Effects of prenatal alcohol exposure at school age. II. Attention and behavior.
Alcohol, a potent teratogen, has been suggested as an etiologic agent in attention deficit disorder with hyperactivity (ADHD), which is often diagnosed in children with fetal alcohol syndrome (FAS) and in children of alcoholics. We studied attentional and behavioral factors associated with diagnosis of this disorder in children selected from a predominantly low-income, black population who were tested as part of a longitudinal follow-up of children with prenatal alcohol exposure. Sixty-eight children with a mean age of 5 years 10 months, born to three groups of mothers, were assessed. These groups consisted of: a) women who reported not drinking during pregnancy (n = 21), b) women who reported drinking throughout pregnancy (n = 25), and c) women who reported drinking an equivalent amount but who stopped drinking after educational intervention during the second trimester (n = 22). Dimensions assessed included factors related to attention on a computerized task, impulsivity, and the presence of psychiatrically significant internalizing and externalizing behaviors. In addition, free play and mother-child interactions were video-taped, and evidence of overactive and noncompliant behaviors were noted. Hyperactivity and impulsive behavior were not evident. Results indicated that children exposed throughout pregnancy showed deficits in the ability to sustain attention and were more often described by teachers, although not by their mothers, as showing attentional and behavioral problems. Problems in both internalizing and externalizing behaviors also were noted by teachers. However, when current drinking was controlled, only externalizing behaviors remained different by group.(ABSTRACT TRUNCATED AT 250 WORDS)


Prolinase and non-specific dipeptidase of human kidney.
Human kidney prolinase, assayed with Pro-Ala, and non-specific dipeptidase, assayed with Gly-Leu, were purified by using DEAE-cellulose, gel-filtration, metal-ion-chelate, hydrophobic and adsorption chromatography and chromatofocusing. Both enzymes gave single peaks of activity that were congruent and the ratio of their activities was constant throughout the purification. Gel filtration indicated an Mr of 100 000 and chromatofocusing a pI of 5.4. Ni2+-chelate chromatography demonstrated the presence of exposed histidine residues on the enzyme and was an effective separative procedure. Polyacrylamide-gel electrophoresis of the final preparation showed the two enzyme activities to be coincident. Both enzyme activities decayed at the same rate at 53 degrees C and were inhibited to the same extent by p-hydroxymercuribenzoate. Of six non-specific dipeptidase substrates tested Gly-Leu gave the highest activity, and of six prolinase substrates Pro-Leu had the highest activity. Gly-Leu was hydrolysed at double the rate of Pro-Leu. Pro-Ala was a competitive inhibitor of activity towards Gly-Leu, and Gly-Leu was a competitive inhibitor of activity towards Pro-Ala. Mixed-substrate studies strongly suggested that Gly-Leu and Pro-Ala were hydrolysed at a common active site. The data are consistent with prolinase and non-specific dipeptidase activity in human kidney being due to a single enzyme.


Pharmacotherapy of acute coronary syndrome: the ACUITY trial.
Bivalirudin, a direct thrombin inhibitor, has unique attributes including predictable pharmacokinetics, a reduction in bleeding complications and avoidance of heparin induced thrombocytopenia. We critically review the role of bivalirudin in the management of patients with acute coronary syndrome in light of the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. Data from the ACUITY trial was critically reviewed along with other contemporary data. In the ACUITY trial, bivalirudin monotherapy was associated with rates of ischemic events that were noninferior to those associated with heparin plus glycoprotein IIb/IIIa inhibition, but was associated with a significantly reduced incidence of major bleeding. Bivalirudin seems to be an attractive antithrombotic agent in patients with acute coronary syndrome undergoing early invasive management.


The impact of normalization and phylogenetic information on estimating the distance for metagenomes.
Metagenomics enables the study of unculturable microorganisms in different environments directly. Discriminating between the compositional differences of metagenomes is an important and challenging problem. Several distance functions have been proposed to estimate the differences based on functional profiles or taxonomic distributions; however, the strengths and limitations of such functions are still unclear. Initially, we analyzed three well-known distance functions and found very little difference between them in the clustering of samples. This motivated us to incorporate suitable normalizations and phylogenetic information into the functions so that we could cluster samples from both real and synthetic data sets. The results indicate significant improvement in sample clustering over that derived by rank-based normalization with phylogenetic information, regardless of whether the samples are from real or synthetic microbiomes. Furthermore, our findings suggest that considering suitable normalizations and phylogenetic information is essential when designing distance functions for estimating the differences between metagenomes. We conclude that incorporating rank-based normalization with phylogenetic information into the distance functions helps achieve reliable clustering results.


Specificity of cyclic GMP activation of a multi-substrate cyclic nucleotide phosphodiesterase from rat liver.
Cyclic nucleotide derivatives have been used as a tool to investigate the existence of distinctive activating and hydrolytic sites on the phosphodiesterase from rat liver activated by cGMP (guanosine 3',5'-monophosphate). This positively cooperative enzyme was stimulated up to 30-fold by 3 microM cGMP when 3 microM cAMP (adenosine 3',5'-monophosphate) was used as substrate. All analogues were less potent activators than cGMP. Most cAMP derivatives were inactive, with two exceptions: 7-deazaadenosine 3',5'-monophosphate and 3'-amino-3'-deoxy-adenosine 3',5'-monophosphate. Benzimidazole ribonucleoside 3',5'-monophosphate, where the two atoms of nitrogen of the pyrimidine ring are missing was a better stimulator than the intact purine-related cyclic derivative. When cAMP and cGMP with identical chemical ligands substituted at the same position were compared, the cGMP analogue was always the more potent activator suggesting that the activating site is sensitive to a guanine-type cyclic nucleotide structure. Degradation of the derivatives by the enzyme was measured by high-performance liquid chromatography: no relation could be established between hydrolysis and effectiveness of activation. In addition, there was no parallelism between inhibitory and activating potency for ten cyclic nucleotide derivatives. Since the chemical interactions between the analogues at the activating site on the one hand and at the catalytic site on the other, are different, it is proposed that the sites are distinct. Consequently, it is suggested that the enzyme operates in steps. In the first activating step, cGMP is fixed by at least two hydrogen bonds at a specific binding site of the enzyme. This is followed by a conformational change of the protein and subsequently a change of the kinetic parameters. In a rather unspecific process and in a second hydrolytic step, several purine-related cyclic nucleotides are converted to the corresponding 5' nucleotides.


An essential hospital package for South Africa--selection criteria, costs and affordability.
In 1995 the Committee of Enquiry into National Health Insurance (NHI) recommended that formally employed individuals and their employers be required to fund at least a minimum package of hospital cover for workers and their dependents. This has recently been echoed in a Department of Health policy paper on social health insurance. This research aims to define and cost a minimum package of essential hospital care for competing (public and private) health insurers in South Africa. CRITERIA FOR PACKAGE DEFINITION: Based on the objectives implict in the NHI Committee report, the following criteria were used to define the essential package: (i) the extent to which there was another appropriate responsible party who should pay for treatment; (ii) the degree of discretion in deciding whether or not to provide treatment (roughly equivalent to 'urgency'); and (iii) the cost and effectiveness of treatment. On the basis of the above criteria, 396 out of 598 possible interventions were included in the package. Using local mine hospital and private sector utilisation rates and mine hospital cost data, it was estimated that the essential inpatient package would cost around R502 per enrollee per year, using 1998 prices, for a working age population and their dependents. Age-sex standardised outpatient care costs in the mine hospital population studied were estimated at R183 per person per year. It was therefore estimated that the total inpatient and outpatient hospital package would cost around R685 per person per year. The results presented in this paper are intended to inform the process of defining a national essential hospital benefit package. Assuming that contributions were proportionally related to income, and that costs should not exceed 6% of wages, the package should be affordable to all of those earning above R20,000 per year. Significant additional work is required, firstly at a technical level to assess the appropriateness of the prioritization approach used here, and secondly to take the debate around essential hospital benefits to broader political and public forums.


[Retinal vascular occlusion: possibilities of a direct oxygen supply to the hypoxic areas].
Treatment of a retinal vascular occlusion consists in restoration of normal oxygenation to the affected area. An experimentally induced increase in arterial CO2 provokes an increase in preretinal CO2 in a hypoxic retinal area which has developed after venous obstruction, but it is ineffective in anoxic areas of an arterial occlusion. However, clinical application of this treatment offers no benefit for the patient. Hyperoxia caused by respiration of a gas mixture of 5% CO2 and 95% O2 is also ineffective. On the other hand, the results of recent studies in which blood is replaced with fluorocarbon solutions are promising. Finally, it is pointed out that in cases of venous occlusion laser coagulation leads to reoxygenation of the inner hypoxic retina.


3'-Azido-3'-deoxythymidine prevents induction of murine acquired immunodeficiency syndrome in C57BL/10 mice infected with LP-BM5 murine leukemia viruses, a possible animal model for antiretroviral drug screening.
Adult C57BL/10 mice (H-2b Fv-1b) inoculated with LP-BM5 murine leukemia virus develop a disease which has many features in common with human acquired immunodeficiency syndrome (AIDS), in particular abnormal lymphoproliferation and severe immunodeficiency. In the present study, we examined the possibility that this murine AIDS (MAIDS) model would be useful for evaluating antiretrovirus drugs in vivo through the use of a well-defined antiretrovirus drug, the reverse transcriptase (RT) inhibitor (H. Mitsuya, K.J. Weinhold, P.A. Furman, M.H. St. Claire, S. Nusinoff-Lehrman, R.C. Gallo, D. Bolognesi, D.W. Barry, and S. Broder, Proc. Natl. Acad. Sci. USA 82:7096-7100, 1985) 3'-azido-3'-deoxythymidine (AZT). We evaluated the effect of AZT treatment on de novo virus infection as well as on the induction of immunodeficiency by various parameters, including RT activity in serum, splenomegaly, proliferative responses against alloantigens and mitogens, soluble-antigen-presenting cell activity, and immunoglobulin G levels in serum. Our results demonstrated that AZT treatment of C57BL/10 mice infected with LP-BM5 murine leukemia virus efficiently prevented the induction of immunodeficiency if started at the time of virus inoculation. Starting AZT treatment 1 week later provided only a partial protective effect. Starting AZT treatment 2 weeks later was associated with suppression of RT activity in serum but no prevention of immunosuppression. This MAIDS model may allow rapid and cost-effective screening for antiretrovirus drugs targeted against retroviral functions shared between human AIDS and MAIDS, such as those encoded by gag, pol, or env.


