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Introduction We evaluated the use of implantable defibrillators (ICDs) in the octogenarian population to analyze the complications associated with ICD implantation; the incidence of appropriate and inappropriate discharges; as well as survival following ICD implantation. Methods We retrospectively evaluated the utilization of ICDs implanted and followed at our institution from 1998 to 2004 in the octogenarian population with systolic dysfunction. A control group was comprised of similar patients under the age of 80. Patients with preserved ventricular function were excluded. Results Two hundred twenty-six patients with systolic dysfunction were evaluated following ICD implantation. There were 51 patients over 80 years of age (mean age: 84 ± 4). A control group of 175 patients less than age 80 (mean age: 66 ± 10) was utilized for comparison. The baseline characteristics, including ejection fraction (25 ± 7%), presence of coronary disease (90%), as well as the incidence of symptomatic arrhythmias (33%) were similar in both groups. The octogenarian population did have a higher percentage of women (31% v. 18% (p = 0.04)). The long-term device related complication rate in the older age group was low (1.9%) and did not differ between groups. Thirty-two percent of the octogenarian group received appropriate ICD therapy over a mean follow-up period of 15 ± 16 months. The older group had fewer inappropriate discharges (6.8% v. 12.6%; p = NS) in comparison to the younger patient group. Although 78.4% of the octogenarian group survived during the follow-up period, there was a significant decrease in survival in this group as evaluated by the Kaplan Meier method (p=0.0003). In multivariate analysis, the only significant predictor of survival was age less than 80. Conclusion The octogenarian population can safely be treated with ICD therapy and in appropriately selected patients; they can be expected to have a high rate of therapeutic ICD utilization. Patients should be carefully selected for ICD implantation as mortality is higher in the octogenarian population and co-morbid conditions may limit the potential survival benefit offered by the ICD. [ABSTRACT FROM PUBLISHER]

Introduction The purpose of this study was to evaluate the efficacy of a dual-coil, active-can implantable cardioverter-defibrillator (ICD) system, implanted for the treatment of ventricular arrhythmias, in cardioversion of spontaneous episodes of atrial fibrillation (AF). Methods The population was derived from 360 patients with icds implanted between July 1997 and June 2001. The study patients were 69 ± 8.9 years old, 83% were male, coronary artery disease was present in 78%, and a prior history of non-permanent AF was present in 54%. Beta blockers were used in 72% of patients and amiodarone in 27% of patients. The mean left ventricular ejection fraction was 31 ± 9%. Echocardiographic evaluation demonstrated moderate to severe left atrial enlargement in 41% of patients. Patients with permanent AF were excluded. Results Atrial fibrillation resulted in an ICD discharge in 23 patients. Successful cardioversion occurred in 79% of episodes of AF with defibrillation energy of 30.5 ± 4.4 joules. In multivariate analysis, no patient characteristics, including left atrial size, ejection fraction, or concurrent use of beta blockers or amiodarone predicted success of cardioversion. Multiple discharges were delivered in 17% of these patients. Conclusion Standard dual-coil, active-can ICD systems are highly successful at converting spontaneous AF that occurs in the clinical setting. There were no specialized defibrillation coils or algorithms required. The use of discriminatory algorithms for prevention of multiple ICD discharges due to atrial arrhythmias needs to be balanced with the high success rate of cardioversion. [ABSTRACT FROM PUBLISHER]

Primary tumoral calcinosis is a rare and benign condition characterized by calcium salt deposition in periarticular soft tissues. It typically presents as a firm, rubbery mass that arises around large joints. While an estimated 250 cases have been described since its discovery, very few cases have been identified in the hand. We present a case of multiple calcified masses in the hand, one of which required meticulous dissection from a digital neurovascular bundle, and our technique for surgical excision. We present this case to lower the threshold for clinical suspicion of tumoral calcinosis for patients who present with a soft tissue mass in the hand. Furthermore, we recommend prompt surgical excision due to low success rates of alternative treatment options and to prevent potential neurovasculature or tendon injury., (Published by Elsevier B.V. on behalf of Society for Indian Hand Surgery and Micro Surgeons.)

