Methicillin-resistant Staphylococcus aureus in cattle food chains - prevalence, diversity, and antimicrobial resistance in Germany.
Livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) have been found in various farm animal species throughout the world. It was the objective of this study to estimate the prevalence of MRSA in different cattle food chains (milk, beef, and veal) in Germany, to analyze the MRSA diversity along each food chain and to compare the characteristics of the different subtypes. Samples were collected between 2009 and 2012 from dairy herds (bulk tank milk), veal herds (dust from the stables), veal calves, and beef cattle at slaughter (nasal swabs) and carcasses of veal calves (surface cuts) and beef as well as veal at retail. Sampling was proportionally distributed over the country according to the cattle population (on-farm sampling), slaughterhouse capacity (abattoir samples), and the human population (meat at retail). Methicillin-resistant S. aureus were isolated using harmonized methods from all sample types and populations investigated. The highest proportion of positive samples was found in nasal swabs from veal calves at slaughter in 2012 (144/320; 45.0%) and the lowest rate in bulk tank milk in 2009 (14/388; 4.1%). Most isolates, irrespective of the origin, were from spa types t011 and t034. Both have been assigned to the clonal complex (CC) 398. Few isolates (15/632; 2.4%) were from spa types not associated with the CC398. Spa-type patterns were similar along individual food chains but differed between food chains. Antimicrobial resistance patterns differed between isolates from the different food chains and spa types. Isolates from the veal chain displayed the highest resistance rates. We conclude that there is substantial diversity in the MRSA prevalence across different cattle production sectors.


Predicting sex, age, general cognition and mental health with machine learning on brain structural connectomes.
There is an increasing expectation that advanced, computationally expensive machine learning (ML) techniques, when applied to large population-wide neuroimaging datasets, will help to uncover key differences in the human brain in health and disease. We take a comprehensive approach to explore how multiple aspects of brain structural connectivity can predict sex, age, general cognitive function and general psychopathology, testing different ML algorithms from deep learning (DL) model (BrainNetCNN) to classical ML methods. We modelled N = 8183 structural connectomes from UK Biobank using six different structural network weightings obtained from diffusion MRI. Streamline count generally provided the highest prediction accuracies in all prediction tasks. DL did not improve on prediction accuracies from simpler linear models. Further, high correlations between gradient attribution coefficients from DL and model coefficients from linear models suggested the models ranked the importance of features in similar ways, which indirectly suggested the similarity in models' strategies for making predictive decision to some extent. This highlights that model complexity is unlikely to improve detection of associations between structural connectomes and complex phenotypes with the current sample size.


The etiology of renal-cell carcinoma.
Experimental renal-cell carcinoma can be induced by many different chemical carcinogens; dimethyl nitrosoamine has been most studied. The disease so induced in experimental animals closely resembles the spontaneous disease in man in histopathology, course, and other characteristics. Two agents that are probably etiological of renal-cell cancer in man are tobacco and the analgesic, phenacetin; however, these materials can account for only a minority of the cases. The predominance of males in adult renal carcinoma might be explained by the more efficient metabolic activation of carcinogens by renal enzymes that are induced by male hormones. Mouse experiments support this hypothesis. Studies utilizing human kidney tissues that would test the hypothesis in man can and should be done. No obvious clues have emerged to explain the wide geographic differences in incidence of renal carcinoma. No group of industrial workers, or of others with a unique environment, has yet been described that has an especially high incidence of renal-cell carcinoma. A minority of renal carcinomas are familial. They represent a number of different diseases, one of which is associated with the von Hippel-Lindau disease. The hereditary renal-cell carcinoma of the Ecker rat, which is transmitted as an autosomal dominant, provides a useful laboratory model for hereditary carcinoma of man. Recently, two human families with renal-cell carcinoma were described in which there were unique chromosomal abnormalities associated with the disease. Such changes have been linked with oncogene activation in the instance of other tumors. Further studies of chromosomal abnormalities in renal-cell carcinoma will probably define a common pattern of chromosomal rearrangements. While estrogen readily induces renal-cell carcinoma in hamsters other species, including man, appear resistant. An excess of renal-cell carcinoma has not been reported in men on chronic estrogen therapy for prostatic carcinoma, nor has it been associated with the DES syndrome. A virus etiology for renal-cell carcinoma in man comparable to that of the Lucke tumor in frogs is unlikely on epidemiologic, ultrastructural morphologic, and other grounds. There is nothing suggesting horizontal transmission in the human disease, and a unique excess of renal-cell carcinomas in immunosuppressed patients or patients with the acquired immunodeficiency syndrome (AIDS) is not apparent. There is overwhelming evidence that renal adenomas represent early adenocarcinomas, or at least precursor lesions; certainly they are closely related to renal-cell carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)


Proteomic analysis of wheat embryos with 2-DE and liquid-phase chromatography (ProteomeLab PF-2D)--a wider perspective of the proteome.
Cereal embryos are a model system to study desiccation tolerance due to their ability to survive extreme water loss during late embryogenesis. To identify proteins accumulating in mature embryos which can be used as potential markers for dehydration tolerance, we compared the embryo proteome from two durum wheat genotypes (Triticum durum Desf.), Mahmoudi (salt and drought sensitive) and Om Rabia3 (salt and drought tolerant). Total protein extracts from wheat embryos were analyzed by using conventional 2-DE and ProteomeLab PF-2D. Analysis using different pH ranges showed that a larger number of fractions were solved by LC, than by conventional 2-DE at extreme technical pHs (pH 4.0-5.0 and pH 6.5-8.0). In contrast, at intermediate pHs (pH 5.0-6.5), resolution was better in 2-DE gels. The two techniques were used in parallel to analyze total protein extracts from embryos of the two wheat varieties. Several proteins belonging to the seed storage family, LEA-type/heat shock proteins, enzyme metabolism and radical scavengers were identified by analysis of trypsin digested peptides via mass spectrometry. These proteins accumulate in different amounts in embryos of tolerant and sensitive wheat varieties. The differences in expression pattern were further validated by enzyme activity, western blotting analysis and correlated with their corresponding mRNA expression by RT-PCR analyses for the corresponding protein. We suggest that the differential expression pattern could be used as a basis for a biochemical screen of tolerance/sensitivity to drought and salt stress in wheat embryos and germplasm.


Psychological processing among caregivers of allogeneic bone marrow transplant recipients: Qualitative findings from a longitudinal study.
To describe caregiver psychological processing during the 12 weeks after transplant and the potential role of positive emotions in caregiving experiences. We conducted a longitudinal qualitative descriptive study and interviewed 11 BMT caregivers monthly for 12-weeks post-transplant about their experiences and psychological processing. We analyzed 38 interviews using directed content analysis based on guiding theories and inductive in vivo coding to develop themes. The majority of participants appraised caregiving as a challenge that needed to be met. Caregivers described feeling positive emotions throughout the time after transplant (gratitude, interest, and hope). We identified two new themes: mirroring (caregiver feelings reflecting patient status) and emotion regulation (hiding negative emotions and displaying positive emotions when with the patient). Findings provide further evidence that interventions focused on emotion regulation and positive emotion experiences during caregiving to reduce the negative effects of caregiving related stress may be promising.


The impact of shiftwork on work--home conflict, job attitudes and health.
The present study was designed to test the impact of rotation and timing of shifts on work--home conflict, job attitudes, health and absenteeism among the military police. A total of 3122 employees participated in the study. Discriminant analysis was used to examine the relationships between rotation and timing of shifts on the one hand, and the outcome measures on the other. Whether employees had fixed dayshifts, fixed non-day shifts including weekends, or rotating shifts with or without weekends, could be predicted on the basis of the experienced work--home conflict, job attitudes, health and absenteeism. Each of the two parameters of shiftwork differentially affected the experience of the outcome measures. Rotation was most clearly related to unfavourable job attitudes (namely job satisfaction, cynicism, turnover intentions and professional efficacy), whereas timing was most clearly related to increased work--home conflict. The results suggest that fixed non-day shifts including weekends (i.e., during highly valuable times) should be avoided in order to minimize the conflict between work and home and that rotation rosters should be designed with a high degree of individualization and flexibility. These seem to be the most promising ways to reduce the negative consequences of shiftwork for employees, their families and organizations.


Evaluation of Five Different Regimes For the Treatment of Vitiligo.
Response of vitiligo patients to five different regimes was evaluated taking only those patients who had either static or progressively increasing lesions. Selection of the regimen depended upon the clinical characteristics of the disease. Each regime was tried for at least 4 months and if a patient didnot improve with one regime, he was shifted to another regime. A patient was considered to have improved, if the lesions started regimenting or the previously progressive lesions stopped increasing further. Regime I consisted of 150 mg levamisol orally on two consecutive days per week, given to 13 cases, it resulted in improvement in 7 (53.80/o). Regime II consisted of levamisole in the same dose combined with once a day topical massage with 0.1% fluocinolone acetonide acetate cream; it led to improvement in 27 (81.8%) of the 33 cases. Regime III consisted of 3 mg betamethasone orally on alternate days combined with levamisole and topical fluocinolone; given to 32 cases, it was successful in 28 (87.50/o). A combination of 2 mg betamethasone orally alternating with 20 mg 8-methoxypsoralen and sun exposure (regime IV) caused improvement in 17 (85%) of the 20 cases. An oral mini pulse consisting of 5 mg betamethasone orally twice a week combined with 50 mg cyclophosphimide daily orally (regime V) was successful in 20 (90.9%) of the 22 cases, the remaining two cases showed unprovement when the dose ofbetamethasonc .was increased from 5 mg to 7.5 mg twice a week. Thus ultimately each one of the 91 patients responded to one or the other regime. The side effects were minimal and insignificant.The degree of improvement at the time of analysis was 100% in 23.3% cases, 50-100% in 44.2'Yo cases and less than 50% in 32.5%, after 4-14 months of treatment. It is felt that the results may be better after a longer follow-up although all patients are not expected to get complete repigmentation.


