Aging impairs peritoneal but not bone marrow-derived macrophage phagocytosis

Aging results in deterioration of the immune system, which is associated with increased susceptibility to infection and impaired wound healing in the elderly. Phagocytosis is an essential process in both wound healing and immune defence. As such, age-related impairments in phagocytosis impact on the health of the elderly population. Phagocytic efficiency in peritoneal macrophages, bone marrow-derived macrophages and bone marrow monocytes from young and old mice was investigated. Aging significantly impaired phagocytosis by peritoneal macrophages, both in vitro and in vivo. However, bone marrow-derived macrophages and bone marrow monocytes did not exhibit age-related impairments in phagocytosis, suggesting no intrinsic defect in these cells. We sought to investigate underlying mechanisms in age-related impairments in phagocytosis by peritoneal macrophages. We hypothesized that microenvironmental factors in the peritoneum of old mice impaired macrophage phagocytosis. Indeed, macrophages from young mice injected into the peritoneum of old mice exhibited impaired phagocytosis. Proportions of peritoneal immune cells were characterized, and striking increases in numbers of T cells, B1 and B2 cells were observed in the peritoneum of old mice compared with young mice. In addition, B cell-derived IL-10 was increased in resting and LPS-activated peritoneal cell cultures from old mice. These data demonstrate that aging impairs phagocytosis by tissue-resident peritoneal macrophages, but not by bone marrow-derived macrophages/monocytes, and suggest that age-related defects in macrophage phagocytosis may be due to extrinsic factors in the tissue microenvironment. As such, defects may be reversible and macrophages could be targeted therapeutically in order to boost immune function in the elderly.

Lack of in vitro-in vivo correlation for a UC781-releasing vaginal ring in macaques

This study describes the preclinical development of a matrix-type silicone elastomer vaginal ring device designed to provide controlled release of UC781, a non-nucleoside re- verse transcriptase inhibitor. Testing of both human- and macaque-sized rings in a sink condition in vitro release model demonstrated continuous UC781 release in quantities consid- ered sufficient to maintain vaginal fluid concentrations at levels 82–860-fold higher than the in vitro IC50 (2.0 to 10.4 nM) and therefore potentially protect against mucosal trans- mission of HIV. The 100-mg UC781 rings were well tolerated in pig-tailed macaques, did not induce local inflammation as determined by cytokine analysis and maintained median con- centrations in vaginal fluids of UC781 in the range of 0.27 to 5.18 mM during the course of the 28-day study. Analysis of residual UC781 content in rings after completion of both the in vitro release and macaque pharmacokinetic studies revealed that 57 and 5 mg of UC781 was released, respectively. The pharmacokinetic analysis of a 100-mg UC781 vaginal ring in pig-tailed macaques showed poor in vivo–in vitro correlation, attributed to the very poor solubility of UC781 in vaginal fluid and resulting in a dissolution-controlled drug release mecha- nism rather than the expected diffusion-controlled mechanism.

Electron-acoustic solitons in an electron-beam plasma system with kappa-distributed electrons

Interaction of a stream of high-energy electrons with the background plasma plays an important role in the astrophysical phenomena such as interplanetary and stellar bow shock and Earth's foreshock emission. It is not yet fully understood how electrostatic solitary waves are produced at the bow shock. Interestingly, a population of energetic suprathermal electrons were also found to exist in those environments. Previously, we have studied the properties of negative electrostatic potential solitary structures exist in such a plasma with excess suprathermal electrons. In the present study, we investigate the existence conditions and propagation properties of electron-acoustic solitary waves in a plasma consisting of an electron beam fluid, a cold electron fluid, and hot suprathermal electrons modeled by a kappa-distribution function. The Sagdeev pseudopotential method was used to investigate the occurrence of stationary-profile solitary waves. We have determined how the electron-acoustic soliton characteristics depend on the electron beam parameters. It is found that the existence domain for solitons becomes narrower with an increase in the suprathermality of hot electrons, increasing the beam speed, decreasing the beam-to-cold electron population ratio. These results lead to a better understanding of the formation of electron-acoustic solitary waves observed in those space plasma systems characterized by kappa-distributed electrons and inertial drifting (beam) electrons.

