Arabidopsis NAP-related proteins (NRPs) contribute to the coordination of plant growth, developmental rate, and age-related pathogen resistance under short days.
Plant nucleosome assembly protein-related proteins (NRPs) are histone chaperons involved in nucleosome turnover. Despite this basic cellular function, the Arabidopsis nrp1-1 nrp2-1 knock out mutant has been reported to exhibit only mild seedling root phenotypes and to significantly affect the expression of only few hundred genes Zhu et al. (2006). Here we report that NRP loss-of-function as well as the ectopic overexpression of At NRP1 significantly affected the growth, development, and the pathogen response of Arabidopsis plants under short day conditions. The nrp1-1 nrp2-1 mutant grew faster and flowered weeks earlier than the wild type and the overexpressor. The latter developed slower and flowered at a lower number of leaves than the mutant and the wild type. Moreover, the mutant was more sensitive, the overexpressor was more tolerant to pathogen-induced necrosis correlating with their more adult and juvenile character, respectively. Transcriptomic comparison of mature non-bolting plants agreed with the phenotypes. The presented and other published data indicate that although NRPs might not be absolutely required for normal plant growth and development, their level needs to be controlled to allow the epigenetic coordination of metabolic, growth, defence and developmental processes during the acclimation to unfavourable growth conditions such as short days.


Time-Course Comparative Metabolite Profiling under Osmotic Stress in Tolerant and Sensitive Tibetan Hulless Barley.
Tibetan hulless barley is widely grown in the extreme environmental conditions of the Qinghai-Tibet Plateau which is characterized by cold, high salinity, and drought. Osmotic stress always occurs simultaneously with drought and its tolerance is a vital part of drought tolerance. The diversity of metabolites leading to osmotic stress tolerance was characterized using widely-targeted metabolomics in tolerant (XL) and sensitive (D) accessions submitted to polyethylene glycol. XL regulated a more diverse set of metabolites than D, which may promote the establishment of a robust system to cope with the stress in XL. Compounds belonging to the group of flavonoids, amino acids, and glycerophospholipids constitute the core metabolome responsive to the stress, despite the tolerance levels. Moreover, 8 h appeared to be a critical time point for stress endurance involving a high accumulation of key metabolites from the class of nucleotide and its derivative which provide the ultimate energy source for the synthesis of functional carbohydrates, lipids, peptides, and secondary metabolites in XL. This intrinsic metabolic adjustment helped XL to efficiently alleviate the stress at the later stages. A total of 22 diverse compounds were constantly and exclusively regulated in XL, representing novel stress tolerance biomarkers which may help improving stress tolerance, especially drought, in hulless barley.


Hepatoprotection by a PGI2 analogue in complete warm ischemia of the pig liver. Prostanoid release from the reperfused liver.
We examined the hepatoprotective effect of a prostaglandin (PG)I2 analogue by analyzing the endogenous release of prostanoid from the pig liver. Fourteen female pigs underwent 1 hr complete hepatic vascular exclusion (HVE); the portal and vena caval circulation was actively decompressed. The animals were divided into one of two groups (n = 7, each) according to pretreatment with the prostacyclin analogue (OP 2507, OP) administered via a mesenteric vein branch for 30 min at a rate of 2 micrograms/kg/min immediately prior to HVE. The plasma levels of prostaglandin E2 (PGE2), 6-keto-prostaglandin F1-alpha (6-keto-PGF1 alpha), and thromboxane B2 (TXB2), from the blood samples from the aorta, the hepatic vein, and the portal vein were serially compared for 60 min after the restoration of blood flow. Other parameters included 7-day survival rate, serum biochemistry, and endotoxin assay. A significant improvement in 7-day survival rate (6/7 vs. 1/7 for the control, P < 0.02) was observed in the OP-treated animals, associated with amelioration of serum transaminase activities but with no differences in plasma endotoxin levels. The reperfused liver progressively and substantially released PGE2 but did not generate other prostanoids (TXB2 and 6-keto-PGF1 alpha). OP pretherapy substantially suppressed hepatic generation of the PGE2 postreflow, correlating with serum transaminase levels (rs = 0.80; P < 0.01, at 60 min). We conclude that the PGI2 analogue ameliorates hepatic ischemia/reperfusion injury by down-regulating PGE2 production from the reperfused liver.


Demonstration of the target molecule of a protective IgE antibody in secretory glands of Schistosoma japonicum larvae.
We have demonstrated that a mouse monoclonal IgE antibody, SJ18 epsilon.1, recognizes a 97 kDa surface molecule (Sj97) of Schistosoma japonicum larvae and that the antibody induces partial but significant protection against the skin to lung-stage of S. japonicum infection. The antibody stimulates eosinophil- and macrophage-mediated killing of schistosomula in vitro. In the present study, we isolated the putative full-length cDNA of Sj97 by screening a lambda gt11 cDNA library from S. japonicum adult worms with SJ18 epsilon.1. The predicted amino acid sequence of the cDNA showed highly significant homology to that of S. mansoni paramyosin, a potential vaccine candidate for schistosomiasis. The deletion mutants of S. japonicum paramyosin were expressed in Escherichia coli and the translation product of 443 amino acid residues of paramyosin was found to be recognized by the antibody. Moreover, we observed by immunoelectron microscopy the presence of paramyosin in the post-acetabular gland as well as in the tegument and muscle layers of the larvae. These results suggest that paramyosin is a secretory protein which may be incorporated into the tegument during the development of schistosomula, thus becoming a target for protective immunity during the migratory phase of the parasite.


How Long Does It Take to Fix a Favorable Mutation, and Why Should We Care?
The time taken for a selectively favorable allele to spread through a single population was investigated early in the history of population genetics. The resulting formulas are based on deterministic dynamics, leading to inaccuracies at allele frequencies close to 0 or 1. To remedy this problem, the properties of the stochastic phases at either end point of allele frequency need to be analyzed. This article uses a heuristic approach to determining the expected times spent in the stochastic and deterministic phases of allele frequency trajectories, for a model of weak selection at a single locus that is valid for inbreeding populations and for autosomal and sex-linked inheritance. The net fixation time is surprisingly insensitive to the level of dominance of a favorable mutation, even with random mating. Approximate expressions for the variance of the net fixation time are also obtained, which imply that there can be substantial stochastic effects even in very large populations. The accuracy of the approximations was evaluated by comparisons with computer simulations. The results reveal some areas that need further investigation if a full understanding of selective sweeps is to be obtained, notably the possibility that fixations of slightly deleterious mutations may be affecting variability at closely linked sites.


Theoretical investigation of the conformational space of baicalin.
Flavonoids are a large group of polyphenolic compounds ubiquitously present in plants. They are important components of human diet. They are recognized as potential drug candidates to be used in the treatment and prevention of a lot of pathological disorders, due to their protective effects. Baicalin (7-glucuronic acid 5, 6-dihydroxyflavone) is one of the main single active constituents isolated from the dried roots of Scutellaria baicalensis Georgi. The great interest on this flavonoid is due to its various pharmacological properties, such as antioxidant, antimicrobial, anti-inflammatory, anticancer and so on, and its high accumulation in the roots of S. baicalensis. The aim of our work was to analyze the geometric and electronic properties of baicalin conformers (BCL), thus performing a complete search on the conformational space of this flavonoid in gas phase and in aqueous solution. The results indicate that the conformational space of baicalin is formed by eight conformers in gas phase and five conformers in aqueous solution optimized at B3LYP/6-311++G** theory level. BCLa2TT and BCLa1TT conformers have low stability in gas phase and very high stability in aqueous solution. This variation is related to a modification in the τ1 angle that represents the relative position of the glucuronide unit respect to the central rings of the flavan nucleus (A and C). This modification was successfully explained by examining the changes in the hydrogen bond (HB) interactions that occur in the region around the hydroxyl group located in position 6 of ring A. Besides, the molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) analyses indicate that BCLa2TT and BCLa1TT conformers are the most favorable conformers for interacting with positively charged species (such as metal ions) in aqueous media (such as biological fluids).


Biodistribution and dosimetry following infusion of antibodies labeled with large amounts of 131I.
Dosimetry and treatment planning for therapeutic infusions of radiolabeled antibodies are usually performed by extrapolation from the biodistribution of trace-labeled antibody. This extrapolation assumes that the biodistribution of high specific activity antibody will be similar to that seen with trace-labeled antibody. However, high doses of radiation result in rapid depletion of lymphoid and hematopoietic cells in lymph nodes, spleen, and marrow with replacement by blood and plasma. If radiolabeled antibody is cleared slowly from blood, this replacement may result in increased radionuclide concentrations in these tissues following infusions of antibody labeled with large amounts of radionuclide. To examine the influence of deposited radiation on the biodistribution of radiolabeled antibody, we treated mice with a constant amount of antibody that was labeled with varying amounts of 131I. Survival was determined in normal specific pathogen-free AKR/Cum mice (Thy1.2+) after infusion of anti-Thy1.1 antibody labeled with 10 to 6500 muCi of 131I, to determine an appropriate range of 131I doses for further study. The dose producing 50% lethality within 30 days following infusion of 131I-labeled antibody was 530 muCi 131I. Biodistribution, bone marrow histology, and dosimetry were subsequently determined after infusion of 500 micrograms of antibody labeled with 10, 250, 500, or 3500 muCi 131I. The amount of 131I did not influence uptake or retention of antibody in blood, liver, lung, or kidney. In contrast, infusion of antibody labeled with 250 to 3500 muCi of 131I led to a dose-related increase in the concentration of 131I in marrow, spleen, lymph node, and thymus. For example, at 96 h after infusion of antibody labeled with 500 or 3500 muCi 131I, concentrations in marrow were 3- to 4-fold higher than after infusion of trace-labeled antibody. The increase in marrow 131I concentrations was associated with depletion of cells and hemorrhage within the marrow space. As a result, estimated mean absorbed doses to marrow, lymph node, spleen, and thymus were 1.2 to 3.1 times higher than would have been predicted from the biodistribution of trace-labeled antibody. These results suggest that the biodistribution of trace-labeled antibody should be an accurate predictor of the behavior of high specific activity antibody in blood and solid organs such as liver and kidney. In contrast, radiation from antibody labeled with large amounts of radionuclide can result in an alteration of the concentration of radiolabeled antibody in rapidly responding tissues such as marrow.(ABSTRACT TRUNCATED AT 400 WORDS)


In adult-to-adult living donor liver transplantation hepaticojejunostomy shows a better long-term outcome than duct-to-duct anastomosis.
Roux-en-Y hepaticojejunostomy (RYHJ) has been the standard biliary reconstruction in adult-to-adult living donor liver transplantation (ALDLT). Recently, duct-to-duct anastomosis (DD) has been introduced. This study compared the outcomes of RYHJ and DD. For 4 years, 74 recipients underwent ALDLT and were followed up for at least 2 years. The patients were divided into three groups, RYHJ group (n = 18), DD with a stent (DD + S) group (n = 35), and DD without a stent (DD - S) group (n = 21). Overall, biliary complications were developed in 32.4% patients. The biliary complication rate was 11.1%, 48.5% and 33.3% in RYHJ, DD + S and DD - S groups, respectively (P = 0.047). Bile leaks occurred in 28.5% of DD + S group. The incidence of biliary stricture was 5.3%, 20.2% and 28.6% in RYHJ, DD + S and DD - S group, respectively. Most complications (83.3%) were resolved nonsurgically. RYHJ has a better long-term outcome than DD in ALDLT. Subgroup analysis of DD group showed that DD - S group had no bile leaks, but still had a higher incidence of bile duct strictures. However, because this study was a retrospective review there are limitations in analyzing the data and confirming the conclusion. A randomized-prospective study will be needed to confirm these findings.


Effects of CPOE-based medication ordering on outcomes: an overview of systematic reviews.
Computerised provider order entry (CPOE) systems are widely used in clinical settings for the electronic ordering of medications, laboratory tests and radiological therapies. However, evidence regarding effects of CPOE-based medication ordering on clinical and safety outcomes is mixed. We conducted an overview of systematic reviews (SRs) to characterise the cumulative effects of CPOE use for medication ordering in clinical settings. MEDLINE, EMBASE, CINAHL and the Cochrane Library were searched to identify published SRs from inception to 12 February 2018. SRs investigating the effects of the use of CPOE for medication ordering were included. Two reviewers independently extracted data and assessed the methodological quality of included SRs. Seven SRs covering 118 primary studies were included for review. Pooled studies from the SRs in inpatient settings showed that CPOE use resulted in statistically significant decreases in medication errors and adverse drug events (ADEs); however, there was considerable variation in the magnitude of their relative risk reduction (54%-92% for errors, 35%-53% for ADEs). There was no significant relative risk reduction on hospital mortality or length of stay. Bibliographic analysis showed limited overlap (24%) among studies included across all SRs. SRs on CPOEs included predominantly non-randomised controlled trials and observational studies with varying foci. SRs predominantly focused on inpatient settings and often lacked comparison groups; SRs used inconsistent definitions of outcomes, lacked descriptions regarding the effects on patient harm and did not differentiate among the levels of available decision support. With five of the seven SRs having low to moderate quality, findings from the SRs must be interpreted with caution. We discuss potential directions for future primary studies and SRs of CPOE.


Is carcinoma breast a different disease in Pakistani population?
Carcinoma of the breast tends to be different in coloured and white races. Is this pattern also expressed in Pakistani population? To answer this query we carried out a retrospectively study of breast cancer on 193 cases who were divided into 2 groups i.e. less than and more than 50 years age groups. In the former group, 93% tumours were of grades II or III and approximately 51% were estrogen receptors negative. In more than 50 years age group, 75% tumors were in grade II and III, with almost 37% being estrogen negative tumors. Majority (75%) of the patients had over 6 cms lump with equal number having positive lymph node status. All these factors point to the fact that besides presenting late, our population has additional unfavourable prognostic factors.


The use of MAOIs in primary care.
Once a mainstay of antidepressant treatment, monoamine oxidase inhibitors (MAOIs) have largely been abandoned in favor of medications with improved safety profiles. However, remission rates for patients with depression remain low, and primary care physicians continue to have patients who either do not respond or only partially respond to newer medications. MAOIs have proven efficacy for depression, particularly for patients with atypical depression, high levels of anxiety, anergic bipolar depression, and treatment-resistant depression. A transdermal delivery system has been developed for an MAOI that avoids the need for patients to follow dietary restrictions and has fewer metabolic and sexual side effects than some newer medications, which may make it particularly suited for use in primary care.


Experimental charge density from electron microscopic maps.
The charge density (CD) distribution of an atom is the difference per unit volume between the positive charge of its nucleus and the distribution of the negative charges carried by the electrons that are associated with it. The CDs of the atoms in macromolecules are responsible for their electrostatic potential (ESP) distributions, which can now be visualized using cryo-electron microscopy at high resolution. CD maps can be recovered from experimental ESP density maps using the negative Laplacian operation. CD maps are easier to interpret than ESP maps because they are less sensitive to long-range electrostatic effects. An ESP-to-CD conversion involves multiplication of amplitudes of structure factors as Fourier transforms of these maps in reciprocal space by 1/d2 , where d is the resolution of reflections. In principle, it should be possible to determine the charges carried by the individual atoms in macromolecules by comparing experimental CD maps with experimental ESP maps.


5-Aminopyrazole-4-Carboxamide-Based Compounds Prevent the Growth of Cryptosporidium parvum.
Cryptosporidium parvum calcium-dependent protein kinase 1 (CpCDPK1) is a promising target for drug development against cryptosporidiosis. We report a series of low-nanomolar CpCDPK1 5-aminopyrazole-4-carboxamide (AC) scaffold inhibitors that also potently inhibit C. parvum growth in vitro Correlation between anti-CpCDPK1 and C. parvum growth inhibition, as previously reported for pyrazolopyrimidines, was not apparent. Nonetheless, lead AC compounds exhibited a substantial reduction of parasite burden in the neonatal mouse cryptosporidiosis model when dosed at 25 mg/kg.


Optical properties and contribution of cuticle to UV protection in plants: experiments with apple fruit.
To assess the UV-screening capacity of plant surface structures, the optical properties of isolated cuticle and detached peel of apple fruit (Malus domestica Borkh., cv. Antonovka) have been studied. It was found that the cuticle exhibits considerable scattering of UV radiation, negligible absorption between 500-800 nm and attenuates UV radiation: on average, cuticular transmittance of non-reflected light amounts to 35.7 +/- 20.2 and 14.2 +/- 7.1% at 375 and 300 nm, respectively. The principal UV-A absorbers in the cuticle were identified as quercetin glycosides with an in vivo absorption maximum near 375 nm and content ranging from 10 to 70 nmol cm(-2). On the shaded side of apple fruit, both UV-A and UV-B absorption by the peel is, to a large extent, governed by cuticular phenolics, whereas on the sunlit surface, the absorption of the peel in the UV-A range is determined mainly by vacuolar peel flavonoids. It is concluded that a massive build-up of flavonoids in the peel cells located just below the cuticle, resulting in trapping of radiation in a broad spectral range, plays a dominant role in the long-term adaptation of apple fruit to elevated levels of solar radiation.


Chemerin effect on transcriptome of the porcine endometrium during implantation determined by RNA-sequencing†.
It is well known that the body's metabolism and reproduction are closely related. Chemerin (CHEM) is one of many biologically active proteins secreted by the adipose tissue involved in the regulation of the energy homeostasis of the organism. In the present study, RNA-sequencing was performed to investigate the differentially expressed genes (DEGs), long non-coding RNAs (lncRNAs), and alternatively spliced (AS) transcripts in the cultured porcine endometrium exposed to chemerin for 24 hours (CHEM; 400 ng/mL) collected during the implantation period (15-16 days of gestation). High-throughput sequencing of transcriptomes was performed on the Illumina NovaSeq 6000 platform (Illumina, USA). In the current study, among all 130 DEGs, 58 were upregulated and 72 were downregulated in the CHEM-treated group. DEGs were assigned to 73 functional annotations. Twelve identified lncRNAs indicated a difference in the expression profile after CHEM administration. Additionally, we detected 386 differentially AS events encompassed 274 protein-coding genes and 2 lncRNAs. All AS events were divided into five alternative splicing types: alternative 3' splice site (A3SS), 5' splice site (A5SS), mutually exclusive exons (MXE), retention intron (RI), and skipping exon (SE). Within all AS events, we identified 42 A3SS, 43 A5SS, 53 MXE, 9 RI, and 239 SE. In summary, CHEM affects the transcriptomic profile of the porcine endometrium, controlling the expression of numerous genes, including those involved in the cell migration and adhesion, angiogenesis, inflammation, and steroidogenesis. It can be assumed that CHEM may be an important factor for a proper course of gestation and embryo development.


Overview of cell synchronization.
Widespread interest in cell synchronization is maintained by the studies of control mechanisms involved in cell cycle regulation. During the synchronization distinct subpopulations of cells are obtained representing different stages of the cell cycle. These subpopulations are then used to study regulatory mechanisms of the cycle at the level of macromolecular biosynthesis (DNA synthesis, gene expression, protein synthesis), protein phosphorylation, development of new drugs, etc. Although several synchronization methods have been described, it is of general interest that scientists get a compilation and an updated view of these synchronization techniques. This introductory chapter summarizes: (1) the basic concepts and principal criteria of cell cycle synchronizations, (2) the most frequently used synchronization methods, such as physical fractionation (flow cytometry, dielectrophoresis, cytofluorometric purification), chemical blockade, (3) synchronization of embryonic cells, (4) synchronization at low temperature, (5) comparison of cell synchrony techniques, (6) synchronization of unicellular organisms, and (7) the effect of synchronization on transfection.


[The role of various opiate receptors in the regulation of the nociceptive reaction of the arterial pressure].
The experiments on alert rats have shown that dissociation in opioid regulation of behavioural and hemodynamic pain manifestations is determined at a spinal opiate receptor level. Opiates and opioids suppress blood pressure nociceptive reactions to mu-opiate receptors, while sigma-opiate receptors are involved into the generation of autonomic activating effect in opiate analgesia.


The future of scientific conferences in the era of the COVID-19 pandemic: Critical analysis and future perspectives.
The global spread of COVID-19 pandemic forced the scientific community to identify new ways of exchanging and transferring the scientific knowledge, also considering that the measures taken to combat the pandemic, such as travel restrictions, closed borders and gathering bans, led to cancellations of many conferences, meetings and workshops. The enhancement of the existing digital platforms and the development of new systems to share scientific knowledge has allowed the scientific community to "meet" again in new virtual environments (e.g., Zoom, Cisco WebEx, Live Stream, Demio, GoToWebinar Seminar, Google Hangouts, Skype, Microsoft Teams, etc.), providing an unprecedented opportunity to reform methods of organizing academic conferences in all disciplines.Starting from the review of the existing literature, this study aimed at investigating the impact of the spreading of virtual conferences on the field of research. The SWOT analysis was used to identify strengths and weaknesses of the scientific conferences organized in the new format, as well as opportunities and threats created by the socio-economic and political context in the era of the COVID-19 pandemic.


