Minimally invasive microneedles for ocular drug delivery

Introduction: Anterior and posterior segment eye diseases are highly challenging to treat, due to the barrier properties and relative inaccessibility of the ocular tissues. Topical eye drops and systemically delivered treatments result in low bioavailability. Alternatively, direct injection of medication into the ocular tissues is clinically employed to overcome the barrier properties, but injections cause significant tissue damage and are associated with a number of untoward side effects and poor patient compliance. Microneedles (MNs) has been recently introduced as a minimally invasive means for localizing drug formulation within the target ocular tissues with greater precision and accuracy than the hypodermic needles.  Areas covered: This review article seeks to provide an overview of a range of challenges that are often faced to achieve efficient ocular drug levels within targeted tissue(s) of the eye. It also describes the problems encountered using conventional hypodermic needle-based ocular injections for anterior and posterior segment drug delivery. It discusses research carried out in the field of MNs, to date.
Expert opinion: MNs can aid in localization of drug delivery systems within the selected ocular tissue. And, hold the potential to revolutionize the way drug formulations are administered to the eye. However, the current limitations and challenges of MNs application warrant further research in this field to enable its widespread clinical application.  

Study of Alternate Pavement Designs, 1968

This report is submitted pursuant to a contract dated August 30, 1967, between the Iowa State Highway Commission and Howard, Needles, Tammen & Bergendoff, Consulting Engineers, in connection with studies determining (11,A) alternate pavement designs, and (11,B) criteria for geometric design studies. Included herein is that portion of the report covering Paragraph 11,A, comprising preparation of alternate type pavement designs (Portland Cement and Asphaltic Concrete) for the Cedar Valley Freeway and proposed US-518 from 1-80 to US-30. These alternate pavement designs consider quality and availability of aggregates, soil conditions and traffic information, to determine details and dimensions of pavement design. Comparative cost studies were prepared from alternate design data and recommendations as to pavement type are presented for Commission review.

A acupunctura como forma de controlo da ansiedade na performance e de resolução de patologias músculo-esqueléticas em músicos

As patologias músculo-esqueléticas apresentam um interesse particular nos tempos atuais, visto terem origem em atividades viciosas, nos movimentos repetitivos, no sedentarismo e na hipertonia muscular relacionada com o stresse no contexto profissional ou pessoal, que é tão comum nos músicos. Por outro lado, a performance musical requer alto nível de habilidade em diversos parâmetros, como coordenação motora, atenção e memória o que a torna numa atividade particularmente suscetível não só às patologias músculo-esqueléticas como também à ansiedade. É aqui que se introduz a acupunctura. É cada vez mais recorrente a procura das terapias complementares e/ou alternativas por parte dos músicos, em contraposição aos métodos utilizados pela medicina convencional. Dos diversos métodos da Medicina Tradicional Chinesa, a acupunctura, encontra-se, talvez entre o mais procurado. A acupunctura pode ser definida como um técnica terapêutica que tem como método predominante a introdução de agulhas na periferia do corpo humano. O efeito das agulhas será o de provocar alterações no sistema energético do paciente que resultarão em mudanças benéficas que ocorrem a nível físico. O que me traz à discussão do tema, para além da problemática das patologias músculo-esqueléticas nos músicos é o crescente número de músicos com problemas de ansiedade e a contribuição desta medicina como alternativa de tratamento.

Der Kauffunger Kalkstein (Bober-Katzbach Gebirge, Polen): Petrographie, Fossilinventar, Stratigraphie

