History and evolution of influenza control through vaccination: from the first monovalent vaccine to universal vaccines.

Influenza is a highly infectious airborne disease with an important epidemiological and societal burden; annual epidemics and pandemics have occurred since ancient times, causing tens of millions of deaths. A hundred years after this virus was first isolated, influenza vaccines are an important influenza prevention strategy and the preparations used display good safety and tolerability profiles. Innovative tools, such as recombinant technologies and intra-dermal devices, are currently being investigated in order to improve the immunological response. The recurring mutations of influenza strains has prompted the recent introduction of a quadrivalent inactivated vaccine. In the near future, scientific research will strive to produce a long-lasting universal vaccine containing an antigen that will offer protection against all influenza virus strains.

Governance, organization, accountability and sustainability of a region-wide school-based deworming program in Loreto, Peru.

Chau Cuica was the name given by the regional government of Loreto in Peru for its school-based deworming program which was initiated in 2012 with a donation of mebendazole from an international non-governmental organization. Embedded in the program from the start was a sentinel surveillance component which consisted of 16 sentinel schools representing Loreto's seven provinces. Coverage rates varied between 35% and 61% over the first two years of the program (and seven deworming cycles). Initial prevalences of soil-transmitted helminth infections were high, with 82.4% of schoolchildren having at least one infection and prevalences of both Ascaris lumbricoides and Trichuris trichiura infections both exceeding 60%. After two years, these prevalences had dropped to 56% for any STH infection, 38% for A. lumbricoides and 34% for T. trichiura. Importantly, the proportions of children with moderate and heavy infections also dropped. Both the regional Ministry of Health and the Ministry of Education were jointly charged to implement this deworming program. The program's costs were estimated to be approximately 22 cents (USD) per child per deworming cycle. The responsibility for the surveillance component was initially undertaken by research partners from a local NGO and a Canadian university, which transferred gradually over the course of the deworming program to being entirely the responsibility of the Ministry of Health. This regional deworming program may serve as a model for other jurisdictions that are planning a school-based deworming program with an integrated surveillance component to monitor impact.

Emerging Chagas disease: trophic network and cycle of transmission of Trypanosoma cruzi from palm trees in the Amazon.

A trophic network involving molds, invertebrates, and vertebrates, ancestrally adapted to the palm tree (Attalaea phalerata) microhabitat, maintains enzootic Trypanosoma cruzi infections in the Amazonian county Paço do Lumiar, state of Maranhão, Brazil. We assessed seropositivity for T. cruzi infections in the human population of the county, searched in palm trees for the triatomines that harbor these infections, and gathered demographic, environmental, and socioeconomic data. Rhodnius pictipes and R. neglectus in palm-tree frond clefts or in houses were infected with T. cruzi (57% and 41%, respectively). Human blood was found in 6.8% of R. pictipes in houses, and 9 of 10 wild Didelphis marsupialis had virulent T. cruzi infections. Increasing human population density, rain forest deforestation, and human predation of local fauna are risk factors for human T. cruzi infections.

Western blot analysis for nitrotyrosine protein adducts in livers of saline-treated and acetaminophen-treated mice.

The hepatic centrilobular necrosis produced by the analgesic/antipyretic acetaminophen correlates with metabolic activation of the drug leading to its covalent binding to protein. However, the molecular mechanism of the toxicity is not known. Recent immunohistochemical analyses using an antinitrotyrosine antiserum indicated that nitrotyrosine protein adducts co-localized with the acetaminophen-protein adducts in the centrilobular cells of the liver. Nitration of proteins is believed to occur by peroxynitrite, a substance formed by the rapid reaction of superoxide with nitric oxide. Nitric oxide and superoxide may be formed by activated Kupffer cells or by other cells. Because we were unable to successfully utilize the commercial antiserum in Western blot analyses of liver fractions, we developed a new antiserum. With our antiserum, liver fractions from saline-treated control and acetaminophen-treated mice were successfully analyzed for nitrated proteins. The immunogen for this new antiserum was synthesized by coupling 3-nitro-4-hydroxybenzoic acid to keyhole limpet hemocyanin. A rabbit immunized with this adduct yielded a high titer of an antiserum that recognized BSA nitrated with peroxynitrite. Immunoblot analysis of nitrated BSA indicated that nitrotyrosine present in a protein sample could be easily detected at levels of 20 pmoles. Immunohistochemical analyses indicated that nitrotyrosine protein adducts were detectable in the centrilobular areas of the liver. Immunoblot analysis of liver homogenates from both saline-treated and acetaminophen-treated mice (300 mg/kg) indicate that the major nitrotyrosine protein adducts produced have molecular weights of 36 kDa, 44 kDa, and 85 kDa. The 85-kDa protein stained with the most intensity. The hepatic homogenates of the acetaminophen- treated mice showed significantly increased levels of all protein adducts.

Evergreen staff: building a tree of knowledge for continuous learning.

