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Objetivo: El objetivo principal del presente estudio fue conocer la situación real de la atención del pie diabético y de riesgo en los centros sanitarios de Atención Primaria de España. Como objetivos secundarios, se estableció determinar si los profesionales de Atención Primaria identifican los procesos de cribado del pie diabético y de riesgo y, si los procesos de cribaje y diagnóstico, precisan implementar estrategias y acciones de mejora en su manejo. Diseño: Estudio cuantitativo, descriptivo y transversal realizado mediante encuesta electrónica autocumplimentada, diseñada ad hoc a través de la aplicación Google Forms, integrada en la plataforma de Google. Marco: Centros sanitarios de Atención Primaria en España. Participantes: Médicos/as y enfermeras/os colegiados/as de Atención Primaria en España. Se obtuvo un tamaño muestral final de 328 encuestados. Variables principales: Se midieron aspectos sociodemográficos y de formación; patologías tratadas; atención prestada por el profesional sanitario a los problemas y afecciones de los pies; procesos de cribado de la neuropatía periférica diabética; sistemas de clasificación de úlceras diabéticas; toma de muestras para cultivo microbiológico y antibiograma y opinión sobre la inclusión del podólogo en el Sistema Público de Salud. Resultados: El 30,8% de los participantes nunca ha recibido formación en pie diabético. La duración de ésta es inferior a 10 horas en casi el 45,0% de los casos. El 57,9% desconoce los cuestionarios de signos y síntomas utilizados para la valoración de la neuropatía periférica diabética. El cuestionario de síntomas positivos, Neuropathy Symptoms Score es el más conocido. El 65,9% de los encuestados reconoce no aplicar ninguno. Conclusión: Se observan déficits de formación relacionados con el nivel de identificación en los procesos de cribado en pie diabético y pie de riesgo. Es necesario implantar acciones de formación que mejoren y fortalezcan los conocimientos en el abordaje de estas entidades patológicas, en concreto los protocolos de cribado y diagnóstico con el fin de prevenir complicaciones y evitar o reducir las amputaciones en el miembro inferior.

The complexity and biologically challenging nature of arid landscapes can generate high inter‐ and intra‐species diversity, although these biomes remain poorly studied. We investigated whether prominent geomorphic features in an Australian arid landscape had similar influences on patterns of intra‐specific genetic diversity of three small mammals with different distribution and life history traits. Specifically, we tested (a) whether mountain ranges harbour high diversity and act as refugia, (b) the extent to which ephemeral river systems pose barriers to gene flow or (c) whether environmental differences explain genetic structure in these species.

Background. Occupational therapy groups have been carried out as interventions in mental health settings across a variety of populations. Limited research explores the lived experience of individuals with depression following participation in recovery oriented occupational therapy groups. Purpose. To better understand how recovery oriented occupational therapy groups shape participants’ personal experience of daily life, including recovery. Method. Five individuals who had previously completed at least one recovery oriented occupational therapy group each participated in two in-depth semi-structured interviews. Analyses of the transcripts were completed using interpretative phenomenological analysis (IPA). Findings. Participants’ experiences of the recovery oriented occupational therapy groups ranged from positive to negative, with variable impacts on their lived experiences. Two major themes emerged: (a) participants’ perception of “normal” and (b) navigation of meaningful participation. Implications. Increased understanding of what aspects of recovery oriented occupational therapy groups are meaningful to individuals with depression can help support their personal recovery process.

Background: Non-surgical blunt traumatic brain injuries (NS-bTBI) interest various non-neurosurgical specialties. Acute coagulopathy is a predictor of morbidity/mortality that can occur after general trauma but not specifically following NS-bTBI. Methods: A total of 141 NS-bTBI patients were included after excluding patients on anti-aggregates/coagulation therapy, or for having medical conditions known as risk factors for coagulopathies or platelet dysfunction. We retrospectively correlated the sequential platelet counts, PT-INR and PTT with quantitative Marshal and Rotterdam scores of serial CTs during hospitalization, as well as with clinical outcomes until discharge. Findings: We observed three distinctive groups with altered platelet counts. The first group 117/141(83%) showed normal platelet counts (150,000-450,000 platelets/mm3) from admission to discharge. A second group, 18/141(13%) patients, developed transient thrombocytopenia (80,000-120,000 platelets/mm3) on days 2 or 3 post trauma. The third group, 6/141(4%) patients, developed thrombocytosis up to an extreme of >1,000,000/mm3 platelets on days 6-9 post trauma. Although patients with thrombocytosis presented with worse admission-GCS scores (8·8±2·9 vs.13±2, p

