Developing a standardized national undergraduate curriculum for future healthcare professionals on self-management support for chronic conditions.
This is a report on the development of the second part of a national undergraduate interprofessional standardized curriculum in chronic disease prevention for healthcare professionals in the Republic of Ireland; National Undergraduate Curriculum for Chronic Disease Prevention and Management Part 2: Self-management Support for Chronic Conditions. The development processes involved in Part 1, Making Every Contact Count for Health Behavior Change, were described earlier. This report presents an overview of the development of a national self-management support curriculum and barriers and enablers encountered. The curriculum was developed by a National Working Group, with interprofessional representation from each of the Higher Education Institutions (HEIs) in Ireland and the national health service, i.e. the Health Service Executive (HSE). All phases of the project were overseen by a Steering Group and supported in each HEI by a local working group. The aim of the curriculum is to introduce standardized self-management support education across all undergraduate and graduate entry healthcare programmes nationally to prepare future healthcare professionals with knowledge, skills and attitudes to support individuals to self-manage their chronic conditions.


[The observe of clinical effect of treating lumbar intervertebral disc herniation by bone setting manipulation of different directions].
To compare the effect between lumbar backwards flexion manipulation and rotating manipulation for treating lumbar intervertebral disc herniation. Two hundred and nine patients of lumbar intervertebral disc herniation, male 131, female 78, the age from 20 to 79 years old, 58 cases of all these patients age above 50. According to diagnosis the ladder of the 92 cases bulging type, 69 hernia type, 48 cases free type. The patients were randomly divided into treatment group (107 cases) and control group (102 cases). All the patients were treated with the three-dimensional computer-controlled traction therapeutic apparatus, with continued traction for 30 minutes. After traction, lumbar backwards flexion manipulation and rotating manipulation were respectively adopted in treatment group and control group (on alternate days one time, 3 times as a course of treatment). The symptoms and signs (including back pain and discomfort, lower limb pain and numbness, powerless urination and defecation, numbness in perineum, straight-leg raising degree, ability of lower extremity walking, work and live) of patients were observed after treatment. All the patients were followed up from 1 to 6 months with an average of 3.2 months. After treatment, the symptoms and signs of patients have markedly improved (P < 0.01), but the lower back pain and discomfort, lower limb walking ability in treatment group were better than control group (P < 0.05). According therapeutic criteria, the effect of treatment group was better than of control group (P < 0.01). In cases with bulging type, 47 in treatment group and 45 in control group, the effect of treatment group was better than of control group (P < 0.05); in cases with hernia type, 35 in treatment group and 34 in control group, there was no significantly difference in effect between two groups (P > 0.05); in cases of free type, 25 in treatment group and 23 in control group, there was no significantly difference in effect between two groups (P > 0.05). The global effect of lumbar backwards flexion manipulation was satisfactory than rotating manipulation for treating lumbar intervertebral disc herniation. But rotating manipulation suited to free type.


Prevention of hepatitis C virus-related hepatocellular carcinoma.
The incidence of hepatocellular carcinoma (HCC) is increasing in North America, Europe, and Japan, caused largely by the high rates of chronic hepatitis C virus (HCV) infection. In such individuals, the risk factors for developing HCC are advancing age, male gender, worsening hepatic fibrosis (particularly cirrhosis), and greater degrees of hepatic inflammation. Additional, potentially modifiable risk factors include coinfection with hepatitis B, excessive alcohol use, iron overload, and diabetes/obesity. Thus, approaches to preventing HCC should focus on eradicating HCV infection, responsible for the inflammation and fibrosis, and also on treating or reducing the modifiable risks, such as through hepatitis B vaccination, decreasing alcohol use, phlebotomy for iron overload, and weight control and diabetes prevention. These approaches have yet to be proven effective. Meta-analyses of standard interferon monotherapy trials in patients with HCV-related cirrhosis suggest that interferon has a small but significant effect on reducing HCC risk, particularly in those who achieve a sustained response. Other studies indicate that the reduction in HCC is greatest if a response is achieved before cirrhosis develops. Secondary prevention when HCC has been ablated or resected may be partially effected with interferon treatment or oral polyprenoic acid. No long-term studies of the effect of the currently recommended regimen of peginterferon and ribavirin have been reported, and no current trials include untreated control groups. Studies of maintenance peginterferon therapy in virological nonresponders are under way in the hope of proving that this approach is effective in decreasing the risk of HCC.


Combined barium meal and cholecystogram--an analysis of 1,444 patients.
Since many dyspeptic patients are still investigated initially by radiology, a policy was initiated whereby all such patients were directly referred for combined simultaneous double-contrast barium meal and cholecystogram. This policy was aimed at reducing patient visits to hospital and increasing diagnostic yield. The results of 1,444 combined procedures are presented. Of these, 310 (25.5%) had a positive finding on barium meal only; 275 (19%) were positive for cholecystogram only; 117 (8.1%) were positive for both examinations; 742 (51.4%) were negative for both examinations. Of all the patients (427) who had a positive finding on barium meal, 27.4% (117) also had a positive finding on cholecystogram. Of all the patients (392) with a positive cholecystogram, 29.8% (117) also had a positive barium meal. Diagnostic yield rose considerably with patient age. It was found that simultaneous barium meal and cholecystogram presented no serious technical difficulties. It was concluded that in patients over 40 years old, this policy improved diagnostic yield as many patients had both gall bladder and upper gastrointestinal pathology. In all other patients this policy markedly reduced the number of hospital visits. Combined simultaneous double-contrast barium meal and cholecystogram is therefore recommended for hospitals which used radiology for the first line investigation of dyspepsia. Also, the general principle of examination of both gall bladder and upper gastrointestinal tract is pertinent where other first line investigations are used.


Solution structure of fatty acid-binding protein from human brain.
Human brain-type fatty acid-binding protein (B-FABP) has been recombinantly expressed in Escherichia coli both unlabelled and 15N-enriched for structure investigation in solution using high-resolution NMR spectroscopy. The sequential assignments of the 1H and 15N resonances were achieved by applying multidimensional homo- and heteronuclear NMR experiments. The ensemble of the 20 final energy-minimized structures, representing human B-FABP in solution, have been calculated based on a total of 2490 meaningful distance constraints. The overall B-FABP structure exhibits the typical backbone conformation described for other members of the FABP family, consisting often antiparallel beta-strands (betaA to betaJ) that form two almost orthogonal beta-sheets, a helix-turn-helix motif that closes the beta-barrel on one side, and a short N-terminal helical loop. A comparison with the crystal structure of the same protein complexed with docosahexaenoic acid reveals only minor differences in both secondary structure and overall topology. Moreover, the NMR data indicate a close structural relationship between human B-FABP and heart-type FABP with respect to fatty acid binding inside the protein cavity.


Evidence for distinct signaling mechanisms in two mammalian olfactory sense organs.
In mammals, olfactory stimuli are detected by sensory neurons at two distinct sites: the olfactory epithelium (OE) of the nasal cavity and the neuroepithelium of the vomeronasal organ (VNO). While the OE can detect volatile chemicals released from numerous sources, the VNO appears to be specialized to detect pheromones that are emitted by other animals and that convey information of behavioral or physiological importance. The mechanisms underlying sensory transduction in the OE have been well studied and a number of components of the transduction cascade have been cloned. Here, we investigated sensory transduction in the VNO by asking whether VNO neurons express molecules that have been implicated in sensory transduction in the OE. Using in situ hybridization and Northern blot analyses, we found that most of the olfactory transduction components examined, including the guanine nucleotide binding protein alpha subunit (G-alpha-olf), adenylyl cyclase type III, and an olfactory cyclic nucleotide-gated (CNG) channel subunit (oCNC1), are not expressed by VNO sensory neurons. In contrast, VNO neurons do express a second olfactory CNG channel subunit (oCNC2). These results indicate that VNO sensory transduction is distinct from that in the OE but raise the possibility that, like OE sensory transduction, sensory transduction in the VNO might involve cyclic nucleotide-gated ion channels.


Transverse mode control in high-contrast grating VCSELs.
This paper presents an extensive numerical analysis of a high-contrast grating VCSEL emitting at 0.98 μm. Using a three-dimensional, fully vectorial optical model, we investigate the influence of a non-uniform grating with a broad range of geometrical parameters on the modal behavior of the VCSEL. Properly designed and optimized, the high-contrast grating confines the fundamental mode selectively in all three dimensions and discriminates all higher order modes by expelling them from its central region. This mechanism makes single mode operation possible under a broad range of currents and could potentially enhance the single-mode output power of such devices. The high-contrast grating design proposed here is the only design for a VCSEL with three-dimensional, selective, optical confinement that requires relatively simple fabrication.


Example of a chaotic crystal: the labyrinth.
Labyrinthine structures often appear as the final steady state of pattern forming systems. Being disordered, they exhibit the same kind of short range positional order as the Newell-Pomeau turbulent crystal. Labyrinths can be seen as a limit case of the texture of disordered rolls with a coherence length of the same order as the wavelength. In the various two-dimensional model equations we looked at, labyrinths and parallel rolls are steady states for the same parameters, their occurrence depending on the initial conditions. Comparing the stability of these two structures, we find that in variational models their energy is very close, rolls always being more stable than labyrinths. For the nonvariational model we propose a numerical experiment which displays a well defined bifurcation from parallel rolls to labyrinths as the more stable state.


Monitoring of Parasite Kinetics in Indian Post-Kala-azar Dermal Leishmaniasis.
The potential reservoirs of leishmaniasis in South Asia include relapsed cases of visceral leishmaniasis (VL), patients with post-kala-azar dermal leishmaniasis (PKDL), and an asymptomatically infected population. Therefore, assessment of cure in terms of parasite clearance, early detection of PKDL, and asymptomatic VL are pivotal for ensuring elimination. This study aimed to monitor the efficacy of miltefosine and liposomal amphotericin B (LAmB) in PKDL based on parasite load. Patients with PKDL were recruited from the dermatology outpatient departments or during active field surveys. Skin biopsies were collected at disease presentation, immediately at the end of treatment, and 6 months later. The presence of parasite DNA was assessed by internal transcribed spacer-1 polymerase chain reaction, and quantified by amplification of parasite kinetoplastid DNA. At disease presentation (n = 184), the median parasite load was 5229 (interquartile range [IQR], 896-50898)/μg genomic DNA (gDNA). Miltefosine cleared the parasites to <10 in the macular (n = 17) and polymorphic (n = 21) variants, and remained so up to 6 months later (<10 parasites). LAmB reduced the parasite burden substantially in macular (n = 34; 2128 [IQR, 544-5763]/µg gDNA) and polymorphic PKDL (n = 36; 2541 [IQR, 650-9073]/µg gDNA). Importantly, in patients who returned 6 months later (n = 38), a resurgence of parasites was evident, as the parasites increased to 5665 (IQR, 1840-17067)/µg gDNA. This study established that quantifying parasite load is an effective approach for monitoring patients with PKDL, wherein miltefosine demonstrated near-total parasite clearance and resolution of symptoms. However, in cases treated with LAmB, the persistence of parasites suggested treatment inadequacy. This needs immediate redressal in view of the leishmaniasis elimination program targeted for 2020.


Human imprinting anomalies in fetal and childhood growth disorders: clinical implications and molecular mechanisms.
Genomic imprinting is among the most important epigenetic mechanisms whereby expression of a subset of genes is restricted to a single parental allele. Loss of imprinting (LOI) through hypo or hyper methylation is involved in various human syndromes. These LOI occur early during development and usually impair growth. Some imprinting syndromes are the consequences of genetic anomalies, such as uniparental disomies (UPD) or copy number variations (deletion or duplications) involving the imprinted domains; others are due to LOI at the imprinting control regions (ICR) regulating each domain. Imprinting disorders are phenotypically heterogeneous, although some share various common clinical features such that diagnosis may be difficult. Multilocus imprinting defects associated with several syndromes have been increasingly reported in recent years, although there are no obvious clinical differences between monolocus and multilocus LOI patients. Subsequently, some rare mutations of transacting factors have been identified in patients with multilocus imprinting defects but they do not explain the majority of the cases; this therefore implies that other factors are involved. By contrast, no mutation of a transacting factor has yet been identified in monolocus LOI. The effect of the environment on the regulation of imprinting is clearly illustrated by studies of assisted reproductive technology (ART). The regulation of imprinting is complex and involves a huge range of genetic and environmental factors; the identification of these factors will undoubtedly help to elucidate the regulation of imprinting and contribute to the understanding of imprinting disorders. This would be beneficial for diagnostics, clinical follow up and the development of treatment guidelines.


First Responders Shape a Prompt and Sharp NF-κB-Mediated Transcriptional Response to TNF-α.
Nuclear factor (NF)-κB controls the transcriptional response to inflammatory signals by translocating into the nucleus, but we lack a single-cell characterization of the resulting transcription dynamics. Here we show that upon tumor necrosis factor (TNF)-α transcription of NF-κB target genes is heterogeneous in individual cells but results in an average nascent transcription profile that is prompt (i.e., occurs almost immediately) and sharp (i.e., increases and decreases rapidly) compared with NF-κB nuclear localization. Using an NF-κB-controlled MS2 reporter we show that the single-cell nascent transcription is more heterogeneous than NF-κB translocation dynamics, with a fraction of synchronized "first responders" that shape the average transcriptional profile and are more prone to respond to multiple TNF-α stimulations. A mathematical model combining NF-κB-mediated gene activation and a gene refractory state is able to reproduce these features. Our work shows how the expression of target genes induced by transcriptional activators can be heterogeneous across single cells and yet time resolved on average.


A severe Morganella morganii endophthalmitis; followed by bacteremia.
Morganella morganii is rarely isolated from nosocomial infections. However, postoperative infections due to Morganella spp. were documented in literature and eye involvements of the infections usually result in severe sequels. We present a severe case infection, which was caused by M. morganii subsp. morganii, firstly appearing as conjunctivitis and complicated by bacteremia. The infectious agent isolated from both conjunctival and consecutive blood cultures. Identification and antimicrobial susceptibility tests were performed with the Vitek 2(®) automated system. The isolate was resistant to cephalosporins and carbapenems and it had ability to produce extended spectrum beta-lactamases. Patient was successfully treated with intravenous ciprofloxacin according to susceptibility test results. This is the first report of M. morganii infection detected as a local infection then complicated by bacteremia.


Laminin and collagen IV distribution and ultrastructure of the basement membrane of the gingiva of the rat incisor.
The continuous growth of the rat incisor is associated with renovation of the junctional epithelium and resorption of the periodontal ligament. The circumdental papilla separates the connective tissue suffering resorption from the rest of the gingiva. Laminin and collagen IV were detected by the immunoperoxidase technique on the basement membrane of all regions of the gingival epithelium of the rat incisor, except the internal basal lamina and the internal surface of the circumdental papilla. The internal basal lamina is formed by a granular electron-dense material, without the organization of a typical basal lamina. Areas of the internal surface of the circumdental papilla, negative for laminin and collagen IV, lack the basal lamina. These data suggest that these molecules are not components of the dento-epithelial junction of the distal surface of the rat incisor. In addition, the basal lamina is absent or fragmented on the internal surface of the circumdental papilla, adjacent to the areas of the connective tissue undergoing resorption.


EphA4 constitutes a population-specific guidance cue for motor neurons.
Motor neurons in the ventral neural tube project axons specifically to their target muscles in the periphery. Although many of the transcription factors that specify motor neuron cell fates have been characterized, less is understood about the mechanisms that guide motor axons to their correct targets. We show that ectopic expression of EphA4 receptor tyrosine kinase alters the trajectories of a specific population of motor axons in the avian hindlimb. Most motor neurons in the medial portion of the lateral motor column (LMC) extend their axons aberrantly in the dorsal nerve trunk at the level of the crural plexus, in the presence of ectopic EphA4. This misrouting of motor axons is not accompanied by alterations in motor neuron identity, settling patterns in the neural tube, or the fasciculation of spinal nerves. However, ectopic EphA4 axons do make errors in pathway selection during sorting in the plexus at the base of the hindlimb. These results suggest that EphA4 in motor neurons acts as a population-specific guidance cue to control the dorsal trajectory of their axons in the hindlimb.


Distribution of suprofen in rats of both sexes.
The tissue distribution of 3H-labeled DL-2-(4-(2-thienylcarbonyl) phenyl) propionic acid (suprofen) after po administration was studied in male, female, and pregnant rats by radiometry. The only tissues with concentrations comparable to plasma levels were those involved in metabolism and excretion (liver and kidney), except for the gastrointestinal tract, and all other tissue levels were very low. In pregnant rats, radioactivity crossed the blood-placenta barrier to a moderate extent and low concentrations were found in fetuses. Radioactivity disappeared from most tissues of male, female, and pregnant rats at rates similar to that from plasma and no appreciable radioactivity was found in rat tissues 24 h after dosing.


Humoral response to SARS-CoV-2 mRNA vaccination in previous non-responder kidney transplant recipients after short-term withdrawal of mycophenolic acid.
Seroconversion rates after COVID-19 vaccination are significantly lower in kidney transplant recipients compared to healthy cohorts. Adaptive immunization strategies are needed to protect these patients from COVID-19. In this prospective observational cohort study, we enrolled 76 kidney transplant recipients with no seroresponse after at least three COVID-19 vaccinations to receive an additional mRNA-1273 vaccination (full dose, 100 μg). Mycophenolic acid was withdrawn in 43 selected patients 5-7 days prior to vaccination and remained paused for 4 additional weeks after vaccination. SARS-CoV-2-specific antibodies and neutralization of the delta and omicron variants were determined using a live-virus assay 4 weeks after vaccination. In patients with temporary mycophenolic acid withdrawal, donor-specific anti-HLA antibodies and donor-derived cell-free DNA were monitored before withdrawal and at follow-up. SARS-CoV-2 specific antibodies significantly increased in kidney transplant recipients after additional COVID-19 vaccination. The effect was most pronounced in individuals in whom mycophenolic acid was withdrawn during vaccination. Higher SARS-CoV-2 specific antibody titers were associated with better neutralization of SARS-CoV-2 delta and omicron variants. In patients with short-term withdrawal of mycophenolic acid, graft function and donor-derived cell-free DNA remained stable. No acute rejection episode occurred during short-term follow-up. However, resurgence of prior anti-HLA donor-specific antibodies was detected in 7 patients.


Stability of implant-abutment interface with a hexagon-mediated butt joint: failure mode and bending resistance.
Clinical data showed that the external hexagon implant system with a gold abutment screw has reduced the problem of screw loosening or fracture. However, the behavior of the implant-abutment joint components with respect to unfavorable bending force is still unclear. This study investigated the joint instability and bending resistance of a single-tooth external hexagon implant system after lateral cyclic loading. Fifteen implant assemblies (Nobel Biocare, Göteborg, Sweden) were divided equally into three groups: A, B, and C. Each assembly consisted of a Brånemark System Mk IV implant (4 x 10 mm) mounted in a brass block, a CeraOne abutment (3 mm), and an experimental cement-retained superstructure. For group A, a centric lateral cyclic load of 50 N was applied for 1.0 x 10(6), whereas for group B, the same load was eccentrically applied for 1.0 x 10(6) cycles. Group C, the control, was not loaded. After cyclic loading, specimens were mounted in a universal testing machine, and the yield and bending strengths were measured (kg). The external hexagon surface texture was examined using a secondary electron microscope. The data were analyzed with one-way analysis of variance and compared by the Tukey test (alpha = .05). For all test specimens, the abutment screw was plastically bent in the unthreaded portion. Group B had a significantly lower mean yield and bending strengths than group C (p = .005 and .010, respectively). Post-cyclic loading photographs showed that group B implants had marked burnishing around the hexagon corners. The bending force abraded both corner areas of the hexagon surface but left the middle area nearly intact for all tested groups. However, group B had the significantly lowest mean abraded area. Within the limits of this study, eccentric rather than centric lateral cyclic loading negatively affected the resistance of the implant-abutment joint to static bending.


Effect of vitamin A supplementation in women of reproductive age on cause-specific early and late infant mortality in rural Ghana: ObaapaVitA double-blind, cluster-randomised, placebo-controlled trial.
Objectives To assess the effect of vitamin A supplementation in women of reproductive age in Ghana on cause- and age-specific infant mortality. In addition, because of recently published studies from Guinea Bissau, effects on infant mortality by sex and season were assessed. Design Double-blind, cluster-randomised, placebo-controlled trial. Setting 7 contiguous districts in the Brong Ahafo region of Ghana. Participants All women of reproductive age (15-45 years) resident in the study area randomised by cluster of residence. All live born infants from 1 June 2003 to 30 September 2008 followed up through 4-weekly home visits. Intervention Weekly low-dose (25 000 IU) vitamin A. Main outcome measures Early infant mortality (1-5 months); late infant mortality (6-11 months); infection-specific infant mortality (0-11 months). Results 1086 clusters, 62 662 live births, 52 574 infant-years and 3268 deaths yielded HRs (95% CIs) comparing weekly vitamin A with placebo: 1.04 (0.88 to 1.05) early infant mortality; 0.99 (0.84 to 1.18) late infant mortality; 1.03 (0.92 to 1.16) infection-specific infant mortality. There was no evidence of modification of the effect of vitamin A supplementation on infant mortality by sex (Wald statistic =0.07, p=0.80) or season (Wald statistic =0.03, p=0.86). Conclusions This is the largest analysis of cause of infant deaths from Africa to date. Weekly vitamin A supplementation in women of reproductive age has no beneficial or deleterious effect on the causes of infant death to age 6 or 12 months in rural Ghana. Trial registration number http://ClinicalTrials.gov: NCT00211341.


Management of persistent bacteremia caused by methicillin-resistant Staphylococcus aureus: a survey of infectious diseases consultants.
We conducted a survey in 2005 of infectious diseases consultants and asked about persistent bacteremia due to methicillin-resistant Staphylococcus aureus. Many consultants perceived an increase in the frequency of illness, and, when presented with vancomycin minimum inhibitory concentrations approaching the limit of the susceptible range, most consultants indicated that they would switch to newer antimicrobial agents for treatment.


7-Hydroxyphthalide: a new natural salicylaldehyde analog from Oulenzia sp. (Astigmata: Winterschmitiidae).
A new salicyl lactone was detected from the unidentified Oulenzia sp. and its chemical structure was elucidated as 7-hydroxyphthalide (7-hydroxy-3H-isobenzofuran-1-one), based on its GC/MS and GC/FT-IR data and SiO2 column behavior. The compound was synthesized by NaBH4 reduction of 3-hydroxyphthalic anhydride. The GC/MS and GC/FT-IR spectra of the natural compound were consistent with those of the synthetic product. Although the compound is known as a medical material, this is the first example of its presence in nature.


Methodology for social accountability: multiple methods and feminist, poststructural, psychoanalytic discourse analysis.
Bridging the gap between the individual and social context, methodology that aims to surface and explore the regulatory function of discourse on subjectivity production moves nursing research beyond the individual level in order to theorize social context and its influence on health and well-being. This article describes the feminist, poststructural, psychoanalytic discourse analysis and multiple methods used in a recent study exploring links between cultural discourses of masculinity, performativity of masculinity, and practices of male violence.


Existence of equilibria in repeated games with long-run payoffs.
SignificanceNash equilibrium, of central importance in strategic game theory, exists in all finite games. Here we prove that it exists also in all infinitely repeated games, with a finite or countably infinite set of players, in which the payoff function is bounded and measurable and the payoff depends only on what is played in the long run, i.e., not on what is played in any fixed finite number of stages. To this end we combine techniques from stochastic games with techniques from alternating-move games with Borel-measurable payoffs.


Strengthen Age Discrimination Protections to Help Confront the Challenge of Population Aging.
A policy imperative in light of population aging in the United States is to increase employment among older workers. However, age discrimination, especially in hiring, can impede efforts to encourage older people to work longer. This commentary reviews evidence on age discrimination and laws prohibiting age discrimination, and discusses recent court rulings that affect the strength of these laws. Based on this review, the commentary proposes a number of policy changes to reduce age discrimination in hiring, including: increasing damages under the Age Discrimination in Employment Act (ADEA) to match the larger damages that some states allow; amending the ADEA to clarify that claims based on statistical differences in the effects of employer policies ("disparate impact claims") are allowed for hiring discrimination, and that the standard for establishing discrimination is not that age was the determining factor in creating the disparity (the "but for" age criterion), rather that it was simply a contributing factor; amending the ADEA to allow intersectional claims regarding age and other group membership - especially regarding discrimination against older women; extending affirmative action for federal contractors to older workers; and considering strengthening the Americans with Disabilities Act (ADA).


Wild rabbits (Oryctolagus cuniculus) as potential carriers of verocytotoxin-producing Escherichia coli.
In summer 2001, visitors to a wildlife park in Norfolk, uk, became infected with verocytotoxin-producing Escherichia coli (vtec) O157, which was associated with wild rabbit faeces. The rabbits lived in an adjacent field together with E coli O157-positive cattle. A pilot study was therefore performed to investigate the factors affecting the association between E coli O157-positive cattle and wild rabbits. Samples of faeces were taken from 16 herds of cattle that lived close to populations of wild rabbits. Analysis by culture and pcr showed that seven of the herds were positive for E coli O157. Faeces were collected from individual rabbits at six of these farms during late winter, when there were few rabbits, and during high summer, when there were many. None of the 32 samples collected on two farms in late winter was positive for E coli O157, but eight of 97 samples collected in summer were positive on four of the six farms. pcr analysis for vtec, including non-O157, showed that 20 of the 97 samples were positive.


Trigger of bronchial hyperresponsiveness development may not always need eosinophilic airway inflammation in very early stage of asthma.
Cough variant asthma (CVA), a suggested precursor of standard bronchial asthma (SBA), is characterized by positive bronchial hyperresponsiveness (BHR) and a chronic cough response to bronchodilator that persists for >8 weeks. Airway inflammation, BHR, and airway obstructive damage were analyzed to assess whether CVA represents early or mild-stage SBA. Patients with newly diagnosed CVA (n = 72) and SBA (n = 84) naive to oral or inhaled corticosteroids and without exacerbated asthma were subjected to spirometry, impulse oscillometry, BHR tests, sputum induction, and fractional exhaled nitric oxide measurements. In the patients with CVA, spirometry demonstrated higher forced expiratory volume in 1 second (FEV1) to forced vital capacity ratio, FEV1 percent predicted, flow volume at 50% of vital capacity % predicted, and flow volume at 25% of vital capacity % predicted values, and impulse oscillometry demonstrated lower R5-Z20, AX, and Fres, and higher X5 values. In addition, the fractional exhaled nitric oxide and sputum eosinophil numbers were lower and the PC20 was higher than in patients with moderate SBA. However, these factors were similar in the patients with CVA and in the patients with intermittent mild SBA. A significantly smaller proportion of the patients with CVA had increased sputum eosinophils than the patients with intermittent mild SBA (p < 0.0001). However, interestingly, among the patients with CVA, no significant differences in the PC20 values were found between the patients with and those without increased sputum eosinophils. All measures of central and peripheral airway obstruction, eosinophilic inflammation, and airway hyperresponsiveness in patients with CVA were milder than in patients with moderate SBA but were similar to those of patients with intermittent mild SBA. In CVA, the BHR was not affected by airway eosinophilic inflammation, which indicated that the very early development of BHR may not always need airway eosinophilic inflammation.


Activity of polymerase proteins of vaccine and wild-type measles virus strains in a minigenome replication assay.
The relative activities of five measles virus (MV) polymerase (L) proteins were compared in an intracellular, plasmid-based replication assay. When coexpressed with N and P proteins from an attenuated strain, L proteins from two attenuated viruses directed the production of up to eight times more reporter protein from an MV minigenome than the three wild-type L proteins. Northern blot analysis demonstrated that the differences in reporter protein production correlated with mRNA transcription levels. Increased activity of polymerases from attenuated viruses equally affected mRNA transcription and minigenome replication. The higher level of transcription may be a consequence of increased template availability or may be an independent effect of the elevated activity of the attenuated polymerases. Coexpression of wild-type L proteins with homologous N and P proteins did not affect the activity of the wild-type polymerases, indicating that the differential activity was a function of the L proteins alone. Use of a minigenome that incorporated two nucleotide changes found in the genomic leader of the three wild-type viruses did not raise the activity of the wild-type L proteins. These data demonstrate that increased polymerase activity differentiates attenuated from wild-type viruses and suggest that functions involved in RNA synthesis contribute to the attenuated phenotype of MV vaccine strains.


Physician perspectives on delays in cancer diagnosis in Alberta: a qualitative study.
Delays in cancer diagnosis have been associated with reduced survival, decreased quality of life after treatment, and suboptimal patient experience. The objective of the study was to explore the perspectives of a group of family physicians and other specialists regarding potentially avoidable delays in diagnosing cancer, and approaches that may help expedite the process. We conducted a qualitative study using interviews with physicians practising in primary and outpatient care settings in Alberta between July and September 2019. We recruited family physicians and specialists who were in a position to discuss delays in cancer diagnosis by email via the Cancer Strategic Clinical Network and the Alberta Medical Association. We conducted semistructured interviews over the phone, and analyzed data using thematic analysis. Eleven family physicians and 22 other specialists (including 7 surgeons or surgical oncologists, 3 pathologists, 3 radiologists, 2 emergency physicians and 2 hematologists) participated in interviews; 22 were male (66.7%). We identified 4 main themes describing 9 factors contributing to potentially avoidable delays in diagnosis, namely the nature of primary care, initial presentation, investigation, and specialist advice and referral. We also identified 1 theme describing 3 suggestions for improvement, including system integration, standardized care pathways and a centralized advice, triage and referral support service for family physicians. These findings suggest the need for enhanced support for family physicians, and better integration of primary and specialty care before cancer diagnosis. A multifaceted and coordinated approach to streamlining cancer diagnosis is required, with the goals of enhancing patient outcomes, reducing physician frustration and optimizing efficiency.


Strain-induced generation of silicon nanopillars.
Silicon metal-assisted chemical etching (MACE) is a nanostructuring technique exploiting the enhancement of the silicon etch rate at some metal-silicon interfaces. Compared to more traditional approaches, MACE is a high-throughput technique, and it is one of the few that enables the growth of vertical 1D structures of virtually unlimited length. As such, it has already found relevant technological applications in fields ranging from energy conversion to biosensing. Yet, its implementation has always required metal patterning to obtain nanopillars. Here, we report how MACE may lead to the formation of porous silicon nanopillars even in the absence of gold patterning. We show how the use of inhomogeneous yet continuous gold layers leads to the generation of a stress field causing spontaneous local delamination of the metal-and to the formation of silicon nanopillars where the metal disruption occurs. We observed the spontaneous formation of nanopillars with diameters ranging from 40 to 65 nm and heights up to 1 μm. Strain-controlled generation of nanopillars is consistent with a mechanism of silicon oxidation by hole injection through the metal layer. Spontaneous nanopillar formation could enable applications of this method to contexts where ordered distributions of nanopillars are not required, while patterning by high-resolution techniques is either impractical or unaffordable.


Complex regulation of nucleoside transporter expression in epithelial and immune system cells.
Nucleoside transporters have a variety of functions in the cell, such as the provision of substrates for nucleic acid synthesis and the modulation of purine receptors by determining agonist availability. They also transport a wide range of nucleoside-derived antiviral and anticancer drugs. Most mammalian cells co-express several nucleoside transporter isoforms at the plasma membrane, which are differentially regulated. This paper reviews studies on nucleoside transporter regulation, which has been extensively characterized in the laboratory in several model systems: the hepatocyte, an epithelial cell type, and immune system cells, in particular B cells, which are non-polarized and highly specialized. The hepatocyte co-expresses at least two Na+-dependent nucleoside transporters, CNT1 and CNT2, which are up-regulated during cell proliferation but may undergo selective loss in certain experimental models of hepatocarcinomas. This feature is consistent with evidence that CNT expression also depends on the differentiation status of the hepatocyte. Moreover, substrate availability also modulates CNT expression in epithelial cells, as reported for hepatocytes and jejunum epithelia from rats fed nucleotide-deprived diets. In human B cell lines, CNT and ENT transporters are co-expressed but differentially regulated after B cell activation triggered by cytokines or phorbol esters, as described for murine bone marrow macrophages induced either to activate or to proliferate. The complex regulation of the expression and activity of nucleoside transporters hints at their relevance in cell physiology.


SPA: a probabilistic algorithm for spliced alignment.
Recent large-scale cDNA sequencing efforts show that elaborate patterns of splice variation are responsible for much of the proteome diversity in higher eukaryotes. To obtain an accurate account of the repertoire of splice variants, and to gain insight into the mechanisms of alternative splicing, it is essential that cDNAs are very accurately mapped to their respective genomes. Currently available algorithms for cDNA-to-genome alignment do not reach the necessary level of accuracy because they use ad hoc scoring models that cannot correctly trade off the likelihoods of various sequencing errors against the probabilities of different gene structures. Here we develop a Bayesian probabilistic approach to cDNA-to-genome alignment. Gene structures are assigned prior probabilities based on the lengths of their introns and exons, and based on the sequences at their splice boundaries. A likelihood model for sequencing errors takes into account the rates at which misincorporation, as well as insertions and deletions of different lengths, occurs during sequencing. The parameters of both the prior and likelihood model can be automatically estimated from a set of cDNAs, thus enabling our method to adapt itself to different organisms and experimental procedures. We implemented our method in a fast cDNA-to-genome alignment program, SPA, and applied it to the FANTOM3 dataset of over 100,000 full-length mouse cDNAs and a dataset of over 20,000 full-length human cDNAs. Comparison with the results of four other mapping programs shows that SPA produces alignments of significantly higher quality. In particular, the quality of the SPA alignments near splice boundaries and SPA's mapping of the 5' and 3' ends of the cDNAs are highly improved, allowing for more accurate identification of transcript starts and ends, and accurate identification of subtle splice variations. Finally, our splice boundary analysis on the human dataset suggests the existence of a novel non-canonical splice site that we also find in the mouse dataset. The SPA software package is available at http://www.biozentrum.unibas.ch/personal/nimwegen/cgi-bin/spa.cgi.


Susceptibility of mouse minute virus to inactivation by heat in two cell culture media types.
Viral contaminations of biopharmaceutical manufacturing cell culture facilities are a significant threat and one for which having a risk mitigation strategy is highly desirable. High temperature, short time (HTST) mammalian cell media treatment may potentially safeguard manufacturing facilities from such contaminations. HTST is thought to inactivate virions by denaturing proteins of the viral capsid, and there is evidence that HTST provides ample virucidal efficacy against nonenveloped or naked viruses such as mouse minute virus (MMV), a parvovirus. The aim of the studies presented herein was to further delineate the susceptibility of MMV, known to have contaminated mammalian cell manufacturing facilities, to heat by exposing virus-spiked cell culture media to a broad range of temperatures and for various times of exposure. The results of these studies show that HTST is capable of inactivating MMV by three orders of magnitude or more. Thus, we believe that HTST is a useful technology for the purposes of providing a barrier to adventitious contamination of mammalian cell culture processes in the biopharmaceutical industry.


[Clinical statistics of outpatients investigated for asbestos-related lung diseases at a general hospital in Tokyo].
We evaluated 122 outpatients who visited our hospital for examination of asbestos-related diseases between November, 2005 and October, 2006. Patients were divided into three groups; occupational exposure, non-occupational exposure and non-exposure groups. The occupational exposure group showed a significantly higher rate of asbestos-related abnormal findings than the non-occupational exposure plus the non-exposure group (33% vs. 5%, respectively; P = 0.001). Pleural plaque was the most common abnormal finding related to asbestos. Only four of 24 patients with pleural plaques could obtain personal health records for workers enjoyed in dangerous work, whereas the rest of them were not able to mainly because they were self-employed. A health support system is necessary to also cover non-employees.


Early intervention for children with or at risk of cerebral palsy.
Quantitative and qualitative analyses of well-conducted scientific studies of therapeutic early intervention for infants and young children with or at risk of a motor handicap failed to find convincing evidence for the efficacy of physical therapy. The shortcomings of present assessment tools are discussed and possible lines of enquiry identified.


A case report on granular cell ameloblastoma - A rare histological entity.
Granular cell ameloblastoma is a rare condition, accounting for 3.5% of all ameloblastoma cases that shows marked transformation in the cytoplasm of tumor cells, which are usually stellate reticulum-like cells. The transformed cells possess very coarse, granular eosinophilic cytoplasm. Granular cell ameloblastoma is aggressive in nature with a marked propensity for recurrence and can progress to metastasis. This article discusses a case report of a 35-year-old female patient diagnosed with granular cell ameloblastoma of the right mandible.


Rapid decrease in delivery of chemotherapy to tumors after anti-VEGF therapy: implications for scheduling of anti-angiogenic drugs.
Current strategies combining anti-angiogenic drugs with chemotherapy provide clinical benefit in cancer patients. It is assumed that anti-angiogenic drugs, such as bevacizumab, transiently normalize abnormal tumor vasculature and contribute to improved delivery of subsequent chemotherapy. To investigate this concept, a study was performed in non-small cell lung cancer (NSCLC) patients using positron emission tomography (PET) and radiolabeled docetaxel ([(11)C]docetaxel). In NSCLC, bevacizumab reduced both perfusion and net influx rate of [(11)C]docetaxel within 5 hr. These effects persisted after 4 days. The clinical relevance of these findings is notable, as there was no evidence for a substantial improvement in drug delivery to tumors. These findings highlight the importance of drug scheduling and advocate further studies to optimize scheduling of anti-angiogenic drugs.


[Health practitioners' evaluation system on risks of contracting cancer due to environmental].
The increase in the number of cancers sprouting from man-made environmental risk factors calls for prevention policies strictly centered on the basis of a fact-sharing and transparent, evidence-based knowledge exchange. However, the related areas which are concerned are quite diverse, and given that the risks are of a cumulative nature, they are very difficult to measure. The information system therefore is complex and infinite. A qualitative study was carried out on the representations held by a variety of specialists who have potential links to the public or groups who might be exposed or at risk, including health professionals, engineers, and NGO and association managers and supervisors. The investigation was based upon a questionnaire which was developed with the assistance and participation of those involved in the management of information regarding professional, ecological or other kinds of risks. This method allowed for the study to favour and objectively prioritise the vision of the health professionals who were interviewed. The results show that the depictions vary depending on how and to what extent the different categories of professionals are involved, and that they reflect for the most part society's fears.


Management of catastrophic haemorrhage in palliative head and neck cancer: creation of a new protocol using simulation.
Catastrophic haemorrhage or carotid blowout a rare but devastating consequence of head and neck cancer. In most cases, this represents a terminal event, and the patient is prescribed pre-emptive analgesia and anxiolytics. There is anecdotal evidence that due to the time taken to prepare the medications that patients do not receive these drugs prior to death. We aimed to identify the drug to patient time using simulated catastrophic haemorrhage simulations. We used the current protocol for this and also proposed a new grab-bag with preprepared anxiolytic and anagelsic medications. Each scenario was repeated 16 times. The mean time for drug administration using the current policy was 124 s compared with 48 s when the grab-bag was used (p<0.01). The new protocol also reduced the variability in the drug to patient time. We aim to implement this new protocol on the head and neck ward.


Systematic Review of En Bloc Resection in the Management of Ewing's Sarcoma of the Mobile Spine with Respect to Local Control and Disease-Free Survival.
There is no consensus on the optimal method of local control in Ewing's sarcoma (ES) of the mobile spine. Recent reports have suggested that en bloc resection may improve local control and survival. The authors therefore performed a systematic review to answer the following questions: (1) What is the outcome of en bloc resection for ES of the mobile spine with respect to local control and disease-free survival (DFS)? (2) How should residual ES of the mobile spine be treated?Inclusion criteria were articles published between the years 1960 and 2014 in English that contained more than five patients. This yielded 204 articles, from which 4 were selected for detailed analysis. The literature was graded for quality, summarized, and presented to a group of spinal oncology experts with consensus recommendations made.All 4 studies were retrospective case series graded as very low quality evidence. Local control strategies included radiotherapy (RT) alone, surgery and RT, or surgery alone. There was no standardized outcome reported across studies with respect to the type of surgical procedure, margins, and outcomes of interest such as local recurrence (LR) and DFS. When the en bloc procedures were pooled together, 2 of the 21 patients with available LR data developed LR (9.5%), and 5 of the 7 patients with available DFS data were disease free at a mean of 76 months. The remaining 2 died at 10 and 29 months, respectively. No studies were identified detailing the treatment of residual ES of the mobile spine.There is no consensus on the optimal method of local control for spinal ES or the treatment of residual disease. A weak recommendation supports that when the en bloc resection is technically possible, in combination with RT, this appears to provide superior local control than RT alone, or incomplete excision and RT. The effect on survival is indeterminate.


Glutamate synthesis via photoreduction of NADP+ by photostable chlorophyllide coupled with polyethylene-glycol.
Chlorophyllide a was coupled with alpha-(3-aminopropyl)-omega-methoxypoly(oxyethylene) (PEG-NH2) to form a PEG-chlorophyllide conjugate through an acid-amide bond. The conjugate catalyzed the reduction of methylviologen in the presence of 2-mercaptoethanol. It also catalyzed the photoreduction of NADP+ or NAD+ in the presence of ascorbate as an electron donor and ferredoxin-NADP+ reductase as the coupling enzyme. Utilizing the reducing power of NADPH generated by PEG-chlorophyllide conjugate under illumination, glutamate was synthesized from 2-oxoglutarate and NH4+ in the presence of glutamate dehydrogenase. PEG-chlorophyllide conjugate was quite stable toward light illumination compared with chlorophyll a. The increase in the molecular weight of PEG in the PEG-chlorophyllide conjugates was accompanied by the enhancement of photostability of the conjugate and also by the increased solubility in the aqueous solution.


High current H2(+) and H3(+) beam generation by pulsed 2.45 GHz electron cyclotron resonance ion source.
The permanent magnet 2.45 GHz electron cyclotron resonance ion source at Peking University can produce more than 100 mA hydrogen ion beam working at pulsed mode. For the increasing requirements of cluster ions (H2(+) and H3(+)) in linac and cyclotron, experimental study was carried out to further understand the hydrogen plasma processes in the ion source for the generation of cluster ions. The constituents of extracted beam have been analyzed varying with the pulsed duration from 0.3 ms to 2.0 ms (repetition frequency 100 Hz) at different operation pressure. The fraction of cluster ions dramatically increased when the pulsed duration was lower than 0.6 ms, and more than 20 mA pure H3(+) ions with fraction 43.2% and 40 mA H2(+) ions with fraction 47.7% were obtained when the operation parameters were adequate. The dependence of extracted ion fraction on microwave power was also measured at different pressure as the energy absorbed by plasma will greatly influence electron temperature and electron density then the plasma processes in the ion source. More details will be presented in this paper.


Records of Coendouichillus (Rodentia, Erethizontidae) from the Lower Urubamba Region of Peru.
Coendouichillus was first described in 2001 by Voss and da Silva, with a range from Amazonian Ecuador to Iquitos, Peru. Here, we describe an adult female Coendouichillus specimen collected in a Tomahawk trap in the forest canopy of the Lower Urubamba Region of Peru in October 2013. We also describe pathologies and behaviors observed through 379 camera trapping photo events (2,196 photos) gathered in natural canopy bridges over the course of a year (7,198 trap nights), including information on activity period over the course of the day and over the course of the lunar cycle. We conservatively estimate that 17 individuals were photographed, including one juvenile. Being 900 km away from Iquitos, Peru (the site of the closest record), discovery of this species in the Lower Urubamba constitutes a significant range extension.


Experience with a double loop guiding catheter for angioplasty of the right coronary artery.
An 8 French (F) double loop guiding (DLG) catheter was developed for percutaneous transluminal coronary angioplasty (PTCA) of the right coronary artery (RCA) and tested in 80 patients: primary use in 59 patients, and after failure of an 8 F right Judkins guiding (RJG) catheter in 21 patients. Primary use resulted in stable intubation of RCA in 55 patients (93%), but PTCA was successful in 50 (91%). Five failures resulted from inability to cross or dilate the lesion. After failure of an 8 F RJG in 21 patients, successful stable intubation of RCA with a DLG was achieved in 19 patients (90%), but PTCA was successful in 17 patients (81%). Failure of RJGs in 21 patients resulted from inability to intubate the RCA in 12 patients, or inadequate back up support by the guiding in 9 patients. DLGs increased the success rate of PTCA of the RCA after failure of RJGs.


Short-term treatment with troglitazone decreases bone turnover in patients with type 2 diabetes mellitus.
Poorly controlled type 2 or non-insulin dependent diabetes mellitus (NIDDM) patients exhibit high bone turnover, which decelerate with treatment according to the degree of improvement in glycemic control. In adults, higher bone turnover results in rapid bone loss. Therefore, deceleration of bone turnover is beneficial for bone. Troglitazone (Tro), a new anti-diabetic drug, is a thiazolidinedione (TZD) which promotes adipocyte differentiation by activating peroxisome proliferator activated receptor gamma (PPARgamma). Because, in the bone marrow, adipocytes and osteoblasts originate in common mesenchymal stem cells that are also essential for osteoclastogenesis, TZDs may directly affect bone metabolism. Thus, we examined the effects of Tro on metabolic bone markers in type 2 DM patients. Tro (400 mg/day) was administered to 33 type 2 DM patients for four weeks. The day before and four weeks after starting Tro, serum and urine samples were collected after overnight fasting. Metabolic bone markers and glycemic indices were assessed. As bone resorption markers, urinary free and total deoxypyridinoline as well as urinary collagen type I C-terminal telopeptide were measured; as bone formation markers, serum bone type and total alkaline phosphatase (BALP and ALP) levels along with osteocalcin (OC) were used. No significant changes in fasting plasma glucose or HbA1c levels were observed in our short-term treatment with Tro. All the bone resorption markers, BALP and ALP were significantly decreased. OC was not significantly changed. The discrepant changes of OC from all the other metabolic bone markers suggest limitation of the use of OC as a reliable bone formation marker in diabetics. Our results that Tro decreased metabolic bone markers before significantly improving glucose metabolism suggest that it has direct effects on bone and decreased bone turnover. TZDs may spare bone mass in NIDDM subjects through its dual effects on glucose and bone metabolism.


Early-onset Parkinson's disease caused by a novel parkin mutation in a genetic isolate from north-eastern Brazil.
We describe clinical and molecular findings in a genetic isolate from north-eastern Brazil with early-onset Parkinson's disease (PD) and a novel mutation in the parkin gene. Genealogical studies could connect 255 individuals, of whom 15 had PD. Geographic isolation and multiple consanguineous marriages initially suggested an autosomal recessive inheritance for PD in these patients. The available individuals were personally examined, and DNA was obtained from 26 members: ten early-onset PD patients, one case with likely neuroleptic-induced parkinsonism and 15 unaffected relatives. The average age at onset of PD symptoms was 30.8 years (range 12-46). Haplotype analysis revealed homozygosity in the PD patients for markers across the PARK2 locus. Genomic sequencing identified a novel homozygous splice-site parkin mutation (IVS1 + 1G/T), which completely co-segregated with the early-onset PD phenotype. cDNA analysis confirmed the total loss of parkin transcript in homozygous mutation carriers, delineating this as a loss-of-function mutation. The case with neuroleptic-induced parkinsonism and 13 of 15 healthy relatives were heterozygous carriers of the mutation. The absence of PD in heterozygous carriers indicates a genuinely recessive nature of this mutation, suggesting that parkin haploinsufficiency is not a relevant risk factor for early- or late-onset PD. However, parkin haploinsufficiency could facilitate the emergence of neuroleptic-induced parkinsonism. The cluster reported here, which to our knowledge is the largest described to date with early-onset PD and parkin mutations, also offers a unique opportunity for the search of modifiers of the parkin-related disease.


Global prevalence of injecting drug use and sociodemographic characteristics and prevalence of HIV, HBV, and HCV in people who inject drugs: a multistage systematic review.
Sharing of equipment used for injecting drug use (IDU) is a substantial cause of disease burden and a contributor to blood-borne virus transmission. We did a global multistage systematic review to identify the prevalence of IDU among people aged 15-64 years; sociodemographic characteristics of and risk factors for people who inject drugs (PWID); and the prevalence of HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) among PWID. Consistent with the GATHER and PRISMA guidelines and without language restrictions, we systematically searched peer-reviewed databases (MEDLINE, Embase, and PsycINFO; articles published since 2008, latest searches in June, 2017), searched the grey literature (websites and databases, searches between April and August, 2016), and disseminated data requests to international experts and agencies (requests sent in October, 2016). We searched for data on IDU prevalence, characteristics of PWID, including gender, age, and sociodemographic and risk characteristics, and the prevalence of HIV, HCV, and HBV among PWID. Eligible data on prevalence of IDU, HIV antibody, HBsAg, and HCV antibody among PWID were selected and, where multiple estimates were available, pooled for each country via random effects meta-analysis. So too were eligible data on percentage of PWID who were female; younger than 25 years; recently homeless; ever arrested; ever incarcerated; who had recently engaged in sex work, sexual risk, or injecting risk; and whose main drugs injected were opioids or stimulants. We generated regional and global estimates in line with previous global reviews. We reviewed 55 671 papers and reports, and extracted data from 1147 eligible records. Evidence of IDU was recorded in 179 of 206 countries or territories, which cover 99% of the population aged 15-64 years, an increase of 31 countries (mostly in sub-Saharan Africa and the Pacific Islands) since a review in 2008. IDU prevalence estimates were identified in 83 countries. We estimate that there are 15·6 million (95% uncertainty interval [UI] 10·2-23·7 million) PWID aged 15-64 years globally, with 3·2 million (1·6-5·1 million) women and 12·5 million (7·5-18·4 million) men. Gender composition varied by location: women were estimated to comprise 30·0% (95% UI 28·5-31·5) of PWID in North America and 33·4% (31·0-35·6) in Australasia, compared with 3·1% (2·1-4·1) in south Asia. Globally, we estimate that 17·8% (10·8-24·8) of PWID are living with HIV, 52·3% (42·4-62·1) are HCV-antibody positive, and 9·0% (5·1-13·2) are HBV surface antigen positive; there is substantial geographic variation in these levels. Globally, we estimate 82·9% (76·6-88·9) of PWID mainly inject opioids and 33·0% (24·3-42·0) mainly inject stimulants. We estimate that 27·9% (20·9-36·8) of PWID globally are younger than 25 years, 21·7% (15·8-27·9) had recently (within the past year) experienced homelessness or unstable housing, and 57·9% (50·5-65·2) had a history of incarceration. We identified evidence of IDU in more countries than in 2008, with the new countries largely consisting of low-income and middle-income countries in Africa. Across all countries, a substantial number of PWID are living with HIV and HCV and are exposed to multiple adverse risk environments that increase health harms. Australian National Drug and Alcohol Research Centre, Australian National Health and Medical Research Council, Open Society Foundation, World Health Organization, the Global Fund, and UNAIDS.


