Usage of C-Reactive Protein Testing in the Diagnosis and Monitoring of Psoriatic Arthritis (PsA): Results from a Real-World Survey in the USA and Europe.

INTRODUCTION: C-reactive protein (CRP) is an important non-specific marker of both acute and chronic inflammation and can be elevated in patients with psoriatic arthritis (PsA). However, the use of CRP testing in the management of PsA can vary. This study investigated how CRP testing is implemented in real-world clinical practice for disease management of PsA. METHODS: A point-in-time survey of rheumatologists and dermatologists and their next six consulting patients with PsA was conducted in France, Germany, Italy, Spain, UK (EU5), and the USA between June and August 2018. Use of CRP testing was obtained by asking the physician to state (yes/no) whether CRP was used to aid PsA diagnosis and/or to monitor the patient's disease activity. The number of CRP tests conducted in the last 12 months for each patient enrolled was provided. RESULTS: Data were collected for 2270 patients (USA, n = 595; EU5, n = 1675). In the EU5, CRP testing was conducted to aid diagnosis in 78.7% of patients (vs. 43.4% in USA) and CRP was used to monitor disease activity in 72.0% (vs. 34.6% in USA). The majority (80.9%) of patients in the EU5 had at least one CRP test in the last 12 months compared to 42.9% in the USA. Patients treated by rheumatologists (vs. dermatologists) were at least 50% more likely to have CRP tested for monitoring purposes, this difference being most pronounced in the USA. In the EU5, CRP testing was conducted a mean ± standard deviation of 2.7 ± 1.7 times during the last 12 months, versus 2.0 ± 1.4 in the USA. CONCLUSIONS: CRP was more commonly used for the diagnosis and monitoring of PsA in Europe compared to the USA and was more commonly ordered by rheumatologists than dermatologists. In the absence of a better serum biomarker of inflammation, more data are needed to understand how CRP testing should be used in the diagnosis and management PsA.

Work absenteeism and disability associated with psoriasis and psoriatic arthritis in the USA-a retrospective study of claims data from 2009 TO 2020.

OBJECTIVES: To compare work absenteeism and short-term disability among adults with psoriasis or psoriatic arthritis (PsA), versus controls in the USA. METHODS: Adults eligible for work absenteeism and/or short-term disability benefits between 1/1/2009 and 4/30/2020 were screened in the IBM® MarketScan® Commercial and Health and Productivity Management Databases. The following groups were defined: (1) psoriasis: ≥ 2 psoriasis diagnoses ≥ 30 days apart and no PsA diagnoses; (2) PsA: ≥ 2 PsA diagnoses ≥ 30 days apart; (3) control: absence of psoriasis and PsA diagnoses. Controls were matched to psoriasis and PsA patients based on age, gender, index year, and comorbidities. Non-recreational work absences and sick leaves were evaluated in absentee-eligible patients, and short-term disability was evaluated in short-term disability-eligible patients. Costs (in 2019 USD) associated with each type of work absence were evaluated. RESULTS: 4261 psoriasis and 616 PsA absentee-eligible and 25,213 psoriasis and 3480 PsA short-term disability-eligible patients were matched to controls. Average non-recreational work absence costs were $1681, $1657, and $1217 for the PsA, psoriasis, and control group, respectively. Compared with psoriasis patients and controls, more PsA patients had sick leaves after 1 year (56.2% versus 55.6% and 41.5%, p < 0.0001). Similarly, short-term disability was more frequent in PsA patients than psoriasis patients and controls at year one (8.8% versus 5.6% and 4.7%, p < 0.0001) and corresponding costs were higher ($605, $406, and $335 on average, p < 0.0001). CONCLUSION: Annual work absenteeism and short-term disability were consistently greater among patients with PsA and psoriasis than controls, highlighting the substantial economic burden of psoriatic disease. Key points • Patients with PsA had greater short-term disability compared with patients with psoriasis and patients with neither psoriasis nor PsA. • Patients with PsA and patients with psoriasis incurred greater non-recreational work absences and sick leaves than patients with neither psoriasis nor PsA.

Healthcare utilization and costs among patients with psoriasis and psoriatic arthritis in the USA-a retrospective study of claims data from 2009 to 2020.

