Characteristics of rheumatoid arthritis patients at first presentation to a specialized rheumatology department

Background: Rheumatoid arthritis (RA) is a chronic, progressive, debilitating, systemic, autoimmune disease that mainly affects the diarthrodial joints. It is the most common form of inflammatory arthritis that occurs in approximately 1% of adults. The main objective is to study the characteristics of patients with Rheumatoid Arthritis (RA) at first presentation to a specialized rheumatology department.Methods: The study included 122 consecutive patients with RA, fulfilling 1987 American College of Rheumatology (ACR) criteria for RA at ‘Joint Disease Clinic’ of rheumatology department, at ISIC, New Delhi.Results: The mean age was 45.3 ± 12.4 years, F:M ratio, 8.4:1; maximum patients (31.1%) belonging to age group 30-40 years. Mean age at onset of symptoms was 38.1 ± 12.9 years and disease duration mode 5 years. 88% patients were literate and 59% referred by other patients. 14.8% patients had family history of RA, 7.38% (all males) were smokers. 16.4% female patients developed symptoms of arthritis within one year after delivery. 44.3% patients had severe, 50.8% moderate, 3.3% mild and 1.6% inactive disease (DAS 28[ESR] scoring system). 28.7% patients were taking treatment from alternative systems, 25.4% from orthopaedicians, 15.6% from internists and 8.2% from rheumatologists. Methotrexate and glucocorticoids were the most prescribed drugs (50.8% each) but in inappropriate doses. 23.8% patients had co-morbidities, hypothyroidism (9%) being the commonest.Conclusions: RA affects middle aged women. Hypothyroidism is the mostly associated autoimmune disease. The majority receive suboptimal / inappropriate treatment before visiting a rheumatologist. Most patients consult a rheumatologist at late stage in the disease often with deformities. Hence, increased awareness is needed about this disease among patients and doctors so that patients get timely referral to a rheumatologist for the proper management of this disease.

Critical Role of VCP/p97 in the Pathogenesis and Progression of Non-Small Cell Lung Carcinoma

Valosin-containing protein (VCP)/p97 is an AAA ATPase molecular chaperone that regulates vital cellular functions and protein-processing. A recent study indicated that VCP expression levels are correlated with prognosis and progression of non-small cell lung carcinoma (NSCLC). We not only verified these findings but also identified the specific role of VCP in NSCLC pathogenesis and progression.Our results show that VCP is significantly overexpressed in non-small cell lung carcinoma (NSCLC) as compared to normal tissues and cell lines (p<0.001). Moreover, we observed the corresponding accumulation of ubiquitinated-proteins in NSCLC cell lines and tissues as compared to the normal controls. VCP inhibition by si/shRNA or small-molecule (Eeyarestatin I, EerI) significantly (p<0.05, p<0.00007) suppressed H1299 proliferation and migration but induced (p<0.00001) apoptosis. Cell cycle analysis by flow cytometry verified this data and shows that VCP inhibition significantly (p<0.001, p<0.003) induced cell cycle arrest in the G0/G1 phases. We also found that VCP directly regulates p53 and NFκB protein levels as a potential mechanism to control tumor cell proliferation and progression. Finally, we evaluated the therapeutic potential of VCP inhibition and observed significantly reduced NSCLC tumor growth in both in vitro and xenograft murine (athymic-nude) models after EerI treatment (p<0.05).Thus, targeting VCP in NSCLC may provide a novel strategy to restore p53 and NFκB levels and ameliorate the growth and tumorigenicity, leading to improved clinical outcomes

Self-resolving information markets: an experimental case study

On traditional information markets (TIMs), rewards are tied to the occurrence (or non-occurrence) of events external to the market, such as some particular candidate winning an election. For that reason, they can only be used when it is possible to wait for some external event to resolve the market. In cases involving long time-horizons or counterfactual events, this is not an option. Hence, the need for a self-resolving information market (SRIM), resolved with reference to factors internal to the market itself. In the present paper, we first offer some theoretical reasons for thinking that, since the only thing that can be expected to be salient to all participants on a SRIM is the content of the question bet on, a convention will arise of taking that question at face value, and betting accordingly, in which case trading behaviour on SRIMs can be expected to be identical to that on TIMs. This is the ‘face value’ hypothesis. If this hypothesis holds, SRIMs have the potential of incorporating the accuracy of TIMs while shedding their limitations in relation to long-term predictions and the evaluation of counterfactuals. We then report on a laboratory experiment that demonstrates that trading behaviour can indeed come out highly similar across SRIMs and TIMs. As such, the study can be thought of as an experimental case study on SRIMs. Finally, we discuss some limitations of the study, and also points towards fruitful areas of future research in light of our results

Hemoglobin-carbon nanotube derived noble-metal-free Fe 5 C 2-based catalyst for highly efficient oxygen reduction reaction

High performance non-precious cathodic catalysts for oxygen reduction reaction (ORR) are vital for the development of energy materials and devices. Here, we report an noble metal free, Fe 5 C 2 nanoparticles-studded sp 2 carbon supported mesoporous material (CNTHb-700) as cathodic catalyst for ORR, which was prepared by pyrolizing the hybrid adduct of single walled carbon nanotubes (CNT) and lyophilized hemoglobin (Hb) at 700 ??C. The catalyst shows onset potentials of 0.92 V in 0.1 M HClO 4 and in 0.1 M KOH which are as good as commercial Pt/C catalyst, giving very high current density of 6.34 and 6.69 mA cm &amp;acirc; &apos;2 at 0.55 V vs. reversible hydrogen electrode (RHE), respectively. This catalyst has been confirmed to follow 4-electron mechanism for ORR and shows high electrochemical stability in both acidic and basic media. Catalyst CNTHb-700 possesses much higher tolerance towards methanol than the commercial Pt/C catalyst. Highly efficient catalytic properties of CNTHb-700 could lead to fundamental understanding of utilization of biomolecules in ORR and materialization of proton exchange membrane fuel cells for clean energy productionope

