Antibiotic timing and errors in diagnosing pneumonia.
The percentage of patients with community-acquired pneumonia (CAP) whose time to first antibiotic dose (TFAD) is less than 4 hours of presentation to the emergency department (ED) has been made a core quality measure, and public reporting has been instituted. We asked whether these time pressures might also have negative effects on the accuracy of diagnosis of pneumonia. We performed a retrospective review of adult admissions for CAP for 2 periods: group 1, when the core quality measure was a TFAD of less than 8 hours; and group 2, when the TFAD was lowered to less than 4 hours. We examined the accuracy of diagnosis of CAP by ED physicians. A total of 548 patients diagnosed as having CAP were studied (255 in group 1 and 293 in group 2). At admission, group 2 patients were 39.0% less likely to meet predefined diagnostic criteria for CAP than were group 1 patients (odds ratio, 0.61; 95% confidence interval, 0.42-0.86) (P = .004). At discharge, there was agreement between the ED physician's diagnosis and the predefined criteria for CAP in 62.0% of group 1 and 53.9% of group 2 patients (P = .06) and between the ED physician's admitting diagnosis and that of the discharging physician in 74.5% of group 1 and 66.9% of group 2 patients (P = .05). The mean (SD) TFAD was similar in group 1 (167.0 [118.6] minutes) and group 2 (157.8 [96.3] minutes). Reduction in the required TFAD from 8 to 4 hours seems to reduce the accuracy by which ED physicians diagnose pneumonia, while failing to reduce the actual TFAD achieved for patients.


Genes and enzymes of the acetyl cycle of arginine biosynthesis in the extreme thermophilic bacterium Thermus thermophilus HB27.
An arginine biosynthetic gene cluster, argC-argJ, of the extreme thermophilic bacterium Thermus thermophilus HB27 was isolated by heterologous complementation of an Escherichia coli acetylornithinase mutant. The recombinant plasmid (pTHM1) conferred ornithine acetyltransferase activity to the E. coli host, implying that T. thermophilus uses the energetically more economic pathway for the deacetylation of acetylornithine. pTHM1 was, however, unable to complement an E. coli argA mutant and no acetylglutamate synthase activity could be detected in E. coli argA cells containing pTHM1. The T. thermophilus argJ-encoded enzyme is thus monofunctional and is unable to use acetyl-CoA to acetylate glutamate (contrary to the Bacillus stearothermophilus homologue). Alignment of several ornithine acetyltransferase amino acid sequences showed no obvious pattern that could account for this difference; however, the monofunctional enzymes proved to have shorter N-termini. Sequence analysis of the pTHM1 3.2 kb insert revealed the presence of the argC gene (encoding N-acetylglutamate-5-semialdehyde dehydrogenase) upstream of the argJ gene. Alignment of several N-acetylglutamate-5-semialdehyde dehydrogenase amino acid sequences allowed identification of two strongly conserved putative motifs for cofactor binding: a putative FAD-binding site and a motif reminiscent of the NADPH-binding fingerprint. The relationship between the amino acid content of both enzymes and thermostability is discussed and an effect of the GC content bias is indicated. Transcription of both the argC and argJ genes appeared to be vector-dependent. The argJ-encoded enzyme activity was twofold repressed by arginine in the native host and was inhibited by ornithine. Both upstream of the argC gene and downstream of the argJ gene an ORF with unknown function was found, indicating that the organization of the arginine biosynthetic genes in T. thermophilus is new.


Clinical use of laser-tissue interactions.
The five interaction mechanisms associated with laser treatment of patients are described. They are the photothermal, photochemical, photoacoustical, photoablative, and photobiostimulation mechanisms. The estimated light penetration depth as a function of wavelength for bloodless, unpigmented tissue is shown and discussed. The availability of suitable lasers and fibers for clinical applications is considered, and future prospects for laser applications are indicated. Some clinical laser treatments based on photothermal and photochemical interactions are described from a biomedical engineering perspective.


Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.
Fetal conditions can in principle be affected by the mother's genotype working through the prenatal environment. Genotypes for 1536 SNPs in 357 cleft candidate genes were available from a previous analysis in which we focused on fetal gene effects. After data-cleaning, genotypes for 1315 SNPs in 334 autosomal genes were available for the current analysis of maternal gene effects. Two complementary statistical methods, TRIMM and HAPLIN, were used to detect multi-marker effects in population-based samples from Norway (562 case-parent and 592 control-parent triads) and Denmark (235 case-parent triads). We analyzed isolated cleft lip with or without cleft palate (iCL/P) and isolated cleft palate only (iCP) separately and assessed replication by looking for genes detected in both populations by both methods. In iCL/P, neither TRIMM nor HAPLIN detected more genes than expected by chance alone; furthermore, the selected genes were not replicated across the two methods. In iCP, however, FLNB was identified by both methods in both populations. Although HIC1 and ZNF189 did not fully satisfy our stringency criterion for replication, they were strongly associated with iCP in TRIMM analyses of the Norwegian triads. Except for FLNB, HIC1 and ZNF189, maternal genes did not appear to influence the risk of clefting in our data. This is consistent with recent epidemiological findings showing no apparent difference between mother-to-offspring and father-to-offspring recurrence of clefts in these two populations. It is likely that fetal genes make the major genetic contribution to clefting risk in these populations, but we cannot rule out the possibility that maternal genes can affect risk through interactions with specific teratogens or fetal genes.


Fibroblast growth factor receptors control epithelial-mesenchymal interactions necessary for alveolar elastogenesis.
The mechanisms contributing to alveolar formation are poorly understood. A better understanding of these processes will improve efforts to ameliorate lung disease of the newborn and promote alveolar repair in the adult. Previous studies have identified impaired alveogenesis in mice bearing compound mutations of fibroblast growth factor (FGF) receptors (FGFRs) 3 and 4, indicating that these receptors cooperatively promote postnatal alveolar formation. To determine the molecular and cellular mechanisms of FGF-mediated alveolar formation. Compound FGFR3/FGFR4-deficient mice were assessed for temporal changes in lung growth, airspace morphometry, and genome-wide expression. Observed gene expression changes were validated using quantitative real-time RT-PCR, tissue biochemistry, histochemistry, and ELISA. Autocrine and paracrine regulatory mechanisms were investigated using isolated lung mesenchymal cells and type II pneumocytes. Quantitative analysis of airspace ontogeny confirmed a failure of secondary crest elongation in compound mutant mice. Genome-wide expression profiling identified molecular alterations in these mice involving aberrant expression of numerous extracellular matrix molecules. Biochemical and histochemical analysis confirmed changes in elastic fiber gene expression resulted in temporal increases in elastin deposition with the loss of typical spatial restriction. No abnormalities in elastic fiber gene expression were observed in isolated mesenchymal cells, indicating that abnormal elastogenesis in compound mutant mice is not cell autonomous. Increased expression of paracrine factors, including insulin-like growth factor-1, in freshly-isolated type II pneumocytes indicated that these cells contribute to the observed pathology. Epithelial/mesenchymal signaling mechanisms appear to contribute to FGFR-dependent alveolar elastogenesis and proper airspace formation.


Organization and function of paraspeckles.
Paraspeckles are a type of subnuclear bodies built on the long noncoding RNA NEAT1 (nuclear paraspeckle assembly transcript 1, also known as MEN-ε/β or VINC-1). Paraspeckles are involved in many physiological processes including cellular stress responses, cell differentiation, corpus luteum formation and cancer progression. Recently, ultra-resolution microscopy coupled with multicolor-labeling of paraspeckle components (the NEAT1 RNA and paraspeckle proteins) revealed the exquisite details of paraspeckle structure and function. NEAT1 transcripts are radially arranged to form a core-shell spheroidal structure, while paraspeckle proteins (PSPs) localize within different layers. Functional dissection of NEAT1 shows that the subdomains of NEAT1_2 are important for RNA stability, isoform switching and paraspeckle assembly via a liquid-liquid phase separation (LLPS) mechanism. We review recent progress on structure and organization of paraspeckles as well as how paraspeckles spatiotemporally control gene regulation through sequestration of diverse proteins and RNAs in cells.


Insights from 20 years of bacterial genome sequencing.
Since the first two complete bacterial genome sequences were published in 1995, the science of bacteria has dramatically changed. Using third-generation DNA sequencing, it is possible to completely sequence a bacterial genome in a few hours and identify some types of methylation sites along the genome as well. Sequencing of bacterial genome sequences is now a standard procedure, and the information from tens of thousands of bacterial genomes has had a major impact on our views of the bacterial world. In this review, we explore a series of questions to highlight some insights that comparative genomics has produced. To date, there are genome sequences available from 50 different bacterial phyla and 11 different archaeal phyla. However, the distribution is quite skewed towards a few phyla that contain model organisms. But the breadth is continuing to improve, with projects dedicated to filling in less characterized taxonomic groups. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system provides bacteria with immunity against viruses, which outnumber bacteria by tenfold. How fast can we go? Second-generation sequencing has produced a large number of draft genomes (close to 90 % of bacterial genomes in GenBank are currently not complete); third-generation sequencing can potentially produce a finished genome in a few hours, and at the same time provide methlylation sites along the entire chromosome. The diversity of bacterial communities is extensive as is evident from the genome sequences available from 50 different bacterial phyla and 11 different archaeal phyla. Genome sequencing can help in classifying an organism, and in the case where multiple genomes of the same species are available, it is possible to calculate the pan- and core genomes; comparison of more than 2000 Escherichia coli genomes finds an E. coli core genome of about 3100 gene families and a total of about 89,000 different gene families. Why do we care about bacterial genome sequencing? There are many practical applications, such as genome-scale metabolic modeling, biosurveillance, bioforensics, and infectious disease epidemiology. In the near future, high-throughput sequencing of patient metagenomic samples could revolutionize medicine in terms of speed and accuracy of finding pathogens and knowing how to treat them.


