Interferon-Inducible CXC Chemokines Directly Contribute to Host Defense against Inhalational Anthrax in a Murine Model of Infection

Chemokines have been found to exert direct, defensin-like antimicrobial activity in vitro, suggesting that, in addition to orchestrating cellular accumulation and activation, chemokines may contribute directly to the innate host response against infection. No observations have been made, however, demonstrating direct chemokine-mediated promotion of host defense in vivo. Here, we show that the murine interferon-inducible CXC chemokines CXCL9, CXCL10, and CXCL11 each exert direct antimicrobial effects in vitro against Bacillus anthracis Sterne strain spores and bacilli including disruptions in spore germination and marked reductions in spore and bacilli viability as assessed using CFU determination and a fluorometric assay of metabolic activity. Similar chemokine-mediated antimicrobial activity was also observed against fully virulent Ames strain spores and encapsulated bacilli. Moreover, antibody-mediated neutralization of these CXC chemokines in vivo was found to significantly increase host susceptibility to pulmonary B. anthracis infection in a murine model of inhalational anthrax with disease progression characterized by systemic bacterial dissemination, toxemia, and host death. Neutralization of the shared chemokine receptor CXCR3, responsible for mediating cellular recruitment in response to CXCL9, CXCL10, and CXCL11, was not found to increase host susceptibility to inhalational anthrax. Taken together, our data demonstrate a novel, receptor-independent antimicrobial role for the interferon-inducible CXC chemokines in pulmonary innate immunity in vivo. These data also support an immunomodulatory approach for effectively treating and/or preventing pulmonary B. anthracis infection, as well as infections caused by pathogenic and potentially, multi-drug resistant bacteria including other spore-forming organisms

Rediscovering the value of families for psychiatric genetics research

As it is likely that both common and rare genetic variation are important for complex disease risk, studies that examine the full range of the allelic frequency distribution should be utilized to dissect the genetic influences on mental illness. The rate limiting factor for inferring an association between a variant and a phenotype is inevitably the total number of copies of the minor allele captured in the studied sample. For rare variation, with minor allele frequencies of 0.5% or less, very large samples of unrelated individuals are necessary to unambiguously associate a locus with an illness. Unfortunately, such large samples are often cost prohibitive. However, by using alternative analytic strategies and studying related individuals, particularly those from large multiplex families, it is possible to reduce the required sample size while maintaining statistical power. We contend that using whole genome sequence (WGS) in extended pedigrees provides a cost-effective strategy for psychiatric gene mapping that complements common variant approaches and WGS in unrelated individuals. This was our impetus for forming the “Pedigree-Based Whole Genome Sequencing of Affective and Psychotic Disorders” consortium. In this review, we provide a rationale for the use of WGS with pedigrees in modern psychiatric genetics research. We begin with a focused review of the current literature, followed by a short history of family-based research in psychiatry. Next, we describe several advantages of pedigrees for WGS research, including power estimates, methods for studying the environment, and endophenotypes. We conclude with a brief description of our consortium and its goals.This research was supported by National Institute of Mental Health grants U01 MH105630 (DCG), U01 MH105634 (REG), U01 MH105632 (JB), R01 MH078143 (DCG), R01 MH083824 (DCG & JB), R01 MH078111 (JB), R01 MH061622 (LA), R01 MH042191 (REG), and R01 MH063480 (VLN).UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Biología Celular y Molecular (CIBCM)UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biologí

Author Correction:Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article

Telemedicine implementation and reimbursement surveys

Association of Telehealth Service Providers (ATSP) SurveysThe ATSP published annual reports from 1997 to 2001 that included information on U.S. teledermatology services [1]. The 2001 report was based on a questionnaire sent to 206 telemedicine programs. The report provided information on the 82 telemedicine programs that responded and included the clinical specialties provided. The ATSP report did not include reimbursement information.2002 AMD Telemedicine/American Telemedicine Association (ATA) Reimbursement SurveyIn 2002, AMD Telemedicine and the ATA conducted a survey of telemedicine reimbursement [2]. The initial survey was sent to approximately 2,000 ATA members. Despite a poor response rate, ATA and AMD Telemedicine identified 141 active U.S. telemedicine programs with 72 of the 141 programs that billed for telemedicine services. These 72 programs were then surveyed by telephone. The survey revealed that 38 of the 72 programs (53%) were reimbursed for telemedicine services by private payers and that 150 private payers reimbursed for telemedicine in 24 states. Blue Cross/Blue Shield reimbursed in 13 states whereas Medicaid reimbursed in only 18 states. Four states had legislations mandating private payer reimbursement of telemedicine services: California SB 1665 (1996), Kentucky HB 177 (2000), Louisiana SB 773 (1995), and Texas HB 2033 (1997). Detailed survey results were posted on the “Private Payer Reimbursement Information Directory” web site (http://www.amdtelemedicine.com/private_payer/index.cfm), which is regularly updated with private payers and states in which Medicaid reimburses for telemedicine. As of June 2005, Blue Cross/Blue Shield reimbursed for telemedicine services in 21 states

Improvement of eumycetoma with itraconazole

Treatment of eumycetoma, both medical and surgical, is difficult and often unsuccessful. We describe a case of maduromycosis, 18 years in duration, with significant improvement after 6 months of itraconazole therapy