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The hirudin-like factors 3 (HLF3) and 4 (HLF4) belong to a new class of leech-derived factors and are present in specimens of the three European medicinal leeches, Hirudo medicinalis, Hirudo verbana, and Hirudo orientalis, respectively. Here we describe the functional analysis of natural and synthetic variants of HLF3 and HLF4. Whereas the natural variants display only very low or no detectable anti-coagulatory activities, modifications within the N-termini in combination with an exchange of the central globular domain have the potency to greatly enhance the inhibitory effects of respective HLF3 and HLF4 variants on blood coagulation. Our results support previous observations on the crucial importance of all parts (both the N- and C-termini as well as the central globular domains) of hirudin and HLF molecules for thrombin inhibition. | Hirudins |
BACKGROUND AND OBJECTIVE: Immunosuppression is characteristic of the luteal phase of the menstrual cycle and is accompanied by an adaptive disgust response to reduce contact with pathogens. However, research has not examined the effects of emotion regulation on disgust during the menstrual cycle. Accordingly, the present study examines the effect of suppression and reappraisal on disgust during the luteal and follicular phases of the menstrual cycle. METHOD: Menstrual cycle phase was estimated in a sample of naturally cycling women (n = 73), and those in the follicular or luteal phase were assigned to suppress or reappraise disgust while watching a disgust-inducing video. Physiological arousal during the video and avoidance of disgust cues in a public restroom after the video were also assessed. RESULTS: No differences were observed in self-reported disgust to the video between those who suppressed and those who reappraised in the luteal phase. However, women in the follicular phase who suppressed reported less disgust than those who reappraised. The emotion regulation strategies did not influence physiology during the video or avoidance after the video as a function of menstrual cycle phase. LIMITATIONS: Hormone assay data was not collected to confirm menstrual cycle phase and a relatively small sample of naturally cycling women was used. CONCLUSIONS: Suppression may be a more effective strategy than reappraisal for reducing verbal disgust in the follicular phase but not in the luteal phase. The implications of these findings for the treatment of disgust-based disorders among women are discussed. | Menstrual Cycle |
The ordinary linear regression method is limited to bivariate data because it is based on the Cartesian representation y = f(x). Using the chain rule, we transform the method to the parametric representation (x(t), y(t)) and obtain a linear regression framework in which the weighted average is used as a parameter for a multivariate linear relation for a set of linearly related variable vectors (LRVVs). We confirm the proposed approach by a Monte Carlo simulation, where the minimum coefficient of variation for error (CVE) provides the optimal weights when forming a weighted average of LRVVs. Then, we describe a parametric linear regression (PLR) algorithm in which the Moore-Penrose pseudoinverse is used to estimate measurement error regression (MER) parameters individually for the given variable vectors. We demonstrate that MER parameters from the PLR and nonlinear ODRPACK methods are quite similar for a wide range of reliability ratios, but ODRPACK is formulated only for bivariate data. We identify scale invariant quantities for the PLR and weighted orthogonal regression (WOR) methods and their correspondences with the partitioned residual effects between the variable vectors. Thus, the specification of an error model for the data is essential for MER and we discuss the use of Monte Carlo methods for estimating the distributions and confidence intervals for MER slope and correlation coefficient. We distinguish between elementary covariance for the y = f(x) representation and covariance vector for the (x(t), y(t)) representation. We also discuss the multivariate generalization of the Pearson correlation as the contraction between Cartesian polyad alignment tensors for the LRVVs and weighted average. Finally, we demonstrate the use of multidimensional PLR in estimating the MER parameters for replicate RNA-Seq data and quadratic regression for estimating the parameters of the conical dispersion of read count data about the MER line. | Linear Models |
The reduction of vanadate (+V) in the presence of 3-mercaptopropionic acid was studied using a chromatographic method for the determination of vanadate (+V) versus vanadyl (+IV) species. Ion chromatography was combined with spectrophotometric investigation of the absorption properties of the solution. The chromatographic method for the separation of vanadate (+V) and vanadyl (+IV) was carried out with an anion exchange column. In the initial reaction mixture containing vanadate (+V) and 3-mercaptopropionic acid, ethylenediaminetetraacetic acid - EDTA was added in an excessive amount relative to the concentration of reactants in the solution. After the ligand exchange reaction, the added EDTA terminates the reduction, allowing redox speciation in the solutions. A strong pH dependence of the reduction rates in the investigated solution was observed. The vanadate reduction seems to proceed in 2 steps: 1) formation of the intermediate vanadate (+V)-thioester; 2) reduction reaction and formation of the vanadyl (+IV)-thiol complex. The obtained results strongly suggest that the reaction of vanadate (+V)-thioester formation is proton catalyzed. It was observed that the overall reduction rates are pH dependent due to the complex vanadate (+V) solution speciation and changes in the ionic form of 3-mercaptopropionic acid. | 3-Mercaptopropionic Acid |
Gastrointestinal (GI) cancers are a group of highly prevalent malignant tumors affecting the gastrointestinal tract. Globally, one in four cancer cases and one in three cancer deaths are estimated to be GI cancers. They can alter digestive and absorption functions, leading to severe malnutrition which may worsen the prognosis of the patients. Therefore, nutritional intervention and monitoring play a fundamental role in managing metabolic alterations and cancer symptoms, as well as minimizing side effects and increasing the effectiveness of chemotherapy. In this scenario, the use of immunonutrients that are able to modulate the immune system and the modification/regulation of the gut microbiota composition have gained attention as a possible strategy to improve the conditions of these patients. The complex interaction between nutrients and microbiota might contribute to maintaining the homeostasis of each individual's immune system; therefore, concurrent use of specific nutrients in combination with traditional cancer treatments may synergistically improve the overall care of GI cancer patients. This work aims to review and discuss the role of immunonutrition and microbiota modulation in improving nutritional status, postoperative recovery, and response to therapies in patients with GI cancer. | Immunonutrition Diet |
Inhibition of dipeptidyl peptidase IV is an important approach for the treatment of type-2 diabetes. In this study, we reported a multistage virtual screening workflow that integrated 3D pharmacophore models, structural consensus docking, and molecular mechanics/generalized Born surface area binding energy calculation to identify novel dipeptidyl peptidase IV inhibitors. After screening our in-house database, two hit compounds, HWL-405 and HWL-892, having persistent high performance in all stages of virtual screening were identified. These two hit compounds together with several analogs were synthesized and evaluated for in vitro inhibition of dipeptidyl peptidase IV. The experimental data indicated that most designed compounds exhibited significant dipeptidyl peptidase IV inhibitory activity. Among them, compounds 35f displayed the greatest potency against dipeptidyl peptidase IV in vitro with the IC50 value of 78 nm. In an oral glucose tolerance test in normal male Kunming mice, compound 35f reduced blood glucose excursion in a dose-dependent manner." | Dipeptidyl-Peptidase IV Inhibitors |
Xanthogranulomatous pyelonephritis is a chronic renal inflammation characterized by destruction and replacement of its parenchyma with granulomatous tissue. This uncommon condition is rare in children. We report on a 5-month-old male infant with a left renal and hepatic mass detected by ultrasound. The case was preoperatively misdiagnosed as Wilms' tumor and total nephrectomy and biopsy from liver lesion were performed. The subsequent histopathological findings confirmed the diagnosis of xanthogranulomatous pyelonephritis for renal and liver lesions. Increasing awareness of this disease should lead to the diagnosis being suspected preoperatively even if it is with unconnected tissue lesions." | Pyelonephritis, Xanthogranulomatous |
Conducting a clinical trial involves various stages of planning and implementation. The three major components involved in clinical trials are the management of data, the quality control to ensure data integrity, and the interpretation of the data at the conclusion of the trial. Although each process is distinct and involves different levels of effort and knowledge to implement, all processes are intimately linked. Data management techniques include the process of data entry and the implementation of an organized, comprehensive approach to quality control. Some guidelines for quality control screening are recommended to address various common issues related to clinical data, such as missing data, invalid cases, subject "outliers," and violation of distributional assumptions relevant to statistical analyses. In order to aid in interpreting the data, conditions that need to be met to make causal inferences are discussed. Taking into account baseline characteristics of the patient sample is also discussed as an extension to maintaining the internal validity of the study. Additionally, some common threats to statistical conclusion validity, including Type I error inflation and the problem of overpowered tests, are highlighted. Finally, the concept of the effect size as an important complement to statistical significance and how the various types of effect size measures can be interpreted within the context of a clinical trial are discussed." | Clinical Trials Data Monitoring Committees |
Mounting evidence is compiling linking the physical organizational structure of chromosomes and the nuclear structure to biological function. At the base of the physical organizational structure of both is the concept of loop formation. This implies that physical proximity within chromosomes is provided for otherwise distal genomic regions and thus hierarchically organizing the chromosomes. Together with entropy many experimental observations can be explained with these two concepts. Among the observations that can be explained are the measured physical extent of the chromosomes, their shape, mechanical behavior, the segregation into territories (chromosomal and territories within chromosomes), the results from chromosome conformation capture experiments, as well as linking gene expression to structural organization. | Chromosome Structures |
Ubiquitination is an intricately regulated post-translational modification that involves the covalent attachment of ubiquitin to a substrate protein. The complex dynamic nature of the ubiquitination process regulates diverse cellular functions including targeting proteins for degradation, cell cycle, deoxyribonucleic acid (DNA) damage repair, and numerous cell signaling pathways. Ubiquitination also serves as a crucial mechanism in protein quality control. Dysregulation in ubiquitination could result in lethal disease conditions such as cancers and neurodegenerative diseases. Therefore, the ubiquitination cascade has become an attractive target for therapeutic interventions. Enormous efforts have been made to detect ubiquitination involving different detection techniques to better grasp the underlying molecular mechanisms of ubiquitination. This review discusses a wide range of techniques stretching from the simplest assays to real-time assays. This includes western blotting/immunoblotting, fluorescence assays, chemiluminescence assays, spectrophotometric assays, and nanopore sensing assays. This review compares these applications, and the inherent advantages and limitations. | Protein Biosynthesis |
Previously unrecognized but clinicopathologically (and often molecularly) distinct types of soft tissue tumor continue to be characterized, allowing wider recognition, more consistent application of diagnostic criteria, more reliable prediction of tumor behavior and enhancement of existing classification schemes. Examples of such 'entities' that have become much better understood over the past decade or so include deep 'benign' fibrous histiocytoma, hemosiderotic fibrolipomatous tumor, PEComa, spindle cell liposarcoma, myoepithelial tumors of soft tissue and spindle cell/sclerosing rhabdomyosarcoma. These tumor types, as well as the insights which they have engendered, are briefly reviewed here. | Neoplasms by Histologic Type |
OBJECTIVES: Variation in trabecular and cortical bone properties is often used to infer habitual behavior in the past. However, the structures of both types of bone are rarely considered together and may even contradict each other in functional interpretations. We examine trabecular and cortical bone properties in various athletes and sedentary controls to clarify the associations between combinations of cortical and trabecular bone properties and various loading modalities. MATERIALS AND METHODS: We compare trabecular and cortical bone properties using peripheral quantitative computed tomography scans of the tibia between groups of 83 male athletes (running, hockey, swimming, cricket) and sedentary controls using Bayesian multilevel models. We quantify midshaft cortical bone rigidity and area (J, CA), midshaft shape index (Imax/Imin), and mean trabecular bone mineral density (BMD) in the distal tibia. RESULTS: All groups show unique combinations of biomechanical properties. Cortical bone rigidity is high in sports that involve impact loading (cricket, running, hockey) and low in nonimpact loaded swimmers and controls. Runners have more anteroposteriorly elliptical midshafts compared to other groups. Interestingly, all athletes have greater trabecular BMD compared to controls, but do not differ credibly among each other. DISCUSSION: Results suggest that cortical midshaft hypertrophy is associated with impact loading while trabecular BMD is positively associated with both impact and nonimpact loading. Midshaft shape is associated with directionality of loading. Individuals from the different categories overlap substantially, but group means differ credibly, suggesting that nuanced group-level inferences of habitual behavior are possible when combinations of trabecular and cortical bone are analyzed. | Cancellous Bone |