Este artículo resume ideas y posicionamientos críticos sobre la Educación de Jóvenes y Adultos (EJA) en la Argentina. Tales ideas son producto de discusiones conceptuales y políticas radicadas en la Facultad de Filosofía y Letras de la Universidad de Buenos Aires donde la autora es investigadora. Estas ideas están también influenciadas por la experiencia en equipos de gestión político pedagógica del Ministerio de Educación Nacional y la militancia sindical que desarrolla la autora. El trabajo contiene precisiones conceptuales sobre la EJA y sus sujetos, la historia reciente de la modalidad y el escenario pedagógico y político actual. En los albores del siglo XXI los cambios en la educación argentina marcaron una etapa de optimismo para la EJA que duró hasta que se produce un giro conservador a fines de 2015 con la llegada al gobierno de la Alianza Cambiemos, una expresión de la derecha democrática que ganó laselecciones por el 51% de los votos.*** Educação de Jovens e Adultos na Argentina. História recente, sujeitos, conjuntura e desafios ***Este artigo resume idéias e posições críticas sobre Educação de Jovens e Adultos (EJA) na Argentina. Essas idéias são produto de discussões conceituais e políticas na Faculdade de Filosofia e Letras da Universidade de Buenos Aires (UBA), onde a autora é pesquisadora e também estão influenciadas pela sua experiência em equipes de gestão político-pedagógica no Ministério da Educação Nacional da Argentina e na militância sindical. O trabalho contém precisões conceituais sobre a EJA e seus sujeitos, a história recente da modalidade e o atual cenário pedagógico e político. Na Argentina, os primeiros anos do século XXI, marcaram uma fase de optimismo para a EJA, que durou até produzida uma virada conservadora no final do ano 2015, com a chegada ao governo da Aliança denominada Cambiemos, expressão da direita democrática que ganhou as eleições nacionais por 51% dos votos.Palavras-chave: Educação. Adultos. Direitos. Política. Neoliberalismo.

Background Exposure to antibiotics may increase the risk of type 2 diabetes. Veterans are at increased risk for diabetes and for exposure to antibiotics. Objective To determine the impact of antibiotic exposure for risk of diabetes. Design Retrospective cohort study. Participants Veterans at the New York Harbor Healthcare System enrolled in primary care, 2004–2014, with ≥2 glycosylated hemoglobin test results Main measures The primary exposure was any antimicrobial prescribed >6 months prior to the date of diabetes diagnosis, loss to follow-up, death, or the end of the study, measured as the number of courses of antimicrobial prescriptions filled and the mean daily dose (MDD). The primary outcome was incident diagnosis of diabetes through 2014, defined ≥2 ICD-9 codes for diabetes or ≥2 prescriptions of diabetes medications, other than metformin. Cox proportional hazards regression was used to model antimicrobial medications, demographic and anthropometric measures, and comorbid cardiovascular conditions to incident diabetes. Models incorporated time varying covariates of antimicrobial medication and MDD to analyze associations by antimicrobial class. Key results Among 14,361 Veterans, 9922 (69.1%) were prescribed any antimicrobial medication during the study period. 1413 (9.8%) individuals developed type 2 diabetes. Increased risk of diabetes was associated with >1 prescription (HR 1.13 [1.01–1.26]) compared to none. Time varying analysis of the total number of cumulative courses prescribed showed increased diabetes risk for cephalosporin (HR 1.17 [1.04–1.31]), macrolide (HR 1.08 [1.03–1.13]) and penicillin (HR 1.05 [1.02–1.07]). MDD showed increased risk per 100-unit (mg) increase in antibiotic exposure from (HR 1.05 [1.02–1.08]) for sulfonamide to (HR 1.70 [1.51–1.92]) for cephalosporin. Conclusion Any and repeated exposure to certain antibiotics may increase diabetes risk among Veterans. Results from this study add to the growing evidence suggesting that antibiotic exposure increases risk for diabetes. Antibiotic stewardship may be enhanced by better understanding this risk, and may lower the incidence of diabetes in populations at risk.