Sulfate-Reducing Naphthalene Degraders Are Picky Eaters.
Polycyclic aromatic hydrocarbons (PAHs) are common organic contaminants found in anoxic environments. The capacity for PAH biodegradation in unimpacted environments, however, has been understudied. Here we investigate the enrichment, selection, and sustainability of a microbial community from a pristine environment on naphthalene as the only amended carbon source. Pristine coastal sediments were obtained from the Jacques Cousteau National Estuarine Research Reserve in Tuckerton, New Jersey, an ecological reserve which has no direct input or source of hydrocarbons. After an initial exposure to naphthalene, primary anaerobic transfer cultures completely degraded 500 µM naphthalene within 139 days. Subsequent transfer cultures mineralized naphthalene within 21 days with stoichiometric sulfate loss. Enriched cultures efficiently utilized only naphthalene and 2-methylnaphthalene from the hydrocarbon mixtures in crude oil. To determine the microorganisms responsible for naphthalene degradation, stable isotope probing was utilized on cultures amended with fully labeled 13C-naphthalene as substrate. Three organisms were found to unambiguously synthesize 13C-DNA from 13C-naphthalene within 7 days. Phylogenetic analysis revealed that 16S rRNA genes from two of these organisms are closely related to the known naphthalene degrading isolates NaphS2 and NaphS3 from PAH-contaminated sites. A third 16S rRNA gene was only distantly related to its closest relative and may represent a novel naphthalene degrading microbe from this environment.


Absence of liver steatosis in HIV-HCV co-infected patients receiving regimens containing tenofovir or abacavir.
In human immunodeficiency virus-hepatitis C virus (HIV-HCV) co-infected patients, steatosis has been independently associated with a number of antiretroviral drugs, including stavudine, especially in patients with non-3 HCV genotypes. We retrospectively investigated the presence of steatosis among HIV-HCV co-infected and HCV mono-infected patients, and the role of tenofovir disoproxil fumarate (TDF) or abacavir (ABC) in determining hepatic steatosis. Liver steatosis was retrospectively evaluated in all consecutive biopsies performed in the period 2000-2008 in HCV mono-infected and HIV-HCV co-infected patients. A steatosis rate of >5 % was considered to be significant, and a multivariate logistic analysis was performed to evaluate factors associated with steatosis. In total, 393 HCV-infected patients underwent liver biopsy during the study period, of whom 205 (52.2 %) were co-infected with HIV. A steatosis rate of >5 % was diagnosed in 33.0 % of HCV mono-infected and in 47.8 % of HIV-HCV co-infected patients (P = 0.003). The rate of steatosis was higher in patients resuming antiretroviral therapy (54.7 %) than in naïve patients (33.3 %; P = 0.006). When the overall population was considered, steatosis was associated to HCV genotype 3 [odds ratio (OR) 4.53, 95 % confidence interval (CI) 2.71-7.58; P < 0.001]. In terms of the use of nucleos(t)ide drugs in HIV co-infected patients, multivariate analysis showed that only in patients with HCV genotypes other than genotype 3 was steatosis related to the use of stavudine (OR 5.38, 95 % CI 1.18-24.53; P = 0.03). The use of TDF (OR 1.07, 95 % CI 0.39-2.88; P = 0.898) or ABC (OR 0.592, 95 % CI 0.09-4.07; P = 0.594) was not associated with steatosis. In HCV mono-infected and HIV-HCV co-infected patients, steatosis appears to be a virus-mediated effect of HCV genotype 3. In HIV patients infected with HCV genotypes other than genotype 3, the risk of developing steatosis was higher in those patients resuming antiretroviral regimens containing old drugs rather than the new antiretrovirals.


"I can see clearly now." fundamentals of breast ultrasound optimization.
Unlike other modalities in breast imaging, breast ultrasound is very operator dependent. Proper characterization and management of breast lesions depends on the knowledge and skill of the radiologist performing the exam. Breast ultrasound optimization continues to evolve as the technology of ultrasound machines improves. The American College of Graduate Medical Education (ACGME) program requirements for graduate medical education in diagnostic radiology recently updated requirements to include competency in ultrasound physics, knobology, and image generation. As trainees are held to high ultrasound optimization standards, practicing radiologists who perform breast ultrasound exams must keep up to date on current breast ultrasound optimization techniques to avoid mischaracterizing and mismanaging breast ultrasound findings. In this paper, ultrasound optimization techniques, including patient positioning, transducer frequency, transducer contact and pressure, depth, gain, focus, tissue harmonic imaging, spatial compounding, dynamic range, speed of sound imaging, Doppler evaluation, and elastography will be described. Multiple ultrasound case examples will be used to illustrate application of these skills. After reading this paper, the reader will be able to apply these techniques to their own breast ultrasound practice, improving characterization and management of breast lesions in their patients.


[New technology for sample preprocessing in NIR analysis].
Sample's moisture content and granularity would have an important influence on NIR veracity. Preprocesssing methods have been used for NIR analysis to achieve better NIR veracity. With Yunnan flue-cured tobacco as study materials, the authors innovatively applied microwave fast drying technology and home pulverizer to tobacco preprocessing, which could finish the preprocessing in 5 min, faster than the traditional methods such as oven drying and sifting. Results showed that: microwave fast drying technology could improve NIR analysis veracity when samples' moisture content had a wide range; influence of samples' granularity on NIR veracity could be eliminated after 25 s home pulverizer shatter. This study can offer a new method for NIR analysis workers to simplify NIR preprocessing.


Overview on prediction, detection, and classification of atrial fibrillation using wavelets and AI on ECG.
Atrial fibrillation (AF) is the most common supraventricular cardiac arrhythmia, resulting in high mortality rates among affected patients. AF occurs as episodes coming from irregular excitations of the ventricles that affect the functionality of the heart and can increase the risk of stroke and heart attack. Early and automatic prediction, detection, and classification of AF are important steps for effective treatment. For this reason, it is the subject of intensive research in both medicine and engineering fields. The latter research focuses on three axes: prediction, classification, and detection. Knowing that AF is often asymptomatic and that its episodes are often very short, its automatic early detection is a very complicated but clinically important task to improve AF treatment and reduce the risks for the patients. This article is a review of publications from the past decade, focusing on AF episode prediction, detection, and classification using wavelets and artificial intelligence (AI). Forty-five articles were selected of which five are about AF in general, four articles compare accuracy, recall and precision between Fourier transform (FT) and wavelets transform (WT), and thirty-six are about detection, classification, and prediction of AF with WT: 15 are based on deep learning (DL) and 21 on conventional machine learning (ML). Of the thirty-six studies, thirty were published after 2015, confirming that this particular research area is very important and has great potential for future research.


Investigation of serum high-sensitive C-reactive protein levels across all mood states in bipolar disorder.
There has been an increasing interest in the role of the immune and inflammatory systems in mood disorders. Mood episodes are associated with changes in acute phase proteins such as high-sensitivity C-reactive protein (hsCRP). The present study investigated serum hsCRP in manic, depressed, and euthymic BD patients as compared to matched healthy controls. Serum hsCRP was assessed using an ultrasensitive assay of particle-enhanced immunoturbidimetric latex agglutination. Serum hsCRP levels were increased in manic BD patients, as compared to euthymic, depressed patients and healthy controls (P < 0.001). These findings add to the notion that changes in the inflammatory system take place during acute episodes of mania.


Managing Hypertension in Patients Aged 75 Years and Older.
On the basis of the available data, we would diagnose a normal blood pressure in elderly persons including those 75 years of age and older if the blood pressure was below 120/80 mmHg. We would diagnose hypertension in elderly persons including those aged 75 years and older if the systolic blood pressure was 130 mmHg and higher or if the diastolic blood pressure was 80 mmHg and higher. We would treat these elderly patients with hypertension to a blood pressure goal of less than 130/80 mmHg if the blood pressure was obtained by automated blood pressure monitoring in a quiet room. We would consider treating high-risk persons aged 75 years and older to a blood pressure goal of less than 120/80 mmHg if they were carefully monitored for serious adverse events. If the blood pressure is more than 20/10 mmHg above the goal blood pressure, we would initiate antihypertensive drug therapy with two antihypertensive drugs. The initial drug of choice for the treatment of hypertension in adults aged 75 years and older should be based on co-morbidities, co-incidental indications, tolerability, and cost.


Novel use of single X-ray absorptiometry for measuring breast density.
Breast density is one of the strongest known breast cancer risk factors. Breast density has primarily been measured by either categorical scores of the proportion of opacity on a screening mammogram or as a ratio of the delineated dense area to the total breast area on a mammogram. These methods are limited by their subjectivity, their lack of absolute reference standards, and lack of automation for clinical use. We present a novel automated method for measuring breast composition we call Breast Compositional Density measured using single X-ray absorptiometry techniques, or BD(SXA). BD(SXA) measures breast compositional density by comparing the opacity on the mammogram to two reference standards imaged with each breast. We present the mathematical derivation of BD(SXA), methods for correcting for radiographic nonuniformity in the mammogram, and in vitro measures of accuracy and repeatability. Using phantoms, BD(SXA) has been shown to have a long-term repeatability of better than 2% for a breast composition range of 0 to 100% fibroglandular density.


Adenoviral-transduced dendritic cells are susceptible to suppression by T regulatory cells and promote interleukin 17 production.
Dendritic cell (DC) vaccines offer a robust platform for the development of cancer vaccines, but their effectiveness is thought to be limited by T regulatory cells (Tregs). Recombinant adenoviruses (RAdV) have been used successfully to engineer tumor antigen expression in DCs, but the impact of virus transduction on susceptibility to suppression by Tregs is unknown. We investigated the functional consequences of exposure to adenovirus on interactions between human monocyte-derived DCs and Tregs. Since the development of Tregs is linked to that of pro-inflammatory Th17 cells, the role of Th17 cells and IL-17-producing Tregs in the context of DC-based immunotherapies was also investigated. We found that Tregs potently suppressed the co-stimulatory capacity of RAdV-transduced DCs, regardless of whether the DCs were maturated by inflammatory cytokines or by exposure to Th1 or Th17 cells. Furthermore, exposure of Tregs to RAdV-exposed DCs increased IL-17 production and suppressive capacity, and correlated with enhanced secretion of IL-1β and IL-6 by DCs. The findings that DCs exposed to RAdV are suppressed by Tregs, promote Treg plasticity, and enhance Treg suppression indicates that strategies to limit Tregs will be required to enhance the efficacy of such DC-based immunotherapies.


