Protocolo de anestesia fija a campo para amputación en un equino

Un equino mestizo macho de 3 años de edad de 320 kg alojado en una ONG fue sometido a una amputación metatarsiana proximal por fractura expuesta del tercer metatarsiano (MIII) en el miembro posterior izquierdo (MPI). El objetivo es describir el protocolo anestésico empleado durante una cirugía traumatológica a campo de duración extensa para lo descripto con este tipo de anestesia total intravenosa (TIVA), con su respectivo monitoreo multiparamétrico. El animal fue medicado durante tres días previo a la cirugía con Fenilbutazona (4,4mg/kg12-24hs), Penicilina (20000UI/kg/12hs), Estreptomicina (8mg/kg/12hs) y gentamicina (6,6mg/kg/24hs). Los prequirúrgicos (hemograma, bioquímica plasmática y ECG) fueron aptos.Facultad de Ciencias Veterinaria

Validation of a score tool for measurement of histological severity in juvenile dermatomyositis and association with clinical severity of disease.

OBJECTIVES: To study muscle biopsy tissue from patients with juvenile dermatomyositis (JDM) in order to test the reliability of a score tool designed to quantify the severity of histological abnormalities when applied to biceps humeri in addition to quadriceps femoris. Additionally, to evaluate whether elements of the tool correlate with clinical measures of disease severity. METHODS: 55 patients with JDM with muscle biopsy tissue and clinical data available were included. Biopsy samples (33 quadriceps, 22 biceps) were prepared and stained using standardised protocols. A Latin square design was used by the International Juvenile Dermatomyositis Biopsy Consensus Group to score cases using our previously published score tool. Reliability was assessed by intraclass correlation coefficient (ICC) and scorer agreement (α) by assessing variation in scorers' ratings. Scores from the most reliable tool items correlated with clinical measures of disease activity at the time of biopsy. RESULTS: Inter- and intraobserver agreement was good or high for many tool items, including overall assessment of severity using a Visual Analogue Scale. The tool functioned equally well on biceps and quadriceps samples. A modified tool using the most reliable score items showed good correlation with measures of disease activity. CONCLUSIONS: The JDM biopsy score tool has high inter- and intraobserver agreement and can be used on both biceps and quadriceps muscle tissue. Importantly, the modified tool correlates well with clinical measures of disease activity. We propose that standardised assessment of muscle biopsy tissue should be considered in diagnostic investigation and clinical trials in JDM

Open-Label Study of Duloxetine for the Treatment of Obsessive-Compulsive Disorder

Background: This study sought to investigate the efficacy of duloxetine for the treatment of obsessive-compulsive disorder (DSM-IV). Methods: Twenty individuals were enrolled in a 17-week, open-label trial of duloxetine at Massachusetts General Hospital. Data were collected between March 2007 and September 2012. Study measures assessing obsessive-compulsive disorder symptoms, quality of life, depression, and anxiety were administered at baseline and weeks 1, 5, 9, 13, and 17. The primary outcome measures were the Yale-Brown Obsessive Compulsive Scale and Clinical Global Improvement scale. Results: For the 12 study completers, pre- and posttreatment analyses revealed significant improvements (P<.05) on clinician- and self-rated measures of obsessive-compulsive disorder symptoms and quality of life. Among the 12 completers, more than one-half (n=7) satisfied full medication response criteria. Intention-to-treat analyses (n=20) showed similar improvements (P<.05) on primary and secondary study outcome measures. Conclusion: The results of this study suggest that duloxetine may provide a significant reduction in symptoms for patients with obsessive-compulsive disorder. ClinicalTrials.gov NCT00464698; http://clinicaltrials.gov/ct2/show/NCT00464698?term=NCT00464698&rank=1

TCR ligand density and affinity determine peripheral induction of Foxp3 in vivo

T cell receptor (TCR) ligation is required for the extrathymic differentiation of forkhead box p3+ (Foxp3+) regulatory T cells. Several lines of evidence indicate that weak TCR stimulation favors induction of Foxp3 in the periphery; however, it remains to be determined how TCR ligand potency influences this process. We characterized the density and affinity of TCR ligand favorable for Foxp3 induction and found that a low dose of a strong agonist resulted in maximal induction of Foxp3 in vivo. Initial Foxp3 induction by weak agonist peptide could be enhanced by disruption of TCR–peptide major histocompatibility complex (pMHC) interactions or alteration of peptide dose. However, time course experiments revealed that Foxp3-positive cells induced by weak agonist stimulation are deleted, along with their Foxp3-negative counterparts, whereas Foxp3-positive cells induced by low doses of the strong agonist persist. Our results suggest that, together, pMHC ligand potency, density, and duration of TCR interactions define a cumulative quantity of TCR stimulation that determines initial peripheral Foxp3 induction. However, in the persistence of induced Foxp3+ T cells, TCR ligand potency and density are noninterchangeable factors that influence the route to peripheral tolerance

Calcium dysregulation, functional calpainopathy, and endoplasmic reticulum stress in sporadic inclusion body myositis

Sporadic inclusion body myositis (IBM) is the most common primary myopathy in the elderly, but its pathoetiology is still unclear. Perturbed myocellular calcium (Ca2+) homeostasis can exacerbate many of the factors proposed to mediate muscle degeneration in IBM, such as mitochondrial dysfunction, protein aggregation, and endoplasmic reticulum stress. Ca2+ dysregulation may plausibly be initiated in IBM by immune-mediated membrane damage and/or abnormally accumulating proteins, but no studies to date have investigated Ca2+ regulation in IBM patients. We first investigated protein expression via immunoblot in muscle biopsies from IBM, dermatomyositis, and non-myositis control patients, identifying several differentially expressed Ca2+-regulatory proteins in IBM. Next, we investigated the Ca2+-signaling transcriptome by RNA-seq, finding 54 of 183 (29.5%) genes from an unbiased list differentially expressed in IBM vs. controls. Using an established statistical approach to relate genes with causal transcription networks, Ca2+ abundance was considered a significant upstream regulator of observed whole-transcriptome changes. Post-hoc analyses of Ca2+-regulatory mRNA and protein data indicated a lower protein to transcript ratio in IBM vs. controls, which we hypothesized may relate to increased Ca2+-dependent proteolysis and decreased protein translation. Supporting this hypothesis, we observed robust (4-fold) elevation in the autolytic activation of a Ca2+-activated protease, calpain-1, as well as increased signaling for translational attenuation (eIF2α phosphorylation) downstream of the unfolded protein response. Finally, in IBM samples we observed mRNA and protein under-expression of calpain-3, the skeletal muscle-specific calpain, which broadly supports proper Ca2+ homeostasis. Together, these data provide novel insight into mechanisms by which intracellular Ca2+ regulation is perturbed in IBM and offer evidence of pathological downstream effects.https://doi.org/10.1186/s40478-017-0427-

Cowries in the archaeology of West Africa: the present picture

Despite the perceived importance of cowrie shells as indicators of long-distance connections in the West African past, their distribution and consumption patterns in archaeological contexts remain surprisingly underexplored, a gap that is only partly explicable by the sparse distribution of archaeological sites within the sub-continent. General writings on the timeline of importation of cowries into West Africa often fail to take into account the latest archaeological evidence and rely instead on accounts drawn from historical or ethnographic documents. This paper is based on a first-hand assessment of over 4500 shells from 78 sites across West Africa, examining chronology, shell species and processes of modification to assess what distribution patterns can tell us about the history of importation and usage of cowries. These first-hand analyses are paralleled by a consideration of published materials. We re-examine the default assumption that two distinct routes of entry existed — one overland from North Africa before the fifteenth century, another coming into use from the time sea links were established with the East African coast and becoming predominant by the middle of the nineteenth century. We focus on the eastern part of West Africa, where the importance of imported cowries to local communities in relatively recent periods is well known and from where we have a good archaeological sample. The conclusion is that on suitably large assemblages shell size can be an indication of provenance and that, while the present archaeological picture seems largely to confirm historical sources, much of this may be due to the discrepancy in archaeological data available from the Sahara/Sahel zone compared to the more forested regions of the sub-continent. Future archaeological work will clarify this matter

Cross-species amplification of 41 microsatellites in European cyprinids: A tool for evolutionary, population genetics and hybridization studies

<p>Abstract</p> <p>Background</p> <p>Cyprinids display the most abundant and widespread species among the European freshwater Teleostei and are known to hybridize quite commonly. Nevertheless, a limited number of markers for conducting comparative differentiation, evolutionary and hybridization dynamics studies are available to date.</p> <p>Findings</p> <p>Five multiplex PCR sets were optimized in order to assay 41 cyprinid-specific polymorphic microsatellite loci (including 10 novel loci isolated from <it>Chondrostoma nasus nasus, Chondrostoma toxostoma toxostoma </it>and <it>Leuciscus leuciscus</it>) for 503 individuals (440 purebred specimens and 63 hybrids) from 15 European cyprinid species. The level of genetic diversity was assessed in <it>Alburnus alburnus, Alburnoides bipunctatus, C. genei, C. n. nasus, C. soetta, C. t. toxostoma, L. idus, L. leuciscus, Pachychilon pictum, Rutilus rutilus, Squalius cephalus </it>and <it>Telestes souffia</it>. The applicability of the markers was also tested on <it>Abramis brama, Blicca bjoerkna </it>and <it>Scardinius erythrophtalmus </it>specimens. Overall, between 24 and 37 of these markers revealed polymorphic for the investigated species and 23 markers amplified for all the 15 European cyprinid species.</p> <p>Conclusions</p> <p>The developed set of markers demonstrated its performance in discriminating European cyprinid species. Furthermore, it allowed detecting and characterizing hybrid individuals. These microsatellites will therefore be useful to perform comparative evolutionary and population genetics studies dealing with European cyprinids, what is of particular interest in conservation issues and constitutes a tool of choice to conduct hybridization studies.</p

