Density and function of inward currents in right atrial cells from chronically fibrillating canine atria

OBJECTIVE: To determine whether I(Na) and I(CaL) are altered in function/density in right atrial (RA) cells from dogs with chronic atrial fibrillation (cAF dogs, episodes lasting at least 6 days) and whether the changes that occur differ from those in dogs with nonsustained or brief episodes of fibrillation (nAF dogs). METHODS: Using whole cell voltage clamp, sodium and calcium current density and function were determined in disaggregated RA cells from nAF, cAF and control atria (Con). Ca(2+) currents were studied with either Ca(2+) or Ba(2+) as charge carrier, as well as with either EGTA or BAPTA as the internal solution Ca(2+) chelator. RESULTS: After rapid atrial pacing, dogs can either fibrillate for short periods of time (nAF) or longer, more sustained periods (cAF). Both the Na(+) and Ca(2+) current decrease in cells of the nAF atria. Na(+) current density remains reduced in cAF cells with some slowing of recovery kinetics. Ca(2+) current density does not further decrease with persistent atrial fibrillation (cAF cells) remaining significantly different from Con cells. However, the difference in density of Ca(2+) currents between nAF and Con cells is negligible when Ba(2+) is charge carrier and when Ca(i) is quickly and effectively chelated with BAPTA. On the contrary, cAF I(BaL) densities remain significantly reduced compared to Con and nAF values when Ba(2+)/BAPTA conditions are used. CONCLUSIONS: Na(+) current density/function does not recover to Con values in cAF. Further these enhanced Ca(2+)-dependent inactivation processes contribute significantly to the reduction of I(CaL) density observed in nAF cells while reduction of Ca(2+) currents in cAF atria is probably by another mechanism     

Evaluation of Factors in Relation with the Non-Compliance to Curative Intent Radiotherapy among Patients of Head and Neck Carcinoma: A Study from the Kumaon Region of India

Introduction:

Radiotherapy (RT)-based curative regimens for head and neck squamous cell carcinomas (HNSCC) deliver a dose of 66–70 Gray (Gy) over a period of 6–7 weeks, and incomplete treatments are unlikely to result in cure. Non-compliance to RT is major contributory factor to treatment failure.

Aims:

To assess the proportion of patients who do not complete planned treatment after initiation of curative RT. This study also aims to explore a possible relationship of non-compliance due to socio-economic, disease-related and treatment-related factors.

Materials and Methods:

The records of HNSCC patients treated from January 2012–December 2013 were audited. Data from the treatment records were to collect patient-related, disease-related, and social demographic parameters. Of the patients who had not completed treatment, the reasons behind the same were investigated.

Results:

Of the 324 patients of HNSCC who were initiated on radical RT, a total of 76 patients were found to have discontinued treatment without authorization of the treating clinician. There was no significant predilection for treatment non-compliance with regards to patient age, educational status, religion, site of the disease, use of neoadjuvant chemotherapy, or use of concurrent chemotherapy. There tended to be a higher association of treatment non-compliance among patients residing >100 km away from the treatment center, patients hailing from hilly regions, patients without the below poverty line (BPL) card, unemployed patients, and patients with stage IV-A/B disease. Of the 76 patients who did not complete treatment, telephonic questionnaire could be obtained from 54 patients. Causes for non-compliance included preference for traditional healers (22.2%), fear of toxicity (7.4%), logistic reasons (18.5%), financial reasons (24.1%), and lack of interest/faith in RT (5.6%).

Conclusion:

There is a high incidence of treatment default among patients of HNSCC during RT in this region. The revelation of the higher propensity for treatment default among patients from distant, hilly regions, unemployed, patients without BPL cards, and stages-IVA/IVB highlights the need for specific interventions for these special populations.     

