Cytologic features of reactive fibroplasia in cutaneous and subcutaneous lesions of dogs: A retrospective study.
Determining reactive fibroplasia from primary neoplastic proliferation can be difficult using the cytologic features of spindle cells. This study aimed to describe qualitative features of benign reactive spindle cells and provide a diagnostic tool to distinguish between fibroplasia and soft tissue sarcoma. Cytologic samples from cutaneous lesions with histopathologically confirmed fibroplasia were reviewed and compared with cytologic samples from confirmed low-grade soft tissue sarcomas. The samples were obtained from the Archive of the Laboratorio Veterinario Bresciano (Brescia; Italy). A total of 25 cytologic samples retrieved from the database fit the selection criteria. For comparison, 25 cytologic samples of histopathologically confirmed soft tissue sarcomas with secondary inflammation were obtained and reviewed from the same database. A low number of singularly distributed spindle cells with mild features of atypia and a high ratio of inflammatory to spindle cells was observed in confirmed cases of fibroplasia. Low cellularity, individualized spindle cells, and an increased inflammatory-to-spindle cell ratio were more indicative of fibroplasia than sarcoma.


Differences in Art Appreciation in Autism: A Measure of Reduced Intuitive Processing.
Art appreciation reflects an initial emotional and intuitive response to artwork evaluation, although this intuitive evaluation can be attenuated by subsequent deliberation. The Dual Process Theory of Autism proposes that individuals with Autism Spectrum Disorder (ASD) have a greater propensity to deliberate and reduced intuition compared to matched controls. Evaluations of high- and low-quality artworks were undertaken by 107 individuals with a diagnosis of ASD and 145 controls. Controls consistently evaluated high-quality artworks to be much better quality than the low-quality artworks, reflecting intuitive processing. The ASD sample showed a reduced difference in evaluations between high- versus low-quality artwork, which reflects reduced intuitive processing and greater deliberative processing and is consistent with predictions by the Dual Process Theory of Autism.


Insensitivity of Water-Oxidation and Photosystem II Activity in Tomato to Chilling Temperatures.
Chilling tomato plants (Lycopersicon esculentum Mill. cv. Rutgers and cv. Floramerica) in the dark resulted in a sizable inhibition in the rate of light- and CO(2)-saturated photosynthesis. However, at low light intensity, the inhibition disappeared and the absolute quantum yield of CO(2) reduction was diminished only slightly. The quantum yield of photosystem II (PSII) electron flow was 18% lower when measured in chloroplasts isolated from chilled leaves than in chloroplasts isolated from unchilled leaves. Even though the maximum rate of PSII turnover in these chloroplasts was 12% lower subsequent to chilling, it was in all cases two or more times that required to support the light- and CO(2)-saturated rate of photosynthesis measured in the attached leaf. The concentration of active PSII centers in chloroplasts isolated from leaves either before or after chilling was determined by measurement of the products of water oxidation from a series of saturating flashes short enough to turnover the electron transport carriers only a single time. There was no significant change in the concentration of active PSII centers due to dark chilling.It was concluded that PSII activity and water oxidation capacity are not significantly impaired in tomato by chilling in the dark and therefore are not primary aspects of the inhibition of CO(2) reduction observed in attached leaves.


Effect of splinting and interproximal contact tightness on load transfer by implant restorations.
To circumvent the difficulty of achieving a passive framework fit, some authors have suggested that multiple adjacent implants be restored individually. This protocol requires that each unit be able to withstand mastication forces. Non-splinted restorations have numerous interproximal contacts that require adjustments prior to placement, with an unknown outcome relative to load transfer. This in vitro simulation study examined the effect of splinting and interproximal contact tightness on passivity of fit and the load transfer characteristics of implant restorations. A photoelastic model of a human partially edentulous left mandible with 3 screw-type implants (3.75 x 10 mm) was fabricated. For non-splinted restorations, individual crowns were fabricated on 3 custom-milled titanium abutments. After the units were cemented, 5 levels of interproximal contact tightness were evaluated: open, ideal (8 microm shim stock drags without tearing), light (ideal +10 microm), medium (ideal + 50 microm), and heavy (ideal + 90 microm). For splinted restorations, five 3-unit fixed partial dentures were fabricated, internally adjusted with silicone disclosing material, and cemented to the model. Changes in stress distribution under simulated non-loaded and loaded conditions (6.8 kg) were analyzed with a polariscope. In the simulated alveolar structures, non-splinted restorations with heavier interproximal contacts were associated with increased tensile stresses between implants; occlusal loads tended to concentrate around the specific loaded implant. Splinted restorations shared the occlusal loads and distributed the stresses more evenly between the implants when force was applied. The load-sharing effect was most evident on the center implant but also was seen on the terminal abutments of the splinted restorations. The results of this in vitro study suggest that excessive contact tightness between individual crowns can lead to a non-passive situation. In this experiment, splinted restorations exhibited better load sharing than non-splinted restorations.


A prototype cloud physics laser nephelometer.
The design and performance characteristics of a prototype cloud physics laser nephelometer are described. The instrument measures radiation scattered from individual cloud droplets, determining droplet concentrations from scattered light-pulse count rates and size distributions from pulse amplitudes.


Effects of child characteristics on the outcomes of a parent support program.
Previous research has reported on the effectiveness of the Signposts program for supporting families of children with an intellectual disability and difficult behaviour (Hudson et al., 2003; Hudson, Cameron, & Matthews, 2008). This paper reports on an investigation of the extent to which child characteristics moderate the effectiveness of the program. Data collected from 689 participants in the Signposts program were analysed to examine if the child characteristics of gender, age, or associated disability impacted on outcomes. The gender analyses produced mean effect sizes of 0.39 for boys and 0.42 for girls; however, this difference was not statistically significant. The age analyses produced mean effect sizes of 0.38 for children aged 2-5 years, 0.42 for children aged 6-12 years, and 0.30 for children aged 13-18 years; however, these differences among the age groups were not statistically significant. The associated disability analyses across 7 groups produced mean effect sizes ranging from 0.31 to 0.75; however, the differences among these groups were not statistically significant. First, gender was not a moderating variable. Second, while the effect size for the older age group seemed to be marginally lower than that of the other two groups, age was not found to be a moderating variable. Finally, type of associated disability was not found to be a moderating variable. Methodological limitations of the study necessitate care in interpreting the findings.


[The cytotoxic activity of natural killer cells in patients with the first episode of endogenous psychosis (a comparative study of test methods)].
Authors studied the cytotoxic activity (CA) of natural killer cells (NK) in 16 schizophrenic patients, aged from 18 to 25 years, with the first episode of psychosis. A significant decrease in CA NK was found in the total group of patients compared to healthy controls that suggested the dysregulation of natural immunity at this stage of disease. The addition of serotonin to the cell culture in vitro in concentrations 10-9 M stimulated the NK activity while the elimination of monocytes resulted in the significant reduction of CA NK. The parallel use of two methods for assessment of CA NK (a radioactive method and an easy and safe method using multifunctional particle size analyzer Multisizer MS-4) revealed similar results.


Addressing the needs of adolescents with treatment resistant depressive disorders: a systematic review of rTMS.
Depressive disorders are among the most commonly experienced mental health concerns and a leading cause of mortality in adolescence. Current treatment guidelines recommend the use of antidepressant medication, cognitive behavioral therapy or both treatments. Unfortunately 40–60% of adolescents fail to respond to these treatments, therefore a new effective alternative treatment modality would be of particular benefit. rTMS is effective in addressing treatment resistant depression in adults and investigation into its effectiveness with adolescent populations has begun. To examine the existing literature regarding the efficacy and safety of rTMS treatment with adolescents experiencing depressive symptoms, especially research conducted since the last published review. A systematic review was conducted in accordance with PRISMA guidelines. The databases of OVID PsycINFO, PubMed, Ovid Medline and Web of Science were searched for research utilizing rTMS treatment with adolescents experiencing depressive symptomology. The review identified seven studies that examined rTMS as a treatment for depressive symptomology in adolescence. Findings indicate rTMS is likely to be an effective treatment for young people with preliminary longitudinal results suggesting maintenance of effects 3 years post-treatment. Reported side effects have included headaches, scalp discomfort and single incidences of hypomania and seizure. All side effects were transitory and did not recur. Preliminary results suggest rTMS is an effective and well tolerated antidepressant treatment for adolescents with treatment resistant depressive symptomology. Further research allowing for comparison across studies is necessary to establish the efficacy of rTMS in adolescent depression.


Effects of the number of sperm and site of uterine semen deposition on conception rate and the number of embryos in weaned sows receiving a single fixed-time insemination.
Reducing the number of sperm needed to produce a litter with artificial insemination (AI) allows greater use of higher genetic merit boars. Induced ovulation with single fixed-time artificial insemination (SFTAI), combined with intrauterine (IUI) or deep uterine insemination (DUI), could improve fertility with low numbers of sperm. The objectives of the study were to determine the fertility effects of sperm numbers and the site of insemination. At weaning (0 h), sows (n = 534) were assigned by parity and estrus induction method (equine chorionic gonadotropin [eCG] or Control) to receive 1,200 × 106 sperm by IUI; 600, 300, or 150 × 106 sperm by IUI or DUI; or 75 × 106 sperm by DUI. At 80 h postweaning, sows received OvuGel and 26 h later a SFTAI using pooled semen. Sows were exposed to boars once daily and ultrasound was performed to determine follicle size and time of ovulation. Following SFTAI, sows were slaughtered 27 d after AI to determine pregnancy and litter traits. Data were analyzed using different models to test for effects of estrus induction, interaction of three levels of sperm (600 to 150) with two levels for site (IUI vs. DUI), and the overall effects of AI method (eight treatments). There was no effect (P > 0.05) of estrus induction on estrus (93%) within 5 d of weaning or on follicle size (6.1 mm) at OvuGel, but wean-to-estrus interval (3.8 vs. 4.0 d) was slightly reduced (P < 0.01) as was AI-to-ovulation interval (15.9 vs. 17.0 h, P = 0.04) for eCG and Control, respectively. There was no effect (P > 0.05) of estrus induction on pregnancy rate (78.6%), number of corpora lutea (CL; 21.7), or number of viable embryos (12.2). There was no effect of number of sperm or site of insemination and no interaction (P > 0.05) on pregnancy rate (range: 80.9% to 70.5%), but AI occurring after ovulation reduced the pregnancy rate (P < 0.02). The total number of embryos (range: 16.5 to 10.3) was not affected by estrus induction, number of sperm, or site of insemination (P > 0.05), but was influenced by AI treatment (P < 0.01). Treatments with a higher number of sperm (1,200 and 600) had more embryos compared with those with a lower number of sperm (300 to 75). The numbers of embryos also increased with the number of CL (P < 0.0001). These results suggest that the lower number of sperm affects litter size more than the pregnancy status. Acceptable fertility can be achieved with low numbers of sperm when using a SFTAI and uterine deposition, but AI-to-ovulation interval and ovulation rate influence final fecundity.