Healthcare institutions breathed a collective sigh of relief on January 1, when efforts made for remediation, testing, and contingency planning for the year 2000 finally paid off. Now that the technology has been improved to ensure compatibility, it is important to keep the momentum going to improve efficiency and increase productivity and patient satisfaction levels. One way to incorporate organizational priorities, goals, and strategy at the departmental level is to develop an education plan that stresses mastering fundamental skills. This article explores the components and role of an education plan and identifies the types of efforts that result in the greatest return. It concludes with a case study.

Information technology implications of case management.

Information technology is a critical component to implementing a comprehensive and effective case management process. The vendor marketplace is aggressively working to address gaps in function and integration. In the meantime, organizations must begin now to plan their case management processes. This is no small task. Most organizations are struggling to develop the necessary manual systems through consensus building on a multidisciplinary basis. Success in developing and implementing a good manual system, although cumbersome, is an essential prerequisite to automation. Major organizational growth and restructuring is already under way in most settings to respond to the pressures of health care reform. Availability of a tight case management process with appropriate information technology support is the key to success.

Abnormal ipsilateral visual field representation in areas 17 and 18 of hypopigmented cats.

We compared the central projections of retinal ganglion cells in temporal retina and the cortical representation of visual fields in areas 17 and 18 in cats with various hypopigmentation phenotypes (albino, heterozygous albino, Siamese, and heterozygous Siamese). In all cats studied, we found that the extent of abnormal ipsilateral visual field representation varied widely, and more of the ipsilateral visual field was represented in area 18 than in area 17. The greatest degree of ipsilateral visual field representation was found in albino cats, followed by Siamese, heterozygous albino and heterozygote Siamese cats, respectively. Additionally, in the different groups there was wide variation in the numbers of contralaterally projecting alpha and beta ganglion cells in temporal retina. In all cases, however, contralaterally projecting alpha cells were found to extend further into temporal retina than beta cells. We found that in each cat studied, the maximum extent of the abnormal ipsilateral visual field representation in areas 18 and 17 corresponded to the location of the 50% decussation line (i.e., the point where 50% of the ganglion cells in temporal retina project to the contralateral hemisphere) for alpha and beta cells, respectively, for that cat. Our results suggest that the extent of the abnormal visual field representations in visual cortex of hypopigmented cats reflects the extent of contralaterally projecting retinal ganglion cells in temporal retina.

Concomitant sensitivity to orientation, direction, and color of cells in layers 2, 3, and 4 of monkey striate cortex.

The receptive field properties of cells in layers 2, 3, and 4 of area 17 (V1) of the monkey were studied quantitatively using colored and broad-band gratings, bars, and spots. Many cells in all regions studied responded selectively to stimulus orientation, direction, and color. Nearly all cells (95%) in layers 2 and 3 exhibited statistically significant orientation preferences (biases), most exhibited at least some color sensitivity, and many were direction sensitive. The degree of selectivity of cells in layers 2 and 3 varied continuously among cells; we did not find discrete regions containing cells sensitive to orientation and direction but not color, and vice versa. There was no relationship between the degree of orientation sensitivity of the cells studied and their degree of color sensitivity. There was also no obvious relationship between the receptive field properties studied and the cells' location relative to cytochrome oxidase-rich regions. Our findings are difficult to reconcile with the hypothesis that there is a strict segregation of cells sensitive to orientation, direction, and color in layers 2 and 3. In fact, the present results suggest the opposite since most cells in these layers are selective for a number of stimulus attributes.

Environmental management: a re-emerging vector control strategy.

Vector control may be accomplished by environmental management (EM), which consists of permanent or long-term modification of the environment, temporary or seasonal manipulation of the environment, and modifying or changing our life styles and practices to reduce human contact with infective vectors. The primary focus of this paper is EM in the control of human malaria, filariasis, arboviruses, Chagas' disease, and schistosomiasis. Modern EM developed as a discipline based primarily in ecologic principles and lessons learned from the adverse environmental impacts of rural development projects. Strategies such as the suppression of vector populations through the provision of safe water supplies, proper sanitation, solid waste management facilities, sewerage and excreta disposal systems, water manipulation in dams and irrigation systems, vector diversion by zooprophylaxis, and vector exclusion by improved housing, are discussed with appropriate examples. Vectors of malaria, filariasis, Chagas' disease, and schistosomiasis have been controlled by drainage or filling aquatic breeding sites, improved housing and sanitation, the use of expanded polystyrene beads, zooprophylaxis, or the provision of household water supplies. Community participation has been effective in the suppression of dengue vectors in Mexico and the Dominican Republic. Alone or combined with other vector control methods, EM has been proven to be a successful approach to vector control in a number of places. The future of EM in vector control looks promising.

Postnatal development of different classes of cat retinal ganglion cells.

