Molecular cloning of hepatitis C virus genome from a single Japanese carrier: sequence variation within the same individual and among infected individuals.
A hepatitis C virus (HCV) genome was isolated and sequenced from a single Japanese patient with chronic non-A, non-B hepatitis. The genome (HCV-JT), which was constructed with 23 cDNA clones, consisted of 9436 nucleotides with a long open reading frame which could encode a sequence of 3010 amino acid residues. To study the sequence variation of the HCV genome in an individual, we analyzed another sequence of the HCV genome (HCV-JT') constructed with different cDNA clones derived from the same patient. The nucleotide variation between HCV-JT and -JT' was less than 1%, and was distributed throughout the genome except in the 5' non-coding region, where no variation was observed. The diversity was higher (1.6%) in the putative envelope protein region than in other regions. The nucleotide and deduced amino acid sequences of HCV-JT showed homologies of about 91 and 95%, respectively, with those of other Japanese HCV isolates. The nucleotide diversity was high in the gp 70 region (corresponding to the NS 1 region of flaviviruses) and low in the 5' non-coding and p22 (putative core protein) regions. A similar pattern of distribution of nucleotide changes was observed on comparison of HCV-JT with an American isolate HCV-US, where the homologies in nucleotide and amino acid sequences were about 79 and 85%, respectively. Base transversions contributed about 50% of the total base exchanges between the Japanese and American HCV sequences, but only 20% or less of those among Japanese HCV or among American HCV sequences. Thus, the Japanese and American HCVs are genetically distinguishable, supporting our earlier prediction that these two HCVs could be classified as different subtypes.


Adversarial style discrepancy minimization for unsupervised domain adaptation.
Mainstream unsupervised domain adaptation (UDA) methods align feature distributions across different domains via adversarial learning. However, most of them focus on global distribution alignment, ignoring the fine-grained domain discrepancy. Besides, they generally require auxiliary models, bringing extra computation costs. To tackle these issues, this study proposes an UDA method that differentiates individual samples without the help of extra models. To this end, we introduce a novel discrepancy metric, termed style discrepancy, to distinguish different target samples. We also propose a paradigm for adversarial style discrepancy minimization (ASDM). Specifically, we fix the parameters of the feature extractor and maximize style discrepancy to update the classifier, which helps detect more hard samples. Adversely, we fix the parameters of the classifier and minimize the style discrepancy to update the feature extractor, pushing those hard samples near the support of the source distribution. Such adversary helps to progressively detect and adapt more hard samples, leading to fine-grained domain adaptation. Experiments on different UDA tasks validate the effectiveness of ASDM. Overall, without any extra models, ASDM reaches a 46.9% mIoU in the GTA5 to Cityscapes benchmark and an 84.7% accuracy in the VisDA-2017 benchmark, outperforming many existing adversarial-learning-based methods.


Global potential, topology, and pattern selection in a noisy stabilized Kuramoto-Sivashinsky equation.
We formulate a general method to extend the decomposition of stochastic dynamics developed by Ao et al. [J. Phys. Math. Gen. 37, L25-L30 (2004)] to nonlinear partial differential equations which are nonvariational in nature and construct the global potential or Lyapunov functional for a noisy stabilized Kuramoto-Sivashinsky equation. For values of the control parameter where singly periodic stationary solutions exist, we find a topological network of a web of saddle points of stationary states interconnected by unstable eigenmodes flowing between them. With this topology, a global landscape of the steady states is found. We show how to predict the noise-selected pattern which agrees with those from stochastic simulations. Our formalism and the topology might offer an approach to explore similar systems, such as the Navier Stokes equation.


Sympathetic fibre sprouting in the skin contributes to pain-related behaviour in spared nerve injury and cuff models of neuropathic pain.
Cuff and spared nerve injury (SNI) in the sciatic territory are widely used to model neuropathic pain. Because nociceptive information is first detected in skin, it is important to understand how alterations in peripheral innervation contribute to pain in each model. Over 16 weeks in male rats, changes in sensory and autonomic innervation of the skin were described after cuff and SNI using immunohistochemistry to label myelinated (neurofilament 200 positive-NF200+) and peptidergic (calcitonin gene-related peptide positive-CGRP+) primary afferents and sympathetic fibres (dopamine β-hydroxylase positive-DBH+) Cuff and SNI caused an early loss and later reinnervation of NF200 and CGRP fibres in the plantar hind paw skin. In both models, DBH+ fibres sprouted into the upper dermis of the plantar skin 4 and 6 weeks after injury. Despite these similarities, behavioural pain measures were significantly different in each model. Sympathectomy using guanethidine significantly alleviated mechanical allodynia 6 weeks after cuff, when peak sympathetic sprouting was observed, having no effect at 2 weeks, when fibres were absent. In SNI animals, mechanical allodynia in the lateral paw was significantly improved by guanethidine at 2 and 6 weeks, and the development of cold hyperalgesia, which roughly paralleled the appearance of ectopic sympathetic fibres, was alleviated by guanethidine at 6 weeks. Sympathetic fibres did not sprout into the dorsal root ganglia at 2 or 6 weeks, indicating their unimportance to pain behaviour in these two models. Alterations in sympathetic innervation in the skin represents an important mechanism that contributes to pain in cuff and SNI models of neuropathic pain.


Liver abscess.
A liver abscess may occur secondary to an umbilical vein catheterization or infection in other parts of the body, and is associated with immune deficiencies, especially chronic granulomatous disease. There are no specific signs and symptoms, but an unexplained fever with upper abdominal tenderness and an enlarged liver were present in all of our cases. A liver-spleen scan is the most useful diagnostic test, demonstrating a filling defect in the liver. A single abscess may be unroofed and drained. When multiple abscesses are found, as many as possible are drained, but long-term specific antibiotic therapy is the most important treatment.


Surprisingly low infertility rate in married type 2 diabetic women: A rather curious paradox to the current opinion of insulin resistance as the joint pathogenesis of poly cystic ovary syndrome and type 2 diabetes mellitus.
Sharing the same pathophysiologic principle which is insulin resistance, type 2 diabetes mellitus (T2DM) and poly cystic ovary syndrome (PCOS) are usually considered closely related and easily interchangeable medical entities. Numerous attempts have been made to document this illusory perspective. Based on a delicate pathophysiologic notion, we believe that fully developed T2DM is infrequently observed with fully featured PCOS. In an observational descriptive study 257 married T2DM women were consecutively included and meticulously investigated for fertility history and, albeit, clinical and biochemical features of PCOS. Of 257 married diabetic women only six (2.3%) had no children. In one case a male problem (azoospermia) and in the second case, late marriage (aged 45 at wedding ceremony) was the cause of infertility. Thus, only four (1.6%) might have been labeled as true female factor infertility. Astounding to report was the average pregnancies for each participant which was 5.1±2.5, ranging from zero to fifteen. we would suggest that, despite the well-established fact of insulin resistance as the common pathophysiologic process for T2DM and PCOS, they are definitely separate medical entities. As a matter of fact T2DM and PCOS are the two opposite aspect of the insulin resistance coin.


Assessment of left ventricular systolic function in fetuses without myocardial hypertrophy of gestational diabetes mellitus mothers using velocity vector imaging.
The aim of this study was to quantifiably assess left ventricular systolic function by velocity vector imaging (VVI) in fetuses without myocardial hypertrophy born to gestational diabetes mellitus (GDM) mothers. Ventricular images (4-chamber) from 60 normal fetuses and 32 GDM fetuses were selected. Myocardial global and segmental peak strain and systolic strain rates were obtained from VVI offline software. Ejection fraction (EF) was also measured to assess fetal cardiac function. EF of normal fetuses and GDM group were 65.55 ± 4.64% and 65.72 ± 4.92%. No difference was found in EF between the control group and GDM group. Global strain and strain rate of GDM groups were -13.74 ± 3.19% and -1.41 ± 0.54 s(-1), respectively and were found to be lower than the normal group (p < 0.05). Six different segmental peak strains and peak systolic strain rates had identical adjacent segments not only in the control group, but also in GDM fetuses. It was concluded that VVI could reflect fetal cardiac function sensitivity. Global strain and strain rate may be useful parameters for assessing the fetal myocardial systolic function in diabetic mothers.


AUTOLOGOUS TRANSFUSION AFMC EXPERIENCE (1992-1996).
In this era of Acquired Immune Deficiency Syndrome (AIDS) and other infectious diseases - complications of homologous blood transfusion, autologous transfusion is the safest possible blood for transfusion. The present study was conducted from January 1992 to August 1996 to analyse the programme of autologous transfusion. A total of 471 pre-operative autologous collections were undertaken out of a total of 27,542 blood collections during this period. The present study shows a significant increase in autologous collections from 0.44 per cent in 1992 to 3.94 per cent till August 1996. 37.1 per cent autologous donors were from the urosurgery ward. Of the total 471 autologous blood units collected, 171 were transfused to the autologous donors (27.5%).


Carotid body remodelling in l-NAME-induced hypertension in the rat.
The carotid body (CB) is a chemoreceptor organ located at the bifurcation of the common carotid artery. It is made up of the carotid glomus, a structure containing type 1 cells surrounded by type 2 cells. The aim of this study was to evaluate the morphological changes of the CB and carotid glomus in the rat model of l-NAME-induced hypertension. Male Wistar rats were divided in two groups: control untreated rats (C) and rats receiving l-NAME 40 mg/kg/day (LN) for 6 weeks. At the end of the experiment, the systolic blood pressure was 63% higher in the LN group compared with the C group. Morphometric analysis showed that the area of the CB was 29% greater in the LN group compared with the C group. The density of nuclei in the CB was similar between groups, but it was 31% less in the carotid glomus of the LN group. Cells in the CB of the LN group displayed cytoplasmic vacuolation and expressed several biogenic amines. There were more elastic fibres, proteoglycans and collagen fibres in the LN group compared with the C group. Immunohistochemistry showed increased expression of nuclear factor kB, substance P, vascular endothelial growth factor and neuronal nitric oxide synthase in the LN group, while expression of the protein gene product 9.5 was decreased. l-NAME alters cell morphology and the expression of extracellular matrix molecules in the CB and carotid glomus in rats with l-NAME-induced hypertension.