In this study, we examined 7B2 (secretogranin V)-like immunoreactivity (IR) in the Japanese red-bellied newt (Cynops pyrrhogaster) pituitary. Results showed that the pars nervosa was filled with immunoreactive granules. In the pars intermedia, all melanotrophs showed 7B2-IR. In the pars distalis, immunoreactive cells were dispersed, and the 7B2-immunoreactive cells were also immunopositive for the beta-subunit of bullfrog luteinizing hormone (fLHbeta). 7B2-IR co-localized with fLHbeta-IR in the same secretory granules. Our results suggest that 7B2 may participate in the secretion processes of gonadotropins in the pars distalis." | Luteinizing Hormone, beta Subunit |
Isatin is an endogenous and a significant category of fused heterocyclic components and has widely been a part of several potential biologically useful synthetics. Since its discovery, tons of research work has been conducted with respect to the synthesis, chemical properties, and biological and industrial applications. It contains an indole nucleus having both lactam and keto moiety, which, while being a part of a molecular framework, exerted several biological effects, viz.; anti-microbial, anti-tubercular, anticonvulsant, anti-cancer, etc. Isatin derivatives are synthetically significant substrates, which can be utilized for the synthesis of huge diversified chemical entities of which few members emerged as drugs. The reason for this review is to provide extensive information pertaining to the chemistry and its significance in altering several pathological states of isatin and its derivatives. A Structure-Activity Relationship study thus developed through a gamut of scientific information indicates the importance of mostly electron-withdrawing groups, halogens, nitro, alkoxy, and, to a minor extent, groups with positive inductive effects, such as methyl at position 1, 5, 6 and 7 of isatin in alleviating several clinical conditions. It is also observed from the survey that the presence of two oxo groups at positions 2 and 3 sometimes becomes insignificant as a fusion with a heterocycle at these positions resulted in a biologically relevant compound. | Therapeutic Uses |
Zimeldine is recently-introduced antidepressant drug. It has a novel pyridylallylamine structure and acts by selective inhibition of 5-hydroxytryptamine re-uptake at central nerve synapses. This communication reports 2 patients who developed neuropathies within 1 week of starting treatment with this drug. This has hitherto not been described. | Brompheniramine |
The effects of light on urediniospore germination and germ tube elongation was studied with eight species of rust fungi that infect ornamental plants or row crops. Exposure of six species of fungi to cool white fluorescent light at 400 or 600 micromol s(-1) m(-2) for 24 h significantly reduced germination with largest decreases typically observed at 600 micromol s(-1) m(-2). Germination and germ tube elongation did not recover during 24 h dark incubation after 18 h exposure to fluorescent light at 600 micromol s(-1) m(-2), indicating the effects were not reversible. Germ tube elongation of all fungi was negatively affected by increased length of exposure to fluorescent light. Increased exposure to fluorescent light differentially affected germination of the fungi with Puccinia hemerocallidis, Phakopsora pachyrhizi, Pucciniastrum vaccinii and Puccinia menthae negatively affected and Puccinia sorghi, Puccinia triticina, Puccinia pelargonii-zonalis and Puccinia iridis relatively unaffected in 10 h incubation. Exposure of Ph. pachyrhizi and P. triticina urediniospores to sunlight rapidly reduced germination and germ tube elongation with no germination observed for Ph. pachyrhizi after 2.5 h. Germ tube elongation but not germination of hydrated urediniospores of Ph. pachyrhizi and P. triticina was significantly reduced compared to dry urediniospores exposed to 10 h fluorescent light followed by 24 h dark incubation. Exposure to fluorescent light (all fungi) or sunlight (two fungi) negatively affected urediniospore germ tube elongation. Differences observed in urediniospore germination between fungi suggest some species have co-evolved with their host for differing light conditions. Our data suggests exposure of urediniospores to strong light could inactivate rust fungi on plant surfaces or in the atmosphere. | Hemerocallis |
1. mCRPC patients with gDDRm exhibit a good response to first abiraterone/enzalutamide treatments, despite this was not statistically significant. 2. The different detections of gDDRm and treatments (abiraterone or enzalutamide), indeed, are influential factors. | Phenylthiohydantoin |
Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder postulated to result from lack of regulation of fusion of the primary lysosomes. In this report we present the MR and CT features of the brain in a patient with known CHS. These findings include diffuse atrophy of the brain with diffuse periventricular decreased density identified with CT, as well as increased signal on the T2-weighted images and lack of enhancement on the T1-weighted images in the periventricular and corona radiata regions. | Chediak-Higashi Syndrome |
Azathioprine is a synthetic purine analog derived from 6-mercaptopurine. It is a purine antagonist and its active metabolites act by disrupting the function of endogenous purines. It has a cytotoxic and immunosuppressive mechanism of action. It is used in dermatology for treatment of immunobullous diseases, generalized eczematous disorders and photodermatoses. There is an enzyme in the metabolism of azathioprine called thiopurine s-methyltransferase (TPMT). It is very important to measure the TPMT activity before initiating therapy so that proper dosing of azathioprine can be achieved. | Azathioprine |
Some 10 low molecular weight heparin products are currently available for commercial use. Enoxaparin and fraxiparin appear to be the most developed low molecular weight heparins. Many well-designed clinical trials have been carried out for different clinical indications with both of these products. As shown in both experimental and clinical settings, the prophylactic antithrombotic efficacy of enoxaparin is distinct from other low molecular weight heparins. Enoxaparin has provided consistently impressive clinical results. Moreover, at comparable dosages, other products have exhibited safety/efficacy profiles different from that of enoxaparin. The clinical performance of each low molecular weight heparin is characteristic of only that particular agent. Besides the commercially available low molecular weight heparin preparations, some 14 other agents are under development at this time. Although each product has similar basic characteristics, their biological actions should be studied carefully. Apart from differences in the physicochemical properties, the pharmacologic actions of these agents may differ significantly. Only results from valid clinical trials will show similarities or differences between the low molecular weight heparins. Other manufacturers should follow the lead of enoxaparin and conduct their own clinical trials on each of their products. | Heparin, Low-Molecular-Weight |
OBJECTIVES: Procrastination is typically assessed via self-report questionnaires. So far, only very few studies have examined actual procrastination behavior, providing inconclusive results regarding the real-life validity of self-reports in this domain. The present study aimed to examine for the first time whether participants' self-reported procrastination can predict their actual behavior on a real-life task. METHODS: For that purpose, we assessed self-reported levels of procrastination [via the Pure Procrastination Scale, PPS] and actual procrastination behavior on a naturalistic task [i.e., having to send in an attendance sheet before a deadline] in 93 participants. RESULTS: Results show that self-reports significantly predicted procrastination behavior. Analyses of underlying dimensions suggest that real-life procrastination can be the result of voluntarily delaying planned actions," but can also have more passive causes such as "running out of time." CONCLUSIONS: Comparing our results with the available literature suggests that PPS self-reports reflect a particularly valid tool to assess real-life procrastination behavior. Findings are discussed in the context of strategies and mechanisms that potential interventions may target in order to reduce procrastination." | Procrastination |
This study tested the viability and efficiency of a hereditary hemoglobinopathy program in which a Brazilian community the town of Braganca Paulista, SP (Brazil)-was involved, were tested focusing school students. The screening of the hemoglobinopathies was done through optional exams for patients by using electrophoresis of hemoglobins and complementary hematological tests. A total of 1,171 individuals, including, 1,118 pupils and 53 of their relatives were tested over a period of 24 months. A total of 47 individuals with hereditary hemoglobin changes were detected-4.0% of the samples examined. The community was fairly receptive to the program which showed a general level of acceptance of 55.4%. The study aroused the interest of the community and motivated the implantation of a special service for diagnosis, genetic counseling and treatment of the hemoglobinopathy carriers in the community where it was undertaken. | Hemoglobin C Disease |
PURPOSE OF REVIEW: Idiopathic intracranial hypertension (IIH) is a potentially blinding disorder of unknown cause, characterized by elevated intracranial pressure in the absence of a mass lesion, venous sinus thrombosis, or meningitis. This review summarizes recent developments and insights from leading treatment trials, emerging treatment options, and evolving ways to evaluate IIH. RECENT FINDINGS: The Idiopathic Intracranial Hypertension Treatment Trial is the first large-scale, randomized, prospective study to evaluate medical treatment of patients with mild vision loss. These data have facilitated our understanding of baseline clinical manifestations, including impact on quality of life and treatment outcomes. Recent hypotheses and studies evaluating the role of cerebral venous sinus stenosis and stenting are discussed. Technological advances in optical coherence tomography are emerging to provide novel ways of evaluating and tracking optic disc swelling in IIH. SUMMARY: Recent changes in defining IIH, understanding the impact and treatment of mild visual loss, and the roles that cerebral venous stenting and optical coherence tomography might have in clinical practice provide the framework to better treat patients with IIH. | Intracranial Hypertension |
For the first time in the USSR the properties of microorganisms of the genus Clostridium have been studied with the use of the gas-chromatographic techniques. The analysis of the quantitative and qualitative composition of extracellular alcohols and carboxylic acids in 99 museum and newly isolated strains of 18 Clostridium species has made it possible to classify these microorganisms with 7 sharply differing groups. The above techniques permit the classification of clostridia with one of the groups within 2 hours if the microbial cultures have been grown in glucose-containing peptone yeast medium. | Clostridiaceae |
Giardia duodenalis is a widespread parasite of mammalian species, including humans. Due to its invariant morphology, investigation on aspects such as host specificity and transmission patterns requires a direct genetic characterization of cysts/trophozoites from host samples. A number of molecular assays have been developed to help unravel the complex epidemiology of this infection. A coherent picture has emerged from those studies, indicating the existence of seven genetic groups (or assemblages), two of which (A and B) are found in both humans and animals, whereas the remaining five (C-G) are host-specific. Sequence-based surveys have identified a number of genotypes within assemblages A and B in animal species, some of which may have zoonotic potential. Recently, however, molecular approaches have been complicated by the recognition of intra-isolate sequence heterogeneity (i.e., mixed templates", that affects identification of subtypes within each assemblage), and by the unreliable assignment of isolates to G. duodenalis assemblages generated by different genetic markers. This raises concerns about previous interpretation of genotyping data, especially when single genetic markers have been used. The mechanisms that may be responsible for these findings, including allelic sequence heterozygosity and meiotic recombination, are discussed." | Giardia |
IMPORTANCE: Approximately 18.6 million people worldwide are affected by a diabetic foot ulcer each year, including 1.6 million people in the United States. These ulcers precede 80% of lower extremity amputations among people diagnosed with diabetes and are associated with an increased risk of death. OBSERVATIONS: Neurological, vascular, and biomechanical factors contribute to diabetic foot ulceration. Approximately 50% to 60% of ulcers become infected, and about 20% of moderate to severe infections lead to lower extremity amputations. The 5-year mortality rate for individuals with a diabetic foot ulcer is approximately 30%, exceeding 70% for those with a major amputation. The mortality rate for people with diabetic foot ulcers is 231 deaths per 1000 person-years, compared with 182 deaths per 1000 person-years in people with diabetes without foot ulcers. People who are Black, Hispanic, or Native American and people with low socioeconomic status have higher rates of diabetic foot ulcer and subsequent amputation compared with White people. Classifying ulcers based on the degree of tissue loss, ischemia, and infection can help identify risk of limb-threatening disease. Several interventions reduce risk of ulcers compared with usual care, such as pressure-relieving footwear (13.3% vs 25.4%; relative risk, 0.49; 95% CI, 0.28-0.84), foot skin measurements with off-loading when hot spots (ie, greater than 2 degrees C difference between the affected foot and the unaffected foot) are found (18.7% vs 30.8%; relative risk, 0.51; 95% CI, 0.31-0.84), and treatment of preulcer signs. Surgical debridement, reducing pressure from weight bearing on the ulcer, and treating lower extremity ischemia and foot infection are first-line therapies for diabetic foot ulcers. Randomized clinical trials support treatments to accelerate wound healing and culture-directed oral antibiotics for localized osteomyelitis. Multidisciplinary care, typically consisting of podiatrists, infectious disease specialists, and vascular surgeons, in close collaboration with primary care clinicians, is associated with lower major amputation rates relative to usual care (3.2% vs 4.4%; odds ratio, 0.40; 95% CI, 0.32-0.51). Approximately 30% to 40% of diabetic foot ulcers heal at 12 weeks, and recurrence after healing is estimated to be 42% at 1 year and 65% at 5 years. CONCLUSIONS AND RELEVANCE: Diabetic foot ulcers affect approximately 18.6 million people worldwide each year and are associated with increased rates of amputation and death. Surgical debridement, reducing pressure from weight bearing, treating lower extremity ischemia and foot infection, and early referral for multidisciplinary care are first-line therapies for diabetic foot ulcers. | Diabetic Foot |