OBJECTIVES: To compare healthcare resource utilization and costs among patients with psoriasis, psoriatic arthritis (PsA), and a control group of patients without psoriasis and PsA in the USA. METHODS: The IBM® MarketScan® Commercial Database was used to identify three adult patient groups from 1/1/2009 through 4/30/2020: (1) Psoriasis: ≥ 2 diagnoses ≥ 30 days apart for psoriasis (no PsA diagnoses); (2) PsA: ≥ 2 diagnoses for PsA; (3) Control: no psoriasis or PsA diagnoses in their entire claims records. Patients with comorbid rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, or ulcerative colitis were excluded from the analyses. Controls were matched 1:1 to psoriasis and PsA patients based on age, gender, index year, and number of non-rheumatological comorbidities. Healthcare resource utilization and costs (in 2019 USD) were evaluated descriptively and through mixed models for five years of follow-up. RESULTS: A total of 142,531 psoriasis and 21,428 PsA patients were matched to the control group (N = 163,959). Annual all-cause healthcare costs per patient were $7,470, $11,062, and $29,742 for the control, psoriasis, and PsA groups, respectively. All-cause healthcare costs increased over time and were significantly greater among PsA vs. psoriasis (p < 0.0001) and the control groups (p < 0.0001). Across all categories of healthcare resources, utilization was greatest among patients with PsA and lowest in the control group. CONCLUSION: Annual healthcare costs and resource utilization were significantly higher with PsA compared with psoriasis and the control group, confirming the substantial economic burden of PsA. The cost disparity between these patient groups highlights a continued unmet medical need. Key Points • Patients with PsA incurred significantly greater healthcare resource utilization and costs than patients with psoriasis and patients without psoriasis and PsA. • Significantly greater costs and healthcare resource utilization were also observed among patients with psoriasis compared with patients without psoriasis and PsA.

Assessing resilience of healthcare infrastructure exposed to COVID-19: emerging risks, resilience indicators, interdependencies and international standards.

In the moment of preparation of this paper, the world is still globally in grip of the Corona (COVID-19) crisis, and the need to understand the broader overall framework of the crisis increases. As in similar cases in the past, also with this one, the main interest is on the "first response". Fully appreciating the efforts of those risking their lives facing pandemics, this paper tries to identify the main elements of the larger, possibly global, framework, supported by international standards, needed to deal with new (emerging) risks resulting from threats like Corona and assess the resilience of systems affected. The paper proposes that future solutions should include a number of new elements, related to both risk and resilience. That should include broadening the scope of attention, currently focused onto preparation and response phases, to the phases of "understanding risks", including emerging risks, and transformation and adaptation. The paper suggests to use resilience indicators in this process. The proposed approach has been applied in different cases involving critical infrastructures in Europe (energy supply, water supply, transportation, etc., exposed to various threats), including the health system in Austria. The detailed, indicator-based, resilience analysis included mapping resilience, resilience stress-testing, visualization, etc., showing, already before the COVID-19, the resilience (stress-testing) limits of the infrastructures. A simpler (57 indicator based) analysis has, then been done for 11 countries (including Austria). The paper links these results with the options available in the area of policies, standards, guidelines and tools (such as the RiskRadar), with focus on interdependencies and global standards-especially the new ISO 31,050, linking emerging risks and resilience.

Propensity score matching/reweighting analysis comparing intravenous golimumab to infliximab for ankylosing spondylitis using data from the GO-ALIVE and ASSERT trials.