Hemocitical responses to environmental stress in invertebrates: a review.
Although invertebrates are recognized by the great facility to accumulate pollutants present in their environment and many of them are used as sentinel species in biomonitoring studies, little is known about the impact of toxicants on the immune system of these animals. In this regard, hemocytes play a fundamental role: these cells circulate freely through the hemolymph of invertebrates and act on the recognition of foreign material to the organism, mediating and effecting the cellular defense, such as phagocytosis, nodulation, and encapsulation. Different morphological types can be recognized but still there is controversy among the researchers about the exact classification of the hemocytes due to the diversity of techniques for the preservation and observation of these cells. In the present study, a review on the main hemocyte responses to environmental stress in different invertebrate organisms is presented, emphasizing the contamination by heavy metals. It is discussed parameters such as: alteration in the number of cells involved in the defense reaction, phagocytic activity, lysosomal responses, and production of reactive oxygen species.


Development of a novel spontaneous metastasis model of human osteosarcoma transplanted orthotopically into bone of athymic mice.
There is a pressing need for in vivo models in which potential antitumor agents can be tested for their ability to inhibit the growth and metastatic spread of human sarcomas. A recent advance in this regard has been the development of a v-Ki-ras-oncogene-transformed human osteosarcoma cell line (KRIB) that efficiently colonizes the lungs of athymic nude mice when cells (1 x 10(5)) are administered by i.v. injection. In the present study, we have utilized this cell line to develop a spontaneous metastasis model in which a small number of tumor cells are injected into the tibial bones of athymic mice. When as few as 1000 KRIB cells are orthotopically implanted into the tibial bones of nude mice, bone tumors, which are radiographically and histologically similar to primary human osteosarcoma, develop within 4 weeks. Furthermore, as in the human disease, cells from these primary tumors subsequently seed the animals' lungs, resulting in reproducible and quantifiable pulmonary metastasis evident both upon gross inspection of the lungs and histologically 6 weeks after tumor inoculation. Surgical amputation of the tumor inoculation site up to 2 weeks after tumor injection prevents pulmonary metastasis, indicating that substantial local (tibial) growth and invasion of the primary tumor for at least 2 weeks is required for subsequent metastasis. Implantation of s.c. 5000 KRIB cells fails to produce local or metastatic tumors. We anticipate that this model will prove to be a powerful tool with which to study the mechanisms of human osteosarcoma growth and pulmonary metastasis, and to assess the efficacy of promising therapeutic agents.


Virtual autopsy in hanging.
The aim of the study was to compare postmortem computed tomographic (CT) imaging findings from a case of hanging with the autopsy findings. The CT showed a good match with autopsy findings especially for bone, soft tissue, and spinal injuries. The CT images of the injuries of the neck obtained by CT scan clearly showed the ligature mark, the hemorrhagic suffusion in the soft tissue (thickening of derma) and in the muscles (sternocleidomastoid) of the neck. Furthermore, CT 3-dimensional reconstruction showed brain edema, fracture of the left posterior horn of the hyoid bone, and a grade 1 retrolisthesis of C5 on C6. This last finding was not detected by autopsy because of the anterior approach that is frequently used in necropsy technique. Nevertheless, the CT virtual autopsy did not show vascular findings (like Amussat mark) because a barium mixture was not injected in the body.


Chemical Composition and Antioxidant Activities of Polysaccharides from Yingshan Cloud Mist Tea.
The study was designed to investigate the chemical composition and antioxidant activities of polysaccharides from Yingshan Cloud Mist Tea. The chemical composition of green tea polysaccharides (GTPS) was analyzed by Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscope (SEM), thermogravimetric (TGA), gas chromatograph (GC), and high-performance gel-permeation chromatography (HPGPC). Then, the antioxidant activities in vitro of GTPS, effects of GTPS on body weight, and the antioxidant activities in chickens were studied. The results showed that GTPS were composed of rhamnose (Rha), arabinose (Ara), xylose (Xyl), mannose (Man), glucose (Glu), and galactose (Gal) in a molar ratio of 11.4 : 26.1 : 1.9 : 3.0 : 30.7 : 26.8 and the average molecular weight was 9.69 × 104 Da. Furthermore, GTPS exhibited obvious capacity of scavenging DPPH radical, hydroxyl radical, and superoxide radical and enhanced the ferric-reducing power in vitro. Last, GTPS significantly increased the body weight of chickens, enhanced the T-AOC, SOD, and GSH-Px level, and decreased the content of MDA in chickens. The results indicated that GTPS might be a kind of natural antioxidant, which had the potential application in feed industry.


Brachyury expression in tailless Molgulid ascidian embryos.
The T-box transcription factor gene Brachyury is important for the differentiation of notochord in all chordates, including the ascidians Halocynthia roretzi and Ciona intestinalis. We isolated Brachyury from molgulid ascidians, which have evolved tailless larvae multiple times independently, and found the genes appear functional by cDNA sequence analyses. We then compared the expression of Mocu-Bra in tailed Molgula oculata embryos to two tailless species, Molgula occulta (Mocc-Bra) and Molgula tectiformis (Mt-Bra). Here we show that both tailless species express Brachyury in the notochord lineage during embryogenesis. Initial expression of Mocu-Bra is normal in tailed M. oculata embryos; 10 precursor notochord cells divide twice to result in 40 notochord cells that converge and extend to make a notochord down the center of the tail. In contrast, in tailless Molgula occulta, Mocc-Bra expression disappears prematurely, and there is only one round of division, resulting in 20 cells in the final notochord lineage that never converge or extend. In M. occulta x M. oculata hybrid embryos, expression of Mocu-Bra is prolonged, and the embryos form a tail with 20 notochord cells that converge and extend normally. However, in Molgula tectiformis, a different tailless ascidian, Mt-Bra was expressed only in the 10 notochord precursor cells, which never divide, converge, or extend. In summary, neither Brachyury function nor the early establishment of the notochord lineage appears to be impaired in tailless embryos. In light of these results, we are continuing to investigate how and why notochord development is lost in tailless molgulid ascidian embryos.


Effect of gender on main clinical chemistry parameters in aged rats.
Clinical laboratory data are crucially important for the diagnosis, prognosis and therapy of aging-related diseases. The age-dependent changes in the findings of routine clinical-chemistry analyses may influence the evaluation of health status of the elderly people. Serum endogenous antioxidant levels and lipid profiles are considered to be related to the progress of age-related diseases. Analyses of these routine parameters are also important for the evaluation in the elderly. Although the analyses of serum biochemical parameters are important, there have been not enough data on changes in the levels of parameters with aging in both genders. However, elderly people generally suffer from aging-related diseases or may be using some medication that interferes with the accuracy of the result; it is thus preferred that the same procedures be applied in aged rats as a model of human aging. Aged Sprague-Dawley rats (24 months) of both genders were used in the current study. Serum total protein, albumin, bilirubin, uric acid, lipid profiles, iron, and total iron-binding capacity levels were determined on the same day of collection by standard clinical chemistry laboratory methods. Serum endogenous antioxidant parameters such as uric acid and bilirubin levels varied with gender in spite of almost no changes in the serum albumin and total iron binding capacity levels. Among the main parameters studied, lipid profile, conjugated bilirubin, and uric acid levels of male rats were significantly higher than in the aged female group. On the other hand, serum unconjugated bilirubin and iron levels were all found to be lower in the aged male group. Our findings support our conviction that serum biochemical parameters of aged rats have a controlling role in differing regulating mechanisms through gender differences. The gender-related data on these main serum clinical chemistry parameters in aged rats would be useful in studies of aging-related disorders using this model.


Alcohol expectancies and sexuality: a self-fulfilling prophecy analysis of dyadic perceptions and behavior.
We evaluated the self-fulfilling prophecy hypothesis that belief in an "alcohol enhances/stimulates sex" expectancy fosters heightened sexual behavior-via effects on intermediate sexual perceptions. To test this notion, we investigated the effects of self-reported alcohol expectancies, alcohol expectancy set and a co-participant's gender and apparent drinking status on dyadic viewing of erotica. Sex-related alcohol expectancies were assessed in 100 male moderate social drinkers. In a subsequent session, participants were led to believe they were consuming either alcoholic or nonalcoholic drinks. No alcohol was actually administered. Each participant rated his sexual arousal, rated an alcohol-drinking or nondrinking co-participant on sexual disinhibition and then viewed erotic slides with the co-participant. Slide viewing times were assessed unobtrusively. Path analysis revealed support for the self-fulfilling prophecy hypothesis: Expectancy score (moderated by alcohol expectancy set) heightened viewing indirectly via effects on sexual arousal (beta = .26) and perceived disinhibition (beta = .25). Sexual arousal in turn predicted perceived disinhibition (beta = .37), which in turn predicted viewing (beta = .23). Co-participant drinking had direct (beta = .21) and indirect (beta = .40 via perceived disinhibition) effects on viewing. Alcohol expectancy variables-apart from alcohol-interactively determined men's responding in a dyadic sexual situation. Consistent with psychosocial formulations, predrinking expectancy steered postdrinking perceptions along an expectancy-congruent course to shape subsequent behavior. Thus, alcohol's role in stimulating men's sexual responding cannot be construed as occurring through a strictly pharmacological mechanism. Speculations about the comparative domains of expectancy versus alcohol explanations are discussed.


Influence of supplemental endoglucanase or xylanase on volatile fatty acid production from ruminant feed by ruminal in vitro cultures.
This study employed two commercial enzyme preparations to examine the effects of endoglucanase, xylanase or their combination on in vitro volatile fatty acid (VFA) production by ruminal microbial populations. Batch ruminal cultures were established with one of various feedstuffs or with a fescue hay-based diet and ruminal fluid from a heifer fed a 40% forage:60% concentrate diet. Addition of xylanase at 135 xylanase units (XU) per ml increased total VFA production from the fescue hay-based diet (44.3 vs. 57.2 mM, p < 0.05) without changing the acetate to propionate (A:P) ratio. Addition of endoglucanase at 2, 3, 4, and 5 carboxymethyl cellulase units (CMCU) per ml increased total VFA production from the fescue hay-based diet on average by 36% (p < 0.05). Addition of 3, 4 and 5 CMCU/ml also decreased (p < 0.05) the A:P ratio. The combined addition of xylanase (135 XU/ml) and endoglucanase (5 CMCU/ml) increased total VFA production from the fescue hay-based diet (40.9 vs. 61.5 mM, p < 0.05) and reduced the A:P ratio (3.4 vs. 1.5, p < 0.05). The effects of endoglucanase and xylanase supplementation on in vitro VFA production varied across the various substrates used. However, endoglucanase supplementation consistently reduced the A:P ratio with all substrates tested. The effects of the enzyme combination were generally greater than either enzyme alone. We conclude that endoglucanase and xylanase activities differ in their ability to affect ruminal VFA production, and endoglucanase but not xylanase, may improve fermentation efficiency by reducing the A:P ratio.


Specificity and functional interplay between influenza virus PA-X and NS1 shutoff activity.
Influenza A viruses modulate host antiviral responses to promote viral growth and pathogenicity. Through viral PA-X and NS1 proteins, the virus is capable of suppressing host protein synthesis, termed "host shutoff." Although both proteins are known to induce general shutoff, specificity of target genes and their functional interplay in mediating host shutoff are not fully elucidated. In this study, we generated four recombinant influenza A/California/04/2009 (pH1N1) viruses containing mutations affecting the expression of active PA-X and NS1. We analyzed viral growth, general shutoff activity, specificity of mRNA targets, and viral gene expressions. Our results showed that PA-X was the major contributor in reducing general host protein expression in the virus-infected cells. Intriguingly, our transcriptomic analysis from infected human airway A549 cells indicate that shutoff-active NS1 specifically targeted host mRNAs related to interferon (IFN) signaling pathways and cytokine release. Specificity of target mRNAs was less evident in PA-X, although it preferentially degraded genes associated with cellular protein metabolism and protein repair. Interestingly, in the presence of shutoff-active NS1, PA-X also degraded viral mRNAs, especially NS segments. The virus expressing shutoff-active NS1 with reduced amount of PA-X expression most efficiently suppressed antiviral and innate immune responses in human cells, indicating that influenza virus needs to optimize the contribution of these two shutoff proteins to circumvent host responses for its optimum growth.


Research misconduct complaints and institutional logics: The case of Hans Eysenck and the British Psychological Society.
A formal complaint was lodged with the British Psychological Society in 1995 that alleged serious scientific misconduct by Hans J Eysenck. The complaint referred to research into the links between personality traits and the causes, prevention and treatment of cancer and heart disease. Using a framework of institutional logics, we criticise the Society's decision not to hear this complaint at a full disciplinary hearing. We urge the BPS to investigate this complaint afresh. We also support calls for the establishment of an independent National Research Integrity Ombudsperson to deal more effectively with allegations of research misconduct.


Enhancing optical characteristics of InAs/InGaAsSb quantum dot structures with long-excited state emission at 1.31 μm.
In this study, the optical properties of InAs quantum dots (QDs) with various strain-reducing layers (SRLs) of GaAsSb and InGaAsSb are characterized using photoluminescence (PL) and time-resolved PL (TRPL) measurements. The room-temperature PL results for the InAs/InGaAsSb QDs revealed stronger emission intensities than InAs QDs capped with an GaAs(1-x)Sb(x) (x = 20%)SRL, although both samples were grown under the same Sb flux during the molecular beam epitaxy process. The InAs/InGaAsSb QDs showed a significant elongation of emission wavelengths to 1450 and 1310 nm for the ground and first-excited state at room temperature. The energy band alignment of the InAs QD heterostructures was found tailoring from type II to type I as the GaAsSb SRL was replaced by InGaAsSb layer, which improved the radiative efficiency and was verified by power-dependent PL and TRPL measurements. Post-growth rapid thermal annealing was applied on the InAs/InGaAsSb QDs to further enhance the QD quality and PL emission efficiency. The greatly improved PL intensity, reduced linewidth, shortened radiative lifetime, with increasing annealing temperature were demonstrated, and InAs/InGaAsSb QDs exhibited enhanced optical characteristics for long-wavelength emission applications.


Otago Glaucoma Surgery Outcome Study: Further Histology and Immunohistochemistry of Molteno Implant Blebs.
To describe findings of light microscopic examination of Molteno implant bleb capsules. Histological and immunohistochemical features of bleb capsules including distribution of apoptotic cells and cell fragments were examined in 11 eyes 0.2 to 30.4 years after Molteno implants. In the superficial layer of capsules, high proportions of cells showed cytological features of apoptosis, with a higher proportion of cells showing specific immunohistochemical features of apoptosis with a mean of 22% (range, 3%-40%) of cells staining positively for Fas ligand. This demonstrated that cells migrating into the superficial capsule were replaced over approximately 1 to 6 days. In the deeper layer a mean of 8% (range, 3%-38%) of apoptosing cells stained positively for Fas ligand. These lower proportions of positively staining cells and cell fragments in the deeper layers, and the presence of occasional positively staining cells on the inner surface of capsules, demonstrated continuous migration of cells into the deeper layers associated with breakdown of connective tissue matrix and the release of numerous membrane-bound vesicles. These findings demonstrated unexpectedly rapid turnover of cells in the superficial layer of the bleb capsule, where most cells were efficiently phagocytosed by nearby monocytic cells, macrophages, and histiocytes; the remaining cells migrating into the deeper layers completed apoptosis and disintegrated with release of collagenolytic enzymes and Fas ligand positive presumed "death messengers" that were carried toward the superficial layers by the aqueous.


Impact of CVS Pharmacy's Discontinuance of Tobacco Sales on Cigarette Purchasing (2012-2014).
To assess the impact of CVS Health's discontinuation of tobacco sales on cigarette purchasing. We used households' purchasing data to assess rates at which households stopped cigarette purchasing for at least 6 months during September 2014 to August 2015 among 3 baseline groups: CVS-exclusive cigarette purchasers, CVS+ (CVS and other retailers), and other-exclusive (only non-CVS retailers). In state-level analyses using retailers' point-of-sale purchase data, an interrupted time series compared cigarette purchasing before (January 2012 to August 2014) and after (September 2014 to April 2015) tobacco removal in 13 intervention states with CVS market share of at least 15% versus 3 control states with no CVS stores. Compared with other-exclusive purchasers, CVS-exclusive purchasers were 38% likelier (95% confidence interval = 1.06, 1.81) to stop cigarette purchasing after tobacco removal. Compared with control states, intervention states had a significant mean decrease of 0.14 (95% confidence interval = 0.06, 0.22) in packs per smoker per month. After CVS's tobacco removal, household- and population-level cigarette purchasing declined significantly. Private retailers can play a meaningful role in restricting access to tobacco. This highlights one approach to reducing tobacco use and improving public health.


Ischemic type biliary lesions in histidine-tryptophan-ketoglutarate (HTK) preserved liver grafts.
Ischemic type biliary lesions lead to considerable morbidity following orthotopic liver transplantation. The exact pathogenesis is unknown. One major hypothesis is that insufficient perfusion of the arterial vessels of the biliary tree, especially under perfusion with the high viscous University of Wisconsin solution, might be responsible for ischemic type biliary lesions. Due to low viscosity, HTK solution is reported to have a lower incidence of biliary complications. However, there is no data concerning ischemic type biliary lesions in HTK preserved livers. In this paper we report our results after orthotopic liver transplantation with special regard to ischemic type biliary lesions in liver grafts preserved with HTK solution. Between 09/1997 and 01/2005 300 liver transplantations were performed in our center. Thirty-two (10.7%) liver grafts were preserved with HTK solution, 268 (89.3%) were preserved with UW solution. Six and 43 grafts showed ischemic type biliary lesions after orthotopic liver transplantation in HTK- (18.8%) and UW- (16.0%) groups, respectively (p=0.696). There was no statistical significant difference between the two groups. Donor related factors, recipient age, indication for transplantation, transplantation technique, immunosuppression and ischemia time were comparable in both groups. Ischemic type biliary lesions occurred with the same frequency in HTK preserved livers compared to UW preserved organs. We suggest that low viscosity of the preservation fluid by itself does not guarantee reliable perfusion of the small arteries of a liver graft and a pressure perfusion might be beneficial even in HTK solution.


The Soviet settlement system--current issues and future prospects.
"A survey of current urban issues and trends in the Soviet Union sets the stage for an analysis of the problems of the urban system of the USSR and discussion of recent efforts at planning and policy development for a national settlement system. The General Scheme of Settlement, issued in 1975 and revised in 1982 to guide the development of such a national system, is examined as is the ensuing debate between two opposing schools of thought as to the best approach for restructuring the urban system."


Cross-border purchasing of cigarettes among smokers in Six Countries of the EUREST-PLUS ITC Europe Surveys.
The availability of lower-cost cigarettes in neighboring countries provides price-sensitive smokers with incentives to purchase cheaper out-of-country cigarettes. This study estimates the prevalence of and factors associated with cross-border purchasing of cheaper cigarettes among smokers from Germany, Greece, Hungary, Poland, Romania, and Spain. The prevalence of cross-border purchasing was estimated by residential location, defined as living in regions bordering a lower-price country (where prices were at least €1/pack lower), regions bordering a similar- or higher-price country, and internal non-border regions. Data were from a survey of nationally representative samples of adult smokers (n=6011) from Germany, Greece, Hungary, Poland, Romania, and Spain. The primary outcome was purchasing cheaper out-of-country cigarettes in the previous six months. Residential location was defined using The Nomenclature of Territorial Units for Statistics (NUTS2 in Germany and NUTS3 in the other countries). Multivariable logistic regression tested differences in purchasing cheaper out-of-country cigarettes by country and residential location. Residential location was associated with purchasing cheaper out-of-country cigarettes in Germany and Poland (p<0.05): 31% of German and 11% of Polish smokers living in regions bordering lower-price countries reported purchasing cheaper out-of-country cigarettes in the previous six months. Smokers living in regions bordering lower-price countries had 4.21 times greater odds of purchasing cheaper out-of-country cigarettes compared to smokers living in non-border regions. Overall, only a minority of smokers in the six countries purchased cheaper cigarettes outside their country. However, smokers living in regions bordering countries where cigarettes were at least €1/pack lower than their home country had significantly higher odds of purchasing cheaper out-of-country cigarettes. This effect was especially prominent among German smokers. Tax harmonization policies designed to minimize cross-border price differentials can eliminate lower-priced alternatives for price-sensitive smokers.