DDT and its metabolites are linked to increased risk of type 2 diabetes among Saudi adults: a cross-sectional study.
Organochlorine (OC) pesticides have recently been associated with type 2 diabetes in several non-Asian general populations. As there is currently an epidemic of type 2 diabetes mellitus in Asia. The prevalence and incidence of diabetes is increasing rapidly worldwide including many Arab Gulf countries. According to a community-based national epidemiological health survey, the overall prevalence of diabetes mellitus in Saudi adults (age group of 30-50 years) is 23.7%. A recent study by Al-Daghri et al. (BMC Med 9:76, 2011) reported that the prevalence of diabetes mellitus in the Kingdom of Saudi Arabia (KSA) is 31.6%. We investigated the associations between OC pesticides and type 2 diabetes in Saudi Arabia using a simple, sensitive, rapid, and selective gas chromatography coupled with mass spectrometry (GC-MS) method that has been recently developed. A total of 280 Saudi adults (136 diabetes mellitus (DM) patients and 144 non-DM controls) were randomly selected from the Riyadh Cohort Study for inclusion. The diagnosis of diabetes was based on established diagnosis and medications taken. Blood dichlorodiphenyltrichloroethane (DDT) and its derivatives were quantified using GC-MS. Residues of DDT and its derivatives were analyzed in serum by means of gas chromatography with a mass spectrometry detector. Associations between DDT exposure and T2DM were analyzed by logistic regression. DDT and its derivatives and serum concentrations of DDT and its derivative DDE showed the strongest and most significant association to type 2 diabetes in both cross-sectional and prospective studies. Associations of DDT and its derivatives varied across different diabetes-related components of the metabolic syndrome. It positively and significantly associated with four of the five of these components especially elevated triacylglycerol, high fasting glucose, high blood pressure, and HOMA-IR but negatively and significantly with HDL. Possible biological mechanisms are discussed. This study confirms previous reports relating organochlorine pesticide (OCP) exposure to diabetes and suggests possible hormonal pathways deserving further exploration. The study will be one of the first to shed light on the associations of serum levels of total DDTs and DDT derivatives among the Saudi Arab ethnicity, and diabetes type 2 chronic noncommunicable diseases are highly prevalent.


[Treatment of autonomic crises (attacks of panic)].
The paper treats of the data on the treatment of 69 patients with vegetative crises (panic attacks) with amitriptyline and clonazepam by the double blind placebo control method. The efficacy of amitriptyline was 77% versus 42% (placebo); that of clonazepam was 84% versus 35% (placebo). The clinical predictors of the placebo efficacy and of each of the drugs in the treatment of the conditions in question have been established.


Evolution of Collective Behaviors for a Real Swarm of Aquatic Surface Robots.
Swarm robotics is a promising approach for the coordination of large numbers of robots. While previous studies have shown that evolutionary robotics techniques can be applied to obtain robust and efficient self-organized behaviors for robot swarms, most studies have been conducted in simulation, and the few that have been conducted on real robots have been confined to laboratory environments. In this paper, we demonstrate for the first time a swarm robotics system with evolved control successfully operating in a real and uncontrolled environment. We evolve neural network-based controllers in simulation for canonical swarm robotics tasks, namely homing, dispersion, clustering, and monitoring. We then assess the performance of the controllers on a real swarm of up to ten aquatic surface robots. Our results show that the evolved controllers transfer successfully to real robots and achieve a performance similar to the performance obtained in simulation. We validate that the evolved controllers display key properties of swarm intelligence-based control, namely scalability, flexibility, and robustness on the real swarm. We conclude with a proof-of-concept experiment in which the swarm performs a complete environmental monitoring task by combining multiple evolved controllers.


Structural comparison of two yeast tRNA Glu 3 genes.
DNA sequences in a 1.7 kb Pst fragment from yeast have been determined. This fragment is part of a yeast 7.4 kb Hind III segment cloned ino pBR322 (pY 5). The fragment carries a single gene for a glutamate tRNA. The coding portion of this gene is identical in sequence to that of the tRNA Glu 3 gene from pY 20 [1]. The flanking regions differ in their sequences, but possible secondary structures within the 5'-flanking regions bear similar features. Sequence homologies between pY 5 and pY 20 were detected far outside the tRNA genes. More surprisingly, extended sequence homologies were seen between the flanking regions of the pY 20 tRNA Glu 3 gene and a tRNA Ser gene [2,3]. We have also checked the known tRNA genes for structural similarities. Hybridization studies indicate that portions of the Pst fragment are repeated within the yeast genome.


PeNGaRoo, a combined gradient boosting and ensemble learning framework for predicting non-classical secreted proteins.
Gram-positive bacteria have developed secretion systems to transport proteins across their cell wall, a process that plays an important role during host infection. These secretion mechanisms have also been harnessed for therapeutic purposes in many biotechnology applications. Accordingly, the identification of features that select a protein for efficient secretion from these microorganisms has become an important task. Among all the secreted proteins, 'non-classical' secreted proteins are difficult to identify as they lack discernable signal peptide sequences and can make use of diverse secretion pathways. Currently, several computational methods have been developed to facilitate the discovery of such non-classical secreted proteins; however, the existing methods are based on either simulated or limited experimental datasets. In addition, they often employ basic features to train the models in a simple and coarse-grained manner. The availability of more experimentally validated datasets, advanced feature engineering techniques and novel machine learning approaches creates new opportunities for the development of improved predictors of 'non-classical' secreted proteins from sequence data. In this work, we first constructed a high-quality dataset of experimentally verified 'non-classical' secreted proteins, which we then used to create benchmark datasets. Using these benchmark datasets, we comprehensively analyzed a wide range of features and assessed their individual performance. Subsequently, we developed a two-layer Light Gradient Boosting Machine (LightGBM) ensemble model that integrates several single feature-based models into an overall prediction framework. At this stage, LightGBM, a gradient boosting machine, was used as a machine learning approach and the necessary parameter optimization was performed by a particle swarm optimization strategy. All single feature-based LightGBM models were then integrated into a unified ensemble model to further improve the predictive performance. Consequently, the final ensemble model achieved a superior performance with an accuracy of 0.900, an F-value of 0.903, Matthew's correlation coefficient of 0.803 and an area under the curve value of 0.963, and outperforming previous state-of-the-art predictors on the independent test. Based on our proposed optimal ensemble model, we further developed an accessible online predictor, PeNGaRoo, to serve users' demands. We believe this online web server, together with our proposed methodology, will expedite the discovery of non-classically secreted effector proteins in Gram-positive bacteria and further inspire the development of next-generation predictors. http://pengaroo.erc.monash.edu/. Supplementary data are available at Bioinformatics online.


Co-phylogeography and morphological evolution of sika deer lice (Damalinia sika) with their hosts (Cervus nippon).
Lice are obligate parasites of mammals and birds and have become an important model for studies of host-parasite co-evolution and co-phylogenetics. Population genetic and phylogeographic studies represent an important bridge between microevolution and co-phylogenetic patterns. We examine co-phylogeographic patterns in sika deer and their parasitic lice. Co-phylogeographic patterns in deer and lice were evaluated using homologous regions of mitochondrial COI sequences. The phylogeographic breaks recovered for deer populations matched those of previous studies. Comparisons of the phylogeographic tree topology for deer lice with that of their hosts revealed a significant level of congruence. However, comparisons of genetic distances between deer and lice suggested that one of the estimated co-divergence events is more likely a recent host switch. Taking into account genetic divergence, there is not strong evidence for complete phylogeographic co-divergence between deer and their parasitic lice. However, mitochondrial phylogenies only track genetic structure of female lineages, and the incongruence between deer and louse phylogeography may be explained by louse migration mediated by male deer. Morphological analysis of head shape variation based on an elliptic Fourier descriptor showed that overall morphological variation contained phylogenetic signal, suggesting that in general morphology of these lice evolves congruent to population history.


External beam radiotherapy for synchronous rectal and prostatic tumors.
Two patients were diagnosed with large rectal tumors and localized prostate cancer. The prostate-specific antigen level at diagnosis was 7.9 ng/mL and 9.0 ng/mL in the 2 patients. Knowledge of the presence of both tumors and their close proximity allowed creation of a modified three-dimensional conformal radiotherapy plan to treat both tumors. The patients had no evidence of rectal tumor recurrence and their prostate-specific antigen level was 0.5 ng/mL and 0.7 ng/mL at 1 and 2 years after therapy, respectively. We conclude that efficient, effective pelvic irradiation can be designed for synchronous rectal and prostate malignancies.


Texture analysis in radionuclide tomographic liver imaging.
In clinical trials assessing the value of radionuclide tomographic liver imaging there has been no significant increase in diagnostic accuracy when conventional views have been viewed with tomographic images. In an effort to increase the diagnostic value of tomography, we have applied some simple methods of texture analysis to both phantom and patient tomograms in order to quantify different uptake patterns. Three algorithms were used which look at the differences between a pixel and its near neighbours. In phantom experiments, the variation of image texture with image noise was quantified. Accurate values of texture were obtained for images of the phantom containing various sizes of cold spots. Detection limits were then calculated for the different sizes of cold spots. It was found that 1.5 cm cold spots could be detected with a collection time of approximately 25 min, the usual collection time for livers being 20 min. The theoretical detection limits were checked experimentally and found to agree well with experimental values. A preliminary clinical survey was made applying texture analysis to eight images from normal livers and eight from abnormal (metastatic) livers. Although the sample was small, good separation between normals and abnormals was obtained.


Factors associated with mammography screening among Reunionese women : a cross-sectional study.
To explore the factors associated with the uptake of mammography screening in Reunionese women aged 50-65 years. This study included all women aged 50 to 65 years participating in a population-based cross-sectional study "FOSFORE". Participants were recruited between March and June 2017 using two sampling frames. The first frame consisted of households with a landline telephone, with or without a mobile line, by first randomly generating a telephone number and then randomly selecting an individual from among all eligible women in the household. The second sampling frame was constituted of women with an exclusive mobile line, who were selected directly if they met the eligibility criteria. Data were weighted for age and socio-professional status to ensure representativeness at the Reunion Island level. Weighted logistic regression was used to calculate odds ratios while adjusting for confounders. 417 women were included in the study; 63.8% were up to date with guidelines on mammography screening and 36.2% were not up to date. Four factors were significantly associated with mammography screening, with an adjusted odds ratio of 2.92 (95% CI 1.51-5.61) for not having an Active Solidarity Income, 1.98 (95% CI 1.22-3.23) for having a regular gynecological follow-up by a physician, 6.53 (95% CI 3.23-13.21) for performing a Pap smear test in the past two years, and 2.07 (95% CI 1.21-3.52) for having an adequate literacy level (HLQ3). The findings of this study suggest that higher socio-economic status is an indicator of participation in mammography screening in La Réunion, and future educational and intervention programs should target women in deprived areas.


