HIV and respiratory illness in the antiretroviral therapy era

Respiratory illness is a common manifestation of HIV infection. The availability of effective antiretroviral therapy (ART) has changed the pattern of respiratory ill-health experienced by people living with HIV (PLWH). Among populations with good access to ART, opportunistic respiratory infections such as Pneumocystis jirovecii pneumonia (PCP) are becoming less frequent. However, there is evidence to suggest that these populations may be at greater risk of serious non-AIDS illness including chronic respiratory disease. Although there is remaining uncertainty about the extent to which HIV represents an independent risk-factor for respiratory illness in individuals with a suppressed HIV viral load and immune reconstitution, in many settings PLWH have greater exposure to risk factors for respiratory illness (in particular tobacco smoking), which contribute to this burden of disease. As HIV-positive populations age, management of these conditions will therefore become increasingly important. Healthcare services need to manage this growing burden of chronic respiratory illness and provide access to preventative measures including smoking cessation and immunisation against vaccine-preventable respiratory infections in a way that is appropriate to the populations served

Role of necroptosis in the pathogenesis of solid organ injury

Necroptosis is a type of regulated cell death dependent on the activity of receptor-interacting serine/threonine-protein (RIP) kinases. However, unlike apoptosis, it is caspase independent. Increasing evidence has implicated necroptosis in the pathogenesis of disease, including ischemic injury, neurodegeneration, viral infection and many others. Key players of the necroptosis signalling pathway are now widely recognized as therapeutic targets. Necrostatins may be developed as potent inhibitors of necroptosis, targeting the activity of RIPK1. Necrostatin-1, the first generation of necrostatins, has been shown to confer potent protective effects in different animal models. This review will summarize novel insights into the involvement of necroptosis in specific injury of different organs, and the therapeutic platform that it provides for treatment

Familial childhood-onset progressive cerebellar syndrome associated with the ATP1A3 mutation

The allelic disorders rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and CAPOS/CAOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural deafness) are caused by ATP1A3 mutations.1–3 Intermediate RDP-AHC phenotypes are emerging. Positional mutations 274, 583, 867, and 923 lead to both RDP and AHC, suggesting different pathomechanisms.4,5 The E818K mutation underlies all reported cases of CAPOS/CAOS, including an AHC-CAPOS overlap syndrome.6 We report a family with features of all 3 ATP1A3-spectrum disorders

Dual modality intravascular optical coherence tomography (OCT) and near-infrared fluorescence (NIRF) imaging: a fully automated algorithm for the distance-calibration of NIRF signal intensity for quantitative molecular imaging

Intravascular optical coherence tomography (IVOCT) is a well-established method for the high-resolution investigation of atherosclerosis in vivo. Intravascular near-infrared fluorescence (NIRF) imaging is a novel technique for the assessment of molecular processes associated with coronary artery disease. Integration of NIRF and IVOCT technology in a single catheter provides the capability to simultaneously obtain co-localized anatomical and molecular information from the artery wall. Since NIRF signal intensity attenuates as a function of imaging catheter distance to the vessel wall, the generation of quantitative NIRF data requires an accurate measurement of the vessel wall in IVOCT images. Given that dual modality, intravascular OCT–NIRF systems acquire data at a very high frame-rate (>100 frames/s), a high number of images per pullback need to be analyzed, making manual processing of OCT–NIRF data extremely time consuming. To overcome this limitation, we developed an algorithm for the automatic distance-correction of dual-modality OCT–NIRF images. We validated this method by comparing automatic to manual segmentation results in 180 in vivo images from six New Zealand White rabbit atherosclerotic after indocyanine-green injection. A high Dice similarity coefficient was found (0.97 ± 0.03) together with an average individual A-line error of 22 µm (i.e., approximately twice the axial resolution of IVOCT) and a processing time of 44 ms per image. In a similar manner, the algorithm was validated using 120 IVOCT clinical images from eight different in vivo pullbacks in human coronary arteries. The results suggest that the proposed algorithm enables fully automatic visualization of dual modality OCT–NIRF pullbacks, and provides an accurate and efficient calibration of NIRF data for quantification of the molecular agent in the atherosclerotic vessel wall.National Institutes of Health (U.S.) (NIH R01HL093717)Merck & Co., Inc

