Antibiotic management of methicillin-resistant Staphylococcus aureus--associated acute pulmonary exacerbations in cystic fibrosis.
To review the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-associated acute pulmonary exacerbations (APEs) in cystic fibrosis (CF). A search of PubMed, MEDLINE, Cochrane Library and Clinicaltrials.gov databases through November 2014 was conducted using the search terms Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, pulmonary exacerbations, and cystic fibrosis. All English-language research articles, case reports, and case series were evaluated. A total of 185 articles were identified related to MRSA and CF; 30 articles that studied treatments of MRSA APE in CF were included. The persistent presence of MRSA in the respiratory tract of patients with CF has been associated with higher morbidity and an increased risk of death. Limited clinical data exist supporting the efficacy of any specific antimicrobial currently available for the treatment of APE secondary to MRSA. Data extrapolated from other populations suggest that vancomycin and linezolid are appropriate first-line treatment options for the treatment of APE secondary to MRSA. Second-line options include doxycycline or minocycline and trimethoprim/sulfamethoxazole, each of which may be useful in patients coinfected with other respiratory pathogens, for which they may provide overlapping coverage. Ceftaroline and ceftobiprole are newer antibiotics that appear to have a potential role in the treatment of APE in CF, but the latter is not currently available to the US market. Although potentially useful, clindamycin is limited by high rates of resistance, telavancin is limited by its toxicity profile, and tigecycline is limited by a lack of demonstrated efficacy for infections that are similar to that seen in the CF population. Studies investigating the clinical utility of the above-cited antibiotics for APE in CF secondary to MRSA are desperately needed to broaden the treatment armamentarium for this medical condition.


The evolving ribosome: from non-coded peptide bond formation to sophisticated translation machinery.
Structural analysis supported by biochemical, mutagenesis and computational evidence, revealed that the contemporary ribosome's active site is a universal symmetrical pocket made of ribosomal RNA. This pocket seems to be the remnant of the proto-ribosome, a dimeric RNA assembly evolved by gene duplication, capable of autonomously catalyzing peptide bond formation and non-coded amino acid polymerization.


Effect of a blueberry nutritional supplement on macronutrients, food group intake, and plasma vitamin E and vitamin C in US athletes.
Antioxidants from a blueberry beverage may impact plasma vitamins. We examined vitamins/food selection in 12 college athletes during 30 days compared with placebo. Blood was collected before and after exercise at the beginning of the study (day 1) and then after a 30-day period of taking a daily supplemental beverage (day 30). The six trials involved blood that was drawn pre-beverage ingestion/pre-exercise (trials 1 and 4), post-beverage ingestion/pre-exercise (trials 2 and 5), and post-beverage ingestion/1 h post-exercise (trials 3 and 6), on day 1 (trials 1, 2, and 3) and day 30 (trials 4, 5, and 6). Analysis of variance revealed non-significant differences for macronutrient or gamma-tocopherol and vitamin C intakes by food frequency questionnaire or plasma vitamins by liquid chromatography. There was a trend (P = 0.083) in the group x time interaction for alpha-tocopherol intake by repeated-measures analysis of variance. Blueberry alpha-tocopherol (23.91 +/- 9.31 mg) was significantly (P < 0.05) higher than placebo alpha-tocopherol intake (7.59 +/- 0.95 mg) on day 1, but not on day 30 (blueberry, alpha-tocopherol = 9.04 +/- 2.35 mg, placebo, alpha-tocopherol = 11.46 +/- 3.65 mg) by pairwise comparisons. Blueberry supplementation did not affect plasma vitamin concentrations or gamma-tocopherol and vitamin C intakes, and may reduce alpha-tocopherol intake in those starting with a higher alpha-tocopherol intake, yet not altering athletes' eating habits.


