Use of levosimendan in acute heart failure.
As a calcium sensitizer and inodilator that augments cardiac contractility without increasing myocardial oxygen demand or exacerbating ischaemia, levosimendan may be well configured to deliver inotropic support in cases of acute heart failure (AHF). Other factors favouring levosimendan in this setting include its extended duration of action due to the formation of an active metabolite and the lack of any attenuation of effect in patients treated with beta-blockers. Effects of levosimendan on systemic haemodynamics include its significant, dose-dependent increases in cardiac output, stroke volume and heart rate, and decreases in right and left ventricular filling and total peripheral resistance. Rapid and sustained reduction in levels of natriuretic peptides is a consistent effect of levosimendan use and potentially favourable effects on other neurohormonal indicators of cardiac distress are also observed. Levosimendan has repeatedly been shown to be effective in relief of symptoms of AHF, notably dyspnoea and fatigue, while mortality data from clinical trials and registries suggest that levosimendan is markedly less likely than catecholaminergic inotropes to worsen prognosis. The vasodilator pharmacology of levosimendan is also pertinent to the drug's use in AHF, in which setting organ under-perfusion is often a key pathology. These considerations suggest that levosimendan may have a more favourable impact on the circumstances of the majority of AHF patients than adrenergic agents that act only or primarily as cardiac stimulants. They also suggest that levosimendan may advantageously be integrated into a comprehensive strategy of early intervention designed and intended to prevent cardiac destabilization worsening to the point where hospitalization is necessary. Levosimendan should be used with caution and with tightened haemodynamic monitoring in patients who have low baseline blood pressure (systolic blood pressure <100 mmHg; diastolic blood pressure <60 mmHg), or who are at risk of a hypotensive episode.


A Qualitative study on diverse perspectives and identities of firearm owners.
Research surrounding firearm ownership is often contextualised within the perspectives of older white men. We expand this description using the perceptions of a diverse group of firearm-owning stakeholders. We conducted semistructured interviews from October 2020 to May 2021 with Colorado/Washington State stakeholders representing (1) firearm ranges/retailers; (2) law enforcement agencies or (3) relevant state/national firearm organisations. Data were analysed using standard qualitative techniques and included 25 participants, representing varied sociocultural groups including racial and ethnic minorities, political minorities and sexual minorities. Participants for this analysis were of different self-identified sociocultural groups including racial and ethnic minorities (African American, Hispanic and Asian), political minorities (liberal) and sexual minorities, defined as Lesbian, Gay, Bisexual, and Transgender (LGBT). Perspectives on firearm ownership included an idea of gun culture as a component of (1) personal identity, (2) an expression of full citizenship and (3) necessary for self-protection. A strong subtheme was the intersection of minority group and firearm owner identities, creating a need for divergent social communities because of ideas on traditional gun culture. These communities are a safe place for individuals belonging to minority groups to escape negative external and internal group associations with firearms. Perspectives on firearms and firearm ownership in the secondary analysis were heterogeneous and related to personal experiences, external and internal group pressures that influence individual behaviour. Understanding the breadth of perspectives on firearm ownership is imperative to engaging individuals for risk reduction. This study adds to the literature by expanding an understanding of the motivation for firearm ownership among diverse communities.


Comparison of breathing pattern and diaphragmatic motion in patients with unilateral cervical radiculopathy and asymptomatic group.
The associations between neck pain and respiratory dysfunction were clarified in patients with neck pain. There is dearth of evidence on pulmonary dysfunction and diaphragmatic excursion in patients with unilateral cervical radiculopathy (CR). The purpose of this study was to compare the breathing pattern and diaphragmatic excursion in patients with unilateral CR with those in an asymptomatic group. Twenty-five patients with unilateral CR and 25 asymptomatic individuals aged between 30 and 55 participated in this study. Diaphragmatic motion, breathing pattern, active cervical range of motion and kinesiophobia were investigated in both groups by using fluoroscopy, manual assessment of respiratory motion (MARM), cervical range of motion device, and Tampa scale of kinesiophobia. Statistical significance was set at 0.05. No statistically significant differences were found between the two groups with regard to sex, age and body mass index. The mean excursion of the hemi diaphragm on the involved side (the side of CR) was significantly lower than that on the uninvolved side in patients with unilateral CR with a large effect size. The excursion of the involved hemi diaphragm in patients was reduced compared to the matched hemi diaphragm in the control group. There was no significant difference between the hemi diaphragms excursion in the control group. The results of the MARM variables showed that the volume of breathing and the percentage rib cage motion in normal and deep breathing were significantly different between the two groups, but there was no significant difference in the balance of breathing between the two groups. Additionally, the active cervical range of motion was reduced in these patients in comparison to the control group, and it was less on the involved side than on the uninvolved side. The results of this study revealed a dysfunctional breathing pattern in normal and deep breathing and a unilateral reduction in diaphragmatic excursion on the side of radiculopathy in patients with unilateral CR compared to the control group.


Risk factors for asthma among young adults in Melbourne, Australia.
Asthma is more prevalent in Australia than in Europe or North America. As part of the European Community Respiratory Health Survey (ECRHS), we investigated exposure to risk factors for asthma among young adults in Melbourne. During this study, 553 randomly selected and 204 symptomatic participants aged between 20 and 44 years completed a detailed respiratory questionnaire, of whom 675 underwent measurement of bronchial hyperreactivity (BHR) by methacholine challenge and 745 had skin prick tests for atopy. Current asthma, defined as BHR and wheeze in the preceding 12 months, was present in 25.5% of those tested. A family history of asthma was a risk factor for current asthma (maternal asthma odds ratio [OR] 2.4, paternal asthma OR 2.1). Current smokers were 1.7 times more likely to have current asthma. A serious respiratory infection before 5 years of age increased the risk of current asthma 2.3-fold. Atopy on skin testing was also strongly associated with current asthma (OR 5.9). The greatest risks were associated with positive skin tests to Cladosporium, house dust mite, cat and rye grass pollen. We conclude that female gender, maternal asthma, smoking, hayfever, early respiratory infection, occupational exposure and atopy are important risk factors for asthma in young adults.


How does directly observed therapy work? The mechanisms and impact of a comprehensive directly observed therapy intervention of highly active antiretroviral therapy in Peru.
From December 2005 through August 2008, we provided community-based accompaniment with supervised antiretroviral therapy (CASA) to impoverished individuals starting highly active antiretroviral therapy. Adherence support was provided for 18 months by a community-based team comprised of several nurses and two types of community health workers: field supervisors and directly observed therapy (DOT) volunteers. To complement our quantitative data collection in 2008 using purposive sampling, we conducted two gender-mixed focus group discussions with 13 CASA patient participants and 13 DOT volunteers from Lima, Peru to identify the mediating mechanisms by which CASA improved well-being, and to understand the benefits of the intervention, as perceived by these individuals. Using standard qualitative methods for the review and analysis of transcripts and interview notes, we identified central themes and developed a coding scheme for categorising participants' statements. Two individuals blinded to each other's coding, coded interview transcripts for theme and content from which a third reviewer compared their coding to arbitrate discrepancies. Additional domains were added if necessary and all domains were integrated into a theoretical scheme. Among the forms of support delivered by the CASA team, DOT volunteers reported emotional support, instrumental support, directly observed therapy, building trust, education, advocacy, exercise of moral authority and preparation for transition off CASA support. CASA participants described outcomes of improved adherence, ability to resume social roles, increased self-efficacy, hopefulness, changes in non-HIV-related behaviour, reduced internalised and externalised stigma, as well as ability to disclose. Both sets of focus group participants highlighted remaining challenges after completion of CASA support: stigma in the community, difficulties achieving economic recovery and persistent barriers to health services. Based on our prior quantitative and qualitative outcomes reported here, we argue that DOT of highly active antiretroviral therapy could be designed to optimise psychosocial recovery during the period of DOT.


Comparison of the mitochondrial genome of Nicotiana tabacum with its progenitor species.
Mitochondrial DNAs from Nicotiana tabacum, an amphiploid, and its putative progenitor species, N. sylvestris and N. tomentosiformis were compared in structure and organization. By using DNA transfer techniques and cloned fragments of known genes from maize and N. sylvestris as labeled probes, the positions of homologous sequences in restriction digests of the Nicotiana species were analyzed. Results indicate that the mitochondrial DNA of N. tabacum was inherited from N. sylvestris. Conservation in organization and sequence homology between mtDNAs of N. tabacum and the maternal progenitor, N. sylvestris, provide evidence that the mitochondrial genome in these species is evolutionarily stable. Approximately one-third of the probed restriction fragments of N. tomentosiformis mtDNA showed conservation of position with the other two species. Pattern variations indicate that extensive rearrangement of mtDNA has occurred in the evolution of these Nicotiana species.


Interaction and complex-formation between the eosinophil cationic protein and alpha 2-macroglobulin.
The interaction between the highly basic and cytotoxic eosinophil cationic protein (ECP) and human plasma proteins is described. The major plasma protein responsible for complex-formation with ECP was shown to be the 'fast' form of alpha 2-macroglobulin (alpha 2M). Large amounts of complexes were observed in a serum obtained from a patient with hypereosinophilic syndrome. The amount of complexes that could be generated in vitro in normal fresh serum was rather low and was even less in fresh citrated plasma. Complex-formation between the non-proteolytic ECP and alpha 2M was augmented in the presence of methylamine. Binding of ECP to alpha 2M was also induced by the proteinases cathepsin G and thrombin, and the binding was competitive with cathepsin G. Methylamine and the proteinases seem to share a common mechanism in inducing binding of ECP. The nature of the ECP-alpha 2M interaction is non-covalent, but withstands high salt concentrations. The interaction with alpha 2M may reflect a mechanism by which the organism protects itself against the deleterious effects of the highly cytotoxic protein ECP.


[An evaluation of the biomechanical parameters of the corneoscleral eye coating in kerato-refractive surgery].
The parameters characterizing the mechanical properties of the cornea and of the adjoining scleral parts as well as the influence produced by radial keratotomy and excimer laser kerato-ablation on the rigid corneal features were studied. The conclusion is that such keratorefractive surgeries (radial keratotomy and excimer laser photo-ablation) worsen the resistant corneal properties. Although the corneal thickness remains unchanged after radial keratotomy, "conditionally weak" sections take shape in the zone of keratotomic scars, in which the probability of ruptures of the cornea at damages to the eyeball increases.


