Neuroserpin polymers cause oxidative stress in a neuronal model of the dementia FENIB.
The serpinopathies are human pathologies caused by mutations that promote polymerisation and intracellular deposition of proteins of the serpin superfamily, leading to a poorly understood cell toxicity. The dementia FENIB is caused by polymerisation of the neuronal serpin neuroserpin (NS) within the endoplasmic reticulum (ER) of neurons. With the aim of understanding the toxicity due to intracellular accumulation of neuroserpin polymers, we have generated transgenic neural progenitor cell (NPC) cultures from mouse foetal cerebral cortex, stably expressing the control protein GFP (green fluorescent protein), or human wild type, G392E or delta NS. We have characterised these cell lines in the proliferative state and after differentiation to neurons. Our results show that G392E NS formed polymers that were mostly retained within the ER, while wild type NS was correctly secreted as a monomeric protein into the culture medium. Delta NS was absent at steady state due to its rapid degradation, but it was easily detected upon proteasomal block. Looking at their intracellular distribution, wild type NS was found in partial co-localisation with ER and Golgi markers, while G392E NS was localised within the ER only. Furthermore, polymers of NS were detected by ELISA and immunofluorescence in neurons expressing the mutant but not the wild type protein. We used control GFP and G392E NPCs differentiated to neurons to investigate which cellular pathways were modulated by intracellular polymers by performing RNA sequencing. We identified 747 genes with a significant upregulation (623) or downregulation (124) in G392E NS-expressing cells, and we focused our attention on several genes involved in the defence against oxidative stress that were up-regulated in cells expressing G392E NS (Aldh1b1, Apoe, Gpx1, Gstm1, Prdx6, Scara3, Sod2). Inhibition of intracellular anti-oxidants by specific pharmacological reagents uncovered the damaging effects of NS polymers. Our results support a role for oxidative stress in the cellular toxicity underlying the neurodegenerative dementia FENIB.


Alterations induced by citrinin in cultured kidney cells.
The cytotoxicity of citrinin was evaluated in an established cell line of baby hamster kidney cells. The primary effect of the mycotoxin was on the adherence of the cells to the culture bottles. Microscopic evaluation of morphological alterations indicated that the cells which were originally elongated and flattened, became swollen and round. Electron microscopic examination showed that citrinin (0.1, 0.5 and 1.0 mM) incubated for 10 hours with cultured cells, promoted drastic alterations of normal mitochondria, with swelling and cell death. Transplasma membrane redox system is inhibited by citrinin (81%). This effect is dependent not only on the toxin concentration, but also on the time of exposure to the cells.


Mechanisms of neutrophil-dependent and neutrophil-independent endothelial cell injury.
The acute inflammatory process is initiated when an extravascular stimulus provokes capillary dilatation and increased permeability, and recruits circulating neutrophils to the site. Damage to vascular structures is seen at these sites and evidence of injury occurs early in the evolution of the lesion. Studies carried out over the past 10 years in a number of laboratories have elucidated many of the biochemical events that lead to endothelial cell damage at sites of inflammation. Activated neutrophils bind tightly to the target cells and this is accompanied by neutrophil generation of superoxide anion and hydrogen peroxide and by release of granule enzymes. Neutrophil-derived hydrogen peroxide gains access to the interior of the target cell where it induces a breakdown of cellular ATP and a build-up of ATP metabolites. Among these are xanthine and hypoxanthine, substrates for xanthine oxidase. Exposure of the target cell to other neutrophil products (specifically, elastase) induces the interconversion of xanthine dehydrogenase to xanthine oxidase. Formation of uric acid from hypoxanthine and xanthine by the oxidase form of the enzyme results concomitantly in the generation of superoxide anion. In addition to providing a source of intracellular reducing equivalents, the target (endothelial) cell is also the source of iron. Target cell iron, maintained in the reduced form by intracellular oxidants, combines with neutrophil-derived hydrogen peroxide to form the highly reactive (and highly toxic) hydroxyl radical. This oxidant is most likely the direct mediator of injury.


Imaging breast cancer response during neoadjuvant systemic therapy.
Neoadjuvant systemic therapy is used to enable breast-conserving surgery in patients with large primary operable breast cancers. It is important to be able to accurately assess response to systemic therapy, both to assist the surgeon and for prognostic purposes. Moreover, a proportion of women will fail to respond to treatment and would potentially benefit from either a change in therapy or earlier surgery rather than continuing completion of the planned course of treatment. Conventional techniques of assessing response (clinical examination, x-ray mammography and breast ultrasound) rely on changes in tumor size, which are often delayed and do not always correlate with pathologic response. This review examines the evidence for functional imaging techniques including scintimammography, functional computed tomography, dynamic magnetic resonance imaging, spectroscopy and positron emission tomography. These techniques measure changes in tumor vasculature, metabolism or proliferation and may prove to be earlier and more sensitive measures of response to systemic therapy, thus enabling tailoring of an individual's treatment.


Prevalence of enamel hypoplasia in deciduous canines of patients with complete cleft lip and palate.
To evaluate the prevalence and type of enamel hypoplasia in deciduous canines of patients with complete unilateral and bilateral cleft lip and palate, as well as its distribution according to gender, dental arch, and side of cleft. Cross sectional. Hospital for Rehabilitation of Craniofacial Anomalies, Bauru, São Paulo, Brazil. Three-hundred twelve Caucasian children (193 boys, 119 girls), aged 3 to 10 years, presenting complete unilateral and bilateral cleft lip and palate were included in this study. A single examiner carried out clinical examination under natural light with a dental probe and dental mirror and, after drying of the tooth, by means of a simplified hypoplasia index. A prevalence of 43.8% was observed for unilateral and 39% for bilateral clefts. Both groups revealed similar distributions regarding the maxillary and mandibular dental arches and gender. Similar distribution was also observed on the cleft and noncleft sides for the unilateral cleft group. The most frequent type and severity was obvious hypoplasia, followed by minimal hypoplasia, both roughly round. The results suggest that the cleft does not influence the occurrence of hypoplasia in deciduous canines.


Foliar pathogenesis and plant water relations: a review.
As the world population grows, there is a pressing need to improve productivity from water use in irrigated and rain-fed agriculture. Foliar diseases have been reported to decrease crop water-use efficiency (WUE) substantially, yet the effects of plant pathogens are seldom considered when methods to improve WUE are debated. We review the effects of foliar pathogens on plant water relations and the consequences for WUE. The effects reported vary between host and pathogen species and between host genotypes. Some general patterns emerge however. Higher fungi and oomycetes cause physical disruption to the cuticle and stomata, and also cause impairment of stomatal closing in the dark. Higher fungi and viruses are associated with impairment of stomatal opening in the light. A number of toxins produced by bacteria and higher fungi have been identified that impair stomatal function. Deleterious effects are not limited to compatible plant-pathogen interactions. Resistant and non-host interactions have been shown to result in stomatal impairment in light and dark conditions. Mitigation of these effects through selection of favourable resistance responses could be an important breeding target in the future. The challenges for researchers are to understand how the effects reported from work under controlled conditions translate to crops in the field, and to elucidate underlying mechanisms.


Protection of adrenocortical activity by dietary casein in ether anaesthetized rats.
Adrenal delta5-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) activity and serum corticosterone level were significantly higher in rats fed with 5% casein or 4% albumin diets after 1 hr of ether anaesthetic stress as compared to the controls, 5% casein and 20% casein (equivalent to 4% albumin) respectively. Ether anaesthesia to 20% casein fed rats caused no change in adrenal delta5-3beta-HSD activity and serum corticosterone level when compared with controls fed 20% casein diet. The results suggest that high milk protein diet may prevent acute stress effects by protecting adrenocortical activity. The present investigation opens up a new area of management of stress.


In situ biodosimetric experiment for space applications.
This paper presents the principles and application of DNA based biological UV dosimeters, as developed by Research Group for Biophysics (RGB). These dosimeters are used for assessing the biological hazard of living systems on the Earth's surface and in different waters (rivers, lakes, seas, etc.). The UV dosimetry system has also been used in the space. In dosimeters a bacterial virus, bacteriophage T7 and polycrystalline uracil thin layers have been used as biological detectors. On the Earth's surface the UV radiation induces dimer formation in phage T7 and in the uracil detector, which was evaluated by loss of viability of the phage particles and by the decrease of the characteristic optical density (OD) of uracil thin layers. Recently the development of human space activities has also increased the need to measure the biological effect of extraterrestrial solar radiation, too. The evaluation of the space samples occurred on ground, thus only the starting and the final state were taken into account. A new improved, automated method is presented below which makes data collection more efficient and also makes the dynamics of the process observable.


Mortality among inpatients with bipolar disorders and COVID-19: a propensity score matching analysis in a national French cohort study.
It remains unknown whether coronavirus disease 2019 (COVID-19) patients with bipolar disorders (BDs) are at an increased risk of mortality. We aimed to establish whether health outcomes and care differed between patients infected with COVID-19 with BD and patients without a diagnosis of severe mental illness. We conducted a population-based cohort study of all patients with identified COVID-19 and respiratory symptoms who were hospitalized in France between February and June 2020. The outcomes were in-hospital mortality and intensive care unit (ICU) admission. We used propensity score matching to control for confounding factors. In total, 50 407 patients were included, of whom 480 were patients with BD. Patients with BD were 2 years older, more frequently women and had more comorbidities than controls without a diagnosis of severe mental illness. Patients with BD had an increased in-hospital mortality rate (26.6% v. 21.9%; p = 0.034) and similar ICU admission rate (27.9% v. 28.4%, p = 0.799), as confirmed by propensity analysis [odds ratio, 95% confidence interval (OR, 95% CI) for mortality: 1.30 (1.16-1.45), p < 0.0001]. Significant interactions between BD and age and between BD and social deprivation were found, highlighting that the most important inequalities in mortality were observed in the youngest [OR, 95% CI 2.28 (1.18-4.41), p = 0.0015] and most deprived patients with BD [OR, 95% CI 1.60 (1.33-1.92), p < 0.001]. COVID-19 patients with BD were at an increased risk of mortality, which was exacerbated in the youngest and most deprived patients with BD. Patients with BD should thus be targeted as a high-risk population for severe forms of COVID-19, requiring enhanced preventive and disease management strategies.