Habitat fragmentation can have profound effects on the distribution of genetic variation within and between populations. Previously, we showed that in the ornate dragon lizard, Ctenophorus ornatus, lizards residing on outcrops that are separated by cleared agricultural land are significantly more isolated and hold less genetic variation than lizards residing on neighbouring outcrops connected by undisturbed native vegetation. Here, we extend the fine-scale study to examine the pattern of genetic variation and population structure across the species' range. Using a landscape genetics approach, we test whether land clearing for agricultural purposes has affected the population structure of the ornate dragon lizard. We found significant genetic differentiation between outcrop populations (FST = 0.12), as well as isolation by distance within each geographic region. In support of our previous study, land clearing was associated with higher genetic divergences between outcrops and lower genetic variation within outcrops, but only in the region that had been exposed to intense agriculture for the longest period of time. No other landscape features influenced population structure in any geographic region. These results show that the effects of landscape features can vary across species' ranges and suggest there may be a temporal lag in response to contemporary changes in land use. These findings therefore highlight the need for caution when assessing the impact of contemporary land use practices on genetic variation and population structure.

The influence of geographic range on species persistence has long been of interest and there is a need for a better understanding of the genetic consequences for species with restricted distributions, particularly with the increasing rate of global species extinctions. However, the genetic effects of restricted range are often confounded by the impacts of population distribution. We compared chloroplast and nuclear genetic diversity and differentiation in two acacias, the restricted, patchily distributed Acacia atkinsiana and the widespread, semi-continuously distributed A. ancistrocarpa. Lower intra-population diversity and higher differentiation between populations were seen in A. atkinsiana compared to its widespread congener, A. ancistrocarpa. There was little evidence of geographical influences on population genetic structure in A. ancistrocarpa whereas A. atkinsiana exhibited nuclear genetic structure with isolation by distance, differentiation of near-coastal populations from those in the ranges, and differentiation of peripheral populations from those in the centre of the distribution. These results are consistent with expectations of the effect of geographic range and population distribution on genetic diversity, but indicate that distribution of populations rather than geographic range has influenced the observed genetic structure. The contrasting patterns observed here demonstrate that conservation approaches for species management and ecological restoration need to consider the distribution of populations in geographically restricted species.

Este trabajo realiza un recorrido por las principales lesiones deportivas por sobrecarga de las extremidades inferiores desde el punto de vista biomecánico. Al mismo tiempo, repasa los principales paradigmas biomecánicos en podología y la aplicación de las teorías biomecánicas emergentes en el estudio de estas lesiones. Con la legislación actual, los estudios biomecánicos clínicos de la marcha deben de realizarse en centros sanitarios y los únicos profesionales sanitarios que pueden realizarlos son los podólogos y los médicos (porque ambas tienen la capacidad de diagnosticar), quedando reservado para los licenciados en educación física, los estudios que se realizan en el terreno de juego o en la pista con la finalidad exclusiva de mejorar el rendimiento deportivo, pero nunca con finalidad de tratar una patología por sobrecarga. This work studies the major sports overload injuries of the lower extremities from the biomechanical point of view. At the same time, the main paradigms of podiatric biomechanics and the application of new biomechanical theories in the study of these lesions are reviewed. With current legislation, clinical gait biomechanical studies should be carried out in health centres and the only health professionals who can perform them are podiatrists and doctors (because they both can diagnose). Graduates in physical education can carry out studies in the field or in the sports court for the sole purpose of improving athletic performance, but never intended to treat a pathology overload. Sin financiación No data (2016) UEM

