A comparison of 0.1% and 0.2% ropivacaine and bupivacaine combined with morphine for postoperative patient-controlled epidural analgesia after major abdominal surgery

peer reviewedRopivacaine (ROPI), which is less toxic and produces less motor block than bupivacaine (BUPI), seems attractive for epidural analgesia. Few data are available concerning dose requirements of epidural ROPI when combined with morphine. In this study, we compared the dose requirements and side effects of ROPI and BUPI combined with small-dose morphine after major abdominal surgery. Postoperatively, 60 patients were randomly allocated (double-blinded manner) to four groups: patient-controlled epidural analgesia with the same settings using 0.1% or 0.2% solution of ROPI or BUPI combined with an epidural infusion of 0.1 mg/h of morphine. Pain scores, side effects, motor block, and local anesthetic consumption were measured for 60 h. Pain scores and the incidence of side effects did not differ among the groups. Consumption of ROPI and BUPI were similar in both 0.1% groups. Doubling the concentration significantly reduced the consumption (milliliters) of BUPI (P < 0.05) but not of ROPI. Consequently, using ROPI 0.2% significantly increased the dose administered as compared with ROPI 0.1% (ROPI 0.1% = 314 +/- 151 mg and ROPI 0.2% = 573 +/- 304 mg at Hour 48; P < 0.05). Patient-controlled epidural analgesia with the 0.1% or 0.2% solution of ROPI or BUPI combined with epidural morphine resulted in comparable analgesia. As compared with ROPI 0.1%, the use of ROPI 0.2% increased consumption of local anesthetic without improving analgesia. IMPLICATIONS: Small-dose (0.1%) ropivacaine and bupivacaine have similar potency and result in comparable analgesia and incidence of side effects

North Atlantic Ocean

RADIALES (IEO), with the support of the Korea Institute for Ocean Science and Technology (KIOST)Versión del edito

Chikungunya Virus Infection

Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitoes, mostly Aedes aegypti and Aedes albopictus. After half a century of focal outbreaks of acute febrile polyarthralgia in Africa and Asia, the disease unexpectedly spread in the past decade with large outbreaks in Africa and around the Indian Ocean and rare autochthonous transmission in temperate areas. This emergence brought new insights on its pathogenesis, notably the role of the A226V mutation that improved CHIKV fitness in Ae. albopictus and the possible CHIKV persistence in deep tissue sanctuaries for months after infection. Massive outbreaks also revealed new aspects of the acute stage: the high number of symptomatic cases, unexpected complications, mother-to-child transmission, and low lethality in debilitated patients. The follow-up of patients in epidemic areas has identified frequent, long-lasting, rheumatic disorders, including rare inflammatory joint destruction, and common chronic mood changes associated with quality-of-life impairment. Thus, the globalization of CHIKV exposes countries with Aedes mosquitoes both to brutal outbreaks of acute incapacitating episodes and endemic long-lasting disorders

The accessory subunit of mitochondrial DNA polymerase gamma determines the DNA content of mitochondrial nucleoids in human cultured cells.

The accessory subunit of mitochondrial DNA polymerase gamma, POLGbeta, functions as a processivity factor in vitro. Here we show POLGbeta has additional roles in mitochondrial DNA metabolism. Mitochondrial DNA is arranged in nucleoprotein complexes, or nucleoids, which often contain multiple copies of the mitochondrial genome. Gene-silencing of POLGbeta increased nucleoid numbers, whereas over-expression of POLGbeta reduced the number and increased the size of mitochondrial nucleoids. Both increased and decreased expression of POLGbeta altered nucleoid structure and precipitated a marked decrease in 7S DNA molecules, which form short displacement-loops on mitochondrial DNA. Recombinant POLGbeta preferentially bound to plasmids with a short displacement-loop, in contrast to POLGalpha. These findings support the view that the mitochondrial D-loop acts as a protein recruitment centre, and suggest POLGbeta is a key factor in the organization of mitochondrial DNA in multigenomic nucleoprotein complexes

Clinical and Virological Factors Influencing the Performance of a NS1 Antigen-Capture Assay and Potential Use as a Marker of Dengue Disease Severity

