202 resultados para Late Endosomes
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PURPOSE: A new magnetic resonance imaging approach for detection of myocardial late enhancement during free-breathing was developed. METHODS AND RESULTS: For suppression of respiratory motion artifacts, a prospective navigator technology including real-time motion correction and a local navigator restore was implemented. Subject specific inversion times were defined from images with incrementally increased inversion times acquired during a single dynamic scout navigator-gated and real-time motion corrected free-breathing scan. Subsequently, MR-imaging of myocardial late enhancement was performed with navigator-gated and real-time motion corrected adjacent short axis and long axis (two, three and four chamber) views. This alternative approach was investigated in 7 patients with history of myocardial infarction 12 min after i. v. administration of 0.2 mmol/kg body weight gadolinium-DTPA. CONCLUSION: With the presented navigator-gated and real-time motion corrected sequence for MR-imaging of myocardial late enhancement data can be completely acquired during free-breathing. Time constraints of a breath-hold technique are abolished and optimized patient specific inversion time is ensured.
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BACKGROUND: The envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV) can efficiently pseudotype lentiviral vectors. Some strains of LCMV exploit high affinity interactions with α-dystroglycan (α-DG) to bind to cell surfaces and subsequently fuse in low pH endosomes. LCMV strains with low α-DG affinity utilize an unknown receptor and display unique tissue tropisms. We pseudotyped non-primate feline immunodeficiency virus (FIV) vectors using LCMV derived glycoproteins with high or low affinity to α-DG and evaluated their properties in vitro and in vivo. METHODS: We pseudotyped FIV with the LCMV WE54 strain envelope glycoprotein and also engineered a point mutation in the WE54 envelope glycoprotein (L260F) to diminish α-DG affinity and direct binding to alternate receptors. We hypothesized that this change would alter in vivo tissue tropism and enhance gene transfer to neonatal animals. RESULTS: In mice, hepatic α- and β-DG expression was greatest at the late gestational and neonatal time points. When displayed on the surface of the FIV lentivirus the WE54 L260F mutant glycoprotein bound weakly to immobilized α-DG. Additionally, LCMV WE54 pseudotyped FIV vector transduction was neutralized by pre-incubation with soluble α-DG, while the mutant glycoprotein pseudotyped vector was not. In vivo gene transfer in adult mice with either envelope yielded low transduction efficiencies in hepatocytes following intravenous delivery. In marked contrast, neonatal gene transfer with the LCMV envelopes, and notably with the FIV-L260F vector, conferred abundant liver and lower level cardiomyocyte transduction as detected by luciferase assays, bioluminescent imaging, and β-galactosidase staining. CONCLUSIONS: These results suggest that a developmentally regulated receptor for LCMV is expressed abundantly in neonatal mice. LCMV pseudotyped vectors may have applications for neonatal gene transfer. ABBREVIATIONS: Armstrong 53b (Arm53b); baculovirus Autographa californica GP64 (GP64); charge-coupled device (CCD); dystroglycan (DG); feline immunodeficiency virus (FIV); glycoprotein precursor (GP-C); firefly luciferase (Luc); lymphocytic choriomeningitis virus (LCMV); nuclear targeted β-galactosidase (ntLacZ); optical density (OD); PBS/0.1% (w/v) Tween-20 (PBST); relative light units (RLU); Rous sarcoma virus (RSV); transducing units per milliliter (TU/ml); vesicular stomatitis virus (VSV-G); wheat germ agglutinin (WGA); 50% reduction in binding (C50).
