CD4+:CD8+T Cell Ratio Normalization and the Development of AIDS Events in People with HIV Starting Antiretroviral Therapy

We identify factors associated with the normalization of the CD4+:CD8+ T cell ratio among UK Collaborative HIV Cohort study participants, and describe the association of the CD4+ and CD8+ T cell counts and the CD4+:CD8+ T cell ratio, with the risk of new AIDS events among individuals who achieve a suppressed viral load. Participants initiating combination antiretroviral therapy (cART) after 2006 with a CD4+:CD8+ T cell ratio 500 vs. ≤200 cells/mm3, adjusted hazard ratio (95% confidence interval): 7.93 (6.97–9.01)], low CD8+ T cell count [>1,150 vs. ≤500 cells/mm3: 0.18 (0.16–0.21)], and low CD4+:CD8+ T cell ratio [>0.8 vs. 500 vs. ≤200 cells/mm3: adjusted rate ratio 0.24 (0.16–0.34)] and CD4+:CD8+ T cell ratio [>0.8 vs. <0.2: 0.33 (0.21–0.52)] were independently associated with a new AIDS event. One third of study participants experienced ratio normalization after starting cART. CD4+ T cell count and CD4+:CD8+ T cell ratio are both individually associated with ratio normalization and the development of new AIDS events after cART

Salt-Enrichment Impact on Biomass Production in a Natural Population of Peatland Dwelling Arcellinida and Euglyphida (Testate Amoebae)

This is the final version. Available on open access from Springer Verlag via the DOI in this recordUnicellular free-living microbial eukaryotes of the order Arcellinida (Tubulinea; Amoebozoa) and Euglyphida (Cercozoa; SAR), commonly termed testate amoebae, colonise almost every freshwater ecosystem on Earth. Patterns in the distribution and productivity of these organisms are strongly linked to abiotic conditions—particularly moisture availability and temperature—however, the ecological impacts of changes in salinity remain poorly documented. Here, we examine how variable salt concentrations affect a natural community of Arcellinida and Euglyphida on a freshwater sub-Antarctic peatland. We principally report that deposition of wind-blown oceanic salt-spray aerosols onto the peatland surface corresponds to a strong reduction in biomass and to an alteration in the taxonomic composition of communities in favour of generalist taxa. Our results suggest novel applications of this response as a sensitive tool to monitor salinisation of coastal soils and to detect salinity changes within peatland palaeoclimate archives. Specifically, we suggest that these relationships could be used to reconstruct millennial scale variability in salt-spray deposition—a proxy for changes in wind-conditions—from sub-fossil communities of Arcellinida and Euglyphida preserved in exposed coastal peatlands.Natural Environment Research Council (NERC

Attention bias modification: the Emperor's new suit?

A series of primarily laboratory-based studies found attention bias modification in socially anxious participants to lead to reduced anxiety. It is argued that the failure to replicate the positive results of attention bias modification in the study of Carlbring et al. may be due to reasons other than the application through the Internet. A number of controlled studies failed to replicate the positive effects of attention bias modification in clinically rather than subclinically socially anxious subjects. Given the lack of robust evidence for attention bias modification in clinically socially anxious individuals, the author is inclined to consider attention bias modification as 'the Emperor's new suit'. Results achieved with regular Internet-based treatments for social anxiety disorder based on cognitive therapy and exposure methods are much better than those achieved with attention bias modification procedures delivered 'face to face' in clinically distressed participants. Given the lack of robust evidence for attention bias modification in clinical samples, there is no need yet to investigate the implementation of attention bias modification through the Internet

Association between canine leishmaniosis and Ehrlichia canis co-infection: a prospective case-control study