Dengue is the most prevalent arthropod-borne disease in tropical regions. The clinical manifestation may vary from asymptomatic to potentially fatal dengue shock syndrome. Early laboratory confirmation of dengue diagnosis is essential since many symptoms are not specific. Dengue non-structural protein 1 (NS1) may be used in simple antigen-capture ELISA for early detection of dengue virus infection. Our result demonstrated that the Platelia NS1 antigen detection kit had a quite low overall sensitivity. However, sensitivity rises significantly when used in combination with MAC-ELISA. When taking into account the various forms of dengue infection, the NS1 antigen detection was found relatively high in patients sampled during the first 3 days of fever onset, in patients with primary infection, DENV-1 infection, with high level of viremia and in mild form of dengue fever. In asymptomatically infected individuals, RT-PCR assay has proved to be more sensitive than NS1 antigen detection. Moreover, the NS1 antigen level correlated significantly with high viremia and low level of NS1 antigen was associated with more severe disease

2nd International External Quality Control Assessment for the Molecular Diagnosis of Dengue Infections

Dengue viruses (DENV) are the most widespread arthropod-borne viruses which have shown an unexpected geographic expansion, as well as an increase in the number and severity of outbreaks in the last decades. In this context, the accurate diagnosis and reliable surveillance of dengue infections are essential. The laboratory diagnosis of dengue relies on the use of several methods detecting markers of DENV infection present in patient serum. Molecular diagnosis methods are usually rapid, sensitive, and simple when correctly standardized. Moreover, PCR-based diagnosis techniques are able to readily detect DENV during the acute phase of the disease and may assume an important role in dengue diagnosis and surveillance. Different reverse transcriptase PCR (RT-PCR) methods have been developed and are currently available and should be standardized in each laboratory to maintain high quality performance. In this work an External quality assessment (EQA) activity has been carried out to evaluate the accuracy and quality of laboratory data for the molecular diagnosis and surveillance of dengue, which involved worldwide dengue reference laboratories. In conclusion, RT-PCR techniques for dengue diagnosis applied by the participating laboratories demonstrated the need of further improvement in most laboratories

Virus-Like Particles of SARS-Like Coronavirus Formed by Membrane Proteins from Different Origins Demonstrate Stimulating Activity in Human Dendritic Cells

The pathogenesis of SARS coronavirus (CoV) remains poorly understood. In the current study, two recombinant baculovirus were generated to express the spike (S) protein of SARS-like coronavirus (SL-CoV) isolated from bats (vAcBS) and the envelope (E) and membrane (M) proteins of SARS-CoV, respectively. Co-infection of insect cells with these two recombinant baculoviruses led to self-assembly of virus-like particles (BVLPs) as demonstrated by electron microscopy. Incorporation of S protein of vAcBS (BS) into VLPs was confirmed by western blot and immunogold labeling. Such BVLPs up-regulated the level of CD40, CD80, CD86, CD83, and enhanced the secretion of IL-6, IL-10 and TNF-α in immature dendritic cells (DCs). Immune responses were compared in immature DCs inoculated with BVLPs or with VLPs formed by S, E and M proteins of human SARS-CoV. BVLPs showed a stronger ability to stimulate DCs in terms of cytokine induction as evidenced by 2 to 6 fold higher production of IL-6 and TNF-α. Further study indicated that IFN-γ+ and IL-4+ populations in CD4+ T cells increased upon co-cultivation with DCs pre-exposed with BVLPs or SARS-CoV VLPs. The observed difference in DC-stimulating activity between BVLPs and SARS CoV VLPs was very likely due to the S protein. In agreement, SL-CoV S DNA vaccine evoked a more vigorous antibody response and a stronger T cell response than SARS-CoV S DNA in mice. Our data have demonstrated for the first time that SL-CoV VLPs formed by membrane proteins of different origins, one from SL-CoV isolated from bats (BS) and the other two from human SARS-CoV (E and M), activated immature DCs and enhanced the expression of co-stimulatory molecules and the secretion of cytokines. Finding in this study may provide important information for vaccine development as well as for understanding the pathogenesis of SARS-like CoV