Hemoproteids (Apicomplexa: Haemoproteidae) from South African tortoises (Cryptodira: Testudinidae).
Terrestrial tortoises, Chersina angulata (Schweigger, 1812), Kinixys belliana belliana Gray, 1831, K. lobatsiana Power, 1927, K. natalensis Hewitt, 1935, and Stigmochelys pardalis (Bell, 1828), both wild (n = 84) and captive (n = 70), were examined for hematozoans from the provinces of Gauteng, Kwazulu-Natal, North West, and Western Cape, South Africa. In Giemsa-stained blood films, 2 species of hemoproteids were identified, 1 previously described, that is, Haemoproteus testudinalis ( Laveran, 1905 ) Wenyon, 1915, the other unknown. Haemoproteus testudinalis occurred in 2/27 wild K. lobatsiana and 1/41 S. pardalis and 2/2 captive K. lobatsiana from the North West and Gauteng, respectively, whereas Haemoproteus sp. A was recorded in 1 of 3 captive K. natalensis from Kwazulu-Natal. Haemoproteus testudinalis had pale blue-stained, often vacuolated, halteridial macrogametocytes, pale pink-stained microhalterdial to halteridial microgametocytes, and dark, scattered, often bacillus-like hemozoin granules. Haemoproteus natalensis n. sp. had ameboid growth stages, blue-stained halteridial to circumnuclear macrogametocytes, purple-stained circumnuclear microgametocytes, and brownish, often clustered, pigment granules. It is recommended that Haemoproteus balazuci Dias, 1953, become a junior synonym of H. testudinalis.


The molecular physiology of increased egg desiccation resistance during diapause in the invasive mosquito, Aedes albopictus.
Photoperiodic diapause is a crucial adaptation to seasonal environmental variation in a wide range of arthropods, but relatively little is known regarding the molecular basis of this important trait. In temperate populations of the mosquito Aedes albopictus, exposure to short-day (SD) lengths causes the female to produce diapause eggs. Tropical populations do not undergo a photoperiodic diapause. We identified a fatty acyl coA elongase transcript that is more abundant under SD versus long-day (LD) photoperiods in mature oocyte tissue of replicate temperate, but not tropical, A. albopictus populations. Fatty acyl CoA elongases are involved in the synthesis of long chain fatty acids (hydrocarbon precursors). Diapause eggs from a temperate population had one-third more surface hydrocarbons and one-half the water loss rates of non-diapause eggs. Eggs from a tropical population reared under SD and LD photoperiods did not differ in surface hydrocarbon abundance or water loss rates. In both a temperate and tropical population, composition of hydrocarbon chain lengths did not differ between eggs from SD versus LD conditions. These results implicate the expression of fatty acyl coA elongase and changes in quantity, but not composition, of egg surface hydrocarbons as important components of increased desiccation resistance during diapause in A. albopictus.


Attachment and mental and physical health: self-compassion and mattering as mediators.
Research shows a strong link between adult attachment and mental and physical health, but little is known about the mechanisms that underlie these relationships. The present study examined self-compassion and mattering, two constructs from positive psychology literature, as potential mediators. Using survey data from a sample of 208 college students, relationships among attachment, self-compassion, mattering, and functional health were explored. Correlational analyses indicated that attachment anxiety and avoidance were strongly related to the mental health component of functional health. Mediation analyses indicated that mattering and self-compassion mediated the relationships between attachment orientation (i.e., levels of avoidance and anxiety) and mental health. These findings suggest that individuals' abilities to be kind toward themselves and their sense of belonging and being important to others are pathways through which attachment orientation relates to mental health.


Getting hypervirulent Klebsiella pneumoniae on the radar screen.
Two pathotypes of Klebsiella pneumoniae cause human infections, classical (cKp) and hypervirulent (hvKp) K. pneumoniae. The present understanding of genetic elements, the need for an accurate test to identify hvKp, the clinical implications of infection, the knowledge gap on how and why hvKp colonization transitions to infection, and potential infection prevention and control issues for hvKp are discussed. Infections because of hvKp are increasingly recognized worldwide. Its ability to cause organ and life-threatening disease in healthy individuals from the community merits concern, which has been magnified by increasing descriptions of multiply drug-resistant (MDR) and extensively drug-resistant (XDR) strains. Increased capsule and siderophore production by hvKp relative to cKp are critical virulence traits. Asians are most commonly infected, but whether this is mediated by a genetic susceptibility, or increased exposure and colonization is unknown. Specific studies about the epidemiology and transmission of hvKp are lacking, but precautions are appropriate for MDR/XDR strains and perhaps all infected/colonized individuals. hvKp is evolving into an increasingly concerning pathogen, in part because of the development of XDR strains. An accurate test to identify hvKp is needed for optimal clinical care, epidemiological, and research studies. An improved understanding of how infection develops, if a genetic susceptibility exists, and appropriate infection prevention and control measures also are needed.


Identification of vascular postsynaptic alpha 1- and alpha 2-adrenoceptors in man.
We studied postsynaptic alpha-adrenoceptors in human blood vessels by measuring the influence on forearm blood flow induced by intra-arterial infusions of selective alpha 1- and alpha 2-adrenoceptor agonists (methoxamine, B-HT 933, clonidine and guanfacine) and antagonists (doxazosin and yohimbine). The studies were done in healthy volunteers, and forearm blood flow was measured by plethysmography. All agonists produced a significant and dose-dependent vasoconstriction. The effect of B-HT 933 was completely abolished by the concomitant infusion of yohimbine, whereas it was hardly influenced by doxazosin. The effect of methoxamine was prevented by doxazosin and little influenced by yohimbine. The vasoconstriction by clonidine and guanfacine was partially prevented by both doxazosin and yohimbine. The single intra-arterial infusion of yohimbine, as well as doxazosin, resulted in vasodilation. These findings provide strong evidence for the existence of postsynaptic alpha 1- as well as alpha 2-adrenoceptors, both mediating vasoconstriction and contributing to basal vascular tone. The (patho-)physiological significance of this subdivision of alpha-adrenoceptors remains to be elucidated.


Rapid change in the symbolic functioning of very young children.
A remarkable difference in the understanding of the symbolic relation between a scale model and the larger space that it represented was displayed by two age groups of young children. Three-year-old children who observed an object being hidden in a model knew where to find an analogous object hidden in the corresponding location in a room, but 2.5-year-old children did not. The success of the group of older children reveals an advance in their cognitive flexibility: they think of a model in two ways at the same time--both as the thing itself and as a symbol for something else.


Sporulation-specific expression of the yvgW (cadA) gene and the effect of blockage on spore properties in Bacillus subtilis.
The yvgW gene of Bacillus subtilis has been reported to encode a product which resembles CPx-type ATPase having a function related to Cd2+ and Zn2+ resistance through efflux of this metal. We recently showed that yvgW gene product is also important for sporulation in B. subtilis. The present study was focused on the functional characterization of yvgW in the sporulation process of B. subtilis. The analysis of yvgW expression showed that a significant expression took place during the late stage of sporulation (T5-T8). The deletion of spoIIAC and spoIIGB genes, encoding for sigmaF and sigmaE, respectively, resulted in the complete elimination of yvgW-lacZ expression while the deletion of the spoIIIG coding for sigmaG decreased the yvgW-lacZ expression to only 37% that of the wild type level. In contrast, the deletion of spoIVCB gene coding for sigmaK had no significant effects on the yvgW-lacZ expression. Transcription initiation site of yvgW during sporulation was determined by 5'-RACE-PCR, indicating that -10 and -35 sequences exhibited very good homology with the consensus sequences recognized by RNA polymerase containing sigmaE. Moreover, through the construction of yvgWDelta537-1351::spc, yvgW mutant cells were investigated for their spore properties, such as their resistance profiles against heat, chloroform and lysozyme, pointing out that spores of the mutant cells showed high sensitivity to heat and chloroform, but resistance to lysozyme. The level of dipicolinic acid was also significantly reduced to approximately 63% in yvgW spores as compared to wild type spores. Furthermore, the analyses of the nutrition-specific germination and outgrowth characteristics of the null mutant and the wild type cells revealed no defect in the initiation of yvgW spore germination but they returned to vegetative state more slowly than the wild type spores in minimal medium.


Stress bleeding prophylaxis with sucralfate. Pathophysiologic basis and clinical use.
The development of acute stress bleeding in intensive-care patients occurs on a multifactorial basis. The basic mechanism lies in the imbalance between aggressive and protective factors. Most intensive care patients show a reduced acid secretion, a reduction of the gastric mucosal blood flow, and a decreased mucus and bicarbonate secretion. Sucralfate enhances most of the defensive mechanisms. These actions are the pathophysiologic basis of the efficacy of sucralfate in the prevention of stress bleeding. Because sucralfate has only a minor influence on the gastric pH and at the same time has proven bactericidal effects, gastric and gut bacterial overgrowth is significantly reduced. These effects explain the observed differences in mortality between sucralfate and alkalinizing drugs like antacids or H2-antagonists. The indications and limits of sucralfate in stress bleeding prophylaxis are pointed out.


Titin force is enhanced in actively stretched skeletal muscle.
The sliding filament theory of muscle contraction is widely accepted as the means by which muscles generate force during activation. Within the constraints of this theory, isometric, steady-state force produced during muscle activation is proportional to the amount of filament overlap. Previous studies from our laboratory demonstrated enhanced titin-based force in myofibrils that were actively stretched to lengths which exceeded filament overlap. This observation cannot be explained by the sliding filament theory. The aim of the present study was to further investigate the enhanced state of titin during active stretch. Specifically, we confirm that this enhanced state of force is observed in a mouse model and quantify the contribution of calcium to this force. Titin-based force was increased by up to four times that of passive force during active stretch of isolated myofibrils. Enhanced titin-based force has now been demonstrated in two distinct animal models, suggesting that modulation of titin-based force during active stretch is an inherent property of skeletal muscle. Our results also demonstrated that 15% of the enhanced state of titin can be attributed to direct calcium effects on the protein, presumably a stiffening of the protein upon calcium binding to the E-rich region of the PEVK segment and selected Ig domain segments. We suggest that the remaining unexplained 85% of this extra force results from titin binding to the thin filament. With this enhanced force confirmed in the mouse model, future studies will aim to elucidate the proposed titin-thin filament interaction in actively stretched sarcomeres.


