Research on Safety Helmet Detection Algorithm Based on Improved YOLOv5s.
Safety helmets are essential in various indoor and outdoor workplaces, such as metallurgical high-temperature operations and high-rise building construction, to avoid injuries and ensure safety in production. However, manual supervision is costly and prone to lack of enforcement and interference from other human factors. Moreover, small target object detection frequently lacks precision. Improving safety helmets based on the helmet detection algorithm can address these issues and is a promising approach. In this study, we proposed a modified version of the YOLOv5s network, a lightweight deep learning-based object identification network model. The proposed model extends the YOLOv5s network model and enhances its performance by recalculating the prediction frames, utilizing the IoU metric for clustering, and modifying the anchor frames with the K-means++ method. The global attention mechanism (GAM) and the convolutional block attention module (CBAM) were added to the YOLOv5s network to improve its backbone and neck networks. By minimizing information feature loss and enhancing the representation of global interactions, these attention processes enhance deep learning neural networks' capacity for feature extraction. Furthermore, the CBAM is integrated into the CSP module to improve target feature extraction while minimizing computation for model operation. In order to significantly increase the efficiency and precision of the prediction box regression, the proposed model additionally makes use of the most recent SIoU (SCYLLA-IoU LOSS) as the bounding box loss function. Based on the improved YOLOv5s model, knowledge distillation technology is leveraged to realize the light weight of the network model, thereby reducing the computational workload of the model and improving the detection speed to meet the needs of real-time monitoring. The experimental results demonstrate that the proposed model outperforms the original YOLOv5s network model in terms of accuracy (Precision), recall rate (Recall), and mean average precision (mAP). The proposed model may more effectively identify helmet use in low-light situations and at a variety of distances.


Derepression of F factor function in Salmonella typhimurium.
In Salmonella typhimurium LT2 the F factor of Escherichia coli K-12 replicates normally but is repressed; Flac+ cells give no visible lysis on solid media with male-specific phages, low frequency transfer of Flac+ (0.001-0.007 per donor cell), few f2 infective centers (0.002-0.006 per cell), and they propagate male-specific phages to low titers. Thus they display a Fin+ (fertility inhibition) phenotype. This repression, owing to pSLT, a 60 Mdal plasmid normally resident in S. typhimurium, was circumvented by the following materials: (i) Flac+ plasmids from E. coli with mutations in finP or traO; (ii) a S. typhimurium line which had been cured of pSLT; (iii) pKZl, a KmR plasmid in the same Inc group as pSLT, which caused expulsion of pSLT and made Fin- lines; (iv) F-Fin- mutants which originated spontaneously and which are present in most Hfr strains of S. typhimurium. Strains which are derepressed for F function by the above methods give visible lysis on solid media with male-specific phages, ca. 1.0 Lac+ recombinants per donor cell in conjugal transfer, ca. 0.82 f2 infective centers per cell, over 80% of cells with visible F pili, and propagation of male-specific phages to high titer. These data confirm earlier observations that pSLT represses F by the FinOP system. In addition, it shows that there is no other mechanism which represses F function in S. typhimurium. If donor function is derepressed by one of the above methods, and if rough recipient strains are used, F-mediated conjugation in S. typhimurium LT2 is as efficient as in E. coli K-12.


Effects of hemodialysis on hearing threshold.
71 chronic renal failure patients undergoing long-term hemodialysis were evaluated for the effects of a dialysis event on hearing function. Osmotically active serum constituents were examined for relationship to fluctuating hearing threshold levels. Reliabiliity of hearing levels was found to be better in those patients tested without an intervening dialysis event. Those patients tested before and after hemodialysis demonstrated greater hearing fluctuation than those patients evaluated between dialysis events. This threshold fluctuation was unrelated to serum urea nitrogen, creatinine, K+, Na+, Ca++, or glucose. It was concluded that hearing test reliability in dialyzing renal patients is resonably good, but test results are likely to be more consistent if testing is accomplished a number of hour after a given dialysis event. Contrary to a number of reports in the recent literature, no direct relationship between hearing level fluctuation and fluctuation in individual osmotically active serum constituents appeared to be present.


Identification of a peptide binding protein that plays a role in antigen presentation.
The helper T-cell response to globular proteins appears, in general, to require intracellular processing of the antigen, such that a peptide fragment containing the T-cell antigenic determinant is released and transported to and held on the surface of an Ia-expressing, antigen-presenting cell. However, the molecular details underlying these phenomena are largely unknown. The means by which antigenic peptides are anchored on the antigen-presenting cell surface was investigated. A cell surface protein is identified that was isolated by its ability to bind to a 24-amino acid peptide fragment of pigeon cytochrome c, residues 81-104, containing the major antigenic determinant for B10.A mouse T cells. This peptide binding protein, purified from [35S]methionine-labeled cells, appears as two discrete bands of approximately equal to 72 and 74 kDa after NaDodSO4/PAGE. The protein can be eluted from the peptide affinity column with equivalent concentrations of either the antigenic pigeon cytochrome c peptide or the corresponding nonantigenic peptide of mouse cytochrome c. However, it does not bind to the native cytochromes c, either of pigeon or mouse, and thus the protein appears to recognize some structure available only in the free peptides. This protein plays a role in antigen presentation as evidenced by the ability of rabbit antibodies raised against it to block the activation of an antigen-specific T-cell hybrid by antigen-presenting cells and pigeon cytochrome c. Its expression is not major histocompatibility complex-restricted in that the blocking activity of the antisera can be absorbed on spleen cells from mice of different haplotypes. This peptide binding protein can be isolated from a variety of cell types, including B cells, T cells, and fibroblasts. The anchoring of processed peptides on the cell surface by such a protein may play a role in antigen presentation--facilitating the interaction of antigenic peptides with Ia and/or the T-cell receptor.


Repeated short-term daily exercise ameliorates oxidative cerebral damage and the resultant motor dysfunction after transient ischemia in rats.
Long-term exercise prior to brain ischemia enhances the activities of antioxidant enzymes and leads to a significant reduction in brain damage and neurological deficits in rats subjected to transient middle cerebral artery occlusion. However, it has not been established whether relatively short-term exercise generates similar results following middle cerebral artery occlusion. We aimed to determine whether short-term exercise could reduce oxidative damage and prevent sensori-motor dysfunction. Male Wistar rats were subjected to perform daily exercise on a treadmill for 30 min at a speed of 15 m/min for 3 weeks, followed by a 90-min middle cerebral artery occlusion. Animals were assessed after middle cerebral artery occlusion for neurological deficits and sensori-motor function. Brain tissues were processed to evaluate infarct volume and oxidative damage. Oxidative stress was assessed using immunohistochemistry for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine. Antioxidant enzymes were evaluated using immunohistochemistry for thioredoxin and activity assay for superoxide dismutase. Exercise for 3 weeks decreased the severity of paralysis and impairment in forelimb motor coordination. Furthermore, exercise had effect on superoxide dismutase and reduced the infarct volume and the number of cells immunopositive for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine. Our results suggest that pre-conditioning treadmill exercise for 3 weeks is useful for ameliorating ischemia-induced brain injury.


Arginyl-glycyl-aspartic acid sequences and fibrinogen binding to platelets.
Human fibrinogen has an Arg-Gly-Asp-Ser (RGDS) sequence at residues 572-575 of its A alpha-chain. Although RGDS-containing peptides inhibit fibrinogen binding to stimulated platelets, these peptides also inhibit platelet binding of human fibrinogen fragment X and rat fibrinogen, which lack RGDS sequences corresponding to A alpha 572-575. Thus competition between free RGD-containing peptides and internal RGDS sequence at A alpha 572-575 is not the basis for their inhibition of fibrinogen binding to platelets. Addition of a Thr to the carboxy-terminus and an Asn to the amino-terminus of the RGDS sequence, the amino acids corresponding to A alpha 576 and 571 respectively, reduced the inhibitory potency of RGDS-containing peptides by fourfold to tenfold. Arg-Gly-Asp-Phe (RGDF) corresponds to A alpha 95-98, and the RGDF peptide was an effective inhibitor of fibrinogen binding, fourfold to fivefold more potent than RGDS. Thus, local primary structure may play an important role in regulating the capacity of RGD sequences in proteins to interact with specific adhesion receptors.


[Research progress of chemical constituents and biological activities of essential oil of Pistacia lentiscus].
Pistacia lentiscus,which belongs to foreign medicine resources,is widely distributed in the Mediterranean and Middle Eastern area. The essential oils are a mixture of several volatile compounds mainly monoterpenes and sesquiterpenes obtained from different parts of P. lentiscus by hydrodistillation. The variability of chemical composition,biological activities and content of essential oil is strongly affected by extraction technology,environmental and sex factors. It is indicated that essential oils of P. lentiscus have kinds of biological activities such as antibacterial,anticancer,anti-atherogenesis,antioxidant,anti-inflammatory and insecticidal activities.Many scholars hold the opinion that combination of different components with synergistic and/or additive actions should account for their biological activities. Due to its diverse efficacy and special taste,the essential oil of P. lentiscus has been extensively used in medicine,food and cosmetics industries. A mini review of chemical constituents and biological activities of essential oil of P. lentiscus in the past20 years is made here to provide valuable reference for the construction of " the Belt and Road".


Achieving behavioral control with millisecond resolution in a high-level programming environment.
The creation of psychophysical tasks for the behavioral neurosciences has generally relied upon low-level software running on a limited range of hardware. Despite the availability of software that allows the coding of behavioral tasks in high-level programming environments, many researchers are still reluctant to trust the temporal accuracy and resolution of programs running in such environments, especially when they run atop non-real-time operating systems. Thus, the creation of behavioral paradigms has been slowed by the intricacy of the coding required and their dissemination across labs has been hampered by the various types of hardware needed. However, we demonstrate here that, when proper measures are taken to handle the various sources of temporal error, accuracy can be achieved at the 1 ms time-scale that is relevant for the alignment of behavioral and neural events.


Antecedent events in amyotrophic lateral sclerosis.
To identify antecedent events contributing to the development of amyotrophic lateral sclerosis, we studied 25 amyotrophic lateral sclerosis patients in whom we tabulated the incidence of factors previously associated with motor neuron disease and compared the incidences with those found in 25 hospitalized patients and 25 normal people. More amyotrophic lateral sclerosis patients reported exposure to lead and mercury, participation in athletics, and consumption of large quantities of milk. Exposure to lead and mercury, athletic participation, and milk ingestion are possible risk factors that may predispose to the development of amyotrophic lateral sclerosis.