Clinical Forms of Chikungunya in Gabon, 2010

Chikungunya fever (CHIK) is a disease caused by a virus transmitted to humans by infected mosquitos. The virus is responsible for multiple outbreaks in tropical and temperate areas worldwide, and is now a global concern. Clinical and biological features of the disease are poorly described, especially in Africa, where the disease is neglected because it is considered benign. During a recent CHIK outbreak that occurred in southeast Gabon, we prospectively studied clinical and biological features of 270 virologically confirmed cases. Fever and arthralgias were the predominant symptoms. Furthermore, variable and distinct clinical pictures including pure febrile, pure arthralgic and unusual forms (neither fever nor arthralgias) were detected. No severe forms or deaths were reported. These findings suggest that, during CHIK epidemics, some patients may not have classical symptoms (fever and arthralgias). Local surveillance is needed to detect any changes in the pathogenicity of this virus

The Mediterranean Sea Regime Shift at the End of the 1980s, and Intriguing Parallelisms with Other European Basins

Background: Regime shifts are abrupt changes encompassing a multitude of physical properties and ecosystem variables, which lead to new regime conditions. Recent investigations focus on the changes in ecosystem diversity and functioning associated to such shifts. Of particular interest, because of the implication on climate drivers, are shifts that occur synchronously in separated basins. Principal Findings: In this work we analyze and review long-term records of Mediterranean ecological and hydro-climate variables and find that all point to a synchronous change in the late 1980s. A quantitative synthesis of the literature (including observed oceanic data, models and satellite analyses) shows that these years mark a major change in Mediterranean hydrographic properties, surface circulation, and deep water convection (the Eastern Mediterranean Transient). We provide novel analyses that link local, regional and basin scale hydrological properties with two major indicators of large scale climate, the North Atlantic Oscillation index and the Northern Hemisphere Temperature index, suggesting that the Mediterranean shift is part of a large scale change in the Northern Hemisphere. We provide a simplified scheme of the different effects of climate vs. temperature on pelagic ecosystems. Conclusions: Our results show that the Mediterranean Sea underwent a major change at the end of the 1980s that encompassed atmospheric, hydrological, and ecological systems, for which it can be considered a regime shift. We further provide evidence that the local hydrography is linked to the larger scale, northern hemisphere climate. These results suggest that the shifts that affected the North, Baltic, Black and Mediterranean (this work) Seas at the end of the 1980s, that have been so far only partly associated, are likely linked as part a northern hemisphere change. These findings bear wide implications for the development of climate change scenarios, as synchronous shifts may provide the key for distinguishing local (i.e., basin) anthropogenic drivers, such as eutrophication or fishing, from larger scale (hemispheric) climate drivers

Antibody-mediated enhancement aggravates chikungunya virus infection and disease severity

The arthropod-transmitted chikungunya virus (CHIKV) causes a flu-like disease that is characterized by incapacitating arthralgia. The re-emergence of CHIKV and the continual risk of new epidemics have reignited research in CHIKV pathogenesis. Virus-specific antibodies have been shown to control virus clearance, but antibodies present at sub-neutralizing concentrations can also augment virus infection that exacerbates disease severity. To explore this occurrence, CHIKV infection was investigated in the presence of CHIKV-specific antibodies in both primary human cells and a murine macrophage cell line, RAW264.7. Enhanced attachment of CHIKV to the primary human monocytes and B cells was observed while increased viral replication was detected in RAW264.7 cells. Blocking of specific Fc receptors (FcγRs) led to the abrogation of these observations. Furthermore, experimental infection in adult mice showed that animals had higher viral RNA loads and endured more severe joint inflammation in the presence of sub-neutralizing concentrations of CHIKV-specific antibodies. In addition, CHIKV infection in 11 days old mice under enhancing condition resulted in higher muscles viral RNA load detected and death. These observations provide the first evidence of antibody-mediated enhancement in CHIKV infection and pathogenesis and could also be relevant for other important arboviruses such as Zika virus