Positive, negative and controlled durotaxis.

Cell migration is a physical process central to life. Among others, it regulates embryogenesis, tissue regeneration, and tumor growth. Therefore, understanding and controlling cell migration represent fundamental challenges in science. Specifically, the ability of cells to follow stiffness gradients, known as durotaxis, is ubiquitous across most cell types. Even so, certain cells follow positive stiffness gradients while others move along negative gradients. How the physical mechanisms involved in cell migration work to enable a wide range of durotactic responses is still poorly understood. Here, we provide a mechanistic rationale for durotaxis by integrating stochastic clutch models for cell adhesion with an active gel theory of cell migration. We show that positive and negative durotaxis found across cell types are explained by asymmetries in the cell adhesion dynamics. We rationalize durotaxis by asymmetric mechanotransduction in the cell adhesion behavior that further polarizes the intracellular retrograde flow and the protruding velocity at the cell membrane. Our theoretical framework confirms previous experimental observations and explains positive and negative durotaxis. Moreover, we show how durotaxis can be engineered to manipulate cell migration, which has important implications in biology, medicine, and bioengineering.

Whole-genome analysis of extraintestinal Escherichia coli sequence type 73 from a single hospital over a 2 year period identified different circulating clonal groups.

Sequence type (ST)73 has emerged as one of the most frequently isolated extraintestinal pathogenic Escherichia coli. To examine the localized diversity of ST73 clonal groups, including their mobile genetic element profile, we sequenced the genomes of 16 multiple-drug resistant ST73 isolates from patients with urinary tract infection from a single hospital in Sydney, Australia, between 2009 and 2011. Genome sequences were used to generate a SNP-based phylogenetic tree to determine the relationship of these isolates in a global context with ST73 sequences (n=210) from public databases. There was no evidence of a dominant outbreak strain of ST73 in patients from this hospital, rather we identified at least eight separate groups, several of which reoccurred, over a 2 year period. The inferred phylogeny of all ST73 strains (n=226) including the ST73 clone D i2 reference genome shows high bootstrap support and clusters into four major groups that correlate with serotype. The Sydney ST73 strains carry a wide variety of virulence-associated genes, but the presence of iss, pic and several iron-acquisition operons was notable.

Generic nature of long-range repulsion mechanism on a bulk insulator?

Dynamic atomic force microscopy measurements are reported that provide evidence for the presence of long-range repulsion in molecular self-assembly on a bulk insulator surface. We present the structures formed from four different benzoic acid derivatives on the (10.4) cleavage plane of calcite kept in ultra-high vacuum. These molecules have in common that they self-assemble into molecular stripes when deposited onto the surface held at room temperature. For all molecules tested, a detailed analysis of the stripe-to-stripe distance distribution reveals a clear deviation from what would be expected for randomly placed, non-interacting stripes (i.e., geometric distribution). When excluding kinetic effects during growth, this result gives evidence for a long-range repulsion mechanism acting during the assembly of these stripes. The fact that this finding is robust against changes in the molecular structure indicates a generic nature of the observed mechanism, implying a ubiquitous origin such as electrostatic repulsion. Finally, we discuss parameters that might affect the unambiguous observation of this generic repulsion under specific experimental conditions.

Diacetylene polymerization on a bulk insulator surface.