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Few studies have aimed to reconstruct landscape change in the area of Eretria (South Central Euboea, Greece) during the last 6000 years. The aim of this paper is to partially fill in this gap by examining the interaction be- tween Mid- to Late Holocene shoreline evolution and human occupation, which is documented in the area from the Late Neolithic to the Late Roman period (with discontinuities). Evidence of shoreline displacements is derived from the study of five boreholes (maximum depth of 5.25 m below the surface) drilled in the lowlands of Eretria. Based on sedimentological analyses and micro/macrofaunal identifications, different facies have been identified in the cores and which reveal typical features of deltaic progradation with marine, lagoonal, fluvio- deltaic and fluvial environments. In addition, a chronostratigraphy has been obtained based on 20 AMS 14C radio- carbon dates performed on samples of plant remains and marine/lagoonal shells found in situ. The main sequences of landscape reconstruction in the plain of Eretria can be summarized as follows: a marine environ- ment predominated from ca. 4000 to 3200 cal. BC and a gradual transition to shallow marine conditions is ob- served ca. 3200-3000 cal. BC due to the general context of deltaic progradation west of the ancient city. Subsequently, from ca. 3000 to 2000 cal. BC, a lagoon occupied the area in the vicinity of the Temple of Apollo and the settlement's development was restricted to several fluvio-deltaic levees, thus severely limiting human activities in the plain. From ca. 2000 to 800 cal. BC, a phase of shallow marine presence prevailed and constrained settlement on higher ground, forcing abandonment of the major part of the plain. Finally, since the eighth century BC, the sea has regressed southward and created the modern landscape.
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Sternal osteomyelitis and poststernotomy mediastinitis is a severe and life-threatening complication after the cardiac surgery. The incidence ranges up to 3% with a mortality rate up to 29%. In addition, postoperative infections after sternotomy are associated with prolonged hospital stay, increased healthcare costs and impaired quality of patient life, representing an economic and social burden. The emergence of increasing antimicrobial resistant bacteria augments the importance of postsurgical infections since the antimicrobial choices are becoming limited. Furthermore, the incidence of infection is an indicator for the quality of patient care in the international benchmark studies. Although several therapy strategies are nowadays present in clinical practice, there is a lack of evidence-based surgical consensus for treatment of this surgical complication. In most cases the poststernotomy mediastinitis involves surgical revision with debridement, open dressing and/or vacuum-assisted therapy. After the granulation tissue on open chest wound is achieved, secondary closure and/or reconstruction with vascularized soft tissue flaps, such as omentum or pectoral muscle is performed. It seems there is a need for more effective surgical treatment of poststernotomy wound infections, which may address the prolonged hospitalization and reduce the number of surgical interventions and with this also the perioperative morbidity. In light of this we propose a randomized study comparing new delayed primary closure of the sternum to the secondary vacuum-assisted closure.
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PURPOSE: Evidence has accumulated in recent years suggestive of a genetic basis for a susceptibility to the development of radiation injury after cancer radiotherapy. The purpose of this study was to assess whether patients with severe radiation-induced sequelae (RIS; i.e., National Cancer Institute/CTCv3.0 grade, > or =3) display both a low capacity of radiation-induced CD8 lymphocyte apoptosis (RILA) in vitro and possess certain single nucleotide polymorphisms (SNP) located in candidate genes associated with the response of cells to radiation. EXPERIMENTAL DESIGN: DNA was isolated from blood samples obtained from patients (n = 399) included in the Swiss prospective study evaluating the predictive effect of in vitro RILA and RIS. SNPs in the ATM, SOD2, XRCC1, XRCC3, TGFB1, and RAD21 genes were screened in patients who experienced severe RIS (group A, n = 16) and control subjects who did not manifest any evidence of RIS (group B, n = 18). RESULTS: Overall, 13 and 21 patients were found to possess a total of <4 and > or =4 SNPs in the candidate genes. The median (range) RILA in group A was 9.4% (5.3-16.5) and 94% (95% confidence interval, 70-100) of the patients (15 of 16) had > or =4 SNPs. In group B, median (range) RILA was 25.7% (20.2-43.2) and 33% (95% confidence interval, 13-59) of patients (6 of 18) had > or =4 SNPs (P < 0.001). CONCLUSIONS: The results of this study suggest that patients with severe RIS possess 4 or more SNPs in candidate genes and low radiation-induced CD8 lymphocyte apoptosis in vitro.
