Old and New Approaches for Assessing Sweating.
The evaluation of sweating activities contributes to both medical services and social living. There are several old and new approaches for assessing sweating. These methods are mainly composed of adopted techniques that focus on detecting small amounts of water on the skin surface. For many years, the iodine-starch reaction has been applied in various settings to evaluate sweat on the skin surface. However, methodology based on the coloration of sweat is in a constant state of evolution, and multiple advancements have been made. Furthermore, common fingerprinting is not just used for obtaining personal-identifying information anymore as it can also provide scientifically important information for sweat-pore mapping and sweat-component analysis. Additionally, there are multiple techniques for the quantitative measurement of sweat volume and dynamic intravital imaging of sweat, and these are also continually evolving. This chapter provides an overview of the old and new approaches for assessing sweating.


Imaging secondary metabolism of Streptomyces sp. Mg1 during cellular lysis and colony degradation of competing Bacillus subtilis.
Soil streptomycetes are saprotrophic bacteria that secrete numerous secondary metabolites and enzymes for extracellular functions. Many streptomycetes produce antibiotics thought to protect vegetative mycelia from competing organisms. Here we report that an organism isolated from soil, Streptomyces sp. Mg1, actively degrades colonies and causes cellular lysis of Bacillus subtilis when the organisms are cultured together. We predicted that the inhibition and degradation of B. subtilis colonies in this competition depends upon a combination of secreted factors, including small molecule metabolites and enzymes. To begin to unravel this complex competitive phenomenon, we use a MALDI imaging mass spectrometry strategy to map the positions of metabolites secreted by both organisms. In this report, we show that Streptomyces sp. Mg1 produces the macrolide antibiotic chalcomycin A, which contributes to inhibition of B. subtilis growth in combination with other, as yet unidentified factors. We suggest that efforts to understand competitive and cooperative interactions between bacterial species benefit from assays that pair living organisms and probe the complexity of metabolic exchanges between them.


Forced-rupture of cell-adhesion complexes reveals abrupt switch between two brittle states.
Cell adhesion complexes (CACs), which are activated by ligand binding, play key roles in many cellular functions ranging from cell cycle regulation to mediation of cell extracellular matrix adhesion. Inspired by single molecule pulling experiments using atomic force spectroscopy on leukocyte function-associated antigen-1 (LFA-1), expressed in T-cells, bound to intercellular adhesion molecules (ICAM), we performed constant loading rate (rf) and constant force (F) simulations using the self-organized polymer model to describe the mechanism of ligand rupture from CACs. The simulations reproduce the major experimental finding on the kinetics of the rupture process, namely, the dependence of the most probable rupture forces (f*s) on ln rf (rf is the loading rate) exhibits two distinct linear regimes. The first, at low rf, has a shallow slope, whereas the slope at high rf is much larger, especially for a LFA-1/ICAM-1 complex with the transition between the two occurring over a narrow rf range. Locations of the two transition states (TSs) extracted from the simulations show an abrupt change from a high value at low rf or constant force, F, to a low value at high rf or F. This unusual behavior in which the CACs switch from one brittle (TS position is a constant over a range of forces) state to another brittle state is not found in forced-rupture in other protein complexes. We explain this novel behavior by constructing the free energy profiles, F(Λ)s, as a function of a collective reaction coordinate (Λ), involving many key charged residues and a critical metal ion (Mg2+). The TS positions in F(Λ), which quantitatively agree with the parameters extracted using the Bell-Evans model, change abruptly at a critical force, demonstrating that it, rather than the molecular extension, is a good reaction coordinate. Our combined analyses using simulations performed in both the pulling modes (constant rf and F) reveal a new mechanism for the two loading regimes observed in the rupture kinetics in CACs.


Synthesis of an Fe(terpy-cage)2 dumbbell.
An azide masked amine is used to obtain a cage of lower symmetry that possess one terpy-group in an exo-position. This group can coordinate to iron(ii), yielding selectively an easy to purify Fe(terpy-cage)2 dumbbell. The dumbbell can also be obtained in a one pot reaction, which proceeded without isolation of the exo-functionalized cage.


Allergen immunotherapy and allergic rhinitis: false beliefs.
Over the last 100 years, several persistent misconceptions or 'false beliefs' have built up around allergen immunotherapy and its use in allergic rhinitis. This is perhaps because enthusiastic physicians administered complex allergen extracts to a diverse population of patients suffering from heterogeneous atopic conditions. Here, we review evidence that counters seven of these 'false beliefs.' 1. The symptoms of allergic rhinitis can be more heterogeneous, more severe and more troublesome in everyday life than many physicians believe. Large-scale epidemiological surveys show that the majority of allergic rhinitis patients have at least one symptom severe enough to interfere with sleep quality, productivity and/or well-being. 2. Allergen immunotherapy is not necessarily suitable for all allergic rhinitis patients (notably those with mild symptoms). Recent evidence from double-blind, placebo-controlled, randomized clinical trials suggests that the more severe the disease, the greater the treatment effect. 3. Allergen immunotherapy is often accused of lack of efficacy (relative to pharmacotherapy, for example). However, there are now many meta-analyses, systematic reviews and high-quality clinical trials that find overwhelmingly in favor of the efficacy of allergen immunotherapy (including sublingual formulations) in allergic rhinitis induced by pollen and, increasingly, other allergens. 4. Natural-exposure and challenge-chamber trials have shown that symptom relief may become apparent within months or even weeks of the initiation of allergen immunotherapy. 5. In pollen-induced allergic rhinitis, several years of subcutaneous or sublingual allergen immunotherapy are associated with sustained clinical efficacy after subsequent treatment cessation - confirming the disease-modifying nature of this therapy. 6. Most patients seeking treatment for allergic rhinitis are polysensitized, and allergen immunotherapy has proven efficacy in large, robust clinical trials in these groups. Polysensitization is not a contraindication to allergen immunotherapy. 7. Sublingual allergen immunotherapy is safe for home administration. A recent review calculated that 1 billion doses were administered worldwide between 2000 and 2010 and found that the 11 case reports of anaphylaxis (all non-fatal) corresponded to non-standard practice. Modern, evidence-based medicine has generated more than enough robust evidence to remove misconceptions about allergen immunotherapy and allergic rhinitis.


Clinical review: severe asthma.
Severe asthma, although difficult to define, includes all cases of difficult/therapy-resistant disease of all age groups and bears the largest part of morbidity and mortality from asthma. Acute, severe asthma, status asthmaticus, is the more or less rapid but severe asthmatic exacerbation that may not respond to the usual medical treatment. The narrowing of airways causes ventilation perfusion imbalance, lung hyperinflation, and increased work of breathing that may lead to ventilatory muscle fatigue and life-threatening respiratory failure. Treatment for acute, severe asthma includes the administration of oxygen, beta2-agonists (by continuous or repetitive nebulisation), and systemic corticosteroids. Subcutaneous administration of epinephrine or terbutaline should be considered in patients not responding adequately to continuous nebulisation, in those unable to cooperate, and in intubated patients not responding to inhaled therapy. The exact time to intubate a patient in status asthmaticus is based mainly on clinical judgment, but intubation should not be delayed once it is deemed necessary. Mechanical ventilation in status asthmaticus supports gas-exchange and unloads ventilatory muscles until aggressive medical treatment improves the functional status of the patient. Patients intubated and mechanically ventilated should be appropriately sedated, but paralytic agents should be avoided. Permissive hypercapnia, increase in expiratory time, and promotion of patient-ventilator synchronism are the mainstay in mechanical ventilation of status asthmaticus. Close monitoring of the patient's condition is necessary to obviate complications and to identify the appropriate time for weaning. Finally, after successful treatment and prior to discharge, a careful strategy for prevention of subsequent asthma attacks is imperative.


Optimality principles in sensorimotor control.
The sensorimotor system is a product of evolution, development, learning and adaptation-which work on different time scales to improve behavioral performance. Consequently, many theories of motor function are based on 'optimal performance': they quantify task goals as cost functions, and apply the sophisticated tools of optimal control theory to obtain detailed behavioral predictions. The resulting models, although not without limitations, have explained more empirical phenomena than any other class. Traditional emphasis has been on optimizing desired movement trajectories while ignoring sensory feedback. Recent work has redefined optimality in terms of feedback control laws, and focused on the mechanisms that generate behavior online. This approach has allowed researchers to fit previously unrelated concepts and observations into what may become a unified theoretical framework for interpreting motor function. At the heart of the framework is the relationship between high-level goals, and the real-time sensorimotor control strategies most suitable for accomplishing those goals.


A 65-Year-Old Man With Concerns of Hemoptysis After Recent Motor Vehicle Accident and Blunt Trauma to Chest.
A 65-year-old man with a medical history of anxiety and depression came to the ED with concerns of coughing blood-tinged phlegm for the past 3 days. Four days before the presentation, the patient had a motor vehicle accident as a restrained driver with airbag deployment. The patient struck his chest against the steering wheel. He was evaluated at a level 1 trauma center and underwent a whole-body scan, including a CT scan of the chest, which showed no acute abnormalities. Apart from mild-to-moderate bruising and tenderness on the right side of his face, nose, and anterior chest, the patient was stable and was discharged the next day. After returning home, the patient started coughing blood-tinged phlegm, which became progressively bloodier for the next 3 days, achieving individual posttussive volumes of 1 T of frank blood. In the ED, the patient denied any similar symptoms in the past. He denied any recent or distant known history of malignancy, infections, or travel outside the United States. He lives by himself and previously worked various jobs. He endorsed active tobacco use and smoking 3 to 6 cigarettes per day for the past 20 years with 5 pack-year history. Patient reported consuming one to two alcohol drinks per month.


Correlation between macroscopic and microscopic diseases on splenectomies performed in the surgical management of ovarian cancer.
Surgical management of primary or recurrent ovarian cancer with extensive upper abdominal disease may require splenectomy to achieve complete cytoreduction. The aims of this series were to correlate the macroscopic exploration with the microscopic analysis of the spleen and to evaluate the morbidity of patients submitted to this procedure for primary and recurrent disease. Data concerning patients who underwent splenectomy at the time of management of the primary (initial group) or recurrent disease were reviewed. The characteristics and survival of patients were analyzed. The correlation between macroscopic suspected lesion and histological results and morbidity according to the Dindo classification was studied. From 1995 to 2008, 58 patients (42 in the initial group and 16 in the recurrence group) underwent a splenectomy in our institution. Except for 3 cases requiring splenectomy for hemostatic reasons, the macroscopically suspected splenic lesion was confirmed by histology in 32 (80%) of 40 cases in the initial group and in 14 (93%) of 15 cases in the recurrence group. Eighteen patients (26.5%) had a morbidity grade strictly superior to 2, and in all the factors we tested, only pelvic posterior exenteration was a risk factor for high morbidity (P = 0.02). When splenic lesions are macroscopically suspected during cytoreductive surgery for an ovarian cancer, most of the time the disease is confirmed by histology. When required to accomplish complete cytoreduction, splenectomy seemed to be justified.


Leptin inhibits insulin secretion induced by cellular cAMP in a pancreatic B cell line (INS-1 cells).
The effect of leptin on insulin secretion is controversial due to conflicting results in the literature. In the present study, we incubated insulin-producing rat insulinoma INS-1 cells for 60 min and examined the effects of recombinant murine leptin (20 nmol/l). We found that leptin (0.1-100 nmol/l) did not affect the insulin response to glucose (1-20 mmol/l). However, when cells were incubated with agents that increase the intracellular content of cAMP, i.e., glucagon-like peptide-1 (100 nmol/l), pituitary adenylate cyclase activating polypeptide (100 nmol/l), forskolin (2.5 micromol/l), dibutyryl-cAMP (1 mmol/l), or 3-isobutyl-1-methylxanthine (100 micromol/l), leptin significantly reduced insulin secretion (by 34-58%, P < 0.05-0.001). In contrast, when insulin secretion was stimulated by the cholinergic agonist carbachol (100 micromol/l) or the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (1 micromol/l), both of which activate protein kinase C, leptin was without effect. We conclude that leptin inhibits insulin secretion from INS-1 cells under conditions in which intracellular cAMP is increased. This suggests that the cAMP-protein kinase A signal transduction pathway is a target for leptin to inhibit insulin secretion in insulin-producing cells.


Association of a Giant Lymphoma Mass With Occupational Benzene Exposure.
Benzene is a chemical widely used in industrial settings and known to have hematopoietic toxicity. Previous literature has been inconsistent regarding a direct association of benzene exposure with lymphoma. A young patient with a strong history of benzene exposure presented with a 17-cm chest wall lymphoma and purulent drainage from the mass. He underwent resection of the mass. Pathologic analysis revealed a high-grade diffuse large B-cell lymphoma. The wound ultimately healed well and the patient received adjuvant chemotherapy. Though the overall literature has been inconsistent regarding the association of benzene with lymphoma, our report highlights the possibility that a very extensive exposure history may be a risk factor for the development of lymphoma.


The cadherin protein CDH19 mediates cervical carcinoma progression by regulating AKT/NF-κB signaling.
The cell adhesion protein cadherin 19 (CDH19) has been reported to be involved in various types of cancer, but its role in cervical carcinoma remains unknown. We collected and analyzed the patients' data using the GEPIA Kaplan-Meier plotter databases. CDH19 was overexpressed in cervical carcinoma cells to assess its effect on cell proliferation and activation of AKT and NF-κB signaling pathways. A xenograft mouse model was established to study the function of CDH19 in vivo. We found that CDH19 expression was significantly downregulated in cervical carcinoma tissues compared to adjacent normal tissues. Patients with high expression of CDH19 had a significantly better overall survival rate than those with low CDH19 expression. CDH19 expression was negatively correlated with the expression of the proliferation marker Ki-67, and overexpression of CDH19 significantly inhibited cervical carcinoma cell proliferation. Furthermore, overexpression of CDH19 suppressed the activation of the AKT and NF-κB signaling pathways, and CDH19-overexpressing cervical carcinoma tumors exhibited significantly slower growth in vivo. CDH19 plays an important role in cervical carcinoma by suppressing both cell proliferation and the activation of AKT and NF-κB signaling pathways. Therefore, CDH19 may be a potential therapeutic target for cervical carcinoma.


Cardiac cyclic nucleotides and norepinephrine during neural sympathetic stimulation.
The role of the cardiac cyclic nucleotides, adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP), and norepinephrine (NE) in cardiac responses to stimulation of the left ansa subclavia were studied in anesthetized open-chest dogs. In three groups of dogs undergoing stimulation for 6 min with impulse frequencies of 4, 10, or 20 Hz and 5 V, left ventricular levels of cAMP, cGMP, and NE were determined at the end of the stimulation period and compared to control dogs. A significant elevation in cAMP (avg 67%) was found at all three frequencies. Myocardial NE decreased by an average of 58% from control by the end of the stimulation period, regardless of the stimulation frequency. The rate of left ventricular pressure rise (LV dP/dt) was found to be linearly related to the increase in myocardial cAMP (P less than 0.01) rather than to NE levels found after stimulation. Propranolol administered before ansa subclavia stimulation caused significant decreases in both cAMP and LV dP/dt, whereas the muscarinic agonist carbachol, caused increases in cGMP and NE and a decrease in LV dP/dt accompanied by a nonsignificant decline in cAMP. The elevation in levels of cGMP and NE and the decrease in LV dP/dt to carbachol were blocked with atropine. Results from pretreating dogs with propranolol and carbachol followed by neural sympathetic stimulation indicated the importance of beta-adrenergic and muscarinic receptors in modifying cardiac function through the production of the cyclic nucleotides. Sustained cardiac responses during ansa subclavia stimulation at physiological levels could be related to the accelerated synthesis of endogenous cAMP.


Crop improvement in the 21st century.
Crop yields increased dramatically in the 20th century as recorded on Broadbalk or in world averages. The vast majority of that increase has occurred since the last world war and has been powered by changes in the genetic potential of the crop and in the way in which it has been managed. Nevertheless, the challenge to feed a world population that is likely to rise to 8 billion is formidable, particularly since recent analyses suggest that the rate of increase in yields of several crops may have dropped over the last decade. What are the opportunities to meet this challenge and to continue to improve the yields of our crops? Improvements in agronomy are likely to be more concerned with efficiency and elegance rather than in major breakthroughs. More sophisticated crop protection chemicals designed on the basis of vastly increased screening potentials and (at last?) possibilities of rational design will be supplemented by a battery of decision support systems to aid management choices which can be precisely implemented. Genetic improvement is the area in which to-look for the major breakthroughs. The broad potential of recombinant DNA technology will provide the possibility of both molecular analyses of crop productivity and ways in which it may be possible to improve that productivity. The goal of analysis may be approached in three ways: starting at the beginning by generating complete sequences of the plant genome; starting at the end by genetic analysis of phenotypes using genetic marker technology; or, starting in the middle, by metabolic analysis. Improvements may be obtained by re-assorting what has been achieved through enhanced breeding technologies, by randomly induced change, and by generation of totally new possibilities through biochemical engineering. Examples of all approaches will be given. The onset of genomics will provide massive amounts of information, but the success will depend on using that to improve crop phenotypes. The ability to meet the challenges of the 21st century will depend on the ability to close that 'phenotype gap'.


A passive and programmable 3D paper-based microfluidic pump for variable flow microfluidic applications.
Paper has attracted significant attention recently as a microfluidic component and platform, especially in passive pumping devices due to its porous and uniform absorbing nature. Many investigations on 1D and 2D fluid flows were carried out. However, no experimental work has been reported on the three-dimensional effect in porous geometry to improve pumping characteristics in microchannels. Therefore, in this study, the fluid flow in 3D paper-based passive pumps was investigated in microchannels using cylindrical pumps. The effect of pump diameter, porosity, and programmability was investigated to achieve desired flow variations. The results indicated that the flow rate of water increased with an increase in the diameter and porosity of paper pumps. Maximum flow rates achieved for 14 mm diameter pumps of 0.5 and 0.7 porosities were 5.29 mm3/s (317.4 μl/min) and 6.97 mm3/s (418.2 μl/min), respectively. The total volume of fluid imbibition ranged between 266 and 567 μl for 8 and 14 mm diameter pumps, respectively. Moreover, 3D passive pumps can transport larger volumes of liquid with an improved flow rate, programmability, and control, in addition to being inexpensive and simple to design and fabricate. Most importantly, a single 3D paper pump showed an increasing, decreasing, and constant flow rate all in a single microchannel. With these benefits, the passive pumps can further improve the pumping characteristics of microfluidic platforms enabling a cost effective and programmable point-of-care diagnostic device.


Rabbit model for Chlamydia pneumoniae infection.
A rabbit model was established for Chlamydia pneumoniae infection that may be helpful to understand the pathogenesis of disease in humans. Twelve, pathogen-free, 1-month-old New Zealand White rabbits were inoculated with 1.0 x 10(7) to 5.0 x 10(7) CFU of purified C. pneumoniae (ATCC strain VR 1310) via the nasopharynx (1 rabbit died immediately postinoculation, and 11 were available for study). Five controls were inoculated with the carrier buffer. Ten of the 11 study rabbits demonstrated serological evidence of acute infection (immunoglobulin G antibodies, 1:8 to > 1:16), with the weakest response at 7 days and the strongest response at 28 days, whereas none of the controls showed any seroconversion. Study animals were sacrificed in batches of three, on days 7, 14, 21, and 28, but controls were sacrificed on days 7 and 28. Two-thirds of the animals demonstrated evidence of bronchiolitis and pneumonia on days 7 and 14 and resolution by day 21. Two study rabbits demonstrated, on histology, early and intermediate lesions of atherosclerosis: one animal (day 7) showed the accumulation of foamy macrophages (fatty streak) in the arch of the aorta, and the other animal (day 14) showed spindle cell proliferation of smooth muscle cells (intermediate lesion). Focal periaortitis was seen in the same animal (day 7). C. pneumoniae elementary bodies were demonstrated by immunocytochemical stain in the lungs (n = 2), liver (n = 3), spleen (n = 5), and aorta (n = 2), one of which corresponded to the intermediate lesion. C. pneumoniae was cultured from the lungs (n = 2), liver (n = 2), spleen (n = 2), and aortic arch (n = 1). All histopathological, immunocytochemical, and cultural studies were negative in the controls. Hence, the rabbit provides a useful animal model for the study of C. pneumoniae infection and its complications, particularly atherosclerosis.


High density micromass cultures of embryonic limb bud mesenchymal cells: an in vitro model of endochondral skeletal development.
To study the mechanisms regulating endochondral skeletal development, we examined the characteristics of long-term, high density micromass cultures of embryonic chicken limb bud mesenchymal cells. By culture Day 3, these cells underwent distinct chondrogenesis, evidenced by cellular condensation to form large nodules exhibiting cartilage-like morphology and extracellular matrix. By Day 14, extensive cellular hypertrophy was seen in the core of the nodules, accompanied by increased alkaline phosphatase activity, and the limitation of cellular proliferation to the periphery of the nodules and to internodular areas. By Day 14, matrix calcification was detected by alizarin red staining, and calcium incorporation increased as a function of culture time up to 2 to 3 wk and then decreased. X-ray probe elemental analysis detected the presence of hydroxyapatite. Analogous to growth cartilage developing in vivo, these cultures also exhibited time-dependent apoptosis, on the basis of DNA fragmentation detected in situ by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), ultrastructural nuclear morphology, and the appearance of internucleosomal DNA degradation. These findings showed that cellular differentiation, maturation, hypertrophy, calcification, and apoptosis occurred sequentially in the embryonic limb mesenchyme micromass cultures and indicate their utility as a convenient in vitro model to investigate the regulatory mechanisms of endochondral ossification.


