Multigeneration Cross-Contamination of Mail with Bacillus anthracis Spores.

The release of biological agents, including those which could be used in biowarfare or bioterrorism in large urban areas, has been a concern for governments for nearly three decades. Previous incidents from Sverdlosk and the postal anthrax attack of 2001 have raised questions on the mechanism of spread of Bacillus anthracis spores as an aerosol or contaminant. Prior studies have demonstrated that Bacillus atrophaeus is easily transferred through simulated mail handing, but no reports have demonstrated this ability with Bacillus anthracis spores, which have morphological differences that may affect adhesion properties between spore and formite.

Decontamination efficacy of three commercial-off-the-shelf (COTS) sporicidal disinfectants on medium-sized panels contaminated with surrogate spores of Bacillus anthracis.

In the event of a wide area release and contamination of a biological agent in an outdoor environment and to building exteriors, decontamination is likely to consume the Nation's remediation capacity, requiring years to cleanup, and leading to incalculable economic losses. This is in part due to scant body of efficacy data on surface areas larger than those studied in a typical laboratory (5×10-cm), resulting in low confidence for operational considerations in sampling and quantitative measurements of prospective technologies recruited in effective cleanup and restoration response. In addition to well-documented fumigation-based cleanup efforts, agencies responsible for mitigation of contaminated sites are exploring alternative methods for decontamination including combinations of disposal of contaminated items, source reduction by vacuuming, mechanical scrubbing, and low-technology alternatives such as pH-adjusted bleach pressure wash.

Modeling the clinical phenotype of BTK inhibition in the mature murine immune system.

Inhibitors of Bruton's tyrosine kinase (BTK) possess much promise for the treatment of oncologic and autoimmune indications. However, our current knowledge of the role of BTK in immune competence has been gathered in the context of genetic inactivation of btk in both mice and man. Using the novel BTK inhibitor PF-303, we model the clinical phenotype of BTK inhibition by systematically examining the impact of PF-303 on the mature immune system in mice.

Current options in the management of pellucid marginal degeneration.

Purpose: To review and evaluate current and future directions in the diagnosis and surgical management of pellucid marginal degeneration (PMD), including penetrating keratoplasty, full-thickness crescentic wedge resection (FTCWR), deep anterior lamellar keratoplasty (DALK), crescentic lamellar wedge resection (CLWR), crescentic lamellar keratoplasty, tuck-in lamellar keratoplasty (TILK), toric phakic intraocular lens (PIOL) implantation, intrastromal corneal ring segment implantation (ICRS), corneal collagen cross-linking (CXL), and combined therapies. This is the first review article looking at the literature specific to PMD.

Methods: Review of published studies.

Selectively targeting an inactive conformation of interleukin-2-inducible T-cell kinase by allosteric inhibitors.

ITK (interleukin-2-inducible T-cell kinase) is a critical component of signal transduction in T-cells and has a well-validated role in their proliferation, cytokine release and chemotaxis. ITK is an attractive target for the treatment of T-cell-mediated inflammatory diseases. In the present study we describe the discovery of kinase inhibitors that preferentially bind to an allosteric pocket of ITK.

Quantitative analysis of target coverage and germinal center response by a CXCL13 neutralizing antibody in a T-dependent mouse immunization model.

Purpose: Study the impact of CXCL13 neutralization on germinal center (GC) response in vivo, and build quantitative relationship between target coverage and pharmacological effects at the target tissue.

Methods: An anti-CXCL13 neutralizing monoclonal antibody was dosed in vivo in a T-dependent mouse immunization (TDI) model. A quantitative site-of-action (SoA) model was developed to integrate antibody PK and total CXCL13 levels in serum and spleen towards estimating target coverage as a function of dose.

Selective inhibition of BTK prevents murine lupus and antibody-mediated glomerulonephritis.

Autoantibody production and immune complex deposition within the kidney promote renal disease in patients with lupus nephritis. Thus, therapeutics that inhibit these pathways may be efficacious in the treatment of systemic lupus erythematosus. Bruton's tyrosine kinase (BTK) is a critical signaling component of both BCR and FcR signaling.

CDR-restricted engineering of native human scFvs creates highly stable and soluble bifunctional antibodies for subcutaneous delivery.

While myriad molecular formats for bispecific antibodies have been examined to date, the simplest structures are often based on the scFv. Issues with stability and manufacturability in scFv-based bispecific molecules, however, have been a significant hindrance to their development, particularly for high-concentration, stable formulations that allow subcutaneous delivery. Our aim was to generate a tetravalent bispecific molecule targeting two inflammatory mediators for synergistic immune modulation.

Corneal biomechanics in iatrogenic ectasia and keratoconus: A review of the literature.

The Ocular Response Analyzer (ORA) (Reichert Ophthalmic Instruments, Buffalo, NY) allows direct measurement of corneal biomechanical properties. Since its introduction, many studies have sought to elucidate the clinical applications of corneal hysteresis (CH) and corneal resistance factor (CRF). More recently, detailed corneal deformation signal waveform analysis (WA) has potentially expanded the diagnostic capabilities of the ORA.

