Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

A polymeric nanomedicine diminishes inflammatory events in renal tubular cells

The polyglutamic acid/peptoid 1 (QM56) nanoconjugate inhibits apoptosis by interfering with Apaf-1 binding to procaspase-9. We now describe anti-inflammatory properties of QM56 in mouse kidney and renal cell models. In cultured murine tubular cells, QM56 inhibited the inflammatory response to Tweak, a non-apoptotic stimulus. Tweak induced MCP-1 and Rantes synthesis through JAK2 kinase and NF-kB activation. Similar to JAK2 kinase inhibitors, QM56 inhibited Tweak-induced NF-kB transcriptional activity and chemokine expression, despite failing to inhibit NF-kB-p65 nuclear translocation and NF-kB DNA binding. QM56 prevented JAK2 activation and NF-kB-p65(Ser536) phosphorylation. The anti-inflammatory effect and JAK2 inhibition by QM56 were observed in Apaf-12/2 cells. In murine acute kidney injury, QM56 decreased tubular cell apoptosis and kidney inflammation as measured by downmodulations of MCP-1 and Rantes mRNA expression, immune cell infiltration and activation of the JAK2-dependent inflammatory pathway. In conclusion, QM56 has an anti-inflammatory activity which is independent from its role as inhibitor of Apaf-1 and apoptosis and may have potential therapeutic relevance.This work was supported by grants from the Instituto de Salud Carlos III (www.isciii.es), FIS: PI07/0020, CP08/1083, PS09/00447 and ISCIII-RETICS REDINREN RD 06/0016; Sociedad Española de Nefrología (www.senefro.org). Álvaro Ucero, Sergio Berzal and Carlos Ocaña supported by Fundacion Conchita Rabago (www.fundacionconchitarabago.net), Alberto Ortiz by the Programa de Intensificación de la Actividad Investigadora in the Sistema Nacional de Salud of the Instituto de Salud Carlos III and the Agencia ‘‘Pedro Lain Entralgo’’ of the Comunidad de Madrid and CIFRA S-BIO 0283/2006 www.madrid.org/lainentralgo) and Adrián Ramos, by FIS (Programa Miguel Servet)

Low Doses of Bisphenol A and Diethylstilbestrol Impair Ca(2+) Signals in Pancreatic α-Cells through a Nonclassical Membrane Estrogen Receptor within Intact Islets of Langerhans

Glucagon, secreted from pancreatic α-cells integrated within the islets of Langerhans, is involved in the regulation of glucose metabolism by enhancing the synthesis and mobilization of glucose in the liver. In addition, it has other extrahepatic effects ranging from lipolysis in adipose tissue to the control of satiety in the central nervous system. In this article, we show that the endocrine disruptors bisphenol A (BPA) and diethylstilbestrol (DES), at a concentration of 10(−9) M, suppressed low-glucose–induced intracellular calcium ion ([Ca(2+)](i)) oscillations in α-cells, the signal that triggers glucagon secretion. This action has a rapid onset, and it is reproduced by the impermeable molecule estradiol (E(2)) conjugated to horseradish peroxidase (E-HRP). Competition studies using E-HRP binding in immunocytochemically identified α-cells indicate that 17β-E(2), BPA, and DES share a common membrane-binding site whose pharmacologic profile differs from the classical ER. The effects triggered by BPA, DES, and E(2) are blocked by the Gαi- and Gα(o)-protein inhibitor pertussis toxin, by the guanylate cyclase–specific inhibitor 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one, and by the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester. The effects are reproduced by 8-bromo-guanosine 3′,5′-cyclic monophosphate and suppressed in the presence of the cGMP-dependent protein kinase inhibitor KT-5823. The action of E(2), BPA, and DES in pancreatic α-cells may explain some of the effects elicited by endocrine disruptors in the metabolism of glucose and lipid

Is the meiofauna a good indicator for climate change and anthropogenic impacts?

Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research

Hypolithic and soil microbial community assembly along an aridity gradient in the Namib Desert

The Namib Dessert is considered the oldest desert in the world and hyperarid for the last 5 million years. However, the environmental buffering provided by quartz and other translucent rocks supports extensive hypolithic microbial communities. In this study, open soil and hypolithic microbial communities have been investigated along an East–West transect characterized by an inverse fog-rainfall gradient. Multivariate analysis showed that structurally different microbial communities occur in soil and in hypolithic zones. Using variation partitioning, we found that hypolithic communities exhibited a fog-related distribution as indicated by the significant East– West clustering. Sodium content was also an important environmental factor affecting the composition of both soil and hypolithic microbial communities. Finally, although null models for patterns in microbial communities were not supported by experimental data, the amount of unexplained variation (68–97 %) suggests that stochastic processes also play a role in the assembly of such communities in the Namib Desert.Web of Scienc

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

Exploiting visual cues for safe and flexible cyber-physical production systems

Human workers are envisioned to work alongside robots and other intelligent factory modules, and fulfill supervision tasks in future smart factories. Technological developments, during the last few years, in the field of smart factory automation have introduced the concept of cyber-physical systems, which further expanded to cyber-physical production systems. In this context, the role of collaborative robots is significant and depends largely on the advanced capabilities of collision detection, impedance control, and learning new tasks based on artificial intelligence. The system components, collaborative robots, and humans need to communicate for collective decision-making. This requires processing of shared information keeping in consideration the available knowledge, reasoning, and flexible systems that are resilient to the real-time dynamic changes on the industry floor as well as within the communication and computer network infrastructure. This article presents an ontology-based approach to solve industrial scenarios for safety applications in cyber-physical production systems. A case study of an industrial scenario is presented to validate the approach in which visual cues are used to detect and react to dynamic changes in real time. Multiple scenarios are tested for simultaneous detection and prioritization to enhance the learning surface of the intelligent production system with the goal to automate safety-based decisions