Causative mutations and premature cardiovascular disease in patients with heterozygous familial hypercholesterolaemia.
Background Familial hypercholesterolemia is a common autosomal dominant disease, caused by mutations leading to elevated low-density lipoprotein (LDL) cholesterol and, if untreated, to premature cardiovascular disease. Methods Patients (young adults with a family history of hypercholesterolaemia or premature cardiovascular disease) with LDL cholesterol concentration ≥4.9 mmol/l, after excluding Familial Combined Hyperlipidaemia, were evaluated for causative mutations, Dutch Lipid Clinic Network score calculation and non-invasive ultrasound examination of carotid arteries. Results Of the 263 patients, 210 were heterozygotes for LDL receptor ( LDLR) mutations, four had APOB gene mutations, one PCSK9 gene mutation, while 48 had no evidence of mutations. Among 194 unrelated index cases 149 had mutations (77%). Among patients with LDLR mutations ( n = 145), there were five compound heterozygotes, 75 patients with null mutations and 65 with missense mutations. As many as 178 patients underwent a follow-up and treatment (statin ± ezetimibe), achieving a mean reduction of 49% in LDL cholesterol, with 21% of patients reaching the LDL goal of 2.6 mmol/l. In a multivariate analysis, carotid plaques, at ultrasound examination, were associated with the presence of genetic mutation ( p = 0.001), LDL cholesterol ( p < 0.001), Dutch Lipid Clinic Network score ( p < 0.001), independently of age, gender, smoking habits and systolic blood pressure. The presence of carotid plaque ( p = 0.017), LDL cholesterol ( p < 0.003), Dutch Lipid Clinic Network score ( p < 0.001) were independently associated with premature cardiovascular disease. Conclusions We identified patients with causative mutations in 82% of the cases under study. In addition to LDL cholesterol and Dutch Lipid Clinic Network score, carotid plaques in ultrasound evaluation provide direct evidence of premature vascular disease and are associated with high risk for cardiovascular events.


Estimation of internal and external exposures of terrestrial reference organisms to natural radionuclides in the environment.
In this paper, an estimation of the doses absorbed by terrestrial reference organisms due to naturally occurring radionuclides is described. For terrestrial organisms under normal circumstances, external exposure is estimated to be of the order of 0.1-0.4 mGy a(-1), depending on size and habitat, and the main contributor is 40K. Internal background exposures of terrestrial organisms are more variable. Again, 40K is an important contributor giving doses of the order of 0.3 mGy a(-1). The exposures of muscles and plant tissues to uranium, thorium, radium, lead and polonium are lower, but liver, bone and kidney may be exposed at levels of 0.1-1 mGy a(-1) absorbed dose. There can also be significant increases in the received dose under specific environmental conditions as is the case for burrowing mammals that receive relatively high lung doses due to the inhalation of radon and its progeny.


Ab initio phonon dispersions of transition and noble metals: effects of the exchange and correlation functional.
We compare the performance of the Wu and Cohen (WC, 2006 Phys. Rev. B 73 235116) and of the PBEsol (2008 Phys. Rev. Lett. 100 136406) exchange and correlation functionals on the phonon dispersions of face-centered cubic metals copper, silver, gold, nickel, palladium, platinum, rhodium, and iridium. The WC and the PBEsol frequencies are found to be close to each other and intermediate between the local density approximation (LDA) and the Perdew, Burke, and Ernzerhof (PBE) result (1996 Phys. Rev. Lett. 77 3865). In copper, silver, palladium, platinum, and rhodium, the WC and PBEsol frequencies match the experimental inelastic neutron scattering data better than the LDA or PBE. In nickel, gold, and iridium, PBE (for nickel) or LDA (for gold and iridium) remain the best functionals among these four possibilities.


Increased entropy of signal transduction in the cancer metastasis phenotype.
The statistical study of biological networks has led to important novel biological insights, such as the presence of hubs and hierarchical modularity. There is also a growing interest in studying the statistical properties of networks in the context of cancer genomics. However, relatively little is known as to what network features differ between the cancer and normal cell physiologies, or between different cancer cell phenotypes. Based on the observation that frequent genomic alterations underlie a more aggressive cancer phenotype, we asked if such an effect could be detectable as an increase in the randomness of local gene expression patterns. Using a breast cancer gene expression data set and a model network of protein interactions we derive constrained weighted networks defined by a stochastic information flux matrix reflecting expression correlations between interacting proteins. Based on this stochastic matrix we propose and compute an entropy measure that quantifies the degree of randomness in the local pattern of information flux around single genes. By comparing the local entropies in the non-metastatic versus metastatic breast cancer networks, we here show that breast cancers that metastasize are characterised by a small yet significant increase in the degree of randomness of local expression patterns. We validate this result in three additional breast cancer expression data sets and demonstrate that local entropy better characterises the metastatic phenotype than other non-entropy based measures. We show that increases in entropy can be used to identify genes and signalling pathways implicated in breast cancer metastasis and provide examples of de-novo discoveries of gene modules with known roles in apoptosis, immune-mediated tumour suppression, cell-cycle and tumour invasion. Importantly, we also identify a novel gene module within the insulin growth factor signalling pathway, alteration of which may predispose the tumour to metastasize. These results demonstrate that a metastatic cancer phenotype is characterised by an increase in the randomness of the local information flux patterns. Measures of local randomness in integrated protein interaction mRNA expression networks may therefore be useful for identifying genes and signalling pathways disrupted in one phenotype relative to another. Further exploration of the statistical properties of such integrated cancer expression and protein interaction networks will be a fruitful endeavour.


The role of MiR-324-3p in polycystic ovary syndrome (PCOS) via targeting WNT2B.
To investigate the expression of microRNA-324-3p (miR-324-3p) in polycystic ovary syndrome (PCOS) and its effects on the proliferation and apoptosis of ovarian granulosa cells. A total of 60 Sprague-Dawley (SD) rats were randomly divided into normal group (n=30) and experimental group (n=30). Rats in the experimental group were intramuscularly injected with dehydroepiandrosterone (DHEA) (6 mg/100 g of body weight) and 0.2 mL oil for injection, while those in normal group were intramuscularly injected with 0.2 mL oil for injection. The ovarian tissues of PCOS model rats were removed to extract the total ribose nucleic acid (RNA). The expression of miR-324-3p was detected via reverse transcription-polymerase chain reaction (RT-PCR). Primary ovarian granulosa cells were isolated and cultured, and NC-miRNA and miR-324-3p mimic were transfected into cells. After 48 h, cell proliferation and apoptosis were detected via cell counting kit 8 (CCK-8) and flow cytometry assay, respectively. The targeted molecule of miR-324-3p was explored using bioinformatics, and dual-luciferase assay was performed to verify the effect of miR-324-3p on WNT2B expression. Granulosa cells were co-transfected with WNT2B-small-interfering RNA (siRNA) and miR-324-3p mimic, and then cell proliferation and apoptosis were detected via CCK-8 and flow cytometry assay, respectively. The expression of miR-324-3p in ovarian tissues of PCOS group was significantly lower than that of normal group (p < 0.01). After transfection with miR-324-3p mimic into granulosa cells, cell proliferation was significantly inhibited and cell apoptosis was promoted (p < 0.01). MiR-324-3p exerted its effect on granulosa cells by directly targeting WNT2B. Silencing WNT2B expression could reverse the effects of miR-324-3p on proliferation and apoptosis of granulosa cells (p < 0.05). The expression of miR-324-3p in the ovary of PCOS rats is decreased significantly. Overexpression of miR-324-3p can reduce the proliferation and induce the apoptosis of granulosa cells via targeting of WNT2B.


The metabolic rate of the biosphere and its components.
We assessed the relationship between rates of biological energy utilization and the biomass sustained by that energy utilization, at both the organism and biosphere level. We compiled a dataset comprising >10,000 basal, field, and maximum metabolic rate measurements made on >2,900 individual species, and, in parallel, we quantified rates of energy utilization, on a biomass-normalized basis, by the global biosphere and by its major marine and terrestrial components. The organism-level data, which are dominated by animal species, have a geometric mean among basal metabolic rates of 0.012 W (g C)-1 and an overall range of more than six orders of magnitude. The biosphere as a whole uses energy at an average rate of 0.005 W (g C)-1 but exhibits a five order of magnitude range among its components, from 0.00002 W (g C)-1 for global marine subsurface sediments to 2.3 W (g C)-1 for global marine primary producers. While the average is set primarily by plants and microorganisms, and by the impact of humanity upon those populations, the extremes reflect systems populated almost exclusively by microbes. Mass-normalized energy utilization rates correlate strongly with rates of biomass carbon turnover. Based on our estimates of energy utilization rates in the biosphere, this correlation predicts global mean biomass carbon turnover rates of ~2.3 y-1 for terrestrial soil biota, ~8.5 y-1 for marine water column biota, and ~1.0 y-1 and ~0.01 y-1 for marine sediment biota in the 0 to 0.1 m and >0.1 m depth intervals, respectively.


Novel virus influenza A (H1N1sw) in South-Eastern France, April-August 2009.
In April 2009, the first cases of pandemic (H1N1)-2009 influenza [H1N1sw] virus were detected in France. Virological surveillance was undertaken in reference laboratories of the seven French Defence Zones. We report results of virological analyses performed in the Public Hospitals of Marseille during the first months of the outbreak. (i) Nasal swabs were tested using rapid influenza diagnostic test (RIDT) and two RT-PCR assays. Epidemiological characteristics of the 99 first suspected cases were analyzed, including detection of influenza virus and 18 other respiratory viruses. During three months, a total of 1,815 patients were tested (including 236 patients infected H1N1sw virus) and distribution in age groups and results of RIDT were analyzed. (ii) 600 sera received before April 2009 and randomly selected from in-patients were tested by a standard hemagglutination inhibition assay for antibody to the novel H1N1sw virus. (iii) One early (May 2009) and one late (July 2009) viral isolates were characterized by sequencing the complete hemagglutinine and neuraminidase genes. (iiii) Epidemiological characteristics of a cluster of cases that occurred in July 2009 in a summer camp were analyzed. This study presents new virological and epidemiological data regarding infection by the pandemic A/H1N1 virus in Europe. Distribution in age groups was found to be similar to that previously reported for seasonal H1N1. The first seroprevalence data made available for a European population suggest a previous exposure of individuals over 40 years old to influenza viruses antigenically related to the pandemic (H1N1)-2009 virus. Genomic analysis indicates that strains harbouring a new amino-acid pattern in the neuraminidase gene appeared secondarily and tended to supplant the first strains. Finally, in contrast with previous reports, our data support the use of RIDT for the detection of infection in children, especially in the context of the investigation of grouped cases.


