Mechanics of the human hamstring muscles during sprinting.
An understanding of hamstring mechanics during sprinting is important for elucidating why these muscles are so vulnerable to acute strain-type injury. The purpose of this study was twofold: first, to quantify the biomechanical load (specifically, musculotendon strain, velocity, force, power, and work) experienced by the hamstrings across a full stride cycle; and second, to determine how these parameters differ for each hamstring muscle (i.e., semimembranosus (SM), semitendinosus (ST), biceps femoris long head (BF), biceps femoris short head (BF)). Full-body kinematics and ground reaction force data were recorded simultaneously from seven subjects while sprinting on an indoor running track. Experimental data were integrated with a three-dimensional musculoskeletal computer model comprised of 12 body segments and 92 musculotendon structures. The model was used in conjunction with an optimization algorithm to calculate musculotendon strain, velocity, force, power, and work for the hamstrings. SM, ST, and BF all reached peak strain, produced peak force, and formed much negative work (energy absorption) during terminal swing. The biomechanical load differed for each hamstring muscle: BF exhibited the largest peak strain, ST displayed the greatest lengthening velocity, and SM produced the highest peak force, absorbed and generated the most power, and performed the largest amount of positive and negative work. As peak musculotendon force and strain for BF, ST, and SM occurred around the same time during terminal swing, it is suggested that this period in the stride cycle may be when the biarticular hamstrings are at greatest injury risk. On this basis, hamstring injury prevention or rehabilitation programs should preferentially target strengthening exercises that involve eccentric contractions performed with high loads at longer musculotendon lengths.


Correlated bursts of activity in the neonatal hippocampus in vivo.
The behavior of immature cortical networks in vivo remains largely unknown. Using multisite extracellular and patch-clamp recordings, we observed recurrent bursts of synchronized neuronal activity lasting 0.5 to 3 seconds that occurred spontaneously in the hippocampus of freely moving and anesthetized rat pups. The influence of slow rhythms (0.33 and 0.1 hertz) and the contribution of both gamma-aminobutyric acid A-mediated and glutamate receptor-mediated synaptic signals in the generation of hippocampal bursts was reminiscent of giant depolarizing potentials observed in vitro. This earliest pattern, which diversifies during the second postnatal week, could provide correlated activity for immature neurons and may underlie activity-dependent maturation of the hippocampal network.


Development of strategies for SNP detection in RNA-seq data: application to lymphoblastoid cell lines and evaluation using 1000 Genomes data.
Next-generation RNA sequencing (RNA-seq) maps and analyzes transcriptomes and generates data on sequence variation in expressed genes. There are few reported studies on analysis strategies to maximize the yield of quality RNA-seq SNP data. We evaluated the performance of different SNP-calling methods following alignment to both genome and transcriptome by applying them to RNA-seq data from a HapMap lymphoblastoid cell line sample and comparing results with sequence variation data from 1000 Genomes. We determined that the best method to achieve high specificity and sensitivity, and greatest number of SNP calls, is to remove duplicate sequence reads after alignment to the genome and to call SNPs using SAMtools. The accuracy of SNP calls is dependent on sequence coverage available. In terms of specificity, 89% of RNA-seq SNPs calls were true variants where coverage is >10X. In terms of sensitivity, at >10X coverage 92% of all expected SNPs in expressed exons could be detected. Overall, the results indicate that RNA-seq SNP data are a very useful by-product of sequence-based transcriptome analysis. If RNA-seq is applied to disease tissue samples and assuming that genes carrying mutations relevant to disease biology are being expressed, a very high proportion of these mutations can be detected.


Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing.
Rous sarcoma virus was shown to induce in chicken embryo fibroblasts (CEF) a 4.1-kilobase mRNA (designated CEF-147) encoding a 603-amino acid protein. Analysis of the protein sequence showed that it shared 59% amino acid identity with sheep prostaglandin G/H synthase, the enzyme that catalyzes the rate-limiting steps in the production of prostaglandins. Significant differences, at both the protein and mRNA levels, existed between the src oncogene product-inducible prostaglandin synthase and the protein isolated and cloned from sheep seminal vesicle, suggesting that the src-inducible prostaglandin synthase may be a new form of the enzyme. A distinguishing feature of src-inducible prostaglandin synthase mRNA is its low abundance in nonproliferating chicken embryo fibroblasts and its relatively high abundance in src-transformed cells. Additionally, the majority of the src-inducible prostaglandin synthase RNA present in nonproliferating cells was found to be nonfunctional because of the presence of an unspliced intron that separated the signal peptide from the remainder of the protein. Upon mitogenic stimulation, this intron was removed, resulting in the induction of fully-spliced CEF-147 mRNA.


Comparison of residual NAPL source removal techniques in 3D metric scale experiments.
This study compared four treatment techniques for the removal of a toluene/n-decane as NAPL (Non Aqueous Phase Liquid) phase mixture in identical 1 cubic meter tanks filled with different kind of sand. These four treatment techniques were: oxidation with persulfate, surfactant washing with Tween80®, sparging with air followed by ozone, and thermal treatment at 80°C. The sources were made with three lenses of 26×26×6.5cm, one having a hydraulic conductivity similar to the whole tank and the two others a value 10 times smaller. The four techniques were studied after conditioning the tanks with tap water during approximately 80days. The persulfate treatment tests showed average removal of the contaminants but significant flux decrease if density effects are considered. Surfactant flushing did not show a highly significant increase of the flux of toluene but allowed an increased removal rate that could lead to an almost complete removal with longer treatment time. Sparging removed a significant amount but suggests that air was passing through localized gas channels and that the removal was stagnating after removing half of the contamination. Thermal treatment reached 100% removal after the target temperature of 80°C was kept during more than 10d. The experiments emphasized the generation of a high-spatial heterogeneity in NAPL content. For all the treatments the overall removal was similar for both n-decane and toluene, suggesting that toluene was removed rapidly and n-decane more slowly in some zones, while no removal existed in other zones. The oxidation and surfactant results were also analyzed for the relation between contaminant fluxes at the outlet and mass removal. For the first time, this approach clearly allowed the differentiation of the treatments. As a conclusion, experiments showed that the most important differences between the tested treatment techniques were not the global mass removal rates but the time required to reach 99% decrease in the contaminant fluxes, which were different for each technique.


ST1710-DNA complex crystal structure reveals the DNA binding mechanism of the MarR family of regulators.
ST1710, a member of the multiple antibiotic resistance regulator (MarR) family of regulatory proteins in bacteria and archaea, plays important roles in development of antibiotic resistance, a global health problem. Here, we present the crystal structure of ST1710 from Sulfolobus tokodaii strain 7 complexed with salicylate, a well-known inhibitor of MarR proteins and the ST1710 complex with its promoter DNA, refined to 1.8 and 2.10 A resolutions, respectively. The ST1710-DNA complex shares the topology of apo-ST1710 and MarR proteins, with each subunit containing a winged helix-turn-helix (wHtH) DNA binding motif. Significantly large conformational changes occurred upon DNA binding and in each of the dimeric monomers in the asymmetric unit of the ST1710-DNA complex. Conserved wHtH loop residues interacting with the bound DNA and mutagenic analysis indicated that R89, R90 and K91 were important for DNA recognition. Significantly, the bound DNA exhibited a new binding mechanism.


Consequences of winning: the role of gambling outcomes in the development of irrational beliefs.
The development and maintenance of gambling and problem gambling with its corresponding irrational beliefs may be fundamentally linked to patterns of wins and losses during electronic gaming machine (EGM) play. The current study investigated the extent to which irrational thoughts and erroneous perceptions of chance differed based on individual wins or losses. Undergraduate students (n = 45) completed questionnaires assessing irrational beliefs and perceptions of chance prior to and following EGM play with credits rather than money. It was found that players who lost reported a significantly greater decrease in irrational thoughts and erroneous perceptions of chance and significantly fewer superstitious beliefs than winning players following play. Future studies are needed to further investigate the relationship of winning to cognitive distortions to guide education and interventions.


Biomarkers indicate mixture toxicities of fluorene and phenanthrene with endosulfan toward earthworm (Eisenia fetida).
α-Endosulfan and some polycyclic aromatic compounds (PAHs) are persistent in the environment and can reach crop products via contaminated agricultural soils. They may even be present as mixtures in the soil and induce mixture toxicity in soil organisms such as earthworms. In this study, the combined toxicities of PAHs with α-endosulfan were determined in Eisenia fetida adults using an artificial soil system. α-Endosulfan and five PAHs were tested for their acute toxicity toward E. fetida in artificial soils. Only α-endosulfan, fluorene, and phenanthrene showed acute toxicities, with LC50 values of 9.7, 133.2, and 86.2 mg kg-1, respectively. A mixture toxicity assay was conducted using α-endosulfan at LC10 and fluorene or phenanthrene at LC50 in the artificial soils. Upon exposure to the mixture of fluorene and α-endosulfan, earthworms were killed in increasing numbers owing to their synergistic effects, while no other mixture showed any additional toxicity toward the earthworms. Along with the acute toxicity results, the biochemical and molecular changes in the fluorene- and phenanthrene-treated earthworms with or without α-endosulfan treatment demonstrated that enhancement of glutathione S-transferase activity was dependent on the addition of PAH chemicals, and the HSP70 gene expression increased with the addition of α-endosulfan. Taken together, these findings contribute toward understanding the adverse effects of pollutants when present separately or in combination with other types of chemicals.


Actions of prostaglandin F2alpha and prolactin on intercellular adhesion molecule-1 expression and monocyte/macrophage accumulation in the rat corpus luteum.
Expression of intercellular adhesion molecule-1 (ICAM-1) and the accumulation of monocytes/macrophages are inflammatory events that occur during PRL (PRL)-induced regression of the rat corpus luteum. Here we have compared the ability of prostaglandin F2alpha (PGF) and PRL to induce, in rat corpora lutea, inflammatory events thought to perpetuate luteal regression. Immature rats were ovulated with eCG-hCG and then hypophysectomized (Day 0), which resulted in a single cohort of persistent, functional corpora lutea. On Days 9-11, the rats received twice daily injections of saline, PGF (Lutalyse, 250 microg/injection), or PRL (312 microg/injection) to induce luteal regression. Surprisingly, luteal weight and plasma progestin concentrations (progesterone and 20alpha-dihydroprogesterone) did not differ between PGF-treated rats and controls; whereas both luteal weight and plasma progestins declined significantly in PRL-treated rats. Furthermore, corpora lutea of PGF-treated rats and controls contained relatively minimal ICAM-1 staining and few monocytes/macrophages. In contrast, but as expected, corpora lutea of PRL-treated rats stained intensely for ICAM-1 and contained numerous monocytes/macrophages. In an additional experiment, there was no indication that luteal prostaglandin F2alpha receptor mRNA diminished as a result of hypophysectomy. These findings suggest that prolactin, not PGF, induces the inflammatory events that accompany regression of the rat corpus luteum.