Background and Purpose: We present the first case of combined arterial (vertebral artery dissection) and venous [central sinus vein thrombosis (CSVT)] diseases presenting as Opalski syndrome in a female patient following induced delivery. Case Description: A 32-year-old woman was admitted to our institute two weeks after induced delivery with intriguing neurological findings that were finally diagnosed as a combined venous-arterial disease. Although she was referred diagnosed with CSVT, her neurological findings indicated Wallenberg ‘plus’ syndrome with ipsilateral hemiparesis (Opalski syndrome), further confirmed by neuroimaging revealing arterial disease (vertebral artery dissection) combined with incidental acute CSVT. Coagulation, gynecological and cardiac problems were ruled out. Treatment consisted of continuous heparin with rigorous control of her blood pressure. Nine days later, the patient was discharged with prominent improvements. Most of the symptoms resolved following 3 months of rehabilitation. Conclusions: Atypical strokes (such as Opalski syndrome) might present in postpartum patients. This rare diagnosis should be suspected in patients with Wallenberg ‘plus’ syndrome, and neuroimaging studies for determining the presence of arterial disease and brain stem lesions should be performed. Concomitant CSVT is rare and might mislead. Fine diagnosis followed by immediate conservative treatment can be of great benefit.

We isolated 11 new polymorphic microsatellite markers from Acacia atkinsiana, a plant species endemic to the Pilbara region in Western Australia. Next generation (454) sequencing was used to identify 28 microsatellite markers that were trialled in individuals across the species range. Characterisation of 11 of these loci in 24 individuals from a single population yielded between two and nine alleles per locus, and observed heterozygosity ranged from 0.042 to 0.958. Four loci that amplified in A. atkinsiana were also successfully amplified and polymorphic in Acacia ancistrocarpa. These loci will be valuable for assessing population genetic structure in A. atkinsiana and identifying seed sources for rehabilitation of disturbed sites.

An important question for the conservation of species dwelling in fragmented habitats is whether changes to the intervening landscape create a barrier to gene flow. Here, we make use of the spatial distribution of the granite outcrop-dwelling lizard, Ctenophorus ornatus, to compare inferred levels of gene flow between outcrops in a nature reserve with that between outcrops in the adjacent agricultural land. Genetic variation, relatedness and subdivision were compared within groups of individuals from different outcrops similar in size and distance apart at each site. In the agricultural land, we found significantly lower genetic variation within outcrops and greater genetic differentiation between outcrops than in the reserve. Further, the rate at which genetic divergence between outcrops increased over geographical distance was significantly greater in the agricultural land than in the reserve. We also found that individuals were more closely related within outcrops but more distantly related between outcrops in the cleared land. These effects occur over a small spatial scale with an average distance between outcrops of less than five kilometres. Thus, even though land clearing around the outcrops leaves outcrop size unchanged, it restricts gene flow, reducing genetic variation and increasing population structure, with potentially negative consequences for the long-term persistence of the lizards on these outcrops.

αMUPA transgenic mice spontaneously consume less food compared with their wild type (WT) ancestors due to endogenously increased levels of the satiety hormone leptin. αMUPA mice share many benefits with mice under caloric restriction (CR) including an extended life span. To understand mechanisms linked to cardiac aging, we explored the response of αMUPA hearts to ischemic conditions at the age of 6, 18, or 24 months. Mice were subjected to myocardial infarction (MI) in vivo and to ischemia/reperfusion ex vivo. Compared to WT mice, αMUPA showed functional and histological advantages under all experimental conditions. At 24 months, none of the WT mice survived the first ischemic day while αMUPA mice demonstrated 50% survival after 7 ischemic days. Leptin, an adipokine decreasing under CR, was consistently ~60% higher in αMUPA sera at baseline. Leptin levels gradually increased in both genotypes 24h post MI but were doubled in αMUPA. Pretreatment with leptin neutralizing antibodies or with inhibitors of leptin signaling (AG-490 and Wortmannin) abrogated the αMUPA benefits. The antibodies also reduced phosphorylation of the leptin signaling components STAT3 and AKT specifically in the αMUPA myocardium. αMUPA mice did not show elevation in adiponectin, an adipokine previously implicated in CR-induced cardioprotection. WT mice treated for short-term CR exhibited cardioprotection similar to that of αMUPA, however, along with increased adiponectin at baseline. Collectively, the results demonstrate a life-long increased ischemic tolerance in αMUPA mice, indicating the attenuation of cardiac aging. αMUPA cardioprotection is mediated through endogenous leptin, suggesting a protective pathway distinct from that elicited under CR.

