Melanoma formation in Xiphophorus: a model system for the role of receptor tyrosine kinases in tumorigenesis.
Cancer is one of the most frequent fatal human diseases. It is a genetic disease, and molecular analysis of the genes involved revealed that they belong to several distinct classes of molecules, one of which is the receptor tyrosine kinases. Neoplastic transformation is regarded as the result of a multistep process and, in most cases, it is hard to evaluate what the initial events in tumor formation are. What makes it difficult to approach this question is the paucity of animals models for tumorigenesis allowing investigation of the mechanisms leading to uncontrolled cell proliferation. Melanoma formation in Xiphophorus is one of these model systems. Here, overexpression and activation of a receptor tyrosine kinase causes neoplastic transformation of pigment cells. Xiphophorus provides all the advantages of a well-characterized genetic system. In addition, some crucial components of the transformation pathway have been identified at the molecular level. As a vertebrate, Xiphophorus might serve as a model system to aid understanding, in more general terms, of the mechanisms of tumorigenesis in human diseases.


[Dongfeng-Tongji cohort: methodology of the survey and the characteristics of baseline and initial population of follow-up program].
To explore the effects of related environment, occupational, lifestyle, genetic factors as well as their interactions on the etiology of major chronic diseases in an occupational population. Dongfeng-Tongji cohort (DFTJ cohort), one of the large prospective cohort studies with biobank. Baseline study was conducted in Shiyan city, Hubei province from 2008 to 2009. This cohort study included questionnaire, physical examination and tests on blood samples. Dongfeng-Tongji cohort was followed up every 5 years and the first follow-up program was completed, from April to October in 2013. During the first follow-up period in 2013, questionnaire, physical examination, clinical and blood sample tests were conducted again. 27 009 retired participants with mean age of 63.6 years including 44.6% males, were recruited in this study. In the first follow-up program in 2013, among 38 295 subjects (44.7% males), 40.5% of them received diploma from high school or above. Prevalence rates of current regular smokers were 33.6% in men and 2.0% in women and the rates on current alcohol drinkers were 39.9% in men and 10.6% in women. The prevalence rates on self-reported hypertension, hypercholesterolemia, diabetes mellitus, coronary heart disease, stroke, chronic bronchitis, and asthma were 41.1%, 24.3%, 13.9%, 16.7%, 5.1%, 12.7% and 4.0%, respectively. The self-reported prevalence of hypertension and stroke in males was higher than that in females. 25 978 individuals who were involved in the baseline database successfully completed the followed up program in 2013, with the follow-up rate as 96.2%. The DFTJ cohort study offered us an opportunity to explore the effects of environmental, genetic, as well as their interactions with major chronic diseases in a Chinese occupational population.


Exhaled nitric oxide after beta2-agonist inhalation and spirometry in asthma.
Exhaled nitric oxide (ENO) is used increasingly as a surrogate marker of airway inflammation in research protocols that may incorporate standard efficacy measures, such as spirometry before and after bronchodilator, which could affect ENO measurements. In seven healthy volunteers and 11 mild asthmatic subjects, we measured ENO before and serially for 1 h after spirometry. On two additional days in the subjects with asthma, we reexamined the effect of spirometry as before, followed by the serial measurement of ENO for 1 h after two puffs of salbutamol (100 microgram/puff) by metered-dose inhaler or matching placebo. As early as 1 min after spirometry, ENO fell by 13% and 10% in the normal and asthmatic subjects, respectively. In both groups, ENO returned to baseline over 1 h. In the asthmatic subjects, salbutamol caused a significant mean increase of the order of 10 parts per billion in ENO (p < 0.001) for 1 h as compared with placebo inhaler. We conclude that spirometry and beta2-agonist may perturb ENO values and recommend that studies control for these factors.


Routinely recorded patient safety events in primary care: a literature review.
Existing patient-level data can be used to measure and monitor patient safety. Data from sources including electronic patient records are routinely collected in primary care and may be suitable for adverse event screening, such as patient safety indicators. To inform the feasibility of developing primary care measures of patient harm, information about routinely collected data is needed. A literature review was conducted to determine the types of adverse events that are routinely recorded in primary care. We searched ASSIA, Cochrane Library, Embase, HMIC, ISI Web of Science, Medline and PsycInfo databases, grey literature and websites. We included only original research studies in English where routinely collected patient data were used to identify adverse events occurring in primary or ambulatory care settings. Adverse events were defined as unexpected and undesirable patient outcomes arising from health care contact. Of 5029 citations identified, 15 were reviewed. Twelve studies used multiple data sources. Approximately 6.5% of adult emergency admissions were due to drug-related events (n = 1225). Between 0.7% and 2.3% of deaths following adverse events were attributed to treatment in primary care. A large proportion of adverse events resulting in the most severe harm may be preventable. For example, one study estimated that 42% of serious adverse drug events were avoidable. There is limited use of routinely collected data to measure adverse events in primary care despite large volumes of data generated. The potential for using readily available data recorded in primary care for active patient safety surveillance needs further exploration.


Cell adhesion, spreading, and motility of GM3-expressing cells based on glycolipid-glycolipid interaction.
Cell lines expressing varying levels of ganglioside GM3 at the cell surface show different degrees of adhesion and spreading on solid phase coated with such glycosphingolipids (GSLs) as Gg3 (GalNAc beta 1----4Gal beta 1----4Glc beta 1----1Cer), LacCer (Gal beta 1----4Glc beta 1----1Cer), or Gb4 (GalNAc beta 1----3Gal alpha 1----4Gal beta 1----4Glc beta 1----1Cer) (where Cer is ceramide), which may have structures complementary to GM3, but not on solid phase coated with various other GSLs. The degree of cell adhesion and spreading on Gg3 was correlated with the degree of cell-surface GM3 expression, as defined by reactivity with anti-GM3 monoclonal antibody (mAb) DH2. Only cells with high GM3 expression adhered on solid phase coated with LacCer or Gb4. Adhesion of GM3-expressing cells on Gg3-, LacCer-, and Gb4-coated solid phase is based on interaction of GM3 with Gg3 and, to a lesser extent, with LacCer and Gb4, as demonstrated by: (i) the interaction of the GM3 liposome with solid phase coated with Gg3, LacCer, and Gb4, respectively; (ii) the abolition of cell adhesion on each GSL-coated solid phase by treatment of cells with mAb DH2 or sialidase; and (iii) the inhibition of cell adhesion by treatment of GSL-coated solid phase with mAb specific to each GSL. Sialosyllactosyl-lysyllysine conjugate was bound to Gg3 adsorbed on a C18 silica gel column in the presence of bivalent cation, suggesting that the carbohydrate moiety of GM3 is involved in GM3-Gg3 interaction. Not only the adhesion and spreading of GM3-expressing cells, but also their cell motility was greatly enhanced on Gg3-coated solid phase, as determined by Transwell assay and phagokinetic track assay on a gold sol-coated surface. Spreading and motility of GM3-expressing cells on Gg3-coated solid phase were both inhibited by treatment of cells with mAb DH2 or sialidase. These results provide evidence that not only cell adhesion, but also spreading and motility in these cell lines are controlled by complementary GSL-GSL interaction.


Flicker-photometric spectral sensitivity in the presence of chromatic surrounds.
Flicker-photometric spectral sensitivity is measured in the presence and absence of superimposed monochromatic surrounds. Although color appearance depends on surround wavelength, the shape of the flicker-spectral-sensitivity functions are unaffected. These findings indicate both a lack of cone-cone inhibition within the achromatic channel and independence of the achromatic and chromatic channels.


The role of radiotherapy for metastatic epidural spinal cord compression.
Radiotherapy alone is the most common treatment for metastatic epidural spinal cord compression (MESCC). Decompressive surgery followed by radiotherapy is generally indicated only in 10-15% of MESCC cases. Chemotherapy has an unclear role and may be considered for selected patients with hematological or germ-cell malignancies. If radiotherapy alone is given, it is important to select the appropriate regimen. Similar functional outcomes can be achieved with short-course radiotherapy regimens and longer-course radiotherapy regimens. Longer-course radiotherapy is associated with better local control of MESCC than short-course radiotherapy. Patients with a more favorable survival prognosis (expected survival of ≥6 months) should receive longer-course radiotherapy, as they may live long enough to develop a recurrence of MESCC. Patients with an expected survival of <6 months should be considered for short-course radiotherapy. A recurrence of MESCC in the previously irradiated region after short-course radiotherapy may be treated with another short-course of radiotherapy. After primary administration of longer-course radiotherapy, decompressive surgery should be performed if indicated. Alternatively, re-irradiation can be performed using high-precision techniques to reduce the cumulative dose received by the spinal cord. Larger prospective trials are required to better define the appropriate treatment for the individual patient.


Non-linear developmental trajectory of electrical phenotype in rat substantia nigra pars compacta dopaminergic neurons.
Neurons have complex electrophysiological properties, however, it is often difficult to determine which properties are the most relevant to neuronal function. By combining current-clamp measurements of electrophysiological properties with multi-variate analysis (hierarchical clustering, principal component analysis), we were able to characterize the postnatal development of substantia nigra dopaminergic neurons' electrical phenotype in an unbiased manner, such that subtle changes in phenotype could be analyzed. We show that the intrinsic electrical phenotype of these neurons follows a non-linear trajectory reaching maturity by postnatal day 14, with two developmental transitions occurring between postnatal days 3-5 and 9-11. This approach also predicted which parameters play a critical role in phenotypic variation, enabling us to determine (using pharmacology, dynamic-clamp) that changes in the leak, sodium and calcium-activated potassium currents are central to these two developmental transitions. This analysis enables an unbiased definition of neuronal type/phenotype that is applicable to a range of research questions.


Social vole parents force their mates to baby-sit.
Parental care has been categorized into direct and indirect investment. The former includes direct contact with the offspring, as in lactation or huddling with the pups, and the latter includes activities such as nest building or hoarding food for the guarding mate. We report here an unfamiliar type of parental behavior in which one parent aggressively forces its mate to stay in the nest with the pups. In this "forced baby-sitting," one parent grasps the fur of its mate and drags it toward the nest. The behavior was observed in 6 of 10 pairs of the social vole (Microtus socilalis guentheri) and was typically executed by the male. Dragging the mate to the nest was not correlated with other parental behaviors; neither could we explain why/when it occurred. However, this behavioral pattern was eye catching, and its goal was obviously to enforce the mate to stay in the nest with the pups.