Radiation-induced mutation at tandem repeat DNA Loci in the mouse germline: spectra and doubling doses.
The spectra and dose response for mutations at expanded simple tandem repeat (ESTR) loci in the germline of male mice acutely exposed to low-LET X or gamma rays at pre-meiotic stages of spermatogenesis were compared in five strains of laboratory mice. Most mutation events involved the gain or loss of a relatively small number of repeat units, and the distributions of length changes were indistinguishable between the exposed and control males. Overall, a significant bias toward gains of repeats was detected, with approximately 60% of mutants showing gains. The values for ESTR mutation induction did not differ substantially between strains. The highest values of doubling dose were obtained for two genetically related strains, BALB/c and C.B17 (mean value 0.98 Gy). The estimates of doubling dose for three other strains (CBA/H, C57BL/6 x CBA/H F1 and 129SVJ x C57BL/6) were lower, with a mean value of 0.44 Gy. The dose response for ESTR mutation across all five strains was very close to that for the specific loci (Russell 7-locus test). The mechanisms of ESTR mutation induction and applications of this system for monitoring radiation-induced mutation in the mouse germline are discussed.


Whole-Brain N-Acetylaspartate Concentration Is Preserved during Mild Hypercapnia Challenge.
Although NAA is often used as a marker of neuronal health and integrity in neurologic disorders, its normal response to physiologic challenge is not well-established and its changes are almost always attributed exclusively to brain pathology. The purpose of this study was to test the hypothesis that the neuronal cell marker NAA, often used to assess neuronal health and integrity in neurologic disorders, is not confounded by (possibly transient) physiologic changes. Therefore, its decline, when observed by using (1)H-MR spectroscopy, can almost always be attributed exclusively to brain pathology. Twelve healthy young male adults underwent a transient hypercapnia challenge (breathing 5% CO2 air mixture), a potent vasodilator known to cause a substantial increase in CBF and venous oxygenation. We evaluated their whole-brain NAA by using nonlocalizing proton MR spectroscopy, venous oxygenation with T2-relaxation under spin-tagging MR imaging, CBF with pseudocontinuous arterial spin-labeling, and the cerebral metabolic rate of oxygen, during normocapnia (breathing room air) and hypercapnia. There was insignificant whole-brain NAA change (P = .88) from normocapnia to hypercapnia and back to normocapnia in this cohort, as opposed to highly significant increases: 28.0 ± 10.3% in venous oxygenation and 49.7 ± 16.6% in global CBF (P < 10(-4)); and a 6.4 ± 10.9% decrease in the global cerebral metabolic rate of oxygen (P = .04). Stable whole-brain NAA during normocapnia and hypercapnia, despite significant global CBF and cerebral metabolic rate of oxygen changes, supports the hypothesis that global NAA changes are insensitive to transient physiology. Therefore, when observed, they most likely reflect underlying pathology resulting from neuronal cell integrity/viability changes, instead of a response to physiologic changes.


Effective therapy for nephritis in (NZB x NZW)F1 mice with triptolide and tripdiolide, the principal active components of the Chinese herbal remedy Tripterygium wilfordii Hook F.
Triptolide and tripdiolide are thought to be active components of the Chinese antirheumatic herbal remedy Tripterygium wilfordii Hook F, which has been shown to be effective in treating murine lupus nephritis. This study was undertaken to examine the therapeutic effect of triptolide and tripdiolide on established lupus nephritis in (NZB x NZW)F1 mice. (NZB x NZW)F1 mice were treated with vehicle, triptolide, or tripdiolide for 15 weeks beginning at the age of 29 weeks (after the development of lupus nephritis). Body weight, proteinuria, and anti-double-stranded DNA (anti-dsDNA) antibodies were monitored, and the kidney and spleen were assessed histologically. Culture supernatants of spleen mononuclear cells were assayed for cytokines. By 28 weeks, most (NZB x NZW)F1 mice had developed lupus nephritis. Vehicle-treated mice exhibited progressive proteinuria, hypoalbuminemia, elevated blood urea nitrogen (BUN) levels, and evidence of severe nephritis. In contrast, proteinuria and BUN levels were significantly reduced in mice treated with either triptolide or tripdiolide as compared with those treated with vehicle. There was no hypoalbuminemia or apparent evidence of lupus nephritis in mice treated with either of the 2 diterpenoids. At 44 weeks of age, the survival rate in mice treated with vehicle (35.7%) was markedly lower than that in mice treated with either triptolide (87.5%) or tripdiolide (88.2%). The mean level of anti-dsDNA antibody in mice treated with tripdiolide was lower than that in the vehicle-treated mice upon completion of the treatment course. Production of tumor necrosis factor, interleukin-6, and monocyte chemoattractant protein 1 by spleen cells was also decreased after diterpenoid therapy. Therapy with triptolide or tripdiolide significantly ameliorated lupus nephritis in (NZB x NZW)F1 mice, reduced cytokine and chemokine production, and prolonged survival.


Efficacy of a single dose of trazodone hydrochloride given to cats prior to veterinary visits to reduce signs of transport- and examination-related anxiety.
OBJECTIVE To evaluate the efficacy of a single dose of trazodone for reducing anxiety in cats during transport to a veterinary hospital and facilitating handling during veterinary examination. DESIGN Double-blind, placebo-controlled, randomized crossover study. ANIMALS 10 healthy client-owned cats (2 to 12 years of age) with a history of anxiety during transport or veterinary examination. PROCEDURES Each cat was randomly assigned to first receive trazodone hydrochloride (50 mg) or a placebo PO. The assigned treatment was administered, and each cat was placed in a carrier and transported by car to a veterinary clinic, where it received a structured veterinary examination. Owners scored their cat's signs of anxiety before, during, and after transport and examination. The veterinarian also assessed signs of anxiety during examination. After a 1- to 3-week washout period, each cat received the opposite treatment and the protocol was repeated. RESULTS Compared with placebo, trazodone resulted in a significant improvement in the cats' signs of anxiety during transport. Veterinarian and owner scores for ease of handling during veterinary examination also improved with trazodone versus the placebo. No significant differences were identified between treatments in heart rate or other physiologic variables. The most common adverse event related to trazodone administration was signs of sleepiness. CONCLUSIONS AND CLINICAL RELEVANCE Oral administration of a single dose of trazodone to cats prior to a veterinary visit resulted in fewer signs of transport- and examination-related anxiety than did a placebo and was generally well tolerated by most cats. Use of trazodone in this manner may promote veterinary visits and, consequently, enhance cat welfare.


Micro-arrayed human embryonic stem cells-derived cardiomyocytes for in vitro functional assay.
The heart is one of the least regenerative organs in the body and any major insult can result in a significant loss of heart cells. The development of an in vitro-based cardiac tissue could be of paramount importance for many aspects of the cardiology research. In this context, we developed an in vitro assay based on human cardiomyocytes (hCMs) and ad hoc micro-technologies, suitable for several applications: from pharmacological analysis to physio-phatological studies on transplantable hCMs. We focused on the development of an assay able to analyze not only hCMs viability, but also their functionality. hCMs were cultured onto a poly-acrylamide hydrogel with tunable tissue-like mechanical properties and organized through micropatterning in a 20×20 array. Arrayed hCMs were characterized by immunofluorescence, GAP-FRAP analyses and live and dead assay. Their functionality was evaluated monitoring the excitation-contraction coupling. Micropatterned hCMs maintained the expression of the major cardiac markers (cTnT, cTnI, Cx43, Nkx2.5, α-actinin) and functional properties. The spontaneous contraction frequency was (0.83±0.2) Hz, while exogenous electrical stimulation lead to an increase up to 2 Hz. As proof of concept that our device can be used for screening the effects of pathological conditions, hCMs were exposed to increasing levels of H(2)O(2). Remarkably, hCMs viability was not compromised with exposure to 0.1 mM H(2)O(2), but hCMs contractility was dramatically suppressed. As proof of concept, we also developed a microfluidic platform to selectively treat areas of the cell array, in the perspective of performing multi-parametric assay. Such system could be a useful tool for testing the effects of multiple conditions on an in vitro cell model representative of human heart physiology, thus potentially helping the processes of therapy and drug development.


Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation.
The male-specific lethal dosage compensation complex (MSL-DCC) selectively assembles on the X chromosome in Drosophila males and activates gene transcription by twofold through histone acetylation. An MSL recognition element (MRE) sequence motif nucleates the initial MSL association, but how it is recognized remains unknown. Here, we identified the CXC domain of MSL2 specifically recognizing the MRE motif and determined its crystal structure bound to specific and nonspecific DNAs. The CXC domain primarily contacts one strand of DNA duplex and employs a single arginine to directly read out dinucleotide sequences from the minor groove. The arginine is flexible when bound to nonspecific sequences. The core region of the MRE motif harbors two binding sites on opposite strands that can cooperatively recruit a CXC dimer. Specific DNA-binding mutants of MSL2 are impaired in MRE binding and X chromosome localization in vivo. Our results reveal multiple dynamic DNA-binding modes of the CXC domain that target the MSL-DCC to X chromosomes.