Electron-acoustic solitons in an electron-beam plasma system with kappa-distributed electrons

We investigate the existence conditions and propagation properties of electron-acoustic solitary waves in a plasma consisting of an electron beam fluid, a cold electron fluid, and a hot suprathermal electron component modeled by a k-distribution function. The Sagdeev pseudopotential method was used to investigate the occurrence of stationary-profile solitary waves. We have determined how the soliton characteristics depend on the electron beam parameters. It is found that the existence domain for solitons becomes narrower with an increase in the suprathermality of hot electrons, increasing the beam speed, and decreasing the beam-to-cold electron population ratio.

Dublin 1916: theatre of revolt

In his essay, Anti-Object, Kengo Kuma proposes that architecture cannot and should not be understood as object alone but instead always as series of networks and connections, relationships within space and through form. Some of these relationships are tangible, others are invisible. Stan Allen and James Corner have also called for an architecture that is more performative and operative – ‘less concerned with what buildings look like and more concerned with what they do’ – as means of effecting a more intimate and promiscuous relationship between infrastructure, urbanism and buildings. According to Allen this expanding filed offers a reclamation of some of the areas ceded by architecture following disciplinary specialization:

‘Territory, communication and speed are properly infrastructural problems and architecture as a discipline has developed specific technical means to deal with these variables. Mapping, projection, calculation, notation and visualization are among architecture’s traditional tools for operating at the very large scale’.

The motorway may not look like it – partly because we are no longer accustomed to think about it as such – but it is a site for and of architecture, a territory where architecture can be critical and active. If the limits of the discipline have narrowed, then one of the functions of a school of architecture must be an attempt occupy those areas of the built environment where architecture is no longer, or has yet to reach. If this is a project about reclamation of a landscape, it is also a challenge to some of the boundaries that surround architecture and often confine it, as Kuma suggests, to the appreciation of isolated objects.

M:NI 2014-15
We tend to think of the motorway as a thing or an object, something that has a singular function. Historically this is how it has been seen, with engineers designing bridges and embankments and suchlike with zeal … These objects like the M3 Urban Motorway, Belfast’s own Westway, are beautiful of course, but they have caused considerable damage to the city they were inflicted upon.

Actually, it’s the fact that we have seen the motorway as a solid object that has caused this problem. The motorway actually is a fluid and dynamic thing, and it should be seen as such: in fact it’s not an organ at all but actually tissue – something that connects rather than is. Once we start to see the motorway as tissue, it opens up new propositions about what the motorway is, is used for and does. This new dynamic and connective view unlocks the stasis of the motorway as edifice, and allows adaptation to happen: adaptation to old contexts that were ignored by the planners, and adaptation to new contexts that have arisen because of or in spite of our best efforts.

Motorways as tissue are more than just infrastructures: they are landscapes. These landscapes can be seen as surfaces on which flows take place, not only of cars, buses and lorries, but also of the globalized goods carried and the lifestyles and mobilities enabled. Here the infinite speed of urban change of thought transcends the declared speed limit [70 mph] of the motorway, in that a consignment of bananas can cause soil erosion in Equador, or the delivery of a new iphone can unlock connections and ideas the world over.

So what is this new landscape to be like? It may be a parallax-shifting, cognitive looking glass; a drone scape of energy transformation; a collective farm, or maybe part of a hospital. But what’s for sure, is that it is never fixed nor static: it pulses like a heartbeat through that most bland of landscapes, the countryside. It transmits forces like a Caribbean hurricane creating surf on an Atlantic Storm Beach: alien forces that mutate and re-form these places screaming into new, unclear and unintended futures.

And this future is clear: the future is urban. In this small rural country, motorways as tissue have made the whole of it: countryside, mountain, sea and town, into one singular, homogenous and hyper-connected, generic city.

Goodbye, place. Hello, surface!

MNI: Motorway Notation Network

In his essay, Anti-Object, Kengo Kuma proposes that architecture cannot and should not be understood as object alone but instead always as series of networks and connections, relationships within space and through form. Some of these relationships are tangible, others are invisible. Stan Allen and James Corner have also called for an architecture that is more performative and operative – ‘less concerned with what buildings look like and more concerned with what they do’ – as means of effecting a more intimate and promiscuous relationship between infrastructure, urbanism and buildings. According to Allen this expanding filed offers a reclamation of some of the areas ceded by architecture following disciplinary specialization:

‘Territory, communication and speed are properly infrastructural problems and architecture as a discipline has developed specific technical means to deal with these variables. Mapping, projection, calculation, notation and visualization are among architecture’s traditional tools for operating at the very large scale’.

The motorway may not look like it – partly because we are no longer accustomed to think about it as such – but it is a site for and of architecture, a territory where architecture can be critical and active. If the limits of the discipline have narrowed, then one of the functions of a school of architecture must be an attempt occupy those areas of the built environment where architecture is no longer, or has yet to reach. If this is a project about reclamation of a landscape, it is also a challenge to some of the boundaries that surround architecture and often confine it, as Kuma suggests, to the appreciation of isolated objects.

M:NI 2014-15
We tend to think of the motorway as a thing or an object, something that has a singular function. Historically this is how it has been seen, with engineers designing bridges and embankments and suchlike with zeal … These objects like the M3 Urban Motorway, Belfast’s own Westway, are beautiful of course, but they have caused considerable damage to the city they were inflicted upon.

Actually, it’s the fact that we have seen the motorway as a solid object that has caused this problem. The motorway actually is a fluid and dynamic thing, and it should be seen as such: in fact it’s not an organ at all but actually tissue – something that connects rather than is. Once we start to see the motorway as tissue, it opens up new propositions about what the motorway is, is used for and does. This new dynamic and connective view unlocks the stasis of the motorway as edifice, and allows adaptation to happen: adaptation to old contexts that were ignored by the planners, and adaptation to new contexts that have arisen because of or in spite of our best efforts.

Motorways as tissue are more than just infrastructures: they are landscapes. These landscapes can be seen as surfaces on which flows take place, not only of cars, buses and lorries, but also of the globalized goods carried and the lifestyles and mobilities enabled. Here the infinite speed of urban change of thought transcends the declared speed limit [70 mph] of the motorway, in that a consignment of bananas can cause soil erosion in Equador, or the delivery of a new iphone can unlock connections and ideas the world over.

So what is this new landscape to be like? It may be a parallax-shifting, cognitive looking glass; a drone scape of energy transformation; a collective farm, or maybe part of a hospital. But what’s for sure, is that it is never fixed nor static: it pulses like a heartbeat through that most bland of landscapes, the countryside. It transmits forces like a Caribbean hurricane creating surf on an Atlantic Storm Beach: alien forces that mutate and re-form these places screaming into new, unclear and unintended futures.

And this future is clear: the future is urban. In this small rural country, motorways as tissue have made the whole of it: countryside, mountain, sea and town, into one singular, homogenous and hyper-connected, generic city.

Goodbye, place. Hello, surface!

Perceived difficulty of various steps of manual small incision cataract surgery among trainees in rural China

Background: The perceived difficulty of steps of manual small incision cataract surgery among trainees in rural China was assessed. Design: Cohort study. Participants: Fifty-two trainees at the end of a manual small incision cataract surgery training programme. Methods: Participants rated the difficulty of 14 surgical steps using a 5-point scale, 1 (very easy) to 5 (very difficult). Demographic and professional information was recorded for trainees. Main Outcome Measure: Mean ratings for surgical steps. Results: Questionnaires were completed by 49 trainees (94.2%, median age 38 years, 8 [16.3%] women). Twenty six (53.1%) had performed ≤50 independent cataract surgeries prior to training. Trainees rated cortical aspiration (mean score±standard deviation=3.10±1.14) the most difficult step, followed by wound construction (2.76±1.08), nuclear prolapse into the anterior chamber (2.74±1.23) and lens delivery (2.51±1.08). Draping the surgical field (1.06±0.242), anaesthetic block administration (1.14±0.354) and thermal coagulation (1.18±0.441) were rated easiest. In regression models, the score for cortical aspiration was significantly inversely associated with performing >50 independent manual small incision cataract surgery surgeries during training (P=0.01), but not with age, gender, years of experience in an eye department or total number of cataract surgeries performed prior to training. Conclusions: Cortical aspiration, wound construction and nuclear prolapse pose the greatest challenge for trainees learning manual small incision cataract surgery, and should receive emphasis during training. Number of cases performed is the strongest predictor of perceived difficulty of key steps. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