The Saccharomyces cerevisiae YLL012/YEH1, YLR020/YEH2, and TGL1 genes encode a novel family of membrane-anchored lipases that are required for steryl ester hydrolysis.
Sterol homeostasis in eukaryotic cells relies on the reciprocal interconversion of free sterols and steryl esters. The formation of steryl esters is well characterized, but the mechanisms that control steryl ester mobilization upon cellular demand are less well understood. We have identified a family of three lipases of Saccharomyces cerevisiae that are required for efficient steryl ester mobilization. These lipases, encoded by YLL012/YEH1, YLR020/YEH2, and TGL1, are paralogues of the mammalian acid lipase family, which is composed of the lysosomal acid lipase, the gastric lipase, and four novel as yet uncharacterized human open reading frames. Lipase triple-mutant yeast cells are completely blocked in steryl ester hydrolysis but do not affect the mobilization of triacylglycerols, indicating that the three lipases are required for steryl ester mobilization in vivo. Lipase single mutants mobilize steryl esters to various degrees, indicating partial functional redundancy of the three gene products. Lipase double-mutant cells in which the third lipase is expressed from the inducible GAL1 promoter have greatly reduced steady-state levels of steryl esters, indicating that overexpression of any of the three lipases is sufficient for steryl ester mobilization in vivo. The three yeast enzymes constitute a novel class of membrane-anchored lipases that differ in topology and subcellular localization.


The safety of afatinib for the treatment of non-small cell lung cancer.
Lung cancer tumors present EGFR mutations associated with an increased response rate to tyrosine kinase inhibitors (TKIs). Afatinib acts as an irreversible pan-ErbB-TKI. Areas covered: This review summarizes the results of clinical trials in NSCLC regarding its safety and efficacy. Expert opinion: Afatinib in 40 mg doses is highly effective in patients with NSCLC and EGFR mutations, improving progression-free survival and disease-related symptoms compared to chemotherapy. Additionally, afatinib has a better response rate and shows a small benefit in progression free survival compared to first-generation TKIs, and patients with exon 19 deletion could represent a subgroup with better prognosis and overall survival. Diarrhea, mucositis and rash are frequent adverse events induced by afatinib, these can impair quality of life and sometimes afatinib discontinuation is necessary. Management of adverse events, including early antidiarrheal treatment and prophylactic or early antibiotic management can reduce the gastrointestinal and cutaneous adverse events, respectively. Different risk factors, including malnourishment, sarcopenia, and low body surface might be associated with a higher toxicity risk, and these groups of patients could begin treatment with a low dose of afatinib followed by a close evaluation on tolerability and toxicity in order to slowly increase the dosage of afatinib.


Presurgical window of opportunity trial design as a platform for testing anticancer drugs: Pros, cons and a focus on breast cancer.
The high attrition rate is a major issue in anticancer drug development. Among the alternative trial designs, presurgical window of opportunity trials envision a short course treatment in the time window between diagnostic biopsy and surgery in a moderately-sized patient population. This approach allows testing therapeutics when pre- and post-treatment tumor tissues are available for comprehensive molecular analyses. The emerging evidence may help define the ability of a given agent to modulate its target(s) and help obtain a broader picture of the molecular changes operated by the treatment. The resulting gain may outweigh the potential harms for patients in the early disease setting. Window of opportunity trials have been extensively applied to breast cancer. Overall, a wider use of these trial designs might lead to the identification of potential responders, ineffective drugs or combinations, and ultimately contribute to enhance the efficiency of the clinical developmental process.


Primary central nervous system vasculitis with prominent leptomeningeal enhancement: a subset with a benign outcome.
Primary central nervous system vasculitis (PCNSV) is an uncommon condition that affects the brain and spinal cord. This study was undertaken to evaluate the clinical features and outcomes among patients with PCNSV who presented with prominent gadolinium meningeal enhancement on magnetic resonance imaging (MRI). Through retrospective review using the Mayo Clinic medical records linkage system, we identified 101 consecutive patients with PCNSV based on brain biopsy or conventional angiography (or both) between January 1, 1983, and December 31, 2003. We evaluated data on demographics, clinical findings, laboratory studies, imaging, biopsy of brain or spinal cord (or both), treatment, and neurologic outcome. MRIs showed prominent leptomeningeal enhancement in 8 of 101 patients with PCNSV. In 6 of those 8, cerebral angiography or magnetic resonance angiography results were normal, but biopsy of the brain or spinal cord showed vasculitis in all 8. Granulomatous vascular inflammation was found in 6 specimens and was associated in 4 cases with vascular deposits of beta-amyloid peptide. All 8 patients had a prompt response to therapy, with resolution of the MRI meningeal enhancement. Although 3 of the 8 patients had relapses during followup, the overall outcome was favorable. Patients with meningeal enhancement, compared with patients without enhancement, more commonly had substantial abnormalities of cerebrospinal fluid (100% versus 58%; P = 0.02) and amyloid angiopathy (50% versus 12%; P = 0.03). Prominent gadolinium leptomeningeal enhancement on MRI may point to a distinct subtype of PCNSV with small leptomeningeal artery vasculitis and rapid response to therapy.


A GPU tool for efficient, accurate, and realistic simulation of cone beam CT projections.
Simulation of x-ray projection images plays an important role in cone beam CT (CBCT) related research projects, such as the design of reconstruction algorithms or scanners. A projection image contains primary signal, scatter signal, and noise. It is computationally demanding to perform accurate and realistic computations for all of these components. In this work, the authors develop a package on graphics processing unit (GPU), called gDRR, for the accurate and efficient computations of x-ray projection images in CBCT under clinically realistic conditions. The primary signal is computed by a trilinear ray-tracing algorithm. A Monte Carlo (MC) simulation is then performed, yielding the primary signal and the scatter signal, both with noise. A denoising process specifically designed for Poisson noise removal is applied to obtain a smooth scatter signal. The noise component is then obtained by combining the difference between the MC primary and the ray-tracing primary signals, and the difference between the MC simulated scatter and the denoised scatter signals. Finally, a calibration step converts the calculated noise signal into a realistic one by scaling its amplitude according to a specified mAs level. The computations of gDRR include a number of realistic features, e.g., a bowtie filter, a polyenergetic spectrum, and detector response. The implementation is fine-tuned for a GPU platform to yield high computational efficiency. For a typical CBCT projection with a polyenergetic spectrum, the calculation time for the primary signal using the ray-tracing algorithms is 1.2-2.3 s, while the MC simulations take 28.1-95.3 s, depending on the voxel size. Computation time for all other steps is negligible. The ray-tracing primary signal matches well with the primary part of the MC simulation result. The MC simulated scatter signal using gDRR is in agreement with EGSnrc results with a relative difference of 3.8%. A noise calibration process is conducted to calibrate gDRR against a real CBCT scanner. The calculated projections are accurate and realistic, such that beam-hardening artifacts and scatter artifacts can be reproduced using the simulated projections. The noise amplitudes in the CBCT images reconstructed from the simulated projections also agree with those in the measured images at corresponding mAs levels. A GPU computational tool, gDRR, has been developed for the accurate and efficient simulations of x-ray projections of CBCT with realistic configurations.


Benefit of adjuvant brachytherapy versus external beam radiation for early breast cancer: impact of patient stratification on breast preservation.
Brachytherapy after lumpectomy is an increasingly popular breast cancer treatment, but data concerning its effectiveness are conflicting. Recently proposed "suitability" criteria guiding patient selection for brachytherapy have never been empirically validated. Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we compared women aged 66 years or older with invasive breast cancer (n=28,718) or ductal carcinoma in situ (n=7229) diagnosed from 2002 to 2007, treated with lumpectomy alone, brachytherapy, or external beam radiation therapy (EBRT). The likelihood of breast preservation, measured by subsequent mastectomy risk, was compared by use of multivariate proportional hazards, further stratified by American Society for Radiation Oncology (ASTRO) brachytherapy suitability groups. We compared 1-year postoperative complications using the χ(2) test and 5-year local toxicities using the log-rank test. For patients with invasive cancer, the 5-year subsequent mastectomy risk was 4.7% after lumpectomy alone (95% confidence interval [CI], 4.1%-5.4%), 2.8% after brachytherapy (95% CI, 1.8%-4.3%), and 1.3% after EBRT (95% CI, 1.1%-1.5%) (P<.001). Compared with lumpectomy alone, brachytherapy achieved a more modest reduction in adjusted risk (hazard ratio [HR], 0.61; 95% CI, 0.40-0.94) than achieved with EBRT (HR, 0.22; 95% CI, 0.18-0.28). Relative risks did not differ when stratified by ASTRO suitability group (P=.84 for interaction), although ASTRO "suitable" patients did show a low absolute subsequent mastectomy risk, with a minimal absolute difference in risk after brachytherapy (1.6%; 95% CI, 0.7%-3.5%) versus EBRT (0.8%; 95% CI, 0.6%-1.1%). For patients with ductal carcinoma in situ, EBRT maintained a reduced risk of subsequent mastectomy (HR, 0.40; 95% CI, 0.28-0.55; P<.001), whereas the small number of patients treated with brachytherapy (n=179) precluded definitive comparison with lumpectomy alone. In all patients, brachytherapy showed a higher postoperative infection risk (16.5% vs 9.9% after lumpectomy alone vs 11.4% after EBRT, P<.001); higher incidence of breast pain (22.9% vs 11.2% vs 16.7%, P<.001); and higher incidence of fat necrosis (15.3% vs 5.3% vs 7.7%, P<.001). In this study era, brachytherapy showed lesser breast preservation benefit compared with EBRT. Suitability criteria predicted differential absolute, but not relative, benefit in patients with invasive cancer.