Expert systems for human service programs.
Although computer programs called "expert systems" do not necessarily emulate the heuristics and logic used by human experts, they can consistently produce useful, better-than-average recommendations. Backward and forward reasoning chains have applicability to human service problems in social work, education, and vocational rehabilitation. There is increasing evidence that useful expert systems that do not require exotic languages and machines will soon begin inroads toward their staggering potential for "helping people" in human services make better decisions in matters of eligibility determination, casework quality control, written service plans for clients or students, job placement, service acquisition, policy interpretation, and other concerns.


Electrochemical amphotericity and NIR absorption induced via the step-wise protonation of fused quinoxaline-tetrathiafulvalene-pyrroles.
We describe an effective approach to producing electrochemical amphoteric character and tuning optical properties. Reversible step-wise protonation of quinoxaline annulated TTF-pyrrole derivatives promotes intramolecular electron-transfer and leads to formation of stable, fully charge-separated diradical states. This allows for the creation of low bandgap systems and NIR optical properties.


The challenge of post-operative peritonitis after gastrointestinal surgery.
Post-operative peritonitis (PP) is a life-threatening hospital-acquired intra-abdominal infection with high rates of mortality. Diffuse PP remains a challenge for surgeons. Prognosis and outcome of patients are directly related to early diagnosis and prompt intervention. The diagnosis of PP may be difficult because there are no specific clinical signs and laboratory tests to reject or confirm the diagnosis. Atypical clinical features may be responsible for a delay in reoperation. An early diagnosis and prompt treatment is crucial to prevent the development of organ failure and improve the outcome of the patients with PP. The cornerstones in the management of patients with PP are early hemodynamic support, prompt source control and adequate antimicrobial therapy.


Change of the duodenal mucosa-associated microbiota is related to intestinal metaplasia.
In this study, we aimed to investigate the characteristics of the duodenal mucosal microbiota of patients with intestinal metaplasia (IM) and compare it with those of the gastric mucosal microbiota. We collected the duodenal and gastric mucosal samples from 10 adult patients with IM and 10 healthy controls (HC). The V3-V4 region of the bacterial 16S rRNA gene was examined by high throughput sequencing method. The diversity of the HC duodenal microbiota was higher than that of IM patient based on the Shannon and Simpson index while the Chao indices of IM duodenal mucosal microbiota was significantly higher than that of gastric mucosal microbiota of patients with IM. There was a marked difference in the duodenal microbiota structure between patients with IM and HC (ANOSIM, R = 1, P = 0.001). We also found that the Helicobacter pylori infection in gastric mucosa did not influence the structure of duodenal mucosal microbiota. The gastric mucosal microbiota structure significantly differed between patients with IM and HC who were H. pylori-negative (ANOSIM, R = 0.452, P = 0.042) or H. pylori-positive (ANOSIM, R = 0.548, P = 0.003), respectively. For duodenal mucosal microbiota, genera Lactococcus, Flavobacterium, Psychrobacter, Mysroides, Enhydrobacter, Streptococcus, and Leuconostoc were enriched in patients with IM. In contrast, genera Bacillus, Solibacillus, Lysinibacillus, Exiguobacterium, Oceanobacillus, and Paenibacillus were enriched in HC. A marked dysbiosis duodenal mucosal microbiota in patients with IM was observed, and this dysbiosis might be responsible for IM pathogenesis.


Failed development and vulnerability to climate change in central Asia: implications for food security and health.
This article presents results of research undertaken to identify factors that affect the vulnerability of rural Mongolian herders to climate change. Findings suggest that models of market development instituted since 1990 have failed to recognize and support key elements of the pastoralist adaptive strategy. A retreating state presence has led to the collapse of regulatory regimes needed to safeguard critical common resources. This in turn has produced considerable social differentiation in the countryside, a breakdown in cooperative institutions, and conflicts over water and pasture. In a context of climate change, these changes seriously threaten the sustainability of the rural economy, leading to livelihood insecurity, growing rural poverty, and increasing rates of migration to shantytowns surrounding the capital city of Ulaanbaatar. The newly vulnerable poor are at higher risk for poor health and malnutrition.