Molecular electronics has great potential to surpass known limitations in conventional silicon-based technologies. The development of molecular electronics devices requires reliable strategies for connecting functional molecules by wire-like structures. To this end, diacetylene polymerization has been discussed as a very promising approach for contacting single molecules with a conductive polymer chain. A major challenge for future device fabrication is transferring this method to bulk insulator surfaces, which are mandatory to decouple the electronic structure of the functional molecules from the support surface. Here, we provide experimental evidence for diacetylene polymerization of 3,3'-(1,3-butadiyne-1,4-diyl)bisbenzoic acid precursors on the (10.4) surface of calcite, a bulk insulator with a band gap of around 6 eV. When deposited on the surface held at room temperature, ordered islands with a (1 × 3) superstructure are observed using dynamic atomic force microscopy. A distinct change is revealed upon heating the substrate to 485 K. After heating, molecular stripes with a characteristic inner structure are formed that excellently match the expected diacetylene polymer chains in appearance and repeat distance. The corresponding density functional theory computations reveal molecular-level bonding patterns of both the (1 × 3) superstructure and the formed striped structure, confirming the assignment of on-surface diacetylene polymerization. Transferring the concept of using diacetylene polymerization for creating conductive connections to bulk insulator surfaces paves the way towards application-relevant systems for future molecular electronic devices.

Interações entre antiparasitários e alimentos / Interactions between antiparasitic drugs and food

O uso, por vezes indiscriminado, de antiparasitários pode levar a consequências importantes na saúde do indivíduo, principalmente relacionadas a alterações no sistema gastrointestinal. As interações entre fármacos e nutrientes podem ocorrer quando um alimento ou nutriente altera a resposta esperada de um medicamento ou quando este interfere sobre o estado nutricional do indivíduo. Essa alteração da eficácia pode resultar em falha no tratamento ou até mesmo na toxicidade do fármaco. A fim de conhecer, identificar e prevenir interações indesejáveis entre antiparasitários e alimentos, o presente artigo de revisão aborda os principais fármacos e alimentos ou nutrientes envolvidos, bem como as consequências que tais interações podem acarretar ao indivíduo. O estado nutricional é de suma importância nas infecções parasitárias, pois é o determinante entre uma maior carga de parasitos ou a resistência total contra a infecção. De forma geral, indivíduos parasitados são inapetentes e emagrecidos, o que em crianças pode comprometer o desenvolvimento físico e intelectual. Portanto, o conhecimento e uma correta orientação médica, farmacêutica e nutricional levam a um tratamento bem sucedido...

The often indiscriminate use of antiparasitic drugs can lead to serious consequences for the health of the individual, mainly related to alterations in the gastrointestinal system. Interactions between drugs and nutrients may occur when a food or nutrient changes the expected response of a drug or when a medicine interferes with the individual's nutritional status. These changes may result in treatment failure or even toxicity of the drug. As an aid to the detection, identification and prevention of undesirable interactions between foods and antiparasite drugs, in this review we discuss the major drugs and foods or nutrients involved and the consequences that these interactions can have for the individual. Nutritional status is important in parasitic infections, as it is a factor determining the parasite load level or the total resistance against infection. Generally, individuals infected by parasites have a poor appetiteand are emaciated, which in children can damage physical and intellectual development. Therefore, knowledge of the parasite and proper medical, pharmaceutical and nutritional guidance lead to a more successful treatment...

[Effectiveness trial for prevention of occupational injuries in the wood processing industry]. / Un trial di efficacia nella prevenzione degli infortuni nel settore del legno.

BACKGROUND: Training is a key tool to improve prevention and safety management at the workplace. Few studies have aimed at assessing quality of training and its outcomes. OBJECTIVES AND METHODS: This paper describes the rationale, design, content, and evaluation of an ongoing randomized controlled trial aimed at assessing the effectiveness of a training programme designed to reduce the risk of occupational injuries among employees of the wood processing industry. DISCUSSION AND CONCLUSIONS: Well designed, targeted training programmes could represent a feasible means of reducing work injuries by improving employers' behaviour and attitudes towards safety; nevertheless, these kinds of interventions have a considerable impact both in terms of human resources and in terms of cost. For these reasons, assessment of effectiveness and knowledge-sharing should be considered as essential phases of injury prevention programmes.

[Active search of work related diseases: the example of carpal tunnel syndrome in Pordenone's area]. / La ricerca attiva delle malattie professionali: l'esempio della sindrome del tunnel carpale in provincia di Pordenone.