Patent foramen ovale in a large population of ischemic stroke patients: diagnosis, age distribution, gender, and race

BACKGROUND: Patent foramen ovale (PFO) is a well-recognized risk factor for ischemic strokes. The true prevalence of PFO among stroke patients is still under debate. Transesophageal echocardiography (TEE) is the "gold standard" in diagnosing PFO but the physiology requires right-to-left atrial shunting. In this report, we evaluate the prevalence of PFO in a diverse group of ischemic stroke patients studied by TEE. METHODS: TEE of 1,663 ischemic stroke patients were reviewed for cardiac source of embolism, including PFO and atrial septal aneurysm (ASA). Agitated saline bubble injection was performed to look for right to left atrial shunting. Success of maneuvers to elevate right atrial pressure (RAP) was noted by looking at the atrial septal bulge. RESULTS: Among 1,435 ischemic stroke patients analyzed, the presence or absence of PFO could not be determined in 32.1% because bulging of the septum could not be demonstrated in patients with negative contrast study despite aggressive maneuvers to elevate RAP. Of the remaining 974 patients, 294 patients (30.2%) had a PFO. The mean age was 61.5 years in both groups, with a bimodal distribution of PFO and the highest prevalence occurring in < or =30-year-old group. Prevalence of PFO was similar in men (32.4%) and women (28.15%, P = 0.15); and in Caucasian (32.1%) and African American (27.7%; P = 0.15). ASA was present in 2.02% and hypermobile septum in 2.49% of the 1,435 patients. PFO was seen in 79.3% of the patients with ASA. CONCLUSION: Successful elevation of RAP cannot be achieved in a significant number of patients undergoing TEE and determination of PFO may be difficult. In our series, the true prevalence of PFO among ischemic stroke patients was 30.2% taking into account only those patients who showed no shunting despite bulging of the atrium septum into the left atrium (PFO absent group) during the contrast study. There was no gender or racial difference in the prevalence of PFO, but there was a bimodal distribution in prevalence with age.     

Epstein-Barr virus latent infection membrane protein 1 TRAF-binding site induces NIK/IKK alpha-dependent noncanonical NF-kappaB activation

Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1)-induced NF-kappaB activation is important for infected cell survival. LMP1 activates NF-kappaB, in part, by engaging tumor necrosis factor (TNF) receptor-associated factors (TRAFs), which also mediate NF-kappaB activation from LTbetaR and CD40. LTbetaR and CD40 activation of p100/NF-kappaB2 is now known to be NIK/IKKalpha-dependent and IKKbeta/IKKgamma independent. In the experiments described here, we found that EBV LMP1 induced p100/NF-kappaB2 processing in human lymphoblasts and HEK293 cells. LMP1-induced p100 processing was NIK/IKKalpha dependent and IKKbeta/IKKgamma independent. Furthermore, the LMP1 TRAF-binding site was required for p100 processing and p52 nuclear localization, whereas the LMP1 death domain-binding site was not. Moreover, the LMP1 TRAF-binding site preferentially caused RelB nuclear accumulation. In murine embryo fibroblasts (MEFs), IKKbeta was essential for LMP1 up-regulation of macrophage inflammatory protein (MIP)-2, TNFalpha, I-TAC, ELC, MIG, and CXCR4 RNAs. Interestingly, in IKKalpha knockout MEFs, LMP1 hyperinduced MIP-2, TNFalpha, and I-TAC expression, consistent with a role for IKKalpha in down-modulating canonical IKKbeta activation or its effects. In contrast, LMP1 failed to up-regulate CXCR4 and MIG RNA in IKKalpha knockout MEFs, indicating a dependence on noncanonical IKKalpha activation. Furthermore, LMP1 up-regulation of MIP-2 RNA in MEFs was both IKKbeta- and IKKgamma-dependent, whereas LMP1 upregulation of MIG and I-TAC RNA was fully IKKgamma independent. Thus, LMP1 induces typical canonical IKKbeta/IKKgamma-dependent, atypical canonical IKKbeta-dependent/IKKgamma-independent, and noncanonical NIK/IKKalpha-dependent NF-kappaB activations; NIK/IKKalpha-dependent NF-kappaB activation is principally mediated by the LMP1 TRAF-binding site.     