Effects of dietary-induced hyperparathyroidism on the parathyroid hormone-receptor-adenylate cyclase system of canine kidney. Evidence for postreceptor mechanism of desensitization.
The present studies were designed to examine the consequences of chronic mild elevations of endogenous parathyroid hormone (PTH) in vivo on the PTH receptor-adenylate cyclase system of canine kidney cortex. Hyperparathyroidism was induced in normal dogs by feeding a diet low in calcium, high in phosphorus to the animals for a period of 6-9 wk. This maneuver resulted in a two to threefold increase in the plasma levels of carboxy-terminal immunoreactive PTH. This degree of hyperparathyroidism is similar to that seen in patients with hyperparathyroidism and normal renal function. After 6-9 wk on the diet the animals were killed and basolateral renal cortical membranes prepared for the study of the PTH receptor-adenylate cyclase system in vitro. The dietary hyperparathyroidism resulted in desensitization of the PTH-responsive adenylate cyclase (Vmax 3,648 +/- 654 pmol cyclic (c)AMP/mg protein per 30 min in hyperparathyroid animals vs. 5,303 +/- 348 in normal controls). The Kact (concentration of PTH required for half-maximal enzyme activation) was unchanged. However, PTH receptor binding (125I-norleucyl8-norleucyl18-tyrosinyl34, 125I[Nle8, Nle18, Tyr34] bPTH (1-34) NH2 as radioligand) was not different in the two groups of animals. Thus, dietary hyperparathyroidism resulted in an uncoupling of the PTH receptor-adenylate cyclase system. This defect was not corrected by guanyl nucleotides in vitro, and the effects of guanyl nucleotides on PTH binding and enzyme activation appeared normal. NaF-stimulated enzyme activity was reduced in the hyperparathyroid animals (8,285 +/- 607 pmol cAMP/mg protein per 30 min vs. 10,851 +/- 247 in controls). These data indicate that desensitization of the PTH-responsive adenylate cyclase system of canine kidney as a result of mild chronic elevations of endogenous PTH is due to a postreceptor defect, demonstrable by NaF activation, not corrected by guanyl nucleotides, leading to abnormal PTH-receptor adenylate cyclase coupling.


Single nucleotide polymorphisms affect both cis- and trans-eQTLs.
Single nucleotide polymorphisms (SNPs) between microarray probes and RNA targets can affect the performance of expression array by weakening the hybridization. In this paper, we examined the effect of the SNPs on Affymetrix GeneChip probe set summaries and the expression quantitative trait loci (eQTL) mapping results in two eQTL datasets, one from mouse and one from human. We showed that removing SNP-containing probes significantly changed the probe set summaries and the more SNP-containing probes we removed the greater the change. Comparison of the eQTL mapping results between with and without SNP-containing probes showed that less than 70% of the significant eQTL peaks were concordant regardless of the significance threshold. These results indicate that SNPs do affect both probe set summaries and eQTLs (both cis and trans), thus SNP-containing probes should be filtered out to improve the performance of eQTL mapping.


Identification of synaptosomal proteins binding to monomeric and oligomeric α-synuclein.
Monomeric α-synuclein (αSN) species are abundant in nerve terminals where they are hypothesized to play a physiological role related to synaptic vesicle turn-over. In Parkinson's disease (PD) and dementia with Lewy body (DLB), αSN accumulates as aggregated soluble oligomers in terminals, axons and the somatodendritic compartment and insoluble filaments in Lewy inclusions and Lewy neurites. The autosomal dominant heritability associated to mutations in the αSN gene suggest a gain of function associated to aggregated αSN. We have conducted a proteomic screen to identify the αSN interactome in brain synaptosomes. Porcine brain synaptosomes were fractionated, solubilized in non-denaturing detergent and subjected to co-immunoprecipitation using purified recombinant human αSN monomers or oligomers as bait. The isolated αSN binding proteins were identified with LC-LTQ-orbitrap tandem mass spectrometry and quantified by peak area using Windows client application, Skyline Targeted Proteomic Environment. Data are available via ProteomeXchange with identifier PXD001462. To quantify the preferential binding an average fold increase was calculated by comparing binding to monomer and oligomer. We identified 10 proteins preferentially binding monomer, and 76 binding preferentially to oligomer and a group of 92 proteins not displaying any preferred conformation of αSN. The proteomic data were validated by immunoprecipitation in both human and porcine brain extracts using antibodies against monomer αSN interactors: Abl interactor 1, and myelin proteolipid protein, and oligomer interactors: glutamate decarboxylase 2, synapsin 1, glial fibrillary acidic protein, and VAMP-2. We demonstrate the existence of αSN conformation selective ligands and present lists of proteins, whose identity and functions will be useful for modeling normal and pathological αSN dependent processes.


Static cold storage preservation of ischemically damaged kidneys. a comparison between IGL-1 and UW solution.
Especially in damaged organs, adequate organ preservation is critically important to maintain viability. Institut Georges Lopez-1 (IGL-1) is a new preservation solution, with an extracellular sodium/potassium ratio and polyethylene glycol as a colloid. The influence of warm and cold ischemia was evaluated in a rat Lewis-Lewis transplant model with a follow up of 14 days. Eight groups of donation after cardiac death donor kidneys were studied with warm ischemia of 0 and 15 min followed by 0- or 24-h cold storage (CS) preservation in IGL-1 or UW-CSS. Blood was collected daily during the first week and at day 14. Recipients were placed in metabolic cages at day 4 and 14 after transplantation allowing urine collection and adequate measurement of glomerular filtration rate. Focussing on inflammation, reactive oxygen species production, proximal tubule damage, proteinuria, histology, and renal function after transplantation we could not show any relevant difference between IGL-1 and UW-CSS. Furthermore, the combination of 15-min warm ischemia and by 24-h cold ischemia did not result in life sustaining kidney function after transplantation, irrespective of the used solution. In the present experiment, static CS preservation of ischemically damaged rat kidneys in either IGL-1 or UW-CSS rendered equal results after transplantation.


Emergence of CTX-M Group 1-ESBL producing Klebsiella pneumonia from a tertiary care centre in Karachi, Pakistan.
Extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae have been reported previously from Pakistan but the genotypic characteristics of these enzymes is not known. Hence the aim of the study was first to characterise the genotypic content of these beta-lactamases and secondly to assess the clonal relationship of these isolates. We analysed 65 non-duplicate ESBL positive, K. pneumoniae isolates prospectively collected based on phenotype as detected using the two-disc method. Isolates were collected from different sources: blood cultures (46.15%; n = 30); tracheal aspirates (24.6%; n = 16); urine (10.7%; n = 7); wound swabs, pus and tissue (18.4%; n = 12). ESBL production was confirmed by the ESBL E-test method and the presence of the blaCTX-M encoding genes was confirmed by polymerase chain reaction. The clonal relationship of clinical isolates was studied by Pulsed Field Gel Electrophoresis. The results showed that 93.84% (n = 61) isolates of K. pneumoniae were positive for the blaCTX-M-1 group. One isolate showed PCR signals for blaCTX-M-25 group. None of our isolates were positive for CTX-M groups 2, 8 and 9. The majority of blaCTX-M positive isolates were genetically unrelated and no epidemic clones were identified. This study reports the emergence of CTX-M groups 1 and 25 producing isolates of K. pneumoniae with genetic diversity in Karachi, Pakistan.


Insulin resistance postburn: underlying mechanisms and current therapeutic strategies.
The profound hypermetabolic response to burn injury is associated with insulin resistance and hyperglycemia, significantly contributing to the incidence of morbidity and mortality in this patient population. These responses are present in all trauma, surgical, or critically ill patients, but the severity, length, and magnitude is unique for burn patients. Although advances in therapeutic strategies to attenuate the postburn hypermetabolic response have significantly improved the clinical outcome of these patients during the past years, therapeutic approaches to overcome stress-induced hyperglycemia have remained challenging. Intensive insulin therapy has been shown to significantly reduce morbidity and mortality in critically ill patients. High incidence of hypoglycemic events and difficult blood glucose titrations have led to investigation of alternative strategies, including the use of metformin, a biguanide, or fenofibrate, a peroxisome proliferator-activated receptor (PPAR)-gamma agonist. Nevertheless, weaknesses and potential side affects of these drugs reinforces the need for better understanding of the molecular mechanisms underlying insulin resistance postburn that may lead to novel therapeutic strategies further improving the prognosis of these patients. This review aims to discuss the mechanisms underlying insulin resistance induced hyperglycemia postburn and outlines current therapeutic strategies that are being used to modulate hyperglycemia after thermal trauma.


Association of plasma homocysteine with coronary artery calcification in different categories of coronary heart disease risk.
To Investigate the association of plasma homocystelne with coronary artery calcification (CAC) in strata based on 10-year risk of coronary heart disease (CHD) in a cohort enriched in persons with hypertension. Fasting plasma homocystelne was measured by liquid chromatography electrospray tandem mass spectrometry. Coronary artery calcification was measured noninvasively by electron beam computed tomography and CAC score calculated using the method of Agatston et al. The 10-year CHD risk was calculated based on the Framingham risk score. The association of homocysteine with log-transformed CAC score was assessed in the pooled sample and within each risk stratum by linear regression after adjustment for conventional risk factors. In the 1071 participants studied, homocysteine was associated with CAC quantity (P = .01) after adjustment for CHD risk factors (age, male sex, total and high-density lipoproteln cholesterol, diabetes, history of smoking, body mass Index, and systolic blood pressure), serum creatinine, and statin and hypertension medication use. When the association was assessed in strata based on 10-year CHD risk, homocysteine was significantly (P = .003) associated with CAC quantity in participants at Intermediate 10-year risk of CHD (6%-20%) independent of other risk factors but not in those at lower risk or higher risk. Plasma homocysteine is associated with quantity of CAC Independent of CHD risk factors. When studied in categories of 10-year CHD risk, the association was significant in participants at intermediate risk but not in those at low or high risk. Plasma homocysteine levels may have clinical utility as a marker of CHD risk in such individuals.