A 5-year-old, intact male, stray dog was presented in poor body condition, with pallor, muzzle deformity, multiple oozing fistulas with grass awns, bilateral sanguinopurulent nasal discharge and a fleshy friable mass occupying part of the hard palate. A friable mass occupying both nasal cavities was found on rhinoscopy. The dog had moderate nonregenerative normochromic-microcytic anemia, thrombocytopenia, hyperglobulinemia, and hypoalbuminemia. Cytologic preparations of the nasal and oral masses contained a neoplastic population of round cells with intracytoplasmic and extracellular vacuoles. Leishmania amastigotes also were observed, in the cytoplasm of macrophages and, occasionally, within neoplastic cells. A diagnosis of transmissible venereal tumor and concurrent leishmaniosis was made. Treatment with vincristine and allopurinol resulted in complete resolution of clinical signs and disappearance of the masses. The presence of amastigotes in neoplastic TVT cells may suggest an alternative mode of transmission of canine leishmaniosis where these diseases co-exist.

2003 marks 15 years of publication of Advanced Materials-the journal's crystal annlvcrsary Crystals of all typex-from liquid to photonic - have long occupied materials scientists. making this anniversury a purticularly relevant one. The events and innovations that have contributed to the present success of Advanced Materials are highlighted in this Editorial and a glimpse is given of what this year holds in store.

El abordaje de los aspectos políticos de la relación entre educación o formación y trabajo constituye un espacio privilegiado para la discusión de una amplia gama de aspectos y dimensiones que atraviesan el campo de esta problemática. En este artículo, analizamos dos experiencias educativas -los bachilleratos populares y contraprestaciones educativas en los planes sociales-, entendidos como dispositivos de injerencia de la regulación estatal. Ya sea por las características distintivas de los sujetos, como por la intensidad del sentido político, en ambos espacios el Estado regula y define las relaciones entre sujetos y educación. Si bien se trata de dos ámbitos que difieren por sus formatos y objetivos político-pedagógicos, creemos que en ambos el tipo de vinculación con el Estado define los modos de relación y las prácticas educativas que se generan. Por otro lado, las dos experiencias tienen en común que, además de estar relacionados con el derecho a la educación, también lo están con otro derecho: el derecho al trabajo. No obstante, en este punto existen diferencias sustantivas entre los objetivos explícitos de ambos espacios no sólo en términos de concepción sino de intencionalidad política.

Major histocompatibility complex (MHC) gene polymorphism is thought to be driven by host-parasite co-evolution, but the evidence for an association between the selective pressure from parasites and the number of MHC alleles segregating in a population is scarce and inconsistent. Here, we characterized MHC class I polymorphism in a lizard whose habitat preferences (rock outcrops) lead to the formation of well-defined and stable populations. We investigated the association between the load of ticks, which were used as a proxy for the load of pathogens they transmit, and MHC class I polymorphism across populations in two types of habitat: undisturbed reserves and agricultural land. We hypothesized that the association would be positive across undisturbed reserve populations, but across fragmented agricultural land populations, the relationship would be distorted by the loss of MHC variation due to drift. After controlling for habitat, MHC diversity was not associated with tick number, and the habitats did not differ in this respect. Neither did we detect a difference between habitats in the relationship between MHC and neutral diversity, which was positive across all populations. However, there was extensive variation in the number of MHC alleles per individual, and we found that tick number was positively associated with the average number of alleles carried by lizards across reserve populations, but not across populations from disturbed agricultural land. Our results thus indicate that local differences in selection from parasites may contribute to MHC copy number variation within species, but habitat degradation can distort this relationship.

We describe the isolation and development of 18 polymorphic microsatellite loci for the western rock lobster Panulirus cygnus (Decapoda: Palinuridae). The loci were tested in 37 individuals from a single population situated near the centre of the species’ distribution. No evidence of linkage disequilibrium was detected between any pair of loci. However, seven loci showed significant departures from Hardy–Weinberg expectations. The number of alleles per locus ranged from three to 31.

We describe the isolation and development of 20 polymorphic microsatellite loci for the ornate dragon lizard Ctenophorus ornatus. Characterization of these loci in 29 individuals from a single population yielded between five and twenty alleles per locus. Expected heterozygosities ranged from 0.32 to 1.00 and only one locus deviated from Hardy–Weinberg expectations. There was no evidence of linkage disequilibrium between any pair of loci.