Reduction of subacute stent thrombosis (SAT) using heparin-coated stents in a large-scale, real world registry

PURPOSE: This study was designed to compare the rates of subacute stent thrombosis (SAT) among patients receiving heparin-coated stents to patients receiving bare-metal stents in real world, contemporary coronary interventions. BACKGROUND: Controlled trials with heparin-coated coronary stents have shown a trend toward decreased rates of SAT. METHODS AND RESULTS: The data in this study were collected from a single, large cardiac center over a period of 9 months. All patients who underwent coronary stent implantation during this 9-month period were included in the study (1,288 patients; 1,366 procedures; 2,231 stents). All patients were treated with aspirin and clopidogrel (or ticlopidine) after stenting. Primary thrombotic outcome was defined as angiographically documented SAT and/or sudden unexplained cardiac death (SCD) within 30 days of the procedure. Follow-up data (1,264/1,276 patients) were obtained in 99% of patients. A total of 337 patients received 543 heparin-coated stents (BX Velocity Hepacoat) and 939 patients received bare-metal stents (1,688 stents). SAT was seen in 25/1,024 procedures (2.44%) in the bare-metal stent group and 1/342 procedures (0.29%) in the heparin-coated stent group. Primary thrombotic outcomes (SAT or SCD) were observed in 31/1,024 procedures (3.03%) in the bare-metal stent cohort and in 2/342 procedures (0.58%) in the heparin-coated stent group. The vast majority (96%) of the patients who had SAT within 30 days had initial stent placement for an acute coronary syndrome (p<0.0001). CONCLUSION: This large, single-center registry demonstrates a significant reduction of SAT using heparin-coated stents compared to bare-metal stents in real world coronary interventions.     

Phytoplankton nutrient dynamics and flow cytometry based population study of a eutrophic wetland habitat in eastern India,a Ramsar site

Phytoplankton diversity, their abundance based on flow cytometric (FCM) analysis and seasonal nutrient dynamics were investigated from a waste water fed wetland of Eastern India (88° 24.641′E and 22° 33.115′N). The primary objective of the study was to correlate the seasonal fluctuations in phytoplankton abundance to the environmental variables. Total chlorophyll content and FCM based cell counts were used to characterize and quantify the phytoplankton population. Multivariate statistical methods were employed in predicting the possible relationships between biotic and abiotic variables. Distinct seasonal variations characterized by high abundance during the pre-summer period compared to other seasons were detected. The results indicated that environmental factors like water temperature and nutrients, such as various forms of nitrogen and phosphate, influenced the seasonal phytoplankton accumulation. Cluster analysis and non-metric multidimensional scaling helped analyze the seasonal distribution of phytoplankton based on their composition. The dominant genera among the entire phytoplankton community were Scenedesmus spp. of Chlorophyta, followed by Merismopedia spp. of Cyanoprokaryota. Around 3.7 × 10⁵ phytoplankton mL⁻¹ were recorded during the study period. Due to the very high count of individual species in the community, FCM based counting was applied for determination of Species Diversity Index. The entire population was divided into 13 subpopulations based on the cell sorting method and the seasonal abundance in each sub-population was illustrated.

Phytoplankton diversity, their abundance based on flow cytometric (FCM) analysis and seasonal nutrient dynamics were investigated from a waste water fed wetland of Eastern India (88° 24.641′E and 22° 33.115′N).     

Nonreconstruction Options for Treating Medial Ulnar Collateral Ligament Injuries of the Elbow in Overhead Athletes

Purpose of Review

This review aims to describe the nonreconstructive options for treating ulnar collateral ligament (UCL) injuries ranging from nonoperative measures, including physical therapy and biologic injections, to ligament repair with and without augmentation.

Recent Findings

Nonoperative options for UCL injuries include guided physical therapy and biologic augmentation with platelet-rich plasma (PRP). In some patients, repair of the UCL has shown promising return to sport rates by using modern suture and suture anchor techniques. Proximal avulsion injuries have shown the best results after repair. Currently, there is growing interest in augmentation of UCL repair with an internal brace.

Summary

The treatment of UCL injuries involves complex decision making. UCL reconstruction remains the gold standard for attritional injuries and complete tears, which occur commonly in professional athletes. However, nonreconstructive options have shown promising results for simple avulsion or partial thickness UCL injuries. Future research comparing reconstructive versus nonreconstructive options is necessary.