A Targeted Nanosystem for Detection of Inflammatory Diseases via Fluorescent/Optoacoustic Imaging and Therapy via Modulating Nrf2/NF-κB Pathways.
Inflammatory diseases are sometimes devastating and notoriously difficult to treat. Precisely modulating inflammatory signaling pathways is a promising approach for treating inflammatory diseases. Herein, a multifunctional nanosystem is developed for active targeting, activatable imaging and on-demand therapy against inflammatory diseases through modulating inflammatory pathways. A chromophore-drug dyad (QBS-FIS) is synthesized by linking a chromophore and a Nrf2 (nuclear factor E2-related factor) activator fisetin through boronate bond which serves as fluorescence quencher and ROS (reactive oxygen species)-responsive linker. QBS-FIS molecules form nanoparticles in water and are coated with macrophage cell membrane to ensure active targeting toward inflammation site. To further improve therapeutic efficacy, a NF-kB (nuclear-factor kappa-light-chain-enhancer of activated B cells) inhibitor thalidomide is co-encapsulated to afford the nanosystem (QBS-FIS&Thd@MM). Upon administration into mice, the nanosystem migrates to inflammatory site and pathological ROS therein cleaves the boronate bonds, thereby activating the chromophore for imaging liver/kidney inflammatory diseases for disease diagnosis and recovery evaluation via fluorescence and optoacoustic imaging as well as releasing the active drugs for treating acute liver inflammation through activating Nrf2 pathway and inhibiting NF-kB pathway. The 3D multispectral optoacoustic tomography imaging is applied to precisely locate the inflammatory foci in a spatiotemporal manner.


Racial discrimination, racial/ethnic segregation, and health behaviors in the CARDIA study.
Racial discrimination has been associated with unhealthy behaviors, but the mechanisms responsible for these associations are not understood and may be related to residential racial segregation. We investigated associations between self-reported racial discrimination and health behaviors before and after controlling for individual- and neighborhood-level characteristics; and potential effect modification of these associations by segregation. We used data from the longitudinal Coronary Artery Risk Development in Young Adults (CARDIA) study for 1169 African-Americans and 1322 whites. To assess racial discrimination, we used a four category variable to capture the extent and persistence of self-reported discrimination between examination at years 7 (1992-1993) and 15 (2000-2001). We assessed smoking status, alcohol consumption, and physical activity at year 20 (2005-2006). Segregation was examined as the racial/ethnic composition at the Census tract level. Discrimination was more common in African-Americans (89.1%) than in whites (40.0%). Living in areas with high percentage of blacks was associated with less reports of discrimination in African-Americans but more reports in whites. After adjustment for selected characteristics including individual- and neighborhood-level socioeconomic conditions and segregation, we found significant positive associations of discrimination with smoking and alcohol consumption in African-Americans and with smoking in whites. African-Americans experiencing moderate or high discrimination were more physically active than those reporting no discrimination. Whites reporting some discrimination were also more physically active than those reporting no discrimination. We observed no interactions between discrimination and segregation measures in African-Americans or whites for any of the three health behaviors. Racial discrimination may impact individuals' adoption of healthy and unhealthy behaviors independent of racial/ethnic segregation. These behaviors may help individuals buffer or reduce the stress of discrimination.


Population Pharmacokinetic and Exposure-Response Analysis of Weekly Teriparatide in Osteoporosis Patients.
Teriparatide is a potent therapeutic agent for the treatment of osteoporosis. One of the aims of this analysis was to develop a population pharmacokinetic (PPK) model to understand the pharmacokinetic characteristics of the once-weekly formulation of teriparatide. Another aim was to develop an exposure-response model to describe the relationship between change in bone mineral density (BMD) and teriparatide exposure after weekly subcutaneous administration. The PPK analysis showed that apparent total body clearance was significantly influenced by estimated creatinine clearance and the presence of osteoporosis. A data set consisting of lumbar spine BMD values for 513 osteoporosis patients whose area under the concentration-time curve (AUC) of teriparatide acetate was estimated by the developed PPK model was then compiled. Exposure-response analysis showed that the percentage change from baseline of BMD was well described by a function of the AUC of teriparatide acetate, time, and coadministration of alfacalcidol and a calcium preparation. The analysis indicated that AUC is an important parameter for predicting BMD response to once-weekly teriparatide in osteoporosis patients.


Extracellular Vesicles and Carried miRNAs in the Progression of Renal Cell Carcinoma.
The formation and maintenance of renal cell carcinomas (RCC) involve many cell types, such as cancer stem and differentiated cells, endothelial cells, fibroblasts and immune cells. These all contribute to the creation of a favorable tumor microenvironment to promote tumor growth and metastasis. Extracellular vesicles (EVs) are considered to be efficient messengers that facilitate the exchange of information within the different tumor cell types. Indeed, tumor EVs display features of their originating cells and force recipient cells towards a pro-tumorigenic phenotype. This review summarizes the recent knowledge related to the biological role of EVs, shed by renal tumor cells and renal cancer stem cells in different aspects of RCC progression, such as angiogenesis, immune escape and tumor growth. Moreover, a specific role for renal cancer stem cell derived EVs is described in the formation of the pre-metastatic niche. We also highlight the tumor EV cargo, especially the oncogenic miRNAs, which are involved in these processes. Finally, the circulating miRNAs appear to be a promising source of biomarkers in RCC.


Effects of fluid shear stress on polyelectrolyte multilayers by neutron scattering studies.
The structure of layer-by-layer (LbL) deposited nanofilm coatings consists of alternating polyethylenimine (PEI) and polystyrenesulfonate (PSS) films deposited on a single crystal quartz substrate. LbL-deposited nanofilms were investigated by neutron reflectomery (NR) in contact with water in the static and fluid shear stress conditions. The fluid shear stress was applied through a laminar flow of the liquid parallel to the quartz/polymer interface in a custom-built solid-liquid interface cell. The scattering length density profiles obtained from NR results of these polyelectrolyte multilayers (PEM), measured under different shear conditions, showed proportional decrease of volume fraction of water hydrating the polymers. For the highest shear rate applied (ca. 6800 s(-1)) the water volume fraction decreased by approximately 7%. The decrease of the volume fraction of water was homogeneous through the thickness of the film. Since there were not any significant changes in the total polymer thickness, it resulted in negative osmotic pressures in the film. The PEM films were compared with the behavior of thin films of thermoresponsive poly(N-isopropylacrylamide) (pNIPAM) deposited via spin-coating. The PEM and pNIPAM differ in their interactions with water molecules, and they showed opposite behaviors under the fluid shear stress. In both cases the polymer hydration was reversible upon the restoration of static conditions. A theoretical explanation is given to explain this difference in the effect of shear on hydration of polymeric thin films.


The use of photodynamic therapy to treat hidradenitis suppurativa a review and critical analysis.
Hidradenitis Suppurativa (HS) is an inflammatory disease that results in abscesses, keloids, and fistulas. Acne inversa is likely to result from aberrant cellular immunity and dysfunction of the hair follicle in which coagulase negative staphylococcus (CONS) and perhaps other bacteria appear e.g Corynebacterium sp.to play a role by creating biofilms and stimulating the immune system. One treatment that has been proposed for HS is photodynamic therapy. The cases series reported are small and not double blinded. As of October of 2104, 8 articles with 64 patients report success with photodynamic therapy using 5-aminolevulinic acid (PDT-ALA) or its methyl ester (PDT-MAL). One of these 8 reports noted superiority of the free methylene blue gel over niosomal methylene blue gel. Another report described success in a 27-patient trial using intralesional 5-aminolevulinic acid (ALA) in saline at a concentration of 1%. This was administered at a dose of 0.2 ml per cm3 and an HS fistula was irradiated by a continuous 630-nm laser diode through a 1-mm thick optical fiber to 1 Watt per cm3 for 3 minutes (180 Joules). However, 3 articles reported failure with PDT-ALA or pulse dye laser-mediated photodynamic therapy (PDL-PDT) and one article note 1 failure and 1 success. We suggest that it is the ability of PDT-ALA or PDT-MAL to break up the bio-film produced by CONS and other antibacterial effects that account for its success in treating HS in patients in whom bio-film plays a pivotal part of their pathogenesis. Other effects are also possible as well. Other mechanisms by which PDT may improve HS include cytotoxic effects, which cause selective cell necrosis, and immunomodulatory effects. The data suggests that if PDT is to be used, it should be with MAL or intralesional ALA. Note that there are a variety of causes of HS. These include hyperkeratosis of in the follicular infundibulum, aberrant cellular immunity, down regulations of defensins in stage III HS, and the infiltration of neutrophils, mast cells, plasma cells, and lymphocytes into the affected follicle, among others. However, it is likely that in individual cases one cause is primary and others secondary. In conclusion, PDT is not a first line treatment for HS but in some cases could be added as an adjuvant to therapies such as clindamycin and rifampin.


The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus micro- and macrovascular complications: avenues for a mechanistic-based therapeutic approach.
A growing body of evidence suggests that oxidative stress plays a key role in the pathogenesis of micro- and macrovascular diabetic complications. The increased oxidative stress in subjects with type 2 diabetes is a consequence of several abnormalities, including hyperglycemia, insulin resistance, hyperinsulinemia, and dyslipidemia, each of which contributes to mitochondrial superoxide overproduction in endothelial cells of large and small vessels as well as the myocardium. The unifying pathophysiological mechanism that underlies diabetic complications could be explained by increased production of reactive oxygen species (ROS) via: (1) the polyol pathway flux, (2) increased formation of advanced glycation end products (AGEs), (3) increased expression of the receptor for AGEs, (4) activation of protein kinase C isoforms, and (5) overactivity of the hexosamine pathway. Furthermore, the effects of oxidative stress in individuals with type 2 diabetes are compounded by the inactivation of two critical anti-atherosclerotic enzymes: endothelial nitric oxide synthase and prostacyclin synthase. Of interest, the results of clinical trials in patients with type 2 diabetes in whom intensive management of all the components of the metabolic syndrome (hyperglycemia, hypercholesterolemia, and essential hypertension) was attempted (with agents that exert a beneficial effect on serum glucose, serum lipid concentrations, and blood pressure, respectively) showed a decrease in adverse cardiovascular end points. The purpose of this review is (1) to examine the mechanisms that link oxidative stress to micro- and macrovascular complications in subjects with type 2 diabetes and (2) to consider the therapeutic opportunities that are presented by currently used therapeutic agents which possess antioxidant properties as well as new potential antioxidant substances.


Environmental process descriptors for TNT, TNT-related compounds and picric acid in marine sediment slurries.
Process descriptors were determined for picric acid, TNT, and the TNT-related compounds 2,4DNT, 2,6DNT, 2ADNT, 4ADNT, 2,4DANT, 2,6DANT, TNB and DNB in marine sediment slurries. Three marine sediments of various physical characteristics (particle size ranging from 15 to >90% fines and total organic carbon ranging from <0.10 to 3.60%) were kept in suspension with 20ppt saline water. Concentrations of TNT and its related compounds decreased immediately upon contact with the marine sediment slurries, with aqueous concentrations slowly declining throughout the remaining test period. Sediment-water partition coefficients could not be determined for these compounds since solution phase concentrations were unstable. Kinetic rates and half-lives were influenced by the sediment properties, with the finer grained, higher organic carbon sediment being the most reactive. Aqueous concentrations of picric acid were very stable, demonstrating little partitioning to the sediments. Degradation to picramic acid was minimal, exhibiting concentrations at or just above the detection limit.