The diabetes susceptibility locus Idd5.1 on mouse chromosome 1 regulates ICOS expression and modulates murine experimental autoimmune encephalomyelitis.
Linkage analysis and congenic mapping in NOD mice have identified a susceptibility locus for type 1 diabetes, Idd5.1 on mouse chromosome 1, which includes the Ctla4 and Icos genes. Besides type 1 diabetes, numerous autoimmune diseases have been mapped to a syntenic region on human chromosome 2q33. In this study we determined how the costimulatory molecules encoded by these genes contribute to the immunopathogenesis of experimental autoimmune encephalomyelitis (EAE). When we compared levels of expression of costimulatory molecules on T cells, we found higher ICOS and lower full-length CTLA-4 expression on activated NOD T cells compared with C57BL/6 (B6) and C57BL/10 (B10) T cells. Using NOD.B10 Idd5 congenic strains, we determined that a 2.1-Mb region controls the observed expression differences of ICOS. Although Idd5.1 congenic mice are resistant to diabetes, we found them more susceptible to myelin oligodendrocyte glycoprotein 35-55-induced EAE compared with NOD mice. Our data demonstrate that higher ICOS expression correlates with more IL-10 production by NOD-derived T cells, and this may be responsible for the less severe EAE in NOD mice compared with Idd5.1 congenic mice. Paradoxically, alleles at the Idd5.1 locus have opposite effects on two autoimmune diseases, diabetes and EAE. This may reflect differential roles for costimulatory pathways in inducing autoimmune responses depending upon the origin (tissue) of the target Ag.


Diagnosis of Classic Homocystinuria in Two Boys Presenting with Acute Cerebral Venous Thrombosis and Neurologic Dysfunction after Normal Newborn Screening.
Homocystinuria, caused by cystathionine β-synthase deficiency, is a rare inherited disorder involving metabolism of methionine. Impaired synthesis of cystathionine leads to accumulation of homocysteine that affects several organ systems leading to abnormalities in the skeletal, cardiovascular, ophthalmic and central nervous systems. We report a 14-month-old and a 7-year-old boy who presented with neurologic dysfunction and were found to have cerebral venous sinus thromboses on brain magnetic resonance imaging (MRI)/magnetic resonance venogram (MRV) and metabolic and hypercoagulable work-up were consistent with classic homocystinuria. The 14-month-old boy had normal newborn screening. The 7-year-old boy initially had an abnormal newborn screen for homocystinuria but second tier test that consisted of total homocysteine was normal, so his newborn screen was reported as normal. With the advent of expanded newborn screening many treatable metabolic disorders are detected before affected infants and children become symptomatic. Methionine is the primary target in newborn screening for homocystinuria and total homocysteine is a secondary target. Screening is usually performed after 24-48 h of life in most states in the US and some states perform a second screen as a policy on all tested newborns or based on when the initial newborn screen was performed. This is done in hopes of detecting infants who may have been missed on their first screen. In the United Kingdom, NBS using dried blood spot is performed at 5 to 8 days after birth. It is universally known that methionine is a poor target and newborn screening laboratories have used different cutoffs for a positive screen. Reducing the methionine cutoff increases the sensitivity but not necessarily the specificity of the test and increasing the cutoff will miss babies who may have HCU whose levels may not be high enough to be detected at their age of ascertainment. It is not clear whether adjusting methionine level to decrease the false negative rates combined with total homocysteine as a second-tier test can be used effectively and feasibly to detect newborns with HCU. Between December 2005 and December 2020, 827,083 newborns were screened in Kentucky by MS/MS. Kentucky NBS program uses the postanalytical tools offered by the Collaborative Laboratory Integrated Reports (CLIR) project which considers gestational age and birthweight. One case of classical homocystinuria was detected and two were missed on first and second tier tests respectively. The newborn that had confirmed classical homocystinuria was one of twenty-three newborns that were referred for second tier test because of elevated methionine (cutoff is >60 µmol/L) and/or Met/Phe ratio (cutoff is >1.0); all 23 dried blood spots had elevated total homocysteine. One of the subjects of this case report had a normal methionine on initial screen and the other had a normal second-tier total homocysteine level. The performance of methionine and total homocysteine as screening analytes for homocystinuria suggest that it may be time for newborn screening programs to consider adopting next generation sequencing (NGS) platforms as alternate modality of metabolic newborn screening. Because of cost considerations, newborn screening programs may not want to adopt NGS, but the downstream healthcare cost incurred due to missed cases and the associated morbidity of affected persons far exceed costs to newborn screen programs. Since NGS is becoming more widely available and inexpensive, it may be feasible to change testing algorithms to use Newborn Metabolic NGS as the primary mode of testing on dry blood specimens with confirmation with biochemical testing. Some commercial laboratories have Newborn Screening Metabolic gene panel that includes all metabolic disorders on the most comprehensive newborn screening panel in addition to many other conditions that are not on the panel. A more targeted NGS panel can be designed that may not cost much and eventually help avoid the pitfalls associated with delayed diagnosis and cost of screening.


Induction of continuous expanding infrarenal aortic aneurysms in a large porcine animal model.
A large animal model with a continuous expanding infrarenal aortic aneurysm gives access to a more realistic AAA model with anatomy and physiology similar to humans, and thus allows for new experimental research in the natural history and treatment options of the disease. 10 pigs (group A) underwent infrarenal aortic dissection, balloon dilatation, infusion of elastase into the lumen and placement of a stenosing cuff around the aorta. 10 control pigs (group B) underwent a sham procedure. The subsequent 28 days the AP-diameters of the aneurysms were measured using ultrasound, hereafter the pigs were euthanized for inspection and AAA wall sampling for histological analysis. In group A, all pigs developed continuous expanding AAA's with a mean increase in AP-diameter to 16.26 ± 0.93 mm equivalent to a 57% increase. In group B the AP-diameters increased to 11.33 ± 0.13 mm equivalent to 9.3% which was significantly less than in group A (p < 0.001). In group A, a significant negative association between the preoperative weight and the resulting AP-diameters was found. Histology shoved more or less complete resolution of the elastic tissue in the tunica media in group A. The most frequent complication was a neurological deficit in the lower limbs. In pigs it's possible to induce continuous expanding AAA's based upon proteolytic degradation and pathological flow, resembling the real life dynamics of human aneurysms. Because the lumbars are preserved, it's also a potential model for further studies of novel endovascular devices and their complications.


Home-based visual field test for glaucoma screening comparison with Humphrey perimeter.
To present a home-based visual field examination method using a PC monitor or virtual reality glasses and evaluate the reliability of the method by comparing the results with those of the Humphrey perimeter, in order to assess the possibility of glaucoma screening through the Internet. Software implementing a supra-threshold algorithm for the central 24° (52 points) of visual field at three threshold levels: 1) -4 db, 2) -8 db, and 3) -12 db, from the age-expected sensitivity was used for the purpose of testing. The software uses the web camera as a "virtual photometer" in order to detect room luminosity and allows self-testing using a computer monitor or virtual reality glasses using an Android smartphone with a 6-inch display. The software includes an expert system to analyze the visual field image and validate the reliability of the results. It also allows the physician to combine the results from two or more tests into a single test in order to achieve higher statistical accuracy of the final result. A total of ten patients, 20 eyes tested×52 points per eye=1,040 visual field test points, were compared point to point to those obtained using the Humphrey perimeter for the same patients, as they appeared randomly and consecutively at the glaucoma department within hours. Good receiver operating characteristic/area under the curve coefficient was found, ranging from 0.762 to 0.837 (P<0.001). Sensitivity ranged from 0.637 to 0.942, and specificity ranged from 0.735 to 0.497. The home-based visual field test exhibits a reasonable receiver operating characteristic curve when compared to the Humphrey perimeter, without the need of specialized equipment. The test may be useful for glaucoma screening.


Illusory movement of stationary stimuli in the visual periphery: evidence for a strong centrifugal prior in motion processing.
Visual input is remarkably diverse. Certain sensory inputs are more probable than others, mirroring statistical regularities of the visual environment. The visual system exploits many of these regularities, resulting, on average, in better inferences about visual stimuli. However, by incorporating prior knowledge into perceptual decisions, visual processing can also result in perceptions that do not match sensory inputs. Such perceptual biases can often reveal unique insights into underlying mechanisms and computations. For example, a prior assumption that objects move slowly can explain a wide range of motion phenomena. The prior on slow speed is usually rationalized by its match with visual input, which typically includes stationary or slow moving objects. However, this only holds for foveal and parafoveal stimulation. The visual periphery tends to be exposed to faster motions, which are biased toward centrifugal directions. Thus, if prior assumptions derive from experience, peripheral motion processing should be biased toward centrifugal speeds. Here, in experiments with human participants, we support this hypothesis and report a novel visual illusion where stationary objects in the visual periphery are perceived as moving centrifugally, while objects moving as fast as 7°/s toward fovea are perceived as stationary. These behavioral results were quantitatively explained by a Bayesian observer that has a strong centrifugal prior. This prior is consistent with both the prevalence of centrifugal motions in the visual periphery and a centrifugal bias of direction tuning in cortical area MT, supporting the notion that visual processing mirrors its input statistics.


Repetitive use of levosimendan for treatment of chronic advanced heart failure: clinical evidence, practical considerations, and perspectives: an expert panel consensus.
The intravenous inodilator levosimendan was developed for the treatment of patients with acutely decompensated heart failure. In the last decade scientific and clinical interest has arisen for its repetitive or intermittent use in patients with advanced chronic, but not necessarily acutely decompensated, heart failure. Recent studies have suggested long-lasting favourable effects of levosimendan when administered repetitively, in terms of haemodynamic parameters, neurohormonal and inflammatory markers, and clinical outcomes. The existing data, however, requires further exploration to allow for definitive conclusions on the safety and clinical efficacy of repetitive use of levosimendan. A panel of 30 experts from 15 countries convened to review and discuss the existing data, and agreed on the patient groups that can be considered to potentially benefit from intermittent treatment with levosimendan. The panel gave recommendations regarding patient dosing and monitoring, derived from the available evidence and from clinical experience. The current data suggest that in selected patients and support out-of-hospital care, intermittent/repetitive levosimendan can be used in advanced heart failure to maintain patient stability. Further studies are needed to focus on morbidity and mortality outcomes, dosing intervals, and patient monitoring. Recommendations for the design of further clinical studies are made.


