as their initial treatment
The Dynamics of Ca2+ Ions within the Solvation Shell of Calbindin D9k
The encounter of a Ca2+ ion with a protein and its subsequent
binding to specific binding sites is an intricate process that cannot be fully
elucidated from experimental observations. We have applied Molecular Dynamics to
study this process with atomistic details, using Calbindin D9k (CaB) as a model
protein. The simulations show that in most of the time the Ca2+
ion spends within the Debye radius of CaB, it is being detained at the 1st and
2nd solvation shells. While being detained near the protein, the diffusion
coefficient of the ion is significantly reduced. However, due to the relatively
long period of detainment, the ion can scan an appreciable surface of the
protein. The enhanced propagation of the ion on the surface has a functional
role: significantly increasing the ability of the ion to scan the protein's
surface before being dispersed to the bulk. The contribution of this mechanism
to Ca2+ binding becomes significant at low ion concentrations,
where the intervals between successive encounters with the protein are getting
longer. The efficiency of the surface diffusion is affected by the distribution
of charges on the protein's surface. Comparison of the Ca2+
binding dynamics in CaB and its E60D mutant reveals that in the wild type (WT)
protein the carboxylate of E60 function as a preferred landing-site for the
Ca2+ arriving from the bulk, followed by delivering it to
the final binding site. Replacement of the glutamate by aspartate significantly
reduced the ability to transfer Ca2+ ions from D60 to the final
binding site, explaining the observed decrement in the affinity of the mutated
protein to Ca2+
Effects of season and reproductive state on lipid intake and fatty acid composition of gastrointestinal tract contents in the European hare
We investigated lipid content and fatty acid (FA) composition of gastrointestinal tract contents in free-living, herbivorous European hares (Lepus europaeus). Mean crude fat content in hare stomachs and total gastrointestinal (GI) tracts was higher than expected for typical herbivore forages and peaked in late fall when hares massively deposited body fat reserves. Changes of FA proportions in different parts of the GI-tract indicated a highly preferential absorption of polyunsaturated fatty acids (PUFA). A further reduction of PUFA content in the caecum, along with the appearance of odd-chained FAs in caecum, caecotrophes, and colon content, pointed to a biohydrogenation of PUFA in the hare’s hindgut. GI-tract contents showed significant seasonal changes in their FA composition. Among PUFA, α-linolenic acid peaked in spring while linoleic acid was predominant in late summer and fall, which probably reflected changes in the plant composition of forage. However, independent of seasonal changes, GI-tracts of lactating females showed a significantly (+33%) higher content of linoleic acid, a FA that is known to increase reproductive performance in European hares. This finding suggests that lactating females actively selected dietary plants rich in linoleic acid, a PUFA that may represent a limited resource for European hares
Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores
The myosin-directed chaperone UNC-45B is essential for sarcomeric organization and muscle function from Caenorhabditis elegans to humans. The pathological impact of UNC-45B in muscle disease remained elusive. We report ten individuals with bi-allelic variants in UNC45B who exhibit childhood-onset progressive muscle weakness. We identified a common UNC45B variant that acts as a complex hypomorph splice variant. Purified UNC-45B mutants showed changes in folding and solubility. In situ localization studies further demonstrated reduced expression of mutant UNC-45B in muscle combined with abnormal localization away from the A-band towards the Z-disk of the sarcomere. The physiological relevance of these observations was investigated in C. elegans by transgenic expression of conserved UNC-45 missense variants, which showed impaired myosin binding for one and defective muscle function for three. Together, our results demonstrate that UNC-45B impairment manifests as a chaperonopathy with progressive muscle pathology, which discovers the previously unknown conserved role of UNC-45B in myofibrillar organization
A Schistosome cAMP-Dependent Protein Kinase Catalytic Subunit Is Essential for Parasite Viability
Eukaryotes, protozoan, and helminth parasites make extensive use of protein kinases to control cellular functions, suggesting that protein kinases may represent novel targets for the development of anti-parasitic drugs. Because of their central role in intracellular signaling pathways, cyclic nucleotide–dependent kinases such as cAMP-dependent protein kinase (PKA) represent promising new targets for the treatment of parasitic infections and neoplastic disorders. However, the role of these kinases in schistosome biology has not been characterized and the genes encoding schistosome PKAs have not been identified. Here we provide biochemical evidence for the presence of a PKA signaling pathway in adult Schistosoma mansoni and show that PKA activity is required for parasite viability in vitro. We also provide the first full description of a gene that encodes a PKA catalytic subunit in S. mansoni, named SmPKA-C. Finally we demonstrate, through RNA interference, that SmPKA-C contributes to the PKA activity we detected biochemically and that inhibition of SmPKA-C expression in adult schistosomes results in parasite death. Together our data show that SmPKA-C is a critically important gene product and may represent an attractive therapeutic target for the treatment and control of schistosomiasis
Cost-effectiveness and budget impact analyses of a colorectal cancer screening programme in a high adenoma prevalence scenario using MISCAN-Colon microsimulation model
This economic evaluation showed a screening intervention with a major health gain that also produced net savings when a long follow-up was used to capture the late economic benefit. The number of colonoscopies required was high but remain within the capacity of the Basque Health Service. So far in Europe, no other population Colorectal Cancer screening programme has been evaluated by budget impact analysis
Crackling Noise
Crackling noise arises when a system responds to changing external conditions
through discrete, impulsive events spanning a broad range of sizes. A wide
variety of physical systems exhibiting crackling noise have been studied, from
earthquakes on faults to paper crumpling. Because these systems exhibit regular
behavior over many decades of sizes, their behavior is likely independent of
microscopic and macroscopic details, and progress can be made by the use of
very simple models. The fact that simple models and real systems can share the
same behavior on a wide range of scales is called universality. We illustrate
these ideas using results for our model of crackling noise in magnets,
explaining the use of the renormalization group and scaling collapses. This
field is still developing: we describe a number of continuing challenges
T2-weighted cardiovascular magnetic resonance in acute cardiac disease
Cardiovascular magnetic resonance (CMR) using T2-weighted sequences can visualize myocardial edema. When compared to previous protocols, newer pulse sequences with substantially improved image quality have increased its clinical utility. The assessment of myocardial edema provides useful incremental diagnostic and prognostic information in a variety of clinical settings associated with acute myocardial injury. In patients with acute chest pain, T2-weighted CMR is able to identify acute or recent myocardial ischemic injury and has been employed to distinguish acute coronary syndrome (ACS) from non-ACS as well as acute from chronic myocardial infarction
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