In the recent years working related pathologies of the upper limbs have raised at the top of ranking of diseases reported to INAIL in the Northern East Area of Italy. In 2004 658 cases of tendinitis have been filed and 361 cases of the Carpal Tunnel Syndrome (CTS) reported on a total of 1317 and 864 cases respectively in the whole Italian territory. The phenomenon (6.8% of total occupational disease in Pordenone province) interests essentially women and various working environments widely represented. We have worked together with an important Diagnose and Treatment Medical Centre to find new cases of professional illnesses, initially focusing our efforts on the CTS. We have identified 26 new cases of CTS as possibly originated from working conditions and we have filled 11 reports to the Judicial Authorities. In a training meeting with Orthopedic Doctors we have disclosed the results of our research while at the same time we have also divulged our knowledge on the importance of the working environment in the onset of the CTS providing the tools for a correct reporting of suspect cases.

Confiabilidade intra e interexaminadores de dois métodos de medida da amplitude ativa de dorsiflexão do tornozelo em indivíduos saudáveis / Intrarater and interrater reliability of two methods for measuring the active range of motion for ankle dorsiflexion in healthy subjects

INTRODUÇÃO: A medida da amplitude do movimento (ADM) é um importante parâmetro utilizado na avaliação e no acompanhamento fisioterapêutico, conseqüentemente, a confiabilidade dessa medida e dos instrumentos utilizados devem ser avaliados. OBJETIVOS: O objetivo deste estudo foi avaliar a confiabilidade das medidas intra-examinador e interexaminador da ADM ativa de dorsiflexão do tornozelo, por meio da goniometria e de forma mais funcional em cadeia cinética fechada (CCF). MATERIAIS E MÉTODOS: Dois examinadores realizaram, em dois dias de teste, as mensurações de ambos os membros de 22 sujeitos saudáveis. A ADM ativa de dorsiflexão foi medida primeiro com o sujeito em prono, utilizando o goniômetro universal e, posteriormente, com o sujeito em dorsiflexão, na posição ortostática com o pé testado sobre uma fita métrica. O coeficiente de correlação intraclasse (CCI) foi utilizado para a análise da confiabilidade das medidas, e o teste t pareado e independente foi utilizado para verificar a diferença entre as médias de dois dias de teste e entre os dois examinadores, respectivamente. RESULTADOS: Os coeficientes de correlação intraclasse (CCI) demonstraram de baixa a moderada confiabilidade intra-examinador, com CCI: 0,32 a 0,72, e moderada confiabilidade interexaminador, com CCI de 0,57 e 0,66 para a goniometria. Para a medida em CCF a confiabilidade foi alta tanto para a condição intra-examinador (CCI de 0,93 e 0,96 para os tornozelos direito e esquerdo, respectivamente) quanto para interexaminador (CCI de 0,98 e 0,99 para os tornozelos direito e esquerdo, respectivamente). CONCLUSÃO: Esses resultados indicaram que a confiabilidade da avaliação em CCF é maior que a do goniômetro universal, e isso indica ser um método confiável para sua aplicação clínica ao envolver o mesmo ou diferentes avaliadores.

BACKGROUND: Range of motion (ROM) measurements are an important parameter for physiotherapeutic assessment and follow-up. Consequently, the reliability of such measurements and the instruments utilized must be evaluated. OBJETIVE: To evaluate the intrarater and interrater reliability of active ROM measurements for ankle dorsiflexion using a goniometer and the more functional method of closed kinetic chains (CKC). METHOD: Two examiners measured both ankles of 22 healthy subjects, on two test days. The active ROM for dorsiflexion was first measured with the subject in the prone position using a universal goniometer and subsequently with the subject in the orthostatic position, with the foot to be tested in dorsiflexion on a measuring tape. The intraclass correlation coefficient (ICC) was used to analyze the reliability of the measurements, and Student's t test for paired and independent samples was used to investigate differences between the means for the two test days and between the two examiners, respectively. RESULTS: The ICC showed low to moderate intrarater reliability (ICC: 0.32-0.72) and moderate interrater reliability (ICC: 0.57-0.66) for the goniometer measurements. For the CKC measurements, both intrarater reliability and interrater reliability were high: intrarater ICC of 0.93 and 0.96 for the right and left ankles, respectively; interrater ICC of 0.98 and 0.99 for the right and left ankles, respectively. CONCLUSION: These results indicated that the reliability of the CKC evaluation was greater than the reliability of the universal goniometer. This shows that CKC is a reliable method for clinical application involving the same or different examiners.