Population genomics from pool sequencing.
Next generation sequencing of pooled samples is an effective approach for studies of variability and differentiation in populations. In this paper we provide a comprehensive set of estimators of the most common statistics in population genetics based on the frequency spectrum, namely the Watterson estimator θW, nucleotide pairwise diversity Π, Tajima's D, Fu and Li's D and F, Fay and Wu's H, McDonald-Kreitman and HKA tests and FST, corrected for sequencing errors and ascertainment bias. In a simulation study, we show that pool and individual θ estimates are highly correlated and discuss how the performance of the statistics vary with read depth and sample size in different evolutionary scenarios. As an application, we reanalyse sequences from Drosophila mauritiana and from an evolution experiment in Drosophila melanogaster. These methods are useful for population genetic projects with limited budget, study of communities of individuals that are hard to isolate, or autopolyploid species.


Competencies in physical therapy: a resource for written self-assessment and clinical performance evaluation and a component of a department's quality assurance program.
This article was written to demonstrate how clinical competence in ultrasound administration can be reviewed. A team of two members of the Minnesota Competency Consortium developed two tests: 1) a written examination that could be used as a tool to assess the knowledge of physical therapists in physical therapy departments and 2) a skills-mastery check list to assess ultrasound treatment skills. Both tests followed the competency hierarchy of Competencies in Physical Therapy: An Analysis of Practice. As one component of a physical therapy department's quality assurance program, the tests also were used to identify educational needs in order to develop programs to meet those needs.


Study of changes of properties in thermically and hydrothermically treated feeds. 2. N fractions in fermentation medium at the incubation of treated feeds under in vitro conditions.
In the extensive experiments in vitro degradation ability of hydrothermically and thermically treated feeds have been studied. The feeds used were soybean meal, horse bean, alfalfa meal, field pea. The feeds have been treated at 90, 110 and 130 degrees C for 30, 60 and 90 min. The treated feeds have been tested both for microbial degradation ability due to rumen microflora and enzymatic degradation ability via pepsin and trypsin. The fact has been regarded as an important finding that the degradation ability of nitrogenous compounds had been restricted effectively by hydrothermic treatment that was manifested by low ammonia-N levels in fermentation medium (11.3; 8.8; 15.9 and 1.1% out of nitrogen contents in the different feeds). On the other hand improved protein enzymatic digestibility have been recorded in treated feeds as compared with native ones.


Helping adolescents with greater psychosocial needs: evaluation of a positive youth development program.
The Tier 2 Program of the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes), designed and implemented primarily by school social workers, attempts to help adolescents with greater psychosocial needs. After completion of the Tier 2 Program in the Full Implementation Phase (2006/07 school year), 10,255 Secondary 1 students in 207 schools responded to the Subjective Outcome Evaluation Form (Form C) to assess their views of the program, instructors, and perceived effectiveness of the program. Results showed that high proportions of the respondents had positive perceptions of the program and the instructors, and roughly four-fifths of the respondents regarded the program as helpful to them. Pearson correlation analyses showed that perceptions of the program and instructors were significantly correlated with perceived effectiveness of the program. Participants who joined volunteer training activities generally had higher global subjective outcome evaluation scores than did participants who attended programs without volunteer training activities.


Ticagrelor versus clopidogrel in real-world patients with ST elevation myocardial infarction: 1-year results by propensity score analysis.
European guidelines recommend the use of ticagrelor versus clopidogrel in patients with ST elevation myocardial infarction (STEMI). This recommendation is based on inconclusive results and subanalyses from clinical trials. Few data are available on the effects of ticagrelor in a real-world population. To compare the effects of ticagrelor and clopidogrel in a real-world STEMI population, we conducted a pre-post case-control study examining all patients with STEMI included in the Cardio-STEMI Sanremo registry between February 2011 and June 2013. Cases and controls were defined according to P2Y12 inhibitors, correcting the bias due to lack of randomization by propensity score analysis. Ticagrelor was introduced in 2012 in both in-hospital and pre-hospital settings independently of this study. Of the 416 patients enrolled in the Cardio-STEMI registry, 401 with a definite diagnosis of STEMI were included in this study. One hundred forty-two patients received ticagrelor and 259 received clopidogrel. Regarding clinical presentation and procedural data, those in the ticagrelor group had lower CRUSADE scores (23 [14-36] vs 27 [18-38]; p = 0.015] but a higher proportion of radial access (33% vs 14%; p < 0.001), percutaneous coronary intervention (PCI; 92% vs 81 %; p = 0.002) and primary PCI ≤ 12 h (82% vs 66%; p = 0.001). The patients in the ticagrelor group had a higher procedural success rate (100% vs. 96%; p = 0.044). There was no difference in Bleeding Academic Research Consortium bleeding and in unadjusted incidence of hospital major adverse cardiovascular events (MACE; cardiac death, myocardial infarction, or stroke) but there was a significant reduction in unadjusted cardiac hospital death in the ticagrelor group (0.7% vs 5.4%; p = 0.024). After correcting for propensity score, hospital death (p = 0.22) and hospital MACE (p = 0.96) did not differ in both groups. The unadjusted survival at 1 year after STEMI was higher in the ticagrelor group (97.8% vs 87.8%; p = 0.024), and this result was confirmed by propensity score analysis (hazard ratio = 0.29 [0.08-0.99]; p = 0.048). In this real-word propensity score analysis, ticagrelor did not affect the risk of MACE during the hospital phase, or the incidence of hospital bleeding in patients with STEMI. However, in this mono-centric experience, ticagrelor resulted in improved 1-year survival, even after correction by propensity score.


[A case of toxoplasmosis with dermatomyositis].
We report a case of dermatomyositis (DM) in a 15-year-old female with toxoplasmosis after ingestion of raw bovine liver. Facial erythema and cervical lymphadenopathy preceded myalgia and muscle weakness of the extremities. The diagnostic criteria of DM was fulfilled because of symmetrical and proximal dominant muscle weakness, elevation of myogenic enzyme (CPK, GOT, LDH, myoglobin, aldorase), myogenic pattern of electromyogram, skeletal muscle biopsy showing interstitial myositis with mild destruction of muscle fiber, and facial erythema. Immunological findings showed IgG anti-toxoplasma antibody to be 1340 IU/ml and IgM to be 7.0 (Cut off index 0.7), suggesting acute toxoplasmosis. Treatment with prednisolone for DM and acetylspiramycin for toxoplasmosis was successful. Toxoplasmosis should be considered as a possibility in patients with myositis.


[Neonatal screening for hemoglobinopathies: a one-year experience in the public health system in Rio Grande do Sul State, Brazil].
Hemoglobinopathies are the most common inherited disorders in humans; the most frequent are hemoglobins S and C (Hb S and Hb C). Studies in Brazil show the high prevalence of Hb S and Hb C heterozygotes, indicating the need for diagnosis to allow medical care and suitable genetic counseling. This study evaluates the prevalence of hemoglobin patterns in different areas of Rio Grande do Sul State, Brazil, using neonatal data from the public health system. Blood samples from 117,320 newborns, obtained by heel stick, and 2,389 blood samples from parents of newborns, obtained by venopuncture, were submitted to IEF and HPLC. Among the newborns, 1,629 (1.4%) showed abnormal hemoglobin patterns: 1,342 FAS; 225 FAC; 45 FAD; 2 FSC; 1 FS and 26 variant hemoglobin heterozygotes. We conclude that the methods used are able to identify a broad variety of hemoglobin patterns with high specificity and sensitivity. The information is of paramount importance for transmitting knowledge in the public health field, besides facilitating planning and resource allocation.


Children with Burn Injury Have Impaired Cardiac Output during Submaximal Exercise.
Burn trauma damages resting cardiac function; however, it is currently unknown if the cardiovascular response to exercise is likewise impaired. We tested the hypothesis that, in children, burn injury lowers cardiac output (Q˙) and stroke volume (SV) during submaximal exercise. Five children with 49% ± 4% total body surface area (BSA) burned (two female, 11.7 ± 1 yr, 40.4 ± 18 kg, 141.1 ± 9 cm) and eight similar nonburned controls (five female, 12.5 ± 2 yr, 58.0 ± 17 kg, 147.3 ± 12 cm) with comparable exercise capacity (peak oxygen consumption [peak V˙O2]: 31.9 ± 11 vs 36.8 ± 8 mL O2·kg·min, P = 0.39) participated. The exercise protocol entailed a preexercise (pre-EX) rest period followed by 3-min exercise stages at 20 W and 50 W. V˙O2, HR, Q˙ (via nonrebreathing), SV (Q˙/HR), and arteriovenous O2 difference ([a-v]O2diff, Q˙/ V˙O2) were the primary outcome variables. Using a 2-way factorial ANOVA (group [G] × exercise [EX]), we found that Q˙ was approximately 27% lower in the burned than the nonburned group at 20 W of exercise (burned 5.7 ± 1.0 vs nonburned: 7.9 ± 1.8 L·min) and 50 W of exercise (burned 6.9 ± 1.6 vs nonburned 9.2 ± 3.2 L·min) (G-EX interaction, P = 0.012). SV did not change from rest to exercise in burned children but increased by approximately 24% in the nonburned group (main effect for EX, P = 0.046). Neither [a-v] O2diff nor V˙O2 differed between groups at rest or exercise, but HR response to exercise was reduced in the burn group (G-EX interaction, P = 0.004). When normalized to BSA, SV (index) was similar between groups; however, Q˙ (index) remained attenuated in the burned group (G-EX interaction, P < 0.008). Burned children have an attenuated cardiovascular response to submaximal exercise. Further investigation of hemodynamic function during exercise will provide insights important for cardiovascular rehabilitation in burned children.