The microbial ecosystem of fermented food is greatly disturbed by human activities.Jiuyao is important saccharification starter for brewing huangjiu. The interaction between environmental factors and microorganisms significantly affected the microbial community structure at different stages of Jiuyao manufacturing. This study combined environmental factor analysis and high-throughput sequencing technology to comprehensively analyze the specific changes of microbial community and environmental factors in each fermentation stage of Jiuyao production and their correlation. The results showed that the activities of liquefaction enzyme, glycosylation enzyme and acid protease reached the highest value on the 8 th day (192 h) after the beginning of fermentation, and the cellulase activity reached the highest value at the end of fermentation. Pediococcusï¼Â37.5 %-58.2 %ï¼Â, Weissellaï¼Â9.2 %-27.0 %ï¼ and Pelomonasï¼Â0.1 %-12.1 %ï¼ were the main microbial genera in the genus bacteria, and Saccharomycopsisï¼Â37.1 %-52.0 %ï¼Â, Rhizopusï¼Â12.5 %-31.0 %ï¼ and Saccharomycesï¼Â4.0 %-20.5 %ï¼ were the main microbial genera in the genus fungi. The results of correlation analysis showed that the microbial communities in Jiuyao were closely related to environmental factors. Most microbial communities were positively correlated with temperature, but negatively correlated with ambient humidity, CO(2) concentration, acidity and water content of Jiuyao. In addition, the transcription levels of enzymes related to microbial glucose metabolism in Jiuyao were higher in the late stage of Jiuyao fermentation. Interestingly, these enzymes had high transcription levels in fungi such as Saccharomycopsis, Rhizopus and Saccharomyces, as well as in bacteria such as Pediococcus and Lactobacillus. This study provides a reference for revealing the succession rule of microbial community structure caused by environmental factors during the preparation of Jiuyao in Shaoxing Huangjiu. | Fermented Beverages |
A response to and comment on The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury, by Haleema Shakur, Ian Roberts, et al." | Bradykinin B2 Receptor Antagonists |
OBJECTIVES: To review how the Apgar score is used in published clinical research as well as who uses it, and how this may have changed between 1989-90 and 2018-19. METHODS: Pubmed search for English publications using MeSH Terms apgar score" OR "apgar" AND "score" AND "humans" for epochs 1989-90 & 2018-19. The location and specialty of first author, primary purpose and how the Apgar score was used was recorded. RESULTS: There was a 61% increase in number of publications in 2018-19 compared to 1989-90, from all regions except North America. The most common purpose for using the Apgar was to assess newborn status after pregnancy/delivery interventions. There were 50 different definitions of a significant score. Definition of significance was influenced by specialty in 2018-19 and by study purpose in both epochs. CONCLUSIONS: Most studies using the Apgar score are focused on the mother. There is no consistent definition of a significant score. Development of any future newborn assessment tools should account for the multiple purposes for which the Apgar score is used." | Apgar Score |
A comprehensive study was made on the activity concentrations, concentration factors, and radiation exposure impact of the main naturally occurring radionuclides in blue mussels collected in the Mediterranean Sea. The results showed that the concentrations of the measured radionuclides were site-specific and all detectable in gram-size samples of the soft tissues of the mussels, especially, some activity concentrations can reach as high as 16.8-102 Bq kg(-1) for (210)Po, 16.7-66.8 Bq kg(-1) for (40)K and 0.602-3.21 Bq kg(-1) for (210)Pb. The obtained mean concentration factors in the soft tissues of the mussel samples are 6.30 +/- 2.40 for (238)U and (234)U, 4.68 +/- 1.73 for (235)U, (2.72 +/- 1.73) x 10(4) for (232)Th and (230)Th, 480 +/- 265 for (228)Th, 33.3 +/- 13.3 for (226)Ra, 100 +/- 52 for (224)Ra and 29.0 +/- 14.7 for (228)Ra, (1.22 +/- 0.72) x 10(4) for (210)Po, 517 +/- 280 for (210)Pb and 2.57 +/- 0.80 for (40)K. The estimated mean committed effective doses of (238)U, (234)U, (235)U, (232)Th, (230)Th, (228)Th, (226)Ra, (224)Ra, (228)Ra, (210)Po, (210)Pb and (40)K to an adult due to mussel ingestion are 0.073 +/- 0.027, 0.089 +/- 0.035, 0.0030 +/- 0.0011, 0.128 +/- 0.098, 0.117 +/- 0.081, 0.056 +/- 0.031, 0.145 +/- 0.058, 0.0487 +/- 0.0250, 0.395 +/- 0.200, 352 +/- 209, 6.00 +/- 3.25 and 1.74 +/- 0.54 muSv a(-1), respectively. Among the elements or nuclides, (210)Po is the dominant dose contributor which contributes 96.9% of total dose fraction, and the relative dose contribution is in the order of (210)Po > (210)Pb > (40)K > radium >/= thorium >/= uranium. | Mytilus edulis |
We have studied the effects of Ba++, a known K+ channel blocker, on the electrophysiological properties of the glial cells of Necturus optic nerve. The addition of Ba++ reversibly depolarized glial cells by 25-50 mV; the half maximal deplorization was obtained with a Ba++ concentration of approximately 0.3 mM. In the presence of Ba++, the sensitivity of the membrane to changes in K+ was reduced and there was evidence of competition between K+ and Ba++ for the K+ channel. These effects, which were accompanied by a large increase in the input resistance of the glial cells, indicate that Ba++ blocks the K+ conductance in glial cells of Necturus optic nerve. With the K+ conductance reduced, we were able to investigate the presence of other membrane conductances. We found that in the presence of Ba++, the addition of HCO3- caused a Na+-dependent hyperpolarization that was sensitive to the disulfonic stilbene SITS (4-acetamido-4'-isothiocyanostilbene-2, 2'-disulfonic acid). Removal of Na+ resulted in a HCO3- -dependent, SITS-sensitive depolarization. These results are consistent with the presence in the glial membrane of an electrogenic Na+/HCO3- cotransporter in which Na+, HCO3-, and net negative charge are transported in the same direction. In Cl- -free solutions, the Ba++-induced depolarization increased, suggesting a small permeability to Cl-. Using voltage-sensitive dyes and a photodiode array for multiple site optical recording, the distribution of potential changes in response to square pulses of intracellularly injected current were recorded before and after the addition of increased and the decay of amplitude as a function of distance decreased. Such results indicate that Ba++ increases the membrane resistance more than the resistance of the intercellular junctions. | Necturus maculosus |
Reservoir souring, which is the production of H(2)S mainly by sulfate-reducing microorganisms (SRM) in oil reservoirs, has been a long-standing issue for the oil industry. While biocides have been frequently applied to control biogenic souring, the effects of biocide treatment are usually temporary, and biocides eventually fail. The reasons for biocide failure and the long-term response of the microbial community remain poorly understood. In this study, one-time biocide treatments with glutaraldehyde (GA) and an aldehyde-releasing biocide (ARB) at low (100 ppm) and high (750 ppm) doses were individually applied to a complex SRM community, followed by 1 year of monitoring of the chemical responses and the microbial community succession. The chemical results showed that souring control failed after 7 days at a dose of 100 ppm regardless of the biocide type and lasting souring control for the entire 1-year period was achieved only with ARB at 750 ppm. Microbial community analyses suggested that the high-dose biocide treatments resulted in 1 order of magnitude lower average total microbial abundance and average SRM abundance, compared to the low-dose treatments. The recurrence of souring was associated with reduction of alpha diversity and with long-term microbial community structure changes; therefore, monitoring changes in microbial community metrics may provide early warnings of the failure of a biocide-based souring control program in the field. Furthermore, spore-forming sulfate reducers (Desulfotomaculum and Desulfurispora) were enriched and became dominant in both GA-treated groups, which could cause challenges for the design of long-lasting remedial souring control strategies. IMPORTANCE Reservoir souring is a problem for the oil and gas industry, because H(2)S corrodes the steel infrastructure, downgrades oil quality, and poses substantial risks to field personnel and the environment. Biocides have been widely applied to remedy souring, but the long-term performance of biocide treatments is hard to predict or to optimize due to limited understanding of the microbial ecology affected by biocide treatment. This study investigates the long-term biocide performance and associated changes in the abundance, diversity, and structure of the souring microbial community, thus advancing the knowledge toward a deeper understanding of the microbial ecology of biocide-treated systems and contributing to the improvement of current biocide-based souring control practices. The study showcases the potential application of incorporating microbial community analyses to forecast souring, and it highlights the long-term consequences of biocide treatment in the microbial communities, with relevance to both operators and regulators. | Oil and Gas Fields |
Desmoid tumors are rare, clonal collections of benign fibrous tissue that exhibit a highly variable clinical course. This article presents a comprehensive review of desmoid tumors and summarizes the current literature pertaining to clinical presentation, diagnostic modalities, pathogenesis, prognostic factors, and management options. | Neoplasms, Fibrous Tissue |
It is known that lymph node metastasis lowers the survival rates in laryngeal carcinoma. This study aimed to investigate the effect of extranodal extension in lymph node metastasis on survival. The demographic characteristics and histopathologic results of 81 patients who underwent total laryngectomy and neck dissection due to advanced larynx squamous cell carcinoma between 2011 and 2018 were reviewed retrospectively. The patients were divided into 3 groups by lymph node metastasis status as reactive lymph node (group 1), lymph node metastasis without detected extranodal extension (group 2), and lymph node metastasis with detected extranodal extension (group 3). Survival analysis was performed between these 3 groups. In the patient population with a mean age of 61.56 years consisting of 6 females and 75 males, demographic characteristics between groups were comparable. Overall survival (OS) rates were detected to be 81% in group 1, 69.2% in group 2, and 61.5% in group 3. Two-year OS rates were detected to be 66.7% in group 1, 46.2% in group 2, and 38.5% in group 3. Statistical difference was detected between group 1 and group 3 both for OS and 2-year OS (P = .014, P = .008, respectively). No statistical difference was detected between group 2 and group 1, and between group 2 and group 3. In this study, we found a negative effect of detecting neck lymphadenopathy metastasis and extranodal extension on survival in patients who underwent total laryngectomy and neck dissection due to advanced laryngeal carcinoma. | Extranodal Extension |
Mammalian skin, the outer covering of the body, is composed of three layers, i.e. the epidermis, the dermis and the subcutaneous white adipose tissue (SWAT). While the contribution of epidermis and dermis to the skin's immune function is well established, the role, if any, of SWAT in this regard has yet to be determined. Human SWAT is made up of lobules which consist mainly of adipocytes and are subdivided and separated from each other by vascularized septae of connective tissue. An immunophenotypic analysis of liposuction-derived SWAT demonstrated that healthy subcutaneous fat tissue, although showing no overt signs of inflammation, harbors an indigenous system of immunocytes. As opposed to epidermis and dermis, they belong mainly to the mononuclear phagocyte lineage and, to a lesser extent, represent T-lymphocytes. Their phenotype indicates that these two major subsets of SWAT leukocytes are primarily concerned with ant-inflammatory and/or regulatory functions. It thus appears that SWAT is more than a cushion protecting against mechanical trauma, and may subserve immunomodulatory functions aimed at preventing or, at least, mitigating exaggerated immune and/or inflammatory reactions.. | Adipose Tissue, White |
Effective and efficient delivery of health care is one of the critical issues facing the nation today. Currently, nearly 13% of the nation's GDP in spent on Health Care. Perhaps one-half of the increase in health care costs have been linked to the acquisition of new medical technology. This paper examines some of the issues relating to the acquisition and dissemination of the use of medical technology by acute care and outpatient facilities and discusses the rationing of medical technology. The paper concludes by identifying some of the approaches to controlling health care costs through the rationing of technology that have been presented in the literature and outlines the evolving new paradigm that is being advanced to address the issues of cost containment and access to health care. | Technology, High-Cost |
Diseases with T-helper cell subset imbalance involve multiple systems and organs. In addition to this, the pathogenesis of these diseases is always complex, and involves Th1, Th2, Th9, Th17, Th22, and Tfh cells. T-helper cell subset imbalance mediates immune responses to various pathogenic factors, by secreting specific cytokines. Although several studies have revealed the specific mechanisms of the occurrence and development of these diseases from different aspects, there is still a need for more comprehensive and in-depth studies that can compensate for the corresponding gaps in the diagnosis, targeted therapy, and prognosis of these diseases. N6-methyladenosine(m(6)A) modification is the most prevalent and abundant post-transcriptional modification in eukaryotic RNAs. In recent years, the critical role of m(6)A modification has been confirmed in multiple diseases with T-helper cell subset imbalance. m(6)A modification affects the immune cell development, inflammatory processes, biological behaviour of tumours, and immune response in these diseases. In this review, we focussed on how the enzymes involved in m(6)A modification, directly or indirectly, influence the pathogenesis and phenotype of various diseases with T-helper cell subset imbalance, and could therefore, serve as potential diagnostic markers and therapeutic targets for these diseases. In addition, this review also discusses the focus of future research in this area. Finally, we summarise the prospects of m(6)A modification in immunotherapy and chemotherapy. | T-Lymphocytes |
A concise and enantioselective total synthesis of (+)-jungermatrobrunin A (1), which features a unique bicyclo[3.2.1]octene ring skeleton with an unprecedented peroxide bridge, was accomplished in 13 steps by making use of a late-stage visible-light-mediated Schenck ene reaction of (-)-1alpha,6alpha-diacetoxyjungermannenone C (2). Along the way, a UV-light-induced bicyclo[3.2.1]octene ring rearrangement afforded (+)-12-hydroxy-1alpha,6alpha-diacetoxy-ent-kaura-9(11),16-dien-15-one (4). These divergent photo-induced skeletal rearrangements support a possible biogenetic relationship between (+)-1, (-)-2, and (+)-4. | Octanes |
(D)-mannitol is widely used in the pharmaceutical and medical industries as an important precursor of antitumor drugs and immune stimulants. However, the cost of the current enzymatic process for (D)-mannitol synthesis is high, thus not suitable for commercialization. To address this issue, an efficient mannitol dehydrogenase LpGDH used for the conversion and a glucose dehydrogenase BaGDH used for NADH regeneration were screened, respectively. These two enzymes were co-expressed in Escherichia coli BL21(DE3) to construct a two-enzyme cascade catalytic reaction for the efficient synthesis of d-mannitol, with a conversion rate of 59.7% from (D)-fructose achieved. The regeneration of cofactor NADH was enhanced by increasing the copy number of Bagdh, and a recombinant strain E. coli BL21/pETDuet-Lpmdh-Bagdh-Bagdh was constructed to address the imbalance between cofactor amount and key enzyme expression level in the two-enzyme cascade catalytic reaction. An optimized whole cell transformation process was conducted under 30 âÂÂ, initial pH 6.5, cell mass (OD(600)) 30, 100 g/L (D)-fructose substrate and an equivalent molar concentration of glucose. The highest yield of (D)-mannitol was 81.9 g/L with a molar conversion rate of 81.9% in 5 L fermenter under the optimal conversion conditions. This study provides a green and efficient biotransformation method for future large-scale production of (D)-mannitol, which is also of great importance for the production of other sugar alcohols. | Mannitol Dehydrogenases |
Recently, the lung has received increasing attention as a metabolic organ. In this role, the lung modulates the composition of the arterial blood by several mechanisms: removing active substances from the plasma, releasing substances into the plasma, temporarily holding substances from circulation, and activating or inactivating substances that pass through the lungs. In this report, the procedures proposed by different investigators for in vivo noninvasive assessment of the lung metabolic functions are reviewed. Most procedures are based on an estimation of the clearance of plasma amines by the lung endothelial cells. This clearance is assessed by measuring the lung uptake or the extraction fraction of an intravenously (IV) injected radiolabeled amine. Our own procedure, which assesses the number of free pulmonary endothelial amine receptors, is discussed in detail. In our procedure, the number of receptors was computed using the number of injected molecules of amine and determining the lung extraction fraction of the amine during its first pass through the lungs. In goats, using N-isopropyl-p-iodoamphetamine labeled with 123I as the radiopharmaceutical, the total number of endothelial lung amine receptors was found to be 1.589 X 10(20). The methods for studying the lung metabolic functions, which are discussed in this report can be applied in humans to evaluate either physiological or pathological conditions. | Iofetamine |
BACKGROUND: Flea-borne infections are distributed worldwide. Up to date there are no reports about microorganisms associated to fleas in Ecuador. METHODS: Seventy-one Pulex irritans and 8 Ctenocephalides felis fleas were removed from dogs in two Ecuadorian areas (Pastaza and Chimborazo Provinces) in December 2012. DNA extracts were tested by polymerase chain reaction (PCR) assays targeting universal 16S rRNA, as well as screened for the presence of Rickettsia spp. (gltA, htrA, ompB, sca4 and ompA genes) and Bartonella spp. (rpoB, gltA and ITS genes). RESULTS: Our results showed the presence of 'Candidatus Rickettsia asemboensis' (highly similar to R. felis) in C. felis and Wolbachia spp. endosimbionts in P. irritans collected from animals in Ecuador. No fleas were found to be positive for any Bartonella species or Yersinia pestis. CONCLUSIONS: Clinicians should be aware of the potential risk of this new Candidatus Rickettsia sp. and keep in mind other flea-borne infections since these flea species frequently bite humans. | Ctenocephalides |
The main aim of this work is to provide a detailed analysis of the reproductive cycle of Beryx splendens in the Juan Fernandez Archipelago. The gonadosomatic index (I(G)) and maturity ogives in both sexes were estimated using an extensive database collected by onboard scientific observers between January 2006 and October 2009. A histological analysis of maturation was also completed for females collected between May and December 2001. Variations in both I(G) and proportion of mature individuals were observed in fish with a fork length (L(F)) >37 cm for females and >33 cm for males. The main reproductive season was in the austral winter and spring (June to November). Fork length at 50% maturity (L(50)) was estimated as 39.67 cm for females (95% c.i. =39.34, 40.02 cm) and 36.88 cm for males (95% c.i. =36.45, 37.36 cm) using macroscopic analysis of gonads. Estimates for females using histological data varied slightly with an estimated L(50) of 43.67 cm (95% c.i. =42.82, 44.91 cm). Changes in I(G) and maturity were modelled as a function of month and L(F) within a generalized additive model framework. A high porportion of immature individuals were found throughout the year. The results of this study are compared with reproductive traits reported for B. splendens in other areas of its distribution and are discussed with reference to exploitation, vulnerability and conservation of the B. splendens stock in Juan Fernandez Archipelago. | Sexual Maturation |
Data on incidence of foot rot were collected over 2 years in a mixed herd of both Bos taurus and Bos indicus breed types. The level of infection was significantly higher in the Bos taurus breeds than in the Bos indicus breeds and raises the possibility of using resistant breeds where foot rot constitutes a major economic problem. | Foot Rot |
BACKGROUND: Malaria is the major cause of morbidity and mortality in Angola. The most vulnerable groups to Plasmodium falciparum infection are pregnant women and children under five years of age. The use of an intermittent preventive treatment (IPT) with sulphadoxine/pyrimethamine (SP) in pregnant women was introduced in Angola in 2006 by the National Malaria Control Programme, and currently this strategy has been considered to be used for children malaria control. Considering the previous wide use of SP combination in Angola, together to the reported cases of SP treatment failure it is crucial the evaluation of the prevalence of five mutations in pfdhfr and pfdhps genes associated to P. falciparum resistance to SP before the introduction of S/P IPT in children. METHODS: The study was conducted in five provinces, with different transmission intensities: Huambo, Cabinda, Uige, Kwanza Norte, and Malanje. The detection of the mutations in pfdhfr and pfdhps genes was carried out in 452 P. falciparum blood samples by PCR RFLP. RESULTS: For pfdhfr gene, 90,3% of the samples carried the mutation 51I, with 7.5% of mixed infections; 51% carried wild type allele 59C, with 29.2% mixed infections and; 99.1% of isolates harboured the mutant allele 108N. Concerning, pfdhps gene, 83,1% were mutant type 437G with 11% mixed infections , while 87% of the studied isolates were wild type for codon 540. DISCUSSION: This is the first representative epidemiological study of the whole Angola country on the prevalence of the genotypes associated with SP chemoresistance. A high frequency of individual mutations in both genes (51I and 108N in pfdhfr, and 437G in pfdhps) was found, besides a low prevalence of the quintuple mutation. CONCLUSION: The data showed that the implementation IPT using SP in children needs to be reviewed. | Sulfadoxine |
Despite decreases in atherosclerotic coronary vascular disease over the last several decades, atherosclerosis remains a major cause of mortality in developed nations. One possible contributor to this residual risk is oxidant stress, which is generated by the inflammatory response of atherosclerosis. Although there is a wealth of in vitro, cellular, and animal data supporting a protective role for antioxidant vitamins and nutrients in the atherosclerotic process, the best clinical trials have been negative. This may be due to the fact that antioxidant therapies are applied too little and too late." This review considers the role of vitamin C, or ascorbic acid in preventing the earliest inflammatory changes in atherosclerosis. It focuses on the three major vascular cell types involved in atherosclerosis: endothelial cells, vascular smooth muscle cells, and macrophages. Ascorbate chemistry, recycling, and function are described for these cell types, with emphasis on whether and how the vitamin might affect the inflammatory process. For endothelial cells, ascorbate helps to prevent endothelial dysfunction, stimulates type IV collagen synthesis, and enhances cell proliferation. For vascular smooth muscle cells, ascorbate inhibits dedifferentiation, recruitment, and proliferation in areas of vascular damage. For macrophages, ascorbate decreases oxidant stress related to their activation, decreases uptake and degradation of oxidized LDL in some studies, and enhances several aspects of their function. Although further studies of ascorbate function in these cell types and in novel animal models are needed, available evidence generally supports a salutary role for this vitamin in ameliorating the earliest stages of atherosclerosis." | Ascorbic Acid |
PURPOSE: To study the correlation between subretinal hyperreflective material (SHRM) seen on spectral domain optical coherence tomography at baseline and visual outcomes after intravitreal bevacizumab injection in neovascular age-related macular degeneration. METHODS: Consecutive patient charts with treatment-naive center-involved neovascular age-related macular degeneration treated with 3 monthly intravitreal bevacizumab's, continued as needed, from 2011 to 2014 were reviewed. Baseline spectral domain optical coherence tomography SHRM parameters (height, width, area, reflectivity, border definition, and homogeneity) and established optical coherence tomography biomarkers of neovascular activity (intraretinal fluid, subretinal fluid, retinal volume, central retinal thickness, and pigment epithelial detachment presence) were collected. These baseline parameters were correlated with visual acuity at baseline, 3 and 12 months. RESULTS: Seventy-three eyes of 73 patients, 47 (64.4%) having central SHRM at baseline, were studied. Mean age was 79.2 +/- 8.9 years. Mean best-corrected visual acuity was 0.70 +/- 0.57 logarithm of the minimum angle of resolution (20/100), 0.73 +/- 0.55 (20/107), and 0.76 +/- 0.63 (20/115) at baseline, 3 and 12 months, respectively. Baseline parameters with a significant predictive value of 12-month visual acuity by univariate analysis were presence of intraretinal fluid, presence of SHRM, highly reflective SHRM, well-defined SHRM borders, and thick SHRM. These parameters, with the exception of high reflectivity, were significant on multivariate regression analysis. The most predictive baseline parameter was well-defined SHRM borders. CONCLUSION: This study supports the use of SHRM as a prognostic biomarker when interpreting optical coherence tomography in neovascular age-related macular degeneration. Baseline parameters predicting poorer vision 1 year after intravitreal bevacizumab treatment were as follows: presence of central SHRM, well-defined SHRM borders, intraretinal fluid, and thicker SHRM. | Subretinal Fluid |
From the blood culture of an HIV-positive patient with a febrile syndrome (CD4 count 385 cells/microL and viral load nondetectable), Brucella canis was isolated. The patient was presumptively infected from his dogs, which tested positive, and showed good outcome after the therapy with doxycycline-ciprofloxacin, and the HIV infection would seem not to have been influenced by brucellosis. To our knowledge, no other case of B. canis in the setting of HIV infection has been reported in the literature, and the emerging zoonotic potential of the disease in urban areas should be considered. | Brucella canis |
Studies on fish parasites in Pampulha dam, Belo Horizonte, Minas Gerais, Brazil, found specimens of Poecilia reticulata Peters, 1859 harboring natural infection by larval stages of tapeworms. A total of 250 specimens of P. reticulata were collected and analyzed between February and August 2010, of which 23 were found infected (prevalence 9.2%) with one metacestode each (mean intensity 1, mean abundance 0.09). The analyses of the parasites, particularly the morphology of rostellar hooks, made it possible to identify Glossocercus auritus (Rudolphi, 1818). This is the first report of G. auritus metacestode in South America and P. reticulata is a newly known host for this parasite. | Poecilia |
PURPOSE: The Department of Radiology at the University Hospital Innenstadt Munich provides all clinical departments of a large university hospital with several radiology units at different locations. During the last four years all units have been fully digitalized with a stepwise installation of a PACS. The PACS also processes images from the Nuclear Medicine Department. METHODS: As image modalities, archive systems and review workstations, we use devices from multiple vendors, which are integrated into a consistent system using the DICOM standard. The hospital has developed its own RIS and an Internet information system, which provides access to all reports and images from radiology for all clinical departments inside the hospital. Additionally, other clinical information such as laboratory results or ECG examinations are available through the system. RESULTS: After one year of operation, the system succeeded in the clinical routine work as the primary source for radiological reports and images as well as for laboratory values. CONCLUSION: The advantages of digitalization were, besides reduction of film cost, especially optimizations of work flow with access to digital images from everywhere at any time. | Radiology Information Systems |
While Parkinson's disease (PD) is traditionally characterized by dopaminergic neuron degeneration, several neurotransmitters and neuromodulators besides dopamine are also involved in the onset and progression of the disease and its symptoms. The other principal neurotransmitters/neuromodulators known to control basal ganglia functions and, in particular, motor functions, are GABA, glutamate, serotonin (5-HT), noradrenaline, acetylcholine, adenosine and endocannabinoids. Among these, adenosine is the most relevant, acting through its adenosine A(2A) receptor. Work in experimental models of PD has established the effects of A(2A) receptor antagonists, including the alleviation of disrupted dopamine functions and improved efficacy of dopamine replacement therapy. Moreover, positive interactions between A(2A) receptor antagonists and both D(2) and D(1) receptor agonists have been described in vitro at the receptor-receptor level or in more complex in vivo models of PD, respectively. In addition, the interactions between A(2A) receptor antagonists and glutamate ionotropic GluN(2B)-containing N-Methyl-d-aspartic acid receptors, or metabotropic glutamate (mGlu) receptors, including both mGlu(5) receptor inhibitors and mGlu(4) receptor activators, have been reported in both in vitro and in vivo animal models of PD, as have positive interactions between A(2A) and endocannabinoid CB(1) receptor antagonists. At the same time, a combination of A(2A) receptor antagonists and 5-HT(1A)-5-HT(1B) receptor agonists have been described to modulate the expression of dyskinesia induced by chronic dopamine replacement therapy." | Adenosine A2 Receptor Antagonists |
