Optimizing heroin-assisted treatment (HAT): Assessment of the contribution of direct ethanol metabolites in identifying hazardous and harmful alcohol use

Heavy alcohol consumption may accelerate the progression of hepatitis C-related liver disease and/or limit efforts at antiviral treatment in opioid-dependent patients receiving heroin-assisted treatment (HAT). Our study aims to assess alcohol intake among HAT patients by self-reports compared to direct ethanol metabolites.

Isolated GH deficiency type II: knockdown of the harmful Delta3GH recovers wt-GH secretion in rat tumor pituitary cells

Isolated GH deficiency type II (IGHD II) is the autosomal dominant form of GHD. In the majority of the cases, this disorder is due to specific GH-1 gene mutations that lead to mRNA missplicing and subsequent loss of exon 3 sequences. When misspliced RNA is translated, it produces a toxic 17.5-kDa GH (Delta3GH) isoform that reduces the accumulation and secretion of wild-type-GH. At present, patients suffering from this type of disease are treated with daily injections of recombinant human GH in order to maintain normal growth. However, this type of replacement therapy does not prevent toxic effects of the Delta3GH mutant on the pituitary gland, which can eventually lead to other hormonal deficiencies. We developed a strategy involving Delta3GH isoform knockdown mediated by expression of a microRNA-30-adapted short hairpin RNA (shRNA) specifically targeting the Delta3GH mRNA of human (shRNAmir-Delta3). Rat pituitary tumor GC cells expressing Delta3GH upon doxycycline induction were transduced with shRNAmir-Delta3 lentiviral vectors, which significantly reduced Delta3GH protein levels and improved human wild-type-GH secretion in comparison with a shRNAmir targeting a scrambled sequence. No toxicity due to shRNAmir expression could be observed in cell proliferation assays. Confocal microscopy strongly suggested that shRNAmir-Delta3 enabled the recovery of GH granule storage and secretory capacity. These viral vectors have shown their ability to stably integrate, express shRNAmir, and rescue IGHD II phenotype in rat pituitary tumor GC cells, a methodology that opens new perspectives for the development of gene therapy to treat IGHD patients.

Efficacy of quality criteria to identify potentially harmful information: a cross-sectional survey of complementary and alternative medicine web sites.

BACKGROUND: Many users search the Internet for answers to health questions. Complementary and alternative medicine (CAM) is a particularly common search topic. Because many CAM therapies do not require a clinician's prescription, false or misleading CAM information may be more dangerous than information about traditional therapies. Many quality criteria have been suggested to filter out potentially harmful online health information. However, assessing the accuracy of CAM information is uniquely challenging since CAM is generally not supported by conventional literature. OBJECTIVE: The purpose of this study is to determine whether domain-independent technical quality criteria can identify potentially harmful online CAM content. METHODS: We analyzed 150 Web sites retrieved from a search for the three most popular herbs: ginseng, ginkgo and St. John's wort and their purported uses on the ten most commonly used search engines. The presence of technical quality criteria as well as potentially harmful statements (commissions) and vital information that should have been mentioned (omissions) was recorded. RESULTS: Thirty-eight sites (25%) contained statements that could lead to direct physical harm if acted upon. One hundred forty five sites (97%) had omitted information. We found no relationship between technical quality criteria and potentially harmful information. CONCLUSIONS: Current technical quality criteria do not identify potentially harmful CAM information online. Consumers should be warned to use other means of validation or to trust only known sites. Quality criteria that consider the uniqueness of CAM must be developed and validated.

Eemian and Holocene sea-surface conditions in the southern Black Sea: organic-walled dinoflagellate cyst record from core 22-GC3

In order to compare the sea-surface conditions in the Black Sea during the Holocene and Eemian, sapropelic parts of marine core 22-GC3 (42°13.53′N/36°29.55′E, 838 m water depth) were studied for organic-walled dinoflagellate cyst content. The record shows a change from freshwater/brackish assemblages (Pyxidinopsis psilata, Spiniferites cruciformis, and Caspidinium rugosum) to more marine assemblages (Lingulodinium machaerophorum and Spiniferites ramosus complex) during each interglacial, due to the inflow of saline Mediterranean water. The lacustrine–marine transitions in 22-GC3 occurred at ~ 8.3 cal kyr BP during the early Holocene and ~ 128 kyr BP during the early Eemian, slightly later compared to the onset of interglacial conditions on the adjacent land. Dinoflagellate cyst assemblages reveal higher sea-surface salinity (~ 28–30) (e.g. Spiniferites pachydermus, Bitectatodinium tepikiense, and Spiniferites mirabilis) around ~ 126.5–121 kyr BP in comparison to the Holocene (~ 15–20) as well as relatively high sea-surface temperature (e.g. Tuberculodinium vancampoae, S. pachydermus, and S. mirabilis) especially at ~ 127.6–125.3 kyr BP. Establishment of high sea-surface salinity during the Eemian correlates very well with reconstructed relatively high global sea-level and is explained as a combined effect of increased Mediterranean supply and high temperatures at the beginning of the last interglacial. The observed changes in the dinocyst record highlight the importance of nutrients for the composition of the Eemian and Holocene dinocyst assemblages.

