Elevated glycohemoglobin HbA1c is associated with low back pain in nonoverweight diabetics

Background Context

Low back pain (LBP) is a common complaint in clinical practice of multifactorial origin. Although obesity has been thought to contribute to LBP primarily by altering the distribution of mechanical loads on the spine, the additional contribution of obesity-related conditions such as diabetes mellitus (DM) to LBP has not been thoroughly examined.

Effect of lacosamide on ethanol induced conditioned place preference and withdrawal associated behavior in mice: Possible contribution of hippocampal CRMP-2

BackgroundExcessive consumption of ethanol is known to activate the mTORC1 pathway and to enhance the Collapsin Response Mediator Protein-2 (CRMP-2) levels in the limbic region of brain. The latter helps in forming microtubule assembly that is linked to drug taking or addiction-like behavior in rodents. Therefore, in this study, we investigated the effect of lacosamide, an antiepileptic drug and a known CRMP-2 inhibitor, which binds to CRMP-2 and inhibits the formation of microtubule assembly, on ethanol-induced conditioned place preference (CPP) in mice.MethodsThe behavior of mice following ethanol addiction and withdrawal was assessed by performing different behavioral paradigms. Mice underwent ethanol-induced CPP training with alternate dose of ethanol (2 g/kg, po) and saline (10 ml/kg, po). The effect of lacosamide on the expression of ethanol-induced CPP and on ethanol withdrawal associated anxiety and depression-like behavior was evaluated. The effect of drug on locomotor activity was also assessed and hippocampal CRMP-2 levels were measured.ResultsEthanol-induced CPP was associated with enhanced CRMP-2 levels in the hippocampus. Lacosamide significantly reduced the expression of ethanol-induced CPP and alleviated the levels of hippocampal CRMP-2 but aggravated withdrawal-associated anxiety and depression in mice.ConclusionThe present study demonstrated the beneficial effect of lacosamide in attenuation of expression of ethanol induced conditioned place preference via reduction of hippocampal CRMP-2 level. These findings suggest that lacosamide may be investigated further for ethanol addiction but not for managing withdrawal.     

Improved Late Graft Survival and Half-Lives in Pediatric Kidney Transplantation: A Single Center Experience

We evaluated variables associated with improved late graft survival in 290 children transplanted between 11/1/1984 and 12/31/1997, and who had > 1 year graft survival. We studied the following variables: age, gender, race, primary disease (diseases prone to recurrence, i.e. hemolytic uremic syndrome, focal segmental glomerulosclerosis or oxalosis vs. others), primary vs. retransplant; donor source, acute tubular necrosis, acute rejection episodes in the first year, transplant era and discharge serum creatinine. Graft half-life was defined as the time taken for 1/2 of the grafts functioning at 1 year to fail. There were 205 living donor and 85 cadaveric transplant. The cumulative graft survival at 5 and 10 years was 88% and 75% for living donor, and 72% and 46% for cadaveric, respectively. Multivariate analyses showed a higher late graft survival to be associated with: no acute rejection episodes (risk ratio 0.16, p = 0.0001), age 2-5 years (risk ratio 0.24, p = 0.0007), living donor (risk ratio 0.46, p = 0.017), primary nonrecurrent disease (risk ratio 0.29, p = 0.001), Caucasian race (risk ratio 0.40, p = 0.006). A high half-life was seen with living donor transplant (21.3 years) and the age group 2-5 years (27.5 years). Further, living donor patients with no acute rejection episodes had the best half-life of 37.6 years, while children with hemolytic uremic syndrome, focal segmental glomerulosclerosis or oxalosis had the lowest overall half-life of 5.6 years. This study finds that living donor, no acute rejection episodes, age 2-5 years, Caucasian race and having a disease not prone to recurrence are strong predictors of late graft survival. Hence, preferential use of living donor and prevention of acute rejection episodes in the first year are key variables that can improve long-term renal graft survival in children.     

Metastatic mammary carcinoma of the middle ear

Malignancies of the middle ear and mastoid are rare and secondaries in the ear are extremely rare. A rare case of metastic adenocarcinoma from the breast is presented herewith.     

