Photocatalytic reactivity tuning by heterometal and addenda metal variation in Lindqvist polyoxometalates.
A systematic study into the effects of metal substitution on the visible-light photocatalytic activity of prototype metal oxide cluster anions is presented. Four isostructural Lindqvist clusters [V(x)M(6-x)O19]((2+x)-) (M = W, Mo, x = 1, 2) with photooxidative activity in the visible range are reported. It is shown that the photooxidative performance correlates with the number of vanadium atoms in the cluster. Further, two divergent reaction mechanisms are observed depending on the type of addenda metal (i.e. Mo or W) used. When comparing the reactivity under aerated vs. de-aerated conditions, it was found that molybdate-based clusters show significantly increased reaction rates in the absence of oxygen; in contrast, marginally reduced reaction rates were observed for the tungstate-based species under de-aerated conditions. Wavelength-dependent quantum efficiency studies provide insight into the visible-light reactivity of all four species. Radical scavenging experiments suggest that the photocatalysis proceeds via formation of hydroxyl radicals. Cluster recycling studies demonstrate the robust nature of the homogeneous photocatalysts.


In vitro decapsidation of turnip yellow mosaic virus investigated by cryo-electron microscopy: a model for the decapsidation of a small isometric virus.
The in vitro decapsidation of a small isometric plant virus, turnip yellow mosaic virus (TYMV), was investigated by cryo-electron microscopy. Cryo-electron micrographs of TYMV and empty shells show that rapidly frozen virions still contain their RNA. Images of vitrified virions resemble closely those previously obtained by negative staining. Rapidly frozen virions decapsidate upon thawing although they remain well dispersed on the grid. The escape of the RNA through a hole at the periphery of the capsid could be visualized. The results suggest a model for the in situ decapsidation of small icosahedral viruses.


Insulin inhibits the accumulation of the major lung surfactant apoprotein in human fetal lung explants maintained in vitro.
In the present study, we characterized the proteins associated with a purified lamellar body fraction isolated from human fetal lung explants. We then raised antibodies directed against the major human surfactant apoprotein, a 35-K glycoprotein, and used the technique of immunoblot analysis to evaluate the content of the surfactant apoprotein in human fetal lung explants maintained in serum-free medium in vitro. We found that the 35K surfactant apoprotein was undetectable in homogenates of fetal lung tissue before culture; the surfactant apoprotein was induced in the cultured explants coincident with the appearance of differentiated type II cells. Insulin, at concentrations as low as 2.5 ng/ml, caused marked inhibition of the accumulation of the 35K protein in the cultured fetal lung tissue. The inhibitory effect of insulin was dose dependent and was apparent as early as day 2 of incubation. When explants were cultured in medium containing insulin plus cortisol, the amount of immunoreactive surfactant apoprotein was reduced compared to that of explants cultured in control medium or explants cultured with cortisol alone. On the other hand, as reported previously, insulin and cortisol, in combination, stimulated phosphatidylcholine synthesis. These findings are indicative that the phospholipid and apoprotein components of surfactant are regulated independently. The results of our studies suggest that fetal hyperinsulinemia may cause the production of a surfactant deficient in the 35K apoprotein, and this may provide an explanation for the increased incidence of respiratory distress syndrome in infants of diabetic mothers.


Evidence-based diagnosis and treatment for specific learning disabilities involving impairments in written and/or oral language.
Programmatic, multidisciplinary research provided converging brain, genetic, and developmental support for evidence-based diagnoses of three specific learning disabilities based on hallmark phenotypes (behavioral expression of underlying genotypes) with treatment relevance: dysgraphia (impaired legible automatic letter writing, orthographic coding, and finger sequencing), dyslexia (impaired pseudoword reading, spelling, phonological and orthographic coding, rapid automatic naming, and executive functions; inhibition and rapid automatic switching), and oral and written language learning disability (same impairments as dyslexia plus morphological and syntactic coding and comprehension). Two case studies illustrate how these differential diagnoses can be made within a conceptual framework of a working memory architecture and generate treatment plans that transformed treatment nonresponders into treatment responders. Findings are discussed in reference to the importance of (a) considering individual differences (diagnosis of impaired hallmark phenotypes) in planning and evaluating response to instruction and modifying instruction when a student is not responding; (b) recognizing that teaching may change epigenetic gene expression at one stage of schooling, but not the underlying gene sequences that render individuals still vulnerable as curriculum requirements increase in nature, complexity, and volume in the upper grades; and (c) using evidence-based diagnoses of specific learning disabilities that are consistent across states for free and appropriate education K to 12 and for accommodations throughout higher education and professional credentialing.


Site-saturation mutagenesis of Tyr-105 reveals its importance in substrate stabilization and discrimination in TEM-1 beta-lactamase.
The conserved Class A beta-lactamase active site residue Tyr-105 was substituted by saturation mutagenesis in TEM-1 beta-lactamase from Escherichia coli in order to clarify its role in enzyme activity and in substrate stabilization and discrimination. Minimum inhibitory concentrations were calculated for E. coli cells harboring each Y105X mutant in the presence of various penicillin and cephalosporin antibiotics. We found that only aromatic residues as well as asparagine replacements conferred high in vivo survival rates for all substrates tested. At position 105, the small residues alanine and glycine provide weak substrate discrimination as evidenced by the difference in benzylpenicillin hydrolysis relative to cephalothin, two typical penicillin and cephalosporin antibiotics. Kinetic analyses of mutants of interest revealed that the Y105X replacements have a greater effect on K(m) than k(cat), highlighting the importance of Tyr-105 in substrate recognition. Finally, by performing a short molecular dynamics study on a restricted set of Y105X mutants of TEM-1, we found that the strong aromatic bias observed at position 105 in Class A beta-lactamases is primarily defined by a structural requirement, selecting planar residues that form a stabilizing wall to the active site. The adopted conformation of residue 105 prevents detrimental steric interactions with the substrate molecule in the active site cavity and provides a rationalization for the strong aromatic bias found in nature at this position among Class A beta-lactamases.


Bioactivity studies on Cassia alata Linn. leaf extracts.
The hexane, chloroform and ethyl acetate extracts of the leaves of Cussia alata Linn. were tested for their antimutagenic, antifungal, analgesic, antiinflammatory and hypoglycaemic activities. At a dosage of 5 mg/20 g mouse, the hexane extract was analgesic as it reduced the number of squirms induced by acetic acid by 59.5%. Both the hexane and EtOAc extracts exhibited antiinflammatory activity at a dosage of 5 mg/20 g mouse with a 65.5% and 68.2% decrease in carrageenan-induced inflammation, respectively. The chloroform extract was antimutagenic, at a dosage of 2 mg/20 g mouse, with a 65.8% inhibition in the mutagenicity of tetracycline. It was also the most active against Trichophyton mentagrophytes, at a concentration of 50 mg/mL but it had no activity against Candida albicans. The hexane and EtOAc extracts showed some activity against both organisms, with the EtOAc extract being more active against C. albicans. The EtOAc extract was hypoglycaemic. At a dosage of 5 mg/20 g mouse, it decreased the blood sugar level of mice by 58.3%. Pharmacological studies showed that all extracts caused an immediate decrease in motor activity, enophthalmus, hyperemia, micturition and diarrhoea. At a dosage of 150 mg/20 g mouse, the EtOAc extract caused paralysis, screen grip loss and enophthalmus accompanied by drooping and closure of the eyelids.


[Depressive symptoms in the elderly. Prevalence and associated factors].
To estimate the prevalence of depressive symptoms in people older than 64 and to analyze their association with sociodemographic factors, frailty markers, and disabling diseases. A survey-based, cross-sectional descriptive study was carried out. The sample was composed of 417 elderly people living in Guadalajara (Spain), selected on the basis of health cards. Depressive symptoms were assessed using Yesavage's test (cut-off: 6 or more items). The questionnaire contained sociodemographic and clinical items and evaluation scales for cognitive impairment, disability, and social risk. The frailty markers studied were age over 80 years old, female sex, cognitive impairment, disability, polypharmacy, comorbidity, and social risk. The prevalence of depressive symptoms was 19.7% (95% CI, 15.9-23.4) and clinical depression was diagnosed in 5% (95% CI, 2.3-7.7). Depressive symptoms were more frequent in elderly individuals living in rural environments than in those living in urban areas (p < 0.05). These symptoms increased with age (p linear trend < 0.001) and were associated with social risk (p < 0.001), comorbidity (p < 0.001), cognitive impairment (p < 0.01), and disability (p < 0.05). When a multivariate statistical analysis was applied using logistic regression models, only comorbidity (odds ratio [OR] = 2.38; 95% CI, 1.35-4.20) and social risk (OR = 2.69; 95% CI, 1.50-4.83) were significantly associated. The prevalence of depressive symptoms is very high in the elderly, four times higher than a diagnosis of clinical depression. Social risk and comorbidity are strongly associated with depressive symptoms.


Interfacial and bulk nanostructure of liquid polymer nanocomposites.
Liquid polymer nanocomposites (l-PNCs) have been prepared using silica nanoparticles with diameters of 15 nm (l-PNC-15) and 24 nm (l-PNC-24), and Jeffamine M-2070, an amine-terminated ethylene oxide/propylene oxide (PEO/PPO, ratio 31/10) copolymer. Jeffamine M-2070 was used as the host liquid in which the particles were suspended and was also grafted onto the particle surface to prevent aggregation. The grafting density of Jeffamine M-2070 on the particle surfaces was ∼0.75 chains nm(-2). When the total polymer content (surface layer + host) was greater than ∼30 wt %, the PNC was a liquid, while at lower polymer volume fractions the PNC was solid. In this work, the bulk and surface structures of l-PNCs with ∼70 wt % polymer and 30% silica are characterized and compared. Small-angle neutron scattering (SANS) was used to probe the bulk structure of the l-PNCs and revealed that the particles are well-dispersed with minor clustering in l-PNC-15 and substantial clustering in l-PNC-24. This is attributed to stronger van der Waals attractions between particles due to the larger particle size in l-PNC-24. Corresponding effects were revealed using tapping mode atomic force microscopy (TM-AFM) at the l-PNC-air interface; clustering was minimal on the surface of l-PNC-15 but significant for l-PNC-24 droplets. In regions of the l-PNC where the particles were well-dispersed, the spacing between particles is consistent with their volume fractions. This is the first time that the distribution of polymer and particles within l-PNCs has been imaged in situ.


A Novel Four Single-Sideband M-QAM Modulation Scheme Using a Shadow Equalizer for MIMO System Toward 5G Communications.
Single-sideband (SSB) modulation through Hilbert transformation has successfully transmitted data using only half the bandwidth of the traditional scheme for the same amount of contained information. Toward this end, the four single-sideband (4-SSB) approach for high order modulation is a promising approach for the next-generation communications by applying soft-input soft-output (SISO) equalizer algorithms over orthogonal frequency division multiplexing (OFDM). However, OFDM is challenging for realizing the feasible 5G communications, compared to the emerging techniques, e.g., non-orthogonal multiple access (NOMA), orthogonal multiple access (OMA) or multiple-input multiple-output (MIMO). Since the 4-SSB is an orthogonal modulation which was successfully applied over the traditional OFDM, in this article, we propose a novel 4-SSB modulation scheme over OFDM Guard Interval (GI) and massive MIMO. Besides the carrier signal, from the receiver side, we also apply the shadow equalizer algorithm in the uncoded and coded environment using turbo codes to achieve the 4-SSB with high efficiency from low complexity and energy consumption for 5G. The evaluation results validate that our system consumes lower energy due to low complexity gained from same number of iterations without the heavy decoding as of the 4-SSB SISO based on the turbo equalizer. In addition, the 4-SSB over the OFDM GI achieves the best performance among the relevant approaches conducted in 4-SSB. The proposal then acts as a practical communication system designed to solve the inter-symbol interference (ISI) induced by additional Hilbert transform in the wireless environment toward fifth generation (5G), given that turbo code is considered as a potential channel coding scheme for 5G radio specification.


Marketing to rural seniors: opportunities for the service sector.
A recent study of rural Midwestern elderly consumers revealed a need for and interest in purchasing services designed for this sizeable and rapidly growing market. The study investigated the levels of need for 54 proposed services which could be provided through non-governmental institutions (businesses and non-profit organizations), along with the elderly consumer's ability and willingness to pay a "reasonable price" for the services. Based on the research findings, those service categories possessing market potential are presented and recommendations for marketing to rural elderly consumers are discussed.


Alteration of the exopolysaccharide production and the transcriptional profile of free-living Frankia strain CcI3 under nitrogen-fixing conditions.
We investigated the effect of different nitrogen (N) sources on exopolysaccharide (EPS) production and composition by Frankia strain CcI3, a N2-fixing actinomycete that forms root nodules with Casuarina species. Frankia cells grown in the absence of NH4Cl (i.e., under N2-fixing conditions) produced 1.7-fold more EPS, with lower galactose (45.1 vs. 54.7 mol%) and higher mannose (17.3 vs. 9.7 mol%) contents than those grown in the presence of NH4Cl as a combined N-source. In the absence of the combined N-source, terminally linked and branched residue contents were nearly twice as high with 32.8 vs. 15.1 mol% and 15.1 vs. 8.7 mol%, respectively, than in its presence, while the content of linearly linked residues was lower with 52.1 mol% compared to 76.2 mol%. To find out clues for the altered EPS production at the transcriptional level, we performed whole-gene expression profiling using quantitative reverse transcription PCR and microarray technology. The transcription profiles of Frankia strain CcI3 grown in the absence of NH4Cl revealed up to 2 orders of magnitude higher transcription of nitrogen fixation-related genes compared to those of CcI3 cells grown in the presence of NH4Cl. Unexpectedly, microarray data did not provide evidence for transcriptional regulation as a mechanism for differences in EPS production. These findings indicate effects of nitrogen fixation on the production and composition of EPS in Frankia strain CcI3 and suggest posttranscriptional regulation of enhanced EPS production in the absence of the combined N-source.


Surface asymmetry of coated spherical nanoparticles.
We validate the nonspherical grafting arrangement of isotropically coated spherical nanoparticles as very recently proposed. We utilize localized surface plasmon resonance enhanced dynamic polarized and depolarized light scattering from Au nanoparticles, the spherical symmetry of which was revealed by single-particle dark-field spectroscopy. The same Au nanospheres are grafted with ligands of different chemistry and length. The wavelength dependent depolarization ratio and the two transport coefficients of these nanoparticles, obtained from the dynamic light scattering experiment, can only be reconciled with the TEM data, the single UV/vis extinction spectrum, and the dark-field spectroscopy experiments if their coating is described as asymmetric. Spatially anisotropic graft distribution on spherical nanoparticles impacts their assembly and understanding its origin will help control the structure and properties of polymer nanocomposites.


Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update.
Purpose To update the ASCO guideline for antiemetics in oncology. Methods ASCO convened an Expert Panel and conducted a systematic review of the medical literature for the period of November 2009 to June 2016. Results Forty-one publications were included in this systematic review. A phase III randomized controlled trial demonstrated that adding olanzapine to antiemetic prophylaxis reduces the likelihood of nausea among adult patients who are treated with high emetic risk antineoplastic agents. Randomized controlled trials also support an expanded role for neurokinin 1 receptor antagonists in patients who are treated with chemotherapy. Recommendation Key updates include the addition of olanzapine to antiemetic regimens for adults who receive high-emetic-risk antineoplastic agents or who experience breakthrough nausea and vomiting; a recommendation to administer dexamethasone on day 1 only for adults who receive anthracycline and cyclophosphamide chemotherapy; and the addition of a neurokinin 1 receptor antagonist for adults who receive carboplatin area under the curve ≥ 4 mg/mL per minute or high-dose chemotherapy, and for pediatric patients who receive high-emetic-risk antineoplastic agents. For radiation-induced nausea and vomiting, adjustments were made to anatomic regions, risk levels, and antiemetic administration schedules. Rescue therapy alone is now recommended for low-emetic-risk radiation therapy. The Expert Panel reiterated the importance of using the most effective antiemetic regimens that are appropriate for antineoplastic agents or radiotherapy being administered. Such regimens should be used with initial treatment, rather than first assessing the patient's emetic response with less-effective treatment. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .


Chromium and arsenic speciation analysis in meats by HPLC-ICP-MS in the presence of hydrolyzed oat proteins with radical scavenging activities.
Transition metals play an important role in a wide variety of biological processes, but their functions are dependent on the quantity and the type of species present. Specific forms of arsenic (As) and chromium (Cr) are associated with oxidative stress, cellular damage and inflammation. The aim of this research was to test in a food system whether, in the presence of hydrolyzed oat proteins, arsenic or chromium will exist predominantly in a specific oxidative state, and to evaluate the potential implication of promoting or decreasing oxidative stress. Eight hydrolyzed proteins with different degrees of radical scavenging activities were produced by combining two extraction methods and four proteases. The addition of hydrolysates to ground chicken meat decreased lipid hydroperoxides by up to 50% when stored at 4 °C but had no effect at -20 °C. The ratio of pentavalent arsenic (As(V)) to arsenobetaine (AsB) in meat was about 2:1 but in the presence of the hydrolysates, meanwhile, the amount of AsB detected was 3-fold higher depending on the storage condition. This was due to better extraction of AsB in the presence of hydrolysates rather than to the conversion of other species. Data on chromium showed that Cr(VI) contents decreased from 14.3 ± 0.1 to 6.3 ± 0.5 μg/g while concentrations of Cr(III) increased from 2.8 ± 0. 2 to 8.6 ± 0.7 μg/g. In summary, the addition of hydrolyzed oat proteins to chicken meat enhanced the extraction of AsB, and had little effect on arsenic speciation during storage meanwhile, there was a reduction of Cr(VI) to Cr(III) which was in part due to the relative content of thiol groups. Additionally, there was a reduction of lipid oxidation in meats that contained the oat protein hydrolysates.


Molecular genetic epidemiology of age-related hearing impairment.
Genetic epidemiology focuses on the genetic determinants in the etiology of disease among populations and seeks to elucidate the role of genetic factors and their interaction with environmental factors in disease occurrence. In recent years, genetic epidemiological research has become more focused on complex diseases, and human genome analysis technology has made remarkable advances. Age-related hearing impairment (ARHI) is a complex trait, which results from a multitude of confounding intrinsic and extrinsic factors. Although the number of genetic investigations of ARHI is increasing at a surprising rate, the etiology of ARHI is not firmly established. In this article, we review (1) the methodological strategies used to analyze genetic factors that contribute to human ARHI, (2) several representative investigations, and (3) specific genetic risk factors for human ARHI identified in previous work.


Reactivity of old yellow enzyme with alpha-NADPH and other pyridine nucleotide derivatives.
The reaction of Old Yellow Enzyme (OYE) with pyridine nucleotides has been examined using steady state kinetics, rapid reaction kinetics, and equilibrium binding. alpha-NADPH, beta-NADPH, and the acid breakdown products of NADPH all bind to oxidized OYE with dissociation constants below 1 microM. These complexes produce characteristic red shifts in the absorption spectrum of OYE. A similar red shift which occurs after multiple turnovers of OYE with NADPH has been found to be due to an impurity in the NADPH preparation, possibly an acid breakdown product. Anions such as chloride, acetate, azide, and phenolates compete with the pyridine nucleotides for binding to a common site in oxidized OYE. Anaerobic reduction of OYE by NADPH proceeds via two intermediates to establish a readily reversible equilibrium. In contrast to most other NADPH-dependent enzymes, both alpha- and beta-NADPH are capable of reducing OYE, and alpha-NADPH is more effective. Using beta-[4(R)-2H]NADPH, a primary deuterium isotope effect was observed in the reduction reaction. Results from rapid reaction and steady state studies showed that reduction of OYE was rate limiting in turnover. Consistent with this, the turnover number with alpha-NADPH was significantly higher than that with beta-NADPH.


Small Diameter Xenogeneic Extracellular Matrix Scaffolds for Vascular Applications.
Currently, despite the success of percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) remains among the most commonly performed cardiac surgical procedures in the United States. Unfortunately, the use of autologous grafts in CABG presents a major clinical challenge as complications due to autologous vessel harvest and limited vessel availability pose a significant setback in the success rate of CABG surgeries. Acellular extracellular matrix (ECM) scaffolds derived from xenogeneic vascular tissues have the potential to overcome these challenges, as they offer unlimited availability and sufficient length to serve as "off-the-shelf" CABGs. Unfortunately, regardless of numerous efforts to produce a fully functional small diameter xenogeneic ECM scaffold, the combination of factors required to overcome all failure mechanisms in a single graft remains elusive. This article covers the major failure mechanisms of current xenogeneic small diameter vessel ECM scaffolds, and reviews the recent advances in the field to overcome these failure mechanisms and ultimately develop a small diameter ECM xenogeneic scaffold for CABG. Impact Statement Currently, the use of autologous vessel in coronary artery bypass graft (CABG) is common practice. However, the use of autologous tissue poses significant complications due to tissue harvest and limited availability. Developing an alternative vessel for use in CABG can potentially increase the success rate of CABG surgery by eliminating complications related to the use of autologous vessel. However, this development has been hindered by an array of failure mechanisms that currently have not been overcome. This article describes the currently identified failure mechanisms of small diameter vascular xenogeneic extracellular matrix scaffolds and reviews current research targeted to overcoming these failure mechanisms toward ensuring long-term graft patency.