Background: Favorable clinical outcomes are difficult to achieve in long-standing persistent atrial fibrillation (LSPAF) with catheter ablation (CA). The CONVERGE (Convergence of Epicardial and Endocardial Ablation for the Treatment of Symptomatic Persistent Atrial FIbrillation) trial evaluated the effectiveness of hybrid convergent (HC) ablation vs endocardial CA., Objective: The study sought to evaluate the safety and effectiveness of HC vs CA in the LSPAF subgroup from the CONVERGE trial., Methods: The CONVERGE trial was a prospective, multicenter, randomized trial that enrolled 153 patients at 27 sites. A post hoc analysis was performed on LSPAF patients. The primary effectiveness was freedom from atrial arrhythmias off new or increased dose of previously failed or intolerant antiarrhythmic drugs (AADs) through 12 months. The primary safety endpoint was major adverse event incidence through 30 days with HC. Key secondary effectiveness measures included (1) percent of patients achieving ≥90% AF burden reduction vs baseline and (2) AF freedom., Results: Sixty-five patients (42.5% of total enrollment) had LSPAF; 38 in HC and 27 in CA. Primary effectiveness was 65.8% (95% confidence interval [CI] 50.7%-80.9%) with HC vs 37.0% (95% CI 5.1%-52.4%) with CA ( P = .022). Through 18 months, these rates were 60.5% (95% CI 50.0%-76.1%) with HC vs 25.9% (95% CI 9.4%-42.5%) with CA ( P = .006). Secondary effectiveness rates were higher than CA with HC at 12 and 18 months. Freedom from atrial arrhythmias off AADs was 52.6% (95% CI 36.8%-68.5%) and 47.4% (95% CI 31.5%-63.2%) with HC at 12 and 18 months vs 25.9% (95% CI 9.4%-42.5%) and 22.2% (95% CI 6.5%-37.9%) with CA, respectively (12 months: P = .031; 18 months: P = .038). Three (7.9%) major adverse events occurred within 30 days of HC., Conclusion: Post hoc analysis demonstrated effectiveness and acceptable safety of HC compared with CA in LSPAF., (© 2022 Heart Rhythm Society. Published by Elsevier Inc.)

This study sought to determine (1) whether the use of a narrow border-zone voltage of 0.1 to 0.25 mV predicts the ventricular tachycardia (VT) exit site better than when using the conventional 0.5 to 1.5 mV window and (2) the feasibility of utilizing the Rhythmia mapping system (Boston Scientific, Natick, MA, USA) to map hemodynamically unstable VT without hemodynamic support. The Ablation of ischemic VT is challenging especially in the setting of hemodynamic instability, yet efficient and accurate mapping of VT and VT substrate is critical for procedural success. In this study, a total of 24 patients with ischemic cardiomyopathy and recurrent monomorphic VT underwent mapping and ablation using the Rhythmia system. Contact-force sensing ablation catheters were use in two cases. In patients with mappable VTs, the distance between the exit site and border zone was calculated for border zone-voltage windows of 0.5 to 1.5 mV and 0.1 to 0.25 mV. The percentage of LV scar for each patient was visually estimated into quartiles of scar burden in both windows. Twenty patients were inducible into VT, while 15 patients had mappable VTs for a total of 16 VTs (11 stable VTs and five unstable VTs). There were no adverse complications in patients who underwent mapping in unstable VT. The mean distance from the VT exit site to the border zone was 13.3 mm in the conventional window and 3.4 mm in the narrow window (95% confidence interval: 4.0-15.8; p = 0.003). Separately, 94% (15/16) of the VTs were mapped to the narrow border-zone voltage versus 31% (5/16) using the conventional border zone (p = 0.0006). The use of a narrow 0.1- to 0.25-mV border-zone window highlights relevant scar and constitutes a border zone where VT exit sites are frequently located. We also found that exit sites of hemodynamically unstable VTs can be identified without an increase in procedural complications using the Orion catheter (Boston Scientific, Natick, MA, USA)., Competing Interests: Dr. Yang has received consulting fees and speakers honoraria from Boston Scientific. The other authors report no conflicts of interest for the published content., (Copyright: © 2020 Innovations in Cardiac Rhythm Management.)

