214 research outputs found
The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial
Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam.This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial-induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events.In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in co-infected populations. In this trial, we will examine how anthelmintic treatment impacts host susceptibility to diarrheal infections, with the aim of informing deworming programs of any indirect effects of mass anthelmintic administrations on co-infecting enteric pathogens.ClinicalTrials.gov: NCT02597556 . Registered on 3 November 2015
Comparative Analysis of Gene Regulation by the Transcription Factor PPARα between Mouse and Human
Studies in mice have shown that PPARalpha is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPARalpha in human liver. Here we set out to compare the function of PPARalpha in mouse and human hepatocytes via analysis of target gene regulation
Genome-Wide Association Study of Plasma Polyunsaturated Fatty Acids in the InCHIANTI Study
Polyunsaturated fatty acids (PUFA) have a role in many physiological processes, including energy production, modulation of inflammation, and maintenance of cell membrane integrity. High plasma PUFA concentrations have been shown to have beneficial effects on cardiovascular disease and mortality. To identify genetic contributors of plasma PUFA concentrations, we conducted a genome-wide association study of plasma levels of six omega-3 and omega-6 fatty acids in 1,075 participants in the InCHIANTI study on aging. The strongest evidence for association was observed in a region of chromosome 11 that encodes three fatty acid desaturases (FADS1, FADS2, FADS3). The SNP with the most significant association was rs174537 near FADS1 in the analysis of arachidonic acid (AA; pâ=â5.95Ă10â46). Minor allele homozygotes had lower AA compared to the major allele homozygotes and rs174537 accounted for 18.6% of the additive variance in AA concentrations. This SNP was also associated with levels of eicosadienoic acid (EDA; pâ=â6.78Ă10â9) and eicosapentanoic acid (EPA; pâ=â1.07Ă10â14). Participants carrying the allele associated with higher AA, EDA, and EPA also had higher low-density lipoprotein (LDL-C) and total cholesterol levels. Outside the FADS gene cluster, the strongest region of association mapped to chromosome 6 in the region encoding an elongase of very long fatty acids 2 (ELOVL2). In this region, association was observed with EPA (rs953413; pâ=â1.1Ă10â6). The effects of rs174537 were confirmed in an independent sample of 1,076 subjects participating in the GOLDN study. The ELOVL2 SNP was associated with docosapentanoic and DHA but not with EPA in GOLDN. These findings show that polymorphisms of genes encoding enzymes in the metabolism of PUFA contribute to plasma concentrations of fatty acids
Observation of associated near-side and away-side long-range correlations in âsNN=5.02ââTeV proton-lead collisions with the ATLAS detector
Two-particle correlations in relative azimuthal angle (ÎÏ) and pseudorapidity (Îη) are measured in âsNN=5.02ââTeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1ââÎŒb-1 of data as a function of transverse momentum (pT) and the transverse energy (ÎŁETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Îη|<5) ânear-sideâ (ÎÏâŒ0) correlation that grows rapidly with increasing ÎŁETPb. A long-range âaway-sideâ (ÎÏâŒÏ) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ÎŁETPb, is found to match the near-side correlation in magnitude, shape (in Îη and ÎÏ) and ÎŁETPb dependence. The resultant ÎÏ correlation is approximately symmetric about Ï/2, and is consistent with a dominant cosâĄ2ÎÏ modulation for all ÎŁETPb ranges and particle pT
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
Selective targeting of microglia by quantum dots
<p>Abstract</p> <p>Background</p> <p>Microglia, the resident immune cells of the brain, have been implicated in brain injury and various neurological disorders. However, their precise roles in different pathophysiological situations remain enigmatic and may range from detrimental to protective. Targeting the delivery of biologically active compounds to microglia could help elucidate these roles and facilitate the therapeutic modulation of microglial functions in neurological diseases.</p> <p>Methods</p> <p>Here we employ primary cell cultures and stereotaxic injections into mouse brain to investigate the cell type specific localization of semiconductor quantum dots (QDs) in vitro and in vivo. Two potential receptors for QDs are identified using pharmacological inhibitors and neutralizing antibodies.</p> <p>Results</p> <p>In mixed primary cortical cultures, QDs were selectively taken up by microglia; this uptake was decreased by inhibitors of clathrin-dependent endocytosis, implicating the endosomal pathway as the major route of entry for QDs into microglia. Furthermore, inhibiting mannose receptors and macrophage scavenger receptors blocked the uptake of QDs by microglia, indicating that QD uptake occurs through microglia-specific receptor endocytosis. When injected into the brain, QDs were taken up primarily by microglia and with high efficiency. In primary cortical cultures, QDs conjugated to the toxin saporin depleted microglia in mixed primary cortical cultures, protecting neurons in these cultures against amyloid beta-induced neurotoxicity.</p> <p>Conclusions</p> <p>These findings demonstrate that QDs can be used to specifically label and modulate microglia in primary cortical cultures and in brain and may allow for the selective delivery of therapeutic agents to these cells.</p