K562 erythroleukemia cells express cytokeratins 8, 18, and 19 and epithelial membrane antigen that disappear after induced differentiation.
The effects of differentiation-modulating drugs were studied on the expression of intermediate filaments (IFs) in the human K562 erythroleukemic cell line. The untreated cells contained typical cytoplasmic coiling bundles, positive for both vimentin and cytokeratin as judged by indirect immunofluorescence microscopy with monoclonal antibodies (Mabs). Some of the cells also showed bright immunoreactivity for epithelial membrane antigen (EMA), as revealed with a Mab and polyclonal antiserum. When exposed to hemin or to sodium butyrate, most of the cells became cytokeratin negative within 3 days and showed dispersion of vimentin fibrils. Upon exposure to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), the amount of both vimentin and cytokeratin appeared to be greatly increased within 3 days and was found both in dispersed cytoplasmic fibrils, in large spherical, eccentric aggregates, as well as in cytoplasmic fibrils in cells spreading on fibronectin. TPA induced a complete loss of proliferation, as judged by immunostaining with the Mab Ki-67. The effects of TPA were found to be irreversible and could be induced by only a short exposure to the drug. Western blotting analysis and monoclonal antibodies to individual cytokeratins revealed that untreated K562 cells expressed Mr 52,000 (No. 8), 46,000 (No. 18), and 40,000 (No. 19) cytokeratin polypeptides, which disappeared when the cells were exposed to hemin or to sodium butyrate to induce erythroid differentiation but were greatly enhanced when exposed to TPA. The monoclonal anti EMA antibody reacted in K562 cells with a single Mr 320,000 polypeptide that was also revealed in MCF-7 breast carcinoma cells. Human bone marrow cells or other leukemic cell lines with erythroid differentiation capacity (HEL and KG-1) did not contain cytokeratin- or EMA-immunoreactive cells, suggesting that in K562 cells these properties may rather represent abnormal cytodifferentiation or retrodifferentiation toward early embryonic mesenchymal cells, than a more general expression of epithelial features in human leukemic cells.


Accelerated pathway evolution in mouse-like rodents involves cell cycle control.
Rodents include both the cancer-susceptible short-lived mouse and the two unrelated cancer-resistant long-lived mole-rats. In this work, their genomes were analyzed with the goal to reveal pathways enriched in genes, which are more similar between the mole-rats than between the mouse and the naked mole-rat. The pathways related to cell cycle control were prominent. They include external signal transduction and all cell cycle stages. There are several stem cell pathways among them. The other enriched pathways involve ubiquitin-dependent protein degradation, immunity, mRNA splicing, and apoptosis. The ubiquitin-dependent protein degradation is a core of network of enriched pathways. However, this phenomenon is not specific for the mouse and the mole-rats. The other muroid species show features similar to the mouse, whereas the non-muroid rodents and the human show features similar to the mole-rats. The higher ratio of non-synonymous to synonymous nucleotide substitutions (dN/dS) indicates the accelerated evolution of revealed pathways in the muroid rodents (except the blind mole-rat). Paradoxically, the dN/dS averaged over the whole genome is lower in the muroids, i.e., the purifying selection is generally stronger in them. In practical sense, these data suggest caveat for using muroid rodents (mouse, rat, and hamsters) as biomedical models of human conditions involving cell cycle and show the network of pathways where muroid genes are most different (compared with non-muroid) from human genes. The guinea pig is emphasized as a more suitable rodent model for biomedical research involving cell cycle.


Two algorithms for the three-dimensional reconstruction of tomograms.
Three-dimensional (3-D) surface reconstructions provide a method to view complex anatomy contained in a set of computed tomography (CT), magnetic resonance imaging (MRI), or single photon emission computed tomography tomograms. Existing methods of 3-D display generate images based on the distance from an imaginary observation point to a patch on the surface and on the surface normal of the patch. We believe that the normalized gradient of the original values in the CT or MRI tomograms provides a better estimate for the surface normal and hence results in higher quality 3-D images. Then two algorithms that generate 3-D surface models are presented. The new methods use polygon and point primitives to interface with computer-aided design equipment. Finally, several 3-D images of both bony and soft tissue show the skull, spine, internal air cavities of the head and abdomen, and the abdominal aorta in detail.


Optimizing pumped insulin delivery.
The use of portable devices for the subcutaneous infusion of insulin may facilitate the attainment of improved glycemic control in selected patients with insulin-dependent diabetes mellitus. Successful use of a program of continuous subcutaneous insulin infusion requires patient cooperation and motivation, routine monitoring of glycemia, and attention to food intake and activity. This article describes an approach by which patients may optimize glycemic control utilizing a set of algorithms based on patient-determined blood glucose measurements. The algorithms permit programming the insulin infusion device to achieve the desired control.


Hormonal, auxological and clinical follow-up in children with connatal HIV infection. Personal records.
HIV infection and antiretroviral drugs have relevant endocrine implications, affecting growth and pubertal development. Moreover stature impairment cannot depend only on decreased hormonal secretion. We studied for 7 years growth, puberty, bone maturation, hormonal secretion [Growth Hormone (GH) basal and after stimulation with Clonidin and Insulin, Insulin-like Growth Factor 1 (IGF-1), Insulin-like Growth Factor Binding Protein 3 (IGFBP-3), FSH, LH- gonadic hormones axis, ACTH, Cortisol, TSH, fT4, T4, T3, anti-thyroid antibodies, Leptin] of 10 HIV-infected children. In 3 patients stature was <-2 SDS in the first 2 years and in prepubertal age, with intervals of improved growth. The weight was >2 SDS in 6 children, <-2 SDS in 1 girl, while the other 3 patients had a weight <-2SDS only in the first 2 years of life. Height growth velocity was >10 degrees Centile all over the years of follow-up in 9 patients, while weight growth velocity was pathological in 5. Leptinemia showed higher levels at the beginning of follow up: 0.82-11.68 ng/L (M+/-DS: 3.29+/-4.15) than at the end of the study: 0.2-3 ng/L (M+/-DS: 1.65+/-1.01). Leptin levels showed a statistically significant correlation with CD4/CD8 count (P: 0.010; r: 0.916) and with the CDC stage (P: 0.006; r: 0.937), meaning a strong link to the severity of the disease. A good clinical control of HIV infection can guarantee growth within physiological centile in most of HIV-infected children. Over all IGFBP-3 and IGF-1 are good markers of growth, more usable than GH.


[The underreporting of perinatal mortality: 10 years' experience of active surveillance in Barcelona].
Perinatal mortality is considered a good effectiveness health care indicator during pregnancy, deliver and early perinatal period. The aims of this investigation were to describe the magnitude and tendency of underreporting perinatal mortality in Barcelona, Spain from 1985 to 1994 and to determine underreporting predictive variables. Perinatal deaths between 1985 and 1994 were studied according to WHO international statistics criteria and deaths from 1988 to 1994 were also studied according to the WHO national statistics criteria. Sources of information were: Statistical Deaths Certificates and the Active Surveillance Registry that collect information about perinatal deaths directly from hospitals. A perinatal death was considered underreported if it was registered in the Active Surveillance Register but not in the Statistical Death Certificate. 24.5% perinatal deaths were underreported from 1985 to 1995 (according to international statistics criteria) and 24.9% from 1988 to 1994 (according national statistics criteria). In both periods underreporting decreased. Deaths in the first 24 hours of live (OR = 1.8; CI 95% = 1-3), newborns weight between 1,000 and 1,499 g (OR = 1.5; CI 95% = 0.6-3.8), hospitals with mortality registry (OR = 4; CI 95% = 2.2-7.1) and the first years of the study (OR = 0.7; CI 95% = 0.7-0.8) were predictive of underreporting. Underreporting perinatal deaths decreased during the study period. Deaths of newborns with low birth weight and who lived less than 24 hours were more underreported. The work developed by Active Surveillance Registry contributed to the decense of underreporting perinatal deaths.


Subchronic Toxicity of the New Iodine Complex in Dogs and Rats.
Background: Complexes of iodine (povidone-iodine and cadexomers) are among the most important antiseptics used in clinical and veterinary medicines. However, high local irritation activity and systemic toxicity limits their oral administration. The purpose of the study was to compare the effect of a new complex of iodine (PA, potentiator of anticancer antibiotics), in which iodine is coordinated by carbohydrates and polypeptides) on the organisms of rats and dogs treated orally with the drug for 30 days. Methods: Wistar rats and Beagle dogs served as experimental animal models. Effect of PA on the animal organism was examined through the measurements of hormones level changes, hematological and clinical chemistry parameters alterations, necropsy and histological examination. Results: The established maximum tolerated dose (MTD) of 2,000 mg/kg PA led to a decrease in the rate of body weight gain in male and female rats. Changes in hematological and certain biochemical parameters in rats at doses of 1,000 and 2,000 mg/kg were observed. Histological study of the thyroid gland revealed changes in the shape and size of the follicles along with colloid resorption. Administration of a half of MTD (180 mg/kg) and lower doses did not result in any change in dogs (thyroid-stimulating hormone, triiodothyronine, and thyroxine). Conclusions: The results of our study show that the pathogenetic action of PA takes place along the path of induction of an inflammatory response with the development of thyrotoxicosis, rather than hypothyroidism. The mechanism of induction of an inflammatory response is also confirmed by histological studies of lesions of the thyroid gland and testes in rats (Figure S1). The no-observed-adverse-effect level (NOAEL) of PA is estimated to be 180 mg/kg (or iodine 22.8 mg/kg) in dogs, which is equivalent to 100 mg/kg (or iodine 12.3 mg/kg) in humans.


Simultaneous measurement of liquid surface tension and contact angle by light reflection.
We present an optical method of simultaneous measurement of liquid surface tension, contact angle, and the curved liquid surface shape, which uses the light reflection from this liquid surface due to the wettability. When an expanded and collimated laser beam is incident upon the curved liquid surfaces vertically, the special light reflection pattern, which includes a dark central region and a bright field outside, was observed. A critical spot on the curved liquid surface was found, and the dark field distribution is related to both the width of incidence beam and this critical spot. In our experiment, the different dark field distribution patterns were recorded when the width of the incidence beam changed. The liquid surface tension, contact angle, and the liquid surface shape were measured simultaneously. The proposed method is a new effective tool for present wetting characterization methods.