Investigation of the substrate recognition of Drosophila melanogaster nucleoside kinase by site directed mutagenesis.
The deoxyribonucleoside kinase of Drosophila melanogaster (Dm-dNK) has a broad substrate specificity and a higher catalytic rate than other known deoxyribonucleoside kinases. Therefore it is a natural candidate for possible use as a suicide gene in combined gene/chemotherapy of cancer. We have performed site directed mutagenesis and tested different truncated forms of the enzyme in order to increase the affinity for ganciclovir.


The hepatitis B virus precore protein is retrotransported from endoplasmic reticulum (ER) to cytosol through the ER-associated degradation pathway.
The hepatitis B virus precore protein is closely related to the nucleocapsid core protein but is processed distinctly in the cell and plays a different role in the viral cycle. Precore is addressed to the endoplasmic reticulum (ER) through a signal peptide, and the form present in the ER is the P22 protein. P22 is then cleaved in its C-terminal part to be secreted as HBe antigen. In addition, a cytosolic form of 22 kDa less characterized has been observed. Precore gene was shown to be implicated in viral persistence, but until now, the actual protein species involved has not been determined. Our work focuses on the cytosolic form of precore. Using human cells expressing precore and a convenient fractionation assay, we demonstrated that the cytosolic form is identical to the ER form and retrotransported in the cytoplasm through the ER-associated degradation pathway. This cellular machinery translocates misfolded proteins to the cytoplasm, where they are ubiquitinated on lysine residues and degraded by proteasome. We showed that precore escapes proteasome due to its low lysine content and accumulates in the cytosol. The role of this retrotransport was investigated. In the presence of precore, we found a specific redistribution of the Grp78/BiP chaperone protein to cytosol and demonstrated a specific interaction between precore and Grp78/BiP. Altogether, these data support the idea that the hepatitis B virus develops a strategy to take advantage of the ER-associated degradation pathway, allowing distinct subcellular localization and probably distinct roles for the viral precore protein.


Effectiveness of a peer support intervention for antenatal depression: a feasibility study.
A feasibility study for a randomised controlled trial to assess the acceptability, recruitment, feasibility and effectiveness of a peer support intervention for women with antenatal depression. The key premise of peer support is based upon the trust and empathetic understanding engendered by common experiences. Twenty pregnant women were recruited by their community midwife using the Whooley questionnaire at between 28-30 weeks' gestation to ascertain their level of mood and general mental health. Women identified as having potential antenatal depression were randomly assigned into a control group (routine care alone which includes contact with a midwife and in some case an obstetric Doctor with access to a GP if required) or intervention group (6-weekly visits from a peer support worker in addition to routine care). Participants from both the control and intervention group, and the Peer Support Workers (PSWs) were then interviewed at the end of the six-week period. All participants, and the PSW's, were also asked to keep log books during the trial to record their feelings and experiences. The results were then analysed using thematic analysis. The analysis of qualitative data from the PSWs, and the participants in the intervention group, suggest the peer support intervention is acceptable, helpful and supportive to both pregnant women and, indeed, the PSWs. The women within the intervention group valued the peer support highly, reporting that being able to speak openly to a PSW meant that feelings of alienation, abnormality, isolation and stigma were replaced with social support, confidence, self-esteem and hope for recovery. The PSWs reported a positive impact upon their own wellbeing and a realisation that they had, indeed, moved forward with their lives. A proportion of the women randomised to the control group described feelings of disappointment and frustration with the lack of support currently available to them. This feasibility study suggests a full randomised controlled trial (RCT) is warranted given the high recruitment, adherence, and acceptability of the intervention to participants.


Predictors of Clostridium difficile infection severity in patients hospitalised in medical intensive care.
To describe and analyse factors associated with Clostridium difficile infection (CDI) severity in hospitalised medical intensive care unit patients. We performed a retrospective cohort study of 40 patients with CDI in a medical intensive care unit (MICU) at a French university hospital. We include patients hospitalised between January 1, 2007 and December 31, 2011. Data on demographics characteristics, past medical history, CDI description was collected. Exposure to risk factors associated with CDI within 8 wk before CDI was recorded, including previous hospitalisation, nursing home residency, antibiotics, antisecretory drugs, and surgical procedures. All included cases had their first episode of CDI. The mean incidence rate was 12.94 cases/1000 admitted patients, and 14.93, 8.52, 13.24, 19.70, and 8.31 respectively per 1000 admitted patients annually from 2007 to 2011. Median age was 62.9 [interquartile range (IQR) 55.4-72.40] years, and 13 (32.5%) were women. Median length of MICU stay was 14.0 d (IQR 5.0-22.8). In addition to diarrhoea, the clinical symptoms of CDI were fever (> 38 °C) in 23 patients, abdominal pain in 15 patients, and ileus in 1 patient. The duration of diarrhoea was 13.0 (8.0-19.5) d. In addition to diarrhoea, the clinical symptoms of CDI were fever (> 38 °C) in 23 patients, abdominal pain in 15 patients, and ileus in 1 patient. Prior to CDI, 38 patients (95.0%) were exposed to antibiotics, and 12 (30%) received at least 4 antibiotics. Fluoroquinolones, 3(rd) generation cephalosporins, coamoxiclav and tazocillin were prescribed most frequently (65%, 55%, 40% and 37.5%, respectively). The majority of cases were hospital-acquired (n = 36, 90%), with 5 cases (13.9%) being MICU-acquired. Fifteen patients had severe CDI. The crude mortality rate within 30 d after diagnosis was 40% (n = 16), with 9 deaths (9 over 16; 56.3%) related to CDI. Of our 40 patients, 15 (37.5%) had severe CDI. Multivariate logistic regression showed that male gender [odds ratio (OR): 8.45; 95%CI: 1.06-67.16, P = 0.044], rising serum C-reactive protein levels (OR = 1.11; 95%CI: 1.02-1.21, P = 0.021), and previous exposure to fluoroquinolones (OR = 9.29; 95%CI: 1.16-74.284, P = 0.036) were independently associated with severe CDI. We report predictors of severe CDI not dependent on time of assessment. Such factors could help in the development of a quantitative score in ICU's patients.


Risk management in air protection in the Republic of Croatia.
In the Republic of Croatia, according to the Air Protection Act, air pollution assessment is obligatory on the whole State territory. For individual regions and populated areas in the State a network has been established for permanent air quality monitoring. The State network consists of stations for measuring background pollution, regional and cross-border remote transfer and measurements as part of international government liabilities, then stations for measuring air quality in areas of cultural and natural heritage, and stations for measuring air pollution in towns and industrial zones. The exceeding of alert and information threshold levels of air pollutants are related to emissions from industrial plants, and accidents. Each excess represents a threat to human health in case of short-time exposure. Monitoring of alert and information threshold levels is carried out at stations from the state and local networks for permanent air quality monitoring according to the Air Quality Measurement Program in the State network for permanent monitoring of air quality and air quality measurement programs in local networks for permanent air quality monitoring. The State network for permanent air quality monitoring has a developed automatic system for reporting on alert and information threshold levels, whereas many local networks under the competence of regional and local self-governments still lack any fully installed systems of this type. In case of accidents, prompt action at all responsibility levels is necessary in order to prevent crisis and this requires developed and coordinated competent units of State Administration as well as self-government units. It is also necessary to be continuously active in improving the implementation of legislative regulations in the field of crises related to critical and alert levels of air pollutants, especially at local levels.


Why Did the ACA Co-Op Program Fail? Lessons for the Health Reform Debate.
The ACA created a new type of nonprofit health insurance entity, the "Consumer Operated and Oriented Plan" ("co-op"). Most of the newly created co-ops soon lost money, and only 4 of the original 23 remain. We interviewed key stakeholders and conducted in-depth case studies of 3 of these co-ops. We discovered that politicians and regulators made it unlikely the program could succeed, that most of the co-ops did not have the management capacity to overcome these political obstacles, and that even those with good managers lacked the needed fiscal resilience. We also considered lessons suggested for those proposing a newly created "public option." The main one is that a successful public option requires a supportive political environment, strong management, and significant fiscal capacity, none of which comes easily. A better route may be a quasi-public option in which the government subcontracts the operation of its newly created plan to a private firm. Although it is uncertain whether federal regulators have the capacity to hold such private for-profit firms accountable, pragmatism suggests that a combination of public-sector regulation and private-sector implementation may be the most direct path toward a US version of affordable universal coverage.


Adaptive response to Eimeria acervulina in rearing hens is affected by suboptimal incubation temperature and heat exposure in later life.
This study aimed to investigate whether suboptimal incubation (SI) temperature in weeks 1 and 3 of layer embryo incubation affects their development and post-hatch adaptive capacity during infectious challenges, by using Eimeria as a model infection under normal and immediately after more challenging environmental conditions of 72 h heat exposure. Eggs (n = 160 per treatment) were incubated at optimal (OI = 37.8°C continuously) or suboptimal eggshell temperature (36.7°C, 37.8°C and 38.9°C in weeks 1, 2 and 3, respectively). At day 33 of age, half the chickens of each incubation treatment were exposed to 72 h heat (35°C), whereas the other half remained under control conditions (21°C). At day 36 of age, all chickens were inoculated with 1 ml of a phosphate buffer saline solution containing 25 000 sporulated Eimeria acervulina oocysts/ml. The adaptive response to E. acervulina was measured by BW gain and FI from days 0 to 3 post infection (p.i.), days 3 to 5 p.i. and days 5 to 7 p.i., and by oocyst production (days 4 and 7 p.i.) and lesion scores in the duodenum (day 3, 4 and 7 p.i.). Our results demonstrated that SI temperatures in weeks 1 and 3 of incubation resulted in a reduction in yolk-free BW, chick length and navel condition. Moreover, SI temperature appeared to reduce the adaptive capacity to E. acervulina. This was demonstrated by tendencies to lower FI (P = 0.07) and BW gain (P = 0.08), more duodenal lesions (P = 0.09) and higher oocyst production (P = 0.02) after inoculation of E. acervulina. Higher lesion scores and faecal oocyst numbers were especially found when suboptimal incubation was combined with heat exposure preceding the infection. In conclusion, SI layer chickens tend to be less able to cope with an infectious challenge post hatch.


Myocardial ischaemia in asphyxia neonatorum. Electrocardiographic, enzymatic and histological correlations.
Serial electrocardiograms and creatine kinase (CK) isoenzyme activities were studied prospectively in 20 asphyxiated term newborn infants and 43 normal neonates. By adapting a previously described grading system for ischaemic changes, a degree of electrocardiographic ischaemia was defined which occurred almost solely in asphyxiated infants. Infants with this degree of abnormality had significantly higher mean CK-MB and MM activities than other asphyxiated infants at 0, 8 and 28 hours. Histological changes of peripartum myocardial necrosis were seen in 4 of the 5 infants on whom an autopsy was performed, and either electrocardiogram or CK-MB was abnormal in all four. It is concluded that myocardial injury in the newborn period is often associated with CK-MB release, but in view of the lack of cardiac-specificity of CK-MB in newborn infants, caution is urged in the interpretation of elevated isoenzyme activity in the neonate.


Relationship between urbanization and CO2 emissions depends on income level and policy.
We investigate empirically how national-level CO2 emissions are affected by urbanization and environmental policy. We use statistical modeling to explore panel data on annual CO2 emissions from 80 countries for the period 1983-2005. Random- and fixed-effects models indicate that, on the global average, the urbanization-emission elasticity value is 0.95 (i.e., a 1% increase in urbanization correlates with a 0.95% increase in emissions). Several regions display a statistically significant, positive elasticity for fixed- and random-effects models: lower-income Europe, India and the Sub-Continent, Latin America, and Africa. Using two proxies for environmental policy/outcomes (ratification status for the Kyoto Protocol; the Yale Environmental Performance Index), we find that in countries with stronger environmental policy/outcomes, urbanization has a more beneficial (or, a less negative) impact on emissions. Specifically, elasticity values are -1.1 (0.21) for higher-income (lower-income) countries with strong environmental policy, versus 0.65 (1.3) for higher-income (lower-income) countries with weak environmental policies. Our finding that the urbanization-emissions elasticity may depend on the strength of a country's environmental policy, not just marginal increases in income, is in contrast to the idea of universal urban scaling laws that can ignore local context. Most global population growth in the coming decades is expected to occur in urban areas of lower-income countries, which underscores the importance of these findings.


Rhodamine 6G and 800 J-heteroaggregates with enhanced acceptor luminescence (HEAL) adsorbed in transparent SiO2 GLAD thin films.
An enhanced fluorescent emission in the near infrared is observed when the Rhodamine 800 (Rh800) and 6G (Rh6G) dyes are coadsorbed in porous SiO(2) optical thin films prepared by glancing angle deposition (GLAD). This unusual behavior is not observed in solution and it has been ascribed to the formation of a new type of J-heteroaggregates with enhanced acceptor luminescence (HEAL). This article describes in detail and explains the main features of this new phenomenology previously referred in a short communication [J. R. Sánchez-Valencia, J. Toudert, L. González-García, A. R. González-Elipe and A. Barranco, Chem. Commun., 2010, 46, 4372-4374]. It is found that the efficiency and characteristics of the energy transfer process are dependent on the Rh6G/Rh800 concentration ratio which can be easily controlled by varying the pH of the solutions used for the infiltration of the molecules or by thermal treatments. A simple model has been proposed to account for the observed enhanced acceptor luminescence in which the heteroaggregates order themselves according to a "head to tail" configuration due to the geometrical constrains imposed by the SiO(2) porous matrix thin film. The thermal stability of the dye molecules within the films and basic optical (absorption and fluorescence) principles of the HEAL process are also described.


Medication adherence: emerging use of technology.
Adherence to proven, effective medications remains low, resulting in high rates of clinical complications, hospital readmissions, and death. The use of technology to identify patients at risk and to target interventions for poor adherence has increased. This review focuses on research that tests these emerging technologies and evaluates the effect of technology-based adherence interventions on cardiovascular outcomes. Recent studies have evaluated technology-based interventions to improve medication adherence by using pharmaceutical databases, tailoring educational information to individual patient needs, delivering technology-driven reminders to patients and providers, and integrating in-person interventions with electronic alerts. Cellular phone reminders and in-home electronic technology used to communicate reminder messages have shown mixed results. Only one study has shown improvement in both adherence and clinical outcome. Current trials suggest that increasing automated reminders will complement but not replace the benefits seen with in-person communication for medication taking. Integration of in-person contacts with technology-driven medication adherence reminders, electronic medication reconciliation, and pharmaceutical databases may improve medication adherence and have a positive effect on cardiovascular clinical outcomes. Opportunities for providers to monitor the quality of care based on new adherence research are evolving and may be useful as standards for quality improvement emerge.


Structural and kinetic differences between human and Aspergillus fumigatus D-glucosamine-6-phosphate N-acetyltransferase.
Aspergillus fumigatus is the causative agent of aspergillosis, a frequently invasive colonization of the lungs of immunocompromised patients. GNA1 (D-glucosamine-6-phosphate N-acetyltransferase) catalyses the acetylation of GlcN-6P (glucosamine-6-phosphate) to GlcNAc-6P (N-acetylglucosamine-6-phosphate), a key intermediate in the UDP-GlcNAc biosynthetic pathway. Gene disruption of gna1 in yeast and Candida albicans has provided genetic validation of the enzyme as a potential target. An understanding of potential active site differences between the human and A. fumigatus enzymes is required to enable further work aimed at identifying selective inhibitors for the fungal enzyme. In the present study, we describe crystal structures of both human and A. fumigatus GNA1, as well as their kinetic characterization. The structures show significant differences in the sugar-binding site with, in particular, several non-conservative substitutions near the phosphate-binding pocket. Mutagenesis targeting these differences revealed drastic effects on steady-state kinetics, suggesting that the differences could be exploitable with small-molecule inhibitors.


Comparison of a Modified Antegrade and Retrograde Ureteral Double-J Stenting Techniques during Laparoscopic and Robotic Pyeloplasty.
To compare the effect of a modified antegrade and retrograde double-J stenting techniques on stenting and operation time in patients who underwent laparoscopic or robotic pyeloplasty. A total of 74 patients undergoing transperitoneal laparoscopic or robotic pyeloplasty were enrolled into this study. The antegrade (Group 1) and retrograde (Group 2) techniques were compared for operation time, stenting time, complication, and reoperation rates. There were 41 and 33 patients in Groups 1 and 2, respectively. Both groups were similar in terms of age, side, and gender distribution. The mean operation times were 122.4 and 139.7 min in Groups 1 and 2, respectively (p < 0.001). The stenting times were 2.39 and 14.15 min in Groups 1 and 2, respectively (p < 0.001). The reoperation and complication rates were 7.3 and 6%, respectively, and similar for both groups (p = 1). Our new technique significantly shortens the duration of laparoscopic and robotic pyeloplasty without compromising success and complication rates.


Energy response of EBT3 radiochromic films: implications for dosimetry in kilovoltage range.
The objective of this study is to evaluate the suitability of recently introduced radiochromic film EBT3 for clinical dosimetry in the kilovoltage (kV) range. For this purpose, a kV X-ray irradiator, X RAD 320ix in the range 70 to 300 kVp, a clinical 60Co source, a 6 MV and an 18 MV X-ray clinical beam from a Varian linear accelerator were calibrated following AAPM dosimetry protocols. EBT3 films from two different EBT3 batches were placed side-by-side on the surface of a water phantom; doses from 0.5 to 4 Gy were delivered. Similarly, irradiations were performed for 60Co and 6 and 18 MV beams in a water equivalent phantom. Films were reproducibly placed at the center of a flatbed scanner and 48-bit RGB scans were obtained both pre- and postirradiations. Net optical density (netOD) and response for a given radiation quality relative to 60Co was determined for each EBT3 film. The netOD of the red color showed reproducible response (within 1%) for both batches when irradiated using the 60Co source. For a given dose of 1 Gy of kVp X-ray, the response relative to 60Co using the three color channels (red, green, and blue) decreases with decrease in kVp, reaching a maximum underresponse of ~ 20% for the 70 kVp. A significant underresponse of ~ 5% was observed at 300kVp. Responses of MV X-ray beams with respect to 60Co at the 1 Gy dose level showed no statistically significant difference. A relatively small difference in the response was observed between the two EBT3 batches used in this study in the kV X-ray range.


Selective targeting of gene transfer to vascular endothelial cells by use of peptides isolated by phage display.
Gene transfer to vascular cells is a highly inefficient and nonselective process, defined by the lack of specific cell-surface receptors for both nonviral and viral gene delivery vectors. We used filamentous phage display to isolate a panel of peptides that have the ability to bind selectively and efficiently to quiescent human umbilical vein endothelial cells (HUVECs) with reduced or negligible binding to nonendothelial cells, including vascular smooth muscle cells and hepatocytes. By direct biopanning on HUVECs and a second approach involving preclearing steps before panning on HUVECs, we isolated and sequenced 140 individual phages and identified 59 peptides. We selected 7 candidates for further investigation by secondary screening of homogeneous phages on a panel of cell types. Using adenovirus-mediated gene transfer as a model gene delivery system, we cloned the peptide SIGYPLP and the positive control peptide KKKKKKK upstream of the S11e single-chain Fv ("adenobody") directed against the knob domain of the adenovirus to create fusion proteins. Adenovirus-mediated gene transfer via fiber-dependent infection was blocked with S11e, whereas inclusion of the KKKKKKK peptide retargeted gene transfer. The peptide SIGYPLP, however, retargeted gene delivery specifically to endothelial cells with a significantly enhanced efficiency over nontargeted adenovirus and without transduction of nontarget cells. Our study demonstrates the feasibility of using small, novel peptides isolated via phage display to target gene delivery specifically and efficiently to HUVECs and highlights their use for retargeting both viral and nonviral gene transfer to vascular endothelial cells for future clinical applications.


Identification and characterization of the aroma-impact components of Thai fish sauce.
Comprehensive analysis of the potent odorants in Thai premium fish sauce samples was accomplished by use of complementary volatile isolation methods combined with gas chromatography-olfactometry (GC-O) and GC-mass spectrometry. Odorants of intermediate and low volatility were determined by direct solvent extraction/solvent-assisted flavor evaporation (DSE-SAFE) and aroma extract dilution analysis (AEDA). Meanwhile, static headspace dilution analysis (SHDA) and headspace solid-phase microextraction (H-SPME) were used to determine the highly volatile odorants. Results of AEDA indicated the importance (log3FD factor≥6) of five acidic odorants (butanoic acid, 3-methylbutanoic acid, 4-hydroxy-2,5-dimethyl-3(2H)-furanone, 4-hydroxy-2-ethyl-5-methyl-3(2H)-furanone, and 2-phenylacetic acid) and four neutral/basic odorants (3-methylbutanal, (Z)-1,5-octadien-3-one, phenylacetaldehyde, and o-aminoacetophone). Results of SHDA indicated the predominant (log3FD factors≥5) headspace odorants were methanethiol, 2-methylpropanal, 2-methylbutanal, 3-methylbutanal, dimethyl trisulfide, 3-(methylthio)propanal, and butanoic acid. Concentrations for 21 odorants were determined by stable isotope dilution analysis (SIDA), and their odor-activity values (OAVs) were calculated. Among these, methanethiol, 2-methylpropanal, 3-methylbutanal, dimethyl trisulfide, 3-(methylthio)propanal, and butanoic acid had the highest OAVs (>500). Results of aroma recombination and omission studies revealed the importance of acids, aldehydes, and sulfur-containing compounds to the overall aroma of the Thai fish sauce.


Does the proteasome inhibitor bortezomib sensitize to DNA-damaging therapy in gastroenteropancreatic neuroendocrine neoplasms? - A preclinical assessment in vitro and in vivo.
Well-differentiated gastroenteropancreatic neuroendocrine neoplasms are rare tumors with a slow proliferation. They are virtually resistant to many DNA-damaging therapeutic approaches, such as chemo- and external beam therapy, which might be overcome by DNA damage inhibition induced by proteasome inhibitors such as bortezomib. In this study, we assessed several combined treatment modalities in vitro and in vivo. By cell-based functional analyses, in a 3D in ovo and an orthotopic mouse model, we demonstrated sensitizing effects of bortezomib combined with cisplatin, radiation and peptide receptor radionuclide therapy (PRRT). By gene expression profiling and western blot, we explored the underlying mechanisms, which resulted in an impaired DNA damage repair. Therapy-induced DNA damage triggered extrinsic proapoptotic signaling as well as the induction of cell cycle arrest, leading to a decreased vital tumor volume and altered tissue composition shown by magnetic resonance imaging and F-18-FDG-PET in vivo, however with no significant additional benefit related to PRRT alone. We demonstrated that bortezomib has short-term sensitizing effects when combined with DNA damaging therapy by interfering with DNA repair in vitro and in ovo. Nevertheless, due to high tumor heterogeneity after PRRT in long-term observations, we were not able to prove a therapeutic advantage of bortezomib-combined PRRT in an in vivo mouse model.


Non-fatal mirtazapine overdose.
We report the case of intoxication of a 41-year-old female patient suffering from major depression with mirtazapine complicated by severe hypothermia. The patient was brought to an intensive care unit 10 hours after intake of 1200 mg mirtazapine and 20 mg lorazepam and laying outside at outdoor temperatures below 0 degree C. The mirtazapine plasma-level was 368 ng/ml still after 41 hours. Body temperature was reduced to 26 degrees C and rhabdomyolysis due to hypothermia was observed. Cardial and respiratory function was compromised and intubation was necessary. The patient recovered without persisting somatic impairment.


PET imaging of very late antigen-4 in melanoma: comparison of 68Ga- and 64Cu-labeled NODAGA and CB-TE1A1P-LLP2A conjugates.
Melanoma is a malignant tumor derived from epidermal melanocytes, and it is known for its aggressiveness, therapeutic resistance, and predisposition for late metastasis. Very late antigen-4 (VLA-4; also called integrin α4β1) is a transmembrane noncovalent heterodimer overexpressed in melanoma tumors that plays an important role in tumor growth, angiogenesis, and metastasis by promoting adhesion and migration of cancer cells. In this study, we evaluated 2 conjugates of a high-affinity VLA-4 peptidomimetic ligand, LLP2A, for PET/CT imaging in a subcutaneous and metastatic melanoma tumor. LLP2A was conjugated to 1,4,8,11-tetraazacyclotetradecane-1-(methane phosphonic acid)-8-(methane carboxylic acid) (CB-TE1A1P) and 2-(4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl)pentanedioic acid (NODAGA) chelators for (68)Ga and (64)Cu labeling. The conjugates were synthesized by solid-phase peptide synthesis, purified by reversed-phase high-performance liquid chromatography, and verified by liquid chromatography mass spectrometry. Saturation and competitive binding assays with B16F10 melanoma cells determined the affinity of the compounds for VLA-4. The biodistributions of the LLP2A conjugates were evaluated in murine B16F10 subcutaneous tumor-bearing C57BL/6 mice. Melanoma metastasis was induced by intracardiac injection of B16F10 cells. PET/CT imaging was performed at 2, 4, and 24 h after injection for the (64)Cu tracers and 1 h after injection for the (68)Ga tracer. (64)Cu-labeled CB-TE1A1P-PEG4-LLP2A and NODAGA-PEG4-LLP2A showed high affinity to VLA-4, with a comparable dissociation constant (0.28 vs. 0.23 nM) and receptor concentration (296 vs. 243 fmol/mg). The tumor uptake at 2 h after injection was comparable for the 2 probes, but (64)Cu-CB-TE1A1P-PEG4-LLP2A trended toward higher uptake than (64)Cu-NODAGA-PEG4-LLP2A (16.9 ± 2.2 vs. 13.4 ± 1.7 percentage injected dose per gram, P = 0.07). Tumor-to-muscle and tumor-to-blood ratios from biodistribution and PET/CT images were significantly higher for (64)Cu-CB-TE1A1P-PEG4-LLP2A than (64)Cu-NODAGA-PEG4-LLP2A (all P values < 0.05). PET/CT imaging of metastatic melanoma with (68)Ga-NODAGA-PEG4-LLP2A and (64)Cu-NODAGA-PEG4-LLP2A showed high uptake of the probes at the site of metastasis, correlating with the bioluminescence imaging of the tumor. These data demonstrate that (64)Cu-labeled CB-TE1A1P/NODAGA LLP2A conjugates and (68)Ga-labeled NODAGA-LLP2A are excellent imaging agents for melanoma and potentially other VLA-4-positive tumors. (64)Cu-CB-TE1A1P-PEG4-LLP2A had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a PET imaging agent for melanoma.


Development of a New Outcome Prediction Model in Early-stage Squamous Cell Carcinoma of the Oral Cavity Based on Histopathologic Parameters With Multivariate Analysis: The Aditi-Nuzhat Lymph-node Prediction Score (ANLPS) System.
The aim of this study was to evaluate the histopathologic parameters that predict lymph node metastasis in patients with oral squamous cell carcinoma (OSCC) and to design a new assessment score on the basis of these parameters that could ultimately allow for changes in treatment decisions or aid clinicians in deciding whether there is a need for close follow-up or to perform early lymph node dissection. Histopathologic parameters of 336 cases of OSCC with stage cT1/T2 N0M0 disease were analyzed. The location of the tumor and the type of surgery used for the management of the tumor were recorded for all patients. The parameters, including T stage, grading of tumor, tumor budding, tumor thickness, depth of invasion, shape of tumor nest, lymphoid response at tumor-host interface and pattern of invasion, eosinophilic reaction, foreign-body giant cell reaction, lymphovascular invasion, and perineural invasion, were examined. Ninety-two patients had metastasis in lymph nodes. On univariate and multivariate analysis, independent variables for predicting lymph node metastasis in descending order were depth of invasion (P=0.003), pattern of invasion (P=0.007), perineural invasion (P=0.014), grade (P=0.028), lymphovascular invasion (P=0.038), lymphoid response (P=0.037), and tumor budding (P=0.039). We designed a scoring system on the basis of these statistical results and tested it. Cases with scores ranging from 7 to 11, 12 to 16, and ≥17 points showed LN metastasis in 6.4%, 22.8%, and 77.1% of cases, respectively. The difference between these 3 groups in relation to nodal metastasis was very significant (P<0.0001). A patient at low risk for lymph node metastasis (score, 7 to 11) had a 5-year survival of 93%, moderate-risk patients (score, 12 to 16) had a 5-year survival of 67%, and high-risk patients (score, 17 to 21) had a 5-year survival of 39%. The risk of lymph node metastasis in OSCC is influenced by many histologic parameters that are not routinely analyzed in pathologic reports. These significant independent factors were graded to design a scoring system that permits accurate evaluation of the risk of metastasis with accuracy independent of the traditional TNM system or isolated histologic parameters. The need for neck node dissection can be predicted depending upon the scores obtained.


Training Skills in Minimally Invasive, Robotic and Open Surgery: Brain Activation as an Opportunity for Learning.
The advantages of the robotic approach in surgery are undisputed. However, during surgical training, how this technique influences the learning curve has not been described. We provide a tentative model for analyzing the learning curves associated with observation and active participation in learning different surgical techniques, using functional imaging. Forty medical students were enrolled and assigned to 4 groups who underwent training in robotic (ROB), laparoscopic (LAP), or open (OPEN) surgery, and a control group that performed motor training without surgical instruments. Surgical/motor training included six 1-h sessions completed over 6 days of the same week. All subjects underwent functional magnetic resonance imaging (fMRI) scanning sessions, before and after surgical training during. Twenty-three participants completed the study. The 3 surgical groups exhibited different learning curves during training. The main effects of the day of training (p < 0.01) and the group (p < 0.01) as well as a significant interaction of day of training group (p < 0.01) were observed. The performance increased in the first 4 days, reaching a peak at day 4, when all groups were considered together. The OPEN group showed the best performance compared to all other groups (p < 0.04). The OPEN group showed a rapid improvement in performance, which peaked at day 4 and decreased on the last day. Similarly, the LAP group showed a steady increase in the number of exercises they completed, which continued for the entire training period and reached a peak on the last day. However, the participants training in ROB surgery, after a performance initially indistinguishable from that of the LAP group, had a dip in their performance, quickly followed by an improvement and reaching a plateau on day 4. fMRI analysis documented the different involvement of the cortical and subcortical areas based on the type of training. Surgical training modified the activation of some brain regions during both observation and the execution of tasks. Differences in the learning curves of the 3 surgical groups were noted. Functional brain activity represents an interesting starting point to guide training programs.


Quantitation of antibody uptake on A group erythrocytes using immunoautoradiography and monoclonal IgM anti-A.
The number of antibody molecules on individual erythrocytes was counted in A1, A2, A3 B and A group individuals using immunoautoradiography (IAR) and monoclonal IgM anti-A1. Quantitation was also done for A group pregnant women. The number of antibody molecules on different red cells of an individual varied widely. Gross variations were also noted in cells of different individuals from one and the same group. The mean values of the uptake of the number of antibody molecules showed the following range A1 greater than A2 greater than Ax greater than A3B. When compared to the average for total A1 adults, red cells of pregnant women and newborn infants showed a 10.7% and 19.7% reduction respectively, in antibody uptake. The mean number of antibody molecules per A1 adult red cells was 5.6 +/- 3 X 10(4), while A2 had 0.85 +/- 0.35 X 10(4) molecules, thus showing a significant quantitative variation.


Platelet rich concentrate: basic science and current clinical applications.
Improvements in resuscitation, dissemination of ATLS protocols, and growth of regional and local trauma centers has increased the survivability after severe traumatic injuries. Furthermore, advances in medical management have increased life expectancy and also patients with orthopaedic injuries. While mechanical stabilization has been a hallmark of orthopaedic fracture care, orthobiologics are playing an increasing role in the management of these patients with complex injuries. Platelet-rich concentrate is an autologous concentration of platelets and growth factors, including transforming growth factor-beta (TGF-beta), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF). The enhancement of bone and soft tissue healing by the placement of supraphysiologic concentration of autologous platelets at the site of tissue injury or surgery is supported by basic science and clinical studies. Due to the increased concentration and release of these factors, platelet-rich plasma can potentially enhance the recruitment and proliferation of tenocytes, stem cells, and endothelial cells. A better understanding of platelet function and appropriate clinical use is essential in achieving the desired outcomes of platelet-rich concentrate in orthopaedic clinical applications.


Predictors of falls and hospitalization outcomes in elderly patients admitted to an acute geriatric unit.
We aimed to identify fall incidence, predictors and characteristics and to investigate hospitalization outcomes for elderly inpatients. In 340 men and 280 women consecutively admitted to a Acute Geriatric Ward of a University Hospital the following variables were evaluated: demographics, clinical history, main disease responsible for hospitalization, comorbidity (cumulative illness rating scale: CIRS 1 and 2) gait and balance deficit (Tinetti's scales), cognition/function (short portable mental status questionnaire: SPMSQ); activities of daily living: ADL; instrumental activities of daily living: IADL; delirium (confusion assessment method: CAM), drugs administered during hospitalization. Overall 80 falls occurred in 70 patients. The incidence rate of falls was of 6.0 per 1000 patient-days with 2.0 falls per bed/year. Age (relative risk=RR=1.050; 95% confidence interval=CI=1.013-1.087), delirium (RR=3.577; 95% CI 1.096-11.672), diabetes (RR=5.913; 95% CI 1.693-20.644), balance deficit (RR=0.914; 95% CI 0.861-0.970) and polypharmacy (RR=1.226; 95% CI 1.122-1.340) were independently predictive of falling. Fallers had a prolonged length of stay (LOS) (35.5+/-47.8 days vs. 23.2+/-27.2; p=0.01) and more frequent nursing home placements (12.9% vs.5.6%; p<0.005). The knowledge of falling predictors might help in planning specific preventive strategies to improve the patients' global health status and to reduce the costs of medical care.


Interest in non-social novel stimuli as a function of age in rhesus monkeys.
Human cognitive and affective life changes with healthy ageing; cognitive capacity declines while emotional life becomes more positive and social relationships are prioritized. This may reflect an awareness of limited lifetime unique to humans, leading to a greater interest in maintaining social relationships at the expense of the non-social world in the face of limited cognitive and physical resources. Alternately, fundamental biological processes common to other primate species may direct preferential interest in social stimuli with increasing age. Inspired by a recent study that described a sustained interest in social stimuli but diminished interest in non-social stimuli in aged Barbary macaques, we carried out a conceptual replication to test whether old rhesus monkeys lost interest in non-social stimuli. Male and female macaques (Macaca mulatta; N = 243) 4-30 years old were tested with a food puzzle outfitted with an activity monitor to evaluate their propensity to manipulate the puzzle in order to free a food reward. We found no indication that aged monkeys were less interested in the puzzle than young monkeys, nor were they less able to solve it.


Nonadditive effects of consumption in an intertidal macroinvertebrate community are independent of food availability but driven by complementarity effects.
Suboptimal environmental conditions are ubiquitous in nature and commonly drive the outcome of biological interactions in community processes. Despite the importance of biological interactions for community processes, knowledge on how species interactions are affected by a limiting resource, for example, low food availability, remains limited. Here, we tested whether variation in food supply causes nonadditive consumption patterns, using the macroinvertebrate community of intertidal sandy beaches as a model system. We quantified isotopically labeled diatom consumption by three macroinvertebrate species (Bathyporeia pilosa, Haustorius arenarius, and Scolelepis squamata) kept in mesocosms in either monoculture or a three-species community at a range of diatom densities. Our results show that B. pilosa was the most successful competitor in terms of consumption at both high and low diatom density, while H. arenarius and especially S. squamata consumed less in a community than in their respective monocultures. Nonadditive effects on consumption in this macroinvertebrate community were present and larger than mere additive effects, and similar across diatom densities. The underlying species interactions, however, did change with diatom density. Complementarity effects related to niche-partitioning were the main driver of the net diversity effect on consumption, with a slightly increasing contribution of selection effects related to competition with decreasing diatom density. For the first time, we showed that nonadditive effects of consumption are independent of food availability in a macroinvertebrate community. This suggests that, in communities with functionally different, and thus complementary, species, nonadditive effects can arise even when food availability is low. Hence, at a range of environmental conditions, species interactions hold important potential to alter ecosystem functioning.


Molecular prognostic factors in diffuse large B-cell lymphoma.
The treatment of patients with diffuse large B-cell lymphoma (DLBCL) has been guided traditionally by clinical parameters such as the Ann Arbor Staging Classification for Hodgkin's disease. Although the International Prognostic Index (IPI) represents the most widely accepted prognostic model, there is still a marked variability in outcome within identical IPI subgroups, reflecting the heterogeneity of this malignancy. Use of DNA microarray, real-time reverse transcription polymerase chain reaction, and tissue array immunohistochemistry methodologies makes the development of new classifications possible based on molecular profiling. The molecular classification of DLBCL may lead to the grouping of specific disease entities sharing similar biologic features, clinical behavior, and outcome. Once tested and validated, this new generation of prognostic models should become an integral part of the daily practice, providing valuable additional information to the currently existing clinically based predictive models. To accomplish these goals and to be in a position in which existing or new prognostic models can be easily tested and validated, there is a strong need to collect frozen and paraffin-embedded material that can be used for RNA extraction and construction of tissue arrays, respectively. Such materials should be gathered as an integral part of any planned study.


Delinquency abstainers in adolescence and educational and labor market outcomes in midlife: A population-based 25-year longitudinal study.
Research has suggested that adolescent delinquency abstainers might have unfavorable characteristics, impeding their access to peer networks. However, recent studies have emphasized the possible heterogeneity of abstainers. We know little about the long-term adaption of delinquency abstainers. We identify subtypes of delinquency abstainers and investigate subsequent adult academic careers, income levels, and possible marginalization in the labor market. We use the population-based Young in Norway Longitudinal study, where participants (N = 2,494) are followed up by surveys and registers from their teens until their mid-30s. By means of latent class analysis, abstainers were divided in three groups according to degree of social integration. Results showed that delinquency abstainers performed as well or better in adulthood than those with moderate delinquency involvement and markedly better than the highly delinquent. Lonely abstainers performed just as well as all other groups when it comes to higher education and earnings. However, they had a higher probability of marginalization in the labor market than the social abstainers. We conclude that no group fared better than delinquency abstainers with strong social ties. The outcomes of the lonely abstainers were close to those of the majority. Thus, in this cohort who came of age in the 1990s, delinquency abstainers are not particularly vulnerable, and theory about abstainers needs to be modernized. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


RACK1 mediates multiple hormone responsiveness and developmental processes in Arabidopsis.
The scaffold protein RACK1 (Receptor for Activated C Kinase 1) serves as an integrative point for diverse signal transduction pathways. The Arabidopsis genome contains three RACK1 orthologues, however, little is known about their functions. It is reported here that one member of this gene family, RACK1A, previously identified as the Arabidopsis homologue of the tobacco arcA gene, mediates hormone responses and plays a regulatory role in multiple developmental processes. RACK1A expresses ubiquitously in Arabidopsis. Loss-of-function mutations in RACK1A confer defects in multiple developmental processes including seed germination, leaf production, and flowering. rack1a mutants displayed reduced sensitivity to gibberellin and brassinosteroid in seed germination, hypersensitivity to abscisic acid in seed germination and early seedling development, and hyposensitivity to auxin in adventitious and lateral root formation. These results provide the first genetic evidence that RACK1A is involved in multiple signal transduction pathways.


Nodular sclerosing Hodgkin's disease presenting as nephrotic syndrome.
A case of nephrotic syndrome due to minimal change renal disease was associated with minimally symptomatic nodular sclerosing Hodgkin's disease in a 15-year-old girl. Although minimal renal disease is the most frequently described biopsy finding in this paraneoplastic syndrome, the combination of nodular sclerosing Hodgkin's disease and minimal renal disease is uncommon. Four cases of this association have been reported in the literature. This case makes five.


In vitro Generation of Cytotoxic T Cells With Potential for Adoptive Tumor Immunotherapy of Multiple Myeloma.
Multiple myeloma is a life-threatening hematological malignancy, which is rarely curable by conventional therapies. Immunotherapy, using tumor antigen-specific, cytotoxic T-lymphocytes, may represent an alternative or additional treatment for multiple myeloma. In this study, we used hybrid cell lines, generated by fusion of an EBV B-lymphoblastoid cell line (B-LCL) and myeloma cells, to stimulate in vitro peripheral blood lymphocytes (PBLs) from patients with multiple myeloma. We investigated induction of antigen-specific, cytotoxic T-lymphocytes to the well-defined tumor associated antigens (TAAs) hTERT, MUC1, MAGE-C1 and CS1, which have been shown to be expressed in a high proportion of cases of multiple myeloma. HLA-A2-peptide pentamer staining, interferon-γ and perforin ELISpot assays, as well as cytotoxicity assays were used. Following several rounds of in vitro stimulation, the hybrid cell lines induced antigen-specific, cytotoxic T-lymphocytes to four candidate TAAs in PBLs from HLA-A2+ multiple myeloma patients, using known HLA-A2 restricted peptide epitopes of the TAAs. In contrast, the HLA-A2+ myeloma cell line U266 failed to induce antigen-specific, cytotoxic T-lymphocytes in vitro. Our data indicate that B-LCL/myeloma hybrid cell lines induce antigen-specific, cytotoxic T-lymphocytes in PBLs isolated from multiple myeloma patients in vitro and may represent a novel strategy for use in adoptive immunotherapy of multiple myeloma.


Hypothermic action of chlorpromazine in monkeys.
1 In the conscious monkey (Macaca cyclopis) intravenous administration of chlorpromazine 0.1-8.0 mg/kg produced a fall of rectal temperature of 0.3 to 3.5 degrees C after a latency of 3.5 to 10.8 minutes. The course of hypothermia lasted from 125 to 600 min or more. 2 Direct injection of chlorpromazine 100-800 mug into the lateral or fourth cerebral ventricle produced a similar fall of 0.3 to 2.0 degrees C but with shorter latency (2 to 3.5 min) and with a duration of 94 to 375 minutes. 3 Two distinct structures in the brain stem, namely, the preoptic anterior hypothalamus (POAH) and medulla oblongata, responded to direct injection of chlorpromazine 200 mug. The sensitivity was slightly higher in the POAH than in the medulla. Structures in between were not sensitive. 4 The results suggest that chlorpromazine works principally through the central nervous system, i.e. the POAH and medulla oblongata, to mediate its hypothermic effect.


Outcomes of the Management of Distal Radius Fractures in the Last 5 Years: A Meta-analysis of Randomized Controlled Trials.
Objective Over the last decades, volar locking plates (VLPs) have been the mainstay treatment for distal radius fractures (DRFs). With the growing body of evidence, we systematically reviewed studies on recent VLP modifications. Methods A systematic search was performed in the PubMed/MEDLINE database for studies published in English in the past five years. The inclusion criteria were randomized controlled trials (RCTs) on the operative treatment of DRFs. We excluded ongoing trials and studies not directly addressing DRF. The primary outcomes assessed were subjective (such as the scores on the Disabilities of the Arm, Shoulder and Hand [DASH] questionnaire, the Patient-rated Wrist Evaluation [PRWE], the European Quality of Life-5 Dimensions [EQ-5D], the 36-item Short Form Health Survey [SF-36], and the Visual Analog Scale [VAS]) and objective clinical outcomes (the complication rate). Results We identified 29 articles published from 2016 to 2020 with high quality of evidence, except for one, which had evidence of moderate quality. In total, 3,079 DRFs were analyzed in the present study. All studies except one had a greater proportion of female participants, and only in 1 study the mean age of the sample was < 40 years old. There were no significant differences between the VLP and external fixation (EF) in terms of the scores on the DASH ( p = 0.18) and PRWE ( p = 0.77). The VLP alone without pronator quadratus (PQ) repair yielded significantly better outcomes. Conclusion In unstable fractures, the VLP and EF yielded comparable long-term results. There is no clear benefit of adding PQ repair to current the VLP surgical technique. Level of Evidence Level I.


An ultrasonic imaging system based on a new SAFT approach and a GPU beamformer.
The design of newer ultrasonic imaging systems attempts to obtain low-cost, small-sized devices with reduced power consumption that are capable of reaching high frame rates with high image quality. In this regard, synthetic aperture techniques have been very useful. They reduce hardware requirements and accelerate information capture. However, the beamforming process is still very slow, limiting the overall speed of the system. Recently, general-purpose computing on graphics processing unit techniques have been proposed as a way to accelerate image composition. They provide excellent computing power with which a very large volume of data can easily and quickly be processed. This paper describes a new system architecture that merges both principles. Thus, using a minimum-redundancy synthetic aperture technique to acquire the signals (2R-SAFT), and a graphics processing unit as a beamformer, we have developed a new scanner with full dynamic focusing, both on emission and reception, that attains real-time imaging with very few resources.


BRAF Heterogeneity in Melanoma.
In the era of molecular targeted therapy, the accurate detection of BRAF mutation in melanoma has become increasingly important. With the advances of molecular analyses and immunohistochemistry, the presence of BRAF mutational heterogeneity in melanoma has been widely recognized. Although most patients with melanoma have a homogeneous BRAF mutation status because the BRAF mutation occurs at an early stage of melanoma development and acts as a driver gene mutation, BRAF mutational heterogeneity does exist, among different tumor sites of a single patient (intertumor heterogeneity) and/or even within a single tumor (intratumor heterogeneity). To summarize the published reports, about 10% of melanoma patients may show intertumorally discordant BRAF status and about 15% of BRAF-mutated melanomas may have intratumor BRAF heterogeneity, although the reported results vary strikingly among the studies and methods used. Considering the BRAF heterogeneity of melanoma, a single biopsy from a single tumor may not be sufficient to uncover the entire BRAF status of a patient. Multiple samples from different sites may be preferable to assess the indication of BRAF/MEK inhibitors, as recommended by the current clinical guidelines. The impact of BRAF heterogeneity on patient survival or the response to treatment with BRAF/MEK inhibitors is an interesting issue, but requires further investigation.


[Diagnostic evaluation of endouterine manual aspiration for the detection of endometrial hyperplasia and cancer in patients with abnormal uterine bleeding].
The objective was to determinate the diagnostic value of manual vacuum aspiration with Karman cannula (MVA) for the detection of endometrial hyperplasia and cancer in patients with abnormal uterine bleeding. Fifty patients with abnormal uterine bleeding were evaluated with MVA prior to dilatation and curettage (D&C). The needing of cervical dilatation was noted. A matched analysis of the histological reports with Wilcoxon contrast test was performed. In order to calculate the diagnostic value, the histological examination of the tissue recollected by D&C was defined as gold-standard. Sensitivity, specificity, pre-test probability (prevalence), post-test probabilities (predictive values) and likelihood-ratios were calculated. No significant difference between either histological reports in matched analysis and the insufficient samples proportion was detected. Cervical dilatation was performed more frequently to D&C (p = 0.0002). The pre-test probability (prevalence) of endometrial hyperplasia/cancer was 20%. Two cases of hyperplasia were not detected by MVA (negative false 20%). The endometrial biopsy for MVA showed a sensitivity of 71% and specificity 93%. The post-test probabilities for an abnormal and normal biopsy (positive and negative predictive values) were 62.5% and 95.2%, respectively. The corresponding likelihood-ratios were 10.23 and 0.3, respectively. The endometrial biopsy for MVA has a high diagnostic value, similar to D&C, in the detection of endometrial hyperplasia/cancer in patients with abnormal uterine bleeding with the advantage to be an office procedure without either risks and costs of D&C.


The metabolism of deoxyguanosine and guanosine in human B and T lymphoblasts. A role for deoxyguanosine kinase activity in the selective T-cell defect associated with purine nucleoside phosphorylase deficiency.
Purine nucleoside phosphorylase (NP; EC 22.214.171.124) deficiency is associated with defective T-cell and normal B-cell immunity. Biochemical mechanisms were investigated by measuring deoxyguanosine and guanosine metabolism in normal T and B lymphoblasts and NP-deficient B lymphoblasts. Deoxyguanosine kinase activity was specifically measured by using an anti-NP antibody to prevent alternative-product formation. Kinase activity towards deoxyguanosine was significantly higher in T-cells, whereas NP activity was similar in both B- and T-cells. Only in T-cells was dGTP produced from exogenous deoxyguanosine, and this was prevented by the simultaneous addition of deoxycytidine, which resulted in a concomitant increase in GTP synthesis. Inhibition by 8-aminoguanosine of NP activity in T lymphoblasts increased formation of dGTP and decreased that of GTP from deoxyguanosine and decreased the formation of GTP from guanosine. These data suggest a central role for deoxyguanosine kinase activity in the T-cell selectivity of the immune defect.


Type of dietary fat and insulin resistance.
Animal studies have already shown the possibility to modulate insulin action by changing not only the amount of total fat, but also the type of fat. In these studies, saturated fat significantly increased insulin resistance, long- and short-chain omega(3) fatty acids significantly improved it, whereas the effects of monounsaturated and omega(6) polyunsaturated fatty acids ranged somewhere in between the two. A recent multicenter study (the Kanwu study) on humans has shown that shifting from a diet rich in saturated fatty acids to one rich in monounsaturated fat improved insulin sensitivity in healthy people, while a moderate omega(3) supplementation did not affect it; this second finding confirms previous results in type 2 diabetic patients with hypertriglyceridemia. There are also other aspects of the metabolic syndrome that can be influenced by the different type of dietary fat, particularly blood pressure and lipid metabolism. With respect to blood pressure, the majority of studies show that omega(3) fatty acids are able to reduce blood pressure in hypertensive patients, but not in normotensive individuals; this result has been confirmed also by the Kanwu study, where no changes in blood pressure were seen after omega(3) supplementation in healthy people. On the other hand, in this study, the change from saturated to monounsaturated fatty acids was able to significantly reduce diastolic blood pressure. As to the lipid abnormalities more frequently present in the metabolic syndrome (i.e., hypertriglyceridemia and low HDL cholesterol), the main effects are related to omega(3) fatty acids, which surely reduce triglyceride levels, but at the same time increase LDL cholesterol. In conclusion, there is so far sound evidence in humans that the quality of dietary fat is able to influence insulin resistance and some of the related metabolic abnormalities.


Novel oral anticoagulants for atrial fibrillation.
Three novel oral anticoagulants (NOACS)-dabigatran etexilate, rivaroxaban, and apixaban-have been approved in many countries for stroke prevention in atrial fibrillation, because they are associated with the same or lower rates of stroke, bleeding (particularly intracranially) and death compared with warfarin; and unlike warfarin, they can be given in fixed doses without routine coagulation monitoring. The effects of NOACs compared with warfarin are consistent in almost all populations and patient subgroups studied. Pharmacoeconomic analyses indicate that the NOACs are also cost-effective in Europe and North America. The lack of an antidote to the NOACs in patients who experience major bleeding has not been associated with a worse outcome among patients treated with NOACs compared with warfarin in secondary analyses. Multiple guidelines for the management of AF now recommend the NOACs for stroke prevention among atrial fibrillation (AF) patients at risk for stroke.


Validation of SenseWear Armband in children, adolescents, and adults.
SenseWear Armband (SW) is a multisensor monitor to assess physical activity and energy expenditure. Its prediction algorithms have been updated periodically. The aim was to validate SW in children, adolescents, and adults. The most recent SW algorithm 5.2 (SW5.2) and the previous version 2.2 (SW2.2) were evaluated for estimation of energy expenditure during semi-structured activities in 35 children, 31 adolescents, and 36 adults with indirect calorimetry as reference. Energy expenditure estimated from waist-worn ActiGraph GT3X+ data (AG) was used for comparison. Improvements in measurement errors were demonstrated with SW5.2 compared to SW2.2, especially in children and for biking. The overall mean absolute percent error with SW5.2 was 24% in children, 23% in adolescents, and 20% in adults. The error was larger for sitting and standing (23%-32%) and for basketball and biking (19%-35%), compared to walking and running (8%-20%). The overall mean absolute error with AG was 28% in children, 22% in adolescents, and 28% in adults. The absolute percent error for biking was 32%-74% with AG. In general, SW and AG underestimated energy expenditure. However, both methods demonstrated a proportional bias, with increasing underestimation for increasing energy expenditure level, in addition to the large individual error. SW provides measures of energy expenditure level with similar accuracy in children, adolescents, and adults with the improvements in the updated algorithms. Although SW captures biking better than AG, these methods share remaining measurements errors requiring further improvements for accurate measures of physical activity and energy expenditure in clinical and epidemiological research.