Development and validation of psychological status questionnaire for parents of infantile hemangiomas.
Infantile hemangioma (IH) is the most frequent benign tumor of infancy which impacts the psychological status of parents of affected children. Parental psychological status has a significant effect on the therapeutic effect and long-term prognosis of IH children. However, no standard questionnaires had been established previously to assess the psychological status of Chinese parents of children with IH. This study prospectively developed and validated a psychological status instrument for the assessment of parents of patients with IH and to identify clinical features with effects on the psychological status. A total of 350 parents completed the 35-item Psychologic Status Questionnaire for parents of Infantile Hemangiomas (IH-PSQ) and provided demographic information. The IH-PSQ was refined via item analysis, validity analysis (including exploratory factor analysis and criterion-related validity) and reliability analysis (including internal consistency reliability, split half reliability, and test-retest reliability). The dimensionality of the items was evaluated using factor analysis, with results suggesting 5 factors: anxiety, depression, psychological imbalance, disease shame, and disease fear. The final instrument consists of 4 scales with a total of 23 items. Construct validity was demonstrated and IH-PSQ showed good internal coherence (Cronbach's α: 0.957), good split half reliability (0.971), and good test-retest reliability (correlation coefficient: 0.967). The correlation coefficient between the Self-Rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) of children with IH was 0.874 and 0.754, respectively. Multiple linear regression analysis found that some characteristics will affect the score of IH-PSQ. The IH-PSQ contains 5 dimensions and 23 entries, and with good reliability and validity, can objectively and effectively evaluate the psychological status of IH parents. Certain clinical characteristics of IH families, including parents' own factors (including their monthly income and cultural level) and disease-related factors of affected children (including the duration of illness, tumor size, with or without complications, single or multiple, whether being treated or not), were associated with a greater impact on IH-PSQ.


A novel enrichment program using cascading mentorship to increase diversity in the health care professions.
The authors describe an innovative summer enrichment program based on a cascading mentorship model to transfer knowledge and skills from faculty to medical students to undergraduate students and finally to high school students. The program was designed to give high school students a glimpse of life in medical school and enhance the teaching and leadership skills of underrepresented undergraduate and medical students. Started in 2010 with 30 high school students and 9 college and medical student coaches, the University of California, Irvine, School of Medicine Summer Premed Program expanded rapidly over the next two summers and enrolled a total of 253 high school students, 48 college students, and 12 medical students. The college and medical student coaches, the majority of whom were underrepresented in medicine (URIM), reported that the program enhanced their teaching and leadership skills and self-confidence, motivated them toward careers in academic medicine, and raised their awareness about the importance of cultural diversity. The authors present the details of this interactive, structured program and describe how URIM student empowerment, near-peer teaching, science socialization, and support from the institution's leadership and faculty members provided a climate that fostered belonging, a sense of personal transformation, and professional development among students from different levels of education and diverse backgrounds. Long-term follow-up of the participants' career choices is needed.


Calculation of the Contact Angle of Polymer Melts on Tool Surfaces from Viscosity Parameters.
It is of great importance for polymer processing whether and how viscosity influences the wettability of tool surfaces. We demonstrate the existence of a distinct relationship between the contact angle of molten polymers and zero shear viscosity in this paper. The contact angle of molten polypropylene and polymethylmethacrylate on polished steel was studied in a high temperature chamber using the sessile drop method. A high pressure capillary rheometer with a slit die was employed to determine the shear viscosity curves in a low shear rate range. A linear relation between the contact angle and zero shear viscosity was obtained. Furthermore, the contact angle and the zero shear viscosity values of the different polymers were combined to one function. It is revealed that, for the wetting of tool surfaces by molten polymers, a lower viscosity is advantageous. Furthermore, a model based on the temperature shift concept is proposed which allows the calculation of the contact angle of molten polymers on steel for different temperatures directly from shear viscosity data.


Preoperative misdiagnosis analysis and accurate distinguish intrathymic cyst from small thymoma on computed tomography.
To evaluate the role of computed tomography (CT) in preoperative diagnosis of intrathymic cyst and small thymoma, and determine the best CT threshold for distinguish intrathymic cyst from small thymoma. We retrospectively reviewed the medical records of 30 patients (17 intrathymic cyst and 13 small thymoma) who had undergone mediastinal masses resection (with diameter less than 3 cm) under thoracoscope between January 2014 and July 2015 at our hospital. Clinical and CT features were compared and receiver-operating characteristics curve (ROC) analysis was performed. The CT value of small thymoma [39.5 HU (IQR, 33.7-42.2 HU)] was significantly higher than intrathymic cyst [25.8 HU (IQR, 22.3-29.3 HU), P=0.004]. When CT value was 31.2 HU, it could act as a threshold for identification of small thymoma and intrathymic cyst (the sensitivity and specificity was 92.3% and 82.4%, respectively). The ΔCT value of enhanced CT value with the non-enhanced CT value was significantly different between small thymoma [18.7 HU (IQR, 10.9-19.0 HU)] and intrathymic cyst [4.3 HU (IQR, 3.0-11.7 HU), P=0.04]. The density was more homogenous in intrathymic cyst than small thymoma, and the contour of the intrathymic cyst was more smoothly than small thymoma. Preoperative CT scans could help clinicians to identify intrathymic cyst and small thymoma, and we recommend 31.2 HU as the best thresholds. Contrast-enhanced CT scans is useful for further identification of the two diseases.


Overview of the symposium on public health significance of genomics and eco-genetics.
Genomic and genetic information is rapidly becoming a major element in public health research and emerging public health practice. This symposium reviews the methods, findings, and significance of genome-wide association studies from epidemiological and statistical points of view. We examine infectious and inflammatory components of gene-environment interaction in the respiratory system. We note the need for nutrient and dietary data and many other kinds of environmental exposure data in population-based genomic studies. Then we explore the sufficiency of a well-informed family history for public health and family counseling purposes. Finally, in an era of direct-to-consumer genomic test promotion, we review the evidence on the critical question, will genetic risk profiles motivate individuals and families to choose more healthful behaviors? This symposium builds on the foundation of the symposium on Public Health Genetics in Volume 21 (2000) of the Annual Review of Public Health.


The role of care-seeking behavior and patient communication pattern in online health information-seeking behavior - a cross-sectional survey.
online health information-seeking behaviour has been on the increase and patients are seeking more responsibility in decisions about their health. Previous studies have mostly predicted online health information-seeking behaviour with demographic characteristics and not current behaviours driven by improving online information. The study attempts to bridge the gap between fast-developing patient online health information-seeking behaviour and health behaviour research. a cross-sectional survey was conducted in the Ghanaian city of Accra. Descriptive statistical analysis was used to reveal frequencies and range of scores on measurement scales. All measurement scales used in the study were tested for reliability. Univariate analysis was used to find correlations and key properties of the dependent and independent variables. Multivariate analysis was used to test hypotheses. one hundred and eighteen (118) adults were surveyed. Cronbach alpha reliabilities of measurement scales ranged from .71 to .91. The hypothesis that care seeking behaviour and patient communication pattern predict online health information seeking behaviour, was supported (r = .45, standard error = 5.84) by a multiple linear regression. patients are engaged in online health information seeking because they want to be more active in decisions about their health. Findings further suggest that patients rely on online information to direct communications with their caregivers.


Analysis of Job Failure and Prediction Model for Cloud Computing Using Machine Learning.
Modern applications, such as smart cities, home automation, and eHealth, demand a new approach to improve cloud application dependability and availability. Due to the enormous scope and diversity of the cloud environment, most cloud services, including hardware and software, have encountered failures. In this study, we first analyze and characterize the behaviour of failed and completed jobs using publicly accessible traces. We have designed and developed a failure prediction model to determine failed jobs before they occur. The proposed model aims to enhance resource consumption and cloud application efficiency. Based on three publicly available traces: the Google cluster, Mustang, and Trinity, we evaluate the proposed model. In addition, the traces were also subjected to various machine learning models to find the most accurate one. Our results indicate a significant correlation between unsuccessful tasks and requested resources. The evaluation results also revealed that our model has high precision, recall, and F1-score. Several solutions, such as predicting job failure, developing scheduling algorithms, changing priority policies, or limiting re-submission of tasks, can improve the reliability and availability of cloud services.


Broadband and low insertion loss Stark cell for microwave spectroscopy.
A groove guide cell for Stark modulation spectroscopy has been constructed and tested. This structure with quasi-unique mode propagation between two isolated plates is well adapted to application of a modulation voltage. The insertion losses are low (0.6 dB for a 3-m-long cell, and R band) and the cell is free of internal reflection. A metallic casing enclosing the plates acts as a shield against electrical interference, prevents low-voltage breakdown, and reduces wall adsorption of the gas. The performance of the cell is not affected by temperature variation (-80 degrees to 25 degrees C). A high sensitivity has been obtained by converting the cell into a 3-m-long, high-Q cavity. This type of cell appears to particularly recommend itself for use in intensity measurements, broadband spectroscopy, analytical studies, and high frequency range work.


Glycine receptors and brain development.
Glycine receptors (GlyRs) are ligand-gated chloride ion channels that mediate fast inhibitory neurotransmission in the spinal cord and the brainstem. There, they are mainly involved in motor control and pain perception in the adult. However, these receptors are also expressed in upper regions of the central nervous system, where they participate in different processes including synaptic neurotransmission. Moreover, GlyRs are present since early stages of brain development and might influence this process. Here, we discuss the current state of the art regarding GlyRs during embryonic and postnatal brain development in light of recent findings about the cellular and molecular mechanisms that control brain development.


Effectiveness of focal vs. balloon radiofrequency ablation devices in the treatment of Barrett's esophagus.
The safety and efficacy of radiofrequency ablation (RFA) in treatment of Barrett's esophagus (BE)-associated dysplasia has been well established. The effectiveness of focal and balloon RFA devices has not been compared. Therefore, the aim of our study was to assess the effectiveness of focal and balloon RFA devices in the treatment of BE by calculating absolute and percentage change in BE length with RFA therapy by comparing pre- and post-treatment BE length. This is a retrospective cross-sectional study of patients who underwent at least one treatment with either focal and/or balloon RFA devices who were identified from two tertiary centers. Patients' demographics, hiatal hernia, pre- and post-treatment BE length, prior use of endoscopic therapies and number of sessions were recorded. Sixty-one patients who had undergone 161 RFA treatment sessions met inclusion criteria. There was no significant difference in percentage change in BE length with greater number of RFA sessions. RFA with a focal device resulted in greater percentage reduction in BE length compared to the balloon system (73% vs. 39%, p < 0.01). After adjusting for initial BE length, pre-treatment BE length, hernia status, prior endoscopic mucosal resection (EMR), prior RFA, and prior EMR/RFA sessions, RFA with a focal device at each session remained an independent predictor for a significant reduction in BE extent as compared to the balloon system. The focal RFA device alone was more effective in treatment of BE compared to the balloon system, with a greater reduction in extent of BE. The focal RFA device for endoscopic eradication therapy of BE should be considered the preferred technique.


Lateral mobility of erythrocyte membrane proteins studied by the fluorescence photobleaching recovery technique.
Erythrocyte membrane peripheral and integral proteins have been isolated and purified, and the lateral diffusion of these proteins in a well-defined phospholipid bilayer matrix (dimyristoylphosphatidylcholine) has been studied by fluorescence photobleaching recovery measurements. Our own instrument for the recovery measurements is described and some data for lipid diffusions are compared with those previously reported by other investigators. The peripheral proteins (spectrin and band 4.1) diffuse rapidly on the lipid membrane in its fluid phase. The diffusion constant of approximately 5 x 10(-8) cm2 . s-1 (30 degrees C) was only a little smaller than that for lipid diffusion. The diffusion was greatly slowed down when the host lipid matrix became solid. The integral protein band 3 also diffuses rapidly in the fluid membrane. The diffusion constant of 1.6 x 10(-8) cm2 . s-1 (30 degrees C) was smaller than those for lipids and for the peripheral proteins. The lateral motion is compatible with diffusion of a cylinder with radius 3 nm in a two dimensional matrix with an inner viscosity of 2 poises and an inner thickness of 4 nm. The band 3 lateral motion was restricted by binding of the cytoskeletal component proteins (ankyrin, spectrin, actin, and band 4.1) to the reconstituted membranes. The diffusion constant decreased to half. The results provide a basis for the elucidation of transmembrane control mechanisms in more complex cellular systems.


Real time ultrasound, arterial pulsation and neonatal cerebral infarction.
This paper describes an infant whose cranial ultrasound scan showed marked unilateral cerebral arterial pulsation and enlargement without other abnormality. Subsequent computerized tomogram showed extensive cortical infarction in an area not readily accessed by ultrasound. It is concluded that the real time dimension of cranial ultrasound is of diagnostic value in the absence of demonstrable parenchymal or intraventricular abnormality.


Chemokines and chemokine receptors in leukocyte trafficking.
Chemokines regulate inflammation, leukocyte trafficking, and immune cell differentiation. The role of chemokines in homing of naive T lymphocytes to secondary lymphatic organs is probably the best understood of these processes, and information on chemokines in inflammation, asthma, and neurological diseases is rapidly increasing. Over the past 15 years, understanding of the size and functional complexity of the chemokine family of peptide chemoattractants has grown substantially. In this review, we first present information regarding the structure, expression, and signaling properties of chemokines and their receptors. The second part is a systems physiology-based overview of the roles that chemokines play in tissue-specific homing of lymphocyte subsets and in trafficking of inflammatory cells. This review draws on recent experimental findings as well as current models proposed by experts in the chemokine field.


Localized modes in one-dimensional symmetric Thue-Morse quasicrystals.
We present occurrence of the strongly localized modes with high transmission in one dimensional symmetric Thue-Morse quasicrystals. This quasicrystal has some interesting properties, including (i) there are strongly localized modes in separated regions which are around odd semi-quarter-wave thickness of the system, (ii) both the frequency of localized mode and the thicknesses of the space layer to appear localized modes are variant for different generation orders of the system, and (iii) the sharpness of the resonant peaks in the transmission spectra increases as the generation order of the system increases.


An in vivo assay of the mutagenic potential of imidacloprid using sperm head abnormality test and dominant lethal test.
To assess the mutagenic effects of imidacloprid in germ cells of Swiss albino male mice by sperm head abnormality (SHA) assay and dominant lethal test (DLT). Swiss albino mice were exposed to imidacloprid (22, 11 and 5.5 mg/kg/day) along with 3% gum acacia as vehicle control through oral route for 7, 14 and 28 days for SHA assay and for 28 days for DLT. The epididymal sperm smear in 1% eosin stain was analyzed for SHAs. In DLT, male mice were allowed to mate with females after 1, 3 and 6 weeks of end of pesticide treatment. The uterine contents of the sacrificed females were observed for live and dead implants. The analysis of test and control groups data was done by one way ANOVA at p < 0.05. Exposure of all dose levels of imidacloprid (22, 11 and 5.5 mg/kg/day) for seven days did not induce significant SHAs while they induced significant SHAs compared with the control group following exposure for 14 and 28 days. The analysis of uterine content revealed a significant increase in the number of dead implants/female compared with the vehicle control in only those females which were mated with male mice after six weeks of treatment of highest dose level of imidacloprid. The dominant lethal mutations were observed only at spermatogonial stage. Long-term exposure of pesticide generated SHAs even at lowest dose level (5.5 mg/kg/day for 14 days) and mutagenic effects at spermatogonial stage at highest dose level (22 mg/kg/day for 28 days).


Turkey Astrovirus Type 1 (TAstV-1) and Chicken Astrovirus (CAstV) Detection in Brazilian Chicken Flocks.
Astrovirus is a common cause of enteritis in humans and domestic animals. Here we report the detection of turkey astrovirus type 1 (TAstV-1) and chicken astrovirus (CAstV) in avian farms. Sixty fecal sample pools (five or six birds of the same flock), from chickens without apparent clinical symptoms of enteric disease from farms located in six Brazilian states, were screened by an ORF1b PCR, followed by nucleotide sequencing of amplified products and phylogenetic analysis. Six samples tested positive for TAstV-1 and two for CAstV. One positive sample of each detected virus (TAstV-1 and CAstV) had the complete ORF2 sequenced. Data for the ORF2 sequence indicate that Brazilian TAstV-1 was divergent from TAstV-1 (United States), previously described infecting turkeys, and Brazilian CAstV clustered together with the U.K. group, subgroup B-II, associated with enteritis and growth retardation in chicks. This study provides updated information about CAstV and the first report of detection of TAstV-1 in Brazilian chickens, supporting the diagnostic of enteritis and epidemiologic surveillance in poultry health.


Varieties of learning and memory in animals.
It is often assumed that there is more than one kind of learning--or more than one memory system--each of which is specialized for a different function. Yet, the criteria by which the varieties of learning and memory should be distinguished are seldom clear. Learning and memory phenomena can differ from one another across species or situations (and thus be specialized) in a number of different ways. What is needed is a consistent theoretical approach to the whole range of learning phenomena, and one is explored here. Parallels and contrasts in the study of sensory systems illustrate one way to integrate the study of general mechanisms with an appreciation of species-specific adaptations.


Ureido group-specific antibodies are induced in rabbits immunized with citrulline- or homocitrulline-containing antigens.
The specificities and cross-reactions of antibodies induced by citrulline- and homocitrulline-containing proteins may give implications on the role of citrulline- and homocitrulline-binding antibodies in the pathogenesis and progression of rheumatoid arthritis (RA). Here we use rabbits as an experimental model of antibody development in RA. Thirty-two animals were immunized with peptide antigens containing either homocitrulline or citrulline. The sera were tested for binding to CCP and MCV antigens and to peptide sequences related to carboxyterminal telopeptides of type I and II collagens and containing arginine, citrulline, or homocitrulline. The binding of CCP and MCV antigens to antisera against homocitrulline-containing immunogens could be inhibited by human serum albumin containing homocitrulline, whereas similar binding to sera against citrulline-containing immunogens was not inhibited. The antisera induced with citrulline-containing collagen telopeptides recognized type I collagen-related antigens in a sequence-specific manner, as antibody binding to both citrulline- and homocitrulline-containing peptides was inhibited by corresponding citrullinated and native peptides. In contrast, type II collagen-related peptides were recognized by the antisera in a ureido group-specific manner, as their binding to homocitrulline-containing peptide was inhibited by both citrulline- and homocitrulline-containing, but not native peptide. Binding of the citrullinated type II collagen peptide could only be inhibited by the similarly citrullinated peptide. In conclusion, antibodies induced with citrulline or homocitrulline-containing antigens bound antigens in a ureido group-specific manner, recognizing citrulline and homocitrulline also in other sequences than those used in the original immunization. In competitive situations the amino acid present in the immunization antigen was favored.


Management of an endoscopy center during the outbreak of COVID-19: Experience from West China Hospital.
Since the outbreak of the coronavirus disease 2019 (COVID-19), various measures have been taken to protect against the infection. As droplet and contact transmission are the main routes of COVID-19 infection, endoscopy centers are considered to be high-risk areas for exposure to COVID-19. We have undertaken several countermeasures in our endoscopic center during the pandemic, and have gained significant experience in terms of prevention and control of COVID-19. We here present our experience and strategies adopted for preventing hospital infection in our endoscopy center during the COVID-19 pandemic. We describe our management of the environment, endoscope, patients, and medical staff, and our self-made masks.


Sleep Dependent Memory Consolidation in Children with Autism Spectrum Disorder.
Examine the role of sleep in the consolidation of declarative memory in children with autism spectrum disorder (ASD). Case-control study. Home-based study with sleep and wake conditions. Twenty-two participants with ASD and 20 control participants between 9 and 16 y of age. Participants were trained to criterion on a spatial declarative memory task and then given a cued recall test. Retest occurred after a period of daytime wake (Wake) or a night of sleep (Sleep) with home-based polysomnography; Wake and Sleep conditions were counterbalanced. Children with ASD had poorer sleep efficiency than controls, but other sleep macroarchitectural and microarchitectural measures were comparable after controlling for age and medication use. Both groups demonstrated better memory consolidation across Sleep than Wake, although participants with ASD had poorer overall memory consolidation than controls. There was no interaction between group and condition. The change in performance across sleep, independent of medication and age, showed no significant relationships with any specific sleep parameters other than total sleep time and showed a trend toward less forgetting in the control group. This study shows that despite their more disturbed sleep quality, children with autism spectrum disorder (ASD) still demonstrate more stable memory consolidation across sleep than in wake conditions. The findings support the importance of sleep for stabilizing memory in children with and without neurodevelopmental disabilities. Our results suggest that improving sleep quality in children with ASD could have direct benefits to improving their overall cognitive functioning.