Nanomolar cationic dendrimeric sulfadiazine as potential antitoxoplasmic agent.

The high doses of sulfadiazine (SDZ), used in synergistic combination with pyrimethamine, are mainly responsible for severe side effects and discontinuation of toxoplasmosis treatments. In the search for new strategies that improve the efficacy of treatments with reduced doses of SDZ, we have determined the performance of cationic G4 (DG4) and anionic G4.5 (DG4.5) poly(amidoamine) (PAMAM) dendrimers to act as SDZ nanocarriers. Both dendrimers could efficiently load SDZ (SDZ-DG4 and SDZ-DG4.5) up to a ratio of 30 molecules SDZ per dendrimer molecule. The MTT assay on Vero and J774 cells showed no cytotoxicity for DG4.5 and its SDZ complex incubated between 0.03 and 33 microM of dendrimer concentration. On the other hand, DG4 and its SDZ complex resulted cytotoxic when incubated at dendrimer concentrations higher than 3.3 microM. Finally, complexes and empty dendrimers were in vitro tested against Vero cells infected with RH strain of Toxoplasma gondii along 4h of treatment. For SDZ-DG4.5 and DG4.5 to cause an infection decrease between 25 and 40%, respectively, a dendrimer concentration of 33 microM was required; however, SDZ-DG4 produced the highest infection decrease of 60% at 0.03 microM. These preliminary results, achieved with nanomolar doses of SDZ-DG4 as unique active principle, point to this complex as a suitable potential candidate for antitoxoplasmic therapy.

Estudo da confiabilidade da força aplicada durante a mobilização articular ântero-posterior do tornozelo / Reliability study on the force applied during anteroposterior mobilization of the ankle joint

INTRODUÇÃO: Os fatores que contribuem para a eficiência da manobra de mobilização articular são a intensidade e a reprodutibilidade da força aplicada durante a mobilização, por um ou por diferentes examinadores. OBJETIVO: Avaliar a confiabilidade intra e interexaminador da força de mobilização ântero-posterior da articulação do tornozelo, grau III e IV de Maitland. MÉTODO: Os dois tornozelos de 35 voluntários assintomáticos foram mobilizados por dois examinadores experientes com o procedimento. Uma miniplataforma de força foi posicionada sob a perna do voluntário a fim de captar as forças obtidas durante as manobras de mobilização e seu sinal foi convertido e armazenado em um software DasyLab4.0, o que permitiu o registro dos picos mínimo e máximo das curvas da força aplicada. A análise da confiabilidade foi realizada através do coeficiente de correlação intraclasse (CCI). Para avaliar o erro sistemático das medidas foi utilizado o teste t pareado e o teste t independente, para as condições intra e interexaminadores, respectivamente. O método de Bland e Altman avaliou os limites de concordância das medidas entre os examinadores. RESULTADOS: Os dados demonstraram alta confiabilidade intra-examinador. A confiabilidade inter-examinador foi baixa e moderada para a força máxima e mínima respectivamente, durante a mobilização ântero-posterior da articulação do tornozelo. CONCLUSÃO: Esses dados sugerem que a força aplicada durante a mobilização articular grau III e IV de Maitland no tornozelo, apresenta alta confiabilidade intra-examinador e baixa para interexaminador.