Clinical evaluation of three incision size-dependent phacoemulsification systems.

PURPOSE:

To compare the outcomes of cataract surgery performed with 3 incision size-dependent phacoemulsification groups (1.8, 2.2, and 3.0 mm).

DESIGN:

Prospective randomized comparative study.

METHODS:

One hundred twenty eyes of 120 patients with age-related cataract (grades 2 to 4) were categorized according to the Lens Opacities Classification System III. Eligible subjects were randomly assigned to 3 surgical groups using coaxial phacoemulsification through 3 clear corneal incision sizes (1.8, 2.2, and 3.0 mm). Different intraoperative and postoperative outcome measures were obtained, with corneal incision size and surgically induced astigmatism as the main clinical outcomes.

RESULTS:

There were no statistically significant differences in most of the intraoperative and postoperative outcome measures among the 3 groups. However, the mean cord length of the clear corneal incision was increased in each group after surgery. The mean maximal clear corneal incision thickness in the 1.8-mm group was significantly greater than for the other groups at 1 month. The mean surgically induced astigmatism in the 1.8- and 2.2-mm groups was significantly less than that in the 3.0-mm group after 1 month, without significant difference between the 1.8- and 2.2-mm groups.

CONCLUSIONS:

With appropriate equipment, smaller incisions may result in less astigmatism, but the particular system used will influence incision stress and wound integrity, and may thus limit the reduction in incision size and astigmatism that is achievable.

Doxorubicin induces the cleavage of Poly (ADP-ribose) polymerase, a marker of programmed cell death (apoptosis) in mouse cardiomyocytes

Cancer is one of the leading causes of death in the world. Despite this, a growing number of people are surviving the disease due to medical advancements and the development of numerous new therapies. Doxorubicin, a chemotherapeutic agent, is a widely-used and successful first-line anti-tumour treatment. However, the established toxic and deleterious effects of the drug on the cardiovascular system confer increased risk of congestive heart failure, thereby necessitating the use of reduced doxorubicin doses. In order to investigate how these events are initiated, mouse cardiomyocytes (HL-1) were treated in vitro with varying concentrations of doxorubicin (0.5-4.0 µmol/L). Following treatment (24h), a marked level of cell death was observed in comparison to untreated cardiomyocytes; the level of death appeared to correlate with the concentration of the drug used. Western blotting revealed the cleavage of full length Poly (ADP-ribose) polymerase (PARP) into 89 and 24kDa fragments, a process which is instrumental in triggering programmed cell death/apoptosis. Importantly, results suggested that this event may be independent of caspase 3 cleavage and thus activation. A number of previous studies have reported a functional role for both Mitofusin-2 (Mfn2) and NADPH oxidase 2 (Nox2) in the cardiotoxic response. Given that PARP cleavage is a validated indicator of cellular apoptosis, these results clearly indicate that this marker could be used in future studies when determining if depletion of the above proteins would cause a reduction in or eradicate the pro-apoptotic action of this agent on cardiomyocytes. Such investigations may lead to significant developments in ensuring that doxorubicin can achieve its full therapeutic anti-tumour potential without causing the subsequent deleterious effects on the cardiovascular system.