OBJECTIVE: To compare the relative efficacy of intravenous golimumab (GOL IV) and infliximab (IFX) for active ankylosing spondylitis (AS). METHODS: Propensity score (PS) methods were used to compare the efficacy of GOL IV 2 mg/kg and IFX 5 mg/kg using individual patient data (IPD) from the active arms of the phase 3 GO-ALIVE and ASSERT studies. Outcomes included the proportion of patients with a ≥ 20% improvement in the Assessment of Spondyloarthritis International Society Criteria (ASAS20), change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) score, and change from baseline in C-reactive protein (CRP) levels from weeks 4-52. RESULTS: Before matching, 105 patients were treated with GOL IV and 201 patients were treated with IFX. After matching on all covariates, 118 patients were included in the ASAS20 analysis, 96 in the BASFI analysis, and 160 in the CRP analysis. After matching, GOL IV showed significantly greater improvement in ASAS20 response than IFX for weeks 28-44 (e.g., OR = 9.05 [95% CI 1.62-50.4] at week 44) and was comparable in change from baseline in BASFI scores and CRP levels to IFX at all time points. Results were robust for inclusion of different sets of covariates in scenario analyses. CONCLUSIONS: This is the first analysis of its kind to leverage clinical trial data to compare two biologics using PS methods in the treatment of active AS. Overall, GOL IV was associated with greater improvement in ASAS20 response than IFX in patients with AS at 28, 36, and 44 weeks of follow-up. Key Points • Although intravenous golimumab (GOL IV) and infliximab (IFX) are the only two IV-based tumor necrosis factor (TNF) inhibitors with demonstrated phase 3 clinical efficacy in patients with ankylosing spondylitis (AS), no study has evaluated their comparative efficacy in a head-to-head trial. • Propensity score matching was used to derive indirect treatment comparisons of GOL IV and IFX for ≥ 20% in the Assessment of Spondyloarthritis International Society Criteria (ASAS20), change in Bath Ankylosing Spondylitis Functional Index (BASFI), and change in C-reactive protein (CRP) using individual patient data from the GO-ALIVE and ASSERT phase 3 trials. • Propensity score matched indirect comparisons showed improved relative efficacy of GOL IV compared to IFX; after matching for up to 16 baseline covariates, GOL IV was associated with significantly greater odds of ASAS20 response at weeks 28, 36, and 44 than IFX as well as equivalent changes from baseline in BASFI and CRP. • This novel application of propensity score matching using data from phase 3 trials, the first analysis of its kind in AS, allowed adjustment for important imbalances in prognostic factors between trials to generate estimates of comparative efficacy between GOL IV and IFX in the absence of a head-to-head trial between these treatments.

A systematic review and network meta-analysis of current and investigational treatments for active ankylosing spondylitis.

OBJECTIVE: To compare the relative efficacy of current and investigational biologic and oral small molecule (OSM) treatments for active ankylosing spondylitis (AS). METHODS: A systematic literature review was conducted to identify all phase 2/3 randomized trials of interest in patients with AS. Outcomes assessed were ≥ 20% improvement in the Assessment of Spondyloarthritis International Society Criteria (ASAS20) and change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) and C-reactive protein (CRP) at weeks 12-16. Bayesian network meta-analyses were conducted for outcomes using a random effects model. Baseline-risk adjustment was also conducted to account for differences in placebo response across studies. Surface Under the Cumulative Ranking curve (SUCRA) values are reported, reflecting the relative probability that intervention was the best of all interventions. RESULTS: The investigational agent tofacitinib 5 mg was the top-ranked treatment (SUCRA, 93%) for ASAS20 response, followed by intravenous (IV) golimumab 2 mg/kg (90%). Golimumab IV 2 mg/kg and infliximab 5 mg/kg were the top two ranked treatments for change from baseline in BASFI (golimumab IV, 81%; infliximab, 80%) and change from baseline in CRP (infliximab, 90%; golimumab IV, 82%). CONCLUSIONS: Two approved therapies (golimumab IV, infliximab) and one investigational product ranked highest for efficacy in AS. Key Points • Although golimumab IV, infliximab, and tofacitinib ranked highest for efficacy in AS, differences in efficacy between approved and investigational therapies were not statistically significant.

Investigation of HZE particle fluxes as a space radiation hazard for future Mars missions.

Manned Mars missions planned in the near future of very low solar activity period and hence higher than acceptable radiation doses due mainly to the Galactic Cosmic Rays (GCR), would require special techniques and technological development for maintaining the good health of the astronauts. The present study is an attempt to make an assessment and characterise the coming years in terms of solar activity and space radiation environment especially due to the abundance of highly energetic heavy ions (known as HZE charged particles). These HZE particle fluxes constitute a major hazard to the astronauts and also to the critical electronic components of the spacecraft. Recent data on the HZE species (from B to Ni) obtained from ACE spacecraft shows a clear enhancement of the particle fluxes between the solar cycle 23 and solar cycle 24 (~between SSN peaks 2002 and 2014) due to the persisting low sunspot numbers of the latter cycle. The peak values of these cosmic ray fluxes occur with a time lag of about a year of the corresponding minimum value of the sunspots of a particular 11-year cycle which is pseudo-periodic in nature. This is demonstrated by the Fourier and Wavelet transform analyses of the long duration (1700-2018) yearly mean sunspot number data. The same time series data is also used to train a Hybrid Regression Neural Network (HRNN) model to generate the predicted yearly mean sunspot numbers for the solar cycle 25 (~2019-2031). The wavelet analysis of this new series of annual sunspot numbers including the predictions up to the end of 2031 shows a clear trend of continuation of the low solar activity and hence continuation of very high HZE fluxes prevailing in Solar cycle 24 into the solar cycle 25 and perhaps beyond.

