33 research outputs found
Antenatal oligohydramnios of renal origin: long-term outcome
Background. Prognosis of fetuses with renal oligohydramnios (ROH) is often still regarded as poor. Neonatal complications and the long-term follow-up of fetuses with ROH in two pediatric centres are described. Method. 23 fetuses (16 males, 7 females) were included as patients. Primary diseases included congenital anomalies of the kidney and urinary tract (n = 16), autosomal recessive polycystic kidney disease (n = 4) and renal tubular dysgenesis (n = 3). The analysis includes retrospective chart review. Results. Seven children died (30%), the majority (n = 4, 17%) within the neonatal period due to pulmonary hypoplasia and renal insufficiency. Fourteen patients (61%) required postnatal mechanical ventilation for a median of 4 (range 1-60) days; 11 infants had an associated pneumothorax. All 16 surviving children have chronic kidney disease (CKD) at a current median age of 5.7 years (range 0.5-14.5), managed conservatively in eight patients [median glomerular filtration rate 51 (range 20-78) ml/min/1.73 m2]. Eight patients reached end-stage renal disease at a median age of 0.3 years (range 2 days to 8.3 years), including one patient with pre-emptive kidney transplantation. Five of the patients requiring dialysis underwent successful renal transplantation at a median age of 3.5 years (range 2.5-4). Growth was impaired in seven children requiring growth hormone treatment. Cognitive and motor development was normal in 12 (75%) of the 16 patients and showed a delay in four children, including two with associated syndromal features. Conclusion. ROH is not always associated with a poor prognosis and long-term outcome in survivors is encouraging. The high incidence of neonatal complications and long-term morbidity due to CKD requires a multidisciplinary management of these childre
The positive experience of encountering wolves in the wild
Large carnivores often impact human livelihoods and well‐being. Previous research has mostly focused on the negative impacts of large carnivores on human well‐being but has rarely considered the positive aspects of living with large carnivores. In particular, we know very little on people's direct experiences with large carnivores like personal encounters and on people's awareness and tolerance toward their exposure to large carnivores. Here, we focus on the wolf (Canis lupus), and report on a phone survey in Germany. We examined whether encounters with wolves were positive or negative experiences and quantified people's awareness and tolerance related to their exposure to wolves. We found that the majority of people reported positive experiences when encountering wolves, regardless of whether wolves were encountered in the wild within Germany, in the wild abroad, or in captivity. The frequency of encounters did not affect the probability to report positive, neutral, or negative experiences. Moreover, people in Germany expressed a high tolerance of living in close vicinity to wolves. These findings are novel and important because they highlight the positive aspects of living in proximity with large carnivores in human‐dominated landscapes
News selection and framing: the media as a stakeholder in human-carnivore coexistence
The media widely covers large carnivores and their impacts on human livelihood and plays an important role in their conservation. Yet, we know little about how species identity affects news selection, framing, accuracy and information flow. We investigated the online coverage of two cases of attacks or alleged attacks on humans alternatingly attributed to wolves and dogs in Greece and Germany. The period during which wolves were considered the primary suspects for the attacks was covered by up to two times more articles than when dogs were suspected. Wolves were presented as more likely suspects for the attacks than dogs, and wolf articles contained more inaccuracies measured as title-text mismatches. Press agencies played a significant role in the selection and dissemination of wolf news. We suggest that conservation scientists, journalists and policy makers work together to ensure an accurate representation in the media of human-carnivore coexistence and its challenges
Early Clinical Manifestations Associated with Death from Visceral Leishmaniasis
The visceral leishmaniasis (VL) is a disease potentially fatal if not diagnosed and treated opportunely. This article presents the results of the study on the manifestations identified at the time of the clinical suspicion of the VL cases. This study was conducted in Belo Horizonte, the capital of the State of Minas Gerais, located in southeastern Brazil. This study is both timely and substantive because the Belo Horizonte is an area of transmission of VL, with one of the highest VL-death proportions of Brazil. The patients with higher risk of death had at least one of the following characteristics: ≥60 years, weakness, HIV co-infection, bleeding, jaundice and other associated infections. During the period 2002–2009, 8% to 22% of the patients with VL progressed to death in Belo Horizonte, whilst the proportion in the country was much lower and varied between 5% and 9%. This study has identified vulnerable patients who are at higher risk of death from VL and who would benefit from early predictive evaluation of the prognostic. Hence, the knowledge regarding the factors associated with death may contribute for clinical management and for reduction of deaths from VL
Estimating the Fitness Cost of Escape from HLA Presentation in HIV-1 Protease and Reverse Transcriptase
Human immunodeficiency virus (HIV-1) is, like most pathogens, under selective pressure to escape the immune system of its host. In particular, HIV-1 can avoid recognition by cytotoxic T lymphocytes (CTLs) by altering the binding affinity of viral peptides to human leukocyte antigen (HLA) molecules, the role of which is to present those peptides to the immune system. It is generally assumed that HLA escape mutations carry a replicative fitness cost, but these costs have not been quantified. In this study, we assess the replicative cost of mutations which are likely to escape presentation by HLA molecules in the region of HIV-1 protease and reverse transcriptase. Specifically, we combine computational approaches for prediction of in vitro replicative fitness and peptide binding affinity to HLA molecules. We find that mutations which impair binding to HLA-A molecules tend to have lower in vitro replicative fitness than mutations which do not impair binding to HLA-A molecules, suggesting that HLA-A escape mutations carry higher fitness costs than non-escape mutations. We argue that the association between fitness and HLA-A binding impairment is probably due to an intrinsic cost of escape from HLA-A molecules, and these costs are particularly strong for HLA-A alleles associated with efficient virus control. Counter-intuitively, we do not observe a significant effect in the case of HLA-B, but, as discussed, this does not argue against the relevance of HLA-B in virus control. Overall, this article points to the intriguing possibility that HLA-A molecules preferentially target more conserved regions of HIV-1, emphasizing the importance of HLA-A genes in the evolution of HIV-1 and RNA viruses in general
Lymphotoxin expression in human and murine renal allografts
The kidney is the most frequently transplanted solid organ. Recruitment of inflammatory cells, ranging from diffuse to nodular accumulations with defined microarchitecture, is a hallmark of acute and chronic renal allograft injury. Lymphotoxins (LTs) mediate the communication of lymphocytes and stromal cells and play a pivotal role in chronic inflammation and formation of lymphoid tissue. The aim of this study was to assess the expression of members of the LT system in acute rejection (AR) and chronic renal allograft injury such as transplant glomerulopathy (TG) and interstitial fibrosis/tubular atrophy (IFTA). We investigated differentially regulated components in transcriptomes of human renal allograft biopsies. By microarray analysis, we found the upregulation of LT beta, LIGHT, HVEM and TNF receptors 1 and 2 in AR and IFTA in human renal allograft biopsies. In addition, there was clear evidence for the activation of the NF kappa B pathway, most likely a consequence of LT beta receptor stimulation. In human renal allograft biopsies with transplant glomerulopathy (TG) two distinct transcriptional patterns of LT activation were revealed. By quantitative RT-PCR robust upregulation of LTa, LT beta and LIGHT was shown in biopsies with borderline lesions and AR. Immunohistochemistry revealed expression of LT beta in tubular epithelial cells and inflammatory infiltrates in transplant biopsies with AR and IFTA. Finally, activation of LT signaling was reproduced in a murine model of renal transplantation with AR. In summary, our results indicate a potential role of the LT system in acute renal allograft rejection and chronic transplant injury. Activation of the LT system in allograft rejection in rodents indicates a species independent mechanism. The functional role of the LT system in acute renal allograft rejection and chronic injury remains to be determined
A Role for Tissue Factor in Cell Adhesion and Migration Mediated by Interaction with Actin-binding Protein 280
Tissue factor (TF), the protease receptor initiating the coagulation system, functions in vascular development, angiogenesis, and tumor cell metastasis by poorly defined molecular mechanisms. We demonstrate that immobilized ligands for TF specifically support cell adhesion, migration, spreading, and intracellular signaling, which are not inhibited by RGD peptides. Two-hybrid screening identified actin-binding protein 280 (ABP-280) as ligand for the TF cytoplasmic domain. Extracellular ligation of TF is necessary for ABP-280 binding. ABP-280 recruitment to TF adhesion contacts is associated with reorganization of actin filaments, but cytoskeletal adaptor molecules typically found in integrin-mediated focal contacts are not associated with TF. Chimeric molecules of the TF cytoplasmic domain and an unrelated extracellular domain support cell spreading and migration, demonstrating that the extracellular domain of TF is not involved in the recruitment of accessory molecules that influence adhesive functions. Replacement of TF's cytoplasmic Ser residues with Asp to mimic phosphorylation enhances the interaction with ABP-280, whereas Ala mutations abolish coprecipitation of ABP-280 with immobilized TF cytoplasmic domain, and severely reduce cell spreading. The specific interaction of the TF cytoplasmic domain with ABP-280 provides a molecular pathway by which TF supports tumor cell metastasis and vascular remodeling