Isolation of acute-phase proteins from plasma for determination of fractional synthesis rates by a stable isotope tracer technique.
Because of the unavailability of convenient tracer methods, there is no information on the kinetic changes responsible for the increased or decreased pool sizes of the acute-phase proteins (APPs) during the metabolic response to trauma and infections. We have developed a stable isotope tracer method to measure the synthesis rates of the APPs transferrin, haptoglobin, and alpha1-antitrypsin. The proteins were isolated from plasma by either direct or sequential immunoprecipitation and purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. With the exception of haptoglobin, the major band of each protein and its standard ran to a position corresponding to its molecular mass. The major band of haptoglobin and its standard ran to a position corresponding to a molecular mass of slightly less than 44 kDa, which corresponds to the haptoglobin beta chain, molecular mass 42.5 kDa. To measure the fractional synthesis rates (FSRs) of these proteins, three children were infused with 2H3-leucine for 8 h, and the amount of 2H3-leucine incorporated into the proteins was measured by gas chromatography-mass spectrometry. The plateau isotopic enrichment of very low density lipoprotein-apoB-100-bound leucine was used to estimate the isotopic enrichment of the hepatic protein synthetic precursor pool. FSRs (%/day) of the proteins were haptoglobin, 50 +/- 8; transferrin, 19 +/- 1.1; and "alpha"1-antitrypsin, 10 +/- 1. 5.


PDBj Mine: design and implementation of relational database interface for Protein Data Bank Japan.
This article is a tutorial for PDBj Mine, a new database and its interface for Protein Data Bank Japan (PDBj). In PDBj Mine, data are loaded from files in the PDBMLplus format (an extension of PDBML, PDB's canonical XML format, enriched with annotations), which are then served for the user of PDBj via the worldwide web (WWW). We describe the basic design of the relational database (RDB) and web interfaces of PDBj Mine. The contents of PDBMLplus files are first broken into XPath entities, and these paths and data are indexed in the way that reflects the hierarchical structure of the XML files. The data for each XPath type are saved into the corresponding relational table that is named as the XPath itself. The generation of table definitions from the PDBMLplus XML schema is fully automated. For efficient search, frequently queried terms are compiled into a brief summary table. Casual users can perform simple keyword search, and 'Advanced Search' which can specify various conditions on the entries. More experienced users can query the database using SQL statements which can be constructed in a uniform manner. Thus, PDBj Mine achieves a combination of the flexibility of XML documents and the robustness of the RDB. Database URL: http://www.pdbj.org/


Novel strategies for development of hemorrhagic fever arenavirus live-attenuated vaccines.
Several arenaviruses, chiefly Lassa virus (LASV), cause hemorrhagic fever (HF) disease in humans and pose significant public health problems in their endemic regions. Moreover, HF arenaviruses represent credible biodefense threats. There are not FDA-approved arenavirus vaccines and current anti-arenaviral therapy is limited to an off-label use of ribavirin that is only partially effective. Live-attenuated vaccines (LAV) represent the most feasible approach to control HF arenaviruses within their endemic regions. Different platforms, including recombinant viral vectors expressing LASV antigens, and the use of attenuated reassortant arenaviruses, have been used to develop LAV candidates against LASV with promising results in animal models of LASV infection, but none of them has entered a clinical trial. These vaccine efforts have been the subject of recent reviews and will not be examined in this review, which is focused on new avenues for the development of safe and effective LAV to combat HF arenaviruses. Expert commentary: The development of arenavirus reverse genetics has provided investigators with a novel powerful approach to manipulate the genomes of HF arenaviruses, which has opened new avenues for the rapid development of safe and effective LAV to combat these human pathogens.


Factors associated with lower knowledge of HIV and STI transmission, testing and treatment among MSM in Ireland: findings from the MSM Internet Survey Ireland (MISI) 2015.
Poor knowledge regarding STI and HIV transmission, testing and treatment among men who have sex with men (MSM) may be contributing to their disproportionate burden of STIs. However, factors which predispose MSM to having this low knowledge are less understood. The aim of this study was to identify factors associated with having lower knowledge of HIV and STI transmission, testing and treatment among MSM. The MSM Internet Survey Ireland 2015 was a self-completed online national survey available to MSM living in Ireland. Thirteen factual statements were used to assess participants' knowledge of HIV and STI transmission, testing and treatment. Respondents were defined as having 'lower knowledge' if they indicated prior knowledge of fewer than 11 true statements. Multivariable-adjusted logistic regression was used to identify factors associated with having lower knowledge. 3090 MSM completed the survey, of whom 2905 (94%) were included in this study. Thirty-six per cent (n=1055) had lower knowledge of HIV and STI transmission, testing and treatment. The factors associated with having lower knowledge included being 18-24 years of age (vs >40 years; adjusted OR (aOR) 1.98, 95% CI 1.50 to 2.61), born in Ireland (vs outside Ireland; aOR 1.62, 95% CI 1.25 to 2.10) and being out to none of their contacts (vs out to most/all; aOR 1.69, 95% CI 1.20 to 2.37). Knowledge was also lower among those who never tested for HIV (vs tested negative within last 12 months; aOR 2.32, 95% CI 1.88 to 2.86) and among MSM who never visited an MSM-specific health promotion website (vs visited website; aOR 1.81, 95% CI 1.45 to 2.25). A range of demographic factors, sexual health variables and use of MSM-specific sexual health promotion materials are associated with low knowledge regarding HIV and STI transmission, testing and treatment among MSM in Ireland. Engagement with the main national MSM-specific sexual health promotion website was associated with higher knowledge levels.


Metabolic basis for the differential susceptibility of Gram-positive pathogens to fatty acid synthesis inhibitors.
The rationale for the pursuit of bacterial type 2 fatty acid synthesis (FASII) as a target for antibacterial drug discovery in Gram-positive organisms is being debated vigorously based on their ability to incorporate extracellular fatty acids. The regulation of FASII by extracellular fatty acids was examined in Staphylococcus aureus and Streptococcus pneumoniae, representing two important groups of pathogens. Both bacteria use the same enzymatic tool kit for the conversion of extracellular fatty acids to acyl-acyl carrier protein, elongation, and incorporation into phospholipids. Exogenous fatty acids completely replace the endogenous fatty acids in S. pneumoniae but support only 50% of phospholipid synthesis in S. aureus. Fatty acids overcame FASII inhibition in S. pneumoniae but not in S. aureus. Extracellular fatty acids strongly suppress malonyl-CoA levels in S. pneumoniae but not in S. aureus, showing a feedback regulatory system in S. pneumoniae that is absent in S. aureus. Fatty acids overcame either a biochemical or a genetic block at acetyl-CoA carboxylase (ACC) in S. aureus, confirming that regulation at the ACC step is the key difference between these two species. Bacteria that possess a stringent biochemical feedback inhibition of ACC and malonyl-CoA formation triggered by environmental fatty acids are able to circumvent FASII inhibition. However, if exogenous fatty acids do not suppress malonyl-CoA formation, FASII inhibitors remain effective in the presence of fatty acid supplements.


Hyperglycemia-Triggered Sphingosine-1-Phosphate and Sphingosine-1-Phosphate Receptor 3 Signaling Worsens Liver Ischemia/Reperfusion Injury by Regulating M1/M2 Polarization.
Hyperglycemia aggravates hepatic ischemia/reperfusion injury (IRI), but the underlying mechanism for the aggravation remains elusive. Sphingosine-1-phosphate (S1P) and sphingosine-1-phosphate receptors (S1PRs) have been implicated in metabolic and inflammatory diseases. Here, we discuss whether and how S1P/S1PRs are involved in hyperglycemia-related liver IRI. For our in vivo experiment, we enrolled diabetic patients with benign hepatic disease who had liver resection, and we used streptozotocin (STZ)-induced hyperglycemic mice or normal mice to establish a liver IRI model. In vitro bone marrow-derived macrophages (BMDMs) were differentiated in high-glucose (HG; 30 mM) or low-glucose (LG; 5 mM) conditions for 7 days. The expression of S1P/S1PRs was analyzed in the liver and BMDMs. We investigated the functional and molecular mechanisms by which S1P/S1PRs may influence hyperglycemia-related liver IRI. S1P levels were higher in liver tissues from patients with diabetes mellitus and mice with STZ-induced diabetes. S1PR3, but not S1PR1 or S1PR2, was activated in liver tissues and Kupffer cells under hyperglycemic conditions. The S1PR3 antagonist CAY10444 attenuated hyperglycemia-related liver IRI based on hepatic biochemistry, histology, and inflammatory responses. Diabetic livers expressed higher levels of M1 markers but lower levels of M2 markers at baseline and after ischemia/reperfusion. Dual-immunofluorescence staining showed that hyperglycemia promoted M1 (CD68/CD86) differentiation and inhibited M2 (CD68/CD206) differentiation. Importantly, CAY10444 reversed hyperglycemia-modulated M1/M2 polarization. HG concentrations in vitro also triggered S1P/S1PR3 signaling, promoted M1 polarization, inhibited M2 polarization, and enhanced inflammatory responses compared with LG concentrations in BMDMs. In contrast, S1PR3 knockdown significantly retrieved hyperglycemia-modulated M1/M2 polarization and attenuated inflammation. In conclusion, our study reveals that hyperglycemia specifically triggers S1P/S1PR3 signaling and exacerbates liver IRI by facilitating M1 polarization and inhibiting M2 polarization, which may represent an effective therapeutic strategy for liver IRI in diabetes.