Fatty acid biosynthesis in Mycobacterium tuberculosis: lateral gene transfer, adaptive evolution, and gene duplication.
Mycobacterium tuberculosis is a high GC Gram-positive member of the actinobacteria. The mycobacterial cell wall is composed of a complex assortment of lipids and is the interface between the bacterium and its environment. The biosynthesis of fatty acids plays an essential role in the formation of cell wall components, in particular mycolic acids, which have been targeted by many of the drugs used to treat M. tuberculosis infection. M. tuberculosis has approximately 250 genes involved in fatty acid metabolism, a much higher proportion than in any other organism. In silico methods have been used to compare the genome of M. tuberculosis CDC1551 to a database of 58 complete bacterial genomes. The resulting alignments were scanned for genes specifically involved in fatty acid biosynthetic pathway I. Phylogenetic analysis of these alignments was used to investigate horizontal gene transfer, gene duplication, and adaptive evolution. It was found that of the eight gene families examined, five of the phylogenies reconstructed suggest that the actinobacteria have a closer relationship with the alpha-proteobacteria than expected. This is either due to either an ancient transfer of genes or deep paralogy and subsequent retention of the genes in unrelated lineages. Additionally, adaptive evolution and gene duplication have been an influence in the evolution of the pathway. This study provides a key insight into how M. tuberculosis has developed its unique fatty acid synthetic abilities.


Quantitative analysis of neutral glycosphingolipids from human lymphocyte subpopulations.
The glycosphingolipids of normal human lymphocytes from individual donors were analysed by high-pressure liquid chromatography. In addition, purified T- and B-lymphocytes were examined separately. Lactosylceramide was shown to be the major neutral glycosphingolipid in human lymphocytes, and monohexosylceramide, trihexosylceramide, globoside and paragloboside were all detected in smaller amounts. Analysis of purified B- and T-cell fractions revealed that each of these populations contained a similar qualitative profile for neutral glycosphingolipids, but that quantitatively, B-cells contained several times more of each glycosphingolipid per cell than did T-cells.


[Changes in the blood vessels of the lungs under physical loads at high altitude].
Changes of the pulmonary artery branches in rats at the state of relative physiological rest undergo two stages during the process of individual adaptation for 60 days. The first is characterized with generalized decrease of the lumen and with thickening of the vascular wall as a result of reflectory spasm and edematous swelling of the arteries, the second--with a relative dilatation of the lumen and with decreasing thickness of the vascular wall, as a result of decreasing reflectory spasm and edematous phenomena. The physical load increases the organism's elevated oxygen consumption under conditions of high-altitude, which is increased by itself; this intensifies the function of the pulmonary blood bed. In combination with the edematous phenomena, the wall of the pulmonary artery becomes sharply thickened in the first stage. In the second stage the tissue mechanisms are switched on for satisfaction of oxygen consumption. Therefore, the load on the right part of the heart and on the pulmonary vessels decreases edematous phenomena, the thickness of the wall in the pulmonary artery branches decline, in comparison with the data of the first stage. The thickness of the wall in the first stage is combined with a manifested constriction of the lumen, and the relative thinning of the vascular wall--with dilatation.


Concentration of nutrients from urine and reject water from anaerobically digested sludge.
Experiments with concentration of nutrients from source separated urine and reject water from digestion of sludge in sewage treatment plants (STP) have been performed in laboratory and pilot scale. The methods tested were membrane filtration with reverse osmosis (RO), evaporation, and precipitation of phosphorus and distillation of ammonia. In membrane filtration, pre-filtration with particle separation at 5-10 microm was enough to avoid clogging of the membranes. Separation of phosphorus (P), potassium (K) and sulphur (S) was almost 100%, while separation of nitrogen (N) was dependent on pH. The capacity of flux increased with temperature and pressure. In evaporation, all P, K and S were still in the concentrate, while pH had to be decreased to 4.5 to avoid significant loss of N. In precipitation and distillation, about 90% of P could be recovered from urine as magnesium ammonium phosphate (MAP) just by adding MgO. For the reject water pH was first increased by aeration to remove CO2. Ammonium can be distilled from the water phase after precipitation of MAP, without further increase of pH. At least 80-90% of N can be distilled in 5-10% of the total volume. The article also discusses the quality of different products, cost of separation, and energy and chemical demand.


[The review of the European Union documents relating to contamination of aflatoxins in food].
In the following review, Polish and European Union legislation, concerning maximum level of aflatoxins in foodstuffs, was reported. In this moment, no specific requirements exist but according to Food and Nutrition Law all kind of food ought to be free from aflatoxins. Practically, maximum aflatoxins level should be below the detection limit of official analytical method (thin layer chromatography)--5 micrograms/kg and 0.05 microgram/l for milk. Commission Directive 98/53/EC laying down the sampling methods and the methods of analysis for aflatoxins in foodstuffs and Commission Regulation No 152/98 setting maximum levels for aflatoxins in foodstuffs were presented. Also, Ministry of Health Draft Regulation, concerning maximum levels of contamination in food is prepared in accordance with EU regulation, was reported.


Association of +62 G>A Polymorphism in the Resistin Gene with Type 2 Diabetes Mellitus among Thais: Case-Control Study.
Resistin gene (RETN) polymorphisms in humans may have a role in the pathogenesis of Type 2 Diabetes Mellitus (T2DM) and insulin resistance. There is still lack of evidence on association between +62 G>A polymorphism in the RETN and T2DM among Thais. To determine the effect of polymorphisms at +62 G>A of RETN on Thai T2DM. This matched case control study was conducted with a total of 360 samples from all regions of Thailand (180 Thai new T2DM cases and 180 non-T2DM Thais for control) were enrolled. The RETN +62G>A polymorphism were detected using the Polymerase Chain Reaction (PCR) method. Conditional logistic regression was performed to test the association between +62 G>A polymorphism and T2DM. Among 360 samples that were enrolled, only 350 samples completed molecular analysis. It was found that GA+AA genotype frequencies in T2DM cases was higher than control by 16% (95% CI: 6.0%, 27.0%, p-value=0.002). After adjustments for possible confounders, multivariable analyses by conditional logistic regression showed that the RETN+62 G>A polymorphism was statistically associated with Thai T2DM (ORadjusted =1.84, 95% CI: 1.03, 3.31, p-value=0.04). Other factors such as; low educational attainment (ORadjusted=3.87, 95%CI: 1.60, 9.36), hypertension (ORadjusted=3.07, 95%CI: 1.56, 6.04), had both obese father and mother (ORadjusted=1.94, 95%CI: 1.06, 3.56) and triglyceride≥150 (ORadjusted=2.18, 95% CI: 1.18, 4.02) were statistically associated with Thai T2DM (p-value<0.05). While regular consumption of glutinous rice was found to be a protective factor (ORadjusted=0.29, 95%CI: 0.13, 0.64). These findings suggest that RETN polymorphism at position +62 G>A may increase the susceptibility to T2DM in Thais.


A retrospective study of the inheritance of peromelia in Angora goats.
Peromelia, agenesia of the distal parts of the limbs, has been reported as a congenital defect in several animal species. In Angora goats, cases occur in a familiar pattern consistent with an autosomal recessively inherited defect. To obtain further evidence on the inheritance of peromelia in Angora goats, breeding results for goats being daughters of known carriers and which were then mated to a known carrier were analysed. Of 45 kids born in 1993 and 1994, five kids had peromelia. This corresponded to the expected 7:1 segregation. The difference between the number of affected male and female kids was not statistically significant. Peromelia affected kids occurred significantly more frequently among goats selected in the breeding study than among other goats in the respective herds. The study demonstrated that peromelia is inherited as an autosomal recessive defect. Based on knowledge obtained in a previous study, the genotype probably has varying degrees of expressivity.


Context-dependent expression of the foraging gene in field colonies of ants: the interacting roles of age, environment and task.
Task allocation among social insect workers is an ideal framework for studying the molecular mechanisms underlying behavioural plasticity because workers of similar genotype adopt different behavioural phenotypes. Elegant laboratory studies have pioneered this effort, but field studies involving the genetic regulation of task allocation are rare. Here, we investigate the expression of the foraging gene in harvester ant workers from five age- and task-related groups in a natural population, and we experimentally test how exposure to light affects foraging expression in brood workers and foragers. Results from our field study show that the regulation of the foraging gene in harvester ants occurs at two time scales: levels of foraging mRNA are associated with ontogenetic changes over weeks in worker age, location and task, and there are significant daily oscillations in foraging expression in foragers. The temporal dissection of foraging expression reveals that gene expression changes in foragers occur across a scale of hours and the level of expression is predicted by activity rhythms: foragers have high levels of foraging mRNA during daylight hours when they are most active outside the nests. In the experimental study, we find complex interactions in foraging expression between task behaviour and light exposure. Oscillations occur in foragers following experimental exposure to 13 L : 11 D (LD) conditions, but not in brood workers under similar conditions. No significant differences were seen in foraging expression over time in either task in 24 h dark (DD) conditions. Interestingly, the expression of foraging in both undisturbed field and experimentally treated foragers is also significantly correlated with the expression of the circadian clock gene, cycle Our results provide evidence that the regulation of this gene is context-dependent and associated with both ontogenetic and daily behavioural plasticity in field colonies of harvester ants. Our results underscore the importance of assaying temporal patterns in behavioural gene expression and suggest that gene regulation is an integral mechanism associated with behavioural plasticity in harvester ants.


Different cell cycle kinetic effects of N1,N11-diethylnorspermine-induced polyamine depletion in four human breast cancer cell lines.
Polyamine analogues are presently undergoing clinical evaluation in the treatment of cancer. To better understand under what circumstances treatment with a polyamine analogue will yield beneficial results, we have investigated the effect of N,N-diethylnorspermine (DENSPM) on cell cycle kinetics of the human breast cancer cell lines SK-BR-3, MCF-7, HCC1937, and L56Br-C1. A bromodeoxyuridine-DNA flow cytometry method was used to evaluate the treatment with 10 micromol/l DENSPM on cell cycle kinetics. A correlation between polyamine pool size after DENSPM treatment and cell cycle kinetic effects was found. The most sensitive cell cycle phase was the S phase, followed by an effect on the G2+M phase and then the G1/S transition. The levels of a number of cell cycle regulatory proteins such as cyclin E1, cyclin A2, and cyclin B1 were lowered by DENSPM treatment, which may explain the effects on cell cycle kinetics. The two cell lines that were most sensitive to DENSPM treatment belong to the basal-like subtype of breast cancer and they were deficient with respect to p53, BRCA1, and RB1.