The treatment of AF has evolved over the past decade with increasing use of catheter ablation in patients refractory to medical therapy. While pulmonary vein isolation using endocardial catheter ablation has been successful in paroxysmal AF, the results have been more controversial in patients with long-standing persistent AF where extrapulmonary venous foci are increasingly recognised in the initiation and maintenance of AF. Hybrid ablation is the integration of minimally invasive epicardial ablation with endocardial catheter ablation, and has been increasingly used in this population with better results. The aim of this article was to analyse and discuss the evidence for the integration of catheter and minimally invasive surgical approaches to treat AF with specific focus on convergent ablation and exclusion of the left atrial appendage using a surgically applied clip., Competing Interests: Disclosure: AK, KM, NS, DD, YG and FY received consulting fees from Atricure. All other authors have no conflicts of interest to declare., (Copyright © 2020, Radcliffe Cardiology.)

Building blocks of photonic integrated circuitry (PIC), optical waveguides, have long been considered transparent. However, the inevitable Fresnel reflection from waveguide facets limits their transparency. This limitation becomes more severe in high-index waveguides in which the transparency may drop to 65%. We overcome this inherent optical property of high-index waveguides by engineering an appropriate facet landscape made of sub-wavelength artificial features unit cells. For this, we develop a semi-analytical formalism for predicting the metasurface parameters made of high-index dielectric materials, to be engraved on the facets of optical waveguides, based on Babinet's principle: either extruded from the waveguide facet or etched into it. Our semi-analytical model predicts the shape of anti-reflective metasurface unit cells to achieve transmission as high as 98.5% in near-infrared from 1 μm to 2 μm. This new class of metasurfaces may be used for the improvement of PIC devices for communication and sensing, where device transparency is crucial for high signal-to-noise ratios., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We demonstrate that the non-Hermitian Hamiltonian approach can be used as a universal tool to design and describe a performance of single photon quantum electrodynamical circuits (cQED). As an example of the validity of this method, we calculate a novel six port quantum router, constructed from four qubits and three open waveguides. We have obtained analytical expressions, which describe the transmission and reflection coefficients of a single photon in general form taking into account the spread qubit's parameters. We show that, due to naturally derived interferences, in situ tuning the probability of photon detection in desired ports.

Towards the construction of pressure-dependent phase diagrams of binary alloy systems, both thermophysical measurements and thermodynamic modeling are employed. High-accuracy measurements of sound velocity, density, and electrical resistivity were performed for selected metallic elements from columns III to V and their alloys in the liquid phase. Sound velocity measurements were made using ultrasonic techniques, density measurements using the gamma radiation attenuation method, and electrical resistivity measurements were performed using the four probe method. Sound velocity and density data, measured at ambient pressure, were incorporated into a thermodynamic model to calculate the pressure dependence of binary phase diagrams. Electrical resistivity measurements were performed on binary systems to study phase separation and identify phase transitions in the liquid state.

Arachidonic acid metabolites resulting from the cyclooxygenase (COX), lipoxygenase, and cytochrome P450 oxidase enzymatic pathways play pro- and anti-inflammatory roles in allergic airway inflammation (AAI) and asthma. Expression of COX-2 and soluble epoxide hydrolase (sEH) are elevated in allergic airways and their enzymatic products (e.g., prostaglandins and diols of epoxyeicosatrienoic acids, respectively) have been shown to participate in the pathogenesis of AAI. Here, we evaluated the outcome of inhibiting the COX-2 and sEH enzymatic pathways with a novel dual inhibitor, PTUPB, in A. alternata -induced AAI. Allergen-challenged mice were administered with 10 or 30 mg/kg of PTUPB, celecoxib (selective COX-2 inhibitor), t -TUCB (selective sEH inhibitor) or vehicle daily by gavage and evaluated for various features of AAI. PTUPB and t -TUCB at 30 mg/kg, but not celecoxib, inhibited eosinophilic infiltration and significantly increased levels of anti-inflammatory EETs in the lung tissue of allergen-challenged mice. t -TUCB significantly inhibited allergen-induced IL-4 and IL-13, while a less pronounced reduction was noted with PTUPB and celecoxib. Additionally, t -TUCB markedly inhibited eotaxin-2, an eosinophil-specific chemokine, which was only marginally reduced by PTUPB and remained elevated in celecoxib-treated mice. PTUPB or t -TUCB administration reversed allergen-induced reduction in levels of various lipid mediators in the lungs, with only a minimal effect noted with celecoxib. Despite the anti-inflammatory effects, PTUPB or t -TUCB did not reduce allergen-induced airway hyperresponsiveness (AHR). However, development of structural changes in the allergic airways, such as mucus hypersecretion and smooth muscle hypertrophy, was significantly inhibited by both inhibitors. Celecoxib, on the other hand, inhibited only airway smooth muscle hypertrophy, but not mucus hypersecretion. In conclusion, dual inhibition of COX-2 and sEH offers no additional advantage relative to sEH inhibition alone in attenuating various features associated with A. alternata -induced AAI, while COX-2 inhibition exerts only moderate or no effect on several of these features. Dual sEH/COX-2 inhibition may be useful in treating conditions where eosinophilic inflammation co-exists with pain-associated inflammation., (Copyright © 2019 Dileepan, Rastle-Simpson, Greenberg, Wijesinghe, Kumar, Yang, Hwang, Hammock, Sriramarao and Rao.)