Attenuated T Cell Responses to a High-Potency Ligand In Vivo

According to this study, the strongest T cell receptor ligands in vitro do not necessarily induce the strongest T cell responses in vivo, suggesting that vaccine designers may need to reconsider their strategies

Low fitness at low latitudes: Wintering in the tropics increases migratory delays and mortality rates in an Arctic breeding shorebird

Publisher's version (útgefin grein)Evolutionary theories of seasonal migration generally assume that the costs of longer migrations are balanced by benefits at the non-breeding destinations. We tested, and rejected, the null hypothesis of equal survival and timing of spring migration for High Arctic breeding sanderling Calidris alba using six and eight winter destinations between 55°N and 25°S, respectively. Annual apparent survival was considerably lower for adult birds wintering in tropical West Africa (Mauritania: 0.74 and Ghana: 0.75) than in three European sites (0.84, 0.84 and 0.87) and in subtropical Namibia (0.85). Moreover, compared with adults, second calendar-year sanderlings in the tropics, but not in Europe, often refrained from migrating north during the first possible breeding season. During northward migration, tropical-wintering sanderlings occurred at their final staging site in Iceland 5–15 days later than birds wintering further north or south. Namibia-wintering sanderlings tracked with solar geolocators only staged in West Africa during southward migration. The low annual survival, the later age of first northward migration and the later passage through Iceland during northward migration of tropical-wintering sanderlings, in addition to the skipping of this area during northward but not southward migration by Namibia-wintering sanderlings, all suggest they face issues during the late non-breeding season in West Africa. Migrating sanderlings defy long distances but may end up in winter areas with poor fitness prospects. We suggest that ecological conditions in tropical West Africa make the fuelling prior to northward departure problematic.Annual expeditions to Mauritania were organized by NIOZ, and we especially thank Maarten Brugge, Anne Dekinga, Jutta Leyrer and Bernard Spaans for their contributions. The Parc National du Banc d'Arguin granted research permits and facilitated access. J.R. and T.S.L.V. thank Aarhus University for logistical support at Zackenberg. Benoît Sittler organized expeditions to Karupelv Valley. The Farlington Ringing Group provided cannon‐net equipment. This work was supported by two grants from the Netherlands Polar Programme (851.40.072 and 866.15.207) of the Netherlands Organisation for Scientific research (NWO) and from the Metawad project awarded by Waddenfonds (WF209925) to JR and TP. The measurements in Mauritania had their beginnings in the Prins Bernhard Cultuurfondsprijs to TP. JR and TP also received INTERACT grants for Transnational Access from the European Community's Seventh Framework Programme (grant agreement No262693). JR received a generous donation from World Wildlife Fund Netherlands. JAA was supported by FCT (SFRH/BPD/91527/2012). OG and Loïc Bollache were supported by the French Polar Institute (IPEV; program ‘1036 Interactions') and TL by a Veni grant (no. 016.Veni.192.245) from NWO. The authors declare no conflict of interest. This study is based on the efforts of more than 2,000 observers reporting colour‐ringed sanderlings. We especially thank Guðmundur Örn Benediktsson, John Bowler, Ruth Croger, Anne de Potier, Benjamin Gnep, Kim Fischer, Kirsten Grond, Eileen Hughes, Hilger Lemke, Pedro Lourenço, Andy Johnson, Pierre Leon, Jelle Loonstra, Sebastien Nedellec, Afonso Rocha, Brian Rogers, Ron Summers, Jan van Dijk and Hein Verkade. Anneke Bol, Marco van der Velde and Yvonne Verkuil molecularly sexed the majority of birds, Maria Teixeira and Jérôme Moreau sexed eight individuals. Ron Porter created flags for geolocator attachment. Eldar Rakhimberdiev answered questions concerning FLightR and Allert Bijleveld, Jesse Conklin, Rosemarie Kentie, Thomas Oudman, Janne Ouwehand, Emma Penning, Eldar Rakhimberdiev, Brett Sandercock, Ron Summers, Yvonne Verkuil and two reviewers critically commented on drafts. Benjamin Gnep created Figure.Peer Reviewe

Multiple Sclerosis Risk Variant HLA-DRB1*1501 Associates with High Expression of DRB1 Gene in Different Human Populations

The human leukocyte antigen (HLA) DRB1*1501 has been consistently associated with multiple sclerosis (MS) in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL) for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS). We found that the Tag of DRB1*1501, rs3135388 A allele, correlated with high expression of DRB1, DRB5 and DQB1 genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of DQB1, DRB5 and DRB1, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of DRB1 and DQB1 alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the DRB1*1501 allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the DR/DQ expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone