A comparison between interrupted and continuous suturing techniques in keratoplasty.
A comparison between continuous and interrupted techniques of suturing in penetrating keratoplasties was made using autologous grafts in rabbits. Wound strength was determined using both a tensiometer and blow-out pressure measurements. Histologic examination of the wounds was also carried out, and clinical observations were made of the behavior of vascular growth through the wound in prevascularized corneas to further characterize the suturing techniques and the healing process. We found no difference in blow-out pressures between the two groups, but a significant increase in healing in the interrupted suture group, as measured by the tensiometer, was observed. Other differences were noted in the clinical course and histology, including a greater ease of vessels traversing the wound and more inflammatory cells in the wound area with interrupted sutures.


Current Concepts in the Management of Periodontitis.
Periodontitis is a common disorder affecting >40% of adults in the United States. Globally, the severe form of the disease has a prevalence of 11%. In advanced cases, periodontitis leads to tooth loss and reduced quality of life. The aetiology of periodontitis is multifactorial. Subgingival dental biofilm elicits a host inflammatory and immune response, ultimately leading to irreversible destruction of the periodontium (i.e. alveolar bone and periodontal ligament) in a susceptible host. In order to successfully manage periodontitis, dental professionals must understand the pathogenesis, primary aetiology, risk factors, contributing factors and treatment protocols. Careful diagnosis, elimination of the causes and reduction of modifiable risk factors are paramount for successful prevention and treatment of periodontitis. Initial non-surgical periodontal therapy primarily consists of home care review and scaling and root planing. For residual sites with active periodontitis at periodontal re-evaluation, a contemporary regenerative or traditional resective surgical therapy can be utilised. Thereafter, periodontal maintenance therapy at a regular interval and long-term follow-ups are also crucial to the success of the treatment and long-term retention of teeth. The aim of this review is to provide current concepts of diagnosis, prevention and treatment of periodontitis. Both clinical and biological rationales will be discussed.


Treatment of acute hypertension in patients with intracerebral hemorrhage using American Heart Association guidelines.
To determine the feasibility and safety of treatment of acute hypertension in patients with intracerebral hemorrhage within 24 hrs of symptom onset. Elevated blood pressure, observed in up to 56% of patients with intracerebral hemorrhage, may predispose to hematoma expansion; on the other hand, reduction of blood pressure may reduce hematoma expansion and subsequent death and disability. Single-center prospective registry supplemented by retrospective chart review. University-affiliated medical center with dedicated stroke service. All patients admitted to the stroke service with spontaneous intracerebral hemorrhage and acute hypertension within 24 hrs of symptom onset. Patients were treated with intravenous nicardipine within 24 hrs of symptom onset to reduce and maintain mean arterial pressure of <130 mm Hg. The mean arterial pressure goal was consistent with the American Heart Association guidelines. The primary outcome was the tolerability of the treatment as assessed by achieving and maintaining the mean arterial pressure goals for 24 hrs after initiation of intravenous nicardipine infusion. Other end points ascertained were: neurologic deterioration defined by a decline in Glasgow Coma Scale from pretreatment assessment by >or=2 points or increase in National Institutes of Health Stroke Scale score by >or=2 points and hemorrhage growth defined as an increase in the volume of intraparenchymal hemorrhage of >33% as measured by image analysis on the 24-hr computed tomographic scan compared with the baseline computed tomographic scan. Rates of favorable outcome and death were ascertained at 1 month. Of the total 46 patients admitted with intracerebral hemorrhage in our service, 29 patients were treated. Mean age of the treated patients was 58 +/- 13 yrs; ten were women. Initial National Institutes of Health Stroke Scale ranged from 1 to 38. The primary outcome of tolerability was achieved in 25 of the 29 patients (86%). Neurologic deterioration was observed in 4 of 29 patients. Hematoma enlargement was observed in five patients. Favorable outcome (defined as modified Rankin scale of <or=2) and death at 1-month was observed in 11 (38%) and 9 (31%) of the 29 patients, respectively. We observed a high rate of tolerability among patients with intracerebral hemorrhage who were treated with intravenous nicardipine using mean arterial pressure goals defined by American Heart Association guidelines within 24 hrs of symptom onset.


Design, expression, and immunogenicity of a soluble HIV trimeric envelope fragment adopting a prefusion gp41 configuration.
The human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (Env) is comprised of non-covalently associated gp120/gp41 subunits that form trimeric spikes on the virion surface. Upon binding to host cells, Env undergoes a series of structural transitions, leading to gp41 rearrangement necessary for fusion of viral and host membranes. Until now, the prefusion state of gp41 ectodomain (e-gp41) has eluded molecular and structural analysis, and thus assessment of the potential of such an e-gp41 conformer to elicit neutralizing antibodies has not been possible. Considering the importance of gp120 amino (C1) and carboxyl (C5) segments in the association with e-gp41, we hypothesize that these regions are sufficient to maintain e-gp41 in a prefusion state. Based on the available gp120 atomic structure, we designed several truncated gp140 variants by including the C1 and C5 regions of gp120 in a gp41 ectodomain fragment. After iterative cycles of protein design, expression and characterization, we obtained a variant truncated at Lys(665) that stably folds as an elongated trimer under physiologic conditions. Several independent biochemical/biophysical analyses strongly suggest that this mini-Env adopts a prefusion e-gp41 configuration that is strikingly distinct from the postfusion trimer-of-hairpin structure. Interestingly, this prefusion mini-Env, lacking the fragment containing the 2F5/4E10 neutralizing monoclonal antibody binding sites, displays no detectable HIV-neutralizing epitopes when employed as an immunogen in rabbits. The result of this immunogenicity study has important implications for HIV-1 vaccine design efforts. Moreover, this engineered mini-Env protein should facilitate three-dimensional structural studies of the prefusion e-gp41 and serve to guide future attempts at pharmacologic and immunologic intervention of HIV-1.


Comparison of chlorpromazine, haloperidol and pimozide in the treatment of phencyclidine psychosis: DA-2 receptor specificity.
Three neuroleptics were used to treat phencyclidine (PCP) psychosis. These included chlorpromazine, a DA-1 and DA-2 dopamine antagonist with noradrenergic effects; haloperidol, a predominantly DA-2 antagonist with noradrenergic effects; and pimozide a predominantly DA-2 antagonist with no noradrenergic activity. Three cohorts of randomly selected young white adult males were studied. Responses to haloperidol and pimozide were statistically equivalent and both were significantly superior to chlorpromazine. These results further support the role of the DA-2 receptor in PCP psychosis and tend to rule out a noradrenergic role. The authors therefore suggest that DA-2 blockers, such as haloperidol or pimozide be employed as treatment of choice in PCP psychosis.


Large influence of cholesterol on solute partitioning into lipid membranes.
Cholesterol plays an important role in maintaining the correct fluidity and rigidity of the plasma membrane of all animal cells, and hence, it is present in concentrations ranging from 20 to 50 mol %. Whereas the effect of cholesterol on such mechanical properties has been studied exhaustively over the last decades, the structural basis for cholesterol effects on membrane permeability is still unclear. Here we apply systematic molecular dynamics simulations to study the partitioning of solutes between water and membranes. We derive potentials of mean force for six different solutes permeating across 20 different lipid membranes containing one out of four types of phospholipids plus a cholesterol content varying from 0 to 50 mol %. Surprisingly, cholesterol decreases solute partitioning into the lipid tail region of the membranes much more strongly than expected from experiments on macroscopic membranes, suggesting that a laterally inhomogeneous cholesterol concentration and permeability may be required to explain experimental findings. The simulations indicate that the cost of breaking van der Waals interactions between the lipid tails of cholesterol-containing membranes account for the reduced partitioning rather than the surface area per phospholipid, which has been frequently suggested as a determinant for solute partitioning. The simulations further show that the partitioning is more sensitive to cholesterol (i) for larger solutes, (ii) in membranes with saturated as compared to membranes with unsaturated lipid tails, and (iii) in membranes with smaller lipid head groups.


Mouse hepatitis virus stem-loop 4 functions as a spacer element required to drive subgenomic RNA synthesis.
The 5' 140 nucleotides of the mouse hepatitis virus (MHV) 5' untranslated region (5'UTR) are predicted to contain three secondary structures, stem-loop 1 (SL1), SL2, and SL4. SL1 and SL2 are required for subgenomic RNA synthesis. The current study focuses on SL4, which contains two base-paired regions, SL4a and SL4b. A series of reverse genetic experiments show that SL4a is not required to be base paired. Neither the structure, the sequence, nor the putative 8-amino-acid open reading frame (ORF) in SL4b is required for viral replication. Viruses containing separate deletions of SL4a and SL4b are viable. However, deletion of SL4 is lethal, and genomes carrying this deletion are defective in directing subgenomic RNA synthesis. Deletion of (131)ACA(133) just 3' to SL4 has a profound impact on viral replication. Viruses carrying the (131)ACA(133) deletion were heterogeneous in plaque size. We isolated three viruses with second-site mutations in the 5'UTR which compensated for decreased plaque sizes, delayed growth kinetics, and lower titers associated with the (131)ACA(133) deletion. The second-site mutations are predicted to change either the spacing between SL1 and SL2 or that between SL2 and SL4 or to destabilize the proximal portion of SL4a in our model. A mutant constructed by replacing SL4 with a shorter sequence-unrelated stem-loop was viable. These results suggest that the proposed SL4 in the MHV 5'UTR functions in part as a spacer element that orients SL1, SL2, and the transcriptional regulatory sequence (TRS), and this spacer function may play an important role in directing subgenomic RNA synthesis.


Grazing angle Mach-Zehnder interferometer using reflective phase gratings and a polychromatic, un-collimated light source.
Normal incidence Talbot-Lau interferometers in x-ray applications have the drawbacks of low fringe visibility with polychromatic sources when the wave propagation distance is increased to achieve higher phase sensitivity, and when fabrication limits the attainable grating density. In contrast, reflective gratings illuminated at grazing angles have dramatically higher effective densities than their physical values. However, new designs are needed for far field interferometers using grazing angle geometry with incoherent light sources. We show that, with the appropriate design and choice of reflective phase gratings, there exist pairs of interfering pathways of exactly equal lengths independent of the incoming beam's incidence angle and wavelength. With a visible light grazing angle Mach-Zehnder interferometer, we show the conditions for achieving near ideal fringe visibility and demonstrate both absolute and differential phase-contrast imaging. We also describe the design parameters of an x-ray interferometer and key factors for its implementation.