[Evaluation of energy intake and the nourishment status of women aged 19-25 with different physical activity].
The aim of the study was to evaluate the way of nutrition and the status of nourishment among women aged 19-25 with different physical activity and gain the knowledge on the nourishing value of a daily food rations and the formation of basic anthropometric indicators of nourishment status depending of the lifestyle. Voluntary research was carried out in the years 2004-2005 on 180 women aged 19-25 in Bielsko-Biala. The group of females of low physical activity comprised of 100 students of Academy of Science and Arts and a group of high physical activity, 80 women attending regularly (at least twice a week throughout a year) fitness club classes. The way of nutrition was estimated by means of 24 hour nutritional interview. The received result after considering an unavoidable waste reduction were applied to the nutritional standard at the level of safe consumption for women aged 19-25 of low and moderate physical activity. In the evaluation of nourishment status BMI rate and the content of fat tissue was determined by the method of bioelectrical impedance. The quantitative assessment of the way of nutrition shows a lowered supply of energy derived from food, pointing out the lack of energetic balance in the tested persons aged 19-25. The average energetic daily food ration value in active women was 72.4% and physically non-active 84.7% of daily energetic demand. Daily nutritional rations were found to have nonbalanced content of basic nutritional ingredients. Relatively high supply of proteins and fat, especially among non-active women was accompanied by a lowered supply of carbohydrates (approx. 70% of recommended consumption). Furthermore, nonsufficient supply of nutritional fibre was also reported (approx. 70%). The research of nourishment status proves that the highest percentage of women irrespective of their physical activity shows the correct value of BMI rate. Physical activity level in women differentiates their body content in this way that the average level of fat tissue in physically active women is lower than in less active (17% vs 22%).


Seroprevalence, cost per donation and reduction in blood supply due to positive and indeterminate results for infectious markers in a blood bank in Lima, Peru.
Safety in Transfusion Medicine is subject to regulations and government legislation within a total quality framework. The aim of this study was to evaluate the impact of seroprevalence and indeterminate results on lost units and cost per donation. A prospective cross-sectional study was performed in the Blood Bank and Transfusion Therapy Department of the Hospital Central de la Policia Nacional del Perú in Lima, Peru. All completed donations (replacement/voluntary) without complications were included in this study. Every donation met the institutional requirements and quality criteria of Programa Nacional de Hemoterapia y Bancos de Sangre (PRONAHEBAS). Data analysis was achieved using the Statistical Package for the Social Sciences. A total of 7723 donations were evaluated during 2014 and 2015 with 493 being seropositive (overall prevalence 5.25%) and 502 having indeterminate results (overall prevalence 5.35%). Thus total loss was 995units, 437.8L of blood and 49,750 US dollars. The most common seropositive infectious markers were the core antibody of hepatitis B virus (2.82%) and syphilis (1.02%), and the most common indeterminate results were Chagas disease (1.27%) and the core antibody of hepatitis B virus (1.26%). There was no significant change in the prevalence of seropositivity (p-value=0.243) or indeterminate results (p-value=0.227) over the two-year period of the study. A statistical correlation was found between the cost per lost donation and the most prevalent markers (rho=0.848; p-value=<0.001). Seroprevalence was lower than the regional mean, but the prevalence of indeterminate results was elevated causing a great impact on blood supply and economic losses to this institution.


Congenital Bronchobiliary Fistula: A Case Report and Literature Review.
Congenital bronchobiliary fistula (CBBF) is a rare disease. Children with CBBF mostly have atypical clinical manifestations that can be easily missed. We report a case of a child with CBBF who was diagnosed with fistulography with the help of an endobronchial blocker and a fiberoptic bronchoscope. The CBBF was successfully removed by thoracoscopic surgery.


Dissociable effects of systemic and orbitofrontal administration of adrenoceptor antagonists on yohimbine-induced motor impulsivity.
The α2-adrenoceptor antagonist, yohimbine, is commonly used as a pharmacological stressor. Its behavioural effects are typically attributed to elevated noradrenaline release via blockade of central, inhibitory autoreceptors. We have previously reported that yohimbine increases motor impulsivity in rats on the five-choice serial reaction time task (5CSRTT), a cognitive behavioural assessment which measures motor impulsivity and visuospatial attention. Furthermore, this effect depended on cyclic adenomonophosphate (cAMP) signalling via cAMP response element binding (CREB) protein in the orbitofrontal cortex (OFC). However, the role of specific adrenoceptors in this effect is not well-characterised. We therefore investigated whether the pro-impulsive effects of systemic yohimbine could be reproduced by direct administration into the OFC, or attenuated by intra-OFC or systemic administration of prazosin and propranolol-antagonists at the α1- and β-adrenoceptor, respectively. Male Long-Evans rats were trained on the 5CSRTT and implanted with guide cannulae aimed at the OFC. Systemically administered α1- or β-adrenoceptor antagonists attenuated yohimbine-induced increases in premature responding. In contrast, local infusion of yohimbine into the OFC reduced such impulsive responding, while blockade of α1- or β-adrenoceptors within the OFC had no effect on either basal or yohimbine-stimulated motor impulsivity. Direct administration of selective antagonists at the α1-, α2- or β-adrenoceptor into the OFC therefore produce clearly dissociable effects from systemic administration. Collectively, these data suggest that the pro-impulsivity effect of yohimbine can be modulated by adrenergic signalling in brain areas outside of the OFC, in addition to non-adrenergic signalling pathways within the OFC.


Photoelectrochemical Behavior and Computational Insights for Pristine and Doped NdFeO3 Thin-Film Photocathodes.
Among the different strategies that are being developed to solve the current energy challenge, harvesting energy directly from sunlight through a tandem photoelectrochemical cell (water splitting) is most attractive. Its implementation requires the development of stable and efficient photocathodes, NdFeO3 being a suitable candidate among ternary oxides. In this study, transparent NdFeO3 thin-film photocathodes have been successfully prepared by a citric acid-based sol-gel procedure, followed by thermal treatment in air at 640 °C. These electrodes show photocurrents for both the hydrogen evolution and oxygen reduction reactions. Doping with Mg2+ and Zn2+ has been observed to significantly enhance the photoelectrocatalytic performance of NdFeO3 toward oxygen reduction. Magnesium is slightly more efficient as a dopant than Zn, leading to a multiplication of the photocurrent by a factor of 4-5 for a doping level of 5 at % (with respect to iron atoms). This same trend is observed for hydrogen evolution. The beneficial effect of doping is primarily attributed to an increase in the density and a change in the nature of the majority charge carriers. DFT calculations help to rationalize the behavior of NdFeO3 by pointing to the importance of nanostructuring and doping. All in all, NdFeO3 has the potential to be used as a photocathode in photoelectrochemical applications, although efforts should be directed to limit surface recombination.


Virulence of a Porphyromonas gingivalis W83 mutant defective in the prtH gene.
In a previous study we cloned and determined the nucleotide sequence of the prtH gene from Porphyromonas gingivalis W83. This gene specifies a 97-kDa protease which is normally found in the membrane vesicles produced by P. gingivalis and which cleaves the C3 complement protein under defined conditions. We developed a novel ermF-ermAM antibiotic resistance gene cassette, which was used with the cloned prtH gene to prepare an insertionally inactivated allele of this gene. This genetic construct was introduced by electroporation into P. gingivalis W83 in order to create a protease-deficient mutant by recombinational allelic exchange. The mutant strain, designated V2296, was compared with the parent strain W83 for proteolytic activity and virulence. Extracellular protein preparations from V2296 showed decreased proteolytic activity compared with preparations from W83. Casein substrate zymography revealed that the 97-kDa proteolytic component as well as a 45-kDa protease was missing in the mutant. In in vivo experiments using a mouse model, V2296 was dramatically reduced in virulence compared with the wild-type W83 strain. A molecular survey of several clinical isolates of P. gingivalis using the prtH gene as a probe suggested that prtH gene sequences were conserved and that they may have been present in multiple copies. Two of 10 isolates did not hybridize with the prtH gene probe. These strains, like the V2296 mutant, also displayed decreased virulence in the mouse model. Taken together, these results suggest an important role for P. gingivalis proteases in soft tissue infections and specifically indicate that the prtH gene product is a virulence factor.


Preparing the Gut with Antibiotics Enhances Gut Microbiota Reprogramming Efficiency by Promoting Xenomicrobiota Colonization.
Gut microbiota plays multiple important roles in intestinal and physiological homeostasis, and using fecal microbiota transplantation (FMT) to reprogram gut microbiota has demonstrated promise for redressing intestinal and physiological disorders. This study tested the alterations in reprogramming efficiency caused by different gut preparation procedures and explored the associated underlying mechanisms. We prepared the guts of mice for FMT by administering one of the three most-clinically used pretreatments [antibiotics, bowel cleansing (BC) solution, or no pretreatment], and we found that preparing the gut with antibiotics induced a more efficient modification of the gut bacterial community than was induced by either of the other two pretreatment types. The increased efficiency of antibiotic treatment appeared to occur via increasing the xenomicrobiota colonization. Further analysis demonstrated that antibiotic treatment of mice induced intestinal microbiota disruption, mostly by expelling antibiotic-sensitive bacteria, while the indigenous microbiota was maintained after treatment with a BC solution or in the absence of pretreatment. The amount of antibiotic-resistant bacteria increased shortly after antibiotics usage but subsequently decreased after FMT administration. Together, these results suggest that FMT relied on the available niches in the intestinal mucosa and that preparing the gut with antibiotics facilitated xenomicrobiota colonization in the intestinal mucosa, which thus enhanced the overall gut microbiota reprogramming efficiency.


Hair cell protection from aminoglycoside ototoxicity by adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor.
Aminoglycosides are commonly used antimicrobial drugs that often have ototoxic side effects. The ototoxicity often involves permanent loss of cochlear hair cells (HCs). Neurotrophic factors have been shown to protect a variety of tissues, including HCs, from toxic trauma. To determine if glial cell line-derived neurotrophic factor (GDNF) can protect cochlear HCs from trauma, we inoculated an adenoviral vector encoding the human GDNF gene into guinea pig cochleae via the round window membrane 4 days prior to injection of aminoglycosides. Control groups showed little or no negative influence of the viral inoculation on cochlear structure and function. In contrast, ears that were inoculated with the GDNF vector had better hearing and fewer missing HCs after exposure to the ototoxins, as compared with controls. Our results demonstrate the feasibility of gene therapy for cochlear application and suggest that virus-mediated overexpression of GDNF may be developed as a valuable prevention against trauma-induced HC death.


Sequential changes in NK and ADCC effector cell function after organ transplantation in man.
Antibody-dependent cellular (K cell) cytotoxicity (ADCC) and cellular cytotoxicity against natural killer (NK) targets exerted by the same cells were both measured sequentially in ten patients after renal transplantation using conventional immunosuppression. Cytotoxicity against NK targets appeared to correlate more closely with rejection episodes than did assays of ADCC activity during the same period. An apparent rise in NK activity was frequently accompanied by a fall in ADCC activity. Collectively these data suggest that the previously reported increase in NK activity during rejection episodes may represent a manifestation of the appearance of non-clonally activated T-cells in peripheral blood during rejection.


Measuring change in controlled longitudinal studies.
This paper examines the implications of the correlational structure of repeated measurements for three indices of change that can be used to evaluate treatment effects in longitudinal studies with scheduled assessment times and fixed total duration. The generalized least squares (GLS) regression of repeated measurements on time, which is usually reserved for complex mixed model solutions, takes the correlational structure of the repeated measurements into account, whereas simple gain scores and ordinary least squares (OLS) regression calculations do not. Nevertheless, the GLS solution is equivalent to OLS under conditions of compound symmetry and is equivalent to the analysis of simple gain scores in the presence of an autoregressive (order 1) correlational structure. The understanding of these relationships is important with regard to the frequently heard criticisms of the simpler definitions of treatment response in repeated measurement designs.


Molecular genetics complexity impeding research progress in breast and ovarian cancers.
Breast and ovarian cancer are heterogeneous diseases. While breast cancer accounts for 25% of cancers worldwide, ovarian cancer accounts for 3.5% of all cancers and it is considered to be the most lethal type of cancer among women. In Oman, breast cancer accounts for 25% and ovarian cancer for 4.5% of all cancer cases. Various risk factors, including variable biological and clinical traits, are involved in the onset of breast and ovarian cancer. Although highly developed diagnostic and therapeutic methods have paved the way for better management, targeted therapy against specific biomarkers has not yet shown any significant improvement, particularly in triple-negative breast cancer and epithelial ovarian cancer, which are associated with high mortality rates. Thus, elucidating the mechanisms underlying the pathology of these diseases is expected to improve their prevention, prognosis and management. The aim of the present study was to provide a comprehensive review and updated information on genomics and proteomics alterations associated with cancer pathogenesis, as reported by several research groups worldwide. Furthermore, molecular research in our laboratory, aimed at identifying new pathways involved in the pathogenesis of breast and ovarian cancer using microarray and chromatin immunoprecipitation (ChIP), is discussed. Relevant candidate genes were found to be either up- or downregulated in a cohort of breast cancer cases. Similarly, ChIP analysis revealed that relevant candidate genes were regulated by the E2F5 transcription factor in ovarian cancer tissue. An ongoing study aims to validate these genes with a putative role as biological markers that may contribute to the development of targeted therapies for breast and ovarian cancer.


COVID-19 Health Education Activities: An Analysis of a National Sample of Certified Health Education Specialists (CHES®/MCHES®) in Response to the Global Pandemic.
The National Commission of Health Education Credentialing, Inc. (NCHEC) created the Category 1 COVID-19 Claim Form Opportunity to document how Certified Health Education Specialists (CHES®) and Master Certified Health Education Specialists (MCHES®) assisted communities during the COVID-19 pandemic. Using data submitted by CHES®/MCHES® (n = 3,098 claim forms), the purpose of this study was to (a) describe the settings where CHES® and MCHES® completed their pandemic work and (b) assess differences in the type of pandemic work completed by CHES® compared with MCHES® based on specific Areas of Responsibility (AOR) for Health Education Specialists. Findings showed that CHES® and MCHES® engaged in seven AOR during the pandemic, with the largest proportion of CHES® (n = 859; 33%) and MCHES® (n = 105; 21.9%, documenting COVID-19-related activities in health departments. CHES® reported higher engagement than MCHES® in activities such as COVID-19 reporting/tracking, χ2 (1, N = 3,098) = 27.3, p < .001; outbreak response, χ2 (1, N = 3,098) = 4.3, p = .039; and vaccination, χ2 (1, N = 3,098) = 5.2, p = .023. Conversely, MCHES® reported higher participation than CHES® in screening/testing, χ2 (1, N = 3,098) = 174.2, p < .001; administration of budgets/operations, χ2 (1, N = 3,098) = 30.1, p < .001; and adapting educational activities at college/universities, χ2 (1, N = 3,098) = 46.1, p < .001. CHES® were more likely than MCHES® to indicate working in all AOR except for Area 2-Plan Health Education/Promotion. Results support that employer-verified health education skills in all AOR were transferable during COVID-19, especially for CHES® employed within state/county health departments.


An insight into the transmission role of insect vectors based on the examination of gene characteristics of African swine fever virus originated from non-blood sucking flies in pig farm environments.
Insect vector transmitted pathogens from contaminated environments are a key potential risk for public health. Meanwhile, transmission by non-blood sucking flies needs to be considered. Sequencing and phylogenetic tree analyses were used to study African swine fever virus (ASFV) genes derived from flies collected from pig farms that were infected with ASFV. The major differential genes were analyzed the encoded proteins, particularly their conformation, physico-chemical features, and interactions identified by immunophenotyping. Results showed that the ASFV p72 and D117L genes from these non-blood sucking flies identified by morphology have high sequence similarity from ASFV genotype II strains, however, A179L is found in an independent cluster, with five amino acid substitutions; four of which are in a continuous sequence. Moreover, the binding of a BH3 peptide into a surface groove formed by α-helices of ASFV A179L from the non-blood sucking flies is consistent with that of representative ASFV genotype II strains, Georgia/2007.They only differ in the direction of spatial interaction of six conserved amino residues. Many hydrophilic amino residues are located at the canonical ligand-binding groove of A179L from flies, with hydrophobic amino residues located at the corresponding positions in A179L of the Georgia/2007.Furthermore, analysis of protein interactions by immunophenotyping revealed that both A179Ls have similar roles in regulating autophagy and apoptosis. In conclusion, the main genes that differ between ASFV from flies and Georgia/2007 were similar in structure and protein interaction, while exhibiting differences in physico-chemical features and amino acid variations. Understanding the mechanical transmission characteristics of non-blood sucking flies is important.


mAb 5-1-6 nephropathy and nephrin.
It is well established that the glomerular capillary wall consists of three layers: endothelial cell, glomerular basement membrane, and the slit diaphragm bridging foot processes of glomerular epithelial cell. Which structure in the glomerular capillary wall represents the primary filter for retaining plasma proteins is not clearly elucidated. An anti-slit diaphragm monoclonal antibody (mAb) 5-1-6 causes massive proteinuria in rats by single intravenous injection, which clearly indicates that the slit diaphragm plays a critical role for maintaining the barrier function of the glomerular capillary wall. Recently, we concluded that mAb 5-1-6 recognized a rat homolog of nephrin, a gene product of NPHS1. The expression of nephrin decreased in puromycin aminonucleoside nephropathy and adriamycin nephropathy as well as mAb 5-1-6-induced nephropathy, which suggested that nephrin was involved in the development of proteinuria in these proteinuric states. In mAb 5-1-6 nephropathy, the slit diaphragm was maintained morphologically normal, although nephrin expression dramatically decreased. The finding suggested that nephrin was not a sole component of the slit diaphragm. To better understand the structure of the slit diaphragm, it is particularly important to identify other components that build up the structure of the slit diaphragm together with nephrin.


Ambisense sendai viruses are inherently unstable but are useful to study viral RNA synthesis.
Ambisense Sendai virus (SeV) was prepared in order to study the control of viral RNA synthesis. In these studies, we found that the relative ratios of genomes/antigenomes formed during infection are largely determined by the relative strengths of the replication promoters, independent of the presence of a functional mRNA start site. We also found that the ability of the viral polymerase (vRdRP) to respond to an mRNA editing site requires prior (re)initiation at an mRNA start site, similar to the acquisition of vRdRP processivity in the absence of nascent chain coassembly. During these studies, the inherent instability of ambisense SeV upon passage in embryonated chicken eggs was noted and was found to be associated with a point mutation in the ambisense mRNA (ambi-mRNA) start site that severely limited its expression. Since the interferon (IFN)-induced antiviral state is mediated in part via double-stranded RNA (dsRNA), the efficiency of the ambi-mRNA poly(A)/stop site was examined. This site was found to operate in a manner similar to that of other SeV mRNA poly(A)/stop sites, i.e., at approximately 95% efficiency. This modest level of vRdRP read-through is apparently tolerable for natural SeV because the potential to form dsRNA during infection remains limited. However, when mRNAs are expressed from ambisense SeV antigenomes, vRdRP read-through of the ambi-mRNA poly(A)/stop site creates a capped transcript that can potentially extend the entire length of the antigenome, since there are no further poly(A)/stop sites here. In support of this hypothesis, loss of ambi-mRNA expression during passage of ambisense SeV stocks in eggs is also characterized by conversion of virus that grows poorly in IFN-sensitive cultures and is relatively IFN sensitive to virus that grows well even in IFN-pretreated cells that restrict vesicular stomatitis virus replication, i.e., the wild-type SeV phenotype. The selection of mutants unable to express ambi-mRNA on passage in chicken eggs is presumably due to increased levels of dsRNA during infection. How natural ambisense viruses may deal with this dilemma is discussed.


The sonographic appearance of benign and malignant thyroid diseases and their histopathology correlate: demystifying the thyroid nodule.
The thyroid gland is one of the largest endocrine glands in the human body. It functions as a regulator of metabolism. Diseases involving the thyroid range from benign to malignant and can be associated with major morbidity and mortality. Ultrasound (US) imaging of the thyroid gland is prompted because of a palpable mass on clinical examination; abnormality of thyroid function tests; incidental finding on other imaging modalities, that is, nuclear scintigraphy or computed tomography scan; screening for patients with risk factors for malignancy, such as multiple endocrine neoplasia type II; or prior neck radiation treatment.Ultrasound is an excellent, noninvasive, and cost-effective diagnostic tool in the detection and characterization of thyroid disease. Most thyroid diseases have pathognomonic features on US, which are of diagnostic importance and lead to appropriate clinical management. Ultrasound plays an important role in differentiating benign from malignant thyroid disease, thereby triaging patients for US-guided fine-needle aspiration. Ultimately, thyroid US, in conjunction with thyroid function tests, can aid in characterizing various thyroid diseases.The main objective of this pictorial essay is to illustrate the sonographic appearance of various benign and malignant diseases of the thyroid with their histopathology correlations. Management of thyroid nodules using US-guided fine-needle aspiration is also briefly discussed.


The genomic landscape of chronic lymphocytic leukaemia: biological and clinical implications.
Chronic lymphocytic leukaemia (CLL) remains at the forefront of the genetic analysis of human tumours, principally due its prevalence, protracted natural history and accessibility to suitable material for analysis. With the application of high-throughput genetic technologies, we have an unbridled view of the architecture of the CLL genome, including a comprehensive description of the copy number and mutational landscape of the disease, a detailed picture of clonal evolution during pathogenesis, and the molecular mechanisms that drive genomic instability and therapeutic resistance. This work has nuanced the prognostic importance of established copy number alterations, and identified novel prognostically relevant gene mutations that function within biological pathways that are attractive treatment targets. Herein, an overview of recent genomic discoveries will be reviewed, with associated biological and clinical implications, and a view into how clinical implementation may be facilitated.


Lattice Boltzmann Simulation of the Kinetics Process of Methane Diffusion with the Adsorption-Desorption Hysteresis Effect in Coal.
The occurrence of coalbed methane adsorption-desorption hysteresis has been widely observed, but a unified understanding of its mechanism is lacking, and the factors affecting its degree are unclear. This study introduces a microscale LB model for gas diffusion-adsorption-desorption in porous media that also accounts for the adsorption-desorption hysteresis effect. The accuracy of the model has been validated using previous experimental data, and the primary controlling factors of adsorption-desorption hysteresis were analyzed. The findings are as follows: (1) In the process of methane diffusion-adsorption-desorption, Knudsen diffusion dominates in micro- and mesopores, while viscous flow prevails in macropores; our model can adaptively adjust gas transport regimes across a broad range of pore sizes and pressures. (2) The desorption amount and rate are close relative to the correction factors α and β. A higher α value corresponds to greater initial adsorption as well as longer desorption time, whereas a lower β value implies weaker desorption capacity and a slower desorption rate. (3) Pore size can affect gas diffusion-adsorption-desorption kinetics, where larger pore size corresponds to efficient gas diffusivity; when r < 10 nm, the desorption process is mainly controlled by the desorption rate. Overall, this study has offered new insights into the mechanism behind methane adsorption-desorption hysteresis at the microscale, identified primary controlling factors of methane diffusion-adsorption-desorption process, and provided a foundation for numerical simulations and experiments related to the adsorption-desorption hysteresis.


Analogous assembly mechanisms and functional guilds govern prokaryotic communities in mangrove ecosystems of China and South America.
As an important coastal "blue carbon sink," mangrove ecosystems contain microbial communities with an as-yet-unknown high species diversity. Exploring the assemblage and structure of sediment microbial communities therein can aid in a better understanding of their ecosystem functioning, such as carbon sequestration and other biogeochemical cycles in mangrove wetlands. However, compared to other biomes, the study of mangrove sediment microbiomes is limited, especially in diverse mangrove ecosystems at a large spatial scale, which may harbor microbial communities with distinct compositions and functioning. Here, we analyzed 380 sediment samples from 13 and 8 representative mangrove ecosystems, respectively, in China and South America and compared their microbial features. Although the microbial community compositions exhibited strong distinctions, the community assemblage in the two locations followed analogous patterns: the assemblages of the entire community, abundant taxa, rare taxa, and generalists were predominantly driven by stochastic processes with significant distance-decay patterns, while the assembly of specialists was more likely related to the behaviors of other organisms in or surrounding the mangrove ecosystems. In addition, co-occurrence and topological network analysis of mangrove sediment microbiomes underlined the dominance of sulfate-reducing prokaryotes in both the regions. Moreover, we found that more than 70% of the keystone and hub taxa were sulfate-reducing prokaryotes, implying their important roles in maintaining the linkage and stability of the mangrove sediment microbial communities. This study fills a gap in the large-scale analysis of microbiome features covering distantly located and diverse mangrove ecosystems. Here, we propose a suggestion to the Mangrove Microbiome Initiative that 16S rRNA sequencing protocols should be standardized with a unified primer to facilitate the global-scale analysis of mangrove microbiomes and further comparisons with the reference data sets from other biomes.IMPORTANCEMangrove wetlands are important ecosystems possessing valuable ecological functions for carbon storage, species diversity maintenance, and coastline stabilization. These functions are greatly driven or supported by microorganisms that make essential contributions to biogeochemical cycles in mangrove ecosystems. The mechanisms governing the microbial community assembly, structure, and functions are vital to microbial ecology but remain unclear. Moreover, studying these mechanisms of mangrove microbiomes at a large spatial scale can provide a more comprehensive insight into their universal features and can help untangle microbial interaction patterns and microbiome functions. In this study, we compared the mangrove microbiomes in a large spatial range and found that the assembly patterns and key functional guilds of the Chinese and South American mangrove microbiomes were analogous. The entire communities exhibited significant distance-decay patterns and were strongly governed by stochastic processes, while the assemblage of specialists may be merely associated with the behaviors of the organisms in mangrove ecosystems. Furthermore, our results highlight the dominance of sulfate-reducing prokaryotes in mangrove microbiomes and their key roles in maintaining the stability of community structure and functions.


Zinc status or supplementation and its relation to soil-transmitted helminthiasis in children: A systematic review.
Soil-transmitted helminths (STHs) parasitic infection is known as one of the most common infections around the world affecting more than a quarter of the world's population. The relationship between STH infections and micronutrient deficiencies are closely related and often coexist among the affected population. The study, therefore, aimed to summarise the available literature focusing on the effect of zinc status/deficiency or supplementation on STH infection or reinfection in children. For this purpose, we adopted a systematic approach and searched the existing literature on PubMed, Scopus, and Cochrane Library databases. A search term was entered to retrieve the available data. A total of 12 articles were included in this review after applying the inclusion/exclusion criteria. Most of the included studies reported a lower zinc status in children affected with any parasitic infection. Regarding the effect of zinc status and supplementation on parasitic infection in children, we found only a few studies (n = 4) with inconsistent result findings. This review reported that children infected with STH have lower zinc levels; however, a limited number of studies showed the effect of zinc supplements on the risk of STH warrants the need for further studies in this regard.


Polycythemia causing posterior segment vascular occlusions.
A 44-year-old male patient presented with features suggestive of transient central retinal artery occlusion (CRAO) followed by permanent CRAO and lateral posterior ciliary artery occlusion. He had diagnostic features of polycythemia vera (PV). When presented for the first time, the patient had features of ocular ischemia such as ocular pain, conjunctival congestion, and retinal opacification but with normal arm-to-retina time and normal arteriovenous transit time. During the second presentation, he had ocular pain, congested conjunctiva, retinal opacification, cherry red spot with box-carrying of retinal vessels, and choroidal infarct (Amalric's sign). He had lost light perception in that eye. Patients with polycythemia are prone to multifocal vascular occlusions and this can be the presenting feature in PV. A timely diagnosis and prompt management can prevent these repeated thromboembolic occlusive episodes.


A new method for the preparation of metaphase chromosomes for flow analysis.
A new method for the preparation of metaphase chromosomes for flow analysis has been evaluated. It has been shown that this method, which involves detergent lysis of metaphase cells and polyamines to stabilize the DNA, yields lower coefficients of variation and background levels in the DNA histograms than is currently obtained by hexylene glycol based methods. A conventional flow cytometer (FACS-II) has been used to resolve the human karyotype into about 14 peaks after ethidium bromide staining and excitation with a relatively low level of illumination (0.4 W at 488 nm). Flow karyotypes have also been obtained from suspension cell lines, in particular from the mouse cell line, Friend 707/B10. The only disadvantage of this method is that the chromosomes are highly condensed and therefore banding studies on sorted chromosomes may not be possible.


Orthopaedics injuries in male professional football players in Brazil: a prospective comparison between two divisions.
Football is a high-speed contact sport and the risk of injury is high. The objective of this study was to compare the two main divisions (A1 and A2) of the São Paulo Football Championship and to perform a correlation analysis of the variables studied. A prospective study was conducted using an electronic questionnaire previously developed by the Medical Committee of the São Paulo Football Federation. The questionnaire was sent to the doctors of the teams playing in the A1 and A2 divisions of the São Paulo Football Championship after each round. Setting: 2016 São Paulo Football Championship. The comparison of divisions A1 and A2 showed few significant differences among the various variables analysed in this study. The only significant differences were for right-side involvement in division A1 (p=0.044) and morning matches in division A2 (p<0.001). The correlation analysis of the variables studied showed expected associations, including sprains with a higher rate of need for surgery, ultrasound with muscle strains and moderate severity (8-28 days lost) with muscle strains. Despite the differences between the two divisions regarding budgets and team characteristics, there was a little difference in the variables analysed and there were associations such as sprains with a higher rate of need for surgery, ultrasound with muscle strains and moderate severity (8-28 days lost) with muscle strains. II b, individual cohort study.


Optimal felodipine dose when combined with metoprolol in arterial hypertension: a Swedish multicenter study within primary health care. Swedish General Practitioner Felodipine Study Group.
In a multicenter study comprising 23 Swedish primary health care centers, felodipine extended-release (ER) tablets in doses of 5, 10, and 20 mg were compared double-blind with placebo when given in addition to metoprolol controlled-release (CR) tablets 100 mg. All medication was given once daily in the morning. Altogether, 251 hypertensive patients with a diastolic blood pressure greater than 95 mm Hg after 4 weeks of treatment with placebo in combination with metoprolol CR 100 mg were randomized to four parallel groups. After 4 weeks of treatment, there were significantly greater reductions in blood pressure with all doses of felodipine ER than with placebo, both 2 and 24 h after intake of the tablets. Twelve patients were withdrawn because of adverse reactions. Of these, one patient was taking placebo, one 5 mg of felodipine ER, four 10 mg of felodipine ER, and six patients 20 mg of felodipine ER. When combined with metoprolol, 5 mg of felodipine ER seemed to be less effective than higher doses, but was very well tolerated. Adding 10 mg of felodipine ER to the basal metoprolol appeared to be optimal if both the effect and adverse reactions were taken into consideration.


Spermatid-specific expression of protamine 1 in transgenic mice.
Protamines are abundant basic proteins involved in the condensation of sperm chromatin. In the mouse, protamine genes are transcribed postmeiotically in round spermatids. We have cloned and sequenced the mouse protamine 1 gene. Ten lines of transgenic mice harboring marked protamine 1 sequences were generated by microinjection of fertilized eggs. Transcription of the transgene is restricted to round spermatids and in several cases exceeds that of the endogenous gene. The cis-acting sequences required for tissue-specific protamine expression reside on a 2.4-kilobase restriction fragment. Prospects for using transgenic mice to address fundamental questions of male germ-cell development are discussed.


Interaction of CD154 with different receptors and its role in bidirectional signals.
In addition to its classical receptor, CD40, it is now well established that CD154 also binds αIIbβ3, α5β1, and αMβ2 integrins. Although these integrins are all members of the same family, they bind CD154 differently. The current investigation aims to analyze the interaction of CD154 with α5β1 and αMβ2 and investigate its role in bidirectional signals in various human cell lines. Results obtained herein indicate that the CD154 residues involved in the interaction with α5β1 are N151 and Q166, whereas those involved in αMβ2 binding are common to residues required for CD40, namely Y145 and R203. Soluble CD40/CD154 or αMβ2/CD154 complexes do not interfere with the binding of CD154 to α5β1-positive cells, but inhibit the binding of CD154 to CD40- or αMβ2-positive cells, respectively. Ligation of CD154 on CD154-positive cells with soluble CD40, αIIbβ3, α5β1, or αMβ2 stimulates intracellular signaling, including MAPK phosphorylation. Given that CD154 exists as a trimer, our data strongly suggest that CD154 may bind concomitantly to two receptors of the same or different family, and biologically activate cells expressing both receptors. The characterization of CD154/receptor interactions helps the identification of new therapeutic targets for the prevention and/or treatment of CD154-associated autoimmune and inflammatory diseases.


Flexible pressure sensors with a highly pressure- and strain-sensitive layer based on nitroxyl radical-grafted hollow carbon spheres.
The spherical structure of hollow carbon spheres (HCSs) makes their contact resistance and tunnel resistance extremely sensitive to the distance between them, which can be used as a conductive filler for high-sensitivity pressure sensors. Compared with one- and two-dimensional carbon-based materials, HCSs require a higher filling concentration for constructing an effective conductive network due to their average conductivity, which affects the mechanical properties of the sensor. In a single-electron system, electrons are transferred by hopping between the nitroxyl radical monomers and when the distance between the monomers is shortened, the electron transfer rate of nitroxyl radical compounds can be increased, thus further improving their conductivity. In this work, a composite of nitroxyl radical-modified hollow carbon spheres (HCS-g-NO˙) and polydimethylsiloxane (PDMS) polymer is introduced, and the resistivity of HCS-g-NO˙ is about one magnitude lower than that of HCSs at the same filling concentration. A flexible piezoresistive sensor with HCS-g-NO˙@PDMS as the sensitive layer coated on the PET electrode is presented, in which the spacing between HCS-g-NO˙ changes, causing changes in the contact and tunnel resistances in the sensitive layer when mechanical stresses are applied. The sensor achieved a piezoresistive response of -0.55 kPa-1 and the tensile response of 211 , and a sensor array of nine pixels was successfully demonstrated; thus, it can be used as a high sensitivity pressure and strain sensor.


Long-Term Aging Behavior of Plastic/Styrene Butadiene Rubber (SBR) Composite Modified Bitumen.
The reuse of recycled waste plastics has long been attempted in pavement engineering as bitumen modifier. It was revealed that waste plastics can significantly enhance the high-temperature performance of bitumen and bitumen mixtures. Even so, the application of waste plastics as a bitumen modifier is still not widespread. This is attributable to the generally poor low-temperature performance of plastic-modified bitumen, which often fails to meet specification requirements. For this purpose, styrene butadiene rubber (SBR) was selected to improve the low-temperature performance of plastic-modified bitumen. However, due to the long-term aging process, the composite and structure of the modified bitumen will change, which negatively impacts its performance. The objective of this study is to investigate the long-term aging behavior of plastic/SBR composite-modified bitumen. For this purpose, waste polyethylene was used as a plastic modifier and was mixed with base bitumen and 3% SBR at ratios 4.5%, 6% and 7.5%. The rheological properties and molecular weight distribution of base bitumen, plastic and plastic/SBR-modified bitumen before and after long-term aging were measured. Results show that the incorporation of plastic can improve the complex modulus, rutting factor and percent recovery of bitumen and reduce the non-recoverable creep compliance of the bitumen, indicating the modification process enhances the high-temperature performance of bitumen. The enhancement effect is more pronounced with the increase of plastic content. For modified bitumen with 7.5% plastic modifier, the complex modulus of modified bitumen is increased by 1127.55% compared to base bitumen. The addition of 3% SBR modifier can further improve the high-temperature performance of the modified bitumen. In addition, the modification process also increases the large molecule size percentage (LMSP) and weight average molecular weight of bitumen. Compared with weight average molecular weight, the LMSP correlates well with the rheological properties of modified bitumen. In accordance with the complex modulus, using the LMSP and weight average molecular weight of bitumen before and after aging, the corresponding aging index was calculated. The quantitative results showed that the addition of plastic modifier can improve the aging resistance of bitumen, but the enhancement effect is not as obvious as that of SBR modifier.


[Clinical significance of peripheral blood circular DNA level measurements in patients with acute myocardial infarction].
To explore clinical value of circular DNA in acute myocardial infarction. Venous blood (2 ml/head) of 40 healthy control and 40 patients with acute myocardial infarction within 48h of onset of illness and convalescent period was collected. The level of plasma circular DNA was detected by duplex real-time polymerase chain reaction assay. The levels of myocardial enzyme spectrum and cardiac troponin T (cTnT) were detected by biochemistry method. The level of circular DNA in control group and group of acute myocardial infarction before treatment was (21.5 +/- 10.7) ng/ml and (253.6 +/- 45.7) ng/ml, respectively (P = 0.000). The levels of serum myocardial enzyme spectrum and cTnT before treatment in patients with acute myocardial infarction were significantly higher than those of control group (P < 0.05). The level of circular DNA after treatment in patients with acute myocardial infarction was significantly decreased compared with that before treatment (P = 0.000), the levels of myocardial enzyme spectrum and cTnT were also significantly reduced (P < 0.05). There was significant correlation between the level of circular DNA and those of CK-MB and cTnT, r = 0.613, 0.654, P = 0.032, 0.021. Circular DNA can be used as a marker of sensitively reflecting myocardial cell injury.


[Protease-antiprotease balance in patients with invasive carcinoma of the cervix and uterus before and after radiotherapy].
Malignant cells have the ability to invade and metastasize in great part because they secrete proteolytic enzymes. In order to investigate if the abnormal proteinase/antiproteinase balance of cancer bearing patients changes when the malignant tumor is destroyed, we studied 50 patients with invasive carcinoma of the cervix and 33 healthy women as a control group. Patients with cancer were treated with radiation according to the protocols of our hospital. The following serum determinations were performed: plasminogen activators (PA), cathepsin B (CB), antiproteinase alpha-1-antitrypsin (A1AT), trypsin inhibitory capacity (TIC) and antiproteolitic activity ratio (AAR), all of them before and after treatment. Serum proteolytic activity was elevated manyfold in all patients with invasive tumor as well A1AT. The antiproteolytic activity however, was significantly reduced to about 50% of its normal value in the same group of patients. In patients with good response to radiotherapy (tumor necrosis) a great reduction of proteinase activity as well as a recovery to normal of the AAR was observed. Contrary, in those with a poor response after radiation, proteolytic activity remained elevated and AAR diminished. It is concluded that serum PA, CB, A1AT and AAR values can be precise indicators of the presence of malignancy. These tests might be also of help for improving follow-up studies and for better prognostic estimates.


Correlations of Four Genetic Single Nucleotide Polymorphisms in Brain-Derived Neurotrophic Factor with Posttraumatic Stress Disorder.
To investigate the correlations of four genetic single nucleotide polymorphisms (SNPs) of brain-derived neurotrophic factor (BDNF) with posttraumatic stress disorder (PTSD). A total of 300 patients with sporadic PTSD and 150 healthy subjects (the control group) were selected according to the diagnostic criteria of PTSD (DSM-IV), and the genotypes of the BDNF SNPs G-712A, C270T, rs6265, and rs7103411 were detected by polymerase chain reaction and direct DNA sequencing to determine intergroup differences in the genotypes and allele frequencies; the p values were corrected with the permutation test. The genotypes and allele frequencies of the SNPs G-712A, rs6265, and rs7103411 of BDNF showed no significant intergroup differences (p>0.05). However, the genotype and allele frequencies of C270T showed significant differences between the PTSD group and the control group (p<0.05). The SNP C270T of BDNF may be associated with PTSD. Individuals carrying the polymorphic T allele of C270T may be more likely to suffer from PTSD.


Kupffer cells depress hepatocyte protein synthesis on cold storage of the rat liver.
The causes of liver failure after transplantation are multifactorial. An understanding of the mechanisms of injury to the liver could help to define methods to improve preservation and transplantation. We measured protein synthesis by 3H-leucine incorporation into acid precipitable protein in rat liver tissue slices, isolated hepatocytes, and isolated perfused liver (IPL) after cold storage for 24 or 48 hr in University of Wisconsin (UW) solution. Some rats were pretreated with dexamethasone prior to liver harvest. Protein synthesis was depressed in all in vitro models after 24 hr storage. The percent decrease was greater in tissue slices and IPL (about 70% decrease relative to fresh livers) than in isolated hepatocytes (about 30% decrease). Dexamethasone pretreatment improved protein synthesis significantly after 24 hr preservation in tissue slices and in IPL, but had no significant effect on protein synthesis in isolated hepatocytes. The greater loss of protein synthesis in tissue slices and IPL compared with that in isolated hepatocytes was considered in relation to the presence of Kupffer cells in the former systems and lack of Kupffer cells in the isolated cell suspensions. Kupffer cells generate cytotoxins that could cause injury to metabolically depressed hepatocytes or endothelial cells. Dexamethasone has been shown to modulate Kupffer cell inhibition of hepatocyte functions. The results suggest that preservation damage to hepatocytes sensitizes them to further damage on reperfusion by Kupffer cell-generated agents.


Soluble CD146, an innovative and non-invasive biomarker of embryo selection for in vitro fertilization.
Although progress was made in in vitro fertilization (IVF) techniques, the majority of embryos transferred fail to implant. Morphology embryo scoring is the standard procedure for most of IVF centres for choosing the best embryo, but remains limited since even the embryos classified as "top quality" may not implant. As it has been shown that i) CD146 is involved in embryo implantation and ii) membrane form is shed to generate soluble CD146 (sCD146), we propose that sCD146 in embryo supernatants may constitute a new biomarker of embryo selection. Immunocytochemical staining showed expression of CD146 in early embryo stages and sCD146 was detected by ELISA and Western-blot in embryo supernatants from D2. We retrospectively studied 126 couples who underwent IVF attempt. The embryo culture medium from each transferred embryo (n = 222) was collected for measurement of sCD146 by ELISA. Significantly higher sCD146 concentrations were present in embryo supernatants that did not implant (n = 185) as compared to those that successfully implanted (n = 37) (1310 +/- 1152 pg.mL-1 vs. 845+/- 1173 pg.mL-1, p = 0.024). Sensitivity analysis performed on single embryo transfers (n = 71) confirmed this association (p = 0.0054). The computed ROC curve established that the optimal sCD146 concentration for embryo implantation is under 1164 pg.mL-1 (sensitivity: 76%, specificity: 48%, PPV: 25% and NPV: 92%). Over this sCD146 threshold, the implantation rate was significantly lower (9% with sCD146 levels >1164 pg.ml-1 vs. 22% with sCD146 levels ≤ 1164 pg.mL-1, p = 0.01). Among the embryos preselected by morphologic scoring, sCD146 determination could allow a better selection of the embryo(s), thus improving the success of elective single embryo transfer. This study establishes the proof of concept for the use of sCD146 as a biomarker for IVF by excluding the embryo with the highest sCD146 level. A multicentre prospective study will now be necessary to further establish its use in clinical practice.


Evaluating health planning: empirical evidence on HSA regulation of prepaid group practices.
The regulation of HMOs by health planning agencies serves as a "tracer" to aid in evaluating HSAs, and as a source of empirical evidence for the heretofore largely theoretical health policy debate between market reformers and regulators. Two complementary studies (the authors' 1979 survey investigating the hospitalization policies of prepaid group practices, and AMPI 's study of all HMO applications submitted to HSAs from 1975 through mid-1978) provide information about the extent of HMO applications to planning agencies, the rate of rejections, the burden of the planning process of HMOs, and the possibility that negative perceptions of regulation may have led HMOs to refrain from activities requiring planning approval. Both studies reveal that health planning review was detrimental to 20 to 30 percent of HMOs. Thus data collected during the period of extensive HSA regulation of HMOs seem to justify the current policy that gives HSAs only very limited authority over HMOs.


Improving the matching degree between remotely sensed phenological dates and physiological growing stages of soybean by a dynamic offset-adjustment strategy.
Crop phenology provides crucial information for determining the appropriate timing of farm management practices and predicting crop yields. Satellite remote sensing has become a burgeoning tool for rapid phenological monitoring over wide spatial regions. However, there are significant timing gaps between the satellite-based phenological feature points and ground-observed physiological growing stages of the target. In this study, a dynamic offset-adjustment strategy that aims to improve the matching degree of the above two is proposed and tested with soybean across 16 states in the United States. A series of remotely sensed phenological transition dates that are characteristics of key growing stages of soybean were retrieved using MODIS time series data over the period 2000-2020 and the offset adjustments to the dates were identified by dynamically adjusting offset values till the minimum RMSE between the remote sensing-based and the ground-observed dates of physiological growing stages were obtained. The results indicated that the offset-adjustment strategy can significantly improve the alignments between remotely sensed phenological dates and field-based physiological growing stages of soybean in contrast to these without taking adjustment, with the average RMSE dropping by 58.58 %, 51.59 %, 31.15 %, 25.33 %, 24.67 % in the downturn, peak of season (POS), upturn, stabilization and recession dates, respectively. Among tested remotely sensed characteristics, the end of season (EOS) dates show the greatest alignment with its corresponding physiological growing stage, i.e., the dropping leaves stage. Comparison of the performance of the upturn date and start of season (SOS) in monitoring the date of the emerged stage indicates that the later one exhibits a better consistency with the ground-observed emerged stage after taking the adjustment, with the average RMSE dropping by 56.52 %. The proposed offset-adjustment strategy offers an approach for adjusting remotely sensed characteristics so to make them more consistent with the ground-observed crop physiological growing stages.


Intestinal epithelial organoids fuse to form self-organizing tubes in floating collagen gels.
Multiple recent examples highlight how stem cells can self-organize in vitro to establish organoids that closely resemble their in vivo counterparts. Single Lgr5+ mouse intestinal stem cells can be cultured under defined conditions forming ever-expanding epithelial organoids that retain cell polarization, cell type diversity and anatomical organization of the in vivo epithelium. Although exhibiting a remarkable level of self-organization, the so called 'mini-guts' have a closed cystic structure of microscopic size. Here, we describe a simple protocol to generate macroscopic intestinal tubes from small cystic organoids. Embedding proliferating organoids within a contracting floating collagen gel allows them to align and fuse to generate macroscopic hollow structures ('tubes') that are lined with a simple epithelium containing all major cell types (including functional stem cells) of the small intestine. Cells lining the central contiguous lumen closely resemble the epithelial cells on luminal villi in vivo, whereas buds that protrude from the main tube into the surrounding matrix closely resemble crypts. Thus, the remarkable self-organizing properties of Lgr5+ stem cells extend beyond the level of the microscopic cystic organoid to the next, macroscopic, level of tube formation.


Scaling and crossovers in activated escape near a bifurcation point.
Near a bifurcation point a system experiences a critical slowdown. This leads to scaling behavior of fluctuations. We find that a periodically driven system may display three scaling regimes and scaling crossovers near a saddle-node bifurcation where a metastable state disappears. The rate of activated escape W scales with the driving field amplitude A as ln W proportional, variant ( A(c) -A)(xi), where A(c) is the bifurcational value of A. With increasing field frequency the critical exponent xi changes from xi=3/2 for stationary systems to a dynamical value xi=2 and then again to xi=3/2. The analytical results are in agreement with the results of asymptotic calculations in the scaling region. Numerical calculations and simulations for a model system support the theory.


Effect of Early Versus Late Azathioprine Therapy in Pediatric Ulcerative Colitis.
We aimed at describing the efficacy of azathioprine (AZA) in pediatric ulcerative colitis, comparing the outcomes of early (0-6 months) versus late (6-24 months) initiation of therapy. Children with ulcerative colitis treated with AZA within 24 months of diagnosis were included. Corticosteroid (CS)-free remission and mucosal healing (MH), assessed by endoscopy or fecal calprotectin, at 12 months were the primary outcomes. Patients were also compared for CS-free remission and MH, need for treatment escalation or surgery, number of hospitalizations, and adverse events during a 24-month follow-up. A total of 121 children entered the study (median age 10.5 ± 4.0 years, 59% girls). Seventy-six (63%) started AZA between 0 and 6 months (early group) and 45 (37%) started between 6 and 24 months (late group). Seventy-five percent and 53% of patients in the early and late group, respectively, received CS at the diagnosis (P = 0.01). CS-free remission at 1 year was achieved by 30 (50%) of the early and 23 (57%) of the late patients (P = 0.54). MH occurred in 37 (37%) patients at 1 year, with no difference between the 2 groups (33% early, 42% late; P = 0.56). No difference was found for the other outcomes. Introduction of AZA within 6 months of diagnosis seems not more effective than later treatment to achieve CS-free remission in pediatric ulcerative colitis. MH does not depend on the timing of AZA initiation; however, because of the incomplete comparability of the 2 groups at the diagnosis and the use of fecal calprotectin as a surrogate marker of MH, our results should be further confirmed by prospective studies.


Schistosoma mansoni: a comparative study of schistosomula transformed mechanically and by skin penetration. Electrophysiological responses to a wide range of substances.
Volume conducted potentials were recorded from schistosomula of Schistosoma mansoni transformed mechanically (MS) and by skin penetration (SS). The spontaneous electrical activity recorded consisted of bi- and triphasic transients ranging from 20 to 200 microV in amplitude and 10 to 300 msec in duration. Low amplitude potentials occurred at a much greater frequency than large amplitude potentials, which appeared to correlate with peristaltic-like contractions of the schistosomulum's musculature. Electrical activity in the schistosomulum was highly sensitive to a number of agents believed to affect metabolic pathways, the neuromuscular system or the host/parasite interface of adult schistosomes. Among the most reactive substances were potassium antimony tartrate, eserine, poly-L-arginine and potassium cyanide. Over a wide range of experimental treatments, electrophysiological responses in schistosomula transformed from cercariae by mechanical decaudation and skin penetration were remarkably similar, supporting the notion that MS are suitable material for in vitro immunochemical, biochemical and physiological study. Some treatments, however, were more or less effective in altering electrophysiological activity and motility in the schistosomulum than in adult S. mansoni. This suggests that significant physiological alterations may occur during development from skin stage to adult parasites concomitant with immunochemical and morphological changes already known to occur.


Fungal Production and Manipulation of Plant Hormones.
Living organisms are part of a highly interconnected web of interactions, characterised by species nurturing, competing, parasitizing and preying on one another. Plants have evolved cooperative as well as defensive strategies to interact with neighbour organisms. Among these, the plant-fungus associations are very diverse, ranging from pathogenic to mutualistic. Our current knowledge of plant-fungus interactions suggests a sophisticated coevolution to ensure dynamic plant responses to evolving fungal mutualistic/pathogenic strategies. The plant-fungus communication relies on a rich chemical language. To manipulate the plant defence mechanisms, fungi produce and secrete several classes of biomolecules, whose modeof- action is largely unknown. Upon perception of the fungi, plants produce phytohormones and a battery of secondary metabolites that serve as defence mechanism against invaders or to promote mutualistic associations. These mutualistic chemical signals can be co-opted by pathogenic fungi for their own benefit. Among the plant molecules regulating plant-fungus interaction, phytohormones play a critical role since they modulate various aspects of plant development, defences and stress responses. Intriguingly, fungi can also produce phytohormones, although the actual role of fungalproduced phytohormones in plant-fungus interactions is poorly understood. Here, we discuss the recent advances in fungal production of phytohormone, their putative role as endogenous fungal signals and how fungi manipulate plant hormone balance to their benefits.


Taxoids from Taxus chinensis.
Two new taxoids, 13,15-epoxy-13-epi-taxayunnasin A (1) and taxchinin N (2), were isolated from the leaves and stems of Taxus chinensis. Compound 2 is the first taxoid to be reported with an alpha,beta-unsaturated lactone at C-4, C-5, C-20, and C-2. The structure of 1 was elucidated by spectroscopic analysis and confirmed by semisynthesis from taxayunnasin A, while 2 was determined structurally using spectroscopic methods and by single-crystal X-ray diffraction.


Expression of FLOWERING LOCUS C and a frameshift mutation of this gene on chromosome 20 differentiate a summer and winter annual biotype of Camelina sativa.
The nature of the vegetative to reproductive transition in the shoot apical meristem of Camelina sativa summer annual cultivar CO46 and winter annual cultivar Joelle was confirmed by treating seedlings with or without 8 weeks of vernalization. True to their life cycle classification, Joelle required a vernalization treatment to induce bolting and flowering, whereas CO46 did not. In this study, whole genome sequence, RNAseq, and resequencing of PCR-amplified transcripts for a key floral repressor were used to better understand factors involved in the flowering habit of summer and winter biotypes at the molecular level. Analysis of transcriptome data indicated that abundance for one of the three genes encoding the floral repressor FLOWERING LOCUS C (FLC; Csa20 g015400) was 16-fold greater in Joelle compared to CO46 prior to vernalization. Abundance of this transcript decreased only slightly in CO46 postvernalization, compared to a substantial decrease in Joelle. The results observed in the winter annual biotype Joelle are consistent with repression of FLC by vernalization. Further characterization of FLC at both the genome and transcriptome levels identified a one base deletion in the 5th exon coding for a keratin-binding domain in chromosome 20 of CO46 and Joelle. The one base deletion detected in chromosome 20 FLC is predicted to result in a frameshift that would produce a nonfunctional protein. Analysis of whole genome sequence indicated that the one base deletion in chromosome 20 FLC occurred at a greater ratio in the summer biotype CO46 (2:1) compared to the winter biotype Joelle (1:4); similar trends were also observed for RNAseq and cDNA transcripts mapping to chromosome 20 FLC of CO46 and Joelle.


Current Usage of Traditional Chinese Medicine in the Management of Breast Cancer: A Practitioner's Perspective.
Introduction This qualitative study seeks to explore the role within the context of Australian breast cancer oncology treatments that traditional Chinese medicine (TCM) practitioners play in the treatment of breast cancer. Methods Semistructured interviews were used on 2 groups: the first group was TCM practitioners who were recognized experts in breast cancer, and the second group consisted of TCM practitioners who treated breast cancer as part of their practice but were not recognized experts. Data analysis was achieved through grounded theory with open coding. Results The main themes reported on here are the following: the role of TCM in the biomedical management of breast cancer, TCM strategies for the management of breast cancer, and the perceived holistic approach of the TCM practitioner and the importance of a TCM diagnosis in the role of breast cancer care. Discussion The role of TCM in biomedical breast cancer management is a supportive one; however, this role is difficult as there is a lack of understanding of TCM by biomedical practitioners. The viewpoints of practitioners differed on key strategies of TCM: diagnosis, and treatment protocols. Patients sought the holistic approach of TCM practitioners as they felt it addressed all aspects of their health and not just the symptoms relating to breast cancer. Conclusion The lack of an integrated medicine approach in relation to TCM makes it difficult to demonstrate the value of the contribution TCM can make to biomedicine in the field of breast care oncology. Effectiveness studies are needed that can accurately represent TCM in this field.


Meeting report: Messages from Moscow--the BSAC at the ninth IACMAC International Congress on Antimicrobial Therapy.
The organizing committee of the Russian Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy invited an international delegation of representatives, including nine BSAC members, to contribute to their ninth congress in Moscow at the end of May 2007. The event demonstrated the value of comparing experience in the context of an educational meeting and how efficient organization can overcome potential communication problems when simultaneous audio and slide translations are used to best effect.


Safety and immunogenicity of a live oral bivalent typhoid fever (Salmonella typhi Ty21a)-cholera (Vibrio cholerae CVD 103-HgR) vaccine in healthy adults.
The safety and immunogenicity of the live oral attenuated vaccine strains vibrio cholerae CVD 103-HgR and Salmonella typhi Ty21a were evaluated alone or in a combined bivalent formulation in four groups composed of 185 healthy European adults. All presentations were well tolerated. The serum anti-S. typhi lipopolysaccharide immunoglobulin G and immunoglobulin A antibody responses were comparable for all groups (66 to 72% seroconversion). The serum vibriocidal antibody seroconversion rate ranged from 78 to 92.5% (P > 0.05) among the groups. However, the peak and geometric mean vibriocidal antibody titers were significantly higher (P < 0.005) in the groups which received the bivalent formulation along with two doses of Ty21a than in the group which received CVD 103-HgR followed by two doses of killed Escherichia coli K-12 placebo. The ingestion of a placebo shortly after CVD 103-HgR may have suppressed the magnitude of the immune response. These findings demonstrate the feasibility of producing multivalent live oral attenuated vaccines.


Acute arsenic toxicity alters cytochrome P450 and soluble epoxide hydrolase and their associated arachidonic acid metabolism in C57Bl/6 mouse heart.
Acute arsenic (As(III)) exposure has been reported to cause cardiac toxicity, however this toxicity was never linked to the disturbance in cytochrome P450 (P450)-mediated arachidonic acid metabolism. Therefore, we investigated the effect of acute As(III) toxicity on the expression of P450 and soluble epoxide hydrolase (sEH) and their associated arachidonic acid metabolism in mice hearts. As(III) toxicity was induced by a single intraperitoneal injection of 12.5 mg/kg of As(III). Our results showed that As(III) treatment caused a significant induction of the cardiac hypertrophic markers in addition to Cyp1b1, Cyp2b, Cyp2c, Cyp4f, and sEH gene expression in mice hearts. Furthermore, As(III) increased sEH protein expression and activity in hearts with a consequent decrease in 11,12-, and 14,15-epoxyeicosatrienoic acids (EETs) formation. Whereas the formation of 8,9-, 11,12-, 14,15-dihydroxyeicosatrienoic acids (DHETs) was significantly increased. As(III) also increased sEH mRNA and protein expression levels in addition to the hypertrophic markers which was reversed by knockdown of sEH in H9c2 cells. In conclusion, acute As(III) toxicity alters the expression of several P450s and sEH enzymes with a consequent decrease in the cardioprotective EETs which may represent a novel mechanism by which As(III) causes progressive cardiotoxicity. Furthermore, inhibiting sEH might represent a novel therapeutic approach to prevent As(III)-induced hypertrophy.


Cutaneous malignant melanoma incidence rates in Norway.
The incidence rates of cutaneous malignant melanoma (CMM) increase throughout the world, in spite of introduction of strategies for prevention. However, a decrease in incidence rates is observed in some countries. If the reason for this could be found, it might be useful to transfer the knowledge to other fields of medicine. CMM age-standardized incidence rates in different age groups in Norway were obtained from NORDCAN for the years 1970-1989 and 1990-2009. Until 1990, the CMM rates increased, but after that time a stabilization or a decrease was observed for young age groups (15-54 years old), while in older generations (>55 years old) the rates continued to increase. The decreasing CMM pattern in young age groups may be due to changing patterns to sunlight in sunbathing and use of sunbeds.


The onset of virus shedding and clinical signs in chickens infected with high-pathogenicity and low-pathogenicity avian influenza viruses.
Some avian influenza viruses may be transmissible to mammals by ingestion. Cats and dogs have been infected by H5N1 avian influenza viruses when they ate raw poultry, and two human H5N1 infections were linked to the ingestion of uncooked duck blood. The possibility of zoonotic influenza from exposure to raw poultry products raises concerns about flocks with unrecognized infections. The present review examines the onset of virus shedding and the development of clinical signs for a variety of avian influenza viruses in chickens. In experimentally infected birds, some high-pathogenicity avian influenza (HPAI) and low-pathogenicity avian influenza (LPAI) viruses can occur in faeces and respiratory secretions as early as 1 to 2 days after inoculation. Some HPAI viruses have also been found in meat 1 day after inoculation and in eggs after 3 days. There is no evidence that LPAI viruses can be found in meat, and the risk of their occurrence in eggs is poorly understood. Studies in experimentally infected birds suggest that clinical signs usually develop within a few days of virus shedding; however, some models and outbreak descriptions suggest that clinical signs may not become evident for a week or more in some H5 or H7 HPAI-infected flocks. During this time, avian influenza viruses might be found in poultry products. LPAI viruses can be shed in asymptomatically infected or minimally affected flocks, but these viruses are unlikely to cause significant human disease.


Robustness of the Photo Anxiety Questionnaire: changing the sequence of stimuli and photographs.
In a split-ballot experiment (N=458) we tested, first, to what extent the logical presentation of the Photo Anxiety Questionnaire forces respondents into the usual response pattern, that is, a higher reported anxiety on items mentioning a time closer to dental treatment. Secondly, we tested whether subjects use the nonverbal response scale or merely use the position of the photographs on the scale when answering the questions. The original questionnaire had the highest reliability and was least influenced by response bias. Changing the order of the photographs on the response scale did not alter the response pattern, implying that subjects do react to the intensity displayed in the photographs and not just to the position of the photograph on the scale. Because changing the order of the items altered the response pattern only marginally, the response pattern usually found does not seem to be the direct consequence of the logical presentation of the Photo Anxiety Questionnaire.


Context effects on the processing of action-relevant object features.
In 4 experiments, we investigated the effects of object affordance in reach-to-grasp actions. Participants indicated whether a depicted small or large object was natural or manmade by means of different object-grasping responses (i.e., with a power or a precision grip). We observed that the size of the depicted object affected the grasping kinematics (grip aperture) and the reach-onset times of compatible and incompatible actions. Additional experiments showed that the effect of perceived object size on motor response was modulated by contextual action information and the observation of others' actions with the object. Thus, beyond the observation of object affordance effects in natural grasping actions, this study suggests that the coupling between object perception and action is not static and obligatory. Behavioral effects of action-relevant object features seem rather to depend on contextual action information.


Compatible Rhizosphere-Competent Microbial Consortium Adds Value to the Nutritional Quality in Edible Parts of Chickpea.
Chickpea is used as a high-energy and protein source in diets of humans and livestock. Moreover, chickpea straw can be used as alternative of forage in ruminant diets. The present study evaluates the effect of beneficial microbial inoculation on enhancing the nutritional values in edible parts of chickpea. Two rhizosphere-competent compatible microbes (Pseudomonas fluorescens OKC and Trichoderma asperellum T42) were selected and applied to seeds either individually or in consortium before sowing. Chickpea seeds treated with the microbes showed enhanced plant growth [88.93% shoot length at 60 days after sowing (DAS)] and biomass accumulation (21.37% at 120 DAS). Notably, the uptake of mineral nutrients, viz., N (90.27, 91.45, and 142.64%), P (14.13, 58.73, and 56.84%), K (20.5, 9.23, and 35.98%), Na (91.98, 101.66, and 36.46%), Ca (16.61, 29.46, and 16%), and organic carbon (28.54, 17.09, and 18.54%), was found in the seed, foliage, and pericarp of the chickpea plants, respectively. Additionally, nutritional quality, viz., total phenolic (59.7, 2.8, and 17.25%), protein (9.78, 18.53, and 7.68%), carbohydrate content (26.22, 30.21, and 26.63%), total flavonoid content (3.11, 9.15, and 7.81%), and reducing power (112.98, 75.42, and 111.75%), was also found in the seed, foliage, and pericarp of the chickpea plants. Most importantly, the microbial-consortium-treated plants showed the maximum increase of nutrient accumulation and enhancement in nutritional quality in all edible parts of chickpea. Nutritional partitioning in different edible parts of chickpea was also evident in the microbial treatments compared to their uninoculated ones. The results thus clearly demonstrated microbe-mediated enhancement in the dietary value of the edible parts of chickpea because seeds are consumed by humans, whereas pericarp and foliage (straw) are used as an alternative of forage and roughage in ruminant diets.


[Drugs and health. 2. Study on the presence, use, storage and disposal of drugs in a sample of families in Adria (Rovigo) Local Health Unit 31, Venetian region].
As part of a health education scheme for the schools on "Drugs and Health", a questionnaire was distributed to a number of pupils in order to ascertain the domestic presence, use, conservation, and disposal of drugs. The questionnaire proved a very effective system for the extension of the educational project to the families of the pupils, but the information thus gathered was only of limited value. On the average, in the family 12.8 different type of drugs were present, mainly ethical drugs (76.6%). Most drugs were Articulars, Analgesics-antipyretics and Bronchopulmonary drugs. Only 30.2% of the drugs kept at home were currently used. Self-treatment (14.9%) and self-prescription (8.1%) were noted, as well as improper use of the drugs (5.9%). No answer to the questionnaire mentioned the presence of expired drugs: probably they were disposed of during the survey at home. Although these facts showed the positive effects of the educational project, nonetheless it was not possible to establish the real number of drugs kept at home. The way the answers to the questionnaire were biased and the fact that it was meant to be part of the project, have reduced the objectivity of the information thus obtained, underlining, however, its educational value.


Comparison of serum tumor markers for intrahepatic cholangiocarcinoma and hepatocellular carcinoma.
Serum tumor markers such as alpha-fetoprotein (AFP), carcinoembryonic antigen, carbohydrate antigen (CA) 19-9, CA242, and CA50 were analyzed to evaluate their diagnostic values in single and combined tests for distinguishing intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC). Preoperative serum levels of AFP, carcinoembryonic antigen, CA19-9, CA242, and CA50 were measured in 45 ICC and 76 HCC patients. The serum levels and the positive rate of AFP, CA19-9, and CA242 were significantly different between the ICC patients and HCC patients. Although AFP (-) was the most sensitive assay for distinguishing ICC from HCC (91.1%), its specificity was significantly lower than that of CA242 (+) and CA19-9 (+). The combination of AFP (-) and CA242 (+) afforded a high specificity of 94.3 per cent and showed highest accuracy (78.5%). Evaluation of patients without liver cirrhosis also showed similar results. The diagnostic value of CA242 (+) is better than that of CA19-9 (+) and AFP (-) in distinguishing ICC from HCC. Combined detection of AFP (-) and CA242 (+) can improve the specificity and accuracy of diagnosing ICC.


Two-dimensional echocardiographic identification of a right ventricle tumor.
A metastatic tumor in the right ventricle was clearly visualized using two-dimensional echocardiography. The location, size, and mobility of the tumor were easily demonstrated. Two-dimensional echocardiography is superior to M-mode echocardiography in such cases.


Intermolecular resonance energy transfer between two lutein pigments in light-harvesting complex II studied by frenkel exciton models.
The energy transfer pathways in light-harvesting complex II are complicated and the discovery of the energy transfer between the two luteins revealed an unelucidated important role of carotenoids in the energy flow. This energy transfer between the two S2 states of luteins was for the first time investigated using Frenkel exciton models, using a hybrid scheme of molecular mechanics and quantum mechanics. The results show the energy flow between the two luteins under the Förster resonance energy transfer mechanism. The energy transfer caused by energy level resonance occurs in configurations with small energy gaps. This energy transfer pathway is particularly sensitive to conformation. Moreover, according to the statistical characteristics of the data of the energy gaps and coupling values between LUTs, we proposed stochastic exciton Hamiltonian models to facilitate clarification of the energy transfer among pigments in antenna complexes.


STEP Matters: Historiographical Considerations.
In this introduction, we revisit major discussions around historical themes and historiographical issues that took place during the fifteen-year life of STEP (Science and Technology at the European Periphery). We will attempt to draw the profile of STEP, and put forth some concrete proposals as to its prospects of collaboration with other groups and societies. We also elaborate on the rationale behind the selection of topics presented in this issue, analyse questions posed and challenges faced, and offer some historiographical comments on the potential of the STEP perspective in the context of international scholarship.


Stabilization of the predominant disease-causing aldolase variant (A149P) with zwitterionic osmolytes.
Hereditary fructose intolerance (HFI) is a disease of carbohydrate metabolism that can result in hyperuricemia, hypoglycemia, liver and kidney failure, coma, and death. Currently, the only treatment for HFI is a strict fructose-free diet. HFI arises from aldolase B deficiency, and the most predominant HFI mutation is an alanine to proline substitution at position 149 (A149P). The resulting aldolase B with the A149P substitution (AP-aldolase) has activity that is <100-fold that of the wild type. The X-ray crystal structure of AP-aldolase at both 4 and 18 °C reveals disordered adjacent loops of the (α/β)(8) fold centered around the substitution, which leads to a dimeric structure as opposed to the wild-type tetramer. The effects of osmolytes were tested for restoration of structure and function. An initial screen of osmolytes (glycerol, sucrose, polyethylene glycol, 2,4-methylpentanediol, glutamic acid, arginine, glycine, proline, betaine, sarcosine, and trimethylamine N-oxide) reveals that glycine, along with similarly structured compounds, betaine and sarcosine, protects AP-aldolase structure and activity from thermal inactivation. The concentration and functional moieties required for thermal protection show a zwitterion requirement. The effects of osmolytes in restoring structure and function of AP-aldolase are described. Testing of zwitterionic osmolytes of increasing size and decreasing fractional polar surface area suggests that osmolyte-mediated AP-aldolase stabilization occurs neither primarily through excluded volume effects nor through transfer free energy effects. These data suggest that AP-aldolase is stabilized by binding to the native structure, and they provide a foundation for developing stabilizing compounds for potential therapeutics for HFI.


The severity grading of acute cholecystitis following the Tokyo Guidelines is the most powerful predictive factor for conversion from laparoscopic cholecystectomy to open cholecystectomy.
The relationship between the severity assessment of acute cholecystitis based on the Tokyo Guidelines and the risk for conversion from laparoscopic surgery to open surgery has been assessed in few previous reports, with conflicting results. A retrospective review of patients with acute cholecystitis within a single system from 2010 to 2013 was performed. The diagnosis and severity of acute cholecystitis were assigned by the Tokyo Guidelines 2013 (TG13). The primary outcome measure was conversion to open cholecystectomy. During the period of study, 493 patients were operated by laparoscopy for acute cholecystitis. Laparoscopic cholecystectomy was intraoperatively converted to open surgery in 56 cases (11.4%). The multivariate analysis showed that the risk factors for conversion to open surgery included male gender (OR: 2.15; IC95% [1.18-3.9]), diabetes (OR: 2.22; IC95% [1.13-4.33]), total bilirubin levels (OR: 1.02; IC95% [1-1.05]), and the TG13 severity classification (OR: 4.44; IC95% [2.25-8.75]). The independent risk factors for conversion to open surgery included male sex, diabetes mellitus, total bilirubin level, and TG13 grade. TG13 grade was found to be the most powerful predictive factor for conversion as it had the highest OR.


An implant-supported rehabilitation case using innovative provisional restoration design and conversion as diagnostic and treatment modalities.
This article reviews and details a maxillary anterior implant-supported rehabilitation case that required an interdisciplinary approach. An innovative technique is presented, in which a transitional acrylic and wrought wire removable partial denture was converted at chairside to a provisional fixed bridge on the day of Stage II implant surgery. This technique underscores and illustrates the importance of diagnosis, planning, and sequential, coordinated treatment in dental rehabilitation.


The A. thaliana disease resistance gene RPS2 encodes a protein containing a nucleotide-binding site and leucine-rich repeats.
In plants, resistance to a pathogen is frequently correlated with a genetically defined interaction between a plant resistance gene and a corresponding pathogen avirulence gene. A simple model explains these gene-for-gene interactions: avirulence gene products generate signals (ligands), and resistance genes encode cognate receptors. The A. thaliana RPS2 gene confers resistance to the bacterial pathogen P. syringae carrying the avirulence gene avrRpt2. A map-based positional cloning strategy was used to identify RPS2. The identification of RPS2 was verified using a newly developed transient assay for RPS2 function and by genetic complementation in transgenic plants. RPS2 encodes a novel 105 kDa protein containing a leucine zipper, a nucleotide-binding site, and 14 imperfect leucine-rich repeats.