Analysis of the substantia innominata volume in patients with Parkinson's disease with dementia, dementia with lewy bodies, and Alzheimer's disease.
The substantia innominata (SI) contains the nucleus basalis of Meynert, which is the major source of cholinergic input to the cerebral cortex. We hypothesized that degeneration of the SI and its relationship to general cognitive performance differs in amyloidopathy and synucleinopathy. We used magnetic resonance imaging (MRI)-based volumetric analysis to evaluate the SI volume in patients with amnestic mild cognitive impairment (aMCI), Alzheimer's disease (AD), Parkinson's disease-mild cognitive impairment (PD-MCI), PD with dementia (PDD), dementia with Lewy bodies (DLB), and healthy elderly controls. The correlation between SI volume and general cognitive performance, measured using the Korean version of the Mini-Mental State Examination (K-MMSE), was examined. Compared to control subjects, the mean normalized SI volume was significantly decreased in all of the other groups. The normalized SI volume did not differ between the subjects with PDD and DLB, whereas it was significantly smaller in subjects with PDD (p = 0.029) and DLB (p = 0.011) compared with AD. In subjects with PD-related cognitive impairment (PD-MCI, PDD, or DLB), there was a significant positive correlation between the SI volume and K-MMSE score (r = 0.366, p < 0.001), whereas no correlation was seen in subjects with AD-related cognitive impairment (aMCI or AD). Our data suggest that the SI loss is greater in synucleinopathy-related dementia (PDD or DLB) than in AD and that the contribution of the SI to cognitive performance is greater in synucleinopathy than in amyloidopathy.


Gastrocnemius mitochondrial respiration: are there any differences between men and women?
Work on human and mouse skeletal muscle by our group and others has demonstrated that aging and age-related degenerative diseases are associated with mitochondrial dysfunction, which may be more prevalent in males. There have been, however, no studies that specifically examine the influence of male or female sex on human skeletal muscle mitochondrial respiration. The purpose of this study was to compare mitochondrial respiration in the gastrocnemius of adult men and women. Gastrocnemius muscle was obtained from male (n = 19) and female (n = 11) human subjects with healthy lower-extremity musculoskeletal and arterial systems and normal ambulatory function. All patients were undergoing operations for the treatment of varicose veins in their legs. Mitochondrial respiration was determined with a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles. Complex I-, II-, III-, and IV-dependent respiration was measured individually and normalized to muscle weight, total protein content, and citrate synthase (CS, index of mitochondrial content). Male and female patients had no evidence of musculoskeletal or arterial disease and did not differ with regard to age, race, body mass index, or other clinical characteristics. Complex I-, II-, III-, and IV-dependent respiration normalized to muscle weight, total protein content, and CS did not statistically differ for males compared with females. Our study evaluates, for the first time, gastrocnemius mitochondrial respiration of adult men and women who have healthy musculoskeletal and arterial systems and normal ambulatory function. Our data demonstrate there are no differences in the respiration of gastrocnemius mitochondria between men and women.


[Ultrastructure of esophageal epithelium under normal conditions and in dysplastic foci].
Electron microscopic examinations of the ultrastructure of normal esophageal epithelium of an adult man revealed submicroscopic features of each epithelial layer. A specific structure of epithelial cells is represented by tonofibrils. Glycogen is found only in the prickle-cell and superficial layers. In the latter there were some signs of incomplete keratinization. Hyperplasia of the prickle-cell and superficial layers epithelium was accompanied by accumulation of glycogen and marked parakeratosis with disintegration of the nucleus, formation of keratin fibrils, and destruction of desmosomal bonds. Dysplastic changes in the esophageal epithelium were heterogenous and presented a whole set of ultrastructural rearrangements. We distinguish two variants of dysplasia. In the "dark-cell" variant there were hypertrophy and hyperchromia of the nucleus, deep invaginations of the nuclear membrane, swelling of the mitochondria, appearance of myelin-like structures in the matrix, increased number of free ribosomes, polysomes, and lipids, formation of tonofibrillar-keratohyaline complexes, increased number of cytoplasmic processes. The "clear-cell" variant was characterized by nuclear hypertrophy, marked dilation of cisterns of the rough endoplasmic reticulum, extensive vesicle formation, keratohyaline granules, few cytoplasmic outgrowths, dilation of the intercellular space.


Circadian entrainment to light-dark cycles involves extracellular nitric oxide communication within the suprachiasmatic nuclei.
The ability to synchronize to light-dark (LD) cycles is an essential property of the circadian clock, located in mammals within the hypothalamic suprachiasmatic nuclei (SCN). Single light pulses activate nitric oxide (NO) intracellular signaling, leading to circadian phase-shifts required for synchronization. In addition, extracellular NO has a role in the SCN paracrine communication of photic phase advances. In this work, the extracellular nitrergic transmission was assessed in steady-state synchronization to LD cycles of locomotor rhythms in the golden hamster (Mesocricetus auratus). Extracellular NO levels were pharmacologically decreased in vivo with the specific scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO). Hamsters were subjected to LD cycles different from normal 24 h (LD 14 : 10) cycles (i.e. T-cycles), with a single 30-min light pulse presented either every 23 h (T23 cycles), or every 25 h (T25 cycles), thus allowing synchronization by advances or delays, respectively. Acute PTIO intracerebroventricular microinjections, delivered 30 min previous to the light pulse, inhibited synchronization by phase advances to T23 cycles, but did not alter phase delays under T25 cycles. In addition, NO scavenging inhibited light-induced expression of PERIOD1 protein at circadian time 18 (i.e. the time for light-induced phase advances). These findings demonstrate the role of extracellular NO communication within the SCN in the steady-state synchronization to LD cycles.


Impact of a surgical ward breakfast buffet on nutritional intake in postoperative patients: A prospective cohort pilot study.
An early return to normal intake and early mobilization enhances postoperative recovery. However, one out of six surgical patients is undernourished during hospitalization and approximately half of the patients eat 50% or less of the food provided to them. We assessed the use of newly introduced breakfast buffets in two wards for gastrointestinal and oncological surgery and determined the impact on postoperative protein and energy intake. A prospective pilot cohort study was conducted to assess the impact of the introduction of breakfast buffets in two surgical wards. Adult patients had the opportunity to choose between an attractive breakfast buffet and regular bedside breakfast service. Primary outcomes were protein and energy intake during breakfast. We asked patients to report the type of breakfast service and breakfast intake in a diary over a seven-day period. Prognostic factors were used during multivariable regression analysis. A total of 77 patients were included. The median percentage of buffet use per patient during the seven-day study period was 50% (IQR 0-83). Mean protein intake was 14.7 g (SD 8.4) and mean energy intake 332.3 kcal (SD 156.9). Predictors for higher protein intake included the use of the breakfast buffet (β = 0.06, p = 0.01) and patient weight (β = 0.13, p = 0.01). Both use of the breakfast buffet (β = 1.00, p = 0.02) and Delirium Observation Scale scores (β = -246.29, p = 0.02) were related to higher energy intake. Introduction of a breakfast buffet on a surgical ward was associated with higher protein and energy intake and it could be a promising approach to optimizing such intake in surgical patients. Large, prospective and preferably randomized studies should confirm these findings.


Iliac vein aneurysms: a comprehensive review.
Introduction: Iliac vein aneurysm is a rare clinical entity. Iliac venous tract is the least commonlocation for venous aneurysms. There are a few cases of common, external and internal iliac veinaneurysms in the literature. However, undiagnosed and ruptured iliac venous aneurysms couldhave hazardous consequences. Herein, we reviewed all literature cases of iliac vein aneurysms.Their potential diagnostic and therapeutic challenges are discussed. Literature Review: Following a systematic search, 50 cases of iliac venous aneurysms wereidentified. We used MEDLINE [1900-March 2018] and EMBASE [until March 2018]. MeSHterms of iliac vein/veins/venous, hypogastric, inferior vena cava and aneurysm/aneurysms wereused. Fifty patients with venous aneurysms located in common, external or internal iliac veinswere found in our systematic search. Seventeen patients were female (35.4%) and 31 patients weremale (64.6%). The age range was 13 to 70 years of age. The aneurysm was located in right side in17 patients (34%). It was located in left side in 29 patients (58%) and it was bilateral in 4 patients(8%). The aneurysm was located in common, external and internal iliac veins in 15 (30%), 31(62%) and 4 (8%) patients respectively. The aneurysm was due to a previous arteriovenousfistula (AVF) in 19 patients (38%) and of them, 16 patients (32%) had a history of AVF resultingfrom a previous trauma. 29 patients (59.2%) underwent open surgical treatment. Five patients(10.2%) underwent endovascular treatment. One patient (2.0%) underwent hybrid treatment.Conservative treatment was used in 14 patients (28.6%). Conclusion: Iliac vein aneurysms are extremely rare. Its diagnosis necessitates precise clinicalsuspicion and the treatment is based on patients' clinical scenario and radiological features. Bothopen and endovascular techniques could be feasible. Iliac vein aneurysms are more commonin men. Left sided aneurysms are more common. The most common anatomic location isexternal iliac vein. The most common cause of iliac aneurysms is dilatation of vein secondary toa traumatic AVF.


Comparison and implications of PM₂.₅ carbon fractions in different environments.
The concentrations of PM₂.₅ carbon fractions in rural, urban, tunnel and remote environments were measured using the IMPROVE thermal optical reflectance (TOR) method. The highest OC1 and EC1 concentrations were found for tunnel samples, while the highest OC2, OC3, and OC4 concentrations were observed for urban winter samples, respectively. The lowest levels of most carbon fractions were found for remote samples. The percentage contributions of carbon fractions to total carbon (TC) were characterized by one peak (at rural and remote sites) and two peaks (at urban and tunnel sites) with different carbon fractions, respectively. The abundance of char in tunnel and urban environments was observed, which might partly be due to traffic-related tire-wear. Various percentages of optically scattering OC and absorbing EC fractions to TC were found in the four different environments. In addition, the contribution of heating carbon fractions (char and soot) indicated various warming effects per unit mass of TC. The ratios of OC/EC and char/soot at the sites were shown to be source indicators. The investigation of carbon fractions at different sites may provide some information for improving model parameters in estimating their radiative effects.


