CO-MORBIDITY OF CARDIOVASCULAR DISEASES AND RHEUMATOID ARTHRITIS

Rheumatoid Arthritis (RA) is a chronic disease related to swelling of joints which leads to restriction in movement due to pain and deformity in mainly in feet, ankle, wrist and fingers. It is an autoimmune disease and the manifestations caused due to its occurrence are not clearly understood. In today's time, it has been observed that comorbid conditions account for most of the deaths as they influence the outcome of RA and limit therapeutic options. The most common comorbid conditions which are diagnosed in RA patients are generally cardiovascular abnormalities, several infections, certain mental disorders and malignancies. Among which cardiovascular comorbid diseases are the most common kind relating to disorders of heart and blood vessel that eventually leads to severe conditions like angina, myocardial infarction (MI), stroke, rheumatic heart disease and many more. RA affects the quality of life of patients directly or indirectly but it mainly shows a significant increase in the prevalence of cardiovascular diseases. Hence, it is essential to diagnose and understand about the related manifestations when one is suffering from Rheumatoid Arthritis. These studies will aid to make better treatment and management strategies. Hence, an attempt has been made in this review article regarding the epidemiology, impact of both the diseases and related risk factors. It also gives information in brief about the pathological causes of the comorbidity and summarizes measures that may be used in the prevention and treatment of these conditions

Modelling the interactions of NO in a-SiO2

Nitric oxide (NO) is often used for the passivation of SiC/SiO2 metal oxide semiconductor (MOS) devices. Although it is established experimentally, using XPS, EELS, and SIMS measurements, that the 4H-SiC/SiO2 interface is extensively nitridated, the mechanisms of NO incorporation and diffusion in amorphous (a)-SiO2 films are still poorly understood. We used Density Functional Theory (DFT) to simulate the diffusion of NO through a-SiO2 and correlate local steric environment in amorphous network to interstitial NO (NOi) incorporation energy and migration barriers. Using an efficient sampling technique we identify the energy minima and transition states for neutral and negatively charged NOi molecules. Neutral NO interacts with the amorphous network only weakly with the smallest incorporation energies in bigger cages. On the other hand NOi -1 binds at the intrinsic precursor sites for electron trapping

Daily activity during stability and exacerbation of chronic obstructive pulmonary disease

BACKGROUND: During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data. METHODS: Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer. Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators. RESULTS: The 73 COPD patients (88% male) had a mean (+/-SD) age 71(+/-8) years and FEV1 53(+/-16)% predicted. They recorded pedometer data on a median 198 days (IQR 134-353). At exacerbation onset, symptom count rose by 1.9(+/-1.3) and PEF fell by 7(+/-13) l/min. Mean daily step count fell from 4154(+/-2586) steps/day during a preceding baseline week to 3673(+/-2258) step/day during the initial 7 days of exacerbation (p = 0.045). Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = -0.56; p < 0.001). Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001). Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030).Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002). CONCLUSIONS: COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time

Iron overload causes endolysosomal deficits modulated by NAADP-regulated 2-pore channels and RAB7A

Various neurodegenerative disorders are associated with increased brain iron content. Iron is known to cause oxidative stress, which concomitantly promotes cell death. Whereas endolysosomes are known to serve as intracellular iron storage organelles, the consequences of increased iron on endolysosomal functioning, and effects on cell viability upon modulation of endolysosomal iron release remain largely unknown. Here, we show that increasing intracellular iron causes endolysosomal alterations associated with impaired autophagic clearance of intracellular protein aggregates, increased cytosolic oxidative stress and increased cell death. These effects are subject to regulation by NAADP, a potent second messenger reported to target endolysosomal TPCNs (2-pore channels). Consistent with endolysosomal iron storage, cytosolic iron levels are modulated by NAADP, and increased cytosolic iron is detected when overexpressing active, but not inactive TPCNs, indicating that these channels can modulate endolysosomal iron release. Cell death triggered by altered intralysosomal iron handling is abrogated in the presence of an NAADP antagonist or when inhibiting RAB7A activity. Taken together, our results suggest that increased endolysosomal iron causes cell death associated with increased cytosolic oxidative stress as well as autophagic impairments, and these effects are subject to modulation by endolysosomal ion channel activity in a RAB7A-dependent manner. These data highlight alternative therapeutic strategies for neurodegenerative disorders associated with increased intracellular iron load

Inflammatory thresholds and the species-specific effects of colonising bacteria in stable chronic obstructive pulmonary disease

There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients. We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort

Development and characterization of controlled release mucoadhesive tablets of captopril

