Dextran and protamine-based solid lipid nanoparticles as potential vectors for the treatment of X-linked juvenile retinoschisis

This is a copy of an article published in the Human gene therapy © 2012 copyright Mary Ann Liebert, Inc.; Human gene therapy is available online at: http://online.liebertpub.com.

Development of appropriateness explicit criteria for cataract extraction by phacoemulsification

Background: Consensus development techniques were used in the late 1980s to create explicit criteria for the appropriateness of cataract extraction. We developed a new appropriateness of indications tool for cataract following the RAND method. We tested the validity of our panel results. Methods: Criteria were developed using a modified Delphi panel judgment process. A panel of 12 ophthalmologists was assembled. Ratings were analyzed regarding the level of agreement among panelists. We studied the influence of all variables on the final panel score using linear and logistic regression models. The explicit criteria developed were summarized by classification and regression tree analysis. Results: Of the 765 indications evaluated by the main panel in the second round, 32.9% were found appropriate, 30.1% uncertain, and 37% inappropriate. Agreement was found in 53% of the indications and disagreement in 0.9%. Seven variables were considered to create the indications and divided into three groups: simple cataract, with diabetic retinopathy, or with other ocular pathologies. The preoperative visual acuity in the cataractous eye and visual function were the variables that best explained the panel scoring. The panel results were synthesized and presented in three decision trees. Misclassification error in the decision trees, as compared with the panel original criteria, was 5.3%. Conclusion: The parameters tested showed acceptable validity for an evaluation tool. These results support the use of this indication algorithm as a screening tool for assessing the appropriateness of cataract extraction in field studies and for the development of practice guidelines.

Embryogenesis of Heterobranchus longifilis (Curvier and Valenciennes, 1840)

Studies on development of H. longifilis (Curvier and Valenciennes, 1840) were conducted at a temperature of 25EC ( 1Ec) in aquaria tanks continuous development were monitored with the use of wild Heerbrugy photomacroscope and length of yolk and larva were monitored using Stereo Olympus microscope with ocular micrometer. The division into animal and vegetal poles was observed 22 minutes after activation. The first cleavage occurred 65 minutes after activation while the second division which was perpendicular to the first line of division occurred 74 minutes after activation. This was quickly followed by the third and fourth cleavage at 80th and 82nd minutes after activation respectively. Morular stage was reached at 4 hours 20 minutes with formation of optic bud at 14 hours 35 minutes. (DBO) Developing embryo hatched after 27 hours of activation at a mean length of 6.63 and mean yolk length of 2.17. Yolk size decrease at an average rate of 38.5 % till the 5th day of total absorption. Growth of larvae proceeded faster in tail-anus region than in anus-snout portion of the body. The rate of yolk absorption and larva development (survival) as monitored in this work gives important information in Research and development programme for H. longifilis larva - an important aspect of Research development and implementation of appropriate technologies in small scale fisheries

Wireless parylene-based retinal implant

The degeneration of the outer retina usually causes blindness by affecting the photoreceptor cells. However, the ganglion cells, which consist of optic nerves, on the middle and inner retina layers are often intact. The retinal implant, which can partially restore vision by electrical stimulation, soon becomes a focus for research. Although many groups worldwide have spent a lot of effort on building devices for retinal implant, current state-of-the-art technologies still lack a reliable packaging scheme for devices with desirable high-density multi-channel features. Wireless flexible retinal implants have always been the ultimate goal for retinal prosthesis. In this dissertation, the reliable packaging scheme for a wireless flexible parylene-based retinal implants has been well developed. It can not only provide stable electrical and mechanical connections to the high-density multi-channel (1000+ channels on 5 mm × 5 mm chip area) IC chips, but also survive for more than 10 years in the human body with corrosive fluids.