Preferences for the sex-composition of children in Europe: a multilevel examination of its effect on progression to a third child.
Comparative research on the preferred sex of children in Western societies has generally focused on women only and ignored the role of gender equity and the need for children's economic support in old age. A multilevel analysis extends existing research by examining, for both men and women and across 24 European countries, the effect of the preferred sex-composition of offspring on whether parents have or intend to have a third child. Using the European Social Survey (2004/5), a multilevel (random coefficient) ordered logit regression of that intention (N = 3,323) and a binary logistic multilevel model of the transition to a third child (N = 6,502) demonstrate the presence of a mixed-sex preference. In countries with a high risk of poverty in old age, a preference for sons is found, particularly for men. In societies where there is lower gender equity, both men and women have a significant preference for boys.


Structure determination and dynamics of peptides overlapping the catalytic hairpin of the Ras-specific GEF Cdc25(Mm).
Ras proteins are small G proteins playing a major role in eukaryotic signal transduction. Guanine nucleotide exchange factors (GEF) stimulate GDP/GTP exchange, resulting in the formation of the active Ras-GTP complex. In mammalian cells, two major Ras-specific GEF exist: Sos-like and Cdc25-like. To date, structural data are available only for Cdc25(Mm). We designed and synthesized Cdc25(Mm)-derived peptides spanning residues corresponding to the hSos1 HI helical hairpin that has been implicated in the GEF catalytic mechanism. NMR experiments on a chemically synthesized Cdc25(Mm)(1178-1222) peptide proved that helix I readily reaches a conformation very similar to the corresponding helix in hSos1, while residues corresponding to helix H in hSos1 show higher conformational flexibility. Molecular dynamics studies with the appropriate solvent model showed that different conformational spaces are available for the peptide. Since helix H is making several contacts with Ras and a Cdc25(Mm)(1178-1222) peptide is able to bind nucleotide-free Ras in a BIAcore assay, the peptide must be able to obtain the proper Ras-interacting conformation, at least transiently. These results indicate that rational design and improvement of the Ras-interacting peptides should take into account conformational and flexibility features to obtain molecules with the appropriate biochemical properties.


Antibiotic and sulfonamide residues from Food Safety Inspection Service bob veal calf tissues by region, from October 1987 to September 1988.
Of 3,095 bob veal carcasses declared positive to the calf antibiotic and sulfonamide test (CAST) performed by USDA-FSIS personnel during the fiscal year 1988, 967 were submitted to USDA-FSIS laboratories for intensified antimicrobial evaluation of kidney, liver, and muscle specimens. In the western region, CAST-positive specimens were analyzed from certified calves, that is, calves declared free of antimicrobials by their producers. In the midwestern and eastern regions, 20% of the CAST-positive carcass submissions were certified and 20% had not been certified. Among the regions, neomycin was the most commonly reported agent from kidney specimens; however, there were some distinct differences among regions (24.6% of the specimens in the Midwest, 37.4% in the East, and 46.8% in the West). Reports of gentamicin in specimens also were different among regional laboratories (9.0% in the Midwest, 12.1% in the East, 3.1% in the West). Sulfamethazine was less frequently reported by the western laboratory, never exceeding 2% among the 3 tissues tested, whereas the eastern and midwestern laboratories had at least 1 tissue type that was greater than or equal to 9%. Not all specimens were subjected to sulfonamide evaluation. Regional patterns were noticed for unidentified microbial inhibitors, which were most evident for liver in which 24.6% of the specimens at the western laboratory were classified as having unidentified microbial inhibitors, and only 6.3% of specimens at the eastern laboratory were classified as having unidentified microbial inhibitors.


Water entry of a body which moves in more than six degrees of freedom.
The water entry of a three-dimensional smooth body into initially calm water is examined. The body can move freely in its 6 d.f. and may also change its shape over time. During the early stage of penetration, the shape of the body is approximated by a surface of double curvature and the radii of curvature may vary over time. Hydrodynamic loads are calculated by the Wagner theory. It is shown that the water entry problem with arbitrary kinematics of the body motion, can be reduced to the vertical entry problem with a modified vertical displacement of the body and an elliptic region of contact between the liquid and the body surface. Low pressure occurrence is determined; this occurrence can precede the appearance of cavitation effects. Hydrodynamic forces are analysed for a rigid ellipsoid entering the water with 3 d.f. Experimental results with an oblique impact of elliptic paraboloid confirm the theoretical findings. The theoretical developments are detailed in this paper, while an application of the model is described in electronic supplementary materials.


Objective and subjective vasomotor symptom outcomes in the CBT-Meno randomized controlled trial.
Objective: Vasomotor symptoms (hot flashes, night sweats) are common during the menopausal transition. Pharmacotherapy is effective but is associated with health risks for some women. There is an increasing demand for non-pharmacological interventions. The CBT-Meno protocol is a psychological intervention targeting a range of common menopausal symptoms. We compared the impact of CBT-Meno vs. waitlist on objective and subjective measures of vasomotor symptoms and on the relationship between vasomotor symptoms and sleep difficulties.Materials: The participants were 36 perimenopausal or postmenopausal women with co-occurring depressive symptoms who participated in the CBT-Meno trial (clinicaltrials.gov NCT02480192). Subjective measures included the Hot Flash Related Daily Interference Scale, the Greene Climacteric Scale, and the Pittsburgh Sleep Quality Inventory. Objective (physiological) and 'in-the-moment' measures of vasomotor symptoms were assessed with sternal skin conductance.Results: Greater improvements in vasomotor 'bothersomeness' and 'interference' were observed in the CBT-Meno condition compared to the waitlist condition. No between-group differences were observed in vasomotor frequency (subjectively or objectively recorded) or severity ratings. Sleep disturbance was unrelated to objectively measured vasomotor symptom frequency.Conclusion: The CBT-Meno trial improved subjective but not objective (physiological) measures of vasomotor symptoms. Self-reported sleep difficulties were unrelated to subjective or objective vasomotor symptoms.


Perceptions and knowledge toward mobile-health among the college going students in Coastal South India.
Among the manifold uses of mobile phones, mobile-health (mHealth) has been an important one, which is the practice of public health initiatives by awareness raising and communication campaigns. Optimum utilization of mHealth is possible only through adequate awareness. Hence, we aimed to study the perceptions and knowledge about mHealth among college going students in Mangalore, India. A cross-sectional study was conducted in March 2014 among 627 students in selected engineering (302 students) and medical colleges (325 students) in Mangalore, India. Colleges were selected using convenience sampling (nonrandom) method. Data were collected using semi-structured self-administered questionnaire and analyzed. Overall, 48.9% were males, 61.4% belonged to 18-20 years age group. The awareness about mobile phone health utilities among medical and engineering students was found to be similar. Among those who were aware of the concept of mHealth (74 [11.2%]), 40 (54.1%) were medical students. Marginally higher proportion of medical students felt mHealth could be helpful in protecting the patients' confidentiality and would help in better communication with the patients. There was high level of general awareness about mHealth among the subjects. However, many specific areas had limited knowledge among both the streams of students, hence highlighting the need for increasing awareness and sensitization.


[Gene expression and activity regulation of two calmodulin binding protein kinases in tobacco seedling].
Two different calmodulin-binding protein kinase cDNAs (NtCBK1/2) have been isolated from tobacco. To understand the CBK protein activity regulation, we compared the activity regulation of NtCBK1 and NtCBK2 by pH, Mg(2+) concentration and Na(+) concentration. We found the autophosphorylation of NtCBK1/2 reached the maximum in pH 7.5 and 8 respectively; Mg(2+) and Na(+) shown different effects on the activity of NtCBKs, high and low Mg(2+) concentrations both inhibited the activity of NtCBKs, but Na+ had little effect on the kinase activity. In addition, to obtain further insight about the physiological roles of individual NtCBKs, we detected the expression profiles of CBKs. The results revealed different patterns of expression of NtCBK1 and NtCBK2. Both are largely expressed in leaf and flower; but in stem and root, NtCBK1 gene had stronger expression than NtCBK2. NtCBK2 expression was induced by GA treatment, while NtCBK1 expression remained unchanged under GA treatment. Expression of both NtCBK1 and NtCBK2 increased in response to salt stress, the former to a greater extent, and both expressions did not change under high/low temperature, drought, NAA and ABA treatments.


[Effect of beta-blockers on the cardiac rhythm variability in patients with hypertension].
As many as 29 patients with arterial hypertension were examined. All patients were instituted a 3-week antihypertensive therapy with metoprolol. Against the background of intake of metoprolol, there occurs a rise in indices for variability of the heart's rhythm. Augmentation of total power of the spectrum due to metoprolol occurs largely because of enhancement of the parasympathetic activity which can be regarded as a positive effect on the sympathicopara-sympathetical control. In apparent enhancement of the parasympathetic nervous system against the background of ingestion of metoprolol the activity of the sympathetic component is not inhibited, the drug leading to redistribution of influences toward that portion of the autonomic nervous system which had been more inhibited before the intake of the drug.


Electrophysiologic findings in amyloid myopathy.
Myopathy is an uncommon manifestation of systemic amyloidosis. A retrospective chart review of 17 patients seen between 1975 and 1997 with biopsy-proven amyloid myopathy was performed to characterize the electrophysiologic features. Nerve conduction study abnormalities occurred in 14 of 17 patients (82%). The most common abnormality was a low peroneal and/or tibial compound muscle action potential amplitude (n = 9). Mild abnormalities also occurred in seven other nerves. Repetitive stimulation at 2 Hz in 10 nerves was normal. Electromyography demonstrated fibrillation potentials in 69% of muscles, most frequently in the gluteus medius (90%) and paraspinals (87%). The fibrillation potentials were sparse in 60%. Short-duration, low-amplitude motor unit potentials (MUPs) were found in 72% of the muscles examined, were mild in 81%, and were more common in proximal muscles. Long-duration MUPs were found in 19% of muscles and a mixed population of MUPs in 4%. These findings are similar to those of common chronic, inflammatory myopathies.