Self-Rated Health Status and Risk of Ischemic Heart Disease in the China Kadoorie Biobank Study: A Population-Based Cohort Study.
Self-rated health (SRH) is a strong predictor of mortality in different populations. However, the associations between SRH measures and risk of ischemic heart disease (IHD) have not been extensively explored, especially in a Chinese population. More than 500 000 adults from 10 cities in China were followed from baseline (2004-2008) through December 31, 2013. Global and age-comparative SRH were reported from baseline questionnaires. Incident IHD cases were identified through links to well-established disease registry systems and the national health insurance system. During 3 423 542 person-years of follow-up, we identified 24 705 incident cases of IHD. In multivariable-adjusted models, both global and age-comparative SRH was significantly associated with incident IHD. Compared with excellent SRH, the hazard ratios for good, fair, and poor SRH were 1.02 (95% confidence interval [CI], 0.98-1.07), 1.32 (95% CI, 1.27-1.37), and 1.76 (95% CI, 1.68-1.85), respectively. Compared with better age-comparative SRH, the hazard ratios for same and worse age-comparative SRH were 1.23 (95% CI, 1.19-1.27) and 1.78 (95% CI, 1.70-1.86), respectively. The associations persisted in all subgroup analyses, although they were slightly modified by study location, education, and income levels. A simple questionnaire for self-assessment of health status was significantly associated with incident IHD in Chinese adults. Individuals and healthcare providers can use SRH measures as a convenient tool for assessing future IHD risk.


Use and misuse of buprenorphine in the management of opioid addiction.
Buprenorphine was approved in late 2004 for the treatment of opioid abuse and dependence in specially trained and certified physicians' offices. At the time of the approval, there was a regulatory concern that given the anticipated wide exposure there would be unexpectedly high levels of abuse in the high-risk population for which it was intended. To assess its abuse potential, the authors recruited more than 1000 individuals seeking treatment for prescription opioid abuse from 100 stand-alone (i.e., self-pay or insurance) drug abuse treatment programs around the country to determine whether they misused buprenorphine in the past 30 days to get high. The results indicate that there was a time-related increase in the number of subjects who used buprenorphine to get high, reaching 30-35 percent of individuals completing a questionnaire in the second quarter of 2006. At this time, it was equivalent to the misuse of methadone, both of which, however, were considerably lower than hydrocodone and oxycodone. Thereafter, the number of individuals using buprenorphine to get high dropped in a near linear fashion to less than 20 percent of those completing a questionnaire in the second quarter of 2007, significantly lower than that for methadone, oxycodone, and hydrocodone. The most likely interpretation of these data is that the poly-substance-abusing population, for whom buprenorphine is intended, experimented with this medication for its mood-altering effects for a period of time, but presumably because of its lack of euphorogenic properties, its use has now dissipated. Additionally, support for this conclusion is the very rare endorsement of buprenorphine as a primary drug (<3 percent of the total sample). Thus, the results indicate that it is unlikely that buprenorphine abuse will ever reach the epidemic that was feared by some regulatory groups and that its use in opioid detoxification and maintenance should continue.


[Electroneurophysiologic studies of patients with reflex syndromes of cervical osteochondrosis].
In 21 patients with reflex syndromes of cervical osteochondrosis aged 24-63 years the authors studied short latent somatosensory evoked potentials (EP) in response to stimulation of the median nerve, the rate of impulse conduction along the efferent fibers of the ulnar and median nerves determined with the help of the P wave. The findings obtained by both methods showed a bilateral (on the side of pain and contralaterally) decrease in the rate of impulse conduction along the ulnar and median nerves. The study of the somatosensory systems by registration of EP on the side of pain revealed an increased amplitude and diminished latency of the P9 component which reflects manifestations of irritation of cervical cerebrospinal nodes.


The effect of two fractions of radiation, delivered in air or in hyperbaric oxygen, on the Fib/T tumour in WHT mice pretreated with a hypoxic gas mixture.
The response of the Fib/T tumour to equal fractions of radiation, spaced by an interval of 24 hours, was determined in tumour-bearing mice that were pretreated either with 8% oxygen for 48 h or with air. An increase in tumour cell kill occurred in the group of animals that received a low oxygen pretreatment. Tumour cell kill was further and significantly increased if mice were retained in the low oxygen environment for the 24-h interval between radiation fractions. Possible explanations for these findings are proposed and discussed. The effect of a 48 h 8% oxygen exposure in modifying the response of the Fib/T tumour to two fractions of radiation, both delivered in hyperbaric oxygen, was also investigated. The low oxygen pretreatment did not significantly alter the tumour response to radiation given under conditions of hyperbaric oxygenation.


Morphological observations and rates of protein synthesis in rat muscles incubated in vitro.
Isolated soleus and extensor digitorum longus muscles from small (40 or 70 g) rats developed a central and substantial (13-57%) loss of glycogen and alpha-glucan phosphorylase activity after incubation for up to 2 h in vitro. The central 'core' of the muscles showed a marked decrease in the rate of protein synthesis. It is suggested that during brief periods of incubation the central core of isolated rat muscles becomes hypoxic, and that consequently the viability of such muscles must be in question.


Electrolyte disturbances in elderly patients with severe diarrhea due to cholera.
The purpose of this clinical study was to evaluate prospectively electrolyte disturbances in elderly patients with severe diarrhea due to cholera. A total of 20 adult (Group I; < 60 yr) and 22 elderly (Group II; > or = 60 yr) patients were studied. In all patients, extracellular fluid (ECF) volume reexpansion was achieved with normal saline at 50 mL/kg per hour. Once a diuresis of 40 mL/h was achieved, intravenous therapy was discontinued and patients' ECF volumes were reexpanded orally with a polyelectrolyte solution. Blood and urine samples were obtained on admission, at the time when adequate diuresis ensued, and after 12 h of oral ECF volume reexpansion. On admission, both groups had severe ECF volume contraction but only mild increases in osmolality (308 +/- 12 and 310 +/- 13 mosmol/kg for Groups I and II respectively; P = NS). Acidemia (pH) was equally severe in both (Group I: 7.13 +/- 0.11; Group II: 7.11 +/- 0.09; P = NS), and the anion gap was comparably increased in both groups (30 +/- 8 and 26 +/- 7 mmol/L for Groups I and II, respectively; P = NS). None of the patients was hypokalemic at the time of admission (Group I: 4.3 +/- 0.5 mmol/L; Group II: 4.5 +/- 0.5 mmol/L; P = NS). Adequate diuresis was achieved at 2.0 +/- 0.7 h in both groups. At the end of the rapid ECF volume reexpansion phase, the anion gap normalized in both groups (Group I: 15.6 +/- 3.7 mmol/L; Group II: 14.4 +/- 2.8 mmol/L; P = NS), and serum potassium concentrations remained normal (Group I: 4.4 +/- 0.4 mmol/L; Group II: 4.1 +/- 0.4 mmol/L; P = NS). We conclude that use of aggressive intravenous hydration with normal saline followed by oral ECF volume reexpansion allows prompt correction of electrolyte abnormalities in adult and elderly patients with severe diarrhea as a result of cholera.


Quantifying the early health status benefits of successful chronic total occlusion recanalization: Results from the FlowCardia's Approach to Chronic Total Occlusion Recanalization (FACTOR) Trial.
Data on the health status benefits of percutaneous coronary intervention for coronary chronic total occlusions (CTOs), a principal indication for the procedure, are lacking. In the FlowCardia Approach to CTO Recanalization (FACTOR) trial, patients (n=125) completed the Seattle Angina Questionnaire (SAQ) at baseline and 1 month after percutaneous coronary intervenion. One-month health status outcomes were compared by multivariable analysis, adjusting for group differences between those whose CTO was successfully and unsuccessfully recanalized. These changes were also analyzed according to baseline symptoms. Procedural success was 55% (n=64) and independently associated with angina relief (difference between those with successful and unsuccessful percutaneous coronary intervention [Delta] in SAQ angina frequency=9.5 points; 95% confidence interval, 1.6 to 17.5; P=0.019), improved physical function (Delta in SAQ physical limitation=13.1 points; 95% confidence interval, 5.1 to 21.1; P=0.001), and enhanced quality of life (Delta in SAQ quality of life [QoL]=20.3 points; 95% confidence interval, 11.9 to 28.6; P<0.001). The benefit of successful percutaneous coronary intervention was greatest in symptomatic patients as compared with asymptomatic patients although statistically significantly so only for QoL (DeltaSAQ angina frequency domain=10.3 versus 4.3 points, P=0.51, Deltaphysical limitation =15.9 versus 6.3 points, P=0.25; DeltaQoL=27.3 versus 8.5 points, P=0.047). Successful CTO recanalization is associated with significant early improvements in patient symptoms, function, and QoL but only among symptomatic patients. Percutaneous treatment of a CTO offers the potential to provide significant health status benefits in symptomatic patients.


Enteropathogenic Escherichia coli enteritis: evaluation of the gnotobiotic piglet as a model of human infection.
The pathogenicity of classical enteropathogenic Escherichia coli strains of human origin was investigated in gnotobiotic piglets. One to two day old piglets in groups of four were infected perorally with approximately 10(8) colony forming units of one of eight enteropathogenic E coli strains or a non-pathogenic control strain. Animals were necropsied 24 or 48 hours after infection and their intestines were subjected to histological examination, quantitative bacterial culture and estimation of lactase activity. Four enteropathogenic E coli strains caused mild to moderate diarrhoea in nine of the 16 piglets inoculated with them. Piglets given two of these strains later became moribund. One enteropathogenic E coli strain caused a severe illness unaccompanied by diarrhoea. Inflammation of the intestinal mucosa occurred with all eight enteropathogenic E coli strains, but not with the control strain. Pathological changes were most pronounced in the distal ileum and colon and adherent bacteria were seen on the surface of the inflamed mucosa. The extent of the inflammatory response in infected piglets for the most part paralleled the severity of the clinical signs, the degree of bacterial colonisation and the reduction in lactase activity. Electron microscopic examination of tissue from piglets infected with three different strains showed that bacterial adherence to the apical plasma membrane of epithelial cells was accompanied by distinctive ultrastructural changes. These included degeneration of the microvillous brush border, together with cupping and pedestal formation of the plasma membrane at sites of bacterial attachment. The same changes have been seen in naturally occurring enteropathogenic E coli diarrhoea in humans and rabbits. The combined clinical and pathological findings indicate that the neonatal gnotobiotic piglet is a suitable model of infection with enteropathogenic E coli.


Ankrd2 in Mechanotransduction and Oxidative Stress Response in Skeletal Muscle: New Cues for the Pathogenesis of Muscular Laminopathies.
Ankrd2 (ankyrin repeats containing domain 2) or Arpp (ankyrin repeat, PEST sequence, and proline-rich region) is a member of the muscle ankyrin repeat protein family. Ankrd2 is mostly expressed in skeletal muscle, where it plays an intriguing role in the transcriptional response to stress induced by mechanical stimulation as well as by cellular reactive oxygen species. Our studies in myoblasts from Emery-Dreifuss muscular dystrophy 2, a LMNA-linked disease affecting skeletal and cardiac muscles, demonstrated that Ankrd2 is a lamin A-binding protein and that mutated lamins found in Emery-Dreifuss muscular dystrophy change the dynamics of Ankrd2 nuclear import, thus affecting oxidative stress response. In this review, besides describing the latest advances related to Ankrd2 studies, including novel discoveries on Ankrd2 isoform-specific functions, we report the main findings on the relationship of Ankrd2 with A-type lamins and discuss known and potential mechanisms involving defective Ankrd2-lamin A interplay in the pathogenesis of muscular laminopathies.


Elevated levels of neopterin in sleep-disordered breathing.
Sleep-disordered breathing (SDB) is increasingly being recognized as an independent risk factor for hypertension and cardiovascular disease. Recent evidence suggests that the maladaptive physiologic response to SDB, particularly cardiovascular effects, may result in part from systemic inflammation. Although abnormal cytokine levels have been documented in SDB, data on whether SDB is associated with cellular activation are limited. Thus, this investigation sought to determine whether neopterin, a marker released by activated macrophages, is increased in SDB. Fifty-five men, free of medical comorbidity, undergoing polysomnography had fasting serum tested for neopterin levels. Multivariable regression methods were used to quantify the association between neopterin and quartiles of the apnea hypopnea index (AHI) while accounting for body mass index, waist circumference, and percentage of body fat. Quartiles of AHI (I: < 3.83 events per hour; II: 3.83 to 11.98 events per hour; III: 11.99 to 36.82 events per hour; IV > 36.82 events per hour) indicated a range from no SDB through severe SDB. Compared to the subjects in the first AHI quartile, serum neopterin levels were higher by 3.0%, 10.9%, and 26.5% in the second, third, and fourth AHI quartiles, respectively (p < 0.001for linear trend). Neopterin levels also were higher in those with greater degree of sleep-related hypoxemia, more stage 1 sleep, and less stage 2 sleep. The results of this study indicate that severity of SDB independently associates with serum levels of neopterin, a marker for macrophage activation that may play an important role in the pathogenesis of SDB-related cardiovascular disease.


Utilization of cardiothoracic surgeons for operative penetrating thoracic trauma and its impact on clinical outcomes.
Large series reporting outcomes for penetrating thoracic trauma have identified injury pattern and injury severity scoring as predictors of poor outcome. However, the impact of surgical expertise on patient outcomes has not been previously investigated. We sought to determine how often board-certified cardiothoracic surgeons are utilized for operative thoracic trauma and whether this has an effect on patient outcomes. A level I trauma center registry was queried between 2003 and 2011. Records of patients undergoing surgery as a result of penetrating thoracic trauma were retrospectively reviewed. Patient demographics, injuries, injury severity, utilization of a cardiothoracic surgical operative consult and outcomes were recorded. Patients operated on by cardiothoracic surgeons were compared with patients operated on by trauma surgeons using stepwise multivariate analyses to determine the factors associated with utilization of cardiothoracic surgeons for operative thoracic trauma and survival. Cardiothoracic surgeons were used in 73.0% of cases (162 of 222) over the study period. The use of cardiothoracic surgeons increased incrementally both overall (38.5% to 73.9%), and for emergent/urgent cases (31.8% to 73.3%). When comparing patients undergoing operation on an emergent/urgent basis by cardiothoracic versus trauma surgeons, there was no significant difference with regard to demographics, mechanism of injury, injury severity scoring, or surgical morbidity. Stepwise logistic regression showed the presence of a cardiothoracic surgeon to be independently associated with survival (odds ratio 4.70; p = 0.019). Use of cardiothoracic surgeons for operative thoracic trauma increased over the study period. Outcomes for severely injured patients with elevated chest injury scores or decreased revised trauma scores may be improved with appropriate operative consultation with a board-certified cardiothoracic surgeon.


Targeted overexpression of the angiogenesis inhibitor thrombospondin-1 in the epidermis of transgenic mice prevents ultraviolet-B-induced angiogenesis and cutaneous photo-damage.
Chronic ultraviolet-B irradiation of the skin results in epidermal hyperplasia, degradation of extracellular matrix molecules, and formation of wrinkles. To characterize the biologic role of the vascular system in the mediation of ultraviolet-B-induced skin damage, we performed quantitative analyses of cutaneous blood vessels of mice after 10 wk of ultraviolet-B irradiation. Skin vascularization was greatly increased after chronic ultraviolet-B exposure with a significant increase of both the number and the size of dermal blood vessels, associated with upregulation of vascular endothelial growth factor expression in the hyperplastic epidermis. To directly study whether inhibition of angiogenesis may diminish ultraviolet-B-induced cutaneous damage, wild-type and transgenic mice with skin-specific overexpression of the endogenous angiogenesis inhibitor thrombospondin-1 were subjected to the same ultraviolet-B irradiation regimen. Ultraviolet-B-irradiated thrombospondin-1 transgenic mice showed a significantly reduced skin vascularization, decreased endothelial cell proliferation, and increased endothelial cell apoptosis rates, compared with wild-type mice. Moreover, dermal photo-damage and wrinkle formation were greatly reduced in thrombospondin-1 transgenic mice. These results reveal an important role of the cutaneous vascular system in mediating ultraviolet-B-induced skin damage and suggest inhibition of angiogenesis as a potential new approach for the prevention of chronic cutaneous photo-damage.


Surface oxidase and oxidative stress propagation in aging.
This report summarizes new evidence for a plasma-membrane-associated hydroquinone oxidase designated as CNOX (constitutive plasma membrane NADH oxidase) that functions as a terminal oxidase for a plasma membrane oxidoreductase (PMOR) electron transport chain to link the accumulation of lesions in mitochondrial DNA to cell-surface accumulations of reactive oxygen species. Previous considerations of plasma membrane redox changes during aging have lacked evidence for a specific terminal oxidase to catalyze a flow of electrons from cytosolic NADH to molecular oxygen (or to protein disulfides). Cells with functionally deficient mitochondria become characterized by an anaerobic metabolism. As a result, NADH accumulates from the glycolytic production of ATP. Elevated PMOR activity has been shown to be necessary to maintain the NAD(+)/NADH homeostasis essential for survival. Our findings demonstrate that the hyperactivity of the PMOR system results in an NADH oxidase (NOX) activity capable of generating reactive oxygen species at the cell surface. This would serve to propagate the aging cascade both to adjacent cells and to circulating blood components. The generation of superoxide by NOX forms associated with aging is inhibited by coenzyme Q and provides a rational basis for the anti-aging activity of circulating coenzyme Q.


Diurnal variability of delta13C and delta18O of atmospheric CO2 in the urban atmosphere of Kraków, Poland.
This article presents the results of measurements of the isotopic composition and concentration of atmospheric carbon dioxide, performed on air samples from Kraków (Southern Poland) in different seasons of the year. A simple isotope mass balance model has been applied to determine the contributions of different sources of CO2 to the urban atmosphere of Kraków city: the latitudinal/regional background, biospheric contributions and anthropogenic emissions. The calculations show that during the summer and early autumn the dominant contribution to local CO2 peaks is the biosphere, making up to 20% of atmospheric CO2 during the nocturnal temperature inversion in the lower troposphere. During early spring and winter, anthropogenic emissions are the main local source.


A salt-activated inositol 1,3,4,5-tetrakisphosphate 3-phosphatase at the inner surface of the human erythrocyte membrane.
The localization of the human erythrocyte membrane Ins(1,3,4,5)P4 3-phosphatase was investigated by saponin permeabilization of resealed 'isoionic' erythrocyte ghosts. This enzyme is active at the inner face of the plasma membrane, at the same site as a specific 5-phosphatase that degrades both Ins (1,4,5)P3 and Ins(1,3,4,5)P4. In the presence of EDTA, Ins(1,4,5)P3 was the only product of Ins(1,3,4,5)P4 metabolism. However, when Mg2+ was present both the 5-phosphatase and the 3-phosphatase attacked Ins (1,3,4,5)P4, directly forming Ins(1,3,4)P3 and Ins(1,4,5)P3;some Ins(1,4)P2 was also formed as a product of 5-phosphatase attack on the liberated Ins(1,4,5)P3. The Ins(1,3,4,5)P4 3-phosphatase was potently activated by KCl, thus making the route of metabolism of Ins(1,3,4,5)P4 by erythrocyte ghosts strikingly sensitive to variations in ionic strength: at 'cytosolic' K+ and Mg2+ levels, 3-phosphatase activity slightly predominated over 5-phosphatase. Ins(1,3,4,5)P4 3-phosphatase was potently inhibited by Ins-(1,3,4,5,6)P5 and InsP6 at levels lower than those often observed within cells. This leaves open the question as to whether the cellular function of inositol polyphosphate 3-phosphatase is to participate in a physiological cycle that interconverts Ins(1,3,4,5)P4 and Ins(1,4,5)P3 or to metabolize other inositol polyphosphates in the cytosol compartment of cells.


Pseudomonas aeruginosa cytotoxin ExoU is injected into phagocytic cells during acute pneumonia.
ExoU, a cytotoxin translocated into host cells via the type III secretion system of Pseudomonas aeruginosa, is associated with increased mortality and disease severity. We previously showed that impairment of recruited phagocytic cells allowed survival of ExoU-secreting P. aeruginosa in the lung. Here we analyzed types of cells injected with ExoU in vivo using translational fusions of ExoU with a beta-lactamase reporter (ExoU-Bla). Cells injected with ExoU-Bla were detectable in vitro but not in vivo, presumably due to the rapid cytotoxicity induced by the toxin. Therefore, we used a noncytotoxic ExoU variant, designated ExoU(S142A)-Bla, to analyze injection in vivo. We determined that phagocytic cells in the lung were frequently injected with ExoU(S142A). Early during infection, resident macrophages constituted the majority of cells into which ExoU was injected, but neutrophils and monocytes became the predominant types of cells into which ExoU was injected upon recruitment into the lung. We observed a modest preference for injection into neutrophils over injection into other cell types, but in general the repertoire of injected immune cells reflected the relative abundance of these cells in the lung. Our results indicate that phagocytic cells in the lung are injected with ExoU and support the hypothesis that ExoU-mediated impairment of phagocytes has a role in the pathogenesis of pneumonia caused by P. aeruginosa.