Evaluation of optimal conditions for anionic surfactant removal in wastewater.
This study was conducted to find the optimal conditions for removing anionic surfactants in wastewater using the coagulant-flocculant method. Optimal conditions must be found to minimize the amount of metal materials that can cause secondary contamination and to improve performance. Five parameters were selected to investigate their influence on surfactant removal. The ranges of the independent variables were 0.5-5% for coagulant concentration, 0.1-1% for flocculant concentration, and 20-650 mg/L for surfactant concentration; the coagulant type was FeCl3·6H2O or Ca(OH)2; and the pH ranged from 2 to 10. The experimental results were analyzed with Minitab 19.1 to find the optimal conditions to maximize the removal rate of surfactant. In this study, a total of 20 experiments were carried out using a half fractional factorial design (FFD) including two center points with a resolution of 5 and a pseudo-center point. The results demonstrated that coagulant concentration, flocculant concentration, and pH were significant independent variables with respect to surfactant removal. The fitted regression equation confirmed that the surfactant removal rate was maximized when the coagulant concentration was 5%, the flocculant concentration was 0.1%, and the pH was 10.


[Characteristics of beta 2-adrenergic regulation of gastric secretion, hemostasis and cardiac rhythm in patients with duodenal ulcer and a history of hemorrhagic complications (effect of alupent)].
The effect of intravenous infusion of alupent (0.1 microgram/kg/min for 1 h) on the main parameters of gastric secretion, thromboelastogram, electrocoagulogram, ADP-induced platelet aggregation, the kinetics of fibrinolysis and vegetative regulation of the cardiac rhythm was studied in 59 subjects (10 healthy males, 23 patients suffering from peptic ulcer of the duodenum with a history of hemorrhages, 26 patients with uncomplicated duodenal ulcer). In healthy subjects and in patients with uncomplicated ulcer, the beta 2-adrenoagonist caused an increase in the volume of basal secretion, production of acid and pepsin, acceleration of blood coagulation, and fibrinolysis activation. At the same time in 2/3 of patients with a history of hemorrhages due to duodenal ulcer alupent inhibited gastric secretion of acid and pepsin and, along with stimulation of plasmic factors of coagulation, inhibited activated fibrinolysis. Vegetative dysfunction in patients with uncomplicated ulcer was marked by the predominance of the parasympathetic regulation of the cardiac rhythm, whereas in patients with a history of hemorrhages by sympatheticotonia. These features of beta 2-adrenergic regulation can be used for predicting hemorrhages and development of pathogenetically validated treatment methods.


A scoping study of pulmonary paracoccidioidomycosis: severity classification based on radiographic and tomographic evaluation.
The lungs have great importance in patients with paracoccidioidomycosis since they are the portal of entry for the infecting fungi, the site of quiescent foci, and one of the most frequently affected organs. Although they have been the subject of many studies with different approaches, the severity classification of the pulmonary involvement, using imaging procedures, has not been carried out yet. This study aimed to classify the active and the residual pulmonary damage using radiographic and tomographic evaluations, according to the area involved and types of lesions.


Enhanced bromate control during ozonation: the chlorine-ammonia process.
Potentially carcinogenic bromate forms during the ozonation of bromide-containing waters. Some water treatment facilities have had to use ammonia addition and pH depression to minimize bromate formation, but these processes may prove to be insufficient to comply with upcoming regulations. The chlorine-ammonia process (Cl2-NH3), consisting of prechlorination followed by ammonia addition priorto ozonation is shown to cause a 4-fold decrease in bromate formed when compared to the ammonia-only process. Experiments revealed three key mechanisms: (i) oxidation by HOCl of Br- to HOBr and its subsequent masking by NH3 as NH2Br; (ii) decrease of HO- exposure through halogenation of Dissolved Natural Organic Matter (DNOM) by HOCI and scavenging of HO by NH2Cl; and (iii) DNOM acting as a bromine sink after oxidation of Br- to HOBr. At an ozone exposure of 6 mg/L x min and pH 8, conventional ozonation of Lake Zurich water spiked with 560 microg/L Br- formed 35 microg/L BrO3-, whereas the application of the Cl2-NH3 process resulted in 5 microg/L BrO3-. Additional pH depression to pH 6 further decreased bromate formation by a factor of 4. Trihalomethanes (THM) and cyanogen chloride (CNCl), that mayform during prechlorination and monochloramination, respectively, were well below regulatory limits. The chlorine-ammonia process holds strong promise for water treatment facilities struggling with a bromate formation problem during ozonation.


The influence of maternal BMI and age in twin pregnancies on insulin resistance in the offspring.
There is strong evidence that low birth weight is associated with glucose intolerance and diabetes in adults. We have carried out a twin study to distinguish among maternal influences, which affect both twins; fetoplacental influences, which are unique to each twin; and the genetic factors that may underlie this association. We identified a sample of 423 twin pairs (250 monozygotic and 173 dizygotic) from the East Flanders Prospective Twin Survey who were born between 1964 and 1982. Data collected in this study included the mother's body composition and weight gain during pregnancy, the twins' birth weights, and gestational age. The twins (aged 18-34 years) attended a research center for measurement of height, weight, and waist-to-hip ratio as well as fasting glucose, proinsulin, and insulin concentrations. Among twin pairs discordant for birth weight, we found little evidence that the lighter twin had abnormal glucose-insulin metabolism in adult life. However, both a low prepregnancy maternal BMI and older maternal age at delivery were associated with hyperinsulinemia and evidence of insulin resistance in the offspring. Fasting insulin increased by 1.3% (95% CI 0.1-2.6%) per unit fall in maternal BMI and by 1.1% (0.02-2.0%) per year increase in maternal age. These associations were independent of the twins' BMI and waist-to-hip ratio and their zygosity. These novel findings suggest that in twin pregnancies, maternal factors are more important than fetoplacental factors in determining glucose-insulin metabolism in the offspring.


[Impact of phthisiosurgery on the development of morphological studies of the lung].
The paper describes the most important developmental stages of phthisiomorphology in chronological order, by using as an example the work of the Pathomorphology Laboratory, Central Tuberculosis Research Institute, since its organization. It also shows the stages of phthisiosurgery with the inestimable scientific and practical contribution of the works by L. K. Bogush and his followers from the formation of lung surgery to today's achievements. The authors give examples of the long-term working partnership of surgeons and morphologists in the development of these two disciplines, which was fruitful in deciding many issues of phthisiology.


[Computer-assisted interactive didactic system in radiology].
A computer-assisted didactic interactive system for radiology is described; it was implemented on a widely available, cost-effective personal computer with advanced graphic features. A set of suitable CT images was selected and digitized with a specific software that also allowed to process the acquired images. After adding graphic and textual comments, the images were ready to be put in the tutorial. A second software tool was used to manage the image display and to control the correct sequence of the interactive steps of the tutorial. A series of computer-driven multiple-choice questions was prepared to provide the user with a tool improving his/her knowledge of the topics covered by the system, in a simple and unconventional way. The tutorial was designed so that both the absolute number and the percentage of correct answers can be displayed and the critical evaluation of incorrect answers is automatically performed; in the end, the system goes back to the first screen and the tutorial can be run again. The system performance is good with standard hardware; it can be markedly improved with the integration of peripherals--i.e. hard disk. In the next future, the commercial availability of more advanced storage media (videodisks and optical disks) will dramatically improve the archiving capacity and will reduce access times.


[Role of Azathioprine in steroid resistant non infectious ocular inflammatory diseases].
Topical and systemic steroids are the first line of treatment of non infectious inflammatory ocular disease. Immunosuppresants are reserved as a second line treatment. To evaluate the role of Azathioprine (AZA) as a coadyuvant immunosuppressive treatment for non infectious ocular inflammatory diseases (OIDs) resistant to systemic steroid therapy in a retrospective, noncomparative interventional case series. Patients using oral Prednisone due to an active or recurrent OID, without clinical response, and not receiving any other immunosuppressive treatment were studied. A standard protocol of oral Prednisone (0.5 mg/kg/ day) and oral AZA (2-3 mg/kg/day) during one year was used. Ocular and systemic monthly evaluations were done including relapse rate, steroid dosage, inflammatory score and visual acuity. Thirty patients (10 male) aged 18-75 years (mean 44 years) were studied. Three had bilateral anterior uveitis, one had pars planitis, four had diffuse uveitis, eight Vogt-Koyanahi-Harada syndrome, three Behget's disease, three necrotizing scleritis and eight had retinochoroidopathy A complete initial response was observed in 26 patients (87%). The time of response was between 1 to 6 months (mean 2.65 months). Seventeen percent of these had a relapse 6 to 12 months after AZA was started. In 61 %, visual acuity improved. The ocular inflammatory score decreased in 86.5%. Eleven patients had mild controlled side effects that did not require discontinuation of AZA. Combined systemic steroid and oral AZA therapy is safe and effective in controlling steroid resistant non infectious inflammatory ocular diseases.


Electronic Health Literacy in Swiss-German Parents: Cross-Sectional Study of eHealth Literacy Scale Unidimensionality.
Parents often use digital media to search for information related to their children's health. As the quantity and quality of digital sources meant specifically for parents expand, parents' digital health literacy is increasingly important to process the information they retrieve. One of the earliest developed and widely used instruments to assess digital health literacy is the self-reported eHealth Literacy Scale (eHEALS). However, the eHEALS has not been psychometrically validated in a sample of parents. Given the inconsistency of the eHEALS underlying factor structure across previous reports, it is particularly important for validation to occur. This study aimed to determine the factor structure of the German eHEALS measure in a sample of parents by adopting classic and modern psychometric approaches. In particular, this study sought to identify the eHEALS validity as a unidimensional index as well as the viability for potential subscales. A cross-sectional design was used across two purposive sampling frames: online and paper administrations. Responses were collected between January 2018 and May 2018 from 703 Swiss-German parents. In addition to determining the sampling characteristics, we conducted exploratory factor analysis of the eHEALS by considering its ordinal structure using polychoric correlations. This analysis was performed separately for online-based and paper-based responses to examine the general factor strength of the eHEALS as a unidimensional index. Furthermore, item response theory (IRT) analyses were conducted by fitting eHEALS to a bifactor model to further inspect its unidimensionality and subscale viability. Parents in both samples were predominantly mothers (622/703, 88.5%), highly educated (538/703, 76.9%), of Swiss nationality (489/703, 71.8%), and living with a partner (692/703, 98.4%). Factor analyses of the eHEALS indicated the presence of a strong general factor across both paper and online samples, and the Wilcoxon rank-sum test indicated that the eHEALS total sum score was not significantly different between the paper and online samples (P=.12). Finally, the IRT analyses indicated negligible multidimensionality, insufficient subscale reliability after accounting for the eHEALS general factor, and a reduced subset of items that could serve as a unidimensional index of the eHEALS across the paper and online samples. The German eHEALS evidenced good psychometric properties in a parent-specific study sample. Factor analyses indicated a strong general factor across purposively distinct sample frames (online and paper). IRT analyses validated the eHEALS as a unidimensional index while failing to find support for subscale usage.