Dinoflagellate cyst assemblages, oxygen isotope records of foraminifera, and alkenone and Mg/Ca-based SST estimates for the time interval 3.40-3.18 Ma (Late Pliocene) from five North Atlantic and Caribbean sediment cores

The early Late Pliocene (3.6 to ~3.0 million years ago) is the last extended interval in Earth's history when atmospheric CO2 concentrations were comparable to today's and global climate was warmer. Yet a severe global glaciation during marine isotope stage (MIS) M2 interrupted this phase of global warmth ~3.30 million years ago, and is seen as a premature attempt of the climate system to establish an ice-age world. Our geochemical and palynological records from five marine sediment cores along a Caribbean to eastern North Atlantic transect show that increased Pacific-to-Atlantic flow via the Central American Seaway weakened the North Atlantic Current (NAC) and attendant northward heat transport prior to MIS M2. The consequent cooling of the northern high latitude oceans permitted expansion of the Greenland ice sheet during MIS M2, despite near-modern atmospheric CO2 concentrations. Before and after MIS M2, heat transport via the NAC was crucial in maintaining warm climates comparable to those predicted for the end of this century.

Late Pliocene and Early Pleistocene dinoflagellate cysts and sea surface temperture reconstruction for several IODP and DSDP sites in the North Atlantic

In an attempt to document the palaeoecological affinities of individual extant and extinct dinoflagellate cysts, Late Pliocene and Early Pleistocene dinoflagellate cyst assemblages have been compared with geochemical data from the same samples. Mg/Ca ratios of Globigerina bulloides were measured to estimate the spring-summer sea-surface temperatures from four North Atlantic IODP/DSDP sites. Currently, our Pliocene-Pleistocene database contains 204 dinoflagellate cyst samples calibrated to geochemical data. This palaeo-database is compared with modern North Atlantic and global datasets. The focus lies in the quantitative relationship between Mg/Ca-based (i.e. spring-summer) sea-surface temperature (SSTMg/Ca) and dinoflagellate cyst distributions. In general, extant species are shown to have comparable spring-summer SST ranges in the past and today, demonstrating that our new approach is valid for inferring spring-summer SST ranges for extinct species. For example, Habibacysta tectata represents SSTMg/Ca values between 10° and 15°C when it exceeds 30% of the assemblage, and Invertocysta lacrymosa exceeds 15% when SSTMg/Ca values are between 18.6° and 23.5°C. However, comparing Pliocene and Pleistocene SSTMg/Ca values with present day summer values for the extant Impagidinium pallidum suggests a greater tolerance of higher temperatures in the past. This species occupies more than 5% of the assemblage at SSTMg/Ca values of 11.6-17.9°C in the Pliocene and Pleistocene, whereas present day summer SSTs are around -1.7 to 6.9°C. This observation questions the value of Impagidinium pallidum as reliable indicator of cold waters in older deposits, and may explain its bipolar distribution.