Rapid trachoma assessment in Kersa District, Southwest Ethiopia.
Trachoma is the leading cause of infectious blindness worldwide. Though trachoma can be treated with antibiotics (active trachoma) or surgery (trachomatous trichiasis), it is still endemic in most parts of Ethiopia. Despite the prevalence of this infectious disease in different parts of the country, district level data is lacking. This study was thus conducted to assess the prevalence estimate of trachoma and its risk factors in Kersa District, Southwest Ethiopia. A community based cross sectional Rapid Assessment of Trachoma was conducted using a WHO guideline. Six sub-districts were selected from Kersa District based on primary high risk assessment and from each sub-district; 21-27 households were randomly selected. Active trachoma for children aged 1-9 years, trachomatous trichiasis for people above 15 years old and environmental risk factors for trachoma were assessed. Data were analyzed using SPSS version 16. The overall prevalence estimate of active trachoma was 25.2% (95% CI: 20.7-30.4%). Forty three percent of children had unclean faces, 11.5% of households had water source at more than half hour walking distance, 18.2% did not have functional latrine, and 95.3% of the households had solid waste disposal within a distance of 20 meters. Households with environmental risk factors were at an increased risk to active trachoma, but the association was not statistically significant (p>0.05). The prevalence estimate of trachomatous trichiasis inclusive of "trachoma suspects" was 4.5%. Trachoma is endemic in Kersa District with active trachoma being a public health problem in the studied sub-districts. Hence, SAFE strategy should be implemented.


Extensive venous thrombosis in a healthy young man with a short inferior vena cava syndrome treated successfully with rivaroxaban.
We report a case of an incidental finding of congenital absence of the intrahepatic segment of the inferior vena cava (IVC) complicated by extensive bilateral deep venous thrombosis (DVT) with significant oedema following a long-distance road trip. Initially the patient failed treatment with standard anticoagulation therapy with enoxaparin and warfarin. However, he has responded to the new oral antifactor-Xa anticoagulant (rivaroxaban). Within a few days, rivaroxaban improved the oedema and DVT. The significant features of this case are the unusual presentation, the poor response to initial standard anticoagulation therapy and the beneficial outcomes when managed with the novel new anticoagulant. The patient has continued the new treatment regularly for the last 12 months with good toleration and without side effects. This report presents the findings, management and outcomes in a case of extensive bilateral DVT in a previously healthy young man who was found to have a congenital short IVC.


Impact of a web-based module on trainees' ability to interpret neonatal cranial ultrasound.
Accurate interpretations of neonatal cranial ultrasound (CUS) studies are essential skills for physicians in neonatal intensive care units (NICUs) in order to properly diagnose and manage brain injury. However, these skills are not formally taught to pediatric and neonatal-perinatal medicine (NPM) trainees in Canada. Therefore, our study describes the design, implementation, and evaluation of a new web-based learning (WBL) module that focuses on teaching these skills. Trainees' needs assessment survey, sent to all NPM and pediatrics trainees (n = 62), concluded that most of them feel uncomfortable with their ability to interpret CUS, highlighting the need for a new educational intervention. The needs assessment informed the development of the WBL module, which we evaluated using questionnaires and pre-and post-testing methods to measure participants' satisfaction, knowledge gain, skills development, and behaviour changes. Only trainees rotating through the NICU over 6 months (n = 23) were invited to participate in all the evaluation steps. We used the ADDIE instructional design model as a framework for this project. Respondents were very satisfied with the module, and their baseline knowledge increased significantly after studying and engaging with the module. The post-test score was 76% (p < 0.001) compared to the pre-test mean score of 42%. Tests for CUS interpretation skills assessment showed that 49% of pre-test answers were incorrect compared to 8% in the post-test (p < 0.001). Seventy-eight percent of trainees (n = 18) responded to a survey conducted a year after implementation, and 78% of the respondents (n = 14) reported that they still used these skills and shared this knowledge with junior trainees. A WBL module for teaching neonatal CUS interpretation considerably improved trainees' knowledge and enhanced their skills in interpreting neonatal CUS.


Relationship between tongue pressure and dysphagia in stroke patients.
Although poststroke dysphagia is an important issue for determining prognosis, the pathophysiology of oral-phase dysphagia has yet to be clarified due to a lack of adequate devices and protocols. The present study investigated the relationships between swallowing pressure production by the tongue and dysphagia in stroke patients using a newly developed method of tongue pressure measurement with a sensor sheet system. Subjects were 64 stroke patients, including 30 patients with dysphagia. A T-shaped sensor sheet with 5 measuring points was attached to the hard palate to record tongue pressure while swallowing 5 ml of water. The average maximal magnitude and incidence of abnormalities such as asynchronous and/or polyphasic patterns in tongue pressure waves in 5 locations were compared between patients with and without dysphagia. The average maximal tongue pressure was significantly smaller in patients with dysphagia than in those without dysphagia. Asynchronous and polyphasic patterns showed a sensitivity of 63 and 87%, and a specificity of 91 and 71%, respectively, for identifying patients with dysphagia. Tongue pressure production during swallowing appears closely related to poststroke dysphagia. Tongue pressure measurement appears useful for evaluating the pathophysiology of oral-phase dysphagia in stroke patients.


Modelling antecedents of blood donation motivation among non-donors of varying age and education.
Understanding blood donation motivation among non-donors is prerequisite to effective recruitment. Two studies explored the psychological antecedents of blood donation motivation and the generalisability of a model of donation motivation across groups differing in age and educational level. An older well-educated population and a younger less well-educated population were sampled. The studies assessed the role of altruism, fear of blood/needles and donation-specific cognitions including attitudes and normative beliefs derived from an extended theory of planned behaviour (TPB). Across both samples, results showed that affective attitude, subjective norm, descriptive norm, and moral norm were the most important correlates of blood donation intentions. Self-efficacy was more important among the younger less well-educated group. Altruism was related to donation motivation but only indirectly through moral norm. Similarly, fear of blood/needles only had an indirect effect on motivation through affective attitude and self-efficacy. Additional analyses with the combined data set found no age or education moderation effects, suggesting that this core model of donation-specific cognitions can be used to inform future practical interventions recruiting new blood donors in the general population.


Diffuse optical signals in response to peripheral nerve stimulation reflect skeletal muscle kinematics.
Previously we have reported a near-infrared optical response in the region occupied by a peripheral nerve that is distal to the site of electrical stimulation of that peripheral nerve. This "intermediate" signal is vascular in nature but its biological origin not been elucidated. In the present study, an animal model of the signal has been created and our human studies expanded to directly investigate the contribution of non-artifactual vascular motion induced by muscle contraction to the biological origin of this signal. Under non-invasive conditions during stimulation of the exposed sciatic nerve of the Sprague-Dawley rat, optical responses are robust. These signals can be abolished both pharmacologically and surgically using methods that eliminate muscle motion while leaving the electrophysiological health of the nerve intact. In human studies, signals that are elicited on stimulation of nerves containing motor axons, both within and outside the predicted imaging volume of the spectrometer, have similar temporal characteristics of those previously observed. Moreover, stimulation of sensory nerves alone does not elicit an optical response. These results strongly suggest that the intermediate signals are derived from stimulus-induced muscle contraction (whether via an innervating nerve or by direct stimulation) causing translational vascular motion within the optically interrogated region.


Dose dependence of acetylcholinesterase activity in neuroblastoma cells exposed to modulated radio-frequency electromagnetic radiation.
Radio-frequency electromagnetic radiation (RFR) at 915 and 147 MHz, when sinusoidally amplitude modulated (AM) at 16 Hz, has been shown to enhance release of calcium ions from neuroblastoma cells in culture. The dose-response relation is unusual, consisting of two power-density "windows" in which enhanced efflux occurs, separated by power-density regions in which no effect is observed. To explore the physiological importance of these findings, we have examined the impact of RFR exposure on a membrane-bound enzyme, acetylcholinesterase (AChE), which is intimately involved with the acetylcholine (ACh) neurotransmitter system. Neuroblastoma cells (NG108), exposed for 30 min to 147-MHz radiation, AM at 16 Hz, demonstrated enhanced AChE activity, as assayed by a procedure using 14C-labeled ACh. Enhanced activity was observed within a time window between 7.0 and 7.5 h after the cells were plated and only when the exposure occurred at power densities identified in a previous report as being effective for altering the release of calcium ions. Thus RFR affects both calcium-ion release and AChE activity in nervous system-derived cells in culture in a common dose-dependent manner.


Coherent dynamics of the charge density wave gap in tritellurides.
The dynamics of the transient electronic structure in the charge density wave (CDW) system RTe3 (R = rare-earth element) is studied using time- and angle-resolved photoemission spectroscopy (trARPES). Employing a three-pulse pump-probe scheme we investigate the effect of the amplitude mode oscillations on the electronic band structure and, in particular, on the CDW energy gap. We observe coherent oscillations in both lower and upper CDW band with opposite phases, whereby two dominating frequencies are modulating the CDW order parameter. This demonstrates the existence of more than one collective amplitude mode, in contrast to a simple Peierls model. Coherent control experiments of the two amplitude modes, which are strongly coupled in equilibrium, demonstrate independent control of the modes suggesting a decoupling of both modes in the transient photoexcited state.


Gender differences in evaluating social-sexual conduct in the workplace.
Qualitative interviews exploring gender differences in perceptions of sexual harassment were conducted with 100 full-time St. Louis area employees. Women more than men reported that telling dirty/sexual jokes was a non-harassing behavior, qualified behaviors as harassing when they happened in the workplace, and considered behaviors as non-harassing when the man's intentions were not harmful. Men more than women reported that requesting a date was a non-harassing behavior, qualified behaviors as harassing when the woman did not welcome the behavior, and considered behaviors as non-harassing when they did not violate workplace norms. Logistic regression analysis predicted the respondent gender with 86% accuracy. Finally, concept mapping suggested that when women think about harassers they are concerned with power and social aptitude, while men seem to be more concerned about the responsibility and psychological adjustment of perpetrators of sexual harassment. When women think about victims of harassment they are concerned with a woman's assertiveness and work effectiveness, while men are more concerned with the psychological state of the woman and how provocative she is when they think about victims of sexual harassment.