Changes in body composition and mitochondrial nucleic acid content in patients switched from failed nucleoside analogue therapy to ritonavir-boosted indinavir and efavirenz.
Body composition changes complicate antiretroviral therapy. Improvements in lipoatrophy after a switch in nucleoside reverse-transcriptase inhibitors (NRTIs) have been demonstrated. We investigated 60 patients switching from failed NRTIs to ritonavir-boosted indinavir and efavirenz. Body composition (assessed by dual-energy x-ray absorptiometry scan and by single-slice computed tomography of the abdomen through the level of the fourth lumbar vertebra [L4] and the mid-right thigh) and fasted metabolics were measured at the baseline time-point at switch and at weeks 48 and 96 thereafter. Mitochondrial DNA and RNA were extracted from right-thigh subcutaneous fat and peripheral-blood mononuclear cells (PBMCs) at weeks 0 and 48. The primary end point was the change in mean limb fat over 48 weeks. At week 96, we observed increases in mean (standard deviation [SD]) limb fat (+620 [974] g; P=.003), L4 subcutaneous adipose tissue (+20 [35] cm(2); P<.001), mid-thigh subcutaneous adipose tissue (+5 [10] cm(2); P<.001), and L4 visceral adipose tissue (+11 [34] cm(2); P=.01), but we also observed reduced lean limb mass (-831 [1,100] g; P=.3). Mean (SD) mtDNA content in subcutaneous fat and in PBMCs increased (+109 [274] and +45 [100] copies/cell, respectively). Improved virological control or immune recovery did not explain the results. Triglyceride, total cholesterol, estimated low-density lipoprotein cholesterol, ratio of total cholesterol to high-density lipoprotein cholesterol, and blood glucose levels deteriorated (i.e., had increased by 206%, 67%, 58%, 19%, and 6%, respectively, at week 96). This regimen was associated with statistically significant but clinically modest increases in peripheral fat, visceral fat, and mitochondrial nucleic acid content. A predominantly adverse metabolic profile developed.


Resistance imparted by vitamin C, vitamin E and vitamin B12 to the acute hepatic glycogen change in rats caused by noise.
The effects of vitamin C, vitamin E and vitamin B12 on the noise-induced acute change in hepatic glycogen content in rats were investigated. The exposure of rats to 95 dB and 110 dB of noise acutely reduced their hepatic glycogens. Vitamin C (ascorbic acid) and vitamin E (alpha-tocopherol) attenuated the noise-induced acute reduction in the hepatic glycogen contents. This result suggests that antioxidants could reduce the change via reactive oxygen species. Vitamin B12 (cobalamin) delayed the noise-induced change, a finding that suggests that vitamin B12 could postpone the acute change via compensating for vitamin B12 deficiency.


Antifungal and antitoxin effects of propolis and its nanoemulsion formulation against Aspergillus flavus isolated from human sputum and milk powder samples.
Aspergillus flavus causes human and animal diseases through either inhalation of fungal spores or ingestion of mycotoxins as aflatoxins produced in human and animal feed as secondary metabolites. This study was aimed to detect the incidence of A. flavus and its aflatoxins in human sputum and milk powder samples and explore the efficacy of pure propolis (PP) and propolis nanoemulsion (PNE) as natural decontaminants against fungal growth and its released aflatoxins. A. flavus was isolated by mycological culture and identified macroscopically and microscopically. Coconut agar medium and thin-layer chromatography (TLC) were used to qualitatively detect aflatoxins in the isolated strains. Toxins were extracted from toxigenic strains by the fast extraction technique. The quantitative detection of toxin types was explored by high-performance liquid chromatography (HPLC). PNE was prepared by a novel method using natural components and characterized by Fourier-transform infrared spectroscopy, Zetasizer, and transmission electron microscopy. The effects of PP and PNE on A. flavus growth and its toxin were determined by the well-diffusion method and HPLC. The mycological culture showed that 30.9% and 29.2% of sputum and milk powder samples were positive for A. flavus, respectively. TLC confirmed the production of 61.8% and 63.2% aflatoxin by the isolated strains in sputum and milk powder, respectively. PP and PNE showed antifungal activity on A. flavus growth with mean±standard error (SE) inhibition zones of 27.55±3.98 and 39.133±5.32 mm, respectively. HPLC revealed positive contamination of toxin extracts with AFB1, AFB2, and AFG2 at 0.57±0.026, 0.28±0.043, and 0.1±0.05 mg/L, respectively. After treatment with PP and PNE, a significant decrease in AFB1, AFB2, and AFG2 concentrations was observed. This study suggested using propolis and its nanoformulation as antifungal and antitoxins in human medicine and the food industry to increase the food safety level and stop food spoilage.


Hemispheric asymmetry in the induction of false memories.
The purpose of this study was to investigate hemispheric asymmetry in verbal memory by using a false recognition paradigm and a standard list learning paradigm, which can induce high false recognition for semantically related distractors. The experiment showed that the LH could discriminate the targets from the related distractors more accurately than the RH. This result was attributed to the hemispheric difference in the hit rate rather than in false recognition. The results of the present study suggest that the model of RH coarse semantic coding and LH fine semantic coding is applicable not only to language processing but also to verbal memory.


Cotranscription of the genes encoding two P700 chlorophyll a apoproteins with the gene for ribosomal protein CS14: determination of the transcriptional initiation site by in vitro capping.
Transcription of the psaA operon in tobacco chloroplasts has been studied. This operon contains in linear sequence the genes encoding the P700 chlorophyll a A1 and A2 apoproteins (psaA and psaB) and the gene encoding the ribosomal CS14 protein (rps14). Northern blot hybridization revealed that a 5.2 kb transcript hybridizes to psaA, psaB, and rps14, but not to the fMet-tRNA (trnfM) gene which follows. Primer extension and in vitro capping assays indicated that the transcriptional initiation site is 194 bp upstream of psaA. The 3' end of the transcript was determined by S1 mapping to be 105 bp downstream of rps14. The transcript is calculated to be 5,207 nucleotides long.


The making and breaking of Yugoslavia and its impact on health.
The creation of nation-states in Europe has generally been assumed to be intrinsic to modernization and to be irreversible. The disintegration of Czechoslovakia, the Soviet Union, and Yugoslavia demonstrates that the process is not irreversible. I argue that in the case of Yugoslavia, (1) disintegration was caused by the interaction between domestic policies with regard to nationalities and integration into the global economy and (2) the impact of the disintegration of the federation on health care and public health systems has been profound. Improving and converging measures of mortality before the collapse gave way to increasing disparities afterward. The lesson is that processes of individual and social modernization do not result in improvements in health and well-being that are necessarily irreversible or shared equally.


Freezing stress response in woody tissues observed using low-temperature scanning electron microscopy and freeze substitution techniques.
The objective of the current research was to examine the response of woody plant tissues to freezing stress by using scanning electron microscopy (SEM). Nonsupercooling species red osier dogwood (Cornus stolonifera Michx.), weeping willow (Salix babylonica L.), and corkscrew willow (Salix matsudana Koidz. f. tortuosa Rehd.) survived freezing stress as low as -60 degrees C. Cell collapse of ray parenchyma cells of these species was expected but did not occur. It was concluded that ray parenchyma cells of these species do not fit into either the supercooling or extracellular freezing classifications. Tissues from flowering dogwood (Cornus florida L.), apple (Malus domestica Borkh. cv "Starking III"), red oak (Quercus rubra L.), scarlet oak (Quercus coccinea Muench.), and red ash (Fraxinus pennsylvanica Marsh) were confirmed as supercooling species, and did not survive exposures below -40 degrees C. Ray parenchyma cells of these species did not collapse in response to freezing stress, as was expected. Cell collapse along the margins of voids were observed in bark of all seven species. Voids were the result of extracellular ice crystals formed in the bark during exposure to freezing stress. Tissues prepared by freeze substitution techniques were found to be adequately preserved when compared to those prepared by conventional fixation and low temperature SEM techniques. A freezing protocol for imposing freezing stress at temperatures lower than experienced naturally in the area where the study was conducted was developed that produced responses comparable to those observed in specimens collected in the field during natural freezing events.


[In vivo confocal microscopic characteristics of limbal stem cell deficiency].
Objective: To investigate the cellular changes and quantitative analysis of basal cell density (BCD) and corneal epithelial thickness (CET) in limbal stem cell deficiency (LSCD) by in vivo confocal microscopy (IVCM). Methods: Prospective case-control study. A total of 35 eyes of 23 patients diagnosed with LSCD and 25 eyes from normal subjects were included in this study. Based on slit-lamp presentation and the global consensus on classification, the LSCD patients were classified into LSCD Ⅰ, LSCD Ⅱ and LSCD Ⅲ. Confocal images of the central cornea, and the superior, inferior, nasal and temporal limbus were inspected by IVCM. Morphologic characteristics of LSCD were summarized. The BCD and CET in all locations were measured. ANVOA or Kruskal-Wallis test was used for analysis when appropriate. A receiver operating characteristic was used to detect the diagnosis efficiency of BCD and CET. Results: The characteristics in the corneal epithelium of LSCD on IVCM included nested corneal epithelial cells, goblet cells with hyper-reflective spots, irregular basal cells and decreasing subbasal nerve density. The mean BCD of the LSCD group was (8 976±1 096) cells/mm2 in the central cornea. Compared to the control group, the BCD in the central cornea, superior, inferior, nasal and temporal limbus decreased by 30.2%, 26.0%, 28.7%, 29.3% and 30.2%, respectively (all P<0.007). The CET in the central cornea was (47.3±8.1) μm. The CET in the central cornea, superior, inferior, nasal and temporal limbus decreased by 27.9%, 23.7%, 20.6%, 26.9% and 23.1%, respectively, compared to the control group (all P<0.007). There was a decline of BCD and CET in more serious LSCD. Additionally, the decline of BCD and CET was shown in the unaffected region. The receiver operating characteristic showed the diagnosis efficiency of BCD in the corneal center and limbus (0.931 and 0.916) was superior to CET (0.853 and 0.817). Conclusions: There was a series of characteristic cellular changes in LSCD on IVCM. Both BCD and CET decreased significantly in LSCD. The BCD had higher diagnostic efficiency for LSCD.(Chin J Ophthalmol, 2020, 56:447-455).


Conserved homeodomain proteins interact with MADS box protein Mcm1 to restrict ECB-dependent transcription to the M/G1 phase of the cell cycle.
Two homeodomain proteins, Yox1 and Yhp1, act as repressors at early cell cycle boxes (ECBs) to restrict their activity to the M/G1 phase of the cell cycle in budding yeast. These proteins bind to Mcm1 and to a typical homeodomain binding site. The expression of Yox1 is periodic and directly correlated with its binding to, and repression of, ECB activity. The absence of Yox1 and Yhp1 or the constitutive expression of Yox1 leads to the loss of cell-cycle regulation of ECB activity. Therefore, the cell-cycle-regulated expression of these repressors defines the interval of ECB-dependent transcription. Twenty-eight genes, including MCM2-7, CDC6, SWI4, CLN3, and a number of genes required during late M phase have been identified that are coordinately regulated by this pathway.