Differentiation of Dictyostelium discoideum mutant cells in a shaken suspension culture and the effect of cyclic AMP.
In Dictyostelium discoideum, 16 mutants in which cells differentiate into spores and stalk cells without normal morphogenesis were isolated. All these mutants are rapidly developing and capable of differentiating in a shaken suspension of phosphate buffer. The developmental kinetics of specific activities of enzymes in one of the mutants, HTY 1851, cultured in the suspension was compared with that in the parental strain, X2, developed on a solid surface. Most of the enzyme activities appeared much earlier and the peaks of the activities were lower in HTY1851 than X2, but the order or appearance of the activities was the same in both the strains cultured under the conditions described above. These results suggest that the biochemical steps in the development of the mutant in a shaken suspension are essentially the same as those of the parental strain X2 on a solid surface. It was also found that addition of cyclic AMP (2.5 X 10-5 M to 1 X 10-4 M) to the mutant cell suspension 6-8 h after the initiation of development induced an increase in the number of spores and the specific activities of some enzymes to values twice as high as those of an untreated control.


Experimental evidence of genome-wide impact of ecological selection during early stages of speciation-with-gene-flow.
Theory predicts that speciation-with-gene-flow is more likely when the consequences of selection for population divergence transitions from mainly direct effects of selection acting on individual genes to a collective property of all selected genes in the genome. Thus, understanding the direct impacts of ecologically based selection, as well as the indirect effects due to correlations among loci, is critical to understanding speciation. Here, we measure the genome-wide impacts of host-associated selection between hawthorn and apple host races of Rhagoletis pomonella (Diptera: Tephritidae), a model for contemporary speciation-with-gene-flow. Allele frequency shifts of 32 455 SNPs induced in a selection experiment based on host phenology were genome wide and highly concordant with genetic divergence between co-occurring apple and hawthorn flies in nature. This striking genome-wide similarity between experimental and natural populations of R. pomonella underscores the importance of ecological selection at early stages of divergence and calls for further integration of studies of eco-evolutionary dynamics and genome divergence.


[Nosologic descriptions of lesions of the oral mucosa].
This article describes extensively and systematically oral mucosa diseases. Macroscopical aspects are particularly described in order to give the dentist all important elements of differential diagnosis. This nosological description is based on a clinical approach: white and pigmented lesions are distinguished from ulcerated and benign so as malignant tumoral lesions. Specifically on the oral mucosa located lesions and oral mucosa lesions of systemic diseases are described.


Barotrauma associated with high-frequency jet ventilation for hypoxic salvage.
Most reports describe reduction in proximal airway pressures with high-frequency jet ventilation. This led us to speculate that high-frequency jet ventilation might reduce barotrauma by providing alveolar ventilation at lower airway pressures. We describe a group of patients in whom a high incidence of barotrauma was observed after institution of high-frequency jet ventilation despite reduction in measured airway pressures. Fifteen hypoxic patients who could not be treated with conventional ventilation and who had no roentgenographic evidence of barotrauma were entered into the study. Airway pressures were measured during conventional ventilation and at 2 and 24 hours after high-frequency jet ventilation. Despite significant reduction in peak inspiratory and mean airway pressures, pneumothorax developed in seven of the 15 patients, an average of 21 hours after initiation of high-frequency jet ventilation. Five patients had bilateral pneumothorax and three developed tension pneumothorax. Despite reductions in proximal airway pressures, barotrauma is a significant potential complication of high-frequency jet ventilation in patients with noncompliant lungs. We currently place bilateral prophylactic thoracostomy tubes in patients with adult respiratory distress syndrome prior to initiation of high-frequency jet ventilation.


Assessment of left ventricular size and function in horses using anatomical M-mode echocardiography.
To study the applicability of anatomical M-mode (AMM) for assessment of left ventricular (LV) size and function in horses, evaluate agreement with conventional M-mode (CMM), determine reliability, and establish reference intervals for AMM measurements. 98 horses; 13.1 +/- 5.6 years; 538 +/- 78 kg. Two-dimensional and M-mode recordings were analyzed retrospectively. Standard LV dimensions and indices of LV function, including time intervals, were measured in CMM and compared with AMM studies in long-axis (lx) and short-axis (sx) views. The percentages of measureable cycles were 99%, 97%, and 90% for routine LV studies in CMM(sx), AMM(sx), and AMM(lx) mode. For time intervals, >or= 93% of cycles could be measured using AMM compared to a maximum of 77% using CMM. AMM(sx) measurements agreed well with CMM(sx) measurements for LV studies; the agreement of AMM(lx) with CMM(sx) was markedly lower. The LV ejection time and the duration of electromechanical systole, but not the LV pre-ejection period and the index of myocardial performance, showed fair agreement between methods. Intraobserver and interobserver measurement variabilities were low for most variables. AMM can replace CMM for assessment of LV dimensions in horses, but is not recommended for measurement of time intervals.


The Relationship between Trait Anxiety and Driving Behavior with Regard to Self-reported Iranian Accident Involving Drivers.
THE AIMS OF THIS STUDY INCLUDED: Determination of the most common driver behavior in drivers and also analyzing the relationship between trait anxiety (TA) with subscale of driving behavior (lapses, errors, ordinary and aggressive violations). This cross-sectional study was conducted on 168 drivers that having crash. The self-reporting of the drivers was determined by using Manchester driving behavior questionnaire (DBQ) and Spielberger State-Trait Anxiety Inventory. Independent t-test showed that violations factor (ordinary and aggressive) are the most common behavior in drivers, Pearson correlation revealed that TA had a significant direct positive relation with all DBQ subscales especially error and lapses factor (P < 0.01) also Pearson correlation showed that age had a negative significant relation with factors of DBQ. It can be concluded from the results (according to the relation between TA with error and lapses factor) that the rate of TA is destructive effective on the memory performance and process in the drivers and cause absent minded and memory imperfect function and process in these people during the driving.


[Ecological aspects of human pathogens Ehrlichia and Bartonella].
The review presents data on the natural circulation of Bartonellas and Erlichias with the participation of lice, fleas, mosquitoes, Ixodes ticks, as well as rodents, large wild mammals, and domestic animals. It outlines the human infection routes that are mainly associated with the attack of infected carriers and with the contacts with different warm-blooded animals. The risk of bartonellosis spread is evidenced by the data showing that 12.3% of clothes lice collected from homeless individuals in Moscow turned out to be infected. In a focus of erlichiasis, the infection rates of Ambliomma americanum and Ixodes scapularis were 4.9 and as high as 20%, respectively; 100% of white-tailed deers (Odocoileus virginianus) were seropositive. However, many issues associated with the preservation of these natural vectors, with the route of their transmission to human beings and animals are to be studied.


Baicalein suppresses 17-β-estradiol-induced migration, adhesion and invasion of breast cancer cells via the G protein-coupled receptor 30 signaling pathway.
Flavonoids are structurally similar to steroid hormones, particularly estrogens, and therefore have been studied for their potential effects on hormone-dependent cancers. Baicalein is the primary flavonoid derived from the root of Scutellaria baicalensis Georgi. In the present study, we investigated the effects of baicalein on 17β-estradiol (E2)-induced migration, adhesion and invasion of MCF-7 and SK-BR-3 breast cancer cells. The results demonstrated that baicalein suppressed E2-stimulated wound-healing migration and cell‑Matrigel adhesion, and ameliorated E2-promoted invasion across a Matrigel-coated Transwell membrane. Furthermore, baicalein interfered with E2-induced novel G protein-coupled estrogen receptor (GPR30)-related signaling, including a decrease in tyrosine phosphorylation of epidermal growth factor receptor (EGFR) as well as phosphorylation of extracellular signal-regulated kinase (ERK) and serine/threonine kinase Akt, without affecting GPR30 expression. The results also showed that baicalein suppressed the expression of GPR30 target genes, cysteine-rich 61 (CYR61) and connective tissue growth factor (CTGF) induced by E2. Furthermore, baicalein prevented GPR30-related signaling activation and upregulation of CYR61 and CTGF mRNA levels induced by G1, a specific GPR 30 agonist. The results suggest that baicalein inhibits E2-induced migration, adhesion and invasion through interfering with GPR30 signaling pathway activation, which indicates that it may act as a therapeutic candidate for the treatment of GPR30-positive breast cancer metastasis.


In vivo validation and 3D visualization of broadband ultrasound molecular imaging.
Ultrasound can selectively and specifically visualize upregulated vascular receptors through the detection of bound microbubbles. However, most current ultrasound molecular imaging methods incur delays that result in longer acquisition times and reduced frame rates. These delays occur for two main reasons: 1) multi-pulse imaging techniques are used to differentiate microbubbles from tissue and 2) acquisition occurs after free bubble clearance (>6 minutes) in order to differentiate bound from freely circulating microbubbles. In this paper, we validate tumor imaging with a broadband single pulse molecular imaging method that is faster than the multi-pulse methods typically implemented on commercial scanners. We also combine the single pulse method with interframe filtering to selectively image targeted microbubbles without waiting for unbound bubble clearance, thereby reducing acquisition time from 10 to 2 minutes. The single pulse imaging method leverages non-linear bubble behavior by transmitting at low and receiving at high frequencies (TLRH). We implemented TLRH imaging and visualized the accumulation of intravenously administrated integrin-targeted microbubbles in a phantom and a Met-1 mouse tumor model. We found that the TLRH contrast imaging has a ~2-fold resolution improvement over standard contrast pulse sequencing (CPS) imaging. By using interframe filtering, the tumor contrast was 24.8±1.6 dB higher after the injection of integrin-targeted microbubbles than non-targeted control MBs, while echoes from regions lacking the target integrin were suppressed by 26.2±2.1 dB as compared with tumor echoes. Since real-time three-dimensional (3D) molecular imaging provides a more comprehensive view of receptor distribution, we generated 3D images of tumors to estimate their volume, and these measurements correlated well with expected tumor sizes. We conclude that TLRH combined with interframe filtering is a feasible method for 3D targeted ultrasound imaging that is faster than current multi-pulse strategies.