Calcareous dinoflagellate cycst in the mid-Cenomanian Boreal realm

A transect from the bathyal to proximal shelf facies of the Boreal Realm was investigated to compare spatial and temporal distribution changes of calcareous dinoflagellate cysts (c-dinocysts) throughout the mid-Cenomanian in order to gain information on the ecology of these organisms. Pithonelloideae dominated the cyst assemblages to more than 95% on the shelf, a prevalence that can be observed throughout most of the Upper Cretaceous. The affinity of this group with the dinoflagellates, which is still controversially discussed, can be confirmed, based on evidence from morphological features and distribution patterns. The consistent prevalence of Pithonella sphaerica and P. ovalis in c-dinocyst assemblages throughout the Upper Cretaceous indicates that they were produced more frequently than cysts of the other species and might, therefore, represent a vegetative dinoflagellate life stage. P. sphaerica and P. ovalis are interpreted as eutrophic species. P. sphaerica is the main species in a marginal-shelf upwelling area, offshore Fennoscandia. Here, sedimentary cyclicity appears to have been reduced to the strongest light/dark changes, while in the outer shelf sediments, light/dark cycles are well-developed and show pronounced temporal assemblage changes. Cyclic fluctuations in the P. sphaerica / P. ovalis ratio reflect shifts of the preferred facies zones and indicate changes in surface mixing patterns. During periods of enhanced surface mixing most parts of the shelf were well-ventilated, and nutrient-enriched surface waters led to high productivity and dominance of the Pithonelloideae. These conditions on the shelf contrasted with those in the open ocean, where more oligotrophic and probably stratified waters prevailed, and an assemblage with very few Pithonelloideae and dominance of Cubodinellum renei and Orthopithonella ? gustafsonii was characteristic. While orbitally-forced light/dark sedimentary cyclicity of the shelf sections was mainly related to surface-water carbonate productivity changes, no cyclic modulation of productivity was observed in the oceanic profile. Therefore, dark layer formation in the open ocean was predominantly controlled by the cyclic establishment of anoxic bottom water conditions. Orbitally-forced interruptions in mixing on the shelf resulted in cyclic periods of stratification and oligotrophy in the surface waters, an expansion of oceanic species to the outer shelf, and a shelfward shift of pithonelloid-facies zones, which were probably related to shelfward directed oceanic ingressions.

Dinoflagellate cyst counts and age model from sediment samples of ODP Hole 175-1085A

Sediment samples from ODP Site 1085 were investigated in order to obtain more information on the initiation and development of the Benguela upwelling system during the middle and upper Miocene. In particular, our intent was to establish the causes of the upwelling as well as the response of the upwelling regime to the development of the Antarctic Circumpolar Current. Based on changes in the calcareous dinoflagellate cyst association, we found an initial increase of the dinoflagellate cyst productivity, probably related to the initiation of upwelling about 11.8 Ma ago. Two distinct increases in cyst productivity in conjunction with temperature decreases of the upper water masses reflect upwelling pulses off Namibia and occur at the end of the Miocene cooling events Mi5 (about 11.5 Ma) and Mi6 (about 10.5 Ma). Both cooling events are associated with an ice volume increase in Antarctica and are thought to have led to an increase in southeasterly winds, possibly causing these two upwelling pulses. We demonstrate a decrease in dinoflagellate cyst productivity and enhanced terrigenous input via the Orange River after the Mi5 event. At about 11.1 Ma, the dinoflagellate cyst productivity increases again. The polar cyst species Caracomia arctica occurs here for the first time. This implies an influence of subantarctic mode water and therefore a change in the quality of the upwelling water which allowed the Benguela upwelling to develop into modern conditions. From about 10.4 Ma, C. arctica forms a permanent part of the association, pointing to an establishment of the upwelling regime.

Radiance, irradiance, and remote sensing reflectance during the North Sea Coast Harmful Algal Bloom (NORCOHAB II) HEINCKE cruise HE302

In this study four data quality flags are presented for automated and unmanned above-water hyperspectral optical measurements collected underway in the North Sea, The Minch, Irish Sea and Celtic Sea in April/May 2009. Coincident to these optical measurements a DualDome D12 (Mobotix, Germany) camera system was used to capture sea surface and sky images. The first three flags are based on meteorological conditions, to select erroneous incoming solar irradiance (ES) taken during dusk, dawn, before significant incoming solar radiation could be detected or under rainfall. Furthermore, the relative azimuthal angle of the optical sensors to the sun is used to identify possible sunglint free sea surface zones. A total of 629 spectra remained after applying the meteorological masks (first three flags). Based on this dataset, a fourth flag for sunglint was generated by analysing and evaluating water leaving radiance (LW) and remote sensing reflectance (RRS) spectral behaviour in the presence and absence of sunglint salient in the simultaneously available sea surface images. Spectra conditions satisfying "mean LW (700-950 nm) < 2 mW/m**2/nm/Sr" or alternatively "minimum RRS (700-950 nm) < 0.010/Sr", mask the most measurements affected by sunglint, providing efficient flagging of sunglint in automated quality control. It is confirmed that valid optical measurements can be performed 0° <= theta <= 360° although 90° <= theta <= 135° is recommended.