Management of Colonic Trauma: Six-Year Experience at Henry Ford Hospital

Surgical management of 114 patients with colonic injuries related to trauma who were treated over a six-year period is reviewed. Eighty-three (73%) injuries were secondary to gunshot wounds. Twenty-six patients (24%) had isolated colonic injuries. The majority of patients (60%)) were treated with colostomies: exteriorization of the injury, repair with proximal colostomy, or resection with colostomy and mucous fistula. Exteriorization of repaired colon, primary repair, and resection with primary anastomosis were performed in 40% of the patients. Six patients (5.3%) in our series died, and 24% had complications directly related to the colon injury. Based on this study, no standard method for treatment of colonic trauma is advised. Colostomy is recommended for patients with massive multiple intra-abdominal injuries and gross fecal contamination. In selected patients, primary repair may be performed

High-Affinity-Assisted Nanoscale Alloys as Remarkable Bifunctional Catalyst for Alcohol Oxidation and Oxygen Reduction Reactions

A key challenge in developing fuel cells is the fabrication of low-cost electrocatalysts with high activity and long durability for the two half-reactions, i.e., the methanol/ethanol oxidation reaction (MOR/EOR) and the oxygen reduction reaction (ORR). Herein, we report a conductivity-enhanced bifunctional electrocatalyst of nanoscale-coated Pt-Pd alloys on both tin-doped indium (TDI) and reduced graphene oxide (rGO), denoted as Pt-Pd@TDI/rGO. The mass activities of Pt in the Pt-Pd@TDI/rGO hybrid toward MOR, EOR, and ORR are 2590, 1500, and 2690 mA/mg, respectively. The ORR Pt specific activity and mass activity of the electrocatalyst are 17 and 28 times larger, respectively, than commercial Pt/C catalysts. All these remarkable catalytic performances are attributed to the role of TDI in enhancing the catalytic activity,by protecting Pt from oxidation as well as rapid mass/charge transfer due to the synergistic effect between surface Pt-Pd alloys and TDI/rGO

Early-Age-Related Changes in Proteostasis Augment Immunopathogenesis of Sepsis and Acute Lung Injury

adult) mechanisms that augment immunopathogenesis of sepsis and acute lung injury. model to standardize the efficacy of salubrinal (inhibitor of eIF2α de-phosphorylation) in controlling the accumulation of ubiquitinated proteins and the NFκB levels. Finally, we evaluated the therapeutic efficacy of salubrinal to correct proteostasis-imbalance in the adult mice based on its ability to control CLP induced IL-6 secretion or recruitment of pro-inflammatory cells.Our data demonstrate the critical role of early-age-related proteostasis-imbalance as a novel mechanism that augments the NFκB mediated inflammation in sepsis and ALI. Moreover, our data suggest the therapeutic efficacy of salubrinal in restraining NFκB mediated inflammation in the adult or older subjects

Development of PEGylated PLGA nanoparticle for controlled and sustained drug delivery in cystic fibrosis

<p>Abstract</p> <p>Background</p> <p>The mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene results in CF. The most common mutation, ΔF508-CFTR, is a temperature-sensitive, trafficking mutant with reduced chloride transport and exaggerated immune response. The ΔF508-CFTR is misfolded, ubiquitinated, and prematurely degraded by proteasome mediated- degradation. We recently demonstrated that selective inhibition of proteasomal pathway by the FDA approved drug PS-341 (pyrazylcarbonyl-Phe-Leuboronate, a.k.a. Velcade or bortezomib) ameliorates the inflammatory pathophysiology of CF cells. This proteasomal drug is an extremely potent, stable, reversible and selective inhibitor of chymotryptic threonine protease-activity. The apprehension in considering the proteasome as a therapeutic target is that proteasome inhibitors may affect proteostasis and consecutive processes. The affect on multiple processes can be mitigated by nanoparticle mediated PS-341 lung-delivery resulting in favorable outcome observed in this study.</p> <p>Results</p> <p>To overcome this challenge, we developed a nano-based approach that uses drug loaded biodegradable nanoparticle (PLGA-PEG^PS-341) to provide controlled and sustained drug delivery. The <it>in vitro </it>release kinetics of drug from nanoparticle was quantified by proteasomal activity assay from days 1-7 that showed slow drug release from day 2-7 with maximum inhibition at day 7. For <it>in vivo </it>release kinetics and biodistribution, these drug-loaded nanoparticles were fluorescently labeled, and administered to C57BL6 mice by intranasal route. Whole-body optical imaging of the treated live animals demonstrates efficient delivery of particles to murine lungs, 24 hrs post treatment, followed by biodegradation and release over time, day 1-11. The efficacy of drug release in CF mice (<it>Cftr^-/-</it>) lungs was determined by quantifying the changes in proteasomal activity (~2 fold decrease) and ability to rescue the <it>Pseudomonas aeruginosa </it>LPS (<it>Pa</it>-LPS) induced inflammation, which demonstrates the rescue of CF lung disease in murine model.</p> <p>Conclusion</p> <p>We have developed a novel drug delivery system to provide sustained delivery of CF "correctors" and "anti-inflammatories" to the lungs. Moreover, we demonstrate here the therapeutic efficacy of nano-based proteostasis-modulator to rescue <it>Pa-LPS </it>induced CF lung disease.</p