Autoantibodies in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease in which the predominant autoantibodies are antinuclear antibodies (ANA) reactive with DNA and histones, and antibodies reactive with the non-histone extractable nuclear antigens (ENA), Sm and Ro. Racial differences demonstrable in predisposition to SLE are also evident in the prevalence of autoantibodies, the frequency of anti-Sm and anti-Ro being 2-4 times higher in Asians with SLE than in Caucasians with SLE. Autoantibodies have also played a role in the classification of lupus and the recognition of multisystem autoimmune diseases that fail to meet the classical criteria for the identification of patients with SLE but appear to be variants of lupus. Anti-Ro is a diagnostic marker for subacute cutaneous lupus, anti-(U1)RNP a marker for mixed connective tissue disease, antibodies to phospholipids a marker for the syndrome comprising stroke, fetal wastage, thromboembolism and thrombocytopenia and antibodies to histones a marker for lupus induced by the drugs hydralazine and procainamide. There is still no unaminity on whether these antibodies play an integral role in the disease process or whether they are "epiphenomena". The challenge for research in the 1980s is the understanding of the relationship of these antibodies to the pathogenesis of SLE.


Distinct roles of the receptor tyrosine kinases c-ErbB and c-Kit in regulating the balance between erythroid cell proliferation and differentiation.
In the bone marrow, multipotent and committed hematopoietic progenitors have to closely regulate their balance between sustained proliferation without differentiation (self renewal) and entering a terminal differentiation pathway. A useful model to analyze this regulation at the molecular level is committed avian erythroid progenitors. These are induced to undergo long-term self renewal by the ligand-activated receptor tyrosine kinase (RTK) c-ErbB, in cooperation with steroid hormone receptors. This self-renewal induction by c-ErbB even occurs in the presence of differentiation factors (erythropoietin and insulin). Under the same conditions, the RTK c-Kit is unable to sustain erythroid progenitor self renewal, stimulating cell proliferation without arresting terminal differentiation. Two mechanisms are involved in these differential activities of c-Kit and c-ErbB. The first one, differential regulation of receptor expression, proved to be of minor importance, because c-Kit was unable to induce self renewal, even if exogenously expressed from a retrovirus at high levels. Rather our results support the second mechanism, i.e., that receptor-specific signal transduction is responsible for the differential biological activity of c-Kit and c-ErbB: (a) specific tyrosine kinase inhibitors (tryphostins) were found which selectively inhibited the biological function of either c-Kit or c-ErbB in erythroblasts but did not affect ligand-induced autophosphorylation of either RTK; and (b) c-ErbB selectively induced SHC phosphorylation and STAT5 activation. The Ras pathway was similarly activated by c-Kit and c-ErbB. The c-ErbB-specific tyrphostin AG30 specifically blocked STAT5 activation, implicating this signal transducer in c-ErbB-induced self renewal.


Carbon nanotube-polymer based nanocomposite as electrode material for the detection of paraoxon.
Biosensor based on the inhibition of enzymes has been used for the detection of organophosphorous compounds wherein amperometic method has been employed. Carbon nanotubes (CNT) has been grown over YNi3 alloy hydrides and purified for further use. The high surface area and the acidic sites created during the purification of CNT with oxidizing acids have been exploited for the adsorption and entrapment of the enzyme acetylcholine esterase. In the present work, conducting polymer polypyrrole has been uniformly coated over the CNT surface using chemical oxidative technique. The nanocomposite was characterized by scanning electron microscopy (SEM) and High resolution transmission electron microscopy (HRTEM). In the present report high catalytic activity of CNT towards the electroxidation of thiocholine has been utilized for the detection of organophosphorous compound paraoxon. Developed biosensor uses the principal of acetylcholinesterase inhibition by nerve agent and hence reduction in oxidation current of thiocholine for the detection of paraoxon. Synthesized PPY-MWNT nanocomposite has been used for the electrode preparation over GC electrode. Due to high porosity of polymer and high electrical conductivity of CNT, a detection level of 3 nM paraoxon could be achieved. The details of fabrication of the sensor and the dependence of the sensitivity have been discussed.


General surgery in adult hemophiliacs.
From 1976 to 1984, 23 operations were performed on 22 patients with hemophilia (18 patients with factor VIII and four with factor IX deficiency). Elective procedures included resection of abdominal aortic aneurysm, liver transplantation, vagotomy/pyloroplasty, insertion of Mousseau-Barbin tube, colectomy, cholecystectomy, inguinal herniorrhaphy (four patients), colonoscopy/polypectomy, mediastinoscopy, arteriovenous fistula for dialysis, anal fistulectomy, and miscellaneous skin and soft-tissue procedures (five patients). Emergency operations were appendectomy (two patients), repair of bleeding liver biopsy site, and repair of an incarcerated inguinal hernia. There were two deaths (9%) within 30 days of operation, neither directly caused by the coagulopathy. Four patients had bleeding after surgery, which was treated with additional cryoprecipitate or factor concentrate. There were no nonhemorrhagic complications. Before operation, appropriate replacement therapy with factor VIII concentrate, cryoprecipitate, or fresh-frozen plasma was provided. Coagulation factor levels were measured before operation and monitored daily after operation. Generally, factor levels were raised to at least 1.0 U/ml and maintained at greater than 0.5 U/ml for 7 to 14 days after operation. However, when patients were treated with fresh-frozen plasma, plasma exchange was performed and factor levels of approximately 0.35 U/ml were achieved before surgery. We conclude that operations in patients with hemophilia can be accomplished safely with careful monitoring of coagulation factor levels and appropriate replacement therapy.


Extracellular Matrix Protein Ratios in the Human Heart and Vessels: How to Distinguish Pathological From Physiological Changes?
Cardiovascular pathology is often accompanied by changes in relative content and/or ratios of structural extracellular matrix (ECM) proteins within the heart and elastic vessels. Three of these proteins, collagen-I, collagen-III, and elastin, make up the bulk of the ECM proteins in these tissues, forming a microenvironment that strongly dictates the tissue biomechanical properties and effectiveness of cardiac and vascular function. In this review, we aim to elucidate how the ratios of collagen-I to collagen-III and elastin to collagen are altered in cardiovascular diseases and the aged individuum. We elaborate on these major cardiovascular ECM proteins in terms of structure, tissue localization, turnover, and physiological function and address how their ratios change in aging, dilated cardiomyopathy, coronary artery disease with myocardial infarction, atrial fibrillation, aortic aneurysms, atherosclerosis, and hypertension. To the end of guiding in vitro modeling approaches, we focus our review on the human heart and aorta, discuss limitations in ECM protein quantification methodology, examine comparability between studies, and highlight potential in vitro applications. In summary, we found collagen-I relative concentration to increase or stay the same in cardiovascular disease, resulting in a tendency for increased collagen-I/collagen-III and decreased elastin/collagen ratios. These ratios were found to fall on a continuous scale with ranges defining distinct pathological states as well as a significant difference between the human heart and aortic ECM protein ratios.


[Contradiction model to prevent addictions in university students from Kraków].
Students' community is a peculiar environment where the problems of psychoactive substance using has been raised for many years, whereas the real scale and extent of the phenomenon has not been appreciated enough so far. Results of the preliminary research carried on in 2000 and 2004 indicate a considerable degree of the popularity both of alcohol and drugs among students. Therefore both the continuation and widening of the activity of Polish Anti Drug Action "University Free from Abuse" is necessary. In October 2004 the Council of the Rectors of Krakow Universities came to a decision about the necessity of the beginning of an action which aims at the diagnosis and counteraction of the problems in question. In December the outpatient clinic was established with the help of the Clinic of Toxicology. It aims at the prophylaxis, diagnosis and treatment of the addiction. As to prophylaxis, lectures for the first year students have been provided. Their role is to inform about the ethanol, psychoactive substance impact as well as the action of addiction. Lectures have been connected with a public-opinion poll which led to the estimation of the scale of the problem. At the same time the Clinic has rendered both diagnostic and therapeutic service for drug users and alcoholics and their relatives from the above-mentioned environment. There are plants to spread the prophylaxis among more students. Among others the secondary prophylaxis and the creation of consulting points is our aim.


CD20 expression in B-cell precursor acute lymphoblastic leukemia is common in Mexican patients and lacks a prognostic value.
Classification of acute lymphoblastic leukemia (ALL) by flow cytometric immunophenotyping characterizes the disease and delineates potential therapeutic intervention. We retrospectively analyzed CD20 expression in 143 patients with newly diagnosed precursor B-cell ALL. CD20 was observed in 61% of patients at diagnosis. There was no correlation between CD20 expression and age, white blood cell count, or cytogenetic abnormalities. Despite the fact that CD20-positive ALL patients had a tendency toward a worse outcome, there was no significant difference between patients with and without CD20 expression in 3-year overall survival 65 vs. 82% (P = 0.14), and cumulative incidence of relapse 36 vs. 18% (P = 0.3) in pediatric patients and 51 vs. 53% (P = 0.31) and 35 vs. 38% (P = 0.6) in adults, respectively. In conclusion, CD20 expression appears to be more common in Mexican patients with newly diagnosed precursor B-cell ALL higher than in Caucasian populations and lacks prognostic value.


Detection of RET proto-oncogene point mutations in paraffin-embedded pheochromocytoma specimens by nonradioactive single-strand conformation polymorphism analysis and direct sequencing.
The suitability of formalin-fixed and paraffin-embedded tumor material was evaluated for molecular analysis of the RET proto-oncogene. We analyzed exons 10, 11, and 16 for point mutations in seven sporadic and six multiple endocrine neoplasia (MEN) 2A-associated pheochromocytomas by a nonradioactive single-strand conformation polymorphism assay followed by nonradioactive direct sequencing of PCR-amplified DNA using an automated DNA sequencer. All MEN 2A-associated pheochromocytomas contained a heterozygous missense germline mutation within cystine codons of the cysteine-rich extracellular domain encoded by exons 10 and 11. Mutations were located in codon 619 (TGC-->TCC; Cys-->Ser) in one, in codon 635 (TGC-->CGC; Cys--Arg) in three, and in codon 635 (TGC-->TAC; Cys-->Tyr) in two pheochromocytomas. No tumor-specific (somatic) mutations were detected in exons 10, 11, and 16 of the sporadic pheochromocytomas. These data support recent findings that germline point mutations that are clustered in distinct cysteine codons of the RET proto-oncogene are involved in the neoplastic phenotype of the MEN 2A syndrome. Our results demonstrate that both nonradioactive single-strand conformation polymorphism and direct sequencing are suitable methods to detect single base substitutions in DNA extracted from archival material.


Dose effect on intramuscular metabolic stress during low-intensity resistance exercise with blood flow restriction.
Our previous study reported that metabolic stress in skeletal muscle achieved by combining moderate blood flow restriction (BFR) with low-intensity resistance exercise at 20% of one repetition maximum (1 RM) could not reach the level achieved by high-intensity resistance exercise. Since the previous protocol is typical of current regimens of this type, we sought in this study to optimize the exercise protocol for low-intensity resistance exercise with BFR by examining the dose effects of exercise intensity and pressure. Twelve healthy subjects participated in this study. They were asked to perform unilateral plantar flexion for 2 min (30 repetitions/min) under six different conditions: two resistance exercises (20% 1 RM and 65% 1 RM) without BFR, and four BFR protocols. The four BFR protocols included three different exercise intensities (20, 30, and 40% 1 RM) with moderate pressure (MP) using 130% of systolic blood pressure (147+/-17 mmHg, mean+/-SD) and 20% 1 RM with high pressure at 200 mmHg. Intramuscular metabolites and pH were obtained by 31P-magnetic resonance spectroscopy. Significant dose effects on intramuscular metabolites and pH were observed for exercise intensity (P<0.001) but not for BFR pressure. The BFR protocol combining 30% 1 RM with MP had similar results as the high-intensity load at 65% 1 RM. Intramuscular metabolic stress during BFR exercise might be susceptible to increasing exercise intensity. To replace high-intensity resistance exercise, the BFR protocol might require an intensity of >or=30% 1 RM.


Comparison of a polyglycolic-polylactic acid suture to black silk and plain catgut in human oral tissues.
A polylactic-polyglycolic acid synthetic absorbable suture material (Vicryl, Polyglactin 910) was compared with black silk and plain catgut in human oral tissues. Inflammation was graded clinically and histologically after seven days. Handling characteristics, including suture retention, were evaluated. Vicryl and black silk sutures produced comparable inflammation after seven days. Plain catgut sutures were usually absorbed before seven days, but when retained generally produced a more severe reaction. The polylactic-polyglycolic acid suture is braided and dyed, and has handling characteristics similar to those of black silk. Although they are absorbable, Vicryl sutures may be retained longer than desired and probably should be used like silk when exposed to the oral cavity.


Economic impacts of tipping points in the climate system.
Climate scientists have long emphasized the importance of climate tipping points like thawing permafrost, ice sheet disintegration, and changes in atmospheric circulation. Yet, save for a few fragmented studies, climate economics has either ignored them or represented them in highly stylized ways. We provide unified estimates of the economic impacts of all eight climate tipping points covered in the economic literature so far using a meta-analytic integrated assessment model (IAM) with a modular structure. The model includes national-level climate damages from rising temperatures and sea levels for 180 countries, calibrated on detailed econometric evidence and simulation modeling. Collectively, climate tipping points increase the social cost of carbon (SCC) by ∼25% in our main specification. The distribution is positively skewed, however. We estimate an ∼10% chance of climate tipping points more than doubling the SCC. Accordingly, climate tipping points increase global economic risk. A spatial analysis shows that they increase economic losses almost everywhere. The tipping points with the largest effects are dissociation of ocean methane hydrates and thawing permafrost. Most of our numbers are probable underestimates, given that some tipping points, tipping point interactions, and impact channels have not been covered in the literature so far; however, our method of structural meta-analysis means that future modeling of climate tipping points can be integrated with relative ease, and we present a reduced-form tipping points damage function that could be incorporated in other IAMs.


[Views of students of extension nursing studies about cancer prophylaxis].
Cancer prophylaxis seems nowadays to be the more and more powerful tool in fight with these serious diseases. The aim of this work is to find out opinions of students of nursing extension studies on contemporary cancer prophylaxis. The question about possibilities of practical efforts for prophylaxis and early detection of cancer was directed to 160 students of four consecutive years (2002-2006), at the end of the fourth year of lasting five and a half years extension nursing studies, during ending exam on subject: oncological nursing. There were 154 women and 6 men, predominantly at their third decade of life, with nursing experience approximately more than 5 years. Out of 160 asked students, 131 of them firstly indicated necessity of breast cancer prophylaxis, 117 mentioned lung cancer, 113 cervix cancer, 95 colorectal cancer, 33 prostate cancer. In families with cancer problems, more frequent control investigations (23 answers), and genetic tests (16) were called for. Patients should be qualified to appropriate risk groups (13) and controlled more frequently there (24). Apart from necessary wide education in media (126) personal contact with patient to discuss his or her personal problems relating to cancer is needed (91). If atypical symptoms are self-detected by patients it should alert them to not neglect and contact family physician (33). Healthy diet (62) containing fresh vegetables and fruits (73), high fibre diet (42) with less animal fat (38) and less red meat (30), containing no preservative agents (45) is recommended. Increased physical activity (84) to cease or reduce smoking (102), and alcohol intake (55), limited exposition to ultraviolet rays (49), and systematic controls of breast (105), uterus cervix (88), lungs (77), colon (55) and prostate (28) are proposed. The pollution of environment by combustion gases and smokes (34) not excluding risk factors of medical workplace (29) are mentioned as cancerogenic factors. In the time of increasing incidence of cancer in Poland it is necessary to elaborate a complex model of primary cancer prophylaxis and early detection of it and to implement it in practice. For better effectiveness of such systemic solution wide involvement of nursing staff is mandatory. Nurses should be, very well and consciously prepared to play their role through adequate educational efforts undertaken during nursing studies.


A novel live attenuated anthrax spore vaccine based on an acapsular Bacillus anthracis Sterne strain with mutations in the htrA, lef and cya genes.
We recently reported the development of a novel, next-generation, live attenuated anthrax spore vaccine based on disruption of the htrA (High Temperature Requirement A) gene in the Bacillus anthracis Sterne veterinary vaccine strain. This vaccine exhibited a highly significant decrease in virulence in murine, guinea pig and rabbit animal models yet preserved the protective value of the parental Sterne strain. Here, we report the evaluation of additional mutations in the lef and cya genes, encoding for the toxin components lethal factor (LF) and edema factor (EF), to further attenuate the SterneΔhtrA strain and improve its compatibility for human use. Accordingly, we constructed seven B. anthracis Sterne-derived strains exhibiting different combinations of mutations in the htrA, cya and lef genes. The various strains were indistinguishable in growth in vitro and in their ability to synthesise the protective antigen (PA, necessary for the elicitation of protection). In the sensitive murine model, we observed a gradual increase (ΔhtrA<ΔhtrAΔcya<ΔhtrAΔlef<ΔhtrAΔlefΔcya) in attenuation - up to 108-fold relative to the parental Sterne vaccine strain. Most importantly, all various SterneΔhtrA derivative strains did not differ in their ability to elicit protective immunity in guinea pigs. Immunisation of guinea pigs with a single dose (109 spores) or double doses (>107spores) of the most attenuated triple mutant strain SterneΔhtrAlefMUTΔcya induced a robust immune response, providing complete protection against a subsequent respiratory lethal challenge. Partial protection was observed in animals vaccinated with a double dose of as few as 105spores. Furthermore, protective immune status was maintained in all vaccinated guinea pigs and rabbits for at least 40 and 30weeks, respectively.


Effects of Periodontal Pathogens Porphyromonas gingivalis and Aggregatibacter actinomucetemcomitans on Modeling Subgingival Microbiome and Impairment of Oral Epithelial Barrier.
Periodontitis is an exemplar of dysbiosis associated with the coordinated action of multiple members within the microbial consortium. The Polymicrobial Synergy and Dysbiosis hypothesis proposes a dynamic host-microbiome balance, with certain modulators capable of disrupting eubiosis and driving shifts towards dysbiosis within community. However, these factors remain to be explored. We established a Porphyromonas gingivalis (P. gingivalis)- or Aggregatibacter actinomucetemcomitans (A. actinomucetemcomitans)-modified subgingival microbiome model and 16S rRNA sequencing revealed that P. gingivalis and A. actinomucetemcomitans altered the microbiome structure and composition indicated by α and β diversity metrics. P. gingivalis increased subgingival dysbiosis index (SDI), while A. actinomucetemcomitans resulted in a lower SDI. Furthermore, P. gingivalis-stimulated microbiomes compromised epithelium function and reduced expression of tight junction proteins, whereas A. actinomucetemcomitans yielded mild effects. In conclusion, by inoculating P. gingivalis, we created dysbiotic microcosm biofilms in vitro resembling periodontitis-related subgingival microbiota, exhibiting enhanced dysbiosis and impaired epithelium integrity.


Campomelic dysplasia and malignant hyperthermia.
Campomelic dysplasia (CD) is a rare clinical entity, usually fatal in the first year of life. It is characterised by bowing and angulations of long bones, along with other congenital anomalies. The occurrence of malignant hyperthermia is rare, but it has been associated with skeletal dysplasias. The authors present the case of a boy, born at 40 weeks of gestational age, with multiple congenital anomalies and subsequently diagnosed with CD, who died at 16 months of age as a consequence of malignant hyperthermia.


Sirt6 deficiency results in progression of glomerular injury in the kidney.
Aging is associated with an increased incidence and prevalence of renal glomerular diseases. Sirtuin (Sirt) 6, a nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase, has been shown to protect against multiple age-associated phenotypes; however it is unknown whether Sirt6 has a direct pathophysiologic role in the kidney. In the present study, we demonstrate that Sirt6 is expressed in the kidney and aging Sirt6-deficient mice exhibit renal hypertrophy with glomerular enlargement. Sirt6 deletion induces podocyte injury, including decreases in slit diaphragm proteins, foot process effacement, and cellular loss, resulting in proteinuria. Knockdown of Sirt6 in cultured primary murine podocytes induces shape changes with loss of process formation and cell apoptosis. Moreover, Sirt6 deficiency results in progressive renal inflammation and fibrosis. Collectively, these data provide compelling evidence that Sirt6 is important for podocyte homeostasis and maintenance of glomerular function, and warrant further investigation into the role of Sirt6 in age-associated kidney dysfunction.