C18:3-GM1a induces apoptosis in Neuro2a cells: enzymatic remodeling of fatty acyl chains of glycosphingolipids.
GM1a [Gal beta1-3GalNAc beta1-4(NeuAc alpha2-3)Gal beta1-4Glc beta1-1Cer] is known to support and protect neuronal functions. However, we report that alpha-linolenic acid-containing GM1a (C18:3-GM1a), which was prepared using the reverse hydrolysis reaction of sphingolipid ceramide N-deacylase, induced apoptosis in neuronal cells. Intranucleosomal DNA fragmentation, chromatin condensation, and caspase activation, all typical features of apoptosis, were observed when mouse neuroblastoma Neuro2a cells were cultured with C18:3-GM1a but not GM1a containing stearic acid (C18:0) or oleic acid (C18:1). The phenotype of Neuro2a cells induced by C18:3-GM1a was similar to that evoked by lyso-GM1a. However, lyso-GM1a caused a complete disruption of lipid microdomains of Neuro2a cells and hemolysis of sheep erythrocytes, whereas C18:3-GM1a did neither. C18:3-GM1a, but not lyso-GM1a, was found to be abundant in lipid microdomains after the removal of loosely bound GM1a by BSA. The activation of stress-activated protein kinase/c-Jun N-terminal kinase in Neuro2a cells was observed with lyso-GM1a but not C18:3-GM1a. These results indicate that the mechanism of apoptosis induced by C18:3-GM1a is distinct from that caused by lyso-GM1a. This study also clearly shows that fatty acid composition of gangliosides significantly affected their pharmacological activities when added to the cell cultures and suggests why naturally occurring gangliosides do not possess polyunsaturated fatty acids as a major constituent.


Vertical position, rotation, and tipping of molars without antagonists.
There has been a general belief that permanent teeth without antagonists overerupt, creating, after some time, considerable clinical problems. However, very few studies in the literature support this statement. The purpose of this investigation was to examine the position of molars that had been unopposed for a long period and to test the hypothesis that overeruption does affect every tooth without an antagonist. Fifty-three individuals were examined clinically, and dental casts were taken to evaluate the position of unopposed molars. There were 84 molars (61 in the maxilla and 23 in the mandible) with a documented period of at least 10 years without antagonists. Among these teeth, 25 molars had neither an antagonist nor a mesially adjacent tooth. A qualitative method was used to evaluate the position of the molars in the vertical direction: (1) teeth with no sign of overeruption, (2) teeth with slight overeruption (< 2 mm), and (3) teeth with moderate to severe overeruption (> or = 2 mm). Of the 84 molars examined, 15 teeth (18%) revealed no signs of overeruption, 49 teeth (58%) displayed overeruption of less than 2 mm, and 20 teeth (24%) showed moderate to severe overeruption. Individuals with molars that had lost their antagonists in adult age had a lower risk for overeruption than the other subjects examined. The existence of adjacent teeth was important for the position of the unopposed molar in a mesiodistal or buccolingual direction. Molar rotation was more frequent in the maxilla, whereas tipping was more common in the mandible. It is concluded that not all molars without antagonists overerupt, not even in a long-term perspective.


Self-assembled nanostructures of long-acting GnRH analogs modified at position 7.
It is well known that GnRH analogs can self-assemble into amyloid fibrils and that the duration of action of GnRH analogs depends on the ability of the amyloid to slowly release active peptides. The aim of this study was to investigate the influence of the amino acid residues at position 7 of GnRH analogues on peptide self-assembly. It was found that the dominant shape of the nanostructure can be changed when the structures of the residues at position 7 differ significantly from that of leucine in Degarelix. When the backbone length was extended (peptide 9), or the side chain of the residue at position 7 was replaced by an aromatic ring (peptide 6), or the rotation of the amide bond was restricted (peptide 8), the nanostructure changed from fibrils to vesicles. The results also indicate that the increasing hydrophilicity had little influence on the nanostructure morphology. In addition, a suitable release rate was found to play a more important role for the duration of the peptide action by maintaining the equilibrium between the drug concentration and the persistent release time, while the nanostructure shape was found to exert little influence on the duration of the peptide action.


High frequency optoacoustic arrays using etalon detection.
Two-dimensional phased arrays for high frequency (>30 MHz) ultrasonic imaging are difficult to construct using conventional piezoelectric technology. A promising alternative involves optical detection of ultrasound, where the array element size is defined by the focal spot of a laser beam. Element size and spacing on the order of a few microns are easily achieved, suitable for imaging at frequencies exceeding 100 MHz. We have previously shown images made from a receive-only, two-dimensional optoacoustic array operating at 10 to 50 MHz. The main drawback of optical detection has been poor sensitivity when compared with piezoelectric detection. In this paper, we explore a different form of optical detection demonstrating improved sensitivity and offering a potentially simple method for constructing two-dimensional arrays. Results from a simple experiment using an etalon sensor confirm that the sensitivity of etalon detection is comparable with piezoelectric detection. This paper concludes with a proposal for a high frequency optoacoustic array system using an etalon.


Sodium bicarbonate versus normal saline for protection against contrast nephropathy.
Contrast-induced nephropathy (CIN) is a form of acute kidney injury and a significant source of morbidity and mortality. We defined CIN as an increase in serum creatinine (SCr) of 25% or more within 48 hours of receiving contrast. We retrospectively compared sodium bicarbonate with normal saline for prevention of CIN. One hundred and eighty-seven patients exposed to contrast during cardiac angiography, treated prophylactically either with sodium bicarbonate (n = 89) or with normal saline (n = 98), were studied. Baseline characteristics of both groups were similar in terms of age, amount of contrast, presence of diabetes mellitus, and use of furosemide and angiotensin-converting enzyme inhibitor. Patients in bicarbonate group had more severe renal disease with higher baseline SCr (1.58 +/- 0.5 mg/dL vs. 1.28 +/- 0.3 mg/dL, p = 0.001) and lower estimated glomerular filtration rate (eGFR, 51.06 +/- 14.0 mL/min vs. 62.3+/-13.5 mL/min, p = 0.001) compared to the normal saline group. After the contrast exposure, there was significant drop in eGFR (6.4%) and increase in SCr (11.3%) in the normal saline group and no significant change in the bicarbonate group. Three patients (3.4%) in the bicarbonate group as opposed to 14 patients (14.3%) in the normal saline group developed CIN (p = 0.011). Two patients in the normal saline group and none in the bicarbonate group needed dialysis. There was no significant difference in serum creatinine at three-month follow-up in either group. The above findings suggest that hydration with intravenous sodium bicarbonate is more effective than normal saline in preventing contrast-induced nephropathy.


Addressing the social determinants of inequities in physical activity and sedentary behaviours.
Participation in both physical activity and sedentary behaviours follow a social gradient, such that those who are more advantaged are more likely to be regularly physically active, less likely to be sedentary, and less likely to experience the adverse health outcomes associated with inactive lifestyles than their less advantaged peers. The aim of this paper is to provide, in a format that will support policymakers and practitioners, an overview of the current evidence base and highlight promising approaches for promoting physical activity and reducing sedentary behaviours equitably at each level of 'Fair Foundations: The VicHealth framework for health equity'. A rapid review was undertaken in February-April 2014. Electronic databases (Medline, PsychINFO, SportsDISCUS, CINAHL, Scopus, Web of Science, Cochrane Library, Global Health and Embase) were searched using a pre-defined search strategy and grey literature searches of websites of key relevant organizations were undertaken. The majority of included studies focussed on approaches targeting behaviour change at the individual level, with fewer focussing on daily living conditions or broader socioeconomic, political and cultural contexts. While many gaps in the evidence base remain, particularly in relation to reducing sedentary behaviour, promising approaches for promoting physical activity equitably across the three levels of the Fair Foundations framework include: community-wide approaches; support for local and state governments to develop policies and practices; neighbourhood designs (including parks) that are conducive to physical activity; investment in early childhood interventions; school programmes; peer- or group-based programmes; and targeted motivational, cognitive-behavioural, and/or mediated individual-level approaches.


Rapid identification of Helicobacter pylori and assessment of clarithromycin susceptibility from clinical specimens using FISH.
Helicobacter pylori remains one of the most common bacterial infections worldwide. Clarithromycin resistance is the most important cause of H. pylori eradication failures. Effective antibiotic therapies in H. pylori infection must be rapidly adapted to local resistance patterns. We investigated the prevalence of clarithromycin resistance due to mutations in positions 2142 and 2143 of 23SrRNA gene of H. pylori by fluorescence in situ hybridisation (FISH), and compared with culture and antimicrobial susceptibility testing in 234 adult patients with dyspepsia who were enrolled. Antrum and corpus biopsy specimens were obtained for rapid urease test, histopathology and culture. Epsilometer test was used to assess clarithromycin susceptibility. H. pylori presence and clarithromycin susceptibility were determined by FISH in paraffin-embedded biopsy specimens. We found that 164 (70.1%) patients were positive for H. pylori based on clinical criteria, 114 (69.5% CI 62.5-76.6%) were culture positive, and 137 (83.5% CI 77.8-89.2%) were FISH positive. Thus the sensitivity of FISH was significantly superior to that of culture. However specificity was not significantly different (91.4 versus 100.0%, respectively). The resistance rate to clarithromycin for both antrum and corpus was detected in H. pylori-positive patients; 20.2% by FISH and 28.0% by E-test.The concordance between E-test and FISH was only 89.5% due to the presence of point mutations different from A2143G, A2142G or A2142C. We conclude that FISH is significantly more sensitive than culture and the E-test for the detection of H. pylori and for rapid determinination of claritromycin susceptibility. The superior hybridisation efficiency of FISH is becoming an emerging molecular tool as a reliable, rapid and sensitive method for the detection and visualisation of H. pylori, especially when the management of H. pylori eradication therapy is necessary. This is particularly important for the treatment of patients with H. pylori eradication failure.