Genetic Regulation of Shoot Architecture.
Shoot architecture is determined by the organization and activities of apical, axillary, intercalary, secondary, and inflorescence meristems and by the subsequent development of stems, leaves, shoot branches, and inflorescences. In this review, we discuss the unifying principles of hormonal and genetic control of shoot architecture including advances in our understanding of lateral branch outgrowth; control of stem elongation, thickness, and angle; and regulation of inflorescence development. We focus on recent progress made mainly in Arabidopsis thaliana, rice, pea, maize, and tomato, including the identification of new genes and mechanisms controlling shoot architecture. Key advances include elucidation of mechanisms by which strigolactones, auxins, and genes such as IDEAL PLANT ARCHITECTURE1 and TEOSINTE BRANCHED1 control shoot architecture. Knowledge now available provides a foundation for rational approaches to crop breeding and the generation of ideotypes with defined architectural features to improve performance and productivity.


Visualization of mRNA Expression in Pseudomonas aeruginosa Aggregates Reveals Spatial Patterns of Fermentative and Denitrifying Metabolism.
Gaining insight into the behavior of bacteria at the single-cell level is important given that heterogeneous microenvironments strongly influence microbial physiology. The hybridization chain reaction (HCR) is a technique that provides in situ molecular signal amplification, enabling simultaneous mapping of multiple target RNAs at small spatial scales. To refine this method for biofilm applications, we designed and validated new probes to visualize the expression of key catabolic genes in Pseudomonas aeruginosa aggregates. In addition to using existing probes for the dissimilatory nitrate reductase (narG), we developed probes for a terminal oxidase (ccoN1), nitrite reductase (nirS), nitrous oxide reductase (nosZ), and acetate kinase (ackA). These probes can be used to determine gene expression levels across heterogeneous populations such as biofilms. Using these probes, we quantified gene expression across oxygen gradients in aggregate populations grown using the agar block biofilm assay (ABBA). We observed distinct patterns of catabolic gene expression, with upregulation occurring in particular ABBA regions both within individual aggregates and over the aggregate population. Aerobic respiration (ccoN1) showed peak expression under oxic conditions, whereas fermentation (ackA) showed peak expression in the anoxic cores of high metabolic activity aggregates near the air-agar interface. Denitrification genes narG, nirS, and nosZ showed peak expression in hypoxic and anoxic regions, although nirS expression remained at peak levels deeper into anoxic environments than other denitrification genes. These results reveal that the microenvironment correlates with catabolic gene expression in aggregates, and they demonstrate the utility of HCR in unveiling cellular activities at the microscale level in heterogeneous populations. IMPORTANCE To understand bacteria in diverse contexts, we must understand the variations in behaviors and metabolisms they express spatiotemporally. Populations of bacteria are known to be heterogeneous, but the ways this variation manifests can be challenging to characterize due to technical limitations. By focusing on energy conservation, we demonstrate that HCR v3.0 can visualize nuances in gene expression, allowing us to understand how metabolism in Pseudomonas aeruginosa biofilms responds to microenvironmental variation at high spatial resolution. We validated probes for four catabolic genes, including a constitutively expressed oxidase, acetate kinase, nitrite reductase, and nitrous oxide reductase. We showed that the genes for different modes of metabolism are expressed in overlapping but distinct subpopulations according to oxygen concentrations in a predictable fashion. The spatial transcriptomic technique described here has the potential to be used to map microbial activities across diverse environments.


Low molecular weight heparin in portal vein thrombosis of cirrhotic patients: only therapeutic purposes?
Cirrhosis has always been regarded as hemorrhagic coagulopathy caused by the reduction in the hepatic synthesis of procoagulant proteins. However, with the progression of liver disease, the cirrhotic patient undergoes a high rate of thrombotic phenomena in the portal venous system. Although the progression of liver failure produces a reduction in the synthesis of anticoagulant molecules, a test able to detect the patients with hemostatic balance shifting towards hypercoagulability has not yet been elaborated. The need of treatment and/or prophylaxis of cirrhotic patients is demonstrated by the increased mortality, the risk of bleeding from esophageal varices, and the mortality of liver transplantation, when portal vein thrombosis (PVT) occurs even if current guidelines do not give indications about PVT treatment in cirrhosis. In view of the general feeling that the majority of cirrhotic patients at an advanced stage may be in a procoagulant condition (suggested by the sharp increase in the prevalence of PVT), it is presumable that a prophylaxis of this population could be of benefit. The safety and the efficacy of prophylaxis and treatment with enoxaparin in patients with cirrhosis demonstrated by a single paper suggest this option only in controlled trials and, currently, there are no sufficient evidences for a recommendation in the clinical practice.


What questions should newborn screening long-term follow-up be able to answer? A statement of the US Secretary for Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children.
The US Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children provides guidance on reducing the morbidity and mortality associated with heritable disorders detectable through newborn screening. Efforts to systematically evaluate health outcomes, beyond long-term survival, with a few exceptions, are just beginning. To facilitate these nascent efforts, the US Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children initiated a project to define the major overarching questions to be answered to assure that newborn screening is meeting its goal of achieving the best quality outcome for the affected children and their families. The questions identified follow the central components of long-term follow-up-care coordination, evidence-based treatment, continuous quality improvement, and new knowledge discovery-and are framed from the perspectives of the state and nation, primary and specialty healthcare providers, and the impacted families. These overarching questions should be used to guide the development of long-term follow-up data systems, quality health indicators, and specific data elements for evaluating the newborn screening system.


Holographic spatial coherence analysis of a laser.
We show that the second-order coherent-mode representation of a stationary quasi-monochromatic scalar light beam can be experimentally characterized by dual-mode holographic interference using an arbitrary basis. Analysis of the laser beam emitted from a stable spherical mirror cavity, using a mismatched Hermite-Gaussian basis, recovered the profiles and powers of a set of cavity modes with the expected spot size, including a hybrid of frequency degenerate modes. Observed near- and far-field irradiance transverse profiles and associated M2 parameter measures confirmed the results.


Histological and ultrastructural studies of rats exposed to carbaryl.
The aim of the study was to assess the general toxic effects of dermally applied carbaryl, based on histological and ultrastructural examinations of internal organs and to relate these effects to earlier own studies where 14C carbaryl was used for determining the pesticide penetration. The pesticide was applied in doses of 1/5 and 1/10 LD50, administered to the tail skin of male Wistar rats 4 hours daily, for 4 weeks except Saturdays and Sundays. After the experiment, the animals were anaesthetized and the following organs were taken for histological study: brain, lung, heart, liver, kidney, skin from the site of exposure and skin from a place at least 2 cm distant from the exposure site. Lung, liver, kidney, heart and skin were used for ultrastructural studies. Dermal application of carbaryl resulted only in slight histological changes in skin, liver, brain and lung. Even in brain and liver, where large amounts of 14C carbaryl, compared to other organs (lung, kidney, heart), where the intensity of histologic changes was earlier stated to below. Ultrastructural changes were observed in skin, liver, lung, heart and kidney.


Cloning of the pleiotropic T locus in soybean and two recessive alleles that differentially affect structure and expression of the encoded flavonoid 3' hydroxylase.
Three loci (I, R, and T) control pigmentation of the seed coats in Glycine max and are genetically distinct from those controlling flower color. The T locus also controls color of the trichome hairs. We report the identification and isolation of a flavonoid 3' hydroxylase gene from G. max (GmF3'H) and the linkage of this gene to the T locus. This GmF3'H gene was highly expressed in early stages of seed coat development and was expressed at very low levels or not at all in other tissues. Evidence that the GmF3'H gene is linked to the T locus came from the occurrence of multiple RFLPs in lines with varying alleles of the T locus, as well as in a population of plants segregating at that locus. GmF3'H genomic and cDNA sequence analysis of color mutant lines with varying t alleles revealed a frameshift mutation in one of the alleles. In another line derived from a mutable genetic stock, the abundance of the mRNAs for GmF3'H was dramatically reduced. Isolation of the GmF3'H gene and its identification as the T locus will enable investigation of the pleiotropic effects of the T locus on cell wall integrity and its involvement in the regulation of the multiple branches of the flavonoid pathway in soybean.


[Development of Eimeria tenella in a nonspecific host: the mouse].
The existence of extra-intestinal stages of a chick coccidium, Eimeria tenella, has been demonstrated in a non-specific host, the mouse. Between 1 and 14 days after inoculation the lungs and blood of mice were periodically infective for chicks. This is consistent with parasite development, rather than survival in the lungs and passage of free elements by the bloodstream. This type of development with extra-intestinal stages in a non-specific host has certain analogies with a related genus Toxoplasma. The type of development remains to be demonstrated.


In vivo evidence for the role of CD44s in promoting breast cancer metastasis to the liver.
The hyaluronan receptor CD44 plays an important role in facilitating invasion and metastasis of a variety of tumors, including breast carcinomas. CD44 functions as a bioactive signaling transmitter. Although a number of studies have implicated CD44 in breast tumor invasion, the evidence is still circumstantial. We have developed a tetracycline-regulated CD44s (standard form) system in the weakly metastatic breast cancer cell MCF7, which exhibits low endogenous expression of CD44 and generated a new cell line, MCF7F-B5. Induction of CD44s alone affected the growth characteristics of MCF7F-B5 cells by increasing their abilities to proliferate, migrate, and invade in vitro. In addition, we have identified and validated cortactin as a novel transcriptional target of hyaluronan/CD44s signaling in underpinning breast tumor invasion. To test these observations in vivo, we developed a doxycycline (DOX)-regulated CD44s breast cancer xenograft model. Induction of CD44s did not affect the growth rate or local invasion of the primary tumor. However, although no mice from the +DOX group developed metastasis, 8 of 11 mice from the -DOX group developed secondary tumors to the liver only. Interestingly, metastatic breast tumors expressed high levels of CD44. This study provides in vivo evidence for the role of the standard form of CD44 in promoting breast tumor invasion and metastasis to the liver.