Abstract Background In the Mediterranean basin, Leishmania infantum is a major cause of disease in dogs, which are frequently co-infected with other vector-borne pathogens (VBP). However, the associations between dogs with clinical leishmaniosis (ClinL) and VBP co-infections have not been studied. We assessed the risk of VBP infections in dogs with ClinL and healthy controls. Methods We conducted a prospective case-control study of dogs with ClinL (positive qPCR and ELISA antibody for L. infantum on peripheral blood) and clinically healthy, ideally breed-, sex- and age-matched, control dogs (negative qPCR and ELISA antibody for L. infantum on peripheral blood) from Paphos, Cyprus. We obtained demographic data and all dogs underwent PCR on EDTA-blood extracted DNA for haemoplasma species, Ehrlichia/Anaplasma spp., Babesia spp., and Hepatozoon spp., with DNA sequencing to identify infecting species. We used logistic regression analysis and structural equation modelling (SEM) to evaluate the risk of VBP infections between ClinL cases and controls. Results From the 50 enrolled dogs with ClinL, DNA was detected in 24 (48%) for Hepatozoon spp., 14 (28%) for Mycoplasma haemocanis, 6 (12%) for Ehrlichia canis and 2 (4%) for Anaplasma platys. In the 92 enrolled control dogs, DNA was detected in 41 (45%) for Hepatozoon spp., 18 (20%) for M. haemocanis, 1 (1%) for E. canis and 3 (3%) for A. platys. No Babesia spp. or “Candidatus Mycoplasma haematoparvum” DNA was detected in any dog. No statistical differences were found between the ClinL and controls regarding age, sex, breed, lifestyle and use of ectoparasitic prevention. A significant association between ClinL and E. canis infection (OR = 12.4, 95% CI: 1.5–106.0, P = 0.022) was found compared to controls by multivariate logistic regression. This association was confirmed using SEM, which further identified that younger dogs were more likely to be infected with each of Hepatozoon spp. and M. haemocanis, and dogs with Hepatozoon spp. were more likely to be co-infected with M. haemocanis. Conclusions Dogs with ClinL are at a higher risk of co-infection with E. canis than clinically healthy dogs. We recommend that dogs diagnosed with ClinL should be tested for E. canis co-infection using PCR

COMPUESTOS FUNCIONALES DE LA LECHE MATERNA

Newborns have special nutritional requirements due to the incomplete development of their organic systems, which will diminish once the organs acquire full functionality. In the complete development of the infant organism, not only the correct nutrition of the child has a great contribution, but also many other functional compounds naturally present in breast milk such as Hormones, growth factors, neuropeptides, anti-inflammatory agents and immunomodulator agents. A thorough review of the scientific literature regarding the properties and occurrence of such functional compounds in breast milk has been carried out due to their importance in the elaboration of infant food. Therefore, the main objective of this work was to give enough scientific evidence for the use of these compounds as functional ingredients in the production of infant formulas. In general, infant formulas lack in these bioactive compounds, hence their supplementation with bioactive compounds as ingredients might increase the nutritional value of the infant formulas achieving the same positive effects that human milk has on infants.Los recién nacidos poseen unas necesidades nutritivas especiales debido al incompleto desarrollo de sus sistemas de órganos, que irán abandonando conforme estos sistemas vayan adquiriendo su completa funcionalidad. Al correcto desarrollo del organismo infantil va a contribuir no sólo la correcta nutrición del niño, sino también la acción de muchos compuestos funcionales presentes en la leche materna, entre los que destacan: hormonas, factores de crecimiento, neuropéptidos, agentes antiinflamatorios y agentes inmunomoduladores. Debido a la importancia que tienen estos compuestos en la alimentación infantil hemos realizado una revisión bibliográfica sobre sus diferentes propiedades y su presencia en la leche materna, con el objetivo de poder justificar el empleo de estos productos como ingredientes funcionales en la elaboración de las fórmulas infantiles. En general, dichas fórmulas son deficitarias en estos compuestos bioactivos, por lo que su adición como ingrediente podría incrementar la calidad nutricional de las fórmulas infantiles consiguiendo los mismos efectos positivos que sobre el niño tiene la lactancia materna

Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

Drivers of Holocene peatland carbon accumulation across a climate gradient in northeastern North America