Long-term outcome after discharge from a stroke rehabilitation unit.
The evidence is compelling that stroke units are effective when compared to management of patients on general medical wards. However, the evidence remains equivocal that better outcome is sustained in the longer term. This paper reports an investigation of cognitive and emotional outcome, environmental consequences, social activities, and physical outcome in 57 consecutive one-year survivors of a stroke discharged from a stroke and neurological rehabilitation unit. Satisfaction with inpatient and outpatient services was also investigated. Results were compared with previously reported studies of long-term outcome after stroke. Mean Barthel activities of daily living score at one year or more post-stroke was 16.8. Arm function was impaired in 43% of the participants in the study. Nearly half had cognitive and emotional problems, 19% communication problems, and 25% problems with access both inside and outside their house. All but four of the one-year survivors were less active after their stroke than before. More than 40% were dissatisfied with at least one aspect of inpatient and/or outpatient services. The long-term consequences of stroke in all areas investigated were considerable and in line with previous reports. Some suggestions for reducing these effects are made, including better information for patients about stroke and rehabilitation, improved access to psychology services, detailed assessment prior to hospital discharge of the patient's living environment and effective coordination with social services to improve access to their living environment.


Nudge me, help my baby: on other-regarding nudges.
There is an increasing interest in the possibility of using nudges to promote people's health. Following the advances in developmental biology and epigenetics, it is clear that one's health is not always the result of one's own choices. In the period surrounding pregnancy, maternal choice behaviour has a significant influence on perinatal morbidity and mortality as well as the development of chronic diseases later in life. One's health is thus a matter of one's own as well as one's maternal choices. Therefore, self-regarding and other-regarding nudges should be considered as viable strategies to promote health. In this article, we introduce the concept of other-regarding nudges. We use the harm principle and the principle of beneficence to justify these other-regarding nudges. We conclude by stressing the importance of a fair assessment of expectations towards the nudgee, when determining whether a nudge is aimed at preventing harm or promoting a good.


Normal-tension glaucoma (Low-tension glaucoma).
Glaucoma is now considered an abnormal physiology in the optic nerve head that interacts with the level of intraocular pressure (IOP), with the degree and rate of damage depending on the IOP and presumably the degree of abnormal physiology. Diagnosis of normal-tension glaucoma (NTG), defined as glaucoma without a clearly abnormal IOP, depends on recognizing symptoms and signs associated with optic nerve vulnerability, in addition to absence of other explanations for disc abnormality and visual field loss. Among the findings are a halo or crescent of absence of retinal pigment epithelium around the disc, bilateral pre-chiasmal visual field defects, splinter hemorrhages at the disc margin, vascular dysregulation (low blood pressure, cold hands and feet, migraine headache with aura, and the like), or a family history of glaucoma. Possibly relevant, is a history of hemodynamic crisis, arterial obstructive disease, or sleep apnea. Neurological evaluation with imaging is needed only for atypical cases or ones that progress unexpectedly. Management follows the same principle of other chronic glaucomas, to lower the IOP by a substantial amount, enough to prevent disabling visual loss. However, many NTG cases are non-progressive. Therefore, it may often be wise in mild cases to determine whether the case is progressive and the rate of progression before deciding on how aggressivene to be with therapy. Efforts at neuroprotection and improvement in blood flow have not yet been shown effective.


Residual appendicitis following incomplete laparoscopic appendectomy.
Growing popularity of laparoscopic interventions must bring along a thorough knowledge of possible complications inherent to the laparoscopic technique. With these two cases of residual appendicitis following incomplete appendectomy, the authors want to warn for this complication. Surgeons should be aware of residual appendicitis as a possible cause of acute abdomen at any time following a laparoscopic appendectomy.


Thyroid function in young children with Down syndrome.
A retrospective review of thyroid function tests (TFTs) was performed on 49 young children (aged 4 months to 3 years) with Down syndrome compared with age-matched controls screened for hypothyroidism because of developmental delay or failure to thrive. Three of the 49 children with Down syndrome had congenital hypothyroidism; of the three, one had Hirschsprung's disease and two had duodenal atresia. Thyroiditis was uncommon, with only two children having thyroid antibodies present: one had acquired hypothyroidism and the other acquired hyperthyroidism. Twenty-seven percent of the Down syndrome cohort had mildly increased thyrotropin (TSH) and normal thyroxine levels. When compared with children with Down syndrome who had normal TFTs, no significant differences in sex, growth rate, maternal age, associated anomalies, developmental or specific thyroid symptoms were present. Transient elevations of TSH level were common in children with Down syndrome whether or not TSH values were initially normal or elevated. Routine neonatal and sequential thyroid screening in young children with Down syndrome is warranted.


Lycopene Inhibits Smoke-Induced Chronic Obstructive Pulmonary Disease and Lung Carcinogenesis by Modulating Reverse Cholesterol Transport in Ferrets.
Chronic obstructive pulmonary disease (COPD) and lung cancer share the same etiologic factor, cigarette smoking. Higher consumption of dietary lycopene has been associated with lower risks of COPD and lung cancer in smokers. We investigated whether lycopene feeding protects against COPD and lung cancer in ferrets, a nonrodent model that closely mimics cigarette smoke (CS)-induced chronic bronchitis, emphysema, and lung tumorigenesis in human. We also explored whether the protective effect of lycopene is associated with restoring reverse cholesterol transport (RCT), a key driver in persistent inflammation with CS exposure. Ferrets (4 groups, n = 12-16/group) were exposed to a combination of tobacco carcinogen (NNK) and CS with or without consuming lycopene at low and high doses (equivalent to ∼30 and ∼90 mg lycopene/day in human, respectively) for 22 weeks. Results showed that dietary lycopene at a high dose significantly inhibited NNK/CS-induced chronic bronchitis, emphysema, and preneoplastic lesions, including squamous metaplasia and atypical adenomatous hyperplasia, as compared with the NNK/CS alone (P < 0.05). Lycopene feeding also tended to decrease the lung neoplastic lesions. Furthermore, lycopene feeding significantly inhibited NNK/CS-induced accumulation of total cholesterol, and increased mRNA expression of critical genes related to the RCT (PPARα, LXRα, and ATP-binding cassette transporters ABCA1 and ABCG1) in the lungs, which were downregulated by the NNK/CS exposure. The present study has provided the first evidence linking a protective role of dietary lycopene against COPD and preneoplastic lesions to RCT-mediated cholesterol accumulation in lungs.


Elevated temperature inhibits SARS-CoV-2 replication in respiratory epithelium independently of IFN-mediated innate immune defenses.
The pandemic spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of Coronavirus Disease 2019 (COVID-19), represents an ongoing international health crisis. A key symptom of SARS-CoV-2 infection is the onset of fever, with a hyperthermic temperature range of 38 to 41°C. Fever is an evolutionarily conserved host response to microbial infection that can influence the outcome of viral pathogenicity and regulation of host innate and adaptive immune responses. However, it remains to be determined what effect elevated temperature has on SARS-CoV-2 replication. Utilizing a three-dimensional (3D) air-liquid interface (ALI) model that closely mimics the natural tissue physiology of SARS-CoV-2 infection in the respiratory airway, we identify tissue temperature to play an important role in the regulation of SARS-CoV-2 infection. Respiratory tissue incubated at 40°C remained permissive to SARS-CoV-2 entry but refractory to viral transcription, leading to significantly reduced levels of viral RNA replication and apical shedding of infectious virus. We identify tissue temperature to play an important role in the differential regulation of epithelial host responses to SARS-CoV-2 infection that impact upon multiple pathways, including intracellular immune regulation, without disruption to general transcription or epithelium integrity. We present the first evidence that febrile temperatures associated with COVID-19 inhibit SARS-CoV-2 replication in respiratory epithelia. Our data identify an important role for tissue temperature in the epithelial restriction of SARS-CoV-2 independently of canonical interferon (IFN)-mediated antiviral immune defenses.


New Nutraceutical Combination Reduces Blood Pressure and Improves Exercise Capacity in Hypertensive Patients Via a Nitric Oxide-Dependent Mechanism.
Background High blood pressure (BP) has long been recognized as a major health threat and, particularly, a major risk factor for stroke, cardiovascular disease, and end-organ damage. However, the identification of a novel, alternative, integrative approach for the control of BP and cardiovascular protection is still needed. Methods and Results Sixty-nine uncontrolled hypertension patients, aged 40 to 68 years, on antihypertensive medication were enrolled in 2 double-blind studies. Forty-five were randomized to placebo or a new nutraceutical combination named AkP05, and BP, endothelial function, and circulating nitric oxide were assessed before and at the end of 4 weeks of treatment. Twenty-four patients were randomized to diuretic or AkP05 for 4 weeks and underwent a cardiopulmonary exercise test to evaluate the effects of AkP05 on functional capacity of the cardiovascular, pulmonary, and muscular systems. Vascular and molecular studies were undertaken on mice to characterize the action of the single compounds contained in the AkP05 nutraceutical combination. AkP05 supplementation reduced BP, improved endothelial function, and increased nitric oxide release; cardiopulmonary exercise test revealed that AkP05 increased maximum O2 uptake, stress tolerance, and maximal power output. In mice, AkP05 reduced BP and improved endothelial function, evoking increased nitric oxide release through the PKCα/Akt/endothelial nitric oxide synthase pathway and reducing reactive oxygen species production via NADPH-oxidase inhibition. These effects were mediated by synergism of the single compounds of AkP05. Conclusions This is the first study reporting positive effects of a nutraceutical combination on the vasculature and exercise tolerance in treated hypertensive patients. Our findings suggest that AkP05 may be used as an adjunct for the improvement of cardiovascular protection and to better control BP in uncontrolled hypertension.