A dipole-dipole interaction tuning the photoluminescence of silicon quantum dots in a water vapor environment.
The optical properties of silicon quantum dots (Si QDs) depend on the working conditions, which are critical for their application in optoelectronic devices and fluorescent tags. However, how a humid environment, most common in daily life, influences the photoluminescence (PL) of Si QDs has not been fully understood yet. Herein, we applied time-dependent density functional calculations to show that the adsorption of water molecules would exhibit distinct effects on the PL spectra of Si QDs as a function of size. In particular, the PL of Si QDs presents dual band emission with the adsorption of the cyclic water trimer (H2O)3 under common humid conditions, completely different from the PL of Si QDs under other conditions. The transition dipole moment decomposition analysis shows that the additional emission peak originates from the single Si-Si stretched bond of Si QDs induced by the dipole-dipole interaction between the cyclic water trimer and Si QDs. Moreover, the PL characteristics are size dependent. As the size increases from Si17H24 (the diameter of 0.6 nm) to Si52H52 (1.4 nm), the dipole-dipole interaction energy between (H2O)3 and Si QDs rapidly decreases from 19.1 × 10-22 J to 6.0 × 10-26 J, resulting in a single peak of PL of (H2O)3 adsorption on Si52H52. This study not only gives a deep understanding of PL of Si QDs under humid conditions, but also provides a new perspective on the development of optical devices based on Si QDs.


Variations of light and temperature regimes and resulting effects on reproductive parameters in medaka (Oryzias latipes).
In seasonally breeding fish species, altered fecundity, fertility, and spawning interval are associated with changes in environmental cues such as temperature and photoperiod. To determine quantitative impact of these cues on a suite of reproductive endpoints, groups of medaka (Oryzias latipes; two breeding pairs per group) were subjected to varying photoperiod and temperature regimes. Embryo production ceased after photoperiod reduction from 16L:8D to 8L:16D (at 25 degrees C). A severe decline in production was observed after a temperature decrease of 10 degrees C (25 degrees C to 15 degrees C [16L:8D]). Under reduced photoperiod, histologic analysis showed no mature ova and moderate oocyte atresia in all individuals. However, reduced temperature (15 degrees C) produced only mild oocyte atresia and fewer mature ova. Under both reduced photoperiod and reduced temperature regimes, mature spermatozoa were observed. Offspring viability, along with spawning interval, were not affected by photoperiod reduction. Temperature change had no effect on offspring viability but caused an increase in spawning interval. A shortened photoperiod profoundly affected medaka reproduction, whereas decreased temperature reduced, but did not arrest, fertility; reduced photoperiod decreased fecundity. These findings have important implications for culture of medaka as well as use of this teleost model for reproductive toxicology studies.


Weather variation affects the dispersal of grasshoppers beyond their elevational ranges.
Understanding how abiotic conditions influence dispersal patterns of organisms is important for understanding the degree to which species can track and persist in the face of changing climate.The goal of this study was to understand how weather conditions influence the dispersal pattern of multiple nonmigratory grasshopper species from lower elevation grassland habitats in which they complete their life-cycles to higher elevations that extend beyond their range limits.Using over a decade of weekly spring to late-summer field survey data along an elevational gradient, we explored how abundance and richness of dispersing grasshoppers were influenced by temperature, precipitation, and wind speed and direction. We also examined how changes in population sizes at lower elevations might influence these patterns.We observed that the abundance of dispersing grasshoppers along the gradient declined 4-fold from the foothills to the subalpine and increased with warmer conditions and when wind flow patterns were mild or in the downslope direction. Thirty-eight unique grasshopper species from lowland sites were detected as dispersers across the survey years, and warmer years and weak upslope wind conditions also increased the richness of these grasshoppers. The pattern of grasshoppers along the gradient was not sex biased. The positive effect of temperature on dispersal rates was likely explained by an increase in dispersal propensity rather than by an increase in the density of grasshoppers at low elevation sites.The results of this study support the hypothesis that the dispersal patterns of organisms are influenced by changing climatic conditions themselves and as such, that this context-dependent dispersal response should be considered when modeling and forecasting the ability of species to respond to climate change.


Extraction of high methoxyl pectin from unripe waste Ponkan mandarine (Citrus reticulata Blanco cv. Ponkan) with an eco-friendly solvent.
The aqueous batch extraction of pectin from unripe Ponkan mandarin was evaluated for potential application in the food industry. A small central composite design with 4 variables (temperature, volume to mass ratio, pH, and mean particle size) and 3 levels was applied for pectin extraction optimization. Also, the kinetic of the pectin yield extraction was investigated at temperatures 70-90 °C, stirring rate of 100-700 rpm, ultrasound pretreatment system, and modeling using four mathematical models. The pectin extraction process was evaluated by yield of pectin and esterification degree. FTIR, TGA, and DTA were performed to evaluate the quality of pectin obtained. The small central composite design demonstrated that temperature and volume to mass ratio were significant variables, and the highest yield of pectin extraction was 11.62 % obtained at temperature and volume to molar ratio of 81.9 °C and 33.9 v/w %, respectively. Besides, the esterification degree showed higher than 70 % for all extraction conditions, suggesting high methoxyl pectin. The kinetics showed the stirring rate and the ultrasound pretreatment did not cause any significant alteration, while high temperatures proved to be beneficial to the rate and the yield of the pectin extraction. The best fit was provided by Fick's law, suggesting the extraction process is limited by internal mass transfer. FTIR showed the functional groups expected for pectin, and TGA and DTA indicated that the pectin obtained is proper for most food products, as only above 200 °C the pectin should degrade.


Analysis of nickel-titanium versus stainless steel instrumentation by means of direct digital imaging.
This study compared step-back preparations in curved canals using nickel-titanium (Ni-Ti) K-files and stainless steel K-files. Forty canals in mesial roots of mandibular molars were embedded in casting resin and cross-sectioned at three levels: 1 to 2 mm from the apical foramen, middle of the curve, and coronal. Direct digital computer images were recorded before and after instrumentation. Superimposition of the images combined with digital subtraction computer software allowed direct measurement of area instrumented, distance of transportation, and shape analysis. The computer software calculated absolute center of gravity for each image analyzed to get a full 360-degree interpretation of the canal transport. Time of instrumentation was recorded. Results showed Ni-Ti files to cause significantly less transportation and remain more centered at the apical level (p < 0.05). Area removed by Ni-Ti and stainless steel files was not significantly different (p < 0.05). Time of instrumentation was not significantly different for Ni-Ti and stainless steel instruments (p < 0.05). Cross-sectional shape of the instrumented canal was not significantly different (p < 0.05).


Reconstruction of Cell Surface Densities of Ion Pumps, Exchangers, and Channels from mRNA Expression, Conductance Kinetics, Whole-Cell Calcium, and Current-Clamp Voltage Recordings, with an Application to Human Uterine Smooth Muscle Cells.
Uterine smooth muscle cells remain quiescent throughout most of gestation, only generating spontaneous action potentials immediately prior to, and during, labor. This study presents a method that combines transcriptomics with biophysical recordings to characterise the conductance repertoire of these cells, the 'conductance repertoire' being the total complement of ion channels and transporters expressed by an electrically active cell. Transcriptomic analysis provides a set of potential electrogenic entities, of which the conductance repertoire is a subset. Each entity within the conductance repertoire was modeled independently and its gating parameter values were fixed using the available biophysical data. The only remaining free parameters were the surface densities for each entity. We characterise the space of combinations of surface densities (density vectors) consistent with experimentally observed membrane potential and calcium waveforms. This yields insights on the functional redundancy of the system as well as its behavioral versatility. Our approach couples high-throughput transcriptomic data with physiological behaviors in health and disease, and provides a formal method to link genotype to phenotype in excitable systems. We accurately predict current densities and chart functional redundancy. For example, we find that to evoke the observed voltage waveform, the BK channel is functionally redundant whereas hERG is essential. Furthermore, our analysis suggests that activation of calcium-activated chloride conductances by intracellular calcium release is the key factor underlying spontaneous depolarisations.


Hot summers raise public awareness of toxic cyanobacterial blooms.
Water quality of eutrophic lakes is threatened by harmful cyanobacterial blooms, which are favored by summer heatwaves and expected to intensify with global warming. Societal demands on surface water for drinking, irrigation and recreation are also highest in summer, especially during dry and warm conditions. Here, we analyzed trends in online searches to investigate how public awareness of cyanobacterial blooms is impacted by temperature in nine different countries over almost twenty years. Our findings reveal large seasonal and interannual variation, with more online searches for harmful cyanobacteria in temperate regions during hot summers. Online searches and media attention increased even more steeply with temperature than the incidence of cyanobacterial blooms, presumably because lakes attract more people during warm weather. Overall, our study indicates that warmer summers not only increase cyanobacterial bloom incidence, but also lead to a pronounced increase of the public awareness of toxic cyanobacterial blooms.


Exploring the knowledge, attitudes and needs of advance care planning in older Chinese Australians.
To identify factors that influence the engagement of Chinese Australians with advance care planning. Despite the benefits of advance care planning, there is a low prevalence of advance care planning in the Chinese Australian community. Reasons for this are often cited as cultural considerations and taboos surrounding future medical planning and death; however, other logistical factors may also be important. This qualitative study used a thematic analysis grounded theory approach to explore facilitators and barriers to engagement in advance care planning. Semistructured interviews were conducted in-language (Mandarin or Cantonese) exploring the views of a purposive sample of 30 community-dwelling older Chinese Australians within Victoria, Australia. Three key themes were identified: knowledge of, attitudes towards and needs for undertaking advance care planning amongst the Chinese Australians. There was a low awareness of advance care planning amongst the participants and some confusion regarding the concept. Most participants reported positive attitudes towards advance care planning but acknowledged that others may be uncomfortable discussing death-related topics. Participants would want to know the true status of their health and plan ahead in consultation with family members to reduce the burden on the family and suffering for themselves. Language was identified as the largest barrier to overcome to increase advance care planning awareness. In-language materials and key support networks including GPs, family and Chinese community groups were identified as ideal forums for the promotion of advance care planning. The participants of this study were open to conversations regarding future medical planning and end-of-life care, suggesting the low uptake of advance care planning amongst Chinese Australians is not culturally motivated but may be due a lack of knowledge relating to advance care planning. The results highlight the need to provide access to appropriate in-language advance care planning resources and promotion of advance care planning across the Chinese community.


