Localization and targeting of voltage-dependent ion channels in mammalian central neurons

The intrinsic electrical properties and the synaptic input-output relationships of neurons are governed by the action of voltage-dependent ion channels. The localization of specific populations of ion channels with distinct functional properties at discrete sites in neurons dramatically impacts excitability and synaptic transmission. Molecular cloning studies have revealed a large family of genes encoding voltage-dependent ion channel principal and auxiliary subunits, most of which are expressed in mammalian central neurons. Much recent effort has focused on determining which of these subunits coassemble into native neuronal channel complexes, and the cellular and subcellular distributions of these complexes, as a crucial step in understanding the contribution of these channels to specific aspects of neuronal function. Here we review progress made on recent studies aimed to determine the cellular and subcellular distribution of specific ion channel subunits in mammalian brain neurons using in situ hybridization and immunohistochemistry. We also discuss the repertoire of ion channel subunits in specific neuronal compartments and implications for neuronal physiology. Finally, we discuss the emerging mechanisms for determining the discrete subcellular distributions observed for many neuronal ion channels.     

Electronic Health Data Predict Outcomes After Aneurysmal Subarachnoid Hemorrhage

Backgroud

Using electronic health data, we sought to identify clinical and physiological parameters that in combination predict neurologic outcomes after aneurysmal subarachnoid hemorrhage (aSAH).

Methods

We conducted a single-center retrospective cohort study of patients admitted with aSAH between 2011 and 2016. A set of 473 predictor variables was evaluated. Our outcome measure was discharge Glasgow Outcome Scale (GOS). For laboratory and physiological data, we computed the minimum, maximum, median, and variance for the first three admission days. We created a penalized logistic regression model to determine predictors of outcome and a multivariate multilevel prediction model to predict poor (GOS 1–2), intermediate (GOS 3), or good (GOS 4–5) outcomes.

Results

One hundred and fifty-three patients met inclusion criteria; most were discharged with a GOS of 3. Multivariate analysis predictors of mortality (AUC 0.9198) included APACHE II score, Glasgow Come Scale (GCS), white blood cell (WBC) count, mean arterial pressure, variance of serum glucose, intracranial pressure (ICP), and serum sodium. Predictors of death/dependence versus independence (GOS 4–5)(AUC 0.9456) were levetiracetam, mechanical ventilation, WBC count, heart rate, ICP variance, GCS, APACHE II, and epileptiform discharges. The multiclass prediction model selected GCS, admission APACHE II, periodic discharges, lacosamide, and rebleeding as significant predictors; model performance exceeded 80% accuracy in predicting poor or good outcome and exceeded 70% accuracy for predicting intermediate outcome.

Conclusions

Variance in early physiologic data can impact patient outcomes and may serve as targets for early goal-directed therapy. Electronically retrievable features such as ICP, glucose levels, and electroencephalography patterns should be considered in disease severity and risk stratification scores.

     

Acute reversible monoparesis in multiple neurocysticercosis: A case report and review of literature

Focal neurological deficit like monoparesis due to cortical lesions is a rare entity. In spite of the common presentations like seizures and headaches in neurocysticercosis, occurrence of reversible monoparesis is an atypical phenomenon. Even in the absence of infarct or hemorrhages, manifestation of neural deficit due to compressive effect only is an interesting finding. And on top of that, reversible nature of the deficit in space occupying lesion is a rare occurrence in the existing literature. Here, we describe a known case of neurocysticercosis with reversible acute monoparesis secondary to multiple neurocysticercosis. The variations with which neurocysticercosis can present broaden our understanding in its pathophysiology and management protocol.     

Treatment of Acetabular Bone Defect in Revision of Total Hip Arthroplasty Using 3D Printed Tantalum Acetabular Augment

Objective

The treatment of acetabular defects is one of the most difficult challenges of revision of total hip arthroplasty (RTHA), and tantalum is regarded as a promising bone substitute material. This study aims to investigate the effectiveness of 3D printed acetabular augment used in RTHA for the treatment of acetabular bone defect.

Methods

A retrospective analysis of the clinical data of seven patients who had undergone RTHA was carried out using 3D printed acetabular augment from January 2017 to December 2018. The CT data of the patients were exported to Mimics 21.0 software (Materialise, Leuven, Belgium), and the acetabular bone defect augment were designed, printed and then implanted during operation. The postoperative Harris score, visual analogue scale (VAS) score and prosthesis position were observed to evaluate the clinical outcome. A I-test was used for preoperative and postoperative comparison of the paired-design dataset.

Results

A firm attachment of the bone augment to the acetabulum during operation without any complications was found during the follow-up time 2.8–4.3 years. The VAS score of all patients was found 6.9 ± 1.4 before operation and was 0.7 ± 0.7 at the last follow-up (P ≤ 0.001), and the Harris hip scores, were 31.9 ± 10.3 and 73.3 ± 12.8 before operation, and at the last follow-up (P ≤ 0.001), respectively. Moreover, no loosening sign between the bone defect augment and the acetabulum was observed during the entire implantation period.

Conclusion

3D printed acetabular augment is effective in reconstructing the acetabulum following an acetabular bone defect revision, which enhances the hip joint function and eventually makes a satisfactory stable prosthetic.     

Metabolic inflammatory volume and total inflammatory glycolysis: novel parameters to evaluate PET-CT disease activity in Takayasu arteritis

Clinical Rheumatology - To evaluate diagnostic accuracy for active Takayasu arteritis (TAK) for two novel 18F-fluorodeoxyglucose PET-CT parameters, the inflammatory volume (MIV) and total...     

Pleural effusion in Takayasu arteritis: think infection rather than disease activity!

Clinical Rheumatology -     

Comprehensive review: Frailty in pancreas transplant candidates and recipients

Well-selected patients with kidney disease and diabetes mellitus who undergo simultaneous kidney-pancreas transplantation often experience dramatic improvements in quality of life and long-term survival compared to those who remain on medical therapy. Over the past several years the importance of frailty in the pancreas transplant candidate and recipient populations has grown. More patients with advanced age have entered the waitlist, and complications from prolonged diabetes, even in younger patients, have created increased evidence of risk for frailty. Given these concerns, and the broad challenges facing pancreas transplantation volumes overall, we generated this review to help establish the impact and implications. We summarize the interplay of immunological factors, aging, environmental factors, diabetes mellitus, and chronic kidney disease that put these patients at risk for frailty. We discuss its measurement and recommend a combination of two instruments (both well-validated and one entirely objective). We describe the outcomes for patients before and after pancreas transplantation who may have frailty, and what interventions can be taken to mitigate its effects. Broader investigation into frailty in the pancreas transplant population is needed to better understand how to select patients for pancreas transplantation and to how manage its consequences thereafter.     

Cardiovascular risks associated with Janus kinase inhibitors: peering outside the black box

Clinical Rheumatology - Considerable controversy related to the cardiovascular safety of Janus kinase inhibitors (JAKinibs) has arisen following the results of the ORAL Surveillance trial. In this...