Peatlands are an important component of the Holocene global carbon (C) cycle and the rate of C sequestration and storage is driven by the balance between net primary productivity and decay. A number of studies now suggest that climate is a key driver of peatland C accumulation at large spatial scales and over long timescales, with warmer conditions associated with higher rates of C accumulation. However, other factors are also likely to play a significant role in determining local carbon accumulation rates and these may modify past, present and future peatland carbon sequestration. Here, we test the importance of climate as a driver of C accumulation, compared with hydrological change, fire, nitrogen content and vegetation type, from records of C accumulation at three sites in northeastern North America, across the N-S climate gradient of raised bog distribution. Radiocarbon age models, bulk density values and %C measurements from each site are used to construct C accumulation histories commencing between 11,200 and 8000cal. years BP. The relationship between C accumulation and environmental variables (past water table depth, fire, peat forming vegetation and nitrogen content) is assessed with linear and multivariate regression analyses. Differences in long-term rates of carbon accumulation between sites support the contention that a warmer climate with longer growing seasons results in faster rates of long-term carbon accumulation. However, mid-late Holocene accumulation rates show divergent trends, decreasing in the north but rising in the south. We hypothesise that sites close to the moisture threshold for raised bog distribution increased their growth rate in response to a cooler climate with lower evapotranspiration in the late Holocene, but net primary productivity declined over the same period in northern areas causing a decrease in C accumulation. There was no clear relationship between C accumulation and hydrological change, vegetation, nitrogen content or fire, but early successional stages of peatland growth had faster rates of C accumulation even though temperatures were probably lower at the time. We conclude that climate is the most important driver of peatland accumulation rates over millennial timescales, but that successional vegetation change is a significant additional influence. Whilst the majority of northern peatlands are likely to increase C accumulation rates under future warmer climates, those at the southern limit of distribution may show reduced rates. However, early succession peatlands that develop under future warming at the northern limits of peatland distribution are likely to have high rates of C accumulation and will compensate for some of the losses elsewhere

The Molecular Clockwork of the Fire Ant Solenopsis invicta

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

User needs elicitation via analytic hierarchy process (AHP). A case study on a Computed Tomography (CT) scanner

Background: The rigorous elicitation of user needs is a crucial step for both medical device design and purchasing. However, user needs elicitation is often based on qualitative methods whose findings can be difficult to integrate into medical decision-making. This paper describes the application of AHP to elicit user needs for a new CT scanner for use in a public hospital. Methods: AHP was used to design a hierarchy of 12 needs for a new CT scanner, grouped into 4 homogenous categories, and to prepare a paper questionnaire to investigate the relative priorities of these. The questionnaire was completed by 5 senior clinicians working in a variety of clinical specialisations and departments in the same Italian public hospital. Results: Although safety and performance were considered the most important issues, user needs changed according to clinical scenario. For elective surgery, the five most important needs were: spatial resolution, processing software, radiation dose, patient monitoring, and contrast medium. For emergency, the top five most important needs were: patient monitoring, radiation dose, contrast medium control, speed run, spatial resolution. Conclusions: AHP effectively supported user need elicitation, helping to develop an analytic and intelligible framework of decision-making. User needs varied according to working scenario (elective versus emergency medicine) more than clinical specialization. This method should be considered by practitioners involved in decisions about new medical technology, whether that be during device design or before deciding whether to allocate budgets for new medical devices according to clinical functions or according to hospital department

ELF5 modulates the estrogen receptor cistrome in breast cancer.

Acquired resistance to endocrine therapy is responsible for half of the therapeutic failures in the treatment of breast cancer. Recent findings have implicated increased expression of the ETS transcription factor ELF5 as a potential modulator of estrogen action and driver of endocrine resistance, and here we provide the first insight into the mechanisms by which ELF5 modulates estrogen sensitivity. Using chromatin immunoprecipitation sequencing we found that ELF5 binding overlapped with FOXA1 and ER at super enhancers, enhancers and promoters, and when elevated, caused FOXA1 and ER to bind to new regions of the genome, in a pattern that replicated the alterations to the ER/FOXA1 cistrome caused by the acquisition of resistance to endocrine therapy. RNA sequencing demonstrated that these changes altered estrogen-driven patterns of gene expression, the expression of ER transcription-complex members, and 6 genes known to be involved in driving the acquisition of endocrine resistance. Using rapid immunoprecipitation mass spectrometry of endogenous proteins, and proximity ligation assays, we found that ELF5 interacted physically with members of the ER transcription complex, such as DNA-PKcs. We found 2 cases of endocrine-resistant brain metastases where ELF5 levels were greatly increased and ELF5 patterns of gene expression were enriched, compared to the matched primary tumour. Thus ELF5 alters ER-driven gene expression by modulating the ER/FOXA1 cistrome, by interacting with it, and by modulating the expression of members of the ER transcriptional complex, providing multiple mechanisms by which ELF5 can drive endocrine resistance