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OBJECTIVE: Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset myopathy that progresses subacutely. If associated with a monoclonal gammopathy of unknown significance (MGUS), the outcome is unfavorable: the majority of these patients die within 1 to 5 years of respiratory failure. This study aims to qualitatively assess the long-term treatment effect of high-dose melphalan (HDM) followed by autologous stem cell transplantation (SCT) in a series of 8 patients with SLONM-MGUS. METHODS: We performed a retrospective case series study (n = 8) on the long-term (1-8 years) treatment effect of HDM followed by autologous SCT (HDM-SCT) on survival, muscle strength, and functional capacities. RESULTS: Seven patients showed a lasting moderate-good clinical response, 2 of them after the second HDM-SCT. All of them had a complete, a very good partial, or a partial hematologic response. One patient showed no clinical or hematologic response and died. CONCLUSIONS: This case series shows the positive effect of HDM-SCT in this rare disorder. Factors that may portend an unfavorable outcome are a long disease course before the hematologic treatment and a poor hematologic response. Age at onset, level and type of M protein (κ vs λ), and severity of muscle weakness were not associated with a specific outcome. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with SLONM-MGUS, HDM-SCT increases the probability of survival and functional improvement.
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OBJECTIVES: Inequalities and inequities in health are an important public health concern. In Switzerland, mortality in the general population varies according to the socio-economic position (SEP) of neighbourhoods. We examined the influence of neighbourhood SEP on presentation and outcomes in HIV-positive individuals in the era of combination antiretroviral therapy (cART). METHODS: The neighbourhood SEP of patients followed in the Swiss HIV Cohort Study (SHCS) 2000-2013 was obtained on the basis of 2000 census data on the 50 nearest households (education and occupation of household head, rent, mean number of persons per room). We used Cox and logistic regression models to examine the probability of late presentation, virologic response to cART, loss to follow-up and death across quintiles of neighbourhood SEP. RESULTS: A total of 4489 SHCS participants were included. Presentation with advanced disease [CD4 cell count <200 cells/μl or AIDS] and with AIDS was less common in neighbourhoods of higher SEP: the age and sex-adjusted odds ratio (OR) comparing the highest with the lowest quintile of SEP was 0.71 [95% confidence interval (95% CI) 0.58-0.87] and 0.59 (95% CI 0.45-0.77), respectively. An undetectable viral load at 6 months of cART was more common in the highest than in the lowest quintile (OR 1.52; 95% CI 1.14-2.04). Loss to follow-up, mortality and causes of death were not associated with neighbourhood SEP. CONCLUSION: Late presentation was more common and virologic response to cART less common in HIV-positive individuals living in neighbourhoods of lower SEP, but in contrast to the general population, there was no clear trend for mortality.
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Individuals who are unaware of their HIV infection constitute a fragile and a critical population both from a personal and from a community-based point of view: if the infection is diagnosed too late, the outcome can be complicated by AIDS-defining diseases, whose prognosis may remain unfavourable even after the initiation of a potent antiretroviral therapy. These patients contribute to the virus spreading into the community, owing to a high viral load. It is now necessary to recognise the limits of a risk behaviour and disease-driven HIV screening policy. Since 2006, the American guidelines recommend a routine HIV testing for all patients age 13 to 64 years unless they specifically refuse the test (opt-out). In Switzerland, the recommendations remain so far risk-centred.
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In the circum-Pacific ophiolitic belts, when no other biogenic constituents are found, radiolarians have the potential to provide significant biostratigraph- ic information. The Santa Rosa Accretionary Complex, which crops out in several half-windows (Carrizal, Sitio Santa Rosa, Bahia Nancite, Playa Naranjo) along the south shores of the Santa Elena Peninsula in northwestern Costa Rica, is one of these little-known ophiolitic mélanges. It contains various oceanic assemblages of alkaline basalt, radiolarite and polymictic breccias. The radiolarian biochronology presented in this work is mainly based by correlation on the biozonations of Carter et al. (2010), Baumgartner et al. (1995b), and O'Dogherty (1994) and indicate an Early Jurassic to early Late Cretaceous (early Pliensbachian to earliest Turonian) age for the sediments associated with oceanic basalts or recovered from blocks in breccias or megabreccias. The 19 illus- trated assemblages from the Carrizal tectonic window and Sitio Santa Rosa contain in total 162 species belonging to 65 genera. The nomenclature of tecton- ic units is the one presented by (Baumgartner and Denyer, 2006). This study brings to light the Early Jurassic age of a succession of radiolarite, which was previously thought to be of Cretaceous age, intruded by alkaline basalts sills (Unit 3). The presence of Early Jurassic large reworked blocks in a polymictic megabreccia, firstly reported by De Wever et al. (1985) is confirmed (Unit 4). Therefore, the alkaline basalt associated with the radiolarites of these two units (and maybe also Units 5 and 8) could be of Jurassic age. In the Carrizal tectonic window, Middle to early Late Jurassic radiolarian chert blocks associ- ated with massive tholeitic basalts and Early Cretaceous brick-red ribbon cherts overlying pillow basalts are interpreted as fragments of a Middle Jurassic oceanic basement accreted to an Early Cretaceous oceanic Plate, in an intra-oceanic subduction context. Whereas, the knobby radiolarites and black shales of Playa Carrizal are indicative of a shallower middle Cretaceous paleoenvironment. Other remnants of this oceanic basin are found in Units 2, 6, and 7, which documented the rapid approach of the depocentre to a subduction trench during the late Early Cretaceous (Albian-Cenomanian), to possibly early Late Cretaceous (Turonian).