Controlling nanomaterial shape beyond its basic dimensionality is a concurrent challenge tackled by several growth and processing avenues. One of these is strain engineering of nanowires, implemented through the growth of asymmetrical heterostructures. Here, we report metal-organic molecular beam epitaxy of bent InP/InAs core/shell nanowires brought by precursor flow directionality in the growth chamber. We observe the increase of bending with decreased core diameter. We further analyze the composition of a single nanowire and show through supporting finite element simulations that strain accommodation following the lattice mismatch between InP and InAs dominates nanowire bending. The simulations show the interplay between material composition, shell thickness, and tapering in determining the bending. The simulation results are in good agreement with the experimental bending curvature, reproducing the radius of 4.3 µm (±10%), for the 2.3 µm long nanowire. The InP core of the bent heterostructure was found to be compressed at about 2%. This report provides evidence of shape control and strain engineering in nanostructures, specifically through the exchange of group-V materials in III-V nanowire growth.

We explore the discrete nature of waveguide modes and the effective medium concept to achieve an ultra-compact highly efficient mode conversion device in a high-index platform such as a silicon waveguide. The proposed device is based on a co-directional coupler that has a periodic variation in its refractive index along the propagation direction. The transverse variation of the index profile is calculated based on the interference pattern between the modes of interest. We show that mode conversion can be realized with dielectric metasurfaces engraved in the silicon waveguide. We derive the equation for effective index and show proof-of-concept numerical results of the device performance. We obtain conversion efficiencies of 95.4% between the TE 0 -TE 1 modes over 8.91 μm interaction distance and 96.4% between the TE 0 -TE 2 over 6.32 μm. The resulting coupling coefficient changes as a function of the interaction distance in a sinusoidal manner, which is crucial for constructive energy transfer from one mode to another. Such mode coupling devices have the potential for application in dispersion compensations, wavelength division multiplexing systems, and sensing.

All-dielectric nanophotonics lies at a forefront of nanoscience and technology as it allows to control light at the nanoscale using its electric and magnetic components. Bulk silicon does not experience any magnetic response, nevertheless, we demonstrate that the metasurface made of silicon parallelepipeds allows to excite the magnetic dipole moment leading to the broadening and enhancement of the absorption. Our investigations are underpinned by the numerical predictions and the experimental verifications. Also surprisingly we found that the resonant electric quadrupole moment leads to the enhancement of reflection. Our results can be applied for a development of absorption based devices from miniature dielectric absorbers, filters to solar cells and energy harvesting devices.

