Targeted management buffers negative impacts of climate change on the hihi, a threatened New Zealand passerine

In order to buffer the risks climate change poses to biodiversity, managers need to develop new strategies to cope with an increasingly dynamic environment. Supplementary Feeding (SF) is a commonly-used form of conservation management that may help buffer the impacts of climate change. However, the role of SF as an adaptation tool is yet to be fully understood. Here we used the program MARK to quantify the relationship between weather (average temperature and total precipitation) and vital rates (survival and recruitment) of an island bird population, the hihi Notiomystis cincta, for which long term demographic data are available under periods of little and ad libitum SF. We then used predictive population modelling to project this population’s dynamics under each management strategy and several climate change scenarios in accordance with the Intergovernmental Panel on Climate Change predictions. Our stochastic population projections revealed that ad libitum SF likely buffer the population against heavier rainfall and more stochastic precipitation patterns; no buffering effect on temperature was detected. While the current SF approach is unlikely to prevent local extinction of the population under increasing temperatures, SF still presents itself as a valuable climate change adaptation tool by delaying extinction. To the best of our knowledge, this is the first study to quantify the interaction between climate and SF intensity of a threatened population. We call for on-going critical evaluation of management measures, and suggest that novel adaptation solutions that combine current approaches are required for conserving species with limited opportunity for dispersal

In vivo assessment of gastrotomy closure with over-the-scope clips in an experimental model for varicocelectomy

BACKGROUND: Gastrotomy closure remains the major limiting factor for human translation of transgastric surgery; the over-the-scope clip (OTSC) system was proposed as a possibility for this purpose. Transgastric access is good for a pelvic approach, making varicocelectomy a possible indication for natural orifice transluminal endoscopic surgery (NOTES). OBJECTIVE: To evaluate the reliability of the OTSC system in vivo after transgastric testicular vessel ligation (varicocelectomy model). DESIGN: There were 3 experimental groups (5 animals in each): groups 1 and 3, gastrotomy dilation up to 18 mm, surgery was performed with a double-channel endoscope; group 2, gastrotomy dilation up to 13 mm, surgery was performed with a single-channel endoscope. SETTING: Surgical Sciences Research Domain, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal. INTERVENTIONS: Bilateral testicular vessel ligation by transgastric access. Gastrotomy closed with the largest version of OTSC system (12 mm): a single clip in groups 1 and 2, and 2 clips in group 3. Animals were monitored for 2 weeks, killed, and submitted for necropsy. MAIN OUTCOME MEASUREMENTS: Adequacy of closure and healing after the use of the OTSC system. Statistical analysis. RESULTS: Vessel ligation was easily achieved in all groups. Although differences in the complication rate did not reach statistical significance (P = .099), there was a clear tendency for a better prognosis in groups 2 and 3 than group 1. In fact, only 2 animals from group 1 had complications related to incomplete gastrotomy closure. LIMITATIONS: Small number of animals per group; nonrandomized study. CONCLUSIONS: The OTSC system was shown to be easy and efficient for gastrotomy closure in a survival experimental model of varicocelectomy, when correctly matching the gastrotomy size with the clip size and/or number

Third-generation cholecystectomy by natural orifices: transgastric and transvesical combined approach (with video)

BACKGROUND:An isolated transgastric port has some limitations in performing transluminal endoscopic cholecystectomy. However, transvesical access to the peritoneal cavity has recently been reported to be feasible and safe.OBJECTIVE:To assess the feasibility and the technical benefits of transgastric and transvesical combined approach to overcome the limitations of isolated transgastric ports.DESIGN:We created a transgastric and transvesical combined approach to perform cholecystectomy in 7 consecutive anesthetized female pigs. The transgastric access was achieved after perforation and dilation of the gastric wall with a needle knife and with a balloon, respectively. Under cystoscopic control, an ureteral catheter, a guidewire, and a dilator of the ureteral sheath were used to place a transvesical 5-mm overtube into the peritoneal cavity. By using a gastroscope positioned transgastrically and a ureteroscope positioned transvesically, we carried out cholecystectomy in all animals.RESULTS:Establishment of transvesical and transgastric accesses took place without complications. Under a carbon dioxide pneumoperitoneum controlled by the transvesical port, gallbladder identification, cystic duct, and artery exposure were easily achieved in all cases. Transvesical gallbladder grasping and manipulation proved to be particularly valuable to enhance gastroscope-guided dissection. With the exclusion of 2 cases where mild liver-surface hemorrhage and bile leak secondary to the sliding of cystic clips occurred, all remaining cholecystectomies were carried out without incidents.LIMITATIONS:Once closure of the gastric hole proved to be unreliable when using endoclips, the animals were euthanized; necropsy was performed immediately after the surgical procedure.CONCLUSIONS:A transgastric and transvesical combined approach is feasible, and it was particularly useful to perform a cholecystectomy through exclusive natural orifices

Cefaleias secundárias de causa vascular

Neste artigo serão abordadas as patologias vasculares que mais frequentemente se acompanham de cefaleias como manifestação inaugural ou predominante e que não devem ser ignoradas ou desvalorizadas pelos clínicos, dado que são frequentemente a chave para o diagnóstico precoce em situações agudas isoladas, ou sobrepostas a situações de cefaleias crónicas, podendo estas funcionar como elemento confundidor, numa abordagem menos atenta

CD56bright natural killer cells preferentially kill proliferating CD4+ T cells

Human CD56br natural killer (NK) cells represent a small subset of CD56+ NK cells in circulation and are largely tissue-resident. The frequency and number of CD56br NK cells in blood has been shown to increase following administration of low-dose IL-2 (LD-IL2), a therapy aimed to specifically expand CD4+ regulatory T cells (Tregs). Given the potential clinical application of LD-IL-2 immunotherapy across several immune diseases, including the autoimmune disease type 1 diabetes, a better understanding of the functional consequences of this expansion is urgently needed. In this study, we developed an in vitro co-culture assay with activated CD4+ T cells to measure NK cell killing efficiency. We show that CD56br and CD56dim NK cells show similar efficiency at killing activated CD4+ conventional T (Tconv) and Treg cell subsets. However, in contrast to CD56dim cells, CD56br NK cells preferentially target highly proliferative cells. We hypothesize that CD56br NK cells have an immunoregulatory role through the elimination of proliferating autoreactive CD4+ Tconv cells that have escaped Treg suppression. These results have implications for the interpretation of current and future trials of LD-IL-2 by providing evidence for a new, possibly beneficial immunomodulatory mechanism of LD-IL-2-expanded CD56br NK cells

Endogenous production of ghrelin and beneficial effects of its exogenous administration in monocrotaline-induced pulmonary hypertension

We investigated the endogenous production of ghrelin as well as cardiac and pulmonary vascular effects of its administration in a rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH). Adult Wistar rats randomly received a subcutaneous injection of MCT (60 mg/kg) or an equal volume of vehicle. One week later, animals were randomly assigned to receive a subcutaneous injection of ghrelin (100 mug/kg bid for 2 wk) or saline. Four groups were analyzed: normal rats treated with ghrelin (n = 7), normal rats injected with saline (n = 7), MCT rats treated with ghrelin (n = 9), and MCT rats injected with saline (n = 9). At 22-25 days, right ( RV) and left ventricular (LV) pressures were measured, heart and lungs were weighted, and samples were collected for histological and molecular analysis. Endogenous production of ghrelin was almost abolished in normal rats treated with ghrelin. In MCT-treated animals, pulmonary expression of ghrelin was preserved, and RV myocardial expression was increased more than 20 times. In these animals, exogenous administration of ghrelin attenuated PH, RV hypertrophy, wall thickening of peripheral pulmonary arteries, and RV diastolic disturbances and ameliorated LV dysfunction, without affecting its endogenous production. In conclusion, decreased tissular expression of ghrelin in healthy animals but not in PH animals suggests a negative feedback in the former that is lost in the latter. A selective increase of ghrelin mRNA levels in the RV of animals with PH might indicate distinct regulation of its cardiac expression. Finally, ghrelin administration attenuated MCT-induced PH, pulmonary vascular remodeling, and RV hypertrophy, indicating that it may modulate PH

Sequence variation of Epstein-Barr virus: viral types, geography, codon usage and diseases

138 new Epstein-Barr virus (EBV) genome sequences have been determined. 125 of these and 116 from previous reports were combined to produce a multiple sequence alignment of 241 EBV genomes, which we have used to analyze variation within the viral genome. The type 1/type2 classification of EBV remains the major form of variation and is defined mostly by EBNA2 and EBNA3, but the type 2 SNPs at the EBNA3 locus extend into the adjacent gp350 and gp42 genes, whose products mediate infection of B cells by EBV. A small insertion within the BART miRNA region of the genome was present in 21 EBV strains. EBV from saliva of USA patients with chronic active EBV infection aligned with the wild type EBV genome, with no evidence of WZhet rearrangements. The V3 polymorphism in the Zp promoter for BZLF1 was found to be frequent in nasopharyngeal carcinoma cases both from Hong Kong and Indonesia. Codon usage was found to differ between latent and lytic cycle EBV genes and the main forms of variation of the EBNA1 protein have been identified.IMPORTANCE Epstein-Barr virus causes most cases of infectious mononucleosis and post-transplant lymphoproliferative disease. It contributes to several types of cancer including Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B cell lymphoma, nasopharyngeal carcinoma and gastric carcinoma. EBV genome variation is important because some of the diseases associated with EBV have very different incidences in different populations and geographic regions - differences in the EBV genome might contribute to these diseases. Some specific EBV genome alterations that appear to be significant in EBV associated cancers are already known and current efforts to make an EBV vaccine and antiviral drugs should also take account of sequence differences in the proteins used as targets

In vitro and in vivo performance of methacrylated gellan gum hydrogel formulations for cartilage repair

Methacrylated gellan gum (GGMA) formulation is proposed as a second‐generation hydrogel for controlled delivery of cartilage‐forming cells into focal chondral lesions, allowing immediate in situ retention of cells and 3D filling of lesion volume, such approach deemed compatible with an arthroscopic procedure. Formulation optimization was carried out in vitro using chondrocytes and adipose mesenchymal stromal/stem cells (ASCs). A proof‐of‐concept in vivo study was conducted using a rabbit model with induced chondral lesions. Outcomes were compared with microfracture or non‐treated control. Three grading scores were used to evaluate tissue repair after 8 weeks by macroscopic, histological and immunohistochemical analysis. Intense collagen type II and low collagen type I gene and protein expression were achieved in vitro by the ASC + GGMA formulation, in light with development of healthy chondral tissue. In vivo, this formulation promoted significantly superior de novo cartilage formation compared with the non‐treated group. Maintenance of chondral height and integration with native tissue was further accomplished. The physicochemical properties of the proposed GGMA hydrogel exhibited highly favorable characteristics and biological performance both in vitro and in vivo, positioning itself as an attractive xeno‐free biomaterial to be used with chondrogenic cells for a cost‐effective treatment of focal chondral lesions

Kalirin: a novel genetic risk factor for ischemic stroke

Cerebrovascular and cardiovascular diseases are the leading causes of death and disability worldwide. They are complex disorders resulting from the interplay of genetic and environmental factors, and may share several susceptibility genes. Several recent studies have implicated variants of the Kalirin (KALRN) gene with susceptibility to cardiovascular and metabolic phenotypes, but no studies have yet been performed in stroke patients. KALRN is involved, among others, in the inhibition of inducible nitric oxide synthase, in the regulation of ischemic signal transduction, and in neuronal morphogenesis, plasticity, and stability. The goal of the present study was to determine whether SNPs in the KALRN region on 3q13, which includes the Ropporin gene (ROPN1), predispose to ischemic stroke (IS) in a cohort of Portuguese patients and controls. We genotyped 34 tagging SNPs in the KALRN and ROPN1 chromosomal region on 565 IS patients and 517 unrelated controls, and performed genotype imputation for 405 markers on chromosome 3. We tested the single-marker association of these SNPs with IS. One SNP (rs4499545) in the ROPN1-KALRN intergenic region and two SNPs in KALRN (rs17286604 and rs11712619) showed significant (P < 0.05) allelic and genotypic (unadjusted and adjusted for hypertension, diabetes, and ever smoking) association with IS risk. Thirty-two imputed SNPs also showed an association at P < 0.05, and actual genotyping of three of these polymorphisms (rs7620580, rs6438833, and rs11712039) validated their association. Furthermore, rs11712039 was associated with IS (0.001 < P < 0.01) in a recent well-powered genomewide association study (Ikram et al. 2009). These studies suggest that variants in the KALRN gene region constitute risk factors for stroke and that KALRN may represent a common risk factor for vascular diseases