Meta-Tyrosine Induces Cytotoxic Misregulation of Metabolism in Escherichia coli.
The non-protein amino acid meta-Tyrosine (m-Tyr) is produced in cells under conditions of oxidative stress, and m-Tyr has been shown to be toxic to a broad range of biological systems. However, the mechanism by which m-Tyr damages cells is unclear. In E. coli, the quality control (QC) function of phenyalanyl-tRNA synthetase (PheRS) is required for resistantce to m-Tyr. To determine the mechanism of m-Tyr toxicity, we utilitized a strain of E. coli that expresses a QC-defective PheRS. The global responses of E. coli cells to m-Tyr were assessed by RNA-seq, and >500 genes were differentially expressed after the addition of m-Tyr. The most strongly up-regulated genes are involved in unfolded-protein stress response, and cells exposed to m-Tyr contained large, electron-dense protein aggregates, indicating that m-Tyr destabilized a large fraction of the proteome. Additionally, we observed that amino acid biosynthesis and transport regulons, controlled by ArgR, TrpR, and TyrR, and the stringent-response regulon, controlled by DksA/ppGpp, were differentially expressed. m-Tyr resistant mutants were isolated and found to have altered a promoter to increase expression of the enzymes for Phe production or to have altered transporters, which likely result in less uptake or increased efflux of m-Tyr. These findings indicate that when m-Tyr has passed the QC checkpoint by the PheRS, this toxicity of m-Tyr may result from interfering with amino acid metabolism, destabalizing a large number of proteins, and the formation of protein aggregates.


Tryptophan fluorescence quenching in rabbit skeletal myosin rod.
The solvent accessibility of the four tryptophans of rabbit skeletal muscle myosin rod was investigated using steady-state and time-resolved fluorescence quenching by iodide, acrylamide, and cesium. The quenching by iodide and acrylamide was biphasic; the discrete, long lifetime component was quenched with bimolecular collision constants (kq) of 1 x 10(9) M-1 s-1 and 1.6 x 10(9) M-1 s-1, respectively, while the Gaussian distributed, short lifetime component was quenched with a kq value of 0.3 x 10(9) M-1 s-1 and 0.04 x 10(9) M-1 s-1, respectively. Comparison with kq values for N-acetyl-tryptophanamide indicated that the fractional solvent accessibility was about 25% for the long and less than 10% for the short lifetime component. Cesium quenching was monophasic and provided evidence of an excess of positive charge around these tryptophans. Our findings cast doubt on the general application of the simple coiled-coil model to describe coiled-coil interactions in this protein in solution.


Multi-resistant gram-negative organisms in Maryland: a statewide survey of resistant Acinetobacter baumannii.
Following the development of multi-resistant Acinetobacter baumannii at several area hospitals, a volunteer task force from the Greater Baltimore Chapter of the Association of Professionals in Infection Control and Epidemiology, Inc (APIC) set out to assess the situation throughout the state. A survey was disseminated to all 70 acute, general, and specialty hospitals in Maryland. The response rate was 57%, and multi-resistant Acinetobacter was the most prevalent resistant gram-negative organism reported.


Formation of aggregates of tryptic fragments derived from the carboxyl-terminal half of pea phytochrome and localization of the site of contact between the fragments by amino-terminal amino acid sequence analysis.
Limited trypsinization of large pea (Pisum sativum cv. Alaska) phytochrome and subsequent size-exclusion chromatography (SEC) in 0.1 M Na phosphate, pH 7.8, yielded a high-molecular-mass aggregate of tryptic fragments of phytochrome. Further SEC in 0.1 M Tris-HCl, pH 7.5, plus various concentrations of NaSCN, indicated that the tryptic-fragment complex contained an aggregate of 7 fragments of molecular mass from 38 to 55 kDa. The amino-terminal sequence of each fragment was determined from the samples electroblotted from sodium dodecylsulfate polyacrylamide gels onto polyvinylidene difluoride membranes, in order to localize the various fragments on the phytochrome polypeptide chain. All of the 7 fragments in the aggregate were found to be derived from the carboxyl-terminal half of phytochrome. A portion of the polypeptide chain (from Ala-752 to Arg-1000) common to all the tryptic fragments has been assigned as the site(s) of contact of the fragments. The tryptic-fragment complex, as well as large phytochrome itself, has been shown by SEC to dissociate to monomers in 2 M NaSCN. The result indicates that the main force involved in maintaining the complex and in contacts between monomers of phytochrome is non-ionic in nature. Relationship between the contact site(s) of the tryptic-fragment complex and large phytochrome monomer is discussed.


Parallel investigations of the effects of adenosine on evoked potentials and cyclic AMP accumulation in hippocampus slices of the rat.
In slices of rat hippocampus, adenosine and its receptor agonist, 2-chloro-adenosine, were both found to (a) enhance the intracellular accumulation of cyclic adenosine monophosphate (cAMP) and (b) depress neuronal evoked responses to electrical stimulation. The differences in the dose/effect curves for the biochemical and electrophysiological changes cast doubt on a causal relationship between the two effects.


Prophylaxis of indwelling urethral catheter infection: clinical experience with a modified Foley catheter and drainage system.
With the application of the oligodynamic bactericidal property of silver ions, modification of the urinary catheter and drainage system has been found effective in the prevention of urinary tract infections owing to prolonged bladder catheterization. The newly devised catheter and open drainage system were used in 102 patients for bladder catheterization postoperatively or in those with urinary retention for periods ranging from 4 to 77 days. During the period of indwelling catheterization usually no antibiotics were administered and no patient had overt bacteriuria (more than 10(5) bacteria per ml.) or symptoms of urethritis. In contrast, all 20 patients in the control group who had the conventional type of indwelling catheters had bacteriuria within 4 days of catheterization. The data obtained indicate that effective prevention of urinary tract infection, which frequently is associated with indwelling urethral catheterization, can be achieved by the use of the modified catheter and drainage system.


Drug use among Puerto Rican youth: an exploration of generational status differences.
An analysis of the relationship between generational status, or a migrational experience, and adolescent drug use takes advantage of a natural experiment--the migration of Puerto Ricans to the continental United States and their immigration back to the island. Although researchers have studied different sources of variation in adolescent drug use behavior, few have examined the drug use experience of the same ethnic group in varying sociocultural settings. The present study focused on the drug use involvement of four generational status groups of Puerto Rican adolescents in two different settings--New York City and San Juan, Puerto Rico. The groups surveyed in New York City were: New York Ricans (New York City-born Puerto Ricans) and New York migrants (island-born Puerto Rican adolescents). The two groups identified in Puerto Rico were: Puerto Rican islanders (adolescents who had never lived outside of Puerto Rico) and Puerto Rican immigrants (New York City-born youngsters of Puerto Rican parentage whose families had returned to live on the island). In this study, it was hypothesized that the more the perceived environment dimensions of the different generational status groups have characteristics conducive to drug use, the greater the drug use involvement of the groups will be. The analysis confirmed that the drug use involvement of the four groups of Puerto Rican adolescents paralleled the exposure of the groups to a host society, New York City, which has a higher prevalence of adolescent drug use than the culture of origin, Puerto Rico. In addition, it was found that the longer New York migrants lived in New York City, the greater was their drug use involvement. The roles of various other sociodemographic factors (i.e. gender, grade level, family structure and socioeconomic status) in relation to adolescent drug use were also investigated. Two important conditional relationships were documented. First, the impact of length of time living in New York City varied with the adolescent's gender, with higher risk of drug involvement observed for female migrants. Second, socioeconomic status was associated with Puerto Rican adolescents' drug use involvement in the New York City subgroups, but not among the students in Puerto Rico.


C-Reactive Protein as Predictive Biomarker for Response to Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: A Retrospective Study.
The standard of care for the treatment of locally advanced rectal cancer is neoadjuvant chemoradiotherapy (nCRT) followed by surgery, but complete response rates are reduced. To find predictive biomarkers of response to therapy, we conducted a retrospective study evaluating blood biomarkers before nCRT. Hemoglobin (Hg), C-reactive protein (CRP), platelets, carcinoembryonic antigen, carbohydrate antigen 19.9 levels, and neutrophil/lymphocyte ratio were obtained from 171 rectal cancer patients before nCRT. Patients were classified as responders (Ryan 0-1; ycT0N0), 59.6% (n = 102), or nonresponders (Ryan 2-3), 40.3% (n = 69), in accordance with the Ryan classification. A logistic regression using prognostic pretreatment factors identified CRP ≤ 3.5 (OR = 0.05; 95%CI: 0.01-0.21) as a strong independent predictor of response to treatment. Multivariate analysis showed that CRP was an independent predictor of disease-free survival (DFS) (HR = 5.48; 95%CI: 1.54-19.48) and overall survival (HR = 6.10; 95%CI 1.27-29.33) in patients treated with nCRT. Platelets were an independent predictor of DFS (HR = 3.068; 95%CI: 1.29-7.30) and OS (HR= 4.65; 95%CI: 1.66-13.05) and Hg was revealed to be an independent predictor of DFS (HR = 0.37; 95%CI: 0.15-0.90) in rectal cancer patients treated with nCRT. The lower expression of CRP is independently associated with an improved response to nCRT, DFS, and OS.


Differences in compositions and effects of VOCs from vehicle emission detected using various methods.
Vehicle exhaust and oil fuel evaporation emit volatile organic compounds (VOCs). The differences in VOC compositions and their effects determined using different methods have not been addressed sufficiently. In this study, VOC samples are obtained from single gasoline and diesel vehicle exhausts using a portable emission measurement system, from a tunnel in Yichang City, and from gasoline and diesel evaporation at gas stations. A total of 107 VOCs are analysed. The calculated VOC source profiles (based on VOC source profiles of single-vehicle type and vehicle fleet composition in the tunnel) and the tested source profiles (from a tunnel test) are compared. The results show that gasoline burning can reduce alkenes from a mass fraction of 53.1% (for evaporation) to 3.6% (for burning), as well as increase the mass fraction of alkenes from 1.3% (for diesel evaporation) to 34.0% (for diesel burning). The calculated VOC source profiles differed from the tested VOC source profiles, with a coefficient of divergence of 0.6. Ethane, ethylene, n-undecane, and n-dodecane are used to distinguish VOCs in gasoline and diesel exhausts. Cis-2-butene, 2-methylpentane, m/p-xylene, o-xylene, and n-decane can be used to separate gasoline from diesel. The xylene/ethylbenzene ratios accurately reveal the photochemical age. Gasoline burning increases health risks associated with VOCs compared with gasoline evaporation. Furthermore, it modifies the main contributor to ozone formation potential. This study is expected to facilitate refined VOC source apportionment and studies pertaining to speciated emission inventories.


The effect of dose and vehicle on early tissue damage and regenerative activity after chloroform administration to mice.
The relationship between the acute toxicity of orally-administered chloroform and its long-term tumorigenic potential was studied in male mice of the CFLP outbred Swiss albino mouse strain. A single dose of approximately 18 mg CHCl3/kg had no detectable acute toxic effect on the liver or kidneys and did not stimulate regenerative activity, whereas both toxicity and subsequent tissue regeneration were observed with single doses of about 60 mg/kg or higher. The severity of the toxic effects and regenerative changes was greater when corn oil was used as a vehicle for chloroform than when the vehicle was a toothpaste base. In earlier long-term studies in mice of the same strain, kidney tumours occurred in males given 60 mg/kg/day throughout life but not in mice given 17 mg/kg/day. The tumour response was greater when the 60-mg/kg/day dose was given in an oily vehicle than when it was given in toothpaste. The findings are consistent with the hypothesis that early acute toxic change and subsequent repair are a sine qua non for tumorigenesis in the kidney and liver in response to chloroform.


Repeated liver resection for recurrence of colorectal cancer metastases.
Resection of liver metastases is accepted as treatment for diverse tumours, implying a survival improvement. Metastases often recur after first hepatectomy and, very few would be potentially resectable. A retrospective study of 18 patients undergoing repeated hepatectomies (two or more liver resections in the same patient) due to metastases of colorectal cancer between 1988 and 2006 was performed. Thirteen men and five women, mean age 57.55 years, participated. In all patients, repeated liver resection was performed due to recurrence of the metastases. Complications rate after first hepatectomy was 11.1% and after the second 16.6%. Mortality rate was 11.1% after second hepatectomy, and there was no mortality after third hepatectomy. Three- and 5-year survival after colectomy was 88.9% and 77.8%, respectively; after first hepatectomy 3- and 5-year survival was 88.9% and 61.1%, respectively; after second hepatectomy, 3- and 5-year survival was 83.3% and 61.1% respectively; and 3-year survival after third hepatectomy was 67%. Repeated resections by expert surgeons for recurrent liver metastases can be safely performed, with low morbidity and mortality rates similar to first hepatectomies. Repeated resections of liver metastases of colorectal cancer improve global survival.


Changes in ascorbate peroxidase, catalase, guaiacol peroxidase and superoxide dismutase activities in common bean (Phaseolus vulgaris) nodules under salt stress.
To analyse nodular antioxidant enzyme expression in response to salt stress, Phaseolus vulgaris genotype BAT477 was inoculated with reference strain CIAT899, and treated with 50 mM NaCl. Plant growth, nodulation and nitrogen fixing activity were analysed. Results showed that: (1) all parameters, particularly in nodules, were affected by salt treatments, and (2) confirmed preferential growth allocation to roots. The ARA was significantly decreased by salt treatments. Protein dosage confirmed that nodules were more affected by salt treatment than were roots. We analysed superoxide dismutase, catalase, ascorbate peroxidase and peroxidase in nodules, roots and a free rhizobial strain. Our results indicated that SOD and CAT nodular isozymes had bacterial and root origins. The SOD expressed the same CuZn, Fe and Mn SOD isoforms in nodules and roots, whereas in free rhizobia we found only one Fe and Mn SOD. APX and POX nodule and root profiles had only root origins, as no rhizobial band was detected. Under salt stress, plant growth, nitrogen fixation and activities of antioxidant defense enzymes in nodules were affected. Thus, these enzymes appear to preserve symbiosis from stress turned out that NaCl salinity lead to a differential regulation of distinct SOD and POX isoenzyme. So their levels in nodules appeared to be consistent with a symbiotic nitrogen fixing efficiency hypothesis, and they seem to function as the molecular mechanisms underlying the nodule response to salinity.


Role of membrane sterol and redox system in the anti-candida activity reported for Mo-CBP2, a protein from Moringa oleifera seeds.
Plant proteins are emerging as an alternative to conventional treatments against candidiasis. The aim of this study was to better understand the mechanism of action of Mo-CBP2 against Candida spp, evaluating redox system activity, lipid peroxidation, DNA degradation, cytochrome c release, medium acidification, and membrane interaction. Anti-candida activity of Mo-CBP2 decreased in the presence of ergosterol, which was not observed with antioxidant agents. C. albicans treated with Mo-CBP2 also had catalase and peroxidase activities inhibited, while superoxide dismutase was increased. Mo-CBP2 increased the lipid peroxidation, but it did not alter the ergosterol profile in live cells. External medium acidification was strongly inhibited, and cytochrome c release and DNA degradation were detected. Mo-CBP2 interacts with cell membrane constituents, changes redox system enzymes in C. albicans and causes lipid peroxidation by ROS overproduction. DNA degradation and cytochrome c release suggest apoptotic or DNAse activity. Lipid peroxidation and H+-ATPases inhibition may induce the process of apoptosis. Finally, Mo-CBP2 did not have a cytotoxic effect in mammalian Vero cells. This study highlights the biotechnological potential of Mo-CBP2 as a promising molecule with low toxicity and potent activity. Further studies should be performed to better understand its mode of action and toxicity.


Mental status examination of children with learning problems.
Questionnaires were submitted to 163 board-certified/eligible child neurologists to determine whether they employed a consistent approach to the mental status examination of children with learning problems and whether this approach appropriately emphasized the assessment of higher and related cortical functions. The responders' frequency of testing in 6 major categories of mental status function was independent of their age, sex, board-certified/eligible status, type of practice, and years elapsed since completion of training. The results of the entire study group and comparisons among demographic subgroups demonstrated a progressive decline in testing frequency with increasing complexity of mental status function. Child neurologists' approach to the mental status examination was remarkably uniform across a wide range of demographic variables. Higher and related cortical functions are tested significantly less often in children with learning problems than are other more elementary categories of mental status function; therefore, the importance of the mental status examination in this context must be questioned. It is likely that the diagnosis ascribed to a child with learning problems is based on findings other than those provided by the mental status examination.


Molecular mechanisms mediating the action of diazepam on GABA receptors.
Two types of crude synaptic membranes have been prepared which differ in their kinetic properties to bind 3H-GABA in a Na+-free medium. One type (B) has one type of receptor (affinity or KD about 0.2 micrometer), the other type (A) has two populations of receptors which have a high (0.16 micrometer) and a low ((.02 micrometer) KD for GABA binding. This difference is due to the presence of a selective endogenous inhibitor of the high affinity receptor for GABA, a thermostable protein of about 15,000 molecular weight. Inhibitor action is counteracted by diazepam (7 X 10(-7) M), competitively. Clonazepam is more active but chlordiazepoxide is less active than diazepam. Two enantiomers of a benzodiazepine were studied. One of them is endowed with anxiolytic activity and nullifies the action of the endogenous inhibitor on high affinity GABA binding, the other is devoid of anxiolytic activity and is inactive against the inhibitor. The endogenous protein inhibitor also competitively blocks the high affinity binding of 3H-diazepam to Type A membranes. It is concluded that the endogenous inhibitor and diazepam act on the same receptor; and suggested that the endogenous inhibitor may be the natural ligand for the brain receptors that bind benzodiazepines with high affinity.


A typical patient simulation and dosimetry data sheet.
A typical, comprehensive "Patient Simulation & Dosimetry Data" sheet has been developed. It contains all essential patient simulation, treatment and radiation dosimetry parameters and also relevant anatomical diagrams. The form can be used for any radiation therapy modality.


The hemoregulatory peptide N-acetyl-ser-asp-lys-pro impairs angiotensin I-induced contractions in rat aorta.
The hemoregulatory peptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is degraded by ACE. This study was designed to examine the effect of Ac-SDKP on the contractions to angiotensin I. Experiments were performed on rat aortic rings with endothelium exposed to nitro-L-arginine. Ac-SDKP (10 and 100 microM) significantly augmented angiotensin I ED20 (from 2.0+/-0.4 to 4.2+/-1.0 and 5.0+/-0.9 nM) and ED50 (from 4.3+/-0.7 to 8.6+/-1.0 and 10.7+/-1.3 nM, respectively), but did not alter its maximal response. The contractions to angiotensin II were not affected by Ac-SDKP. No degradation of exogenous Ac-SDKP nor detectable release of endogenous Ac-SDKP were observed in the incubation medium. These results suggest that Ac-SDKP impairs angiotensin I response by inhibiting ACE and subsequent angiotensin II formation.


Surgical treatment of benign neurogenic tumours of the mediastinum: a single institution report.
Neurogenic tumours of the mediastinum are uncommon neoplasms arising from nerve tissues within the thorax. We sought to evaluate and compare the outcome following surgical resection of such tumours by VATS, open thoracotomy, and by either combined with hemilaminectomy. From February 1992 to March 2007, 93 patients underwent surgical resection of neurogenic tumours of the mediastinum in our institution. A videothoracoscopic approach was used in 57 cases (61.3%) (group V), of which 44 underwent VATS only and 13 required conversion to open approach. In the remaining 36 cases, 32 patients underwent thoracotomy (group T) and 4 had combined procedure with the neurosurgeons (group N). No postoperative mortality was reported. Postoperative morbidity rate was 23.6% (22/93; 14 of group T, 4 of group N, and 4 of group V; p<0.0001). Histology showed benign neurogenic tumours in all patients. Statistical analysis showed differences between the two groups (group V and T respectively) in mean operative time (111.3+/-58.2 min vs 149.06+/-77.05 min; p: 0.01), median postoperative stay (4 days vs 6 days p: 0.0009) and median postoperative pain on day 1, day 7 and 1 month after surgery (respectively p<0.0001, p<0.0001 and p: 0.001). At a mean follow-up of 73 months no patients showed recurrence of the tumour. VATS represents the gold standard for the treatment of benign neurogenic tumours of the mediastinum with better results in terms of morbidity, operative time, postoperative stay and postoperative pain compared to open approach. Dumbbell tumours require a combined thoracic and neurosurgical approach.


The accelerated biodegradation and mineralization of acetaminophen in the H2O2-stimulated upflow fixed-bed bioreactor (UFBR).
The biodegradation and mineralization of acetaminophen (ACT) was evaluated in the upflow fixed-bed bioreactor (UFBR) inoculated with a biomass containing mixture of Pseudomonas spp. and Bacillus spp. as the dominant bacteria under H2O2 stimulation. The effect of various main operational variables was evaluated on the performance of the UFBR for ACT removal. The maximum ACT removal was obtained at the H2O2:ACT molar ratio of 14. H2O2 induced the bacteria in biofilm for the in-situ generation of peroxidase resulted in the acceleration of ACT decomposition into more biodegradable intermediates. Over 99% of ACT and 72% of its TOC at initial ACT concentrations up to 300 mg/L could be eliminated under optimum H2O2:ACT molar ratio in the batch UFBR within 12 h recirculation time. The specific biodegradation rate of ACT increased from 1.0 to 4.1 mg ACT/gbiomass.h when the inlet loading rate was increased from 8.3 to 41.7 g ACT/m3.h. In addition, the complete biodegradation and TOC removal of ACT was observed in the continuous UFBR at the hydraulic retention time of 6 h and the presence of 1-20 g/L salinity without inhibition. The presence of H2O2 could efficiently stimulate the production of bacterial peroxidase, which in turn resulted in the acceleration of ACT biodegradation and mineralization. Therefore, the H2O2-stimulated UFBR is an efficient and viable technique for in-situ production of peroxidase used for acceleration of ACT biodegradation.


Correction to: Housing gaps, mosquitoes and public viewpoints: a mixed methods assessment of relationships between house characteristics, malaria vector biting risk and community perspectives in rural Tanzania.
Following publication of the original article [1], the author flagged that the clause "and competing household priorities" was missing from the second sentence of the conclusion section of the Abstract; while this clause was in the Conclusion section of the main article text.


Investigating time dependent brain distribution of nevirapine via mass spectrometric imaging.
Central nervous system (CNS) HIV infection causes brain tissue inflammation and tissue deficit that contributes to neuroAIDS. This complication is escalated by the blood-brain barrier (BBB), which prevents easy access to antiretroviral drugs entering the CNS. In this study the aims were to investigate the BBB membrane penetration and brain localization patterns of Nevirapine (NVP) using Imaging Mass Spectrometry (MSI). Sprague-Dawley rats received an intraperitoneal dose of NVP (50 mg kg-1). Plasma and brain samples were harvested, and mass spectrometric methods were then applied to determine the pharmacokinetic properties and localization patterns of NVP in the brain. The pharmacokinetic parameters demonstrated a rapid bio-distribution of NVP in plasma and brain. The plasma Cmax was 6320 ng mL-1 and the brain Cmax was 1923 ng mL-1, both at a Tmax of 0.25 h. MSI of coronal brain sections showed that NVP penetrated and localized in the brain regions implicated with the development of HIV associated neurodegeneration. NVP has great potential to combat neuroAIDS.


Nonoperative Management (Including Ultrasound-Guided Injections) of Proximal Biceps Disorders.
Nonoperative management of conditions of the long head of biceps tendon (LHBT) involves a multifaceted approach, addressing the entire shoulder complex in addition to conditions that involve the LHBT. LHBT pathologic conditions are divided into 3 categories: inflammation, instability and rupture. This article provides an overview of a nonoperative treatment algorithm that addresses these specific categories and includes a review of ultrasound-guided injection techniques used in the diagnosis and management of LHBT disorders.


Assessment of radioligands for PET imaging of cyclooxygenase-2 in an ischemic neuronal injury model.
Cyclooxygenase-2 (COX-2) plays crucial roles in progressive neuronal death in ischemic brain injury. In the present study, we evaluated two radiolabeled COX-2 selective inhibitors, [11C]celecoxib and [11C]rofecoxib, as positron emission tomography (PET) tracers for COX-2 imaging in normal and ischemic mouse brains. We also took advantage of our newly-generated antibody highly selective for mouse COX-2 to prove accumulation of the radioligands in regions enriched with COX-2. In vitro autoradiography demonstrated specific binding of high-concentration [11C]rofecoxib but not [11C]celecoxib to the cerebellum and brain stem of normal brains wherein COX-2 immunoreactivity in neurons was most abundantly observed. Meanwhile, both of these radioligands failed to detect COX-2 expression in PET assays despite their excellent brain permeability. Hypoperfusion-induced ischemia caused marked necrotic neuron death accompanied by gliosis and enhancement of neuronal COX-2 immunoreactivity in the hippocampus. Correspondingly, in vitro autoradiographic binding of [11C]rofecoxib was increased in the injured hippocampus compared to the uninjured contralateral region, but failed in living brains of ischemia model likewise. Our work provides the rationale for monitoring COX-2 as a biomarker reflecting ischemic brain injuries and demonstrates that [11C]rofecoxib, not [11C]celecoxib, is useful for in vitro assays of COX-2, but its affinity would be insufficient for in vivo PET visualization.


Reduction in erythrocytic GSH level and stability in Plasmodium vivax malaria.
The existence of haemolytic anaemia in malaria indicates disturbances in red cell stability due to physical as well as metabolic stress attributable to the malarial parasite. As erythrocytic reduced glutathione (GSH) is involved in maintaining the integrity of red cells, the status of erythrocytic GSH was studied in 40 patients infected with Plasmodium vivax before and after therapy with chloroquine. 40 normal subjects, age- and sex-matched, were studied as controls. The level of erythrocytic GSH of malaria patients during infection and before therapy was significantly lower in comparison with controls (P less than 0.0005). Instability of GSH was recorded in 17 of 40 patients, while none of the controls showed such a defect. There was a progressive decrease in GSH level and stability of the host red cells with increasing parasitaemia. Normal values were obtained following therapy and cure of malaria indicating that the changes in GSH level and stability are induced by P. vivax. Alterations in the GSH metabolism may represent one of the factors contributing to the severity of anaemia in malaria due to P. vivax infection.


[Tympanostomy tube otorrhea: microbiological epidemiology, pathogen susceptibility to local antibiotics and bactericidal power of the rifamycin-olfloxacin combination].
We studied the microbiological epidemiology of tympanostomy tube otorrhea, rifamycin and ofloxacin sensitivity of pathogens isolated from these otorrheas, and the bactericidal power of the rifamycine-ofloxacin combination. A prospective study was conducted in 1997 with cultures of otorrhea aspirates, in vitro study of pathogen resistance to rifamycin and ofloxacin, bacteriocidal study of the rifamycin-ofloxacin combination. One hundred eight aspirates were obtained from 98 children (mean age 5 years). Ten aspirates were sterile, 32 had more than one pathogen. The more frequent pathogens were Pseudomonas aeruginosa (Pa) (n=35), Staphylococcus aureus (Sa) (n=27), Haemophilus influenae (Hi) (n=12) and Streptococcus pneumoniae (Sp) (n=9). All Hi, all Sp, 86.3% of the Sa (MIC(90) 0.25 mg/l) and none of the Pa were rifamycin sensitive. All Hi, 97.7% of the Pa (MIC(90) 0.5 mg/l), 73,1% of the Sa (MIC(90) 0.24 mg/l) and none of the Sp were ofloxacin sensitive. The rifamycin-ofloxacin combination led to a 4 log CFU/ml decrease in 6 hours for Sp, and in 24 hours for Pa, Hi and Sa. The rifamycin-ofloxacin combination is bactericidal for bacteria causing tympanostomy tube otorrhea. Otic drops with this combination should be considered as the first line treatment for such otorrhea.


Green and red fluorescent protein vectors for use in biofilm studies of the intrinsically resistant Burkholderia cepacia complex.
Cystic fibrosis isolates of the Burkholderia cepacia complex (BCC) have demonstrated a propensity to associate intimately with Pseudomonas aeruginosa in mixed community biofilms, which may impact on their overall pathogenicity during infection of the lungs in cystic fibrosis. Here, we describe the construction and use of novel green and red fluorescent protein expression vectors suitable for labeling biofilm cells of multi-resistant clinical isolates of the BCC for microscopic analysis of both single species biofilms and mixed community associations with P. aeruginosa. Antimicrobial susceptibility testing established that tetracycline and/or trimethoprim were suitable selective agents for widespread use in BCC. The green and red fluorescent protein genes, driven by constitutively active promoters, were cloned into two mobilizable plasmids pBBR1MCS-3 and pBBR1Tp, carrying tetracycline and trimethoprim resistance cassettes, respectively. The fluorescence of transformed BCC and P. aeruginosa planktonic cells was detectable using fluorescence microscopy and/or fluorometry. The plasmids were stable in the absence of selection for at least 3 days in planktonic and biofilm cultures, and fluorescence was still visible in a 4-day glass coverslip flow cell biofilm. The plasmids functioned well to distinguish the two species in a mixed community biofilm, with no indications of plasmid transfer between species or cross-talk of the fluorescent signals. These vectors represent the first green and red fluorescent vectors to be constructed and analyzed specifically for wide spread use in BCC and P. aeruginosa single and mixed biofilm cultures.


Design and synthesis of new tetrahydroquinolines derivatives as CETP inhibitors.
This letter describes the discovery and SAR optimization of tetrazoyl tetrahydroquinoline derivatives as potent CETP inhibitors. Compound 6m exhibited robust HDL-c increase in hCETP/hApoA1 double transgenic model and favorable pharmacokinetic properties.


4,6-α-Glucanotransferase activity occurs more widespread in Lactobacillus strains and constitutes a separate GH70 subfamily.
Family 70 glycoside hydrolase glucansucrase enzymes exclusively occur in lactic acid bacteria and synthesize a wide range of α-D-glucan (abbreviated as α-glucan) oligo- and polysaccharides. Of the 47 characterized GH70 enzymes, 46 use sucrose as glucose donor. A single GH70 enzyme was recently found to be inactive with sucrose and to utilize maltooligosaccharides [(1→4)-α-D-glucooligosaccharides] as glucose donor substrates for α-glucan synthesis, acting as a 4,6-α-glucanotransferase (4,6-αGT) enzyme. Here, we report the characterization of two further GH70 4,6-αGT enzymes, i.e., from Lactobacillus reuteri strains DSM 20016 and ML1, which use maltooligosaccharides as glucose donor. Both enzymes cleave α1→4 glycosidic linkages and add the released glucose moieties one by one to the non-reducing end of growing linear α-glucan chains via α1→6 glycosidic linkages (α1→4 to α1→6 transfer activity). In this way, they convert pure maltooligosaccharide substrates into linear α-glucan product mixtures with about 50% α1→6 glycosidic bonds (isomalto/maltooligosaccharides). These new α-glucan products may provide an exciting type of carbohydrate for the food industry. The results show that 4,6-αGTs occur more widespread in family GH70 and can be considered as a GH70 subfamily. Sequence analysis allowed identification of amino acid residues in acceptor substrate binding subsites +1 and +2, differing between GH70 GTF and 4,6-αGT enzymes.


Systematic review of self-concept measures for primary school aged children with cerebral palsy.
This study involved a systematic review aimed to identify self-concept measures that provided published psychometrics for primary school aged children (8-12 years) with cerebral palsy (CP). Six electronic databases (PubMed, MEDLINE, CINAHL, PsycINFO, PsycARTICLES and Web of Science) were searched to identify assessments that (1) measured self-concept; (2) in children aged 8-12 years; (3) with CP; (4) with psychometrics available. The Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist was used to evaluate psychometric properties and the CanChild Outcome Measure Rating Form was used to evaluate clinical utility. Search yielded 271 papers, of which five met inclusion criteria. These papers reported five measures of self-concept with psychometric properties for the target population: the Rosenberg Self-Esteem Index, Self-Description Questionnaire-I, Self-Perception Profile for Children (original) and two separate modifications of the Self-Perception Profile for Children. Currently, no self-concept measures published in English had sufficient psychometric data for children with CP. The Self-Description Questionnaire-I and the Self-Perception Profile for Children were promising options. Further research is required (a) to determine self-concept construct components important for children with CP and (b) to examine the relative strength, validity, reliability and clinical utility of self-concept measures for the target population.


Mode of Presentation in 1070 Patients With Perforated Epithelial Appendiceal Tumors, Predominantly with Pseudomyxoma Peritonei.
Perforated epithelial appendiceal tumors are uncommon and can give rise to pseudomyxoma peritonei. Pseudomyxoma peritonei is rare, almost always of appendiceal origin, and presents in various ways relevant to abdominal surgeons. The aim of this study was to report the mode of presentation of pseudomyxoma peritonei of appendiceal origin in patients treated in a high-volume UK peritoneal malignancy center. A retrospective observational study was conducted. This was a single-center study. Retrospective analysis of a prospective database of consecutive patients undergoing surgery between March 1994 and December 2016 was performed. Mode of presentation was classified into 7 categories: "histological diagnosis at abdominal surgery for presumed appendicitis," "probable pseudomyxoma peritonei" based on abnormality on cross-sectional imaging (± image-guided biopsy)," "abnormal imaging (other cause suspected) and operative finding of pseudomyxoma peritonei," "diagnostic laparoscopy," "ovarian mass," "new-onset hernia," and "miscellaneous." Overall, 1070 patients underwent surgery (female 61%, male 39%); median age was 57. The mode of presentation was abnormality on cross-sectional imaging in 324 of 1070 patients (30.3%), histological diagnosis at emergency surgery for presumed appendicitis in 203 of 1070 patients (19%), and abnormal imaging with eventual pseudomyxoma peritonei diagnosis in 180 of 1070 patients (16.8%); 124 of 651 women (19.2%) presented with an ovarian mass. New-onset hernia was the presenting feature in 9.9%; 83 of 1070 patients (7.7%) were diagnosed at diagnostic laparoscopy, and 32 of 1070 patients (3%) were described as "miscellaneous." Overall, 775 of 1070 patients (72.4%) had complete cytoreductive surgery with 10-year survival of 63.5%. Results are limited by the retrospective nature of the study, radiological improvements over the study period, and the number of patients who had overlapping features at presentation. Perforated appendiceal tumors present in various ways but predominantly at cross-sectional imaging or coincidentally at laparoscopy or laparotomy. All abdominal surgeons will occasionally encounter cases, often unexpectedly, and recognition and referral to a specialized unit results in excellent outcomes in most cases. See Video Abstract at http://links.lww.com/DCR/B256. MODO DE PRESENTACIÓN EN 1070 PACIENTES CON TUMORES EPITELIALES APENDICULARES PERFORADOS, PREDOMINANTEMENTE CON PSEUDOMIXOMA PERITONEAL: Los tumores epiteliales apendiculares perforados son poco frecuentes y pueden dar lugar a Pseudomyxoma peritonei. El pseudomixoma peritoneal es raro, casi siempre de origen apendicular, y se presenta de diversas formas relevantes para los cirujanos abdominales.El objetivo fue informar el modo de presentación del Pseudomixoma peritoneal de origen apendicular en pacientes tratados en un centro de malignidad peritoneal de alto volumen en el Reino Unido.Se realizó un estudio observacional retrospectivo.Este fue un estudio de centro único.Análisis retrospectivo de una base de datos prospectiva de pacientes consecutivos sometidos a cirugía entre marzo de 1994 y diciembre de 2016.El modo de presentación se clasificó en 7 categorías: "diagnóstico histológico en la cirugía abdominal por presunta apendicitis", "probable Pseudomixoma peritoneal" basado en la anormalidad en la imagen de corte transversal (biopsia guiada por imagen +/-), "imagen anormal (se sospecha otra causa) y hallazgo quirúrgico de Pseudomixoma peritoneal", "laparoscopia diagnostica", "masa ovarica", "hernia de reciente aparicion" y "varios".En total, 1070 pacientes fueron operados (mujeres 61%, hombres 39%); edad media 57. El modo de presentación fue anormalidad en la imágen transversal en 324/1070 (30.3%), el diagnóstico histológico en cirugía de emergencia por presunta apendicitis en 203/1070 (19%), la imágen anormal con eventual diagnóstico de Pseudomixoma peritoneal en 180 / 1070 (16.8%), 124/651 (19.2%) las mujeres presentaron una masa ovárica. La hernia de reciente aparición fue la característica de presentación en 9.9%, 83/1070 (7.7%) fueron diagnosticados por laparoscopia diagnóstica y 32/1070 (3%) "misceláneos". En general, 775/1070 (72,4%) se sometió a cirugía citorreductora completa con una supervivencia a 10 años del 63,5%.Una deficiencia es que los resultados están limitados por la naturaleza retrospectiva del estudio, las mejoras radiológicas a lo largo del período de estudio, y varios pacientes tenían características superpuestas en la presentación.Los tumores apendiculares perforados se presentan de varias maneras, pero predominantemente en imágenes transversales o casualmente en laparoscopia o laparotomía. Todos los cirujanos abdominales encontrarán ocasionalmente con casos, a menudo inesperados, y el reconocimiento y la derivación a una unidad especializada da lugar a excelentes resultados en la mayoría de los casos. Consulte Video Resumen en http://links.lww.com/DCR/B256.).


Immunocytochemical and immunoelectron microscopy study of dendritic cells in the caecal tonsils of chickens infected with Eimeria tenella.
In the present study S-100 protein containing cells in the caecal tonsil were investigated, both at light microscopic and at electron microscopic levels, after oral coccidia inoculation (Eimeria tenella). The birds were infected with a single (Day 0) or two (Days 0 and 21) infective doses of 500 oocysts. Immunoelectron reactivity for S-100 protein was demonstrated in infected chickens, but not in controls. It was found in follicular dendritic cells and interdigitating dendritic cells which were present in the germinal center and diffuse lymphoid tissue respectively, both of them being located in the deep lymphoid tissue near the muscular layer and around the deep glands. Outside the lymphoid tissue, immunoreactivity for S-100 protein was found in cells lying between the epithelial cells of the deep crypt epithelium. Positivity for S-100 protein was observed at 3, 12, 18, 24 and 48 h after the first inoculation as well as on Days 3, 5, 6, 7, 8, 25 and 30 of the experiment. Positive reaction for S-100 protein was detected both while schizont (the more immunogenic stage) development occurs and the number of sporozoites in the caeca lumen was higher, as well as when the production of oocysts reached a maximum. Complementary studies demonstrated that S-100 positive dendritic cells gave a negative reaction for esterase activity, whereas a subset of S-100 negative intraepithelial lymphocytes located between epithelial cells lining the deep glands exhibited esterase activity. These esterase positive cells are hypothesized to be involved in the regulation of local defences.


Identifying specific kinase substrates through engineered kinases and ATP analogs.
Intracellular signaling by protein kinases controls many aspects of cellular biochemistry and physiology. Determining the direct substrates of protein kinases is important in understanding how these signaling enzymes exert their effect on cellular functions. One of the recent developments in this area takes advantage of the similarity in the ATP binding domains of protein kinases, where a few conserved amino acids containing large side chains come in close contact with the N-6 position of bound ATP. Mutation of one or more of these residues generates a "pocket" in the ATP binding site that allows the mutant kinase, but not other cellular kinases, to utilize analogs of ATP with bulky substituents synthesized onto the N-6 position. The use of such a mutated kinase and radiolabeled ATP analogs allows for the specific labeling of direct substrates of the kinase within a mixture of cellular proteins. We have recently reported the generation of "pocket" mutants of extracellular regulated kinase 2 (ERK2) and their use in the identification of two novel substrates of ERK2. In this report, we discuss the generation and characterization of ERK2 mutants that utilize analogs of ATP and describe the methodology used to identify ERK2-associated substrates. We also describe the direct labeling of ERK2 substrates in cell lysates. These methodologies can be adapted for use with other protein kinases to increase the understanding of intracellular signal transduction.


2008 white paper for implementing strategies and interventions for cardiovascular prevention in Italy.
The present article for improving strategies and interventions for cardiovascular prevention in Italy represents the collaborative work of several scientific societies that recognize their own role and mission in the field of prevention of cardiovascular diseases. It originates from the need, felt in many European and non-European countries, as well as at the level of the EU, to rapidly promote strategies and interventions to better prevent cardiovascular diseases.The main reason for producing this article is represented by the growing clinical and socioeconomic impact that cardiovascular diseases will have in Italy in the next few years. This, in fact, will bring serious problems regarding the ability to sustain the entire national healthcare system in Italy.This article reviews some of the major data available on projections of cardiovascular diseases and their social and economic burden. This article represents a White Paper, and it is conceived as a new starting point, proposing general specific interventions, addressed to decision-makers, stakeholders, institutions, citizens, physicians, healthcare workers, organizations and industries. These proposals are listed, and briefly discussed, leading to the development of a 'call-to-action', aimed at reducing the incidence of cardiovascular diseases and their impact on the healthcare system, even in the short to medium term.


Polytetrafluoroethylene patch venoplasty for outflow reconstruction in living donor liver transplantation: two case reports.
Outflow obstruction may lead to liver congestion and eventual graft failure after living donor liver transplantation. Various methods of venoplasty provide wider outflow tracts. Most series have suggested use of autologous or allogenic grafts for patch venoplasty. We used a polytetrafluorethylene patch in two patients. Both showed good patency of the outflow tract at Doppler ultrasonography at 7 months and 4 months posttransplantation. A polytetrafluoroethylene patch may be a good alternative when no other autologous or allogeneic vascular patch is available or when the situation is critical.


Characterization of silica-coated hematite and application to the formation of composite particles including egg yolk PC liposomes.
According to the method of Ohmori et al. (J. Colloid Interface Sci. 150 (1992) 594), a procedure is examined for the buildup of uniform silica layers on monodispersed hematite particles. It appears that the silica layer resulting is homogeneous and the layer thickness is controlled by the concentration of tetraethylorthosilicate (TEOS) in the medium. Further, egg PC liposomes, a typical biocolloid, are introduced onto the silica-coated hematite particle. The formation was proceeded by two types of processes: (1) heterocoagulation between the silica-coated hematite and egg PC liposomes by controlling the concentration of LaCl(3) in the medium, or (2) buildup using two proteins (lysozyme or cytochrome C) as binder molecules. These results were analyzed by zeta-potential measurements and a contact-type X-ray microscope, which is a unique technique for obtaining X-ray images of biological specimens in water with high resolution.


