Chronic total hip arthroplasty instability—Causes and cures

Chronic instability following total hip arthroplasty (THA) is a complex problem and is the most common reason for revision THA. Understanding the etiology of instability is paramount to choosing the appropriate treatment. In general, component malposition should always be addressed. Abductor deficiency, being seen more often with metal on metal THA failures, is a difficult problem to address that typically requires the use of a constrained liner. The use of dual mobility articulations have recently become popular and have demonstrated good early results for preventing re-revision in patients at high risk for instability.     

Age and gender-dependent alternative splicing of P/Q-type calcium channel EF-hand

Ca(v)2.1 Ca(2+) channels (P/Q-type), which participate in various key roles in the CNS by mediating calcium influx, are extensively spliced. One of its alternatively-spliced exons is 37, which forms part of the EF hand. The expression of exon 37a (EFa form), but not exon 37b (EFb form), confers the channel an activity-dependent enhancement of channel opening known as Ca(2+)-dependent facilitation (CDF). In this study, we analyzed the trend of EF hand splice variant distributions in mouse, rat and human brain tissues. We observed a developmental switch in rodents, as well as an age and gender bias in human brain tissues, suggestive of a possible role of these EF hand splice variants in neurophysiological specialization. A parallel study performed on rodent brains showed that the data drawn from human and rodent tissues may not necessarily correlate in the process of aging.     

Can botulinum toxin put the restless legs syndrome to rest?

The restless legs syndrome (RLS), affecting between 3% and 15% of the population, is characterised by an urge to move the legs during wakefulness, associated with a range of unpleasant sensory symptoms, especially when sitting or lying down at night. The symptoms can even be painful, and lead to sleep disturbances and depression. RLS is treated with dopaminergic agents, anticonvulsants, opioids, clonidine and benzodiazepines. In a small percentage of cases, RLS is refractory to treatment, requiring combination therapy. Botulinum toxin (BTX), derived from the exotoxin of Clostridium botulinum, cleaves soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, causing chemodenervation of cholinergic neurons. BTX has been demonstrated to ameliorate pain syndromes, possibly by reducing peripheral and central sensitization to pain. We postulate that BTX can be injected subcutaneously to the lower limbs to effect amelioration of the symptoms of RLS.     

Computer prediction of allergen proteins from sequence-derived protein structural and physicochemical properties

BACKGROUND: Computational methods have been developed for predicting allergen proteins from sequence segments that show identity, homology, or motif match to a known allergen. These methods achieve good prediction accuracies, but are less effective for novel proteins with no similarity to any known allergen. METHODS: This work tests the feasibility of using a statistical learning method, support vector machines, as such a method. The prediction system is trained and tested by using 1005 allergen proteins from the Allergome database and 22,469 non-allergen proteins from 7871 Pfam families. RESULTS: Testing results by an independent set of 229 allergen and 6717 non-allergen proteins from 7871 Pfam families show that 93.0% and 99.9% of these are correctly predicted, which are comparable to the best results of other methods. Of the 18 novel allergen proteins non-homologous to any other proteins in the Swissprot database, 88.9% is correctly predicted. A further screening of 168,128 proteins in the Swissprot database finds that 2.9% of the proteins are predicted as allergen proteins, which is consistent with the estimated numbers from motif-based methods. CONCLUSIONS: Our study suggests that SVM is a potentially useful method for predicting allergen proteins and it has certain capability for predicting novel allergen proteins. Our software can be accessed at .     

Identification of neutralizing linear epitopes from the VP1 capsid protein of Enterovirus 71 using synthetic peptides

Enterovirus 71 (EV71) is the main causative agent of Hand, foot and mouth disease (HFMD) and has been associated with severe neurological diseases resulting in high mortalities. Currently, there is no vaccine available and treatment is limited to palliative care. In this study, antisera were raised in mice against 95 overlapping synthetic peptides spanning the VP1 capsid protein of EV71. Two peptides, SP55 and SP70, containing amino acid 163-177 and 208-222 of VP1, respectively, are capable of eliciting neutralizing antibodies against EV71 in the in vitro microneutralization assay. SP70 was identified to be particularly potent in eliciting a neutralizing antibody titer comparable to that obtained with a whole virion-immune serum. Immunization of mice with either SP55 or SP70 triggered an EV71-specific IgG response as high as that obtained with the whole virion as immunogen. The IgG sub-typing revealed that the neutralizing antibodies elicited by both synthetic peptides are likely belonging to the IgG1 sub-type. Alignment with databases showed that the amino acid residues of SP70 are highly conserved amongst the VP1 sequences of EV71 strains from various sub-genogroups. Altogether, these data indicate that SP70 represents a promising candidate for an effective synthetic peptide-based vaccine against EV71.     

Predicting Failure Load of the Femur with Simulated Osteolytic Defects using Noninvasive Imaging Technique in a Simplified Load Case

Currently, there is no proven sensitive or specific method for predicting pathological fracture of the femur. The clinical management of lytic femoral metastases is based on geometric measurement of the bone, of the defect, or both. However, the mechanical behavior of a structure depends on both its material and geometric properties. Our hypothesis is that a change in bone structural properties as the result of tumor induced osteolysis determines the fracture risk in bones with skeletal metastases. We developed a method of QCT (Quantitative Computed Tomography) combined with engineering beam analysis as a noninvasive tool for measuring the material and geometric properties of the femur with simulated lytic defects in the intertrochanteric region. In this ex-vivo study we prove that engineering beam structural analysis applied to serial transaxial QCT scans through human femora with simulated lytic defects at the proximal femur predicts the load at failure and location of fracture better than current clinical guidelines. Structural rigidity measured by QCT in this study may be used to predict the load carrying capacity of femurs with metastatic defects and, furthermore, may be used when the tumor has weakened the bone sufficiently such that pathological fracture is imminent and prophylactic stabilization is necessary.