Aqueous synthesis of highly stable CdTe/ZnS Core/Shell quantum dots for bioimaging.

In this work, we report the synthesis, characterization and biological application of highly stable CdTe/ZnS (cadmium tellurite/zinc sulphide) Core/Shell (CS) quantum dots (QDs) capped with mercaptosuccinic acid (MSA). The CS QDs were synthesized using a simple one-pot aqueous method. The synthesized CdTe/ZnS CS QDs were found to exhibit excellent stability even 100 days after preparation and also showed better photoluminescence quantum yield (PLQY) of about 50% compared with that of only CdTe QDs which was nearly 12%. The formation of the CdTe/ZnS CS was confirmed by high-resolution transmission electron microscopy (HR-TEM), and Fourier transform infra-red (FTIR) and X-ray diffraction (XRD) analyses. Further, on extending our study towards bioimaging of E. coli cells using the QDs samples, we found that CdTe/ZnS CS QDs showed better results compared with CdTe QDs.

Live attenuated malaria vaccine designed to protect through hepatic CD8⁺ T cell immunity.

Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8(+) T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8(+), IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.

Circadian modulation of sodium-potassium ATPase and sodium - proton exchanger in human erythrocytes: in vitro effect of melatonin.

Melatonin (N-acetyl-5-methoxytrptamine) is a pineal secretory product which is involved in the regulation of circadian rhythm and participates in many physiological functions. It also acts as a potent antioxidant and a powerful free radical scavenger. The membrane-associated Na+/K+-ATPase and Na+/H+ exchanger in erythrocytes play an important role in maintaining cytosolic pH, ionic homeostasis, cell osmolarity and in the regulation of transmembrane ion movement. The present work was undertaken to determine the role of melatonin in modulating the activity of Na+/K+-ATPase and Na+/H+ exchanger in human erythrocytes. Our observation shows circadian modulation of Na+/K+-ATPase and Na+/H+ exchanger which may have important therapeutic implications. Exogenous melatonin modulated the activities of Na+/K+-ATPase and Na+/H+ exchanger in human red blood cells, this effect may in part be explained due to the antioxidative effect of melatonin and also due to modulation of membrane fluidity. Further work is needed to understand the mechanism of action.

Strain relaxation and vacancy creation in thin platinum films.

Synchrotron based combined in situ x-ray diffractometry and reflectometry is used to investigate the role of vacancies for the relaxation of residual stress in thin metallic Pt films. From the experimentally determined relative changes of the lattice parameter a and of the film thickness L the modification of vacancy concentration and residual strain was derived as a function of annealing time at 130 °C. The results indicate that relaxation of strain resulting from compressive stress is accompanied by the creation of vacancies at the free film surface. This proves experimentally the postulated dominant role of vacancies for stress relaxation in thin metal films close to room temperature.

Comparison of automated intermittent low volume bolus with continuous infusion for labour epidural analgesia.

Delivery of local anaesthetics via automated intermittent bolus has been shown to improve epidural analgesia compared to delivery via continuous epidural infusion. However the optimal bolus volume has not been investigated. This randomised, double-blind study compared the analgesic efficacy of automated intermittent bolus (volume 2.5 ml every 15 minutes) with that of a continuous epidural infusion (10 ml/hour) for the maintenance of labour epidural analgesia, to determine whether the advantages previously demonstrated for automated intermittent bolus over continuous epidural infusion are retained at this low bolus volume. With the approval of the Hospital Ethics Committee, we recruited 50 parturients who received combined spinal epidural analgesia with intrathecal ropivacaine 2 mg and fentanyl 15 microg. For epidural maintenance, participants were randomised to either the automated intermittent bolus group (2.5 ml automated intermittent epidural boluses of ropivacaine 0.1% plus fentanyl 2 microg/ml delivered over a two-minute period every 15 minutes) or the continuous epidural infusion group (continuous epidural infusion of ropivacaine 0.1% plus fentanyl 2 microg/ml at 10 ml/hour). The primary study outcome was the incidence of pain during labour that required management with supplemental epidural analgesia. There were no significant differences between the two regimens in terms of breakthrough pain (automated intermittent bolus 36% [9/25] vs continuous epidural infusion 32% [8/25], P = 0.77). At the doses used in this study, maintenance of labour analgesia using automated intermittent bolus at a bolus volume of 2.5 ml every 15 minutes does not decrease the incidence of breakthrough pain or improve analgesic efficacy compared to continuous epidural infusion.