Transfoam Visco: evaluation of a viscoelastic foam mattress.
It is both a massive financial commitment and a huge financial decision to standardize mattresses in a large trust. It should only be undertaken after evaluation of the evidence of efficacy supplied by relevant companies, together with independent research and reports by healthcare professionals. In addition, evaluation of the equipment should be made by back care advisers, from a user-safety viewpoint and physiotherapists, occupational therapists concerning rehabilitation. Ward-based nurses and patients need to assess equipment for comfort, ease of repositioning individual, and ability to relieve pressure. This article outlines the process by which a static mattress was evaluated for ease of movement, pressure relief and comfort by patients and healthcare professionals. The possible longevity of the mattress was considered as secondary relevance; however, cost-effectiveness and quality of product are essential in today's acute healthcare setting.


Purification, crystallization and preliminary X-ray diffraction of human S100A15.
Human S100A15 is a novel member of the S100 family of EF-hand calcium-binding proteins and was recently identified in psoriasis, where it is significantly upregulated in lesional skin. The protein is implicated as an effector in calcium-mediated signal transduction pathways. Although its biological function is unclear, the association of the 11.2 kDa S100A15 with psoriasis suggests that it contributes to the pathogenesis of the disease and could provide a molecular target for therapy. To provide insight into the function of S100A15, the protein was crystallized to visualize its structure and to further the understanding of how the many similar calcium-binding mediator proteins in the cell distinguish their cognate target molecules. The S100A15 protein has been cloned, expressed and purified to homogeneity and produced two crystal forms. Crystals of form I are triclinic, with unit-cell parameters a = 33.5, b = 44.3, c = 44.8 angstroms, alpha = 71.2, beta = 68.1, gamma = 67.8 degrees and an estimated two molecules in the asymmetric unit, and diffract to 1.7 angstroms resolution. Crystals of form II are monoclinic, with unit-cell parameters a = 82.1, b = 33.6, c = 52.2 angstroms, beta = 128.2 degrees and an estimated one molecule in the asymmetric unit, and diffract to 2.0 angstroms resolution. This structural analysis of the human S100A15 will further aid in the phylogenic comparison between the other members of the S100 protein family, especially the highly homologous paralog S100A7.


High Levels of Copper, Zinc, Iron and Magnesium, but not Calcium, in the Cerebrospinal Fluid of Patients with Fahr's Disease.
Patients with marked calcification of the basal ganglia and cerebellum have traditionally been referred to as having Fahr's disease, but the nomenclature has been criticized for including heterogeneous etiology. We describe 3 patients with idiopathic bilateral striatopallidodentate calcinosis (IBSPDC). The patients were a 24-year-old man with mental deterioration, a 57-year-old man with parkinsonism and dementia, and a 76-year-old woman with dementia and mild parkinsonism. The former 2 patients showed severe calcification of the basal ganglia and cerebellum, and the latter patient showed severe calcification of the cerebellum. We found significantly increased levels of copper (Cu), zinc (Zn), iron (Fe) and magnesium (Mg), using inductively coupled plasma mass spectrometry in the CSF of all these 3 patients. The increased levels of Cu, Zn, Fe and Mg reflect the involvement of metabolism of several metals and/or metal-binding proteins during the progression of IBSPDC. More numerous patients with IBSPDC should be examined in other races to clarify the common mechanism of the disease and to investigate the specific treatment.


Synthesis of fluorinated mucin core 2 branched oligosaccharides with the potential of novel substrates and enzyme inhibitors for glycosyltransferases and sulfotransferases.
Syntheses of fluorinated mucin core 2 tri- and tetrasaccharides modified at the C-3 or C-4 position of the pertinent galactose residue are reported. These compounds were used for the study of sialyltransferases and 3-O-sulfotransferases involved in the biosynthesis of O-glycans. Our acceptor substrate specificity studies on three cloned sialyltransferases (Sia-Ts) revealed that a 3- or 4-fluoro substituent in beta1,4Gal resulted in poor acceptors for alpha2,6(N)Sia-T and alpha2,3(N)Sia-T, whereas 4-fluoro-Galbeta1,3GalNAcalpha was a good acceptor for alpha2,3(O)Sia-T. Uniquely, 4-F-Galbeta1,4GlcNAcbeta1,6(Galbeta1,3)GalNAcalpha-OBn was an inhibitor of alpha2,6(N)Sia-T activity but not alpha2,3(N)Sia-T activity. Further we found that the activities of only Gal 3-O-sulfotransferases and not sialyltransferases were adversely affected by a C-3 fluoro substituent at the other Gal terminal of mucin core 2. The strategy of building branched mucin core 2 structures by three glycosidation sequence coupling three classes of glycosyl donors with the reactivity-matching acceptors proved to be successful in syntheses of modified mucin-type core structures of O-glycan. The relative poor yields of the glycosylations using fluorinated galactosyl donors indicated that the fluorine modification dramatically decreased the donor reactivity due to electron-withdrawing effect.


Identification and characterization of ten new water gaps in seeds and fruits with physical dormancy and classification of water-gap complexes.
Physical dormancy (PY) occurs in seeds or fruits of 18 angiosperm families and is caused by a water-impermeable palisade cell layer(s) in seed or fruit coats. Prior to germination, the seed or fruit coat of species with PY must become permeable in order to imbibe water. Breaking of PY involves formation of a small opening(s) (water gap) in a morpho-anatomically specialized area in seeds or fruits known as the water-gap complex. Twelve different water-gap regions in seven families have previously been characterized. However, the water-gap regions had not been characterized in Cucurbitaceae; clade Cladrastis of Fabaceae; subfamilies Bombacoideae, Brownlowioideae and Bythnerioideae of Malvaceae; Nelumbonaceae; subfamily Sapindoideae of Sapindaceae; Rhamnaceae; or Surianaceae. The primary aims of this study were to identify and describe the water gaps of these taxa and to classify all the known water-gap regions based on their morpho-anatomical features. Physical dormancy in 15 species was broken by exposing seeds or fruits to wet or dry heat under laboratory conditions. Water-gap regions of fruits and seeds were identified and characterized by use of microtome sectioning, light microscopy, scanning electron microscopy, dye tracking and blocking experiments. Ten new water-gap regions were identified in seven different families, and two previously hypothesized regions were confirmed. Water-gap complexes consist of (1) an opening that forms after PY is broken; (2) a specialized structure that occludes the gap; and (3) associated specialized tissues. In some species, more than one opening is involved in the initial imbibition of water. Based on morpho-anatomical features, three basic water-gap complexes (Types-I, -II and -III) were identified in species with PY in 16 families. Depending on the number of openings involved in initial imbibition, the water-gap complexes were sub-divided into simple and compound. The proposed classification system enables understanding of the relationships between the water-gap complexes of taxonomically unrelated species with PY.


Localised pityriasis rosea-like eruption during radiotherapy. Report of 2 cases.
Pityriasis rosea is a common skin condition that presents acutely with asymptomatic, scaly and oval plaques, usually in a well-recognised distribution over the trunk. Two men developed ovoid, scaly and annular lesions limited to the radiotherapy field during treatment for pelvic malignancies and without a preceding herald patch. Other causes of the eruption were excluded on clinical and pathological grounds and the histopathological features were consistent with a pityriasis rosea-like eruption. In both cases the lesions resolved spontaneously by 8 weeks. These are the first reported cases of a localised pityriasis rosea-like eruption arising during radiotherapy.


Three-dimensional reconstruction of maxillae using spiral computed tomography and its application in postoperative adult patients with unilateral complete cleft lip and palate.
To establish a method to analyze malformed maxillae of postoperative adult patients with unilateral complete cleft lip and palate in 3 dimensions. A total of 35 landmarks were defined and used to reconstruct 3-dimensional maxillary images of healthy Chinese Han subjects and 30 postoperative Chinese Han adult patients (17 men and 13 women, with mean age of 19.07 years) with unilateral complete cleft lip and palate. This was done using spiral computed tomography, and their corresponding parameters were analyzed using SimPlant software, version 11.04, and compared by t test using SAS software, version 6.12. Of the 7 centered landmarks, A and ANS in the patients were obviously deviated to the nonoperative side (P < .01) and the symmetrical landmark pairs INM'-INM, SNM'-SNM and SPr'-SPr, but not MA'-MA, SoF'-SoF, and LPAC-LPA in the infraorbital region and piriform aperture peritreme in healthy subjects were shifted toward the coordinate sagittal plane S. The data also showed that the maxillae in the patients' operative side were hypoplastic, especially in the posteroanterior direction compared with the nonoperative side and healthy subjects. The proposed method can precisely measure the distances of the maxillary landmarks to 3-dimensional coordinates and has application potential in evaluating maxillary deformity in patients with postoperative unilateral complete cleft lip and palate.


The structure of calreticulin C-terminal domain is modulated by physiological variations of calcium concentration.
Calreticulin is an abundant endoplasmic reticulum resident protein that fulfills at least two basic functions. Firstly, due to its ability to bind monoglucosylated high mannose oligosaccharides, calreticulin is a central component of the folding quality control system of glycoproteins. On the other hand, thanks to its capacity to bind high amounts of calcium, calreticulin is one of the main calcium buffers in the endoplasmic reticulum. This last activity resides on a highly negatively charged domain located at the C terminus. Interestingly, this domain has been proposed to regulate the intracellular localization of calreticulin. Structural information for this domain is currently scarce. Here we address this issue by employing a combination of biophysical techniques and molecular dynamics simulation. We found that calreticulin C-terminal domain at low calcium concentration displays a disordered structure, whereas calcium addition induces a more rigid and compact conformation. Remarkably, this change develops when calcium concentration varies within a range similar to that taking place in the endoplasmic reticulum upon physiological fluctuations. In addition, a much higher calcium concentration is necessary to attain similar responses in a peptide displaying a randomized sequence of calreticulin C-terminal domain, illustrating the sequence specificity of this effect. Molecular dynamics simulation reveals that this ordering effect is a consequence of the ability of calcium to bring into close proximity residues that lie apart in the primary structure. These results place calreticulin in a new setting in which the protein behaves not only as a calcium-binding protein but as a finely tuned calcium sensor.


An Open-Structure Treadmill Gait Trainer: From Research to Application.
Lower limb rehabilitation robots are designed to enhance gait function in individuals with motor impairments. Although numerous rehabilitation robots have been developed, only few of these robots have been used in practical health care, particularly in China. The objective of this study is to construct a lower limb rehabilitation robot and bridge the gap between research and application. Open structure to facilitate practical application was created for the whole robot. Three typical movement patterns of a single leg were adopted in designing the exoskeletons, and force models for patient training were established and analyzed under three different conditions, respectively, and then a control system and security strategy were introduced. After establishing the robot, a preliminary experiment on the actual use of a prototype by patients was conducted to validate the functionality of the robot. The experiment showed that different patients and stages displayed different performances, and results on the trend variations across patients and across stages confirmed the validity of the robot and suggested that the design may lead to a system that could be successful in the treatment of patients with walking disorders in China. Furthermore, this study could provide a reference for a similar application design.


Risk Factors for the Mortality in Hospitalized Patients with COVID-19: A Brief Report.
The cumulative rate of death of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated better recognizing the risk factors of the disease and the COVID-19-induced mortality. This cross-sectional study aimed to determine the potential risk factors that predict COVID-19-related mortality concentrating on the initial recorded laboratory tests. We extracted admission's medical records of a total of 136 deaths related to COVID-19 and 272 discharged adult inpatients (≥18 years old) related to four referral centers from February 24th to April 12th, 2020, in Isfahan, Iran, to figure out the relationship between the laboratory findings and mortality beyond demographic and clinical findings. We applied the independent sample t test and a chichi square test with SPSS software to compare the differences between the survivor and non-survivor patients. A P value of less than 0.05 was considered significant. Our results showed that greater length of hospitalization (P≤0.001), pre-existing chronic obstructive pulmonary disease (P≤0.001), high pulse rate, hypoxia (P≤0.001), and high computed tomography scan score (P<0.001), in addition to high values of some laboratory parameters, increase the risk of mortality. Moreover, high neutrophil/lymphocyte ratio (OR, 1.890; 95% CI, 1.074-3.325, P=0.027), increased creatinine levels (OR, 15.488; 95% CI, 0.801-299.479, P=0.07), and elevated potassium levels (OR, 13.400; 95% CI, 1.084-165.618, P=0.043) independently predicted in-hospital death related to COVID-19 infection. These results emphasized the potential role of impaired laboratory parameters for the prognosis of fatal outcomes in adult inpatients.


Repeated testing produces superior transfer of learning relative to repeated studying.
The present research investigated whether test-enhanced learning can be used to promote transfer. More specifically, 4 experiments examined how repeated testing and repeated studying affected retention and transfer of facts and concepts. Subjects studied prose passages and then either repeatedly restudied or took tests on the material. One week later, they took a final test that had either the same questions (Experiment 1a), new inferential questions within the same knowledge domain (Experiments 1b and 2), or new inferential questions from different knowledge domains (Experiment 3). Repeated testing produced superior retention and transfer on the final test relative to repeated studying. This finding indicates that the mnemonic benefits of test-enhanced learning are not limited to the retention of the specific response tested during initial learning but rather extend to the transfer of knowledge in a variety of contexts.


Polyphosphate kinase is a component of the Escherichia coli RNA degradosome.
The Escherichia coli degradosome is a multienzyme complex with four major protein components: the endoribonuclease RNase E, the exoribonuclease PNPase, the RNA helicase RhlB and enolase. The first three of these proteins are known to have important functions in mRNA processing and degradation. In this work, we identify an additional component of the degradosome, polyphosphate kinase (PPK), which catalyses the reversible polymerization of the gamma-phosphate of ATP into polyphosphate (poly(P)). An E. coli strain deleted for the ppk gene showed increased stability of the ompA mRNA. Purified His-tagged PPK was shown to bind RNA, and RNA binding was prevented by hydrolysable ATP. Chemical modification of RNA by PPK, for example the addition or removal of 3' or 5' terminal phosphates, could not be detected. However, polyphosphate was found to inhibit RNA degradation by the degradosome in vitro. This inhibition was overcome by the addition of ADP, required for the degradation of polyphosphate and for the regeneration of ATP by PPK in the degradosome. Thus, PPK in the degradosome appears to maintain an appropriate microenvironment, removing inhibitory polyphosphate and NDPs and regenerating ATP.


Purification, crystallization and preliminary X-ray analysis of isocitrate dehydrogenase kinase/phosphatase from Escherichia coli.
The Escherichia coli aceK gene encodes isocitrate dehydrogenase kinase/phosphatase (EC 126.96.36.199), a bifunctional protein that phosphorylates and dephosphorylates isocitrate dehydrogenase (IDH), resulting in its inactivation and activation, respectively. This reversible (de)phosphorylation directs isocitrate, an intermediate of the citric acid cycle, to either go through the full cycle or to enter the glyoxylate bypass. In the present study, the AceK protein from E. coli has been purified and crystallized. Three crystal forms were obtained from very similar crystallization conditions. The crystals belong to space groups P4(1)2(1)2, P3(2)21 and P2(1)2(1)2(1) and diffracted X-rays to resolutions of 2.9, 3.0 and 2.7 A, respectively.


Duration of apnoea in anaesthetized children required for desaturation of haemoglobin to 95%: comparison of three different breathing gases.
In this study, we compared three gas compositions to determine if the duration of apnoea for SpO2 to decrease is proportionate to the oxygen fraction of the gas prior to apnoea. Twenty-five patients ASA physical status 1-2 aged two months to 12 years were included in the study. Anaesthesia was induced via a mask with 5% sevoflurane and 66% N2O in oxygen. After paralysis with vecuronium (0.12 mg.kg-1, i.v.) the trachea was intubated and anaesthesia was maintained with sevoflurane and N2O in oxygen. When cardiovascular stability was obtained, the patient was randomly set to breathe one of three gas compositions: 1. oxygen (FiO2 1.0), 2. N2O/O2 (FiO2 0.4), and 3. air/O2 (FiO2 0.4). All three gas compositions included 2-4% of sevoflurane to maintain anaesthesia. After more than eight min of each gas breathing, apnoea was begun by disconnecting the breathing circuit from the tracheal tube. The time from the start of apnoea (SpO2 100%) to SpO2 of 95% (T95) was measured. T95 measured after breathing N2O/O2 and air/O2 were 34.6 +/- 5.7 and 28.8 +/- 4.7% of that measured after oxygen breathing (P < 0.001 vs oxygen breathing, P < 0.001 vs oxygen and N2O/O2 breathing), respectively. Preoxygenation before intubation was validated to delay the haemoglobin desaturation brought about by apnoea. An induction technique using a low FiO2 will allow rapid haemoglobin desaturation.


Nonrandom use of J alpha gene segments. Influence of V alpha and J alpha gene location.
TCR genes (alpha, beta, gamma, and delta) undergo rearrangement during development in the thymus. The repertoire of alpha beta and gamma delta cells is shaped first by genetic processes that control rearrangement and expression and then by intercellular processes that "select" cells expressing only particular receptors. In this report, alpha chain transcripts from different stages of ontogeny were examined to determine the influence of V and J gene location on the thymic repertoire. J alpha gene segments were not used equally by V alpha genes. The frequency of J alpha use, and thus the alpha chain repertoire, was influenced by at least three factors: the location of the V gene, the location of the J gene, and the age of the animal. V genes that are proximal to the J alpha region preferentially use the most 5' J alpha gene segments. In contrast, a V alpha gene that is distal to the J alpha region was rarely joined to these same 5' J alpha gene segments in thymocytes from adult animals. We suggest that the data are most easily explained by the frequent occurrence of secondary rearrangements in which a V alpha J alpha rearranged gene would be replaced by the joining of a flanking V alpha gene to a flanking J alpha gene segment. Finally, the evidence suggests that there may be differences in the extent of secondary rearrangements between fetal and adult animals.


Quantum dot spin coherence governed by a strained nuclear environment.
The interaction between a confined electron and the nuclei of an optically active quantum dot provides a uniquely rich manifestation of the central spin problem. Coherent qubit control combines with an ultrafast spin-photon interface to make these confined spins attractive candidates for quantum optical networks. Reaching the full potential of spin coherence has been hindered by the lack of knowledge of the key irreversible environment dynamics. Through all-optical Hahn echo decoupling we now recover the intrinsic coherence time set by the interaction with the inhomogeneously strained nuclear bath. The high-frequency nuclear dynamics are directly imprinted on the electron spin coherence, resulting in a dramatic jump of coherence times from few tens of nanoseconds to the microsecond regime between 2 and 3 T magnetic field and an exponential decay of coherence at high fields. These results reveal spin coherence can be improved by applying large magnetic fields and reducing strain inhomogeneity.


Auranofin therapy in juvenile rheumatoid arthritis: a 48-week phase II study.
A 48-week phase II open, uncontrolled study of auranofin (AF) in patients juvenile rheumatoid arthritis (JRA) was conducted to assess efficacy, tolerance and serum gold levels, and to consider the feasibility of further controlled studies (phase III) in such patients. The study group included 25 patients (20 F, 5 M) with active pauciarticular (n = 4) or polyarticular (n = 21) JRA. Median age was 100 months (range 62-176); median disease duration was 55 months (range 13-155). AF was given at 0.1 mg/kg/day divided into 2 doses, and increases to maximum of 6 mg/day were permitted if clinical improvement was insufficient. Nonsteroidal anti-inflammatory drugs and physiotherapy also were allowed. Significant improvement (p less than or equal to 0.05) was observed in the various joint counts and articular indices, as well as in the physician's global assessment of health. Some subjective functional measurements also were improved, but the differences were not statistically significant. There were no clinically important trends in the laboratory measurements. No patient was withdrawn because of adverse reactions; 1 was withdrawn because of disease exacerbation and 3 for lack of response. Mild adverse reactions were seen in 9 patients: 6 had abdominal pain, 6 diarrhea/loose stools, 1 nausea, 3 rash, 2 pruritus. Two patients had dosage reduced because of loose stools. Serum gold levels varied greatly; increased dosage usually resulted in increased serum levels. Occurrence of adverse reactions or response to therapy was not related to increases in dose or to serum gold levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Smoking in an industrial population. An analysis by birth cohort.
Between 1981 and 1984, 10,923 male and 624 female employees of the Australian petroleum industry were interviewed and the information that was collected included a detailed life-time smoking history. Comparison with another survey suggested that, in terms of smoking habits at least, this industrial population did not differ substantially from the general population. On the assumption that reasons for entering and leaving the industry are unconnected with smoking habit, the data were analysed by birth cohorts. In men, each successive generation has contained fewer smokers at every age over 20 years and this is due both to a reduction in the rate of starting to smoke, and to an increase in the cessation rates. In the case of women, the situation is reversed, and successive generations show an increasing prevalence and increasing starting rates.