T4 endonuclease VII. Importance of a histidine-aspartate cluster within the zinc-binding domain.
The DNA junction-resolving enzyme endonuclease VII of bacteriophage T4 contains a zinc-binding region toward the N-terminal end of the primary sequence. In the center of this 39-amino acid section (between residues 38 and 44) lies the sequence HLDHDHE, termed the His-acid cluster. Closely related sequences are found in three other proteins that have similar zinc-binding motifs. We have analyzed the function of these residues by a site-directed mutagenesis approach, modifying single amino acids and studying the properties of the resulting N-terminal protein A fusions. No sequence changes within the His-acid cluster led to a change in zinc content of the protein, indicating that these residues are not involved in the coordination of zinc. We found that the N-terminal aspartate residue (Asp-40) and the two histidine residues (His-41 and His-43) within the cluster are essential for junction-cleavage activity of the proteins. However, all sequence variations within this region generate proteins that retain their ability to bind to four-way DNA junctions (with minor changes in binding affinity in some cases) and to distort their global structure in the same manner as active enzymes. We conclude that the process of cleavage can be uncoupled from those of binding to and distortion of the junction. It is probable that some amino acid side chains of the His-acid cluster participate in the phosphodiester cleavage mechanism of endonuclease VII. The essential aspartate residue might be required for coordination of catalytic metal ions.


Twist: a new player in the epithelial-mesenchymal transition of the peritoneal mesothelial cells.
The peritoneal membrane is a vital structure for peritoneal dialysis (PD) patients. It has been increasingly recognized that the transition of the peritoneal lining mesothelial cells into a more fibroblastic phenotype is a key step in peritoneal membrane injury. Relevant literature was reviewed and summarized. Epithelial-to-mesenchymal transition (EMT) is a basic cellular process that occurs in a variety of physiologic and pathologic processes. The hallmark of this process is a loss of epithelial markers, and E-cadherin is a prototypical epithelial transmembrane protein. E-cadherin expression is suppressed at many levels and the gene is regulated by a family of transcription factors. Twist is one of the lesser studied E-cadherin regulatory factors, which belongs to a larger family of basic helix-loop-helix DNA-binding proteins. In this issue of Nephrology Dialysis Transplantation, Cuixiang Li reports on in vitro experiments where the expression of Twist led to a decreased expression of E-cadherin and the evidence of EMT. In an in vivo model of dialysate exposure, Li demonstrates that Twist expression is increased in the injured peritoneal tissues. These important observations are the first to link Twist to mesothelial cell EMT and peritoneal membrane injury. Like most novel observations, this paper leaves many questions unanswered. Twist is only one of several transcription factors involved in EMT and how these factors interact will require further investigations. Furthermore, the question of whether Twist interacts at multiple levels in the EMT process, or simply gives an initial push to the process, is left unanswered. Finally, to bring these early significant findings to the bedside as potential therapies for PD patients will require further innovation.


Analysis of the Usage Context of an mHealth Application for Equestrians.
One possibility to support veterinarians in times of a vet shortage is by providing animal owners with a technical decision support for deciding whether their animal needs to be seen by a vet. As the first step in the user-centered development of such an mHealth application for equestrians, an analysis of the context of use was done. The analysis was carried out by reviewing existing literature and conducting an online survey with 100 participants. Characteristics of the user group and the usage context are presented using an adaptation of the four layers of diversity. Many equestrians are lacking health-related knowledge and competencies as well as social networks supporting them in decision making and gaining further information. This may apply to owners of other animal species in broad ranges as well. The results of the analysis provide information to software developers and researchers on mHealth applications for pet owners in general and equestrians in particular to focus their work on the users' needs and therefore provide efficient results/software.


Comparative studies on the in vitro properties of phytases from various microbial origins.
The physical and chemical properties of six crude phytase preparations were compared. Four of these enzymes (Aspergillus A, Aspergillus R, Peniophora and Aspergillus T) were produced at commercial scale for the use as feed additives while the other two (E. coli and Bacillus) were produced at laboratory scale. The encoding genes of the enzymes were from different microbial origins (4 of fungal origin and 2 of bacterial origin, i.e., E. coli and Bacillus phytases). One of the fungal phytases (Aspergillus R) was expressed in transgenic rape. The enzymes were studied for their pH behaviour, temperature optimum and stability and resistance to protease inactivation. The phytases were found to exhibit different properties depending on source of the phytase gene and the production organism. The pH profiles of the enzymes showed that the fungal phytases had their pH optima ranging from 4.5 to 5.5. The bacterial E. coli phytase had also its pH optimum in the acidic range at pH 4.5 while the pH optimum for the Bacillus enzyme was identified at pH 7.0. Temperature optima were at 50 and 60 degrees C for the fungal and bacterial phytases, respectively. The Bacillus phytase was more thermostable in aqueous solutions than all other enzymes. In pelleting experiments performed at 60, 70 and 80 degrees C in the conditioner, Aspergillus A, Peniophora (measurement at pH 5.5) and E. coli phytases were more heat stable compared to other enzymes (Bacillus enzyme was not included). At a temperature of 70 degrees C in the conditioner, these enzymes maintained a residual activity of approximately 70% after pelleting compared to approximately 30% determined for the other enzymes. Incubation of enzyme preparations with porcine proteases revealed that only E. coli phytase was insensitive against pepsin and pancreatin. Incubation of the enzymes in digesta supernatants from various segments of the digestive tract of hens revealed that digesta from stomach inactivated the enzymes most efficiently except E. coli phytase which had a residual activity of 93% after 60 min incubation at 40 degrees C. It can be concluded that phytases of various microbial origins behave differently with respect to their in vitro properties which could be of importance for future developments of phytase preparations. Especially bacterial phytases contain properties like high temperature stability (Bacillus phytase) and high proteolytic stability (E. coli phytase) which make them favourable for future applications as feed additives.


Co-Electrospun Silk Fibroin and Gelatin Methacryloyl Sheet Seeded with Mesenchymal Stem Cells for Tendon Regeneration.
Silk fibroin (SF) is a promising biomaterial for tendon repair, but its relatively rigid mechanical properties and low cell affinity have limited its application in regenerative medicine. Meanwhile, gelatin-based polymers have advantages in cell attachment and tissue remodeling but have insufficient mechanical strength to regenerate tough tissue such as tendons. Taking these aspects into account, in this study, gelatin methacryloyl (GelMA) is combined with SF to create a mechanically strong and bioactive nanofibrous scaffold (SG). The mechanical properties of SG nanofibers can be flexibly modulated by varying the ratio of SF and GelMA. Compared to SF nanofibers, mesenchymal stem cells (MSCs) seeded on SG fibers with optimal composition (SG7) exhibit enhanced growth, proliferation, vascular endothelial growth factor production, and tenogenic gene expression behavior. Conditioned media from MSCs cultured on SG7 scaffolds can greatly promote the migration and proliferation of tenocytes. Histological analysis and tenogenesis-related immunofluorescence staining indicate SG7 scaffolds demonstrate enhanced in vivo tendon tissue regeneration compared to other groups. Therefore, rational combinations of SF and GelMA hybrid nanofibers may help to improve therapeutic outcomes and address the challenges of tissue-engineered scaffolds for tendon regeneration.


Detection of QTL for growth rate in the blacklip abalone (Haliotis rubra Leach) using selective DNA pooling.
The objective of this study was to identify QTL for growth rate in the blacklip abalone Haliotis rubra using selective DNA pooling. Three full-sibling families of H. rubra derived from crosses of wild broodstock were used. DNA was extracted from the largest and smallest 10% of progeny and combined into two pools for each phenotypic tail. The DNA pools were typed with 139 microsatellites, and markers showing significant differences between the peak height ratios of alleles inherited from the parents were individually genotyped and analysed by interval mapping. A strong correlation (r = 0.94, P < 0.001) was found between the t-values from the analysis of pools and the t-values from the analysis of individual genotypes. Based on the interval mapping analysis, QTL were detected on nine linkage groups at a chromosome-wide P < 0.01 and one linkage group at a chromosome-wide P < 0.05. The study demonstrated that selective DNA pooling is efficient and effective as a first-pass screen for the discovery of QTL in an aquaculture species.


Upregulation of Human Endogenous Retrovirus-K Is Linked to Immunity and Inflammation in Pulmonary Arterial Hypertension.
Immune dysregulation has been linked to occlusive vascular remodeling in pulmonary arterial hypertension (PAH) that is hereditary, idiopathic, or associated with other conditions. Circulating autoantibodies, lung perivascular lymphoid tissue, and elevated cytokines have been related to PAH pathogenesis but without a clear understanding of how these abnormalities are initiated, perpetuated, and connected in the progression of disease. We therefore set out to identify specific target antigens in PAH lung immune complexes as a starting point toward resolving these issues to better inform future application of immunomodulatory therapies. Lung immune complexes were isolated and PAH target antigens were identified by liquid chromatography tandem mass spectrometry, confirmed by enzyme-linked immunosorbent assay, and localized by confocal microscopy. One PAH antigen linked to immunity and inflammation was pursued and a link to PAH pathophysiology was investigated by next-generation sequencing, functional studies in cultured monocytes and endothelial cells, and hemodynamic and lung studies in a rat. SAM domain and HD domain-containing protein 1 (SAMHD1), an innate immune factor that suppresses HIV replication, was identified and confirmed as highly expressed in immune complexes from 16 hereditary and idiopathic PAH versus 12 control lungs. Elevated SAMHD1 was localized to endothelial cells, perivascular dendritic cells, and macrophages, and SAMHD1 antibodies were prevalent in tertiary lymphoid tissue. An unbiased screen using metagenomic sequencing related SAMHD1 to increased expression of human endogenous retrovirus K (HERV-K) in PAH versus control lungs (n=4). HERV-K envelope and deoxyuridine triphosphate nucleotidohydrolase mRNAs were elevated in PAH versus control lungs (n=10), and proteins were localized to macrophages. HERV-K deoxyuridine triphosphate nucleotidohydrolase induced SAMHD1 and proinflammatory cytokines (eg, interleukin 6, interleukin 1β, and tumor necrosis factor α) in circulating monocytes, pulmonary arterial endothelial cells, and also activated B cells. Vulnerability of pulmonary arterial endothelial cells (PAEC) to apoptosis was increased by HERV-K deoxyuridine triphosphate nucleotidohydrolase in an interleukin 6-independent manner. Furthermore, 3 weekly injections of HERV-K deoxyuridine triphosphate nucleotidohydrolase induced hemodynamic and vascular changes of pulmonary hypertension in rats (n=8) and elevated interleukin 6. Our study reveals that upregulation of the endogenous retrovirus HERV-K could both initiate and sustain activation of the immune system and cause vascular changes associated with PAH.