Established and novel approaches for teaching and learning of veterinary parasitology in Berlin.
The teaching of veterinary parasitology to the large number of students at the Freie Universität Berlin is mainly limited to conventional face-to-face lectures, supplemented by practical classes. Extensive parasite descriptions and diagnostic techniques are at the core of the practical classes, which are also intended to emphasise key biological and veterinary aspects covered in lectures. Further in-depth and specific learning is achieved within a detailed framework of elective courses, with defined learning outcomes for small groups of students, focusing on themes such as 'diagnosis and treatment of ectoparasites in companion animals' or 'zoonotic parasites'. Additionally, structured excursions are designed to offer experience through collaborative international investigations. Organ-based approaches are also an integral part of our veterinary parasitology teaching, done in collaboration with the clinical and para-clinical departments, either via face-to-face interactions or online. Wide-ranging themes, such as 'causes of colic in horses' or 'atopic dermatitis in dogs' are covered. Recently, diverse blended learning elements were introduced into the curriculum (e.g., QuerVet), which makes teaching and learning more flexible, in terms of time and space, and fosters self-directed learning and participation among the students. A new platform to provide online lectures for students, termed VET Talks, was launched in 2015 by the International Veterinary Student's Association (IVSA), and is as a publicly available educational support system for students. Provided free to veterinary students throughout the world, this platform offers students the opportunity to access lectures on interesting topics by outstanding speakers who are nominated by their students. Finally, continuing education (CE) opportunities are provided through specific Masters courses (Master of Equine Medicine, Master of Small Animal Sciences), classical seminars and recent webinars.


Experimental traumatic spinal cord injury.
Animal models are important to develop therapies for individuals suffering from spinal cord injuries. For this purpose, rats are commonly preferred. In sharp injury models, spinal cord is completely or incompletely cut to assess axonal regeneration. On the other hand, spinal cord is compressed or contused to mimic the human injury in blunt injury models for understanding as well as managing the secondary pathophysiologic processes following injury. Especially, contusions are thought to be biomechanically similar to vertebral fractures and/or dislocations and thus provide the most realistic experimental setting in which to test potential neuroprotective and regenerative strategies.


Integrative analysis of prognostic long non-coding RNAs with copy number variation in bladder cancer.
Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely NR2F1-AS1, LINC01138, THUMPD3-AS1, LOC101928489,and TMEM147-AS1,and a risk-score signature related to overall survival in BLCA was identified. Moreover, validated results in another independent Gene Expression Omnibus (GEO) dataset, GSE31684, were consistent with these results. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the mitogen-activated protein kinase (MAPK) signaling pathway, focal adhesion pathway, and Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway were enriched in a high-risk score pattern, suggesting that imbalance in these pathways is closely related to tumor development. We revealed the prognosis-related lncRNAs by analyzing the expression profiles of lncRNAs and CNVs, which can be used as prognostic biomarkers for BLCA.


Hpr6.6 protein mediates cell death from oxidative damage in MCF-7 human breast cancer cells.
Reactive oxygen species (ROS) cause cell death and are associated with a variety of maladies, from trauma and infection to organ degeneration and cancer. Cells mount a complex response to oxidative damage that includes signaling from transmembrane receptors and intracellular kinases. We have analyzed the response to oxidative damage in human breast cancer cells expressing the Hpr6.6 (human membrane progesterone receptor) protein. Although Hpr6.6 is related to a putative progesterone-binding protein, Hpr6.6 is widely expressed in epithelial tissues and shares close homology with a budding yeast damage response protein called Dap1p (damage response protein related to membrane progesterone receptor). We report here that the Hpr6.6 protein regulates the response to oxidative damage in breast cancer cells. Expression of Hpr6.6 in MCF-7 cells sensitized the cells to death following long-term/low dose or short-term/high dose treatment with hydrogen peroxide. Cell death did not occur through a typical apoptotic mechanism and corresponded with hyperphosphorylation of the Akt and IkappaB proteins. However, inhibition of Akt activation and IkappaB degradation had no effect on Hpr6.6-mediated cell death, suggesting that Hpr6.6 regulates cell death through a novel oxidative damage response pathway. Our work indicates a key regulatory function for Hpr6.6 in epithelial tissues exposed to oxidative damage.


A catalog of CasX genome editing sites in common model organisms.
DpbCasX, also called Cas12e, is an RNA-guided DNA endonuclease isolated from Deltaproteobacteria. In this paper I characterized the CasX-compatible genome editing sites in the reference genomes of yeast (Saccharomyces cerevisiae), flatworms (Caenorhabditis elegans), flies (Drosophila melanogaster), zebrafish (Danio rerio), mouse (Mus musculus), rats (Rattus norvegicus), and humans (Homo sapiens). Across those genomes there were > 27,000 CasX sites per megabase on average. More than 90% of genes in each genome had at least one unique site overlapping an exon, with median unique sites per gene of 6-45. I also annotated sites in the GRCm38 reference and 15 additional mouse strain genomes. The presence of specific guide sequences varied amongst the strains, with CAST/EiJ and PWK/PhJ showing the greatest divergence from the reference strain. The high density of CasX sites and number of exon overlapping sites suggests that CasX has the potential to be used as a common genome editor.


Clinical observation of 32 cases with transplantation of autologous bone marrow stem cells on diabetes and its complications.
By observing the curative effect of autologous stem cells changes before and after the treatment, to explore the stem cell treatment of diabetes and its complications. 32 patients were type 2 diabetic patients with different complications. By intravenous injection of autologous stem cells, observe improving symptoms, signs and auxiliary examination of patients after three months. Evaluation index: glycated hemoglobin level; ankle brachial pressure index (ABI); limb electromyogram; 24h urine protein quantity. Diabetic complications of different systems and glycated hemoglobincan be effectively improved. This research and application of autologous bone marrow stem cell transplantation for treatment of type 2 diabetes chronic complications achieves certain results, non-toxic side effects occuring. Just only preliminary observes the clinical effect, a small sample size. We need to expand the sample and observation period further for the long-term efficacy and side effects.


Combination photodynamic therapy and bevacizumab for choroidal neovascularization associated with toxoplasmosis.
A 14-year-old girl presenting with visual loss in both eyes was diagnosed to have healed toxoplasma retinochoroiditis in the right eye with active choroidal neovascularization (CNV) secondary to toxoplasmosis in the left. She underwent combination photodynamic therapy (PDT) and intravitreal bevacizumab as primary treatment. PDT was performed as per the 'Treatment of Age-related Macular Degeneration by Photodynamic therapy' study protocol and was followed by intravitreal bevacizumab after 2 days. CNV regressed at 8 weeks of follow-up and remained stable at 8 months of follow-up. The initial visual acuity improved from 20/120 to 20/30. Combination therapy with PDT and intravitreal bevacizumab appears to be effective in the treatment of CNV secondary to toxoplasma retinochoroiditis.


Leveraging Systems Immunology to Optimize Diagnosis and Treatment of Inborn Errors of Immunity.
Inborn errors of immunity (IEI) are monogenic disorders that can cause diverse symptoms, including recurrent infections, autoimmunity and malignancy. While many factors have contributed, the increased availability of next-generation sequencing has been central in the remarkable increase in identification of novel monogenic IEI over the past years. Throughout this phase of disease discovery, it has also become evident that a given gene variant does not always yield a consistent phenotype, while variants in seemingly disparate genes can lead to similar clinical presentations. Thus, it is increasingly clear that the clinical phenotype of an IEI patient is not defined by genetics alone, but is also impacted by a myriad of factors. Accordingly, we need methods to amplify our current diagnostic algorithms to better understand mechanisms underlying the variability in our patients and to optimize treatment. In this review, we will explore how systems immunology can contribute to optimizing both diagnosis and treatment of IEI patients by focusing on identifying and quantifying key dysregulated pathways. To improve mechanistic understanding in IEI we must deeply evaluate our rare IEI patients using multimodal strategies, allowing both the quantification of altered immune cell subsets and their functional evaluation. By studying representative controls and patients, we can identify causative pathways underlying immune cell dysfunction and move towards functional diagnosis. Attaining this deeper understanding of IEI will require a stepwise strategy. First, we need to broadly apply these methods to IEI patients to identify patterns of dysfunction. Next, using multimodal data analysis, we can identify key dysregulated pathways. Then, we must develop a core group of simple, effective functional tests that target those pathways to increase efficiency of initial diagnostic investigations, provide evidence for therapeutic selection and contribute to the mechanistic evaluation of genetic results. This core group of simple, effective functional tests, targeting key pathways, can then be equitably provided to our rare patients. Systems biology is thus poised to reframe IEI diagnosis and therapy, fostering research today that will provide streamlined diagnosis and treatment choices for our rare and complex patients in the future, as well as providing a better understanding of basic immunology.


Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual effect on CRE and AP1 elements.
Vasopressin plays an essential role for the regulation of water balance by activating the collecting duct-specific water channel, aquaporin-2 (AQP2). Here we present evidence that vasopressin may also act as a long-term, transcriptional regulator of AQP2. The studies were performed on LLC-PK1 cells, which normally express V2 receptor (V2R) and which were transfected with a fragment of the human AQP2 promoter. Activation of the adenylate cyclase-coupled V2R in LLC-PK1 cells induced phosphorylation of adenosine 3',5'-cyclic monophosphate (cAMP) responsive element binding protein (CREB) and expression of c-Fos. Binding of these factors to the CRE and AP1 site did, in combination, lead to AQP2 promoter activation. These results establish the role of vasopressin as a regulator of transcription and are the first example of how a message from a highly specific receptor is, via a dual effect of the cAMP signal on CREB and immediate early gene expression, transduced to the transcription of a final target protein with known biological effects.


Effects of particle size, helium gas pressure and microparticle dose on the plasma concentration of indomethacin after bombardment of indomethacin-loaded poly-L-lactic acid microspheres using a Helios gun system.
We investigated the effects of the particle size of indomethacin-loaded poly-L-lactic acid microspheres (IDM-loaded PLA MS), the helium pressure used to accelerate the particles, and the bombardment dose of PLA MS on the plasma concentration of IDM after bombarding with IDM-loaded PLA MS of different particle size ranges, 20-38, 44-53 and 75-100 microm, the abdomen of hairless rats using the Helios gene gun system (Helios gun system). Using larger particles and a higher helium pressure, produced an increase in the plasma IDM concentration and the area under the plasma concentration-time curve (AUC) and resultant F (relative bioavailability with respect to intracutaneous injection) of IDM increased by an amount depending on the particle size and helium pressure. Although a reduction in the bombardment dose led to a decrease in C(max) and AUC, F increased on decreasing the bombardment dose. In addition, a more efficient F was obtained after bombarding with IDM-loaded PLA MS of 75-100 microm in diameter at each low dose in different sites of the abdomen compared with that after bolus bombardment with a high dose (dose equivalent). These results suggest that the bombardment injection of drug-loaded microspheres by the Helios gun system is a very useful tool for delivering a variety of drugs in powder form into the skin and systemic circulation.


Analysis of dairy cattle movements in the northern region of Thailand.
Dairy farming in northern Thailand is expanding, with dairy cattle populations increasing up to 8% per year. In addition, disease outbreaks frequently occur in this region, especially foot-and-mouth disease and bovine tuberculosis. Our goal was to quantify the underlying pattern of dairy cattle movements in the context of infectious disease surveillance and control as movements have been identified as risk factors for several infectious diseases. Movements at district levels within the northern region and between the northern and other regions from 2010 to 2017 were recorded by the Department of Livestock Development. Analyzed data included origin, destination, date and purpose of the movement, type of premise of origin and destination, and type and number of moved cattle. Social network analysis was performed to demonstrate patterns of dairy cattle movement within and between regions. The total numbers of movements and moved animals were 3,906 and 180,305, respectively. Decreasing trends in both the number of cattle moved and the number of movements were observed from 2010 to 2016, with increases in 2017. The majority (98%) of the animals moved were male dairy calves, followed by dairy cows (1.7%). The main purpose of the movements was for slaughter (96.3%). Most movements (67.4%) were shipments from central to northern regions, involving 87.1% of cattle moved. By contrast, 56% of the movements for growing and selling purposes occurred within the northern region, commonly involving dairy cows. Constructed movement networks showed heterogeneity of connections among districts. Of 110 districts, 28 were found to be influential to the movement networks, among which 11 districts showed high centrality measures in multiple networks stratified for movement purposes and regions, including eight districts in the northern and one district in each of the central, eastern, and lower northeastern regions of Thailand. These districts were more highly connected than others in the movement network, which may be important for disease transmission, surveillance, and control.


The effectiveness of repetitive paravertebral block with ropivacaine and dexmedetomidine for the prevention of postherpetic neuralgia in patients with acute herpes zoster.
Herpes zoster (HZ) is a disease caused by the reactivation of the varicella zoster virus. Postherpetic neuralgia (PHN) is the most common complication of HZ. Repetitive paravertebral block with local anaesthetics and dexmedetomidine for the prevention of PHN in patients with acute herpes zoster. 104 patients with acute herpes zoster were randomly divided into two groups. Group Rop received repetitive paravertebral block with 0.25% ropivacaine 20 ml per 72 h three times. Group Dex received repetitive paravertebral block with a mixture of 0.25% ropivacaine 20 ml and dexmedetomidine 20 µg per 72 h three times. Patients were permitted to take tramadol when the visual analogue scale (VAS) ≥ 4. The incidence of zoster-related pain was recorded at 1, 3, and 6 months after the end of treatments; VAS scores and the dose of rescue drug were recorded at 1 week, 2 weeks, 1 month, 3 months, and 6 months after the end of treatments. At 1 month post therapy, the incidence of zoster-related pain was 11% in Group Dex, compared with 35% in Group Rop (p = 0.005). At 3 months post therapy, the incidence of zoster-related pain in Group Dex was still significantly lower than in Group Rop. The VAS scores and the dose of rescue drug in Group Dex were also significantly lower than in Group Rop at each time point (p < 0.05). Repetitive paravertebral block with local anaesthetics and dexmedetomidine in patients with acute herpes zoster can significantly reduce the incidence of zoster-related pain.


Assessing the Effect of Waterpipe Smoking on Cancer Outcome - a Systematic Review of Current Evidence
Background: Waterpipe smoking (WPS) is widely believed to be a safe and hazard-free tobacco habit. However, a number of studies have indicated that exposure to several toxicants and carcinogens through WPS is strongly related to serious health hazards. The current paper presents a narrative review on the effects of WPS on cancer outcome. Methods: The addressed focused question was "Is there an association between waterpipe smoking and cancer outcome?" PubMed, Medline, EMBASE, ISI Web of Science and the Cochrane databases were searched until June 2015 using the key words "Waterpipe", "Hookah", "Narghileh", "Shisha", "Hubbly Bubbly" "cancer" in various combinations. Letters to the Editor, review articles, case-reports and unpublished articles were excluded. Results: A total of 16 studies were included: six on lung cancer, three on oesophageal cancer, two on gastric cancer, two on bladder cancer, and one each on nasopharyngeal, pancreatic and prostate cancers. Our search did not yield any study that evaluated the risk of oral cancer in WPS users. The available evidence showed a significant association of WPS with lung cancer (UOR 6.0, 95% CI 1.78–20.26); however, no association was observed with bladder, nasopharyngeal, pancreatic and prostate cancers. Gastric (OR 3.4, 95% CI 1.7-7.1) and oesophageal cancers (OR 1.85, 95% CI 1.41-2.44) were observed to have weak associations with WPS. Conclusion: Regardless of the limitations, there is sufficient evidence to suggest associations of WPS with cancer, particularly in the lung. Future well-designed studies are required to identify and quantify with confidence all the health effects of this form of smoking.


RORα Induces KLF4-Mediated M2 Polarization in the Liver Macrophages that Protect against Nonalcoholic Steatohepatitis.
The regulation of M1/M2 polarization in liver macrophages is closely associated with the progression of nonalcoholic steatohepatitis (NASH); however, the mechanism involved in this process remains unclear. Here, we describe the orphan nuclear receptor retinoic-acid-related orphan receptor α (RORα) as a key regulator of M1/M2 polarization in hepatic residential Kupffer cells (KCs) and infiltrated monocyte-derived macrophages. RORα enhanced M2 polarization in KCs by inducing the kruppel-like factor 4. M2 polarization was defective in KCs and bone-marrow-derived macrophages of the myeloid-specific RORα null mice, and these mice were susceptible to HFD-induced NASH. We found that IL-10 played an important role in connecting the function of M2 KCs to lipid accumulation and apoptosis in hepatocytes. Importantly, M2 polarization was controlled by a RORα activator, JC1-40, which improved symptoms of NASH. Our results suggest that the M2-promoting effects of RORα in liver macrophages may provide better therapeutic strategies against NASH.


AmotP130 regulates Rho GTPase and decreases breast cancer cell mobility.
Angiomotin (Amot) is a newly discovered, multifunctional protein that is involved in cell migration and angiogenesis. However, the role of its isoform, AmotP130, in the regulation of cytoskeleton and metastasis of breast cancer, is unclear. The aim of this study was to investigate the role of AmotP130 in the reorganization of the actin cytoskeleton and the changes of morphology in breast cancer cells through the Rho pathway that influences the invasion and migration of cells. The results suggested that AmotP130 suppressed the invasion ability through remodelling the cytoskeleton of breast cancer cells, including the actin fibre organization and focal adhesion protein turnover. Global transcriptome changes in breast cancer cells following knockdown of AmotP130 identified pathways related with the cytoskeleton and cell motility that involved the Rho GTPase family. From database analyses, changes in the Rho GTPase family of proteins were identified as possible prognostic factors in patients with breast cancer. We have been suggested that AmotP130 suppressed the invasion ability through remodelling of the cytoskeleton of breast cancer cells, involving regulation of the Rho pathway. The cytoskeleton-related pathway components may provide novel, clinically therapeutic targets for breast cancer treatment.


Clinical and metabolic characteristics of polycystic ovary syndrome without polycystic ovary: a pilot study on Chinese women.
To demonstrate clinical features of a patient subgroup presenting with polycystic ovary syndrome (PCOS) without polycystic ovary morphology. Retrospective study. Hospital-based IVF center. In the present study, 876 PCOS patients were selected from women who visited the Reproductive Medicine Center at Shandong Provincial Hospital, Shandong University, between September 2004 and October 2006. Women with PCOS were divided into two groups based on ultrasound image: group A, PCOS patients with classic polycystic ovary (n = 800); group B, PCOS patients without polycystic ovary morphology (n = 76). The following available data were analyzed in the large cohort of women: body height, weight, waistline, hip circumference, hirsutism scores, family history, serum sex hormone levels, blood glucose levels, insulin levels, and blood lipid levels. An oral glucose tolerance test and insulin release test were performed for each woman. After overnight fasting, blood samples were collected to determine fasting blood glucose, LH, FSH, T, PRL, E(2), and blood lipid levels. Height, weight, waistline, hip circumference, Ferriman-Gallwey grade for hirsutism, gonadal hormone results, blood lipid level, blood glucose tolerance, each-moment insulin level, and family history were determined for the two groups. No statistical difference was observed between groups in age, body height and weight, waistline, hip circumference, FSH, LH, PRL, E(2), each-moment blood glucose, and each-moment insulin. There were significantly higher hirsutism scores (6.31 +/- 6.44 vs. 4.18 +/- 4.96) and serum T levels (80.71 +/- 17.89 vs. 66.35 +/- 33.31) in group B than in group A. Cholesterol (4.99 +/- 1.01 vs. 4.70 +/- 0.91) and low-density lipoprotein (3.59 +/- 1.17 vs. 3.03 +/- 1.10) were both significantly higher in group B than in group A. In addition, significantly higher rates of diabetes mellitus and hypertension were observed in patients' first-grade relatives in group B than in group A. Patients with PCOS without polycystic ovaries had higher cholesterol and low-density lipoprotein and possibly had a higher incidence of developing long-term complications.


In situ EXAFS analysis of the temperature-programmed reduction of Cu-ZSM-5.
High resolution in situ EXAFS during temperature-programmed reduction was performed on Cu-ZSM-5 to elucidate the state of copper under reaction conditions. Improvements in hardware and software allowed rapid acquisition of both XANES and EXAFS data during reduction, in particular, allowing observation of characteristic preedge features from various Cu oxidation states. EXAFS fitting and factor analysis of the normalized XANES edge were performed in an attempt to determine the number and type of Cu species present. The data suggests that initially only Cu(2+) is present in two different locations on the zeolite; both states reduce to Cu(1+) in both H(2) and CO, but under different conditions. Under H(2) conditions, migration of Cu(1+) to Cu(0) clusters is observed at 450 degrees C, while no metallic state is observed during CO reduction.


The intron of the yeast actin gene contains the promoter for an antisense RNA.
Using Northern blot analysis we have detected an approximately 840 nucleotide-long RNA which is complementary to the 5' leader sequence and the first ten nucleotides of the coding sequence of the yeast actin (ACT1) messenger RNA. We have determined two transcription start sites for this actin antisense RNA (ASR1), both within the ACT1 intron, at about 80 and 90 nucleotides downstream from the 5' splice site. Analysis of a cDNA clone showed that this RNA species overlaps the entire trailer sequence and approximately 20 nucleotides of the coding sequence of the nearby yeast YPT1 gene.


Metabolic dysfunction-associated fatty liver disease and risk of incident chronic kidney disease: A nationwide cohort study.
The recently proposed metabolic dysfunction-associated fatty liver disease (MAFLD) has been suggested to better reflect the metabolic components of fatty liver disease (FLD), compared to nonalcoholic fatty liver disease (NAFLD). This study investigated whether MAFLD identifies a higher proportion of individuals at risk of developing chronic kidney disease (CKD). 268,946 participants aged 40-64 years, who underwent National Health Insurance Service health examinations between 2009 and 2015 were included. Participants were categorized by presence of FLD, according to MAFLD or NAFLD. In participants with FLD, participants were categorized into three groups: non-metabolic risk (non-MR) NAFLD, MAFLD but not NAFLD, and overlapping FLD. Incident CKD was defined as the occurrence of eGFR < 60 mL/min/1.73m2 or proteinuria (≥ trace) on two consecutive health examinations. 73,726 (27.4%) and 88,762 (33.0%) participants had NAFLD and MAFLD, respectively. During a median follow-up of 5.1 years, CKD occurred in 8,335 (6.2/1,000 person-years) participants. Compared to non-NAFLD participants, the adjusted hazard ratio (aHR) for incident CKD was 1.33 (95% CI, 1.27-1.39; P < 0.001) for participants with NAFLD. Compared to non-MAFLD participants, the aHR for participants with MAFLD was 1.39 (95% CI, 1.33-1.46; P < 0.001). When the analysis was confined to participants with FLD, compared to non-MR NAFLD participants, the aHRs for participants with MAFLD but not NAFLD, and those with overlapping FLD were 1.18 (95% CI, 1.01-1.39; P = 0.040) and 1.36 (95% CI, 1.19-1.54; P < 0.001), respectively. MAFLD identified a higher proportion of individuals at risk of developing CKD than NAFLD.


[Glomus caroticum, jugulare and vagale--problems in diagnosis and treatment].
The paraganglia tissue in 80% is located in suprarenal glands. The rest (20%) are with close association with autonomic nerves and some cranial nerves. Paraganglioma, being tumors arising from the paraganglion cells of the parasympathetic system, were first reported in man in 1935. Although histologically these tumors have been shown to contain neurosecretory granules, they are rarely functional. There are four kinds of paragangliomas: deriving from carotid artery baroreceptors (glomus caroticum), internal jugular vein (glomus jugulare); placed along vagal nerve (glomus vagale) and paragangliomas of tympanic cavity (glomus tympanicum). The first three of them are clinically recognized as tumor of the neck. Authors present group of 7 patients with paragangliomas treated in ENT Department in Poznań in the years 1994-2004. There were treated 4 patients with glomus caroticum, two with glomus vagale and one patient with glomus jugulare. All patients were treated surgically. In one case in group with glomus caroticum in histological examination tendency to infiltration of internal carotid artery was stated (chemodectoma malignum). The tumor was removed totally with partial excision of communis, external and internal carotid artery. The internal carotid artery was closed by the tumor. Authors underline three aspects of process of treatment in whole group of patients: diagnostic problems, way of treatment and long term results.


Studies on purified eel acetylcholine receptor and anti-acetylcholine receptor antibody.
Rabbit antiserum against purified Electrophorus electricus acetylcholine receptor is studied using an immunoprecipitin assay to measure either antibody titer or concentration of toxin-binding sites in solubilized receptor preparations. This antiserum, unlike control serum, blocks the electrophysiological response of the electroplax to carbamylcholine. Toxin (alpha-neurotoxin, Naja naja) and several cholinergic ligands produce partial inhibition of the reaction of antiserum with purified acetylcholine receptor. Evidence is presented that some of the toxin-binding sites on receptor, purified by affinity chromatography on toxin-agarose conjugates, are occluded by toxin. In addition, evidence is presented that antireceptor antiserum will cause precipitation of more toxin-binding sites present in an initial extract than in purified receptor preparations.


The crystal structure of the β subunit of luteinizing hormone and a model for the intact hormone.
The β subunit of bovine luteinizing hormone (LH) was crystallized and its structure solved to 3.15 Å resolution by molecular replacement using human chorionic gonadotropin (hCG) β subunit as search model. The asymmetric unit contains two copies of the β subunit that are related by a non-crystallographic symmetry (NCS) two-fold axis, both copies of which contain proteolytic cleavages after amino acid 100. It is noteworthy that the oligosaccharide moieties covalently attached at asparagine 13 were particularly pronounced in the electron density, allowing seven sugar residues to be defined. The α subunit of LH, which is common to all glycosylated gonadotropin hormones, was placed by superposition of hCG on the LH beta subunits, thereby yielding a model for the intact hormone.


Pharmacokinetics of rocuronium bromide in paediatric patients.
Rocuronium 0.8 mg kg-1 was given to 22 children between the ages of 3 months and 8 years during anaesthesia with N2O/O2, 60:40, and halothane. Blood samples were collected for 360 min for determination of rocuronium concentrations. The pharmacokinetics were best described by a two-compartment model. Two models were fitted, one proportional to weight and the other adjusted for age. Using the first model, volumes and clearances were all proportional to weight: in the second model, only the volume of the second compartment and clearance from the central compartment were proportional to age. The results do not support the use of body surface area, rather than weight for the calculation of paediatric doses of rocuronium. In this study, the volume of the central compartment was larger than the figure obtained in an adult population.


[The judicialisation of health as a means ensuring access to medicines].
A systematic review, focusing on the judicialisation of health regarding gaining access to medicines, was aimed at understanding the impact of lawsuits on the organisation of public health services. Original articles published between 2007 and 2011 in the pertinent national and international literature were analysed, resulting in 49,239 articles being found in Science Direct and BIREME databases. Results The survey indicated a predominance of literature from Brazil, mainly the southeast, as well as a study from Colombia. The aforementioned chronic disease-related claims involved diabetes, high blood pressure, cancer and rheumatoid arthritis. Forming part of specific Unified Healthcare System programmes highlighted the difficulty in gaining access to the appropriate medicine and consequent health judicialisation demonstrated the fragility of existing public policy. It was concluded that the courts (despite being a strategy for ensuring access to medicine) were unable to deal with the current spate of lawsuits, thereby leading to disruption regarding the flow of public systems.


OptiClust, an Improved Method for Assigning Amplicon-Based Sequence Data to Operational Taxonomic Units.
Assignment of 16S rRNA gene sequences to operational taxonomic units (OTUs) is a computational bottleneck in the process of analyzing microbial communities. Although this has been an active area of research, it has been difficult to overcome the time and memory demands while improving the quality of the OTU assignments. Here, we developed a new OTU assignment algorithm that iteratively reassigns sequences to new OTUs to optimize the Matthews correlation coefficient (MCC), a measure of the quality of OTU assignments. To assess the new algorithm, OptiClust, we compared it to 10 other algorithms using 16S rRNA gene sequences from two simulated and four natural communities. Using the OptiClust algorithm, the MCC values averaged 15.2 and 16.5% higher than the OTUs generated when we used the average neighbor and distance-based greedy clustering with VSEARCH, respectively. Furthermore, on average, OptiClust was 94.6 times faster than the average neighbor algorithm and just as fast as distance-based greedy clustering with VSEARCH. An empirical analysis of the efficiency of the algorithms showed that the time and memory required to perform the algorithm scaled quadratically with the number of unique sequences in the data set. The significant improvement in the quality of the OTU assignments over previously existing methods will significantly enhance downstream analysis by limiting the splitting of similar sequences into separate OTUs and merging of dissimilar sequences into the same OTU. The development of the OptiClust algorithm represents a significant advance that is likely to have numerous other applications. IMPORTANCE The analysis of microbial communities from diverse environments using 16S rRNA gene sequencing has expanded our knowledge of the biogeography of microorganisms. An important step in this analysis is the assignment of sequences into taxonomic groups based on their similarity to sequences in a database or based on their similarity to each other, irrespective of a database. In this study, we present a new algorithm for the latter approach. The algorithm, OptiClust, seeks to optimize a metric of assignment quality by shuffling sequences between taxonomic groups. We found that OptiClust produces more robust assignments and does so in a rapid and memory-efficient manner. This advance will allow for a more robust analysis of microbial communities and the factors that shape them.


A novel type of deletion in the CDKN2A gene identified in a melanoma-prone family.
Linkage to the CDKN2A locus has been demonstrated in approximately 50% of families with hereditary malignant melanoma but only a subgroup of these harbor identified mutations. We here report a Norwegian melanoma-prone family with a novel large germline deletion removing 13707 bps of the CDKN2A gene, including exon 1alpha and approximately half of exon 2. Our finding is the first reported large CDKN2A germline deletion with a breakpoint located within an exon. This type of deletion is not detectable through the direct exon sequencing and may also escape identification by use of multiplex ligation-dependent probe amplification (MLPA) analysis. Here, the defect was identified through detection of a truncated p14(ARF) mRNA and loss of p16(INK4a) mRNA expression from the affected allele. Our finding suggests that atypical, large deletions in the CDKN2A gene may explain linkage to the 9p21 chromosome band without identified gene mutations among melanoma-prone families. Thus, it illustrates the need to include p14(ARF)- and p16(INK4a) transcript analysis when searching for unknown mutations within the CDKN2A locus in melanoma-prone families. Similar deletions with atypical breakpoints may affect other genes involved in cancer disposition, and the need to examine gene transcripts in high-risk families with no mutation identified through conventional testing should be considered.