The device is based on a parylene-metal-parylene sandwich structure. In which, the adhesion between the parylene layers and the metals embedded in the parylene layers have been studied. Integration technology for high-density multi-channel IC chips has also been addressed and tested with dummy and real 268-channel and 1024-channel retinal IC chips. In addition, different protection schemes have been tried in application to IC chips and discrete components to gain the longest lifetime. The effectiveness has been confirmed by the accelerated and active lifetime soaking test in saline solution. Surgical mockups have also been designed and successfully implanted inside dog's and pig's eyes. Additionally, the electrodes used to stimulate the ganglion cells have been modified to lower the interface impedance and shaped to better fit the retina. Finally, all the developed technologies have been applied on the final device with a dual-metal-layer structure.

MEMS for Diabetic Retinopathy

As the worldwide prevalence of diabetes mellitus continues to increase, diabetic retinopathy remains the leading cause of visual impairment and blindness in many developed countries. Between 32 to 40 percent of about 246 million people with diabetes develop diabetic retinopathy. Approximately 4.1 million American adults 40 years and older are affected by diabetic retinopathy. This glucose-induced microvascular disease progressively damages the tiny blood vessels that nourish the retina, the light-sensitive tissue at the back of the eye, leading to retinal ischemia (i.e., inadequate blood flow), retinal hypoxia (i.e., oxygen deprivation), and retinal nerve cell degeneration or death. It is a most serious sight-threatening complication of diabetes, resulting in significant irreversible vision loss, and even total blindness.

Unfortunately, although current treatments of diabetic retinopathy (i.e., laser therapy, vitrectomy surgery and anti-VEGF therapy) can reduce vision loss, they only slow down but cannot stop the degradation of the retina. Patients require repeated treatment to protect their sight. The current treatments also have significant drawbacks. Laser therapy is focused on preserving the macula, the area of the retina that is responsible for sharp, clear, central vision, by sacrificing the peripheral retina since there is only limited oxygen supply. Therefore, laser therapy results in a constricted peripheral visual field, reduced color vision, delayed dark adaptation, and weakened night vision. Vitrectomy surgery increases the risk of neovascular glaucoma, another devastating ocular disease, characterized by the proliferation of fibrovascular tissue in the anterior chamber angle. Anti-VEGF agents have potential adverse effects, and currently there is insufficient evidence to recommend their routine use.

In this work, for the first time, a paradigm shift in the treatment of diabetic retinopathy is proposed: providing localized, supplemental oxygen to the ischemic tissue via an implantable MEMS device. The retinal architecture (e.g., thickness, cell densities, layered structure, etc.) of the rabbit eye exposed to ischemic hypoxic injuries was well preserved after targeted oxygen delivery to the hypoxic tissue, showing that the use of an external source of oxygen could improve the retinal oxygenation and prevent the progression of the ischemic cascade.

The proposed MEMS device transports oxygen from an oxygen-rich space to the oxygen-deficient vitreous, the gel-like fluid that fills the inside of the eye, and then to the ischemic retina. This oxygen transport process is purely passive and completely driven by the gradient of oxygen partial pressure (pO₂). Two types of devices were designed. For the first type, the oxygen-rich space is underneath the conjunctiva, a membrane covering the sclera (white part of the eye), beneath the eyelids and highly permeable to oxygen in the atmosphere when the eye is open. Therefore, sub-conjunctival pO₂ is very high during the daytime. For the second type, the oxygen-rich space is inside the device since pure oxygen is needle-injected into the device on a regular basis.

To prevent too fast or too slow permeation of oxygen through the device that is made of parylene and silicone (two widely used biocompatible polymers in medical devices), the material properties of the hybrid parylene/silicone were investigated, including mechanical behaviors, permeation rates, and adhesive forces. Then the thicknesses of parylene and silicone became important design parameters that were fine-tuned to reach the optimal oxygen permeation rate.