Bovine sponge amnion stimulates socket healing: A histological analysis.
Bovine sponge amnion (BSA) is made from bovine amniotic membrane, which contains several growth factors with the ability to suppress inflammation and stimulate the healing process. The healing process of the socket is clinically marked by the proliferation of fibroblasts, formation of new blood vessels, and closure of the wound site. Fibroblasts and new blood vessels are the common histological indicators of tissue regeneration. Twenty-four lower anterior teeth were extracted from the rats. The socket was then applied with BSA and sutured, while a control group was only sutured. The animals were scarified 3, 7, and 14 days after application, and the mandibular was isolated. Histological analysis of socket tissue used the staining of hematoxylin and eosin to analyze the new blood vessels and fibroblasts. An independent t-test was used to analyze the fibroblasts and new blood vessels in each group, with P < 0.05 considered as significant. The number of fibroblasts is higher in the BSA group compared others groups at 3, 7, and 14 days (P < 0.05). The new blood vessel count is higher compared to the control group at only 3 and 7 days (P < 0.05). BSA aids the regeneration of the socket after tooth extraction by stimulating fibroblast proliferation and formation of new blood vessels.


Composition and Functional Characteristics and Influencing Factors of Bacterioplankton Community in the Huangshui River, China.
Bacterial community plays a key role in environmental and ecological processes of river ecosystems. Given the special climatic and geographical conditions, studying the compositional characteristics of microorganisms in highland rivers and the relationship between such microorganisms and water physicochemical factors is important for an in-depth understanding of microbial ecological mechanisms. In the present study, high-throughput sequencing was used to investigate and study the bacterioplankton community of the Huangshui River in the ecotone zone of the Qinghai Plateau and Loess Plateau. The results showed that the Huangshui River had significantly lower alpha diversity than the plain rivers. Despite the similarity in their environmental conditions, the main taxonomic compositions of the bacterial communities were distinct between the Huangshui River and polar regions (the Arctic and Antarctica). Proteobacteria accounted for the largest proportion (30.79-99.98%) of all the sequences, followed by Firmicutes (0-49.38%). Acidiphilium was the most numerous genera, which accounted for 0.03-86.16% of the assigned 16S reads, followed by Acidocella (0-95.9%), both belonging to Alphaproteobacteria. The diverse taxa of potential pathogens, such as Acinetobacter, Pseudomonas, and Aeromonas, were also identified. A principal coordinates analysis, coupled with a canonical correspondence analysis, showed spatial variations in the bacterial community composition. The water physical properties (e.g., Cr6+, total phosphorus, and CODMn); altitude; and land use (e.g., urban land cover and aquaculture) determined the distribution of the bacterioplankton composition. PICRUSt2 revealed that the overall functional profiles of the bacterial communities in different samples were similar, and our results suggested the potential health risks of water sources in this area. This work provided valuable insight into the composition of the plankton bacterial community and its relationship with the environmental factors in the Huangshui River in the ecotone zone of the Qinghai Plateau and Loess Plateau and a theoretical foundation for ecological health management.


Designing Incentives to Change Behaviors: Examining College Student Intent Toward Healthy Diets.
College is a time when young adults establish lifestyle habits. This research examines how personalization and limited resources might be balanced most effectively when designing incentives to shift college students' intentions toward positive dietary changes. A randomized 2 × 2 experiment (Coaching/Coupons × Fruits and Vegetables/Low Fat) was conducted, where respondents were exposed to virtual interventions and asked pre- and post-intervention about their intent to eat healthy. Results suggest that interventions may incentivize students, but are dependent on student characteristics. On-campus students and students with more knowledge about healthy diets were more likely to increase their intent when offered coaching; students living off campus and those with less knowledge resonated with coupons. On- and off-campus students differed in their positive responses to eating fruits and vegetables versus low fat foods, respectively. Younger students may be more susceptible to interventions. Findings may be useful in designing meaningful incentives for college students.


Calcium and hypertension.
Although the complexities of cardiovascular physiology preclude any one factor from assuming the role of the key determinant of elevated blood pressure, the large body of evidence that is accumulating based on epidemiologic observation and studies in experimental and human hypertension support the contention that maintenance of normal calcium metabolism is associated with a lower arterial pressure. Dietary calcium supplementation in human essential hypertension appears to be an effective nonpharmacologic means of lowering blood pressure in some patients, especially those with evidence of a calcium-deficient state. In addition, preliminary evidence has raised questions as to whether a relationship exists between salt sensitivity and disordered calcium homeostasis in some hypertensive patients, and whether there is an important role for calcium in the regulation of other hormonal systems involved in blood pressure regulation.


The recovery of optical quality after laser vision correction.
To evaluate the optical quality after laser in situ keratomileusis (LASIK) or serial photorefractive keratectomy (PRK) using a double-pass system and to follow the recovery of optical quality after laser vision correction. This study measured the visual acuity, manifest refraction and optical quality before and one day, one week, one month, and three months after laser vision correction. Optical quality parameters including the modulation transfer function, Strehl ratio and intraocular scattering were evaluated with a double-pass system. This study included 51 eyes that underwent LASIK and 57 that underwent PRK. The optical quality three months post-surgery did not differ significantly between these laser vision correction techniques. Furthermore, the preoperative and postoperative optical quality did not differ significantly in either group. Optical quality recovered within one week after LASIK but took between one and three months to recover after PRK. The optical quality of patients in the PRK group seemed to recover slightly more slowly than their uncorrected distance visual acuity. Optical quality recovers to the preoperative level after laser vision correction, so laser vision correction is efficacious for correcting myopia. The double-pass system is a useful tool for clinical assessment of optical quality.


Fragment-based screening with natural products for novel anti-parasitic disease drug discovery.
Introduction: Fragment-based drug discovery can identify relatively simple compounds with low binding affinity due to fewer binding interactions with protein targets. FBDD reduces the library size and provides simpler starting points for subsequent chemical optimization of initial hits. A much greater proportion of chemical space can be sampled in fragment-based screening compared to larger molecules with typical molecular weights (MWs) of 250-500 g mol-1 used in high-throughput screening (HTS) libraries. Areas covered: The authors cover the role of natural products in fragment-based drug discovery against parasitic disease targets. They review the approaches to develop fragment-based libraries either using natural products or natural product-like compounds. The authors present approaches to fragment-based drug discovery against parasitic diseases and compare these libraries with the 3D attributes of natural products. Expert opinion: To effectively use the three-dimensional properties and the chemical diversity of natural products in fragment-based drug discovery against parasitic diseases, there needs to be a mind-shift. Library design, in the medicinal chemistry area, has acknowledged that escaping flat-land is very important to increase the chances of clinical success. Attempts to increase sp3 richness in fragment libraries are acknowledged. Sufficient low molecular weight natural products are known to create true natural product fragment libraries.


Efficient polycyclic aromatic hydrocarbons dihydroxylation in direct micellar systems.
Optimization of whole-cell bioconversion of the polycyclic aromatic hydrocarbons (PAHs) anthracene, phenanthrene, and naphthalene to the enantiomerically pure corresponding cis-dihydroxydihydro derivatives by the Escherichia coli JM109 (pPS1778) recombinant strain, carrying the naphthalene dioxygenase and corresponding regulatory genes cloned from Pseudomonas fluorescens N3, in micellar systems, is presented. We show that direct microemulsion systems, where a nonionic surfactant such as 1.5% (v/v) Triton X-100 plus 0.6% to 1.0% (v/v) selected oils are able to solubilize the PAHs tested at relatively high concentrations (initial concentrations in the reaction medium > or =10 mM for naphthalene and phenanthrene and > or =2 mM for anthracene), and allow for more efficient substrate bioconversion. These media, while not affecting bacteria viability and performance, provide increased efficiency and final product yields (100% for naphthalene, >30% for anthracene, >60% for phenanthrene). The phase behavior of the direct microemulsion systems for the different substrates and oils utilized was monitored as a function of their volume fraction by light scattering experiments, and related to the bioconversion results. For anthracene and phenanthrene, the dihydroxylated products have an inhibitory effect on the conversion reactions, thus hindering complete turnover of the substrates. We ascertain that such inhibition is reversible because removal of the products formed allowed the process to start over at rates comparable to initial rates. To allow for complete conversion of the PAHs tested a stepwise or continuous separation of the product formed from the micellar reaction environment is being developed.


Syrian Refugee Women's Health in Lebanon, Turkey, and Jordan and Recommendations for Improved Practice.
Since 2011, an estimated nine million Syrian refugees have fled to neighboring countries, and over four million have fled to neighboring countries of Lebanon, Turkey, and Jordan. Seventy five percent of Syrian refugees are women and children. In times of conflict, women's health disproportionately suffers. Based on an assessment of academic literature and international policy and development reports, this study explores the vulnerabilities of Syrian women and girls in Lebanon, Turkey, and Jordan, and how these countries approach Syrian refugee women's health care. In all settings, sexual and gender-based violence, reduced use of modern contraceptives, menstrual irregularity, unplanned pregnancies, preterm birth, and infant morbidity are ongoing issues. Recommendations for improved practice include taking a multilevel approach to eliminate social and service delivery barriers that prevent access to care, conducting thorough needs assessments, and creating policy and programmatic solutions that establish long term care for Syrian refugee women.


Short communication: bendamustine-related hemolytic anemia in chronic lymphocytic leukemia.
Immune hemolytic anemia (IHA) may complicate the course of chronic lymphocytic leukemia (CLL), especially in patients with advanced disease, and as a complication of treatment with chlorambucil or fludarabine. Bendamustine, a novel agent with both alkylating and purine-analog properties, was approved in the USA for use in CLL in 2008. Since then, clinical data on its adverse events are accumulating. IHA related to bendamustine was seldom described and is thus reported and reviewed. We assessed five cases of CLL patients complicated by IHA, out of 31 treated with bendamustine for a relapse of their disease. Also reviewed are previous case reports in the literature. Bendamustine-related IHA is more common than suspected (16 %). No such cases were found in non-CLL patients. Personal history of fludarabine-triggered AIHA may be a risk factor for this complication (recorded in 4/5 patients, 80 %). The mechanism is thought to be related to the loss of T cell regulatory control as described for other agents. Physicians using bendamustine for the treatment for CLL should be aware of this complication.