A meta-analysis of the use of a transanal drainage tube to prevent anastomotic leakage after anterior resection by double-stapling technique for rectal cancer.
The safety and efficacy of transanal drainage tube (TDT) placement to decrease the risk of postoperative anastomotic leakage after rectal cancer surgery has not been validated. The objective of this meta-analysis was to evaluate the usefulness of a TDT for the prevention of anastomotic leakage after an anterior resection for rectal cancer. The PubMed and Cochrane Library databases were searched for studies comparing TDT and non-TDT. The endpoint utilized in this study was defined as the rates of anastomotic leakage and re-operation. The relative effects of these variables were synthesized using Review Manager 5.1 software. Four trials including 909 participants (401 TDT cases and 508 non-TDT cases) met our inclusion criteria. The weighted mean anastomotic leakage rate was 4% [95% confidence interval (CI) 1-6%], and a significantly lower risk of anastomotic leakage was identified in the TDT group compared with the non-TDT group [odds ratio (OR) 0.30; 95% CI 0.16-0.55; p = 0.0001]. Furthermore, there were significant differences between the TDT and non-TDT groups in terms of the re-operation rate (OR 0.18; 95% CI 0.07-0.44; p = 0.0002). No significant covariates related to anastomotic leakage or re-operation were identified in meta-regression analysis. Both the anastomotic leakage and re-operation rates for all studies lay inside the 95% confidence interval boundaries. No visible publication bias was found by visual assessment of the funnel plot (Egger's test; anastomotic leakage: p = 0.056, re-operation: p = 0.681). Placement of a TDT is an effective and safe procedure that can decrease the rate of anastomotic leakage and re-operation after an anterior resection.


Increase of lung neutrophils in hypersensitivity pneumonitis is associated with lung fibrosis.
Hypersensitivity pneumonitis (HP) is characterized by a T-cell-mediated alveolitis, and the putative role of other inflammatory cells in its pathogenesis remains unclear. In this study we determined whether increased quantities of neutrophils were present in HP lungs, and if they were positive for gelatinase B and collagenase-2. Fifteen nonsmoking patients with subacute/chronic active HP were included. Lung samples were analyzed using myeloperoxidase antibody, and neutrophil/total cell ratio was evaluated by digital processing. All HP tissue samples exhibited variable quantities of neutrophils located inside vessels, and in the interstitial and alveolar spaces. Lung neutrophil percentage ranged from 0.7% to 4.8% (2.1 +/- 1.4%). There was a positive correlation between the percentage of lung neutrophils and the percentage of lung fibrosis (r = 0.6, p < 0.02). Tissue neutrophils showed intense immunoreactive collagenase-2 and gelatinase B staining. Additionally, gelatinolytic activities corresponding to progelatinases A and B and their activated forms, were several-fold increased in the bronchoalveolar lavage fluid (BALF) from patients with HP as compared with control subjects. These findings suggest that in HP lungs there is a persistent traffic of neutrophils loaded with gelatinase B and collagenase-2 that may play a role in the lung damage and in the fibrotic response.


Cardiovascular Risk in Men Aged Over 40 in Boa Vista, Brazil.
Cardiovascular disease is the most common cause of disease in the developed world. Early detection and risk prediction are a key component in reducing cardiovascular mortality. The Framingham Risk Score uses age, sex, cholesterol, blood pressure, diabetes, and smoking to calculate the 10-year risk probability of developing cardiovascular disease for a given patient. The aim of this study was to examine cardiovascular disease risk in men aged over 40 years in Boa Vista, Brazil and identify socioeconomic factors contributing to the risk. This was an epidemiological, cross-sectional, descriptive study. Physical examination and questionnaire survey were conducted on the participants. Of the 598 participants (average age = 55.38 ± 10.77 years), 346 completed all the examinations and answered the survey, while 252 completed the survey and the physical examinations but did not undertake the laboratory tests. A large proportion of participants were overweight (42.6%) or obese (23.6%), 14.5% were hypertensive, and 71.9% were prehypertensive. Consumption of red meat and junk food was high, while participation in the exercise was low. Framingham scores ranged from -3 to 13 (mean score: 3.86 ± 3.16). A total of 204 participants (34.1%) had a low risk of cardiovascular disease, 98 (16.4%) had a medium risk, and 44 (7.4%) possessed high risk. Increased abdominal circumference (P = 0.013), resting pulse (P = 0.002), and prostate-specific antigen levels (P < 0.001) were associated with increased risk of cardiovascular disease. Our study highlights a worrying trend in increasing obesity and hypertension, most likely associated with increasingly poor diet and reduced participation in exercises. As the Brazilian population ages, this will drive increasing rates of cardiovascular mortality unless these trends are reversed. This study suggests that such campaigns should focus on men over the age of 40, who are married or divorced and of lower income.


Subjective versus objective evaluation of hypnotic efficacy: experience with zolpidem.
There is little published literature on the correlation between subjective and objective efficacy of hypnotics. We wanted to determine whether there was a correlation between the patient's subjective evaluation of the efficacy of the hypnotic with the polysomnographic (PSG) findings. We studied 16 patients with chronic insomnia (sleep latency, greater than or equal to 30 minutes; total sleep time, greater than 240 but less than 420 minutes) for 11 nights who took placebos on nights 1 and 2, zolpidem (imidazopyridine) on nights 3-9 and placebo on nights 10 and 11. Patients completed a questionnaire each morning following PSG, which evaluated subjective sleep quality, sleep latency and total sleep time. These data were compared to PSG findings to answer specific questions about sleep latency reduction, efficacy of the hypnotic after a week's use, sleep quality after discontinuing the drug, and any correlation between subjective and objective measures. PSG findings indicated a shortened sleep latency, increased total sleep time, decreased total wake time and increased sleep efficiency when patients ingested zolpidem 30 minutes before bedtime. We found that after 7 nights (nights 3-9) the drug was still effective in reducing sleep latency and increasing total sleep time. Upon withdrawal (nights 10 and 11) sleep returned to baseline (nights 1 and 2). Subjectively, the patients confirmed those findings on the questionnaire, as well as a subjective reduction in the number of awakenings and, interestingly, a subjective increase in the time spent awake after sleep. Many of the objective variables we examined correlated highly with the subjective variables. While on zolpidem, subjects believed and were objectively shown to have a decreased sleep latency, increased total sleep time and decreased time awake before persistent sleep, although they tended to overestimate sleep latency and time spent awake before persistent sleep and underestimated total sleep time. Although the correlation between objective and subjective measures was high for the group, in individual patients there was an impressive difference between the two, and the highest coefficient of variation between a subjective and objective measures was 0.453. No correlations were found with subjective measures of refreshing quality of sleep, decrease in number of awakenings, how sleepy patients felt in the morning or their ability to concentrate in the morning. Thus, we believe the PSG remains the keystone in the evaluation of hypnotic efficacy.


Mass transport perspective on an accelerated exclusion process: analysis of augmented current and unit-velocity phases.
In an accelerated exclusion process (AEP), each particle can "hop" to its adjacent site if empty as well as "kick" the frontmost particle when joining a cluster of size ℓ≤ℓ(max). With various choices of the interaction range, ℓ(max), we find that the steady state of AEP can be found in a homogeneous phase with augmented currents (AC) or a segregated phase with holes moving at unit velocity (UV). Here we present a detailed study on the emergence of the novel phases, from two perspectives: the AEP and a mass transport process (MTP). In the latter picture, the system in the UV phase is composed of a condensate in coexistence with a fluid, while the transition from AC to UV can be regarded as condensation. Using Monte Carlo simulations, exact results for special cases, and analytic methods in a mean field approach (within the MTP), we focus on steady state currents and cluster sizes. Excellent agreement between data and theory is found, providing an insightful picture for understanding this model system.


Neurocysticercosis presenting as bipolar disorder: a case report.
Neurocysticercosis is the most common neuro-parasitosis caused by the larval stage of Taenia solium. The most common manifestations include seizures and hydrocephalus. Psychiatric abnormalities are relatively rare but depressive symptoms are frequent in patients with neurocysticercosis. However, mania as a presentation is relatively rare. Pregnancy and the postpartum period are relatively vulnerable times and they can lead to reactivation of existing neurocysterci lesions. We are discussing the case of a 23-year-old female patient with neurocysticercosis leading to the reactivation of lesions in the peripartum and postpartum period leading to bipolar affective disorder. Improvement in the patient was seen with a combination of antipsychotics, antihelmintics, antiepileptics and steroids, along with improved radiological signs of neurocysterci lesions. Although neurocysticercosis is a common illness, its prevalence presenting as a manic episode is merely 2.6% and, hence, missed easily. Therefore, it is important to rule out organic aetiology in patients even with a classic presentation of bipolar affective disorder and those having any other neurological symptoms and signs.


Mortality of radiologists and pathologists in the Radiation Registry of Physicians.
The overall and cause-specific mortality experience of male radiologists and a comparable group of medical specialists, pathologists, who were included in the Radiation Registry of Physicians, is presented. The study population consists of an early-entry cohort of physicians who were members of either the American College of Radiology or the College of American Pathologists as of Jan. 1, 1962, and a late-entry cohort of similar members who joined these societies between January 1962, and June 1972. The purpose of the study was to determine if occupational exposure to low levels of ionizing radiation resulted in excess mortality from all causes and specific causes, or decreased survival patterns for radiologists compared with pathologists over the 16-year period, 1962 to 1977. The data revealed that radiologists and pathologists were comparable regarding overall mortality experience for all entrants, the early-entry cohort, and the late-entry cohort. Further analyses revealed a gradient in mortality between the two specialties, with the largest differences in the earliest birth subcohorts for all three groups, and a significant excess in mortality among radiologists in those subcohorts of the late-entry cohort born before 1920. Such a gradient may indicate an exposure effect associated with time of first exposure or duration of exposure, but not associated with time of entry into a professional society. Nevertheless, overall age-specific and age-adjusted mortality rates among radiologists and pathologists were lower in the late-entry cohort compared with the early-entry cohort, thus indicating some effect of time of entry within each specialty.(ABSTRACT TRUNCATED AT 250 WORDS)


Synchrotron X-ray-induced photoreduction of ferric myoglobin nitrite crystals gives the ferrous derivative with retention of the O-bonded nitrite ligand.
Exposure of a single crystal of the nitrite adduct of ferric myoglobin (Mb) at 100 K to high-intensity synchrotron X-ray radiation resulted in changes in the UV-vis spectrum that can be attributed to reduction of the ferric compound to the ferrous derivative. We employed correlated single-crystal spectroscopy with crystallography to further characterize this photoproduct. The 1.55 A resolution crystal structure of the photoproduct reveals retention of the O-binding mode for binding of nitrite to the iron center. The data are consistent with cryogenic generation and trapping, at 100 K, of a ferrous d(6) Mb(II)(ONO)* complex by photoreduction of the ferric precursor crystals using high-intensity X-ray radiation.