[Stress imaging in coronary artery disease: state of the art]. / Stress imaging nella cardiopatia ischemica: stato dell'arte.

To date, several diagnostic tools allow an accurate non-invasive evaluation of coronary artery disease; this is due to the great progress in echocardiographic and nuclear imaging techniques in the last 10 years. The large availability of different stress imaging techniques allows to choose the most appropriate technique for each patient according to the clinical characteristics. This paper presents the state of the art of echocardiographic and nuclear stress imaging for the diagnosis of coronary artery disease and for the prognostic stratification of infarcted patients. Advantages and limits of the different techniques are described rather than putting in competition echo and nuclear cardiology as has often been done in the past. Cardiologists should select among the various techniques on the basis of clinical characteristics of single patients, center's experience and an objective evaluation of economical aspects.

Serological survey of selected pathogens of free-ranging foxes in southern Argentina, 1998--2001.

A serological survey was conducted in the Patagonia region of Argentina to estimate the prevalence of nine disease agents within the populations of free-ranging culpeo (Dusicyon culpaeus) and grey (Dusicyon griseus) foxes. The disease agents were Aujeszky's disease virus (ADV), Brucella, canine adenovirus (CAV), canine distemper virus (CDV), canine parvovirus (CPV), Encephalitozoon cuniculi, Leptospira, Neospora caninum, and Toxoplasma gondii. A total of 84 foxes were sampled (28 culpeo and 56 grey), and 73% of the sera had antibodies against one or more pathogens. Among these seropositive sera, 47% of them reacted to only one antigen, while the other 53% reacted to multiple antigens. The presence of antibodies to Toxoplasma (20%), Neospora (44%), Leptospira (30%) and Brucella (18%) suggests that these organisms actively circulate in the area. Antibodies against CDV, CAV and CPV were detected in 2%, 5% and 5% of foxes, respectively. Regarding Encephalitozoon cuniculi and ADV, no evidence of either was found.

Vacunas combinadas: pentavalentes y hexavalentes. Introducción en la vacunación infantil / Vaccines combined: pentavalents and hexavalents. Incorporation in the primary vaccination on infants

La incorporación de mayor número de vacunas en los calendarios infantiles ha abierto nuevas vías de investigación. Este trabajo consiste en hacer una revisión bibliográfica sobre las vacunas combinadas con la intención de analizar su evolución y especialmente la inmunogenicidad, seguridad de las vacunas pentavalentes y hexavalentes. Las vacunas pentavalentes y hexavalentes parecen ser seguras y no se han comunicado reacciones adversas de relevancia clínica. Ambas llegan a parámetros subrogados de protección. Queda por definir más concretamente la duración del efecto protector así como establecer la eficacia y efectividad vacunal. Por el momento sólo existen estudios en Fase III, donde demuestran su aceptable inmunogenicidad, reactogenicidad, mayor aceptabilidad al reducir el número de inyecciones y menores costes de almacenamiento, tiempo de administración y material utilizado. Por todo ello hace posible su futura inclusión de forma sistemática en el calendario vacunal. (AU)

Experimental transmission of Sarcocystis speeri Dubey and Lindsay, 1999 from the South American opossum (Didelphis albiventris) to the North American opossum (Didelphis virginiana).

Sarcocystis speeri Dubey and Lindsay, 1999 from the South American opossum Didelphis albiventris was successfully transmitted to the North American opossum Didelphis virginiana. Sporocysts from a naturally infected D. albiventris from Argentina were fed to 2 gamma-interferon knockout (KO) mice. The mice were killed 64 and 71 days after sporocyst feeding (DAF). Muscles containing sarcocysts from the KO mouse killed 71 DAF were fed to a captive D. virginiana; this opossum shed sporocysts 11 days after ingesting sarcocysts. Sporocysts from D. virginiana were fed to 9 KO mice and 4 budgerigars (Melopsittacus undulatus). Schizonts, sarcocysts, or both of S. speeri were found in tissues of all 7 KO mice killed 29-85 DAF; 2 mice died 39 and 48 DAF were not necropsied. Sarcocystis stages were not found in tissues of the 4 budgerigars fed S. speeri sporocysts and killed 35 DAE These results indicate that S. speeri is distinct from Sarcocystis falcatula and Sarcocystis neurona, and that S. speeri is present in both D. albiventris and D. virginiana.