Avaliação do desempenho in vivo do biovidro FastOs™

O conceito de bioatividade surgiu com a descoberta, no início década de 70, de que algumas composições vítreas (ex.: 45S5 Bioglass®), tinham a capacidade de estabelecer uma ligação direta e estável com os tecidos vivos. Desde então, este grupo de biomateriais tem vindo a receber uma atenção cada vez maior por parte dos investigadores, tendo como motivação principal a busca de novas composições com propriedades mais adequadas para a regeneração óssea do que as composições comercialmente disponíveis. Na presente tese, avaliou-se o desempenho in vivo de duas composições de biovidro do sistema diopsite (CaMgSi2O6) - fluorapatite (Ca5(PO4)3F) - fosfato tricálcico (3CaO•P2O5) aplicados em defeitos ósseos de tamanho não crítico em carneiros, tendo também sido avaliada a biocompatibilidade dos biomateriais através da aplicação subcutânea de placas dos mesmos vidros. O trabalho realizado também incluiu a avaliação dos materiais in vitro, através de estudos de biomineralização em fluido corporal simulado e estudos de degradação. Os biomateriais foram comparados com o biovidro 45S5 Bioglass®, sendo que em termos de bioatividade in vitro, as duas composições investigadas apresentaram um maior potencial bioativo, levando à formação de uma camada superficial de hidroxiapatite carbonatada, em contraste com a formação de calcite na composição comercial, sob condições idênticas. Os testes de degradação in vitro também apresentaram resultados melhores para as duas novas composições, traduzidos por variações de pH e taxas de degradação menores do que os observados no caso do 45S5 Bioglass®. A avaliação in vivo dos implantes subcutâneos permitiu apurar a biocompatibilidade dos biovidros testados, tendo sido considerados ligeiramente irritantes. Os resultados relativos à aplicação dos pós de vidro bioativo nos defeitos ósseos não foram obtidos em tempo útil de modo a poderem ser incluídos na presente tese. Considerando o desempenho in vitro e a biocompatibilidade dos materiais estudados, estes podem apontar-se como materiais promissores para aplicações em engenharia de tecidos, particularmente na regeneração do tecido ósseo.

Impossible Participation

The chapter critiques the rise of participation in art since the 1990s – a development that sees artists and curators searching continually for new and increased levels of audience inclusion. While there has been much discussion about what might be gained by participating in an artwork, we ask what might be lost by this act. We also question the extent to which participation is a useful social or aesthetic strategy in circumstances where it remains bound by the institutional structures of the artworld. For this reason, our work is an attempt to transform the broader ‘apparatus of art’ and to create works in which the roles assigned to individuals and groups remain fluid and subject to continuous negotiation. As a means of an attempt at resisting absorption into the institutional structures of the artworld, we privilege a form of participation that remains immanent in the work, but that never crystallizes into a single or definable role. Kathryn Brown , art historian and editor of Interactive Contemporary Art, says, ‘It is, perhaps, a fitting end to the discussions of the present volume that the most interesting and valuable form of participation envisaged by Freee is one that must remain impossible.’

Multilayered non-invasive temperature estimation from backscattered ultrasound

Roughly one in four breast cancer survivors report some degree of arm oedema. Lymphoedema is a build-up of excess lymph fluids in the tissues. Persistent lymphoedema leads to pain, diminished limb function, increased risk of infection, soft tissue fibrosis, and severe cases can be grossly disfiguring. From a mechanics perspective, the lymphoedemous tissue may be thought of as a two phase composite, consisting of both fluid and solid phases. Here we discuss the use of composites mixture theory to model the mechanics of lymphoedemous tissues. By treating the tissue as a fluid-solid composite, rules-of-mixtures may be used to estimate the effective moduli in terms of the properties of the individual components and their respective volume fractions in these two states.