Development and standardization of an immuno-quantified solid phase assay for HIV-1 aspartyl protease activity and its application to the evaluation of inhibitors.
The catELISA technique was modified and standardized for measuring HIV-1 aspartyl protease activity and evaluating the potency of synthetic peptide inhibitors. This immuno-quantified solid phase assay combines the use of an immobilized C-terminal biotinylated peptide as substrate, a crude enzyme preparation, and a highly specific antiserum elicited against the C-terminal product of the enzyme reaction. A standard curve of this C-terminal product was constructed to determine the enzyme activity. This assay, which requires less enzyme and substrate, is more sensitive than the conventional HPLC method. The amounts of C-terminal peptide produced in solution as determined from ELISA and HPLC standard curves were comparable. Analogues of peptidomimetics designed in our laboratory were assayed for their potency to inhibit the enzyme. One of them, H4, which is a hydroxyethylamine isostere of the Phe-Pro peptide bond, was a powerful inhibitor.


Linking Global Youth Tobacco Survey (GYTS) data to the WHO Framework Convention on Tobacco Control (FCTC): The case for Tunisia.
The World Health Organization (WHO) had launched the Framework convention on Tobacco Control (FCTC) in 2003 in order to curve the epidemic of tobacco use worldwide. Since most smokers begin to smoke before the age of 18 years, Global Youth Tobacco Survey (GYTS) has been developed in order to monitor tobacco smoking among adolescents. Our aim was to assess smoking among Tunisian youth using GYTS 2017 data. GYTS is cross-sectional, two cluster school-based survey to produce a representative sample of students aged 13-15 years. It was conducted in 2017 in 67 secondary schools in Tunisia. The investigation tool was an anonymously answered questionnaire, which contained core questions about six majors tobacco related topics. Lifetime cigarettes and waterpipe prevalence were 7.8% (14.4% of boys, 1.6% of girls, p<0.001) and 7.2% (13% of boys, 2.8% of girls, p<0.001), respectively. Among cigarette smokers, 62.5% were able to buy their own cigarettes. Overall, 23.5% of cigarette smokers and 41.5% of waterpipe smokers were not able to buy their products because of their age. Sixty percent of smokers wanted to quit and 56.4% had already tried to stop. Half of the respondents were exposed to SHS in their homes and 62.1% in indoor public places. In Tunisia, tobacco prevalence among youth is high. Youth have free access to tobacco products and smoke-free regulations are only partially respected.


[Computerized analysis of inverted repeats in Mycobacterium tuberculosis genome].
Thermodynamic stable inverted repeats, capable of stabilizing nuclease-influenced mRNA, have been determined for M. tuberculosis slowly growing isolates H37Rv and CDC1551 with the completely sequenced genome. The genome of laboratory strain H37Rv may contain 50 pin structures formed by inverted repeats, whose stem varies in length from 11 to 28 nucleotide pairs (n.p.), the loop size being equal to 4-5 nucleotides and free energy deltaG=-15.2 to -56.2 kcal/mol. The genome of strain CDC1551 (clinical isolate) having a high level of virulence contains 47 pins. Each of the two isolates contains 8 long inverted repeats with a length of 48-62 nucleotides and free energy deltaG=-38.9 to -56.2 kcal/mol; of these, 6 pins are completely similar. At the same time in the genome of strain CDC1551, in contrast to that of strain H37Rv, a highly stable pin 58 nucleotides long is localized at 5'-end. The localization of the highly stable pin with deltaG=-53.9 kcal/mol in the area of 5'-end of isolate CDC1551 may lead to a different degree of stabilization of RNA-transcripts in M. tuberculosis CDC1551 in comparison with isolate H37Rv. This may, in its turn, serve as one of the reasons of differences in the virulence of strains. The possibility of the formation of pins with stems of 11 n.p. and longer has been visually cofirmed with the use of atomic power microscopy. The possibility of the participation of the secondary structures formed by pins in the protection of mRNA of slowly growing pathogenic M. tuberculosis from the degrading activity of RNases is discussed.


Reduction of protein kinase MARK4 in the brains of experimental scrapie rodents and human prion disease correlates with deposits of PrP(Sc).
Microtubule affinity-regulating kinase 4 (MARK4) belongs to a family of kinases that are able to actively phosphorylate the neuronal microtubule-associate proteins (MAPs), such as tau, MAP2 and the ubiquitous MAP4. Abnormal changes in tubulin and the profiles of tau have been previously reported in the human brain and animal transmissible spongiform encephalopathies (TSEs), which may be associated with abnormal alterations of various cellular kinases. To elucidate the possible role of MARK4 in TSE pathogenesis, the MARK4 levels in the brain tissues of scrapie-infected rodents and human prion diseases were evaluated using western blotting and immunohistochemical assays. The results revealed that at terminal stages of the diseases, MARK4 levels in the brain tissues of the scrapie 263K-infected hamsters, 139A-infected mice and a case of Creutzfeldt-Jakob disease (CJD, G114V gCJD) correlated with amounts of PrP(Sc) deposits that were almost undetectable. On the other hand MARK4 signals were noticeable in the brain tissues of a fatal familial insomnia (FFI) patient without PrP(Sc). The reduction of MARK4 was closely related to the prolonged incubation times. These results could be reproduced in SK-N-SH and PC12 cell lines after being exposed to the synthetic peptide PrP106-126. Accordingly, the levels of phosphorylated tau at Ser262 (p-tau262) in cultured cells exposed to PrP106-126, or the ratios of p-tau262/total tau in the brain tissues of 263K-infected hamsters were also significantly decreased. According to our data there is a correlation between a TSE pathological-associated decline of MARK4 in the brain tissues with the deposits of PrP(Sc). Reduction of MARK4 will result in abnormalities of tau phosphorylation, and possibly induce further detachment of microtubules and hinder microtubule transportation.


Acute stress disorder, alcohol use, and perception of safety among hospital staff after the sniper attacks.
This study examined emotional and behavioral effects on hospital staff after a series of sniper shootings in the Washington, D.C., area. Employees of a large tertiary care military hospital were anonymously surveyed about their perceptions of safety and threat, changes in activities, and peritraumatic dissociation as possible risk factors for acute stress disorder, depression, and increased alcohol use the week after the sniper suspects were captured. Of 382 study participants, whose average age was 39 years, 24 (6 percent) met criteria for acute stress disorder, 13 (3 percent) reported increased alcohol use, and 31 (8 percent) met criteria for depression. Risk factors for acute stress disorder were female sex (odds ratio [OR]=2.59), increased alcohol use (OR=5.1), comorbid depression (OR=7.28), lower perceived safety, higher perceived threat, higher levels of peritraumatic dissociation, and greater numbers of decreased activities. Risk factors for increased alcohol use were comorbid depression (OR=4.02), lower perceived safety, higher perceived threat, and higher levels of peritraumatic dissociation. Risk factors for depression were lower perceived safety and higher levels of peritraumatic dissociation. The sniper shootings were associated with substantial changes in perceived safety and threat assessment as well as decreased activities outside the home among highly educated hospital employees. Levels of acute stress disorder were similar to levels of posttraumatic stress disorder in New York City after the terrorist attacks of September 11, 2001. Peritraumatic dissociation was associated not only with acute stress disorder but also with depression and increased alcohol use after the attacks.


Methanopterin and methanogenic bacteria.
Methanogenic bacteria comprise a selected group of microorganisms that derive their energy for growth from the hydrogen-dependent reduction of CO2 to methane or the disproportionation of reduced one-carbon compounds and acetate to CO2 and methane. In the reduction and oxidation steps at the formyl, hydroxymethyl and methyl level the one-carbon unit remains bound to the reduced form of methanopterin, a pterin derivative typical of methanogenic bacteria. In addition, the reduced methanopterin, 5,6,7,8-tetrahydromethanopterin, is involved in a number of anabolic reactions. Methanopterin is structurally and functionally the counterpart of folic acid found in other organisms. In this review the occurrence and properties of methanopterin and its derivatives, as well as the biosynthesis and the role in the different catabolic and anabolic reactions are discussed against the background of folic acid biochemistry.


Breast Cancer Screening in Survivors of Childhood Cancer.
Women who survived childhood cancers or cancers at a young age are at high risk for breast cancer later in life. The accentuated risk is notable among those treated at a young age with a high radiation dose but also extends to survivors treated with therapies other than or in addition to radiation therapy. The predisposing risk factors are complex. Advances in radiation therapy continue to curtail exposure, yet the risk of a second cancer has no dose threshold and a long latency period, and concurrent use of chemotherapy may have an additive effect on long-term risk of cancer. Early screening with annual mammography and MRI is recommended for chest radiation exposure of 10 Gy or greater, beginning 8 years after treatment or at age 25 years, whichever is later. However, there is a lack of recommendations for those at high risk without a history of radiation therapy. Because mortality after breast cancer among survivors is higher than in women with de novo breast cancer, and because there is a higher incidence of a second asynchronous breast cancer in survivors than that in the general population, regular screening is essential and is expected to improve mortality. However, awareness and continuity of care may be lacking in these young patients and is reflected in their poor screening attendance. The transition of care from childhood to adulthood for survivors requires age-targeted and lifelong strategies of education and risk prevention that are needed to improve long-term outcomes for these patients. © RSNA, 2023 See the invited commentary by Chikarmane in this issue. Quiz questions for this article are available through the Online Learning Center.


Validation of an automated spectrophotometric assay for the determination of cholinesterase activity in canine serum.
The determination of enzymatic activity of cholinesterase is a useful diagnostic method to detect exposure to anticholinesterase compounds in human and in veterinary medicine. We validated a modification of the Ellman method in canine serum and applied it to the diagnosis of dogs poisoned with anticholinesterase substances. The method used butyrylthiocholine as substrate and potassium hexacyanoferrate as chromophore. The reference range calculated on 60 clinically healthy dogs was set between 3405 and 6561 U/L (chi-square test for normal distribution, p > 0.05). The overall mean intra-assay and inter-assay coefficients of variation were 0.53% and 3.83%, respectively. The assay was linear when using two sera with 12,538 U/L and 6604 U/L serum cholinesterase activity (r(2) = 0.997) and 0.999, respectively). The mean recovery values of pooled sera with a mean pseudocholinesterase (PChE) activity of 12,081 U/L and pooled sera with a mean PChE activity of 3415 U/L were 103.5% and 102.8%, respectively. Six dogs with a diagnosis of anticholinesterase compound intoxication showed a decrease in cholinesterase activity of at least 50% of normal activity with a mean +/- SD of 487 +/- 291 U/L ranging from 169 to 847 U/L. This technique conforms to the current standard for precision, linearity and accuracy and is a useful method for the complementary diagnosis of organophosphate or carbamate insecticide intoxication in dogs.


Thermochromic Artificial Nacre Based on Montmorillonite.
Nacre-inspired nanocomposites have attracted a great deal of attention in recent years because of their special mechanical properties and universality of the underlying principles of materials engineering. The ability to respond to external stimuli will augment the high toughness and high strength of artificial nacre-like composites and open new technological horizons for these materials. Herein, we fabricated robust artificial nacre based on montmorillonite (MMT) that combines robustness with reversible thermochromism. Our artificial nacre shows great potential in various fields such as aerospace and sensors and opens an avenue to fabricate artificial nacre responsive to other external stimuli in the future.


[Sausage-related Listeria monocytogenes infection].
Infection with Listeria monocytogenes is rare and mainly seen in immunosuppressed patients. Infection with L. monocytogenes has a mortality rate of 30%. We present a case report of L. monocytogenes bacteraemia and endocarditis in a 70-year-old man with several co-morbidities and following four major surgical procedures. This illustrates the findings and characteristics in one of the 16 patients who died in 2013 and 2014 this summer due to sausage-related L. monocytogenes infection.


Induction of labor versus expectant management of large-for-gestational-age infants in nulliparous women.
There is no apparent consensus on obstetric management, i.e., induction of labor or expectant management of women with suspected large-for-gestational-age (LGA)-fetuses. To further examine the subject, a nationwide population-based cohort study from the Swedish Medical Birth Register in nulliparous non-diabetic women with singleton, vertex LGA (>90th centile) births, 1992-2013, was performed. Delivery of a live-born LGA infant induced at 38 completed weeks of gestation in non-preeclamptic pregnancies, was compared to those of expectant management, with delivery at 39, 40, 41, or 42 completed weeks of gestation and beyond, either by labor induction or via spontaneous labor. Primary outcome was mode of delivery. Secondary outcomes included obstetric anal sphincter injury, 5-minute Apgar<7 and birth injury. Multivariable logistic regression analysis was performed to control for potential confounding. We found that among the 722 women induced at week 38, there was a significantly increased risk of cesarean delivery (aOR = 1.44 95% CI:1.20-1.72), compared to those with expectant management (n = 44 081). There was no significant difference between the groups in regards to risk of instrumental vaginal delivery (aOR = 1.05, 95% CI:0.85-1.30), obstetric anal sphincter injury (aOR = 0.81, 95% CI:0.55-1.19), nor 5-minute Apgar<7 (aOR = 1.06, 95% CI:0.58-1.94) or birth injury (aOR = 0.82, 95% CI:0.49-1.38). Similar comparisons for induction of labor at 39, 40 or 41 weeks compared to expectant management with delivery at a later gestational age, showed increased rates of cesarean delivery for induced women. In women with LGA infants, induction of labor at 38 weeks gestation is associated with increased risk of cesarean delivery compared to expectant management, with no difference in neonatal morbidity.


Vedolizumab, a humanized mAb against the α4β7 integrin for the potential treatment of ulcerative colitis and Crohn's disease.
Advances in immunology and genetics have identified new therapeutic targets to control inflammation and symptoms in patients with inflammatory bowel diseases (IBD). Despite the success of anti-TNF therapies in the treatment of IBD, a considerable proportion of patients are refractory to treatment, highlighting an unmet medical need for new therapies. Molecules that direct the trafficking of inflammatory cells, such as the α4β7 integrin, are attractive targets for new drug candidates. The α4β7 integrin is involved in lymphocyte recruitment to the normal and inflamed gut mucosa, and the lymphoid tissue. The pan-α4 integrin neutralizing mAb, natalizumab, is not gut-selective but has demonstrated efficacy in IBD. However, treatment was associated with the occurrence of progressive multifocal leukoencephalopathy, which has limited its use, especially in Europe. Vedolizumab (MNL-0002), Millennium Pharmaceutical's gut-specific, α4β7 integrin-neutralizing mAb, does not affect peripheral blood cell counts and appears to lack systemic effects. Data from phase II clinical trials of vedolizumab demonstrated efficacy with an attractive safety profile, especially in ulcerative colitis. Large phase III, multicenter trials in both ulcerative colitis and Crohn's disease will provide valuable data for the ongoing development of vedolizumab, which might evolve as a new anti-inflammatory treatment option for the management of therapy-refractory patients.


Salt-bridging effects on short amphiphilic helical structure and introducing sequence-based short beta-turn motifs.
Determining the minimal sequence necessary to induce protein folding is beneficial in understanding the role of protein-protein interactions in biological systems, as their three-dimensional structures often dictate their activity. Proteins are generally comprised of discrete secondary structures, from α-helices to β-turns and larger β-sheets, each of which is influenced by its primary structure. Manipulating the sequence of short, moderately helical peptides can help elucidate the influences on folding. We created two new scaffolds based on a modestly helical eight-residue peptide, PT3, we previously published. Using circular dichroism (CD) spectroscopy and changing the possible salt-bridging residues to new combinations of Lys, Arg, Glu, and Asp, we found that our most helical improvements came from the Arg-Glu combination, whereas the Lys-Asp was not significantly different from the Lys-Glu of the parent scaffold, PT3. The marked 310-helical contributions in PT3 were lessened in the Arg-Glu-containing peptide with the beginning of cooperative unfolding seen through a thermal denaturation. However, a unique and unexpected signature was seen for the denaturation of the Lys-Asp peptide which could help elucidate the stages of folding between the 310 and α-helix. In addition, we developed a short six-residue peptide with β-turn/sheet CD signature, again to help study minimal sequences needed for folding. Overall, the results indicate that improvements made to short peptide scaffolds by fine-tuning the salt-bridging residues can enhance scaffold structure. Likewise, with the results from the new, short β-turn motif, these can help impact future peptidomimetic designs in creating biologically useful, short, structured β-sheet-forming peptides.


Theoretical investigation of intramolecular vibrational energy redistribution in HFCO and DFCO induced by an external field.
The present paper is devoted to a full quantum mechanical study of the intramolecular vibrational energy redistribution in HFCO and DFCO. In contrast to our previous studies [Pasin et al., J. Chem. Phys. 124, 194304 (2006) and 126, 024302 (2007)], the dynamics is now performed in the presence of an external time-dependent field. This more closely reflects the experimental conditions. A six-dimensional dipole surface is computed. The multiconfiguration time-dependent Hartree method is exploited to propagate the corresponding six-dimensional wave packets. Special emphasis is placed on the excitation of the out-of-plane bending vibration and on the dissociation of the molecule. In the case of DFCO, we predict that it is possible to excite the out-of-plane bending mode of vibration and to drive the dissociation to DF+CO with only one laser pulse with a fixed frequency and without excitation of an electronic state.


The rostral raphe pallidus nucleus mediates pyrogenic transmission from the preoptic area.
Fever is the widely known hallmark of disease and is induced by the action of the nervous system. It is generally accepted that prostaglandin (PG) E(2) is produced in response to immune signals and then acts on the preoptic area (POA), which triggers the stimulation of the sympathetic system, resulting in the production of fever. Actually, the EP3 subtype of PGE receptor, which is essential for the induction of fever, is known to be localized in POA neurons. However, the neural pathway mediating the pyrogenic transmission from the POA to the sympathetic system remains unknown. To identify the neuronal groups involved in the fever-inducing pathway, we first investigated Fos expression in medullary regions of rats after central administrations of PGE(2). PGE(2) application to the lateral ventricle or directly to the POA strikingly increased the number of Fos-positive neurons in the rostral part of the raphe pallidus nucleus (rRPa). Most of these neurons did not exhibit serotonin immunoreactivity. Microinjection of muscimol, a GABA(A) receptor agonist, into the rRPa blocked fever and thermogenesis in brown adipose tissue induced by intra-POA as well as by intracerebroventricular PGE(2) applications. Furthermore, neural tract tracing studies revealed a direct projection from EP3 receptor-expressing POA neurons to the rRPa. Our results demonstrate that the rRPa, which has never been associated with the fever mechanism, mediates the pyrogenic neurotransmission from the POA to the peripheral sympathetic effectors contributing to fever development.


Response to antiretroviral therapy among patients exposed to three classes of antiretrovirals: results from the EuroSIDA study.
There is an increasing proportion of HIV-positive patients exposed to all licensed classes of antiretrovirals, and the response to salvage regimens may be poor. Among over 8500 patients in EuroSIDA, the proportion of treated patients exposed to nucleosides, protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitor (NNRTI) increased from 0% in 1996 to 47% in 2001. Four-hundred-and-thirteen patients, who had failed virologically two highly active antiretroviral therapy (HAART) regimens and experienced all three main drug classes, started a salvage regimen of at least three drugs, in which at least one new PI or NNRTI was included. Median viral load was 4.7 log copies/ml [Interquartile range (IQR) 4.2-5.2], CD4 lymphocyte count 150/mm3 (IQR 60-274/mm3) and follow-up 14 months. Of these patients, 283 (69%) subsequently experienced at least a 1 log decline in viral load and 202 (49%) achieved a viral load < 500 copies/ml. Conversely, the CD4 count halved from the baseline value in 88 (21%), and 45 (11%) experienced a new AIDS-defining disease. In multivariable analyses, a 1 log viral load reduction was related to baseline viral load [relative hazard (RH) 1.27 per 1 log higher; P = 0.008], a previous viral load of less than 500 copies/ml (RH 1.69; P = 0.002), more recent initiation of the regimen (RH 1.36 per year more recent; P = 0.02), number of new drugs in the regimen (RH 1.20 per drug; P = 0.02), time since start of antiretroviral therapy (RH 0.94 per extra year; P = 0.035) and time spent on HAART with viral load > 1000 copies/ml (RH 0.96 per extra month; P = 0.0001). Analysis of factors associated with CD4 count decline and new AIDS disease also indicated improved outcomes in more recent times and a tendency for a better response in those starting more new drugs, but no relationship with the total number of drugs. Outcomes in people starting salvage regimens appear to depend on the number of new drugs started but not on the total number of drugs being used.


Design and implementation of a continuous microwave heating system for ballast water treatment.
A continuous microwave system to treat ballast water inoculated with different invasive species was designed and installed atthe Louisiana State University Agricultural Center. The effectiveness of the system to deliver the required heating loads to inactivate the organisms present was studied. The targeted organisms were microalgae (Nannochloropsis oculata), zooplankton at two different growth stages (newly hatched brine shrimp-Artemia nauplii and adult Artemia), and oyster larvae (Crassosstrea virginica). The system was tested at two different flow rates (1 and 2 liters per min) and power levels (2.5 and 4.5 kW). Temperature profiles indicate that, depending on the species present and the growth stage, the maximum temperature increase will vary from 11.8 to 64.9 degrees C. The continuous microwave heating system delivered uniform and near-instantaneous heating at the outlet proving its effectiveness. The power absorbed and power efficiency varied for the species present. More than 80% power utilization efficiency was obtained at all flow rate and microwave power combinations for microalgae, Artemia nauplii and adults. Test results indicated that microwave treatment can be an effective tool for ballast water treatment, and current high treatment costs notwithstanding, this technique can be added as supplemental technology to the palette of existing treatment methods.


Hyponatremia secondary to acute urinary retention.
Acute urinary retention is a rare cause of hyponatremia. Symptomatic acute hyponatremia is of grave medical concern and needs to be managed aggressively. In our two cases with acute urinary retention, a simple bladder catheterization and drainage of urine followed by conservative management resulted in complete resolution of symptoms and normalization of sodium levels. Association of bladder distension and hyponatremia is considered to be due to release of vasopressin triggered by bladder distension itself or by pain due to bladder distension. These cases are presented to bring to light an unusual and easily treatable cause of hyponatremia.


[Influencing factors for lymphocyte subsets in children aged 0-6 years].
To investigate the influencing factors for lymphocyte subsets in children 0 to 6 years of age. Umbilical artery blood samples from 45 healthy full-term infants and venous blood samples from 79 healthy children between 0 and 6 years were collected. According to the methods of delivery, the full-term infants were divided into vaginal delivery group (n=22) and cesarean section group (n=23). Healthy children were divided into different age groups: 28 days to 12 months (n=25), 1-3 years (n=26), and 3-6 years (n=28). Lymphocyte subsets were examined by flow cytometry. The influencing factors including delivery method, sex, and age, which might have an effect on the lymphocyte subsets, were analyzed. There were significant differences in T and Ts cell counts, percentage of B cells, and percentage and count of natural killer (NK) cells between the full-term infants of vaginal delivery and cesarean section (P<0.05). The absolute counts and percentages of different lymphocyte subsets showed no significant differences between males and females in healthy children (P>0.05). The counts of all lymphocyte subsets except Ts and NK cells varied significantly between different age groups (P<0.05). Lymphocyte subsets in children under 6 years of age are more profoundly affected by age. Delivery method is also a contributing factor in newborn infants. The reference range of lymphocyte subsets in children should be established for different age groups.


Synthesis of Arbitrary Quantum Circuits to Topological Assembly.
Given a quantum algorithm, it is highly nontrivial to devise an efficient sequence of physical gates implementing the algorithm on real hardware and incorporating topological quantum error correction. In this paper, we present a first step towards this goal, focusing on generating correct and simple arrangements of topological structures that correspond to a given quantum circuit and largely neglecting their efficiency. We detail the many challenges that will need to be tackled in the pursuit of efficiency. The software source code can be consulted at https://github.com/alexandrupaler/tqec.


Analysis of the common bean (Phaseolus vulgaris L.) transcriptome regarding efficiency of phosphorus use.
Common bean is a highly important food in tropical regions, where most production occurs on small farms with limited use of technology and, consequently, greater vulnerability to abiotic stresses such as nutritional stress. Usually phosphorus (P) is the most limiting nutrient for crop growth in these regions. The aim of this study was to characterize the gene expression profiles of the genotypes of common bean IAC Imperador (P-responsive) and DOR 364 (P-unresponsive) under different P concentrations using RNA-seq transcriptome sequencing technology. Plants were grown hydroponically, with application of two P concentrations (4.00 mg L-1 restrictive level and 8.00 mg L-1 control level). Differential expression analyses, annotation, and functional classification were performed comparing genotypes within each P rate administered and comparing each genotype response to the different P levels. Considering differential expression analyses within genotypes, IAC Imperador exhibited 1538 up-regulated genes under P restriction and 1679 up-regulated genes in the control, while DOR 364 exhibited 13 up-regulated genes in the control and only 2 up-regulated genes under P restriction, strongly corroborating P-unresponsiveness of this genotype. Genes related to phosphorus restriction were identified among the differentially expressed genes, including transcription factors such as WRKY, ERF, and MYB families, phosphatase related genes such as pyrophosphatase, acid phosphatase, and purple acid phosphatase, and phosphate transporters. The enrichment test for the P restriction treatment showed 123 enriched gene ontologies (GO) for IAC Imperador, while DOR 364 enriched only 24. Also, the enriched GO correlated with P metabolism, compound metabolic processes containing phosphate, nucleoside phosphate binding, phosphorylation, and also response to stresses. Thus, this study proved to be informative to phosphorus limitation in common bean showing global changes at transcript level.


Methyl cyanide induces alpha to beta transition and aggregation at high concentrations in E-state of human serum albumin.
We have studied the effect of 2,2,2-trifluoroethanol (TFE), an alpha-helix inducer, versus methyl cyanide (MeCN), a beta-sheet inducer, on acid-denatured human serum albumin (HSA) using far-UV circular dichroism, intrinsic fluorescence, 1-anilino-8-naphthalene sulfonate binding, and acrylamide quenching studies. Interestingly, at pH 2.0, where the recovery and resolution of the protein in reverse phase chromatography is high, its secondary structure remains unchanged even in the presence of very high concentration (76% v/v) of MeCN. Gain of 23 and 34% alpha-helicity was observed in the presence of 20 and 50% TFE, respectively. At pH 7.3, HSA aggregates in the presence of 40% MeCN, but it remains soluble up to 75% MeCN at pH 2.0. The results seem to be important for HSA isolation and purification.


Carrier-free, water dispersible and highly luminescent dye nanoparticles for targeted cell imaging.
We develop a new strategy of using surface functionalized small molecule organic dye nanoparticles (NPs) for targeted cell imaging. Organic dye (2-tert-butyl-9,10-di(naphthalen-2-yl)anthracene, TBADN) was fabricated into NPs and this was followed by surface modification with an amphipathic surfactant poly(maleic anhydride-alt-1-octadecene)-polyethylene glycol (C18PMH-PEG) through hydrophobic interactions to achieve good water dispersibility and bio-environmental stability. It should be noted that no additional inert materials were added as carriers, thus the dye-loading capacity of the resulting TBADN NPs is obviously higher than those of previously reported carrier-based structures. This would lead to much larger absorption and then much higher brightness. The resulting TBADN NPs possess comparable, if not higher, brightness than CdSe/ZnS quantum dots under the same conditions, with favorable biocompatibility. Significantly, TBADN NPs are readily conjugated with folic acid, and successfully applied in targeted cell imaging. These results show that water dispersible and highly stable organic NPs would be a promising new class of fluorescent probe for bioapplications in cellular imaging and labeling. This strategy may be straightforwardly extended to other organic dyes to achieve water dispersible NPs for cell imaging and drug delivery.


First insights into the unexplored two-component system YehU/YehT in Escherichia coli.
Two-component systems (TCSs) consisting of a membrane-anchored histidine kinase (HK) and a response regulator (RR) with DNA-binding activity. are major players in signal transduction in prokaryotes. Whereas most TCSs in Escherichia coli are well characterized, almost nothing is known about the LytS-like HK YehU and the corresponding LytTR-like RR YehT. To identify YehT-regulated genes, we compared the transcriptomes of E. coli cells overproducing either YehT or the RR KdpE (control). The expression levels of 32 genes differed more than 8-fold between the two strains. A comprehensive evaluation of these genes identified yjiY as a target of YehT. Electrophoretic mobility shift assays with purified YehT confirmed that YehT interacts directly with the yjiY promoter. Specifically, YehT binds to two direct repeats of the motif ACC(G/A)CT(C/T)A separated by a 13-bp spacer in the yjiY promoter. The target gene yjiY encodes an inner membrane protein belonging to the CstA superfamily of transporters. In E. coli cells growing in media containing peptides or amino acids as a carbon source, yjiY is strongly induced at the onset of the stationary-growth phase. Moreover, expression was found to be dependent on cyclic AMP (cAMP)/cAMP receptor protein (CRP). It is suggested that YehU/YehT participates in the stationary-phase control network.


Bombesin-induced desensitization of enzyme secretion in dispersed acini from guinea pig pancreas.
Incubating dispersed acini from guinea pig pancreas with bombesin and then washing the cells to remove bombesin reduced the subsequent stimulation of amylase secretion caused by bombesin, litorin, or ranatensin by as much as 80%, but did not alter the stimulation of amylase secretion caused by cholecystokinin, carbamylcholine, A23187 or vasoactive intestinal peptide. This bombesin-induced desensitization was reversible, and the onset of the process, as well as its reversal, were time and temperature dependent. Neither desensitization or resensitization were inhibited by abolishing protein synthesis. The concentrations of bombesin required to cause desensitization were in the same range as those required to stimulate amylase secretion. Incubating pancreatic acini with vasoactive intestinal peptide did not reduce the subsequent stimulation of amylase secretion caused by vasoactive intestinal peptide, bombesin, or cholecystokinin. These results indicate that bombesin-induced desensitization of pancreatic acini reflects changes that occur at or close to the bombesin receptor.


Designing a novel red to near-infrared persistent phosphor CaMgGe2O6:Mn2+,Sm3+ based on a vacuum referred binding energy diagram.
In this work, we designed and successfully synthesized a novel germanate-based persistent luminescence (PersL) phosphor host, CaMgGe2O6, via a solid-state reaction. We constructed an empirical energy level scheme of the CaMgGe2O6:Ln2+/Ln3+ phosphors according to the Dorenbos model. Then, we successfully theoretically predicted the choice of the optimal codopant of CaMgGe2O6:Mn2+ phosphors using this empirical energy level scheme. As a result, after co-doping with Sm3+, the PersL intensity is increased 16 times and the time duration is effectively improved 52 times due to the high concentration of new traps. CaMgGe2O6:Mn2+,Sm3+ shows red to near-infrared long persistent emission located at 675 nm, which can be sustained for about 60 minutes above the recognizable intensity level (≥0.32 mcd m-2), and the persistence duration of samples was three times that of the red commercial phosphor Y2O2S:Eu3+. The experimental results coincide well with the theoretical predictions. These results demonstrate that the strategy concepts of this work are feasible for the design of persistent luminescence materials. Moreover, a possible afterglow mechanism is studied and discussed with the assistance of thermoluminescence (TL) curves.


Conventional physical therapy and physical therapy based on reflex stimulation showed similar results in children with myelomeningocele.
We aimed to investigate whether infants with myelomeningocele would improve their motor ability and functional independence after ten sessions of physical therapy and compare the outcomes of conventional physical therapy (CPT) to a physical therapy program based on reflex stimulation (RPT). Twelve children were allocated to CPT (n = 6, age 18.3 months) or RPT (n = 6, age 18.2 months). The RPT involved proprioceptive neuromuscular facilitation. Children were assessed with the Gross Motor Function Measure and the Pediatric Evaluation of Disability Inventory before and after treatment. Mann-Whitney tests compared the improvement on the two scales of CPT versus RPT and the Wilcoxon test compared CPT to RPT (before vs. after treatment). Possible correlations between the two scales were tested with Spearman correlation coefficients. Both groups showed improvement on self-care and mobility domains of both scales. There were no differences between the groups, before, or after intervention. The CPT and RPT showed similar results after ten weeks of treatment.


Haemodynamic effects of intravenous diltiazem at rest and exercise in patients with coronary artery disease.
The acute effects of intravenous diltiazem on exercise performance were studied in 10 patients with coronary artery disease. Haemodynamic measurements were made at rest and during exercise before and after 0.5 mg kg-1 of diltiazem. Diltiazem prolonged the duration of exercise (+2.85 min, P less than 0.001) and delayed the onset of ischaemic ST depression or angina in all patients. The highest tolerated heart rate and pressure rate product were increased in all but one patient after diltiazem. At rest diltiazem decreased mean arterial pressure (-10.8%, P less than 0.005), systemic vascular resistance (SVR) (-11.8%, P less than 0.05) and left ventricular stroke work index (SWI) (-14.1%, P less than 0.005). During exercise under diltiazem therapy, at the level achieved before the drug, the pulmonary capillary wedge pressure (-30%, P less than 0.005) and the SVR (-13.6%, P less than 0.02) were lowered, the SWI (+13%, P less than 0.01) was increased; at the end of exercise only the SVR (-14%, P less than 0.05) was reduced. Two patients experienced angina on lying down and one had orthostatic hypotension after exercise with diltiazem. This study indicates that intravenous diltiazem is a potentially useful agent for the treatment of angina by reducing myocardial oxygen demand at rest and by improving left ventricular performances on exercise.


Goblet Cell Carcinoma of the Appendix with Synchronous Adenocarcinoma of the Cecum: Distinct or Related Entities?
Goblet cell carcinoma (GCC) is a rare primary tumor of the appendix characterized by both epithelial and neuroendocrine components containing goblet cells. While in the past, the GCC has been associated with neuroendocrine tumors, recent studies consider that GCC is closer to adenocarcinoma than a neuroendocrine component. The association between gastro-intestinal (GI) carcinoids and second primary malignancies (SPMs) is widely described in the literature, but there is no reported case of GCC and synchronous adjacent adenocarcinoma of the colon. We describe the first case in the literature, to our knowledge, of synchronous colorectal adenocarcinoma of the cecum and GCC of the appendix that are incidentally discovered in the resected primary cancer specimen. The association between the two neoplasms seems to be not causal and maybe the "paracrine-effect theory" may explain the development of a second tumor close to the primary.


Oncogene expression and immunoglobulin synthesis in a North American Burkitt (NAB-2) lymphoma cell line with a 8;22 chromosome translocation.
A Burkitt's lymphoma (BL) cell line, (NAB-2) deriving from a North American patient, exhibited a 8;22 (q22;q11-12) translocation involving the c-myc gene and lambda immunoglobulin genes. In addition, NAB-2 cells have two other consistent translocations: a 1;5 (p22;q23) and a 3;7 (p25;q22), with breakpoints close to the location of N-ras, fms, and raf-1 protooncogenes, respectively. In situ hybridization with myc, N-ras, and raf-1 radiolabeled DNA probes to NAB-2 chromosomes showed that none of these genes was relocated as a result of translocation. However, by Northern blot analysis, the myc mRNA was represented by two transcripts, one approximately 2.4 kb and the other considerably larger (74 kb). The raf-1 gene transcript was also detected in NAB-2 cells; however, its size and level were similar to those seen in two other BL lines. On the other hand, the N-ras, fms, and fgr genes, which are frequently activated in BL, were not actively transcribed. NAB-2 cells also have a chromatid defect visible as an achromatic region on the short arm of chromosome 2 near the locus of the kappa immunoglobulin gene. This alteration, which is a viral modification site caused by the Epstein-Barr virus or viral products, had no influence on immunoglobulin synthesis, as NAB-2 cells concordant to the 8;22 translocation were positive for cytoplasmic and surface lambda light chains. Although NAB-2 cells exhibit several chromosomal abnormalities, only translocation, 8;22 was associated with gene alterations relevant to the neoplastic development of this malignancy.


L-DOPA potentiation of the serotonergic deficits due to a single administration of 3,4-methylenedioxymethamphetamine, p-chloroamphetamine or methamphetamine to rats.
The role of dopamine in the serotonergic neurotoxicity of 3,4-methylenedioxymethamphetamine, p-chloroamphetamine, methamphetamine, N-ethyl-3,4-methylenedioxyamphetamine and fenfluramine was assessed by determining the long-term effect of their coadministration with the dopamine precursor, L-DOPA (L-2,4-dihydroxyphenylalanine). L-DOPA administration potentiated the regional deficits in brain concentrations of serotonin measured one week after a single high dose of 3,4-methylenedioxymethamphetamine, p-chloroamphetamine or methamphetamine but did not alter the neurochemical response to N-ethyl-3,4-methylenedioxyamphetamine nor to fenfluramine. Consistent with this, in vitro release studies found the latter two agents to be the weakest of the five at increasing [3H]dopamine efflux from preloaded rat striatal slices. As an estimate of in vivo release, the effect of each agent on striatal dopamine concentrations was determined. Only those agents showing a synergism with L-DOPA in the long-term studies also produced changes in striatal dopamine consistent with an increase in transmitter release and synthesis. These results provide additional support for the hypothesis that dopamine release plays a role in the neurotoxicity of methylenedioxymethamphetamine, p-chloroamphetamine and methamphetamine. The lack of effect of L-DOPA on the neurotoxicity of fenfluramine as well as the modest effects of fenfluramine on dopamine release indicate this drug may produce its long-term effects on the serotonergic system through a unique mechanism not involving dopamine.


Language Assessment With Children Who Speak Nonmainstream Dialects: Examining the Effects of Scoring Modifications in Norm-Referenced Assessment.
We compared outcomes from 2 measures of language ability in children who displayed a range of dialect variation: 1 using features that do not contrast between mainstream American English (MAE) and nonmainstream dialects (NMAE), and 1 using contrastive features. We investigated how modified scoring procedures affected the diagnostic accuracy of the measure with contrastive features. Second-grade students (N = 299; 167 White, 106 African American, 26 other) completed measures of language variation and ability (the Diagnostic Evaluation of Language Variation-Screening Test and the Clinical Evaluation of Language Fundamentals-Fourth Edition [CELF-4]). The CELF-4 was scored with and without the recommended scoring modifications for children who spoke African American English. Partial correlations controlling for socioeconomic status revealed small to moderate correlations between measures of language ability and the use of NMAE features. Modified scoring yielded higher scores for children who spoke African American English and a reduced association between the use of NMAE features and CELF-4 scores. Modified scoring also affected the diagnostic accuracy of the CELF-4, resulting in a lower positive likelihood ratio and a higher negative likelihood ratio. The decision to apply scoring modifications affects both the false positive and false negative rates. Implications for language assessment for children who speak NMAE dialects are discussed, including the need for further investigation.


Effect of temperature, water-phase salt and phenolic contents on Listeria monocytogenes growth rates on cold-smoked salmon and evaluation of secondary models.
Salting and smoking are ancient processes for fish preservation. The effects of salt and phenolic smoke compounds on the growth rate of L. monocytogenes in cold-smoked salmon were investigated through physico-chemical analyses, challenge tests on surface of cold-smoked salmon at 4 degrees C and 8 degrees C, and a survey of the literature. Estimated growth rates were compared to predictions of existing secondary models, taking into account the effects of temperature, water phase salt content, phenolic content, and additional factors (e.g. pH, lactate, dissolved CO2). The secondary model proposed by Devlieghere et al. [Devlieghere, F., Geeraerd, A.H., Versyck, K.J., Vandewaetere, B., van Impe, J., Debevere, J., 2001. Growth of Listeria monocytogenes in modified atmosphere packed cooked meat products: a predictive model. Food Microbiology 18, 53-66.] and modified by Giménez and Dalgaard [Giménez, B., Dalgaard, P., 2004. Modelling and predicting the simultaneous growth of Listeria monocytogenes and spoilage micro-organisms in cold-smoked salmon. Journal of Applied Microbiology 96, 96-109.] appears appropriate. However, further research is needed to understand all effects affecting growth of L. monocytogenes in cold-smoked salmon and to obtain fully validated predictive models for use in quantitative risk assessment.


[Effect of compound gardenia oil and jujube seed oil on learning and memory in ovariectomized rats].
To observe the effect of compound of gardenia oil and jujube seed oil learning and memory in ovariectomized rats and its mechanism. Animals were randomly divided into six groups: sham group, model group, estrogen group, low dose group, middle dose group and high dose group. The ovariectomized rat models were established by resection of the lateral ovaries. The effect of compound of gardenia oil and jujube seed oil on learning and memory in ovariectomized rats was observed by means of Morris water maze. Acetylcholinesterase (AchE) and nitric oxide synthase (NOS) activities in rat brain were determined. The compound of gardenia oil and jujube seed oil could shorten the incubation period of appearance in castration rats and increase the number passing through Yuan Ping table in ovariectomized rats. As the training time extended, the incubation period of appearance was gradually shortened. The compound of gardenia oil and jujube seed oil could increase NOS activity, and decrease AChE activity in brain of ovariectomized rats. The compound of jujube seed oil and gardenia oil could promote the learning and memory in ovariectomized rats. This effect may be related with the increase in activities of NOS, AchE in rat brain.


Dissipative dynamics of charged polarons in organic molecules.
Within a non-adiabatic dynamical method, we simulate charged polaron motion and dissociation in an organic molecule in the presence of dissipation. The dissipation, represented by damping, is introduced to investigate the influence of temperature on the mobility of carriers. We find that the velocity of the polaron has an inversely linear dependence on the damping, and hence the relationship between mobility and temperature is a power law, which is in agreement with the corresponding experiments. We also find that the velocity of the polaron exhibits a continuous dependence on the electric field in the presence of dissipation. In addition, we find that, in the presence of dissipation, the critical field that dissociates a polaron is reduced.


Improving cancer care in India: prospects and challenges.
The World Cancer Report, a 351 - page global report issued by International Agency for Research on Cancer (IARC) tells us that cancer rates are set to increase at an alarming rate globally (Stewart and Kleiues 2003). Cancer rates could increase by 50 % to 15 million new cases in the year 2020. This will be mainly due to steadily aging populations in both developed and developing countries and also to current trends in smoking prevalence and the growing adoption of unhealthy lifestyles. The report also reveals that cancer has emerged as a major public health problem in developing countries, matching its effect in industrialized nations. Healthy lifestyles and public health action by governments and health practitioners could stem this trend, and prevent as many as one third of cancers worldwide. In a developing country such as India there has been a steady increase in the Crude Incidence Rate (CIR) of all cancers affecting both men and women over the last 15 years. The increase reported by the cancer registries is nearly 12 per cent from 1985 to 2001, representing a 57 per cent rise in India's cancer burden. The total number of new cases, which stood at 5.3 lakhs Care lakh is 100,000 in 1985 has risen to over 8.3 lakhs today. The pattern of cancers has changed over the years, with a disturbing increase in cases that are linked to the use of tobacco. In 2003, there were 3.85 lakhs of cases coming under this category in comparison with 1.94 lakhs cases two decades ago. Lung cancer is now the second most common cancer among men. Earlier, it was in fifth place. Among women in urban areas, cancer of the uterine cervix had the highest incidence 15 years ago, but it has now been overtaken by breast cancer. In rural areas, cervical cancer remains the most common form of the disease (The Hindu 2004).


Vestibular-evoked myogenic potentials.
This article reviews the literature on vestibular-evoked myogenic potential testing, a short latency electromyogram evoked by high acoustic stimuli and recorded via surface electrodes over the sternocleidomastoid muscle. Applications and refinements of this technique are described for different pathologies and in adults and children. Various techniques for electrode placement have been described to elicit a vestibular-evoked myogenic potential response, which has been clinically investigated in normal individuals, under pathological conditions, and in adult and pediatric patients. As vestibular-evoked myogenic potential amplitude is linearly related to the level of background activity of the sternocleidomstoid muscle, maintaining steady contraction of the muscle can be challenging in some patients. Vestibular-evoked myogenic potential testing may provide additional information about the vestibular system and allow site of lesion testing (e.g. saccule and inferior vestibular nerve) in patients of all ages. Its role has yet to be defined in the diagnosis and treatment of common vestibular disorders, including Meniere's disease, vestibular neuronitis, labyrinthitis, and other diseases. Further research is needed to support its clinical usefulness in patients with balance disorders, to optimize patient selection, and to establish its cost effectiveness.


Differential analysis of RNA-seq incorporating quantification uncertainty.
We describe sleuth (http://pachterlab.github.io/sleuth), a method for the differential analysis of gene expression data that utilizes bootstrapping in conjunction with response error linear modeling to decouple biological variance from inferential variance. sleuth is implemented in an interactive shiny app that utilizes kallisto quantifications and bootstraps for fast and accurate analysis of data from RNA-seq experiments.


Balanced Fluid Versus Saline-Based Fluid in Post-operative Severe Traumatic Brain Injury Patients: Acid-Base and Electrolytes Assessment.
Normal saline (NS) is a common fluid of choice in neurosurgery and neuro-intensive care unit (ICU), but it does not contain other electrolytes and has the potential to cause hyperchloremic metabolic acidosis with prolonged infusion. These problems may be reduced with the availability of balanced fluid (BF), which becomes a more physiological isotonic solution with the presence of complete electrolyte content. This study aimed to compare the changes in electrolytes and acid-base between NS and BF (Sterofundin® ISO) therapy for post-operative severe traumatic brain injury (TBI) patients in neuro-ICU. Sixty-six severe TBI patients who required emergency craniotomy or craniectomy and were planned for post-operative ventilation were randomised into NS (n = 33) and BF therapy groups (n = 33). The calculation of maintenance fluid given was based on the Holliday-Segar method. The electrolytes and acid-base parameters were assessed at an 8 h interval for 24 h. The data were analysed using repeated measures ANOVA. The NS group showed a significant lower base excess (-3.20 versus -1.35, P = 0.049), lower bicarbonate level (22.03 versus 23.48 mmol/L, P = 0.031), and more hyperchloremia (115.12 versus 111.74 mmol/L, P < 0.001) and hypokalemia (3.36 versus 3.70 mmol/L, P < 0.001) than the BF group at 24 h of therapy. The BF group showed a significantly higher level of calcium (1.97 versus 1.79 mmol/L, P = 0.003) and magnesium (0.94 versus 0.80 mmol/L, P < 0.001) than the NS group at 24 h of fluid therapy. No significant differences were found in pH, pCO2, lactate, and sodium level. BF therapy showed better effects in maintaining higher electrolyte parameters and reducing the trend toward hyperchloremic metabolic acidosis than the NS therapy during prolonged fluid therapy for postoperative TBI patients.


[Changes in heart and circulatory function following 4-weeks' endurance training].
On 144 patients with an average age of 47.1 years who were admitted to a four-week cure for heart and circulation the changed behaviour of heart and circulation at rest and under submaximal load by means of ergometry was assessed according to the variability of the pulse rate, the arterial blood pressure and the maximal volume of oxygen intake (VO2 max). A four-week training in perseverance run--performed according to several training impulses--effects a bradycardization, improvement in the patient's physical health (VO2 max) and a decrease of initially increased systolic and diastolic blood pressure values. A daily perseverance training of 60 min with intensities about 50% VO2 max is the most effective and also well applicable and dosable training impulse for older and less efficient persons during cure. The cardiac volume (size of the heart) does not show an ascertained change after cure.


Inhibition of gap junction-mediated intercellular communication by alpha-linolenate.
The purpose of this investigation was to assess whether alterations in the fatty acid composition of rat liver epithelial (WB-F344) cell phospholipids would modulate gap junction-mediated intercellular communication (GJIC). WB-F344 cells were grown to confluency in culture medium supplemented with one of seven different fatty acids at a concentration of 50 microM for 48 h. Only alpha-linoleate (18:3 n-3) significantly inhibited GJIC. Saturated fatty acids (12:0, 16:0, and 18:0), a monounsaturated fatty acid (18:1 n-9), and n-6 polyunsaturated fatty acids (18:2 and 20:4) did not affect GJIC. The alpha-linolenate-induced inhibition of GJIC was not due to the activation of protein kinase C or intracellular hydroperoxide production, two lipid-dependent parameters previously shown to inhibit GJIC. In addition, alpha-linolenate did not alter membrane fluidity. Although the mechanism by which alpha-linolenate inhibits GJIC is unclear, changes in the fatty acid composition of cell phospholipids may be of critical importance. Subsequent to supplementation with alpha-linolenate, WB-F344 cell phospholipids had reduced 20:4 n-6 and elevated n-3 fatty acids. The results of this investigation emphasize the importance of current research into the influence of lipids on cell function and identify a new mechanism by which gap junctions can be modulated.


Toward N,P-Doped π-Extended PAHs: A One-Pot Synthesis to Diannulated 1,4,2-Diazaphospholium Triflate Salts.
A novel method for the one-pot synthesis of diannulated 1,4,2-diazaphospholium triflate salts by a Me3SiOTf-mediated self-condensation of dichlorophosphaneyl aza-(poly)cyclic aromatic hydrocarbons (aza-(P)AHs; namely, pyridine, quinoline, phenanthridine, and benzo[d]thiazole) is reported. The diannulated 1,4,2-diazaphospholium triflate salts are characterized by multinuclear NMR spectroscopy, X-ray analysis, as well as their calculated NICS values, underlining their aromatic character. Quantum mechanical calculations shed light on the intermolecular reaction mechanism. Follow up chemistry, such as the halogenation reaction with XeF2 or SO2Cl2 with the dipyridinium derivative selectively yields the respective dihalo-σ4,λ5- and tetrahalo-σ5,λ6-diazaphospholium triflate salts. The dihalo-σ4,λ5-diazaphospholium triflate salt serves well as a surrogate for the introduction of the cationic 2-(1,2'-bipyridin)-1-iumyl ligand (1,2'-bipyl), the monocationic structural isomer of the prototypical 2,2'-bipyridine ligand (2,2'-bipy).


Development of a New Decision Tree to Rapidly Screen Chemical Estrogenic Activities of Xenopus laevis.
During the last past decades, there is an increasing number of studies about estrogenic activities of the environmental pollutants on amphibians and many determination methods have been proposed. However, these determination methods are time-consuming and expensive, and a rapid and simple method to screen and test the chemicals for estrogenic activities to amphibians is therefore imperative. Herein is proposed a new decision tree formulated not only with physicochemical parameters but also a biological parameter that was successfully used to screen estrogenic activities of the chemicals on amphibians. The biological parameter, CDOCKER interaction energy (Ebinding ) between chemicals and the target proteins was calculated based on the method of molecular docking, and it was used to revise the decision tree formulated by Hong only with physicochemical parameters for screening estrogenic activity of chemicals in rat. According to the correlation between Ebinding of rat and Xenopus laevis, a new decision tree for estrogenic activities in Xenopus laevis is finally proposed. Then it was validated by using the randomly 8 chemicals which can be frequently exposed to Xenopus laevis, and the agreement between the results from the new decision tree and the ones from experiments is generally satisfactory. Consequently, the new decision tree can be used to screen the estrogenic activities of the chemicals, and combinational use of the Ebinding and classical physicochemical parameters can greatly improves Hong's decision tree.


Natural products targeting FcεRI receptor for anti-allergic therapeutics.
Mast cells and basophils are important contributors for development of allergic reactions. The activation of these cells via cross-linking of IgE bound to FcεRI by allergen causes the generation of allergic mediators and the reaction of immediate hypersensitivity. Obviously, FcεRI is considered as a key trigger of acute allergic responses. Consequently, FcεRI is regarded as a potential target for downregulation of allergic diseases. So far, numerous synthetic agents have been reported for inhibition of FcεRI expression and FcεRI-IgE interaction. Meanwhile, natural products have received much attention due to their efficacy and safety. Recently, numerous anti-allergic agents from natural products have been revealed as promising inhibitors of allergic reactions via inhibiting the expression of FcεRI subunits as well as blocking FcεRI activation. Thus, the present contribution is mainly focused to describe natural products targeting FcεRI receptor and to emphasize their applicable potential as anti-allergic foods. PRACTICAL APPLICATIONS: Phlorotannins, epigallocatechin-3-gallate, peptides, chitooligosaccharides, and other natural products have been revealed as potential inhibitors of allergic responses. These bioactive agents target to FcεRI receptor by inhibiting expression of FcεRI and blocking interaction of FcεRI-IgE. Hence, these compounds could be applied as functional ingredients of anti-allergic foods.