Effect of cardamonin on hepatic ischemia reperfusion induced in rats: Role of nitric oxide.
Ischemia reperfusion (I/R) injury is a cellular damage in a hypoxic organ following the restoration of oxygen delivery. It may occur during organ transplantation, trauma and hepatectomies. Nitric oxide (NO) effects during hepatic I/R are complicated. The iNOS-derived NO has a deleterious effect, whereas eNOS-derived NO has a protective effect in liver I/R. Cardamonin (CDN) is an anti-inflammatory molecule and a novel iNOS inhibitor, and Nω-Nitro-L-arginine (L-NNA) is a NOS inhibitor. L-Arginine is a precursor of NOS. This study was designed to investigate the possible protective effects of CDN on hepatic I/R and the role of NO. Wistar rats were randomly divided into 5 groups (Sham, I/R, CDN, L-NNA and L-arginine). Liver ischemia was induced for 45min then reperfusion was allowed for 1h. L-Arginine and CDN ameliorated the deleterious effects of I/R through reducing the oxidative stress and hepatocyte degeneration. Both molecules decreased the elevated inflammatory cytokines and increased the antiapoptotic marker, Bcl2. Both agents increased NO and eNOS expression and decreased iNOS expression. In conclusion, increased NO/eNOS and suppression of iNOS expression have protective effects on I/R injury. While inhibition of eNOS and reduction of NO have deleterious effects on I/R injury. For the first time, we demonstrated that cardamonin improved functional and structural abnormalities of the liver following I/R by improving oxidative stress and inflammation and increasing the availability of NO produced by eNOS. Treatment with cardamonin could be a promising strategy in patients with hepatic I/R injury in different clinical situations.


Effects of monofunctional adducts of platinum(II) complexes on thermodynamic stability and energetics of DNA duplexes.
Effects of adducts of [PtCl(NH3)3]Cl or chlorodiethylenetriamineplatinum(II) on DNA stability were studied with emphasis on thermodynamic origins of that stability. Oligodeoxyribonucleotide duplexes (15-bp) containing the single, site-specific monofunctional adduct at G-residues of the central sequences TGT/ACA or 5'-AGT/5'-ACT were prepared and analyzed by differential scanning calorimetry, temperature-dependent ultraviolet absorption and circular dichroism. The unfolding of the platinated duplexes was accompanied by relatively small unfavorable free energy terms. This destabilization was enthalpic in origin. On the other hand, a relatively large reduction of melting temperature (T(m)) was observed as a consequence of the monofunctional adduct in the TGT sequence, whereas T(m) due to the adduct in the AGT sequence was reduced only slightly. We also examined the efficiency of the mammalian nucleotide excision repair system to remove from DNA the monofunctional adducts and found that these lesions were not recognized by this repair system. Thus, rather thermodynamic than thermal characterization of DNA adducts of monofunctional platinum compounds is a property implicated in the modulation of downstream effects such as protein recognition and repair.


Share of mass transit miles traveled and reduced motor vehicle fatalities in major cities of the United States.
The USA leads the developed world in motor vehicle fatalities, presenting a critical public health threat. We examined whether an increasing share of mass transit use, relative to vehicle miles traveled on public roads, was associated with reduced motor vehicle fatalities. We used annual city-level data for the USA from 1982-2010 provided by the Fatality Accident Reporting System, the Texas A&M Transportation Institute, the Census Bureau, and the National Oceanic and Atmospheric Administration to estimate a structural equation model of the factors associated with mass transit miles and motor vehicle fatalities. The final analytic data included 2,900 observations from 100 cities over 29 years. After accounting for climate, year, and the economic costs of driving, an increasing share of mass transit miles traveled per capita was associated with reduced motor vehicle fatalities. The costs of congestion to the average commuter and gas prices were positively associated with increasing the share of mass transit miles traveled. The economic costs of driving increased over time, while both the fatality rate and the share of mass transit miles traveled decreased over time. Increasing the share of mass transit miles traveled may be associated with fewer motor vehicle miles traveled. Increasing mass transit uptake may be an effective public health intervention to reduce motor vehicle fatalities in cities.


Gaze stability of observers watching Op Art pictures.
It has been the matter of some debate why we can experience vivid dynamic illusions when looking at static pictures composed from simple black and white patterns. The impression of illusory motion is particularly strong when viewing some of the works of 'Op Artists, such as Bridget Riley's painting Fall. Explanations of the illusory motion have ranged from retinal to cortical mechanisms, and an important role has been attributed to eye movements. To assess the possible contribution of eye movements to the illusory-motion percept we studied the strength of the illusion under different viewing conditions, and analysed the gaze stability of observers viewing the Riley painting and control patterns that do not produce the illusion. Whereas the illusion was reduced, but not abolished, when watching the painting through a pinhole, which reduces the effects of accommodation, it was not perceived in flash afterimages, suggesting an important role for eye movements in generating the illusion for this image. Recordings of eye movements revealed an abundance of small involuntary saccades when looking at the Riley pattern, despite the fact that gaze was kept within the dedicated fixation region. The frequency and particular characteristics of these rapid eye movements can vary considerably between different observers, but, although there was a tendency for gaze stability to deteriorate while viewing a Riley painting, there was no significant difference in saccade frequency between the stimulus and control patterns. Theoretical considerations indicate that such small image displacements can generate patterns of motion signals in a motion-detector network, which may serve as a simple and sufficient, but not necessarily exclusive, explanation for the illusion. Why such image displacements lead to perceptual results with a group of Op Art and similar patterns, but remain invisible for other stimuli, is discussed.


The impact of the global budget system on dynamics of dental manpower and utilization of dental services.
This study aimed to investigate dentists' supply and practice patterns following the implementation of the global budget system in Taiwan. Data of reimbursement claims, municipal socioeconomic status and dental manpower were collected from the National Health Insurance administration, the Ministry of Internal Affair, and the Ministry of Health and Welfare, respectively. A multivariate linear regression method was used for data analysis. A municipality that reported a higher percentage of tertiary educated population (t = 3.718, P < 0.001), a higher per capita income (t = 6.172, P < 0.001), a higher population density (t = 6.172, P < 0.001), or a lower percentage of elderly population (t = -2.506, P = 0.014) was more likely to have a higher number of dentists per 100,000 population. A municipality that reported a higher Herfindahl-Hirschman Index (HHI) value (t = 2.880, P = 0.005) was more likely to show a higher move-out rate among dentists. The rate was lower after the implementation of the global budget system (t = -2.436, P = 0.018). A municipality that had a higher percentage of elderly population (t = 3.628, P < 0.001), a lower percentage of young population (t = -2.138, P = 0.035), or a higher rate of population growth (t = 4.412, P < 0.001) was more likely to display a higher move-in rate among dentists. The percentage of amalgam restorations in total claims reduced from 19.82% to 17.94%, while the percentage of tooth-colored material restorations increased from 25.46% to 28.79%. This study has demonstrated a stabilizing effect of the global budget system on dynamics of dental manpower in Taiwan. A relationship between HHI and dentists' move-out rate has been found. The relationship between municipal socioeconomic status and the density of dentists has also been confirmed. In addition, reduced utilization of amalgam restorations was accompanied by increased utilization of tooth-colored material restorations. Further investigations are indicated.


Laparoscopic management of advanced renal cell carcinoma with renal vein and inferior vena cava thrombus.
To report the results and oncological efficacy of laparoscopic radical nephrectomy (LRN) in patients with renal cell carcinoma with renal vein and inferior vena cava thrombus. We performed retrospective record review of 41 patients who underwent LRN along with venous thrombectomy at 2 Canadian centers from 2002 to 2012 by dedicated laparoscopic surgeons. The mean age and body mass index of the 41 study patients (34 males and 7 female) were 64.4 years and 28.7 kg/m(2), respectively. Median tumor size was 9.3 cm; 39 patients had renal vein thrombus, and 2 had inferior vena cava thrombus. Nine patients (22%) had metastatic disease to begin with and underwent laparoscopic cytoreductive nephrectomy. Median estimated blood loss, operative time, and length of stay were 100 mL (range, 50-400 mL), 134.5 minutes (range, 99-183 minutes), and 4 days (range, 4-6 days), respectively. There were 4 (9.7%) grade 2 complications. There was no intraoperative death. Mean duration of follow-up was 42 months (range, 6-107 months). Of 32 patients with localized disease, 4 (12.5%) died of progressive disease, 3 (9.3%) died of unrelated causes, and 3 patients (9.3%) were lost to follow-up. Twenty-two patients (68.7%) were alive at a mean follow-up of 47 months. LRN and venous thrombectomy for advanced renal tumors with venous thrombus are safe procedures in experienced hands with significant laparoscopic skills. The short-term oncological data are encouraging and advocate the efficacy of this procedure in this subset of patients, although longer follow-up is required in larger number of patients to further define its role.


Dysphagia in Patients with Acute Ischemic Stroke: Early Dysphagia Screening May Reduce Stroke-Related Pneumonia and Improve Stroke Outcomes.
Dysphagia is associated with poor outcome in stroke patients. Studies investigating the association of dysphagia and early dysphagia screening (EDS) with outcomes in patients with acute ischemic stroke (AIS) are rare. The aims of our study are to investigate the association of dysphagia and EDS within 24 h with stroke-related pneumonia and outcomes. Over a 4.5-year period (starting November 2007), all consecutive AIS patients from 15 hospitals in Schleswig-Holstein, Germany, were prospectively evaluated. The primary outcomes were stroke-related pneumonia during hospitalization, mortality, and disability measured on the modified Rankin Scale ≥2-5, in which 2 indicates an independence/slight disability to 5 severe disability. Of 12,276 patients (mean age 73 ± 13; 49% women), 9,164 patients (74%) underwent dysphagia screening; of these patients, 55, 39, 4.7, and 1.5% of patients had been screened for dysphagia within 3, 3 to <24, 24 to ≤72, and >72 h following admission. Patients who underwent dysphagia screening were likely to be older, more affected on the National Institutes of Health Stroke Scale score, and to have higher rates of neurological symptoms and risk factors than patients who were not screened. A total of 3,083 patients (25.1%; 95% CI 24.4-25.8) had dysphagia. The frequency of dysphagia was higher in patients who had undergone dysphagia screening than in those who had not (30 vs. 11.1%; p < 0.001). During hospitalization (mean 9 days), 1,271 patients (10.2%; 95% CI 9.7-10.8) suffered from stroke-related pneumonia. Patients with dysphagia had a higher rate of pneumonia than those without dysphagia (29.7 vs. 3.7%; p < 0.001). Logistic regression revealed that dysphagia was associated with increased risk of stroke-related pneumonia (OR 3.4; 95% CI 2.8-4.2; p < 0.001), case fatality during hospitalization (OR 2.8; 95% CI 2.1-3.7; p < 0.001) and disability at discharge (OR 2.0; 95% CI 1.6-2.3; p < 0.001). EDS within 24 h of admission appeared to be associated with decreased risk of stroke-related pneumonia (OR 0.68; 95% CI 0.52-0.89; p = 0.006) and disability at discharge (OR 0.60; 95% CI 0.46-0.77; p < 0.001). Furthermore, dysphagia was independently correlated with an increase in mortality (OR 3.2; 95% CI 2.4-4.2; p < 0.001) and disability (OR 2.3; 95% CI 1.8-3.0; p < 0.001) at 3 months after stroke. The rate of 3-month disability was lower in patients who had received EDS (52 vs. 40.7%; p = 0.003), albeit an association in the logistic regression was not found (OR 0.78; 95% CI 0.51-1.2; p = 0.2). Dysphagia exposes stroke patients to a higher risk of pneumonia, disability, and death, whereas an EDS seems to be associated with reduced risk of stroke-related pneumonia and disability.