5-hydroxytryptamine in the carotid body of the cat.
Glomus cells, at least in the carotid body of cats, contain catechol and indolamines. Cells containing adrenaline, noradrenaline, and 5-hydroxytryptamine were identified.


Energy scale-up and mode-quality enhancement of the LED-pumped Nd:YAG Q-switched laser achieving a millijoule green pulse.
An efficient LED pumping module is explored for the demonstration of energy scaling of passively Q-switched output to millijoule high-pulse-energy level. For the free-running operation at fundamental wavelength, the highest optical conversion efficiency of 23.7% is reached. By using a Cr4+:YAG crystal as the saturable absorber, the passively Q-switched output energy is up to 14.5 mJ in a compact setup. The laser resonator is further optimized to shorten the output pulse width and to obtain better mode quality. The pulse width of the Q-switched emission is as short as 25 ns, and the peak power is up to 0.7 MW. With such a highly efficient configuration, the extracavity second-harmonic generation at 532 nm can be achieved with 4.5 mJ pulse energy.


Brain structural changes following adaptive cognitive training assessed by Tensor-Based Morphometry (TBM).
Tensor-Based Morphometry (TBM) allows the automatic mapping of brain changes across time building 3D deformation maps. This technique has been applied for tracking brain degeneration in Alzheimer's and other neurodegenerative diseases with high sensitivity and reliability. Here we applied TBM to quantify changes in brain structure after completing a challenging adaptive cognitive training program based on the n-back task. Twenty-six young women completed twenty-four training sessions across twelve weeks and they showed, on average, large cognitive improvements. High-resolution MRI scans were obtained before and after training. The computed longitudinal deformation maps were analyzed for answering three questions: (a) Are there differential brain structural changes in the training group as compared with a matched control group? (b) Are these changes related to performance differences in the training program? (c) Are standardized changes in a set of psychological factors (fluid and crystallized intelligence, working memory, and attention control) measured before and after training, related to structural changes in the brain? Results showed (a) greater structural changes for the training group in the temporal lobe, (b) a negative correlation between these changes and performance across training sessions (the greater the structural change, the lower the cognitive performance improvements), and (c) negligible effects regarding the psychological factors measured before and after training.


Using developmental principles to assist preschoolers in developing numeracy and literacy.
In a yoked control design, 4-yr.-olds (N = 39) in a Head Start program played numerous structured games involving either the oddity principle or letter identification and letter sounds. The children's mean age was 53.2 mo.; SD = 4.1 mo. Three were Middle Eastern, 14 were Latino, 7 were East African, and 15 were African American. Children showed better mastery of oddity after playing games directed at this concept, and numeracy scores on the Woodcock-Johnson III were better for children who had played this type of game. Woodcock-Johnson III Letter-Word scores for children who had played the oddity and seriation or letter games were equivalent. These results are consistent with other research indicating that the understanding of oddity relations may be a key transitional thinking which supports quantitative and verbal development at the preschool-kindergarten interface. The standardized test scores indicate that guided play directed at this aspect of cognitive growth or more narrowly directed at early literacy can produce equivalent knowledge of letters.


Selective requirement of PI3K/PDK1 signaling for Kras oncogene-driven pancreatic cell plasticity and cancer.
Oncogenic Kras activates a plethora of signaling pathways, but our understanding of critical Ras effectors is still very limited. We show that cell-autonomous phosphoinositide 3-kinase (PI3K) and 3-phosphoinositide-dependent protein kinase 1 (PDK1), but not Craf, are key effectors of oncogenic Kras in the pancreas, mediating cell plasticity, acinar-to-ductal metaplasia (ADM), and pancreatic ductal adenocarcinoma (PDAC) formation. This contrasts with Kras-driven non-small cell lung cancer, where signaling via Craf, but not PDK1, is an essential tumor-initiating event. These in vivo genetic studies together with pharmacologic treatment studies in models of human ADM and PDAC demonstrate tissue-specific differences of oncogenic Kras signaling and define PI3K/PDK1 as a suitable target for therapeutic intervention specifically in PDAC.


[Ureteropelvic junction syndromes: antenatal diagnosis].
Seventy-four hydronephrosis by uretero-pelvic obstruction, discovered by antenatal real-time ultrasound, have been managed on sixty-one children. Three groups, with a specific management, are distinguished. The minimal forms have been only watched over (15 cases). The average forms have been operated (49 cases); considering the results (3 immediate complications and 2 early stenoses), it seems better to wait for 4 months to operate and to place a drain in renal cavities. In major forms (silent kidney on IVP), the diagnosis and therapeutic management use the percutaneous nephrostomy (10 cases). The interest of antenatal diagnosis of uretero-pelvic obstructions is to allow to operate, not only before the renal deterioration emphasizes, but principally before septic complications.


Classification of facial-emotion expression in the application of psychotherapy using Viola-Jones and Edge-Histogram of Oriented Gradient.
Psychotherapy requires appropriate recognition of patient's facial-emotion expression to provide proper treatment in psychotherapy session. To address the needs this paper proposed a facial emotion recognition system using Combination of Viola-Jones detector together with a feature descriptor we term Edge-Histogram of Oriented Gradients (E-HOG). The performance of the proposed method is compared with various feature sources including the face, the eyes, the mouth, as well as both the eyes and the mouth. Seven classes of basic emotions have been successfully identified with 96.4% accuracy using Multi-class Support Vector Machine (SVM). The proposed descriptor E-HOG is much leaner to compute compared to traditional HOG as shown by a significant improvement in processing time as high as 1833.33% (p-value = 2.43E-17) with a slight reduction in accuracy of only 1.17% (p-value = 0.0016).


Oral squamous cell carcinoma arising around osseointegrated dental implants.
This literature review investigates the occurrence of oral squamous cell carcinoma (OSCC) around osseointegrated dental implants (DI). Databases were searched from 1989 up to and including November 2011. The eligibility criteria were as follows: (1) original studies, (2) clinical studies and case reports, (3) reference lists of the relevant original and review articles, (4) intervention: occurrence of OSSC around osseointegrated DI, and (5) articles published only in English language. Fourteen studies were included. In nine studies, the dental implant patients with diagnosed OSCC had previously been exposed to cancer. In five studies, the patients presented with a history of habitual tobacco smoking and alcohol consumption. OSCC is more likely to arise around osseointegrated DI in patients with a previous history of cancer. However, the role of other factors including tobacco and alcohol usage cannot be disregarded.


Hematopoietic Stem Cell Transplantation Stabilizes Cerebral Vasculopathy in High-Risk Pediatric Sickle Cell Disease Patients: Evidence From a Referral Transplant Center.
Severe sickle cell disease (SCD) can present with different vaso-occlusive manifestations with cerebral vasculopathy (CV) as one of the most serious complications. Hematopoietic stem cell transplant (HSCT) is the ultimate therapy for this complication. The aim of this study was to assess the outcome and impact of HSCT on severe SCD patients with CV complications. Twenty-five consecutive transplants-naive pediatric SCD patients with CV complications underwent HSCT at our institution between 1993 and 2015, using bone marrow as stem cells source from fully match related donors were included. Neurologic evaluation was done both clinically and radiologically before transplantation and regularly following the HSCT. With a median follow-up of 52.2 ± 5.8 months, the cumulative probability of overall survival (OS) at 3 years was 92.0% and event-free survival (EFS) was 88%. Significant neurologic improvements were observed in most of the patients clinically. Different neurologic complications were assessed. The neurologic manifestations before and after HSCT were hemiparesis (11, 1), seizures (13, 8), focal neurologic deficit (4, 2), loss of conscious (2, 1) headache (6, 1), and psychological symptoms (5, 2). Post-HSCT radiological imaging was done in 15 patients, which showed stabilization of CV among all. Allogeneic HSCT in patients with severe SCD presenting with CV complications including moyamoya vasculopathy showed favorable outcome with significant clinical neurologic improvement and stabilization of the disease. None of the patients with severe vasculopathy underwent neurological vascular by-pass surgery prior to HSCT.


Epidemiological overview of HIV/AIDS in pregnant women from a state of northeastern Brazil.
To learn the epidemiological characteristics of HIV infection in pregnant women. Descriptive study with quantitative approach. The study population was composed of pregnant women with HIV/AIDS residing in the state of Alagoas. Data were organized into variables and analyzed according to the measures of dispersion parameter relevant to the arithmetic mean and standard deviation (X ± S). Between 2007 and 2015, 773 cases of HIV/AIDS were recorded in pregnant women in Alagoas. The studied variables identified that most of these pregnant women were young, had low levels of education and faced socioeconomic vulnerability. It is necessary to include actions aimed at increasing the attention paid to women, once the assurance of full care and early diagnosis of HIV are important strategies to promote adequate treatment adherence and reduce the vertical transmission.


Analysis of Campylobacter jejuni antigens with monoclonal antibodies.
To develop monoclonal reagents for antigenic analysis and serotyping of Campylobacter spp., hybridoma cell lines were produced by fusion of mouse myeloma cells and spleen cells from mice immunized with Formalin-treated Campylobacter jejuni organisms. An enzyme immunoassay was used for preliminary screening of the cell culture supernatants and ascites. Twenty-nine clones which reacted with the immunogen were obtained. Seven of these clones were positive in passive hemagglutination tests with sheep erythrocytes coated with boiled saline extract of whole bacteria; four of these reacted with the purified polysaccharide preparation and with the autoclaved saline extract, but not with lipopolysaccharide prepared from the immunogen strain. Two of the antipolysaccharide clones agglutinated live bacteria in slide tests. Four additional clones gave positive slide agglutination tests with live bacteria, but in tube testing no clones agglutinated Formalin-treated bacteria. No cross-reactions with unrelated bacteria were seen, but several clones reacted in the enzyme immunoassay with many of the 24 Campylobacter strains studied. The clone which gave the highest mean enzyme immunoassay values with Campylobacter coli and C. jejuni strains also reacted with Campylobacter fetus subsp. veneralis and C. fetus subsp. fetus strains. This clone also gave the highest enzyme immunoassay value with an acid glycine extract of the immunogen, which indicates the presence of common antigens in the extract. The results suggest that monoclonal antibodies may be used to devise serotyping schemes for Campylobacter spp.