Removal of Pb(II) ions from aqueous solution by adsorption using bael leaves (Aegle marmelos).

Biosorption of Pb(II) on bael leaves (Aegle marmelos) was investigated for the removal of Pb(II) from aqueous solution using different doses of adsorbent, initial pH, and contact time. The maximum Pb loading capacity of the bael leaves was 104 mg g(-1) at 50 mg L(-1) initial Pb(II) concentration at pH 5.1. SEM and FT-IR studies indicated that the adsorption of Pb(II) occurs inside the wall of the hollow tubes present in the bael leaves and carboxylic acid, thioester and sulphonamide groups are involved in the process. The sorption process was best described by pseudo second order kinetics. Among Freundlich and Langmuir isotherms, the latter had a better fit with the experimental data. The activation energy E(a) confirmed that the nature of adsorption was physisorption. Bael leaves can selectively remove Pb(II) in the presence of other metal ions. This was demonstrated by removing Pb from the effluent of exhausted batteries.

Delta FosB overexpression in the nucleus accumbens enhances sexual reward in female Syrian hamsters.

Repeated activation of the mesolimbic dopamine system results in persistent behavioral alterations accompanied by a pattern of neural plasticity in the nucleus accumbens (NAc). As the accumulation of the transcription factor Delta FosB may be an important component of this plasticity, the question addressed in our research is whether Delta FosB is regulated by sexual experience in females. We have shown that female Syrian hamsters, given sexual experience, exhibit several behavioral alterations including increased sexual efficiency with naïve male hamsters, sexual reward and enhanced responsiveness to psychomotor stimulants (e.g. amphetamine). We recently demonstrated that sexual experience increased the levels of Delta FosB in the NAc of female Syrian hamsters. The focus of this study was to explore the functional consequences of this induction by determining if the constitutive overexpression of Delta FosB by adeno-associated virus (AAV) vectors in the NAc could mimic the behavioral effects of sexual experience. Animals with AAV-mediated overexpression of Delta FosB in the NAc showed evidence of sexual reward in a conditioned place preference paradigm under conditions in which control animals receiving an injection of AAV-green fluorescent protein (GFP) into the NAc did not. Sexual behavior tests further showed that males paired with the AAV-Delta FosB females had increased copulatory efficiency as measured by the proportion of mounts that included intromission compared to males mated with the AAV-GFP females. These results support a role for Delta FosB in mediating natural motivated behaviors, in this case female sexual behavior, and provide new insight into the possible endogenous actions of Delta FosB.

Dynamic response of wall shear stress on the stenosed artery.

The present study deals with an appropriate mathematical model of an artery in the presence of constriction in which the generated wall shear stress due to blood flow is analysed. The geometry of the stenosed arterial segment in the diseased state, causing malfunction of the cardiovascular system, is formed mathematically. The flowing blood contained in the stenosed artery is treated as non-Newtonian and the flow is considered to be two-dimensional. The motion of the arterial wall and its effect on local fluid mechanics is not ruled out from the present pursuit. The flow analysis applies the time-dependent, two-dimensional incompressible nonlinear Navier-Stokes equations for non-Newtonian fluids. The flow-field can be obtained primarily following the radial coordinate transformation, using the appropriate boundary conditions and finally adopting a suitable finite difference scheme numerically. The influences of flow unsteadiness, the arterial wall distensibility and the presence of stenosis on the flow-field and the wall shear stresses are quantified in order to indicate the susceptibility to atherosclerotic lesions and thereby to validate the applicability of the present theoretical model.

Numerical simulation of unsteady generalized Newtonian blood flow through differently shaped distensible arterial stenoses.

An updated numerical simulation of unsteady generalized Newtonian blood flow through differently shaped distensible arterial stenoses is developed. A shear-thinning fluid modelling the deformation dependent viscosity of blood is considered for the characterization of generalized Newtonian behaviour of blood. The arterial model is treated as two-dimensional and axisymmetric with an outline of the stenosis obtained from a three-dimensional casting of a mildly stenosed artery. The full Navier-Stokes equations governing blood flow are written in the dimensionless form and the solution is accomplished by finite time-step advancement through their finite difference staggered grid representations. The marker and cell (MAC) method comprising the use of a set of marker particles moving with the fluid is used for the purpose. Results are obtained for three differently shaped stenoses - irregular, smooth and cosine curve representations. The present results do agree well with those of existing investigations in the steady state, but contrary to their conclusions the present findings demonstrate that the excess pressure drop across the cosine and the smooth stenoses is caused by neither their smoothness nor their higher degree of symmetry relative to the irregular stenosis, but is rather an effect of area cover with respect to the irregular stenosis. This effect clearly prevails throughout the entire physiological range of Reynolds numbers. Further the in-depth study in flow patterns reveals the development of flow separation zones in the diverging part of the stenosis towards the arterial wall, and they are influenced by non-Newtonian blood rheology, distensibility of the wall and flow unsteadiness in order to validate the applicability of the present model.

