Does three-dimensional power Doppler ultrasound help in discrimination between benign and malignant ovarian masses?
To determine if tumor vascularity as assessed by three-dimensional (3D) power Doppler ultrasound can be used to discriminate between benign and malignant ovarian tumors, if adding 3D power Doppler ultrasound to gray-scale imaging improves differentiation between benignity and malignancy, and if 3D power Doppler ultrasound adds more to gray-scale ultrasound than does two-dimensional (2D) power Doppler ultrasound. One hundred and six women scheduled for surgery because of an ovarian mass were examined with transvaginal gray-scale ultrasound and 2D and 3D power Doppler ultrasound. The color content of the tumor scan was rated subjectively by the ultrasound examiner on a visual analog scale. Vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were calculated in the whole tumor and in a 5-cm(3) sample taken from the most vascularized area of the tumor. Logistic regression analysis was used to build models to predict malignancy. There were 79 benign tumors, six borderline tumors and 21 invasive malignancies. A logistic regression model including only gray-scale ultrasound variables (the size of the largest solid component, wall irregularity, and lesion size) was built to predict malignancy. It had an area under the receiver-operating characteristics (ROC) curve of 0.98, sensitivity of 100%, false positive rate of 10%, and positive likelihood ratio (LR) of 10 when using the mathematically best cut-off value for risk of malignancy (0.12). The diagnostic performance of the 3D flow index with the best diagnostic performance, i.e. VI in a 5-cm(3) sample, was superior to that of the color content of the tumor scan (area under ROC curve 0.92 vs. 0.80, sensitivity 93% vs. 78%, false positive rate 16% vs. 27% using the mathematically best cut-off value). Adding the color content of the tumor scan or FI in a 5-cm(3) sample to the logistic regression model including the three gray-scale variables described above improved diagnostic performance only marginally, an additional two tumors being correctly classified. Even though 2D and 3D power Doppler ultrasound can be used to discriminate between benign and malignant ovarian tumors, their use adds little to a correct diagnosis of malignancy in an ordinary population of ovarian tumors. Objective quantitation of the color content of the tumor scan using 3D power Doppler ultrasound does not seem to add more to gray-scale imaging than does subjective quantitation by the ultrasound examiner using 2D power Doppler ultrasound.


Global transcriptomic analysis of breast cancer and normal mammary epithelial cells infected with Borrelia burgdorferi.
The bacterial spirochete Borrelia burgdorferi, the causative agent of Lyme Disease, can disseminate and colonize various tissues and organs, orchestrating severe clinical symptoms including arthritis, carditis, and neuroborreliosis. Previous research has demonstrated that breast cancer tissues could provide an ideal habitat for diverse populations of bacteria, including B. burgdorferi, which is associated with a poor prognosis. Recently, we demonstrated that infection with B. burgdorferi enhances the invasion and migration of triple-negative MDA-MB-231 cells which represent a type of breast tumor with more aggressive cancer traits. In this study, we hypothesized that infection by B. burgdorferi affects the expression of cancer-associated genes to effectuate breast cancer phenotypes. We applied the high-throughput technique of RNA-sequencing on B. burgdorferi-infected MDA-MB-231 breast cancer and normal-like MCF10A cells to determine the most differentially expressed genes (DEG) upon infection. Overall, 142 DEGs were identified between uninfected and infected samples in MDA-MB-231 while 95 DEGs were found in MCF10A cells. A major trend of the upregulation of C-X-C and C-C motif chemokine family members as well as genes and pathways was associated with infection, inflammation, and cancer. These genes could serve as potential biomarkers for pathogen-related tumorigenesis and cancer progression which could lead to new therapeutic opportunities.


Incretin-based therapy for type 2 diabetes mellitus: pancreatic and extrapancreatic effects.
The prevalence of type 2 diabetes mellitus has increased at an alarming rate in recent years. Recent estimations project that 366 million people could have diabetes by 2030. The incretin system emerges as a new target for type 2 diabetes therapy, and new molecules are being approved for its use in humans since the year 2005. These agents could be divided into 2 main groups, glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 inhibitors. Endogenous GLP-1 is an incretin hormone composed by a 30-amino acid peptide and is secreted from L-cells in distal small intestine in response to calorie intake, causing a glucose-dependent β-cell response resulting in a restoration of the first-phase insulin response. Additionally, GLP-1 regulates glucagon production, which leads to inhibition of glucogenolysis and gluconeogenesis in the liver. Synthetic molecules such as exenatide and liraglutide have been developed to bind GLP-1 receptor and mimic GLP-1 effects in pancreatic cells and other target organs.


[Release of beta-alanine from the frog skeletal muscle determined by thin-layer chromatography].
The release of beta-alanine from the resting and contracting frog sartorius muscles was demonstrated by the two-dimensional thin-layer chromatography. The release of beta-alanine from indirectly stimulated muscles of frogs in winter was about 230% higher than at rest. When synaptic transmission was blocked by d-tubocurarine the release of beta-alanine from directly stimulated muscles did not exceed the release at rest. Thus, activation of neuromuscular synapse leads to increased beta-alanine release from contracting muscle.


A developmental perspective on neuroeconomic mechanisms of contingency management.
This paper provides a developmental overview of relevant theory and research on delay discounting and neuroeconomics, and their implications for contingency management (CM) approaches to treatment. Recent advances in the neuroscience of decision making have the potential to inform treatment development for adolescent substance use in general, and CM treatments in particular. CM interventions may be informed by research on delay discounting, a type of decision making that reflects how individuals value immediate versus delayed rewards. Delay discounting reliably distinguishes substance abusers from nonabusers and is a significant predictor of individual differences in response to substance use treatments. Discounting may also be important in predicting response to CM, as CM attempts to directly influence this decision-making process, shifting the preference from the immediate rewards of use to delayed rewards for choosing not to use. Multiple neural processes underlie decision making, and those processes have implications for adolescent substance abuse. There are significant neurodevelopmental processes that differentiate adolescents from adults. These processes are implicated in delay discounting, suggesting that adolescence may reflect a period of plasticity in temporal decision making. Understanding the neural mechanisms of delay discounting has led to promising working memory interventions directly targeting the executive functions that underlie individual choices. These interventions may be particularly helpful in combination with CM interventions that offer immediate rewards for brief periods of abstinence, and may show particular benefit in adolescence due to the heightened neural plasticity of systems that underlie temporal discounting in adolescence.


Combining acoustic and electrical hearing.
The concept of combining electrical stimulation for high-frequency sound with acoustic hearing for low-frequency information was tested. In addition, whether residual hearing can be preserved when an electrode is placed into the inner ear up to 10 mm and whether place of electrical stimulation influences speech perception were tested. A single-subject clinical trial design was employed. Six postlingual adults with severe high-frequency hearing impairment were recruited to participate in the study. A new six-channel cochlear implant was designed for the clinical trial. The intracochlear electrodes were either 6 or 10 mm in length based on a Nucleus CI-24 multichannel implant. Monosyllabic word understanding and consonant identification testing in a recorded sound-only condition were used to assess changes in speech perception. Follow-up was greater than 12 months. Acoustic hearing was preserved in all six subjects (n = 3, 6-mm electrodes; n = 3, 10-mm electrodes). Preoperative monosyllabic word and sentence scores were unchanged in all subjects following implantation. A 30% to 40% improvement in consonant recognition occurred with the 10-mm electrode. The subjects with 10-mm electrodes were able to understand 83% to 90% of the monosyllabic words using the implant plus binaural hearing aids. Scores were more than doubled when compared with preoperative scores with hearing aids only. The human ear has the capability to integrate both acoustic and high-frequency electrically processed speech information. Placement of a short, 10-mm electrode does not appear to damage residual low-frequency inner ear hair cell function, interfere with the micro mechanics of normal cochlear vibration, or decrease residual speech perception. The improvement in speech recognition was due primarily to the increased perception of higher-frequency consonantal speech cues, and this improvement took several months to become apparent. Such a device can provide a substantial benefit in speech understanding to individuals with severe high-frequency hearing loss, while still maintaining the benefits of the residual lower-frequency acoustic hearing. The position of the electrode and the place of frequency information within the cochlea were shown to be important factors in the success of such a device.


Improvement of bio-cementation at low temperature based on Bacillus megaterium.
A low production rate for calcium carbonate with microbial solidification technology at low temperatures often restricts its application. For this reason, adding urea to the medium and the domestication of Bacillus megaterium at low temperature were proposed to produce more calcium carbonate based on an analysis of growth characteristics, urease activity, and the production rates for calcium carbonate under different conditions. Sand solidification tests were conducted to demonstrate improvements caused by the methods. The results showed that the higher the temperature, the faster the growth of Bacillus megaterium and the stronger the urease activity. Growth was fastest and urease activity strongest at a pH of 8. Adding urea to the medium and the domestication of B. megaterium at low temperature can both improve the production rate, effectively increasing calcium carbonate precipitation at low temperature. Combining the two methods resulted in greater improvement of the production rate for calcium carbonate. The two methods were also found to improve the effect of sand solidification. Therefore, our study provides a solid foundation for the actual engineering application of bio-cementation technology at low temperature.


Activities, productivity, and compensation of men and women in the life sciences.
To determine whether professional activities, professional productivity, and salaries of life sciences faculty differ by gender. The authors undertook this study because previous studies found differences in the academic experiences of women and men. In 2007, the authors conducted a mailed survey of 3,080 life sciences faculty at the 50 universities whose medical schools received the greatest amount of National Institutes of Health funding in 2004. The response rate was 74% (n = 2,168). The main outcome measures were a faculty member's total number of publications; number of publications in the past three years; average impact score of the journals in which he or she had published; professional activities; work hours per week; the numbers of hours spent specifically in teaching, patient care, research, professional activities, and administrative activities; and annual income. Among professors, the women reported greater numbers of hours worked per week and greater numbers of administrative and professional activities than did the men. Female faculty members reported fewer publications across all ranks. After control for professional characteristics and productivity, female researchers in the life sciences earned, on average, approximately $13,226 less annually than did their male counterparts. Men and women in the academic life sciences take on different roles as they advance through their careers. A substantial salary gap still exists between men and women that cannot be explained by productivity or other professional factors. Compensation and advancement policies should recognize the full scope of the roles that female researchers play.


