Citations

Abstract Allergic sensitization in asthma develops as a consequence of complex interactions between T cells and antigen-presenting cells. We have developed several in vivo models to study allergen-specific T cell and B cell function and their relevance to allergic airway hyperresponsiveness (AHR), focusing on the role of the costimulatory molecules CD80 and CD86. Treatment of mice with anti-CD86, but not anti-CD80, significantly inhibited increased serum levels of ovalbumin (OA)-specific IgE and IgG1, airway eosinophilia, and AHR both after 10 d of OA aerosol exposure (in the absence of adjuvant) and after intraperitoneal sensitization followed by repeated airway challenges. Inhibition of AHR was associated with decreased IL-4 and IL-5 levels in the BAL fluid of sensitized mice, suggesting impaired Th2 function in anti-CD86-treated animals. This effect was not seen when mice received treatment only before allergen challenge, indicating that anti-CD86 acts through inhibition of allergic sensitization and not simply by inhibiting the influx of inflammatory cells. These data suggest that the CD86 costimulatory ligand plays a major role in the development of allergic inflammation and AHR in allergen-challenged mice. Further, this study demonstrates that T–B cell interactions during allergic sensitization are amenable to therapeutic manipulation and that selective blockade of accessory signals can be an effective means for modulating distinct T cell functions.

Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer’s disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain’s connectivity pattern, allowing us to discover genetic variants that affect the human brain’s wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer’s disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism ( MACROD2 ), development ( NEDD4 ), and mental retardation ( UBE2A ) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases.

Radiographs were studied of 91 feet in 62 patients with the diagnosis of bunionette and no prior bunionette or hallux valgus operations. Various radiologic measurements were compared to a matched control group with no bunionette symptoms or previous forefoot operations. The bunionette group had a significantly increased metatarsophalangeal 5 angle, intermetatarsal 4–5 angle, and intermetatarsal 1–2 angle compared to the control group. Bunionettes were not commonly associated with lateral bowing of the fifth metatarsal or with an increased fifth metatarsal head width. Symmetry was noted between symptomatic and opposite asymptomatic feet, with the exception of an increased intermetatarsal 4–5 angle in the symptomatic feet.

Objective: Therapeutic goals for chronic mental disorders like major depressive disorder (MDD) and schizophrenia have evolved in parallel with the growing medical knowledge about the course and treatment of these disorders. Although the knowledge base regarding the clinical course of ADHD, a chronic psychiatric disorder, has evolved beyond symptomatic improvement and short-term treatment response, long-term goals, such as functional remission, have not yet been clearly defined. Method: A PubMed literature search was conducted to investigate the therapeutic goals of pharmacologic treatment referenced in the published literature from January 1998 through February 2010 using the following commonly used ADHD treatments as keywords: amphetamine, methylphenidate, atomoxetine, lisdexamfetamine, guanfacine, and clonidine. This search was then combined with an additional search that included the following outcome keywords: remission, relapse, remit, response, normal, normalization, recovery, and effectiveness. Results: Our search identified 102 publications. The majority (88.2% [90/102]) of these contained predefined criteria for treatment response. Predefined criteria for normalization and remission and/or relapse were presented in 4.9% (5/102), 12.7% (13/102), and 3.9% (4/102) of publications, respectively. There was a lack of consistency between the instruments used to measure outcomes as well as the criteria used to define treatment response, normalization, and remission as well as relapse. Conclusion: The therapeutic goals in treating ADHD should address optimal treatment outcomes that go beyond modest reductions of ADHD symptoms to include syndromatic, symptomatic, and functional remission. Future work should focus on reliable and valid tools to measure these outcomes in the clinical trial setting.

PurposeTo investigate the influence of portal pressure on the shear stiffness of the liver and spleen in a well‐controlled in vivo porcine model with magnetic resonance elastography (MRE). A significant correlation between portal pressure and tissue stiffness could be used to noninvasively assess increased portal venous pressure (portal hypertension), which is a frequent clinical condition caused by cirrhosis of the liver and is responsible for the development of many lethal complications.Materials and MethodsDuring multiple intraarterial infusions of Dextran‐40 in three adult domestic pigs in vivo, 3D abdominal MRE was performed with left ventricle and portal catheters measuring blood pressure simultaneously. Least‐squares linear regressions were used to analyze the relationship between tissue stiffness and portal pressure.ResultsLiver and spleen stiffness have a dynamic component that increases significantly following an increase in portal or left ventricular pressure. Correlation coefficients with the linear regressions between stiffness and pressure exceeded 0.8 in most cases.ConclusionThe observed stiffness–pressure relationship of the liver and spleen could provide a promising noninvasive method for assessing portal pressure. Using MRE to study the tissue mechanics associated with portal pressure may provide new insights into the natural history and pathophysiology of hepatic diseases and may have significant diagnostic value in the future. J. Magn. Reson. Imaging 2013;38:809–815. © 2013 Wiley Periodicals, Inc.

Aims: The NCDR CathPCI Registry collects detailed clinical, process-of-care and outcomes data for patients undergoing coronary angiography and percutaneous coronary intervention (PCI) in the USA. The registry contributes to quality of care by providing data feedback on a wide range of performance metrics to participating centres and by facilitating local and national quality improvement efforts. Interventions: No treatments are mandated, participating centres receive routine quality-of-care and outcomes performance feedback reports and access to a quality dashboard for personalized performance reports. Population: Patients undergoing cardiac catheterization and PCI are retrospectively identified. No informed consent is required, as data are anonymised. From inception in 1998, more than 12 million records have been submitted from 1577 participating US centres. Baseline data: Approximately 250 fields encompassing patient demographics, medical history and risk factors, hospital presentation, initial cardiac status, procedural details, medications, laboratory values, and in-hospital outcomes. Linkages with outside sources of data have permitted longitudinal outcomes assessment in some cases. Centre personnel enter the data into the registry, in some cases facilitated by software vendors. There are non-financial incentives for centre participation. Data completeness is noteworthy with most fields missing at rates less than 5%. A comprehensive data quality program is employed to enhance data validity. Endpoints: Main outcome measures include quality process metrics and in-hospital patient outcomes. Data are available for research by application to: http://www.ncdr.com