Removal of copper from aqueous solution using newspaper pulp as an adsorbent.

Newspaper pulp was found to be a potential adsorbent for removal of copper from aqueous medium. Detail adsorption study of Cu on newspaper pulp was investigated. Batch adsorption study was carried out as a function of contact time, adsorbent dose, temperature (303-323 K). The experimental data was analyzed using Freundlich, Langmuir, Dubinin-Radushkevich (D-R) and Redlich-Peterson (R-P) isotherm models. It was found that Freundlich, Langmuir and R-P models fitted well. pH variation study revealed that the adsorption increased with increase in pH of the solution. Maximum loading capacity was found to be 30 mg g(-1) at 20 mg L(-1) of initial Cu concentration. Adsorption data were analyzed using two kinetic models, Lagergren first order and pseudo second order. It was observed that pseudo second order represented the best correlation. Langmuir isotherm was used to obtain the thermodynamic parameters such as free energy (DeltaG degrees ), enthalpy (DeltaH degrees ) and entropy (DeltaS degrees ) of adsorption. The negative value of free energy and positive value of enthalpy change indicate that the adsorption of Cu on newspaper pulp is a spontaneous process and endothermic. The results of activation energy also confirmed that the adsorption of Cu on newspaper pulp is physical in nature. Present investigation emphasized that newspaper pulp may be utilized as a low cost adsorbent for copper removal.

Analysis of pulsatile blood flow in constricted bifurcated arteries with vorticity-stream function approach.

This theoretical investigation deals with an analysis of pulsatile blood flow in a model bifurcated artery having a stenosis in the parent arterial lumen. The geometry of the bifurcated arterial segment with an implanted stenosis in the parent duct is given an appropriate mathematical shape with the introduction of suitable curvature at the lateral junction and the flow divider. The vascular wall deformability is duly accounted for although the development of atherosclerosis in the arteries reduces its elastic property to some extent. The streaming blood contained in the bifurcated artery is treated to be Newtonian. The flow dynamic analysis applies two-dimensional unsteady incompressible nonlinear Navier-Stokes equations rewritten in the vorticity-stream function formulation. Following a radial coordinate transformation, these equations are solved numerically by a finite difference scheme with the approximate choice of the inlet and boundary conditions in concert with the biophysical point of view. The final numerical results are highlighted at the end of the paper through the exhibition of the wall shear stress and several time-variant patterns of streamlines and vorticity contours of the flow phenomena, which are highly influenced by the severity of the stenosis and the angle of bifurcation. The applicability of the present model is thus established.

RIP1 links inflammatory and growth factor signaling pathways by regulating expression of the EGFR.

There is considerable interest in understanding how inflammatory responses influence cell proliferation and cancer. In this study, we show that the receptor-interacting protein (RIP1), a critical mediator of inflammation and stress-induced NF-kappaB activation, regulates the expression of the epidermal growth factor receptor (EGFR). Mouse embryo fibroblasts (MEFs) derived from RIP1 knockout mice express very high levels of the EGFR. Reconstitution of RIP1(-/-) MEFs with RIP1 results in a lowering of EGFR levels. RIP1 influences EGFR at the mRNA level by regulating the EGFR promoter. Expression of RIP1 inhibits the EGFR promoter. RIP1 downregulates EGFR expression by interfering with the function of Sp1, which is a key activator of EGFR transcription. RIP1 suppresses Sp1 activity and overexpression of Sp1 reverses RIP1-mediated repression of the EGFR promoter. RIP1 is present both in the cytoplasm and in the nucleus. RIP1 coimmunoprecipitates with Sp1 in vivo and binds directly to Sp1 in vitro. A RIP1 mutant lacking the death domain fails to suppress Sp1 activity and the EGFR promoter, suggesting a critical role for the RIP1 death domain in EGFR regulation. Thus, our study identifies a new link between inflammatory and growth factor signaling pathways mediated by RIP1 and provides insight into the mechanism used by RIP1 to regulate EGFR levels.