Multiple cis-regulatory elements and the yeast sulphur regulatory network are required for the regulation of the yeast glutathione transporter, Hgt1p

HGT1 encodes a high-affinity glutathione transporter in the yeast Saccharomyces cerevisiae that is induced under sulphur limitation. The present work demonstrates that repression by organic sulphur sources is under the control of the classic sulphur regulatory network, as seen by the absence of expression in a met4 background. Cysteine appeared to be the principal regulatory molecule, since elevated levels were seen in str4 strains (deficient in cysteine biosynthesis) that could be repressed by elevated levels of cysteine, but not by methionine or glutathione. Investigations into cis-regulatory elements revealed that the previously described motif, a 9-bp cis element, CCGCCACAC, located at the –356 to –364 region of the promoter could in fact be refined to a 7-bp CGCCACA motif that is also repeated at –333 to –340. The second copy of this motif was essential for activity, since mutations in the core region of the second copy completely abolished activity and regulation by sulphur sources. Activity, but not regulation, could be restored by reintroducing an additional copy upstream of the first copy. A third region, GCCGTCTGCAAGGCA, conserved in the HGT1 promoters of the different Saccharomyces spp, was observed at –300 to –285 but, while mutations in this region did not lead to any loss in repression, the basal and induced levels were significantly increased. In contrast to a previous report, no evidence was found for regulation by the VDE endonuclease. The strong repression at the transport level by glutathione seen in strains overexpressing HGT1 was due to a glutathione-dependent toxicity in these cells.     

Direct versus indirect transfer for traumatic brain injury to James Cook University Hospital: a retrospective study

IntroductionPatients with traumatic brain injury are referred to the neurosurgical unit at James Cook University Hospital, Middlesbrough, either from local accident and emergency departments (direct transfer from the scene) or from other hospitals (indirect transfer). This study looked at the outcome in both groups.Material and methodsThis was a retrospective observational study using trauma audit research network data for patients treated for traumatic brain injury at the neurosurgery department at the neurosurgical unit at James Cook University Hospital.ResultsA total of 356 patients with traumatic brain injury were admitted under the care of neurosurgeons; 143 (40%) of these patients had a neurosurgical procedure. Of the patients undergoing a neurological procedure, 111 patients were transferred directly while 32 were indirect transfers; 213 patients were managed conservatively. Of those managed conservatively, 165 were transferred directly while 48 were indirect transfers.We compared the length of hospital stay and Glasgow Outcome Scale score for the patients based on whether they were conservatively managed or required surgery in the direct and indirect transfer groups. The difference in the length of stay in the surgical and conservative groups following direct and indirect transfer was insignificant (p = 0.07). The time to the operation in direct and indirect transfer was also not statistically significant (p = 0.06).ConclusionPatients are as safe, if not safer, by reaching the nearest trauma unit with facilities for resuscitation and imaging.     

Platelet glycoprotein VI-dependent thrombus stabilization is essential for the intraportal engraftment of pancreatic islets

Platelet activation and thrombus formation have been implicated to be detrimental for intraportal pancreatic islet transplants. The platelet-specific collagen receptor glycoprotein VI (GPVI) plays a key role in thrombosis through cellular activation and the subsequent release of secondary mediators. In aggregometry and in a microfluidic dynamic assay system modeling flow in the portal vein, pancreatic islets promoted platelet aggregation and triggered thrombus formation, respectively. While platelet GPVI deficiency did not affect the initiation of these events, it was found to destabilize platelet aggregates and thrombi in this process. Interestingly, while no major difference was detected in early thrombus formation after intraportal islet transplantation, genetic GPVI deficiency or acute anti-GPVI treatment led to an inferior graft survival and function in both syngeneic mouse islet transplantation and xenogeneic human islet transplantation models. These results demonstrate that platelet GPVI signaling is indispensable in stable thrombus formation induced by pancreatic islets. GPVI deficiency resulted in thrombus destabilization and inferior islet engraftment indicating that thrombus formation is necessary for a successful intraportal islet transplantation in which platelets are active modulators.     

Tuberculous otitis media-are we missing it ?

Tuberculosis of the middle ear it a rare disease. Due to change in the typical clinical pattern and decrease in incidence, there is a delayed or missed diagnosis and can lead to increased morbidity. We pretent 5 cases of Tuberculous Otitis Media treated over a period of 2 years, highlighting the fact that it must be considered as a differential diagnosis of persistent suppurative otitis media.