Although several reports suggest that Alzheimer's disease (AD) is associated with shortened telomere length, the clinical relevance of this has not yet been fully elucidated. This study was conducted to clarify the correlation of telomere length with clinical characteristics and ApoE phenotypes in 74 AD patients. Telomere length was determined from genomic DNA extracted from whole blood by quantitative real-time polymerase chain reaction. We found no significant difference in telomere length between the AD and non-dementia elderly control (n = 35) groups. Furthermore, no significant correlation was found among telomere length and the severity of cognitive decline and disease duration, age, or gender difference. However, telomere length was significantly shorter in AD patients with the ApoE4 homozygote than in those with the ApoE4 heterozygote (p < .001) and noncarriers (p < .001). These findings suggest that shortened telomere length may be associated with the ApoE4 homozygote in AD patients. | Telomere Shortening |
BACKGROUND: Mutism and dense retrograde amnesia are found both in organic and dissociative contexts. Moreover, dissociative symptoms may be modulated by right prefrontal activity. A single case, M.R., developed left hemiparesis, mutism and retrograde amnesia after a high-voltage electric shock without evidence of lasting brain lesions. M.R. suddenly recovered from his mutism following a mild brain trauma 2 years later. METHODS: M.R.'s neuropsychological pattern and anatomoclinical correlations were studied through (i) language and memory assessment to characterize his deficits, (ii) functional neuroimaging during a standard language paradigm, and (iii) assessment of frontal and left insular connectivity through diffusion tractography imaging and transcranial magnetic stimulation. A control evaluation was repeated after recovery. FINDINGS: M.R. recovered from the left hemiparesis within 90 days of the accident, which indicated a transient right brain impairment. One year later, neurobehavioral, language and memory evaluations strongly suggested a dissociative component in the mutism and retrograde amnesia. Investigations (including MRI, fMRI, diffusion tensor imaging, EEG and r-TMS) were normal. Twenty-seven months after the electrical injury, M.R. had a very mild head injury which was followed by a rapid recovery of speech. However, the retrograde amnesia persisted. DISCUSSION: This case indicates an interaction of both organic and dissociative mechanisms in order to explain the patient's symptoms. The study also illustrates dissociation in the time course of the two different dissociative symptoms in the same patient. | Mutism |
A thermostable glycoside hydrolase family-10 xylanase originating from Rhodothermus marinus was cloned and expressed in the methylotrophic yeast Pichia pastoris (SMD1168H). The DNA sequence from Rmxyn10A encoding the xylanase catalytic module was PCR-amplified and cloned in frame with the Saccharomyces cerevisiae alpha-factor secretion signal under the control of the alcohol oxidase (AOX1) promotor. Optimisation of enzyme production in batch fermentors, with methanol as a sole carbon source, enabled secretion yields up to 3gl(-1) xylanase with a maximum activity of 3130Ul(-1) to be achieved. N-terminal sequence analysis of the heterologous xylanase indicated that the secretion signal was correctly processed in P. pastoris and the molecular weight of 37kDa was in agreement with the theoretically calculated molecular mass. Introduction of a heat-pretreatment step was however necessary in order to fold the heterologous xylanase to an active state, and at the conditions used this step yielded a 200-fold increase in xylanase activity. Thermostability of the produced xylanase was monitored by differential-scanning calorimetry, and the transition temperature (T(m)) was 78 degrees C. R. marinus xylanase is the first reported thermostable gram-negative bacterial xylanase efficiently secreted by P. pastoris. | Rhodothermus |
The purpose of our study was to determine whether a toxic arrhythmogenic dose of digitalis administered to an in vivo preparation would affect the neuronal uptake of norepinephrine, serotonin and dopamine in brain tissue and norepinephrine in cardiac tissue. This was investigated by intoxicating anesthetized cats with deslanoside, removing cardiac and brain tissue at the onset of ventricular fibrillation, and examining the ability of brain tissue to accumulate [3H]-NE, [3H]-T-HT and [3H]-DA and cardiac tissue to accumulate [3H]-NE. It was found that deslanoside inhibited uptake of [3H]-NE into the left ventricle and [3H]5-HT into the area postrema. These selective effects may reflect greater blood flow to these regions or different sensitivities of the transport mechanisms for these amines. This inhibition of uptake into both left ventricular tissue and area postrema may contribute to some of the cardiovascular and emetic effects seen with digitalis drugs. | Deslanoside |
OBJECTIVES: The National Institute of Dental and Craniofacial Research funded three practice-based research networks (PBRNs), NW-PRECEDENT, PEARL and DPBRN to conduct studies relevant to practicing general dentists. These PBRNs collaborated to develop a questionnaire to assess the impact of network participation on changes in practice patterns. This report presents results from the initial administration of the questionnaire. METHODS: Questionnaires were administered to network dentists and a non-network reference group. Practice patterns including caries diagnosis and treatment, pulp cap materials, third molar extraction, dentine hypersensitivity treatments and endodontic treatment and restoration were assessed by network, years in practice, and level of network participation. Test-retest reliability of the questionnaire was evaluated. RESULTS: 950 practitioners completed the questionnaire. Test-retest reliability was good-excellent (kappa>0.4) for most questions. Significant differences in responses by network were not observed. The use of caries risk assessment forms differed by both network participation (p<0.001) and years since dental degree (p=0.026). Recent dental graduates are more likely to recommend third molar removal for preventive reasons (p=0.003). CONCLUSIONS: Practitioners in the CONDOR research networks are similar to their US colleagues. As a group, however, these practitioners show a more evidence-based approach to their practice. Dental PBRNs have the potential to improve the translation of evidence into daily practice. Designing methods to assess practice change and the associated factors is essential to addressing this important issue." | National Institute of Dental and Craniofacial Research (U.S.) |
Amphibian skin is well known as a source of peptides homologous to bioactive peptides found in mammalian gut and brain. A systematic investigation of the skin secretions from Xenopus laevis revealed several peptides not derivable from known precursors. The sequence elucidation, utilizing fast atom bombardment/mass spectrometry, of two peptides, PGS and PGS Gly-10;Lys-22, is reported. These have been independently characterized and named magainins and found to have antimicrobial activity. A mixed sequence oligonucleotide probe complementary to the mRNA sequence coding for PGS was synthesized and used to screen a Xenopus skin cDNA library. A full length cDNA species encoding prepro-PGS was isolated and characterized, and its sequence is reported. The deduced precursor sequence was found to contain one copy of PGS Gly-10;Lys-22 and five copies of PGS. The proteolytic processing of this prepro-polypeptide is discussed. | Magainins |
The literature on acardiac monsters has been reviewed. The following conclusions were drawn: 1. The probability of their appearance seems considerably higher among monoamniotic than diamniotic monochorionic twin pairs. 2. They seem more likely to occur within monozygotic (MZ) pairs in higher multiple births than in MZ twins. 3. The data are consistent with the suggestion that there is a slight female excess among them." | Abnormalities, Severe Teratoid |
Bacillus species producing a thermostable phytase was isolated from soil, boiled rice, and mezu (Korean traditinal koji). The activity of phytase increased markedly at the late stationary phase. An extracellular phytase from Bacillus sp. KHU-10 was purified to homogeneity by acetone precipitation and DEAE-Sepharose and phenyl-Sepharose column chromatographies. Its molecular weight was estimated to be 46 kDa on gel filtration and 44 kDa on SDS-polyacrylamide gel elctrophoresis. Its optimum pH and temperature for phytase activity were pH 6.5-8.5 and 40 degrees C without 10 mM CaCl2 and pH 6.0-9.5 and 60 degrees C with 10 mM CaCl2. About 50% of its original activity remained after incubation at 80 degrees C or 10 min in the presence of 10 mM CaCl2. The enzyme activity was fairly stable from pH 6.5 to 10.0. The enzyme had an isoelectric point of 6.8. As for substrate specificity, it was very specific for sodium phytate and showed no activity on other phosphate esters. The Km value for sodium phytate was 50 microM. Its activity was inhibited by EDTA and metal ions such as Ba2+, Cd2+, Co2+, Cr3+, Cu2+, Hg2+, and Mn2+ ions. | 6-Phytase |
As current clinical approaches for lower urinary tract (LUT) dysfunction such as pharmacological and electrical stimulation treatments lack target specificity, thus resulting in suboptimal outcomes with various side effects, a better treatment modality with spatial and temporal target-specificity is necessary. In this study, we delivered optogenetic membrane proteins, such as channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), to bladder smooth muscle cells (SMCs) of mice using either the Cre-loxp transgenic system or a viral transfection method. The results showed that depolarizing ChR2-SMCs with blue light induced bladder contraction, whereas hyperpolarizing NpHR-SMCs with yellow light suppressed PGE(2)-induced overactive contraction. We also confirmed that optogenetic contraction of bladder smooth muscles in this study is not neurogenic, but solely myogenic, and that optogenetic light stimulation can modulate the urination in vivo. This study thus demonstrated the utility of optogenetic modulation of smooth muscle as a means to actively control the urinary bladder contraction with spatial and temporal accuracy. These features would increase the efficacy of bladder control in LUT dysfunctions without the side effects of conventional clinical therapies. | Halorhodopsins |
Spinal infection is a significant cause of morbidity. Despite advances in antibiotic treatment regimens, the incidence is not decreasing due at least in part to an increase in 'at-risk' populations, namely the elderly and the immunocompromised. Prompt diagnosis is greatly facilitated by early and appropriate imaging techniques together with microbiological assessment following culture from blood, needle aspirate and biopsy material. This article gives an overview of imaging of spinal infection with an emphasis on MR imaging, which has greatly contributed to early diagnosis, thus allowing implementation of timely appropriate treatment. | Spondylitis |
PURPOSE OF REVIEW: Despite a significant body of literature related to the treatment of gambling disorder, there are still an insufficient number of evaluation studies regarding their effectiveness or firm conclusions on specific treatment elements that contribute to it. The aim of this article was to provide a review of scientific results regarding the treatment of gambling disorder, to present the most commonly applied modalities of treatment and to explore the elements of the most successful therapeutic interventions. RECENT FINDINGS: A substantial body of literature has shown that the most successful therapeutic protocols are psychological interventions, especially based on cognitive-behavioral therapy/methods and/or motivational interviewing. Other interventions with promising results include different self-help interventions and mindfulness. Interventions such as couples therapy and support groups, may have positive effects in terms of increasing therapeutic adherence and retention, while pharmacotherapy is especially useful in patients with comorbidities. SUMMARY: Gambling disorder is a complex mental health problem caused by a wide spectrum of different biological, psychological, and social risk factors. Treatment options for gambling disorder need to be wide, flexible, accessible, and economically justified, providing early inclusion, retention, and sustainability of long-term effects of the treatment, that is, abstinence and higher quality of psychosocial functioning. | Risk-Taking |
OBJECTIVE: To determine the impact of the particle repositioning maneuver on posterior canal benign paroxysmal positional vertigo-related quality of life using the Medical Outcomes Study 36-Item Short Form Health Survey and the Dizziness Handicap Inventory Short Form. STUDY DESIGN: Prospective, consecutive new cases of posterior canal benign paroxysmal positional vertigo. SETTING: Ambulatory, primary referral hospital. PATIENTS: Forty individuals with posterior canal benign paroxysmal positional vertigo were investigated. The diagnosis was made on the basis of the history of recurrent sudden crisis of vertigo and positional-induced nystagmus during the Dix-Hallpike test. INTERVENTIONS: All patients were treated by a single particle repositioning maneuver, and relapses were investigated at Days 7 and 30 posttreatment. MAIN OUTCOME MEASURES: Percentage of patients with negative Dix-Hallpike test after treatment, scores obtained on the 36-Item Short Form Health Survey and Dizziness Handicap Inventory Short Form before and 30 days after treatment. RESULTS: DHT was found negative in 76% (28 of 37) individuals at 30 days. The eight scales of the 36-Item Short Form Health Survey had a good internal consistency reliability (Cronbach's alpha > 0.7) in patients with posterior canal benign paroxysmal positional vertigo. The average standardized score for each 36-Item Short Form Health Survey scale was compared with the reference population normative data, showing differences with norms for all scales, except for Vitality. After particle repositioning maneuver, patients scored closer to norms, and Social Function and Mental Health scores were significantly higher than the scores obtained before the particle repositioning maneuver (p < 0.05). Dizziness Handicap Inventory Short Form total score significantly decreased from 18.05 +/- 9.91 (mean +/- standard deviation) at the first day to 9.54 +/- 9.94 at 30 days (p < 0.001). All 36-Item Short Form Health Survey scale scores were correlated significantly with Dizziness Handicap Inventory Short Form total scores at 30 days after treatment. CONCLUSIONS: Posterior canal benign paroxysmal positional vertigo has a significant impact on health-related quality of life, and patients experienced a decrease in quality of life as compared with norms. The particle repositioning maneuver improves health-related quality of life in posterior canal benign paroxysmal positional vertigo. | Vertigo |
