Cell-penetrating peptides (CPPs) inhibit Herpes simplex virus entry at low micromolar concentrations and may be useful either as prophylactic or therapeutic agents for herpetic keratitis. The aim of this study was to assess the in vitro and in vivo toxicity of three CPPs-EB, TAT-C, and HOM (penetratin)-for the cornea. Incubation of primary (HK320) or immortalized (THK320) human keratocytes with the EB peptide (up to 100 microM), bHOMd (up to 200 microM), or TAT-C (up to 400 microM) resulted in no evidence of toxicity using a formazan dye-reduction assay. Similar results were obtained with a human trabecular meshwork cell line (TM-1), primary human foreskin fibroblasts (DP-9), Vero, and HeLa cells with EB and TATC. The bHOMd peptide showed some toxicity in Vero and HeLa cells, with CC50 values of 70 and 93 microM, respectively. The EB peptide did not inhibit macromolecular synthesis in Vero cells at concentrations below 150 microM, although cell proliferation was blocked at concentrations of EB above 50 microM. In vivo toxicity was assessed by applying peptides in Dulbecco's modified Eagle's medium to the cornea 4 times daily for 7 d. At concentrations 1000 times the IC50 values, the EB and bHOM peptides showed no toxicity, whereas TAT-C caused some mild eyelid swelling. Some slight epithelial cell sloughing was seen with the bKLA peptide in vivo. These results suggest that these CPPs-and EB in particular-have a favorable toxicity profile, and that further development is warranted.

Health care organizations can magnify the impact of their community service and other philanthropic activities by implementing programs that create shared value. By definition, shared value is created when an initiative generates benefit for the sponsoring organization while also generating societal and community benefit. Because the programs generate benefit for the sponsoring organizations, the magnitude of any particular initiative is limited only by the market for the benefit and not the resources that are available for philanthropy. In this article we use three initiatives in sectors other than health care to illustrate the concept of shared value. We also present examples of five types of shared value programs that are sponsored by health care organizations: telehealth, worksite health promotion, school-based health centers, green and healthy housing, and clean and green health services. On the basis of the innovativeness of health care organizations that have already implemented programs that create shared value, we conclude that the opportunities for all health care organizations to create positive impact for individuals and communities through similar programs is large, and the limits have yet to be defined.

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PURPOSE Inhalational anthrax is an extremely rare infectious disease with nonspecifi c initial symptoms, thus making diagnosis on clinical grounds diffi cult. After a covert release of anthrax spores, primary care physicians will be among the fi rst to evaluate cases. This study defi nes the primary care differential diagnosis of inhalational anthrax. METHODS In May 2002, we mailed survey instruments consisting of 3 randomly chosen case vignettes describing patients with inhalational anthrax to a nationwide random sample of 665 family physicians. Nonrespondents received additional mailings. Physicians were asked to provide their most likely nonanthrax diagnosis for each case. RESULTSThe response rate was 36.9%. Diagnoses for inhalational anthrax were grouped into 35 diagnostic categories, with pneumonia (42%), infl uenza (10%), viral syndrome (9%), septicemia (8%), bronchitis (7%), central nervous system infection (6%), and gastroenteritis (4%) accounting for 86% of all diagnoses. Diagnoses differed signifi cantly between cases that proved to be fatal and those that proved to be nonfatal.CONCLUSIONS Inhalational anthrax resembles common diagnoses in primary care. Surveillance systems for early detection of bioterrorism events that rely only on diagnostic codes will be hampered by false-positive alerts. Consequently, educating frontline physicians to recognize and respond to bioterrorism is of the highest priority. INTRODUCTIONC overt release of anthrax (Bacillus anthracis) spores as an act of terrorism will result in the unknowing and unsuspected exposure of persons. Some of those exposed will become infected through inhalation of spores; many of these persons will manifest some of the constellation of symptoms that can be associated with inhalational anthrax.1 For frontline clinicians-typically physicians, physician assistants, and nursepractitioners in primary care offi ces, urgent care centers, and emergency departments-early recognition of and response to inhalational anthrax is of paramount importance on both individual and populationwide levels. Inhalational anthrax is an extremely rare infectious disease. In 11 recent cases associated with bioterrorism, initial diagnoses were diverse, including gastroenteritis, bacterial meningitis, nonspecifi c viral syndrome, and bronchitis.3-7 A diagnosis of inhalational anthrax can be supported by imaging studies. Defi nitive diagnosis, however, depends on detection of B anthracis through culture, immunohistochemistry, or polymerase chain reaction. 1,8 In past anthrax outbreaks, initial diagnoses were aided by contextual information, such as occupation.9 Covert bioterrorism involving a rare pathogen robs the clinician of most contextual diagnostic clues.Early detection of bioterrorism events has become a national priority since September 11, 2001. 10,11 of electronic medical data has been proposed as one approach providing the "extreme timeliness of detection" necessary for appropriate response. 12 Electronic surveillance uses signal detection theory to id...

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