Virus surveillance in vector insects is potentially of great benefit to public health. Large-scale sequencing of small and long RNAs has previously been used to detect viruses, but without any formal comparison of different strategies. Furthermore, the identification of viral sequences largely depends on similarity searches against reference databases. Here, we developed a sequence-independent strategy based on virus-derived small RNAs produced by the host response, such as the RNA interference pathway. In insects, we compared sequences of small and long RNAs, demonstrating that viral sequences are enriched in the small RNA fraction. We also noted that the small RNA size profile is a unique signature for each virus and can be used to identify novel viral sequences without known relatives in reference databases. Using this strategy, we characterized six novel viruses in the viromes of laboratory fruit flies and wild populations of two insect vectors: mosquitoes and sandflies. We also show that the small RNA profile could be used to infer viral tropism for ovaries among other aspects of virus biology. Additionally, our results suggest that virus detection utilizing small RNAs can also be applied to vertebrates, although not as efficiently as to plants and insects. 相似文献
The axonal microtubule‐associated protein tau is a well‐known regulator of microtubule stability in neurons. However, the putative interplay between tau and End‐binding proteins 1 and 3 (EB1/3), the core microtubule plus‐end tracking proteins, has not been elucidated yet. Here, we show that a cross‐talk between tau and EB1/3 exists in developing neuronal cells. Tau and EBs partially colocalize at extending neurites of N1E‐115 neuroblastoma cells and axons of primary hippocampal neurons, as shown by confocal immunofluorescence analyses. Tau down‐regulation leads to a reduction of EB1/3 comet length, as observed in shRNA‐stably depleted neuroblastoma cells and TAU?/? neurons. EB1/3 localization depends on the expression levels and localization of tau protein. Over‐expression of tau at high levels induces EBs relocalization to microtubule bundles at extending neurites of N1E‐115 cells. In differentiating primary neurons, tau is required for the proper accumulation of EBs at stretches of microtubule bundles at the medial and distal regions of the axon. Tau interacts with EB proteins, as shown by immunoprecipitation in different non‐neuronal and neuronal cells and in whole brain lysates. A tau/EB1 direct interaction was corroborated by in vitro pull‐down assays. Fluorescence recovery after photobleaching assays performed in neuroblastoma cells confirmed that tau modulates EB3 cellular mobility. In summary, we provide evidence of a new function of tau as a direct regulator of EB proteins in developing neuronal cells. This cross‐talk between a classical microtubule‐associated protein and a core microtubule plus‐end tracking protein may contribute to the fine‐tuned regulation of microtubule dynamics and stability during neuronal differentiation.
The elderly undergo cardiac surgery more and more frequently, often present multiple comorbidities, assume chronic therapies, and present a unique physiology. Aim of our study was to analyze the experience of a referral cardiac surgery center with all types of cardiac surgery interventions performed in patients ≥80 years old over a six years’ period.
Methods
A retrospective observational study performed in a university hospital. 260 patients were included in the study (3.5% of the patients undergoing cardiac surgery in the study period).
Results
Mean age was 82 ± 1.8 years. Eighty-five percent of patients underwent elective surgery, 15% unplanned surgery and 4.2% redo surgery. Intervention for aortic valve pathology and coronary artery bypass grafting were performed in 51% and 46% of the patients, respectively. Interventions involving the mitral valve were the 26% of the total, those on the tricuspid valve were 13% and those on the ascending aortic arch the 9.6%. Postoperative low output syndrome was identified in 44 patients (17%). Mortality was 3.9% and most of the patients (91%) were discharged from hospital in good clinical conditions. Hospital mortality was lower in planned vs unplanned surgery: 3.8% vs 14% respectively. Chronic obstructive pulmonary disease (OR 9.106, CI 2.275 – 36.450) was the unique independent predictor of mortality.