Parathyroid hormone-related protein-(1-34) inhibits intrinsic pump activity of isolated murine lymph vessels.
Parathyroid hormone-related protein (PTHrP) was originally found as a tumor-derived vasoactive factor and has also been known to produce significant relaxation of vascular smooth muscles. Thus effects of PTHrP-(1-34), a PTH receptor-binding domain, on spontaneous lymphatic pump activity was investigated in isolated pressurized lymph vessels of mice. Low concentrations (1 x 10(-10) and 3 x 10(-10) M) of PTHrP-(1-34) dilated lymph vessels and reduced the frequency of pump activity, whereas high concentrations (1 x 10(-9) to 1 x 10(-8) M) of PTHrP-(1-34) caused dilation with cessation of the lymphatic pump activity. N(omega)-nitro-L-arginine methyl ester (L-NAME; 3 x 10(-5) M) but not indomethacin (1 x 10(-5) M) significantly reduced the PTHrP-(1-34)-induced inhibitory responses of the lymphatic pump activity. In the presence of L-NAME (3 x 10(-5) M) and L-arginine (1 x 10(-3) M), the L-NAME-induced inhibition in the PTHrP-(1-34)-mediated responses was significantly reduced. Glibenclamide (1 x 10(-6) M) significantly suppressed the inhibitory responses of the lymphatic pump activity induced by PTHrP-(1-34) and S-nitroso-N-acetyl-penicillamine. The PTHrP-(1-34)-mediated inhibitory responses were significantly reduced by treatment with PTHrP-(7-34) (1 x 10(-7) M). These results suggest that PTHrP-(1-34) inhibits spontaneous pump activity of the isolated lymph vessels via PTH receptors and that production and release of endogenous nitric oxide and activation of ATP-sensitive K(+) channels in the lymph vessels contribute to the PTHrP-(1-34)-mediated inhibitory responses of the lymphatic pump activity.


[Penetrating Injury of the Lung with a Glass Splinter].
A 62-year-old man got drunk and dived into the windowpane. He received lacerations on his face and incised wound at his right chest, and was carried to our hospital. Computed tomography showed a glass splinter, about 14 cm of length, in the chest cavity. The patient underwent an emergency thoracotomy and it was found that the glass splinter penetrated through the upper lobe to the hilum. After removing the glass, simple closure by suturing the entrance and exit of the upper lobe was performed. The post operational course was uneventful. Selected patients can be rescued by simple pneumonorrhaphy without resection of lung.


Privatization and trade in health services: a review of the evidence.
Health care provision, like other areas of welfare, has increasingly been subject to processes of privatization and contracting out, leading in some cases to an increased involvement of for-profit corporations. Such processes are likely to interact with processes of liberalization at the international level in ways that we would expect to lead to a growth in the international trading of such services. However, health service provision is usually deeply embedded in state structures at the national level, and the form of such structures varies greatly. The degree and type of private involvement allowed for or facilitated by national-level systems defines the scope for the potential development of international trade in health services. The author reviews existing sources of data on the levels of private provision across advanced capitalist countries, countries in transition from Soviet-type systems, and developing countries, and highlights processes of change that are likely to increase such provision. Private provision is growing slowly but steadily in most countries. While levels of international trade in health services are difficult to ascertain, the interaction between national processes of reform and international processes of liberalization is likely to increase such trade.


The diversity of alleles at the hsd locus in natural populations of Escherichia coli.
In enteric bacteria three discrete families of type I restriction and modification systems (IA, IB and ID) are encoded by alleles of the serB-linked hsd locus. Probes specific for each of the three families were used to monitor the distribution of related systems in 37 of the 72 wild-type Escherichia coli strains comprising the ECOR collection. All 25 members of group A in this collection were screened; 12 were probe-positive, nine have hsd genes in the IA family, two in the IB and one in the ID. Twelve strains, representing all groups other than A, were screened; five were probe-positive, one has hsd genes in the IA family, one in the IB and three in the ID. The type ID genes are the first representatives of this family in E. coli, the probe-negative strains could have alternative families of hsd genes. The type IA and IB systems added at least five new specificities to the five already identified in natural isolates of E. coli. The distribution of alleles is inconsistent with the dendrogram of the bacterial strains derived from other criteria. This discrepancy and the dissimilar coding sequences of allelic hsd genes both imply lateral transfer of hsd genes.


Dissymmetries in fluorescence excitation and emission from single chiral molecules.
Chirality in molecular systems plays profoundly important roles in chemistry and physics. Most chemistry students are introduced to the concept of chirality through demonstrations of the interaction of chiral molecules with polarized light manifested as an "optical rotation" leading to the "(+)" and "(-)" [or dextrorotatory (d-) and levorotatory (l-)] designations of chiral compounds, with the subsequent determination of absolute stereochemical configuration by chemical or physical means enabling application of the familiar "R" and "S" labels. Although the intrinsic molecular parameters that control the dissymmetric light-matter interaction in chiral systems are well understood, we have only recently begun to ask questions regarding the role of local molecular environment and hidden heterogeneities associated with the ensemble-averaged molecular chiroptical response. In this mini-review, we discuss some of our recent research on application of single-molecule spectroscopy as a tool for probing heterogeneities and fluctuations of chiroptical dissymmetries in condensed phase.


Beta-arrestin biased agonism/antagonism at cardiovascular seven transmembrane-spanning receptors.
Heptahelical, G protein-coupled or seven transmembrane-spanning receptors, such as the β-adrenergic and the angiotensin II type 1 receptors, are the most diverse and therapeutically important family of receptors in the human genome, playing major roles in the physiology of various organs/tissues including the heart and blood vessels. Ligand binding activates heterotrimeric G proteins that transmit intracellular signals by regulating effector enzymes or ion channels. G protein signaling is terminated, in large part, by phosphorylation of the agonist-bound receptor by the G-protein coupled receptor kinases (GRKs), followed by βarrestin binding, which uncouples the phosphorylated receptor from the G protein and subsequently targets the receptor for internalization. As the receptor-βarrestin complex enters the cell, βarrestin-1 and -2, the two mammalian βarrestin isoforms, serve as ligand-regulated scaffolds that recruit a host of intracellular proteins and signal transducers, thus promoting their own wave of signal transduction independently of G-proteins. A constantly increasing number of studies over the past several years have begun to uncover specific roles played by these ubiquitously expressed receptor adapter proteins in signal transduction of several important heptahelical receptors regulating the physiology of various organs/ systems, including the cardiovascular (CV) system. Thus, βarrestin-dependent signaling has increasingly been implicated in CV physiology and pathology, presenting several exciting opportunities for therapeutic intervention in the treatment of CV disorders. Additionally, the discovery of this novel mode of heptahelical receptor signaling via βarrestins has prompted a revision of classical pharmacological concepts such as receptor agonism/antagonism, as well as introduction of new terms such as "biased signaling", which refers to ligand-specific activation of selective signal transduction pathways by the very same receptor. The present review gives an overview of the current knowledge in the field of βarrestin-dependent signaling, with a specific focus on CV heptahelical receptor βarrestin-mediated signaling and on "biased" CV heptahelical receptor ligands that promote or inhibit it. Exciting new possibilities for cardiovascular therapeutics arising from the delineation of this βarrestin-dependent signaling are also discussed.


Behavior of non-O157 Shiga toxin-producing Escherichia coli, enteroinvasive E. coli, enteropathogenic E. coli, and enterotoxigenic E. coli strains on alfalfa sprouts.
Data about the behavior of non-O157 Shiga toxin-producing Escherichia coli (non-O157 STEC), enteroinvasive E. coli (EIEC), enterotoxigenic E. coli (ETEC), and enteropathogenic E. coli (EPEC) on seeds and alfalfa sprouts are not available. The behavior of STEC, EIEC, ETEC, and EPEC was determined during germination and sprouting of alfalfa seeds at 20 ± 2°C and 30 ± 2°C and on alfalfa sprouts at 3 ± 2°C. When alfalfa seeds were inoculated with STEC, EIEC, ETEC, or EPEC strains, all these diarrheagenic E. coli pathotypes (DEPs) grew during germination and sprouting of seeds, reaching counts of approximately 5 and 6 log CFU/g after 1 day at 20 ± 2°C and 30 ± 2°C, respectively. However, when the sprouts were inoculated after 1 day of seed germination and stored at 20 ± 2°C or 30 ± 2°C, no growth was observed for any DEP during sprouting at 20 ± 2°C or 30 ± 2°C for 9 days. Refrigeration reduced significantly (P < 0.0.5) the number of viable DEPs on sprouts after 20 days in storage; nevertheless, these decreases have no practical significance for the safety of the sprouts.


Care of adult patients with a temporary tracheostomy.
The insertion of a temporary tracheostomy is a common procedure in the critical care environment. This article aims to explore the evidence relating to the nursing care required for a patient with a temporary tracheostomy in a critical care or acute ward setting. The article focuses on the insertion of a tracheostomy as a planned intervention to improve or enable patient recovery, rather than an emergency procedure for airway obstruction. The procedure is not without risk and aftercare is vital to ensure the patient remains safe and the procedure aids recovery and promotes comfort.