Modulating effects of WT1 on interferon-β-vitamin D association in MS.
To investigate whether those genes involved in the vitamin D pathway modulate the relationship between 25-hydroxyvitamin D (25(OH)D) and IFN-β, the relationship between IFN-β and sun in predicting 25(OH)D, and the interaction between IFN-β and 25(OH)D in modulating relapse risk in patients with MS. Prospective cohort study of 169 participants with MS and genotype data followed 2002-2005. Gene-IFN-β and gene-IFN-β-sun interactions predicting 25(OH)D evaluated by multilevel mixed-effects linear regression. Gene-IFN-β interactions with 25(OH)D in modulating in relapse risk assessed using survival analysis. The cohort was 71.6% female and of mean age 47.8. Two-independent intronic genotyped SNPs (rs10767935 and rs5030244) in WT1 significantly modified the IFN-β-25(OH)D association after adjustment (P(interaction) = 0.001, 0.0002; P(adj) = 0.003, 0.006, respectively). There was a marked difference in the interaction between self-reported sun exposure and IFN-β in predicting 25(OH)D by level of rs10767935, although this did not reach statistical significance. No SNPs modified the interaction between IFN-β and 25(OH)D in predicting relapse. We have demonstrated that two-independent SNPs (rs10767935 and rs5030244) in WT1 modified the IFN-β-25(OH)D association in patients with MS. Some evidence was shown for a difference in the sun-IFN-β-25(OH)D association by level of rs10767935. These findings indicate that WT1 variants may play a role in altering the effects of IFN-β on vitamin D in MS.


PCR assay for improved diagnostics of epitheliotropic disease virus (EEDV) in lake trout Salvelinus namaycush.
Epizootic epitheliotropic disease virus (EEDV) has caused catastrophic losses among hatchery-reared juvenile lake trout Salvelinus namaycush since the early 1980s and remains a major impediment to lake trout restoration in the Great Lakes basin of the USA. Although EEDV has been tentatively designated as a herpesvirus based upon morphological criteria, further characterization of the virus and development of improved detection methods have been hampered by the inability to propagate the virus in cell culture. Recently obtained sequence data for a region of the putative terminase gene from EEDV as well as the related Salmonid herpesvirus 1 and 2 have permitted the development of a polymerase chain reaction (PCR) assay for specific detection of EEDV. The new EEDV PCR demonstrated both an excellent analytic sensitivity and specificity and detected viral DNA as present in the skin of lake trout during periods of active viral outbreaks. In addition, EEDV DNA was detected among healthy appearing juveniles and in the ovarian fluids of spawning adults. Here we describe the development and initial validation steps of the EEDV PCR as a replacement for current diagnostic methods that require virus extraction from the skin, partial purification by isopycnic centrifugation, and visualization of negatively-stained virions by electron microscopy.


UK Fixation of Distal Tibia Fractures (UK FixDT): protocol for a randomised controlled trial of 'locking' plate fixation versus intramedullary nail fixation in the treatment of adult patients with a displaced fracture of the distal tibia.
The treatment of displaced, extra-articular fractures of the distal tibia remains controversial. These injuries are difficult to manage due to limited soft tissue cover, poor vascularity of the area and proximity to the ankle joint. Surgical treatment options are expanding and include locked intramedullary nails, plate and screw fixation and external fixator systems. The nail and plate options are most commonly used in the UK, but controversy exists over which treatment is most clinically and cost-effective. In this multicentre randomised controlled trial we aim to assess ratings of disability 6 months postinjury in patients who have sustained a distal tibia fracture treated with either an intramedullary nail or plate and locking screw fixation. Adult patients presenting at trial centres with an acute fracture of the distal tibia will be considered for inclusion. A total of 320 patients will provide 90% power to detect a difference of 8 points in Disability Rating Index (DRI) score at 6 months at the 5% level. The randomisation sequence is stratified by trial centre and age, and administered via web-based service with 1:1 treatment allocation. Baseline demographic and pre-injury functional data and radiographs will be collected using the DRI, Olerud and Molander, and EuroQol EQ-5D questionnaire. Clinical assessment, early complications and radiographs will be recorded at 6-8 weeks. Functional outcome, health-related quality of life and resource use will be collected at 3, 6 and 12 months postoperatively. The main analysis will investigate differences in DRI 6 months postsurgery, between the two treatment groups, on an intention-to-treat basis. Tests will be two-sided and considered to provide evidence for a significant difference if p values are <0.05. NRES Committee West-Midlands, 6/11/2012 (ref:12/WM/0340). The results of the trial will be disseminated via peer-reviewed publications and presentations at relevant conferences. ISRCTN99771224.


Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation.
The effects of prolonged denervation, independent from those of prolonged axotomy, on the recovery of muscle function were examined in a nerve cross-anastomosis paradigm. The tibialis anterior muscle was denervated for various durations by cutting the common peroneal nerve before a freshly cut tibial nerve was cross-sutured to its distal stump. Nerve regeneration and muscle reinnervation were quantified by means of electrophysiological and histochemical methods. Progressively fewer axons reinnervated the muscle with prolonged denervation; for example, beyond 6 months the mean (+/- SE) motor unit number was 15 +/- 4, which was far fewer than that after immediate nerve suture (137 +/- 21). The poor regeneration after prolonged denervation is not due to inability of the long-term denervated muscle to accept reinnervation because each regenerated axon reinnervated three- to fivefold more muscle fibers than normal. Rather, it is due to progressive deterioration of the intramuscular nerve sheaths because the effects of prolonged denervation were simulated by forcing regenerating axons to grow outside the sheaths. Fewer regenerated axons account for reinnervation of less than 50% of the muscle fibers in each muscle and contribute to the progressive decline in muscle force. Reinnervated muscle fibers failed to fully recover from denervation atrophy: muscle fiber cross-sectional area being 1171 +/- 84 microns2 as compared to 2700 +/- 47 microns2 after immediate nerve suture. Thus, the primary cause of the poor recovery after long-term denervation is a profound reduction in the number of axons that successfully regenerate through the deteriorating intramuscular nerve sheaths. Muscle force capacity is further compromised by the incomplete recovery of muscle fibers from denervation atrophy.


The nature, origin and modification of insoluble organic matter in chondrites, the possibly interstellar source of Earth's C and N.
All chondrites accreted ~3.5 wt.% C in their matrices, the bulk of which was in a macromolecular solvent and acid insoluble organic material (IOM). Similar material to IOM is found in interplanetary dust particles (IDPs) and comets. The IOM accounts for almost all of the C and N in chondrites, and a significant fraction of the H. Chondrites and, to a lesser extent, comets were probably the major sources of volatiles for the Earth and the other terrestrial planets. Hence, IOM was both the major source of Earth's volatiles and a potential source of complex prebiotic molecules. Large enrichments in D and 15N, relative to the bulk solar isotopic compositions, suggest that IOM or its precursors formed in very cold, radiation-rich environments. Whether these environments were in the interstellar medium (ISM) or the outer Solar System is unresolved. Nevertheless, the elemental and isotopic compositions and functional group chemistry of IOM provide important clues to the origin(s) of organic matter in protoplanetary disks. IOM is modified relatively easily by thermal and aqueous processes, so that it can also be used to constrain the conditions in the solar nebula prior to chondrite accretion and the conditions in the chondrite parent bodies after accretion. Here we review what is known about the abundances, compositions and physical nature of IOM in the most primitive chondrites. We also discuss how the IOM has been modified by thermal metamorphism and aqueous alteration in the chondrite parent bodies, and how these changes may be used both as petrologic indicators of the intensity of parent body processing and as tools for classification. Finally, we critically assess the various proposed mechanisms for the formation of IOM in the ISM or Solar System.


Guideline for office spirometry in adults, 2012.
Office spirometry remains an integral part of a comprehensive respiratory evaluation and is used to categorise the nature, severity and progression of respiratory diseases and to measure response to treatment. These updated guidelines are aimed at improving the quality, standardisation and usefulness of office spirometry in South Africa. All equipment should have proof of validation regarding resolution and the system's linearity (consistency). Moreover, equipment must be calibrated daily and quality controlled. It is also important to have standard operating procedures in place, including the documentation of ambient conditions and infection control measures. Adequate spirometry relies on a competent operator, accurate equipment, standardised operating procedures, quality control and patient co-operation. The indication for spirometry in a particular patient should be unambiguous and should be documented. Subjects should be appropriately prepared for testing, and patient details must be documented. Forced vital capacity (FVC) manoeuvres (either closed or open circuit) must be performed strictly according to guidelines, and strict quality assurance methods should be in place, including acceptability criteria (for any given effort) and repeatability (between efforts). Testing should continue until at least 3 acceptable curves are produced (with 2 fulfilling repeatability criteria). Other indices are derived from these efforts. Test results must be categorised and graded according to current guidelines, taking into account the indication for the test and the appropriateness of reference values.


Evaluation of aquaporin-4 antibody assays.
Aquaporin-4 (AQP4) is a water channel protein that is most highly, but not exclusively, expressed in the central nervous system. In 2005 AQP4 was shown to be the antigenic target of neuromyelitis optica-immunoglobulin G (NMO-IgG, or AQP4-IgG), an antibody found specifically in patients with NMO and in formes frustes of NMO, such as longitudinally extensive transverse myelitis (LETM) or optic neuritis (ON). This discovery facilitated the clinical, pathological, and radiological distinction of NMO and the spectrum of NMO-related disorders from classical multiple sclerosis. In addition to its use as a diagnostic tool, AQP4-IgG predicts a high risk of relapse in patients with a clinically isolated syndrome of either LETM or ON. As disability in NMO is attack-related, early diagnosis and treatment are predicted to have a major effect on long-term disability. Thus, the importance of sensitive and specific assays to detect AQP4-IgG cannot be overstated. Both academic institutions and commercial companies have developed assays to identify AQP4-IgG in patients' sera or cerebrospinal fluid. Both AQP4 isoforms from different species have been used as the antigenic target in the form of frozen tissue sections in indirect immunofluorescence assays, partially purified protein for fluorescence immunoprecipitation assay, radioimmunoprecipita-tion assay or enzyme-linked immunosorbent assay, or transfected into cells for cell based assays or flow cytometry. We carried out a systematic review of the literature reporting different methodologies used to identify AQP4-IgG, examine whether longitudinal AQP4-IgG titers predict relapses in seropositive patients, and attempt to establish a reasonable timeframe for retesting negative serum samples.