Importance: Approximately one-third of U.S. life sciences faculty engage in industry consulting. Despite reports that consulting contracts often impinge on faculty and university interests, institutional approaches to regulating consulting agreements are largely unknown., Objective: To investigate the nature of institutional oversight of faculty consulting contracts at U.S. schools of medicine and public health., Design: Structured telephone interviews with institutional administrators. Questions included the nature of oversight for faculty consulting agreements, if any, and views about consulting as a private versus institutional matter. Interviews were analyzed using a structured coding scheme., Setting: All accredited schools of medicine and public health in the U.S., Participants: Administrators responsible for faculty affairs were identified via internet searches and telephone and email follow-up. The 118 administrators interviewed represented 73% of U.S. schools of medicine and public health, and 75% of those invited to participate., Intervention: Structured, 15-30 minute telephone interviews., Main Outcomes and Measures: Prevalence and type of institutional oversight; responses to concerning provisions in consulting agreements; perceptions of institutional oversight., Results: One third of institutions (36%) required faculty to submit at least some agreements for institutional review and 36% reviewed contracts upon request, while 35% refused to review contracts. Among institutions with review, there was wide variation the issues covered. The most common topic was intellectual property rights (64%), while only 23% looked at publication rights and 19% for inappropriately broad confidentiality provisions. Six in ten administrators reported they had no power to prevent faculty from signing consulting agreements. Although most respondents identified institutional risks from consulting relationships, many maintained that consulting agreements are "private.", Conclusions and Relevance: Oversight of faculty consulting agreements at U.S. schools of medicine and public health is inconsistent across institutions and usually not robust. The interests at stake suggest the need for stronger oversight., Competing Interests: The authors have declared that no competing interests exist.

Fatty acid binding protein 4 (FABP4), a member of a family of lipid-binding proteins, is known to play a role in inflammation by virtue of its ability to regulate intracellular events such as lipid fluxes and signaling. Studies have indicated a proinflammatory role for FABP4 in allergic asthma although its expression and function in eosinophils, the predominant inflammatory cells recruited to allergic airways, were not investigated. We examined expression of FABP4 in murine eosinophils and its role in regulating cell recruitment in vitro as well as in cockroach antigen (CRA)-induced allergic airway inflammation. CRA exposure led to airway recruitment of FABP4-expressing inflammatory cells, specifically eosinophils, in wild-type (WT) mice. FABP4 expression in eosinophils was induced by TNF-α as well as IL-4 and IL-13. FABP4-deficient eosinophils exhibited markedly decreased cell spreading/formation of leading edges on vascular cell adhesion molecule-1 and significantly decreased adhesion to intercellular adhesion molecule-1 associated with reduced β2-integrin expression relative to WT cells. Furthermore, FABP4-deficient eosinophils exhibited decreased migration, F-actin polymerization, calcium flux, and ERK(1/2) phosphorylation in response to eotaxin-1. In vivo, CRA-challenged FABP4-deficient mice exhibited attenuated eosinophilia and significantly reduced airway inflammation (improved airway reactivity, lower IL-5, IL-13, TNF-α, and cysteinyl leukotriene C4 levels, decreased airway structural changes) compared with WT mice. In conclusion, expression of FABP4 in eosinophils is induced during conditions of inflammation and plays a proinflammatory role in the development of allergic asthma by promoting eosinophil adhesion and migration and contributing to the development of various aspects of airway inflammation.

Introduction: Spinal fixation is a common surgical procedure. Frequently, fixation for spinal stabilization requires use of instrumentation such as pedicle screws and fixation plates. Aerodigestive and vascular perforations from such procedures are infrequent albeit known complications from these procedures., Presentation of Case: This case details an uncommon situation in which a patient with anterior cervical spine fixation in the distant past was found to have a migratory pedicle screw. The patient had symptoms of neck pain and dysphagia. Radiographic studies were helpful in demonstrating the problem. While undergoing a physical examination, the patient was witnessed to expectorate the screw. Further work up with panendoscopy was undertaken and the patient managed conservatively., Discussion: The upper aerodigestive system rarely experiences perforation from spinal stabilization hardware. When it occurs, management should include a dedicated investigation of the involved portions of the digestive system to avoid further complication., Conclusion: This case presents an rare occurrence of aerodigestive perforation of a spinal pedicle screw which was self-removed., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Atrial fibrosis appears to be a key factor in the genesis and/or perpetuation of atrial fibrillation (AF). The pathological distribution of atrial fibrosis is geographically consistent with the attachments between the posterior left atrium and the pericardium along the reflections where wall stiffness is increased and structural changes are found. While there is a wide range of complex etiological factors and electrophysiological mechanisms in AF, there is evidence for a common pathophysiological pathway that could account for deliberate substrate formation and progression of AF. Anatomical stresses along the atrium, mediated by the elastic modulus mismatch between atrial tissue and the pericardium, result in inflammatory and fibrotic changes which create the substrate for atrial fibrillation. This may explain the anatomical predominance of pulmonary vein triggers earlier in the development of atrial fibrillation and the increasing involvement of the atrium as the disease progresses. Ablative treatments that address the progressive nature of atrial fibrillation and fibrosis may yield improved success rates.