Interleukin 15 is produced by endothelial cells and increases the transendothelial migration of T cells In vitro and in the SCID mouse-human rheumatoid arthritis model In vivo.
The capacity of endothelial cells (EC) to produce IL-15 and the capacity of IL-15 to influence transendothelial migration of T cells was examined. Human umbilical vein endothelial cells expressed both IL-15 mRNA and protein. Moreover, endothelial-derived IL-15 enhanced transendothelial migration of T cells as evidenced by the inhibition of this process by blocking monoclonal antibodies to IL-15. IL-15 enhanced transendothelial migration of T cells by activating the binding capacity of the integrin adhesion molecule LFA-1 (CD11a/CD18) and also increased T cell motility. In addition, IL-15 induced expression of the early activation molecule CD69. The importance of IL-15 in regulating migration of T cells in vivo was documented by its capacity to enhance accumulation of adoptively transferred human T cells in rheumatoid arthritis synovial tissue engrafted into immune deficient SCID mice. These results demonstrate that EC produce IL-15 and imply that endothelial IL-15 plays a critical role in stimulation of T cells to extravasate into inflammatory tissue.


Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model.
Neuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. Molecular chirality can show an entirely different bio-function by means of chiral-specific interaction. In this study, we report that d-chiral glutathione (D-GSH) suppresses the inflammatory response after SCI and leads to axon regeneration of the injured spinal cord to a greater extent than l-chiral glutathione (L-GSH). After SCI, axon regrowth in D-GSH-treated rats was significantly increased compared with that in L-GSH-treated rats (*** p < 0.001). Secondary damage and motor function were significantly improved in D-GSH-treated rats compared with those outcomes in L-GSH-treated rats (** p < 0.01). Moreover, D-GSH significantly decreased pro-inflammatory cytokines and glial fibrillary acidic protein (GFAP) via inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway compared with L-GSH (*** p < 0.001). In primary cultured macrophages, we found that D-GSH undergoes more intracellular interaction with activated macrophages than L-GSH (*** p < 0.001). These findings reveal a potential new regenerative function of chiral GSH in SCI and suggest that chiral GSH has therapeutic potential as a treatment of other diseases.


Inhibitors of the glyoxylate cycle enzyme ICL1 in Candida albicans for potential use as antifungal agents.
Candida albicans is an opportunistic pathogen that causes candidiasis in humans. In recent years, metabolic pathways in C. albicans have been explored as potential antifungal targets to treat candidiasis. The glyoxylate cycle, which enables C. albicans to survive in nutrient-limited host niches and its. Key enzymes (e.g., isocitrate lyase (ICL1), are particularly attractive antifungal targets for C. albicans. In this study, we used a new screening approach that better reflects the physiological environment that C. albicans cells experience during infection to identify potential inhibitors of ICL. Three compounds (caffeic acid (CAFF), rosmarinic acid (ROS), and apigenin (API)) were found to have antifungal activity against C. albicans when tested under glucose-depleted conditions. We further confirmed the inhibitory potential of these compounds against ICL using the ICL enzyme assay. Lastly, we assessed the bioavailability and toxicity of these compounds using Lipinski's rule-of-five and ADMET analysis.


Can self-inhibitory peptides be derived from the interfaces of globular protein-protein interactions?
In this study, we assess on a large scale the possibility of deriving self-inhibitory peptides from protein domains with globular architectures. Such inhibitory peptides would inhibit interactions of their origin domain by mimicking its mode of binding to cognate partners, and could serve as promising leads for rational design of inhibitory drugs. For our large-scale analysis, we analyzed short linear segments that were cut out of protein interfaces in silico in complex structures of protein-protein docking Benchmark 3.0 and CAPRI targets from rounds 1-19. Our results suggest that more than 50% of these globular interactions are dominated by one short linear segment at the domain interface, which provides more than half of the original interaction energy. Importantly, in many cases the derived peptides show strong energetic preference for their original binding mode independently of the context of their original domain, as we demonstrate by extensive computational peptide docking experiments. As an in depth case study, we computationally design a candidate peptide to inhibit the EphB4-EphrinB2 interaction based on a short peptide derived from the G-H loop in EphrinB2. Altogether, we provide an elaborate framework for the in silico selection of candidate inhibitory molecules for protein-protein interactions. Such candidate molecules can be readily subjected to wet-laboratory experiments and provide highly promising starting points for subsequent drug design.


Regression analysis with covariates that have heteroscedastic measurement error.
We consider the estimation of the regression of an outcome Y on a covariate X, where X is unobserved, but a variable W that measures X with error is observed. A calibration sample that measures pairs of values of X and W is also available; we consider calibration samples where Y is measured (internal calibration) and not measured (external calibration). One common approach for measurement error correction is Regression Calibration (RC), which substitutes the unknown values of X by predictions from the regression of X on W estimated from the calibration sample. An alternative approach is to multiply impute the missing values of X given Y and W based on an imputation model, and then use multiple imputation (MI) combining rules for inferences. Most of current work assumes that the measurement error of W has a constant variance, whereas in many situations, the variance varies as a function of X. We consider extensions of the RC and MI methods that allow for heteroscedastic measurement error, and compare them by simulation. The MI method is shown to provide better inferences in this setting. We also illustrate the proposed methods using a data set from the BioCycle study.


The myosin-interacting protein SMYD1 is essential for sarcomere organization.
Assembly, maintenance and renewal of sarcomeres require highly organized and balanced folding, transport, modification and degradation of sarcomeric proteins. However, the molecules that mediate these processes are largely unknown. Here, we isolated the zebrafish mutant flatline (fla), which shows disturbed sarcomere assembly exclusively in heart and fast-twitch skeletal muscle. By positional cloning we identified a nonsense mutation within the SET- and MYND-domain-containing protein 1 gene (smyd1) to be responsible for the fla phenotype. We found SMYD1 expression to be restricted to the heart and fast-twitch skeletal muscle cells. Within these cell types, SMYD1 localizes to both the sarcomeric M-line, where it physically associates with myosin, and the nucleus, where it supposedly represses transcription through its SET and MYND domains. However, although we found transcript levels of thick filament chaperones, such as Hsp90a1 and UNC-45b, to be severely upregulated in fla, its histone methyltransferase activity - mainly responsible for the nuclear function of SMYD1 - is dispensable for sarcomerogenesis. Accordingly, sarcomere assembly in fla mutant embryos can be reconstituted by ectopically expressing histone methyltransferase-deficient SMYD1. By contrast, ectopic expression of myosin-binding-deficient SMYD1 does not rescue fla mutants, implicating an essential role for the SMYD1-myosin interaction in cardiac and fast-twitch skeletal muscle thick filament assembly.


Is testis-sparing surgery safe in small testicular masses? Results of a multicentre study.
Our goal was to evaluate benign and malignant lesions and testicular intraepithelial neoplasia (TIN) in the neighbouring normal-appearing testis tissue in men who underwent radical orchiectomy for testicular mass with a pathologic tumour size of ≤3cm. In this retrospective, multicentre study, data of 252 patients from 11 different institutions were included. Patients were divided into three groups based on tumour size: Group 1 (0-1 cm; n=35), Group 2 (1.1-2cm; n=99), and Group 3 (2.1-3 cm; n=118). Benign lesions and TIN were sought in the neighbouring testicular tissue and compared between groups. Mean patient age was 32.3 years. Benign lesions were reported in 54.3%, 33.3%, and 14.4% of Groups 1, 2, and 3, respectively (p<0.05 between groups). TIN was detected in 20%, 42.4%, and 41.5% of Groups 1, 2, and 3, respectively (p<0.05 for Group 1 vs. Groups 2 and 3; p>0.05 for Groups 2 vs. 3). Multifocality was detected in 8.6%, 4%, and 0% of Groups 1, 2, and 3, respectively (p<0.05 for both Group 1 vs. Group 3 and for Group 2 vs. Group 3; p>0.05 for Group 1 vs. Group 2). A tumour cutoff size of 1.5 cm was found to be significant for detecting benign tumour. TIN and multifocality rates were similar in patients with a tumour size of ≤1.5 vs. >1.5 cm (p>0.05). Benign lesions and TIN in the neighbouring testis were significantly decreased and multifocality was increased in patients with a tumour mass size of ≤1 cm. Testis-sparing surgery should be performed with caution and a safety rim of normal tissue should also be excised.


[Biology and potential of human embryonic stem cells].
Human embryonic stem cells (hESC) are obtained from the inner cell mass from the early embryo at blastocyste stage. Derived in cell lines for the first time in 1998, they can be maintained in culture in an undifferentiated state indefinitely under certain conditions. Two essential properties characterize hESC: pluripotency and self-renewal. Pluripotency is convey by the expression of specific transcription factors such as OCT4 and NANOG, and is under the control of growth factors such as IGF2 and FGFb. Markers used to characterize these cells include surface antigens, notably SSEA-3 and SSEA-4, and nuclear markers such as OCT4. HESC can differentiate into different cell types in vitro. They represent a unique and essential model for early human development research and for regenerative medicine. By their self-renewal capacity and their potential to differentiate into several cell types, hESC are an unlimited source of cells enabling to replace or restore lost or damaged cells in numerous diseases. Even if it is not conceivable today to use them in clinical practice for ethic and scientific reasons, it seems essential to explore the numerous potentialities of these cells. This knowledge might be relevant to handle adult stem cells in vitro and will be mandatory for a therapeutic use of hESC in the future.