Competitive adsorption and selectivity sequence of heavy metals by chicken bone-derived biochar: Batch and column experiment.
The objective of this research was to evaluate adsorption of heavy metals in single- and ternary-metal forms onto chicken bone biochar (CBB). Competitive sorption of heavy metals by CBB has never been reported previously. The maximum adsorption capacities of metals by CBB were in the order of Cu (130 mg g(-1)) > Cd (109 mg g(-1)) > Zn (93 mg g(-1)) in the single-metal adsorption isotherm and Cu (108 mg g(-1)) >> Cd (54 mg g(-1)) ≥ Zn (44 mg g(-1)) in the ternary-metal adsorption isotherm. Cu was the most retained cation, whereas Zn could be easily exchanged and substituted by Cu. Batch experimental data best fit the Langmuir model rather than the Freundlich isotherms. In the column experiments, the total adsorbed amounts of the metals were in the following order of Cu (210 mg g(-1)) > Cd (192 mg g(-1)) > Zn (178) in single-metal conditions, and Cu (156) > Cd (123) > Zn (92) in ternary-metal conditions. Results from both the batch and column experiments indicate that competitive adsorption among metals increases the mobility of these metals. Especially, Zn in single-metal conditions lost it adsorption capacity most significantly. Based on the 3D simulation graphs of heavy metals, adsorption patterns under single adsorption condition were different than under competitive adsorption condition. Results from both the batch and column experiments show that competitive adsorption among metals increases the mobility of these metals. The maximum metal adsorption capacity of the metals in the column experiments was higher than that in the batch experiment indicating other metal retention mechanisms rather than adsorption may be involved. Therefore, both column and batch experiments are needed for estimating retention capacities and removal efficiencies of metals in CBB.


Halogranum gelatinilyticum sp. nov. and Halogranum amylolyticum sp. nov., isolated from a marine solar saltern, and emended description of the genus Halogranum.
Two extremely halophilic archaeal strains, designated TNN44(T) and TNN58(T), were isolated from Tainan marine solar saltern near Lianyungang city, Jiangsu province, China. Cells of the two strains were pleomorphic and Gram-stain-negative; colonies were red-pigmented. Strains TNN44(T) and TNN58(T) were able to grow at 20-50 °C (optimum 37 °C for both), in the presence of 1.4-5.1 M NaCl (optimum 3.4-3.9 M NaCl) and at pH 5.5-9.0 (optimum pH 6.5-7.0); neither strain required Mg(2+) for growth. Cells lysed in distilled water. On the basis of 16S rRNA gene sequence analysis, strains TNN44(T) and TNN58(T) were related closely to Halogranum rubrum RO2-11(T) (96.2 and 97.2 % similarity, respectively). The polar lipids of the two strains were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate (trace), and one major glycolipid and one minor glycolipid chromatographically identical to sulfated mannosyl glucosyl diether and mannosyl glucosyl diether, respectively; other trace unidentified lipids were also detected. The DNA G+C content of strains TNN44(T) and TNN58(T) was 64.0 and 62.0 mol%, respectively. The level of DNA-DNA relatedness between strains TNN44(T) and TNN58(T) was 37.2 %, and these two strains showed a low level of DNA-DNA relatedness with Halogranum rubrum RO2-11(T) (40.6 and 44.4 %, respectively). Two novel species of the genus Halogranum are proposed to accommodate these two strains, Halogranum gelatinilyticum sp. nov. (type strain TNN44(T) = CGMCC 1.10119(T) = JCM 16426(T)) and Halogranum amylolyticum sp. nov. (type strain TNN58(T) = CGMCC 1.10121(T) = JCM 16428(T)).


Synergistic absorbents based on SnFe2O4@ZnO nanoparticles decorated with reduced graphene oxide for highly efficient dye adsorption at room temperature.
Recently, adsorption techniques have emerged as practical and effective methods for removing organic dyes, dramatically extending practical capabilities for treating deleterious pollutants in wastewater. However, an urgent issue restricting the performance of these techniques is that no available absorbents that can be used to treat both cationic and anionic organic dyes have been made with simple and reliable methods until now. Herein, we report a green synthetic strategy for the preparation of SnFe2O4/ZnO nanoparticles decorated on reduced graphene oxide (rGO), exhibiting a remarkably large surface area (120.33 m2 g-1). Substantial adsorption efficiency for removing MB dye was achieved, with 91.3% removal within 20 min at room temperature, and efficiencies of 79.6 to 92.8% are maintained as the pH conditions are varied from 3 to 11. Moreover, under mixed-dye conditions, involving MB, RhB, MO, RB5, and R6G organic materials, with dye concentrations ranging from 0.005 mM to 0.09 mM, an adsorption efficiency of above 50% can be reliably reached within 20 min. Such striking features can be interpreted as arising from a synergistic effect involving the hybrid composite based on a rGO matrix with negative charge and the dispersed SnFe2O4/ZnO nanoparticles with positive charge, additionally offering abundant adsorptive sites to allow reliable dye-adsorption kinetics.


tBuP(NH2)2--a reactive synthon for the synthesis of molecular imidophosphinates of group 13 metals.
Reactions of tBuP(NH(2))(2) with Group 13 trialkyls MR(3) (M=Al, Ga, In; R=Me, tBu) were investigated in detail. According to variable-temperature (VT) NMR investigations, the reaction proceeds stepwise with the initial formation of aminophosphane adducts, which subsequently react to give iminophosphorane adducts and finally the heterocyclic metallonitridophosphinates. BP86/TZVPP (DFT) calculations were performed to verify this reaction pathway, to elucidate the influence of the central Group 13 element on the stability of the reaction intermediates and the heterocycles, as well as to assess the thermodynamics of their formation. The relative stability of free and complexed aminophosphane RP(NH(2))(2) and iminophosphorane R(H(2)N)(H)P=NH (adducts) with P(III) and P(V) centers was studied in more detail with DFT and MP2 methods. In addition, the influence of the substituent R was investigated by variation of R from H to Me, tBu, F, and NH(2). In general, the aminophosphane form was found to be favored for the free ligand, however, upon complexation with MR(3) (M=Al, Ga; R=alkyl) both forms are almost equal in energy.


Conditional deletion of calcium-modulating cyclophilin ligand causes deafness in mice.
Calcium-modulating cyclophilin ligand (Caml) is a ubiquitously expressed cytoplasmic protein that is involved in multiple signaling and developmental pathways. An observation in our laboratory of a protein-protein interaction between Caml and the cytoplasmic region of Cadherin23 led us to speculate that Caml might be important in the inner ear and play a role in the development and/or function of hair cells. To address this question, we generated a mouse line in which Caml expression was eliminated in Atoh1-expressing cells of the inner ear upon administration of tamoxifen. Tamoxifen was administered immediately after birth to neonates to assess the effect of loss of Caml in the inner ear during postnatal development. Hearing in treated animals was tested by auditory brain stem response (ABR) analysis and cochlear pathology was evaluated by light microscopy. Lack of Caml expression in the inner ear leads to severe loss of cochlear hair cells and complete deafness. Elucidating the role of Caml in the inner ear will aid our understanding of the molecular pathways important for auditory development and function.


Microstimulation of the lateral wall of the intraparietal sulcus compared with the frontal eye field during oculomotor tasks.
We compared the effects of intracortical microstimulation (ICMS) of the lateral wall of the intraparietal sulcus (LIP) with those of ICMS of the frontal eye field (FEF) on monkeys performing oculomotor tasks. When ICMS was applied during a task that involved fixation, contraversive saccades evoked in the LIP and FEF appeared similar. When ICMS was applied to the FEF at the onset of voluntary saccades, the evoked saccades collided with the ongoing voluntary saccade so that the trajectory of voluntary saccade was compensated by the stimulus. Thus the resultant saccade was redirected and came close to the endpoint of saccades evoked from the fixation point before the start of voluntary saccade. In contrast, when ICMS was applied to the LIP at the onset of voluntary saccades, the resultant saccade followed a trajectory that was different from that evoked from the FEF. In that case, the colliding saccades were redirected toward an endpoint that was close to the endpoint of saccades evoked when animals were already fixating at the target of the voluntary saccade. This finding suggests that the colliding saccade was directed toward an endpoint calculated with reference to the target of the voluntary saccade. We hypothesize that, shortly before initiation of voluntary saccades, a dynamic process occurs in the LIP so that the reference point for calculating the saccade target shifts from the fixation point to the target of a voluntary saccade. Such predictive updating of reference points seems useful for immediate reprogramming of upcoming saccades that can occur in rapid succession.


Thriving in relation to cognitive impairment and neuropsychiatric symptoms in Swedish nursing home residents.
The purpose of this study was to explore relations among thriving, cognitive function, and neuropsychiatric symptoms (NPS) in nursing home residents. A national, cross-sectional, randomized study of Swedish nursing home residents (N = 4831) was conducted between November 2013 and September 2014. Activities of daily life functioning, cognitive functioning, NPS, and thriving were assessed with the Katz activities of daily living, Gottfries' Cognitive Scale, Nursing Home version of the Neuropsychiatric Inventory, and Thriving of Older People Scale, respectively. Individual NPS were explored in relation to cognitive function. Simple linear and multiple regression models were used to explore thriving in relation to resident characteristics. Aggression and depressive symptoms were identified as negatively associated with thriving regardless of resident cognitive functioning. At higher levels of cognitive functioning, several factors showed associations with thriving; however, at lower levels of cognitive functioning, only the degree of cognitive impairment and the NPS was associated with thriving. Most of the individual NPS formed nonlinear relationships with cognitive functioning with higher symptom scores in the middle stages of cognitive functioning. Exceptions were elation/euphoria and apathy, which increased linearly with severity of cognitive impairment. The lower the cognitive functioning was, the fewer factors were associated with thriving. Aggression and depressive symptoms may indicate lower levels of thriving; thus, targeting these symptoms should be a priority in nursing homes. Copyright © 2017 John Wiley & Sons, Ltd.