Chenopodium album seed extract-induced sperm cell death: exploration of a plausible pathway.
This study was conducted for to explore the plausible pathway of Chenopodium album seed extract (CAE)-mediated sperm cell death. The role of CAE for its spermicidal action was assessed by (a) measuring lipid peroxidation, protein carbonyl content and intracellular glutathione content in CAE exposed sperm cells; (b) assaying antioxidant enzymes like catalase and superoxide dismutase (SOD); (c) analyzing protein expressions by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis; (d) fluorimetric measurement of intracellular H(2)O(2) level and generation of reactive oxygen species (ROS) in CAE-treated sperm cells; and (e) DNA ladder formation study. CAE-induced sperm death is due to (a) lipid peroxidation of the sperm cell membrane, oxidation of some critical cellular proteins and depletion of intracellular reduced gluthathione, indicating production of ROS; (b) activation of Mn-SOD and inactivation of catalase favoring endogenous accumulation of H(2)O(2); (c) generation of O(2)(*-) at an enhanced rate during oxidative stress as evidenced by increased Mn-SOD activity and protein expression; (d) accumulation of ROS in spermatozoa reflected in the fluorimetric experiments; and (e) increased production of O(2)(*-) and H(2)O(2) induced apoptosis-like death in sperm cells as observed by DNA ladder formation. The sperm death mediated by CAE is due to oxidative damage of cellular macromolecules by in situ generation of ROS.


The novel small-molecule antagonist MMG-11 preferentially inhibits TLR2/1 signaling.
Toll-like receptor 2 (TLR2) forms heterodimers with either TLR1 or TLR6 to induce protective early inflammatory responses to pathogen- and damage-associated molecular patterns. However, excessive activation is associated with inflammatory and metabolic diseases. Several TLR2 antagonists have been described but pharmacological characterization is still at an early stage. Previously, we identified the potent and selective TLR2 antagonist MMG-11 by computational modelling and experimental validation. Here, we characterized the TLR2 antagonists MMG-11 and CU-CPT22 as well as the TIR-domain binding TLR2 antagonist C29 in TLR-overexpressing promoter cells as well as human and mouse macrophages. In line with our recent studies, MMG-11 abrogated pro-inflammatory cytokine secretion and NF-κB activation induced by different bacterial TLR2 agonists. MMG-11 preferentially inhibited TLR2/1 signaling in promoter cells stably expressing TLR2 heterodimers and mouse macrophages. Furthermore, the TLR2 antagonist blocked ligand-induced interaction of TLR2 with MyD88 and reduced MAP kinase and NF-κB activation. MMG-11 and CU-CPT22 but not C29 displaced Pam3CSK4 in an indirect binding assay confirming the competitive mode of action of MMG-11 and CU-CPT22. Isobologram analysis revealed additive and synergistic effects when the non-competitive antagonist C29 was combined with the competitive antagonist MMG-11 or CU-CPT22, respectively. In conclusion, we provide evidence that MMG-11 acts as a competitive antagonist with a predominance for the TLR2/1 heterodimer in human and mouse cells. Our results also indicate that MMG-11 is a model compound for studying TLR2 signaling.


Spatial allocation of LID practices with a water footprint approach.
Urban water problems due to stormwater have been aggravated by the higher frequency of high-intensity precipitation events and the increase of paved surfaces. However, with appropriate stormwater management practices, such as low-impact development (LID), stormwater can provide an additional urban water resources rather than cause damage. This study aims to apply a water footprint to location determination of LID practices in the urban area. The LID planning procedure was demonstrated with the highest population density region in Taipei, Taiwan. In order to improve the spatial resolution of LID allocation, the "first-level dissemination area" with 450 residents was used as a spatial unit. The performance of LID practices was then evaluated with the simulation using the Storm Water Management Model (SWMM). Three LID practices, rainwater harvesting systems, permeable pavements, and bioretention systems, were selected. After the water footprint accounting, ten sites were suggested for LID implementation. The runoff reduction rate reached up to 65 % by rainwater harvesting systems or at least 3 % by permeable pavements. This study provides a simpler and more effective approach to ways of integrating an urban water footprint into LID planning and stormwater management in urban areas.


Integrating functional data analysis with case-based reasoning for hypertension prognosis and diagnosis based on real-world electronic health records.
Hypertension is the fifth chronic disease causing death worldwide. The early prognosis and diagnosis are critical in the hypertension care process. Inspired by human philosophy, CBR is an empirical knowledge reasoning method for early detection and intervention of hypertension by only reusing electronic health records. However, the traditional similarity calculation method often ignores the internal characteristics and potential information of medical examination data. In this paper, we first calculate the weights of input attributes by a random forest algorithm. Then, the risk value of hypertension from each medical examination can be evaluated according to the input data and the attribute weights. By fitting the risk values into a risk curve of hypertension, we calculate the similarity between different community residents, and obtain the most similar case according to the similarity. Finally, the diagnosis and treatment protocol of the new case can be given. The experiment data comes from the medical examination of Tianqiao Community (Tongling City, Anhui Province, China) from 2012 to 2021. It contains 4143 community residents and 43,676 medical examination records. We first discuss the effect of the influence factor and the decay factor on similarity calculation. Then we evaluate the performance of the proposed FDA-CBR algorithm against the GRA-CBR algorithm and the CS-CBR algorithm. The experimental results demonstrate that the proposed algorithm is highly efficient and accurate. The experiment results show that the proposed FDA-CBR algorithm can effectively describe the variation tendency of the risk value and always find the most similar case. The accuracy of FDA-CBR algorithm is higher than GRA-CBR algorithm and CS-CBR algorithm, increasing by 9.94 and 16.41%, respectively.


Effect of oestradiol-17 beta and gonadotrophins on prostaglandin production by pre-ovulatory pig follicles superfused in vitro.
Pre-ovulatory pig follicles were superfused in vitro with oestradiol, LH or FSH in the presence and absence of indomethacin. Prostaglandin E2 ANd F2 alpha and oestradiol were measured in the same samples of superfusate. LH and FSH caused an increase in levels of both prostaglandins (approximately 2-fold) but the most marked effect was of oestradiol in PGE2 where a 4-fold increase in levels above controls was observed. In all cases indomethacin inhibited the effects. Both gonadotrophins caused an increase in oestradiol production although the response to LH was much slower than to FSH. The results show a possible relationship between FSH, oestradiol and PG synthesis in the pre-ovulatory pig follicle.


Larvicidal and repellent activity of tetradecanoic acid against Aedes aegypti (Linn.) and Culex quinquefasciatus (Say.) (Diptera:Culicidae).
To investigate the larvicidal and repellent efficacy of tetradecanoic acid against Aedes aegypti (Ae. aegypti) L. and Culex quinquefasciatus (Cx. quinquefasciatus) Say (Diptera: Culicidae). Larvicidal efficacy of tetradecanoic acid was tested at various concentrations against the early third instar larvae of Ae. aegypti and Cx. quinquefasciatus. The repellent activity was determined against two mosquito species at three concentrations viz., 1.0,2.5 and 5.0 ppm under the laboratory conditions. The tetradecanoic acid was found to be more effective against Cx. quinquefasciatus than Ae. aegypti larvae. The LC(50) values were 14.08 ppm and 25.10 ppm, respectively. Tetradecanoic acid showed lesser repellency against Ae. aegypti and Cx. quinquefasciatus. The highest repellency was observed in higher concentration of 5.0 mg/cm(2) provided 100% protection up to 60 and 90 min against Ae. aegypti and Cx. quinquefasciatus respectively. From the results it can be concluded the tetradecanoic acid is a potential for controlling Cx. quinquefasciatus and Ae. aegypti mosquitoes.


Quality of life and surgical satisfaction after vaginal reconstructive vs obliterative surgery for the treatment of advanced pelvic organ prolapse.
We sought to compare quality of life and patient satisfaction after obliterative vs reconstructive surgery. A retrospective cohort study of women who met the following inclusion criteria: age 65 years or older, leading edge of prolapse 4 cm or greater beyond the hymen, and vaginal reconstructive or obliterative surgery. Preoperative responses to the Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) were collected retrospectively. We then mailed the same questionnaires, and the Surgical Satisfaction Questionnaire (SSQ-8), to these subjects postoperatively. Mode of surgery was evenly split (n = 45 per group) between the 90 patients meeting the inclusion criteria. Improvements from the preoperative to postoperative Incontinence Impact Questionnaire and Urogenital Distress Inventory were comparable as were postoperative Surgical Satisfaction Questionnaire scores. Improvements in condition-specific quality of life and postoperative patient satisfaction measures are comparable in women with prolapse who undergo either reconstructive or obliterative surgery.


Neurogenic regulation of cochlear blood flow occurs along the basilar artery, the anterior inferior cerebellar artery and at branch points of the spiral modiolar artery.
The cochlea receives its main blood supply from the basilar artery via the anterior inferior cerebellar artery and the spiral modiolar artery. Morphologic studies have shown sympathetic innervation along the spiral modiolar artery of the gerbil and the guinea pig and functional studies in the isolated in vitro superfused spiral modiolar artery of the gerbil have demonstrated norepinephrine-induced vasoconstrictions via alpha(1A)-adrenergic receptors. It is current unclear whether the sympathetic innervation is physiologically relevant. Stimulation of sympathetic ganglia in guinea pigs has been shown to alter cochlear blood flow in situ. Whether these changes originated from local or more systemic changes in the vascular diameter remained uncertain. The goal of the present study was to demonstrate the presence or absence of neurogenic changes in the diameter of the isolated in vitro superfused spiral modiolar artery, anterior inferior cerebellar artery and basilar artery from the gerbil and the guinea pig. Vascular diameter was monitored by videomicroscopy. Electric field stimulation was used to elicit neurotransmitter release. A reversible inhibitory effect of 10(-6) M tetrodotoxin was taken as criterion to discriminate between neurogenic and myogenic changes in vascular diameter. Mesentery arteries of comparable diameter, which are known to respond with a neurogenic vasoconstriction to electric field stimulation, served as controls. Basilar artery, anterior inferior cerebellar artery, spiral modiolar artery and mesentery arteries constricted in response to electric field stimulation. No dilations were observed. Myogenic and neurogenic vasoconstrictions were observed in all vessels. These observations suggest that the sympathetic innervation of the basilar artery, the anterior inferior cerebellar artery and branch points of the spiral modiolar artery is involved in a physiologically relevant control of the vascular diameter in the gerbil and the guinea pig.


Discrimination of supraventricular tachycardia from sinus tachycardia of overlapping cycle length.
For more than 15 years, pulse generators (PG) have been implanted for the control of tachyarrhythmias. Manually activated systems have not achieved wide acceptance, mainly because of the need for direct patient participation. Automatic antitachycardia PGs have been limited by lack of flexibility of programmable parameters and the inability to discriminate pace-terminable tachycardias from sinus tachycardia. New algorithms for differentiating these tachycardias are becoming available. In addition to high rate detection criteria, there are three additional criteria that might characterize the tachycardias: (1) sudden onset, (2) rate stability, (3) sustained high rate. Future antitachycardia pacing systems will be able to employ even more elaborate algorithms when more sophisticated microprocessor capabilities and new sensors become available.