Objective: To determine case outcomes in a communication-and-resolution program (CRP) implemented to respond to adverse events in general surgery., Study Setting: Five acute-care hospitals in New York City., Study Design: Following CRP implementation, hospitals recorded information about each CRP event for 22 months., Data Collection Methods: Risk managers prospectively collected data in collaboration with representatives from the hospital's insurer. External researchers administered an online satisfaction survey to clinicians involved in CRP events., Principal Findings: Among 125 CRP cases, disclosure conversations were carried out in 92 percent, explanations were conveyed in 88 percent, and apologies were offered in 72.8 percent. Three quarters of events did not involve substandard care. Compensation offers beyond bill waivers were deemed appropriate in 9 of 30 of cases in which substandard care caused harm and communicated in six such cases. In 44 percent of cases, hospitals identified steps that could be taken to improve safety. Clinicians had low awareness of the workings of the CRP, but high satisfaction with their experiences., Conclusions: The bulk of CRPs' work is in investigating and communicating about events not caused by substandard care. These CRPs were quite successful in handling such events, but less consistent in offering compensation in cases involving substandard care., (© Health Research and Educational Trust.)

Objective: To implement a communication-and-resolution program (CRP) in a setting in which liability insurers and health care facilities must collaborate to resolve incidents involving a facility and separately insured clinicians., Study Setting: Six hospitals and clinics and a liability insurer in Washington State., Study Design: Sites designed and implemented CRPs and contributed information about cases and operational challenges over 20 months. Data were qualitatively analyzed., Data Collection Methods: Data from interviews with personnel responsible for CRP implementation were triangulated with data on program cases collected by sites and notes recorded during meetings with sites and among project team members., Principal Findings: Sites experienced small victories in resolving particular cases and streamlining some working relationships, but they were unable to successfully implement a collaborative CRP. Barriers included the insurer's distance from the point of care, passive rather than active support from top leaders, coordinating across departments and organizations, workload, nonparticipation by some physicians, and overcoming distrust., Conclusions: Operating CRPs where multiple organizations must collaborate can be highly challenging. Success likely requires several preconditions, including preexisting trust among organizations, active leadership engagement, physicians' commitment to participate, mechanisms for quickly transmitting information to insurers, tolerance for missteps, and clear protocols for joint investigations and resolutions., (© Health Research and Educational Trust.)

Convergent atrial fibrillation ablation involves extensive epicardial as well as endocardial ablation of the left atrium. We examined whether it changes the morphology of the surface P wave. We reviewed electrocardiograms of 29 patients who underwent convergent ablation for atrial fibrillation. In leads V1, II and III, we measured P wave duration, area and amplitude before ablation, and at 1, 3 and 6 months from ablation. After ablation, there were no significant changes in P wave amplitude, area, or duration in leads II and III. There was a significant reduction in the area of the terminal negative deflection of the P wave in V1 from 0.38 mm(2) to 0.13 mm(2) (p = 0.03). There is also an acute increase in the amplitude and duration of the positive component of the P wave in V1 followed by a reduction in both by 6 months. Before ablation, 62.5% of the patients had biphasic P waves in V1. In 6 months, only 39.2% of them had biphasic P waves. Hybrid ablation causes a reduction of the terminal negative deflection of the P wave in V1 as well as temporal changes in the duration and amplitude of the positive component of the P wave in V1. This likely reflects the reduced electrical contribution of the posterior left atrium after ablation as well as anatomical and autonomic remodeling. Recognition of this altered sinus P wave morphology is useful in the diagnosis of atrial arrhythmias in this patient population., (Copyright © 2016 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.)