In the Western Sudetes (Mts.) in SW Poland carbonate rocks occur which are well known in the older German literature as ’’Kauffung Limestone” or ’’Wojcieszow Limestone” in recent publications, respectively. They are intercalated in sedimentary (shales) and volcanic (greenstone) successions and are, presumed - due to the lack of index fossils - to be Cambrian in age. These deposits occur in a variety of isolated massifs in the Bober-Katzbach Mts. where they have been mined in many quarries in the past. In a single location (Polom quarry near Wojcieszow) they are exploited up until today. The predominantly calcitic rocks display a wide variety of different lithologies and are, consequently, subdivided into the following lithological units which differ in textural characteristics, mineral constituents, and different grades of diagenetic and metamorphic alteration: 1. Calcite Marble: massive, calcitic, chiefly metamorphic recrystallized. 2. Zebra Limestone: dolomitic-calcitic, certain content of metasomatic silica, fine bedding as a result of microbial calcite precipitation or of diagenetic to metamorphic separation of carbonate and silica constituents. 3. Massive matrix Dolomite: compact, of diagenetic to metamorphic origin. 4. Dolomite Marble: metamorphic. 5. Hydrothermal Dolomite: hydrothermal alteration of limestone, postdating the tectonic deformation. The recent appearance of ’’Kauffung Limestone” is mainly a result of regional metamorphosis at low temperature up to about 300°C and locally high pressure. The typical textural features are stress induced, mostly protomylonitic calcite recrystallisation and generally slowly or not infected dolomite crystals. The different reactions of the two carbonate phases are attributed to their mineral properties. Rhyolitic and dacitic dykes penetrating the carbonate rocks are interpreted as a result of post- orogenic, probably Carboniferous or Permian volcanism. Microprobe investigation on the carbonates revealed a stochiometric composition of dolomite and calcite. The stable isotope content (8 c 0,8* ^C) reflects increased crystallisation temperature of the carbonate minerals (8 O von -7,75 bis -15,78). A variety of fossil remains have been extracted from bulk samples, consisting of sponge needles, floral components, foramini- fera, and vertebrate remains the latter two of which indicate a depositional age younger than Ordovician. Due to the stratigraphic re-attribution of the Kauffung Limestone, the hypothesis of a Cambrian/Ordovician rifting in the Western Sudetes should be abandoned.

Design, modelling and preliminary characterisation of microneedle-based electrodes for tissue electroporation in vivo

We analysed the use of microneedle-based electrodes to enhance electroporation of mouse testis with DNA vectors for production of transgenic mice. Different microneedle formats were developed and tested, and we ultimately used electrodes based on arrays of 500 μm tall microneedles. In a series of experiments involving injection of a DNA vector expressing Green Fluorescent Protein (GFP) and electroporation using microneedle electrodes and a commercially available voltage supply, we compared the performance of flat and microneedle electrodes by measuring GFP expression at various timepoints after electroporation. Our main finding, supported by both experimental and simulated data, is that needles significantly enhanced electroporation of testis.

Bio-preservation and bio-active compounds as sustainable strategies to improve quality and safety of fresh and fermented products

The development of new “green” and sustainable approaches to reduce food wastes, guaranteeing food quality, microbiological safety and the environmental sustainability, is of great interest for food industry. This PhD thesis, as part of the European project BioProMedFood (PRIMA–Section2 Programme), was focused on two strategies: the use of natural antimicrobials and the application of microbial strains isolated from spontaneously fermented products. The first part concerned the valorisation of microbial biodiversity of 15 Mediterranean spontaneously fermented sausages, through the isolation of autochthonous lactic acid bacteria (LAB) strains, mainly Latilactobacillus sakei, that were characterised regarding their safety and technological aspects. The most promising strains were tested as bio-protective cultures in fresh sausages, showing promising anti-listerial activity, or as starter cultures in fermented sausages. The second part of the research was focused on the use of natural compounds (phenolic extracts and essential oils from Juniperus oxycedrus needles and Rubus fruticosus leaves) with antimicrobial potential. They were tested in vitro against List. monocytogenes and Enterococcus faecium, showing differences in relation to species and type of extracts, but they hint at important possibilities for applications in specific foods. Concluding, this PhD thesis highlighted the great potential of traditional meat products as an isolation source of new strains with industrial importance. Moreover, the antimicrobial potential of compounds obtained from plant matrices opened promising perspectives to exploit them as “green” strategies to increase fresh food safety. The last topic of research, carry out in collaboration with Department of Nutrition and Food Sciences (University of Granada), investigated the effect of LAB fermentation on avocado leaves by-products, focusing on the bio-availability of phenolic compounds in the plant extracts, caused by microbial metabolism.