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BACKGROUND: Previous studies revealed that acute depressive episodes are associated with both cognitive deficits and modified personality patterns in late life. Whether or not these psychological changes are present after remission remains a matter of debate. To date, no study provided concomitant assessment of cognition and psychological functions in this particular clinical setting. METHOD: Using a cross-sectional design, 58 remitted outpatients (36 with unipolar early-onset depression (EOD) and 22 with bipolar disorder (BD)) were compared to 62 healthy controls. Assessment included detailed neurocognitive measures and evaluation of the five factor personality dimensions (NEO-Personality Inventory). RESULTS: Group comparisons revealed significant slower processing speed, working and episodic memory performances in BD patients. EOD patients showed cognitive abilities comparable to those of elderly controls. In NEO PI assessment, both BD and EOD patients displayed higher Depressiveness facet scores. In addition, the EOD but not BD group had lower Extraversion factor, and Warmth and Positive Emotion facet scores than controls. CONCLUSIONS: After remission from acute affective symptoms, older BD patients show significant impairment in several cognitive functions while neuropsychological performances remained intact in elderly patients with EOD. Supporting a long-lasting psychological vulnerability, EOD patients are more prone to develop emotion-related personality trait changes than BD patients.
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Late Variscan volcanic activity is documented in the Late Carboniferous Salvan-Dorenaz sedimentary basin and in the neighboring basement units of the Aiguilles-Rouges and Mont-Blanc crystalline massifs (Western Alps). Precise U/Pb isotopic dating, zircon morphology and geochemical analyses indicate that volcanism occurred during short-lived pulses and that coexisting crustal and mantle sources were involved in the production of melts. Volcanic and subvolcanic products were emplaced along major N-S to NNE-SSW transtensional fracture zones, similar to the ones that governed intense basement exhumation and that favored the formation and filling of the Late Carboniferous Salvan-Dorenaz continental basin. In the Aiguilles-Rouges massif, dacitic flows outcropping at the base of the Salvan-Dorenaz basin erupted at 308 +/- 3 Ma; they represent the surface equivalent of the nearby Vallorcine peraluminous granite and associated rhyolitic dykes (311 +/- 17 Ma). In the Mont Blanc massif, calc-alkaline rhyolitic dykes were emplaced simultaneously (307 +/- 2 Ma) at shallow crustal levels, but they derive from deeper magma sources denoting enhanced mantellic activity. Recently identified tuffs and volcaniclastic layers embedded at different levels of the Salvan-Dorenaz stratigraphic record testify a 295 +3/-4 Ma old episode of highly explosive volcanism from distant volcanic centers, possibly located in the Aar-Gotthard massifs (Central Alps). Their zircon typology is highly heterogeneous. documenting wall-rock contamination of the melts and/or admixture of crustal sediments, whereas consistent subpopulations point to high-temperature magmas of deep-seated origin and alkaline affinity. The dated volcanic layers from the Salvan-Dorenaz basin set the beginning of the detrital sedimentation at 308 +/- 3 Ma and constrain the deposition of 1.5-1.7 km thick of elastic sediments within a time span of 10-15 Ma. These results infer minimum, long-term subsidence rates during basin evolution in the order of >0.1 mm/a, while in the surrounding basement units estimated exhumation rates are in the range of 1 mm/a. All dated rocks contain inherited zircon populations about 350, 450 or 600 Ma old.