Treatment of, and Candida utilis biomass production from shochu wastewater; the effects of maintaining a low pH on DOC removal and feeding cultivation on biomass production.
Shochu wastewater (SW; alcoholic distillery wastewater) contains large amounts of organic compounds (25,000 - 60,000 COD mg/L), nitrogen (1,000 - 6,000 T-N mg/L), and phosphorus (500 - 1,000 T-P mg/L). Despite its high nutrient content, SW is highly perishable, which limits its utilization for animal feed and fertilizer. Therefore, SW is mainly treated by methane fermentation. On the other hand, a feed yeast, Candida utilis, can utilize various organic compounds and be utilized as a yeast extract source and animal feed. We previously bred a mutant, C. utilis UNA1, that accumulates a large amount of nitrogen. Here, we investigated the use of C. utilis UNA1 to treat highly concentrated SW. With fed-batch cultivation using a 5-L jar fermenter, controlling pH at 5.0 with H2SO4, 62.9% of DOC, 38.4% of DTN, and 44.5% of DTP were stably removed from non-diluted barley shochu wastewater (BSW), and about 16.7 kg of freeze-dried yeast biomass was obtained. The yeast sludge biomass generated from BSW contains about 60% crude protein. Furthermore, using H2SO4 to control pH increased the sulfur content of wastewater, which increased the methionine composition of yeast sludge biomass.


New species of the genus Cyamops Melander from New Zealand (Diptera, Periscelididae, Stenomicrinae).
Two new species of the genus Cyamops (Diptera: Periscelididae), the first from New Zealand, are described. The two newly described species are: Cyamops alessandrae and Cyamops crosbyi. A key to the genera of the subfamily Stenomicrinae and to the species of Cyamops from the Australasian/Oceanian Region and detailed illustrations of structures of the male terminalia are provided.


Release of growth hormone binding protein from IM-9 lymphocytes by endopeptidase is dependent on sulfhydryl group inactivation.
The hydrophilic GH-binding protein of serum is a derivative of the GH receptor. Little is known how this GH binding protein is released from the receptor which is firmly anchored in the plasma membrane. The IM-9 lymphocytes provide a useful laboratory model for studying this process because they are richly endowed with GH receptors and, under special conditions, are able to shed these receptors during incubation. Incubation of IM-9 cells for 90 min at 30 C did not result in the appearance of significant [125I]hGH binding in conditioned medium as determined with an ultrogel AcA 44 minicolumn. When iodoacetamide, 20 mM, or N-ethylmaleimide, 5 mM, was added during incubation, the conditioned medium bound 20-35% of [125I]human(h)GH. p-Chloromercuriphenyl sulfonic acid was less effective in promoting shedding of GH-binding protein. In contrast, aprotinin, phenylmethylsulfonylfluoride (PMSF), bacitracin, leupeptin, pepstatin, phosphoramidon, or chloroquine did not promote release of GH binding protein and did not affect iodoacetamide-induced release. Release was not inhibited by the addition of serum lacking GH binding protein. GH binding protein release was markedly temperature sensitive and practically ceased at 4 C. GH binding protein incubated with [125I] hGH was cross-linked with disuccinimidyl suberate. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence of dithiothreitol the complex migrated with an estimated molecular weight of 100,000 whereas [125I]hGH cross-linked to the membrane-bound GH receptor of the IM-9 cells migrated with an estimated molecular weight of 135,000. The smaller size of the binding protein is consistent with its derivation from the extracellular domain of the GH receptor. Because the release of this GH binding is greatly augmented by iodoacetamide and N-ethylmaleimide, two known sulfhydryl reactive reagents, we suggest that a free sulfhydryl group, either on the GH receptor or on a neighboring protein normally maintains the integrity of the receptor. The loss of this sulfhydryl group destabilizes the receptor and permits a membrane endopeptidase to release the GH binding protein. Cleavage is not dependent on lysosomal action and is not inhibited by protease inhibitors.


Can infants and young children eat enough green leafy vegetables from a single traditional meal to meet their daily vitamin A requirements?
To evaluate the feasibility of providing adequate vitamin A precursors to meet the daily need from a meal oftraditionally cooked green leafy vegetables and boiled rice and to understand mothers' perceptions and acceptance of leafy vegetables for infants and young children, 118 children aged 6 months to 3 years and their mothers were studied. The mothers were interviewed regarding their acceptance and perceptions about giving leafy vegetables to their young children. Their children were served a measured amount of rice and cooked leafy vegetables and mothers were asked to feed the child within about half an hour. Median intakes of leafy vegetables in children aged 6-11 months, 12-17 months and 18-35 months were 41 g, 71 g and 129 g respectively (in terms of raw green leaf). Approximately 40 g green leaf provides the recommended daily allowance for vitamin A precursors. 77% of the under-1-year-old children were breast-fed. The breast-fed children had a lower intake of vegetables than the completely weaned children. 87% of the children were found to like vegetables, 89% of the mothers liked to give vegetables to their children and 74% of the mothers answered that vegetables were good for health. Only two mothers (1.5%) refused to feed their children the leafy vegetables. The results show that leafy vegetables are acceptable to most of the mothers, and that children can eat enough leafy vegetables to meet a day's need of vitamin A precursors. Feasibility of feeding children enough green leafy vegetables at home on a regular basis needs further study.


Physiological characteristics and acute fatigue associated with position-specific speed endurance soccer drills: production vs maintenance training.
Objective: The study aimed to compare the physiological characteristics and acute fatigue associated with position-specific speed endurance production (SEP) and maintenance (SEM) soccer drills.Methods: Twenty male soccer players performed a position specific drill consisting of 8 exercise bouts each lasting ~30 s interspersed by 150 s (SEP) and 60 s (SEM) of passive recovery. A selection of players (n = 10) completed neuromuscular assessments pre and post drill.Results: Players covered greater high speed (12%), very high speed (49%) and sprint (218%) running distances in SEP (P < 0.05, ES: 0.51-0.80). SEP resulted in greater peak (7%) and average (10%) running speeds (P < 0.01, ES: 0.70-0.93). Mean and peak heart rate responses were greater in SEM (4-10%, P < 0.01, ES: 0.97-1.84) whilst blood lactate concentrations were higher following SEP (6%, P < 0.05, ES: 0.42). Reductions in vertical countermovement jump height were more pronounced immediately after SEP (2%, P < 0.05, ES: 0.36) but 24 h post SEM (4%, P < 0.05, ES: 0.52). Horizontal countermovement jump performance was reduced immediately post SEP and SEM (3-5%, P < 0.01, ES: 0.22-0.38) and 24 h post SEM (4%, ES: 0.32).Conclusion: The data demonstrate that position-specific SEP and SEM drills overload different physiological indices and induce small impairments in some neuromuscular measures.


Pharmacologic properties of acebutolol: relationship of hydrophilicity to central nervous system penetration.
Studies in various animal models have shown acebutolol to be a relatively cardioselective beta-adrenoceptor-blocking agent possessing both partial agonist and membrane-stabilizing activities. The latter property may not be significant at clinically used doses. Acebutolol has both antihypertensive and antiarrhythmic effects. As with beta blockers in general, the antihypertensive mechanism of acebutolol is not known. The antiarrhythmic activity of acebutolol may be related to beta blockade. Acebutolol is relatively hydrophilic and does not readily cross the blood-brain barrier, a fact that may be clinically significant in reducing the frequency and severity of central nervous system adverse effects. The pharmacologic profile of diacetolol, acebutolol's major metabolite, is similar to that of the parent compound in beta-blocking potency, cardioselectivity, and partial agonist activity. Diacetolol, however, does not possess membrane-stabilizing activity.


Transformation of carbon tetrachloride in an anaerobic packed-bed reactor without addition of another electron donor.
Carbon tetrachloride (52 microM) was biodegraded for more than 72% in an anaerobic packed-bed reactor without addition of an external electron donor. The chloride mass balance demonstrated that all carbon tetrachloride transformed was completely dechlorinated. Chloroform and dichloromethane were sometimes also found as transformation products, but neither accumulated to significant levels in comparison to the amount of carbon tetrachloride transformed. Transformation of carbon tetrachloride in the absence of an added electron donor suggests that carbon tetrachloride itself is the source of energy for the biological reaction observed, and possibly the source of carbon for cell growth. No such mechanism is yet known. The pathway of carbon tetrachloride transformation is not clear; it may be dehalogenated by hydrolytic reduction to carbon monoxide or formic acid which are electron demanding transformations. Carbon monoxide or formic acid may be further utilized and serve as electron donor. Complete dechlorination of carbon tetrachloride according to this pathway is independent of a second electron donor or electron acceptor, as with a fermentation process. Vancomycin, an inhibitor of gram positive eubacteria, severely inhibited carbon tetrachloride transformation in batch incubations with an enrichment culture from the reactor, indicating that gram positive eubacteria were involved in carbon tetrachloride transformation. Batch experiments with bromoethanesulfonic acid, used to inhibit methanogens, and molybdate, an inhibitor of sulfate reduction in sulfate reducing bacteria, demonstrated that neither methanogens nor sulfate reducers were involved in the complete dechlorination of carbon tetrachloride.


[Skin problems in a swollen lower limb].
Swollen lower limb is a diagnostic challenge for a physician. Common conditions causing swelling of lower extremities are chronic venous insufficiency and abnormalities in lymph drainage. Stasis dermatitis and lymphedema are manifestations of these defects. The most important therapy of both stasis dermatitis and lymphedema is adequate compression therapy. Patient education is important in order to achieve good compliance with compression therapy. The mainstay therapies of skin eczema are corticosteroids and tacrolimus ointment. Patients with stasis dermatitis have a higher risk for contact sensitization, which is important to remember when prescribing topical treatments.


Elevated serum prostaglandin E2 predicts the risk of infection in hepatitis B virus-related acute-on-chronic liver failure patients.
To evaluate the serum Prostaglandin E2 (PGE2) level in Acute-on-chronic liver failure (ACLF) and determine its predicative value for infection. From April 2014 to April 2015, ninety-one patients with hepatitis B virus and ACLF but without infection were enrolled into this prospective study that was carried out at our Hospital. Twenty patients with stable chronic hepatitis B were enrolled from the outpatient department and twenty healthy control subjects without any disease were enrolled from hospital staff. Serum PGE2 levels were determined using ELISA at enrollment. Clinical and laboratory parameters were collected. Receiver operating characteristic (ROC) curves were used to determine optimal cut-off values to predict infection. Significantly higher PGE2 levels were found in patients with ACLF in comparison with healthy controls and patients with stable CHB (P < 0.0001). In ACLF patients, PGE2 levels were significantly higher in patients that eventually developed infection than those without this complication (P < 0.0001). ROC analysis showed that serum PGE2 (area under the ROC curve, 0.83) could predict infection in patients with ACLF with sensitivity of 78.4% and specificity of 81.5% using a threshold of 141 pg/mL. Serum PGE2 is associated with the susceptibility to secondary infections for patients with ACLF. Increased PGE2 serum levels may serve as a potential biomarker for developing infections in ACLF patients.