Synthetic group A streptogramin antibiotics that overcome Vat resistance.
Natural products serve as chemical blueprints for most antibiotics in clinical use. The evolutionary process by which these molecules arise is inherently accompanied by the co-evolution of resistance mechanisms that shorten the clinical lifetime of any given class of antibiotics1. Virginiamycin acetyltransferase (Vat) enzymes are resistance proteins that provide protection against streptogramins2, potent antibiotics against Gram-positive bacteria that inhibit the bacterial ribosome3. Owing to the challenge of selectively modifying the chemically complex, 23-membered macrocyclic scaffold of group A streptogramins, analogues that overcome the resistance conferred by Vat enzymes have not been previously developed2. Here we report the design, synthesis, and antibacterial evaluation of group A streptogramin antibiotics with extensive structural variability. Using cryo-electron microscopy and forcefield-based refinement, we characterize the binding of eight analogues to the bacterial ribosome at high resolution, revealing binding interactions that extend into the peptidyl tRNA-binding site and towards synergistic binders that occupy the nascent peptide exit tunnel. One of these analogues has excellent activity against several streptogramin-resistant strains of Staphylococcus aureus, exhibits decreased rates of acetylation in vitro, and is effective at lowering bacterial load in a mouse model of infection. Our results demonstrate that the combination of rational design and modular chemical synthesis can revitalize classes of antibiotics that are limited by naturally arising resistance mechanisms.


[Management of medical care for the victims of road accidents in traumatology centers of Saint-Petersburg].
The number of road accidents, fatal outcomes and victims exceeded in 1.5 times in Saint-Petersburg in comparison with Moscow. At the average, 600 victims were treated in each of 6 first-level traumatology centers every year. The quantity of patients, who were admitted to 3 second-level traumatology centers, numbered 10 times less. About 300 people entered to others hospitals. The lethality consisted of 15%, 20% and 37%, respectively. There are a lot of matters, that should be discussed, such as an importance of better treatment financing of multitrauma by using compulsory medical insurance system, an optimization of pre-admission treatment and a necessity of patient delivery by mobile medical team using the anaesthesiology and resuscitation.


Intraobserver and interobserver reproducibility of third trimester uterine artery pulsatility index.
The primary aim of the study was to investigate intraobserver and interobserver reproducibility of uterine artery (UtA) pulsatility index (PI) in the third trimester of pregnancy. The secondary aim of the study was to examine whether high maternal body mass index (BMI) or gestational age (GA) influence the reliability of this measurement. Singleton pregnancies in women with known BMI were recruited between 30+0 and 40+0 weeks. UtA PI Doppler measurements were performed prospectively, independently, and blindly by 2 Fetal Medicine Foundation-accredited operators. Intraobserver and interobserver reproducibility was assessed by concordance correlation coefficient (CCC) and intraclass correlation coefficient (ICC); Bland-Altman plots were built and limits of agreement (LoA) were calculated. The analysis was performed for both raw numbers and percentiles. To estimate the intraoperator and interoperator agreement in defining normal and pathological measurements, the assessments were divided in 2 categories-UtA PI <95th percentile/ ≥95th percentile-and Cohen's kappa coefficients were calculated. Results were interpreted according to the cutoffs reported by the True Reproducibility of Ultrasound Techniques review. Correlation between maternal BMI and GA and accuracy of UtA measurements was studied with Spearman's correlation coefficient. Measurements were available in 101 women. For intraobserver reproducibility, ICCs and CCCs were calculated for raw values and percentiles and were 0.912 and 0.835, and 0.837 and 0.716, respectively. For interobserver reproducibility, ICCs and CCCs were 0.809 and 0.732, and 0.677 and 0.576, respectively. This indicates a poor-moderate reproducibility of third trimester UtA PI. LoA were also wide (from a minimum of -0.30-0.35 to a maximum of -0.53-0.62). Cohen's kappa coefficients were 0.478 and 0.418, showing a moderate intraoperator and interoperator agreement in distinguishing between normal and pathological values. No correlation was found between maternal BMI and GA and reproducibility of the measurements. Intraobserver and interobserver reproducibility of third trimester UtA PI as assessed by ICC, CCC, and LoA is only moderate-poor. The agreement between operators in defining pathological and normal measurements is moderate.


The effect of implementation intention on prospective memory: a systematic and meta-analytic review.
Prospective memory (PM) refers to remembering to perform a planned action at a future time. Implementation intention is an encoding method in the form of "if situation Y is encountered, then I will initiate the goal-directed behavior X". It has been applied to improve PM performances. The present study conducted a systematic and meta-analytic review on the effect and mechanism of implementation intention on PM. In the meta-analysis, 36 comparisons were included. The results showed that for healthy young adults, the overall effect of implementation intention in improving PM performances was significant with a medium effect size (d = 0.445). The combined verbal and imagery form of implementation intention had a relatively larger effect size (d = 0.590). For older adults, implementation intention had a medium to large effect size on their PM performances (d = 0.680). As for the mechanism, implementation intention seemed to reduce ongoing task performances in young adults as reflected by longer reaction time (d = 0.224) though the effect size was small. The present study supports the positive effect of implementation intention on PM. The mechanism and potential implications of this promising strategy especially for clinical/sub-clinical people are discussed.


Gray matter involvement in multiple sclerosis.
Gray matter (GM) involvement is detected even in the earliest stages of multiple sclerosis (MS), and GM atrophy occurs at a faster rate than white matter (WM) atrophy early in the disease course. Studies published to date establish that 1) GM involvement and in particular cortical demyelination can be extensive in MS; 2) GM pathology may occur in part independently of WM lesion formation; 3) a primarily GM-related process may be the earliest manifestation of MS; 4) GM involvement is associated with physical disability, fatigue, and cognitive impairment in MS; and 5) GM disease might help explain the observed dissociation between markers of inflammatory demyelination (relapses, WM gadolinium enhancement, WM lesion burden) and disease progression. It remains likely that GM damage is related to WM damage. However, continued studies of GM pathology as well as neuronal and axonal involvement in MS and related experimental models are necessary to better understand the etiology and pathogenesis of the degenerative components.


Determination of vanilmandelic acid in urine by coupled-column liquid chromatography combining affinity to boronate and separation by anion exchange.
An automated liquid chromatographic method for assaying vanilmandelic acid in urine is described. Vanilmandelic acid and potential interfering substances, such as catechol compounds and their metabolites, have been tested for affinity to boronic acid-substituted silica at various pH values. Vanilmandelic acid and the internal standard, isovanilmandelic acid, were bound to the boronate matrix at an acidic pH, whereas for instance catecholamines were unretained and passed through the column. The alpha-hydroxycarboxylic acids were then desorbed by another mobile phase (pH 6.0) and transferred to an anion exchanger for chromatography and electrochemical detection. A relative standard deviation of 2.8% was obtained for the analysis of human urine samples containing 6.6 microM vanilmandelic acid.


A convolutional neural network to filter artifacts in spectroscopic MRI.
Proton MRSI is a noninvasive modality capable of generating volumetric maps of in vivo tissue metabolism without the need for ionizing radiation or injected contrast agent. Magnetic resonance spectroscopic imaging has been shown to be a viable imaging modality for studying several neuropathologies. However, a key hurdle in the routine clinical adoption of MRSI is the presence of spectral artifacts that can arise from a number of sources, possibly leading to false information. A deep learning model was developed that was capable of identifying and filtering out poor quality spectra. The core of the model used a tiled convolutional neural network that analyzed frequency-domain spectra to detect artifacts. When compared with a panel of MRS experts, our convolutional neural network achieved high sensitivity and specificity with an area under the curve of 0.95. A visualization scheme was implemented to better understand how the convolutional neural network made its judgement on single-voxel or multivoxel MRSI, and the convolutional neural network was embedded into a pipeline capable of producing whole-brain spectroscopic MRI volumes in real time. The fully automated method for assessment of spectral quality provides a valuable tool to support clinical MRSI or spectroscopic MRI studies for use in fields such as adaptive radiation therapy planning.


Frontline treatment of acute myeloid leukemia in adults.
Recent years have highlighted significant progress in understanding the underlying genetic and epigenetic signatures of acute myeloid leukemia(AML). Most importantly, novel chemotherapy and targeted strategies have led to improved outcomes in selected genetic subsets. AML is a remarkably heterogeneous disease, and individualized therapies for disease-specific characteristics (considering patients' age, cytogenetics, and mutations) could yield better outcomes. Compared with the historical 5-to 10-year survival rate of 10%, the survival of patients who undergo modern treatment approaches reaches up to 40-50%, and for specific subsets, the improvements are even more dramatic; for example, in acute promyelocytic leukemia, the use of all-trans retinoic acid and arsenic trioxide improved survival from 30 to 40% up to 80 to 90%. Similar progress has been documented in core-binding-factor-AML, with an increase in survival from 30% to 80% upon the use of high-dose cytarabine/fludarabine/granulocyte colony-stimulating factor combination regimens. AML treatment was also recently influenced by the discovery of the superiority of regimens with higher dose Ara-C and nucleoside analogues compared with the "7+3"regimen, with about a 20% improvement in overall survival. Despite these significant differences, most centers continue to use the "7+3" regimen, and greater awareness will improve the outcome. The discovery of targetable molecular abnormalities and recent studies of targeted therapies (gemtuzumab ozagomycin, FLT3 inhibitors, isocitrate dehydrogenase inhibitors, and epigenetic therapies), future use of checkpoint inhibitors and other immune therapies such as chimeric antigen receptor T-cells, and maintenance strategies based on the minimal residual disease evaluation represent novel, exciting clinical leads aimed to improve AML outcomes in the near future.