The passive MEMS oxygen transporter devices were designed, built, and tested in both bench-top artificial eye models and in-vitro porcine cadaver eyes. The 3D unsteady saccade-induced laminar flow of water inside the eye model was modeled by computational fluid dynamics to study the convective transport of oxygen inside the eye induced by saccade (rapid eye movement). The saccade-enhanced transport effect was also demonstrated experimentally. Acute in-vivo animal experiments were performed in rabbits and dogs to verify the surgical procedure and the device functionality. Various hypotheses were confirmed both experimentally and computationally, suggesting that both the two types of devices are very promising to cure diabetic retinopathy. The chronic implantation of devices in ischemic dog eyes is still underway.

The proposed MEMS oxygen transporter devices can be also applied to treat other ocular and systemic diseases accompanied by retinal ischemia, such as central retinal artery occlusion, carotid artery disease, and some form of glaucoma.

Riscos ocupacionais e problemas de saúde associados às condições de trabalho de enfermagem em unidades intensivas hospitalares

Trata-se de um estudo quantitativo, descritivo, visando uma análise das condições de trabalho em unidades intensivas de um hospital universitário no município do Rio de Janeiro. Foi definido como objeto de estudo a percepção dos trabalhadores de enfermagem sobre os riscos ocupacionais e os problemas de saúde inerentes às condições de trabalho em unidades intensivas e como problema de pesquisa: quais os riscos ocupacionais e problemas de saúde relacionados às condições de trabalho, percebidos pelos trabalhadores de enfermagem, em unidades intensivas de um hospital universitário? O objetivo geral foi estudar nas unidades intensivas os riscos ocupacionais e problemas de saúde da equipe de enfermagem e sua relação com condições de trabalho, a partir da percepção dos mesmos. Os objetivos específicos traçados foram: identificar as características pessoais e profissionais dos trabalhadores de enfermagem de unidades intensivas; descrever os fatores de risco do ambiente de trabalho percebidos pelos trabalhadores de enfermagem; levantar os problemas de saúde percebidos pelos trabalhadores e sua relação com o trabalho; analisar a associação entre os problemas de saúde percebidos pelos trabalhadores de enfermagem e as condições do trabalho em unidades intensivas. Participaram da pesquisa 125 profissionais de enfermagem de quatro unidades intensivas do Hospital Universitário (HU) entre Maio e Julho de 2009. A predominância foi de profissionais do sexo feminino, com idade acima dos 40 anos, com mais de um vínculo empregatício e trabalhando no HU há mais de 10 anos. Os riscos ocupacionais mais percebidos pelos trabalhadores foram os ergonômicos, seguido dos biológicos, de acidentes, físicos e químicos. Os problemas de saúde mais frequentes foram varizes, problemas oculares, lombalgias, estresse e depressão, transtornos do sono, lesões de coluna vertebral, dores de cabeça, mudanças no humor, dores musculares crônicas e hipertensão arterial. Pela associação entre riscos ocupacionais e problemas de saúde, conclui-se que os trabalhadores expostos a fatores de riscos ergonômicos e físicos têm maior probabilidade de adquirir problemas de saúde osteoarticulares e circulatórios (varizes). Diante dos dados desta pesquisa faz-se necessário aprofundamento da investigação sobre os fatores de riscos encontrados e possíveis medidas para minimizá-los, mediante novos estudos. Como recomendações destacam-se a criação de um espaço de discussão entre os gerentes e trabalhadores para a elaboração de um programa que vise a promoção e proteção da saúde do trabalhador de enfermagem de unidades intensivas; implementação de medidas de controle específicas para cada tipo de risco evidenciado e a criação de um Comitê de Ergonomia para operacionalizar a implementação das melhorias no HU, a fim de consolidar as transformações esperadas.

Control mechanisms in the human binocular oculomotor system

A study of human eye movements was made in order to elucidate the nature of the control mechanism in the binocular oculomotor system.

We first examined spontaneous eye movements during monocular and binocular fixation in order to determine the corrective roles of flicks and drifts. It was found that both types of motion correct fixational errors, although flicks are somewhat more active in this respect. Vergence error is a stimulus for correction by drifts but not by flicks, while binocular vertical discrepancy of the visual axes does not trigger corrective movements.