Characterization of Sarcocystis falcatula isolates from the Argentinian opossum, Didelphis albiventris.

Two isolates of Sarcocystis falcatula were obtained from the lungs of budgerigars (Melopsittacus undulatus) fed sporocysts from two naturally-infected South American opossums (Didelphis albiventris). The two isolates were designated SF-1A and SF-2A. Both isolates induced fatal infections in budgerigars. Both isolates underwent schizogony in African green monkey kidney cells. The structure of schizonts in the lungs of budgerigars was more variable than that observed in cell culture. The two isolates were identified as S. falcatula by the two species-specific Hinf 1 restriction fragments dervied from digestion of a PCR amplification using primers JNB33/JNB54. Thus, the South American opossum, D. albiventris, is a definitive host for S. falcatula.

Isolation of Sarcocystis falcatula from the South American opossum (Didelphis albiventris) from Argentina.

Sarcocystis sporocysts from the intestines of four opossums (Didelphis albiventris) from Argentina were identified as Sarcocystis falcatula based on schizogonic stages and pathogenicity to budgerigars (Melopsittacus undulatus). Seven budgerigars fed sporocysts from the opossum feces died of acute sarcocystosis 8, 9, 11, 12, and 14 days after inoculation. Schizonts and merozoites found in the lungs and other organs of the budgerigars were identified as S. falcatula based on structure and immunoreactivity with S. falcatula-specific antibody. Sarcocystis falcatula was also isolated in bovine monocyte cell cultures inoculated with lung tissue from a budgerigar that died nine days after ingesting sporocysts. Two budgerigars inoculated subcutaneously with 1,000,000 culture-derived S. falcatula died 11 and 12 days post-inoculation. This is the first report of S. falcatula infection in South America.

Interspecies differences in renal localization of cyclooxygenase isoforms: implications in nonsteroidal antiinflammatory drug-related nephrotoxicity.

Cyclooxygenase (COX) exists in 2 related but unique isoforms: one is constitutive (COX-1) and functions in normal cell physiology, and the other is inducible (COX-2) and is expressed in response to inflammatory stimuli. Nonsteroidal antiinflammatory drugs (NSAIDs) cause renal toxicity following inhibition of renal cyclooxygenases. Humans and animals exhibit differences in susceptibility to NSAID-related renal toxicity, which may be associated with differences in expression of 1 or both isoforms of COX in the kidney. In this study, we evaluated COX-1 and COX-2 expression in the kidneys of mixed-breed dogs, Sprague-Dawley rats, cynomolgus monkeys, and humans. In addition, the effect of volume depletion on renal COX expression was investigated in rats, dogs, and monkeys. COX expression was evaluated using 1 or more of the following procedures: reverse transcriptase polymerase chain reaction, in situ hybridization, and immunohistochemistry. We demonstrated that both COX isoforms are expressed in the kidneys of all species examined, with differences in the localization and level of basal expression. COX-1 is expressed at high levels in the collecting ducts and renal vasculature of all species and in a small number of papillary interstitial cells in rats, monkeys, and humans. Basal levels of COX-2 are present in the maculae densa, thick ascending limbs, and papillary interstitial cells in rats and dogs and in glomerular podocytes and small blood vessels in monkeys and humans. COX-2 expression is markedly increased in volume-depleted rats and dogs but not monkeys. These results indicate that significant interspecies differences exist in the presence and distribution of COX isoforms, which may help explain the difference in species susceptibility to NSAID-related renal toxicity.