The objectives, design and implementation of the INTERGROWTH-21st Project

INTERGROWTH-21st is a multicentre, multiethnic, populationbased project, being conducted in eight geographical areas (Brazil, China, India, Italy, Kenya, Oman, UK and USA), with technical support from four global specialised units, to study growth, health and nutrition from early pregnancy to infancy. It aims to produce prescriptive growth standards, which conceptually extend the World Health Organization (WHO) Multicentre Growth Reference Study (MGRS) to cover fetal and newborn life. The new international standards will describe: (1) fetal growth assessed by clinical and ultrasound measures; (2) postnatal growth of term and preterm infants up to 2 years of age; and (3) the relationship between birthweight, length and head circumference, gestational age and perinatal outcomes. As the project has selected healthy cohorts with no obvious risk factors for intrauterine growth restriction, these standards will describe how all fetuses and newborns should grow, as opposed to traditional charts that describe how some have grown at a given place and time. These growth patterns will be related to morbidity and mortality to identify levels of perinatal risk. Additional aims include phenotypic characterisation of the preterm and impaired fetal growth syndromes and development of a prediction model, based on multiple ultrasound measurements, to estimate gestational age for use in pregnant women without access to early/frequent antenatal care

International standards for fetal brain structures based on serial ultrasound measurements from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.

OBJECTIVE: To create prescriptive growth standards for five fetal brain structures, measured by ultrasound, from healthy, well-nourished women, at low risk of impaired fetal growth and poor perinatal outcomes, taking part in the Fetal Growth Longitudinal Study (FGLS) of the INTERGROWTH-21st Project. METHODS: This was a complementary analysis of a large, population-based, multicentre, longitudinal study. We measured, in planes reconstructed from 3-dimensional (3D) ultrasound volumes of the fetal head at different time points in pregnancy, the size of the parieto-occipital fissure (POF), Sylvian fissure (SF), anterior horn of the lateral ventricle (AV), atrium of the posterior ventricle (PV) and cisterna magna (CM). The sample analysed was randomly selected from the overall FGLS population, ensuring an equal distribution amongst the eight diverse participating sites and of 3D ultrasound volumes across pregnancy (range: 15 - 36 weeks' gestation). Fractional polynomials were used to the construct standards. Growth and development of the infants were assessed at 1 and 2 years of age to confirm their adequacy for constructing international standards. RESULTS: From the entire FGLS cohort of 4321 women, 451 (10.4%) were randomly selected. After exclusions, 3D ultrasound volumes from 442 fetuses born without congenital malformations were used to create the charts. The fetal brain structures of interest were identified in 90% of cases. All structures showed increasing size with gestation and increasing variability for the POF, SF, PV and CM. The 3rd , 5th , 50th , 95th and 97th smoothed centile are presented. The 5th centile of POF and SF were 2.8 and 4.3 at 22 weeks and 4.2 and 9.4mm at 32 weeks respectively. The 95th centile of PV and CM were 8.5 and 7.4 at 22 weeks and 8.5 and 9.4mm at 32 weeks respectively. CONCLUSIONS: We have produced prescriptive size standards for fetal brain structures based on prospectively enrolled pregnancies at low risk of abnormal outcomes. We recommend these as international standards for the assessment of measurements obtained by ultrasound from fetal brain structures

Effect of Water Diffusion on Adhesion Strength

The adhesion strength between Polyethylene (PE) film and Aluminum surface by using the adhesive material (Cyanoacrylate) has been studied. Aluminum (Al) was used as a substrate, and polyethylene (PE) was used as a film adhered to the Al surface. Standard specimens were prepared to use in the peeling test in dry condition, other specimens were immersed in water for 12 days at room temperature. the results for the specimens in the dry condition had shown that high value in the peel force and the peel energy, the peel force was 0.38*103 N/m and the peel energy was 0.605*103 N/m, peeling the film from Al surface leaves a residual of the adhesive material on both adherend, the failure for this specimen were combination of adhesive and cohesive failure. For the specimens that were immersed in water for 12 days, the results had shown that the effect of water on the specimen (Al /PE), where the water diffusion coefficient on the adhesive joint was 1.09*10-14 m2/s and the peel force was 0.062*103 N/m and the peel energy was 0.124*103 N/m, PE film was peeled from Al surface without any resistance

Preparation, investigation and studying the (physical, spectral and biological activity) of new monomers and heterocyclic compounds containing nitrogen and oxygen

This study involves the preparation of seven new compounds, some of them contain two functional groups that are considered condensation monomers. On the other hand, other compounds contain double bonds that are considered addition monomers. They started from 2- amino Thiazole with 2-hydroxy benzaldehyde (salicylaldehyde) in ethanol and hydrochloric acid to prepare azo compound (A), which reacted with acetophenone derivatives (p-bromo, p-chloro and p-hydroxy acetophenone) to prepare chalcone monomers derivatives (H1-H3). Also, the work includes preparing seven-membered heterocyclic rings through two consecutive steps; the first step includes the preparation of Schiff base compound (S). The second step includes the preparation of the oxazepine derivatives (Z1, Z2) through the cyclic closure of compound (S) with the (maleic, phthalic) anhydrides, respectively. All compounds were investigated with FT-IR, H1NMR, and 13CNMR techniques. The physical properties and the antibacterial activity were also studied for all the prepared compounds and showed good results

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin