Evaluation of cognitive functions in the elderly with and without central auditory processing disorder.
Evaluate and compare the performance of cognitive functions between elderly with and without auditory processing disorders. Twenty-eight healthy elderly (14 Control group and 14 Auditory Processing Disorder group - APD group) participated in the study. All elderly were submitted to (central) auditory processing evaluation, P300 event-related potential and brief cognitive battery (BCB). In the comparison between subjects, the Mann-Whitney test was applied and in the intra-subjects comparison, the Wilcoxon signed rank test was used. To verify if there was an association between the performance of the PAC and the cognitive variables, Spearman's correlation was used. There were no statistically significant differences between the Control and APD groups for the cognitive abilities assessed by BCB, as well as for the P300 cognitive potential variables. Elderly with auditory processing disorders do not seem to show greater cognitive difficulties compared to elderly of the same age group without auditory processing disorders, exception of the clock drawing test, whose task involves multiple cognitive functions, including visuospatial processing, executive function, semantic memory, and planning.


Radiation therapy and early breast cancer: current controversies.
Radiation therapy (RT) is an important component of breast cancer treatment. RT reduces local recurrence and breast cancer mortality after breast conservation for all patients and for node-positive patients after a mastectomy. Short courses of RT over 3-4 weeks are generally as effective as longer courses. A patient subgroup where RT can be avoided after conservative surgery has not been consistently identified. A radiation boost reduces the risk of a recurrence in the breast but may be omitted for older patients with good prognosis tumours with clear margins. Axillary recurrences can take a long time to appear, with 35% occurring after 5 years. Leaving disease untreated in regional nodes is associated with reduced survival. Not all patients require radiation after neoadjuvant chemotherapy and a subsequent mastectomy. Modern RT equipment and techniques will further improve survival rates.


Force Control and Motor Unit Firing Behavior Following Mental Fatigue in Young Female and Male Adults.
Purpose: The neuromuscular mechanisms leading to impaired motor performance in the presence of mental fatigue remain unclear. It is also unknown if mental fatigue differentially impacts motor performance in males and females. The purpose of this study was to assess the impact of mental fatigue on force production and motor unit (MU) firing behavior in males and females. Methods: Nineteen participants performed 10-s isometric dorsiflexion (DF) contractions at 20 and 50% maximum voluntary contraction (MVC) before, during, and after completing 22 min of the psychomotor vigilance task (PVT), to induce mental fatigue. The DF force and indwelling MU firing behavior of the tibialis anterior (TA) was measured before and immediately following the PVT and within the first and final minutes of the PVT. Results: Force steadiness and motor unit firing rate (MUFR) variability did not change during or following the PVT at either contraction intensity (p ≥ 0.16). Overall, females had more variability than males in MUFR during the 20% MVCs (15.98 ± 2.19 vs. 13.64 ± 2.19%, p = 0.03), though no sex differences were identified during the 50% MVCs (p = 0.20). Mean MUFR decreased following mental fatigue in both sexes in the 20% MVC condition (14.79 ± 3.20 vs. 12.92 ± 2.53 Hz, p = 0.02), but only in males during the 50% MVC condition (18.65 ± 5.21 vs. 15.03 ± 2.60 Hz, p = 0.01). Conclusions: These results suggest possible sex and contraction intensity-specific neuromuscular changes in the presence of mental fatigue.


Evaluation of the Effectiveness of Two Automated Room Decontamination Devices Under Real-Life Conditions.
To evaluate the effectiveness of automated room decontamination devices, a common aerosolized hydrogen peroxide (aHP) as well as a recent gaseous ozone-based device, which produces the disinfectant reagent without the need of consumables, were tested under real-life conditions. Twenty-two contaminated surfaces were positioned in different areas in a patient room with adjacent bathroom and anteroom. Following the decontamination process bacteria were recovered and reduction factors were calculated after performing quantitative culture. Following the manufactures instructions, the ozone-based device displayed a bactericidal effect (log10 > 5), whereas the aHP system failed for a high bacterial burden and achieves only a complete elimination of a realistic bioburden (log10 2). After increasing the exposure time to 30 min, the aHP device also reached a bactericidal effect. Nevertheless, our results indicate, that further research and development is necessary, to get knowledge about toxicity, efficacy and safety by using in complex hospital conditions and achieve meaningful integration in cleaning procedures, to reach positive effects on disinfection performance.


Involvement of advillin in somatosensory neuron subtype-specific axon regeneration and neuropathic pain.
Advillin is a sensory neuron-specific actin-binding protein expressed at high levels in all types of somatosensory neurons in early development. However, the precise role of advillin in adulthood is largely unknown. Here we reveal advillin expression restricted to isolectin B4-positive (IB4+) neurons in the adult dorsal root ganglia (DRG). Advillin knockout (KO) specifically impaired axonal regeneration in adult IB4+ DRG neurons. During axon regeneration, advillin was expressed at the very tips of filopodia and modulated growth cone formation by interacting with and regulating focal-adhesion-related proteins. The advillin-containing focal-adhesion protein complex was shed from neurite tips during neurite retraction and was detectable in cerebrospinal fluid in experimental autoimmune encephalomyelitis, oxaliplatin-induced peripheral neuropathy, and chronic constriction injury of the sciatic nerve. In addition, advillin KO disturbed experimental autoimmune encephalomyelitis-induced neural plasticity in the spinal-cord dorsal horn and aggravated neuropathic pain. Our study highlights a role for advillin in growth cone formation, axon regeneration, and neuropathic pain associated with IB4+ DRG neurons in adulthood.


Role of neopterin and 7,8-dihydroneopterin in human immunodeficiency virus infection: marker for disease progression and pathogenic link.
Human immunodeficiency virus (HIV) infection is associated with increased concentrations of neopterin derivatives, released in large quantities by human macrophages on stimulation with interferon-gamma (INF-gamma). Neopterin concentrations thus inversely correlate with absolute CD4+ T-cell numbers and strongly predict progression of disease from latency to AIDS. Investigations of hydrogen peroxide-induced chemiluminescence indicated a potential role of neopterin and 7,8-dihydroneopterin in oxygen free radical-mediated processes. Indeed, 7,8-dihydroneopterin is able to enhance tumor necrosis factor alpha (TNF-alpha)-induced apoptosis, accompanied by an increased production of reactive oxygen intermediates (ROIs). In line with this finding, the same combination appears to contribute to the upregulation of HIV replication due to activation of nuclear factor-kappa B (NF-kappa B), a central enhancer element of the HIV LTR promoter. Thus, besides the role of neopterin as sensitive indicator of disease activity in HIV infection, neopterin derivatives apparently are associated with the cascade of events that regulate the HIV production in infected individuals.


A New Method for Optimizing the Size of Axial FOV in TOF-PEM to Improve Performance of the Scanner.
Positron Emission Mammography (PEM) is a nuclear medicine imaging tool, playing a significant role in the diagnosis of patients with breast cancer. These days, many research has been done in order to improve the performance of this system. This study aims to propose a new method for optimizing the size of axial Field of View (FOV) in PEMs and improving the performance of the systems. In this analytical study, a conventional Inveon PET is simulated using GATE in order to validate the simulation. For this simulation, the mean relative difference is 2.91%, showing the precision and correction of simulation and consequently it is benchmarked. In the next step, for design of the new optimized detector, several validated simulations are performed in order to find the best geometry. The best result is obtained with the axial FOV of 101.7 mm. It has 1.6×1.6×15 mm3 lutetium yttrium orthosilicate (LYSO) crystals. The detector consists of 6 block rings with 30 detector blocks in each ring. In this paper, the performance of the scanner is improved and the geometry is optimized. Sensitivity and scatter fraction of the designed scanner are 4.65% and 21.2%, respectively, also noise equivalent count rate (NECR) is 105.442 kcps. The results showed 1 up to 3% improvement in the sensitivity of this new detector compared with different PEMs.


An association of candidate gene haplotypes and bleeding severity in von Willebrand disease (VWD) type 1 pedigrees.
von Willebrand disease (VWD) type 1 is difficult to diagnose because of bleeding variability and low heritability of von Willebrand factor (VWF) levels. We compared a bleeding severity score and bleeding times to candidate gene haplotypes within pedigrees of 14 index cases, using a covariance components model for multivariate traits (Mendel: QTL Association). These pedigrees included 13 affected and 40 unaffected relatives, as defined by plasma ristocetin cofactor (VWF:RCo) levels. The bleeding severity score was derived from a detailed history. Donors were genotyped using a primer extension method, and 9 candidate genes were selected for analysis. VWF:RCo levels had the strongest influence on bleeding severity score and bleeding time. ITGA2 haplotype 2 (807C) and ITGA2B haplotype 1 (Ile(843)) were each associated with increased bleeding severity scores (P < .01 and P < .01, respectively). GP6 haplotype b (Pro(219)) was also associated with increased scores (P = .03) after adjustment for donor age. No association was observed with 6 other candidate genes, GP1BA, ITGB3, VWF, FGB, IL6, or TXA2R. Increased plasma VWF:Ag levels were associated with VWF haplotype 1 (-1793G; P = .02). These results establish that genetic differences in the adhesion receptor subunits alpha(2), alpha(IIb,) and GPVI can influence the phenotype of VWD type 1.


Side effects of oxysterols: cytotoxicity, oxidation, inflammation, and phospholipidosis.
Oxysterols are 27-carbon atom molecules resulting from autoxidation or enzymatic oxidation of cholesterol. They are present in numerous foodstuffs and have been demonstrated to be present at increased levels in the plasma of patients with cardiovascular diseases and in atherosclerotic lesions. Thus, their role in lipid disorders is widely suspected, and they might also be involved in important degenerative diseases such as Alzheimer's disease, osteoporosis, and age-related macular degeneration. Since atherosclerosis is associated with the presence of apoptotic cells and with oxidative and inflammatory processes, the ability of some oxysterols, especially 7-ketocholesterol and 7beta-hydroxycholesterol, to trigger cell death, activate inflammation, and modulate lipid homeostasis is being extensively studied, especially in vitro. Thus, since there are a number of essential considerations regarding the physiological/pathophysiological functions and activities of the different oxysterols, it is important to determine their biological activities and identify their signaling pathways, when they are used either alone or as mixtures. Oxysterols may have cytotoxic, oxidative, and/or inflammatory effects, or none whatsoever. Moreover, a substantial accumulation of polar lipids in cytoplasmic multilamellar structures has been observed with cytotoxic oxysterols, suggesting that cytotoxic oxysterols are potent inducers of phospholipidosis. This basic knowledge about oxysterols contributes to a better understanding of the associated pathologies and may lead to new treatments and new drugs. Since oxysterols have a number of biological activities, and as oxysterol-induced cell death is assumed to take part in degenerative pathologies, the present review will focus on the cytotoxic activities of these compounds, the corresponding cell death signaling pathways, and associated events (oxidation, inflammation, and phospholipidosis).


Transgenerational consequences of plant responses to herbivory: an adaptive maternal effect?
Herbivory has many effects on plants, ranging from shifts in primary processes such as photosynthesis, growth, and phenology to effects on defense against subsequent herbivores and other species interactions. In this study, I investigated the effects of herbivory on seed and seedling characteristics of several families of wild radish (Raphanus raphanistrum) to test the hypothesis that herbivory may affect the quality of offspring and the resistance of offspring to plant parasites. Transgenerational effects of herbivory may represent adaptive maternal effects or factors that constrain or amplify natural selection on progeny. Caterpillar (Pieris rapae) herbivory to greenhouse-grown plants caused plants in some families to produce smaller seeds and those in other families to produce larger seeds compared with undamaged controls. Seed mass was positively associated with probability of emergence in the field. The number of setose trichomes, a putative plant defense, was higher in the progeny of damaged plants in some families and lower in the progeny of damaged plants in other families. In a field experiment, plant families varied in their resistance to several herbivores and pathogens as well as in growth rate and time to flowering. Seeds from damaged parent plants were more likely to become infested with a plant virus. Although herbivory on maternal plants did not directly affect interactions of offspring with other plant parasites, seed mass influenced plant resistance to several attackers. Thus, herbivory affected seed characters, which mediated interactions between plants and their parasites. Finally, irrespective of seed mass, herbivory on maternal plants influenced components of progeny fitness, which was dependent on plant family. Natural selection may act on plant responses to herbivory that affect seedling-parasite interactions and, ultimately, fitness.


Pathogenesis and management of aspirin-intolerant asthma.
In 2-23% of adults with asthma, and rarely in children with asthma, aspirin (acetylsalicylic acid) and non-steroidal anti-inflammatory drugs (NSAIDs) cause asthma exacerbations. Within 3 hours of ingestion of aspirin/NSAIDs, individuals with aspirin-intolerant asthma (AIA) develop bronchoconstriction, often accompanied by rhinorrhea, conjunctival irritation, and scarlet flush. In severe cases, a single therapeutic dose of aspirin/NSAIDs can provoke violent bronchospasm, loss of consciousness, and respiratory arrest. In order to diagnose AIA, oral, inhaled, nasal or intravenous aspirin challenge tests are performed in facilities where experienced physicians are present and emergency treatment is available. The exact differences in the pathogenesis of AIA and other types of asthma are not fully understood. The interference of aspirin/NSAIDs with arachidonic acid metabolism in the lungs plays an important role in the mechanism of AIA; inhibition of cyclo-oxygenase is accompanied by overproduction of cysteinyl leukotrienes (cys-LTs). It has been proposed that overproduction of cys-LTs, together with removal by aspirin/NSAIDs of the 'brake' imposed by the bronchodilator prostaglandin E2, may cause an asthma attack in patients with AIA. Development of a suitable animal model to investigate the pathogenesis of AIA would help to clarify this question. Although it is still controversial whether leukotriene modifiers are more effective in patients with AIA compared with other types of asthma, because LT plays an important role in the pathogenesis of AIA, leukotriene modifiers are the preferred medication for the long-term control of AIA. Add-on efficacy of leukotriene modifiers has been confirmed in patients with AIA already treated with inhaled corticosteroids. However, this does not mean that aspirin/NSAIDs can be safely taken by aspirin-sensitive patients treated with leukotriene modifiers. To prevent attacks of AIA, sensitive patients should avoid the use of aspirin/NSAIDs or use selective cyclo-oxygenase 2 inhibitors when required. When patients with AIA need aspirin for specific situations they should receive aspirin desensitization therapy or treatment with selective cyclo-oxygenase 2 inhibitors.


Can Epstein-Barr virus infect and transform all the B-lymphocytes of human cord blood?
Quantitative aspects of Epstein-Barr virus infection and transformation of human neonatal B-lymphocytes have been investigated. 72 to 90% B-cells were obtained with enrichment. Of the B-cells, 19 to 97% showed nuclear antigen (EBNA) 2 days after infection. A difference between different B-cell donors in susceptibility to infection was noted. Analysis of the virus dose-response curves obtained with twofold virus dilutions showed that one virus particle is sufficient to induce EBNA in a cell. Of the infected cells, 50 to 95% multiplied in microtitre wells containing a human fibroblast feeder layer, while only a small proportion established growing colonies in soft agarose, that could be picked up and subcultured.


Immunohistochemical localization of beta defensins in the endometrium of rat uterus during the postpartum involution period.
β-Defensins are small cationic molecules that have antimicrobial actions against bacteria, fungi and viruses and contribute to mucosal immune responses at epithelial sites. The female reproductive tract is an important site of defensin production. This study was conducted to determine the possible changes in proportions and localization of β-defensin 1-4 in the rat uterus at the 1st, 3th, 5th, 10th and 15th days of postpartum and at the period of diestrus using immunohistochemical techniques. In the present study, it was determined that β-defensin 1-4 were generally found in all structural components of the endometrium (luminal and glandular epithelium, stromal cells and blood vessels) in both the nucleus and the cytoplasm of cells during the involution period and diestrus. Suprisingly, immunoreaction of β-defensin 2 was also observed in the lateral membrane of the luminal and glandular epithelial cells on the 10th day of involution and immunostaining of β-defensin 4 was also localized in the apical membrane of the luminal and glandular epithelial cells. The current study demonstrated β-defensin 1-4 immunoreactivities in the endothelium of blood vessels were stronger throughout the involution period. Although β-defensins 2 and 3 were localized in both the nuclei and the cytoplasm of endothelial cells, β-defensins 1 and 4 were present in only cytoplasm. These results show that the most component of rat endometrium expresses human β-defensin 1-4 in a involution-dependent manner. Therefore it may be asserted that these molecules constitute a organised protection to prevent uterus from probable infections during the involution process.


[Clinico-experimental approaches to studying the hypocholesteremic action of soy proteins].
The effect of diets containing soybean proteins substituting a significant portion of meat proteins was studied in patients with hyperlipidemia, type IIa, and in experiments on rats. It was found that soybean proteins included into the diet induced blood plasma amino acid imbalance, changed the excretion of some amino acids with urine, and significantly diminished the blood plasma cholesterol level. In the experiments on rats a reduced rate was noted in the low-density lipoprotein apoprotein formation and high-density lipoprotein apoprotein regeneration in the blood plasma. It is suggested that the hypocholesterolemic effect of soybean proteins is caused by decreased apoprotein E synthesis and metabolism due to low levels of blood plasma lysine and arginine.


Characteristics of asthma in an older adult population according to sex and control level: Why are asthma symptoms in older women not well-controlled?
The older adult population in Türkiye has increased by 22.6% in the last 5 years, and the characteristics of such patients with asthma remain uninvestigated. Therefore, we aimed to evaluate the characteristics of older adults with asthma according to sex and asthma control status to provide an in-depth overview of asthma in this population in Türkiye. The data of older adults (age 65 years and over) with asthma were obtained from a multicenter, cross-sectional asthma database registry (Turkish Adult Asthma Registry, TAAR) funded by the Turkish Thoracic Society. Comparisons were made based on sex and asthma control levels using the GINA Asthma Symptom Control Questionnaire. Of the 2053 (11.5%) patients registered with the TAAR, 227 were older adults (median age, 69 (8), women, 75.8% [n = 172]). Of these, 46.5% (n = 101) had obesity to some degree. Compared with men, women had lower education, income levels, and employment rates. Additionally, women exhibited a higher prevalence of obesity, hypertension, and thyroid gland disease than men. Being female (OR: 2.99; 95% CI: 1.307-6.880), the presence of gastroesophageal reflux disease (OR: 2.855; 95% CI: 1.330-6.130), and a predicted forced expiratory volume in the first-second value lower than 80% (OR: 2.938; 95% CI: 1.451-5.948) were associated with poorly controlled asthma. Herein, older adults comprised 11.5% of adult patients with asthma. Being female poses a disadvantage in terms of both asthma prevalence and control in the older adult asthmatic population owing to the prevalence of comorbidities and socioeconomic sex-related distinguishing factors.


Decreased neutrophil antioxidative enzyme activities and increased lipid peroxidation in hyperlipoproteinemic human subjects.
Neutrophils have the capacity to produce free radicals. Free radicals are associated with hyperlipoproteinemia and atherosclerotic processes. For this reason, neutrophil superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GR), catalase (Cat) activities and thiobarbituric acid reactive substances (TBARS), as an index of lipid peroxidation, have been studied in hyperlipoproteinemic (HLP) and age-matched normolipidemic groups. Lipid parameters including triglycerides, total cholesterol, plasma TBARS, HDL-cholesterol, LDL-cholesterol, apo A-I, apo B have also been determined. Forty subjects (females 18, males 22) with HLP (mean age 43.8+/-8.7 (S.D.)) and 40 normolipoproteinemic subjects (females 17, males 23; mean age 46.4+/-11) were included in the study. Neutrophils were isolated by Percoll gradient centrifugation from venous blood samples. Methods used were as follows: INT method for SOD, UV method at 340 nm based on oxidation of NADPH for GSH-Px and GR, UV method at 240 nm based on degradation of hydrogen peroxide for catalase, and a method based on reaction with thiobarbituric acid for TBARS. Neutrophil SOD, GSH-Px, and catalase activities were found to be significantly low in the hyperlipoproteinemic group compared with the normolipoproteinemic group. GR activity did not differ between both groups. The mean TBARS level in the neutrophil fraction was found to be significantly higher in hyperlipoproteinemics than in that of the normolipoproteinemics. It was concluded that decreased neutrophil antioxidant enzyme activities in hyperlipoproteinemics may lead to insufficient detoxification of free radicals produced in these cells and contribute to increased lipid peroxidation.


Evaluation of dyes decolourisation by the crude enzyme from Pleurotus sajor-caju grown on sorghum seed media.
The extracellular enzymes from Pleurotus sajor-caju were studied for lignin degrading enzyme patterns and dye decolourisation potential. Laccases are major ligninolytic enzymes excreted by the fungus. The results from a native-PAGE revealed that there were at least two isoenzymes. The crude enzyme had a pH and a temperature optimum at 6.0 and 40 degrees C, respectively when 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) was used as substrate. The pH and thermal stability were at 5.0 and 30 degrees C. The pH optima for decolourisation of Indigo Carmine and Methyl Red were at 5.0 and 6.0, respectively. Indigo Carmine could be decolorized efficiently above 90% within 180 min, whereas Methyl Red could be decolorized only 3.5%. High efficiency decolourisation of Indigo Carmine makes this fungus to be a promise choice in biological treatment of waste water containing Indigo Carmine.


Immunoaffinity column cleanup with liquid chromatography using post-column bromination for determination of aflatoxins in peanut butter, pistachio paste, fig paste, and paprika powder: collaborative study.
A collaborative study was conducted to evaluate the effectiveness of an immunoaffinity column cleanup liquid chromatography (LC) method for the determination of aflatoxin B1 and total aflatoxins at European regulatory limits. The test portion is extracted with methanol-water (8 + 2) for dried figs and paprika, and with methanol-water (8 + 2) plus hexane (or cyclohexane) for peanut butter and pistachios. The sample extract is filtered, diluted with phosphate buffer saline, and applied to an immunoaffinity column. The column is washed with water and the aflatoxins are eluted with methanol. Aflatoxins are quantitated by reversed-phase LC with post-column derivatization (PCD) involving bromination. PCD is achieved with either an electrochemical cell (Kobra cell) and addition of bromide to the mobile phase or pyridinium hydrobromide perbromide. Determination is by fluorescence. Peanut butter, pistachio paste, dried fig paste, and paprika powder samples, both naturally contaminated with aflatoxins and containing added aflatoxins, were sent to 16 collaborators in 16 European countries. Test portions of samples were spiked at levels of 2.4 and 9.6 ng/g for total aflatoxins which included 1.0 and 4.0 ng/g aflatoxin B1, respectively. Recoveries for total aflatoxins ranged from 71 to 92% with corresponding recoveries for aflatoxin B1 of 82 to 109%. Based on results for spiked samples (blind duplicates at 2 levels) as well as naturally contaminated samples (blind duplicates at 4 levels, including blank), the relative standard deviation for repeatability ranged from 4.6 to 23.3% for total aflatoxins and from 3.1 to 20.0% for aflatoxin B1. The relative standard deviation for reproducibility ranged from 14.1 to 34.2% for total aflatoxins, and from 9.1 to 32.2% for aflatoxin B1. The method showed acceptable within-laboratory and between-laboratory precision for all 4 matrixes, as evidenced by HORRAT values <1, at the low levels of determination for both total aflatoxins and aflatoxin B1.


Role of Epithelial-Endothelial Cell Interaction in the Pathogenesis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.
The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health globally. Patients with severe COVID-19 disease progress to acute respiratory distress syndrome, with respiratory and multiple organ failure. It is believed that dysregulated production of proinflammatory cytokines and endothelial dysfunction contribute to the pathogenesis of severe diseases. However, the mechanisms of SARS-CoV-2 pathogenesis and the role of endothelial cells are poorly understood. Well-differentiated human airway epithelial cells were used to explore cytokine and chemokine production after SARS-CoV-2 infection. We measured the susceptibility to infection, immune response, and expression of adhesion molecules in human pulmonary microvascular endothelial cells (HPMVECs) exposed to conditioned medium from infected epithelial cells. The effect of imatinib on HPMVECs exposed to conditioned medium was evaluated. We demonstrated the production of interleukin-6, interferon gamma-induced protein-10, and monocyte chemoattractant protein-1 from the infected human airway cells after infection with SARS-CoV-2. Although HPMVECs did not support productive replication of SARS-CoV-2, treatment of HPMVECs with conditioned medium collected from infected airway cells induced an upregulation of proinflammatory cytokines, chemokines, and vascular adhesion molecules. Imatinib inhibited the upregulation of these cytokines, chemokines, and adhesion molecules in HPMVECs treated with conditioned medium. We evaluated the role of endothelial cells in the development of clinical disease caused by SARS-CoV-2 and the importance of endothelial cell-epithelial cell interaction in the pathogenesis of human COVID-19 diseases.


An inhibitory monoclonal antibody to rabbit brain acetylcholinesterase. Studies on interaction with the enzyme.
A recently isolated monoclonal antibody was found to be a potent and powerful inhibitor of the catalytic activity of rabbit brain acetylcholinesterase (AChE; acetylcholine acetylhydrolase, EC 220.127.116.11), with an IC50 of about 1 nM and a maximal inhibition of at least 90%. The antibody increased the optimal concentration of acetylthiocholine as much as 50-fold, but analysis of the substrate kinetics did not indicate a simple competitive interaction. The antibody markedly reduced the labeling of purified rabbit brain AChE by tritiated diisopropyl fluorophosphate (DFP) and also impeded the binding of propidium iodide, a fluorescent probe thought to be directed toward the peripheral anionic site. The antibody's affinity for enzyme with active sites that were phosphorylated with DFP or occupied by reversible ligands was measurably less than for native enzyme. It is possible that the mechanism of inhibition involves antibody-induced conformational changes that are unfavorable for catalysis.


Bacterial proteomics and vaccine development.
Until recently, the development of vaccines for use in humans relied on the response to attenuated or whole-cell preparations, or empirically selected antigens. The post-genomic era holds the possibility of rational design of novel vaccines for important human pathogens. The discovery and development of these new vaccines is likely to be accomplished through integrated proteomic strategies. Although most proteomic studies are based on two-dimensional gel electrophoresis (2D-PAGE) as a separation technique, new methods have been developed within the past two years that provide complementary information concerning microbial protein expression. The 2D-PAGE technique in combination with Western blotting has been successfully applied in the discovery of antigens from Helicobacter pylori, Chlamydia trachomatis and Borrelia garinii. Two-dimensional semi-preparative electrophoresis has provided complementary information regarding membrane protein expression in a strain of H. pylori. Through two-dimensional liquid chromatography-tandem mass spectrometry, the most comprehensive information to date regarding protein expression in yeast was obtained. This technique may shortly become an important tool in vaccinology. This review of the current state of bacterial proteomics as applied in vaccinology presents analytical techniques for protein separation, proteomics without gels, reverse vaccinology, and functional approaches to the identification of virulence proteins in microbes.


5-aminolevulinic acid-photodynamic therapy for a refractory severe kerion: A case report.
Kerion is a subtype of tinea capitis with a severe inflammatory response, requiring early diagnosis to prevent secondary bacterial infection, folliculitis and permanent alopecia. Oral antifungal drugs are considered the first-line treatment for tinea capitis; however, drugs therapy is challenged by the long treatment duration, side effects, and drug resistance. Photodynamic therapy (PDT) has been widely used to treat dermatomycosis and has shown significant efficacy in recent years. We report the case of a girl who presented with refractory severe kerion following unregulated treatment and insensitivity to itraconazole; however,she was cured with 5-aminolevulinic acid-PDT. The case showed that PDT is a potentially promising alternative treatment for cutaneous fungal infections.


Underdiagnosis of alcoholism by residents in an ambulatory medical practice.
Alcoholism is a widespread illness which in its early stages can be treated effectively. It is important, therefore, that medical residents be able to diagnose alcoholism prior to end-stage disease and organ damage. To assess the ability of residents to diagnose alcoholism, a survey was conducted of 95 patients from the ambulatory care internal medicine practice of the Johns Hopkins Hospital. The patients' alcohol consumption was measured by a self-report questionnaire, and the patients answered an alcoholism questionnaire, the responses to which have been shown to correlate with alcoholism. The questionnaire contains four questions, one each on cutting down on alcohol consumption, annoyance at criticism of alcohol consumption, guilty feelings about alcohol consumption, and use of alcohol early in the day. The answers to the questionnaire were compared with the residents' diagnoses of alcoholism on the medical record. Alcoholism was diagnosed by the residents in only 11 of the 20 patients (55 percent) who had given three or more yes answers on the alcoholism questionnaire and in only 14 of the 31 patients (45 percent) who had given two or more yes answers. (Yes answers indicate that patients suffer from alcoholism.) The residents' diagnosis of alcoholism correlated with signs of physical damage or dependence. These results demonstrate a moderate underdiagnosis of alcoholism by residents in the ambulatory care setting and suggest that diagnosing alcoholism in early stages of the disease should be made a part of the training curriculum.


Timing and necessity of a flexible sigmoidoscopy in patients with symptoms suggestive of haemorrhoids.
This study was performed to determine the probability of finding additional pathology, requiring treatment or follow-up, in patients referred with symptoms suggestive of haemorrhoids. Secondly, to determine, at what age a flexible sigmoidoscopy should be performed in these patients. All patients referred for the treatment of haemorrhoids over a period of 5 years were prospectively included in a database. Data included patient characteristics, clinical information, histopathological analysis and the sigmoidoscopy results. Haemorrhoids were present in 961 (95.6%) of 1005 patients. Of these patients, 692 (72.0%) patients were free from any additional pathology, 161 (16%) patients had diverticulosis, in 15 (1.5%) patients the sigmoidoscopy showed signs of colitis, 116 (11.5%) patients had polyps and a malignancy was present in eight (0.8%) patients. In the age group between 30-40 and 40-50, the presence of additional pathology increased significantly (P < 0.05). No malignancies were found under the age of 40. The vast majority of patients referred for the treatment and analysis of haemorrhoids were free from any additional pathology. But, over the age of 40, the incidence of additional pathology increased significantly. Therefore, we suggest that a flexible sigmoidoscopy should be performed in all patients over the age of 40, with clinical signs of haemorrhoids.


Design and fabrication of PZN-7%PT single crystal high frequency angled needle ultrasound transducers.
A high-frequency angled needle ultrasound transducer with an aperture size of 0.4 x 0.56 mm2 was fabricated using a lead zinc niobate-lead titanate (PZN- 7%PT) single crystal as the active piezoelectric material. The single crystal was bonded to a conductive silver particle matching layer and a conductive epoxy backing material through direct contact curing. A parylene outer matching layer was formed by vapor deposition. Angled needle probe configuration was achieved by dicing at 45 degrees to the single crystal poling direction to satisfy a clinical request for blood flow measurement in the posterior portion of the eye. The electrical impedance magnitude and phase of the transducer were 42 Omega and -63 degrees , respectively. The measured center frequency and the fractional bandwidth at -6 dB were 43 MHz and 45%, respectively. The two-way insertion loss was approximately 17 dB. Wire phantom imaging using fabricated PZN-7%PT single crystal transducers was obtained and spatial resolutions were assessed.


Importance of protein flexibility in ranking inhibitor affinities: modeling the binding mechanisms of piperidine carboxamides as Type I1/2 ALK inhibitors.
Anaplastic lymphoma kinase (ALK) has gained increased attention as an attractive therapeutic target for the treatment of various cancers, especially non-small-cell lung cancer (NSCLC). Recently, piperidine carboxamides were reported as Type I1/2 inhibitors of ALK, which occupy both the ATP binding site and the back ATP hydrophobic cavity in DFG-in conformation. Due to the dynamic behavior of ALK in the binding of Type I1/2 inhibitors, the accurate predictions of the binding structures and relative binding potencies of these inhibitors are quite challenging. In this study, different modeling techniques, including molecular docking, ensemble docking based on multiple receptor conformations, molecular dynamics simulations and free energy calculations, were utilized to explore the binding mechanisms of piperidine carboxamides. Our predictions show that the conventional docking protocols are not sufficient to predict the relative binding potencies of the studied inhibitors with high accuracy, but incorporating protein flexibility before or after docking is quite effective to improve the prediction accuracy. Notably, the binding free energies predicted by MM/GBSA or MM/PBSA based on the MD simulations for the docked poses give the highest correlation with the experimental data, highlighting the importance of the inclusion of receptor flexibility for the accurate predictions of the binding potencies for Type I1/2 inhibitors of ALK. Furthermore, the comprehensive analysis of several pairs of representative inhibitors demonstrates the importance of hydrophobic interactions in improving the binding affinities of the inhibitors with the hot-spot residues surrounding the binding pocket. This work is expected to provide valuable clues for further rational design of novel and potent Type I1/2 ALK inhibitors.


Unemployment and serious suicide attempts.
This study used a case-control design to examine the association between unemployment and risk of medically serious suicide attempt. A sample of 302 individuals who made serious suicide attempts was contrasted with 1028 randomly selected community control subjects. Individuals who made serious suicide attempts reported higher rates of current unemployment (OR = 4.2) than control subjects. This association was similar for males and females. However, even before adjustment for confounding factors it was evident that exposure to unemployment made only a small contribution to suicide attempt risk. The population attributable risk for exposure to unemployment was 7.3%. After adjustment for antecedent childhood, family and educational factors the association between unemployment and risk of serious suicide attempt was reduced but remained significant (OR = 2.1), suggesting that common antecedent factors made a large contribution to risks of both unemployment and serious suicide attempt. When both antecedent family and childhood factors, and psychiatric morbidity were taken into account, unemployment was not significantly related to risks of serious suicide attempt. The results of this study provide support for the contention that much of the association between unemployment and suicidal behaviour is non-causal, and reflects common or correlated factors that contribute to risks of both unemployment and suicidal behaviour. Any remaining association between unemployment and suicide attempt risk appears to arise from the correlation that exists between unemployment and psychiatric disorder.


Effect of postoperative anemia and baseline cardiac risk on serious adverse outcomes after major vascular interventions.
Published data suggest that permissive anemia strategies that allow nadir hemoglobin (nHb) values of 7 g/dL or lower are safe in a variety of clinical settings. The appropriateness of these strategies in patients at high risk for adverse postoperative cardiac events remains unclear. We sought to determine the combined effect of postoperative nHb and cardiac risk status on major complications after vascular surgical interventions. This was a single-institution retrospective analysis of consecutive patients who underwent elective open procedures for occlusive vascular disease and aneurysm repair, either open or endovascular. The Revised Cardiac Risk Index (RCRI) was used to assess baseline cardiac risk. Primary outcome was a composite end point of mortality or major ischemic events (myocardial infarction, stroke, acute kidney injury, or coronary revascularization) within 90 days from the index operation. Secondary outcomes included intensive care unit (ICU) length of stay (LOS) and 90-day respiratory complications (pneumonia, ventilator dependence for >48 hours postoperatively, or reintubation). Hierarchical multivariable regression was used to model each outcome with adjustment for age, type of operation, baseline comorbidities, and intraoperative covariates. We analyzed 2508 operations performed during 8 years in 2106 patients with a mean age of 67 years (range, 45-90 years). In the fully adjusted multivariable model, lower values of nHb increased the risk of the primary composite end point (odds ratio [OR], 1.24; P < .001, representing a 24% increase in the odds of the composite end point for each 1-g/dL increase in nHb). In the same model, RCRI class II (OR, 1.8; P < .001), class III (OR, 2.06; P < .0001), and class IV (OR, 2.35; P < .0001) were associated with progressively increasing odds of the composite end point compared with RCRI class I. An interaction term between transfusion and nHb was not significant statistically, indicating that the harmful effect of anemia was independent of blood transfusion. Lower values of nHb also increased the risk of respiratory complications (OR, 1.41; P = .002) and ICU LOS (average 2.6-day increase per 1-g/dL increase of nHb; P < .0001). Postoperative anemia increases the rate of early postoperative mortality and major ischemic events, particularly in patients at higher baseline cardiac risk. It also adversely affects respiratory complications and ICU LOS. Until a randomized trial definitively settles the issue, restrictive transfusion strategies should be practiced with caution in patients undergoing major vascular interventions.


Construction of recombinant plasmid carrying the lambda DNA fragment responsible for prophage integration.
The recombinant DNA molecules were constructed from plasmid RSF2124 and the EcoRI fragment of lambda DNA containing the genes responsible for prophage integration. The presence of these genes in recombinant plasmids was detected genetically. lambda int-gene was shown to be expressed in either orientation of insertion in the plasmid. We found that recombinant plasmid was able to integrate into chromosome of lambda lysogens. The integration of plasmid into host chromosome was demonstrated by contransduction of chromosome and plasmid markers using generalized transducer P1 and by specialized transduction with lambda phages.


Outcomes following acute poor-grade aneurysmal subarachnoid bleed - Is early definitive treatment better than delayed management?
Patients with poor-grade subarachnoid bleed (World Federation of Neurosurgical Societies grades 4-5) often improve their neurocognitive function months after their ictus. However, it is essential to explore the timing of intervention and its impact on long-term outcome. We compared the long-term outcomes between immediate management within 24 h and delayed management after 24 h in patients following poor-grade subarachnoid bleed. This was a retrospective population-based study, including patients with poor-grade subarachnoid bleed who received definitive management between 1 January 2011 and 31 December 2016 in a large tertiary neurocritical care unit. The primary outcome was adjusted odds ratio of favourable outcome (Glasgow Outcome Scale 4-5) for survivors at 12 months following discharge, as measured by the Glasgow Outcome Scale. The secondary outcomes included adjusted odds ratio of a favourable outcome at discharge, 3 months and 6 months following discharge and survival rate at 28 days, 3 months, 6 months and 12 months following haemorrhage. A total of 111 patients were included in this study: 53 (48%) received immediate management and 58 (52%) received delayed management. The mean time delay from referral to intervention was 14.9 ± 5.8 h in immediate management patients, compared to 79.6 ± 106.1 h in delayed management patients. At 12 months following discharge, the adjusted odds ratio for favourable outcome in immediate management versus delayed management patients was 0.96 (confidence interval (CI) = 0.17, 5.39; p = 0.961). At hospital discharge, 3 months and 6 months, the adjusted odds ratio for favourable outcome was 3.85 (CI = 1.38, 10.73; p = 0.010), 1.04 (CI = 0.22, 5.00; p = 0.956) and 0.98 (CI = 0.21, 4.58; p = 0.982), respectively. There were no differences in survival rate between the groups at 28 days, 3 months, 6 months and 12 months (71.7% in immediate management group vs. 82.8% in delayed management group at 12 months, p = 0.163). Immediate management and delayed management after poor-grade subarachnoid bleed are associated with similar morbidity and mortality at 12 months. Therefore, delaying intervention in poor-grade patients may be a reasonable approach, especially if time is needed to plan the procedure or stabilise the patient adequately.


[Site-specific drug delivery systems. III. Nasal drug delivery].
The nasal cavity has a large surface and a rich blood supplied mucosa. Drugs absorbed by blood vessels pass directly into the systemic circulation, thereby avoiding first-pass metabolism. Numbers of factors limit the intranasal absorption of drugs, especially peptide and protein drugs. These factors are the epithelial and mucus barrier, the rapid mucociliar clearance and the enzymatic activity. Increasing the residence time of the drug formulation in the nasal cavity and a period of contact with nasal mucosa, may improve drug absorption. Approaches to increase the residence time of drug formulations in the nasal cavity usually involve the use of microspheres, liposomes and bioadhesive gels.


Novel transporter screening technology for chemical production by microbial fermentation.
In the fermentative production of compounds by using microorganisms, control of the transporter activity responsible for substrate uptake and product efflux, in addition to intracellular metabolic modification, is important from a productivity perspective. However, there has been little progress in analyses of the functions of microbial membrane transporters, and because of the difficulty in finding transporters that transport target compounds, only a few transporters have been put to practical use. Here, we constructed a Corynebacterium glutamicum-derived transporter expression library (CgTP-Express library) with the fusion partner gene mstX and used a peptide-feeding method with the dipeptide L-Ala-L-Ala to search for alanine exporters in the library. Among 39 genes in the library, five candidate alanine exporters (NCgl2533, NCgl2683, NCgl0986, NCgl0453, and NCgl0929) were found; expression of NCgl2533 increased the alanine concentration in cell culture. The CgTP-Express library was thus effective for finding a new transporter candidate.


Rapid Release of Halocarbons from Saline Water by Iron-Based Photochemistry.
Methyl halides play important roles in stratospheric ozone depletion, but their formation mechanisms are not well defined. This study demonstrated that iron-based photochemistry significantly enhanced alkyl halide production by promoting the reaction of the representative monomer of lignin with halide ions in saline water under solar light irradiation. The methyl chloride (CH3Cl) emission from the light/Fe(III) process was 2 orders of magnitude higher than dark treatment and in the absence of iron. In addition, bromide and iodide showed better reactivity in the formation of the corresponding methyl bromide (CH3Br) and methyl iodide (CH3I). Alkyl halides identified from seawater, brackish water, and salt pan water under sunlight irradiation were positively correlated with the Fe(III) concentrations, indicating that iron-based photochemistry is ubiquitous. This work suggested that the photoinduced formation of methyl radical and redox cycling of iron triggered by the Fenton-like reaction are responsible for the enhanced release of alkyl halides. This study represents an abiotic formation pathway of alkyl halides, which accounts for a portion of the unidentified sources of halocarbons in the ocean.


[Interaction, synergy and antagonism in prospective epidemiological studies].
In public health there is a growing appreciation for the advantage of the additive scale to better understand the impacts of factors involved in a health event. It is necessary to always remember that the concept of statistical interaction is scale dependent. In the causal relationship between a response and the presence of two or more factors, the concepts interaction, synergy and antagonism are the key ideas. The aim of this note is to show an application of the concepts interaction, synergy and antagonism in prospective studies from a public health perspective. We present three scenarios that illustrate analyses of interaction, independence, synergy and antagonism. Stata 12 software was used for fitting models (log-binomial model and Poisson) and estimating parameters. Appendixes are provided with concepts and Stata commands used in the processes of simulation and parameter estimation.


New aspects on the pathophysiology of wound infection and wound healing--the problem of lowered oxygen pressure in the tissue.
There is a correlation between tissue oxygen tension, incidence of infection and disturbance of wound healing. Scientific investigations in recent years have documented that infection and tissue repair are processes consuming oxygen. Animal experiments have shown that oxygenation of the tissue is essential for the elimination of pathogens, the stimulation of phagocytosis as well as for the degradation of dead tissue structures and the synthesis of new tissue structures. Hypoxia and hypovolemia are of crucial significance for the impairment of organ functions. An effective therapy for disorders of oxygenation has not been feasible so far, except for clinical anesthesiological efforts to increase the oxygen saturation of hemoglobin and hyperbaric oxygen therapy. However, it has recently been possible to synthesize an oxygen carrier which supports respiratory oxygen physiologically. With tetrachlorodecaoxide (TCDO), a causal therapeutic concept for the topical treatment of infected hypoxic wounds with chronic disturbance of wound healing has been introduced for the first time.


Commentary: collaborative systematic review may produce and share high-quality, comparative evidence more efficiently.
Systematic reviews are necessary to synthesize available evidence and inform clinical practice and health policy decisions. There has been an explosion of evidence available in many fields; this makes it challenging to keep evidence syntheses up to date and useful. Comparative effectiveness systematic reviews are informative; however, producing these often-large reviews bring intense time and resource demands. This commentary describes the implementation of a systematic review using a collaborative model of evidence synthesis. We are implementing the collaborative review model to update a large Cochrane review investigating the efficacy and comparative effectiveness of the design, delivery, and type of exercise treatment for people with chronic low-back pain. Three key benefits of the collaborative review model for evidence synthesis are (1) team coordination and collaboration, (2) quality control measures, and (3) advanced comparative and other analyses. This new collaborative review model is developed and implemented to produce and share high-quality, comparative evidence more efficiently while building capacity and community within a research field.


Uncovering the Neglected Similarities of Arynes and Donor-Acceptor Cyclopropanes.
Arynes and donor-acceptor (D-A) cyclopropanes are two classes of strained systems having the potential for numerous applications in organic synthesis. The last two decades have witnessed a renaissance of interest in the chemistry of these species primarily because of the mild and robust methods for their generation or activation. Commonly, arynes as easily polarizable systems result in 1,2-disubstitution, whereas D-A cyclopropanes as polarized systems lead to 1,3-bisfunctionalization thereby showing striking similarities. Transformations with 1,2- and 1,3-dipoles afford cyclic structures. With arynes, emerging four-membered rings as intermediates might react further, whereas the analogous five-membered rings obtained from D-A cyclopropanes are most often the final products. However, there are a few cases where these intermediates behave surprisingly differently. This Minireview highlights the parallels in reactivity between arynes and D-A cyclopropanes thereby shedding light on the neglected similarities of these two reactive species.


[Therapeutic management in 154 acromegalic patients].
Acromegaly is a chronic, invalidating disease due in over 95% of cases to a growth hormone (GH) secreting pituitary adenoma. Its clinical manifestations are associated to local complications related to the tumor growth and/or to the metabolic consequences of GH excess. We report here our experience on 154 acromegalic patients. Surgical remission rate using stringent biochemical criteria was 32%, a figure relatively low due to the great number of patients bearing macroadenomas with invasive complications. Primary or adjuvant radiotherapy was able to obtain normalization of biochemical parameters in as much as 65.4% of treated patients. In only 14.0% of acromegalics drug therapy with dopaminergic agents was effective in controlling the disease. By contrast, somatostatinergic analogues were more effective, obtaining a clinical and biochemical remission in 45.7% of the patients. In summary, multimodal therapy of acromegaly can lead to a global safe control of the disease in 55.2% of the cases. The ongoing development of new drugs represents promising alternatives in the management of this disabling condition.


Excess child mortality after discharge from hospital in Kilifi, Kenya: a retrospective cohort analysis.
To explore excess paediatric mortality after discharge from Kilifi District Hospital, Kenya, and its duration and risk factors. Hospital and demographic data were used to describe post-discharge mortality and survival probability in children aged < 15 years, by age group and clinical syndrome. Cox regression models were developed to identify risk factors. In 2004-2008, approximately 111,000 children were followed for 555,000 person-years. We analysed 14,971 discharges and 535 deaths occurring within 365 days of discharge. Mortality was higher in the post-discharge cohort than in the community cohort (age-adjusted rate ratio, RR: 7.7; 95% confidence interval, CI: 6.6-8.9) and declined little over time. An increased post-discharge mortality hazard was found in children aged < 5 years with the following: weight-for-age Z score < -4 (hazard ratio, HR: 6.5); weight-for-age Z score > -4 but < -3 (HR: 3.4); hypoxia (HR: 2.3); bacteraemia (HR: 1.8); hepatomegaly (HR: 2.3); jaundice (HR: 1.8); hospital stay > 13 days (HR: 1.8). Older age was protective (reference < 1 month): 6-23 months, HR: 0.8; 2-4 years, HR: 0.6. Children with at least one risk factor accounted for 545 (33%) of the 1655 annual discharges and for 39 (47%) of the 83 discharge-associated deaths. Hospital admission selects vulnerable children with a sustained increased risk of dying. The risk factors identified provide an empiric basis for effective outpatient follow-up.


A novel approach to evaluating the iron and folate status of women of reproductive age in Uzbekistan after 3 years of flour fortification with micronutrients.
The Uzbekistan 1996 Demographic Health Survey reported 60.4% of women of reproductive age (WRA) had low hemoglobin concentrations (<120 g/L), and anemia was an important public health problem. Fortification of wheat flour was identified as an appropriate intervention to address anemia due to the ubiquitous consumption of wheat flour. A National Flour Fortification Program (NFFP) was implemented in 2005. After 3-years of the NFFP, a national survey using large country-lot quality assurance sampling was carried out to assess iron, folate, hemoglobin and inflammation status of WRA; the coverage and knowledge of the fortified first grade UzDonMakhsulot (UDM) flour/grey loaf program; and consumption habits of women to investigate the dietary factors associated with anemia. Estimated anemia prevalence was 34.4% (95% CI: 32.0, 36.7), iron depletion 47.5% (95% CI: 45.1, 49.9) and folate deficiency 28.8% (95% CI: 26.8, 30.8); the effect of inflammation was minimal (4% with CRP >5 mg/L). Severe anemia was more prevalent among folate deficient than iron depleted WRA. Presence of UDM first grade flour or the grey loaf was reported in 71.3% of households. Among WRA, 32.1% were aware of UDM fortification; only 3.7% mentioned the benefits of fortification and 12.5% understood causes of anemia. Consumption of heme iron-containing food (91%) and iron absorption enhancers (97%) was high, as was the consumption of iron absorption inhibitors (95%). The NFFP coincided with a substantial decline in the prevalence of anemia. Folate deficiency was a stronger predictor of severe anemia than iron depletion. However, the prevalence of iron depletion was high, suggesting that women are not eating enough iron or iron absorption is inhibited. Fortified products were prevalent throughout Uzbekistan, though UDM flour must be adequately fortified and monitored in the future. Knowledge of fortification and anemia was low, suggesting consumer education should be prioritized.


Health information exchange in Finland: Usage of different access types and predictors of paper use.
Timely, complete and accurate patient data is needed in care decisions along the continuum of care. To access patient data from other organizations, there are three types of regional health information exchange systems (RHIS) in use In Finland. Some regions use multiple RHISs while others do not have a RHIS available. The recently introduced National Patient Data Repository (Kanta) is increasingly used for health information exchange (HIE). The purpose of this study was to assess usage of paper, RHISs and Kanta by context in 2017; evolution of paper use over the years; and predictors of paper use in 2017 among Finnish physicians for HIE system development. Data from national electronic health record (EHR) usage and user experience surveys were taken from 2010 (prior to ePrescription system implementation), 2014 (prior to implementation of Kanta) and 2017 (Kanta was in full use in the public sector and in large private organizations). The web-based surveys were targeted to all physicians engaged in clinical work in Finland. Kanta was the most frequently used means of HIE in 2017. Paper use had reduced significantly from 2010 to 2014. The trend continued in 2017. Still, up to half of the physicians reported using paper daily or weekly in 2017. There were great variations in paper use by healthcare sector, available RHIS type and EHR system used. In multivariable analysis (with all other variables constant), predictors of more frequent use of paper than electronic means for HIE were: private sector or hospital, access to Master Patient Index RHIS (type 1), multiple RHIS (type 4) or no RHIS (type 5), two particular EHR systems, older age, less experience, operative, psychiatric or diagnostic specialties, and male gender. Usability of HIE systems including EHRs as access points to HIE need to be improved to facilitate usage of electronic HIE. Usage ensures more timely and complete patient data for safe, coordinated care. Specialty-specific needs and requirements call for more user participation in HIE design. Especially older professionals need training to better exploit HIS for HIE.


Physical activity levels during pregnancy and gestational weight gain among women who are overweight or obese.
There is contradictory research assessing physical activity patterns during pregnancy and postpartum among women who are overweight or obese. The aim of this study was to evaluate physical activity among overweight and obese women over the course of pregnancy and the initial postpartum period. Three hundred and five overweight or obese pregnant women completed physical-activity questionnaires at three time points during pregnancy and at 4-months postpartum. Physical activity declined between early pregnancy and 28-weeks gestation (P<0.001) and declined further at 36-weeks gestation (P<0.001) before increasing significantly at 4-months postpartum (P<0.001). However, reported activity at 4-months postpartum remained significantly lower than that reported in early pregnancy (P<0.001). There was no significant difference either cross-sectionally or for changes over pregnancy and postpartum for total levels or categories of physical activity for women with different body mass index (BMI) or gestational weight gain (GWG). BMI was the only independent predictor of the change in total physical activity over the study and GWG, with women with higher BMI having larger decline of physical activity (β=0.114, s.e.=0.750, P=0.032) and less GWG (β=-0.253, s.e.=0.063, P<0.001). Physical activity declined significantly between early pregnancy and 28-weeks gestation, with a further decline to 36-weeks gestation. At 4-months postpartum, physical activity significantly increased but not to the level of that reported at early pregnancy. SO WHAT?: The promotion of appropriate physical activity should be implemented early in pregnancy and postpartum to prevent the decline in activity we have observed in overweight and obese women. Future research should also explore the barriers and enablers to women engaging in exercise during pregnancy and the postpartum period.


Autism and the cognitive processing triad: a case for revising the criteria in the diagnostic and statistical manual.
The next iteration of the Diagnostic and Statistical Manual of Mental Disorders is due for release in May 2013. The current diagnostic criteria for autism are based on a behavioral triad of impairment, which has been helpful for diagnosis and identifying the need for intervention, but is not useful with regard to developing interventions. Revised diagnostic criteria are needed to better inform research and therapeutic intervention. This article examines the research underpinning the behavioral triad of impairment to consider alternative explanations and a more useful framing for diagnosis and intervention. Contemporary research and literature on autism were used in this study. It is proposed that the cognitive processing triad of impaired abstraction, impaired theory of mind, and impaired linguistic processing become the triad of impairment for autism in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. These are investigable at the diagnostic level and can usefully inform intervention. Further, in addressing the debate on whether restrictive and repetitive behavior should remain central to diagnosis or be replaced by a deficit in imagination, the authors argue that both behavioral manifestations are underpinned by impaired abstraction.


Functional specialization in rhesus monkey auditory cortex.
Neurons in the lateral belt areas of rhesus monkey auditory cortex prefer complex sounds to pure tones, but functional specializations of these multiple maps in the superior temporal region have not been determined. We tested the specificity of neurons in the lateral belt with species-specific communication calls presented at different azimuth positions. We found that neurons in the anterior belt are more selective for the type of call, whereas neurons in the caudal belt consistently show the greatest spatial selectivity. These results suggest that cortical processing of auditory spatial and pattern information is performed in specialized streams rather than one homogeneously distributed system.


Current mapping of lead phthalocyanine thin films in the presence of gaseous dopants.
The structural organization and its effect on conducting pathways in lead phthalocyanine (PbPc) thin films, a nonplanar phthalocyanine, deposited on Si and highly oriented pyrolytic graphite (HOPG) substrates in the presence of iodine and ammonia vapors are presented. Two-dimensional grazing incidence X-ray diffraction studies reveal that the crystalline ordering in pristine PbPc films on Si and HOPG substrates undergoes a drastic molecular rearrangement and surface reconstruction upon iodine doping. The structural rearrangement leads to morphological changes and higher surface roughness in iodine doped PbPc (I-PbPc) films. The obvious enhancement in the current values of I-PbPc is attributed to the introduction of holes as charge carriers. Nanoscale current mapping reveals the presence of percolation pathways in I-PbPc films, on both Si and HOPG substrates, being responsible for the observed high conductance in contrast to the isolated conducting domains in the pristine PbPc system. The broad distribution of current values across various conducting domains on Si is attributed to a mixture of crystalline phases and disordered fractions of I-PbPc, while the narrow distribution of current values observed in the case of HOPG arises from the majorly disordered PbPc molecules. These films also show enhanced sensitivity towards ammonia that is almost four times higher in magnitude than for pristine PbPc films. The current maps show that the adsorption of ammonia molecules disrupts the iodine percolation pathways, thereby imposing a detrimental effect on the conductivity of the PbPc films.


Prevalence of muscle dysmorphia in adolescents: findings from the EveryBODY study.
We sought to provide the first point prevalence estimates of muscle dysmorphia (MD), a form of body dysmorphic disorder characterized by a preoccupation with perceived insufficient muscularity, in adolescents. Data were taken from a survey of 3618 Australian adolescents (11.172-19.76 years; 49.3% girls). Measures captured demographic characteristics, symptoms of MD and eating disorders, psychological distress and functional impairment. Diagnostic criteria for MD developed by Pope et al. (1997, Psychosomatics, 38(6), 548-557) were applied, entailing preoccupation with insufficient muscularity causing significant levels of distress or disability that cannot be better accounted for by an eating disorder. The point prevalence of MD was 2.2% [95% confidence interval (CI) 1.6-3.0%] among boys and 1.4% (95% CI 0.9-2.0%) among girls. Prevalence was not associated with gender (V = 0.031) or socioeconomic status (SES) (partial η2< 0.001), but was marginally associated with older age (partial η2 = 0.001). Boys with MD were more likely than girls with MD to report severe preoccupation with muscularity (V = 0.259) and a weight-lifting regime that interfered with their life (V = 0.286), whereas girls with MD were more likely to report discomfort with body exposure (V = 0.380). While future epidemiological research using diagnostic interviews is needed to verify these estimates, the findings suggest that MD is relatively common from early to late adolescence. Gender differences in MD prevalence may be minimal; however, the symptom profile appears to diverge between boys and girls. These findings provide a platform for future, analytical research designed to inform clinical and public health interventions.


Minimal PD-1 expression in mouse and human NK cells under diverse conditions.
PD-1 expression is a hallmark of both early antigen-specific T cell activation and later chronic stimulation, suggesting key roles in both naive T cell priming and memory T cell responses. Although significant similarities exist between T cells and NK cells, there are critical differences in their biology and functions reflecting their respective adaptive and innate immune effector functions. Expression of PD-1 on NK cells is controversial despite rapid incorporation into clinical cancer trials. Our objective was to stringently and comprehensively assess expression of PD-1 on both mouse and human NK cells under multiple conditions and using a variety of readouts. We evaluated NK cells from primary human tumor samples, after ex vivo culturing, and from multiple mouse tumor and viral models using flow cytometry, quantitative reverse-transcriptase PCR (qRT-PCR), and RNA-Seq for PD-1 expression. We demonstrate that, under multiple conditions, human and mouse NK cells consistently lack PD-1 expression despite the marked upregulation of other activation/regulatory markers, such as TIGIT. This was in marked contrast to T cells, which were far more prominent within all tumors and expressed PD-1. These data have important implications when attempting to discern NK from T cell effects and to determine whether PD-1 targeting can be expected to have direct effects on NK cell functions.


Radiographic prevalence of femoroacetabular impingement in collegiate football players: AAOS Exhibit Selection.
The prevalence of femoroacetabular impingement may be greater in athletes than in the general population because of increased loading of the hip during sports. This study evaluated the radiographs of collegiate football players in order to quantify the prevalence of femoroacetabular impingement in asymptomatic athletes. Sixty-seven male collegiate football players (age, 21 ± 1.9 years) participated in this prospective study. Both hips (n = 134) were evaluated independently by two orthopaedic surgeons for radiographic signs of femoroacetabular impingement. The alpha angle and femoral head-neck offset were measured on frog-leg lateral radiographs. The lateral center-edge angle, acetabular index, crossover sign, and alpha angle were measured on anteroposterior radiographs. Data for continuous variables were averaged between observers prior to assessing prevalence. Cam femoroacetabular impingement was considered to be present if the femoral head-neck offset was <8 mm and/or the alpha angle was >50° on either radiograph. Pincer femoroacetabular impingement was considered to be present if the lateral center-edge angle was >40°, the acetabular index was <0°, and/or a positive crossover sign was detected by both observers. Ninety-five percent of the 134 hips had at least one sign of cam or pincer impingement, and 77% had more than one sign. Twenty-one percent had only one sign of cam femoroacetabular impingement and 57% had both signs. Fifty-two percent had only one sign of pincer femoroacetabular impingement, 10% had two, and 4% had all three signs. Specifically, 72% had an abnormal alpha angle, 64% had a decreased femoral head-neck offset, 61% had a positive crossover sign, 16% had a decreased acetabular index, and 7% had an increased lateral center-edge angle. Fifty percent of all hips had at least one sign of pincer femoroacetabular impingement and at least one sign of cam impingement. Interobserver and intraobserver repeatability was moderate or better for each measure (range, 0.59 to 0.85). Morphologic abnormalities associated with cam and pincer femoroacetabular impingement were common in these collegiate football players. The prevalence of cam and pincer femoroacetabular impingement was substantially higher than the previously reported prevalence in the general population.


Case management workforce in the United States.
The purpose of this study was to investigate and compare characteristics of the case management (CM) workforce in the US by age, years of experience, and original profession. This study was an exploratory, descriptive secondary analysis of demographic and job characteristics of 24,085 certified case managers (CCMs). Descriptive statistics, Chi-square tests, and correlation coefficients were calculated. The majority of the case-management workforce is made up of RNs (93.3%). The CCMs were older, with a mean age of 55.0 years, than were those in their original profession and started to work as CCMs late in their careers. The educational level of RN-CCMs was lower than that of CCMs from other professions. Also, job titles and work settings of CCMs were diverse, with different focus areas depending on clients' needs. The distribution of CCMs was associated with the number of managed-care enrollees. Profiles of CCMs in this study are valuable for clinical practice and can assist with deployment of the CM workforce. To develop and deploy CCMs better matched to societal healthcare needs, characteristics of CCMs should be precisely understood. Managing the CM workforce is expected to be critical because of a shortage of RN workers and aging-of-the-workforce issues in the US.


Transarterial embolization of intractable nasal and oropharyngeal hemorrhage using liquid embolic agents.
Intractable hemorrhage of the nasal or oropharyngeal cavities can be life threatening, and endovascular embolization is one of the few effective treatments for severe recurrent bleeds. Traditionally, embolic particles have been used for transarterial embolization. To investigate the safety and efficacy of a less commonly performed treatment-namely, feeding artery occlusion with liquid embolic agents. We retrospectively reviewed our neurointerventional database for patients who had undergone transarterial embolization for intractable nasal and oropharyngeal hemorrhage with Onyx, N-butyl-2 cyanoacrylate (n-BCA) glue, or both, at our institution over a 5-year period from 2008 to 2013. Forty-six patients who underwent a total of 51 procedures met the inclusion criteria. Causes of hemorrhage included neoplasm n=35 (68.6%), trauma n=12 (23.5%), and idiopathic n=4 (7.9%). The bleeding was oropharyngeal in 66.7%, nasal in 29.4%, and 3.9% originated from both sites. Embolic agents used were n-BCA in 26 cases (51.0%), Onyx in 22 cases (43.1%), and both agents in three cases (5.9%). Mean total procedural time was 93.1 min (range 34-323 min), and mean fluoroscopy time was 39.1 min (10- 121 min). Mean follow-up time was 7.4 months (0.25-36 months). Five of the 46 patients (10.9%) required re-embolization and one (2.0%) rebled during the same hospital stay. One periprocedural cardiovascular adverse event occurred that was unrelated to the embolic agent used, but no other complications were seen. Transarterial embolization with n-BCA or Onyx is a safe and effective treatment for patients with intractable nasal and oropharyngeal hemorrhage. Further prospective studies are warranted to confirm these findings.


[Sensitization against storage mites in allergic rhinopathy].
In the past 15 years, storage mites became more common as an agent in allergic airway disease. Sensitization to storage mites has been reported in farmers and grain workers. There were some studies investigating local populations, especially in the north of Europe. The sensitization to storage mites in a rural population seems to be similar to the rate found for Dermatophagoides. The main diseases caused by storage mites are allergic rhinitis and asthma. Although there is a cross-reactivity between Dermatophagoides pteronyssinus and storage mites, most of the antigens were distinct from house dust mite antigens. In our study, we analysed sera obtained from patients with known house dust mite allergy. Patients with a RAST class 2, 3 or 4 for Dermatophagoides pteronyssinus were tested for specific IgE-antibodies against storage mites. The test was performed using the Melja EAST-technique. We obtained a sensibilization rate of 7% for Acarus siro (d70), 17% for Lepidoglyphus destructor (d71), 3% for Tyrophagus putrescentiae (d72) and 13% for Glycyphagus domesticus (d73). According to our results we can conclude that storage mites are relevant allergens in allergic rhinitis, especially in the rural population in Bavaria. Therefore, routine testing in patients with perennial rhinitis is proposed.


A diamidinatogermylene as a Z-type ligand in a nickel(0) complex.
The reaction of the phosphine functionalized chlorogermylene 1 with Ni(COD)2 (COD = 1,5-cyclooctadiene) afforded the bis-chlorogermylene ligated nickel(0) complex 2 in high yield. The dechlorination reaction of 2 with elemental potassium serendipitously yielded the diamidinatogermylene nickel(0) complex 3. Single-crystal X-ray diffraction analysis reveals that the germanium center in 3 features a pyramidalized geometry, suggesting the germylene moiety in 3 acts as a Z-type ligand, which is further supported by theoretical calculations. Complex 3 represents the first example bearing a Z-type diaminogermylene ligand.


Cloning and identification of microRNAs in bovine alveolar macrophages.
MicroRNAs (miRNAs) are a class of small non-coding RNAs found in both animal and plant cells. These approximately 19-26 nucleotide (nt) single-stranded RNAs play role in regulating gene/protein expression by either directly binding to mRNAs and inducing degradation of their target or by translational inhibition of protein expression. In this report, we described the cloning and identification of 22 microRNAs from bovine alveolar macrophage (AM). Eleven of the 22 miRNAs were novel and have not been previously identified in any species, while eight previously unidentified bovine miRNAs were identical to known ortholog miRNAs from human and/or rat (Bta-miR-141, Bta-miR-187, Bta-miR-191, Bta-miR-448, Bta-miR-589, Bta-miR-873, Bta-miR-463, and Bta-miR-562). These results add to the growing database of new miRNAs and suggest new biological functions for miRNAs in AMs. Specially, our data implicates miRNA regulation of antimicrobial targets in alveolar macrophages of bovine lung.


Does common prescription medication affect the rate of orthodontic tooth movement? A systematic review.
As the taking of any medication may theoretically affect the complex pathways responsible for periodontal tissue homeostasis and the events leading to orthodontic tooth movement, it is considered important for the orthodontist to be able to identify prospective patients' history and patterns of pharmaceutical consumption. To systematically investigate and appraise the quality of the available evidence regarding the effect of commonly prescribed medications on the rate of orthodontic tooth movement. Search without restrictions in eight databases and hand searching until June 2017. Controlled studies investigating the effect of commonly prescribed medications with emphasis on the rate of orthodontic tooth movement. Following study retrieval and selection, relevant data was extracted and the risk of bias was assessed using the SYRCLE's Risk of Bias Tool. Twenty-seven animal studies, involving various pharmacologic and orthodontic interventions, were finally identified. Most studies were assessed to be at unclear or high risk of bias. The rate of orthodontic tooth movement was shown to increase after the administration of diazepam, Vitamin C and pantoprazole, while simvastatin, atorvastatin, calcium compounds, strontium ranelate, propranolol, losartan, famotidine, cetirizine, and metformin decreased the rate of orthodontic tooth movement. No interference with the rate of orthodontic tooth movement was reported for phenytoin, phenobarbital and zinc compounds, whereas, inconsistent or conflicting effects were noted after the administration of L-thyroxine, lithium compounds, fluoxetine and insulin. The quality of the available evidence was considered at best as low. Commonly prescribed medications may exhibit variable effects on the rate of orthodontic tooth movement. Although the quality of evidence was considered at best as low, raising reservations about the strength of the relevant recommendations, the clinician should be capable of identifying patients taking medications and should take into consideration the possible implications related to the proposed treatment. PROSPERO (CRD42015029130).


A Mup promoter-thymidine kinase reporter gene shows relaxed tissue-specific expression and confers male sterility upon transgenic mice.
A hybrid gene was made by fusing the 2.2-kilobase 5' promoter region of a mouse group 1 major urinary protein (Mup) gene to the coding region of the herpes simplex virus type 1 thymidine kinase gene (HSV tk) and introduced into the genomes of mice by microinjection. Transgenic G0 males were sterile, or when fertile did not transmit the foreign gene, and the transgenic male descendants of G0 females were also sterile. Seven "lines" were established by breeding from G0 females and their transgenic female descendants. Six lines expressed HSV thymidine kinase activity in the liver, and activity correlated perfectly with the presence of HSV tk RNA. In three of four lines examined, expression was lower in female than in male liver, and in these lines the same sex difference was observed in the rate of run-on transcription of the foreign genes in liver nuclei. When females of one of the sexually dimorphic lines were treated with testosterone, the levels of HSV tk RNA and thymidine kinase activity were increased, although not to male levels. In these aspects of liver expression, and also in a lack of expression in seven other tissues, the hybrid gene exhibits many of the characteristics of an endogenous group 1 Mup gene. However, the gene was also expressed (at high levels) in the preputial gland and testis, two tissues in which Mup genes are not expressed. The gene, when introduced into five of the seven lines, carried a copy of the Escherichia coli supF gene attached beyond the 3' end of the HSV tk gene, but this did not affect the overall expression pattern. All of the lines were male sterile and expressed HSV thymidine kinase in the testis, but one line showed no activity in the liver, and another showed none in the preputial gland. Testicular expression is therefore the likely cause of sterility. Data are described which suggest that the causes of misexpression in the preputial gland and testis are different. Since expression in each tissue occurred in several lines, the structure of the hybrid gene must be responsible in each case. Five intensively studied lines showed at least four consistently different patterns of relative expression in preputial gland, testis, male liver, and female liver. These differences do not correlate in any way with the copy number of the foreign gene in the different lines and must be due to some other aspect of line specific integration.


Age estimation using radicular dentine transparency: A new innovative approach.
To estimate the age of the individual from radicular dentine transparency and to derive a formula suitable for age estimation in the Indian population, using radicular dentine transparency. Seventy teeth samples of known age were collected from patients belonging to different age groups ranging from 11 to 80 years whose teeth were extracted for various therapeutic purposes. The samples were grouped from A to G according to their age, each group consisting of 10 teeth samples. Buccolingual sections of 100 μm thickness were obtained using hard tissue microtome. The sections were scanned using a flat-bed scanner. The scanning base of the scanner was pasted with a graph sheet and the teeth samples pasted on to the graph sheet were scanned with a resolution of 600 dpi, and the images were stored in a computer. The graph sheet was clearly visible in the area of transparent dentine, and the length of transparent dentine (i.e., the number of millimeters on the graph) was measured from the scanned images, stored in the computer. A strong positive correlation between age and transparency of dentin was noted. The age was estimated with an accuracy of ± 5 years (61.4%) and ± 10 years (12.9%). The present study had a level of agreement of 71.4% with that of Bang and Ramm. Thus, transparency level of the radicular dentin increases with age, and it can be used as a single reliable parameter for age estimation.


Effect of Affective Reward on Cognitive Event-related Potentials and its Relationship with Psychological Pain and Suicide Risk among Patients with Major Depressive Disorder.
The present study aimed to explore the electrophysiological correlates involved in three-dimensional psychological pain and their relationship with suicide in patients with major depressive disorder. The sample comprised 23 and nine patients with major depressive disorder with high and low risk for suicide, respectively, and 24 healthy controls. All participants completed the measurements and performed an event-related potential-based analogue of the affective incentive delay task. The event-related potential components previously associated with motivationally salient cue (contingent negative variation, P2, and cue-P3), target (target-P3), and feedback (reward vs. punishment, feedback-related negativity, and feedback-P3) stimuli were examined. All inventory scores differed significantly among the high-risk, low-risk, and healthy control groups. During the expectant phase, the main effect of group and interaction between group and condition was significant in the average amplitudes of the cue-P2 component. During the feedback phase, the feedback-P3 elicited by positive feedback had a significant main effect of group and of the interaction between group and condition. Specifically, the feedback-P3 elicited by negative feedback in the punitive condition showed significant positive correlations with the total and subscale scores on the Three-Dimensional Psychological Pain Scale. Feedback-P3 may be an electrobiological component underlying the processing of psychological pain in suicidality.


[The effect of economic activities altering water resources on the parasitological situation].
The possibilities and results of impact of some economic activities of man, which alter the hydrological regimen of reservoirs and territory irrigation on the parasitological situation in their area are outlined in the paper. It shows that in some cases economic activities favour the spread and incidence of diseases and in other cases they may lead to a reduction in the rate of infection, make the focus extinct.


Accessing diabetes care in rural Uganda: Economic and social resources.
Non-communicable diseases including type 2 diabetes (T2D) are increasing rapidly in most Sub-Saharan African (SSA) countries like Uganda. Little attention has been given to how patients with T2D try to achieve treatment when the availability of public health care for their disease is limited, as is the case in most SSA countries. In this paper we focus on the landscape of availability of care and the therapeutic journeys of patients within that landscape. Based on fieldwork in south-western Uganda including 10 case studies, we explore the diabetes treatment options in the area and what it takes to access the available treatment. We analyse the resources patients need to use the available treatment options, and demonstrate that the patients' journeys to access and maintain treatment are facilitated by the knowledge and support of their therapy management groups. Patients access treatment more effectively, if they and their family have money, useful social relations, and knowledge, together with the capacity to communicate with health staff. Patients coming from households with high socio-economic status (SES) are more likely to have all of these resources, while for patients with low or medium SES, lack of economic resources increases the importance of connections within the health system.


Plasmodium falciparum PfEMP1 Modulates Monocyte/Macrophage Transcription Factor Activation and Cytokine and Chemokine Responses.
Immunity to Plasmodium falciparum malaria is slow to develop, and it is often asserted that malaria suppresses host immunity, although this is poorly understood and the molecular basis for such activity remains unknown. P. falciparum erythrocyte membrane protein 1 (PfEMP1) is a virulence factor that plays a key role in parasite-host interactions. We investigated the immunosuppressive effect of PfEMP1 on monocytes/macrophages, which are central to the antiparasitic innate response. RAW macrophages and human primary monocytes were stimulated with wild-type 3D7 or CS2 parasites or transgenic PfEMP1-null parasites. To study the immunomodulatory effect of PfEMP1, transcription factor activation and cytokine and chemokine responses were measured. The level of activation of NF-κB was significantly lower in macrophages stimulated with parasites that express PfEMP1 at the red blood cell surface membrane than in macrophages stimulated with PfEMP1-null parasites. Modulation of additional transcription factors, including CREB, also occurred, resulting in reduced immune gene expression and decreased tumor necrosis factor (TNF) and interleukin-10 (IL-10) release. Similarly, human monocytes released less IL-1β, IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and TNF specifically in response to VAR2CSA PfEMP1-containing parasites than in response to PfEMP1-null parasites, suggesting that this immune regulation by PfEMP1 is important in naturally occurring infections. These results indicate that PfEMP1 is an immunomodulatory molecule that affects the activation of a range of transcription factors, dampening cytokine and chemokine responses. Therefore, these findings describe a potential molecular basis for immune suppression by P. falciparum.


Repeatability and heritability of reproductive traits in free-ranging snakes.
The underlying genetic basis of life-history traits in free-ranging animals is critical to the effects of selection on such traits, but logistical constraints mean that such data are rarely available. Our long-term ecological studies on free-ranging oviparous snakes (keelbacks, Tropidonophis mairii (Gray, 1841), Colubridae) on an Australian floodplain provide the first such data for any tropical reptile. All size-corrected reproductive traits (egg mass, clutch size, clutch mass and post-partum maternal mass) were moderately repeatable between pairs of clutches produced by 69 female snakes after intervals of 49-1152 days, perhaps because maternal body condition was similar between clutches. Parent-offspring regression of reproductive traits of 59 pairs of mothers and daughters revealed high heritability for egg mass (h2= 0.73, SE=0.24), whereas heritability for the other three traits was low (< 0.37). The estimated heritability of egg mass may be inflated by maternal effects such as differential allocation of yolk steroids to different-sized eggs. High heritability of egg size may be maintained (rather than eroded by stabilizing selection) because selection acts on a trait (hatchling size) that is determined by the interaction between egg size and incubation substrate rather than by egg size alone. Variation in clutch size was mainly because of environmental factors (h2=0.04), indicating that one component of the trade-off between egg size and clutch size is under much tighter genetic control than the other. Thus, the phenotypic trade-off between egg size and egg number in keelback snakes occurs because each female snake must allocate a finite amount of energy into eggs of a genetically determined size.


Structural basis for distinctive recognition of fibrinogen gammaC peptide by the platelet integrin alphaIIbbeta3.
Hemostasis and thrombosis (blood clotting) involve fibrinogen binding to integrin alpha(IIb)beta(3) on platelets, resulting in platelet aggregation. alpha(v)beta(3) binds fibrinogen via an Arg-Asp-Gly (RGD) motif in fibrinogen's alpha subunit. alpha(IIb)beta(3) also binds to fibrinogen; however, it does so via an unstructured RGD-lacking C-terminal region of the gamma subunit (gammaC peptide). These distinct modes of fibrinogen binding enable alpha(IIb)beta(3) and alpha(v)beta(3) to function cooperatively in hemostasis. In this study, crystal structures reveal the integrin alpha(IIb)beta(3)-gammaC peptide interface, and, for comparison, integrin alpha(IIb)beta(3) bound to a lamprey gammaC primordial RGD motif. Compared with RGD, the GAKQAGDV motif in gammaC adopts a different backbone configuration and binds over a more extended region. The integrin metal ion-dependent adhesion site (MIDAS) Mg(2+) ion binds the gammaC Asp side chain. The adjacent to MIDAS (ADMIDAS) Ca(2+) ion binds the gammaC C terminus, revealing a contribution for ADMIDAS in ligand binding. Structural data from this natively disordered gammaC peptide enhances our understanding of the involvement of gammaC peptide and integrin alpha(IIb)beta(3) in hemostasis and thrombosis.


UK military doctors; stigma, mental health and help-seeking: a comparative cohort study.
Studies suggest that medical doctors can suffer from substantial levels of mental ill-health. Little is known about military doctors' mental health and well-being; we therefore assessed attitudes to mental health, self-stigma, psychological distress and help-seeking among UK Armed Forces doctors. Six hundred and seventy-eight military doctors (response rate 59%) completed an anonymous online survey. Comparisons were made with serving and ex-military personnel (n=1448, response rate 84.5%) participating in a mental health-related help-seeking survey. Basic sociodemographic data were gathered, and participants completed measures of mental health-related stigmatisation, perceived barriers to care and the 12-Item General Health Questionnaire. All participants were asked if in the last three years they had experienced stress, emotional, mental health, alcohol, family or relationship problems, and whether they had sought help from formal sources. Military doctors reported fewer mental disorder symptoms than the comparison groups. They endorsed higher levels of stigmatising beliefs, negative attitudes to mental healthcare, desire to self-manage and self-stigmatisation than each of the comparison groups. They were most concerned about potential negative effects of and peer perceptions about receiving a mental disorder diagnosis. Military doctors reporting historical and current relationship, and alcohol or mental health problems were significantly and substantially less likely to seek help than the comparison groups. Although there are a number of study limitations, outcomes suggest that UK military doctors report lower levels of mental disorder symptoms, higher levels of stigmatising beliefs and a lower propensity to seek formal support than other military reference groups.


Ventral penile lengthening versus dorsal plication for severe ventral curvature in children with proximal hypospadias.
The 2 main approaches to correct severe ventral curvature are dorsal plication of the corpora and ventral corporeal lengthening by tunica albuginea patching. Controversy persists since neither technique has been proved to be superior to the other with respect to initial or long-term outcome. However, to our knowledge a direct comparison of outcome of these 2 procedures has not been previously reported. A retrospective review of the records of 100 consecutive patients who underwent repair of penoscrotal or more proximal defects from 1996 to 2004 was performed. Children were divided into 2 groups, including group 1-32 who underwent a ventral penile lengthening procedure and group 2-68 who underwent dorsal plication. Meatal location, preoperative testosterone stimulation, severe ventral curvature (greater than 45 degrees) at the beginning of operation and after degloving, proximal ventral dissection, urethral plate transection and recurrent ventral curvature were compared between the 2 groups. Mean age was 17 months (range 9 to 56) in patients with ventral penile lengthening and 17.8 months (range 10 to 58) in patients with dorsal plication. Mean followup was 65 (range 29 to 120) and 62 months (range 30 to 116), respectively. Of the 32 group 1 children 30 (93.7%) had penoscrotal or more proximal hypospadias vs 57 of the 68 (83.8%) in group 2. Three of the 32 children who underwent ventral penile lengthening had recurrent ventral curvature vs 19 of the 68 who underwent dorsal plication (9.4% vs 27.9%, p = 0.03). On multivariate analysis dorsal plication remained significantly associated with recurrent ventral curvature independently of the other factors (OR 4.56, 95% CI 1.14-18.28, p = 0.03). Dorsal plication was more often associated with recurrent ventral curvature compared to ventral penile lengthening on univariate and multivariate analysis. Future studies adjusting for proximal ventral dissection and urethral plate transection are necessary to further elucidate the role of each technique in the correction of severe ventral curvature in children with proximal hypospadias.


[The functional role of neurospecific protein S-100 in memory processes].
Elaboration of alimentary conditioned reflex in rats is accompanied by an increase of the level of protein S-100 in the left and right cerebral hemispheres. Amnestic factor M-cholinolytic atropine disturbs the elaborated habit and simultaneously decreases the quantity of protein S-100 up to the level of unlearned animals. The elaboration of conditioned reflex of passive avoidance does not change the content of protein S-100 in the rats brain. Intracisternal injection of antiserum to protein S-100 has an expressed amnestic action. Intracisternal injection of protein S-100 against the background of amnestic action of cholinolytic does not lead to restoration of memory. The cholinolytic and antiserum to protein S-100 mutually potentiate the amnestic effect.