Susceptibility and Immune Defence Mechanisms of Rhynchophorus ferrugineus (Olivier) (Coleoptera: Curculionidae) against Entomopathogenic Fungal Infections.
Insects infected with entomopathogenic fungi, experience physiological changes that influence their growth and immune defence. The potential of nine isolates of entomopathogenic fungi was evaluated after determining percent germination and relative conidial hydrophobicity. However, nutritional indices were evaluated after immersing eighth-instar Rhynchophorus ferrugineus larvae into each isolate suspension (1 × 10⁷ conidia/mL). The results showed that isolates B6884 and M9374 had 44.51% and 39.02% higher conidial hydrophobicity compared with isolate I03011 (least virulent). The results of nutritional index assays revealed a significant reduction in growth indices after infection with different isolates. Compared with control, B6884 and M9374 greatly decreased larval growth by reducing the efficacy of conversion of ingested food (36%-47%) and Efficacy of conversion of digested food (50%-63%). Furthermore, only isolate B6884 induced 100% mortality within 12 days. Compared with control, isolate I03011, possessing the lowest conidial hydrophobicity, only reduced 0.29% of the efficacy of conversion of ingested food (ECI) and 0.48% of the efficacy of conversion of digested food (ECD). Similarly, transcriptomic analysis of genes related to the Red palm weevil (RPW) immune response, including pathogen recognition receptors (C-type lectin and endo-beta-1,4-glucanse), signal modulator (Serine protease-like protein), signal transductors (Calmodulin-like protein and EF-hand domain containing protein) and effectors (C-type lysozyme, Cathepsin L., Defensin-like protein, Serine carboxypeptidase, and Thaumatin-like protein), was significantly increased in larval samples infected with B6884 and M9374. These results suggest that for an isolate to be virulent, conidial hydrophobicity and germination should also be considered during pathogen selection, as these factors could significantly impact host growth and immune defence mechanisms.


Accuracy and Performance Evaluation of Triplet Repeat Primed PCR as an Alternative to Conventional Diagnostic Methods for Fragile X Syndrome.
Conventional diagnosis of fragile X syndrome (FXS) is based on a combination of fragment analysis (FA) and Southern blotting (SB); however, this diagnostic approach is time- and labor-intensive and has pitfalls such as the possibility of missing large number alleles. Triplet repeat primed PCR (TP-PCR) is a current alternative used to overcome these limitations. We evaluated the diagnostic usefulness of TP-PCR compared with the conventional diagnostic protocol consisting of FA and/or SB in terms of allele categorization, repeat number correlation, and zygosity concordance in female genetic carriers. From November 2013 to March 2018, 458 patients (326 males, 132 females) were simultaneously examined using FA and/or SB and TP-PCR by detecting CGG repeat numbers in FMR1 gene and diagnosed as per American College of Medical Genetics guidelines. The TP-PCR results showed high concordance with the FA and/or SB results for all three aspects (allele categorization, repeat number correlation, and zygosity concordance in female genetic carriers). TP-PCR detected CGG expansions ≥200 in all full mutation (FM) allele cases in male patients, as well as both the normal allele (NL) and FM allele in female carriers. In premutation (PM) allele carriers, the TP-PCR results were consistent with the FA and/or SB results. In terms of zygosity concordance in female genetic carriers, 12 NL cases detected by TP-PCR showed a merged peak consisting of two close heterozygous peaks; however, this issue was resolved using a 10-fold dilution. TP-PCR may serve as a reliable alternative method for FXS diagnosis.


The macrophage and HIV: basic concepts and methodologies.
Along with CD4+ T-lymphocytes, macrophage lineage cells serve as primary hosts for HIV replication in vivo. In some tissues such as brain, where T-cell infection is essentially absent, the development of HIV-associated disease is mediated through infection of macrophages. This fact underscores the importance of experimental methods that yield results and conclusions that accurately reflect the mechanisms operational in vivo. Unfortunately, our understanding of key aspects of HIV-macrophage interactions, most notably, features of viral entry, replication, latency and persistence, lags behind that of T-cell infection. While some questions are best approached by direct examination of patient specimens using methods such as immunohistochemistry and phylogenetics, experiments based on HIV infection of macrophages in vitro can, necessarily, identify and elucidate the events, molecular mechanisms, and pathological consequences associated with this infection. In addition, macrophage culture methods can provide for the isolation of infectious HIV from patient blood monocytes and tissue macrophages, as well as subsequent continued propagation of these isolates in their host cell of origin. Maintenance of the host cell pedigree limits the possibility of alteration of viral properties such as chemokine coreceptor usage that may then no longer reflect the situation in vivo. This chapter focuses on HIV infection of macrophages. We describe methods for the cultivation of human blood monocyte-derived macrophages, their infection with HIV and subsequent maintenance, and the isolation of infectious HIV from them. Also included is a protocol using accutase for macrophage detachment. Accutase is a relatively new dissociation medium, used primarily in stem cell research. In our laboratory, it has far out-performed all other methods by providing for the gentle, yet thorough, detachment of macrophages without the need for scraping, and without loss of surface antigens or viability.


Soft thrombus formation in radiofrequency catheter ablation.
During RF catheter ablation, local temperature elevation can result in coagulum formation on the ablation electrode, resulting in impedance rise. A recent study has also demonstrated the formation of a so-called soft thrombus during experimental ablations. This deposit poorly adhered to the catheter tip and did not cause an impedance rise. The mechanism of soft thrombus formation and the role of the natural coagulation system are unknown. The formation of a soft thrombus was investigated experimentally by temperature-controlled RF delivery in heparinized blood at different heparin concentrations and in serum. After 60 seconds of RF delivery in blood with an electrode target temperature of 80 degrees C, a semisolidified mass had formed around the ablation electrode at all heparin concentrations. A smaller but structurally similar deposit had formed after RF delivery in serum. Scanning electron microscopy analysis revealed that these deposits consist of denaturized and aggregated proteins, and not of a classical thrombus. The formation of the so-called soft thrombus resultsfrom heat induced protein denaturation and aggregation and occurs independent of heparin concentration and also in serum. The formation of such deposits may occur at temperatures well below 100 degrees C, which may have important consequences for further development of ablation technologies.


Barriers to implementation of guidelines for the diagnosis and management of undescended testis.
Cryptorchidism or undescended testis (UDT) is one of the most common genital disorders identified at birth. The gold standard for treatment in the US is to surgically bring the UDT into the scrotal sac. In 2014, the American Urologic Association (AUA) presented a guideline for evaluation and treatment of cryptorchidism. We reviewed some of the most recent domestic and international studies examining the results of implementing the AUA and similar guidelines for the diagnosis and management of UDT. In addition, we reviewed some of the more common barriers to the implementation of the AUA guidelines and offered recommendations on how to increase the rate of early detection of UDT, thereby increasing the rate of surgical correction at the appropriate age.


Review of MR image segmentation techniques using pattern recognition.
This paper has reviewed, with somewhat variable coverage, the nine MR image segmentation techniques itemized in Table II. A wide array of approaches have been discussed; each has its merits and drawbacks. We have also given pointers to other approaches not discussed in depth in this review. The methods reviewed fall roughly into four model groups: c-means, maximum likelihood, neural networks, and k-nearest neighbor rules. Both supervised and unsupervised schemes require human intervention to obtain clinically useful results in MR segmentation. Unsupervised techniques require somewhat less interaction on a per patient/image basis. Maximum likelihood techniques have had some success, but are very susceptible to the choice of training region, which may need to be chosen slice by slice for even one patient. Generally, techniques that must assume an underlying statistical distribution of the data (such as LML and UML) do not appear promising, since tissue regions of interest do not usually obey the distributional tendencies of probability density functions. The most promising supervised techniques reviewed seem to be FF/NN methods that allow hidden layers to be configured as examples are presented to the system. An example of a self-configuring network, FF/CC, was also discussed. The relatively simple k-nearest neighbor rule algorithms (hard and fuzzy) have also shown promise in the supervised category. Unsupervised techniques based upon fuzzy c-means clustering algorithms have also shown great promise in MR image segmentation. Several unsupervised connectionist techniques have recently been experimented with on MR images of the brain and have provided promising initial results. A pixel-intensity-based edge detection algorithm has recently been used to provide promising segmentations of the brain. This is also an unsupervised technique, older versions of which have been susceptible to oversegmenting the image because of the lack of clear boundaries between tissue types or finding uninteresting boundaries between slightly different types of the same tissue. To conclude, we offer some remarks about improving MR segmentation techniques. The better unsupervised techniques are too slow. Improving speed via parallelization and optimization will improve their competitiveness with, e.g., the k-nn rule, which is the fastest technique covered in this review. Another area for development is dynamic cluster validity. Unsupervised methods need better ways to specify and adjust c, the number of tissue classes found by the algorithm. Initialization is a third important area of research. Many of the schemes listed in Table II are sensitive to good initialization, both in terms of the parameters of the design, as well as operator selection of training data.(ABSTRACT TRUNCATED AT 400 WORDS)


Associations between sleep and inattentive/hyperactive problem behavior among foster and community children.
Sleep disruption has been linked to numerous neural regulatory problems and problems with social emotional and behavioral functioning, and researchers have shown that sleep disruption is prominent in children with symptoms of attention-deficit hyperactivity disorder. These issues are germane to foster children, who have numerous disparities in areas of self-regulation and psychopathology but for whom there has been very little examination of sleep quality or the associations between poor sleep quality and physiological/behavioral dysregulation. Actigraphy measures were used to examine associations between sleep duration/quality and inattentive/hyperactive problem behavior in a sample of 79 children (aged 5-7 years): 32 foster children and 47 nonmaltreated community children. Of the sleep variables examined, only sleep duration was significantly associated with inattentive/hyperactive problem behavior. These associations were more significant in foster children compared to community children and in boys compared to girls. The results have several implications for prevention and intervention research.