A periodic density functional theory study on the effects of halides encapsulated in SiC nanotubes.
In this paper we present results of density functional theory calculations on the configurations, band structures, and optical properties of halides MCl (M=K,Ag) intercalated single-wall SiC nanotubes. The results show that the M-Cl distances perpendicular to the tube axis are slightly smaller than the ones parallel to the tube axis, which could be due to the axial strain of MCl. The electronic and optical properties of the resulting MCl@SiCNT composite are modified with respect to both the bulk halide and the empty nanotube. It is shown that AgCl affects the structures and properties of SiC nanotubes more significantly than KCl, and that the interaction between the nanotube and the encapsulated halide is stronger for narrower SiC nanotube. The AgCl encapsulation into SiCNTs results in band gap narrowing of AgCl@SiCNTs.


Molecular Identification and Antifungal Susceptibility Patterns of Clinical Dermatophytes Following CLSI and EUCAST Guidelines.
Dermatophytes are associated with superficial infections in humans worldwide. The aim of the present study was to determine the species distribution and susceptibility patterns of clinical dermatophytes. Samples received for routine mycological processing from 124 suspected cases attending a dermatologic clinic in a tertiary care hospital were included in the study. On direct microscopy, 74.1% (92/124) were positive and 53.2% (66/124) grew on culture. The isolates were comprised of Trichophytoninterdigitale (56%) followed by Trichophytontonsurans (25.7%), Trichophytonrubrum (7.5%), Trichophytonviolaceum (4.5%), Microsporumgypseum (4.5%), and Trichophytonverrucosum (1.5%). Conventional mycological identification was concordant with ITS sequencing except for T.mentagrophytes. High minimum inhibitory concentration (MIC) values (geometric mean, >1 µg/mL) were observed for T.tonsurans and T.rubrum to terbinafine and griseofulvin. This study highlights the shift in epidemiology from T.rubrum to T.interdigitale. It also raises a concern of high MICs of terbinafine and griseofulvin among our isolates. Surveillance of antifungal susceptibility patterns can provide clinicians with local MIC data that can further aid in guiding better management in relapse cases of dermatomycosis.


Aneurysmal bone cyst of the zygomatic arch.
We present a case of aneurysmal bone cyst in the jaw investigated with plain film, US, computed tomography (axial, precontrast) and magnetic resonance (1 Tesla, axial T1 weighted before and after Gadolinium administration, axial and coronal T2-weighted after Gadolinium administration). The zygomatic arch is a very rare location for an aneurysmal bone cyst: as far as we know, only a few cases are found in the literature.


High-throughput platform assay technology for the discovery of pre-microrna-selective small molecule probes.
MicroRNAs (miRNA) play critical roles in human development and disease. As such, the targeting of miRNAs is considered attractive as a novel therapeutic strategy. A major bottleneck toward this goal, however, has been the identification of small molecule probes that are specific for select RNAs and methods that will facilitate such discovery efforts. Using pre-microRNAs as proof-of-concept, herein we report a conceptually new and innovative approach for assaying RNA-small molecule interactions. Through this platform assay technology, which we term catalytic enzyme-linked click chemistry assay or cat-ELCCA, we have designed a method that can be implemented in high throughput, is virtually free of false readouts, and is general for all nucleic acids. Through cat-ELCCA, we envision the discovery of selective small molecule ligands for disease-relevant miRNAs to promote the field of RNA-targeted drug discovery and further our understanding of the role of miRNAs in cellular biology.


Mapping of susceptibility and protective loci for acute GVHD in unrelated HLA-matched bone marrow transplantation donors and recipients using 155 microsatellite markers on chromosome 22.
Despite matching donors and recipients for the human leukocyte antigens (HLAs) expressed by the major histocompatibility genomic region of the short arm of chromosome 6, several recipients still develop acute graft-versus-host disease (aGVHD) after bone marrow transplantation (BMT). This is possibly due to non-HLA gene polymorphisms, such as minor histocompatibility antigens (mHas) and genes coding for cytokines. However, a detailed genetic background for aGVHD has not yet been established. To find novel susceptibility and/or protective loci for aGVHD, a whole genome-wide association study of donors and recipients needs to be performed. As the first step to such a study, we retrospectively analyzed polymorphisms of 155 microsatellite markers spread across the long arm of chromosome 22 in 70 pairs of HLA-matched unrelated BMT donors and recipients. We performed individual typing and then compared the markers' allele frequencies (1) between all the aGVHD (grades III and IV GVHD) and GVHD-free (grade 0 GVHD) groups in donors and recipients and (2) between the aGVHD and aGVHD-free groups in donor/recipient pairs that were matched and mismatched for the microsatellite marker's allele. Screening of the microsatellite markers revealed five loci with a significant difference between the aGVHD and GVHD-free groups and revealed eight loci on chromosome 22, where the microsatellite allele mismatched markers were associated with aGVHD. This screening analysis suggests that several aGVHD-associated susceptible and protective loci exist on chromosome 22, which may encompass novel gene regions that need to be elucidated for their role in aGVHD.


Genetic and phenotypic characteristics of baker's yeast: relevance to baking.
Yeasts rarely encounter ideal physiological conditions during their industrial life span; therefore, their ability to adapt to changing conditions determines their usefulness and applicability. This is especially true for baking strains of Saccharomyces cerevisiae. The success of this yeast in the ancient art of bread making is based on its capacity to rapidly transform carbohydrates into CO2 rather than its unusual resistance to environmental stresses. Moreover, baker's yeast must exhibit efficient respiratory metabolism during yeast manufacturing, which determines biomass yield. However, optimal growth conditions often have negative consequences in other commercially important aspects, such as fermentative power or stress tolerance. This article reviews the genetic and physiological characteristics of baking yeast strains, emphasizing the activation of regulatory mechanisms in response to carbon source and stress signaling and their importance in defining targets for strain selection and improvement.


Contemporary antithrombotic strategies in patients with acute coronary syndrome admitted to cardiac care units in Italy: The EYESHOT Study.
Several new antithrombotic therapies have emerged for the treatment of acute coronary syndrome (ACS). We sought to assess contemporary patterns of antithrombotic therapies use in patients with ACS. EYESHOT (EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units) was a nationwide, prospective registry aimed to evaluate antithrombotic strategies employed in patients admitted to intensive cardiac care units (CCUs) for an ACS in Italy. Over a three-week period, 203 CCUs enrolled 2585 consecutive patients: 41.2% with ST-elevation myocardial infarction (STEMI) and 58.8% with non-ST elevation ACS (NSTE-ACS). During hospitalisation, low-molecular-weight heparins, aspirin, and clopidogrel were the most commonly used antithrombotic therapies. Among patients treated with percutaneous coronary intervention (PCI, n=1755), any crossover of heparin therapy occurred in 30.8% of cases, while switching from one P2Y12 inhibitor to another occurred in 3.6% of cases in the CathLab and in 14.2% before discharge. Of the 790 patients who did not receive revascularisation, switching of a P2Y12 inhibitor occurred in 5.7% of cases. At discharge, a new P2Y12 inhibitor (ticagrelor or prasugrel) in association with aspirin was prescribed in 59.5% of STEMI and 33.9% of NSTE-ACS patients: the most powerful predictor for prescription was PCI (odds ratio (OR) 6.18; 95% confidence interval (CI) 4.76-8.01; p<0.0001), whereas age ≥ 75 years was strongly associated with clopidogrel use (OR 0.28; 95% CI 0.22-0.36; p<0.0001). The EYESHOT registry shows the current pattern of antithrombotic treatments for ACS patients admitted to Italian CCUs and provides insights which may help to improve the clinical care of such patients.


Intertrial sources of stimulus control and delayed matching-to-sample performance in humans.
Two experiments compared delayed matching-to-sample (DMTS) accuracy under 2 procedures in adults with mental retardation. In the trial-unique procedure, every trial in a session contained different stimuli. Thus, comparison stimuli that were correct on one trial were never incorrect on other trials in that session (or vice versa). In the 2-sample DMTS procedure, the same 2 comparison stimuli were presented on each trial, and their function changed quasi-randomly across trials conditional upon the sample stimulus. Across 2 experiments, 7 of 8 subjects showed the highest overall accuracy under the trial-unique procedure, and no subject showed consistently higher accuracy under the 2-sample procedure. Negative, exponential decay functions fit to logit p values showed that this difference was due largely to the steeper delay-mediated decline in sample control for the 2-sample procedure. Stimulus-control analyses indicated that, under the 2-sample procedure, the selection of the comparison stimulus on Trial N was often controlled by the comparison stimulus selection on Trial N-1 rather than the Trial-N sample stimulus. This source of competing stimulus control is not present in trial-unique procedures. Experiment 2 manipulated intertrial interval duration. There was a small but consistent increase in accuracy as a function of intertrial interval duration under the 2-sample procedure, but not under the trial-unique procedure.


Structures of peptides from alpha-amino acids methylated at the alpha-carbon.
The structural preferences of peptides (and depsipeptides) from the achiral MeAib and Hib residues, and the chiral Iva, (alpha Me) Val, (alpha Me) Leu, and (alpha Me) Phe residues, as determined by conformational energy computations, x-ray diffraction analyses, and 1H-nmr and spectroscopic studies, are reviewed and compared with literature data on Aib-containing peptides. The results obtained indicate that helical structures are preferentially adopted by peptides rich in these alpha-amino acids methylated at the alpha-carbon. Intriguing experimental findings on the impact of the chirality of Iva, (alpha Me) Val, and (alpha Me) Phe residues on helix screw sense are illustrated.


Mental Health Policy in Ireland 1984-2004: theory, overview and future directions.
Recent years have seen renewed emphasis on the importance of mental health policy as a key component of health and social policy at both national and international levels. In 2001 the European Commission produced a public health framework for mental health in the EU. In the same year, the World Health Organisation devoted its annual health report to mental health and called on countries to formulate, update and implement mental health policies. The EU and WHO initiatives both recognised that the challenges facing mental health policy makers are increasingly transnational in scope, related to issues such as rapid demographic change, increased transnational migration, the protection of human rights and the implementation of a growing number of international laws, directives and protocols in relation to mental health care. Significant progress has been made in the development of Irish mental health services over the past 40 years. Nevertheless, many challenges remain. The aims of this paper are to outline: • Prevailing theoretical perspectives on mental health policy • Mental health policy in Ireland since the last major policy revision in 1984 • Relevant economic and demographic changes in Ireland since 1984 • Relevant clinical, legislative and policy developments in relation to mental health • Future directions for mental health policy. Electronic literature searches were performed using Psyclit (American Psychological Association, 1887-2003), Medline (United States National Library of Medicine, 1985 - 2003), with broad search terms related to mental health policy. Additional books and papers were identified by tracking back through references and consulting with colleagues. Policy documents and selected literature on Irish psychiatric services were reviewed and related to recent literature on mental health policy.


TREM-1 regulates neutrophil chemotaxis by promoting NOX-dependent superoxide production.
Neutrophil migration across tissue barriers to the site of injury involves integration of complex danger signals and is critical for host survival. Numerous studies demonstrate that these environmental signals fundamentally alter the responses of extravasated or "primed" neutrophils. Triggering receptor expressed on myeloid cells 1 (TREM-1) plays a central role in modulating inflammatory signaling and neutrophil migration into the alveolar airspace. Using a genetic approach, we examined the role of TREM-1 in extravasated neutrophil function. Neutrophil migration in response to chemoattractants is dependent upon multiple factors, including reactive oxygen species (ROS) generated either extracellularly by epithelial cells or intracellularly by NADPH oxidase (NOX). We, therefore, questioned whether ROS were responsible for TREM-1-mediated regulation of migration. Thioglycollate-elicited peritoneal neutrophils isolated from wild-type (WT) and TREM-1-deficient mice were stimulated with soluble and particulate agonists. Using electron paramagnetic resonance spectroscopy, we demonstrated that NOX2-dependent superoxide production is impaired in TREM-1-deficient neutrophils. Consistent with these findings, we confirmed with Clark electrode that TREM-1-deficient neutrophils consume less oxygen. Next, we demonstrated that TREM-1 deficient neutrophils have impaired directional migration to fMLP and zymosan-activated serum as compared to WT neutrophils and that deletion or inhibition of NOX2 in WT but not TREM-1-deficient neutrophils significantly impaired direction sensing. Finally, TREM-1 deficiency resulted in decreased protein kinase B (AKT) activation. Thus, TREM-1 regulates neutrophil migratory properties, in part, by promoting AKT activation and NOX2-dependent superoxide production. These findings provide the first mechanistic evidence as to how TREM-1 regulates neutrophil migration.


First Report of Fruit Rot Caused by Fusarium incarnatum-equiseti species complex on Greenhouse Bell Pepper in Malaysia.
In Malaysia, bell pepper (Capsicum annuum var. grossum), also known as sweet pepper or paprika, is one of the highly imported vegetable crops. In 2021 alone, Malaysia imported nearly 74 thousand metric tons of its chilies, including bell peppers, from other countries (DOSM, 2022). Often, farmers grow the bell peppers in moderate to cool conditions within highland regions for local commercial purposes. In June 2022, the Malaysian Agricultural Research and Development Institute (MARDI) in Serdang, Selangor, conducted a research study to grow lowland bell peppers under a glasshouse rain protection system. A disease inspection carried out found fruit rot on approximately 30% of mature bell pepper fruits in the greenhouse. Symptoms appeared as firm and sunken black lesions covered with white to light pink spore masses on the outer surface, which eventually fell off. Infected fruit parts were disinfected with 10% hypochlorite (NaOCl) for 2 min, followed by double washing with sterile distilled water, air-dried, and placed onto potato dextrose agar (PDA). After 3 days of incubation, the fungal colonies that grew from the symptomatic tissue pieces were transferred onto new PDA to obtain pure cultures. The pure fungal colony appeared dense, whitish aerial mycelium that slowly became cream to pinkish-orange after 7 days of incubation at room temperature (25±2 °C). To examine the morphology features, the pure cultures were subbed onto carnation leaf agar (CLA) and incubated at 25±2°C for 14 days. Macroconidia were abundant, slightly curved with tapered apical cells, 3- to 5-septate, and ranged between 21.8 and 34.0 x 3.0 and 5.1 μm. Microconidia were single-celled, often 1-septate, and ranged between 10.0 and 12.6 x 2.1 and 3.4 μm. Chlamydospores were globose and in chains. The fungus was identified as Fusarium sp. according to Fusarium key by Leslie and Summerell (2006). PCR amplification and DNA sequencing were performed using primers EF1F/EF2R and ITS1/ITS4 (O'Donnell et al., 1998; White et al., 1990) to amplify the partial elongation factor 1-alpha (TEF1-α) gene and internal transcribed spacer region (ITS), respectively. The TEF1-α and ITS sequences of this isolate were deposited in GenBank as OQ672911 and OR349657. BLAST analysis with TEF1-α gene sequences revealed 99.74% and 99.33% sequence identity with F. pernambucanum (accession no. ON330424) and Fusarium isolate NRRL 25134 (accession no. JF740755), respectively; both belonged to the Fusarium incarnatum-equiseti species complex (FIESC). BLAST search of the TEF1-α sequence in the database of the International Mycological Association (www.mycobank.org) showed 99.18% identity with FIESC (NRRL 36548). The ITS sequences were 100% identical to those of F. incarnatum (MT563420, MT563419, and MT563418). Pathogenicity test was conducted on three unwounded and three wounded mature red bell pepper fruits (SP299 Red Masta variety). Two healthy bell peppers were used as controls for each treatment. Prior to inoculation, the fruits were surface-sterilized by dipping in 70% ethanol and rinsed twice with sterile distilled water. Unwounded fruits were inoculated with fungal mycelium disks (5 mm diameter), whereas control fruits were inoculated with sterile PDA agar disks. For wound method, 6 µl of spore suspension (1x106 spores/ml) was obtained from 7-day-old cultures and injected (1 mm depth) into the fruit wall using a sterile syringe needle. Control fruits were inoculated with sterile distilled water only. Each fruit was inoculated with the inoculum at three distinct spots and kept in a humid chamber at a temperature of 25±2 °C. The pathogenicity test was done twice. Five days post-inoculation, the control fruits showed no symptoms, whereas all inoculated wounded and non-wounded fruits developed necrotic lesions with white mycelium growing on the inoculation points. The pathogen was successfully re-isolated from the infected fruits and morphologically identified as FIESC, fulfilling Kochs postulates. It has been reported previously that the members of FIESC are responsible for the fruit rot of bell peppers under greenhouse conditions (Ramdial et al., 2016). To the best of our knowledge, this is the first report of FIESC causing fruit rot on greenhouse bell peppers in Malaysia. This fruit rot disease may impose significant constraints on bell pepper production in Malaysia; hence, effective strategies to control the pathogen and prevent disease dispersal should be implemented.


Benchmarking predictions of allostery in liver pyruvate kinase in CAGI4.
The Critical Assessment of Genome Interpretation (CAGI) is a global community experiment to objectively assess computational methods for predicting phenotypic impacts of genomic variation. One of the 2015-2016 competitions focused on predicting the influence of mutations on the allosteric regulation of human liver pyruvate kinase. More than 30 different researchers accessed the challenge data. However, only four groups accepted the challenge. Features used for predictions ranged from evolutionary constraints, mutant site locations relative to active and effector binding sites, and computational docking outputs. Despite the range of expertise and strategies used by predictors, the best predictions were marginally greater than random for modified allostery resulting from mutations. In contrast, several groups successfully predicted which mutations severely reduced enzymatic activity. Nonetheless, poor predictions of allostery stands in stark contrast to the impression left by more than 700 PubMed entries identified using the identifiers "computational + allosteric." This contrast highlights a specialized need for new computational tools and utilization of benchmarks that focus on allosteric regulation.


[Amoebiasis--a problem in patients with ulcerative colitis].
The increasing problem is presented of Entamoeba histolytica invasion in patients with ulcerative colitis. The diagnostic-therapeutic management in five patients with amoebiasis is discussed in detail. This parasitic invasion occurred in five out of 103 patients with ulcerative colitis which accounts for 4.85%. This data is important for the treatment of chronically ill patients with ulcerative colitis.


Light transmission from a twisted nematic liquid crystal: accurate methods to measure the azimuthal anchoring energy.
In this paper, we analyze the light transmission from a twisted nematic liquid crystal (NLC) and we propose two accurate and very direct optical methods to measure the azimuthal anchoring energy. In both of them, a monochromatic beam of wavelength lambda with a polarization vector that rotates at an angular frequency omega impinges on a twisted nematic liquid crystal. The intensity of the transmitted beam is modulated at angular frequency 2omega with a phase shift beta, which is related to the surface azimuthal director angle phi(1) at the investigated interface. It is shown that there exists a special geometry where the simple adiabatic relation phi(1)=beta/2 is satisfied up to second order in the small perturbative parameter alpha=lambda/(2piDelta(n)xi), where Delta(n) is the anisotropy of the refractive indices of the NLC and xi is the twist distortion length. Furthermore, the small residual higher order correction terms can be greatly reduced by choosing a proper geometry for the experiment. With this choice, the range of validity of the adiabatic theory is greatly extended. The perturbative theoretical results are fully confirmed by numerical calculations. The azimuthal anchoring energy coefficient can be obtained by measuring phase shift beta versus the intensity of an applied magnetic field. These methods greatly improve the accuracy of the previous transmitted light techniques and also provide accurate measurements of strong azimuthal anchoring energies.


A Model of Combined Exposure to Nicotine and Tetrahydrocannabinol via Electronic Cigarettes in Pregnant Rats.
Nicotine and cannabis are two of the most commonly consumed licit and illicit drugs during pregnancy, often consumed together via e-cigarettes. Vaping is assumed to be a safer alternative than traditional routes of consumption, yet the potential consequences of prenatal e-cigarette exposure are largely unknown, particularly when these two drugs are co-consumed. In a novel co-exposure model, pregnant Sprague-Dawley rats received nicotine (36 mg/mL), tetrahydrocannabinol (THC) (100 mg/mL), the combination, or the vehicle via e-cigarettes daily from gestational days 5-20, mimicking the first and second human trimesters. Maternal blood samples were collected throughout pregnancy to measure drug and metabolite levels, and core body temperatures before and after exposure were also measured. Pregnant dams exposed to combined nicotine and THC had lower plasma nicotine and cotinine levels than those exposed to nicotine alone; similarly, the combined exposure group also had lower plasma THC and THC metabolite (THC-OH and THC-COOH) levels than those exposed to THC alone. Prenatal nicotine exposure gradually decreased initial core body temperatures each day, with chronic exposure, whereas exposure to THC decreased temperatures during the individual sessions. Despite these physiological effects, no changes were observed in food or water intake, weight gain, or basic litter outcomes. The use of this model can help elucidate the effects of co-exposure to THC and nicotine via e-cigarettes on both users and their offspring. Understanding the effects of co-use during pregnancy is critical for improving education for pregnant mothers about prenatal e-cigarette use and has important implications for public policy.


An adult case of polycystic kidney disease associated with congenital hepatic fibrosis.
Congenital hepatic fibrosis is often associated with infantile, but not with adult polycystic kidney disease. We report the unusual case of an adult patient with polycystic kidney disease complicated by congenital hepatic fibrosis. A 27-year-old women was admitted to our hospital because of gross hematuria due to hemorrhage from renal cysts. She presented hematemesis from ruptured esophageal varices at the age of 14 years. She was diagnosed as having end-stage renal disease due to polycystic kidney disease at the age of 23 years, and maintenance hemodialysis was initiated the following year. Gross hematuria was managed with supportive therapy. However, the patient developed cholangitis and died of sepsis. Postmortem examinations as well as the patient's clinical course suggested that she had an autosomal dominant type of polycystic kidney disease. Histological findings of the liver were compatible with congenital hepatic fibrosis.


Prevalence of pneumococcal serotypes in adults ≥50 years of age.
Currently, majority of studies on antibiotic resistance and serotype prevalence in Streptococcus pneumoniae are in paediatric population and there is limited epidemiologic data pertaining to elderly Indian population. This study was undertaken to assess antibiotic resistance pattern and the coverage of the polysaccharide vaccine 23 (PPV23) in the elderly population. This was a prospective 2-year pneumococcal surveillance study in patients with community-acquired pneumococcal infections of ≥50 years' age group on fifty isolates of S. pneumoniae. Antibiotic susceptibility by Kirby-Bauer disc diffusion method and minimum inhibitory concentration susceptibility testing by E-test method were performed for various antibiotics. All isolates were serotyped by the capsular Quellung method with commercial antisera. All S. pneumoniae isolates were sensitive to penicillin and ceftriaxone. Non-susceptibility to levofloxacin, co-trimoxazole, erythromycin and clindamycin was noted as 16%, 74%, 10% and 6%, respectively. Prevalence of multidrug resistance in S. pneumoniae was observed as 6%. The most common serotypes observed in our study were 19A (14%), 8 (10%), 19F (8%), 3 (6%) and 9N (6%). PCV7, PCV10, PCV13 and PCV23 coverage was observed as 16%, 24%, 48% and 66%, respectively. The non-vaccine serotypes (NVTs) comprised 30% (n = 15) of the isolates. Our study shows different antibiotic susceptibility patterns of S. pneumoniae as compared to other neighbouring regions in Asia. The modest coverage of S. pneumoniae serotypes by PPV23 vaccine and prevalence of diverse NVTs in adult population make it a challenging task to recommend further changes in the future vaccine.


Transformer-Based Named Entity Recognition for Parsing Clinical Trial Eligibility Criteria.
The rapid adoption of electronic health records (EHRs) systems has made clinical data available in electronic format for research and for many downstream applications. Electronic screening of potentially eligible patients using these clinical databases for clinical trials is a critical need to improve trial recruitment efficiency. Nevertheless, manually translating free-text eligibility criteria into database queries is labor intensive and inefficient. To facilitate automated screening, free-text eligibility criteria must be structured and coded into a computable format using controlled vocabularies. Named entity recognition (NER) is thus an important first step. In this study, we evaluate 4 state-of-the-art transformer-based NER models on two publicly available annotated corpora of eligibility criteria released by Columbia University (i.e., the Chia data) and Facebook Research (i.e.the FRD data). Four transformer-based models (i.e., BERT, ALBERT, RoBERTa, and ELECTRA) pretrained with general English domain corpora vs. those pretrained with PubMed citations, clinical notes from the MIMIC-III dataset and eligibility criteria extracted from all the clinical trials on ClinicalTrials.gov were compared. Experimental results show that RoBERTa pretrained with MIMIC-III clinical notes and eligibility criteria yielded the highest strict and relaxed F-scores in both the Chia data (i.e., 0.658/0.798) and the FRD data (i.e., 0.785/0.916). With promising NER results, further investigations on building a reliable natural language processing (NLP)-assisted pipeline for automated electronic screening are needed.


No requirement of HCV 5'NCR for HCV-like particles assembly in insect cells.
To express all three HCV structural proteins in the presence or absence of HCV 5'NCR to investigate the requirement of 5'NCR for the assembly of HCV-like particles in insect cells. HCV structural protein encoding sequences CE1E2 and 5'NCR-CE1E2 were amplified with PCR. Recombinant baculovirus were constructed with recombinant DNA techniques. HCV structural proteins expressed in insect cells were analyzed by immunofluorescence and SDS-PAGE. Immunoprecipitation experiment of insect cell lysates with anti-E2 monoclonal antibody (MAb) was carried out and the immunoprecipitated proteins were subjected to SDS-PAGE and immunoblotting with anti-C, anti-E2 MAbs and HCV positive serum. The virus-like particles in insect cells were visualized by electron microscopy (EM). The HCV-like particles were purified by sucrose gradient centrifugation and identified by EM and immune aggregation EM. The recombinant baculovirus reBV/CE1E2 containing HCV C, E1, E2 genes and reBV/CS containing the same structural protein genes plus 5'NCR were constructed. The insect cells infected with either reBV/CE1E2 or reBV/CS expressed HCV C, E1 and E2 proteins with a molecular weight of 20 kD, 35 kD and 66 kD respectively. The results of immunoprecipitation and the immunoblotting revealed the coimmunoprecipitation of C, E1, and E2 proteins, indicating the interaction of HCV structural proteins expressed in insect cells. Electron microscopy of insect cells infected with reBV/CE1E2 or reBV/CS demonstrated spherical particles (40 to 60 nm in diameter) similar to the HCV virions from sera or hepatic tissues of HCV infected humans. The HCV-like particles were partially purified by sucrose gradient centrifugation, and the purified VLPs showed immuno-reactivity with anti-HCV antibodies. HCV 5'NCR is not required for the assembly of HCV-like particles in insect cells, HCV core and envelope proteins are sufficient for viral particle formation.


Mechanical Properties of the Periodontal System and of Dental Constructs Deduced from the Free Response of the Tooth.
The biomechanical behaviour of the periodontal ligament (PDL) is still not well understood although this topic has been studied for almost 100 years. This study reports on clinical and mathematical studies to determine the constitutive law of the PDL. A set of mechanical parameters of the tooth-PDL system is obtained, and a new method for the evaluation of these parameters from the free response of the tooth is introduced. This response is produced by repeated impacts applied to the gingival tissue in the apical part of the tooth investigated-with the aid of a Periotest exciter. A Doppler ultrasound probe is utilized to determine the response of the tooth-PDL system. The parameters evaluated from these measurements can be considered as the elastometric properties of the dental system investigated. A modal analysis/system identification method is utilized to estimate these parameters. The investigations are carried out for different teeth abutments, both with and without a dental bridge/fixed partial prosthesis (FPP). The differences between the responses of the systems in these two cases are determined with the new method proposed. They are discussed with regard to the specific purposes of the FPP. The study demonstrates that this method can provide the dentist with the necessary objective evaluations regarding the properties and health of the tooth-PDL system, as well as of the construct that is obtained after installing a dental bridge.


Radioimmunoassay, pharmacokinetics, and neuronal release of gastrin-releasing peptide in anesthetized pigs.
Using a newly developed radioimmunoassay for porcine gastrin-releasing peptide in plasma, we studied the pharmacokinetics of this peptide after infusing it into pigs at two dose levels. The disappearance of the peptide from plasma was characterized by two components, a fast one (t 1/2 1.4 min) and a slow one (t 1/2 6.6 min). With the same assay the release of gastrin releasing-peptide from the stomachs of 8 pigs that had been catheterized for selective sampling of fundic and antral blood was studied during vagal and splanchnic stimulation with or without acute adrenalectomy at neutral, acidic, and alkaline intragastric pH. Electrical stimulation of the vagal nerves resulted in a marked increase in both antral and fundic gastrin-releasing peptide release, whereas splanchnic stimulation was without effect. The effects of nerve stimulation were neither influenced by intragastric pH nor by adrenalectomy. Because of its presence in nerves in all layers of the gastric wall, its potent effect on gastrin release, and its release after vagal stimulation, gastrin-releasing peptide is likely to play a role in the vagal control of gastrin release, gastric motility, and acid secretion.


Age shift in patterns of injection drug use among the HIV/AIDS population in Miami-Dade County, Florida.
Analysis of HIV exposure category for 20,034 persons in three age groups (13-29, 30-49, 50 and over) who were alive through 2003 and had been reported to the Florida Department of Health with HIV or AIDS in Miami-Dade County, Florida, found that having a history of injection drug use increases with increasing age (p < .001). Consideration of age-specific HIV risk profiles has implications for primary and secondary HIV prevention interventions, planning, and policy.


Remote, tablet-based assessment of gaze following: a nationwide infant twin study.
Much of our understanding of infant psychological development relies on an in-person, laboratory-based assessment. This limits research generalizability, scalability, and equity in access. One solution is the development of new, remotely deployed assessment tools that do not require real-time experimenter supervision. The current nationwide (Sweden) infant twin study assessed participants remotely via their caregiver's tablets (N = 104, ages 3 to 17 months). To anchor our findings in previous research, we used a gaze-following task where experimental and age effects are well established. Closely mimicking results from conventional eye tracking, we found that a full head movement elicited more gaze following than isolated eye movements. Furthermore, predictably, we found that older infants followed gaze more frequently than younger infants. Finally, while we found no indication of genetic contributions to gaze-following accuracy, the latency to disengage from the gaze cue and orient toward a target was significantly more similar in monozygotic twins than in dizygotic twins, an indicative of heritability. Together, these results highlight the potential of remote assessment of infants' psychological development, which can improve generalizability, inclusion, and scalability in developmental research.


Longitudinal Bone Mineralization Assessment in Children Treated With Long-Term Parenteral Nutrition for Severe Intestinal Failure.
Metabolic bone disease is common in children receiving home parenteral nutrition (HPN) for intestinal failure (IF). Long-term evolution of bone mass in pediatric IF is poorly documented. The aims of this study were (1) to determine the prevalence of low bone mass (LBM) in children receiving HPN for IF, (2) to evaluate the evolution of total bone mineral content (TBMC) during HPN with dual-energy x-ray absorptiometry (DXA), and (3) to identify related factors. All children referred in our HPN center from 2004 to 2014 were eligible. Inclusion criteria were HPN dependence due to noninflammatory IF, at least 2 TBMC assessments, and HPN duration of at least 2 years at last DXA. TBMC was expressed in z score for ideal weight for height (WFH). LBM was defined by a TBMC WFH z score ≤-2 standard deviations (SD). A total of 175 DXAs for 31 children were performed, mean of 5.6 ± 2.9 assessments per child. The median time between first and last DXA recorded was 6.2 years (0.7-16.6). At the first DXA, 14 children (45%) had a LBM. TBMC increased by +0.1 ± 0.04 SD per year of HPN (P = .012). The risk of LBM decreased with an odds ratio of 0.9 per year of HPN (95% confidence interval, 0.92-0.99; P = .018). Lean mass z score and calcium parenteral intakes were related to the TBMC improvement. LBM is common in pediatric IF, but bone status could improve during HPN in these children.


Interaction of ligand-receptor system between stromal-cell-derived factor-1 and CXC chemokine receptor 4 in human prostate cancer: a possible predictor of metastasis.
Interaction of ligand-receptor systems between stromal-cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) is closely involved in the organ specificity of cancer metastasis. We hypothesized that SDF-1-CXCR4 ligand-receptor system plays an important role in prostate cancer metastasis. To test this hypothesis, expression level of SDF-1 and CXCR4 was analyzed in prostate cancer (PC) cell lines (LNCaP, PC3, and DU145) and normal prostate epithelial cell line (PrEC). We also performed migration assay and MTT assay to investigate the chemotactic effect and growth-promoting effect of SDF-1 on DU145 and PC3 cells, respectively. Furthermore, we performed immunohistochemical analysis of CXCR4 expression in tissues from 35 cases of human prostate cancer. CXCR4 expression was detected in all three prostate cancer cell lines, but not in PrECs. SDF-1 significantly enhanced the migration of PC3 and DU145 cells in a dose-dependent manner, and anti-CXCR4 antibody inhibited this chemotactic effect. However, SDF-1 itself did not significantly stimulate the cell growth rate of prostate cancer cell lines. Positive CXCR4 protein was found in 20 out of 35 clinical PC samples (57.1%). Three patients with lung metastasis showed definitely positive CXCR4 immunostaining. Logistic regression analysis revealed that positive expression of CXCR4 protein was an independent and superior predictor for bone metastasis to Gleason sum (P < 0.05). Furthermore, among PC patients with PSA greater than 20 ng/mL, the positive rate of CXCR4 protein was significantly higher in patients with bone metastasis than in those with no bone metastasis (P = 0.017). These findings suggest that the interaction between SDF-1 and CXCR4 ligand-receptor system is involved in the process of PC metastasis by the activation of cancer cell migration. This is the first report to investigate the role of interaction of ligand-receptor systems between SDF-1 and CXCR4 in prostate cancer metastasis.


Dementia RED (Respect Empathy Dignity): Collaborating to build dementia supportive communities in North Wales--reporting on a pilot project (innovative practice).
There is increasing interest in developing dementia supportive communities world wide. Dementia RED (Respect Empathy Dignity) is a unique example from North Wales which is based on the twin concepts of people living with dementia as citizens in their community and developing 'bottom up' rather than 'top down' approaches to dementia supportive communities. Most people with dementia prefer to live at home thus making community connectivity key to maintaining healthy relationships and wellbeing. For those living with dementia, the community plays a pivotal role in providing value, meaning, purpose and acceptance. Building dementia supportive communities helps to raise awareness about dementia in the community through engagement and from identifying champions in the locality to voice issues. Dementia RED is an initiative and service which helps to develop such a philosophy in creating a dementia supportive community.


[Clinical efficacy of montelukast for the treatment of bronchiolitis in infants].
To observe the effect of montelukast treatment on levels of serum leukotriene B4 and urinary leukotriene E4 in infants with bronchiolitis. Seventy-five children who were diagnosed with bronchiolitis between June 2014 and December 2014 were randomly assigned into two groups, one with thirty-eight cases as the montelukast treatment group and another thirty-seven cases as the control group. All of the children were given routine medical treatment. The children in the montelukast treatment group were additionally given montelukast daily (4 mg once a day, for 7 days). The serum leukotriene B4 and urinary leukotriene E4 levels were measured using ELISA before and after treatment. The relationship between serum leukotriene B4 and urinary leukotriene E4 levels was analyzed by Peason correlation analysis. After 7 days of treatment, the serum leukotriene B4 and urinary leukotriene E4 levels in the montelukast treatment and control groups were significantly reduced compared with before treatment (P<0.05). The montelukast treatment group showed significantly lower serum leukotriene B4 and urinary leukotriene E4 levels than the control group (P<0.05). The remission time of cough, wheezing and lung wheezes and the length of hospital stay in the montelukast treatment group were significantly shortened compared with the control group (P<0.05). There was a positive correlation between serum leukotriene B4 and urinary leukotriene E4 levels (r=0.723, P<0.05). Montelukast has a reliable clinical curative efficacy for bronchiolitis in infants, possibly by decreasing serum leukotriene D4 and urinary leukotriene E4 levels.


Tissue distribution of N-acetylprocainamide in rats.
The purpose of this study was to determine the distribution of N-acetylprocainamide (NAPA) in heart, kidney, and liver tissues of rats and their relationship to the plasma concentration after intravenous administration of the drug (100 mg/kg) to 24 Charles River rats. A specific HPLC procedure was used. The plasma and tissue concentrations of NAPA declined biexponentially in parallel, with an elimination half-life of about 1.8 hr. The equilibrium between plasma and the organs tested in this study was attained within 5 min. The tissue/plasma concentration ratio remained constant throughout the study. The tissue/plasma ratios for heart, kidney, and liver were 2.1, 7.9, and 2.4, respectively. The data indicate that: a) these organs have greater affinity to NAPA than do plasma proteins, and b) plasma concentrations may be reliable measures of the therapeutically effective concentrations at the site of action, i.e., the heart tissues.


Suzuki Cross-Coupling for Post-Complexation Derivatization of Non-Racemic Bis-Cyclometalated Iridium(III) Complexes.
A straightforward method for post-complexation derivatizations of diastereo- and enantiomerically pure bis-cyclometalated benzoxazole and benzothiazole iridium(III) complexes is reported. Triflate- and bromine-functionalized iridium(III) complex dimers, represented as [Ir(μ-Cl)(C^N)2 ]2 , were converted to the corresponding diastereomeric complexes, represented as Ir(C^N)2 (N^O), using readily available chiral salicyloxazolines and salicylthiazolines as ancillary ligands, which are represented as N^O. The Ir(C^N)2 (N^O) complexes, formed as mixtures of diastereomers, were then resolved by flash chromatography and the diastereomerically pure complexes Ir(C^N)2 (N^O) subjected to Suzuki cross-couplings. The post-complexation cross-couplings proceed without affecting the metal-located stereocenter and hence provide post-complexation derivatized non-racemic iridium(III) complexes, which were not easily accessible with previous methods. This strategy expands the toolbox to access functionalized non-racemic iridium(III) complexes for diverse applications in the life sciences, materials sciences, and catalysis.


Histology and transcriptome insights into the early processes of intestinal anastomotic healing: a rat model.
Understanding the early processes underlying intestinal anastomotic healing is crucial to comprehend the pathophysiology of anastomotic leakage. The aim of this study was to assess normal intestinal anastomotic healing and disturbed healing in rats to investigate morphological, cellular and intrinsic molecular changes in the anastomotic tissue. Anastomoses were created in two groups of Wistar rats, using four sutures or 12 sutures to mimic anastomotic leakage and anastomotic healing respectively. At 6, 12, 24 hours and 2, 3, 5 and 7 days, anastomotic tissue was assessed macroscopically using the anastomotic complication score and histologically using the modified Ehrlich-Hunt score. Transcriptome analysis was performed to assess differences between anastomotic leakage and anastomotic healing at the first three time points to find affected genes and biological processes. Ninety-eight rats were operated on (49 animals in the anastomotic leakage and 49 in the anastomotic healing group) and seven rats analysed at each time point. None of the animals with 12 sutures developed anastomotic leakage macroscopically, whereas 35 of the 49 animals with four sutures developed anastomotic leakage. Histological analysis showed increasing influx of inflammatory cells up to 3 days in anastomotic healing and up to 7 days in anastomotic leakage, and this increase was significantly higher in anastomotic leakage at 5 (P = 0.041) and 7 days (P = 0.003). Transcriptome analyses revealed large differences between anastomotic leakage and anastomotic healing at 6 and 24 hours, mainly driven by an overall downregulation of genes in anastomotic leakage. Transcriptomic analyses revealed large differences between normal and disturbed healing at 6 hours after surgery, which might eventually serve as early-onset biomarkers for anastomotic leakage.


Dendritic amphiphiles strongly affect the biophysical properties of DPPC bilayer membranes.
Molecular dynamics (MD) simulations were used to gain insight on the molecular interactions in a model biological membrane comprised of a bilayer with DPPC (dipalmitoylphosphotidylcholine) and antimicrobial dendritic amphiphile molecules [RCONHC(CH(2)CH(2)COOH)(3), where R is the saturated hydrocarbon tail (R = n-C(n)H(2n+1)), to be abbreviated as 3CAmn]. This study analyzes different biophysical properties of the equilibrated mixed bilayers, at 300 and 325 K, to determine how the presence of the 3CAmn, in varying concentrations and tail lengths, affects the lipid bilayer. Lipid tail order parameter data, bilayer thickness trends, and qualitative lipid tail tilt observations suggest that a molar ratio of 0.2 3CAm19/DPPC is sufficient to induce a phase transition in the bilayer from gel to liquid crystalline at 300 K. These results also imply that the phase transition temperature of the mixed bilayer decreases upon incorporation of higher concentrations of 3CAm19. Hydrogen bonding takes place between the 3CAmn and DPPC at specific sites, as evidenced by the radial distribution function. Increased hydrogen bonding and the smaller headgroup size of the 3CAmn molecule result in a decrease in the total lateral area with higher concentrations of 3CAm19. Diffusion constants of 3CAmn varied with concentration and tail length; diffusion constants of DPPC and 3CAm19 increased with increasing 3CAm19 concentration at 300 K and shorter 3CAmn tails had higher diffusion constants at both temperatures. These computational studies provide a comprehensive understanding of the biophysical changes to model biological membranes by the association of 3CAmn.


Scalable Access to Arylomycins via C-H Functionalization Logic.
Arylomycins are a promising class of "latent" antibacterial natural products currently in preclinical development. Access to analogues within this family has previously required a lengthy route involving multiple functional group manipulations that is costly and time-intensive on scale. This study presents a simplified route predicated on simple C-H functionalization logic that is enabled by a Cu-mediated oxidative phenol coupling that mimics the putative biosynthesis. This operationally simple macrocyclization is the largest of its kind and can be easily performed on gram scale. The application of this new route to a formal synthesis of the natural product and a collection of new analogues along with their biological evaluation is also reported.


Surveillance for severe hand, foot, and mouth disease from 2009 to 2015 in Jiangsu province: epidemiology, etiology, and disease burden.
Severe hand, foot, and mouth disease (HFMD) is a common childhood illness caused by various enteroviruses. The disease has imposed increased burden on children younger than 5 years old. We aimed to determine the epidemiology, CNS complication, and etiology among severe HFMD patients, in Jiangsu, China. Epidemiological, clinical, and laboratory data of severe HFMD cases were extracted from 2009 to 2015. The CNS complication, annually severe illness rates, mortality rates, severity-PICU admission rates, severity-hospitalization rates, and so on were analyzed to assess the disease burden of severe HFMD. All analyses were stratified by time, region, population, CNS involvement and serotypes. The VP1 gene from EV-A71, CV-A16, CV-A6, CV-A10 and other enteroviruses isolates was amplified. Phylogenetic analysis was performed using MEGA5.0. Seven thousand nine hundred ninety-four severe HFMD cases were reported, of them, 7224 cases were inpatients, 611 were PICU inpatients, and 68 were fatal. The average severe illness rate, mortality rate, severity-fatality rate, severity-PICU admission rate, and severity-hospitalization rate were 14.54, 0.12,8506, 76,430, and 903,700 per 1 million, respectively. The severe illness rate was the highest in the 12-23 months age group, and the greatest mortality rate was in the 6-11 months age group. Geographical difference in severe illness rate and mortality were found. Patients infected with EV-A71 were at a higher proportion in different CNS involvement even death. EV-A71, CV-A16 and other enteroviruses accounted for 79.14, 6.49, and 14.47%, respectively. A total of 14 non-EV-A71/ CV-A16 genotypes including CV-A2, CV-A4, CV-A 6, CV-A9, CV-A10, CV-B1, CV-B2, CV-B3, CV-B4, CV-B5, E-6, E-7, E-18, and EV-C96 were identified. Phylogentic analyses demonstrated that EV-A71 strains belonged to subgenotype C4a, while CV-A16 strains belonged to sub-genotype B1a and sub-genotype B1b of genotype B1. CV-A6 strains were assigned to genogroup F, and CV-A10 strains belonged to genogroup D. Future mitigation policies should take into account the age, region heterogeneities, CNS conditions and serotype of disease. Additional a more rigorous study between the mild and severe HFMD should be warranted to elucidate the difference epidemiology, pathogen spectrum and immunity patterns and to optimize interventions in the following study.


Clinics in diagnostic imaging (177). Medical meniscus bucket-handle tear with medial oblique meniscomeniscal ligament.
A 29-year-old man with a previous football injury to his left knee presented with pain of the same knee. The patient twisted it as he was turning a corner quickly while going up the stairs, leading to internal rotation of his femur on his tibia with his knee in flexion. MR imaging revealed a bucket-handle tear of the medial meniscus, as well as a complete tear of the anterior cruciate ligament. However, image interpretation was complicated by the presence of a medial oblique meniscomeniscal ligament, a rare normal variant among intermeniscal ligaments of the knee. All four recognised variants of intermeniscal ligaments are discussed, with emphasis on their prevalence, imaging and anatomical features, and the way in which they may mimic meniscal tears.


Differentiation Potential of Cultured Extracellular DEAD-Box Helicase 4+ Oogonial Stem Cells from Adult Human Ovaries into Somatic Lineages.
The transdifferentiation potential of human oogonial stem cells (hOSCs) isolated using the antibody against extracellular DEAD-Box Helicase 4 (ecDDX4) remains undetermined. Hence, this study isolated OSCs from ovarian cortical pieces of premenopausal women using ecDDX4 antibody by magnetic activated cell sorting and expanded these cells under embryonic stem cell (ESC)-like culture conditions to inves-tigate their transdifferentiation potential. The number of ecDDX4+ cells obtained was variable in each isolation. When cultured on inactivated mouse embryonic fibroblast feeder layer with human leukemia inhibitory factor (hLIF) and basic fibroblast growth factor (bFGF) in Minimum Essential Medium, the hOSCs aggregated, forming ESC-like colonies. The average size of these cells was around 10 μm. hOSCs in culture were positive for alkaline phosphatase and further formed embryoid bodies (EBs) when grown on low attachment plates containing Essential 6 Medium without hLIF and bFGF. Subsequently, EBs differentiated into 3 germ layers, which were confirmed by staining with beta-III tubulin (TUJ1) for ectoderm, alpha-fetoprotein (AFP) for endoderm, and smooth muscle actin (SMA) for mesoderm. Further, using appropriate induction media, the EBs derived from ecDDX4+ hOSCs were differentiated into somatic lineages such as adipocytes, osteoblasts, cardiomyocytes, and neuronal precursor-like cells, which were confirmed by immunofluorescence using antibodies against specific markers for each cell type. This study corroborated the previous findings that ovaries of adult women possess germ cell progenitors that can be isolated using ecDDX4, and these cells can be manipulated as pluripotent stem cells by culturing them under ESC-like culture conditions akin to their male counterparts, the spermatogonial stem cells. Further, these cells could differentiate into somatic lineages under specific signalling environments.


Polarized cholesterol and phospholipid efflux in cultured gall-bladder epithelial cells: evidence for an ABCA1-mediated pathway.
Gall-bladder epithelial cells (GBEC) are exposed to high concentrations of cholesterol in bile. Whereas cholesterol absorption by GBEC is established, the fate of this absorbed cholesterol is not known. The aim of this study was to determine whether ABCA1 (ATP-binding cassette transporter A1) mediates cholesterol efflux in GBEC. Polarized canine GBEC were cultured on porous membrane filters allowing separate access to apical (AP) and basolateral (BL) compartments. After AP loading of cells with model bile and [14C]cholesterol, cholesterol efflux was measured. Cholesterol loading together with 8-bromo-cAMP treatment, which increased ABCA1 expression, led to a significant increase in cholesterol efflux with apolipoprotein A-I (apoA-I) as the acceptor. Cholesterol efflux was observed predominantly into the BL compartment. Similar results were found for phospholipid efflux. Confocal immunofluorescence microscopy showed a predominantly BL ABCA1 localization. Interestingly, apoA-I added to either the AP or the BL compartments elicited BL lipid efflux with cAMP treatment. No paracellular or transcellular passage of 125I-apoA-I occurred. Ligands for the nuclear hormone receptors liver X receptor alpha (LXRalpha) and retinoid X receptor (RXR) elicited AP and BL cholesterol efflux, suggesting the involvement of both ABCA1- and non-ABCA1-mediated pathways. In summary, BL cholesterol/phospholipid efflux consistent with an ABCA1-mediated mechanism occurs in GBEC. This efflux pathway is stimulated by cAMP and by LXRalpha/RXR ligands, and in the case of the cAMP pathway appears to involve a role for biliary apoA-I.


The alpha helix of ubiquitin interacts with yeast cyclin-dependent kinase subunit CKS1.
Ubiquitin serves as a molecular zipcode to direct and sort ubiquitinylated proteins into distinct biological pathways. Although novel modes of ubiquitin interaction have recently been characterized, conventional ubiquitin-binding domains (UBDs) recognize ubiquitin through a hydrophobic pocket centered around isoleucine 44 and lined by residues in beta sheets 3 and 4. In this study, we report a novel mode of interaction between ubiquitin and the cyclin-dependent kinase subunit of Saccharomyces cerevisiae, Cks1p, an adaptor protein involved in transcriptional regulation through recruitment of proteasomal subunits to gene promoters. Cks1p interacts specifically with monoubiquitin and tetraubiquitin with an affinity several orders of magnitude greater than that of other ubiquitin-binding domains and in an unconventional fashion, which differs from interactions documented so far between ubiquitin and conventional UBDs. The loop between helices alpha 1 and alpha 2, and to a minor extent the N-terminal alpha-helix of Cks1p, are involved in the interaction with the alpha-helix of ubiquitin, instead of its I44-centered hydrophobic pocket. Not only is this the first time the alpha-helix of ubiquitin is implicated in a protein/protein interaction, thereby shedding new light on the mechanisms of ubiquitin recognition, but also the first report of a direct physical interaction between ubiquitin and Cks1p, inferring a role for ubiquitin binding in the transcriptional function of Cks1p.


Identification of App1 as a regulator of phagocytosis and virulence of Cryptococcus neoformans.
Cryptococcus neoformans is a fungal pathogen that, after inhalation, can disseminate to the brain. Host alveolar macrophages (AMs) represent the first defense against the fungus. Once phagocytosed by AMs, fungal cells are killed by a concerted mechanism, involving the host-cellular response. If the cellular response is impaired, phagocytosis of the fungus may be detrimental for the host, since C. neoformans can grow within macrophages. Here, we identified a novel cryptococcal gene encoding antiphagocytic protein 1 (App1). App1 is a cryptococcal cytoplasmic protein that is secreted extracellularly and found in the serum of infected patients. App1 does not affect melanin production, capsule formation, or growth of C. neoformans. Treatment with recombinant App1 inhibited phagocytosis of fungal cells through a complement-mediated mechanism, and Deltaapp1 mutant is readily phagocytosed by AMs. Interestingly, the Deltaapp1 mutant strain showed a decreased virulence in mice deficient for complement C5 (A/Jcr), but it was hypervirulent in mice deficient for T and NK cells (Tgepsilon26). This study identifies App1 as a novel regulator of virulence for C. neoformans, and it highlights that internalization of fungal cells by AMs increases the dissemination of C. neoformans when the host cellular response is impaired.


5-(1-Acetoxyvinyl)-cycloSaligenyl-2',3'-dideoxy-2',3'- didehydrothymidine monophosphates, a second type of new, enzymatically activated cycloSaligenyl pronucleotides.
In our attempt to further develop the cycloSal pronucleotide concept, we report on 5-(1-acetoxyvinyl)-cycloSal-d4TMPs as a new type of enzyme-activated pronucleotides. These compounds were converted into 5-acetyl-cycloSal-d4TMPs by (carboxy)esterase cleavage inside the cells. The enzymatic reaction led to the formation of a strong electron-withdrawing substituent that strongly accelerates the chemical hydrolysis of the cycloSal nucleotide to give d4TMP. For some cycloSal-d4TMPs a separation into the diastereomers was achieved. The absolute configuration was assigned by correlation of circular dichroism spectra with similar compounds. Most of the compounds showed complete retention of antiviral activity in TK-deficient CEM/TK(-) cells, which proves the TK-bypass potential of this approach. Interestingly, (S(P))-isomers of cycloSal phosphate triesters showed better antiviral activity in HIV-2-infected thymidine-kinase deficient CEM/TK(-) cells than their (R(P))-counterparts.


Practical considerations for sensitivity analysis after multiple imputation applied to epidemiological studies with incomplete data.
Multiple Imputation as usually implemented assumes that data are Missing At Random (MAR), meaning that the underlying missing data mechanism, given the observed data, is independent of the unobserved data. To explore the sensitivity of the inferences to departures from the MAR assumption, we applied the method proposed by Carpenter et al. (2007).This approach aims to approximate inferences under a Missing Not At random (MNAR) mechanism by reweighting estimates obtained after multiple imputation where the weights depend on the assumed degree of departure from the MAR assumption. The method is illustrated with epidemiological data from a surveillance system of hepatitis C virus (HCV) infection in France during the 2001-2007 period. The subpopulation studied included 4343 HCV infected patients who reported drug use. Risk factors for severe liver disease were assessed. After performing complete-case and multiple imputation analyses, we applied the sensitivity analysis to 3 risk factors of severe liver disease: past excessive alcohol consumption, HIV co-infection and infection with HCV genotype 3. In these data, the association between severe liver disease and HIV was underestimated, if given the observed data the chance of observing HIV status is high when this is positive. Inference for two other risk factors were robust to plausible local departures from the MAR assumption. We have demonstrated the practical utility of, and advocate, a pragmatic widely applicable approach to exploring plausible departures from the MAR assumption post multiple imputation. We have developed guidelines for applying this approach to epidemiological studies.


Can care of elderly be measured? A method for estimating the individual care of recipients in community health care.
Almost every country in the Western world has great difficulties allocating enough financial resources to meet the needs in the care of the increasing elderly population. The main problem is common to all countries and concerns the efforts to meet elderly persons' needs on an individual level while still maintaining society's responsibility for distributing justice. The aim of this study is to elaborate an instrument for measuring the quality of individual care and staff's working time in order to allocate public resources fairly. The present study gives an account of a new classification system named TiC (Time in Care), indicating how it can be used most effectively and also investigating the validity and reliability of the system. All recipients in 13 sheltered homes for elderly care (n = 505) in a Swedish municipality were surveyed regarding the care they needed, in dimensions of General Care, Medical Care, Cognitive Dysfunction and Rehabilitation, and the time required. Construct validity was assessed by means of factor analysis. The inter-rater agreement of two raters concerning 79 recipients was measured using weighted Kappa. The stability of the instrument and its sensitivity to change were investigated through test-retest reliability measurements, conducted once a month during a six-month period. The content validity of the instrument was also assessed. Factor analysis resulted in a reduction of the number of items from 25 to 16 in three dimensions: General Care, Medical Care and Cognitive Dysfunction. The Kappa analysis showed satisfactory to excellent inter-rater agreement. The care need scores were basically stable but showed sensitivity to change in health status. The instrument was found to be useful and reliable for assessing individual needs in community health care.


Identification of aptamers as specific binders and modulators of cell-surface receptor activity.
In recent years, the SELEX (Systematic Evolution of Ligands by EXponential enrichment) technology has established itself as a powerful tool in basic research with promising applications in diagnostics and therapeutics. Oligonucleotides with high-affinities to their targets, denominated as aptamers, are obtained from partially random oligonucleotide pools by reiterative in vitro selection cycles and screening for binding activity. The original technique allowing the identification of aptamers binding to soluble targets, has recently been extended in order to produce aptamers binding to complex targets including receptors and ion channels embedded in the plasma membrane as well as whole cell surfaces or parasite organisms. In addition to discussing the most recent developments with focus on possible diagnostic and therapeutic application, we provide a simple protocol which has been successfully used to select for RNA aptamers as allosteric modulators of nicotinic receptor activity.


Diaphragm activity in obesity.
DIAPHRAGM ACTIVITY DURING CARBON DIOXIDE BREATHING AND TOTAL CHEST COMPLIANCE DURING DIAPHRAGM RELAXATION WERE MEASURED IN EIGHT OBESE SUBJECTS: four with normal blood gases and four with hypercapnia and hypoxemia. Whereas there were no significant differences in the values of total chest compliance between the two groups, there were marked differences in diaphragm activity. The increase in integrated electrical activity in the diaphragm, per millimeter increment in carbon dioxide tension in the arterial blood, averaged 66 units (range: 48-90) in the obese-normal subjects and 17 units (range: 12-22) in the obese-hypoventilation subjects. These results suggest that an incapacity to increase the activity in the respiratory muscles, to levels necessary to overcome the load caused by obesity, plays a major role in the genesis of respiratory failure in obese subjects.


Emergence of Kawasaki disease related to SARS-CoV-2 infection in an epicentre of the French COVID-19 epidemic: a time-series analysis.
Kawasaki disease is an acute febrile systemic childhood vasculitis, which is suspected to be triggered by respiratory viral infections. We aimed to examine whether the ongoing COVID-19 epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with an increase in the incidence of Kawasaki disease. We did a quasi-experimental interrupted time series analysis over the past 15 years in a tertiary paediatric centre in the Paris region, a French epicentre of the COVID-19 outbreak. The main outcome was the number of Kawasaki disease cases over time, estimated by quasi-Poisson regression. In the same centre, we recorded the number of hospital admissions from the emergency department (2005-2020) and the results of nasopharyngeal multiplex PCR to identify respiratory pathogens (2017-2020). These data were compared with daily hospital admissions due to confirmed COVID-19 in the same region, recorded by Public Health France. Between Dec 1, 2005, and May 20, 2020, we included 230 patients with Kawasaki disease. The median number of Kawasaki disease hospitalisations estimated by the quasi-Poisson model was 1·2 per month (IQR 1·1-1·3). In April, 2020, we identified a rapid increase of Kawasaki disease that was related to SARS-CoV-2 (six cases per month; 497% increase [95% CI 72-1082]; p=0·0011), starting 2 weeks after the peak of the COVID-19 epidemic. SARS-CoV-2 was the only virus circulating intensely during this period, and was found in eight (80%) of ten patients with Kawasaki disease since April 15 (SARS-CoV-2-positive PCR or serology). A second peak of hospital admissions due to Kawasaki disease was observed in December, 2009 (six cases per month; 365% increase ([31-719]; p=0.0053), concomitant with the influenza A H1N1 pandemic. Our study further suggests that viral respiratory infections, including SAR-CoV-2, could be triggers for Kawasaki disease and indicates the potential timing of an increase in incidence of the disease in COVID-19 epidemics. Health-care providers should be prepared to manage an influx of patients with severe Kawasaki disease, particularly in countries where the peak of COVID-19 has recently been reached. French National Research Agency.


Teachers' and Students' Support for Corporal Punishment-A Practice Outlawed by the Government of Kenya.
Application of corporal punishment (CP) in Kenyan schools continues to be controversial in that CP is banned but esteemed by parents, some teachers, and even students. This investigation sought to establish and describe participants' degrees of support for the application of CP in schools in Eldoret Municipality. Randomly selected samples of 86 teachers and 192 students were investigated for their support of CP through survey questionnaires. Data analysis was undertaken using nonparametric and descriptive statistics. Teacher support for CP was found to be undifferentiated by gender, teaching experience, and professional qualification. Teachers with less than 12 years of teaching experience were more pro-CP in attitude compared with their older colleagues. A higher ratio of male-to-female teachers is associated with a greater tendency to apply CP in the schools investigated. Differences in support for CP among students were found by gender, age, and school grade. The findings have implications for school discipline and success of the government ban.


Primary prophylaxis of variceal bleeding in cirrhotics awaiting liver transplantation.
To evaluate the efficacy and safety of prophylactic band ligation and propranolol versus propranolol alone for the primary prophylaxis of variceal bleeding in patients with high-risk esophageal varices listed for liver transplantation. Out of 152 cirrhotic patients included on the waiting list between January 2001 and January 2003, high-risk esophageal varices were detected in 72. These patients were randomized to undergo combined therapy or propranolol monotherapy. The actuarial probabilities of bleeding from esophageal varices and bleeding-related death were calculated by Kaplan-Meier method and compared using the log-rank test. Variceal eradication was achieved in 33 patients (91.6%) in 2.5 +/- 1.4 ligation sessions. The mean daily dose of propranolol was 72 +/- 25mg in the propranolol group and 68 +/- 21 mg in the ligation group. Six percent of patients in the ligation group and 31% in the propranolol group had one episode of bleeding during the 18 months of follow-up (p = 0.03). The actuarial probabilities of bleeding-free survival after 18 months of follow-up, in the ligation and monotherapy groups were 96% and, respectively, 69% (p = 0.04). Endoscopic band ligation associated with propranolol significantly reduces the occurrence of the first episode of variceal bleeding and improves bleeding-related survival in cirrhotics included on the waiting list.


Critical issues in mental health service delivery: what are the priorities?
The director, one other professional, and one para-professional in 515 community mental health centers and 193 state hospitals throughout the United States were asked to rate 57 critical issues in mental health services as to their importance now and five years from now. Issues judged most important now are services for children and for adolescents; five years from now children's services still top the list. Answers to two other questions revealed that respondents placed research on prevention at the top of a list of needed research areas, and that the most useful NIMH service to agencies was person-to-person assistance such as consultation and workshops.


Comparison of three commercially available antibodies for flow cytometric monitoring of P-glycoprotein expression in tumor cells.
Cellular drug resistance to natural products is often due to the presence of an efflux pump which reduces intracellular drug content and chemosensitivity. A 170 kD cell surface resident P-glycoprotein is believed to act as the efflux pump. In the present report, we have compared three commercially available antibodies C-219, JSB-1, and mdr(Ab-1) for use in flow cytometric detection of P-glycoprotein positive cells. Our data show that C219 gives uniformly good results in a variety of murine and human tumor cell lines for detection of P-glycoprotein positive cells. We have also compared data of C219 stained cells analyzed in parallel on a flow cytometer equipped with a small laser (15 mW) and a large laser (5 watt) cell sorter. Data obtained on these two instruments are comparable. A staining protocol and data on dual staining of cells for DNA content by propidium iodide and P-glycoprotein expression after FITC labeling are also presented.