Second, we investigated the non-linearities of the oculomotor system by examining the eye movement responses to point targets moving in two dimensions in a subjectively unpredictable manner. Such motions consisted of hand-limited Gaussian random motion and also of the sum of several non-integrally related sinusoids. We found that there is no direct relationship between the phase and the gain of the oculomotor system. Delay of eye movements relative to target motion is determined by the necessity of generating a minimum afferent (input) signal at the retina in order to trigger corrective eye movements. The amplitude of the response is a function of the biological constraints of the efferent (output) portion of the system: for target motions of narrow bandwidth, the system responds preferentially to the highest frequency; for large bandwidth motions, the system distributes the available energy equally over all frequencies. Third, the power spectra of spontaneous eye movements were compared with the spectra of tracking eye movements for Gaussian random target motions of varying bandwidths. It was found that there is essentially no difference among the various curves. The oculomotor system tracks a target, not by increasing the mean rate of impulses along the motoneurons of the extra-ocular muscles, but rather by coordinating those spontaneous impulses which propagate along the motoneurons during stationary fixation. Thus, the system operates at full output at all times.

Fourth, we examined the relative magnitude and phase of motions of the left and the right visual axes during monocular and binocular viewing. We found that the two visual axes move vertically in perfect synchronization at all frequencies for any viewing condition. This is not true for horizontal motions: the amount of vergence noise is highest for stationary fixation and diminishes for tracking tasks as the bandwidth of the target motion increases. Furthermore, movements of the occluded eye are larger than those of the seeing eye in monocular viewing. This effect is more pronounced for horizontal motions, for stationary fixation, and for lower frequencies.

Finally, we have related our findings to previously known facts about the pertinent nerve pathways in order to postulate a model for the neurological binocular control of the visual axes.

Visão dos trabalhadores acerca das suas condições de trabalho em um centro integrado de saúde

Pesquisa realizada em um Centro Integrado de Saúde inserido no âmbito de uma Instituição de Ensino Superior Particular, situada no Município do Rio de Janeiro. Metodologia fundamentada em uma abordagem quantitativa, não-experimental, apoiada na estatística inferencial descritiva, baseada no problema de estudo: Quais os fatores que caracterizam as condições de trabalho em um Centro Integrado de Saúde (CIS)? Teve como objetivo, analisar a visão dos trabalhadores em um Centro Integrado de Saúde acerca de suas condições de trabalho. Utilizou-se uma população constituída de 73 trabalhadores. Foram aplicados dois instrumentos: o caderno B, que consta de um questionário auto-aplicativo sobre Riscos e Danos e o caderno C que é um formulário de observação sobre as condições de trabalho de Mauro & Mauro (2009) adaptado de Boix e Vogel (1997). Os dados foram analisados através do Programa Statistical Package for the Social Sciences (SPSS) versão 13.0. Na visão dos trabalhadores, os resultados em relação aos riscos (físico, químico, biológico, ergonômico e de acidente) e considerando as variáveis desconhece, não acontece, raramente e freqüentemente, os mesmos indicaram uma freqüência diversificada, embora a maior incidência esteja no grupo de risco biológico com a variável freqüentemente e nos demais a variável raramente. Quanto aos problemas de saúde evidenciados, no questionário B em ordem decrescente, os que se destacaram foram os problemas oculares; lesão por acidente; varizes; dor de cabeça; hipertensão; doenças infecciosas; lombalgias; lesão da coluna vertebral; dores musculares crônicas; problemas de articulação e estresse. Quanto aos resultados do Caderno C, através de observação pelos especialistas, os riscos são variáveis, destacando-se os riscos ergonômicos, os de acidentes e os biológicos. Conclui-se que as condições de trabalho não são satisfatórias evidenciando-se a falta de conhecimento sobre o conteúdo da investigação, assinalados as respostas na alternativa (desconhece) e da aplicação correta das medidas de prevenção de riscos ocupacionais. Recomenda-se neste sentido uma incorporação institucional dos trabalhadores valorizando a capacitação desses profissionais de saúde, com ênfase na promoção da saúde, segurança, meio ambiente de trabalho e os conhecimentos de ergonomia. Como também uma atuação integrada do Serviço Especializado em Engenharia e em Medicina do Trabalho (SESMT) com a Comissão de Biossegurança, além do incentivo à gestão participativa, educação continuada efetiva, e a criação do Comitê de Ergonomia, para a análise e intervenção das propostas.