Sensory-Discriminative Three-Dimensional Body Pain Mobile App Measures Versus Traditional Pain Measurement With a Visual Analog Scale: Validation Study.
To quantify pain severity in patients and the efficacy treatments, researchers and clinicians apply tools such as the traditional visual analog scale (VAS) that leads to inaccurate interpretation of the main sensory pain. This study aimed to validate the pain measurements of a neuroscience-based 3D body pain mobile app called GeoPain. Patients with temporomandibular disorder (TMD) were assessed using GeoPain measures in comparison to VAS and positive and negative affect schedule (PANAS), pain and mood scales, respectively. Principal component analysis (PCA), scatter score analysis, Pearson methods, and effect size were used to determine the correlation between GeoPain and VAS measures. The PCA resulted in two main orthogonal components: first principal component (PC1) and second principal component (PC2). PC1 comprises a combination score of all GeoPain measures, which had a high internal consistency and clustered together in TMD pain. PC2 included VAS and PANAS. All loading coefficients for GeoPain measures in PC1 were above 0.70, with low loadings for VAS and PANAS. Meanwhile, PC2 was dominated by a VAS and PANAS coefficient >0.4. Repeated measure analysis revealed a strong correlation between the VAS and mood scores from PANAS over time, which might be related to the subjectivity of the VAS measure, whereas sensory-discriminative GeoPain measures, not VAS, demonstrated an association between chronicity and TMD pain in locations spread away from the most commonly reported area or pain epicenter (P=.01). Analysis using VAS did not detect an association at baseline between TMD and chronic pain. The long-term reliability (lag >1 day) was consistently high for the pain area and intensity number summation (PAINS) with lag autocorrelations averaging between 0.7 and 0.8, and greater than the autocorrelations for VAS averaging between 0.3 and 0.6. The combination of higher reliability for PAINS and its objectivity, displayed by the lack of association with PANAS as compared with VAS, indicated that PAINS has better sensitivity and reliability for measuring treatment effect over time for sensory-discriminative pain. The effect sizes for PAINS were larger than those for VAS, consequently requiring smaller sample sizes to assess the analgesic efficacy of treatment if PAINS was used versus VAS. The PAINS effect size was 0.51 SD for both facial sides and 0.60 SD for the right side versus 0.35 SD for VAS. Therefore, the sample size required to detect such effect sizes with 80% power would be n=125 per group for VAS, but as low as n=44 per group for PAINS, which is almost a third of the sample size needed by VAS. GeoPain demonstrates precision and reliability as a 3D mobile interface for measuring and analyzing sensory-discriminative aspects of subregional pain in terms of its severity and response to treatment, without being influenced by mood variations from patients.


Population genetic structure of Plasmopara viticola after 125 years of colonization in European vineyards.
SUMMARY To examine the within- and among-population genetic structure of Plamopara viticola oosporic populations in Europe, 8991 lesions from 32 vineyard plots were collected and analysed. Four multi-allelic microsatellite markers were used to genotype the pathogen. All populations had high levels of gene and genotypic diversity. Most populations were in Hardy-Weinberg equilibrium and thus randomly mating. Among P. viticola populations, significant low to moderate genetic differentiation was observed, even between geographically close populations. This genetic differentiation was also evident in the neighbour-joining phylogenetic genetic distance tree, showing clear substructure and distinguishing mainly five clusters based on geographical origin. Significant isolation by distance was found in central European P. viticola populations, suggesting a step-wise migration model. No significant isolation by distance was found within Greek populations, most probably owing to natural geographical barriers such as the sea and mountains, as well as the frequent population bottlenecks occurring in these populations, preventing natural migration among populations. The high variability of P. viticola provides explanation for its successful infestation of the heterogeneous European vineyards in the last 125 years after its introduction.


von Willebrand factor: an emerging target in stroke therapy.
Thrombus formation is of paramount importance in the pathophysiology of acute ischemic stroke. Current antithrombotics used to treat or prevent cerebral ischemia are only moderately effective or bear an increased risk of severe bleeding. von Willebrand factor (VWF) has long been known to be a key player in thrombus formation at sites of vascular damage. While the association between VWF and coronary heart disease has been well studied, knowledge about the role of VWF in stroke is much more limited. However, in recent years, an increasing amount of clinical and preclinical evidence has revealed the critical involvement of VWF in stroke development. This review summarizes the latest insights into the pathophysiologic role of VWF-related processes in ischemic brain injury under experimental conditions and in humans. Potential clinical merits of novel inhibitors of VWF-mediated platelet adhesion and activation as powerful and safe tools to combat thromboembolic disorders including ischemic stroke are discussed. Preclinical and clinical evidence illustrates an important role of VWF in ischemic stroke, suggesting that VWF could become a promising target in stroke therapy.


Pinch and grasp strength: standardization of terminology and protocol.
We implemented a tridirectional survey to begin the standardization process for grasp and pinch terminology and protocols for testing and to improve the communication between rehabilitation professionals who assess hand strength. We surveyed the literature, occupational therapy clinics across the country, and occupational therapy educational programs. Our results reveal the current use, teachings, and recommendations of pinch and grasp strength measurement. The results confirm that the standardization of grasp and pinch terminology and protocols for testing are vitally needed. Specific recommendations to continue this standardization process are recommended.


3D Multislice and Cone-beam Computed Tomography Systems for Dental Identification.
3D Multislice and Cone-beam computed tomography (CBCT) in forensic odontology has been shown to be useful not only in terms of one or a few of dead bodies but also in multiple fatality incidents. 3D Multislice and Cone-beam computed tomography and digital radiography were demonstrated in a forensic examination form. 3D images of the skull and teeth were analysed and validated for long ante mortem/post mortem intervals. The image acquisition was instantaneous; the images were able to be optically enlarged, measured, superimposed and compared prima vista or using special software and exported as a file. Digital radiology and computer tomography has been shown to be important both in common criminalistics practices and in multiple fatality incidents. Our study demonstrated that CBCT imaging offers less image artifacts, low image reconstruction times, mobility of the unit and considerably lower equipment cost.


Single coronary artery with probable origin of the anomalous right coronary artery from a left atrial recurrent branch.
A 62-year-old woman presented for evaluation of chest pain. She ruled out for myocardial infarction, and subsequent non-invasive studies were diagnostic for ischemia. On coronary angiography, she was found to have a previously undescribed variant of single coronary artery, in which the anomalous right coronary artery probably arose from a left atrial recurrent branch. In this patient, the congenital anomaly was an incidental finding, since her clinical presentation was felt to be due to moderate obstructive disease of the left anterior descending artery, in the setting of poorly controlled systemic hypertension.


Liposomes in immunology: the immune response against antigen-containing liposomes.
Three ways of antigen administration to rabbits were compared with respect to the resulting immune responses. Antigen was administered free in solution, entrapped in liposomes or free in solution but together with empty liposomes. Liposomal material showed adjuvant activity when injected together with free antigen, but a much stronger adjuvant effect was found when antigen was injected entrapped in liposomes.


Protection against feline leukemia by vaccination with a subunit vaccine.
An effective vaccine against feline leukemia virus infection has been developed by the collection and concentration of tissue culture medium harvested from a tumor cell line. Lymphoid cells were grown to near saturation density in a normal growth medium and then transferred to a serum-free medium. The serum-free medium was collected, concentrated, and evaluated for its vaccine potential. Cats receiving the vaccine emulsified in complete Freund adjuvant developed high antiviral and antitumor titers and were protected (81%) against virus challenge. Cats receiving the vaccine without an adjuvant developed lower antibody levels and lower protection (53%) from viremia. Age-matched and litter-matched controls developed no antibody to test antigens before the challenge, and 100% became persistently viremic after the challenge. Vaccination with the soluble tumor cell antigen vaccine proved successful in preventing the induction of feline leukemia virus infection.


Defining a "Good Death" in the Pediatric Intensive Care Unit.
Societal attitudes about end-of-life events are at odds with how, where, and when children die. In addition, parents' ideas about what constitutes a "good death" in a pediatric intensive care unit vary widely. To synthesize parents' perspectives on end-of-life care in the pediatric intensive care unit in order to define the characteristics of a good death in this setting from the perspectives of parents. A concept analysis was conducted of parents' views of a good death in the pediatric intensive care unit. Empirical studies of parents who had experienced their child's death in the inpatient setting were identified through database searches. The concept analysis allowed the definition of antecedents, attributes, and consequences of a good death. Empirical referents and exemplar cases of care of a dying child in the pediatric intensive care unit serve to further operationalize the concept. Conceptual knowledge of what constitutes a good death from a parent's perspective may allow pediatric nurses to care for dying children in a way that promotes parents' coping with bereavement and continued bonds and memories of the deceased child. The proposed conceptual model synthesizes characteristics of a good death into actionable attributes to guide bedside nursing care of the dying child.


