Cornea regeneration as an alternative to human donor transplantation

There is a need for an alternative to human donor corneas as the availability of good-quality tissues remains limited, with this situation potentially worsening as the population in many countries is progressively ageing. There have been numerous attempts to develop corneal equivalent as alternatives to donated human corneas as well as prostheses. In this short review, we focus on the efforts in bioengineering implants that promote regeneration by Canadian researchers, including our current team of authors. The examples of technologies developed that we describe include biomaterials that allow for partial regeneration of corneal tissue, self-assembled cornea constructs and cell-free corneal implants that promoted regeneration when evaluated in clinical trials in Europe

Somewhere in Europe (1947): locating Hungary within a shifting geopolitical landscape

Somewhere in Europe/Valahol Európában (Radványi, 1947) was one of the first films made in Hungary after 1945. Financed by the Hungarian Communist Party (MKP), it loudly proclaimed a broad European pertinence in an effort to privilege the universal narrative of childhoods disrupted by the war over narrowly national political concerns. The film’s story of a gang of half-starved children battling for survival in a bombed-out Central European landscape places it squarely within a transnational post-war film-making tradition. Similarities with both Italian neorealism and Soviet socialist realist cinema indicate a shared European experience of the war, but is also attributable to the international training and experience of the film’s personnel. The director Radványi had worked in the Italian industry, while the scriptwriter was the well-known film theorist Béla Balázs, who had worked in Weimar Germany and Soviet Russia. This article argues that in spite of its ostensible commitment to a communist and humanist ideology, the film gives an insight into the Hungarian national obsession with territorial integrity. Hungary’s participation in World War II on the side of the Axis, and its position as a defeated nation under Allied occupation, are seen to complicate the film text. This article contends that in spite its transnational flavour, the film’s focus on lost children wandering a borderless Europe suggests a preoccupation with the country’s uncertain position within a shifting geopolitical landscape. In turn, the film’s official reading by Nemeskürty shows an eagerness to accept the film’s representation of Hungary as a blameless victim of the war, and gives evidence of a need to insert a (false) break between the country’s wartime past as a member of the Axis, and the country’s 1968 present as a member of the Communist world order

Economics of Malaria Prevention in US Travelers to West Africa

Background. Pretravel health consultations help international travelers manage travel-related illness risks through education, vaccination, and medication. This study evaluated costs and benefits of that portion of the health consultation associated with malaria prevention provided to US travelers bound for West Africa. Methods. The estimated change in disease risk and associated costs and benefits resulting from traveler adherence to malaria chemoprophylaxis were calculated from 2 perspectives: the healthcare payer's and the traveler's. We used data from the Global TravEpiNet network of US travel clinics that collect de-identified pretravel data for international travelers. Disease risk and chemoprophylaxis effectiveness were estimated from published medical reports. Direct medical costs were obtained from the Nationwide Inpatient Sample and published literature. Results. We analyzed 1029 records from January 2009 to January 2011. Assuming full adherence to chemoprophylaxis regimens, consultations saved healthcare payers a per-traveler average of $14 (9-day trip) to$372 (30-day trip). For travelers, consultations resulted in a range of net cost of $20 (9-day trip) to a net savings of$32 (30-day trip). Differences were mostly driven by risk of malaria in the destination country. Conclusions. Our model suggests that healthcare payers save money for short- and longer-term trips, and that travelers save money for longer trips when travelers adhere to malaria recommendations and prophylactic regimens in West Africa. This is a potential incentive to healthcare payers to offer consistent pretravel preventive care to travelers. This financial benefit complements the medical benefit of reducing the risk of malaria

Elevation as a proxy for mosquito-borne Zika virus transmission in the Americas.

INTRODUCTION: When Zika virus (ZIKV) first began its spread from Brazil to other parts of the Americas, national-level travel notices were issued, carrying with them significant economic consequences to affected countries. Although regions of some affected countries were likely unsuitable for mosquito-borne transmission of ZIKV, the absence of high quality, timely surveillance data made it difficult to confidently demarcate infection risk at a sub-national level. In the absence of reliable data on ZIKV activity, a pragmatic approach was needed to identify subnational geographic areas where the risk of ZIKV infection via mosquitoes was expected to be negligible. To address this urgent need, we evaluated elevation as a proxy for mosquito-borne ZIKV transmission. METHODS: For sixteen countries with local ZIKV transmission in the Americas, we analyzed (i) modelled occurrence of the primary vector for ZIKV, Aedes aegypti, (ii) human population counts, and (iii) reported historical dengue cases, specifically across 100-meter elevation levels between 1,500m and 2,500m. Specifically, we quantified land area, population size, and the number of observed dengue cases above each elevation level to identify a threshold where the predicted risks of encountering Ae. aegypti become negligible. RESULTS: Above 1,600m, less than 1% of each country's total land area was predicted to have Ae. aegypti occurrence. Above 1,900m, less than 1% of each country's resident population lived in areas where Ae. aegypti was predicted to occur. Across all 16 countries, 1.1% of historical dengue cases were reported above 2,000m. DISCUSSION: These results suggest low potential for mosquito-borne ZIKV transmission above 2,000m in the Americas. Although elevation is a crude predictor of environmental suitability for ZIKV transmission, its constancy made it a pragmatic input for policy decision-making during this public health emergency