A failed RCT to determine if antibiotics prevent mastitis: Cracked nipples colonized with Staphylococcus aureus: A randomized treatment trial [ISRCTN65289389].
BACKGROUND: A small, non-blinded, RCT (randomised controlled trial) had reported that oral antibiotics reduced the incidence of mastitis in lactating women with Staphylococcus aureus (S. aureus)- colonized cracked nipples. We aimed to replicate the study with a more rigorous design and adequate sample size. METHODS: Our intention was to conduct a double-blind placebo-controlled trial to determine if an antibiotic (flucloxacillin) could prevent mastitis in lactating women with S. aureus-colonized cracked nipples. We planned to recruit two groups of 133 women with S. aureus-colonized cracked nipples. RESULTS: We spent over twelve months submitting applications to five hospital ethics committees and seven funding bodies, before commencing the trial. Recruitment to the trial was very slow and only ten women were randomized to the trial after twelve months, and therefore the trial was stopped early. CONCLUSIONS: In retrospect we should have conducted a feasibility study, which would have revealed the low number of women in these Melbourne hospitals (maternity wards and breastfeeding clinics) with damaged nipples. The appropriate use of antibiotics for breastfeeding women with cracked nipples still needs to be tested.


[The dependence of fertility on egg density in Drosophila melanogaster].
The authors investigated the influence of larva competition on the dynamics of Drosophila number in non-overlapping generations. The egg number in generation (n + 1) was evaluated in 10 populations different by egg density in generation n (from 10 to 400 eggs for 3 ml of food in 10 ml test tubes). To estimate the fecundity were used fruit flies collected during three days from the beginning of imago appearance. Only those densities that provide the development without time delay because of competition were used (from 10 to 90). The model of number dynamics was constructed on the base of experimental data. The results of the model testing and experimental evidence allow to conclude: 1) If the time of substrate use is limited in non-overlapping generations the dynamic of population number is in the area of complex cycle regime far from equilibrium. Stable regime of number dynamic is possible only after very strong changes in fitness parameters. 2) Survival of Drosophila preimago is dependent on a number of factors involved successively at the different larva densities. 3) In modelling of number dynamics it is necessary to use a combination of functions that describe all factors successively involved in imago appearance while the density is increasing. 4) The general approach is suggested to determine the dependence of fly numbers in (n + 1) generation on numbers in n generation using only understandable biological parameters.


Effects of cefroxadine on L-leucine absorption in rat jejunum.
The effect of cefroxadine, an aminocephalosporin (beta lactam antibiotic) on rat intestinal L-leucine transport has been studied. Cefroxadine inhibited the L-leucine uptake by the intestinal mucosa in a dose-dependent fashion. In vivo studies showed that cefroxadine reduced L-leucine absorption. This effect was irreversible. Only the active transport component of the absorption was inhibited. Oxygen consumption of the mucosa was reduced by cefroxadine which inhibited the activity of the basolateral (Na(+)-K+) ATPase also.


Electrical excitation of surface plasmons by an individual carbon nanotube transistor.
We demonstrate here the realization of an integrated, electrically driven, source of surface plasmon polaritons. Light-emitting individual single-walled carbon nanotube field effect transistors were fabricated in a plasmonic-ready platform. The devices were operated at ambient conditions to act as an electroluminescence source localized near the contacting gold electrodes. We show that photon emission from the semiconducting channel can couple to propagating surface plasmons developing in the electrical terminals. Our results show that a common functional element can be operated for two different platforms emphasizing thus the high degree of compatibility between state-of-the-art nano-optoelectronics devices and a plasmonic architecture.


Effects of Potassium Deficiency on the Photosynthesis and Respiration of Leaves of Sugar Beet under Conditions of Low Sodium Supply.
Sugar beet plants (Beta vulgaris L. cv. F58-554H1) were germinated and cultured under standardized environmental conditions. The effects of K deficiency on photosynthetic and respiratory CO(2) exchange rates of attached leaves were studied under conditions of low Na supply by withholding both Na and K from the culture medium at cut-off (28 days after planting). Potassium and Na concentrations in the leaf blade and petiole decreased rapidly during the 8 days after cut-off, then more slowly.Photosynthetic CO(2) uptake per unit leaf area decreased rapidly with time after cut-off to 23% of the control rate in 17 days. Mesophyll resistance to CO(2) (r(m)) increased sharply after cut-off, r(m) eventually attaining 8.3 sec cm(-1). Leaf (mainly stomatal) diffusion resistance, r(1)', also increased rapidly from 4 days after cut-off, reaching 1.9 sec cm(-1) 13 days later. The photorespiratory evolution of CO(2) into CO(2)-free air decreased progressively after cut-off, but the rate of dark respiratory CO(2) evolution increased. It was concluded that withholding Na as well as K at cut-off increased the deleterious effects of K deficiency on photosynthesis and stomatal opening.


Reversion of multidrug resistance by co-encapsulation of doxorubicin and cyclosporin A in polyalkylcyanoacrylate nanoparticles.
Individual and combined polyalkylcyanoacrylate nanoparticle formulation of cyclosporin A and doxorubicin were prepared and evaluated in an attempt to show improved growth inhibition efficacy in a resistant cell culture line. The drug loaded nanoparticles were prepared using the well established emulsion polymerization process without using any modification for the hydrophilic doxorubicin drug whereas the incorporation of cyclosporin A needed to wait a moment after the polymerization reaction started. This was necessary to avoid cyclosporin A precipitation and polymer aggregation. Cyclosporin A release from the nanoparticles was rapid probably because the drug was adsorbed onto the nanoparticles surface rather than embedded into the polymeric core. Doxorubicin displayed also a burst effect but with a slower second phase probably related with the nanoparticles bioerosion rate owing to its entrapment in the polymeric network. Finally, it was shown in resistant cell culture experiments that the association of both cyclosporin A and doxorubicin within a single nanoparticle formulation elicited the most effective growth rate inhibition as compared to other combinations of both drugs while using a lower amount of polymer compared to separated nanoparticle formulations. This result was probably due to the synergistic effect achieved by combining the chemo-sensitizing compound cyclosporin A, with an effective cytotoxic drug like doxorubicin.


[How reproducible is blood pressure measurement? Intra- and interindividual blood pressure variability in routine practice].
Considering the reproducibility of blood pressure readings the epidemiologist and the physician in his clinical work take two different points of view. Studying drug effects the epidemiologist is interested in significant differences of blood pressures in a study population. The physician however, who estimates the effect of his prescription given to an individual patient has to compare single blood pressure readings in single individuals. In a pharmacological study we accept without any doubt the need of certain numbers of investigations to define a difference of 10 mm Hg as significant. In clinical routine however we behave quite differently and judge single readings intuitively as equal or different, independent of any statistical considerations. Not only the doctor but also the scientific societies with the highest reputation share the same point of view. In their recommendations they accept an arithmetic mean of two blood pressure readings as sufficient to judge blood pressures in individuals. In order to discuss this topic primarily from the doctors point, we analysed repeated blood pressure readings of 21 volunteers who tested 20 different blood pressure devices. We conclude, that the ongoing practice of judging the blood pressures of the patients meets only the needs of the epidemiologist. Reproducibility of single readings or mean values of two readings however are insufficient to draw satisfactory conclusions from the distributions of blood pressure in single individuals. Due to the short and long term blood pressure variability increasing the numbers of readings within a single day does not improve reproducibility sufficiently. It seems that the amount of blood pressure readings which are necessary to improve reproducibility of "the patients blood pressures" should be increased and taken over several days. If this is true, daily self-recordings should be the most promising approach.


Cyclodextrin-Functionalized Gold Nanorods Loaded with Meclofenamic Acid for Improving N6-Methyladenosine-Mediated Second Near-Infrared Photothermal Immunotherapy.
Cancer immunotherapy has achieved considerable clinical progress in recent years on account of its potential to treat metastatic tumors and inhibit recurrence. However, low patient response rates and dose-limiting toxicity are the major limitations of immunotherapy. Nanoparticle-based photothermal immunotherapy can amplify antitumor immune responses, although poor tumor penetration depth of near-infrared radiation (NIR) and the immunosuppressive tumor microenvironment significantly dampen its effects. We designed a nanoplatform based on gold nanorods for NIR-II-mediated photothermal therapy (PTT) combined with N6-methyladenosine (m6A) demethylase inhibition to achieve enhanced photothermal immunotherapy against prostate cancer. The GNRs were assembled layer by layer with polystyrenesulfonate as the interconnecting layer and then coated with a cationic polymer of γ-cyclodextrin (CD)-cross-linked low-molecular-weight polyethylenimine that was conjugated to an 8-mer peptide targeting the prostate tumor-specific gastrin-releasing peptide receptor. The m6A RNA demethylase inhibitor meclofenamic acid (MA) was then loaded into the CD cavity through hydrophobic interactions. GNR-CDP8MA specifically targeted the prostate tumor cells and selectively accumulated at the tumor site in vivo. In addition, GNR-CDP8MA almost completely ablated prostate cancer cell-derived tumors upon 1208 nm laser irradiation. Mechanistically, NIR-II triggered the release of MA from GNR-CDP8MA, which increased global mRNA m6A methylation and decreased the stability of PDL1 transcripts. Furthermore, GNR-CDP8MA-mediated PTT-induced immunogenic cell death in the primary tumor and consequently enhanced antitumor immunity by activating the antigen-presenting dendritic cells and tumor-specific effector T cells in the metastatic tumors. This study offers insights into synergistic m6A RNA methylation and PTT as an effective strategy for cancer immunotherapy.


DGSLSTM: Deep Gated Stacked Long Short-Term Memory Neural Network for Traffic Flow Forecasting of Transportation Networks on Big Data Environment.
Deep learning and big data techniques have become increasingly popular in traffic flow forecasting. Deep neural networks have also been applied to traffic flow forecasting. Furthermore, it is difficult to determine whether neural networks can be used for accurate traffic flow prediction. Moreover, since the network model is poorly structured and the parameter optimization technique is inappropriate, the traffic flow prediction is inaccurate because of the lack of certainty. The proposed system overcomes these problems by combining multiple simple recurrent long short-term memory (LSTM) neural networks with time traits to predict traffic flow using a deep gated stacked neural network. To deepen the model, the hidden layers have been trained using an unsupervised layer-by-layer approach. This approach provides a systematic representation of the time series data. A systematic representation of hidden layers improves the accuracy of time series forecasting by capturing information at multiple levels. Furthermore, it emphasizes the importance of model structure, random weight initialization, and hyperparameters used in stacked LSTM to enhance predictive performance. The prediction efficacy of the deep gated stacked LSTM model is compared with that of the gated recurrent unit model and the stacked autoencoder model.