Sixty tilted discs were studied by colour photography, including some by fluorescein angiography. Attention was drawn to the contracted, D-shaped outline of the scleral canal, and it was suggested that fewer fibres than normal enter the defective side of the disc. This was supported by examination of the nerve fibre layer and the discovery of field defects in 13 of the 27 eyes in which the visual fields were examined. The similarity of these features with congenital hypoplasia of the optic nerve head was noted. | Optic Disk |
Estramustine, a carbamate ester combining 17 beta-estradiol and nornitrogen mustard, has primarily been employed in the treatment of advanced prostatic carcinoma. However, a significant amount of preclinical investigation has been directed toward estramustine's activity against human malignant glioma. These studies have demonstrated that estramustine has potent antiproliferative effects against malignant glioma both in vitro and in vivo. Similar antimitotic effects also have been demonstrated for other carbamate esters. Estramustine does not impair proliferation of nonneoplastic astrocytes at concentrations that inhibit glioma cells. Although the reasons for this selective activity remain to be determined, it has been shown that malignant gliomas expresses an estramustine-specific binding site, estramustine-binding protein, more than brain tissue. In the clinical situation, an uptake and accumulation of estramustine in human glioma tissue have been demonstrated. Estramustine has been shown to enhance the cytotoxic effects of irradiation in relatively radioresistant glioma cells both in cell culture and in a rat glioma model. Estramustine has been regarded as mainly an anti-mitotic drug but recently other effects such as inhibition of DNA synthesis, induction of apoptosis, and membrane alterations have been shown. This report summarizes the preclinical observations concerning the effects of estramustine and related compounds on human malignant gliomas. These findings form the basis for proposing further laboratory and clinical investigation regarding estramustine and human malignant gliomas. | Estramustine |
Behavioral deficits following inescapable stress (learned helplessness) may serve as an animal model of depression. Previous studies using foot-shock stress to induce learned helplessness and a bar-press test for the stress-induced behavioral deficit have found increased beta-adrenergic receptor density in the hippocampus of learned helpless rats. We replicated these experiments using a tail-shock stress and the shuttle-box test. In our experiments, rats that developed learned helplessness after inescapable stress did not demonstrate any significant differences in beta-adrenergic receptor density or affinity in the frontal cortex, cerebellum, or hippocampus compared to the nonhelpless rats, nor to the tested control rats. These results suggest that beta-adrenergic receptor changes in learned helplessness may depend on the specific stress and test procedures used. | Iodocyanopindolol |
Regulatory peptides and their analogs are being extensively investigated as radiopharmaceuticals for cancer imaging. In particular, cholecystokinin (CCK) receptors of the subtype B (CCK-BR) have been shown to be overexpressed in certain neuroendocrine tumors including medullary thyroid cancer. Our recent work has focused on new methods to radiolabel the CCK8 peptide with (111)In or (99m)Tc for the purpose of developing radiopharmaceuticals for in vivo CCK-B receptor imaging. Labeling of CCK8 with (111)In was achieved at the N-terminus of the peptide by adding, in solid phase, a glutamate coupled diethylenetriaminepentaacetic acid (DTPA) moiety through a glycine linker, yielding DTPA-Glu-G-CCK8. For labeling with (99m)Tc, the CCK8 peptide was modified at its N-terminus by introducing, in the following order--cysteine, glycine, and a diphenylphosphinopropionyl moiety--giving a 10-residue peptide derivative, Phos-GC-CCK8. A cell culture model was developed for the purpose of evaluating the binding properties of these two ligands. The human epidermoid carcinoma cell line, A431, was transfected with a plasmid containing the full coding sequence of the human CCK-BR under a strong viral promoter, obtaining a number of receptors in the range of 2-5 x 10(6) per cell. Control cells were transfected with vector alone. An animal tumor model utilizing these two cell lines was developed to evaluate the specificity of interaction with the CCK-BR and biodistribution properties of the compounds. CCK-BR positive and control cells were subcutaneously injected in opposite flanks of CD1 female nude mice in order to obtain xenografts differing only in their ability to express CCK-B receptors. High performance liquid chromatography (HPLC) and other chromatographic methods were utilized to assess stability of the radiolabeled compounds after injection. Both (111)In-DTPA-Glu-G-CCK8 and (99m)Tc-Phos-GC-CCK8 showed similar binding affinities for cultured CCK-BR expressing cells, with dissociation constants in the range of 20-40 nM. With the two xenograft approach, we were able to demonstrate specific interaction with the receptor of both CCK analogs in our animal model. The data obtained shows rapid specific localization of both compounds on the CCK-BR overexpressing xenografts. Both tracers show rapid plasma clearance of unbound peptide. Clearance of (111)In-DTPA-Glu-G-CCK8 appears to be preferentially through the kidneys, whereas (99m)Tc-Phos-GC-CCK8 clearance occurs both through kidneys and the hepatobiliary system. Both our labeling approaches appear adequate for clinical use of peptide based radiopharmaceuticals, although (99m)Tc-Phos-GC-CCK8 shows elevated accumulation in the gastrointestinal tract, which causes high background activity. | Receptors, Cholecystokinin |
BACKGROUND: Therapeutic drug monitoring (TDM) is increasingly performed for Infliximab (IFX) in patients with Crohn's disease (CD). Reactive TDM is a cost-effective strategy to empiric IFX dose escalation. The cost-effectiveness of proactive TDM is unknown. The aim of this study is to assess the cost-effectiveness of proactive vs reactive TDM in a simulated population of CD patients on IFX. METHODS: We developed a stochastic simulation model of CD patients on IFX and evaluated the expected health costs and outcomes of a proactive TDM strategy compared with a reactive strategy. The proactive strategy measured IFX concentration and antibody status every 6 months, or at the time of a flare, and dosed IFX to a therapeutic window. The reactive strategy only did so at the time of a flare. RESULTS: The proactive strategy led to fewer flares than the reactive strategy. More patients stayed on IFX in the proactive vs reactive strategy (63.4% vs 58.8% at year 5). From a health sector perspective, a proactive strategy was marginally cost-effective compared with a reactive strategy (incremental cost-effectiveness ratio of $146,494 per quality-adjusted life year), assuming a 40% of the wholesale price of IFX. The results were most sensitive to risk of flaring with a low IFX concentration and the cost of IFX. CONCLUSIONS: Assuming 40% of the average wholesale acquisition cost of biologic therapies, proactive TDM for IFX is marginally cost-effective compared with a reactive TDM strategy. As the cost of infliximab decreases, a proactive monitoring strategy is more cost-effective. | Therapeutic Index, Drug |
Opiate peptides are known to elevate circulating GH in man, and data in other animals suggest that acetylcholine may be involved. We have administered the long-acting met-enkephalin analogue DAMME to 6 normal males, and have shown that the resulting elevation in GH is blocked by the specific cholinergic antagonist, pirenzepine. It seems likely that a cholinergic mechanism may interact with opiate-induced changes in GH in man." | D-Ala(2),MePhe(4),Met(0)-ol-enkephalin |
Maternal psychophysiological responses to toddlers' distress to novelty may have important implications for parenting during early childhood that are relevant to children's eventual development of social withdrawal and anxiety. Likely, these responses depend on intrapersonal, interpersonal, and contextual factors. The current study investigated the time course of respiratory sinus arrhythmia (RSA) across two laboratory novelty episodes, one low threat and one moderate threat, in 120 mothers of 2-year-old toddlers. Growth models tested context differences in and correlates of dynamic patterns of RSA. Dynamic patterns differed between tasks and according to mothers' perceptions of and distress about toddler shyness. Thus, changes in mothers' RSA across toddlers' interactions with novelty seem to depend on the context as well as how mothers perceive and respond to their toddlers' shyness. | Respiratory Sinus Arrhythmia |
Recombinant Zantedeschia aethiopica agglutinin (ZAA) was expressed in Escherichia coli as N-terminal His-tagged fusion. After induction with isopropylthio-beta-D-galactoside (IPTG), the recombinant ZAA was purified by metal-affinity chromatography. The purified ZAA protein was applied in anti-fungal assay and the result showed that recombinant ZAA had anti-fungal activity towards leaf mold (Fulvia fulva), one of the most serious phytopathogenic fungi causing significant yield loss of crops. This study suggests that ZAA could be an effective candidate in genetic engineering of plants for the control of leaf mold. | Zantedeschia |
Intensity modulated radiation therapy and brachytherapy are standard techniques of irradiation for the treatment of oral cavity cancers. These techniques are detailed in terms of indication, planning, delineation and selection of the volumes of interest, dosimetry and patients positioning control. This is an update of the guidelines of the French Society of Radiotherapy Correspondence. | Mouth Neoplasms |
The present study examines the DSM-5 Acute Stress Disorder (ASD) diagnostic criteria of exposure, in the context of a natural disaster. The study is based on the reports of 1001 Filipinos following the aftermath of super typhoon Haiyan in 2013. Participants reported exposure to injury, psychological distress and ASD symptoms. Findings indicated the association of criterion A with the prevalence of meeting all other ASD diagnostic criteria and high psychological distress. The diagnostic properties of Criterion A are discussed." | Stress Disorders, Traumatic, Acute |
Theory indicates that numbers of mating types should tend towards infinity or remain at two. The social amoeba, Dictyostelium discoideum, however, has three mating types. It is therefore a mystery how this species has broken the threshold of two mating types, but has not increased towards a much higher number. Frequency-dependent selection on rare types in combination with isogamy, a form of reproduction involving gametes similar in size, could explain the evolution of multiple mating types in this system. Other factors, such as drift, may be preventing the evolution of more than three. We first looked for evidence of isogamy by measuring gamete size associated with each type. We found no evidence of size dissimilarities between gametes. We then looked for evidence of balancing selection, by examining mating type distributions in natural populations and comparing genetic differentiation at the mating type locus to that at more neutral loci. We found that mating type frequency varied among the three populations we examined, with only one of the three showing an even sex ratio, which does not support balancing selection. However, we found more population structure at neutral loci than the mating type locus, suggesting that the three mating types are indeed maintained at intermediate frequencies by balancing selection. Overall, the data are consistent with balancing selection acting on D. discoideum mating types, but with a sufficiently weak rare sex advantage to allow for drift, a potential explanation for why these amoebae have only three mating types. | Sex Distribution |
Although very well adapted to brain study, Magnetic Resonance Imaging (MRI) remains limited by the facilities and capabilities required to acquire data, especially for non-human primates. Addressing the data gaps resulting from these limitations requires making data more accessible and open. In contempt of the regular use of Saimiri sciureus in neuroscience research, in vivo diffusion has yet to be openly available for this species. Here we built and made openly available a unique new resource consisting of a high-resolution, multishell diffusion-weighted dataset in the anesthetized Saimiri sciureus. The data were acquired on 11 individuals with an 11.7 T MRI scanner (isotropic resolution of 400 microm(3)). This paper presents an overview of our dataset and illustrates some of its possible use through example analyses. To assess the quality of our data, we analyzed long-range connections (whole-brain tractography), microstructure (Neurite Orientation Dispersion and Density Imaging), and axon diameter in the corpus callosum (ActiveAx). Constituting an essential new resource for primate evolution studies, all data are openly available. | Saimirinae |
With the surge in genome-wide association studies (GWAS), many have asked the question 'Are linkage studies dead?' In this article, we survey the approaches used in mapping human disease genes, reviewing the analysis strategies that preceded and laid the groundwork for GWAS. We note that earlier approaches are still useful and the development of new methodology is warranted. | Genome-Wide Association Study |
We reviewed our experience in 30 patients with direct Coombs-positive (DAT+) autoimmune hemolytic anemia (AHA) who underwent splenectomy. Twelve patients had idiopathic warm" AHA (group I) and 18 had AHA associated with systemic diseases (group II). Complete response to splenectomy was defined as having normal hemoglobin and reticulocyte count lasting for at least 6 months without subsequent medical therapy. Subnormal but greater than 50% improvement in these parameters with or without medical therapy was considered to be a partial response. Median age was 64 (23-81) in group I and 68 (23-76) in group II. Median follow-up duration was 18 and 10.9 months, respectively. Nine of 11 (82%) evaluable patients with idiopathic AHA and 3 of 16 (19%) patients with associated disease achieved a complete response. Partial response was obtained in 2 (18%) and 6 (37%) patients in groups I and II, respectively. Both complete-response and overall-response rates were statistically different between two groups (P = 0.001 and 0.02). Postoperative courses of group I patients were uneventful except for one who developed a subphrenic abscess. Five patients in group II developed bacterial infections, which were mostly pneumonias. Our findings indicate that splenectomy is an effective treatment approach with low morbidity and mortality in patients with refractory idiopathic AHA. It should, however, be considered cautiously in AHA patients with underlying systemic diseases because of its decreased efficacy and increased surgical morbidity in this subgroup." | Anemia, Hemolytic, Autoimmune |