Sources of medical error in refractive surgery.

Purpose: To evaluate the causes of laser programming errors in refractive surgery and outcomes in these cases.

Methods: In this multicenter, retrospective chart review, 22 eyes of 18 patients who had incorrect data entered into the refractive laser computer system at the time of treatment were evaluated. Cases were analyzed to uncover the etiology of these errors, patient follow-up treatments, and final outcomes.

Astigmatism induced by conventional spherical ablation after PRK and LASIK in myopia with astigmatism < 1.00 D.

Background: The purpose of this study was to evaluate surgically-induced astigmatism after spherical ablation in photorefractive keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK) for myopia with astigmatism < 1.00 D.

Methods: The charts of patients undergoing spherical PRK or LASIK for the correction of myopia with minimal astigmatism of <1.

Laser in situ keratomileusis in patients with collagen vascular disease: a review of the literature.

Purpose: To evaluate the current United States Food and Drug Administration (FDA) recommendations regarding laser in situ keratomileusis (LASIK) surgery in patients with collagen vascular diseases (CVD) and assess whether these patients make appropriate candidates for laser vision correction, and offer treatment recommendations based on identified clinical data.

Methods: A literature search was conducted using PubMed, Medline, and Ovid to identify all existing studies of LASIK in patients with collagen vascular diseases. The search was conducted without date limitations.

Anesthetic keratopathy presenting as bilateral Mooren-like ulcers.

This observational case report describes the development of bilateral Mooren-like ulcers in a patient with anesthetic keratopathy. A 42-year-old man with a recent history of minor eye trauma and pain self-treated with tetracaine eye drops presented with complaints of acutely worsening vision and severe pain bilaterally. His visual acuity at presentation was limited to hand motion.

Laser in-situ keratomileusis in patients with diabetes mellitus: a review of the literature.

Purpose: A growing number of diabetic patients request laser in situ keratomileusis (LASIK) for elective vision correction each year. While the United States Food and Drug Administration considers diabetes a relative contraindication to LASIK surgery, there are several reports in the literature of LASIK being performed safely in this patient population. The purpose of this review was to examine whether diabetes should still be considered a contraindication to LASIK surgery by reviewing the ocular and systemic complications of diabetes, and examining the existing data on the outcomes of LASIK in diabetic patients.

Detection and tracking of a novel genetically tagged biological simulant in the environment.

A variant of Bacillus thuringiensis subsp. kurstaki containing a single, stable copy of a uniquely amplifiable DNA oligomer integrated into the genome for tracking the fate of biological agents in the environment was developed. The use of genetically tagged spores overcomes the ambiguity of discerning the test material from pre-existing environmental microflora or from previously released background material.

Multigeneration cross contamination of mail with Bacillus species spores by tumbling.

In 2001, envelopes loaded with Bacillus anthracis spores were mailed to Senators Daschle and Leahy as well as to the New York Post and NBC News buildings. Additional letters may have been mailed to other news agencies because there was confirmed anthrax infection of employees at these locations. These events heightened the awareness of the lack of understanding of the mechanism(s) by which objects contaminated with a biological agent might spread disease.

Tetracyclines that promote SMN2 exon 7 splicing as therapeutics for spinal muscular atrophy.

There is at present no cure or effective therapy for spinal muscular atrophy (SMA), a neurodegenerative disease that is the leading genetic cause of infant mortality. SMA usually results from loss of the SMN1 (survival of motor neuron 1) gene, which leads to selective motor neuron degeneration. SMN2 is nearly identical to SMN1 but has a nucleotide replacement that causes exon 7 skipping, resulting in a truncated, unstable version of the SMA protein.

Efficient methods for large-area surface sampling of sites contaminated with pathogenic microorganisms and other hazardous agents: current state, needs, and perspectives.

The recovery operations following the 2001 attacks with Bacillus anthracis spores were complicated due to the unprecedented need for large-area surface sampling and decontamination protocols. Since this event, multiple reports have been published describing recovery efficiencies of several surface sampling materials. These materials include fibrous swabs of various compositions, cloth wipes, vacuum socks, and adhesive tapes.

Surface sampling of spores in dry-deposition aerosols.

The ability to reliably and reproducibly sample surfaces contaminated with a biological agent is a critical step in measuring the extent of contamination and determining if decontamination steps have been successful. The recovery operations following the 2001 attacks with Bacillus anthracis spores were complicated by the fact that no standard sample collection format or decontamination procedures were established. Recovery efficiencies traditionally have been calculated based upon biological agents which were applied to test surfaces in a liquid format and then allowed to dry prior to sampling tests, which may not be best suited for a real-world event with aerosolized biological agents.

Three measures of sleep, sleepiness, and sleep deprivation and the risk of injury: a case-control and case-crossover study.

Purpose: Sleepiness and sleep deprivation are associated with injury, but few case-control studies have addressed them. We sought to add to the body of analytic observational studies.

Methods: Case-control and case-crossover study of 2517 injured patients interviewed in person in 3 emergency departments and matched by age, sex, rural versus urban, day of week, and hour of day with 1856 controls.