In-situ development of self-defensive antibacterial biomaterials: phenol-g-keratin-EC based bio-composites with characteristics for biomedical applications

Recently, the development of highly inspired biomaterials with multi-functional characteristics has gained considerable attention, especially in biomedical, and other health-related areas of the modern world. It is well-known that the lack of antibacterial potential has significantly limited biomaterials for many challenging applications such as infection free wound healing and/or tissue engineering etc. In this perspective, herein, a series of novel bio-composites with natural phenols as functional entities and keratin-EC as a base material were synthesised by laccase-assisted grafting. Subsequently, the resulting composites were removed from their respective casting surfaces, critically evaluated for their antibacterial and biocompatibility features and information is also given on their soil burial degradation profile. In-situ synthesised phenol-g-keratin-EC bio-composites possess strong anti-bacterial activity against Gram-positive and Gram-negative bacterial strains i.e., B. subtilis NCTC 3610, P. aeruginosa NCTC 10662, E. coli NTCT 10418 and S. aureus NCTC 6571. More specifically, 10HBA-g-keratin-EC and 20T-g-keratin-EC composites were 100% resistant to colonisation against all of the aforementioned bacterial strains, whereas, 15CA-g-keratin-EC and 15GA-g-keratin-EC showed almost negligible colonisation up to a variable extent. Moreover, at various phenolic concentrations used, the newly synthesised composites remained cytocompatible with human keratinocyte-like HaCaT, as an obvious cell ingrowth tendency was observed and indicated by the neutral red dye uptake assay. From the degradation point of view, an increase in the degradation rate was recorded during their soil burial analyses. Our investigations could encourage greater utilisation of natural materials to develop bio-composites with novel and sophisticated characteristics for potential applications.

Electrospun medicated shellac nanofibers for colon-targeted drug delivery

Medicated shellac nanofibers providing colon-specific sustained release were fabricated using coaxial electrospinning. A solution of 7.5 g shellac and 1.5 g of ferulic acid (FA) in 10 mL ethanol was used as the core fluid, and a mixture of ethanol and N,N-dimethylformamide (8/10 v/v) as the shell. The presence of the shell fluid was required to prevent frequent clogging of the spinneret. The diameters of the fibers (D) can be manipulated by varying the ratio of shell to core flow rates (F), according to the equation D = 0.52F−0.19. Scanning electron microscopy images revealed that fibers prepared with F values of 0.1 and 0.25 had linear morphologies with smooth surfaces, but when the shell fluid flow rate was increased to 0.5 the fiber integrity was compromised. FA was found to be amorphously distributed in the fibers on the basis of X-ray diffraction and differential scanning calorimetry results. This can be attributed to good compatibility between the drug and carrier: IR spectra indicated the presence of hydrogen bonds between the two. In vitro dissolution tests demonstrated that there was minimal FA release at pH 2.0, and sustained release in a neutral dissolution medium. The latter occurred through an erosion mechanism. During the dissolution processes, the shellac fibers were gradually converted into nanoparticles as the FA was freed into solution, and ultimately completely dissolved.

Contraste e alteridade na viagem contemporânea

No mundo contemporâneo globalizado, definido pela sua qualidade essencialmente fluida e instável, o carácter distintivo da viagem parece dissolver-se face à contracção do planeta, à economia das ―trocas simbólicas‖ e a um alegado processo de diluição das diferenças e de homogeneização cultural. Com efeito, a mediatização da sociedade e a proliferação icónica contemporâneas produzem um aparente estado de saturação da geografia real e de multiplicação de lugares enquanto representações e imagens, permitindo pôr em causa a própria necessidade e urgência de deslocação, bem como admitir a abolição do ―estatuto de privilégio‖ de certos lugares e a derradeira quebra no conceito aurático das férias e das viagens, tradicionalmente assente em antinomias cruciais entre o quotidiano/familiar e o diferente/extraordinário. O presente artigo propõe-se abordar o paradigma da mobilidade contemporânea, nomeadamente no que diz respeito à traumática aniquilação do espaço e do tempo e ao seu impacto fortemente disruptivo sobre a dimensão ontológica de uma prática cultural cujo poder aurático se encontra tradicionalmente relacionado com a conquista de distâncias, a percepção de diferenças e a experiência de alteridade. O artigo pretende, por outro lado, refutar a declaração pós-moderna de que a familiarização com o outro conduz a uma diminuição do potencial de choque cultural no turismo contemporâneo, discutindo a relevância e a prevalência da busca de contraste e formas de vivência de alteridade no complexo novelo de motivações da viagem turística contemporânea.