Cardiovascular risk factors-using repeated cross-sectional surveys to assess time trends in socioeconomic inequalities in neighbouring countries.
This study compares trends in socioeconomic inequalities related to key cardiovascular risk factors in neighbouring countries Northern Ireland (NI) and the Republic of Ireland (RoI). Repeated cross-sectional studies. Population based. 3500-4000 in national surveys in NI and 5000-9000 in RoI, aged 20-69 years. Educational attainment was used as a socioeconomic indicator by which the magnitude and direction of trends in inequalities for smoking, diabetes, obesity and physical inactivity in NI and RoI were examined between 1997/1998 and 2007/2011. Gender-specific relative and absolute inequalities were calculated using the Relative Index of Inequality (RII) and Slope Index of Inequality (SII) for both countries. In both countries, the prevalence of diabetes and obesity increased whereas levels of smoking and physical inactivity decreased over time. In NI relative inequalities increased for obesity (RII 1.1 in males and 2.1 in females in 2010/2011) and smoking (RII 4.5 in males and 4.2 in females in 2010/2011) for both genders and absolute inequalities increased for all risk factors in men and increased for diabetes and obesity in women. In RoI greater inequality was observed in women, particularly for smoking (RII 2.8 in 2007) and obesity (RII 8.2 in 2002) and in men for diabetes (RII 3.2 in 2002). Interventions to reduce inequalities in risk factors, particularly smoking, obesity and diabetes are encouraged across both countries.


Identification of Novel Aldose Reductase Inhibitors from Spices: A Molecular Docking and Simulation Study.
Hyperglycemia in diabetic patients results in a diverse range of complications such as diabetic retinopathy, neuropathy, nephropathy and cardiovascular diseases. The role of aldose reductase (AR), the key enzyme in the polyol pathway, in these complications is well established. Due to notable side-effects of several drugs, phytochemicals as an alternative has gained considerable importance for the treatment of several ailments. In order to evaluate the inhibitory effects of dietary spices on AR, a collection of phytochemicals were identified from Zingiber officinale (ginger), Curcuma longa (turmeric) Allium sativum (garlic) and Trigonella foenum graecum (fenugreek). Molecular docking was performed for lead identification and molecular dynamics simulations were performed to study the dynamic behaviour of these protein-ligand interactions. Gingerenones A, B and C, lariciresinol, quercetin and calebin A from these spices exhibited high docking score, binding affinity and sustained protein-ligand interactions. Rescoring of protein ligand interactions at the end of MD simulations produced binding scores that were better than the initially docked conformations. Docking results, ligand interactions and ADMET properties of these molecules were significantly better than commercially available AR inhibitors like epalrestat, sorbinil and ranirestat. Thus, these natural molecules could be potent AR inhibitors.


Novel genetic tools that enable highly pure protein production in Trichoderma reesei.
Trichoderma reesei is an established protein production host with high natural capacity to secrete enzymes. The lack of efficient genome engineering approaches and absence of robust constitutive gene expression systems limits exploitation of this organism in some protein production applications. Here we report engineering of T. reesei for high-level production of highly enriched lipase B of Candida antarctica (calB) using glucose as a carbon source. Multiplexed CRISPR/Cas9 in combination with the use of our recently established synthetic expression system (SES) enabled accelerated construction of strains, which produced high amounts of highly pure calB. Using SES, calB production levels in cellulase-inducing medium were comparable to the levels obtained by using the commonly employed inducible cbh1 promoter, where a wide spectrum of native enzymes were co-produced. Due to highly constitutive expression provided by the SES, it was possible to carry out the production in cellulase-repressing glucose medium leading to around 4 grams per liter of fully functional calB and simultaneous elimination of unwanted background enzymes.


Partially coherent stable and spiral beams.
Stable and spiral coherent beams, which do not change the form of their intensity distribution apart from possible scaling and rotation during propagation and therefore possess self-healing properties, are widely applied in science and technology. On the other hand, it has been found that partially coherent light often provides better output than coherent light. Here we consider two methods for the design and experimental generation of partially coherent stable and spiral beams.


Part 3 of a 4-part series. Lip and common dental care products: trends and alternatives: data from the American Contact Alternatives Group.
To provide updated data on the use of ingredients that are common potential contact allergens in several categories of lip and oral products. To identify useful alternative products with few or no common contact allergens. In November 2009, the full ingredient lists of 5,416 skin, hair, and cosmetic products marketed by the CVS pharmacy chain was copied from CVS.com into Microsoft Word format for analysis. Computer searches were made in Microsoft Word using search/replace and sorting functions to accurately identify the presence of specific allergens in each website product. Percentages of American Contact Dermatitis Society core series allergens (and other common preservatives) were calculated. The use of American Contact Dermatitis Society core series allergens (and other preservatives) in various categories of lip and oral products are reported. Data on allergens and alternatives for lip and oral products is not widely published. This article reviews some of the common potential allergens in lip liners, lipsticks, lip moisturizers, mouthwashes, and toothpastes. Suitable available alternative products for patients with contact allergy are listed.


Food preparation and purchasing roles among adolescents: associations with sociodemographic characteristics and diet quality.
To describe adolescent involvement in preparing and shopping for food and examine if extent of involvement is related to diet quality. Cross-sectional study design. Past week frequency of involvement in preparing and shopping for food was self-reported on the Project EAT (Eating Among Teens) survey. Dietary intake was assessed using the Youth/Adolescent Food Frequency Questionnaire. Middle school and high school students from Minneapolis/St Paul, MN, public schools. Associations between involvement and sociodemographic characteristics were examined using cross tabulations. General linear modeling was used to compare dietary intakes of adolescents across different levels of involvement in preparing and shopping for food. The majority of adolescents reported helping prepare dinner (68.6%) and nearly half reported shopping for groceries (49.8%) at least once during the past week. Greater involvement in these food tasks was related to sex (female), grade level (middle school), race (Asian American), socioeconomic status (low), family meal frequency (high), and weight status (overweight). Frequency of preparing food was related to lower intakes of fat (P<0.01) and higher intakes of fruits and vegetables, fiber, folate, and vitamin A. Preparing was related to lower intakes of carbonated beverages among female adolescents (P<0.01) and lower intakes of fried foods among male adolescents (P<0.01). In contrast, food shopping frequency was related to greater consumption of fried foods among female adolescents (P<0.01). Adolescents should be encouraged to help with meal preparation and may benefit from interventions and programs that teach skills for cooking and making healthful purchasing decisions.


Quantifying admissible undersampling for sparsity-exploiting iterative image reconstruction in X-ray CT.
Iterative image reconstruction with sparsity-exploiting methods, such as total variation (TV) minimization, investigated in compressive sensing claim potentially large reductions in sampling requirements. Quantifying this claim for computed tomography (CT) is nontrivial, because both full sampling in the discrete-to-discrete imaging model and the reduction in sampling admitted by sparsity-exploiting methods are ill-defined. The present article proposes definitions of full sampling by introducing four sufficient-sampling conditions (SSCs). The SSCs are based on the condition number of the system matrix of a linear imaging model and address invertibility and stability. In the example application of breast CT, the SSCs are used as reference points of full sampling for quantifying the undersampling admitted by reconstruction through TV-minimization. In numerical simulations, factors affecting admissible undersampling are studied. Differences between few-view and few-detector bin reconstruction as well as a relation between object sparsity and admitted undersampling are quantified.


Influence of shoulder abduction and lateral trunk tilt on peak elbow varus torque for college baseball pitchers during simulated pitching.
Elbow varus torque is a primary factor in the risk of elbow injury during pitching. To examine the effects of shoulder abduction and lateral trunk tilt angles on elbow varus torque, we conducted simulation and regression analyses on 33 college baseball pitchers. Motion data were used for computer simulations in which two angles-shoulder abduction and lateral trunk tilt-were systematically altered. Forty-two simulated motions were generated for each pitcher, and the peak elbow varus torque for each simulated motion was calculated. A two-way analysis of variance was performed to analyze the effects of shoulder abduction and trunk tilt on elbow varus torque. Regression analyses of a simple regression model, second-order regression model, and multiple regression model were also performed. Although regression analyses did not show any significant relationship, computer simulation indicated that the peak elbow varus torque was affected by both angles, and the interaction of those angles was also significant. As trunk tilt to the contralateral side increased, the shoulder abduction angle producing the minimum peak elbow varus torque decreased. It is suggested that shoulder abduction and lateral trunk tilt may be only two of several determinants of peak elbow varus torque.


c-Met inhibitor synergizes with tumor necrosis factor-related apoptosis-induced ligand to induce papillary thyroid carcinoma cell death.
The Met receptor tyrosine kinase is overexpressed and/or activated in variety of human malignancies. Previously we have shown that c-Met is overexpressed in Middle Eastern papillary thyroid carcinoma (PTC) and significantly associated with an aggressive phenotype, but its role has not been fully elucidated in PTC. The aim of this study was to determine the functional link between the c-Met/AKT signaling pathway and death receptor 5 (DR5) in a large cohort of PTC in a tissue microarray format followed by functional studies using PTC cell lines and nude mice. Our data showed that high expressions of p-Met and DR5 were significantly associated with an aggressive phenotype of PTC and correlated with BRAF mutation. Treatment of PTC cell lines with PHA665752, an inhibitor of c-Met tyrosine kinase, inhibited cell proliferation and induced apoptosis via the mitochondrial pathway in PTC cell lines. PHA665752 treatment or expression of c-Met small interfering (si)RNA resulted in dephosphorylation of c-Met, AKT and its downstream effector molecules. Furthermore, PHA665752 treatment upregulated DR5 expression via generation of reactive oxygen species in PTC cell lines, and synergistically potentiated death receptor-induced apoptosis with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Finally, cotreatment with PHA665752 and TRAIL caused more pronounced effects on PTC xenograft tumor growth in nude mice. Our data suggest that the c-Met/AKT pathway may be a potential target for therapeutic intervention for treatment of PTC refractory to conventionally therapeutic modalities.