Previous investigators have documented the postnatal development of alpha and beta type ganglion cells in cat retinae (Ramoa et al. [1987] Science 237:522-525; Ramoa et al. [1988] J. Neurosci. 8:4239-4261; Dann et al. [1987] Neurosci. Lett. 80:21-26; Dann et al. [1988] J. Neurosci. 8(5):1485-1499). The development of the remaining cells (about 50%), which constitute a heterogeneous group and are referred to here collectively as gamma cells (Boycott and Wässle, '74), has not been studied in detail. The purpose of this study was to compare the postnatal development of alpha, beta, and gamma cells in kitten and adult retinae using horseradish peroxidase histochemistry and the fluorescent dye DiI. In the kitten, alpha, beta, and gamma cells are recognizable. We find, as have others, that kitten alpha and beta cell bodies and dendritic fields are significantly smaller than in the adult. However, kitten gamma cells are nearly adult sized. In fact, at birth the cell bodies of beta cells throughout the retina are significantly smaller than those of gamma cells. During the first 12 weeks of life, alpha and beta cell bodies increase in size from 90% to 680% depending upon eccentricity. Gamma cells hardly increase in size at all. Also, the normal adult center-to-peripheral cell size gradient for alpha and beta cells is not seen in the neonate. Gamma cells show no such gradient in the neonate or adult. Our results suggest that the morphological development of alpha and beta cells occurs later than that of gamma cells and may explain some of the differences in the effects of visual deprivation and surgical manipulation upon the parallel Y-, X-, and W-cell pathways.

Selective depletion of beta cells affects the development of alpha cells in cat retina.

The results of previous studies suggest that class-specific interactions contribute to the development of the different classes of retinal ganglion cells. We tested this hypothesis by examining the morphologies and distributions of alpha (alpha) cells in regions of mature cat retina selectively depleted of beta (beta) cells as a result of visual cortex lesions at birth. We find that alpha cells in regions of central retina depleted of beta cells are abnormally large while alpha cells in regions of peripheral retina depleted of beta cells are abnormally small. The normal central-to-peripheral alpha cell soma-size gradient is absent in hemiretinae depleted of beta cells. The dendritic fields of alpha cells in the border of beta-cell-depleted hemiretina extend preferentially into the beta-cell-poor hemiretina. In spite of this, alpha cell bodies retain their normal retinal distribution and remain distributed in a nonrandom mosaic-like pattern. Thus, it appears that the development of alpha retinal ganglion cells is influenced by interactions both with other alpha cells (class-specific interactions) and with surrounding beta cells (nonclass-specific interactions).

The hospital-health center collaborative: a model for ambulatory care.

In summary, the staff and administration of the Muhlenberg-health center project feel it has thus far been successful in meeting its original goals of reducing duplication, ensuring access, controlling costs, and maintaining quality care. We believe that this model of cooperation benefits both organizations and provides the patients served with an ambulatory care program that is superior to either of its predecessors.

Extrinsic determinants of retinal ganglion cell development in primates.

As in all mammals studied to date, primate retina contains morphologically distinct classes of retinal ganglion cells (Polyak: The Retina. Chicago: University of Chicago Press, '41; Boycott and Dowling: Philos. Trans. R. Soc. Lond. [Biol.] 225:109-184, '69; Leventhal et al.: Science 213:1139-1142, '81; Perry et al.: Neuroscience 12:1101-1123, '84; Rodieck et al.: J. Comp. Neurol. 233:115-132, '85; Rodieck: In H.D. Steklis and J. Erwin (eds): Comparative Primate Biology, Volume 4: Neurosciences. New York: Alan R. Liss, Inc., pp. 203-278, '88). We have now studied the morphologies, central projections, and retinal distributions of the major morphological classes of ganglion cells in the normal adult monkey, the newborn monkey, and the adult monkey in which restricted regions of retina were depleted of ganglion cells at birth as a result of small lesions made around the perimeter of the optic disc. Both old-world (Macaca fascicularis) and new-world (Saimiri sciureus) monkeys were studied. Our results indicate that, at birth, the major morphological classes of monkey retinal ganglion cells are recognizable; cells in central regions are close to adult size whereas cells in peripheral regions are much smaller than in the adult. As in the adult (Stone et al.: J. Comp. Neurol. 150:333-348, '73), in newborn monkeys there is a very sharp division between ipsilaterally and contralaterally projecting retinal ganglion cells (nasotemporal division). Consistent with earlier work (Hendrickson and Kupfer: Invest. Ophthalmol. 15:746-756, '76) we find that the foveal pit in the neonate is immature and contains many more ganglion cells than in the adult. In the adult monkey in which the density of retinal ganglion cells in the central retina was reduced experimentally at birth, the fovea appeared immature, and an abnormally large number of retinal ganglion cells were distributed throughout the foveal pit. The cell bodies and dendritic fields of ganglion cells that developed within cell-poor regions of the central retina were nearly ten times larger than normal. In peripheral regions the effects were smaller. The dendrites of the abnormally toward the foveal pit. They did not extend preferentially into the cell-poor region as do the abnormally large cells on the borders of experimentally induced cell-poor regions of cat central retina (Leventhal et al.: J. Neurosci. 8:1485-1499, '88) or, as we found here, in paracentral regions of primate retina.(ABSTRACT TRUNCATED AT 400 WORDS)