Conclusions
Clinicians should be aware that cardiac surgery can be safely performed at all ages, that risk stratification is mandatory and that hemodynamic treatment to avoid complications is expected.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2253-15-15) contains supplementary material, which is available to authorized users. 相似文献
Dengue is the most important arthropod borne viral disease worldwide in terms
of morbidity and mortality and is caused by any of the four serotypes of
dengue virus (DENV-1 to 4). Brazil is responsible for approximately
80% of dengue cases in the Americas, and since the introduction of
dengue in 1986, a total of 5,944,270 cases have been reported including
21,596 dengue hemorrhagic fever and 874 fatal cases. DENV can infect many
cell types and cause diverse clinical and pathological effects. The goal of
the study was to investigate the usefulness of NS1 capture tests as an
alternative tool to detect DENV in tissue specimens from previously
confirmed dengue fatal cases (n = 23)
that occurred in 2002 in Brazil.
Methodology/Principal Findings
A total of 74 tissue specimens were available: liver
(n = 23), lung
(n = 14), kidney
(n = 04), brain
(n = 10), heart
(n = 02), skin
(n = 01), spleen
(n = 15), thymus
(n = 03) and lymph nodes
(n = 02). We evaluated three tests
for NS1 antigen capture: first generation Dengue Early ELISA (PanBio
Diagnostics), Platelia NS1 (BioRad Laboratories) and the rapid test NS1 Ag
Strip (BioRad Laboratories). The overall dengue fatal case diagnosis based
on the tissues analyzed by Dengue Early ELISA, Platelia NS1 and the NS1 Ag
Strip was 34.7% (08/23), 60.8% (14/23) and 91.3%
(21/23), respectively. The Dengue Early ELISA detected NS1 in 22.9%
(17/74) of the specimens analyzed and the Platelia NS1 in 45.9%
(34/74). The highest sensitivity (78.3%; 58/74) was achieved by the
NS1 Ag Strip, and the differences in the sensitivities were statistically
significant (p<0.05). The NS1 Ag Strip was the most
sensitive in liver (91.3%; 21/23), lung (71.4%; 10/14), kidney
(100%; 4/4), brain (80%; 8/10), spleen (66.6%, 10/15)
and thymus (100%, 3/3) when compared to the other two ELISA
assays.
Conclusions/Significance
This study shows the DENV NS1 capture assay as a rapid and valuable approach
to postmortem dengue confirmation. With an increasing number of DHF and
fatal cases, the availability of new approaches useful for cases
confirmation plays an important tool for the disease surveillance. 相似文献
Praziquantel at 40 mg/kg in a single dose is the WHO recommended treatment for all forms of schistosomiasis, but 60 mg/kg is also deployed nationally.
Methodology/Principal Findings
Four trial sites in the Philippines, Mauritania, Tanzania and Brazil enrolled 856 patients using a common protocol, who were randomised to receive praziquantel 40 mg/kg (n = 428) or 60 mg/kg (n = 428). While the sites differed for transmission and infection intensities (highest in Tanzania and lowest in Mauritania), no bias or heterogeneity across sites was detected for the main efficacy outcomes. The primary efficacy analysis was the comparison of cure rates on Day 21 in the intent-to-treat population for the pooled data using a logistic model to calculate Odd Ratios allowing for baseline characteristics and study site. Both doses were highly effective: the Day 21 cure rates were 91.7% (86.6%–98% at individual sites) with 40 mg/kg and 92.8% (88%–97%) with 60 mg/kg. Secondary parameters were eggs reduction rates (ERR), change in intensity of infection and reinfection rates at 6 and 12 months. On Day 21 the pooled estimate of the ERR was 91% in both arms. The Hazard Ratio for reinfections was only significant in Brazil, and in favour of 60 mg/kg on the pooled estimate (40 mg/kg: 34.3%, 60 mg/kg: 23.9%, HR = 0.78, 95%CI = [0.63;0.96]). Analysis of safety could not distinguish between disease- and drug-related events. 666 patients (78%) reported 1327 adverse events (AE) 4 h post-dosing. The risk of having at least one AE was higher in the 60 than in the 40 mg/kg group (83% vs. 73%, p<0.001). At 24 h post-dosing, 456 patients (54%) had 918 AEs with no difference between arms. The most frequent AE was abdominal pain at both 4 h and 24 h (40% and 24%).
Conclusion
A higher dose of 60 mg/kg of praziquantel offers no significant efficacy advantage over standard 40 mg/kg for treating intestinal schistosomiasis caused by either S. mansoni or S. japonicum. The results of this study support WHO recommendation and should be used to inform policy decisions in the countries.
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