Utilizing a Novel Mobile Health "Selfie" Application to Improve Compliance to Iron Chelation in Pediatric Patients Receiving Chronic Transfusions.
Iron chelation therapy can prevent iron overload for pediatric patients with sickle cell disease and β-thalassemia major; however, adherence is suboptimal. Therefore, we developed an intensive training program (ITP), to improve medication management and disease knowledge. The objectives were to determine feasibility of the ITP and its preliminary impact on adherence, disease knowledge, and health outcomes. Pediatric patients were recruited to participate in the ITP over a 90-day period and were followed for 6 months. The ITP consisted of 3 components: (1) provider-led education modules; (2) patient recording daily videos of at-home medication administration; and (3) provider feedback through video messages through the ITP app. Eleven patients participated (mean=12.4 y). Initially, patients endorsed high satisfaction and ease of use and tracked their medication usage 81% (24 out of 30) of days. At 90 days, adherence rates remained consistent (80%) and disease knowledge retention was high (96%). At 6 months, participants exhibited a clinically relevant decrease in serum ferritin, which trended toward statistical significance (P=0.068). Medication possession ratio did not significantly increase (0.65 to 0.72; not significant). The mobile ITP was feasibly implemented in a clinical setting; in addition, high levels of compliance, disease knowledge retention, and acceptance encourage larger studies evaluating mobile health technology to improve child health parameters.


Glucose absorption and utilization by rat embryos.
There is little doubt that glucose plays a significant nutritional role in early somite embryos. The high glucose utilization of anaerobic glycolysis drops as the activity of the Kreb's cycle and terminal electron transport increase. Concurrently, maturation of mitochondrial cristae and dependence on oxygen supply are taking place. The neuroepithelium of the early somite rat embryo responds in vitro during culture by microvilliar lengthening when exposed to glucose levels of 50 mg/dl or more. At lower glucose concentrations both in whole embryo culture and inside the closed neural tube the microvilli are shorter. Lengthening of the microvilli at room temperature is produced only by d-glucose and 2-deoxyglucose, two hexoses that are absorbed and phosphorylated. Cytochalasin D which disrupts actin polymerization causes ballooning of the microvilli. A role of this microvillar elongation in degenerative changes seen in uncontrolled diabetes and on function of the immune system is proposed. The amniotic cavity is one major portal of entry for glucose during the early somite embryo stage. The 7-fold increase in volume of the amniotic cavity after day 10 allows the rat embryo to convert its axis from dorsal to ventral flexion.


Radiation-induced transformations of methanol molecules in low-temperature solids: a matrix isolation study.
The effect of X-ray irradiation on methanol molecules (CH3OH, CD3OH, and 13CH3OH) isolated in solid noble gas matrices (Ne, Ar, Kr, and Xe) was studied by FTIR spectroscopy at 6 K. CH2OH˙, H2CO, HCO˙ and CO were found to be the main degradation products. Somewhat unexpectedly, the production of CO is quite prominent, even at low doses, and it strongly predominates in low-polarizable matrices (especially, in neon). This result is explained by inefficient quenching of excess energy in the H2CO molecules initially generated from methanol. Relatively small amounts of CH4, CH3˙ and CO2 were also observed directly after irradiation. The latter species presumably originates from methanol dimers or methanol-water complexes. The mechanisms of radiolysis and annealing-induced reactions are discussed and possible implications for the astrochemically relevant ices are considered.


[Study of the use of medicine in elderly living in a city in the South of Santa Catarina (Brazil): a look at the polymedication].
The objective was to evaluate the use of medicines in the elderly population living in a city in the South of Santa Catarina state. It was carried out a transverse study where 104 patients distributed in five Family Health Program covering area were interviewed. 68.3% of the interviewed people were women, 78.8% aged between 60 and 79 years old and most of them with low schooling. The number of medicines in use was 3.5 (DP=2.58) per elderly and the number of daily rate doses were 5.4 (DP=4.78). 64.4% of the elderly people reported to have used the health services two times or more last year. It was observed that 51.9% of the elderly were classified as smaller polymedication and 28.8% as larger polymedication. The classes of medicines that contributed the most to the polymedication were the ones acting in the cardiovascular and nervous system, eating treatment and metabolism mainly used for hypertension, heart and circulatory problems, diabetes, insomnia and depression. It was verified that 16.5% of the elderly people presented risk of having drug-related problems. It was identified the association between the polymedication and the gender, schooling and the frequency they searched for health services. It was noticed that in this population the polymedication may be related to the elderly profile.


Vulvar lichen sclerosus in women of reproductive age.
Vulvar lichen sclerosus (vLS) is an inflammatory skin condition that predominantly affects the vulvar and perianal regions. Approximately 50% of cases present prior to menopause; however, there is a paucity of data on vLS in women of reproductive age as well as during their pregnancies. A retrospective review was performed at two tertiary referral centers to better describe cases of vLS in women of reproductive age. Thirty-three patients with a mean age of 40 years met inclusion criteria. In this group, vulvar pruritus was the most common presenting symptom (52%); 61% had biopsy-proven vLS, 42% had at least one autoimmune condition, 21% had comorbid depression or anxiety, 33% were given an incorrect diagnosis prior to vLS, and 42% had documented nonadherence to topical steroids. Among the eight patients who became pregnant, four had cesarean deliveries and 63% were symptomatic during pregnancy. When treating a woman who presents with vulvar pruritus or skin changes, vLS should be considered.


Hypomanic Experience in Young Adults Confers Vulnerability to Intrusive Imagery After Experimental Trauma: Relevance for Bipolar Disorder.
Emotional mental imagery occurs across anxiety disorders, yet is neglected in bipolar disorder despite high anxiety comorbidity. Furthermore, a heightened susceptibility to developing intrusive mental images of stressful events in bipolar disorder and people vulnerable to it (with hypomanic experience) has been suggested. The current study assessed, prospectively, whether significant hypomanic experience (contrasting groups scoring high vs. low on the Mood Disorder Questionnaire, MDQ) places individuals at increased risk of visual reexperiencing after experimental stress. A total of 110 young adults watched a trauma film and recorded film-related intrusive images for 6 days. Compared to the low MDQ group, the high MDQ group experienced approximately twice as many intrusive images, substantiated by convergent measures. Findings suggest hypomanic experience is associated with developing more frequent intrusive imagery of a stressor. Because mental imagery powerfully affects emotion, such imagery may contribute to bipolar mood instability and offer a cognitive treatment target.


Assessment of Groundwater Quality in CKDu Affected Areas of Sri Lanka: Implications for Drinking Water Treatment.
This study investigated the water quality of the groundwater that was collected from the chronic kidney disease of unknown etiology (CKDu) prevailing areas in the dry zone of Sri Lanka to assess its suitability for drinking purposes, and for the first time a Water Quality Index (WQI) with emphasis on proposing appropriate drinking water treatment method was developed. A total of 88 groundwater samples were collected in dry (December 2016) and wet (May 2017) seasons; high concentrations of water hardness, fluoride, salinity, dissolved organic carbon (DOC), and the general alkaline nature of water were the main issues that were observed for disease incidence. The chemical weathering of the underlying bedrock, followed by ion exchange and precipitation processes, primarily controlled groundwater geochemistry. During the 1985-2017 period, the variations of the annual rainfall and temperature were minimal, which suggests no evidence for major climatic changes within the study areas. Almost all of the samples from the CKDu regions show a low alkali hazard and most of the samples show a medium to high salinity hazard. The DOC of the studied samples was mainly composed of the organic fractions in the following order, as fulvic acids > humic acids > aromatic protein II > soluble microbial by-products, and the molecular weights (MW) of these fractions ranged from 100-3000 Da. Based on the water quality index (WQI) calculations, it was found that only 3.8% in the wet season and 2.6% in the dry season of total water samples were categorized as the "excellent" type, and all other water sources require a further treatment before consumption. As there is an urgent need for establishing proper long-term drinking water treatment technology for the CKDu affected area, these findings can be used as benchmark of raw water quality in the design processes of treatment plants.


Impact of Comorbidity on Fatality Rate of Patients with Middle East Respiratory Syndrome.
To date, 1841 cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported worldwide, with 652 deaths. We used a publically available case line list to explore the effect of relevant factors, notably underlying comorbidities, on fatal outcome of Middle East respiratory syndrome (MERS) cases up to the end of October 2016. A Bayesian Weibull proportional hazards regression model was used to assess the effect of comorbidity, age, epidemic period and sex on the fatality rate of MERS cases and its variation across countries. The crude fatality rate of MERS cases was 32.1% (95% credibility interval (CI): 29.9%, 34.3%). Notably, the incremental change of daily death rate was most prominent during the first week since disease onset with an average increase of 13%, but then stabilized in the remaining two weeks when it only increased 3% on average. Neither sex, nor country of infection were found to have a significant impact on fatality rates after taking into account the age and comorbidity status of patients. After adjusting for age, epidemic period, MERS patients with comorbidity had around 4 times the risk for fatal infection than those without (adjusted hazard ratio of 3.74 (95% CI: 2.57, 5.67)).


Modal characterization using principal component analysis: application to Bessel, higher-order Gaussian beams and their superposition.
The modal characterization of various families of beams is a topic of current interest. We recently reported a new method for the simultaneous determination of both the azimuthal and radial mode indices for light fields possessing orbital angular momentum. The method is based upon probing the far-field diffraction pattern from a random aperture and using the recorded data as a 'training set'. We then transform the observed data into uncorrelated variables using the principal component analysis (PCA) algorithm. Here, we show the generic nature of this approach for the simultaneous determination of the modal parameters of Hermite-Gaussian and Bessel beams. This reinforces the widespread applicability of this method for applications including information processing, spectroscopy and manipulation. Additionally, preliminary results demonstrate reliable decomposition of superpositions of Laguerre-Gaussians, yielding the intensities and relative phases of each constituent mode. Thus, this approach represents a powerful method for characterizing the optical multi-dimensional Hilbert space.