MiR-155 Negatively Regulates Anti-Viral Innate Responses among HIV-Infected Progressors.
HIV infection impairs host immunity, leading to progressive disease. An anti-retroviral treatment efficiently controls viremia but cannot completely restore the immune dysfunction in HIV-infected individuals. Both host and viral factors determine the rate of disease progression. Among the host factors, innate immunity plays a critical role; however, the mechanism(s) associated with dysfunctional innate responses are poorly understood among HIV disease progressors, which was investigated here. The gene expression profiles of TLRs and innate cytokines in HIV-infected (LTNPs and progressors) and HIV-uninfected individuals were examined. Since the progressors showed a dysregulated TLR-mediated innate response, we investigated the role of TLR agonists in restoring the innate functions of the progressors. The stimulation of PBMCs with TLR3 agonist-poly:(I:C), TLR7 agonist-GS-9620 and TLR9 agonist-ODN 2216 resulted in an increased expression of IFN-α, IFN-β and IL-6. Interestingly, the expression of IFITM3, BST-2, IFITM-3, IFI-16 was also increased upon stimulation with TLR3 and TLR7 agonists, respectively. To further understand the molecular mechanism involved, the role of miR-155 was explored. Increased miR-155 expression was noted among the progressors. MiR-155 inhibition upregulated the expression of TLR3, NF-κB, IRF-3, TNF-α and the APOBEC-3G, IFITM-3, IFI-16 and BST-2 genes in the PBMCs of the progressors. To conclude, miR-155 negatively regulates TLR-mediated cytokines as wel l as the expression of host restriction factors, which play an important role in mounting anti-HIV responses; hence, targeting miR-155 might be helpful in devising strategic approaches towards alleviating HIV disease progression.


Several regions in the major histocompatibility complex confer risk for anti-CCP-antibody positive rheumatoid arthritis, independent of the DRB1 locus.
Recent evidence suggests that additional risk loci for RA are present in the major histocompatibility complex (MHC), independent of the class II HLA-DRB1 locus. We have now tested a total of 1,769 SNPs across 7.5Mb of the MHC located from 6p22.2 (26.03 Mb) to 6p21.32 (33.59 Mb) derived from the Illumina 550K Beadchip (Illumina, San Diego, CA, USA). For an initial analysis in the whole dataset (869 RA CCP + cases, 1,193 controls), the strongest association signal was observed in markers near the HLA-DRB1 locus, with additional evidence for association extending out into the Class I HLA region. To avoid confounding that may arise due to linkage disequilibrium with DRB1 alleles, we analyzed a subset of the data by matching cases and controls by DRB1 genotype (both alleles matched 1:1), yielding a set of 372 cases with 372 controls. This analysis revealed the presence of at least two regions of association with RA in the Class I region, independent of DRB1 genotype. SNP alleles found on the conserved A1-B8-DR3 (8.1) haplotype show the strongest evidence of positive association (P ~ 0.00005) clustered in the region around the HLA-C locus. In addition, we identified risk alleles that are not present on the 8.1 haplotype, with maximal association signals (P ~ 0.001-0.0027) located near the ZNF311 locus. This latter association is enriched in DRB1*0404 individuals. Finally, several additional association signals were found in the extreme centromeric portion of the MHC, in regions containing the DOB1, TAP2, DPB1, and COL11A2 genes. These data emphasize that further analysis of the MHC is likely to reveal genetic risk factors for rheumatoid arthritis that are independent of the DRB1 shared epitope alleles.


Vestibular autorotation and electronystagmography testing in patients with dizziness.
One hundred and two patients were evaluated with electronystagmography (ENG) and vestibular autorotation tests (VAT). Results indicate that ENG is the best test in the initial evaluation of the patient whose dizziness is believed to be peripheral in origin; whereas, patients who have sustained head trauma and nondescript dizziness are best evaluated with VAT.


A drive through Web 2.0: an exploration of driving safety promotion on Facebook™.
This study explored Facebook™ to capture the prevalence of driving safety promotion user groups, obtain user demographic information, to understand if Facebook™ user groups influence reported driving behaviors, and to gather a sense of perceived effectiveness of Facebook™ for driving safety promotion targeted to young adults. In total, 96 driving safety Facebook™ groups (DSFGs) were identified with a total of 33,368 members, 168 administrators, 156 officers, 1,598 wall posts representing 12 countries. A total of 85 individuals participated in the survey. Demographic findings of this study suggest that driving safety promotion can be targeted to young and older adults. Respondents' ages ranged from 18 to 66 years. A total of 62% of respondents aged ≤ 24 years and 57.8% of respondents aged ≥ 25 years reported changing their driving-related behaviors as a result of reading information on the DSFGs to which they belonged. A higher proportion of respondents ≥ 25 years were significantly more likely to report Facebook™ and YouTube™ as an effective technology for driving safety promotion. This preliminary study indicates that DSFGs may be effective tools for driving safety promotion among young adults. More research is needed to understand the cognition of Facebook™ users as it relates to adopting safe driving behavior. The findings from this study present descriptive data to guide public health practitioners for future health promotion activities on Facebook™.


[Hemo- and immunostimulating effect of an extract from blood cells of the Central Asian tortoise].
Radiotherapeutic efficacious of the compounds from major organs and tissues of Central Asian tortoise--the animal known for its unique radioresistance, has been checked up. Along with the so well-known compounds as the plasma ones, tortoise spleen extracts (TSE) and the ones from the liver of adult animals and embryos, extracts from kidneys and muscles have been shown to increase the survivability rate of irradiated rats and mice. The compound, that called "Tortezin" shows the highest blood cell cytosol effect. The specific activity and the output are 4 and 12 times higher, than the ones of TSE, respectively. Dose increase factor (DIF) reaches as far as 1.41. The compound possesses considerable immunostimulating activity. The detailed physico-chemical characteristics of the compound, quite sufficient for its identification has been made.


Studying the effects of nucleating agents on texture modification of puffed corn-fish snack.
To improve textural attributes of puffed corn-fish snack, the effects of 1%, 1.5%, and 2% of calcium carbonate, magnesium silicate (talc), sodium bicarbonate as well as 5% and 10% of wheat bran (as the nucleating materials) on textural attributes were studied. Sensory evaluation, bulk density, expansion ratio, maximum force, and count peaks were measured using the Kramer test. The results showed that all of the additives except bran significantly enhanced the texture. Among them, talc at 0.5% was the best to enhance the density and expansion ratio. Effects of using 0.5% talc on puffed corn-fish snack microstructure were studied using scanning electron microscopy. The average cell diameter of 109 ± 48 μm and cell numbers per square centimeter of 67.4 for talc-treated products were obtained, while for nontalc-treated extrudates, average cell diameter of 798 ± 361 μm and cell numbers per square centimeter of 13.9 were found. Incorporation of 0.5% w/w of magnesium silicate reduced (7-fold) the average cell diameter while increased (4-fold) the cell number.


T4-induced RNA ligase joins single-stranded oligoribonucleotides.
RNA ligase isolated from Escherichia coli infected with bacteriophage T4 will catalyze the formation of an intermolecular 3' leads to 5' phosphodiester linkage between an oligoribonucleotide with a free 3'-hydroxyl and another oligoribonucleotide with a 5'-phosphate. Upon reaction with (Ap)5C, nearly quantitative conversion of the hexamer [5'-32P]p(Up)5U to the dodecamer (Ap)5C[3' leads to 5'-32P]p(Up)5U was observed. The product was identified by its mobility on RPC-5 column chromatography, its resistance to alkaline phosphatase, and the appearance of the expected radiolabeled products on hydrolysis with alkali, ribonuclease A, snake venom phosphodiesterase, and spleen phosphodiesterase. The coupling of other pairs of single-stranded oligoribonucleotides has also been demonstrated. The intermolecular joining reaction is probably mechanistically similar to the intramolecular cyclization activity previously reported for Tr RNA ligase. It is expected that this enzyme will be useful for the synthesis of RNA fragments of defined sequence.


[Kinetic properties of alkaline ribonuclease from rat brain].
The rate of hydrolysis of polymeric yeast RNA by highly purified preparation of alkaline RNAse from the post-mitochondrial cellular fraction from the large hemispheres of rat brain was studied. It was shown that the reaction rate is maximal at the substrate concentration of 1-2 mg/ml. The curve of the reaction rate versus substrate concentration was found to be S-shaped. The value of S0,5 was equal to 0,138 mg/ml. The inhibition of alkaline RNAse by its specific protein inhibitor was of a non-competitive type.


Resveratrol protects neurons from cannulae implantation injury: implications for deep brain stimulation.
Brain-implantable electrodes such as those used in deep brain stimulation (DBS) have a promising future in end-stage Parkinson's disease therapy. However, there is considerable injury when electrodes penetrate brain tissue. For instance, broken blood vessels and glial scar formation may impede continual DBS or electrical recording from specific neurons. To begin addressing this key safety issue, we tested the therapeutic potential of resveratrol in reducing brain trauma caused by DBS-like surgery. Microinfusion of resveratrol (10 μM) directly applied to the sub-thalamic nucleus (STN) of the rat brain significantly minimized the formation of astrocytic gliosis in response to a 27-G precision-glide cannula implant. The therapeutic effects of resveratrol extended to the "kill zone", a boundary zone of about 100 μm comprising the cannula implant and surrounding neurons. We also found that resveratrol not only provided almost complete protection from mechanical injury to the brain, but that it also prevented undesirable motor deficits often seen in animals with lesions to the STN. Lastly, continuous infusion of resveratrol over a 4-week period led to the inhibition of pro-apoptotic, neurodegenerative and cell division cycle genes that may be associated with a reduction in astrocytic gliosis and glial scar formation within the STN. Taken together, these data suggest that application of resveratrol to the brain is an effective adjunct surgical procedure for minimizing acute neuronal injury when electrodes are implanted directly into the STN.


Evaluating trauma center structural performance: The experience of a Canadian provincial trauma system.
Indicators of structure, process, and outcome are required to evaluate the performance of trauma centers to improve the quality and efficiency of care. While periodic external accreditation visits are part of most trauma systems, a quantitative indicator of structural performance has yet to be proposed. The objective of this study was to develop and validate a trauma center structural performance indicator using accreditation report data. Analyses were based on accreditation reports completed during on-site visits in the Quebec trauma system (1994-2005). Qualitative report data was retrospectively transposed onto an evaluation grid and the weighted average of grid items was used to quantify performance. The indicator of structural performance was evaluated in terms of test-retest reliability (kappa statistic), discrimination between centers (coefficient of variation), content validity (correlation with accreditation decision, designation level, and patient volume) and forecasting (correlation between visits performed in 1994-1999 and 1998-2005). Kappa statistics were >0.8 for 66 of the 73 (90%) grid items. Mean structural performance score over 59 trauma centers was 47.4 (95% CI: 43.6-51.1). Two centers were flagged as outliers and the coefficient of variation was 31.2% (95% CI: 25.5% to 37.6%), showing good discrimination. Correlation coefficients of associations with accreditation decision, designation level, and volume were all statistically significant (r = 0.61, -0.40, and 0.24, respectively). No correlation was observed over time (r = 0.03). This study demonstrates the feasibility of quantifying trauma center structural performance using accreditation reports. The proposed performance indicator shows good test-retest reliability, between-center discrimination, and construct validity. The observed variability in structural performance across centers and over-time underlines the importance of evaluating structural performance in trauma systems at regular intervals to drive quality improvement efforts.


