Hepatitis E virus mixed infection in immunocompetent patient

We detected 2 hepatitis E virus (HEV) strains in an acutely infected immunocompetent patient. Two populations of genotype 3 virus were observed in the hypervariable regions and open reading frames 2 and 3, indicating multiple infection with hepatitis E virus. Persons with mixed infections may provide the opportunity for virus recombination

Why are we not flooded by involuntary thoughts about the past and future? Testing the cognitive inhibition dependency hypothesis

© The Author(s) 2018In everyday life, involuntary thoughts about future plans and events occur as often as involuntary thoughts about the past. However, compared to involuntary autobiographical memories (IAMs), such episodic involuntary future thoughts (IFTs) have become a focus of study only recently. The aim of the present investigation was to examine why we are not constantly flooded by IFTs and IAMs given that they are often triggered by incidental cues while performing undemanding activities. One possibility is that activated thoughts are suppressed by the inhibitory control mechanism, and therefore depleting inhibitory control should enhance the frequency of both IFTs and IAMs. We report an experiment with a between-subjects design, in which participants in the depleted inhibition condition performed a 60-min high-conflict Stroop task before completing a laboratory vigilance task measuring the frequency of IFTs and IAMs. Participants in the intact inhibition condition performed a version of the Stroop task that did not deplete inhibitory control. To control for physical and mental fatigue resulting from performing the 60-min Stroop tasks in experimental conditions, participants in the control condition completed only the vigilance task. Contrary to predictions, the number of IFTs and IAMs reported during the vigilance task, using the probe-caught method, did not differ across conditions. However, manipulation checks showed that participants’ inhibitory resources were reduced in the depleted inhibition condition, and participants were more tired in the experimental than in the control conditions. These initial findings suggest that neither inhibitory control nor physical and mental fatigue affect the frequency of IFTs and IAMs.Peer reviewedFinal Published versio

Activation of transcription factors by extracellular nucleotides in immune and related cell types

Extracellular nucleotides, acting through P2 receptors, can regulate gene expression via intracellular signaling pathways that control the activity of transcription factors. Relatively little is known about the activation of transcription factors by nucleotides in immune cells. The NF-κB family of transcription factors is critical for many immune and inflammatory responses. Nucleotides released from damaged or stressed cells can act alone through certain P2 receptors to alter NF-κB activity or they can enhance responses induced by pathogen-associated molecules such as LPS. Nucleotides have also been shown to regulate the activity of other transcription factors (AP-1, NFAT, CREB and STAT) in immune and related cell types. Here, we provide an overview of transcription factors shown to be activated by nucleotides in immune cells, and describe what is known about their mechanisms of activation and potential functions. Furthermore, we propose areas for future work in this new and expanding field

Induction of PPM1D following DNA-damaging treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation sites

PPM1D (Wip1), a type PP2C phosphatase, is expressed at low levels in most normal tissues but is overexpressed in several types of cancers. In cells containing wild-type p53, the levels of PPM1D mRNA and protein increase following exposure to genotoxic stress, but the mechanism of regulation by p53 was unknown. PPM1D also has been identified as a CREB-regulated gene due to the presence of a cyclic AMP response element (CRE) in the promoter. Transient transfection and chromatin immunoprecipitation experiments in HCT116 cells were used to characterize a conserved p53 response element located in the 5′ untranslated region (UTR) of the PPM1D gene that is required for the p53-dependent induction of transcription from the human PPM1D promoter. CREB binding to the CRE contributes to the regulation of basal expression of PPM1D and directs transcription initiation at upstream sites. Following exposure to ultraviolet (UV) or ionizing radiation, the abundance of transcripts with short 5′ UTRs increased in cells containing wild-type p53, indicating increased utilization of downstream transcription initiation sites. In cells containing wild-type p53, exposure to UV resulted in increased PPM1D protein levels even when PPM1D mRNA levels remained constant, indicating post-transcriptional regulation of PPM1D protein levels

Cell type-specific anti-cancer properties of valproic acid: independent effects on HDAC activity and Erk1/2 phosphorylation

<p>Abstract</p> <p>Background</p> <p>The anti-epileptic drug valproic acid (VPA) has attracted attention as an anti-cancer agent.</p> <p>Methods</p> <p>The present study investigated effects of VPA exposure on histone deacetylase (HDAC) inhibition, cell growth, cell speed, and the degree of Erk1/2 phosphorylation in 10 cell lines (BT4C, BT4Cn, U87MG, N2a, PC12-E2, CSML0, CSML100, HeLa, L929, Swiss 3T3).</p> <p>Results</p> <p>VPA induced significant histone deacetylase (HDAC) inhibition in most of the cell lines, but the degree of inhibition was highly cell type-specific. Moreover, cell growth, motility and the degree of Erk1/2 phosphorylation were inhibited, activated, or unaffected by VPA in a cell type-specific manner. Importantly, no relationship was found between the effects of VPA on HDAC inhibition and changes in the degree of Erk1/2 phosphorylation, cell growth, or motility. In contrast, VPA-induced modulation of the MAPK pathway downstream of Ras but upstream of MEK (i.e., at the level of Raf) was important for changes in cell speed.</p> <p>Conclusions</p> <p>These results suggest that VPA can modulate the degree of Erk1/2 phosphorylation in a manner unrelated to HDAC inhibition and emphasize that changes in the degree of Erk1/2 phosphorylation are also important for the anti-cancer properties of VPA.</p

Coccolithophores as proxy of seawater changes at orbital-to-millennial scale during middle Pleistocene Marine Isotope Stages 14-9 in North Atlantic core MD01-2446

midlatitude North Atlantic, to reconstruct climatically induced sea surface water conditions throughout Marine Isotope Stages (MIS) 14–9. The data are compared to new and available paleoenvironmental proxies from the same site as well as other nearby North Atlantic records that support the coccolithophore signature at glacial‐interglacial to millennial climate scale. Total coccolithophore absolute abundance increases during interglacials but abruptly drops during the colder glacial phases and deglaciations. Coccolithophore warm water taxa (wwt) indicate that MIS11c and MIS9e experienced warmer and more stable conditions throughout the whole photic zone compared to MIS13. MIS11 was a long‐lasting warmer and stable interglacial characterized by a climate optimum during MIS11c when a more prominent influence of the subtropical front at the site is inferred. The wwt pattern also suggests distinct interstadial and stadial events lasting about 4–10 kyr. The glacial increases of Gephyrocapsa margereli‐G. muellerae 3–4 µm along with higher values of Corg, additionally supported by the total alkenone abundance at Site U1313, indicate more productive surface waters, likely reflecting the migration of the polar front into the midlatitude North Atlantic. Distinctive peaks of G. margereli‐muellerae (>4 µm), C. pelagicus pelagicus , Neogloboquadrina pachyderma left coiling, and reworked nannofossils, combined with minima in total nannofossil accumulation rate, are tracers of Heinrich‐type events during MIS12 and MIS10. Additional Heinrich‐type events are suggested during MIS12 and MIS14 based on biotic proxies, and we discuss possible iceberg sources at these times. Our results improve the understanding of mid‐Brunhes paleoclimate and the impact on phytoplankton diversity in the midlatitude North Atlantic region.Provided by PTCRIS: 58282, C2007-FCT/319/2006info:eu-repo/semantics/publishedVersio

Long-term levetiracetam treatment affects reproductive endocrine function in female Wistar rats

SummaryPurposeSeveral antiepileptic drugs (AEDs) induce changes in endocrine function in women with epilepsy. Levetiracetam (LEV) is one of the newer AEDs, and to date no endocrine side-effects have been reported in humans. However, a recent study on ovarian follicular cells from prepubertal pigs showed that LEV affected basal steroid hormone secretion. The aim of the present study was to investigate possible effects of the drug on endocrine function and ovarian morphology in non-epileptic rats.MethodsThirty female Wistar rats were fed per-orally with either 50mg/kg LEV (n=15) or 150mg/kg LEV (n=15) twice daily for 90–95 days. Twenty rats received a control solution. The rats were killed in the dioestrus phase of the oestrous cycle. Serum concentrations of testosterone, 17β-oestradiol, progesterone, follicle stimulating hormone (FSH), luteinizing hormone (LH) and LEV were measured, and the ovaries examined histologically.ResultsMean ovarian weight showed a significant, dose-dependent increase after LEV treatment. Mean numbers of ovarian follicular cysts were not changed, but the numbers of corpora lutea and secondary follicles were significantly higher in the treated animals. Serum testosterone was significantly increased in treated animals (0.50nmol/l versus 0.16nmol/l in controls, p<0.05), while oestradiol was reduced (67.4 compared to 257.5pmol/l in controls, p<0.05). The low-dose group had significantly lower serum progesterone concentrations than the control group (56.8nmol/l versus 34.7nmol/l, respectively, p<0.05). FSH was reduced in the treated animals (3.3ng/ml versus 5.5ng/ml, p<0.05) while LH was unaffected.ConclusionOur findings indicate a possible effect of LEV on the hypothalamic–pituitary–gonadal (HPG) axis and ovarian morphology in non-epileptic rats. The effects differ from those previously described for other AEDs. Caution must be taken before these results can be applied to humans

Update on the use of aromatase inhibitors in early-stage breast cancer

Aromatase inhibitors are currently included in the 'optimal' management of early-stage breast cancer. Uncertainty remains, however, as to the most appropriate treatment strategy, particularly for newly diagnosed women as they seek to trade off the cost, toxicities and efficacy of the treatment options. Recent publications provide conflicting advice on the role of aromatase inhibitors in the treatment of postmenopausal patients with early-stage hormone receptor-positive breast cancer. This review provides updates on the clinical trials of aromatase inhibitors in early breast cancer and tries to provide practical clinical guidance on their optimal use

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants

BACKGROUND: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. METHODS: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence—defined as fasting plasma glucose of 7·0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs—in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. FINDINGS: We used data from 751 studies including 4 372 000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4·3% (95% credible interval 2·4–7·0) in 1980 to 9·0% (7·2–11·1) in 2014 in men, and from 5·0% (2·9–7·9) to 7·9% (6·4–9·7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28·5% due to the rise in prevalence, 39·7% due to population growth and ageing, and 31·8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. INTERPRETATION: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. FUNDING: Wellcome Trust

Meta-analysis of the incidence of foodborne pathogens in vegetables and fruits from retail establishments in Europe

In this study, a systematic review and meta-analysis were conducted to summarise available information on the occurrence of Salmonella spp. Listeria monocytogenes and shigatoxin-producing Escherichia coli (STEC) in fruits and vegetables sold at retail establishments in several European countries. Overall, L. monocytogenes was the main pathogen detected in all kinds of vegetables, packaged or not (3.4%; 95% CI: 2.15.4%) with Salmonella spp. being the pathogen of lowest incidence (0.9%; 95% CI: 0.51.2%). The pooled occurrence rate of pathogens in either packed or unpacked vegetables was estimated at 1.9% (95% CI: 1.23.1%), with 2.1% of prevalence (95% CI: 1.33.4%) for unpacked vegetables and 1.7% (95% CI: 0.92.9%) for packed ones. For the three pathogens, the category of spices and herbs was the most frequently contaminated with pathogens, whereas salads presented the lowest occurrence. The vegetable category with highest incidence of Salmonella spp. (1.7%; 95% CI: 0.74.1%) and L. monocytogenes (2.2%; 95% CI: 1.04.7%) is leafy greens whilst STEC is more frequently recovered from sprouts (1.9%; 95% CI: 0.55.9%). In the case of fruits, the pooled prevalence estimates for Salmonella spp., L. monocytogenes and STEC were 1.60% (0.54%; 95% CI: 0.554.60%), 1.91% (0.50%; 95% CI: 0.933.88%) and 4.71% (1.52%; 95% CI: 1.7312.2%), correspondingly.Dr. Gonzales-Barron wishes to acknowledge the financial support provided by the Portuguese Foundation for Science and Technology (FCT) through the award of a five-year Investigator Fellowship (IF) in the mode of Development Grants (IF/00570).info:eu-repo/semantics/publishedVersio