Regulation of monocarboxylate transporter MCT1 expression by p53 mediates inward and outward lactate fluxes in tumors.
The monocarboxylate transporter (MCT) family member MCT1 can transport lactate into and out of tumor cells. Whereas most oxidative cancer cells import lactate through MCT1 to fuel mitochondrial respiration, the role of MCT1 in glycolysis-derived lactate efflux remains less clear. In this study, we identified a direct link between p53 function and MCT1 expression. Under hypoxic conditions, p53 loss promoted MCT1 expression and lactate export produced by elevated glycolytic flux, both in vitro and in vivo. p53 interacted directly with the MCT1 gene promoter and altered MCT1 mRNA stabilization. In hypoxic p53(-/-) tumor cells, NF-κB further supported expression of MCT1 to elevate its levels. Following glucose deprivation, upregulated MCT1 in p53(-/-) cells promoted lactate import and favored cell proliferation by fuelling mitochondrial respiration. We also found that MCT1 expression was increased in human breast tumors harboring p53 mutations and coincident features of hypoxia, with higher MCT1 levels associated with poorer clinical outcomes. Together, our findings identify MCT1 as a target for p53 repression and they suggest that MCT1 elevation in p53-deficient tumors allows them to adapt to metabolic needs by facilitating lactate export or import depending on the glucose availability.


Accuracy of the family history method in affective illness. Comparison with direct interviews in family studies.
We interviewed available spouses and first-degree relatives of 140 bipolar and unipolar probands for current and past psychopathology, and assessed interrater reliability. Diagnoses based on direct interviews of relatives were compared with those based on reports of the probands and of all other interviewed family members. Probands underestimated the prevalence of affective illness and other psychiatric disorders in their relatives, and overestimated the age of onset of illness in their ill relatives. Probands reported more accurately about illness in their spouses and parents than in their siblings and children, but accuracy reached acceptable levels for spouses only. Diagnoses on relatives derived by combining reports of all other interviewed family members, including the proband, were slightly more accurate than those based on the proband's reports alone. Good accuracy was obtained only for reports about spouses.


Early therapeutic alliance and treatment outcome in individual and family therapy for adolescent behavior problems.
The impact of early therapeutic alliance was examined in 100 clients receiving either individual cognitive- behavioral therapy (CBT) or family therapy for adolescent substance abuse. Observational ratings of adolescent alliance in CBT and adolescent and parent alliance in family therapy were used to predict treatment retention (in CBT only) and outcome (drug use, externalizing, and internalizing symptoms in both conditions) at post and 6-month follow-up. There were no alliance effects in CBT. In family therapy, stronger parent alliance predicted declines in drug use and externalizing. Adolescents with weak early alliances that subsequently improved by midtreatment showed significantly greater reductions in externalizing than adolescents whose alliances declined. Results underscore the need for ongoing developmental calibration of intervention theory and practice for adolescent clinical populations.


The immune contexture in cancer prognosis and treatment.
Immunotherapy is currently the most rapidly advancing area of clinical oncology, and provides the unprecedented opportunity to effectively treat, and even cure, several previously untreatable malignancies. A growing awareness exists of the fact that the success of chemotherapy and radiotherapy, in which the patient's disease can be stabilized well beyond discontinuation of treatment (and occasionally is cured), also relies on the induction of a durable anticancer immune response. Indeed, the local immune infiltrate undergoes dynamic changes that accompany a shift from a pre-existing immune response to a therapy-induced immune response. As a result, the immune contexture, which is determined by the density, composition, functional state and organization of the leukocyte infiltrate of the tumour, can yield information that is relevant to prognosis, prediction of a treatment response and various other pharmacodynamic parameters. Several complementary technologies can be used to explore the immune contexture of tumours, and to derive biomarkers that could enable the adaptation of individual treatment approaches for each patient, as well as monitoring a response to anticancer therapies.


Employers' awareness and compliance with occupational health and safety regulations in Taiwan.
An investigation of employers' awareness and compliance with occupational health and safety (OHS) regulations was conducted in a representative group of employers randomly selected from the manufacturing industry in Taiwan. A total of 1,003 employers were interviewed by trained public health personnel. Ten questions related to perceptions of general OHS and five practices on OHS regulations were measured. The results of this study show that the employers were better aware of their responsibility for posting safety warnings, personal protection and providing safety and health equipment. They were less aware of their responsibility in minimizing injuries and accidents in the workplace and in not hiring someone who was found unfit for a certain job from pre-employment physical examination. Less than half of employers knew about regulations of environmental monitoring and even fewer had heard of Material Safety Data Sheets. Level of education and size of the plant were highly associated with employers' awareness of OHS and the awareness was the most significant predictor in the five practices of OHS regulations in this study. Promotion of employers' awareness of OHS in small sized industries in particular, is warranted to enhance better compliance, and a focus for these efforts is identified by this investigation.


Clinical use of lefamulin: A first-in-class semisynthetic pleuromutilin antibiotic.
Lefamulin is a novel antibiotic agent within the pleuromutilin derivative class approved for the treatment of community-acquired bacterial pneumonia (CABP) by the United States Food and Drug Administration and the European Commission in 2019 and 2020, respectively. The objective of this article is to provide a summary of clinically relevant data underlying lefamulin and to provide recommendations for its place in therapy. In vitro data establish lefamulin's activity against a number of Gram-positive, Gram-negative and atypical organisms relevant in the treatment of CABP, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, Mycoplasma pneumoniae and Chlamydophila pneumoniae. Two phase-3 studies, the Lefamulin Evaluation Against Pneumonia trials, established non-inferiority of lefamulin against moxifloxacin in the treatment of CABP, including the sequential transition from intravenous to oral therapy and across a broad set of patient demographics and severities. Pooled and post hoc analyses have confirmed these effects for a variety of subgroups and secondary endpoints. Real-world study data post-approval have largely not yet emerged for lefamulin, and there is a need for further investigation into safety/efficacy for off-label indications such as acute bacterial skin and skin structure infections and sexually transmitted infections. Further data regarding tolerability, particularly with long-term use, as well as the emergence of resistance over time, are still undefined.


Myiasis in two box turtles.
Two eastern box turtles (Terrapene carolina carolina) were treated for myiasis caused by Sarcophaga cistudinis. The tortoises were examined because of swellings of the proximal cervical regions. Both fully recovered following surgical removal of multiple larvae.


The association between parathyroid hormone 1‑34 and the Wnt/β‑catenin signaling pathway in a rat model of osteoarthritis.
The aim of the current study was to determine the effect of parathyroid hormone (PTH) 1‑34 on cartilage degeneration, and the association between PTH 1‑34 and factors associated with the Wnt/β‑catenin pathway following anterior cruciate ligament and medial meniscectomy‑induced osteoarthritis (OA) in rats. A total of 64 Sprague‑Dawley rats were randomly divided into the following four groups: Sham‑operated rats with normal saline (NS)‑treatment (n=16); anterior cruciate ligament transection with partial medial meniscectomy (ACLT + MMx) rats with NS‑treatment (n=16); sham‑operated rats treated with PTH 1‑34 (n=16); and ACLT + MMx rats treated with PTH 1‑34 (n=16). PTH (15 µg/kg/day) was administered via subcutaneous injection 5 days per week from the first postoperative day for 2 or 6 weeks. Staining with hematoxylin and eosin and safranin O, and a scoring system modified by Mankin were used to assess the histopathological features of cartilage. The present study detected the expression of PTH 1 receptor (PTH1R), sclerostin, dickkopf Wnt signaling pathway inhibitor 1 (DKK1), β‑catenin and runt‑related transcription factor 2 (RUNX2) in cartilage by immunohistochemical analysis to determine the association between PTH 1‑34 and factors associated with the Wnt/β‑catenin pathway. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to detect the mRNA expression levels of PTH1R and β‑catenin in cartilage. Histological analysis demonstrated that cartilage degeneration was present post‑surgery and gradually increased over time. PTH 1‑34 reduced the Mankin scores in ACLT + MMx rats compared with the NS‑treated ACLT + MMx rats. Immunohistochemistry and RT‑qPCR analysis demonstrated that, in cartilage, PTH 1‑34 treatment increased the mRNA expression and protein levels of PTH1R and β‑catenin, and decreased protein levels of sclerostin, DKK1 and RUNX2 in ACLT + MMx rats compared with the NS‑treated ACLT + MMx group. The present study demonstrated that PTH 1‑34 upregulated the Wnt/β‑catenin signaling pathway and that PTH1‑34 downregulated RUNX2 through an alternative pathway to the Wnt/β‑catenin signaling pathway, in a rat model of OA.


The concepts and principles of equity and health.
In 1984, the 32 member states of the World Health Organization European Region took a remarkable step forward in agreeing unanimously on 38 targets for a common health policy for the Region. Not only was equity the subject of the first of these targets, but it was also seen as a fundamental theme running right through the policy as a whole. However, equity can mean different things to different people. This article looks at the concepts and principles of equity as understood in the context of the World Health Organization's Health for All policy. After considering the possible causes of the differences in health observed in populations--some of them inevitable and some unnecessary and unfair--the author discusses equity in relation to health care, concentrating on issues of access to care, utilization, and quality. Lastly, seven principles for action are outlined, stemming from these concepts, to be borne in mind when designing or implementing policies, so that greater equity in health and health care can be promoted.


Analysis and decomposition of accelerometric signals of trunk and thigh obtained during the sit-to-stand movement.
Piezoresistive accelerometer signals are frequently used in movement analysis. However, their use and interpretation are complicated by the fact that the signal is composed of different acceleration components. The aim of the study was to obtain insight into the components of accelerometer signals from the trunk and thigh segments during four different sit-to-stand (STS) movements (self-selected, slow, fast and fullflexion). Nine subjects performed at least six trials of each type of STS movement. Accelerometer signals from the trunk and thigh in the sagittal direction were decomposed using kinematic data obtained from an opto-electronic device. Each acceleration signal was decomposed into gravitational and inertial components, and the inertial component of the trunk was subsequently decomposed into rotational and translational components. The accelerometer signals could be reliably reconstructed: mean normalised root mean square (RMS) trunk: 6.5% (range 3-12%), mean RMS thigh: 3% (range 2-5%). The accelerometric signals were highly characteristic and repeatable. The influence of the inertial component was significant, especially on the timing of the specific event of maximum trunk flexion in the accelerometer signal. The effect of inertia was larger in the trunk signal than in the thigh signal and increased with higher speeds. The study provides insight into the acceleration signal, its components and the influence of the type of STS movement and supports its use in STS movement analysis.