Head injuries and the risk of concurrent cervical spine fractures.
Cervical spine injuries of variable severity are common among patients with an acute traumatic brain injury (TBI). We hypothesised that TBI patients with positive head computed tomography (CT) scans would have a significantly higher risk of having an associated cervical spine fracture compared to patients with negative head CT scans. This widely generalisable retrospective sample was derived from 3,023 consecutive patients, who, due to an acute head injury (HI), underwent head CT at the Emergency Department of Tampere University Hospital (August 2010-July 2012). Medical records were reviewed to identify the individuals whose cervical spine was CT-imaged within 1 week after primary head CT due to a clinical suspicion of a cervical spine injury (CSI) (n = 1,091). Of the whole cranio-cervically CT-imaged sample (n = 1,091), 24.7% (n = 269) had an acute CT-positive TBI. Car accidents 22.4% (n = 244) and falls 47.8% (n = 521) were the most frequent injury mechanisms. On cervical CT, any type of fracture was found in 6.6% (n = 72) and dislocation and/or subluxation in 2.8% (n = 31) of the patients. The patients with acute traumatic intracranial lesions had significantly (p = 0.04; OR = 1.689) more cervical spine fractures (9.3%, n = 25) compared to head CT-negative patients (5.7%, n = 47). On an individual cervical column level, head CT positivity was especially related to C6 fractures (p = 0.031, OR = 2.769). Patients with cervical spine fractures (n = 72) had altogether 101 fractured vertebrae, which were most often C2 (22.8, n = 23), C7 (19.8%, n = 20) and C6 (16.8%, n = 17). Head trauma patients with acute intracranial lesions on CT have a higher risk for cervical spine fractures in comparison to patients with a CT-negative head injury. Although statistically significant, the difference in fracture rate was small. However, based on these results, we suggest that cervical spine fractures should be acknowledged when treating CT-positive TBIs.


Web-based environmental health education: fish facts.
Nurses and other health professionals are often asked about the benefits and risks of fish consumption. The combination of conflicting media messages about these risks and benefits and limited knowledge has led to confusion about how to properly advise people about safe fish consumption. "Fish Facts for Health Professionals" was the result of a collaborative effort of environmental, public health, medical, nursing, and media experts to create a web-based educational series to address the need for reliable information on fish consumption. Using interviews and real case studies, the 3- to 5-minute media modules provided a strong visual element while remaining conversational. The modules were viewed worldwide, and 121 participants successfully completed the requirements for professional continuing education credit.


Is emotional intelligence relevant to a fighting force?
Over the past decade, the expectations of what the fighting force are tasked to deal with has changed significantly. The high-risk, high-tempo operational environments in which personnel have deployed in recent years have been complex and diverse, creating a spectrum of conflict where having EI would be an essential attribute. EI could be beneficial for the organisation and the individuals involved, and historically, there has been a distinct lack of EI. For it to be better used within the military, the entire concept needs to be explored, accepted and integrated into training throughout the rank structure; from the recruitment process to throughout the career development with support from senior commanders. This article discusses the relevance of emotional intelligence (EI) to the British Armed Forces.


Development of a high sensitivity RT-PCR assay for detection of SARS-CoV-2 in individual and pooled nasopharyngeal samples.
The COVID-19 pandemic requires sensitive detection of the SARS-CoV-2 virus from samples to ensure accurate detection of infected patients, an essential component of effective national track and trace programs. Due to the scaling challenges of large sample numbers, sample pooling is an attractive solution to reduce both extraction and amplification reagent costs, if high sensitivity can be maintained. We demonstrate that the Erba Molecular ErbaMDx SARS-CoV-2 RT-PCR Kit (EM kit) delivers high sensitivity, achieving analytical detection of 5 copies/reaction SARS-CoV-2 genomic RNA, and 200 copies/mL SARS-CoV-2 inactivated virus spiked into nasopharyngeal swab (NP) samples and extracted through workflow. Furthermore, the EM Kit demonstrates high sensitivity in both pooled (1 in 5) and non-pooled NP samples when compared to an FDA Emergency Use Authorization approved assay, following published FDA guidelines. These findings demonstrate that the EM Kit is suitable for sample pooling, with minimal impact on assay performance. As the COVID-19 pandemic progresses, high sensitivity assays such as the EM Kit will have an important role in ensuring high throughput and sensitive testing using pooled samples can be maintained, delivering the most cost-effective sample extraction and amplification option for national test and trace programs.


A unique role for p53 in the regulation of M2 macrophage polarization.
P53 is critically important in preventing oncogenesis but its role in inflammation in general and in the function of inflammatory macrophages in particular is not clear. Here, we show that bone marrow-derived macrophages exhibit endogenous p53 activity, which is increased when macrophages are polarized to the M2 (alternatively activated macrophage) subtype. This leads to reduced expression of M2 genes. Nutlin-3a, which destabilizes the p53/MDM2 (mouse double minute 2 homolog) complex, promotes p53 activation and further downregulates M2 gene expression. In contrast, increased expression of M2 genes was apparent in M2-polarized macrophages from p53-deficient and p53 mutant mice. Furthermore, we show, in mice, that p53 also regulates M2 polarization in peritoneal macrophages from interleukin-4-challenged animals and that nutlin-3a retards the development of tolerance to Escherichia coli lipopolysaccharide. P53 acts via transcriptional repression of expression of c-Myc (v-myc avian myelocytomatosis viral oncogene homolog) gene by directly associating with its promoter. These data establish a role for the p53/MDM2/c-MYC axis as a physiological 'brake' to the M2 polarization process. This work reveals a hitherto unknown role for p53 in macrophages, provides further insight into the complexities of macrophage plasticity and raises the possibility that p53-activating drugs, many of which are currently being trialled clinically, may have unforeseen effects on macrophage function.


Epidemiology abuse: epidemiologic and Psychosocial perspectives on heroin maintenance.
Two perspectives on drug abuse have evolved. Epidemiologic approaches treat drug abuse as if it were an infectious disease and deal with it within the framework of host, agent, and environment. Epidemiologists, approaching drug abuse from a public health standpoint, tend to think in terms of supply reduction. Psychosocial approaches focus on the demand aspect of drug abuse. Interest centers on psychological/sociological explanations of drug-taking behavior, such as psychopathology and alienation, and on unintended consequences of supply-reduction strategies. The author proposes that the two models eomplement each other and need to be integrated. A policy of strict supply reduction for nonaddicts coupled with heroin maintenance for addicts is suggested. Such a policy combines epidemiologic emphasis on supply reduction with psychosocial stress on the impractible nature of addiction and the futility of prohibitionlike approaches.


Effects of combined administration of captopril and DMSA on arsenite induced oxidative stress and blood and tissue arsenic concentration in rats.
We compared the therapeutic efficacy of captopril and a thiol chelating agent, meso 2,3-dimercaptosuccinic acid (DMSA) either individually or in combination against arsenite induced oxidative stress and mobilization of metal in rats. Animals were exposed to 100 ppm arsenite as sodium arsenite in drinking water for six weeks followed by treatment with DMSA (50 mg/kg, orally), captopril (50 mg/kg, intraperitoneally) either alone or in combination, once daily for 5 consecutive days. Arsenite exposure led to a significant depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity, glutathione and platelet levels while significantly increased the level of reactive oxygen species (in RBCs). Hepatic reduced glutathione (GSH) level showed a significant decrease while, thiobarbituric acid reactive substances (TBARS) levels increased on arsenite exposure indicating arsenite induced hepatic oxidative stress. Kidney GSH, GSSG, catalase and TBARS remained unchanged on arsenite exposure. Treatment with DMSA was effective in increasing ALAD activity while, captopril was ineffective when given alone. Captopril when co-administered with DMSA also provided no additional beneficial effect on blood ALAD activity but significant brought altered platelet counts back to the normal value. In contrast, administration of captopril alone provided significant beneficial effects on hepatic oxidative stress, and in combination with DMSA provided a more pronounced recovery in the TBARS level compared to the individual effect of DMSA and captopril. Renal biochemical variables remained insensitive to arsenite and any of the treatments. Interestingly, combined administration of captopril with DMSA had a remarkable effect in depleting total arsenic concentration from blood and soft tissues. These results lead us to conclude that captopril administration during chelation treatment had some beneficial effects particularly on the protection of inhibited blood ALAD activity, and depletion of arsenic level. The study supports our earlier conclusion that a co-administration of an antioxidant is more beneficial than monotherapy with the chelating agents, in order to achieve optimal effects of chelation in arsenite toxicity.


Inhibitors of PI3K/ERK1/2/p38 MAPK Show Preferential Activity Against Endocrine-Resistant Breast Cancer Cells.
Current mainstream pharmacological options for the treatment of endocrine-resistant breast cancer have limitations in terms of their side effect profile and lack of discrimination between normal and cancer cells. In the current study, we assessed the responses of normal breast epithelial cells MCF10A, estrogen receptor-positive (ER+) MCF-7, and ER-silenced pII breast cancer cells to inhibitors (either individually or in combination) of downstream signaling molecules. The expression/activity of ERK1/2, p38 MAPK, and Akt was determined by Western blotting. Cell proliferation, motility, and invasion were determined using MTT, wound healing, and Matrigel assays, respectively. Morphological changes in response to variation in external pH were assessed by light microscopy. Our results demonstrated that the inhibitors of ERK1/2 (PD0325901), p38 MAPK (SB203580), and PI3K (LY294002) preferentially reduce breast cancer cell proliferation. In pII cells, they also reduced motility, invasion, and bleb formation induced by alkaline conditions. Combination treatment with lower concentrations of inhibitors was significantly more effective than single agents and was more effective against the cancer cell lines than the normal MCF10A. In contrast, the commonly used cytotoxic agent paclitaxel did not sufficiently discriminate between the MCF10A and the cancer cells. We concluded that combination therapy using ERK1/2 inhibitor and either p38 MAPK or PI3K inhibitor may provide a greater therapeutic benefit in treating breast cancer by specifically targeting cancer cells with lower doses of each drug than needed individually, potentially reducing unwanted side effects.