Incidence and prevention of ischemic stroke following myocardial infarction: review of current literature.
Myocardial infarction is the leading cause of death today. With the fast progress in pharmacotherapy and revascularization technology, outcomes following a myocardial infarction have become very favorable. While most of the complications from a myocardial infarction can be adequately managed, thus leading to reduced mortality, stroke following a myocardial infarction remains a challenge even today, and can lead to potentially devastating complications. We discuss the incidence, pathophysiology, and management options of non-hemorrhagic stroke following a myocardial infarction.


Cysteine proteinase inhibitors block early steps in hemoglobin degradation by cultured malaria parasites.
Erythrocytic malaria parasites degrade hemoglobin as a source of amino acids for parasite protein synthesis. Cysteine proteinase inhibitors have been shown to block the hydrolysis of globin by cultured parasites, indicating that a malarial cysteine proteinase is required for this process. In the present study, we have evaluated the role of parasite proteinases in earlier steps of hemoglobin degradation, namely the disassociation of the hemoglobin tetramer and the separation of heme from globin. Hemoglobin did not spontaneously denature or release heme under the pH and reducing conditions of the malarial food vacuole, suggesting that parasite enzymatic activity is necessary for early steps in hemoglobin degradation. The incubation of cultured parasites with cysteine proteinase inhibitors inhibited the denaturation of hemoglobin and the release of heme from globin. These results suggest that, in addition to its role in globin hydrolysis, a malarial cysteine proteinase participates in the dissociation of the hemoglobin tetramer and the release of heme from globin. Thus, the malarial cysteine proteinase is a promising target for antimalarial chemotherapy.


Alzheimer Disease: evaluation of a functional MR imaging index as a marker.
To measure changes in functional synchrony in the hippocampus in patients with mild cognitive impairment (MCI) and Alzheimer disease (AD). Three subject groups (nine cognitively healthy elderly control subjects, 10 patients with probable AD, and five subjects with MCI) underwent resting-state functional magnetic resonance (MR) imaging for measurement of functional synchrony in the hippocampus. Functional synchrony was defined and quantified as the mean of the cross-correlation coefficients of spontaneous low frequency (COSLOF) components between possible pairs of voxel time courses in a brain region, or the COSLOF index. The two-tailed Student t test was used to determine differences in the COSLOF index between the control group, the probable AD group, and the MCI group. An operating characteristic curve was calculated to graphically depict the tradeoff between sensitivity and specificity of the COSLOF index. Functional synchrony quantified with the COSLOF index was obtained in AD, MCI, and control subjects. COSLOF index values were significantly lower in AD patients than in control subjects (t = 4.32, P <.0012). For MCI subjects, COSLOF index values were significantly higher than those of AD patients (t = -2.4052, P <.047) but significantly lower than those of control subjects (t = 2.257, P <.043). The exponential-class curve significantly fits the relationship between the COSLOF index and the Mini-Mental Status Examination score (chi(2) = 20.4), indicating the rapid decrease in cognitive capacity below a threshold of the COSLOF index. Our results suggest that the COSLOF index could be used as a noninvasive quantitative marker for the preclinical stage of AD.


Investigation of chemical rinses suitable for very small meat plants to reduce pathogens on beef surfaces.
Numerous antimicrobial interventions are capable of reducing the prevalence of harmful bacteria on raw meat products. There is a need to identify effective and inexpensive antimicrobial interventions that could, in practice, be used in very small meat plants because of limited financial, space, and labor resources. Eight antimicrobial compounds (acetic acid, citric acid, lactic acid, peroxyacetic acid, acidified sodium chlorite, chlorine dioxide, sodium hypochlorite, and aqueous ozone) were applied at various concentrations with small, hand-held spraying equipment, and bactericidal effectiveness was examined. Beef plate pieces were inoculated with fecal slurry containing a pathogen cocktail (Escherichia coli O157:H7, Salmonella Typhimurium, Campylobacter coli, and Campylobacter jejuni) and natural populations of aerobic plate counts, coliforms, and E. coli. Antimicrobial solutions were applied to beef surfaces via a portable, pressurized hand-held spray tank, and treated surfaces were subjected to appropriate methods for the enumeration and isolation of pathogens and hygiene indicators. Relative antimicrobial effectiveness was determined (from greatest to least): (i) organic acids, (ii) peroxyacetic acid, (iii) chlorinated compounds, and (iv) aqueous ozone. Using the equipment described, a 2% lactic acid rinse provided 3.5- to 6.4-log CFU/cm(2) reductions across all bacterial populations studied. Conversely, aqueous ozone yielded 0.02- to 2.9-log CFU/cm(2) reductions in pathogens and hygiene indicators, and did not differ significantly from a control tap water rinse (P = 0.055 to 0.731). This 2% lactic acid rinse will be subsequently combined with a previously described water wash to create a multistep antimicrobial intervention that will be examined under laboratory conditions and validated in very small meat plants.


Does sexual dimorphism exist in flowering phenology traits in anemophilous dioecious species? A test with Rumex acetosa.
Sexual dimorphism in flowering phenology traits may have evolved under sexual selection and vector-mediated selection. The conspicuous sexual dimorphism and sex-specific selection pressures in flowering phenology traits have been investigated mainly in entomophilous dioecious plants, whereas little is known about this in anemophilous plants. We examined sexual dimorphism in flowering onset, flowering peak, flowering duration, maximum proportion of open flowers per inflorescence branch, maximum proportion of newly opening flowers on a given date per branch, and longevity of individual flowers in natural Rumex acetosa populations. Correlations between flowering phenology traits and the degree of flowering overlap with the opposite sex were examined. We also tested whether the overlap of female flowering with male flowering enhanced seed set in female plants. Little sexual dimorphism was observed in flowering onset, peak, duration, and maximum proportion of newly opening flowers. Females had greater floral longevity and greater maximum proportion of open flowers than males. Flowering overlap with the opposite sex significantly increased with the maximum proportion of newly opening flowers and decreased with temporal deviation in the flowering peak in both sexes. Females with greater flowering overlap with males set more seeds in two of the three study populations. In wind-pollinated R. acetosa, little sexual dimorphism in phenological traits may have evolved to achieve synchronous flowering with the opposite sex. Our results suggest that, in angiosperms, not only common selection but also anemophily-specific selection may shape little sexual dimorphism in R. acetosa, unlike in entomophilous plants.


Altered tryptophan metabolism in patients with recurrent functional abdominal pain.
The causes of functional abdominal pain are still unclear. The role of food factors in their pathogenesis has been assessed by many researches, but the obtained results are varied. The aim of present study was to evaluate metabolism of tryptophan, which is substrate for serotonin synthesis and other bioactive compounds, in patients with recurrent functional abdominal pain. Thirty patients with recurrent abdominal pain and 30 healthy subjects were enrolled in this study. Urinary levels of tryptophan (TRP), 5-hydroxyindoleacetic acid(5-HIAA), L-kynurenine (KYN), xanthurenic acid(XA), and quinolinic acid(QA) were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS), and related to creatinine level (mg/gCr), during active phase(day with acute pain), and silence period, which recommended optimalisation of tryptophan intake. 5-HIAA/TRP ratio and KYN/TRP ratio as well as QA level s were significantly higher in patients compared to control group (p<0.001). After reducing TRP consumption, the above results improved, in particular, the level of QA decreased from 6.88±1.04 mg/Cr to 4,32±0.97 mg/gCr (p<0.001). Altered tryptophan metabolism may affect locally-andcentrally mediated recurrent functional abdominal pain.


DNA-assisted self-assembly of pyrene foldamers.
The self-organization of oligopyrene foldamers is described. Bi- and tri-segmental oligomers composed of nucleotides and non-nucleosidic, achiral pyrene monomers form double-stranded helical structures, as shown by absorbance, fluorescence, and CD spectroscopy. The mixed nature of alternating aromatic and phosphate groups ensures water solubility which, in turn, favors folding of the aromatic units. Pyrene molecules also assemble though interstrand stacking interactions. Structural organization of the pyrene units is an intrinsic property of the oligoaryl part and takes place independently from the sequence of the attached DNA. Chirality transfer from DNA to the pyrene segment leads to formation of a double helix, in which neighboring pyrene units are, in the present case, twisted in a right-handed manner. Pyrene helicity is most pronounced in a bi-segmental chimera, in which a DNA stem is present only at one end of the pyrene section.


Continental viewpoints on the concept of reactive psychoses.
Although the Scandinavian concept of reactive psychoses relates to K. Jaspers and although Kretschmer described the prototype of a psychosis of psychogenic/reactive origin (Der sensitive Beziehungswahn), the concept is not so commonly used in German-speaking countries. Important reasons for this refusal may be (1) the sharp distinction between psychosis (which may be explained but not understood) and understandable reactions, which was stressed in rather influential German psychiatric schools in the middle of the century, and (2) the aim of stressing psychological understanding in a broad spectrum of psychiatric illnesses in the Swiss tradition, where the demarcation of particular reactive psychoses seemed to be superfluous. The development of modern concepts stressing the multidimensionality in the etiology of the main groups of psychiatric disorders was certainly influenced by the concept of reactive psychoses but passed it.


Evaluation of pure ground glass pulmonary nodule: a case report.
A pulmonary nodule is a single, nearly spherical, well-circumscribed pulmonary opacity up to 30 mm in diameter and surrounded by aerated lung tissue. In radiographs, pulmonary nodules may appear as solid, completely obscuring the lung parenchyma, or as subsolid, not completely obscuring adjacent tissues. A subsolid pulmonary nodule may be further subclassified as a pure ground glass nodule (pGGN) or a part solid nodule, a mixture of ground glass components and focal opacity obscuring the adjacent tissues. Guidelines for evaluation of solid pulmonary nodules are based on nodule size, recommending vigilance and non-operative management for small nodules (less than 8 mm in diameter) and diagnostic biopsy for nodules with a diameter of 8 mm or more. However, subsolid ground glass pulmonary nodules are an exception to this rule. Although small in size, persistent subsolid nodules are potentially premalignant or malignant. We present the case of a non-smoker who was found to have an incidental pulmonary pGGN. We then discuss the radiologic appearance, histology, clinical outcomes, and evaluation and management strategy of subsolid pulmonary nodules compared with solid nodules.