Trafficking and recruitment of eosinophils during allergic airway inflammation is mediated by the phosphatidylinositol 3-kinase (PI3K) family of signaling molecules. The role played by the p110δ subunit of PI3K (PI3K p110δ) in regulating eosinophil trafficking and recruitment was investigated using a selective pharmacological inhibitor (IC87114). Treatment with the PI3K p110δ inhibitor significantly reduced murine bone marrow-derived eosinophil (BM-Eos) adhesion to VCAM-1 as well as ICAM-1 and inhibited activation-induced changes in cell morphology associated with reduced Mac-1 expression and aberrant cell surface localization/distribution of Mac-1 and α4. Infused BM-Eos demonstrated significantly decreased rolling and adhesion in inflamed cremaster muscle microvessels of mice treated with IC87114 compared with vehicle-treated mice. Furthermore, inhibition of PI3K p110δ significantly attenuated eotaxin-1-induced BM-Eos migration and prevented eotaxin-1-induced changes in the cytoskeleton and cell morphology. Knockdown of PI3K p110δ with siRNA in BM-Eos resulted in reduced rolling, adhesion, and migration, as well as inhibition of activation-induced changes in cell morphology, validating its role in regulating trafficking and migration. Finally, in a mouse model of cockroach antigen-induced allergic airway inflammation, oral administration of the PI3K p110δ inhibitor significantly inhibited airway eosinophil recruitment, resulting in attenuation of airway hyperresponsiveness in response to methacholine, reduced mucus secretion, and expression of proinflammatory molecules (found in inflammatory zone-1 and intelectin-1). Overall, these findings indicate the important role played by PI3K p110δ in mediating BM-Eos trafficking and migration by regulating adhesion molecule expression and localization/distribution as well as promoting changes in cell morphology that favor recruitment during inflammation.

Allergic airway inflammation, including asthma, is usually characterized by the predominant recruitment of eosinophils. However, neutrophilia is also prominent during severe exacerbations. Cell surface-expressed glycans play a role in leukocyte trafficking and recruitment during inflammation. Here, the involvement of UDP-N-acetylglucosamine:α-6-D-mannoside β1,6-N-acetylglucosaminyltransferase V (MGAT5)-modified N-glycans in eosinophil and neutrophil recruitment during allergic airway inflammation was investigated. Allergen-challenged Mgat5-deficient (Mgat5(-/-)) mice exhibited significantly attenuated airway eosinophilia and inflammation (decreased Th2 cytokines, mucus production) compared with WT counterparts, attributable to decreased rolling, adhesion, and survival of Mgat5(-/-) eosinophils. Interestingly, allergen-challenged Mgat5(-/-) mice developed airway neutrophilia and increased airway reactivity with persistent elevated levels of proinflammatory cytokines (IL-17A, TNFα, IFNγ)). This increased neutrophil recruitment was also observed in LPS- and thioglycollate (TG)-induced inflammation in Mgat5(-/-) mice. Furthermore, there was significantly increased recruitment of infused Mgat5(-/-) neutrophils compared with WT neutrophils in the peritoneal cavity of TG-exposed WT mice. Mgat5(-/-) neutrophils demonstrated enhanced adhesion to P-selectin as well as increased migration toward keratinocyte-derived chemokine compared with WT neutrophils in vitro along with increased calcium mobilization upon activation and expression of elevated levels of CXCR2, which may contribute to the increased neutrophil recruitment. These data indicate an important role for MGAT5-modified N-glycans in differential regulation of eosinophil and neutrophil recruitment during allergic airway inflammation.

Non ischemic dilated cardiomyopathy (NIDCM) is a disorder of myocardium. It has varying etiologies. Albeit the varying etiologies of this heart muscle disorder, it presents with symptoms of heart failure, and rarely as sudden cardiac death (SCD). Manifestations of this disorder are in many ways similar to its counterpart, ischemic dilated cardiomyopathy (IDCM). A proportion of patients with NIDCM carries a grave prognosis and is prone to sudden cardiac death from sustained ventricular arrhythmias. Identification of this subgroup of patients who carry the risk of sudden cardiac death despite adequate medical management is a challenge. Yet another method is a blanket treatment of patients with this disorder with anti arrhythmic medications or anti tachyarrhythmia devices like implantable cardioverter defibrillators (ICD). However this modality of treatment could be a costly exercise even for affluent economies. In this review we try to analyze the existing data of risk stratification of NIDCM and its clinical implications in practice.