Organic selenium supplementation increased selenium concentrations in ewe and newborn lamb blood and in slaughter lamb meat compared to inorganic selenium supplementation

Background Selenium is part of the antioxidant defence system in animals and humans. The available selenium concentration in soil is low in many regions of the world. The purpose of this study was to evaluate the effect of organic versus inorganic selenium supplementation on selenium status of ewes, their lambs, and slaughter lambs. Methods Ewes on four organic farms were allocated five or six to 18 pens. The ewes were given either 20 mg/kg inorganic selenium as sodium selenite or organic selenium as selenized nonviable yeast supplementation for the two last months of pregnancy. Stipulated selenium concentrations in the rations were below 0.40 mg/kg dry matter. In addition 20 male lambs were given supplements from November until they were slaughtered in March. Silage, hay, concentrates, and individual ewe blood samples were taken before and after the mineral supplementation period, and blood samples were taken from the newborn lambs. Blood samples from ewes and lambs in the same pens were pooled. Muscle samples were taken from slaughter lambs in March. Selenium concentrations were determined by atomic absorption spectrometry with a hydride generator system. In the ANOVA model, selenium concentration was the continuous response variable, and selenium source and farm were the nominal effect variables. Two-sample t-test was used to compare selenium concentrations in muscle samples from the slaughtered lambs that received either organic or inorganic selenium supplements. Results In all ewe pens the whole blood selenium concentrations increased during the experimental period. In addition, ewe pens that received organic selenium had significantly higher whole blood selenium concentrations (mean 0.28 μg/g) than ewe pens that received inorganic selenium (mean 0.24 μg/g). Most prominent, however, was the difference in their lambs; whole blood mean selenium concentration in lambs from mothers that received organic selenium (mean 0.27 μg/g) was 30% higher than in lambs from mothers that received inorganic selenium (mean 0.21 μg/g). Slaughter lambs that received organic selenium had 50% higher meat selenium concentrations (mean 0.12 mg/kg wet weight) than lambs that received inorganic selenium (mean 0.08 mg/kg wet weight). Conclusion Organic selenium supplementation gave higher selenium concentration in ewe and newborn lamb blood and slaughter lamb meat than inorganic selenium supplementation

Next-generation sequencing of AV nodal reentrant tachycardia patients identifies broad spectrum of variants in ion channel genes.

Atrioventricular nodal reentry tachycardia (AVNRT) is the most common form of regular paroxysmal supraventricular tachycardia. This arrhythmia affects women twice as frequently as men, and is often diagnosed in patients <40 years of age. Familial clustering, early onset of symptoms and lack of structural anomaly indicate involvement of genetic factors in AVNRT pathophysiology. We hypothesized that AVNRT patients have a high prevalence of variants in genes that are highly expressed in the atrioventricular conduction axis of the heart and potentially involved in arrhythmic diseases. Next-generation sequencing of 67 genes was applied to the DNA profile of 298 AVNRT patients and 10 AVNRT family members using HaloPlex Target Enrichment System. In total, we identified 229 variants in 60 genes; 215 missenses, four frame shifts, four codon deletions, three missense and splice sites, two stop-gain variants, and one start-lost variant. Sixty-five of these were not present in the Exome Aggregation Consortium (ExAC) database. Furthermore, we report two AVNRT families with co-segregating variants. Seventy-five of 284 AVNRT patients (26.4%) and three family members to different AVNRT probands had one or more variants in genes affecting the sodium handling. Fifty-four out of 284 AVNRT patients (19.0%) had variants in genes affecting the calcium handling of the heart. We furthermore find a large proportion of variants in the HCN1-4 genes. We did not detect a significant enrichment of rare variants in the tested genes. This could be an indication that AVNRT might be an electrical arrhythmic disease with abnormal sodium and calcium handling

Reliability of Rapid Diagnostic Tests in Diagnosing Pregnancy-Associated Malaria in North-Eastern Tanzania.

Accurate diagnosis and prompt treatment of pregnancy-associated malaria (PAM) are key aspects in averting adverse pregnancy outcomes. Microscopy is the gold standard in malaria diagnosis, but it has limited detection and availability. When used appropriately, rapid diagnostic tests (RDTs) could be an ideal diagnostic complement to microscopy, due to their ease of use and adequate sensitivity in detecting even sub-microscopic infections. Polymerase chain reaction (PCR) is even more sensitive, but it is mainly used for research purposes. The accuracy and reliability of RDTs in diagnosing PAM was evaluated using microscopy and PCR. A cohort of pregnant women in north-eastern Tanzania was followed throughout pregnancy for detection of plasmodial infection using venous and placental blood samples evaluated by histidine rich protein 2 (HRP-2) and parasite lactate dehydrogenase (pLDH) based RDTs (Parascreen™) or HRP-2 only (Paracheck Pf® and ParaHIT®f), microscopy and nested Plasmodium species diagnostic PCR. From a cohort of 924 pregnant women who completed the follow up, complete RDT and microscopy data was available for 5,555 blood samples and of these 442 samples were analysed by PCR. Of the 5,555 blood samples, 49 ((proportion and 95% confidence interval) 0.9% [0.7 -1.1]) samples were positive by microscopy and 91 (1.6% [1.3-2.0]) by RDT. Forty-six (50.5% [40.5 - 60.6]) and 45 (49.5% [39.4 - 59.5]) of the RDT positive samples were positive and negative by microscopy, respectively, whereas nineteen (42.2% [29.0 - 56.7]) of the microscopy negative, but RDT positive, samples were positive by PCR. Three (0.05% [0.02 - 0.2]) samples were positive by microscopy but negative by RDT. 351 of the 5,461 samples negative by both RDT and microscopy were tested by PCR and found negative. There was no statistically significant difference between the performances of the different RDTs. Microscopy underestimated the real burden of malaria during pregnancy and RDTs performed better than microscopy in diagnosing PAM. In areas where intermittent preventive treatment during pregnancy may be abandoned due to low and decreasing malaria risk and instead replaced with active case management, screening with RDT is likely to identify most infections in pregnant women and out-performs microscopy as a diagnostic tool

Observations from Preliminary Experiments on Spatial and Temporal Pressure Measurements from Near-Field Free Air Explosions

It is self-evident that a crucial step in analysing the performance of protective structures is to be able to accurately quantify the blast load arising from a high explosive detonation. For structures located near to the source of a high explosive detonation, the resulting pressure is extremely high in magnitude and highly non-uniform over the face of the target. There exists very little direct measurement of blast parameters in the nearfield, mainly attributed to the lack of instrumentation sufficiently robust to survive extreme loading events yet sensitive enough to capture salient features of the blast. Instead literature guidance is informed largely by early numerical analyses and parametric studies. Furthermore, the lack of an accurate, reliable data set has prevented subsequent numerical analyses from being validated against experimental trials. This paper presents an experimental methodology that has been developed in part to enable such experimental data to be gathered. The experimental apparatus comprises an array of Hopkinson pressure bars, fitted through holes in a target, with the loaded faces of the bars flush with the target face. Thus, the bars are exposed to the normally or obliquely reflected shocks from the impingement of the blast wave with the target. Pressure-time recordings are presented along with associated Arbitary-Langrangian-Eulerian modelling using the LS-DYNA explicit numerical code. Experimental results are corrected for the effects of dispersion of the propagating waves in the pressure bars, enabling accurate characterisation of the peak pressures and impulses from these loadings. The combined results are used to make comments on the mechanism of the pressure load for very near-field blast events

Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model

BACKGROUND: Although Chinese-origin Rhesus macaques (Ch RhMs) infected with simian immunodeficiency virus (SIV) have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established. METHODOLOGY/PRINCIPAL FINDINGS: By randomizing 150 (78 male and 72 female) Ch RhMs with diverse MHC class I alleles into 3 groups (50 animals per group) challenged with intrarectal (i.r.) SIVmac239, intravenous (i.v.) SIVmac239, or i.v. SIVmac251, we evaluated variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs became seropositive for SIV during 1-2 weeks. Plasma viral load (VL) peaked at weeks 1-2 and then declined to set-point levels as from week 5. The set-point VL was 30 fold higher in SIVmac239 (i.r. or i.v.)-infected than in SIVmac251 (i.v.)-infected animals. This difference in plasma VL increased overtime (>100 fold as from week 68). The rates of progression to AIDS or death were more rapid in SIVmac239 (i.r. or i.v.)-infected than in SIVmac251 (i.v.)-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with i.r. or i.v. SIVmac239. The variability (standard deviation) in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (i.r. or i.v.) than in those infected with SIVmac251 (i.v.), allowing that the same treatment-related difference can be detected with one-half fewer animals using SIVmac239 than using SIVmac251. CONCLUSION/SIGNIFICANCE: These results provide solid estimates of variability in bio-clinical endpoints needed when designing studies using the Ch RhM SIV model and contribute to the improving quality and standardization of preclinical studies

Identification of G1-Regulated Genes in Normally Cycling Human Cells

BACKGROUND: Obtaining synchronous cell populations is essential for cell-cycle studies. Methods such as serum withdrawal or use of drugs which block cells at specific points in the cell cycle alter cellular events upon re-entry into the cell cycle. Regulatory events occurring in early G1 phase of a new cell cycle could have been overlooked. METHODOLOGY AND FINDINGS: We used a robotic mitotic shake-off apparatus to select cells in late mitosis for genome-wide gene expression studies. Two separate microarray experiments were conducted, one which involved isolation of RNA hourly for several hours from synchronous cell populations, and one experiment which examined gene activity every 15 minutes from late telophase of mitosis into G1 phase. To verify synchrony of the cell populations under study, we utilized methods including BrdU uptake, FACS, and microarray analyses of histone gene activity. We also examined stress response gene activity. Our analysis enabled identification of 200 early G1-regulated genes, many of which currently have unknown functions. We also confirmed the expression of a set of genes candidates (fos, atf3 and tceb) by qPCR to further validate the newly identified genes. CONCLUSION AND SIGNIFICANCE: Genome-scale expression analyses of the first two hours of G1 in naturally cycling cells enabled the discovery of a unique set of G1-regulated genes, many of which currently have unknown functions, in cells progressing normally through the cell division cycle. This group of genes may contain future targets for drug development and treatment of human disease