Influence of SiO2 content of polyetheretherketone (PEEK) on flexural properties and tensile bond strength to resin cement.
In the present study, the influence of the SiO2 content of polyetheretherketone (PEEK) on the bonding between PEEK and resin cement, and the corresponding mechanical properties, were evaluated. Three experimental PEEK samples with varying amounts of SiO2, and PEEK containing 20 wt% of TiO2 (DK), were investigated. The tensile bond strength (TBS) was evaluated before and after 10,000 thermal cycles, upon polishing, sandblasting, and conditioning of the specimens with BONDMER lightless containing a silane coupling agent, and bonded with ESTECEM II. The crystallinity, flexural modulus, and flexural strength were determined after 10,000 thermal cycles. TBS values were analyzed by two-way ANOVA and a t-test with Bonferroni correction (α<0.05), while the crystallinity, flexural modulus, and flexural strength were analyzed with one-way ANOVA followed by a t-test with Bonferroni correction (α<0.05). The TBS improved with increasing SiO2 content in PEEK; moreover, DK and the sample with 40 wt% SiO2 exhibited the highest flexural strength.


Flow volume loops in patients with goiters.
Plain radiology is the standard means of assessing upper airway obstruction in patients with goiters. Flow volume loop curves will provide additional information, because they allow a quantitative assessment of airflow dynamics in the respiratory cycle. Fifty-one patients had flow volume loops performed before and after thyroidectomy. There was a significant increase in the maximum inspiratory flow rate (3.9 +/- 0.2 versus 4.9 +/- 0.2 L/second, p less than 0.01) after thyroidectomy. Eight of twelve patients with normal tracheal radiology had improved airflow dynamics in the postoperative period. The flow volume loop curve is a simple noninvasive means of assessing airflow dynamics in patients with goiters and may be superior to conventional radiology.


Food selection: problems in understanding how we choose foods to eat.
Understanding food selection will require considerably more than reductionist analyses of the internal workings of individual animals. To understand food choice we will have to examine not only the physiology and behavior of individuals, but also the biological and social environments within which individuals select items to ingest. The biological environment determines patterns of food availability and, over evolutionary time, provides selective pressures which shape sensory-affective responses to flavors, making them adaptive with respect to local conditions. Direct experience of the consequences of ingesting potential foods and interaction with conspecifics that have eaten various foods both affect food choices. These multiple influences, acting at different levels of organization, can bias food selection by individuals in either adaptive or maladaptive directions, depending on the characteristics of the environment in which feeding occurs. The need to understand the relationship between internal organization, individual and social experience and ecological demands may make food choice the most difficult of the core aspects of feeding behavior to analyze satisfactorily.


Nuptial and childbearing customs of the ethnic minorities in China.
The current nuptial customs of the ethnic minorities in China are examined. "Although monogamous marriage has now been adopted by all but a few ethnic communities, variations still exist between different nationalities in the specific forms of marriage and range of intermarriage owing to the uneven nature of historical development. Such variations are shaped by various factors of the given locality and given time such as the socioeconomy, religion, culture and education, and exert direct influence on the childbearing behavior and reproduction of the ethnic population."


Future technologies to address the failed endoprosthesis.
Endovascular aneurysm repair (EVAR) has transformed therapy for aortic aneurysms and introduced an era of widespread use for endovascular procedures in a variety of vascular beds. While dramatic improvements in acute outcomes drove the early enthusiasm for EVAR, a realization that the integrity of the endoprostheses used for EVAR was significantly inferior to results obtained with open surgical reconstruction dampened enthusiasm for their use in low-risk patients and mandated long-term follow-up for EVAR patients. The future of EVAR as a primary approach to aortic aneurysm repair rests on development of technologies and techniques that can reproduce the foundations and, therefore, the results of open surgical reconstruction. Many of these technologies will be used initially to address the failing endoprostheses, but will have a larger role in their application as a primary component of EVAR.


The effect of light and phytochrome on 1-aminocyclopropane-1-carboxylic Acid metabolism in etiolated wheat seedling leaves.
While light-grown wheat leaves produced ethylene at a low rate of <0.1 nanomoles per gram per hour and contained 1-aminocyclopropane-1-carboxylic acid (ACC) at low levels of <2.5 nanomoles per gram, etiolated wheat leaves produced ethylene at a rate of 2 nanomoles per gram per hour and accumulated concentrations of ACC at levels of 40 nanomoles per gram. Upon illumination of 8-day-old etiolated wheat seedlings with white light, the ethylene production rate increased initially, due to the activation of ethylene-forming activity, but subsequently declined to a low level (0.1 nanomoles per gram per hour) at the end of the 6-hour illumination. This light-induced decline in ethylene production rate resulted from a decline (more than 35 nanomoles per gram) in ACC level, which was accompanied by a corresponding increase in 1-(malonylamino)cyclopropane-1-carboxylic acid content. These data indicate that illumination promoted ACC malonylation, resulting in reduced ACC level and consequently reduced ethylene production. However, light did not cause any significant increase in the extractable ACC-malonyltransferase activity. The effect of continuous white light on promotion of ACC malonylation was also observed in intermittent white light or red light. A far-red light treatment following red light partially reversed the red light effect, indicating that phytochrome participates in the promotion of ACC malonylation.


Photodynamic therapy: A next alternative treatment strategy for hepatocellular carcinoma?
Liver cancer is one of the most common cancers in the world. Of all types of liver cancer, hepatocellular carcinoma (HCC) is known to be the most frequent primary liver malignancy and has seriously compromised the health status of the general population. Locoregional thermal ablation techniques such as radiofrequency and microwave ablation, have attracted attention in clinical practice as an alternative strategy for HCC treatment. However, their aggressive thermal effect may cause undesirable complications such as hepatic decompensation, hemorrhage, bile duct injury, extrahepatic organ injuries, and skin burn. In recent years, photodynamic therapy (PDT), a gentle locoregional treatment, has attracted attention in ablation therapy for patients with superficial or luminal tumors as an alternative treatment strategy. However, some inherent defects and extrinsic factors of PDT have limited its use in clinical practice for deep-seated HCC. In this contribution, the aim is to summarize the current status and challenges of PDT in HCC treatment and provide potential strategies to overcome these deficiencies in further clinical translational practice.


A risk stratification model of acute pyelonephritis to indicate hospital admission from the ED.
There are no guidelines regarding the hospitalization of female patients with acute pyelonephritis (APN); therefore, we performed a retrospective analysis to construct a clinical prediction model for hospital admission. We conducted a retrospective analysis of a prospective database of women diagnosed as having APN in the emergency department between January 2006 and June 2012. Independent risk factors for admission were determined by multivariable logistic regression analysis in half of the patients in this database. The risk of admission was categorized into 5 groups. The internal and external validations were conducted using the remaining half of the patients and 192 independent patients, respectively. Independent risk factors for admission were age of 65 years or greater (odds ratio [OR], 2.62; 1 point), chill (OR, 2.40; 1 point), and the levels of segmented neutrophils greater than 90% (OR, 2.00; 1 point), serum creatinine greater than 1.5 mg/dL (OR, 2.41; 1 point), C-reactive protein greater than 10 mg/dL (OR, 2.37; 1 point), and serum albumin less than 3.3 g/dL (OR, 7.36; 2 points). The admission risk scores consisted of 5 categories, which were very low (0 points; 5.9%), low (1 point; 10.7%), intermediate (2 points; 20.7%), high (3-4 points; 51.9%), and very high (5-7 points; 82.8%) risk, showing an area under the curve of 0.770. The areas under the curve of the internal and external validation cohorts were 0.743 and 0.725, respectively. This model can provide a guideline to determine the admission of women with APN in the emergency department.


Public Health in a Federation: Lessons from the Spanish Influenza in Australia.
Public health policy has been identified by scholars as a principal means by which the state has expanded its control over human populations. Yet, as the COVID-19 pandemic has shown, public health responses do not necessarily reinforce the authority and prestige of the state, even while governments employ strict measures such as lockdowns and border closures. This article examines arguments about the nation-making effects of public health measures through an examination of the Spanish influenza outbreak in the recently federated Australian nation during 1919. It examines the effort of the central government to co-ordinate quarantine and other public health measures in the face of serious tensions within the Australian federation. In doing so, the article suggests a need to think more subtly about the role of 'bio-political' events such as public health crises in consolidating state control and fostering exclusionary forms of nationalism. These lessons apply particularly to federal nation-states.


Dimensions of attachment and commitment across the transition to parenthood.
We used structural equation modeling and actor-partner interdependence models to test dyadic associations between adult attachment and changes in relationship commitment at the transition to parenthood in a sample of 182 dual-earner couples. Overall, more avoidant individuals experienced significant changes in commitment at the transition to parenthood; specifically, higher avoidance was associated with decreases in personal confidence and dedication. More anxious fathers experienced increases in personal felt constraint while anxious mothers' commitment remained stable. Partners of more anxious individuals experienced changes in commitment at the transition to parenthood. Higher anxiety was associated with decreases in partners' confidence and dedication and increases in partners' felt constraint. These results suggest that interventions focused on couple relationships at the transition to parenthood should address commitment as well as relationship skills and explore how adult attachment may influence the parents' reactions to stress during this disruptive transition. Future research should examine whether commitment levels recover once the initial stress of the transition to parenthood decreases and family roles and routines renegotiated.


Mosaic 13q13.2-ter deletion restricted to tissues of ectodermal and mesodermal origins.
The '13q-' syndrome shows widely variable manifestations. Investigation of the involvement of different tissues has never been reported in patients with 13q- syndrome previously. We describe a patient with mosaicism for del(13q) and clinical features of 13q- syndrome. The mother of the patient was professionally exposed to aniline colorants and glue components during the whole pregnancy. The patient had dysmorphic features, skeletal anomalies and brain malformations with agenesis of the corpus callosum, vermian hypoplasia and IVth ventricular system abnormalities. Eye examination revealed chorioretinal coloboma and irregular dispersion of retinal pigment in the right eye. The karyotype analyses and the molecular studies performed on peripheral lymphocytes, oral swab and cells of urinary tract were normal whereas a deletion of the long arm of chromosome 13 (13q13.2) was found in skin fibroblasts and in hair cells. We hypothesized that the 13q deletion arose during the third week after conception possibly due to a teratogenic effect and that tissue of mesodermal and ectodermal origin are involved. We suggest analysing a fibroblast karyotype when a diagnosis of 13q- syndrome is suspected on clinical ground. The role of teratogens in causing this type of mosaic chromosome abnormality also warrants further investigation.