Mosaic architecture of the somatic sensory-recipient sector of the cat's striatum.
The striatum is known to have a compartmental organization in which histochemically defined zones called striosomes form branched 3-dimensional labyrinths embedded within the surrounding matrix. We explored how fiber projections from cortical somatic sensory areas representing cutaneous and deep-receptor inputs are organized in relation to this striatal architecture. Areas SI and 3a were mapped electrophysiologically, and distinguishable anterograde tracers (wheat germ agglutinin-HRP and 35S-methionine) were injected into physiologically identified loci. Primary somatic sensory corticostriatal projections were confined to a small, well-defined sector in the dorsolateral corner of the ipsilateral striatum. The somatic sensory afferents were arranged according to a coherent global body map in which rostral body parts were represented more laterally than caudal body parts. Single cortical loci innervated branched and clustered striatal zones that were reminiscent of the striosomes in their range of sizes and shapes yet lay strictly within the extrastriosomal matrix. In contrast to the global orderliness of the striatal body map, there were clear examples of locally complex patterns in which functionally distinct inputs interdigitated with each other. These patterns were often, but not always, produced when corticostriatal afferents carrying different submodality types were labeled. These findings demonstrate the existence of striosome-like striatal compartments within the seemingly uniform extrastriosomal matrix. The principle of mosaic organization thus holds throughout the tissue of the somatic sensory striatum. The striatal architecture delineated here could provide the anatomical substrate for computations requiring cross-modality comparisons within the framework of an overall somatotopy. If a similar multicompartmental architecture also characterizes other striatal regions, as seems likely, it may set general constraints on the nature of associative processing within the striatum as a whole.


Spry1 and spry2 are essential for development of the temporomandibular joint.
The temporomandibular joint (TMJ) is a specialized synovial joint essential for the function of the mammalian jaw. The main components of the TMJ are the mandibular condyle, the glenoid fossa of the temporal bone, and a fibrocartilagenous disc interposed between them. The genetic program for the development of the TMJ remains poorly understood. Here we show the crucial role of sprouty (Spry) genes in TMJ development. Sprouty genes encode intracellular inhibitors of receptor tyrosine kinase (RTK) signaling pathways, including those triggered by fibroblast growth factors (Fgfs). Using in situ hybridization, we show that Spry1 and Spry2 are highly expressed in muscles attached to the TMJ, including the lateral pterygoid and temporalis muscles. The combined inactivation of Spry1 and Spry2 results in overgrowth of these muscles, which disrupts normal development of the glenoid fossa. Remarkably, condyle and disc formation are not affected in these mutants, demonstrating that the glenoid fossa is not required for development of these structures. Our findings demonstrate the importance of regulated RTK signaling during TMJ development and suggest multiple skeletal origins for the fossa. Notably, our work provides the evidence that the TMJ condyle and disc develop independently of the mandibular fossa.


A Missense Variant in ALDH5A1 Associated with Canine Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD) in the Saluki Dog.
Dogs provide highly valuable models of human disease due to the similarity in phenotype presentation and the ease of genetic analysis. Seven Saluki puppies were investigated for neurological abnormalities including seizures and altered behavior. Magnetic resonance imaging showed a diffuse, marked reduction in cerebral cortical thickness, and symmetrical T2 hyperintensity in specific brain regions. Cerebral cortical atrophy with vacuolation (status spongiosus) was noted on necropsy. Genome-wide association study of 7 affected and 28 normal Salukis revealed a genome-wide significantly associated region on CFA 35. Whole-genome sequencing of three confirmed cases from three different litters revealed a homozygous missense variant within the aldehyde dehydrogenase 5 family member A1 (ALDH5A1) gene (XM_014110599.2: c.866G>A; XP_013966074.2: p.(Gly288Asp). ALDH5A1 encodes a succinic semialdehyde dehydrogenase (SSADH) enzyme critical in the gamma-aminobutyric acid neurotransmitter (GABA) metabolic pathway. Metabolic screening of affected dogs showed markedly elevated gamma-hydroxybutyric acid in serum, cerebrospinal fluid (CSF) and brain, and elevated succinate semialdehyde in urine, CSF and brain. SSADH activity in the brain of affected dogs was low. Affected Saluki dogs had striking similarities to SSADH deficiency in humans although hydroxybutyric aciduria was absent in affected dogs. ALDH5A1-related SSADH deficiency in Salukis provides a unique translational large animal model for the development of novel therapeutic strategies.


School-Based Health Education in Yucatan, Mexico about the Chikungunya Virus and Mosquito Illness Prevention.
The Chikungunya virus (CHIKV) has been rapidly spreading throughout Latin America, utilizing pre-existing vectors to infiltrate the immunologically naïve populations. With the current rise of the Zika Virus, there is an urgent need for more rigorous vector control efforts to prevent further Zika breakout. We designed a school-based education module on CHIKV and mosquito prevention and presented it to the local students of ages of 6-18 in a rural town called Sudzal in Yucatan, Mexico. We distributed questionnaires before and after education to test the students' knowledge of CHIKV and mosquito prevention. Chi-squared test was performed to determine the efficacy of the presentation in increasing their knowledge. The education presentation has proven to effectively educate the local residents in several critical methods of mosquito prevention, increasing the average test scores by 67% post-education. These include applying repellent, staying hydrated during recuperation, and cleaning indoor water containers to eliminate breeding sites (P<0.001). Furthermore, the questionnaire captured the residents' behavioral patterns regarding CHIKV and mosquito prevention and identified cultural, ecological, and socioeconomic factors hindering effective implementation of vector control.


Down-regulation of thyroxine-binding globulin messenger ribonucleic acid by 3,5,3'-triiodothyronine in human hepatoblastoma cells.
A sensitive [125I]-T4 binding assay was used to measure serum T4-binding globulin (TBG) in 60 individuals selected on the basis of their total circulating T3 concentrations, and a relationship between TBG and circulating thyroid hormone levels in humans was confirmed. There was a significant correlation between serum TBG and T3 or free T4 index. TBG secretion and TBG messenger ribonucleic acid (mRNA) production were studied with a continuous culture of the human hepatoblastoma cell line, HepG2. Cells were maintained in serum-free media for experimental manipulations. The addition of 100 nmol/L T3 to the cell medium resulted in a time-dependent down-regulation of TBG mRNA to 33 +/- 6% (+/- SD, n = 4) of untreated control levels by 24 h. Suppression of TBG mRNA was first detectable at 8 h (57% of untreated control levels). The effect of T3 was dose-responsive, with half-maximal suppression of TBG mRNA occurring at a bioavailable T3 concentration of approximately 30 pmol/L. The effect of T3 on TBG mRNA was not caused by a change in mRNA stability. Proteins secreted by HepG2 cells bound T4 with an affinity identical to that of normal circulating TBG. Cell secretion of TBG was parallel to total protein secretion and consistent with a TBG secretion rate of 50 ng/10(6) cells per day. Variations in the concentration of secreted binding protein in the presence of T3 corresponded to the changes observed in TBG mRNA. These data show that circulating TBG concentration is negatively correlated with total serum T3 in vivo. The corresponding down-regulation observed between TBG mRNA and secreted protein in HepG2 cells suggests that this effect is the result of the action of T3 on cellular TBG mRNA synthesis.


MANAGEMENT OF ENDOCRINE DISEASE: Differential diagnosis, investigation and therapy of bilateral adrenal incidentalomas.
The investigation and management of unilateral adrenal incidentalomas have been extensively considered in the last decades. While bilateral adrenal incidentalomas represent about 15% of adrenal incidentalomas (AIs), they have been less frequently discussed. The differential diagnosis of bilateral incidentalomas includes metastasis, primary bilateral macronodular adrenal hyperplasia and bilateral cortical adenomas. Less frequent etiologies are bilateral pheochromocytomas, congenital adrenal hyperplasia (CAH), Cushing's disease or ectopic ACTH secretion with secondary bilateral adrenal hyperplasia, primary malignancies, myelolipomas, infections or hemorrhage. The investigation of bilateral incidentalomas includes the same hormonal evaluation to exclude excess hormone secretion as recommended in unilateral AI, but diagnosis of CAH and adrenal insufficiency should also be excluded. This review is focused on the differential diagnosis, investigation and treatment of bilateral AIs.


THE INFLUENCE OF ELECTROLYTES UPON THE ELECTROPHORETIC MIGRATION OF BACTERIA AND OF YEAST CELLS.
1. It seems first of all clear from our results that the effect of electrolytes upon electrophoretic charge is essentially the same, whether one is dealing with silica dust, bacteria, or yeast cells, although certain quantitative differences appear which will later be discussed. 2. The normal negative charge on the suspended particles appears to be slightly increased by very low concentrations of electrolytes, markedly so in the case of yeast cells. Increase in charge due to minimal concentrations of electrolytes has been recorded by Loeb (1922) for collodion particles. 3. Higher concentrations of electrolytes cause a marked and progressive decrease in negative charge, sometimes leading to an isopotential condition and sometimes to a complete reversal of charge with active migration toward the cathode. This effect is apparently due to the cation alone and increases with the valency of the cation, except that the H ion shows specially marked activity, between that of bivalent and trivalent ions. Since NaOH behaves like an ordinary univalent salt, increased alkalinity of a solution does not further depress the charge already depressed by salts; but, since the H ion is much more active than other univalent or bivalent ions, increased acidity does cause a further progressive depression of charge, even in salt solutions. Certain electrolytes appear to show individual peculiarities due to something else than their valency. Thus KCl for example is distinctly more effective than NaCl. Sodium chloride in general appears to exert less influence upon electrophoretic charge, either in low or high dilution, than do other compounds of univalent ions studied. This depressing effect of moderately high concentrations of electrolytes is much less marked with yeast cells than with Bacterium coli. Silica dust is still less affected by monovalent and bivalent ions than are the yeast cells but appears to be more affected than either yeast or Bacterium coli by AlCl(3). 4. Very high concentrations of AlCl(3) (above 10(-2)M) show a third effect, a decrease of the positive charge produced by concentrations of moderate molar strength. This is analogous to phenomena observed for trivalent salts by Northrop and De Kruif (1921-22) and for acid by Winslow, Falk, and Caulfield (1923-24). 5. Organic substances, such as glucose, glycerol, and saponin produce no effect on electrophoretic velocity until they reach a concentration at which viscosity changes are involved. 6. The first two results observed,-(a) the increase in charge as a result of slight additions of electrolytes, and (b) the marked decrease in charge with further concentration of electrolytes, depending on the valency of the cation, so far as vegetable cells are concerned, are entirely in accord with the theory of the Donnan equilibrium as worked out by Loeb (1922). We might assume in explaining such phenomena that the plant cell contains a certain proportion of unbound protein material and that the first modicum of cation which enters the cell is bound by the protein, leading to an increase in the relative negative charge of the cell as compared with its menstruum, while subsequent increments of cation remain unbound in the cell and thus lower its charge. When we find, however, that the same phenomena are apparent with collodion particles, as shown by Loeb, and with silica dust, it seems difficult to apply such a theory, involving the conceptions of a permeable membrane and unbound organic compounds. Loeb (1923-24) suggests that the primary increase may be due to an aggregation of anions in the part of the electrical double layer adjacent to the suspended particles; but why there should be first an aggregation of anions and later (with increasing concentration) an aggregation of cations, is not easy to conceive. The third result,-the reversion to a more negative charge in the presence of a marked excess of trivalent ions,-is again difficult to explain. Loeb, in this connection, postulates the existence of complex ion-protein compounds, which can scarcely be assumed in the case of the silica particles.


Suppression of post-transcriptional gene silencing by a plant viral protein localized in the nucleus.
Post-transcriptional gene silencing (PTGS) is a homology-dependent RNA degradation process that may target RNA exclusively in the cytoplasm. In plants, PTGS functions as a natural defense mechanism against viruses. We reported previously that the 2b protein encoded by cucumber mosaic cucumovirus (CMV) is a virulence determinant and a suppressor of PTGS initiation in transgenic Nicotiana benthamiana. By fusion with the green fluorescent protein, we now show that the CMV 2b protein localizes to the nuclei of tobacco suspension cells and whole plants via an arginine-rich nuclear localization signal, (22)KRRRRR(27). We further demonstrate that the nuclear targeting of the 2b protein is required for the efficient suppression of PTGS, indicating that PTGS may be blocked in the nucleus. In addition, our data indicate that the PTGS suppressor activity is important, but not sufficient, for virulence determination by the 2b protein.


[The mechanism of the therapeutic effect of norethisterone in hyperplastic diseases of the endo- and myometrium in women of reproductive age].
The paper is concerned with results of a study of clinico-biologic effect of a gestagen norsteroid drug--norcolut--on solitary and combined lesions of the endo- and myometrium. Four hundred and thirty-four patients of reproductive age with hyperplasia or polyps of the endometrium, uterine myoma, internal endometriosis or a combination of the pathologies were examined prior to administration of norcolut and during posttreatment cycle to evaluate the influence of the drug on the female reproductive system. Norcolut exerted the regulatory effect on the rhythm and pattern of menstruation and inhibited tumor growth. Also, changes in localization of myoma nodes, normalization of steroid hormone profile, decrease in the level of estradiol and progesterone receptors, and secretory transformation of the endometrium were observed. Those changes resulted in regression of endometrial lesions.


Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain.
Endogenous inflammatory mediators contribute to the pathogenesis of pain by acting on nociceptors, specialized sensory neurons that detect noxious stimuli. Here, we describe a new factor mediating inflammatory pain. We show that platelet-derived growth factor (PDGF)-BB applied in vitro causes repetitive firing of dissociated nociceptor-like rat dorsal root ganglion neurons and decreased their threshold for action potential generation. Injection of PDGF-BB into the paw produced nocifensive behavior in rats and led to thermal and mechanical pain hypersensitivity. We further detailed the biophysical mechanisms of these PDGF-BB effects and show that PDGF receptor-induced inhibition of nociceptive M-current underlies PDGF-BB-mediated nociceptive hyperexcitability. Moreover, in vivo sequestration of PDGF or inhibition of the PDGF receptor attenuates acute formalin-induced inflammatory pain. Our discovery of a new pain-facilitating proinflammatory mediator, which by inhibiting M-current activates nociceptive neurons and thus contributes to inflammatory pain, improves our understanding of inflammatory pain pathophysiology and may have important clinical implications for pain treatment.


Advances in oral anti-arrhythmic therapy: implications for the anaesthetist.
Surgical patients often are receiving antiarrhythmic therapy. Thus, because anaesthetic agents can affect cardiac function and may interact with concurrent antiarrhythmic medications, the anaesthetist should be aware of the electrophysiology associated with dysrhythmias and their management. Tocainide, flecainide, mexiletine, encainide and amiodarone have been introduced recently and each has an unique pattern of bioavailability, metabolism and toxicity. Patients treated with these drugs need special concern as they have abnormal cardiovascular systems and may be at increased risk for perioperative morbidity. In addition, unexpected untoward reactions and toxicity can result from interactions of anaesthetic agents and these drugs. This review discusses normal cardiac electrophysiology, common dysrhythmias and the electrophysiological effects of the newer oral antiarrhythmic drugs.


Automated headspace solid-phase microextraction and in-matrix derivatization for the determination of amphetamine-related drugs in human urine by gas chromatography-mass spectrometry.
An automated extraction and determination method for the gas chromatography (GC)-mass spectrometry (MS) analysis of amphetamine-related drugs in human urine is developed using headspace solid-phase microextraction (SPME) and in-matrix derivatization. A urine sample (0.5 mL, potassium carbonate (5 M, 1.0 mL), sodium chloride (0.5 g), and ethylchloroformate (20 microL) are put in a sample vial. Amphetamine-related drugs are converted to ethylformate derivatives (carbamates) in the vial because amphetamine-related drugs in urine are quickly reacted with ethylchloroformate. An SPME fiber is then exposed at 80 degrees C for 15 min in the headspace of the vial. The extracted derivatives to the fiber are desorbed by exposing the fiber in the injection port of a GC-MS. The calibration curves show linearity in the range of 1.0 to 1000 ng/mL for methamphetamine, fenfluramine, and methylenedioxymethamphetamine; 2.0 to 1000 ng/mL for amphetamine and phentermine; 5.0 to 1000 ng/mL for methylenedioxyamphetamine; 10 to 1000 ng/mL for phenethylamine; and 50 to 1000 ng/mL for 4-bromo-2,5-dimethoxyphenethylamine in urine. No interferences are found, and the time for analysis is 30 min for one sample. Furthermore, this proposed method is applied to some clinical and medico-legal cases by taking methamphetamine. Methamphetamine and its metabolite amphetamine are detected in the urine samples collected from the patients involved in the clinical cases. Methamphetamine, amphetamine, and phenethylamine are detected in the urine sample collected from the victim of a medico-legal case.


The management of intoeing: a review.
Children presenting with an intoeing gait are the most common pediatric problem seen by orthopedists. Most parents are concerned that this rotational problem may result in a permanent disability or impediment of their child's physical performance. The etiologies of these conditions are still debated, although the structural conditions giving rise to intoeing can be correlated with the age of onset. The extent of the rotational problem is determined through physical examination and the measurement of indicative angles. A rotational profile is compiled from the values obtained, allowing the child's progress to be followed. Many children spontaneously resolve the structural problems responsible for their intoeing gait. The success one attributed to the traditional methods for treating intoeing is now believed to be the result of this natural resolution.


Forensic entomology when the evidence is "no insect." Best carrion fly species for predicting maximum postmortem interval in the United Arab Emirates.
The carrion insect species that most quickly deposit offspring on a corpse are, when available, likely to yield a more useful estimate of postmortem interval (PMI) compared to later arrivals. This is in part because the age of the oldest larva will be as close as possible to the PMI when doing a development analysis, and because the preappearance interval (PAI), the time the corpse was exposed before insect colonization, corresponds to the narrowest window of time since death for an insect-free corpse when doing a succession analysis. Given replicated training data a prediction of exposure time for a corpse can be in the form of a confidence set, and the maximum value of that set for an insect-free corpse is a probabilistic version of PAI. To discover the insect species likely to be useful in the early postmortem period in the United Arab Emirates we exposed 216 rat carcasses outdoors at two sites in Dubai over three-day periods during winter. Rats were sampled twice each day without replacement and kept in the lab to allow carrion insects to complete development to the adult stage. The fly species produced in this way were Sarcophaga dux, S. ruficornis, Wohlfahrtia nuba, W. indigens (Sarcophagidae), Chrysomya albiceps (Calliphoridae), and Musca domestica (Muscidae). To the best of our knowledge this is the first record of W. indigens larvae feeding on carrion. While adult C. albiceps and M. domestica were abundant on the carcasses, C. albiceps colonized too slowly to be useful for this type of succession analysis within this time frame, and M. domestica emerged from a single rat. The Sarcophagidae were rapid colonizers, and under these conditions the probability is>90% that a carcass would remain free of S. dux larvae not more than 57 h and free of W. nuba larvae for not more than 51 h.


Health Care Disparities of Ohioans With Developmental Disabilities Across the Lifespan.
We explored health care differences across the lifespan comparing people with developmental disabilities to people without developmental disabilities. Health care disparities are inequities occurring during the provision of and in access to health care that are experienced by socially disadvantaged populations. We discovered significant disparities between persons with and without developmental disabilities in health status, quality, utilization, access, and unmet health care needs. Our results highlight the need to educate health care clinicians on the care of patients with developmental disabilities of all ages.


Resultant pharmacological actions of verapamil: quantification of competitive 5-hydroxytryptamine antagonism in combination with calcium antagonism.
According to previous reports, the effect of verapamil on 5-hydroxytryptamine (5-HT) responses in the rabbit aorta is likely to represent a resultant of 5-HT2-receptor antagonism and Ca++-channel blockade. In practice, verapamil produced rightward displacement and depression of 5-HT-concentration-effect curves in this tissue. Under these conditions, verapamil's competitive property may not be justifiably quantified by analyzing curve displacements. In order to detect and quantify this property, a recently developed concentration-ratios method was applied. This method depends on the effect of the test substance, verapamil here, on the expression of competition by a standard antagonist, spiperone in this study. Analysis of the concentration-ratios produced by spiperone in the presence of verapamil permitted receptor competition by verapamil to be detected. Quantification of this property indicated a pKB of 5.73. This estimate of affinity did not account for the total rightward displacement of 5-HT-concentration-effect curves that verapamil produced, indicating, presumably, that concomitant Ca++-antagonism contributed to these displacements. Also, this estimate of verapamil's 5-HT2-receptor affinity is lower than that derived elsewhere from an analysis of the overall antagonistic effect of verapamil on 5-HT responses in the rabbit aorta. These results illustrate the potentially general utility of the concentration-ratios methods in elucidating resultant pharmacological actions.


Copy number variations and fetal ventriculomegaly.
Ventriculomegaly is one of the most common abnormal sonographic findings, which is associated with congenital infection, chromosomal and additional structural abnormalities. Currently, karyotype analysis is the primary method to detect chromosomal abnormalities in fetuses with ventriculomegaly. Recently, with the introduction of chromosomal microarray analysis (CMA) in prenatal diagnosis, copy number variations (CNVs) have been identified in cases of ventriculomegaly. The purpose of this review is to summarize the current knowledge about the genetic cause of fetal ventriculomegaly, with particular attention to primary articles regarding the association between CNVs and fetal ventriculomegaly. Recent studies have disclosed that in addition to numerical chromosomal abnormalities and large chromosomal imbalances, pathogenic CNVs are another important genetic cause of fetal ventriculomegaly, which may be involved in the pathological process of fetal ventriculomegaly as well as postnatal neurodevelopmental disorders. Furthermore, it is reported that the incidences of pathogenic CNVs in fetuses with ventriculomegaly were associated with the presence of other structural anomalies, but were irrelevant to the severity of ventriculomegaly. CNVs are an important cause of fetal ventriculomegaly and CMA should be offered to all fetuses with ventriculomegaly, regardless of the degree of ventriculomegaly or whether combined with other structural anomalies.


Revealing neuronal function through microelectrode array recordings.
Microelectrode arrays and microprobes have been widely utilized to measure neuronal activity, both in vitro and in vivo. The key advantage is the capability to record and stimulate neurons at multiple sites simultaneously. However, unlike the single-cell or single-channel resolution of intracellular recording, microelectrodes detect signals from all possible sources around every sensor. Here, we review the current understanding of microelectrode signals and the techniques for analyzing them. We introduce the ongoing advancements in microelectrode technology, with focus on achieving higher resolution and quality of recordings by means of monolithic integration with on-chip circuitry. We show how recent advanced microelectrode array measurement methods facilitate the understanding of single neurons as well as network function.


Interactions of Perfluorooctanesulfonate and 6:2 Chlorinated Polyfluorinated Ether Sulfonate with Human Serum Albumin: A Comparative Study.
6:2 Chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) possesses a similar structure to perfluorooctanesulfonate (PFOS) and is the third most important polyfluoroalkyl/perfluoroalkyl substance (PFAS) found in the general population of China. Studies have indicated that 6:2 Cl-PFESA exhibits a stronger bioaccumulative and toxicological potential than PFOS and is thus of considerable environmental concern. Here, the binding characteristics of PFOS and 6:2 Cl-PFESA to human serum albumin (HSA) were explored based on in vitro and in silico methods. In the cell uptake assays, supplementation of HSA in the culture medium hindered diffusion of PFOS and 6:2 Cl-PFESA from the medium into cells. With the addition of 0.5, 10, and 200 μM HSA in the culture medium, the PFOS concentration in cells decreased by 21.4%, 78.1%, and 92.8%, whereas the 6:2 Cl-PFESA concentration in cells decreased by 28.4%, 84.4%, and 93.9%, respectively. Although no statistically significant difference between the reduction of PFOS and 6:2 Cl-PFESA was observed with 200 μM HSA in medium, the significant decrease in cellular 6:2 Cl-PFESA than PFOS after addition of 0.5 and 10 μM HSA implied that 6:2 Cl-PFESA had a stronger binding affinity than PFOS to HSA. Ultrafiltration centrifugation also suggested that 6:2 Cl-PFESA (Kd = 16.7 μM) had a higher affinity than PFOS (Kd = 30.7 μM) to HSA, though the binding molar ratios were similar, with 1 M HSA binding to 3-4 M PFOS/6:2 Cl-PFESA. Limited proteolysis further identified the core HSA peptides that bind to PFOS (peptide II, aa 189-457) and 6:2 Cl-PFESA (peptide I, aa 39-310). Using purified core peptides, 6:2 Cl-PFESA showed a stronger binding affinity than PFOS to both peptides I and II. The binding modes indicated that the chlorine and oxygen atoms in 6:2 Cl-PFESA were likely responsible for its preferential binding to Sudlow site I than to Trp214 or Sudlow site II, with the latter being the optimal binding site for PFOS. Overall, the stronger binding affinity of 6:2 Cl-PFESA to HSA may contribute to its higher bioaccumulation potential than PFOS.


Hepatitis B surface antigen seroconversion is associated with favourable long-term clinical outcomes during lamivudine treatment in HBeAg-negative chronic hepatitis B patients.
The aims of this study were to assess hepatitis B surface antigen (HBsAg) seroconversion and to determine its impact on the natural course of the disease in patients with HBeAg-negative chronic hepatitis B (CHB) during lamivudine (LMV) treatment. A total of 183 consecutive patients with HBeAg-negative CHB who were treated with LMV were included in the study. Data were retrospectively collected from outpatient visit charts. The primary endpoint was HBsAg seroconversion to anti-HBs. The secondary endpoint was to determine the development of cirrhosis. Loss of HBsAg was confirmed in 10 patients and seroconversion to anti-HBs in nine patients during LMV treatment or after its discontinuation. HBsAg seroconversion was achieved on-treatment in four patients after a median treatment duration of 30 months and off-treatment in the remaining five patients in a median 61 months after LMV discontinuation. The cumulative probability of HBsAg seroconversion increased from 0.6% at 1 year and 1.9% at 5 years to 21.5% at 10 years of LMV during and after LMV treatment. HBsAg clearance was preceded by undetectable serum hepatitis B virus (HBV) DNA. The majority of the patients responding to treatment had undetectable HBV DNA levels at 24 weeks of treatment. The cumulative probability of LMV resistance increased from 2.2% at 1 year to 37.3% at 5 years. No baseline parameter predicting either HBsAg seroconversion or the emergence of LMV resistance was identified. None of the patients with HBsAg seroconversion experienced virological breakthrough or disease progression during the follow-up period. These results indicate that HBsAg seroclearance can occur in patients with HBeAg-negative CHB under LMV therapy and predicts better clinical outcome.


In Six-month-old Infants, Prenatal Exposure to Maternal Anxiety is Associated with Less Developed Smooth Pursuit Eye Movements: An Initial Study.
There are an increasing number of reports suggesting an association between maternal anxiety experienced during pregnancy and adverse outcomes of the offspring. However, exploration of the biological changes in the brain that mediate that relationship has been hampered by the lack of appropriate biomarkers. This report represents an initial step exploring whether a potential infant biomarker, smooth pursuit eye movements, may be associated with prenatal exposure to maternal anxiety. Blinded cross-sectional study. Department of Psychiatry, University of Colorado School of Medicine. Data collected from July 2011 to May 2012. Forty-three infants including 34 whose prenatal maternal anxiety status was identified (12 with a known maternal prenatal anxiety diagnosis and 22 without) had eye movements recorded during a smooth pursuit eye movement task at four and/or six months of age. At 6 months of age, infants with prenatal exposure to maternal anxiety, compared to infants without such exposure, spent a higher percentage of time utilizing smooth pursuit (t=2.7, df=24, P=.013), had longer duration of smooth pursuit uninterrupted by saccades (t=2.5, df=24, P=.019), and had decreased frequency of forward saccades (t=3.8, df=24, P=.001). No differences between groups were identified at 4 months of age. Smooth pursuit abnormalities may, at six months of age, be a potential biomarker for prenatal maternal anxiety exposure.


IL-17A reprograms intestinal epithelial cells to facilitate HIV-1 replication and outgrowth in CD4+ T cells.
The crosstalk between intestinal epithelial cells (IECs) and Th17-polarized CD4+ T cells is critical for mucosal homeostasis, with HIV-1 causing significant alterations in people living with HIV (PLWH) despite antiretroviral therapy (ART). In a model of IEC and T cell co-cultures, we investigated the effects of IL-17A, the Th17 hallmark cytokine, on IEC ability to promote de novo HIV infection and viral reservoir reactivation. Our results demonstrate that IL-17A acts in synergy with TNF to boost IEC production of CCL20, a Th17-attractant chemokine, and promote HIV trans-infection of CD4+ T cells and viral outgrowth from reservoir cells of ART-treated PLWH. Importantly, the Illumina RNA-sequencing revealed an IL-17A-mediated pro-inflammatory and pro-viral molecular signature, including a decreased expression of type I interferon (IFN-I)-induced HIV restriction factors. These findings point to the deleterious features of IL-17A and raise awareness for caution when designing therapies aimed at restoring the paucity of mucosal Th17 cells in ART-treated PLWH.


Changes in cervical dysplasia, carcinoma in situ, and cervical cancer after expanding the National Cancer Screening Program to younger women in Korea.
The National Cancer Screening Program of South Korea for cervical cancer was expanded from women aged ≥30 years to women aged ≥20 years in 2016. This study investigated the effect of this policy on occurrence rates of cervical dysplasia, carcinoma in situ, and cervical cancer in women in their twenties. The National Health Information Database for the years 2012-19 was used. The outcome measures were monthly occurrence rates of cervical dysplasia, cervical carcinoma in situ, and cervical cancer. An interrupted time series analysis was performed to investigate whether the number of occurrences changed after policy implementation. For cervical dysplasia, a pre-intervention decreasing trend of 0.3243 per month (P-value < .0001) was found. The post-intervention trend did not differ significantly, although the slope increased at a rate of 0.4622 per month (P-value < .0001). For carcinoma in situ, a trend of increase at 0.0128 per month (P-value = .0099) was seen before policy implementation. The post-intervention trend did not escalate, but the slope showed an increasing trend of 0.0217 per month (P-value < .0001). For cervical cancer, no significant trend was present before intervention. Occurrences of cervical cancer escalated at a rate of 0.0406 per month (P-value < .0001) after policy implementation, and the slope also showed an increasing trend at a rate of 0.0394 per month (P-value < .0001). Expanding the target population for cervical cancer screening increased detection rates for cervical cancer in women aged between 20 and 29 years.


General Backward Model to Identify the Source for Contaminants Undergoing Non-Fickian Diffusion in Water.
Pollutant source identification (PSI) has been conducted for four decades for tracking Fickian diffusive pollutants, while PSI for non-Fickian diffusion, well-documented in aquifers and rivers, requires novel, predictive models. To enable PSI for non-Fickian diffusive pollutants, this study derived a general backward model using the fractional-adjoint approach in sensitivity analysis for dissolved contaminants with transport governed by the spatiotemporal fractional advection-dispersion equation (fADE). The backward fADE contains a self-adjoint time-fractional term for subdiffusion and direction-dependent, non-self-adjoint space-fractional terms for superdiffusion. Field applications showed that the resultant backward location probability density function identified the point source location in all three test cases, one alluvial aquifer and two rivers. The backward model and boundary conditions derived in this study made it possible to reliably and efficiently backtrack pollutants (and may include other constituents, such as bedload) undergoing mixed sub- and superdiffusion in natural aquatic systems. The classical PSI model, however, underestimated the source location since it did not account for solute retention and preferential flow. In addition, the measured tracer snapshots (if available before PSI) can enhance the parameter predictability and improve the applicability of backward fADE PSI. Most importantly, a spatially variable dispersion coefficient is needed in the backward fADE since PSI is most likely scale dependent in natural hydrologic systems.


[Multispiral computed tomography in diagnosis of tumors of the mammary gland].
For the first time, results of multispiral computed tomography (MSCT) with intravenous contrast enhancement in diagnosis of difficult case of breast tumors are presented. This method permits localization and staging of tumor. Contrast enhancement aids to reveal small tumors (less 1 cm). Thin sections and algorithm of high image resolution permit to diagnose microcalcinates which are early and important symptoms of malignant tumor. Evaluation of state of regional lymph nodes, analysis of bones permits to evaluate generalization of the process. MSCT-mammography may be used as amplifying method in diagnosis of breast diseases. This method is also indicated in atypical location of cancer. Further studies of MSCT-mammography permit to increase diagnostic value of this method.


Identification of denitrifier strain T1 as Thauera aromatica and proposal for emendation of the genus Thauera definition.
Bacterial strain, T1, originally isolated by P.J. Evans on the basis of its capacity for toluene degradation under denitrifying conditions, has been classified as Thauera aromatica. In a comprehensive study of strains of this species, it was found that the cells have a different type of flagellar insertion from that of cells of the type species of the genus, Thauera selenatis, suggesting the convenience of an emendation of the description of the genus Thauera. Further studies on a larger collection of strains with the above characteristics may serve in the future as the basis for the creation of a new generic designation.


Effect of omalizumab as add-on therapy on asthma-related quality of life in severe allergic asthma: a Brazilian study (QUALITX).
To assess the impact of omalizumab as an add-on therapy to standard treatment with inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA) on asthma-related quality of life (QoL) in patients with severe allergic asthma. This was a 20-week, randomized, open-label, study involving Brazilian patients (>12 years) with severe persistent allergic asthma inadequately controlled despite regular treatment with, at least, ICS (≥500 μg/day fluticasone or equivalent) + LABA. The primary objective was to assess the mean change from baseline in overall Asthma-related Quality of Life Questionnaire (AQLQ) score in omalizumab-treated patients compared with the control group. Secondary outcome measures included rescue medication use, incidence of asthma exacerbations, perception of treatment efficacy among patients, mean change from baseline in AQLQ score, and >1.5-point increase in overall AQLQ score. In the omalizumab group, overall AQLQ score was 3.2 (0.9) (mean [SD]) at baseline and 4.4 (1.3) at week 20 versus 3.0 (1.0) at baseline and 3.0 (1.1) at week 20 in the control group. Mean change from baseline on overall AQLQ score at week 20 in the omalizumab group was 1.2 (0.2) versus 0 (0.1) in the control group, showing a significant increase in scores from baseline in the omalizumab group (p < .001). There was also a statistically significant difference (p < .001) in the number of patients who showed a >1.5-point increase from baseline in overall AQLQ score after 20 weeks, thus indicating a better QoL in the omalizumab group. There was no significant difference with respect to the use of rescue medication, incidence of asthma exacerbation, and adverse events between treatment groups. The global evaluation of treatment effectiveness was significantly better for omalizumab (p < .001). Omalizumab was well tolerated and significantly improved the overall AQLQ score. Hence, it is a potential add-on therapy for severe persistent allergic asthma not controlled by standard prescribed treatment in Brazilian patients.


Longitudinal study of the profile and predictors of left ventricular mass regression after stentless aortic valve replacement.
The aim of this study was to evaluate the long-term profile and determine the factors that would influence the effect and rate of ventricular mass regression with time after aortic valve replacement with a stentless or a homograft valve. We studied 300 patients during a 10-year period with at least a year of follow-up with a total of 1,273 serial echocardiographic measurements. Left ventricular mass was calculated from M-mode recordings and indexed to body surface area. Longitudinal data analysis was performed using a linear mixed effects model. The mean age (+/- standard deviation) was 65 (+/-14) years, consisting of 216 (72%) males. A stentless valve was implanted in 156 (52%), and a homograft in 144 (48%). The median time (interquartile range) to follow-up was 4.7 (2.8 to 6.6) years. The greatest rate of left ventricular mass regression occurred in the first year after surgery. On multivariable modeling, independent predictors of left ventricular mass were valve size (p = 0.011), left ventricular function (moderate impairment, p = 0.418; severe impairment, p = 0.011), and baseline left ventricular mass (middle tercile, p < 0.001; highest tercile, p < 0.001). Only baseline ventricular mass influenced the rate of subsequent left ventricular mass regression; the greatest rate of regression occurred in patients with the highest baseline values of ventricular mass (p < 0.001). The greatest rate of left ventricular mass regression occurs in the first year with baseline left ventricular mass as the strongest predictor and the only identified variable that influenced the rate of left ventricular mass regression.


Increased production of superoxide anion contributes to dysfunction of the arteriovenous fistula.
Vascular access dysfunction causes morbidity in hemodialysis patients. This study examined the generation and pathobiological significance of superoxide anion in a rat femoral arteriovenous fistula (AVF). One week after AVF creation, there was increased production of superoxide anion accompanied by decreased total superoxide dismutase (SOD) and Cu/Zn SOD activities and induction of the redox-sensitive gene heme oxygenase-1. Immunohistochemical studies of nitrotyrosine formation demonstrated that peroxynitrite, a product of superoxide anion and nitric oxide, was present in increased amounts in endothelial and smooth muscle cells in the AVF. Because uncoupled NOS isoforms generate superoxide anion, and NOS coupling requires tetrahydrobiopterin (BH(4)) as a cofactor, we assessed NOS uncoupling by determining the ratio of BH(4) to dihydrobiopterin (BH(2)); the BH(4)-to-BH(2) ratio was markedly attenuated in the AVF. Because Src is a vasculopathic signaling species upstream and downstream of superoxide anion, such expression was evaluated; expression of Src and phosphorylated Src was both markedly increased in the AVF. Expression of NADPH oxidase (NOX) 1, NOX2, NOX4, cyclooxygenase (COX) 1, COX2, p47(phox), and p67(phox) was all unchanged, as assessed by Western analyses, thereby suggesting that these proteins may not be involved in increased production of superoxide anion. Finally, administration of tempol, a superoxide anion scavenger, decreased neointima formation in the juxta-anastomotic venous segment and improved AVF blood flow. We conclude that the AVF exhibits increased superoxide anion generation that may reflect the combined effects of decreased scavenging by SOD and increased generation by uncoupled NOS, and that enhanced superoxide anion production promotes juxta-anastomotic stenosis and impairs AVF function.


Efficacy of a sequential treatment by belimumab in monogenic systemic lupus erythematosus.
The objective of the study was to report the safety and potential therapeutic effect of belimumab in monogenic systemic lupus erythematosus (SLE). Consecutive children with monogenic SLE treated with belimumab were evaluated retrospectively. Response parameters assessment was completed at the time of initiation of belimumab, at 6 months, and last follow-up visit. Response parameters comprised physician global assessment (physician GA) and parent global assessment (parent GA), global disease activity as measured by SLE disease activity index (SLEDAI), and daily glucocorticoids dose. Undesirable events affecting patients during treatment were also collected. Six children with monogenic SLE proved by genetic testing (five patients with C1q deficiency and one patient with deoxyribonuclease II (DNase II) deficiency), failed glucocorticoids and sequential immunosuppressive medications. Belimumab was added to glucocorticoids and current immunosuppressive medications. The main indications for belimumab initiation were mucocutaneous disease, arthritis, and inability to taper glucocorticoids. All patients tolerated belimumab infusion. No serious events were reported. However, one patient was lost to follow-up and died because of sepsis. Compared to the baseline values, there was an improvement in physician GA, parent GA, and SLEDAI, and a notable reduction in the need of daily corticosteroids. However, there were no significant changes in the complement and ds-DNA antibody levels. Belimumab can be considered as an adjunctive therapeutic option for patients with refractory monogenic SLE. Further follow-up and more patients needed to confirm this finding and a larger prospective study is required for more definitive conclusions.


Antimicrobial susceptibility, virulence determinant carriage and molecular characteristics of Staphylococcus aureus isolates associated with skin and soft tissue infections.
A better understanding of the antimicrobial susceptibility, carriage of virulence determinants and molecular characteristics of Staphylococcus aureus isolates associated with skin and soft tissue infections (SSTIs) may provide further insights related to clinical outcomes with these infections. From January 2012 to September 2013, a total of 128 non-duplicate S. aureus isolates were recovered from patients with SSTIs. All 128 S. aureus SSTI isolates carried at least five virulence genes tested. Virulence genes detected among at least 70% of all tested isolates included hld (100%), hla (95.3%), icaA (96.9%), clf (99.2%), sdrC (79.7%), sdrD (70.3%), and sdrE (72.7%). The prevalence of MRSA isolates with 10 virulence genes tested (54.4%, 31/56) was significantly higher than that among MSSA isolates (35.2%, 25/71) (p<0.05). The positive rates of seb, sen, sem, sdrE and pvl among MRSA isolates were significantly higher than among MSSA isolates (p<0.05). ST7 and ST630 accounting for 10.9% were found to be the predominant STs. The most prevalent spa type was t091 (8.6%). MRSA-ST59-SCCmec IV was the most common clone (12.3%) among MRSA isolates whereas among MSSA isolates the dominant clone was MSSA-ST7 (15.5%). Six main clonal complexes (CCs) were found, including CC5 (52.3%), CC7 (11.7%), CC59 (8.6%), CC88 (6.3%), CC398 (4.7%), and CC121 (3.1%). A higher carriage of seb and sec was found among CC59 isolates. In comparison to CC5 and CC7 isolates, those with the highest carriage rates (>80.0%) of sdrC and sdrD, CC59 isolates had lower prevalence of these two virulence genes. All CC59 isolates were susceptible to gentamicin and trimethoprim/sulfamethoxazole, while CC5 and CC7 isolates had resistance rates to these two antimicrobials of 25.4% and 20.9%, and 40.0% and 40.0%, respectively. The resistance rates for tetracycline, clindamycin, and erythromycin among CC5 isolates were lower than among CC7 and CC59 isolates. In conclusion, the molecular typing of S. aureus SSTI isolates in the present study showed considerable heterogeneity. ST7 and ST630 became prevailing clones. Different S. aureus clones causing SSTIs were associated with specific antimicrobial resistance and virulence gene profiles.