Elevated levels of OH observed in haze events during wintertime in central Beijing
Wintertime in situ measurements of OH, HO2 and RO2 radicals and OH reactivity were made in central Beijing during November and December 2016. Exceptionally elevated NO was observed on occasions, up to âŒ250âppbv. The daily maximum mixing ratios for radical species varied significantly day-to-day over the ranges 1â8Ă106âcmâ3 (OH), 0.2â1.5Ă108âcmâ3 (HO2) and 0.3â2.5Ă108âcmâ3 (RO2). Averaged over the full observation period, the mean daytime peak in radicals was 2.7Ă106, 0.39Ă108 and 0.88Ă108âcmâ3 for OH, HO2 and total RO2, respectively. The main daytime source of new radicals via initiation processes (primary production) was the photolysis of HONO (âŒ83â%), and the dominant termination pathways were the reactions of OH with NO and NO2, particularly under polluted haze conditions. The Master Chemical Mechanism (MCM) v3.3.1 operating within a box model was used to simulate the concentrations of OH, HO2 and RO2. The model underpredicted OH, HO2 and RO2, especially when NO mixing ratios were high (above 6âppbv). The observation-to-model ratio of OH, HO2 and RO2 increased from âŒ1 (for all radicals) at 3âppbv of NO to a factor of âŒ3, âŒ20 and âŒ91 for OH, HO2 and RO2, respectively, at âŒ200âppbv of NO. The significant underprediction of radical concentrations by the MCM suggests a deficiency in the representation of gas-phase chemistry at high NOx. The OH concentrations were surprisingly similar (within 20â% during the day) in and outside of haze events, despite j(O1D) decreasing by 50â% during haze periods. These observations provide strong evidence that gas-phase oxidation by OH can continue to generate secondary pollutants even under high-pollution episodes, despite the reduction in photolysis rates within haze
Hunting dogs as sentinel animals for monitoring infections with Trichinella spp. in wildlife
Diagnosis and management of SilverâRussell syndrome: first international consensus statement
This Consensus Statement summarizes recommendations for clinical diagnosis, investigation and management of patients with SilverâRussell syndrome (SRS), an imprinting disorder that causes prenatal and postnatal growth retardation. Considerable overlap exists between the care of individuals born small for gestational age and those with SRS. However, many specific management issues exist and evidence from controlled trials remains limited. SRS is primarily a clinical diagnosis; however, molecular testing enables confirmation of the clinical diagnosis and defines the subtype. A 'normal' result from a molecular test does not exclude the diagnosis of SRS. The management of children with SRS requires an experienced, multidisciplinary approach. Specific issues include growth failure, severe feeding difficulties, gastrointestinal problems, hypoglycaemia, body asymmetry, scoliosis, motor and speech delay and psychosocial challenges. An early emphasis on adequate nutritional status is important, with awareness that rapid postnatal weight gain might lead to subsequent increased risk of metabolic disorders. The benefits of treating patients with SRS with growth hormone include improved body composition, motor development and appetite, reduced risk of hypoglycaemia and increased height. Clinicians should be aware of possible premature adrenarche, fairly early and rapid central puberty and insulin resistance. Treatment with gonadotropin-releasing hormone analogues can delay progression of central puberty and preserve adult height potential. Long-term follow up is essential to determine the natural history and optimal management in adulthood
Flavor tagged time-dependent angular analysis of the B0s â J/ÏÏ decay and extraction of ÎÎs and the weak phase Ïs in ATLAS
A measurement of the B0sâJ/ÏÏ decay parameters, updated to include flavor tagging is reported using 4.9ââfbâÂč of integrated luminosity collected by the ATLAS detector from âs=7ââTeV pp collisions recorded in 2011 at the LHC. The values measured for the physical parameters are
Ïs=0.12±0.25(stat)±0.05(syst)âârad
ÎÎs=0.053±0.021(stat)±0.010(syst)ââpsâÂč
Îs=0.677±0.007(stat)±0.004(syst)ââpsâÂč
|Aâ„(0)|2=0.220±0.008(stat)±0.009(syst)
|A0(0)|2=0.529±0.006(stat)±0.012(syst)
ÎŽâ„=3.89±0.47(stat)±0.11(syst)âârad
where the parameter ÎÎs is constrained to be positive. The S-wave contribution was measured and found to be compatible with zero. Results for Ïs and ÎÎs are also presented as 68% and 95% likelihood contours, which show agreement with the Standard Model expectations
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