The Potential Prebiotic Berberine Combined With Methimazole Improved the Therapeutic Effect of Graves' Disease Patients Through Regulating the Intestinal Microbiome.
Graves' disease, a typical metabolism disorder, causes diffuse goiter accompanied by ocular abnormalities and ocular dysfunction. Although methimazole (MI) is a commonly used drug for the treatment of GD, the efficacy of methimazole is only limited to the control of clinical indicators, and the side effects of MI should be seriously considered. Here, we designed a 6-month clinical trial that divided the patients into two groups: a methimazole group (n=8) and a methimazole combined with potential prebiotic berberine group (n=10). The effects of both treatments on thyroid function and treatment outcomes in patients with GD were assessed by thyroid index measurements and gut microbiota metagenomic sequencing. The results showed that the addition of berberine restored the patients' TSH and FT3 indices to normal levels, whereas MI alone restored only FT3. In addition, TRAb was closer to the healthy threshold at the end of treatment with the drug combination. MI alone failed to modulate the gut microbiota of the patients. However, the combination of berberine with methimazole significantly altered the microbiota structure of the patients, increasing the abundance of the beneficial bacteria Lactococcus lactis while decreasing the abundance of the pathogenic bacteria Enterobacter hormaechei and Chryseobacterium indologenes. Furthermore, further mechanistic exploration showed that the addition of berberine resulted in a significant upregulation of the synthesis of enterobactin, which may have increased iron functioning and thus restored thyroid function. In conclusion, methimazole combined with berberine has better efficacy in patients with GD, suggesting the potential benefit of berberine combined with methimazole in modulating the composition of intestinal microbes in the treatment of GD, providing new strong evidence for the effectiveness of combining Chinese and Western drugs from the perspective of modulating the intestinal microbiota.


Multi-criteria assessment of county public health capability disparities.
This paper proposes an analytical approach to the assessment of geographic population health disparities that are measured as the consolidation of public health related indicators into geographic-specific scores, and are representative of the level of public health capability within counties in the state of Mississippi. A multi-criteria decision model was employed to develop an additive scoring system that assigns a numerical score of public health capability disparities for a geographical area (county). Routinely collected indicators were used to measure each county's current public health related concerns. These indicators include access, risks, health care quality, and outcomes data. Public health experts rated and ranked indicators to generate indicator weight. A county score was developed to rank Mississippi counties based on relative public health capability. This scoring system depicts population health disparities among Mississippi counties. The model is useful and ideal for establishing expectations and benchmarks for reduction or equalization of disparities. This information can be used to manage geographic population health disparities by guiding policy formulation and implementation.


Contact stress distributions in malreduced intraarticular distal radius fractures.
Residual articular incongruity of the distal radius following intraarticular fracture has been correlated with early osteoarthritis (OA) and a poor clinical outcome. We developed a simple in vitro fracture model of the distal radius to investigate the relationship between degree of articular incongruity and the resulting distribution of radiocarpal contact stress. Twelve fresh-frozen cadaver arms were dissected, packets of Fuji Pressensor film were inserted into the wrist, and the wrist was loaded through its flexor and extensor tendons. We created a simple intraarticular fracture that allowed controlled distal radius articular incongruity. Loading trials were performed for the intact distal radius, for a fully reduced case, and for step-offs of 0.4, 1, 2, and 3 mm. Mean contact stress was significantly greater than the anatomically reduced case at only 3 mm of step-off. Contact area was greater than the anatomically reduced case at 0.4, 1, and 2 mm of step-off. The elevations in contact stress that we observed were only modest, suggesting that other factors may be involved in the pathogenesis of radiocarpal OA in the presence of residual articular incongruity.


Differential Impact of Membrane-Bound and Soluble Forms of the Prognostic Marker Syndecan-1 on the Invasiveness, Migration, Apoptosis, and Proliferation of Cervical Cancer Cells.
Cervical cancer ranks fourth among the most commonly diagnosed malignant tumors in women worldwide. Previously published evidence suggested a possible connection between the expression of the membrane-bound heparan sulfate proteoglycan syndecan-1 (Sdc-1) and the development of cervical carcinoma. Sdc-1 serves as a matrix receptor and coreceptor for receptor tyrosine kinases and additional signaling pathways. It influences cell proliferation, adhesion, and migration and is seen as a modulator of the tumor microenvironment. Following proteolytic cleavage of its extracellular domain in a process called shedding, Sdc-1 can act as a paracrine effector. The loss of Sdc-1 expression is associated with low differentiation of cervical carcinoma and with an increased rate of lymph node metastases. Here, we analyzed the clinical impact of Sdc-1 expression by analysis of public gene expression datasets and studied the effect of an overexpression of Sdc-1 and its membrane-bound and soluble forms on the malignant properties of the human cervical carcinoma cell line HeLa through functional analysis. For this purpose, the HeLa cells were stably transfected with the control plasmid pcDNA3.1 and three different Sdc-1-DNA constructs,encoding wild-type, permanently membrane-bound, and constitutively soluble Sdc-1. In clinical specimens, Sdc-1 mRNA was more highly expressed in local tumor tissues than in normal and metastatic cervical cancer tissues. Moreover, high Sdc-1 expression correlated with a poor prognosis in Kaplan-Meier survival analysis, suggesting the important role of Sdc-1 in the progression of this type of cancer. In vitro, we found that the soluble, as well as the permanently membrane-bound forms of Sdc-1 modulated the proliferation and the cell cycle, while membrane-bound Sdc1 regulated HeLa cell apoptosis. The overexpression of Sdc-1 and its soluble form increased invasiveness. In vitro scratch/wound healing assay, showed reduced Sdc-1-dependent cell motility which was linked to the Rho-GTPase signaling pathway. In conclusion, in cervical cancer Sdc-1 modulates pathogenetically relevant processes, which depend on the membrane-association of Sdc-1.


Immunopathology of chronic viral hepatitis.
This paper reviews the main necro-inflammatory liver lesions observed in chronic viral hepatitis B and their apparent immunological mechanisms. Focal necrosis seems to represent the mechanism for clearance of virus replicating hepatocytes by cytotoxic T lymphocytes under HLA class I restriction and with hepatitis B virus nucleocapsid antigens as target antigen. Piecemeal necrosis involves CD8+ lymphocytes, possibly with hepatocellular membrane autoantigens as target antigen. Confluent lytic necrosis (bridging hepatic necrosis) presumably results from humoral immune mechanisms. Focal necrosis, piecemeal necrosis and confluent lytic necrosis determine the extent of necro-inflammatory activity in liver biopsy specimens, classified as chronic persistent hepatitis (low activity) or chronic active hepatitis (high activity). The extent of necro-inflammatory activity fluctuates during the natural course of chronic viral hepatitis B: from low activity during the viral replicative phase, through high activity in the viral elimination phase, into low activity again in the ensuing viral integration phase. The role of HLA antigens, intercellular adhesion molecules, cytokines and accessory antigen presenting cells is emphasized.


Adult height after growth hormone (GH) treatment for GH deficiency due to cranial irradiation.
The indications and factors affecting the growth in response to treatment with growth hormone (GH) of patients with cranial irradiation-induced GH deficiency remain unclear. The adult heights of 56 patients treated with GH (0.4-0.6 U/kg/week) as daily sc injections were analysed. They had been given 18 or 24 Grays (Gy) cranial irradiation for leukemia (group 1, 26 cases), 50 +/- 1 Gy for various tumors (group 2, 13 cases), 46 +/- 1 Gy for retinoblastoma (group 3, 8 cases), or 34 +/- 2 Gy with spinal irradiation for medulloblastoma (group 4, 9 cases). Twenty- five of these 56 patients had early puberty and were also treated with gonadotropin-releasing hormone (GnRH) analog. The standing (-1.0 +/- 0.2 in group 1, -0.7 +/- 0.3 in group 2, -1.1 +/- 0.3 in group 3, and -2.0 +/- 0.4 SD in group 4) and sitting (-1.8 +/- 0.2 in group 1, -0.4 +/- 0.4 in group 2, -1.2 +/- 0.4 in group 3, and -3. 4 +/-0.4 SD in group 4) adult heights were shor ter (P < 0.05 for standing and P < 0.001 for sitting heights) for group 4 than for each of the other groups. Of the 47 patients given cranial (and not craniospinal) irradiation, sitting adult height was shorter (P = 0. 02) and the difference between standing adult and target heights greater (P = 0.03) in those patients in whom puberty occurred at a normal age than in those treated with GnRH analog. Conclusion. The incomplete catch-up of growth seems to be mainly due to the reduction in sitting height of patients given spinal irradiation and in whom puberty occurred at a normal age. This suggests that GnRH analog treatment should be more widely used to treat children with early and/or rapidly progressing puberty after cranial irradiation.


Regulation of CCR4-NOT complex deadenylase activity and cellular responses by MK2-dependent phosphorylation of CNOT2.
CCR4-NOT complex-mediated mRNA deadenylation serves critical functions in multiple biological processes, yet how this activity is regulated is not fully understood. Here, we show that osmotic stress induces MAPKAPK-2 (MK2)-mediated phosphorylation of CNOT2. Programmed cell death is greatly enhanced by osmotic stress in CNOT2-depleted cells, indicating that CNOT2 is responsible for stress resistance of cells. Although wild-type (WT) and non-phosphorylatable CNOT2 mutants reverse this sensitivity, a phosphomimetic form of CNOT2, in which serine at the phosphorylation site is replaced with glutamate, does not have this function. We also show that mRNAs have elongated poly(A) tails in CNOT2-depleted cells and that introduction of CNOT2 WT or a non-phosphorylatable mutant, but not phosphomimetic CNOT2, renders their poly(A) tail lengths comparable to those in control HeLa cells. Consistent with this, the CCR4-NOT complex containing phosphomimetic CNOT2 exhibits less deadenylase activity than that containing CNOT2 WT. These data suggest that CCR4-NOT complex deadenylase activity is regulated by post-translational modification, yielding dynamic control of mRNA deadenylation.