Roller compaction of moist pharmaceutical powders.
The compression behaviour of powders during roller compaction is dominated by a number of factors, such as process conditions (roll speed, roll gap, feeding mechanisms and feeding speed) and powder properties (particle size, shape, moisture content). The moisture content affects the powder properties, such as the flowability and cohesion, but it is not clear how the moisture content will influence the powder compression behaviour during roller compaction. In this study, the effect of moisture contents on roller compaction behaviour of microcrystalline cellulose (MCC, Avicel PH102) was investigated experimentally. MCC samples of different moisture contents were prepared by mixing as-received MCC powder with different amount of water that was sprayed onto the powder bed being agitated in a rotary mixer. The flowability of these samples were evaluated in terms of the poured angle of repose and flow functions. The moist powders were then compacted using the instrumented roller compactor developed at the University of Birmingham. The flow and compression behaviour during roller compaction and the properties of produced ribbons were examined. It has been found that, as the moisture content increases, the flowability of moist MCC powders decreases and the powder becomes more cohesive. As a consequence of non-uniform flow of powder into the compaction zone induced by the friction between powder and side cheek plates, all produced ribbons have a higher density in the middle and lower densities at the edges. For the ribbons made of powders with high moisture contents, different hydration states across the ribbon width were also identified from SEM images. Moreover, it was interesting to find that these ribbons were split into two halves. This is attributed to the reduction in the mechanical strength of moist powder compacts with high moisture contents produced at high compression pressures.


The influence of periodized resistance training on recreationally active males with chronic nonspecific low back pain.
The most common musculoskeletal health issue is chronic nonspecific low back pain (CLBP). CLBP increases pain and disability, which reduces quality of life (QoL). Generally, pain, disability, and QoL are improved with a moderate volume and intensity of physical activity. Recently, periodized resistance training (PRT) was shown to be effective at improving CLBP in sedentary young, middle-age, and older adults. The purpose of this study was to determine if PRT would increase strength, reduce pain and disability, and improve QoL in recreationally active, moderately trained middle- and older-age males. Forty-five male subjects were divided according to age into 1 of 3 groups: (a) middle-age exercise (ME), (b) old-age exercise (OE), or (c) control (C). All subjects suffered from CLBP and were considered to be moderately trained, participating in recreational ice hockey for 60 minutes, 2 times per wk(-1) for ∼5 months/year along with other recreational activities. The study ran for 16 weeks (3-week familiarization and 13 weeks of testing and PRT) with 5 repetition maximum testing at baseline and weeks 8 and 12. The PRT program systematically and progressively overloaded all major muscle groups (whole-body workout). The results indicate that middle- and old-age recreationally active males with CLBP respond similarly in magnitude to PRT, with improvements in all outcome measures (strength, pain, disability, QoL) across all time points of the study. Clinical significance (≥ 25%) in outcome measures was reached on most variables for the ME and OE groups. The results suggest that PRT may be effectively applied as rehabilitation for moderately trained recreational athletes with CLBP.


Réunion Island prepared for possible Zika virus emergence, 2016.
Zika virus (ZIKV) has recently spread widely and turned into a major international public health threat. Réunion appears to offer conditions particularly favourable to its emergence and therefore prepared to face possible introduction of the virus. We designed a scaled surveillance and response system with specific objectives, methods and measures for various epidemiological phases including a potential epidemic. Several tools were developed in order to (i) detect individual cases (including a large information campaign on the disease and suspicion criteria), (ii) monitor an outbreak through several complementary systems allowing to monitor trends in disease occurrence and geographic spread and (iii) detect severe forms of the disease in collaboration with hospital clinicians. We put the emphasis on detecting the first cases in order to contain the spread of the virus as much as possible and try to avoid progress towards an epidemic. Our two main strengths are a powerful vector control team, and a close collaboration between clinicians, virologists, epidemiologists, entomologists and public health authorities. Our planned surveillance system could be relevant to Europe and island settings threatened by Zika virus all over the world.


Cytosolic p21Waf1/Cip1 increases cell cycle transit in vascular smooth muscle cells.
The intracellular localization of signaling proteins is critical in directing their interactions with both upstream and downstream signaling cascade components. While initially described as a cyclin kinase inhibitor, p21Waf1/Cip1 has since been shown to have bimodal effects on cell cycle progression and cell proliferation, and evidence is emerging that intracellular localization of this protein plays a role in directing its signaling properties by dictating its interactions with downstream molecules. Since we have previously demonstrated a pro-apoptotic and cell cycle inhibitory effect of p21 attenuation after transfection of antisense p21 oligodeoxynucleotides (ODN) in several cell lines, we asked whether cytosolic p21 mediates a positive effect on vascular smooth muscle (VSM) cell cycle transit. We now show that transfection of a nuclear-localization signal deficient (DeltaNLS) p21 construct into VSM cells results in increased cytosolic levels of p21 and causes increased cell cycle transit as measured by [3H]thymidine incorporation. Thus, at least in VSM cells, cytosolic localization of p21 is a means by which this signaling protein transmits pro-mitogenic signals to the proteins responsible for G1/S transition. Furthermore, compartmentalization of p21 may help explain the biphasic nature of p21 in a variety of cell types and may lead to therapeutic advances directed at modulating pathologic cell growth in vascular diseases and cancer.


Prenatal diagnosis and patient preferences in patients with neural tube defects around the advent of fetal surgery in Belgium and Holland.
We review the characteristics and prenatal choices of patients recently evaluated for neural tube defects (NTD) at two tertiary units. The prenatal diagnosis of NTD allows parents to consider all prenatal options. In selected cases of spina bifida aperta this also includes fetal surgery, which we started offering after combined 'in-house' and 'exported' training. This is a retrospective review of prospectively collected data on NTD diagnosed over the last 8 years and recent fetal surgery referrals. A total of 167 patients were referred for assessment at a median of 19 weeks. Cranial lesions were diagnosed significantly earlier than spinal lesions. Of the open spinal lesions, 77% were isolated. Of these, 22% were managed expectantly and 1 (1%) had fetal surgery. There was no correlation between parental decisions on prenatal management with disease-specific severity markers. We had 14 fetal surgery referrals, all but 1 from beyond our typical referral area; 6 of the assessed patients were operated on, 4 were expectantly managed and 4 requested termination of pregnancy (TOP). These pregnancy outcomes were in the expected range. Open spina bifida is mainly diagnosed in the second trimester and 76% of subjects request TOP, irrespective of the severity indicators. The number of local patients considering fetal surgery is low.


A 30-Year Study of Impacts, Recovery, and Development of Critical Effect Sizes for Endocrine Disruption in White Sucker (Catostomus commersonii) Exposed to Bleached-Kraft Pulp Mill Effluent at Jackfish Bay, Ontario, Canada.
Jackfish Bay is an isolated bay on the north shore of Lake Superior, Canada that has received effluent from a large bleached-kraft pulp mill since the 1940s. Studies conducted in the late 1980s found evidence of reductions in sex steroid hormone levels in multiple fish species living in the Bay, and increased growth, condition and relative liver weights, with a reduction in internal fat storage, reduced gonadal sizes, delayed sexual maturation, and altered levels of circulating sex steroid hormones in white sucker (Catostomus commersonii). These early studies provided some of the first pieces of evidence of endocrine disruption in wild animals. Studies on white sucker have continued at Jackfish Bay, monitoring fish health after the installation of secondary waste treatment (1989), changes in the pulp bleaching process (1990s), during facility maintenance shutdowns and during a series of facility closures associated with changing ownership (2000s), and were carried through to 2019 resulting in a 30-year study of fish health impacts, endocrine disruption, chemical exposure, and ecosystem recovery. The objective of the present study was to summarize and understand more than 75 physiological, endocrine, chemical and whole organism endpoints that have been studied providing important context for the complexity of endocrine responses, species differences, and challenges with extrapolation. Differences in body size, liver size, gonad size and condition persist, although changes in liver and gonad indices are much smaller than in the early years. Population modeling of the initial reproductive alterations predicted a 30% reduction in the population size, however with improvements over the last couple of decades those population impacts improved considerably. Reflection on these 30 years of detailed studies, on environmental conditions, physiological, and whole organism endpoints, gives insight into the complexity of endocrine responses to environmental change and mitigation.


Mechanistic Implications of GSK and CREB Crosstalk in Ischemia Injury.
Ischemia-reperfusion (IR) injury is a damage to an organ when the blood supply is less than the demand required for normal functioning, leading to exacerbation of cellular dysfunction and death. IR injury occurs in different organs like the kidney, liver, heart, brain, etc., and may not only involve the ischemic organ but also cause systemic damage to distant organs. Oxygen-glucose deprivation in cells causes oxidative stress, calcium overloading, inflammation, and apoptosis. CREB is an essential integrator of the body's various physiological systems, and it is widely accepted that dysfunction of CREB signaling is involved in many diseases, including ischemia-reperfusion injury. The activation of CREB can provide life to a cell and increase the cell's survival after ischemia. Hence, GSK/CREB signaling pathway can provide significant protection to cells of different organs after ischemia and emerges as a futuristic strategy for managing ischemia-reperfusion injury. Different signaling pathways such as MAPK/ERK, TLR4/MyD88, RISK, Nrf2, and NF-κB, get altered during IR injury by the modulation of GSK-3 and CREB (cyclic AMP response element (CRE)-binding protein). GSK-3 (protein kinase B) and CREB are the downstream targets for fulfilling the roles of various signaling pathways. Calcium overloading during ischemia increases the expression of calcium-calmodulin-dependent protein kinase (CaMK), which subsequently activates CREB-mediated transcription, thus promoting the survival of cells. Furthermore, this review highlights the crosstalk between GSK-3 and CREB, promoting survival and rendering the cells resistant to subsequent severe ischemia.


Withdrawal of statins and risk of subarachnoid hemorrhage.
Vascular endothelium, which can be affected by statins, is believed to play a substantial role in subarachnoid hemorrhage (SAH). Our objective was to estimate the association between use and withdrawal of statins and the risk of SAH. We conducted a population-based case-control study within the PHARMO database. A case was defined as a person hospitalized for SAH (ICD-9-CM code 430) in the period January 1, 1998 to December 31, 2006. Ten randomly chosen controls were matched to each case on age, gender, and calendar date. During the study period 1004 incident cases of SAH were identified. Current use of statins did not significantly decrease the risk of SAH (OR=0.77, 95% CI 0.55 to 1.07). The odds ratio for recent withdrawal compared to nonusers was 1.62 (95% CI 0.96 to 2.73). Compared to current use, recent withdrawal was associated with an increased risk of SAH (OR=2.34, 95% CI 1.35 to 4.05). Interaction analysis showed that the effect of statin withdrawal was highest in patients who had also recently stopped antihypertensive drugs (OR=6.77, 95% CI 2.10 to 21.8). Current use of statins seems to lower the risk of SAH, although the reduction was not significant in new users. Statin withdrawal increased the risk of SAH by a factor 2, even more in patients who had also recently stopped their antihypertensive treatment.


Selective spatial localization of actomyosin motor function by chemical surface patterning.
We have previously described the efficient guidance and unidirectional sliding of actin filaments along nanosized tracks with adsorbed heavy meromyosin (HMM; myosin II motor fragment). In those experiments, the tracks were functionalized with trimethylchlorosilane (TMCS) by chemical vapor deposition (CVD) and surrounded by hydrophilic areas. Here we first show, using in vitro motility assays on nonpatterned and micropatterned surfaces, that the quality of HMM function on CVD-TMCS is equivalent to that on standard nitrocellulose substrates. We further examine the influences of physical properties of different surfaces (glass, SiO(2), and TMCS) and chemical properties of the buffer solution on motility. With the presence of methylcellulose in the assay solution, there was HMM-induced actin filament sliding on both glass/SiO(2) and on TMCS, but the velocity was higher on TMCS. This difference in velocity increased with decreasing contact angles of the glass and SiO(2) surfaces in the range of 20-67 degrees (advancing contact angles for water droplets). The corresponding contact angle of CVD-TMCS was 81 degrees. In the absence of methylcellulose, there was high-quality motility on TMCS but no motility on glass/SiO(2). This observation was independent of the contact angle of the glass/SiO(2) surfaces and of HMM incubation concentrations (30-150 microg mL(-)(1)) and ionic strengths of the assay solution (20-50 mM). Complete motility selectivity between TMCS and SiO(2) was observed for both nonpatterned and for micro- and nanopatterned surfaces. Spectrophotometric analysis of HMM depletion during incubation, K/EDTA ATPase measurements, and total internal reflection fluorescence spectroscopy of HMM binding showed only minor differences in HMM surface densities between TMCS and SiO(2)/glass. Thus, the motility contrast between the two surface chemistries seems to be attributable to different modes of HMM binding with the hindrance of actin binding on SiO(2)/glass.


An Artificial Olfactory System Based on a Memristor Can Simulate Organ Injury and Functions in Air Purification.
Artificial olfactory systems are receiving increasing attention because of their potential applications in humanoid robots, artificial noses, and the next generation of human-computer interactions. However, simulating the human olfactory system, which recognizes, remembers, and automatically takes protective measures against gases, remains a challenge. In this paper, a WO3-TiO2@Ag NPs (silver nanoparticle) gas sensor was prepared by the sol-gel method, and an Al/pectin:AgNP/ITO memristor was prepared by spin coating and vacuum evaporation. The gas sensor has been combined with the memristor to simulate physical damage to humans in a dangerous gas environment for a long time, and an artificial olfactory system is constructed by field-programmable gate array external control. The WO3-TiO2@Ag NPs gas sensor can sense and identify ethanol vapor through changes in resistance, and the signal transmitted to the pectin-based memristor can switch the resistance state of the memristor to store gas information. Furthermore, the activation of the memristor can also trigger rotation of the fan to purify the gas and reduce damage caused by excessive exposure to dangerous gases. This artificial olfactory system provides a promising strategy for the development of artificial intelligence and human-computer interaction systems.


Antioxidant activity and toxicity profile of total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst occurring in South India.
The total triterpene fraction isolated from Ganoderma lucidum, a highly nutritional and popular medicinal mushroom occurring in South India, was evaluated for its antioxidant activity in vitro and in vivo. Total triterpenes successfully scavenged DPPH(+), ABTS(+) and superoxide radicals, showed significant ferric reducing activity and was highly effective in reducing the in vitro lipid peroxidation. Activities of the antioxidant enzymes in blood and tissue were increased by the administration of total triterpenes to Swiss albino mice in vivo. The ability of total triterpenes to scavenge the free radicals and to enhance body's antioxidant defence systems indicates its potential use as an antioxidant. An attempt was also done to gauge the toxicity of total triterpenes using acute and sub acute study models in Swiss albino mice. The results showed that Ganoderma triterpenes did not possess significant toxicity. The findings thus reveal the possible therapeutic use of Ganoderma triterpenes.


Using Tc-99m MIBI scintimammography to differentiate nodular lesions in breast and detect axillary lymph node metastases from breast cancer.
To test the clinical value of using Tc-99m MIBI scintimammography (Tc-99m MIBI SMM) to differentiate nodular lesions in breasts and detect axillary lymph node metastases of breast cancer. The subjects consisted of sixty female patients exhibiting unilateral palpable breast mass. The early and delay static acquisitions were undertaken in all subjects at 10 and 90 min after injection with Tc-99m MIBI. The acquisition included three positions: anterior supine, left lateral prone and right lateral prone. A special device for SMM which was developed by our laboratory was used. The ratio of [(T-B)/(NT-B)] was calculated as radioactivity of mass to that of opposite corresponding tissue, and [(T-B)/(NT-B)] > or = 1.21 was used as the cut-off for semi-quantitative discrimination of malignancy from benignity in semi-quantitative analysis. The final diagnosis was obtained from histology examination in all subjects. Using Tc-99m MIBI SMM to differentiate between nodular lesions in breasts, the diagnostic sensitivity and specificity were 92.9% and 90.6% respectively, the positive predictive value 89.7%, the negative predictive value 93.5%, and the accuracy 91.7%. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy obtained with Tc-99m MIBI SMM for detecting axillary lymph node metastases were 83.3%, 86.1%, 80%, 88.6% and 85% respectively. It is suggested that Tc-99m MIBI SMM may be not only valuable in differentiating malignant lesions from benign nodular masses of breast, but also helpful in detecting axillary lymph node metastases of breast cancer.


Costs of Neonatal Intensive Care for Canadian Infants with Preterm Birth.
To develop and validate an itemized costing algorithm for in-patient neonatal intensive care unit (NICU) costs for infants born prematurely that can be used for quality improvement and health economic analyses. We sourced patient resource use data from the Canadian Neonatal Network database, with records from infants admitted to 30 tertiary NICUs in Canada. We sourced unit cost inputs from Ontario hospitals, schedules of benefits, and administrative sources. Costing estimates were generated by matching patient resource use data to the appropriate unit costs. All cost estimates were in 2017 Canadian dollars and assigned from the perspective of a provincial public payer. Results were validated using previous estimates of inpatient NICU costs and hospital case-cost estimates. We assigned costs to 27 742 infants born prematurely admitted from 2015 to 2017. Mean (SD) gestational age and birth weight of the cohort were 31.8 (3.5) weeks and 1843 (739) g, respectively. The median (IQR) cost of hospitalization before NICU discharge was estimated as $20 184 ($9739-51 314) for all infants; $11 810 ($6410-19 800) for infants born at gestational age of 33-36 weeks; $30 572 ($16 597-$51 857) at gestational age of 29-32 weeks; and $100 440 ($56 858-$159 3867) at gestational age of <29 weeks. Cost estimates correlated with length of stay (r = 0.97) and gestational age (r = -0.65). The estimates were consistent with provincial resource estimates and previous estimates from Canada. NICU costs for infants with preterm birth increase as gestation decreases and length of stay increases. Our cost estimates are easily accessible, transparent, and congruent with previous cost estimates.


Effects of aqueous suspensions of titanium dioxide nanoparticles on Artemia salina: assessment of nanoparticle aggregation, accumulation, and toxicity.
Aquatic stability and impact of titanium dioxide nanoparticles (TiO2 NPs, 10-30 nm) were investigated using Artemia salina. Acute exposure was conducted on nauplii (larvae) and adults in seawater in a concentration range from 10 to 100 mg/L TiO2 NPs for 24 and 96 h. Rapid aggregation occurred in all suspensions of TiO2 NPs to form micrometer size particles. Yet, both nauplii and adults accumulated the aggregates significantly. Average TiO2 content in nauplii ranged from 0.47 to 3.19 and from 1.29 to 4.43 mg/g in 24 and 96 h, respectively. Accumulation in adults was higher ranging from 2.30 to 4.19 and from 4.38 to 6.20 mg/g in 24 and 96 h, respectively. Phase contrast microscopy images revealed that Artemia were unable to excrete the particles. Thus, the TiO2 aggregates filled inside the guts. No significant mortality or toxicity occurred within 24 h at any dose. Lipid peroxidation levels characterized with malondialdehyde concentrations were not statistically different from those of the controls (p > 0.05). These results suggested that suspensions of the TiO2 NPs were nontoxic to Artemia, most likely due to the formation of benign TiO2 aggregates in water. In contrast, both mortality and lipid peroxidation increased in extended exposure to 96 h. Highest mortality occurred in 100 mg/L TiO2 NP suspensions; 18 % for nauplii and 14 % for adults (LC50 > 100 mg/L). These effects were attributed to the particle loading inside the guts leading to oxidative stress as a result of impaired food uptake for a long period of time.