In Situ Distribution of HIV-Binding CCR5 and C-Type Lectin Receptors in the Human Endocervical Mucosa

The endocervical mucosa is believed to be a primary site of HIV transmission. However, to date there is little known about the distribution of the HIV co-receptor CCR5 and the HIV-binding C-type lectin receptors, including Langerin, dendritic cell (DC)-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN) and mannose receptor (MR) at this site. We therefore characterized the expression of these molecules in the endocervix of HIV seronegative women by computerized image analysis. Endocervical tissue biopsies were collected from women (n = 6) undergoing hysterectomy. All study individuals were diagnosed with benign and non-inflammatory diseases. CCR5+ CD4+ CD3+ T cells were found within or adjacent to the endocervical epithelium. The C-type lectin Langerin was expressed by intraepithelial CD1a+ CD4+ and CD11c+ CD4+ Langerhans cells, whereas DC-SIGN+ MR+ CD11c myeloid dendritic cells and MR+ CD68+ macrophages were localized in the submucosa of the endocervix. The previously defined immune effector cells including CD8+, CD56+, CD19+ and IgD+ cells were also found in the submucosa as well as occasional CD123+ BDCA-2+ plasmacytoid dendritic cells. Understanding the spatial distribution of potential HIV target cells and immune effector cells in relation to the endocervical canal forms a basis for deciphering the routes of HIV transmission events in humans as well as designing HIV-inhibiting compounds

Formative evaluation of the telecare fall prevention project for older veterans

<p>Abstract</p> <p>Background</p> <p>Fall prevention interventions for community-dwelling older adults have been found to reduce falls in some research studies. However, wider implementation of fall prevention activities in routine care has yielded mixed results. We implemented a theory-driven program to improve care for falls at our Veterans Affairs healthcare facility. The first project arising from this program used a nurse advice telephone line to identify patients' risk factors for falls and to triage patients to appropriate services. Here we report the formative evaluation of this project.</p> <p>Methods</p> <p>To evaluate the intervention we: 1) interviewed patient and employee stakeholders, 2) reviewed participating patients' electronic health record data and 3) abstracted information from meeting minutes. We describe the implementation process, including whether the project was implemented according to plan; identify barriers and facilitators to implementation; and assess the incremental benefit to the quality of health care for fall prevention received by patients in the project. We also estimate the cost of developing the pilot project.</p> <p>Results</p> <p>The project underwent multiple changes over its life span, including the addition of an option to mail patients educational materials about falls. During the project's lifespan, 113 patients were considered for inclusion and 35 participated. Patient and employee interviews suggested support for the project, but revealed that transportation to medical care was a major barrier in following up on fall risks identified by nurse telephone triage. Medical record review showed that the project enhanced usual medical care with respect to home safety counseling. We discontinued the program after 18 months due to staffing limitations and competing priorities. We estimated a cost of $9194 for meeting time to develop the project.</p> <p>Conclusions</p> <p>The project appeared feasible at its outset but could not be sustained past the first cycle of evaluation due to insufficient resources and a waning of local leadership support due to competing national priorities. Future projects will need both front-level staff commitment and prolonged high-level leadership involvement to thrive.</p

Role of C/EBPβ Transcription Factor in Adult Hippocampal Neurogenesis

[Background]: The dentate gyrus of the hippocampus is one of the regions in which neurogenesis takes place in the adult brain. We have previously demonstrated that CCAAT/enhancer binding protein β (C/EBPβ) is expressed in the granular layer of the dentate gyrus of the adult mouse hippocampus. Taking into account the important role of C/EBPβ in the consolidation of long term memory, the fact that newborn neurons in the hippocampus contribute to learning and memory processes, and the role of this transcription factor, previously demonstrated by our group, in regulating neuronal differentiation, we speculated that this transcription factor could regulate stem/progenitor cells in this region of the brain. [Methodologu/Principal Findings]: Here, we show, using C/EBPβ knockout mice, that C/EBPβ expression is observed in the subset of newborn cells that proliferate in the hippocampus of the adult brain. Mice lacking C/EBPβ present reduced survival of newborn cells in the hippocampus, a decrease in the number of these cells that differentiate into neurons and a diminished number of cells that are proliferating in the subgranular zone of the dentate gyrus. These results were further confirmed in vitro. Neurosphere cultures from adult mice deficient in C/EBPβ present less proliferation and neuronal differentiation than neurospheres derived from wild type mice. [Conclusions/Significance]: In summary, using in vivo and in vitro strategies, we have identified C/EBPβ as a key player in the proliferation and survival of the new neurons produced in the adult mouse hippocampus. Our results support a novel role of C/EBPβ in the processes of adult hippocampal neurogenesis, providing new insights into the mechanisms that control neurogenesis in this region of the brain.This work was supported by a postdoctoral fellowship of the Consejo Superior de Investigaciones Cientificas (M.C.-C.) Grant Sponsor: Ministerio de Investigación y Ciencia; Grant numbers: SAF2007-62811 and SAF2010-16365. CIBERNED is funded by the Instituto de Salud Carlos III.Peer reviewe