Assessment of quality of life in small-cell lung cancer using a Daily Diary Card developed by the Medical Research Council Lung Cancer Working Party.
Three hundred and sixty-nine patients in an MRC study of combination chemotherapy and radiotherapy for small-cell lung cancer of limited extent were asked to complete a Daily Diary Card which enabled an assessment of their quality of life to be made during and after treatment. The information derived from the card suggests that although cytotoxic chemotherapy has an adverse effect upon quality of life, this impairment only affects the first 2 or 3 days following each course of treatment, although there is also a small deterioration which may be associated with the 'nadir' effect of the blood counts about 10 days after each course. These results should assist physicians in counselling patients about the likely effects of treatment. Just over half of the patients (196) were subsequently randomised to either a further six courses of maintenance chemotherapy or no further chemotherapy, and it is also shown that the patients allocated to no maintenance chemotherapy experienced a gradually deteriorating quality of life, as opposed to the brief but more severe adverse effects which occurred following each course in the maintenance chemotherapy group; this supports the hypothesis of a palliative effect in this latter group. The findings demonstrate that the Daily Diary Card is a sensitive instrument capable of yielding useful information.


Accuracy and clinical usefulness of the near-patient testing CoaguChek S international normalised ratio monitor in rural medical practice.
To compare the accuracy and clinical usefulness of the near-patient testing CoaguChek S INR monitor in rural medical practice. DESIGN, SETTING AND MAIN OUTCOME MEASURES: General practices were identified through Australian university departments of rural health. Study investigators trained general practitioners and/or practice nurses in the use of the CoaguChek S INR monitor. General practices obtained a fingerprick sample for testing with the INR monitor to compare with conventional pathology testing for accuracy. An evaluation questionnaire was administered to users of the machine to assess ease of use and clinical usefulness. A total of 169 patients from 15 general practice sites provided 401 paired (CoaguChek S and laboratory) INR results. The CoaguChek S was found to be accurate when compared to laboratory INR (r = 0.89), despite complicating variables such as multiple users of the monitor and multiple laboratories used for comparison with the CoaguChek S INR. Overall, 88% of dual INR measurements were within 0.5 INR units of each other. For laboratory INR </= 1.9, 2.0-3.5 and >/= 3.6, 97%, 90% and 57% of readings were within 0.5 INR units, respectively. Clinical agreement occurred 93% and 90% of the time against published expanded and narrow criteria, respectively. The routine use of near-patient testing, with appropriate training and quality assurance programs, has the potential to increase the safety and efficacy of warfarin therapy in rural and remote communities.


Typing of methicillin-resistant Staphylococcus aureus in a university hospital setting by using novel software for spa repeat determination and database management.
The spa gene of Staphylococcus aureus encodes protein A and is used for typing of methicillin-resistant Staphylococcus aureus (MRSA). We used sequence typing of the spa gene repeat region to study the epidemiology of MRSA at a German university hospital. One hundred seven and 84 strains were studied during two periods of 10 and 4 months, respectively. Repeats and spa types were determined by Ridom StaphType, a novel software tool allowing rapid repeat determination, data management and retrieval, and Internet-based assignment of new spa types following automatic quality control of DNA sequence chromatograms. Isolates representative of the most abundant spa types were subjected to multilocus sequence typing and pulsed-field gel electrophoresis. One of two predominant spa types was replaced by a clonally related variant in the second study period. Ten unique spa types, which were equally distributed in both study periods, were recovered. The data show a rapid dynamics of clone circulation in a university hospital setting. spa typing was valuable for tracking of epidemic isolates. The data show that disproval of epidemiologically suggested transmissions of MRSA is one of the main objectives of spa typing in departments with a high incidence of MRSA.


Coronary heart disease death, nonfatal acute myocardial infarction and other clinical outcomes in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group.
The Multiple Risk Factor Intervention Trial was a randomized clinical study to test whether a special-intervention (SI) program aimed at reducing serum cholesterol levels, blood pressure and cigarette smoking would prevent coronary heart disease (CHD) in middle-aged men. The main endpoint reported here is the percentage of participants experiencing first major CHD events (either nonfatal acute myocardial infarction [AMI] or CHD death) during 7 years of follow-up. This outcome was slightly less frequent in the 6,428 SI men than in the 6,438 men assigned to their usual source of care (UC). However, the relative difference--either 1% (95% confidence interval -17% to 16%) or 8% (95% confidence interval -5% to 20%), depending on how AMI was classified--was not statistically significant. Regression analyses within the SI and UC groups suggested that the cholesterol and cigarette smoking interventions reduced the number of first major CHD events: the associations between lowering the levels of these 2 factors and reductions in CHD rates were significant (p less than 0.001) and of the anticipated magnitude. A similar analysis of antihypertensive treatment in the SI group revealed no favorable association between lowering blood pressure and CHD rate, and other subgroup comparisons suggested that a mixture of beneficial and adverse effects may underlie this finding. Thus, the nonsignificant overall UC/SI contrast in CHD rates may reflect a combination of the expected beneficial effects of the cholesterol and smoking interventions with unexpected heterogeneous effects of the antihypertensive intervention. Seven of 8 other prespecified cardiovascular endpoints occurred less frequently among SI than among UC men, the difference being nominally significant (p less than 0.05) for angina pectoris, congestive heart failure and peripheral arterial disease.


[Epidemiological analysis on a family cluster of COVID-19].
Objective: To understand the possible transmission route of a family cluster of COVID-19 in Zhengzhou and the potential infectivity of COVID-19 in incubation period, and provide scientific evidence for the timely control of infectious source and curb the spread of the epidemic. Methods: Epidemiological investigation was conducted for a family cluster of COVID-19 (8 cases) with descriptive epidemiological method, and respiratory tract samples of the cases were collected for the nucleic acid detection of virus by RT-PCR. Results: Two primary cases, which occurred on 31 January and 1 February, 2020, respectively, had a common exposure history in Wuhan. The other six family members had onsets on 30 January, 31 January, 1 February (three cases) and 3 February, 2020. Conclusions: In this family cluster of COVID-19, six family members were infected through common family exposure to the 2 primary cases. Five secondary cases had onsets earlier than or on the same day as the primary cases, indicating that COVID-19 is contagious in incubation period, and the home isolation in the early phase of the epidemic might lead to the risk of family cluster of COVID-19.


Heat, chloride, and specific conductance as ground water tracers near streams.
Commonly measured water quality parameters were compared to heat as tracers of stream water exchange with ground water. Temperature, specific conductance, and chloride were sampled at various frequencies in the stream and adjacent wells over a 2-year period. Strong seasonal variations in stream water were observed for temperature and specific conductance. In observation wells where the temperature response correlated to stream water, chloride and specific conductance values were similar to stream water values as well, indicating significant stream water exchange with ground water. At sites where ground water temperature fluctuations were negligible, chloride and/or specific conductance values did not correlate to stream water values, indicating that ground water was not significantly influenced by exchange with stream water. Best-fit simulation modeling was performed at two sites to derive temperature-based estimates of hydraulic conductivities of the alluvial sediments between the stream and wells. These estimates were used in solute transport simulations for a comparison of measured and simulated values for chloride and specific conductance. Simulation results showed that hydraulic conductivities vary seasonally and annually. This variability was a result of seasonal changes in temperature-dependent hydraulic conductivity and scouring or clogging of the streambed. Specific conductance fits were good, while chloride data were difficult to fit due to the infrequent (quarterly) stream water chloride measurements during the study period. Combined analyses of temperature, chloride, and specific conductance led to improved quantification of the spatial and temporal variability of stream water exchange with shallow ground water in an alluvial system.


Basic amino acid residues at the carboxy-terminal eleven amino acid region of the phosphoprotein (P) are required for transcription but not for replication of vesicular stomatitis virus genome RNA.
The phosphoprotein (P) of vesicular stomatitis virus (VSV) serotypes New Jersey [P(NJ)] and Indiana [P(I)] contains a highly conserved carboxy-terminal domain which is required for binding to the cognate N-RNA template as well as to form a soluble complex with the nucleocapsid protein N in vivo. We have shown that the deletion of 11 amino acids from the C terminal end of the P(I) protein abolishes both the template binding and the complex forming activity with the N protein. Within this region, there are conserved basic amino acid residues (R260 and K262) that are potential candidates for such interactions. We have generated mutant P proteins by substitution of these basic amino acid residues with alanine and studied their role in both transcription and replication. We have found that the R260A mutant failed to bind to the N-RNA template, whereas the K262A mutant bound efficiently as the wild-type protein. The R260A mutant, as expected, was unable to support mRNA synthesis in vitro in a transcription reconstitution reaction as well as transcription in vivo of a minigenome using a reverse genetic approach. However, the K262A mutant supported low level of transcription (12%) both in vitro and in vivo, suggesting that direct template binding of P protein through the C-terminal domain is necessary but not sufficient for optimal transcription. Using a two-hybrid system we have also shown that both R260A and K262A mutants interact inefficiently with the L protein, suggesting further that the two point mutants display differential phenotype with respect to binding to the template. In addition, both R260A and K262A mutants were shown to interact efficiently with the N protein in vivo, indicating that these mutants form N-P complexes which are presumably required for replication. This contention is further supported by the demonstration that these mutants support efficient replication of a DI RNA in vivo. Since the transcription defective P mutants can support efficient replication, we propose that the transcriptase and the replicase are composed of two distinct complexes containing (L-P2-3) and L-(N-P), respectively.


Innovative method for the brine treatment by electrokinetic principles integrated with solar photovoltaic plants.
With the growing world population and industrial production, the demand for water has been continuously increasing. By 2030, it was estimated that 60.0 % of the world population will not have access to freshwater, which is about 2.50 % of the total global water. For this, a total of over 17,000 operational desalination plants have been constructed worldwide. However, the key barriers to expansion of the desalination treatments are the brine production and energy consumption. In fact, the brine production is 50.0 % higher than the freshwater, and its treatments could account for 5.0-33.0 % of total desalination cost. Here, a new theoretical approach for brine treatments integrated to solar photovoltaic plants (PVs) to supply renewable energy to the whole system has been proposed. This approach consists in combining electrokinetic and electrochemical phenomena to dilute the brine, by using an alkaline clay with high buffering power. This method substantially desalinates the brine to produce new treated seawater, using clean energy, optimizing energetic and management costs. Some hypotheses and secondary effects should validate the model, e.g., relatively high Ca2+ promotes the electro-migration; the Cl2 production reduces the Cl- concentrations; and the production of H2 can be used to store energy. A practical example for PVPs design is shown.