An investigation of the role of gene copy number variations in sorafenib sensitivity in metastatic hepatocellular carcinoma patients.
Background: Metastatic hepatocellular carcinoma (HCC) is a highly aggressive tumor with limited treatment options. While sorafenib has recently been shown to provide a survival advantage in patients with advanced HCC, the overall outcomes such as time to progression (TTP) and overall survival (OS) ought to be further improved. To that end, several targeted agents aimed at amplified oncogenes such as HER2 and FGFR2 have recently been developed. In this study, we aimed to identify genetic markers in the form of copy number variations (CNVs) that influence clinical outcomes post-sorafenib treatment in advanced HCC patients. Methods: We surveyed 38 metastatic HCC patients who were treated with sorafenib for the presence of CNVs using the NanoString nCounter assay. Results: The median TTP and OS for all patients were 2.7 months (95% confidence interval [CI]: 2.0-3.3 months) and 13.4 months (95% CI: 8.4-18.4 months), respectively. Several genes previously implicated in liver cancer were amplified, including CCND1 (n = 4), CDKN1A (n = 2), KRAS (n = 2), MDM2 (n = 1), and ERBB2 (n = 1). However, we found no correlations between CNVs and survival in our sorafenib-treated patients. Conclusions: The clinical features and biomarkers that account for sensitivity to sorafenib in HCC are complicated and remain unclear. Further investigation to identify predictive biomarkers and therapeutic strategies, including combining sorafenib with other target agents, are warranted.


[Toxicity and dose-response (effect) relationship of n-hexane (author's transl)].
A large amount of n-hexane is being widely used in industry as a solvent or a component of the mixed solvents for extraction of vegetable oils, adhesives, paints, and for cleaning, etc. And, many cases of polyneuropathy due to n-hexane have been reported up to now. Recently, studies on the neurotoxicity and metabolism of n-hexane rapidly progressed in many countries. The present review covers clinical signs and symptoms, pathological changes, metabolism, dose-response (effect) in acute exposure, glue or thinner sniffers, workers, animal experiments. The joint effects and the maximal allowable concentration of n-hexane are also briefly discussed.


Adherence to Diet and Body Weight Recommendations among Cancer Survivors after Completion of Initial Cancer Treatment: A Systematic Review of the Literature.
This systematic review of the literature aimed to 1) provide an overview of the extent to which cancer survivors adhere to diet and body weight recommendations after completion of initial treatment and 2) gain insight into characteristics associated with adherence to these recommendations. Four databases were searched for relevant papers. We included observational studies describing adherence to recommendations on body mass index (BMI), waist-to-hip ratio and waist circumference, fruit and vegetable intake, and alcohol consumption of adult (≥18 yr) cancer survivors after the completion of initial treatment (i.e. surgery, chemotherapy, and radiotherapy). Of the 2,830 articles retrieved from the database search, 12 articles were included. Adherence to the recommendation on BMI varied from 34% to 77%; adherence to the fruit and vegetable recommendation varied from 9% to 83%; and adherence to the recommendation on alcohol consumption varied from 62% to 96.8%. Adherence to waist-to-hip ratio (43%) and waist circumference recommendations (11%) was described in one study among overweight breast cancer survivors. The results of these studies generally suggest that adherence to the recommendation on alcohol intake is relatively high and that adherence to the recommendation on body weight and fruit and vegetable intake should particularly be promoted.


Visual evoked potentials in schizophrenia. Intensity effects and hemispheric asymmetry.
Visual evoked potentials (VEP) to different flash intensities were recorded at a central site (Cz) plus at homologous temporal and occipital locations in normal and unmedicated schizophrenic subjects. Schizophrenic patients showed an hemisphere asymmetry of the P100-N120 peak-trough amplitude with smaller left but larger right hemisphere amplitudes than normal. Further, two subgroups of patients were found with abnormalities lateralized to the left hemisphere. One group was found to have abnormal P100 amplitude-intensity patterns at the left temporal site while the other group showed deviant N120 amplitude-intensity patterns at the left occipital location. The clinical significance of these results can be seen in the higher nuclear schizophrenia (PSE-CATEGO) scores in the left temporal subgroup and the higher hypomania and situational anxiety scores in the left occipital group. Patients also showed slower than normal P100 and N120 peak latencies.


[Dermatophytoses in the urban environment and the coexistence of man with dogs and cats].
There have been submitted to clinical exam in laboratory of dermatophytosis and inquired about possible contact with domestic animals (dogs and cats) 158 patients living in the urban area of Fortaleza, that showed lesions suspected of dermatophytosis. This search associated to the obtained data in questionnaires permitted us to identify the frequency of domicile outbreaks. Within the 83 people with dermatosis isolated of human infections, prevailed the anthropophilic species over the zoophilic ones, and that it was observed a confluence of human and animal diagnosis in 100% of the human dermatophytosis zoophilic cases, where the same species were identified in men and contacting animals: M. canis and T. mentagrophytes. As the patients carrying anthropophilic dermatophytosis varied as to the contact with animals, not having been these fungus isolated from none of the contacting animals. Before the low frequency of zoophilic dermatophytosis, it was considered that the intimacy of men with domestic dogs and cats represented was little as a conditional factor of occurrence of dermatophytosis in the urban environment.


A Multiethnic Study of Pre-Diabetes and Diabetes in LMIC.
Diabetes mellitus is one of the leading causes of death and disability worldwide. Approximately three-quarters of people with diabetes live in low- and middle-income countries, and these countries are projected to experience the greatest increase in diabetes burden. We sought to compare the prevalence, awareness, treatment, and control of diabetes in 3 urban and periurban regions: the Southern Cone of Latin America and Peru, South Asia, and South Africa. In addition, we examined the relationship between diabetes and pre-diabetes with known cardiovascular and metabolic risk factors. A total of 26,680 participants (mean age, 47.7 ± 14.0 years; 45.9% male) were enrolled in 4 sites (Southern Cone of Latin America = 7,524; Peru = 3,601; South Asia = 11,907; South Africa = 1,099). Detailed demographic, anthropometric, and biochemical data were collected. Diabetes and pre-diabetes were defined as a fasting plasma glucose ≥126 mg/dl and 100 to 125 mg/dl, respectively. Diabetes control was defined as fasting plasma glucose <130 mg/dl. The prevalence of diabetes and pre-diabetes was 14.0% (95% confidence interval [CI]: 13.2% to 14.8%) and 17.8% (95% CI: 17.0% to 18.7%) in the Southern Cone of Latin America, 9.8% (95% CI: 8.8% to 10.9%) and 17.1% (95% CI: 15.9% to 18.5%) in Peru, 19.0% (95% CI: 18.4% to 19.8%) and 24.0% (95% CI: 23.2% to 24.7%) in South Asia, and 13.8% (95% CI: 11.9% to 16.0%) and 9.9% (95% CI: 8.3% to 11.8%) in South Africa. The age- and sex-specific prevalence of diabetes and pre-diabetes for all countries increased with age (p < 0.001). In the Southern Cone of Latin America, Peru, and South Africa the prevalence of pre-diabetes rose sharply at 35 to 44 years. In South Asia, the sharpest rise in pre-diabetes prevalence occurred younger at 25 to 34 years. The prevalence of diabetes rose sharply at 45 to 54 years in the Southern Cone of Latin America, Peru, and South Africa, and at 35 to 44 years in South Asia. Diabetes and pre-diabetes prevalence increased with body mass index. South Asians had the highest prevalence of diabetes and pre-diabetes for any body mass index and normal-weight South Asians had a higher prevalence of diabetes and pre-diabetes than overweight and obese individuals from other regions. Across all regions, only 79.8% of persons with diabetes were aware of their diagnosis, of these only 78.2% were receiving treatment, and only 36.6% were able to attain glycemic control. The prevalence of diabetes and pre-diabetes is alarmingly high among urban and periurban populations in Latin America, South Asia, and South Africa. Even more alarming is the propensity for South Asians to develop diabetes and pre-diabetes at a younger age and lower body mass index compared with individuals from other low and middle income countries. It is concerning that one-fifth of all people with diabetes were unaware of their diagnosis and that only two-thirds of those under treatment were able to attain glycemic control. Health systems and policy makers must make concerted efforts to improve diabetes prevention, detection, and control to prevent long-term consequences.


Can Artificial Intelligence aid communication? Considering the possibilities of GPT-3 in Palliative care.
This article reviews the developments in artificial intelligence (AI) technologies and their current and prospective applications in endof-life communications. It uses Open AI's generative pre-trained transformer 3 (GPT-3) as a case study to understand the possibilities of AI-aided communication in Palliative Care. Open AI's GPT-3 was taken as a case study where responses were generated through the GPT-3 beta playground (Davinci engine) and were scrutinised by six mental health professionals (MHPs) working in a palliative care setting in India. They were tasked to evaluate the responses generated by the AI (the identity was not revealed until a part of the study was completed) in a simulated palliative care conversation with another MHP posing as a patient. The aim was to undermine whether the professionals were able to detect that the responses were indeed generated by a machine and did they approve or disapprove of the responses. The GPT-3 playground with the right prompts produced remarkable, often surprising texts and responses that imitated human interaction. However, glitches such as redundancy were noticed along with strongly held opinions in certain questions related to faith, death, and life after death. AI-assisted communication in palliative care could be used to train professionals in the palliative care field using it as a simulation in training. It could also be used as a therapeutic intervention for the purpose of engagement and philosophical dialogue after certain modifications. However, it would have its own limitations such as it cannot replace a human agent just yet.


Operations for lymphoedema of the lower limbs. A study of the results in 108 operations utilizing vascularized dermal flaps.
The results of operations for lymphoedema of the lower limbs have been reviewed. In experienced hands the results are very satisfactory. Modifications of the buried dermis flap operation of Thompson have been found to give the best results in patients where the local skin has been in good condition. The chief complication has been the occurrence of localized areas of necrosis, chiefly at the edges of the flaps. It has not been a serious complication but has sometimes prolonged the stay in hospital. It has been associated with haematoma formation. Methods of avoiding this and other complications are discussed in order to improve results still further. There have been no serious complications and no deaths in this series.