Clinician Ethical Perspectives on Extracorporeal Membrane Oxygenation in Practice.
Extracorporeal membrane oxygenation (ECMO) is an expensive and scarce life sustaining treatment provided to certain critically ill patients. Little is known about the informed consent process for ECMO or clinician viewpoints on ethical complexities related to ECMO in practice. We sent a cross-sectional survey to all departments providing ECMO within 7 United States hospitals in January 2021. One clinician from each department completed the 42-item survey representing their department. Fourteen departments within 7 hospitals responded (response rate 78%, N = 14/18). The mean time spent consenting patients or surrogate decision-makers for ECMO varied, from 7.5 minutes (95% CI 5-10) for unstable patients to 20 minutes (95% CI 15-30) for stable patients (p = 0.0001). Few clinician respondents (29%) report patients or surrogate decision-makers always possess informed consent for ECMO. Most departments (92%) have absolute exclusion criteria for ECMO such as older age (43%, cutoffs ranging from 60-75 years), active malignancy (36%), and elevated body mass index (29%). A significant minority of departments (29%) do not always offer the option to withdraw ECMO to patients or surrogate decision-makers. For patients who cannot be liberated from ECMO and are ineligible for heart or lung transplant, 36% of departments would recommend the patient be removed from ECMO and 64% would continue ECMO support. Adequate informed consent for ECMO is a major ethical challenge, and the content of these discussions varies. Use of categorical exclusion criteria and withdrawal of ECMO if a patient cannot be liberated from it differ among departments and institutions.


High Vitamin D-Binding Protein Concentration, Low Albumin, and Mode of Remission Predict Relapse in Crohn's Disease.
Vitamin D (25(OH)D) deficiency occurs in active Crohn's disease (CD) and may be secondary to reduced sunlight exposure and oral intake. Vitamin D-binding protein (VDBP) levels, however, fluctuate less with season and sunlight. The aim, therefore, was to examine patients with CD in remission and determine any associations between VDBP, serum 25(OH)D, and the calculated free 25(OH)D concentrations with the risk of disease flare. Subjects were identified from prospectively maintained inflammatory bowel disease databases at 3 teaching hospitals in Australia. Patients were in steroid-free clinical remission at the time of blood draw and were followed for at least 12 months. Total and epimer-25(OH)D3, VDBP concentrations, and genotypes were determined. A total of 309 patients with CD (46% men) met the inclusion criteria. A disease flare occurred in 100 (32.4%). Serum 25(OH)D3 was deficient (<50 nmol/L) in 36 (12%) and insufficient (50-75 nmol/L) in 107 (35%) patients. Total, free, and epimer-25(OH)D3 serum levels did not predict disease flare. Higher VDBP concentrations, however, significantly correlated with increased risk of disease flare (hazard ratio 1.2, 95% CI, 1.0-1.5). On multivariate analysis, VDBP concentration, low albumin, and medication-induced remission were significantly more associated with disease flare. VDBP genotypes were significantly associated with 25(OH)D and VDBP concentrations but not disease flare. Vitamin D deficiency was uncommon in our patients with CD in remission, and serum 25(OH)D3 did not predict disease flare, whereas higher VDBP concentrations were significantly associated with disease flare. Further investigations to explore the possible mechanisms for this association are warranted.


Honokiol inhibits migration of renal cell carcinoma through activation of RhoA/ROCK/MLC signaling pathway.
Honokiol, a biologically active compound isolated from Magnolia bark, has been shown to possess promising anticancer effect through induction of apoptosis. However, there is a relative lack of information regarding its anti‑metastatic activity. Renal cell carcinoma (RCC) is the most common malignancy of the adult kidney and is known for high risk of metastasis. Clinically, therapeutic methods for metastatic RCC cases are limited and efforts to exploit new treatments are still ongoing. The results of our current investigation first revealed that honokiol suppressed the proliferation of different human RCCs without affecting cell viability. In addition, honokiol inhibited migration of highly metastatic RCC 786‑0 cells and stimulated the activity of small GTPase, RhoA. Furthermore, phosphorylated myosin light chain (MLC) and excessive formation of actin stress fibers were identified in 786‑0 cells treated with honokiol. Interestingly, the pharmacological Rho‑associated protein kinase (ROCK) inhibitor Y‑27632 attenuated contraction of actin stress fibers induced by honokiol and abrogated honokiol‑mediated inhibition of cell migration. Together these important findings suggest that honokiol suppresses the migration of highly metastatic RCC through activation of RhoA/ROCK/MLC signaling and warrants attention in the treatment of RCC metastasis as a novel therapeutic approach.


Air-pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells.
Ambient air pollution is associated with increased cardiovascular morbidity and mortality. We have found that exposure to ambient ultrafine particulate matter, highly enriched in redox cycling organic chemicals, promotes atherosclerosis in mice. We hypothesize that these pro-oxidative chemicals could synergize with oxidized lipid components generated in low-density lipoprotein particles to enhance vascular inflammation and atherosclerosis. We have used human microvascular endothelial cells (HMEC) to study the combined effects of a model air pollutant, diesel exhaust particles (DEP), and oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (ox-PAPC) on genome-wide gene expression. We treated the cells in triplicate wells with an organic DEP extract, ox-PAPC at various concentrations, or combinations of both for 4 hours. Gene-expression profiling showed that both the DEP extract and ox-PAPC co-regulated a large number of genes. Using network analysis to identify coexpressed gene modules, we found three modules that were most highly enriched in genes that were differentially regulated by the stimuli. These modules were also enriched in synergistically co-regulated genes and pathways relevant to vascular inflammation. We validated this synergy in vivo by demonstrating that hypercholesterolemic mice exposed to ambient ultrafine particles exhibited significant upregulation of the module genes in the liver. Diesel exhaust particles and oxidized phospholipids synergistically affect the expression profile of several gene modules that correspond to pathways relevant to vascular inflammatory processes such as atherosclerosis.


Interrogation of side chain biases for oligomannose recognition by antibody 2G12 via structure-guided phage display libraries.
Monoclonal antibodies (mAbs) are essential reagents for deciphering gene or protein function and have been a fruitful source of therapeutic and diagnostic agents. However, developing anticarbohydrate antibodies to target glycans for those purposes has been less successful because the molecular basis for glycan-mAb interactions is poorly understood relative to protein- or peptide-binding mAbs. Here, we report our investigation on glycan-mAb interactions by using the unique architectural scaffold of 2G12, an antibody that targets oligomannoses on the HIV-1 glycoprotein gp120, as the template for engineering highly specific mAbs to target glycans. We first analyzed 24 different X-ray structures of antiglycan mAbs from the Protein Data Bank to determine side chain amino acid distributions in of glycan-mAb interactions. We identified Tyr, Arg, Asn, Ser, Asp, and His as the six most prevalent residues in the glycan-mAb contacts. We then utilized this information to construct two phage display libraries ("Lib1" and "Lib2") in which positions on the heavy chain variable domains of 2G12 were allowed to vary in restricted manner among Tyr, Asp, Ser, His, Asn, Thr, Ala and Pro to interrogate the minimal physicochemical requirements for oligomannose recognition. We analyzed the sequences of 39 variants from Lib1 and 14 variants from Lib2 following selection against gp120, the results showed that there is a high degree of malleability within the 2G12 for glycan recognitions. We further characterized five unique phage clones from both libraries that exhibited a gp120-specific binding profile. Expression of two of these variants as soluble mAbs indicated that, while specificity of gp120-binding was retained, the affinity of these mutants was significantly reduced relative to WT 2G12. Nonetheless, the results indicate these is some malleability in the identity of contact residues and provide a novel insight into the nature of glycan-antibody interactions and how they may differ from protein-antibody binding interactions.


The haemagglutinating activity of Berne virus.
Berne virus possesses haemagglutinating activity which is inhibited by antisera that neutralize the infectivity of the virus. In decreasing order, human, rabbit and guinea-pig erythrocytes were agglutinated whereas agglutination was not observed with rat, goose, chicken or horse red blood cells. This pattern is different from that seen with the closely related Breda virus of cattle. Haemagglutinin was found to co-sediment with viral infectivity in sucrose density gradients. Transmission electron microscopy showed that intact virus particles form bridges between adjacent erythrocytes. The viral envelope was seen at a distance from the erythrocyte surface suggesting that the peplomers possess haemagglutinating activity. Haemagglutination was decreased in the presence of fetuin and gangliosides and also by pretreatment of the erythrocytes with periodate, suggesting that the virus binds to glycoproteins and/or glycolipids on the erythrocyte surface.


Alchembed: A Computational Method for Incorporating Multiple Proteins into Complex Lipid Geometries.
A necessary step prior to starting any membrane protein computer simulation is the creation of a well-packed configuration of protein(s) and lipids. Here, we demonstrate a method, alchembed, that can simultaneously and rapidly embed multiple proteins into arrangements of lipids described using either atomistic or coarse-grained force fields. During a short simulation, the interactions between the protein(s) and lipids are gradually switched on using a soft-core van der Waals potential. We validate the method on a range of membrane proteins and determine the optimal soft-core parameters required to insert membrane proteins. Since all of the major biomolecular codes include soft-core van der Waals potentials, no additional code is required to apply this method. A tutorial is included in the Supporting Information.


The agar-replica technique for dental caries diagnosis. Has its time arrived?
The agar-replica technique of Bahn et al is described. This caries-diagnostic technique detects the site of lactobacillus infection on the teeth. Evidence and logic indicate that this technique is more accurate than current caries-diagnostic methods. The method appears to answer the recent call for diagnostic methods which identify the more subtle expression of the disease, and it helps classify lesions into categories keyed to different treatment strategies.


Intersession variability in single-breath diffusing capacity in diabetics without overt lung disease.
American Thoracic Society guidelines state that a 10% or greater intersession change in diffusing capacity of the lung (DL(CO)) should be considered clinically significant. However, little is known about the short-term intersession variability in DL(CO) in untrained subjects or how variability is affected by rigorous external quality control. To characterize the intersession variability of DL(CO) and the effect of different quality control methods in untrained individuals without significant lung disease. Data were pooled from the comparator arms of 14 preregistration trials of inhaled insulin that included nonsmoking diabetic patients without significant lung disease. A total of 699 participants performed repeated DL(CO) measurements using a highly standardized technique. A total of 948 participants performed repeated measurements using routine clinical testing. The mean intersession absolute change in DL(CO) using the highly standardized method was 1.45 ml/minute/mm Hg (5.64%) compared with 2.49 ml/minute/mm Hg (9.52%) in the routine testing group (P < 0.0001 for both absolute and percent difference). The variability in absolute intersession change in DL(CO) increased with increasing baseline DL(CO) values, whereas the absolute percentage of intersession change was stable across baseline values. Depending on the method, 15.5 to 35.5% of participants had an intersession change of 10% or greater. A 20% or greater threshold would reduce this percentage of patients to 1 to 10%. Intersession variability in DL(CO) measurement is dependent on the method of testing used and baseline DL(CO). Using a more liberal threshold to define meaningful intersession change may reduce the misclassification of normal variation as abnormal change.