El estudio actual trata del desarrollo de los comprimidos mucoadhesivos de captopril, que se diseñaron con el fin de prolongar el tiempo de permanencia gástrica después de la administración oral. Se formularon matrices de comprimidos de captopril mediante diferentes polímeros mucoadhesivos, tales como goma guar, goma xantana, hidroxipropilmetilcelulosa K4M y K15M, a varias concentraciones. Los comprimidos se evaluaron según sus propiedades físicas, uniformidad del contenido, índice de inflamación, fuerza de bioadhesión y liberación farmacológica in vitro. La inflamación se incrementó cuando la concentración y la viscosidad de HPMC aumentaron. Los comprimidos formulados solamente con goma guar y goma xantana se descompusieron con mayor rapidez y se disolvieron completamente en un rango de 5-7 horas, mientras que los comprimidos con HPMC permanecieron intactos y mostraron una liberación lenta de hasta 11-12 horas. Se observó que la formulación F10 con HPMC K15M y goma xantana (1:1) tenía una fuerza bioadhesiva máxima de 31,59±0,05 g y la liberación farmacológica in vitro fue del 91,85%, al final de un periodo de 12 horas con un mecanismo de difusión no de Fick. Los estudios de estabilidad de lotes optimizados mostraron que no hay cambios en la fuerza bioadhesiva y la liberación in vitro cuando se mantiene bajo condiciones de diferentes temperaturas durante 60 días. Se concluyó que la formulación F10 presenta la mejor fuerza bioadhesiva y liberación farmacológica.The present investigation concerns the development of mucoadhesive tablets of Captopril which were designed to prolong the gastric residence time after oral administration. Matrix tablets of Captopril were formulated using different mucoadhesive polymers such as guar gum, xanthan gum, hydroxyl propyl methyl cellulose K4M and K15M in various ratios. The tablets were evaluated for physical properties, content uniformity, swelling index, bioadhesive strength and in-vitro drug release. Swelling was increased as the concentration and viscosity of HPMC increases. Tablets formulated using guar gum and xanthan gum alone were eroded faster and dissolved completely within 5-7 hr, while tablet containing HPMC remain intact and provided slow release up to 11-12 hr. It was evident from the study that the formulation F10 containing HPMC K15M and xanthan gum (1:1) exhibited maximum bioadhesive strength of 31.59±0.05 gm and in vitro drug release was found to be 91.85 % at the end of 12 hr with non-fickian diffusion mechanism. The stability studies of optimized batch showed that there was no change in bioadhesive strength and in-vitro release when stored at different temperature condition for 60 days. It was concluded that formulation F10 shows the better bioadhesive strength and drug release

Learning curves and long-term outcome of simulation-based thoracentesis training for medical students

<p>Abstract</p> <p>Background</p> <p>Simulation-based medical education has been widely used in medical skills training; however, the effectiveness and long-term outcome of simulation-based training in thoracentesis requires further investigation. The purpose of this study was to assess the learning curve of simulation-based thoracentesis training, study skills retention and transfer of knowledge to a clinical setting following simulation-based education intervention in thoracentesis procedures.</p> <p>Methods</p> <p>Fifty-two medical students were enrolled in this study. Each participant performed five supervised trials on the simulator. Participant's performance was assessed by performance score (PS), procedure time (PT), and participant's confidence (PC). Learning curves for each variable were generated. Long-term outcome of the training was measured by the retesting and clinical performance evaluation 6 months and 1 year, respectively, after initial training on the simulator.</p> <p>Results</p> <p>Significant improvements in PS, PT, and PC were noted among the first 3 to 4 test trials (p < 0.05). A plateau for PS, PT, and PC in the learning curves occurred in trial 4. Retesting 6 months after training yielded similar scores to trial 5 (p > 0.05). Clinical competency in thoracentesis was improved in participants who received simulation training relative to that of first year medical residents without such experience (p < 0.05).</p> <p>Conclusions</p> <p>This study demonstrates that simulation-based thoracentesis training can significantly improve an individual's performance. The saturation of learning from the simulator can be achieved after four practice sessions. Simulation-based training can assist in long-term retention of skills and can be partially transferred to clinical practice.</p

Changes in prevalence and load of airway bacteria using quantitative PCR in stable and exacerbated COPD

BACKGROUND: Prevalence and load of airway bacteria in stable and exacerbated chronic obstructive pulmonary disease (COPD) has been previously studied using microbiological culture. Molecular techniques, such as quantitative PCR (qPCR), may be more informative. METHODS: In this study, 373 sputum samples from 134 COPD outpatients were assessed for prevalence and load of typical airway bacteria (Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis) by multiplex qPCR, with 176 samples analysed for atypical bacteria. Paired stable and exacerbation typical bacteria data were compared in 52 patients. We compared routine culture with qPCR in 177/373 samples. RESULTS: Typical bacteria were more prevalent in exacerbation than stable-state paired samples: 30/52 (57.7%) vs. 14/52 (26.9%); p=0.001. In patients who were bacteria-positive at both time points, mean (±1 SEM) load was significantly higher at exacerbation than stable state (108.5(±0.3) vs. 107.2(±0.5) cfu/ml), constituting a 20-fold increase (p=0.011). qPCR was more discriminatory at detecting typical bacteria than microbiological culture (prevalence 59.3% vs. 24.3%; p<0.001). At stable state, higher airway bacterial load correlated with more severe airflow limitation (FEV(1)%predicted) (r=-0.299; p=0.033) and higher inhaled corticosteroid dosage (r=0.382; p=0.008). Mean C-reactive protein was higher in bacterial-associated exacerbations (35.0 Vs 25.1 mg/L; p=0.032). CONCLUSIONS: Airway bacterial prevalence and load increase at COPD exacerbations and are an aetiological factor. qPCR is more discriminatory than culture, identifying higher airway bacterial prevalence. Exacerbations associated with bacterial detection showed a higher mean C-reactive protein level. In the stable state, airway bacterial load is related to more severe airflow limitation and higher inhaled corticosteroid dosage used

The Higgs vacuum uplifted: revisiting the electroweak phase transition with a second Higgs doublet

The existence of a second Higgs doublet in Nature could lead to a cosmological first order electroweak phase transition and explain the origin of the matter-antimatter asymmetry in the Universe. We explore the parameter space of such a two-Higgs-doublet-model and show that a first order electroweak phase transition strongly correlates with a significant uplifting of the Higgs vacuum w.r.t. its Standard Model value. We then obtain the spectrum and properties of the new scalars H0, A0 and H± that signal such a phase transition, showing that the decay A0 → H0Z at the LHC and a sizable deviation in the Higgs self-coupling λhhh from its SM value are sensitive indicators of a strongly first order electroweak phase transition in the 2HDM