Sperm competition theory predicts that males should increase their expenditure on the ejaculate with increasing risk of sperm competition, but decrease their expenditure with increasing intensity. There is accumulating evidence for sperm competition theory, based on examinations of testes size and/or the numbers of sperm ejaculated. However, recent studies suggest that ejaculate quality can also be subject to selection by sperm competition. We used experimental manipulations of the risk and intensity of sperm competition in the cricket, Teleogryllus oceanicus . We found that males produced ejaculates with a greater percentage of live sperm when they had encountered a rival male prior to mating. However, when mating with a female that presented a high intensity of sperm competition, males did not respond to risk, but produced ejaculates with a reduced percentage of live sperm. Our data suggest that males exhibit a fine-tuned hierarchy of responses to these cues of sperm competition.

The purpose of this paper was to assess several measures of utilisation of prenatal care as predictors of birth outcome in a community where the availability and quality of services were equal for all pregnant women. A case-control study was conducted in a small community in Israel, comparing 189 women whose pregnancy resulted in an unfavourable outcome (perinatal mortality, preterm birth and low birthweight at term) with 384 women, matched by birth order, who had a live, full-term infant weighing 2500 g or more. In a multivariable analysis, adjusting for pregnancy complications, maternal age, parity and socio-economic disadvantage, gestational age at initiation of prenatal care was not an independent predictor of unfavourable outcome; neither was lower than the recommended number of visits for the period under care. However, a higher than expected number of visits was associated with unfavourable outcome [odds ratio (OR) = 6.10, 95% CI 2.09-17.78], as was non-compliance with medical recommendations [OR = 2.02, 95% CI 1.24-3.29. The context of prenatal care delivery, as well as the process of care and compliance with recommendations, should be assessed in order to determine the impact of prenatal care on birth outcomes.

Aim Glucose-dependent insulinotropic peptide (GIP) is an incretin hormone that is released from intestinal K cells in response to nutrient ingestion. We aimed to investigate the therapeutic potential of the novel N- and C-terminally modified GIP analogue AC163794. Methods AC163794 was synthesized by solid-phase peptide synthesis. Design involved the substitution of the C-terminus tail region of the dipeptidyl peptidase IV (DPP-IV)-resistant GIP analogue [d-Ala2]GIP(1–42) with the unique nine amino acid tail region of exenatide. The functional activity and binding of AC163794 to the GIP receptor were evaluated in RIN-m5F β-cells. In vitro metabolic stability was tested in human plasma and kidney membrane preparations. Acute insulinotropic effects were investigated in isolated mouse islets and during an intravenous glucose tolerance test in normal and diabetic Zucker fatty diabetic (ZDF) rats. The biological actions of AC163794 were comprehensively assessed in normal, ob/ob and high-fat-fed streptozotocin (STZ)-induced diabetic mice. Acute glucoregulatory effects of AC163794 were tested in diet-induced obese mice treated subchronically with AC3174, the exendatide analogue [Leu14] exenatide. Human GIP or [d-Ala2]GIP(1–42) were used for comparison. Results AC163794 exhibited nanomolar functional GIP receptor potency in vitro similar to GIP and [d-Ala2]GIP(1–42). AC163794 was metabolically more stable in vitro and displayed longer duration of insulinotropic action in vivo versus GIP and [d-Ala2]GIP(1–42). In diabetic mice, AC163794 improved HbA1c through enhanced insulinotropic action, partial restoration of pancreatic insulin content and improved insulin sensitivity with no adverse effects on fat storage and metabolism. AC163794 provided additional baseline glucose-lowering when injected to mice treated with AC3174. Conclusions These studies support the potential use of a novel GIP analogue AC163794 for the treatment of type 2 diabetes.