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations

Preliminary fabrication and characterization of electron beam melted Ti–6Al–4V customized dental implant

The current study was aimed to fabricate customized root form dental implant using additive manufacturing technique for the replacement of missing teeth. The root form dental implant was designed using GeomagicTM and MagicsTM, the designed implant was directly manufactured by layering technique using ARCAM A2TM electron beam melting system by employing medical grade Ti–6Al–4V alloy powder. Furthermore, the fabricated implant was characterized in terms of certain clinically important parameters such as surface microstructure, surface topography, chemical purity and internal porosity. Results confirmed that, fabrication of customized dental implants using additive rapid manufacturing technology offers an attractive method to produce extremely pure form of customized titanium dental implants, the rough and porous surface texture obtained is expected to provide better initial implant stabilization and superior osseointegration

Análise da superfície e osseointegração de implantes dentários com superfícies biomiméticas contedo Ca, Mg e F

Os tratamentos das superfícies dos implantes dentários osseointegráveis sofreram modificações significativas com o objetivo de melhorar a estabilidade primária e secundária. Entre as modificações destaca-se a deposição de íons, como flúor, cálcio e magnésio. Estes íons possuem baixa taxa de degradação no meio corpóreo e ótima interação biológica com as células e com os tecidos ósseos. No presente trabalho, para avaliar os efeitos do F, Ca e do Mg na osseointegração foram realizados ensaios in vitro e in vivo. Implantes foram inseridos em tíbias de coelhos e determinou-se os torques de inserção e remoção após 2, 4 e 8 semanas. Os ensaios in vivo foram complementados pela medida da rugosidade, molhabilidade e análise da superfície em microscopia eletrônica de varredura. Os resultados foram comparados com os obtidos com implantes com a superfície tratada com ácido (superfície Porous) e com deposição de flúor (superfície Porous Nano). Os resultados obtidos mostraram que o torque para remover os implantes Porous 8 semanas após a cirurgia foi de 16,96 + 1,32 N.cm, o tratado com flúor apresentou melhores resultados (17,93 ± 4,47 N.cm) e a superfície com Ca e Mg foi a que apresentou a interface osso-implante com menor resistência (10,83 + 1,20 N.cm). O maior torque indica que a adição de flúor facilita os mecanismos envolvidos na osseointegração dos implantes e permite o carregamento da prótese em tempos menores

Evolution records a Mx tape for anti-viral immunity

Viruses impose diverse and dynamic challenges on host defenses. Diversifying selection of codons and gene copy number variation are two hallmarks of genetic innovation in antiviral genes engaged in host-virus genetic conflicts. The myxovirus resistance (Mx) genes encode interferon-inducible GTPases that constitute a major arm of the cell-autonomous defense against viral infection. Unlike the broad antiviral activity of MxA, primate MxB was recently shown to specifically inhibit lentiviruses including HIV-1. We carried out detailed evolutionary analyses to investigate whether genetic conflict with lentiviruses has shaped MxB evolution in primates. We found strong evidence for diversifying selection in the MxB N-terminal tail, which contains molecular determinants of MxB anti-lentivirus specificity. However, we found no overlap between previously-mapped residues that dictate lentiviral restriction and those that have evolved under diversifying selection. Instead, our findings are consistent with MxB having a long-standing and important role in the interferon response to viral infection against a broader range of pathogens than is currently appreciated. Despite its critical role in host innate immunity, we also uncovered multiple functional losses of MxB during mammalian evolution, either by pseudogenization or by gene conversion from MxA genes. Thus, although the majority of mammalian genomes encode two Mx genes, this apparent stasis masks the dramatic effects that recombination and diversifying selection have played in shaping the evolutionary history of Mx genes. Discrepancies between our study and previous publications highlight the need to account for recombination in analyses of positive selection, as well as the importance of using sequence datasets with appropriate depth of divergence. Our study also illustrates that evolutionary analyses of antiviral gene families are critical towards understanding molecular principles that govern host-virus interactions and species-specific susceptibility to viral infection

Framing the Real: Lefèbvre and NeoRealist Cinematic Space as Practice

In 1945 Roberto Rossellini's Neo-realist Rome, Open City set in motion an approach to cinema and its representation of real life – and by extension real spaces – that was to have international significance in film theory and practice. However, the re-use of the real spaces of the city, and elsewhere, as film sets in Neo-realist film offered (and offers) more than an influential aesthetic and set of cinematic theories. Through Neo-realism, it can be argued that we gain access to a cinematic relational and multidimensional space that is not made from built sets, but by filming the built environment. On the one hand, this space allows us to "notice" the contradictions around us in our cities and, by extension, the societies that have produced those cities, while on the other, allows us to see the spatial practices operative in the production and maintenance of those contradictions. In setting out a template for understanding the spatial practices of Neo-realism through the work of Henri Lefèbvre, this paper opens its films, and those produced today in its wake, to a spatio-political reading of contemporary relevance. We will suggest that the rupturing of divisions between real spaces and the spaces of film locations, as well the blurring of the difference between real life and performed actions for the camera that underlies much of the central importance of Neo-realism, echoes the arguments of Lefèbvre with regard the social production of space. In doing so, we will suggest that film potentially had, and still has, a vital role to play in a critique of contemporary capitalist spatial practices