[Benefits of physical activity and harms of inactivity].
Epidemiological research has consistently shown that physical activity decreases the risk of coronary heart disease, hypertension and stroke. The finding that a low level of physical activity is a major determinant of the growing epidemics of obesity is also firm and consistent. The direct association existing between a sedentary lifestyle and the incidence of diabetes mellitus is solid and of great importance for public health. Additional benefits from a a physically active lifestyle are a reduction in the incidence and prevalence of osteoporosis, lower risk of falls and fractures in the elderly, and a lower risk of anxiety and depression. Although evidence is less consistent, low levels of physical activity have been related to a higher risk of colon, breast and lung cancer. Some preliminary evidence relates physical activity with a lower risk of dementia. During the last three decades a huge amount of epidemiological research has led to uniform conclusions about the benefits of a physically active lifestyle. In spite of this fact, the prevalence of sedentary lifestyles is rising. Therefore, health promotion interventions are urgently needed to reach the objective of engaging in regular and moderate physical activity for at least 30 minutes per day in most, preferably all, days of the week.


Management of posterior fossa dissecting aneurysms.
Treatment and prognosis of 14 patients of posterior fossa arterial dissections (AD) and dissecting aneurysms (DA) in one institution was reviewed. Internal trapping of aneurysm was performed for six patients presenting with SAH (three Vertebral, one posterior cerebral, one posterior inferior cerebellar, one anterior inferior cerebellar DA). The patency of the parent arteries was preserved in four DA patients with SAH (two Vertebral, two Basilar DA), 1 incidental vertebral DA, and one DA patient with brainstem infarction using stents and coils (four patients) or coils only (two patient). Proximal occlusion of parent artery was performed in a vertebral DA with SAH. One patient with a superior cerebellar DA presented with a midbrain infarct developed SAH with spontaneous occlusion of the aneurysm two weeks later. Of the 14 cases, ten were angiographically stable or cured during a follow up period of four to 70 months. one spontaneously resolved and two recurred. There was one death.


Bladder dysfunction in peripheral neuropathies.
Normal bladder function depends on the complex interaction of sensory and motor pathways. Bladder dysfunction can develop as a result of several neurological conditions. It can happen in a number of ways, including diabetic cystopathy, detrusor overactivity, bladder outlet obstruction, and urge and stress urinary incontinence. Diabetic neuropathy is the most common cause of peripheral neuropathy-associated bladder dysfunction. Guillain-Barré syndrome (GBS), human immunodeficiency virus (HIV)-associated neuropathy, chronic inflammatory demyelinating polyneuropathy (CIDP), and amyloid neuropathy are other major causes. The diagnosis of bladder dysfunction should be established by the history of neurological symptoms, neurological examination, and urological evaluation. Functional evaluation of the lower urinary tract includes cystometry, sphincter electromyography, uroflowmetry, and urethral pressure profilometry. Management of urinary symptoms in patients with bladder dysfunction is usually supportive. In some cases, alpha-blocker and/or anti-muscarinic agents are needed to help improve urinary dysfunction. Intermittent self-catheterization is needed occasionally for patients with slow and/or poor recovery.


Improved magnetic resonance myelography of the lumbar spine using image fusion and volumetry.
The goal of this study was to investigate the usefulness and diagnostic potential of an improved MR myelography approach using a dedicated, heavily T2-weighted, 3D MRI sequence in combination with image fusion. A further aim was to compare dural areas and volumes of normal and pathological altered lumbar spine levels, and accuracy in the assessment of the stenoses, with those obtained by postmyelographic CT. Fifty patients underwent myelography, postmyelographic CT, and the improved MR myelography approach using a dedicated, heavily T2-weighted, 3D MRI sequence and image fusion. Dural cross-sectional areas and volumes for normal lumbar levels and levels with stenosis were calculated for postmyelographic CT and MR myelography data. The significant differences and Pearson correlations between dural cross-sectional areas and volumes from L1-2 to L5-S1 of postmyelographic CT and MR myelography were analyzed. The 99% CIs for normal and stenotic levels in patients with claudication distances less than 100 meters were calculated. For both dural areas and volumes in normal lumbar levels, the authors found no significant differences and strong correlations between postmyelographic CT and MR myelography. For the lower lumbar levels (L4-5 and L5-S1) they found significantly larger dural areas on MR myelography compared with postmyelographic CT, but not for the upper levels (L2-3 and L3-4). Dural volume analysis revealed significantly larger volumes for MR myelography at all 4 lumbar levels with stenoses in the cohort (L2-3 to L5-S1). Complete separation with no overlap was found between the 99% CIs for normal levels and stenotic levels. Differences in dural areas and volumes in this study may have been caused by the fact that in the case of a severely compressed thecal sac, the viscosity of the intrathecally applied contrast agent is too high in the framework of myelography. The gravitationally dependent component is thus too low to achieve sufficient fluid contrast. An optimized MR myelography approach-a dedicated 3D MR myelography sequence with high spatial resolution in combination with image fusion-is required to achieve a more reliable diagnosis of lumbar spine stenoses, especially with severe compression, compared with postmyelographic CT. This MR myelography approach may be helpful in preventing overestimation of lumbar spine stenoses. The upper limits of 99% CIs for stenotic levels can be interpreted as an indication for surgical treatment. However, further studies that include postoperative outcomes are required.


An evaluation of the utility of performing body fluid counts on the coulter LH 750.
Performing a manual body fluid count is a tedious, time-consuming, and frequently imprecise process for any clinical laboratory. The ability to perform many of these counts with an automated hematology analyzer has the real potential of making a major impact on laboratory precision and productivity. The manual chamber count is fraught with many variables and is often very technologist/technique dependent, often leading to inaccuracies in test results. Our laboratory undertook a series of studies designed to evaluate the capability of the Coulter LH 750 hematology analyzer to supplement our current manual method in the performance of body fluid analysis. First, we established the performance of our current manual counting method, the gold standard against which LH 750 performance would be judged. We looked at the precision of manual cell counting by having 4 technologists perform manual counts on each of 35 spinal, synovial, peritoneal, and other fluids with white blood cell (WBC) and/or red blood cell (RBC) counts of greater than 0.3 x 10(9) /L and 0.03 x 10(12) /L, respectively. Our results support earlier reports that the variability in counts among technologists using the manual chamber cell count methods is often very significant. After each sample was manually counted, it was analyzed on the Coulter LH 750, and the results were compared with those of our current manual method. Results showed good correlation between the manual and LH 750 methods. Next, we conducted a series of separate tests to evaluate the stability of different cellular elements (WBCs and RBCs) in each of these body fluid types. The study consisted of 2 sets of 4--3-mL samples of each fluid type--which were analyzed on the LH 750 immediately on receipt and after 1 hour, 4 hours, 8 hours, 16 hours, and 24 hours. The findings suggested varying degrees of stability that were dependent on fluid type and initial cell concentration. Finally, we looked at whether it is necessary to perform background counts before analyzing each body fluid sample and the impact of automating body fluid counts on our workload.


Scleral buckling with soft silicone sponge and lamellar scleral dissection.
One hundred cases of primary, nontraumatic, rhegmatogenous retinal separation were operated upon using 1/2 thickness 7.5 mp Silastic silicone sponge as a circumferential implant without an encircling element or suture tension. The use of this method has given 100% successful anatomical reattachment of the retina after a follow-up of 8 months to 3 1/2 years.


Pharmacokinetics in patients with renal failure.
Uremic patients manifest delayed elimination of many drugs prolonging the biological half-life, and impaired excretion of the metabolites of biotransformed drugs, some of which are toxic or biologically active. More subtle changes in bioavailability, distribution, metabolism and pharmacodynamics frequently occur, as well, rendering drug dosing hazardous, especially when the margin of safety is narrow. A review of the pharmacologic abnormalities of individual drugs exemplifies those that provide metabolic loads, those which can be eliminated by dialysis and those that can be used with the least risk. Restricting drugs use in uremic patients to unequivocal indications, limiting doses according to guidelines, restricting the duration of treatment, monitoring plasma drug levels, clinical observations and vigilant suspicion of toxicity would eliminate most toxicologic problems. Physicians must not, however, rely blindly on normograms and cookbook guidelines for dosing potentially toxic drugs.


Is there possibility of vertical transmission of COVID-19: a systematic review.
In order to investigate the clinical features of pregnant women and their neonates with coronavirus disease 2019 (COVID-19) and the evidence of vertical transmission of COVID-19, we retrieved studies included in PubMed, Medline and Chinese databases from January 1, 2000 to October 25, 2020 using relevant terms, such as 'COVID-19', 'vertical transmission' et al. in 'Title/Abstract'. Case reports and case series were included according to the inclusion and exclusion criteria. We conducted literature screening and data extraction, and performed literature bias risk assessment. Total of 13 case series and 16 case reports were collected, including a total of 564 pregnant women with COVID-19 and their 555 neonates, of which 549 neonates received nucleic acid test for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 18 neonates was diagnosed with COVID-19. The positive rate is 3.28%. Amniotic fluid of one woman was tested positive for SARS-CoV-2. The majority of infected neonates were born under strict infection control and received isolation and artificial feeding. Up till now, there is no sufficient evidence to exclude the possibility of vertical transmission for COVID-19 based on the current available data.


Emergency department record keeping and the potential for injury surveillance.
Successful design of injury prevention measures relies on understanding the occurrence and circumstances of injuries, which, in turn, necessitates that good quality data be collected about injured persons. The emergency department (ED) is an important source of injury information. This paper reports the results of a survey of all 129 hospital emergency departments in North Carolina to examine record-keeping practices and determine what information is collected and stored in the EDs. The findings demonstrate that there is considerable variability in the types of data that would be available to a researcher attempting to use ED records. Of special note is the absence of information about the external cause of injury.