Engineering modified Bt toxins to counter insect resistance.
The evolution of insect resistance threatens the effectiveness of Bacillus thuringiensis (Bt) toxins that are widely used in sprays and transgenic crops. Resistance to Bt toxins in some insects is linked with mutations that disrupt a toxin-binding cadherin protein. We show that susceptibility to the Bt toxin Cry1Ab was reduced by cadherin gene silencing with RNA interference in Manduca sexta, confirming cadherin's role in Bt toxicity. Native Cry1A toxins required cadherin to form oligomers, but modified Cry1A toxins lacking one alpha-helix did not. The modified toxins killed cadherin-silenced M. sexta and Bt-resistant Pectinophora gossypiella that had cadherin deletion mutations. Our findings suggest that cadherin promotes Bt toxicity by facilitating toxin oligomerization and demonstrate that the modified Bt toxins may be useful against pests resistant to standard Bt toxins.


Wavelength-Resolution SAR Ground Scene Prediction Based on Image Stack.
This paper presents five different statistical methods for ground scene prediction (GSP) in wavelength-resolution synthetic aperture radar (SAR) images. The GSP image can be used as a reference image in a change detection algorithm yielding a high probability of detection and low false alarm rate. The predictions are based on image stacks, which are composed of images from the same scene acquired at different instants with the same flight geometry. The considered methods for obtaining the ground scene prediction include (i) autoregressive models; (ii) trimmed mean; (iii) median; (iv) intensity mean; and (v) mean. It is expected that the predicted image presents the true ground scene without change and preserves the ground backscattering pattern. The study indicates that the the median method provided the most accurate representation of the true ground. To show the applicability of the GSP, a change detection algorithm was considered using the median ground scene as a reference image. As a result, the median method displayed the probability of detection of 97 % and a false alarm rate of 0 . 11 / km 2 , when considering military vehicles concealed in a forest.


Repetition-induced changes in BOLD response reflect accumulation of neural activity.
Recent exposure to a stimulus improves performance with subsequent identification of that same stimulus. This ubiquitous, yet simple, memory phenomenon is termed priming and has been linked to another widespread phenomenon called repetition suppression, which is a repetition-induced reduction in human brain activation as measured using fMRI. Here, competing models of the neural basis of repetition suppression were tested empirically. In a backward masking paradigm, we found that effectively masked object stimuli showed repetition enhancement of brain activation instead of suppression. This finding is consistent with an Accumulation model, but is inconsistent with a Suppression model of neural activity. Enhanced activation and the improved behavioral performance usually associated with priming are both explained by a shift in peak latency of the population neural activity elicited during identification.


Conserved plant genes with similarity to mammalian de novo DNA methyltransferases.
DNA methylation plays a critical role in controlling states of gene activity in most eukaryotic organisms, and it is essential for proper growth and development. Patterns of methylation are established by de novo methyltransferases and maintained by maintenance methyltransferase activities. The Dnmt3 family of de novo DNA methyltransferases has recently been characterized in animals. Here we describe DNA methyltransferase genes from both Arabidopsis and maize that show a high level of sequence similarity to Dnmt3, suggesting that they encode plant de novo methyltransferases. Relative to all known eukaryotic methyltransferases, these plant proteins contain a novel arrangement of the motifs required for DNA methyltransferase catalytic activity. The N termini of these methyltransferases contain a series of ubiquitin-associated (UBA) domains. UBA domains are found in several ubiquitin pathway proteins and in DNA repair enzymes such as Rad23, and they may be involved in ubiquitin binding. The presence of UBA domains provides a possible link between DNA methylation and ubiquitin/proteasome pathways.


[One-year combination therapy de novo of adefovir dipivoxil and lamivudine for decompensated cirrhosis related to HBV].
To evaluate the efficacy and potential renal impairment of one-year combination therapy de novo of adefovir dipivoxil (ADV) and lamivudine (LMV) for decompensated cirrhosis related to HBV. A total of 36 patients with decompensated cirrhosis related to HBV, nobody had nucleos(t)ide analogs (NAs) treatment history, were recruited and were divided into two group (control group and observation group) randomly. A monotherapy of LMV (100 mg per day) was selected to individuals in control group (n = 18), in contrast, a combination therapy de novo of ADV (10 mg per day) and LMV (100 mg per day) was applied to those in observation group (n = 18). Basic approaches including liver protection, symptom-driven intervention, and supporting therapy, were given to all of the individuals. A course of one year was applied to all. Liver function, Child-Pugh score, serum creatinine (sCr) level, virological response (VR) rate, and virological breakthrough rate were observed pro- and post- treatment, differences between the two populations were analysed statistically. (1) The averages of gender, age, HBeAg status, HBV viral load, sCr level, and Child-Pugh score were all compatible in the two groups at baseline (P > 0.05 for all). (2) At the endpoint of treatment, none of deaths was reported. Comparing with the status before treatment in each group itself, liver function, Child-Pugh score, and viral load were improved statistically (P < 0.01 for all), especially in observed group (P < 0.01 for all variables, vs control group), as for VR rate, result is significant superior to that of control group too (88.89% vs 66.67% , P < 0.05). (3) Virological breakthrough occurred to none in observed group and three cases (16.67%) in control group, all of them were confirmed to be rtM204V variant in the following detection of direct sequencing. (4) Elevated level of sCr didn't arised at the end of treatment in two groups. Present study reveals that in populations with decompensated cirrhosis related to HBV, one-year combination therapy de novo of ADV and LMV is superior to monotherapy of LMV, and the renal safety is favorable within one year.


Prevalence and associated factors of subclinical atherosclerosis in rheumatoid arthritis at the university hospital of Kinshasa.
Rheumatoid arthritis (RA) is associated with a 5 to 10 years reduction in life expectancy due to premature atherosclerosis. This reduction is the consequence of traditional cardiovascular risk factors (TCRF) as well as systemic inflammation. The aim of the present study was to describe the prevalence and factors associated with subclinical atherosclerosis in RA at the University Hospital of Kinshasa (UHK). Patients with a diagnosis of RA based on the 2010 ACR/EULAR criteria were included in this cross-sectional study from 1 June 2014 to 31 May 2015 at the UHK. RA disease activity was measured using the DAS28-ESR. Active RA was defined by a DAS 28 > 2.6. Severe RA was defined by the presence of extra-articular manifestation, joint erosions on X-rays or HAQ ≥0.5. An assessment of subclinical atherosclerosis was performed by the measurement of the carotid intima-media thickness (cIMT) using two-dimensional ultrasonography. Subclinical atherosclerosis was defined by a cIMT ≥0.9 mm. A diagnosis of atheroma plaque was retained when the cIMT was ≥1.5 mm. The association between subclinical atherosclerosis and potential risk factors was modeled using logistic regression analysis. We recruited 75 patients. The average age was 51.8 ± 14.6 years, with a sex ratio F/M of 4. The prevalence of subclinical atherosclerosis was 32%. In logistic regression being a woman of ≥55 years old (aOR 10.6, 95% CI [2.087-53.82], p = 0.028), DAS28-ESR > 2.6 (aOR 3.5,95% CI [1.55-10.38], p = 0.044), severe RA (aOR 32.6,95% CI [1.761-60.37],p = 0.035), high blood pressure (aOR 22.4,95% CI [5.04-99.41], p = 0.005) and obesity (aOR 32.3, 95% CI [2.606-40.73], p = 0.026) emerged as factors associated with subclinical atherosclerosis. Subclinical atherosclerosis is common in RA patients attending the UHK. It appears to be associated with RA disease activity and severity apart from traditional cardiovascular risk factors. These results suggest that early management of subclinical atherosclerosis targeting remaining RA disease activity and cardiovascular risk factors could slow down progression to clinical cardiovascular disease.


Motor coordination, working memory, and academic achievement in a normative adolescent sample: testing a mediation model.
The aim of the present study was to examine whether the relationship between motor coordination and academic achievement is mediated by working memory (WM) in a normative adolescent sample. Participants included 93 adolescents aged 12-16. The Movement Assessment Battery for Children-2 provided three indicators of motor coordination (Manual Dexterity, Aiming and Catching, and Balance), the WM Index of the Wechsler Intelligence Scale for Children-IV and the N-back paradigm provided two indicators of WM, and the Wechsler Individual Achievement Test-II provided three indicators of academic achievement (Word Reading, Spelling, and Numerical Operations). Structural equation modeling, controlling for verbal comprehension, attention deficit hyperactivity disorder symptoms, and socioeconomic status, suggested that the association between motor coordination and academic achievement may be best understood in terms of a mechanism whereby motor coordination (specifically, Aiming and Catching skills) has an indirect impact on academic outcomes via WM. These findings have important implications for the assessment and treatment of motor coordination and learning difficulties as well as in increasing the understanding of the possible neural mechanisms underpinning the relationship between these areas.


[A retrospective analysis of population type variability of the region V3 gp120 in HIV infected patients with a unified infection focus].
Regions of HIV-1 genome, encoding the V3 gp120 region, were sequenced in materials that were sampled from persons belonging to the category of individuals infected from a single source during the Rostov-Elista outbreak. The samples were obtained in 1991-1992 (10 pieces) and in 2000-2001 (16 pieces), which amounts to 8% and 13%, respectively, of a total number of patients infected by the beginning of 1990. It was established that the level of the population variability of amino-acid sequences in region V3 amounted, in 1991-1992, to 5.2% and increased to 9.1% in the samples of 2000-2001. A comparison of amino-acid sequences in region V3 from the collections of 1991-1992 and of 2000-2001 revealed the below amino-acid substitutions: from Ser13 to His, from Ley14 to Phe, from Phe to Ley and from Ley to Ala. An analysis of V3 B-epitope showed that the basic trend of its evolution consists in reciprocal transitions of L to F in position 14 and of F to L in position 20. Such substitutions ensure further changes at the "top" of the V3-loop from GPG to APG.


Siderophore-mediated iron transport: crystal structure of FhuA with bound lipopolysaccharide.
FhuA, the receptor for ferrichrome-iron in Escherichia coli, is a member of a family of integral outer membrane proteins, which, together with the energy-transducing protein TonB, mediate the active transport of ferric siderophores across the outer membrane of Gram-negative bacteria. The three-dimensional structure of FhuA is presented here in two conformations: with and without ferrichrome-iron at resolutions of 2.7 and 2.5 angstroms, respectively. FhuA is a beta barrel composed of 22 antiparallel beta strands. In contrast to the typical trimeric arrangement found in porins, FhuA is monomeric. Located within the beta barrel is a structurally distinct domain, the "cork," which mainly consists of a four-stranded beta sheet and four short alpha helices. A single lipopolysaccharide molecule is noncovalently associated with the membrane-embedded region of the protein. Upon binding of ferrichrome-iron, conformational changes are transduced to the periplasmic pocket of FhuA, signaling the ligand-loaded status of the receptor. Sequence homologies and mutagenesis data are used to propose a structural mechanism for TonB-dependent siderophore-mediated transport across the outer membrane.