INTRODUCTION: Community-acquired urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli have limited oral therapeutic options and pose significant clinical challenges. The goal of this study was to evaluate the in vitro synergy between CFM and AMC against ESBL E. coli with aims to identify an oral treatment option for UTIs. METHODS: Minimum inhibitory concentrations (MICs) of CFM in the presence of AMC were determined for 46 clinical isolates by placing a CFM Etest on a plate with AMC impregnated in the agar. Isolates with CFM MIC </=1 mug/mL in the presence of AMC were considered susceptible to the CFM and AMC combination. Five isolates were then selected for further testing using time-kill analysis in the presence of CFM, AMC, and CFM with AMC. Time-kill curves were plotted to determine synergy over 24 h. RESULTS: AMC improved the activity of CFM against ESBL E. coli isolates by 128-fold in the Etest analysis with 85% of tested isolates being susceptible to the combination. A fourfold or greater reduction in CFM MIC was exhibited in 44 of 46 (96%) isolates when in the presence of AMC. Synergy and bactericidal activity between CFM and AMC were exhibited in each of the five isolates tested by time-kill analysis. DISCUSSION/CONCLUSION: This study found that AMC improves the activity of CFM against ESBL E. coli and that this antibiotic combination has potential as an oral therapeutic option to treat ESBL E. coli UTIs. | Cefixime |
An abnormal increase in glucocorticoid levels is responsible for pathological disorders affecting different organs and systems, and the selective inhibition of appropriate steroidogenic enzymes represents a validated strategy to restore their physiological levels. In continuing our studies on CYP11B inhibitors, in this paper a small series of 6-substituted 3-imidazolylmethylxanthones was designed and synthesized, according to the data acquired from previously reported series of derivatives and from a purposely-performed docking study. The new compounds proved to be potent inhibitors of CYP11B isoforms, being effective on CYP11B1 in the low nanomolar range and improving selectivity with respect to CYP11B2, compared to previously reported related compounds. These data further confirmed that a suitable mutual arrangement of the imidazolylmethyl pharmacophore and a properly selected substituent on the xanthone core allows a fine tuning of the activity towards the different CYPs and further corroborate the role of the xanthone scaffold as a privileged structure in this field. | Cytochrome P450 Family 11 |
Abundant experimental research has shown the potentially damaging effects that the herpes simplex virus (HSV) may have on peripheral or central nervous pathways. Fifty subjects (ages 20-45) with labial herpes virus (HSV-1) and 15 (ages 25-35) with genital herpes virus (HSV-2) were studied through recording spontaneous and optokinetic nystagmus (OKN) and using the eye-tracking-test (ETT) by means of electronystagmography (ENG). Recording was carried out during the first two days after vesicular eruption and seven days later, when cutaneous manifestations had disappeared. Thirty-five of the 50 subjects with HSV-1 showed spontaneous nystagmus, frequently with a vertical component, which in most cases had disappeared by the seventh control day. We recorded qualitative alterations of OKN as well as ETT in 19 patients while in 3 subjects only ETT was abnormal. All the subjects were normal on the seventh control day. At no time did any of the patients with HSV-2 show objective signs involving the peripheral or central vestibular system. Our research shows that HSV infection, especially HSV-1 infection, determines subclinical alterations of the vestibular function, probably due to the involvement of the brainstem. Therefore the virus is to be taken into account in establishing the etiology of "unknown" vertigo." | Vestibulocochlear Nerve Diseases |
The combination of salt and acid is commonly used in the production of many foods, including pickles and fermented foods. However, in our previous studies, the addition of salt significantly reduced the inhibitory effect of acetic acid on Escherichia coli O157:H7 in laboratory media and pickled cucumbers. Therefore, this study was conducted to determine the mechanism by which salt confers resistance against acetic acid in E. coli O157:H7. The addition of high concentrations (up to 9% or 15% [w/v]) of salt increased the resistance of E. coli O157:H7 to acetic acid treatment. Combined treatment with acetic acid and salt showed varying results among different bacterial strains (an antagonistic effect for E. coli O157:H7 and Shigella and a synergistic effect for Listeria monocytogenes and Staphylococcus aureus). The addition of salt increased the cytoplasmic pH of E. coli O157:H7, but decreased the cytoplasmic pH of L. monocytogenes and S. aureus on treatment with acetic acid. Therefore, the addition of salt increases the acid resistance of E. coli O157:H7 possibly by increasing its acid resistance response and consequently preventing the acidification of its cytoplasm by organic acids. | Escherichia coli O157 |
The main focus of this review is the pharmacology and the therapeutic use of chemical related agents, the arylpiperazine derivatives. These compounds produce a variety of behavioural responses and pharmacological effects which directly and principally result from activation of serotonin systems. However, minor modifications in the chemical structure of these products involve important changes in affinity and selectivity for 5-HT receptors since it can also display significant affinity for dopaminergic, adrenergic or histaminergic receptors. The different arylpiperazine drugs therapeutically used are described as well as some compounds presently under investigation. | Piperazines |
BACKGROUND: Fertility desire for a second child has been a lively topic since the implementation of the two-child policy in China. Chinese researchers have explored various factors influencing the fertility desire for a second child. However, there have not been studies on the individual differences in the relative fertility costs and fertility benefits and their effects on fertility desire for a second child. METHODS: A total of 396 participants rated four kinds of relative fertility costs, four kinds of fertility benefits and their fertility desire for a second child. Latent profile analysis (LPA) was used to explore the individual differences in the relative fertility costs and fertility benefits and their effects on fertility desire for a second child. RESULTS: Stepwise regression analysis showed that parenting joy, health risks, mutual care among siblings, the flourishing of family, and time pressure and opportunity cost significantly predicted the fertility desire for the second child. According to the latent profile analysis, the participants were classified into four classes. Participants in the lowest-cost/lowest-benefit and high-cost/medium-benefit classes had low fertility desire for a second child, while those in the low-cost/high-benefit and highest-cost/highest-benefit classes had high fertility desire. CONCLUSION: Fertility benefits have a stronger effect on the fertility desire for a second child than relative fertility costs. Fertility benefits should be paid more attention to than relative fertility costs. | Family Planning Policy |
Measles is a highly contagious viral disease that continues to occur in epidemics in the UK despite efforts to eradicate it. In the acute stage, measles is associated with several complications including otitis media, but some of the most severe consequences of the disease occur months and even years after the initial infection. Worldwide, measles contributes significantly to deaths in childhood and places an additional burden on families already living with the consequence of poverty and conflict. This article aims to develop the reader's understanding of measles, including its pathophysiology, management and associated public health issues. | Measles |
The signal transducer and activator of transcription 3 (STAT3) protein is a major transcription factor involved in many cellular processes, such as cell growth and proliferation, differentiation, migration, and cell death or cell apoptosis. It is activated in response to a variety of extracellular stimuli including cytokines and growth factors. The aberrant activation of STAT3 contributes to several human diseases, particularly cancer. Consequently, STAT3-mediated signaling continues to be extensively studied in order to identify potential targets for the development of new and more effective clinical therapeutics. STAT3 activation can be regulated, either positively or negatively, by different posttranslational mechanisms including serine or tyrosine phosphorylation/dephosphorylation, acetylation, or demethylation. One of the major mechanisms that negatively regulates STAT3 activation is dephosphorylation of the tyrosine residue essential for its activation by protein tyrosine phosphatases (PTPs). There are seven PTPs that have been shown to dephosphorylate STAT3 and, thereby, regulate STAT3 signaling: PTP receptor-type D (PTPRD), PTP receptor-type T (PTPRT), PTP receptor-type K (PTPRK), Src homology region 2 (SH-2) domain-containing phosphatase 1(SHP1), SH-2 domain-containing phosphatase 2 (SHP2), MEG2/PTP non-receptor type 9 (PTPN9), and T-cell PTP (TC-PTP)/PTP non-receptor type 2 (PTPN2). These regulators have great potential as targets for the development of more effective therapies against human disease, including cancer. | STAT3 Transcription Factor |
The Grb10 protein appears to be an adapter protein of unknown function that has been implicated in insulin receptor (IR) signaling. The interaction of this protein with the IR has been shown to be mediated in part by the Src homology 2 (SH2) domain of Grb10. Here we demonstrate the existence of a second novel domain within Grb10 that interacts with the IR and insulin-like growth factor receptor in a kinase-dependent manner. This domain was localized to a region of approximately 50 amino acids, and we term it the BPS domain to denote its location between the PH and SH2 domains. The BPS domain does not bear any obvious resemblance to other known protein interaction domains but is highly conserved among the Grb10-related proteins Grb7 and Grb14. We show that the BPS domain interaction is dependent upon receptor tyrosine kinase activity. Furthermore, interaction of the BPS domain requires the kinase domain of the IR, since mutation of the paired tyrosine residues (Y1150F/Y1151F) within the IR activation loop dramatically reduced the interaction. Last, our data suggest that the presence of two distinct protein interaction domains may help to determine the specificity by which Grb10 interacts with different receptors. Specifically, the IR, which appears to interact most strongly with Grb10, interacts well with both the SH2 and BPS domains. Conversely, the insulin-like growth factor receptor and EGFR, which interact less avidly with Grb10, interact well only with the BPS domain or the SH2 domain, respectively. In summary, our findings demonstrate the existence of a previously unidentified tyrosine kinase activity-dependent binding domain located between the Pleckstrin homology and SH2 domains of Grb10. | GRB10 Adaptor Protein |
In three cases an antenatal diagnosis of isolated Dandy-Walker cyst was made at 22-28 weeks of gestation by ultrasound examination. Biparietal growth and the relative severity of the anomaly remained constant, so that all cases could be safely delivered at term. Postnatally, the diagnosis was confirmed during the first days of life by ultrasound and computed tomography (CT). Early neonatal shunting procedures were performed. Dual shunts were inserted in all three cases, and mental and physical development were observed to be normal during a follow-up of from 1.5 to 4.5 years. Early antenatal diagnosis of Dandy-Walker cyst may improve the prognosis and reduce the mortality, which has been reported to be 30%-48%. Dual shunting of both the cyst in the posterior fossa and the lateral ventricles has proved to be a safe and reliable method during the neonatal period. | Dandy-Walker Syndrome |
Mycobacterium tuberculosis has evolved from a Mycobacterium canettii-like progenitor pool into one of the most successful and widespread human pathogens. The pathogenicity of M. tuberculosis is linked to its ability to secrete/export/release selected mycobacterial proteins, and it is also established that active release of mycobacterial antigens is a prerequisite for strong immune recognition. Recent research has enabled mycobacterial secretion systems and vesicle-based release of mycobacterial antigens to be elucidated, which together with host-related specificities constitute key variables that determine the outcome of infection. Here, we discuss recently discovered, novel aspects on the nature and the regulation of antigen release of the tuberculosis agent with particular emphasis on the biological characterization of mycobacteria-specific ESX/type VII secretion systems and their secreted proteins, belonging to the Esx, PE, and PPE categories. The importance of specific mycobacterial antigen release is probably best exemplified by the striking differences observed between the cellular events during infection with the ESX-1-deficient, attenuated Mycobacterium bovis BCG compared to the virulent M. tuberculosis, which are clearly important for design of more specific diagnostics and more efficient vaccines. | SecA Proteins |
Virus-induced gene silencing (VIGS) is a powerful tool for high-throughput analysis of gene function. Here, we developed the VIGS vector pCF93, from which expression of the cucumber fruit mottle mosaic virus genome is driven by the cauliflower mosaic virus 35S promoter to produce viral transcripts in inoculated plants. To test the utility of the pCF93 vector, we identified candidate genes related to male sterility (MS) in watermelon (Citrullus lanatus), which is recalcitrant to genetic transformation. Specifically, we exploited previously reported reference-based and de novo transcriptome data to define 38 differentially expressed genes between a male-sterile line and its fertile near-isogenic line in the watermelon cultivar DAH. We amplified 200- to 300-bp fragments of these genes, cloned them into pCF93, and inoculated DAH with the resulting VIGS clones. The small watermelon cultivar DAH enabled high-throughput screening using a small cultivation area. We simultaneously characterized the phenotypes associated with each of the 38 candidate genes in plants grown in a greenhouse. Silencing of 8 of the 38 candidate genes produced male-sterile flowers with abnormal stamens and no pollen. We confirmed the extent of gene silencing in inoculated flowers using reverse transcription-qPCR. Histological analysis of stamens from male-fertile and male-sterile floral buds and mature flowers revealed developmental defects and shrunken pollen sacs. Based on these findings, we propose that the pCF93 vector and our VIGS system will facilitate high-throughput analysis for the study of gene function in watermelons. | Citrullus |
Tenofovir disoproxil fumarate is currently the cornerstone of HIV treatment. Although it shows an overall good safety profile, numerous cases of nephrotoxicity have been reported. Tenofovir alafenamide is a novel tenofovir prodrug that has been developed to improve renal safety. Pharmacokinetic studies suggest a better renal tolerance of tenofovir alafenamide than tenofovir disoproxil fumarate, probably because tenofovir plasma concentrations are lower after tenofovir alafenamide administration. Consistently in clinical trials, renal tolerance seems to be improved in patients treated with tenofovir alafenamide. However, some questions remain. First, whether tenofovir can accumulate and lead to nephrotoxicity under specific circumstances after tenofovir alafenamide administration is unknown. Second, only real-world practice" will inform us on the long-term renal safety of tenofovir alafenamide. Last, tenofovir alafenamide renal safety in patients with chronic kidney disease has not been studied in any randomized clinical trial. In conclusion, tenofovir alafenamide appears as a very promising drug and long-term safety will be an important determinant of its expanded use." | Tenofovir |
Many plants show heterophylly, which is variation in leaf form within a plant owing to environmental change. The molecular mechanisms underlying heterophylly have recently been investigated in several plant species. However, little is known about how plants exhibiting heterophylly sense environmental cues. Here, we used Rorippa aquatica (Brassicaceae), which shows heterophylly, to investigate whether a single leaf can sense and transit changes in ambient temperature. The morphology of newly developed leaves after single-leaf warming treatment was significantly different from that of mock-treated control leaves, suggesting that leaves are sensing organs that mediate the responses to changes in ambient temperature in R. aquatica. | Rorippa |
Cancer is a major cause of deaths in humans. Though there has been significant progress in cancer therapy, the limited efficacy and toxicities of current chemo- and radiotherapies have provided an impetus for the search of new therapeutics. A therapeutic approach, which uses viruses for the treatment of cancer termed, oncolytic virotherapy has recently emerged. Newcastle disease virus (NDV) is one such virus with an inherent oncolytic property. NDV causes a highly infectious disease in poultry worldwide. In humans it is reported to have oncolytic and immuno-stimulatory effects. It specifically replicates in tumour cells while sparing normal cells and cause oncolysis. For many years different strains of the NDV have been investigated for treatment of various human cancers. Recent advances in reverse genetics provided investigators the tools to produce recombinant NDV with improved oncolytic property. | Avulavirus |
Furan fatty acids (FuFAs) are important minor fatty acids of food with antioxidative properties. Since their presence in food triacylglycerols (TAGs) had not been documented, we aimed to enzymatically synthesize TAGs with two important FuFAs (9M5 and 11D5). Specifically, the TAGs triolein (OOO), tripalmitin (PPP), trilinolein (LLL), tri-alpha-linolenin (LnLnLn), and tricaprylin (CCC) and 9M5 or 11D5 were reacted with the immobilized lipase from Candida antarctica. All reactions resulted in TAGs with one, two, and three FuFAs in decreasing order. A nomenclature system for FuFA-containing TAGs was suggested by listing FuFAs in (9)M(5) ((11)D(5)) style such as OO(9)M(5) and O(9)M(5)O. Reaction of tri9M5 also resulted TAGs with 1-3 conventional fatty acids. GC/MS spectra of FuFA-containing TAGs featured two fragment ions ([M-RCO](+) and [M-RCOO](+)) along with the diagnostic base peak of FuFAs and the [RCO](+) fragment ion. A data base with fragment and molecular ions of food relevant, FuFA-containing TAGs is presented as well. | Triolein |
BACKGROUND: Cyclic phosphatidic acid (cPA) is a structural analog of lysophosphatidic acid (LPA), but possesses different biological functions, such as the inhibition of autotaxin (ATX), an LPA-synthesizing enzyme. As LPA is a signaling molecule involved in nociception in the peripheral and central systems, cPA is expected to possess analgesic activity. We characterized the effects of cPA and 2-carba-cPA (2ccPA), a chemically stable cPA analog, on acute and chronic pain. RESULTS: (1) The systemic injection of 2ccPA significantly inhibited somato-cardiac and somato-somatic C-reflexes but not the corresponding A-reflexes in anesthetized rats. (2) 2ccPA reduced sensitivity measured as the paw withdrawal response to electrical stimulation applied to the hind paws of mice through the C-fiber, but not Adelta or Abeta. (3) In mice, pretreatment with 2ccPA dose-dependently inhibited the second phase of formalin-induced licking and biting responses. (4) In mice, pretreatment and repeated post-treatments with 2ccPA significantly attenuated thermal hyperalgesia and mechanical allodynia following partial ligation of the sciatic nerve. (5) In rats, repeated post-treatments with 2ccPA also significantly attenuated thermal hyperalgesia and mechanical allodynia following chronic sciatic nerve constriction. CONCLUSIONS: Our results suggest that cPA and its stable analog 2ccPA inhibit chronic and acute inflammation-induced C-fiber stimulation, and that the central effects of 2ccPA following repeated treatments attenuate neuropathic pain. | Cyclic P-Oxides |
BACKGROUND: Preoperative anxiety is very common in adults awaiting all types of surgical procedures, which can interfere with the start and completion of surgery and increase the risk of postoperative complications. In this context, many researchers and clinical practitioners have attempted to use aromatherapy to help adults reduce preoperative anxiety. OBJECTIVE: To investigate systematically the efficacy of aromatherapy on preoperative anxiety in adults. DESIGN: A systematic review and meta-analysis of randomized controlled trials was undertaken. DATA SOURCES: PubMed, Embase, Cochrane Library, Web of Science, PsycINFO and CINAHL were comprehensively searched from their inception to June 2020. REVIEW METHODS: Studies on the use of aromatherapy for treating preoperative anxiety in adults were included. Two reviewers assessed the risk of bias of the included studies independently using the Cochrane Collaboration 'Risk of Bias' tool. Overall meta-analysis and five subgroup analyses regarding the type of control, the type of aroma preparations, delivery mode, session length and surgery type were performed using RevMan 5.3. The Higgins' I(2) (%) statistic was used to measure heterogeneity. A funnel plot and Egger's test were used to evaluate publication bias. RESULTS: Twenty studies comprising 1717 participants were included. The meta-analysis indicated that aromatherapy could significantly ameliorate preoperative anxiety (standard mean difference=-0.57, 95% confidence interval [-0.75, -0.39], p<0.00001) for adults awaiting surgical procedures, compared to placebo control, conventional care and no intervention. The subgroup analysis based on the surgery type showed that aromatherapy had a great improvement on preoperative anxiety for patients awaiting cardiac surgery and relatively low-risk surgery. Lavender oil, citrus species preparations and rose oil were the three most commonly used aroma preparations that could significantly improve preoperative anxiety. Most delivery modes of aromatherapy, including inhalation, massage, and oral administration, were effective. Moreover, short length (</=20 min per session) aromatherapy showed a better effect on preoperative anxiety (mean difference=-5.84, 95% confidence interval [-8.09, -3.59], p<0.00001) than aromatherapy lasting more than 20-minutes per session (mean difference=-2.15, 95% confidence interval [-3.81, -0.49], p = 0.01). CONCLUSION: Aromatherapy is an effective intervention for reducing preoperative anxiety in adults. Short-length aromatherapy inhalation seems to be more worthy of being recommended in clinical settings. More well-designed randomized controlled trials containing a wider range of surgical types and participants from more countries are needed to verify our findings before we can make strong recommendations. | Aromatherapy |
A comparative study of human colon HCT-116 xenograft in nude mice treated with and without peptide RT2 at high doses is performed along with a label-free proteomic analysis of the tissue in order to understand the potential mechanisms by which RT2 acts in vivo against colorectal tumors. RT2 displays no significant systematic toxicity, but reduces tumor growth after either intraperitoneal or intratumoral injection demonstrating it is a safe and efficacious antitumor agent in vivo. Of the 3196 proteins identified by label-free proteomics, 61 proteins appear only in response to RT2 and are involved in cellular processes largely localized in the cells and cell parts. Some of the proteins identified, including CFTR, Wnt7a, TIA1, PADI2, NRBP2, GADL1, LZIC, TLR6, and GPR37, have been reported to suppress tumor growth and are associated with cell proliferation, invasion, metastasis, angiogenesis, apoptosis, and immune evasion. Our work supports their role as tumor biomarkers and reveals RT2 has a complex mechanism of action in vivo. | Heterografts |
BACKGROUND: Longitudinal associations between social phobia (SP), depression and eating disorders (EDs), and the impact of antecedent SP and depression on subsequent treatment seeking for EDs have rarely been explored in prospective adolescent population studies. AIM: We aimed to examine these associations in a large-scale follow-up study among middle adolescents. METHOD: We surveyed 3278 Finnish adolescents with a mean age of 15 years for these disorders. Two years later, 2070 were reached and again surveyed for psychopathology and treatment seeking. Longitudinal associations between the self-reported disorders and treatment-seeking patterns for self-acknowledged ED symptoms were examined in multivariate analyses, controlling for SP/depression comorbidity and relevant socioeconomic covariates. RESULTS: Self-reported anorexia nervosa (AN) at age 15 years predicted self-reported depression at age 17 years. Furthermore, self-reported SP at age 15 years predicted not seeking treatment for bulimia nervosa (BN) symptoms, while self-reported depression at age 15 years predicted not seeking treatment for AN symptoms during the follow-up period. CONCLUSIONS: Adolescents with AN should be monitored for subsequent depression. Barriers caused by SP to help seeking for BN, and by depression for AN, should be acknowledged by healthcare professionals who encounter socially anxious and depressive adolescents, especially when they present with eating problems. | Phobia, Social |
Routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (HRV) in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months. Phylogenetic analysis of 144 HRV-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection. By contrast, protracted infections were found almost exclusively in immunocompromised patients, thus suggesting that host factors rather than the virus genotype modulate disease outcome, in particular the immune response. Complete genome sequencing of five chronic cases to study rhinovirus genome adaptation showed that the calculated mutation frequency was in the range observed during acute human infections. Analysis of mutation hot spot regions between specimens collected at different times or in different body sites revealed that non-synonymous changes were mostly concentrated in the viral capsid genes VP1, VP2 and VP3, independent of the HRV type. In an immunosuppressed lung transplant recipient infected with the same HRV strain for more than two years, both classical and ultra-deep sequencing of samples collected at different time points in the upper and lower respiratory tracts showed that these virus populations were phylogenetically indistinguishable over the course of infection, except for the last month. Specific signatures were found in the last two lower respiratory tract populations, including changes in the 5'UTR polypyrimidine tract and the VP2 immunogenic site 2. These results highlight for the first time the ability of a given rhinovirus to evolve in the course of a natural infection in immunocompromised patients and complement data obtained from previous experimental inoculation studies in immunocompetent volunteers. | Rhinovirus |
Two new species of flea of the genus Plocopsylla, subgenus Plocopsylla, (Siphonaptera: Stephanocircidae) collected from sigmodontine rodents in northwestern Argentina are described and a key to identification of species of the genus Plocopsylla, subgenus Plocopsylla, in Argentina is presented. Plocopsylla (P.) inti is cited for the first time in Argentina, extending its distribution approximately 970 km further south than previously documented. New locality data and flea-host associations are recorded. The contributions of this study are relevant because they increase knowledge of the diversity of flea fauna in northwestern Argentina bordering a plague endemic area and will be useful in the implementation of plague control management plans in the future. | Siphonaptera |
We investigated the antinociceptive and anti-inflammatory activities of the crude ethanolic extract (CEE), its fractions, and the flavonoid isorhamnetin from Aspidosperma tomentosum using models of nociception and inflammation in mice. In the writhing test, the CEE and its fractions (except for soluble phase, CHCl3 100% and EtAcO 100%) at 100 mg/kg p.o. induced antinociceptive activity. Isorhamnetin (100 mu mol/kg, p.o.) was also active. In the hot plate test, only the treatment with the fractions Hex : CHCl3 50%, CHCl3 100%, and CHCl3 : MeOH 5% (100 mg/kg, p.o.) increased the latency time, reversed by the opioid antagonist naloxone. Fractions that were active in the hot plate test did not show catalepsy condition. It was observed that CEE, all fractions, and isorhamnetin reduced the formalin effects in the neurogenic phase. In the inflammatory phase, only CEE, isorhamnetin, and CHCl3 100% and CHCl3 : MeOH 5% fractions were active. CEE and all fractions, except for CHCl3 : MeOH 10% fraction, isorhamnetin, and soluble fraction were able to produce an antioedematogenic activity in the ear capsaicin-induced edema test. In the thioglycolate-induced peritonitis, only EtAcO 100% fraction was not active. The results demonstrate that A. tomentosum has antinociceptive and anti-inflammatory activities in animal models. | Aspidosperma |
The most outstanding Russian anatomists and anthropologists D.A. Zhdanov and B.A. Nikityuk and the leading nutritionist A.A. Pokrovsky were the founders of the Anthroponutritiology, which arose at the junction of Anthropological Anatomy and Nutrition Science and represented a new stage in the integration of these two sciences. Both Sciences, enriching each other with facts, existing methodology and established traditions, implementing modern innovative approaches, bring the physical and nutritional status of individuals closer to the standard (the gold standard"). One of the applied tasks of Anthroponutritiology is the identification of the constitutional dependence of morphophysiological characters and determination of anthropological and clinical associations. Solving problems of Anthroponutritiology is a primary public concern, the most crucial state task. This issue is under the mandate of Federal Research Centre of Nutrition and Biotechnology and biotechnology, which implements this new branch of Science." | Nutritional Sciences |
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