A comparison of the rate of oxygen uptake and the adenosine triphosphate content of routine and experimental BCG preparations.
The ATP content and oxygen uptake rate, two parameters of viability of a BCG suspension, are compared. The lack of correlation between measurements made on fresh routine preparations indicates that the ATP measurements is affected by the degree of dispersion of the preparation. Experimental preparations made under standard conditions (constant semi-dry weight and stepwise dispersive grinding) from cultures of the same age as the fresh routine cultures (14 days) had a smaller ATP content, which correlated well with the respiration rate. In experimental preparations from seven-day cultures this correlation was significant. Between days 7 and 14 the ATP content declined much more rapidly than the respiration rate.


Growth stimulation of tumor-specific cytotoxic T lymphocytes on concanavalin a-immobilized carrier beads.
Human tumor-specific CD4(+) cytotoxic T lymphocytes (CTL) were generated against duodenum papilloma cell line TGBC18TKB from HLA type-matched peripheral blood mononuclear cells. Concanavalin A (Con A) immobilized on carrier beads stimulated growth of the CTL in a long-term culture without repeated antigen stimulation, while soluble Con A induced death of the CTL. The CTL exhibited the target-specific cytotoxicity in a more potent manner than those before the long-term culture in the presence of the immobilized Con A. Enhanced expression of the adhesion molecule, CD11b, was observed on the CTL. These results suggest that immobilized Con A will be useful for continuous growth stimulation and large scale expansion of CTL without tumor antigen.


Engineering interfacial coupling between 3D net-like Ni3(VO4)2 ultrathin nanosheets and MoS2 on carbon fiber cloth for boostinghydrogen evolution reaction.
The use of cheap and efficient electrocatalyst for the production of hydrogen is the key to solving the current energy crisis. Herein, we used a two-step hydrothermal process to fabricate noble-metal-free 3D net-like Ni3(VO4)2 ultrathin nanosheets coupled with MoS2@CFC interface. Unlike the traditional two-dimensional composite materials, Ni3(VO4)2 ultrathin nanosheets intersect with MoS2 nanosheets grown on CFC in a 3D net-like structure (Ni3(VO4)2/MoS2@CFC). Due to the mutual combination of structures and the interfacial coupling cooperation effect between Ni3(VO4)2 nanosheet and MoS2@CFC, the catalytically active area was expanded, and the intrinsic activity toward HER was significantly improved. Ni3(VO4)2/MoS2@CFC showed high activity at the industrial temperature (75 °C), with an overpotential of 77 mV (10 mA/cm2) and a 65 mV/dec Tafel slope. This material showed good stability at 0.5 M H2SO4. This work provides a heterostructure scheme for the construction of a novel noble metal-free electrocatalyst to promote hydrogen evolution reaction.


Temporal lobe epilepsy due to meningoencephaloceles into the greater sphenoid wing: a consequence of idiopathic intracranial hypertension?
Antero-inferior temporal lobe meningoencephaloceles are a rare, but increasingly recognized cause of drug-resistant temporal lobe epilepsy (TLE). In order to evaluate whether these lesions are related to idiopathic intracranial hypertension (IIH), we analyzed clinical and MRI findings of a cohort of patients undergoing presurgical work-up. Seizure onset in the anterior temporal lobe was proven by EEG electrodes in 22 patients, and in 21 patients, anterior temporal lobectomy (mostly with sparing of the hippocampus) was performed. MRI signs of IIH (in particular empty sella) and the volumes of the ventricles and external CSF spaces were determined and related to the body mass index (BMI) and clinical outcome. Six of seven obese (BMI > 30 kg/m2) compared to four of 15 non-obese patients had partial empty or empty sella (p = 0.007). Bilateral lesions were found in all obese and 11 patients. Seizure freedom (Engel class 1A) was achieved in 12 of 21 patients (5 obese compared to 7 non-obese patients). BMI was related to the volume of the external CSF spaces (r = 0.467), and age at seizure onset was higher in obese patients. Roughly a third of patients with temporal lobe epilepsy due to antero-inferior meningoencephaloceles is obese and has MRI signs of idiopathic intracranial hypertension.


Evaluating the diagnostic ability of two automated non-invasive tear film stability measurement techniques.
To evaluate the comparability, discriminative ability, and optimal thresholds for non-invasive tear film breakup time measurements obtained from the Oculus Keratograph 5M and Medmont E300 in detecting other signs and symptoms of dry eye disease, as defined by the TFOS DEWS II diagnostic criteria. One hundred and thirty-four participants (53 male, 81 female), with a mean ± SD age of 48 ± 20 years, were recruited into a prospective, investigator-masked, diagnostic accuracy study. Dry eye symptomology, tear film parameters (including non-invasive Keratograph and Medmont breakup time), and ocular surface staining were evaluated in a single clinical session. Significant positive correlation was observed between the two automated instruments (p < 0.001), although non-invasive breakup time measurements obtained from the Medmont were significantly longer (p < 0.001), and demonstrated greater intra-subject and inter-subject variability (all p < 0.001). The areas under the ROC curves exceeded 0.65 for both instruments, and the discriminative abilities were comparable (p = 0.53). The Youden optimal diagnostic threshold for non-invasive tear film stability measurements obtained from the Keratograph was ≤8 seconds, and the optimal cut-off for breakup time measurements obtained from the Medmont was ≤14 seconds. Despite significant positive correlation, breakup time measurements obtained from the Keratograph and Medmont were not directly interchangeable. Measurements from the Medmont were significantly longer and demonstrated greater intra-subject and inter-subject variability, although the two automated, non-invasive methods for assessing tear film stability exhibited comparable overall performance in diagnosing dry eye disease.


Valosin-containing protein Asp395Gly mutation in a patient with frontotemporal dementia: a case report.
Variants in the valosin-containing protein (VCP) gene were identified as one of the causes for inclusion body myopathy associated with Paget disease of the bone and frontotemporal dementia (FTD). Previously identified pathogenic variants in VCP are associated with frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) pathologically, but p.Asp395Gly VCP was recently reported to cause familial FTD with tauopathy characterized by neurofibrillary tau tangles (NFT) and not FTLD-TDP. We describe the clinical and genetic findings of a patient with p.Asp395Gly valosin-containing protein (VCP), who was diagnosed with FTD without a family history and in the absence of muscle or bone disease comorbidity. The patient was a 62-year-old man, who developed atypical depression at the age of 37 years. Subsequently, he presented with self-centered behavior at the age of 45 years. The self-centered behavior intensified from around the age of 50 years, which was accompanied by the development of executive dysfunction; therefore, he visited our hospital at 52 years of age. Magnetic resonance imaging revealed bilateral frontal lobe atrophy. Brain perfusion single-photon emission computed tomography revealed bilateral frontal lobe hypoperfusion. The patient fulfilled the diagnostic criteria for behavioral variant of FTD. Ten years after the diagnosis, computed tomography of the trunk and limbs, muscle biopsy, and bone scintigraphy revealed the absence of concomitant muscle and bone disease. The concentrations of cerebrospinal fluid (CSF) total tau and phosphorylated tau proteins were 389 pg/mL and 53.2 pg/mL (cut-off: 50 pg/mL), respectively. Genetic analyses were performed using the whole-exome and Sanger sequencing methods. We identified p.Asp395Gly VCP in this patient with pure FTD. p.Asp395Gly VCP was identified in a patient with likely sporadic FTD without concomitant muscle and bone disease. The CSF analysis suggested that our patient may have FTD due to NFT accumulation similar to the familial FTD patients with p.Asp395Gly VCP recently reported. Our findings suggest that a genetic search for the pathogenic variants of VCP should be considered not only for familial FTD, but also for patients with sporadic FTD, even in the absence of comorbid muscle or bone disease.


Reevaluation of the Fexitron 845.
The concept of flash radiography resulted in the development of the Fexitron 845 in the 1960s. Limitations in the technology of screen films (calcium tungstate) at that time displaced the Fexitron as a useful adjunct for clinical dentistry. The recent introduction of the more efficient rare-earth screens requires a reevaluation of the Fexitron 845. This study retests the efficacy of the Fexitron 845 for clinical diagnosis.


The HIF-1 alpha-C/EBP alpha axis.
The hypoxia inducible factors (HIFs) and CCAAT/enhancer binding protein alpha (C/EBP alpha) are transcription factors that mediate adaptive responses to hypoxia and control aspects of energy metabolism, respectively. New evidence suggests that when HIF-1 alpha and C/EBP alpha interact, they bring about reciprocal functional changes, so that the activity of HIF-1 alpha is decreased and that of C/EBP alpha is restricted or increased in a tissue-specific manner. This Journal Club article highlights research depicting interactions between HIF-1 alpha and C/EBP alpha and discusses conditions and tissues in which this interaction might occur.


Sapwood area ofPinus contorta stands as a function of mean size and density.
An indirect test of the relationship between leaf area and the combination of mean size and density is made in stands of lodgepole pine (Pinus contorta Dougl.). Total sapwood cross-sectional area of these stands is a function of the product of density and mean diameter raised to an exponent of about 1.6. Results from other studies, representing four species, suggest that this relationship between sapwood area and the combination of mean size and density may be general. The implications of the relationship are discussed in the context of evapotranspiration, competition and self-thinning.


CPA-catalyzed asymmetric domino thia-Michael/aldol reactions for simultaneous chiral center and axial chirality formation.
A highly enantio- and diastereoselective domino thia-Michael/aldol reaction applying 5H-dibenzo[a,c][7]annulen-5-one as a Michael acceptor, catalyzed by a chiral phosphoric acid (CPA), has been developed. The bridged biaryl adduct contains multiple stereogenic centers in the bridging linkage as well as a thermodynamically controlled stereogenic axis. The energy difference between the two atropodiastereomers is about 9.1 kcal mol-1, which accounts for the observed excellent diastereoselectivity (>20 : 1).


MiR-95-5p involves in the migration and invasion of trophoblast cells by targeting low density lipoprotein receptor-related protein 6.
Low density lipoprotein receptor-related protein 6 (LRP6) has been demonstrated to control trophoblast cell invasion, but its regulatory gene remains undefined. In this study, microRNA (miR) regulating LRP6 were explored to elucidate the potential mechanism of preeclampsia (PE). Firstly, the expression of LRP6 in PE tissues was detected by immunohistochemical staining and quantitative real-time polymerase chain reaction (qRT-PCR) assay. Prediction software predicted that LRP6 might be the target gene of miR-95-5p, and verified by double-luciferase reporter analysis. qRT-PCR assay measured the expression of miR-95-5p in PE tissues and trophoblast cell lines. Then, we transfected miR-95-5p mimic, inhibitor, LRP6, or mimic plus LRP6 into trophoblast cell lines, and analyzed their influences on cell migration and invasion by wound healing and Transwell experiments. The expressions of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors of metalloproteinase (TIMP)-1 in transfected cells were examined by western blot (WB) analysis. LRP6 was low-expressed in PE tissues, while miR-95-5p expression was high-expressed. MiR-95-5p negatively regulated the LRP6 expression in trophoblast cells. Both up-regulated LRP6 and down-regulated miR-95-5p can not only promote the migration and invasion of trophoblast cells, but also raised the expressions of MMP-2 and MMP-9 and inhibited the expression of TIMP-1. The over-expression of miR-95-5p suppressed the metastasis of trophoblast cells and rescued LRP6-induced increase of MMP-2 and MMP-9 and reduction of TIMP-1. MiR-95-5p involved in the migration and invasion of trophoblast cells by targeting LRP6, which might be a potential therapeutic target for PE.