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ABSTRACTThe pollution of air, soil and water by heavy metals through anthropogenic activities is an object of numerous environmental studies since long times. A number of natural processes, such as volcanic activity, hydrothermal fluid circulation and weathering of metal-rich deposits may lead to an additional and potentially important input and accumulation of heavy metals in the environment. In the Swiss and French Jura Mountains, anomalous high cadmium (Cd) concentrations (up to 16 ppm) in certain soils are related to the presence of underlying Cd-enriched (up to 21 ppm) carbonate rocks of Middle to Late Jurassic age. The aim of this study is to understand the processes controlling Cd incorporation into carbonate rocks of Middle and Late Jurassic age and to reconstruct the sedimentary and environmental conditions, which have led to Cd enrichments in these sedimentary rocks.Cd concentrations in studied hemipelagic sections in France vary between 0.1 and 0.5 ppm (mean 0.15 ppm). Trace-element behavior and high Mn concentrations suggest that sediment accumulation occurred in a well-oxygenated environment. Increases in Cd contents in the bulk-rock carbonate sediments may be related to increases in surface-water productivity under oxic conditions and important remineralization of organic matter within the water column. In platform settings preserved in the Swiss Jura Mountains, no correlation is observed between Cd contents and evolution of environmental conditions. Cd concentrations in these platform sections are often below the detection limit, with isolated peaks of up to 21 ppm. These important Cd enrichments are associated with peaks in Zn concentrations and are present in carbonate rocks independently of facies and age. The high Cd contents in these shallow-water carbonate rocks are partly related to the presence of disseminated, Cd-rich (up to 1.8%), sphalerite (ZnS) mineralization. The basement rocks are considered to be the source of metals for sulfide mineralization in the overlying Jurassic strata, as the sphalerite Pb isotope pattern is comparable to that of granite rocks from the nearby southern Black Forest crystalline massif. The Rb-Sr ages of sphalerite samples indicate that a main phase of sphalerite formation occurred near the boundary between the late Middle and early Late Jurassic, at around 162 Ma, as a result of enhanced tectonic and hydrothermal activity in Europe, related to the opening of the Central Atlantic and to the tectonic/thermal subsidence during spreading of the Alpine Tethys. I therefore propose to use unusually high Cd concentrations in carbonates as a tracer of tectonic activity in the Jura Mountains area, especially in the case when important enrichments in Zn co-occur. Paleoproductivity reconstructions based on records of authigenic Cd may be compromised not only by post-depositional redistribution, but also by incorporation of additional Cd from hydrothermal solutions circulating in the rock.The circulation of metal-rich hydrothermal fluids through the sediment sequence, in addition to specific environmental conditions during sedimentation, contributes to the incorporation of Cd into the carbonate rocks. However, only hydrothermal activity has led to the unusually high concentrations of Cd in carbonate rocks of Bajocian-Oxfordian age, through the formation of sphalerite mineralization.
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The late Paleocene - early Eocene sequences of DSDP Leg 10 Sites 86, 94, 95, and 96, Leg 43 Site 384 and ODP Leg 171B Hole 1051A have been re-sampled and re-examined for radiolarians. A new late Paleocene to early Eocene low-latitude radiolarian zonation suited for the correlation of accreted terranes is established by using the Unitary Association (UA) method. This method has the property of attributing equal weight to each species occurrence, which has the advantage of not being dependant on a limited set of key datums. Twenty-two UAs have been erected and correlated to the existing age models (given by nannofossils, planktonic foraminifera and radiolarians) for each site. The 22 UAs have been united into seven Unitary Associations Zones (UA Zones) (JP10-JE4) to increase lateral traceability. Herein we present the resulting composite range chart and correlation between the studied cores. The position of the UA Zones in the Paleogene timescale of.Berggren et al. (1995) have been estimated using a general consensus correlation with calcareous microfossil groups and the existing radiolarian zonation. Reproducible radiolarian events identified in the present work are bound to directly tied and compiled absolute ages given by Nigrini et al. (2006) and Sanfilippo and Nigrini (1998a). The RP zones (Sanfilippo and Nigrini 1998a) and the UA Zones are consistent. Unitary Associations permit to distinguish supplementary zonal subdivisions within RP7 and RP6. Topotypes from DSDP Leg 10 have been illustrated using mainly SEM imaging to facilitate the identification of re-crystallized forms.