Involvement of oxidative stress in protocatechuic acid-mediated bacterial lethality.
The involvement of oxidative stress in protocatechuic acid-mediated bacterial lethality was investigated. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentration (MBC) of protocatechuic acid against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus are 600 and 700 μg/ml, 600 and 800 μg/ml, and 600 and 800 μg/ml, respectively. The optical densities and colony-forming units of protocatechuic acid-treated bacteria decreased in time-dependent manner. Protocatechuic acid (4× MIC) significantly increased the superoxide anion content of E. coli, P. aeruginosa, and S. aureus compared to dimethyl sulfoxide (DMSO). Superoxide dismutase, catalase, and NAD+ /NADH in protocatechuic acid-treated E. coli, P. aeruginosa, and S. aureus increased significantly when compared to DMSO. Conversely, level of reduced glutathione decreased in protocatechuic acid-treated E. coli, P. aeruginosa, and S. aureus, while glutathione disulfide increased when compared to DMSO. Furthermore, malondialdehyde and fragmented DNA increased significantly following exposure to protocatechuic acid. Protocatechuic acid inhibited the activity of complexes I and II. From the above findings, protocatechuic acid enhanced the generation of reactive oxygen species (superoxide anion radical and hydroxyl radical) in E. coli, P. aeruginosa, and S. aureus, possibly by autoxidation, fenton chemistry, and inhibiting electron transport chain resulting in lipid peroxidation and DNA fragmentation and consequentially bacterial cell death.


Current self-complianced and self-rectifying resistive switching in Ag-electroded single Na-doped ZnO nanowires.
We demonstrate current self-complianced and self-rectifying bipolar resistive switching in an Ag-electroded Na-doped ZnO nanowire device. The resistive switching is controlled by the formation and rupture of an Ag nanoisland chain on the surface along the Na-doped ZnO nanowire. Na-doping plays important roles in both the self-compliance and self-rectifying properties.


Semantic-syntactic partial word knowledge growth through reading.
Incidental reading provides a powerful opportunity for partial word knowledge growth in the school-age years. The extent to which children of differing language abilities can use reading experiences to glean partial knowledge of words is not well understood. The purpose of this study was to compare semantic-syntactic partial word knowledge growth of children with higher language skills (HL group; overall language standard scores of 85 or higher) to that of children with relatively lower language skills (LL group; overall receptive or expressive standard score below 85). Thirty-two children, 16 per group, silently read stories containing unfamiliar nouns and verbs 3 times over a 1-week period. Semantic-syntactic partial word knowledge growth was assessed after each reading and 2-3 days later to assess retention. Over time, both groups showed significant partial word knowledge growth, with the HL group showing significantly more growth. In addition, both groups retained knowledge several days later. Regardless of language skill level, children benefit from multiple exposures to unfamiliar words in reading in their development and retention of semantic-syntactic partial word knowledge growth.


Tomographic quantum cryptography: equivalence of quantum and classical key distillation.
The security of a cryptographic key that is generated by communication through a noisy quantum channel relies on the ability to distill a shorter secure key sequence from a longer insecure one. For an important class of protocols, which exploit tomographically complete measurements on entangled pairs of any dimension, we show that the noise threshold for classical advantage distillation is identical with the threshold for quantum entanglement distillation. As a consequence, the two distillation procedures are equivalent: neither offers a security advantage over the other.


Using Reflective Writing as a Predictor of Academic Success in Different Assessment Formats.
Objectives. To investigate whether reflective-writing skills are associated with academic success. Methods. Two hundred sixty-four students enrolled in a pharmacy practice course completed reflective statements. Regression procedures were conducted to determine whether reflective-writing skills were associated with academic success in different assessment formats: written, oral, and video tasks. Results. Reflective-writing skills were found to be a predictor of academic performance in some formats of assessment: written examination; oral assessment task and overall score for the Unit of Study (UoS). Reflective writing skills were not found to predict academic success in the video assessment task. Conclusions. Possessing good reflective-writing skills was associated with improved academic performance. Further research is recommended investigating the impact of reflective skill development on academic performance measures in other health education.


ACA, an inhibitor phospholipases A2 and transient receptor potential melastatin-2 channels, attenuates okadaic acid induced neurodegeneration in rats.
In recent studies, it has been shown that the Transient Receptor Potential Melastatin-2 Channels (TRPM2) and Phospholipases A2 (PLA2) inhibitors may have a protective effect on neurons. This study was aimed to investigate the protective effect of TRPM2 and PLA2 inhibitor N-(p-amylcinnamoyl) Anthranilic Acid (ACA) in a neurodegenerative model induced by Okadaic Acid (OKA). OKA (200ng/10μl) was administered bilateral intracerebroventricularly as a single injection. OKA-treated rats showed significant impairments of spatial memory in Morris Water Maze Test. OKA-induced memory-impaired rats showed increased numbers of degenerated neurons and Caspase-3, tau phosphorylated ser396, β-amyloid positive cells in the hippocampus and cerebral cortex. Furthermore, OKA-treated rats exhibited significantly increased MDA, TNF-α levels, and decreased SOD, GSH-PX enzyme activates and GSH levels of the tissues. ACA administration ameliorated OKA-induced memory impairment in rats. The ACA treatment also increased SOD and GSH-PX enzyme activation and GSH levels, and conversely decreased the levels of MDA, TNF-α. It was found that the numbers of the degenerated neurons and Caspase-3 positive cells of cortex and hippocampus regions were significantly reduced. ACA administration attenuates the oxidative stress and neuroinflammation of OKA-induced neurodegeneration; and ameliorates the cognitive decline and neurodegeneration.


Metacognitive Interpersonal Therapy for Personality Disorders Featuring Emotional Inhibition: A Multiple Baseline Case Series.
Metacognitive interpersonal therapy (MIT) is an integrative psychotherapeutic approach targeting personality disorders (PDs) featuring inhibition and avoidance. The current case series reports the outcome of a time-limited, 12-month MIT intervention for people with PDs featuring emotional inhibition. Seven participants were diagnosed with a PD on the basis of a structured clinical interview. The study followed a multiple baseline design, with baseline measures taken for 3 weeks before intervention. Participants underwent 12 months of weekly MIT sessions, with outcome measures taken every 3 months. Outcome variables were diagnostic recovery, symptom severity, and alexithymia. All participants improved over the course of the 12-month intervention across most measures. For six of the participants, the intervention was a likely driver of change. The current study contributes to a growing evidence base regarding the effectiveness of MIT for the treatment of PDs.


Lung carcinoma in the elderly population. Influence of histology on the inverse relationship of stage to age.
Unlike most cancers, lung carcinoma is more likely to be localized at the time of diagnosis in older age groups when compared to those who are middle-aged. In an attempt to explain this inverse age-stage relationship we studied 9062 histologically confirmed cases of lung carcinoma occurring from 1975 to 1984 obtained from the regional cancer registry for Kansas and western Missouri. They were analyzed according to histologic type, age, sex, and stage at diagnosis. The data suggest that the proportion of squamous cell carcinoma rises and that of adenocarcinoma and small cell undifferentiated carcinoma falls with increasing age. The proportion of staged lung carcinoma with local disease at the time of diagnosis increases with age. In males this trend occurred in all cell types except large cell undifferentiated carcinoma but was most significant for squamous cell carcinoma. Squamous cell carcinoma was the only group to show a significant trend among females. The rise in squamous cell and fall in small cell carcinoma may partially explain the increased prevalence of local stage disease with advancing age.


Functional Brain Imaging in Cornelia de Lange Syndrome: Case Report and Literature review.
Functional brain imaging with brain single photon emission computer tomography (Brain SPECT) has been used for many years in the evaluation of multiple neuro-degenerative and neuro-developmental disorders. Brain SPECT is a nuclear medicine tomographic study performed with a lipophilic radiopharmaceutical labeled with 99mTc-pertechnetate. It is a cerebral perfusion agent that depicts the global and regional perfusion patterns in the cortical gray matter and subcortical structures. Cornelia de Lange syndrome (CdLS) is a rare neuro-developmental and genetic condition, associated to several malformations. There are a limited number of cases reported in the medical literature and few of them report neuro-radiological and/or neuro-pathologic abnormalities. We report a case of a 15 year old patient, clinically diagnosed at birth with CdLS, who presents limited anatomical findings on Computed Tomography and Magnetic Resonance Imaging. To the best of our knowledge, this is the first report of the Brain SPECT findings in this syndrome.


Does the Continuous Performance Test Predict ADHD Symptoms Severity and ADHD Presentation in Adults?
Objective: Our study aimed to provide empirical evidence on the usefulness of one of the most popular neuropsychological tests, the Continuous Performance Test (CPT), as a marker of ADHD severity and presentations among adults. Method: ADHD participants were recruited in a specialized center for the diagnosis and treatment of adults suffering from ADHD (n = 201). Measures included the CPT3™ and ADHD symptoms using a clinical interview and self-reported measures. Results: Only 51.7% of the participants were classified as likely to have a disorder characterized by attention deficit, such as ADHD, by the CPT. The relationships between CPT variables and ADHD symptoms were small. The classification error was 80.3% for the inattentive presentation and 22.5% for the hyperactive presentation when using the CPT to identify ADHD presentations. Conclusion: There was no evidence of the clinical utility of the CPT to assess or monitor ADHD in adult populations diagnosed and treated for ADHD.


Cost-effectiveness analysis of fruquintinib as third-line treatment for patients with metastatic colorectal cancer.
To evaluate the cost-effectiveness of addition of fruquintinib to best supportive care (BSC) in third-line treatment for patients with metastatic colorectal cancer (CRC). To conduct the cost-effectiveness analysis, a Markov model was established to simulate the course of metastatic CRC. Three health states-progression-free survival (PFS), progressive disease (PD), and death-were included. Clinical data were derived from the FRESCO trial and health utility values were extracted from previous literature. The primary outcome of the study was incremental cost-effectiveness ratio (ICER) in US dollars per quality-adjusted life-years (QALYs) from a Chinese societal perspective. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to test the robustness of the study. Addition of fruquintinib to BSC gained 0.54 QALY at a cost of $15,404.57 while the BSC group gained 0.38 QALY at a cost of $9603.94. ICER of fruquintinib versus BSC was $36,253.94/QALY. In the 1-way sensitivity analyses, utility for PD in both groups, utility for PFS in both groups, and cost of fruquintinib significantly influenced the results of the analysis. At the willingness-to-pay threshold of $28,988.40/QALY, probabilities of addition of fruquintinib to BSC or BSC alone as the cost-effective option were 0% and 100%, indicating addition of fruquintinib is not a dominant option compared with BSC. Addition of fruquintinib to BSC is not a cost-effective regimen in the third-line setting for patients with metastatic CRC from the Chinese societal perspective.