Essential Professional Behaviors of Nursing Students and New Nurses: Hospital Nurse Leader Perspectives Survey.
This two-part study was conducted to determine which professional behaviors hospital nurse leaders believe are essential for nursing students to learn in the classroom. Nursing students need to be educated to lead high-quality care in complex health care environments. Little is known regarding the professional behaviors deemed essential for novice nurses. Hospital leaders were surveyed (n = 221) using the Hospital Nurse Leader Perspectives survey. This survey, developed from interviews, includes 41 items in change, communication, conflict, leadership, and self-awareness. The highest-ranked category was communication (n = 159, 72 percent), followed by self-awareness (n = 32, 14.4 percent). The highest items in each category were patient communication, prioritization, expect change, learning from failure, and conflict resolution. The results provide practical information to inform curricula and prepare leaders.


Fertilisability of ovine, bovine or minke whale (Balaenoptera acutorostrata) spermatozoa intracytoplasmically injected into bovine oocytes.
This study was conducted to investigate the possibility of using bovine oocytes for a heterologous fertility test by intracytoplasmic sperm injection (ICSI) and to compare the pronuclear formation of ram, bull and minke whale spermatozoa after injection into bovine oocytes. Bovine oocytes were cultured in vitro for 24 h and those with a polar body were selected for ICSI. Frozen-thawed semen from the three species were treated with 5 mM dithiothreitol for 1 h and spermatozoa were killed by storing them in a -20 degrees C refrigerator before use. ICSI was performed using a Piezo system. Three experiments were designed. In experiment 1, a higher (p < 0.05) male pronuclear formation rate was found in the oocytes injected with ram (52.6%) or bull (53.4%) spermatozoa than with minke whale spermatozoa (39.1%). In experiment 2, sperm head decondensation was detected at 2 h after ICSI in the oocytes injected with a spermatozoon of each species. Male pronuclei were first observed at 4 h in the oocytes injected with ram or bull spermatozoa and at 6 h in oocytes injected with minke whale spermatozoa. The mean diameters of male pronuclei derived from both whale and bull spermatozoa were larger than those from ram spermatozoa (30.4 microm and 28.3 microm vs 22.4 microm, p < 0.005). The mean diameter of female pronuclei in the oocytes injected with whale spermatozoa was also larger than with ram spermatozoa (29.3 microm vs 24.7 microm, p < 0.05). The development of male and female pronuclei was synchronous. In experiment 3, ethanol-activated oocytes injected with a spermatozoon from any of the three species achieved significantly higher (p < 0.05-0.001) cleavage rates than control oocytes. Blastocyst formation was only observed when bull spermatozoa were used. The results of this study indicate that dead foreign spermatozoa can participate in fertilisation activities in bovine oocytes after ICSI.


Abdominal tuberculosis with fatal gastro-intestinal haemorrhage.
We describe a patient who presented with chronic diarrhoea and features of malabsorption, suspected clinically to be due to abdominal tuberculosis and who developed fatal haematochezia a few days into a therapeutic trial of antituberculous chemotherapy. At autopsy, multiple tuberculosis ulcers were found in the jejunum, ileum and descending colon.


Performance of LoRaWAN for Handling Telemetry and Alarm Messages in Industrial Applications.
This paper analyzes the feasibility of the coexistence of telemetry and alarm messages employing Long-Range Wide-Area Network (LoRaWAN) technology in industrial environments. The regular telemetry messages come from periodic measurements from the majority of sensors while the alarm messages come from sensors whose transmissions are triggered by rarer (random) events that require highly reliable communication. To reach such a strict requirement, we propose here strategies of allocation of spreading factor, by treating alarm and regular (telemetry) messages differently. The potential of such allocation strategies has also been investigated under retransmission and diversity of gateways. Both indoor industrial plant and open-field scenarios are investigated. We compare the proposed solution with a benchmark scenario-where no alarm is considered-by using system level simulation. Our results show that it is possible to achieve high reliability with reasonably low delay for the alarm messages without significantly affecting the performance of the regular links.


Comparison of Three types of Tooth Brushes on Plaque and Gingival Indices: A Randomized Clinical Trial.
To compare clinical results of three types of manual tooth brushes on plaque removal efficacy and gingivitis. This study is a single blind randomized trial with crossover design which involved 30 periodontaly healthy individuals. Professional plaque removal and oral hygiene instruction were performed for all the participants in the first step of our study followed by asking them to avoid brushing for 2 days. Thereafter plaque and gingivitis scores were measured using plaque and gingival indices (PI and GI). Then subjects were instructed to use Pulsar tooth brush for a two-week period and then, GI and PI indices were assessed again. After passing one-week period for wash out, subjects didn't brush for 2 days and indices were recorded again. The same procedure was done for CrossAction, and Butler 411 tooth brushes respectively and at the end of the study these variables were analyzed using SPSS software ver.16. Repeated measurement ANOVA test was used to compare the scores between different brushes. Finding of this study reveals that using all three types of tooth brushes resulted in significant plaque and gingivitis reduction compared to baseline levels. Pulsar tooth brush was significantly more effective in diminishing PI and GI than Butler tooth brush (p=0.044 and 0.031 respectively). According to our findings all 3 types of tooth brushes are effective in reduction of plaque and gingivitis and this reduction is significantly greater for Pulsar tooth brush compared to Butler and CrossAction tooth brushes.


The isolation, properties and amino acid sequence of erabutoxin c, a minor neurotoxic component of the venom of a sea snake Katicauda semifasciata.
Erabutoxin c, a minor neurotoxic component of the venom of a sea snake Laticauda semifasciata, was isolated in pure form by repeated column chromatography on CM-cellulose columns. The toxin was crystallizable and monodisperse in rechromatography, disc electrophoresis and isoelectric focusing (isoelectric point, pH9.23-9.25). The molecular weight of the toxin, as estimated by gel filtration, was 7000. The toxin showed the same lethal activity to mice (0.13mug/g body wt., intramuscular injection) and the same effect on isolated frog muscle as erabutoxins a and b, the main toxic components of the venom. The toxin inhibited the acetylcholine contracture but not the potassium chloride contracture of muscle. Erabutoxin c consisted of 62 amino acid residues, containing one fewer lysine and one more histidine than erabutoxin a and one fewer lysine and one more aspartic acid (or asparagine) than erabutoxin b. Erabutoxin c was reduced, S-carboxymethylated and hydrolysed with trypsin. The only fragment different from the corresponding fragments from erabutoxin b was hydrolysed further with pepsin. One of the peptic fragments, which was assumed to have the aspartic acid (or asparagine) residue in question at the C-terminal end, was treated with carboxypeptidase A. The C-terminal residue was found to be an asparagine. It was therefore concluded that erabutoxin c was [51-asparagine]-erabutoxin b.


Coordinated Action of Biological Processes during Embryogenesis Can Cause Genome-Wide Linkage Disequilibrium in the Human Genome and Influence Age-Related Phenotypes.
A role of non-Mendelian inheritance in genetics of complex, age-related traits is becoming increasingly recognized. Recently, we reported on two inheritable clusters of SNPs in extensive genome-wide linkage disequilibrium (LD) in the Framingham Heart Study (FHS), which were associated with the phenotype of premature death. Here we address biologically-related properties of these two clusters. These clusters have been unlikely selected randomly because they are functionally and structurally different from matched sets of randomly selected SNPs. For example, SNPs in LD from each cluster are highly significantly enriched in genes (p=7.1×10-22 and p=5.8×10-18), in general, and in short genes (p=1.4×10-47 and p=4.6×10-7), in particular. Mapping of SNPs in LD to genes resulted in two, partly overlapping, networks of 1764 and 4806 genes. Both these networks were gene enriched in developmental processes and in biological processes tightly linked with development including biological adhesion, cellular component organization, locomotion, localization, signaling, (p<10-4, q<10-4 for each category). Thorough analysis suggests connections of these genetic networks with different stages of embryogenesis and highlights biological interlink of specific processes enriched for genes from these networks. The results suggest that coordinated action of biological processes during embryogenesis may generate genome-wide networks of genetic variants, which may influence complex age-related phenotypes characterizing health span and lifespan.


Responsiveness of different dynamic contrast-enhanced magnetic resonance imaging approaches: a post-hoc analysis of a randomized controlled trial of certolizumab pegol in rheumatoid arthritis.
Objective: The aim was to explore dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as an early marker of therapeutic response in patients with rheumatoid arthritis (RA) starting treatment with certolizumab pegol (CZP).Method: In 40 RA patients initiating CZP (27 patients) or 2 weeks of placebo (PCB) followed by CZP (13 patients), DCE-MRI of the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints was performed at weeks 0, 1, 2, 4, 8, and 16. Using semi-automated software, three methods for drawing volume regions of interest (ROIs) in MCP2-5 and PIP2-5 were applied: 'Standard' (slices: all; joints: MCP2-5 together and PIP2-5 together), 'Detailed' (slices: slices with high-quality visualization; joints: as Standard), and 'Single-joint' (slices: as Detailed; joints: each joint separately). The number of enhancing voxels (Nvoxel), initial rate of enhancement (IRE), and maximum enhancement (ME) were extracted and analysed for each method.Results: Nvoxel in MCP2-5, and IRE and ME in PIP2-5 decreased statistically significantly (Wilcoxon rank-sum test, p < 0.02-0.03) after 16 weeks of treatment for the Standard method. Nvoxel and ME decreased significantly more in the CZP group than in the PCB group after 1 week of treatment, but not at later time-points. There were no significant changes for DCE-MRI parameters for the Detailed and Single-joint methods.Conclusions: Certain DCE-MRI parameters detected decreased inflammation during CZP treatment in RA patients. Using specific criteria for ROIs, as in the Detailed and Single-joint methods, decreased the statistical power and could not show any changes over time.