Evaluation of different similarity indices as measures of succession in arthropod communities of the forest floor after clear-cutting.
Communities of spiders (Araneae) and beetles (Coleoptera) living in the soil and litter of clear-cut areas were compared with those of intact forest stands. Sixteen different indices of similarity were tested on three sets of material: spiders and beetles examined during one year in three clear-cut areas felled 3, 6 and 9 years earlier, and spiders in one clear-cut area examined during 7 successive years after felling. Other sources of evidence showed that succession in the spider community was divergent for at least 7 years after felling.The indices that seemed to express the changes best were: (1) Kendall's rank correlation test, (2) the Bray-Curtis measure, (3) Renkonen's percentage similarity, (4) the correlation coefficient r (2 to 4 after logarithmic transformation of data), (5) the Canberra metric, and (6) the diversity overlap (R 0). The properties of the indices are discussed.


Investigating the biochemical effects of heat stress and sample quenching approach on the metabolic profiling of abalone (Haliotis iris).
Ocean temperatures have been consistently increasing due to climate change, and the frequency of heatwave events on shellfish quality is a growing concern worldwide. Typically, shellfish growing areas are in remote or difficult to access locations which makes in-field sampling and sample preservation of shellfish heat stress difficult. As such, there is a need to investigate in-field sampling approaches that facilitate the study of heat stress in shellfish. This study aims to apply a gas chromatography-mass spectrometry (GC-MS) based metabolomics approach to examine molecular mechanisms of heat stress responses in shellfish using abalone as a model, and compare the effects of different quenching protocols on abalone metabolic profiles. Twenty adult Haliotis iris abalone were exposed to two temperatures (14 °C and 24 °C) for 24 h. Then, haemolymph and muscle tissues of each animal were sampled and quenched with 4 different protocols (liquid nitrogen, dry ice, cold methanol solution and normal ice) which were analyzed via GC-MS for central carbon metabolites. The effects of different quenching protocols were only observed in muscle tissues in which the cold methanol solution and normal ice caused some changes in the observed metabolic profiles, compared to dry ice and liquid nitrogen. Abalone muscle tissues were less affected by thermal stress than haemolymph. There were 10 and 46 compounds significantly influenced by thermal stress in muscle and haemolymph, respectively. The changes of these metabolite signatures indicate oxidative damage, disturbance of amino acid and fatty acid metabolism, and a shift from aerobic metabolism to anaerobic pathways. The study provided insights into the heat response of abalone, which could be useful for understanding the effects of marine heatwaves and summer mortality events on abalone. Dry ice appeared to be a suitable protocol, and safer in-field alternative to liquid nitrogen, for quenching of abalone tissues.


Are we measuring what matters to older people?
Comprehensive geriatric assessment is the core toolkit of geriatric medicine. Awareness of and engagement in comprehensive geriatric assessment are crucial competences for all professionals caring for older people living with frailty. The fundamental tenet of comprehensive geriatric assessment is person centredness, which means orienting problem evaluation and intervention plans around an individual's specific biopsychosocial situation to maximise their function and participation. Person-centred outcomes are frequently neglected from measurements of health-care delivery, service improvement, and research. Instead, systems tend to measure outcomes of the health-care service (ie, resource use) or a person's destination following a health-care process. The absence of person-centred outcome measures risks the delivery of health care that seeks to achieve, and is benchmarked against, outcomes that are not best for the patient. We must, therefore, ensure that the outcomes that matter to older people are being measured.


Reaction time to motion onset of luminance and chromatic gratings is determined by perceived speed.
We measured reaction times for detecting motion onset for sinusoidal gratings whose contrast was modulated in either luminance or chromaticity, for various drift rates and contrasts. In general, reaction times to chromatic gratings were slower than to luminance gratings of matched cone contrast, but the difference in response depended critically on both contrast and speed. At high image speeds there was virtually no difference, whereas at low speeds, the difference was pronounced, especially at low contrasts. At high image speeds there was little dependence of reaction times on contrast (for either luminance or colour), whereas at low speeds the dependence was greater, particularly for chromatic stimuli. This pattern of results is reminiscent of those found for apparent speed of drifting luminance and chromatic gratings. We verified the effects of contrast on perceived speed, and went on to show that the effects of contrast on reaction times are totally predictable by the perceived speed of the stimuli, as if it were perceived rather than physical speed that determined reaction times. Our results support that idea of separate systems for fast and slow motion (with separate channels for luminance and colour at slower speeds), and further suggest that apparent speed and reaction times may be determined at a similar stage of motion analysis.


Gender-Based Occupational Segregation and Sex Differences in Sensory, Motor, and Spatial Aptitudes.
Research on sex differences in humans documents gender differences in sensory, motor, and spatial aptitudes. These aptitudes, as captured by Dictionary of Occupational Titles (DOT) codes, predict the occupational choices of men and women in the directions indicated by this research. We simulate that eliminating selection on these skills reduces the Duncan index of gender-based occupational segregation by 20 % to 23 % in 1970 and 2012, respectively. Eliminating selection on DOT variables capturing other accounts of this segregation has a smaller impact.


Gene expression of survivin and its spliced isoforms associated with proliferation and aggressive phenotypes of prostate cancer.
To assess the effect of survivin gene expression on the proliferation of prostate cancer (PCa) cells and study the association of suvivin and its spliced isoforms gene expression levels with the pathologic grade of PCa. Gene expression of survivin and its spliced isoforms in the LNCaP and PC-3 PCa cell lines was determined using reverse transcriptase-polymerase chain reaction. We knocked down the gene expression of survivin using small interfering RNA and assessed the cell proliferation using the MTS assay. Next, we quantified the gene expression levels of survivin and its isoforms in prostate biopsy samples (PCa, n = 37; benign prostatic hyperplasia, n = 13; PCa after androgen deprivation therapy, n = 12) using the quantitative real-time polymerase chain reaction method. In PCa cells, survivin and survivin-2alpha and survivin-2B were expressed more than survivin-DeltaEx3. The decrease in survivin gene expression by transfection of siRNA was accompanied by the inhibition of cell proliferation of PCa cells (31% and 25% decreased in LNCaP and PC-3 cells, P <0.01). In the prostate biopsy samples, the survivin expression in PCa was significantly greater than that in BPH or PCa after androgen deprivation therapy (PCa, 1; BPH, 0.16; PCa after androgen deprivation therapy, 0.27; P <0.01). In the PCa samples, the survivin expression level was associated significantly with high-grade cancer (Gleason score 8 or 9; Gleason score 7 versus 8 or 9, 1 versus 2.00, respectively; P <0.05). The survivin-2B/survivin ratio in high-grade cancer was lower than that in low-grade (Gleason score 7) cancer (Gleason score 7 versus 8 or 9, 1 versus 0.69; P <0.10). These findings suggest that survivin and its spliced isoforms have associations with PCa cell proliferation and aggressive phenotypes.


[Early neonatal bacterial infections: could superficial bacteriologic samples at birth be limited?].
Without promptly started antibiotic therapy, early neonatal bacterial infections incur a significant mortality. Superficial bacteriologic samples at birth have in France a real place for the diagnosis and the decision to treat a neonate. In order to limit their indication and their choice, the aim of this article was to describe the proportion of neonates with samples and to determine the diagnostic value of the gastric aspirate, the ear swab and the placental sample. Neonates born in the CHRU of Lille in 2005 and staying in the maternity ward were prospectively included. Criteria for samples, type of samples and diagnosis taken were noted. Sensibility, specificity, positive and negative predictive values and likelihood ratios for a positive test and a negative test were calculated. This study included 3918 neonates; 1.7% (65 children) were infected according to our criteria; 42.3% received bacteriologic samples. In accordance with the Anaes guidelines (2002), if mothers were Group B Streptococci positive and received intrapartum antibiotics (up to 2 injections) or did not have any screening test without any other indication of samples, the neonate did not have to receive bacteriologic samples. The gastric aspirate was the best exam thanks to the excellent negative predictive value of its direct examination: 99.4% (IC 95%: 98.8-99.7), its high likelihood ratio for a positive test: 10.04 (IC 95%: 8.29-12.15) and its low likelihood ratio for a negative test: 0.16 (IC 95%: 0.09-0.29); this sample could restrict the antibiotics' ratio given to the neonate. Placental sample could be taken only in certain indications.


[Noninvasive determination of myocardial function in infarct patients].
In a prospective study, the regional ventricular function was assessed by cross sectional echocardiography in 22 patients with coronary heart disease. When compared with angiocardiography, cross sectional echocardiography has proven to be a valuable tool for the evaluation of regional ventricular function.


Chronic obstructive pulmonary disease prevalence in Lebanon: a cross-sectional descriptive study.
Chronic obstructive pulmonary disease (COPD) continues to increase worldwide. The objective of this study was to determine the prevalence of COPD in Lebanese adults. A cross-sectional study was carried out using a multistage cluster sample from all over Lebanon. Residents aged 40 years and over were enrolled. Subjects underwent baseline spirometry and answered a questionnaire. After an albuterol + ipratropium bromide bronchodilator, a posttest was performed. Of 2201 individuals, only 33.3% had never smoked. The prevalence of COPD by the Global Initiative for Chronic Obstructive Lung Disease definition, was 9.7% (95% confidence interval [CI]: 8.5%-10.9%). According to the 5% lower limit of normal definition of COPD, the prevalence was 12.5% (95% CI: 11.2%-13.9%). A total of 20.2% were already diagnosed by a physician. No differences in symptoms across stages of COPD were found, but there was a significant trend for a higher number of visits to the emergency room and to the doctor (P < 0.001), and a higher number of hospitalizations (P < 0.001). Older individuals had an increased risk of COPD (adjusted odds ratio [OR(a)] = 1.05); so did "ever" cigarette smokers (OR(a) = 4.88) and water-pipe smokers (OR(a) = 2.53). This is the first epidemiological study in Lebanon that determined COPD prevalence and the link with water-pipe smoking.