Combination therapy is being increasingly used as a treatment paradigm for metabolic diseases such as diabetes and obesity. In the peptide therapeutics realm, recent work has highlighted the therapeutic potential of chimeric peptides that act on two distinct receptors, thereby harnessing parallel complementary mechanisms to induce additive or synergistic benefit compared to monotherapy. Here, we extend this hypothesis by linking a known anti-diabetic peptide with an anti-obesity peptide into a novel peptide hybrid, which we termed a phybrid. We report on the synthesis and biological activity of two such phybrids (AC164204 and AC164209), comprised of a glucagon-like peptide-1 receptor (GLP1-R) agonist, and exenatide analog, AC3082, covalently linked to a second generation amylin analog, davalintide. Both molecules acted as full agonists at their cognate receptors in vitro, albeit with reduced potency at the calcitonin receptor indicating slightly perturbed amylin agonism. In obese diabetic Lep(ob)/Lep (ob) mice sustained infusion of AC164204 and AC164209 reduced glucose and glycated haemoglobin (HbA1c) equivalently but induced greater weight loss relative to exenatide administration alone. Weight loss was similar to that induced by combined administration of exenatide and davalintide. In diet-induced obese rats, both phybrids dose-dependently reduced food intake and body weight to a greater extent than exenatide or davalintide alone, and equal to co-infusion of exenatide and davalintide. Phybrid-mediated and exenatide + davalintide-mediated weight loss was associated with reduced adiposity and preservation of lean mass. These data are the first to provide in vivo proof-of-concept for multi-pathway targeting in metabolic disease via a peptide hybrid, demonstrating that this approach is as effective as co-administration of individual peptides.

Species inhabiting ancient, geologically stable landscapes that have been impacted by agriculture and urbanisation are expected to have complex patterns of genetic subdivision due to the influence of both historical and contemporary gene flow. Here, we investigate genetic differences among populations of the granite outcrop-dwelling lizard Ctenophorus ornatus, a phenotypically variable species with a wide geographical distribution across the south-west of Western Australia. Phylogenetic analysis of mitochondrial DNA sequence data revealed two distinct evolutionary lineages that have been isolated for more than four million years within the C. ornatus complex. This evolutionary split is associated with a change in dorsal colouration of the lizards from deep brown or black to reddish-pink. In addition, analysis of microsatellite data revealed high levels of genetic structuring within each lineage, as well as strong isolation by distance at multiple spatial scales. Among the 50 outcrop populations’ analysed, non-hierarchical Bayesian clustering analysis revealed the presence of 23 distinct genetic groups, with outcrop populations less than 4 km apart usually forming a single genetic group. When a hierarchical analysis was carried out, almost every outcrop was assigned to a different genetic group. Our results show there are multiple levels of genetic structuring in C. ornatus, reflecting the influence of both historical and contemporary evolutionary processes. They also highlight the need to recognise the presence of two evolutionarily distinct lineages when making conservation management decisions on this species.

El «pie diabético» incluye una serie de síndromes en los que la interacción de la pérdida de la sensación protectora por la presencia de neuropatía sensitiva, el cambio en los puntos de presión a causa de la neuropatía motora, la disfunción autonómica y la disminución del flujo sanguíneo por enfermedad vascular periférica pueden dar lugar a la aparición de lesiones o úlceras inducidas por traumatismos menores que pasan «desapercibidos». Esta situación conlleva una importante morbilidad y un riesgo de amputación elevado. Se puede prevenir con la aplicación de programas de prevención, basados en la detección precoz de neuropatía, evaluación de factores de riesgo asociados, junto a aplicación de un programa estructurado de educación y tratamiento de los factores de riesgo. Incluyen el manejo óptimo de la lesión aguda, con antibioterapia específica y cuidados que favorecen un cicatrización correcta y temprana. Diabetic foot includes a group of syndromes in which the interaction among loss of protective sensation due to sensory peripheral neuropathy, a change in pressure spots due to motor neuropathy, autonomic dysfunction, and decreased blood supply due to peripheral vascular disease can lead to the occurrence of wounds or ulcers usually related to minimal injuries that are usually unnoticed. Diabetic foot is associated with higher morbidity and a high risk of amputation of the foot or limb. These situations can be avoided with an appropriate prevention program, based on the early detection of diabetic neuropathy and assessment of the associated risk factors in addition to structured patient education. Also important are optimal treatment of the acute injury, with specific antibiotics and foot care measures that encourage early and effective healing. Sin financiación 0.104 SJR (2012) Q4, 53/57 Rheumatology UEM