Medication-Related Problems in Liver Transplant Recipients in the Outpatient Setting: A Dutch Cohort Study.
Background: After liver transplantation (LTx), adherence to immunosuppressive medication and avoidance of contra-indicated drugs is essential for long-term survival. This study aimed to investigate the prevalence, types and severity of medication-related problems (MRPs) and interventions initiated by a clinical pharmacist (CP) in a cohort of LTx recipients in the outpatient setting. Method: This study was a retrospective, observational study in LTx recipients that visited the outpatient clinic for an annual check-up. A 20-minutes consultation with a CP consisted of medication reconciliation and consultation about medication, adherence, and adverse drug reactions (ADRs). Discrepancies between actual and intended drug use, and MRPs were identified and the severity of MRPs was assessed. Potential interventions were discussed with the patient and the treating physician and evaluated after one year. Results: The CP counseled 64 LTx recipients and found 96 discrepancies in 37 patients. Most discrepancies (60.4%, n = 58) concerned missing medications. In total, 98 MRPs were identified in 53 patients (median 2; range 1-5 per patient), with a total of 113 interventions. Most frequent MRPs were: ADRs (22.4%, n = 22), nonadherence (19.3%, n = 19), unnecessary drugs (16.3%, n = 16) and undertreatment (12.2%, n = 12). Interventions most frequently proposed included optimization of dosage regimen (21.2%, n = 24), individualized recommendation regarding compliance (16.8%, n = 19) and drug discontinuation (12.4%, n = 14). After one year, 15 of the 19 patients (79%) experienced no longer compliance issues and 27 of the 29 patients (93%) used no drugs with indication issues anymore. Conclusion: The CP in an outpatient monitoring program for LTx recipients can signal relevant discrepancies and MRPs. This leads to interventions that are accepted by both the patients and the physicians, with a positive effect after one year.


PARPST: a PARallel algorithm to find peptide sequence tags.
Protein identification is one of the most challenging problems in proteomics. Tandem mass spectrometry provides an important tool to handle the protein identification problem. We developed a work-efficient parallel algorithm for the peptide sequence tag problem. The algorithm runs on the concurrent-read, exclusive-write PRAM in O(n) time using log n processors, where n is the number of mass peaks in the spectrum. The algorithm is able to find all the sequence tags having score greater than a parameter or all the sequence tags of maximum length. Our tests on 1507 spectra in the Open Proteomics Database shown that our algorithm is efficient and effective since achieves comparable results to other methods. The proposed algorithm can be used to speed up the database searching or to identify post-translational modifications, comparing the homology of the sequence tags found with the sequences in the biological database.


Genomics of adaptation to host-plants in herbivorous insects.
Herbivorous insects represent the most species-rich lineages of metazoans. The high rate of diversification in herbivorous insects is thought to result from their specialization to distinct host-plants, which creates conditions favorable for the build-up of reproductive isolation and speciation. These conditions rely on constraints against the optimal use of a wide range of plant species, as each must constitute a viable food resource, oviposition site and mating site for an insect. Utilization of plants involves many essential traits of herbivorous insects, as they locate and select their hosts, overcome their defenses and acquire nutrients while avoiding intoxication. Although advances in understanding insect-plant molecular interactions have been limited by the complexity of insect traits involved in host use and the lack of genomic resources and functional tools, recent studies at the molecular level, combined with large-scale genomics studies at population and species levels, are revealing the genetic underpinning of plant specialization and adaptive divergence in non-model insect herbivores. Here, we review the recent advances in the genomics of plant adaptation in hemipterans and lepidopterans, two major insect orders, each of which includes a large number of crop pests. We focus on how genomics and post-genomics have improved our understanding of the mechanisms involved in insect-plant interactions by reviewing recent molecular discoveries in sensing, feeding, digesting and detoxifying strategies. We also present the outcomes of large-scale genomics approaches aimed at identifying loci potentially involved in plant adaptation in these insects.


The United Kingdom national microbiological quality assessment scheme.
A comprehensive microbiological quality assessment scheme for the benefit of all clinical microbiological laboratories in the United Kingdom was established in 1974. The main emphasis of the scheme has been on the supply of simulated clinical material for proficiency testing. Of 494 laboratories currently participating in the scheme, 84 are abroad and over 500 specimens have been distributed between 1974 and 1980. A wide variety of specimens are issued. These include specimens for: general bacteriology including isolation, sensitivity testing and serology; mycobacterial bacteriology; syphilis serology; virus isolation; general viral serology; rubella serology; hepatitis B antigen detection; electron microscopy; mycology; parasitology; antibiotic assay; public health specimens including milk and water. Laboratories are requested to examine the specimens using their routine procedures and report their results to the Microbiological Quality Control Laboratory (MQCL). The reports are analysed at MQCL and the summarised results of each distribution are sent to all participants. Each participant receives details of his individual performance on current specimens and an analysis of the previous 6 months, cumulative performance. The performance of all laboratories is reviewed twice yearly and laboratories with results significantly worse than those of their peers are offered the opportunity to seek advice and help from a National Advisory Panel of their professional colleagues. The Scheme is confidential and its main role is educational.


Oestrogen receptor downregulation: an opportunity for extending the window of endocrine therapy in advanced breast cancer.
Advanced breast cancer is largely incurable and current treatment modalities are aimed towards restricting tumour growth, prolonging survival, palliating symptoms and maintaining quality of life (QoL). The development of breast cancer is strongly influenced by endogenous oestrogens (and other growth factors), leading to a strong focus on the development of antioestrogenic compounds for the treatment of hormone-sensitive advanced disease. This is a review of current endocrine therapies available for postmenopausal women with advanced breast cancer, examining the likely impact of newer agents on treatment strategies. In postmenopausal women, current treatment options include tamoxifen, aromatase inhibitors (AIs) and megestrol acetate. Fulvestrant ('Faslodex') is a new, well-tolerated, oestrogen receptor antagonist that has no known agonist effect and is at least as effective as the AI anastrozole for the treatment of postmenopausal patients with metastatic or advanced breast cancer who have progressed on prior endocrine therapy. Fulvestrant maintains QoL throughout successful treatment. Fulvestrant represents a new treatment option for postmenopausal women with advanced disease. New agents that appear to lack cross-resistance with existing treatments may be used to extend the time period during which endocrine therapy may be employed before the need for cytotoxic chemotherapy.


Heterogeneity in endothelial responsiveness to cytokines, molecular causes, and pharmacological consequences.
Microvascular endothelial cells play an essential role in inflammatory diseases. Functional heterogeneity between microvascular segments in normal organ homeostasis has been appreciated for a long time, and more recent studies have revealed heterogeneity in endothelial reactivity to inflammatory stimuli as well. This review summarizes the state-of-the-art knowledge regarding endothelial cell responses to the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1beta, and the bacterial product lipopolysaccharide. It focuses on similarities and differences in reactivity between endothelial cell subsets in vitro and endothelial cells in their pathophysiological environment in vivo, and culminates into a mainly theoretical model of possible intracellular control mechanisms that can assist to ultimately explain the molecular causes of endothelial heterogeneity. The last part of this review contains some pharmacological considerations, and, with the aim to further unravel the molecular basis of in vivo endothelial heterogeneity, descriptions of new techniques that will be essential to achieve this.


Computational modeling of the effects of amyloid-beta on release probability at hippocampal synapses.
The role of amyloid beta (Aβ) in brain function and in the pathogenesis of Alzheimer's disease (AD) remains elusive. Recent publications reported that an increase in Aβ concentration perturbs pre-synaptic release in hippocampal neurons. In particular, it was shown in vitro that Aβ is an endogenous regulator of synaptic transmission at the CA3-CA1 synapse, enhancing its release probability. How this synaptic modulator influences neuronal output during physiological stimulation patterns, such as those elicited in vivo, is still unknown. Using a realistic model of hippocampal CA1 pyramidal neurons, we first implemented this Aβ-induced enhancement of release probability and validated the model by reproducing the experimental findings. We then demonstrated that this synaptic modification can significantly alter synaptic integration properties in a wide range of physiologically relevant input frequencies (from 5 to 200 Hz). Finally, we used natural input patterns, obtained from CA3 pyramidal neurons in vivo during free exploration of rats in an open field, to investigate the effects of enhanced Aβ on synaptic release under physiological conditions. The model shows that the CA1 neuronal response to these natural patterns is altered in the increased-Aβ condition, especially for frequencies in the theta and gamma ranges. These results suggest that the perturbation of release probability induced by increased Aβ can significantly alter the spike probability of CA1 pyramidal neurons and thus contribute to abnormal hippocampal function during AD.


Organization of the department of surgery to facilitate undergraduate education.
The chairman of the department of surgery is responsible for undergraduate education and should develop an organizational structure involving a director of undergraduate education for the every-day running of the undergraduate program and the determination of policies. This person should hold a relatively senior position and should have undergone specialist postgraduate training in educational methods and theory. The director should be supported by appropriate secretarial services and be compensated for this; the director should also sit on the faculty medical curriculum committee to close the circle of policy made at this committee with departmental policy. The departmental undergraduate education committee should include representatives from all hospitals involved in undergraduate education with representatives from the various systems. Some doubling up of representatives can occur. There should be a review process of both teaching methods and faculty teaching. The former will encourage change where appropriate and the latter award individuals for their contribution to the teaching process.


[Parasite-host relations of fleas and rodents].
Not infrequently lice can reach great abundance on rodents. The distribution of lice on animals is uneven. The infection with lice depends not only on the physiological and ecological properties of the host but also on the environmental conditions. The distribution of lice on rodents can be affected by the development of transport communications. If a population of rodents is parasitized by two species of specific lice, they belong to different genera. On single animals only one species of lice occurs as a rule; if two species occur, then one of them is dominant. In this way decreases the interspecific competition between lice. Seasonal and age changes in lice infection are associated with those in host's biology and behaviour under certain climatic conditions. It is clearly displayed in rodents breeding once a year. The infection with lice increase with the rise in rodents abundance. Along with the confirmation of the general rule of poor infection with specific parasites at the borders of the species distribution a case of high infection with lice at the border of the host's distribution was noted. In addition to specific lice, alien species are recorded on small mammals which appear due to exchange of parasites between hosts. Examples are given all conquering new hosts by lice; as a result close species of lice can parasitize phylogenetically distant hosts.