Quality of life in patients with early stage breast carcinoma treated with conservation surgery and radiotherapy. An Italian monoinstitutional study.
To evaluate the quality of life (QOL) in patients with early stage invasive carcinoma of the breast treated with conservative surgery and postoperative irradiation. A mailed survey to examine QOL was conducted in 227 subjects with breast cancer treated in 1990 and 1994 with conservation surgery plus definitive irradiation. The self-compiled questionnaire was developed based on a series of 38 items assessing six core areas of QOL. Furthermore, the patients were requested to evaluate the degree of information provided by the medical staff concerning the disease, the treatment and related side effects and to evaluate the effects of the treatment on their social, overall QOL, and health status. The questionnaire was completed by 156 patients (68.7%) who had a median age of 56 years (range, 28-75 years) at the time of treatment and 59 years (range, 31-82 years) at the time of the study. The physical condition was reported to be good. Data relating to sexual life were provided by more than 90% of the patients. Some limitations in sexuality, some interference with sexual desire, and some modifications during intercourse were reported by 11, 11, and 10 patients, respectively. The subjective evaluations of the cosmetic results of the therapies were judged good-excellent by 56% of the patients, 12 (8%) only had a negative perception of their body image. Twenty-five percent of the sample declared that they felt tense, 19% nervous, 18% lonely, 27% anxious and 16% depressed. Only six patients (4%) declared that the treatment had had a bad on their social life, and 18 (11%) thought that their health status has been affected by the treatment. A worsening of QOL due to the disease or the treatment was reported by 8% of the responders. The amount of information received concerning the treatment and its side effects was considered sufficient by most of the patients. The results of the study revealed a satisfactory health-related QOL in patients treated with breast conservation and postoperative irradiation. A preserved favorable body image and lack of a negative impact on sexuality was observed, even though about half of the patients reported a negative judgement on esthetic outcome. Some patients had persistent psychosocial concerns. No significant additional problems attributable to radiation therapy capable of affecting QOL outcomes were reported.


Predicting Oral Absorption for Compounds Outside the Rule of Five Property Space.
The estimation of the extent of absorption of drug candidates intended for oral drug delivery is an important selection criteria in drug discovery. The use of cell-based transwell assays examining flux across cell-monolayers (e.g., Caco-2 or MDCK cells) usually provide satisfactory predictions of the extent of absorption in vivo. These predictions often fall short of expection for molecules outside the traditional low molecular weight property space. In this manuscript the transwell permeability assay was modified to circumvent potential issues that can be encountered when evaluating the aforementioned drug molecules. Particularly, the addition of albumin in the acceptor compartment to reduce potential binding to cells and the acceptor compartment, improved the predictive power of the assay. Cellular binding and lysosomal trapping effects are significantly reduced for larger molecules, particularly lipophilic bases under these more physiological conditions, resulting in higher recovery values and a better prediction power. The data indicate that lysosomal trapping does not impact the rate of absorption of lipophilic bases in general but is rather an exception. Finally, compounds believed to permeate by passive mechanisms were used in a calibration curve for the effective prediction of the fraction absorbed of molecules of interest in current medicinal chemistry efforts.


An Update on the Role of Serotonin and its Interplay with Dopamine for Reward.
The specific role of serotonin and its interplay with dopamine (DA) in adaptive, reward guided behavior as well as drug dependance, still remains elusive. Recently, novel methods allowed cell type specific anatomical, functional and interventional analyses of serotonergic and dopaminergic circuits, promising significant advancement in understanding their functional roles. Furthermore, it is increasingly recognized that co-release of neurotransmitters is functionally relevant, understanding of which is required in order to interpret results of pharmacological studies and their relationship to neural recordings. Here, we review recent animal studies employing such techniques with the aim to connect their results to effects observed in human pharmacological studies and subjective effects of drugs. It appears that the additive effect of serotonin and DA conveys significant reward related information and is subjectively highly euphorizing. Neither DA nor serotonin alone have such an effect. This coincides with optogenetically targeted recordings in mice, where the dopaminergic system codes reward prediction errors (PE), and the serotonergic system mainly unsigned PE. Overall, this pattern of results indicates that joint activity between both systems carries essential reward information and invites parallel investigation of both neurotransmitter systems.


Quantitative analysis of a presence/absence microbiological assay: the hard surface carrier test of disinfectant efficacy.
The Hard Surface Carrier Test (HSCT) is a presence/absence assay for determining the extent to which chemical disinfectants kill bacteria. The disinfectants are marketed for cleaning surfaces in hospitals, restaurants, the home, etc. In the HSCT, a presence response (or equivalently, a positive carrier) is recorded if one or more bacteria survive among M bacteria attached to a glass carrier and exposed to the chemical disinfectant; otherwise, the response is absence. The presence or absence response is observed for each of many (usually 60) glass carriers and the disinfectant is considered effective if few (e.g., < or = 5%) of the carriers are positive. It would be more satisfactory to microbiologists if effectiveness were based on the fraction of bacteria that survive exposure; denote the expected survival fraction by phi. An equivalent parameter commonly used in antimicrobial research is the log-reduction, denoted by psi, where psi = -log10(phi). Although the number M of bacteria on each exposed carrier is not known, this paper shows it is possible to estimate psi. The suggested estimator is based on the assumption that M follows a gamma distribution. The gamma parameters are estimated using counts of bacteria on the HSCT nonexposed (control) carriers. This paper provides a formula for the standard error of the estimate, a computer simulation technique for calculating the lower confidence limit, and a computer simulation study of these statistical methods.


Pregnant beef cow's nutrition and its effects on postnatal weight and carcass quality of their progeny.
A systematic review (SR) and meta-analysis (MA) were performed to evaluate the effects of different energy levels (metabolizable energy, ME) and crude protein (CP), supplied to pregnant cows, on weight of their progenies at 60 (BW60), 100 (BW100), 180 (BW180) and 205 (BW205) days of age, average daily gain (ADG), and weight, age, loin eye area (LEA), marbling and fat thickness (FT) at slaughter. The SR was performed on two electronic databases. The MA for random effects was performed for each response variable separately. The BW60 was reduced (P<0.001; I2 = 78.9%) when cows consumed CP and ME above the required levels during the third trimester of pregnancy (3TRI). The BW205 was lower (P<0.001; I2 = 92.6%) when cows consumed ME above the recommended levels in the second trimester of pregnancy (2TRI) and 3TRI. Conversely, the ADG was higher when cows consumed CP (P = 0.032; I2 = 96.1%) and ME (P<0.001; I2 = 96.1%) above the required levels. The steers whose mothers consumed CP and ME above the required levels during the 3TRI were slaughtered 5.5 days earlier (P = 0.015; I2 = 98.5%) compared to other steers. The marbling was higher (P<0.001; I2 = 91.7%) in calves born to mothers consuming CP and ME above the recommended levels, regardless of the gestation phase. The FT was higher (P<0.001; I2 = 0%) in the offspring of cows that consumed CP and ME above the required levels during the 3TRI. Thus, CP and ME intake, at levels higher than those recommended by the NRC, by pregnant cows in the 3TRI reduces the progeny weight up to 205 days of age. However, this is advantageous during the finishing phase, as it reduces slaughter age and increases the ADG and carcass quality by improving marbling and FT.


Vitamin D, shedding light on the development of disease in peripheral arteries.
Vitamin D is generally associated with calcium metabolism, especially in the context of uptake in the intestine and the formation and maintenance of bone. However, vitamin D influences a wide range of metabolic systems through both genomic and nongenomic pathways that have an impact on the properties of peripheral arteries. The genomic effects have wide importance for angiogenesis, elastogenesis, and immunomodulation; the nongenomic effects have mainly been observed in the presence of hypertension. Although some vitamin D is essential for cardiovascular health, excess may have detrimental effects, particularly on elastogenesis and inflammation of the arterial wall. Vitamin D is likely to have a role in the paradoxical association between arterial calcification and osteoporosis. This review explores the relationship between vitamin D and a range of physiological and pathological processes relevant to peripheral arteries.


Role and Mechanism of Exosome-Derived Long Noncoding RNA HOTAIR in Lung Cancer.
HOX transcript antisense RNA (HOTAIR) is a long noncoding RNA (lncRNA) that promotes tumor growth and metastasis. Exosomes can mediate intracellular communication in cancer by transferring active molecules. However, the role and mechanism of HOTAIR in nonsmall cell lung cancer (NSCLC) are still unclear. This study mainly explores the role and mechanism of exosome-derived HOTAIR in NSCLC. after the material characterization of the CD63 immune lipid magnetic bead (CD63-IMB), the exosomes in serum of NSCLC patients were captured through CD63-IMB for the corresponding biological characterization. Real-time quantitative reverse transcription PCR (qRT-PCR) was performed to detect the expression level of HOTAIR in tumor tissues, serum, and serum exosome from NSCLC patients. Subsequently, exosome secreted by NCI-H1975 cells with highly expressed HOTAIR was selected to treat low-expression A549 cells and HOTAIR knockdown on NCI-H1975 cells. In this way, action mechanisms of HOTAIR can be investigated by means of qRT-PCR, colony formation assays, and flow cytometry. exosomes can be isolated by CD63-IMB, and taken up by cells effectively; the qRT-PCR results demonstrate that HOTAIR expressions are significantly upregulated in tumor tissues, serums, and exosomes isolated from serums of NSCLC patients. Clinicopathological correlation analysis shows that the upregulation of HOTAIR is closely associated with lymphatic metastasis and tumor node metastasis (TNM) staging (P < 0.05). HOTAIR expressions show a significant increase in A549 cells treated with exosomes derived from NCI-H1975 cells, signifying that both proliferation and migration of A549 cells are promoted, and HOTAIR depletion could inhibit the proliferation and migration of lung cancer cells. HOTAIR is highly expressed in tumor tissues, serums, and serum exosomes of NSCLC patients and its expression has a significant correlation with lymphatic metastasis and TNM staging. Moreover, the exosome may promote NSCLC proliferation and migration through HOTAIR transportation. Therefore, exosome-derived HOTAIR is expected to be a new molecular marker for NSCLC diagnosis, and exosomal transmission of HOTAIR may provide a new approach to NSCLC diagnosis.