Introduction PYY is a 36-residue peptide first isolated from porcine intestine (Figure 1) [1,2]. Two endogenous forms of PYY, PYY(1-36) and the post-DPPIV [3,4] activated PYY(3-36), are released into the circulation following a meal [1,5]. PYY(3-36) appears to be the predominant secreted form. PYY has been known to inhibit gastric, [6] pancreatic and intestinal secretions [7]. PYY binds and activates at least four receptor subtypes (Y1, Y2, Y4 and Y5) [8-10] in rats and humans. These Y receptor subtypes display different patterns of affinity and activation for PYY, PYY(3-36) and synthetically modified PYY analogs. PYY(3-36) is a selective ligand for Y2 and Y5 receptors, implicated in food intake and feeding behavior, respectively [11]. In this study, PYY(3-36) analogs, where each residue of the natural sequence is replaced by L-alanine, and analogs with multiple alanine substitutions were synthesized. The three alanines at positions 7, 12 and 22 were replaced by a D-alanine. The affinity of each analog to the Y family of receptors and the ability of the analogs to decrease acute food intake in mouse are presented. Additionally, the efficacy of a single equimolar dose of PYY(3-36) and a subset of the analogs to reduce body weight in the chronic weight loss assay in the mouse is summarized.

The significance of serum IgG and IgA antibodies to cytomegalovirus (CMV) at various stages of human immune deficiency virus (HIV) infection was studied in 175 homosexual men. Sera were obtained from 123 HIV seropositives [41 asymptomatic, 29 with lymphadenopathy associated syndrome (LAS), 22 with AIDS related complex (ARC), and 31 AIDS patients], 17 HIV seroconverters, and 35 HIV asymptomatic seronegatives. The sera were tested blindly for CMV IgA and IgG antibodies using the immunoperoxidase assay (IPA) and CMV infected human embryo cells. Cross-sectional analysis of CMV IgG antibodies at a titer of greater than or equal to 20 showed 87% and 100% prevalence in the HIV seronegative groups and in the HIV seropositive groups, respectively (P less than 0.05). CMV IgG antibodies at a titer of greater than or equal to 80 were present in significantly higher proportions among the HIV seropositive subjects of the various groups as compared with the HIV seronegative homosexual men. However, in the HIV seronegatives who later seroconverted to HIV, a significantly higher prevalence of CMV antibodies (35%) was detected before HIV seroconversion, as compared with the persistently HIV seronegative subjects (14.3%) (P less than 0.05). The HIV seronegatives pre-HIV seroconversion also exhibited a significantly higher geometric mean titer (GMT) of CMV IgG antibodies (62.17 +/- 0.64) as compared with the persistently HIV seronegatives (34.0 +/- 0.6) (P = 0.03). Significantly higher GMTs of CMV IgG antibodies were detected in all the HIV seropositive groups as compared with the persistently HIV seronegative group. CMV IgG antibodies were not detected in the HIV seronegative subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

The design, synthesis and pharmacology of novel long-acting exenatide analogs for the treatment of metabolic diseases are described. These molecules display enhanced pharmacokinetic profile and potent glucoregulatory and weight lowering actions compared to native exenatide. [Leu(14)]exenatide-ABD is an 88 residue peptide amide incorporating an Albumin Binding Domain (ABD) scaffold. [Leu(14)]exenatide-ABP is a 53 residue peptide incorporating a short Albumin Binding Peptide (ABP). [Leu(14)]exenatide-ABD and [Leu(14)]exenatide-ABP exhibited nanomolar functional GLP-1 receptor potency and were metabolically stable in vitro in human plasma and in a pancreatic digestive enzyme mixture. Both molecules displayed picomolar and nanomolar binding association with albumin across multiple species and circulating half lives of 16 and 11 hours, respectively, post a single IV dose in rats. Unlike exenatide, both molecules elicited robust glucose lowering when injected 1 day prior to an oral glucose tolerance test, indicative of their extended duration of action. [Leu(14)]exenatide-ABD was compared to exenatide in a Lep (ob/ob) mouse model of diabetes. Twice-weekly subcutaneously dosed [Leu(14)]exenatide-ABD displayed superior glucose lowering and weight loss in diabetic mice when compared to continuously infused exenatide at the same total weekly dose. A single oral administration of each molecule via an enteric coated capsule to cynomolgus monkeys showed superior pharmacokinetics for [Leu(14)]exenatide-ABD as compared to [Leu(14)]exenatide-ABP with detectable exposure longer than 14 days. These studies support the potential use of these novel long acting exenatide analogs with different routes of administration for the treatment of type 2 diabetes.