Relationship, communication, and efficiency in the medical encounter: creating a clinical model from a literature review.
While there is consensus about the value of communication skills, many physicians complain that there is not enough time to use these skills. Little is known about how to combine effective relationship development and communication skills with time management to maximize efficiency. Our objective was to examine what physician-patient relationship and communication skills enhance efficiency. We conducted searches of PubMed, EMBASE, and PsychINFO for the date range January 1973 to October 2006. We reviewed the reference lists of identified publications and the bibliographies of experts in physician-patient communication for additional publications. From our initial group of citations (n = 1146), we included only studies written in English that reported original data on the use of communication or relationship skills and their effect on time use or visit length. Study inclusion was determined by independent review by 2 authors (L.B.M. and D.C.D.). This yielded 9 publications for our analysis. The 2 reviewers independently read and classified the 9 publications and cataloged them by type of study, results, and limitations. Differences were resolved by consensus. Three domains emerged that may enhance communication efficiency: rapport building, up-front agenda setting, and acknowledging social or emotional clues. Building on these findings, we offer a model blending the quality-enhancing and time management features of selected communication and relationship skills. There is a need for additional research about communication skills that enhance quality and efficiency.


Effects of Helicobacter pylori infection and long-term proton pump inhibitor use on enterochromaffin-like cells.
Excessive release of gastrin leads to hypertrophy and hyperplasia of enterochromaffin-like cells (ECL) and prolonged stimulation of these cells causes functional impairment. The purpose of this study was to investigate the effect of Helicobacter pylori (H. pylori) infection and long-term proton pump inhibitors (PPI) use on ECL cells. Fifteen patients who underwent endoscopy because of dyspeptic symptoms were enrolled in the present study. Biopsies were taken from corpus and antrum and existence of H. pylori was investigated with culture, cytology and CLOtest. The patients were divided into 3 groups. Group-A: H. pylori-negative, never treated previously with PPI; Group-B: H. pylori-positive, never treated previously with PPI; and group-C: H. pylori-negative and continuously treated with PPI for more than 6 months before the subject recruitment period. The features of ECL cell in oxyntic glands were examined with electron microscopy on biopsy specimens. ECL cells were completely normal in Group A. In group B, moderate hyperplasia and vacuolization was seen in ECL cells. In group C, ECL cell hyperplasia was observed and vacuoles with greater amounts of granules in enlarged vesicles were found more intensely in cytoplasm. The use of PPI for a long period of time and presence of H. pylori infection are risk factors for ECL hyperplasia.


Design, Synthesis of Novel 1,2,3-Triazole Pendent Quinazolinones and Their Cytotoxicity against MCF-7 Cell Line.
A library of 6-(((1-(substitutedphenyl)-1H-1,2,3-triazol-4-yl)methyl) amino)-3-methylquinazolin-4(3H)-one analogues synthesized from Isatin precursor through a series of nitration, reduction, hydrolysis, cyclization and click reaction. The structures of compounds were characterized by spectral data including IR, 1 H-NMR, 13 C NMR and Mass. The novel quinazolinone - 1,2,3-triazoles were screened for their cytotoxicity against the human breast adenocarcinoma cell lines MCF-7 by MTT assay. 4-Isopropyl and 2-bromo substituted analogues executed high activity against MCF-7 cell line with IC50 value of 10.16±0.07 μM and 11.23±0.20 μM compared to the Doxorubicin whose IC50 value is 10.81±0.03 μM. The activity of remaining compounds is good to moderate. Further, the molecular docking studies against the crystal structure of Epidermal Growth Factor Receptor delivered the best binding energies and the interactions such as H-bond and hydrophobic are inevitable. The predicted pharmacokinetic properties results showed that these compounds have more drug likeness properties.


Detection of pneumococci in respiratory secretions: clinical evaluation of gentamicin blood agar.
The use of sheep blood agar containing 5 microng of gentamicin per ml has been suggested as a means of selectively isolating Streptococcus pneumoniae from respiratory secretions. We have tested this method, in parallel with standard methods, on 844 respiratory specimens in a clinical laboratory and have confirmed that the yield of pneumococci can be increased approximately 40% by using agar containing gentamicin. However, since the antibiotic suppresses the growth of staphylococci, group A streptococci, and gram-negative bacilli, gentamicin agar cannot be used as a replacement for the standard method. The requirement for duplicate plating raises the cost per additional pneumococcal isolate to prohibitive amounts. Although the method is useful in studies designed to isolate only pneumococci, it cannot be recommended for the routine clinical laboratory. An unanticipated observation from our study is that the yield of pneumococci in respiratory secretions can be increased 10-fold simply by screening sputum for the presence of leukocytes using the Gram stain. This is in agreement with results reported from other laboratories.


Current concept in the treatment of atopic dermatitis.
Atopic dermatitis (AD) is a common, highly pruritic, and chronic, relapsing, inflammatory skin disorder. There are several modalities, which have been used in the treatment of AD, but current standard therapies have variable efficacy and potential systemic side effects. We reviewed the literature, recent patents and summarized the effective and potential effective treatment alternatives and constituted four categories and steps to achieve the best treatment modalities for each patient with AD. Supportive care, avoidance of skin irritants and allergens, topical creams, phototherapy and systemic drugs are still the best choices of treatment. Optimal effective treatment agents with low side effects are still requested.


Genetic Control of Gonadotrop Differentiation in the Platyfish, Xiphophorus maculatus (Poeciliidae).
A sex-linked gene controlling the age at which the gonadotrops of the pituitary gland differentiate has been discovered in Xiphophorus maculatus. Males homozygous for early differentiation become sexually mature between 10 and 16 weeks; those homozygous for late maturation between 22 and 40 weeks. Heterozygotes are intermediate. Since growth rate decreases when testes mature. the two classes of males differ significantly in adult size.


Discontinuities and unsynapsed regions in meiotic chromosomes have a cis effect on meiotic recombination patterns in normal human males.
During meiosis, homologous chromosome pairing is essential for subsequent meiotic recombination (crossover). Discontinuous chromosome regions (gaps) or unsynapsed chromosome regions (splits) in the synaptonemal complex (SC) indicate anomalies in chromosome synapsis. Recently developed immunofluorescence techniques (using antibodies against SC proteins and the crossover-associated MLH1 protein) were combined with fluorescence in situ hybridization (using centromere-specific DNA probes) to identify bivalents with gaps/splits and to examine the effect of gaps/splits on meiotic recombination patterns during the pachytene stage of meiotic prophase from three normal human males. Gaps were observed only in the heterochromatic regions of chromosomes 9 and 1, with 9q gaps accounting for 90% of these events. Most splits were also found in chromosomes 9 and 1, with 58% of splits occurring on 9q. Gaps and splits significantly altered the distribution of MLH1 foci on the SC. On gapped SC 9q, the frequency of MLH1 foci was decreased compared with controls, and single 9q crossovers tended toward a more distal distribution. Furthermore, the larger the gap the more distal the location of the MLH1 focus closest to the q arm's telomere. MLH1 foci on split SC 9 had distributions similar to those of gapped SC 9; however, splits did not change the frequencies of MLH1 foci on SC 9. This is the first demonstration that gaps and splits have an effect on meiotic recombination in humans.


In vitro and in vivo evaluation of a humanized anti-APRIL antibody.
A proliferation-inducing ligand (APRIL) is overexpressed in many cancers such as colorectal, gastric and liver. Silence APRIL gene or neutralize its expression may serve as therapeutic strategies to manage those cancers. Current phase I clinical trial shows that heavily pretreated patients were well tolerated high dose intravenous infusion. Herein, we report a humanized antibody (Ab) that neutralizes APRIL protein and inhibits cancer cell proliferation both in vitro and in vivo. The Ab was generated through conjugating foreign immunodominant T-helper cell (Th) epitopes to the N- or C-terminal of four soluble APRIL mutants. In vitro anti-proliferation effects were evaluated in both Raji and Jurkat cell lines. In vivo inhibition of tumor growth was determined in a tumor xenograft animal model with green fluorescent protein (GFP) positive Raji cell line. In vitro data demonstrated that this Ab significantly inhibited both Raji and Jurkat cell proliferation in a dose-dependent manner. The molecular imaging data demonstrated in vivo tumor growth delay when animals were treated with Ab. In conclusion, we have developed a humanized anti-APRIL Ab, which is effective in inhibiting tumor cell proliferations both in vitro and vivo. The humanized Ab has potential to reduce the immunoresponse in the clinical situation. This Ab also can be used in other APRIL mediated diseases such as Sjogren syndrome, multiple sclerosis and systemic lupus erythematosus.


[Familial amyloidotic polyneuropathy type I].
Familial amyloidotic polyneuropathy type I is an autosomal dominant inherited disorder characterized by progressive peripheral and autonomic neuropathy, associated with neural and systemic amyloid deposits. The abnormality usually lies in the transthyretin (TTR) gene. We report a 25 years old man with 18 months history of dysesthesias and pain in the toes, abnormal micturition and sexual dysfunction. Neurophysiologically studies disclosed a sensory-motor axonal polyneuropathy. Autonomic tests showed sympathetic and parasympathetic involvement. An electron micrograph of sural nerve revealed amyloid fibrils in the endoneurium. His mother died after a clinical history suggestive, in retrospect, of familial amyloidotic polyneuropathy type I. The clinical and genetic analysis of this cause of polyneuropathy are discussed.