Hezur erlaxazioaren eraginaren analisia hortzetako protesi mekanizatu baten euste torlojuen aurre-tenkaketan.

[EU]Hortzetako protesi osoek edentulismo partzial edo osoa jasaten duten pertsonentzat soluzio alternatibo bat suposatzen dute hortz bakarreko inplanteen aurrean, goialdeko edo behealdeko hortz guztiak (edo batzuk) pieza bakarrarekin ordezkatuz [11]. Protesi sistema hauen pieza bakoitzaren fabrikazioak zehaztasun handia eskatzen du eta aztertu beharreko hainbat faktore daude, amaiera produktuaren funtzionamendua egokia izatea nahi bada. Hauetako aspektu asko aurretik gauzatuak izan diren lanetan jorratu dira jadanik, tolerantzia gap-a eta torlojutze sekuentzia bezalako aldagaiei buruz hainbat ikerkuntza eginez [1]. Lan honen bidez, bi faktore hauez gain hezur erlaxazioaren eragina kontuan hartu nahi da, All On Four sistema batean edukiko duen irismena neurtzeko. Horrela, protesiaren fabrikazio edota ezarpenerako baldintza onargarri minimoak ezagutzea espero da, erabiltzailearentzat protesia egokia suerta dadin.

El plasma rico en factores de crecimiento como alternativa terapéutica en el ojo seco y en defectos epiteliales persistentes

184 p.

Política Nacional de Saúde Bucal: uma análise da reorganização da atenção à saúde bucal em Cascavel e demais municípios integrantes da 10 Regional de Saúde no Estado do Paraná

O Ministério da Saúde (MS), através de sua política de incentivos financeiros, vem promovendo um processo de reorganização da atenção à saúde bucal, com a implantação das Equipes de Saúde Bucal (ESB) na Estratégia Saúde da Família (ESF), no âmbito da atenção básica, e dos Centros de Especialização Odontológica (CEO) e Laboratório Regional de Próteses Dentárias (LRPD), na atenção secundária. Nesse contexto, esta dissertação foca o processo de reorganização da atenção à saúde bucal em Cascavel e nos demais municípios pertencentes à 10 Regional de Saúde do Estado do Paraná. Consideramos que, em tese, este processo de regionalização deve ser orientado pelas diretrizes da Política Nacional de Saúde Bucal (PNSB), que priorizam a atenção básica em saúde bucal através da ESF e trazem ainda como proposta a ampliação da média e alta complexidade em saúde bucal. Foi realizada ampla pesquisa nas bases de dados do DATASUS, relativos à produção das ações de saúde bucal dos 25 municípios pertencentes à 10 Regional de Saúde do Estado do Paraná, no período de janeiro de 1998 a dezembro de 2007. Os dados foram cotejados com aqueles disponibilizados pelo Departamento de Atenção Básica (DAB) relativos à implantação das ESB, CEO e LRPD. Os resultados demonstram que, no âmbito da 10 RS, ocorreu ampliação do acesso e da oferta de ações e serviços de saúde bucal. No entanto, a despeito da ampliação do acesso, há um longo caminho a ser percorrido para que haja avanços significativos nas condições de saúde bucal da população, tal como é a proposta da PNSB.