Cerebrovascular disease risk in older head and neck cancer patients after radiotherapy.
Cerebrovascular disease is common in head and neck cancer patients, but it is unknown whether radiotherapy increases the cerebrovascular disease risk in this population. We identified 6,862 patients (age > 65 years) from the Surveillance, Epidemiology, and End Results (SEER) -Medicare cohort diagnosed with nonmetastatic head and neck cancer between 1992 and 2002. Using proportional hazards regression, we compared risk of cerebrovascular events (stroke, carotid revascularization, or stroke death) after treatment with radiotherapy alone, surgery plus radiotherapy, or surgery alone. To further validate whether treatment groups had equivalent baseline risk of vascular disease, we compared the risks of developing a control diagnosis, cardiac events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, or cardiac death). Unlike cerebrovascular risk, no difference in cardiac risk was hypothesized. Mean age was 76 +/- 7 years. Ten-year incidence of cerebrovascular events was 34% in patients treated with radiotherapy alone compared with 25% in patients treated with surgery plus radiotherapy and 26% in patients treated with surgery alone (P < .001). After adjusting for covariates, patients treated with radiotherapy alone had increased cerebrovascular risk compared with surgery plus radiotherapy (hazard ratio [HR] = 1.42; 95% CI, 1.14 to 1.77) and surgery alone (HR = 1.50; 95% CI, 1.18 to 1.90). However, no difference was found for surgery plus radiotherapy versus surgery alone (P = .60). As expected, patients treated with radiotherapy alone had no increased cardiac risk compared with the other treatment groups (P = .63 and P = .81). Definitive radiotherapy for head and neck cancer, but not postoperative radiotherapy, was associated with excess cerebrovascular disease risk in older patients.


Results of the CARDIA study suggest that higher dietary potassium may be kidney protective.
The association between dietary sodium and potassium intake with the development of kidney disease remains unclear, particularly among younger individuals. Here, we determined whether dietary sodium and potassium intake are associated with incident chronic kidney disease (CKD) using data from 1,030 adults (age 23-35 in 1990-1991) from the Coronary Artery Risk Development In Young Adults study, based on repeated measurements of estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (ACR) from 1995 through 2015. Urinary sodium and potassium excretion (mg/day), calculated from three 24-hour urine collections in 1990-1991, were averaged to measure sodium and potassium intake. Serum creatinine was used to calculate eGFR using the CKD EPI equation; spot urine albumin and creatinine were used to calculate ACR, each at five visits from 1995-1996 through 2015-2016. CKD was defined as decreased eGFR (under 60 ml/min/1.73m2) or the development of albuminuria (ACR over 30 mg/g). We used log binomial regression models adjusted for socio-demographic, behavioral, and clinical factors to determine whether sodium and potassium intake were associated with incident CKD (decreased eGFR or developed albuminuria) among those free of CKD in 1995. Dietary sodium intake was not significantly associated with incident CKD. However, every 1,000 mg/day increment of potassium intake in 1990 was significantly associated with a 29% lower risk of incident albuminuria (relative risk 0.71, 95% confidence interval 0.53, 0.95), but not eGFR. Thus, higher dietary potassium intake may protect against the development of kidney damage, particularly albuminuria.


Rhapso: Automatic Stitching of Mass Segments from Fourier Transform Ion Cyclotron Resonance Mass Spectra.
Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) provides the resolution and mass accuracy needed to analyze complex mixtures such as crude oil. When mixtures contain many different components, a competitive effect within the ICR cell takes place that hampers the detection of a potentially large fraction of the components. Recently, a new data collection technique, which consists of acquiring several spectra of small mass ranges and assembling a complete spectrum afterward, enabled the observation of a record number of peaks with greater accuracy compared to broadband methods. There is a need for statistical methods to combine and preprocess segmented acquisition data. A particular challenge of quadrupole isolation is that near the window edges there is a drop in intensity, hampering the stitching of consecutive windows. We developed an algorithm called Rhapso to stitch peak lists corresponding to multiple different m/z regions from crude oil samples. Rhapso corrects potential edge effects to enable the use of smaller windows and reduce the required overlap between windows, corrects mass shifts between windows, and generates a single peak list for the full spectrum. Relative to a stitching performed manually, Rhapso increased the data processing speed and avoided potential human errors, simplifying the subsequent chemical analysis of the sample. Relative to a broadband spectrum, the stitched output showed an over 2-fold increase in assigned peaks and reduced mass error by a factor of 2. Rhapso is expected to enable routine use of this spectral stitching method for ultracomplex samples, giving a more detailed characterization of existing samples and enabling the characterization of samples that were previously too complex to analyze.


When accurate cytomorphology directs clinical decision: Colonic adenocarcinoma presents initially with an isolated vertebral bone metastasis.
Liver is the most common site for metastasis of colonic adenocarcinoma. Other relatively common metastatic locations include: peritoneum, lungs and ovaries. Rare metastatic sites include: central nervous system, testis, uterus, oral cavity and bones. Though it is rare to have an isolated bone metastasis without liver or visceral involvement in colonic adenocarcinoma, it can occur. Our case illustrates the vital role of an accurate cytopathologic diagnosis in directing the proper clinical decision and management in our young patient. Our patient's first presentation was acute on chronic back pain radiating to his lower extremities with clinical suspicion of tuberculosis spondylitis. The correct cytopathologic diagnosis of the fine needle aspiration from the destructive vertebral lesion led to the establishment of an isolated metastatic colonic adenocarcinoma diagnosis initially and directed the clinical management of our patient.


Infants' symptoms of illness assessed by parents: impact and implications.
OBJECTIVES. Some parents with a sick infant contact a doctor, while others do not. The reasons underlying such parental decisions have not been thoroughly studied. The purpose of this study was to explore how the actual symptoms in the infant were associated with parent-rated illness, illness severity, and the probability of the parents contacting a doctor. DESIGN. A retrospective questionnaire and a prospective diary study covering 14 months of the participating infants' lives. SETTING AND SUBJECTS. The 194 participating infants were followed for three months prospectively from the age of 11 to 14 months using diary cards, and retrospectively from birth until the age of 11 months by a questionnaire. RESULTS. During the three months of the diary card prospective follow-up, the infants had symptoms on average every second day, and the vast majority (92%) had 10 or more days with at least one symptom; 38% of the infants were reported to have had five or more symptoms for more than five days. Fever, earache, and vomiting were the symptoms most likely to cause parents to rate their infant as ill. Earache was the symptom that triggered doctor contact most immediately. The parent-rated illness severity was strongly related to the tendency to contact a doctor. However, this association was markedly weaker when adjustment was made for the infant not eating normally, having a cough, or running a fever. CONCLUSION. Specific symptoms such as fever, earache, and vomiting were strongly associated with the probability of parents rating the infant as ill. An earache would cause the parents to contact a doctor. Fever and vomiting were other symptoms triggering doctor contacts. First, these symptoms could cause the parents to want a doctor's expert evaluation of the infant's illness; second, the parents could expect medication to be necessary; or third, it could just be difficult for the parents to handle the ill infant.


In vitro and clinical investigation of the relationship between CCR5 receptor occupancy and anti-HIV activity of Aplaviroc.
Aplaviroc (GW873140) binds specifically to human cellular CC chemokine receptor 5 (CCR5) and demonstrates potent anti-human immunodeficiency virus activity in vitro in the subnanomolar range. In vitro studies show that aplaviroc selectively inhibits the binding of a particular monoclonal antibody, 45531, to CCR5. Based on this observation, a flow cytometry-based assay was developed to determine percentage CCR5 receptor occupancy (RO). CCR5 receptor occupancy was aplaviroc concentration-dependent and related to anti-human immunodeficiency virus activity in vitro. In the clinical setting, CCR5 receptor occupancy in peripheral blood was >98% in all subjects within 2 to 3 hours of dosing, which is consistent with the peak plasma concentrations of drug. Longitudinal analysis in the drug washout period revealed the time to 50% CCR5 receptor occupancy averaged >100 hours, in both human immunodeficiency virus-positive and human immunodeficiency virus-negative subjects, substantially longer than the plasma pharmacokinetic half-life of 3 hours. The duration of CCR5 receptor occupancy appeared to be dose-dependent and associated with antiviral activity as measured by plasma human immunodeficiency virus RNA nadir following 10 days of multiple dose administration. These data demonstrate that the analysis of CCR5 receptor occupancy, in addition to conventional plasma-based pharmacokinetic measures, provides an informative tool to assist in evaluating the pharmacodynamic and antiviral effects of cellular CC chemokine receptor antagonists.


Biofunctionalized self-propelled micromotors as an alternative on-chip concentrating system.
Sample pre-concentration is crucial to achieve high sensitivity and low detection limits in lab-on-a-chip devices. Here, we present a system in which self-propelled catalytic micromotors are biofunctionalized and trapped acting as an alternative concentrating mechanism. This system requires no external energy source, which facilitates integration and miniaturization.


ELYS/MEL-28 chromatin association coordinates nuclear pore complex assembly and replication licensing.
Xenopus egg extract supports all the major cell-cycle transitions in vitro. We have used a proteomics approach to identify proteins whose abundance on chromatin changes during the course of an in vitro cell cycle. One of the proteins we identified was ELYS/MEL-28, which has recently been described as the earliest-acting factor known to be required for nuclear pore complex (NPC) assembly [1-4]. ELYS interacts with the Nup107-160 complex and is required for its association with chromatin. ELYS contains an AT-hook domain, which we show binds to chromatin with a high affinity. This domain can compete with full-length ELYS for chromatin association, thereby blocking NPC assembly. This provides evidence that ELYS interacts directly with chromatin and that this interaction is essential for NPC assembly and compartmentalization of chromosomal DNA within the cell. Furthermore, we detected a physical association on chromatin between ELYS and the Mcm2-7 replication-licensing proteins. ELYS chromatin loading, NPC assembly, and nuclear growth were delayed when Mcm2-7 was prevented from loading onto chromatin. Because nuclear assembly is required to shut down licensing prior to entry into S phase, our results suggest a mechanism by which these two early cell-cycle events are coordinated with one another.