Recommended standards for newborn ICU design, eighth edition.

This is the eighth edition of the Recommended Standards for Newborn ICU Design. It contains substantive changes in recommendations for patient room size and feeding preparation areas, and a number of refinements of previous Recommended Standards with respect to family space, hand hygiene, lighting and other aspects of the newborn intensive care unit (NICU) design.

The design of neonatal incubators: a systems-oriented, human-centered approach.

OBJECTIVE: This report describes a multidisciplinary design project conducted in an academic setting reflecting a systems-oriented, human-centered philosophy in the design of neonatal incubator technologies. STUDY DESIGN: Graduate students in Architectural Design and Human Factors Engineering courses collaborated in a design effort that focused on supporting the needs of three user groups of incubator technologies: infant patients, family members and medical personnel. Design teams followed established human-centered design methods that included interacting with representatives from the user groups, analyzing sets of critical tasks and conducting usability studies with existing technologies. RESULT: An iterative design and evaluation process produced four conceptual designs of incubators and supporting equipment that better address specific needs of the user groups. CONCLUSION: This report introduces the human-centered design approach, highlights some of the analysis findings and design solutions, and offers a set of design recommendations for future incubation technologies.

beta3 Integrins mediate the cellular entry of hantaviruses that cause respiratory failure.

Newly emerged hantaviruses replicate primarily in the pulmonary endothelium, cause acute platelet loss, and result in hantavirus pulmonary syndrome (HPS). We now report that specific integrins expressed on platelets and endothelial cells permit the cellular entry of HPS-associated hantaviruses. Infection with HPS-associated hantaviruses, NY-1 and Sin Nombre virus (SNV), is inhibited by antibodies to beta3 integrins and by the beta3-integrin ligand, vitronectin. In contrast, infection with the nonpathogenic (no associated human disease) Prospect Hill virus was inhibited by fibronectin and beta1-specific antibodies but not by beta3-specific antibodies or vitronectin. Transfection with recombinant alphaIIb beta3 or alphav beta3 integrins rendered cells permissive to NY-1 and SNV but not Prospect Hill virus infection, indicating that alphaIIb beta3 and alphav beta3 integrins mediate the entry of NY-1 and SNV hantaviruses. Furthermore, entry is divalent cation independent, not blocked by arginine-glycine-aspartic acid peptides and still mediated by, ligand-binding defective, alphaIIb beta3-integrin mutants. Hence, NY-1 and SNV entry is independent of beta3 integrin binding to physiologic ligands. These findings implicate integrins as cellular receptors for hantaviruses and indicate that hantavirus pathogenicity correlates with integrin usage.

A monoclonal antibody that blocks poliovirus attachment recognizes the lymphocyte homing receptor CD44.

A monoclonal antibody, AF3, was previously shown to specifically inhibit poliovirus binding to HeLa cells and to detect a 100-kDa glycoprotein only in cell lines and tissues permissive for poliovirus infection. These results suggested that the 100-kDa protein may be involved in the pathogenesis of poliomyelitis and the cellular function of the poliovirus receptor site. To study further the role of the 100-kDa protein in poliovirus attachment, immunoaffinity purification, amino acid sequencing, and cDNA cloning were undertaken. The results demonstrate that antibody AF3 reacts with the lymphocyte homing receptor CD44, a multifunctional cell surface glycoprotein involved in the homing of circulating lymphocytes to lymph nodes and the modulation of lymphocyte adhesion and activation. Antibody AF3 reacts with a subset of CD44 molecules (AF3CD44H), which appears to be a small fraction of the heterogeneously glycosylated CD44 molecules expressed on hematopoietic and nonhematopoietic cells. Anti-CD44 monoclonal antibodies, previously reported to induce CD44-mediated modulation of lymphocyte activation and adhesion, compete with 125I-AF3 in binding assays, demonstrating functional overlap among the epitopes. The anti-CD44 monoclonal antibody A3D8, which binds to a greater molecular weight range of CD44 than does AF3, inhibits poliovirus binding to a similar degree. CD44 does not act as a poliovirus receptor, since CD44-expressing mouse L-cell transformants did not bind poliovirus. The poliovirus receptor and AF3CD44H may be noncovalently associated, or they may interact through the cytoskeleton or signal transduction pathways.

Identification of the integrin VLA-2 as a receptor for echovirus 1.

Cell surface receptors for echovirus, a common human pathogen, were identified with monoclonal antibodies that protected susceptible cells from infection with echovirus 1. These monoclonal antibodies, which prevented virus attachment to specific receptor sites, recognized the alpha and beta subunits of the integrin VLA-2 (alpha 2 beta 1), a receptor for collagen and laminin. RD rhabdomyosarcoma cells expressed little VLA-2, did not bind to 35S-labeled virus, and resisted infection until transfected with complementary DNA encoding the alpha 2 subunit of VLA-2. Thus, integrins, adhesion receptors important in interactions between cells and with the extracellular matrix, can mediate virus attachment and infection.

Monoclonal antibody identification of a 100-kDa membrane protein in HeLa cells and human spinal cord involved in poliovirus attachment.

Unique receptor sites for poliovirus are considered to be the primary determinant of the virus' cell and tissue-type specificity. To study the poliovirus-cell interaction, eight monoclonal antibodies that specifically block the cytopathic effects of poliovirus were generated by using HeLa cell preparations as immunogen and a newly developed colorimetric screening assay. Plaque-inhibition assays confirmed the viral specificity of the antibodies, and when one antibody, AF3, was used as a probe in immunoblots of cell membrane preparations, it detected a 100-kDa band in only those cell lines and tissues permissive for poliovirus infection. AF3 also specifically inhibited radiolabeled poliovirus binding to cells. In terms of tissue specificity, AF3 detected the 100-kDa band in membrane preparations from human spinal cord but not in organ homogenates of human kidney or in murine tissue, including the central nervous system. Furthermore, AF3 detected the band in a human-mouse hybrid cell line containing human chromosome 19, which confers permissivity for poliovirus infection, but the antibody did not detect the band in a human chromosome 19-deficient subclone. In an immunohistochemical study of the human brainstem, AF3 stained neurons in the reticular formation and clusters of brainstem neurons, consistent with the known pattern of damage caused by poliovirus infection in the brainstem. Furthermore, AF3 reacted with human peripheral mononuclear cells, consistent with the known replication of poliovirus in Peyer's patches and tonsils. These results strongly suggest that the 100-kDa band detected by antibody AF3 is, or is closely associated with, the poliovirus receptor site.

The outcome of hidden neurotic illness treated in general practice.

One thousand patients attending a general practice surgery were asked to complete the general health questionnaire as the first stage of screening for hidden minor psychiatric disorders. Those who had an unexpectedly high score of 20 or more were randomly allocated to doctors or health visitors for treatment. After one year, these two groups were reinterviewed by the doctors and health visitors respectively and comparable rates of recovery were found. After five years, they were interviewed again and a second general health questionnaire completed. It was found that both groups had improved significantly, and that there was no significant difference between them.Poor outcome was associated with problems with children, household or neighbours and with a previous history of psychiatric illness. Improvement was associated with physical treatment of the original disorder, resolution of the original problem and job satisfaction.The implication of these findings for the comparative management of minor psychiatric disorders by general practitioners and non-medical health workers in primary care are discussed.