The cold pressor test: vascular and myocardial response patterns and their stability.
The purposes of the present study were to compare the cardiovascular response patterns evoked by three versions of the cold pressor test (either forehead stimulation or hand or foot immersion) and to determine the reproducibility of the responses over a 2-week interval. Blood pressure, heart rate, stroke volume, cardiac output, total peripheral resistance, and systolic time intervals were obtained during rest and during the cold pressor test in 42 young men. Across conditions, the pressor response was supported by peripheral resistance increases with concomitant stroke volume decreases. Although the response patterns were generally similar across sites, exceptions were apparent for heart rate. Forehead stimulation was characterized by no significant change in heart rate, whereas limb (hand or foot) immersion was associated with significant heart rate acceleration. The responses elicited by the three cold pressor test conditions were reliable and showed little evidence of attenuation over the test-retest interval.


Statins in the prevention of heart failure after myocardial infarction.
Statin therapy has demonstrated clear reductions in the risk of death and recurrent cardiac events in patients with acute coronary syndrome (ACS) and coronary artery disease. Heart failure after myocardial infarction (MI) is associated with increased in-hospital mortality and worse long-term prognosis. Some controversy exists about the effects of statin therapy on heart failure, although the favorable effects of statin therapy likely reduce the risk of heart failure development after MI and ACS. This article reviews data on statin therapy and the incidence of heart failure after MI, discussing mechanisms, safety, and outcomes.


[Coupling of gas chromatography with single photon ionization time-of-flight mass spectrometry and its application to characterization of compounds in diesel].
A novel analytical method coupling gas chromatography (GC) with single photon ionization time-of-flight mass spectrometry (SPI-TOF MS) has been developed. First of all, a double-wall-tube transfer line was built to combine GC with SPI-TOF MS, which realized seamless connection between GC and SPI ion source. Based on this, standard n-pentadecane and benzene/toluene/xylene standard gas mixtures were used to study important voltage parameters of the ion source. After the optimization of the ion source voltages, pure molecular ion peaks of the analytes were obtained in the mass spectra and qualitative analysis of different kinds of organic compounds were eventually realized rapidly and accurately. At last, GC/SPI-TOF MS was applied to the characterization of volatile and semvolatile organic compounds in diesel and two-dimensional spectra of GC×SPI-TOF MS were obtained. Without complicated spectra interpretation and data processing, volatile and semi-volatile organic compounds in diesel have been classified qualitatively by ion mass-to-charge ratio (m/z) in SPI mass spectra, including aliphatic compounds, aromatic compounds and nitrogen-containing compounds with low concentration such as benzopyrroles. Isomeric compounds in diesel were separated and identified by retention times of chromatographic peaks. The results indicate that the proposed analytical method of GC/SPI-TOF MS is suitable for the characterization of complicated samples such as diesel and environmental pollutants with easy operation and high efficiency.


Diffuse pathways convey efferent activity from rostral pontile pneumotaxic center to medullary respiratory regions.
Studies were undertaken to evaluate the hypothesis that diffuse pathways serve to convey efferent activity from the rostral pontile pneumotaxic center to the respiratory regions of medulla. Activation of respiratory mechanisms within the pneumotaxic center was produced by electrical stimulation. In decerebrate, vagotomized, cerebellectomized, paralyzed and ventilated cats, stimulations of the pneumotaxic center produced a premature termination of activities of both phrenic nerves. Such a termination of neural activities was still obtained following hemisection of the brain stem at the pontomedullary junction either ipsilateral or contralateral to the site of stimulation. Likewise, both phrenic activities were terminated by stimulation of the pneumotaxic center after a midsagittal division of the brain stem from the intercollicular level to the medullary obex. These results demonstrate that efferent pathways from the pneumotaxic center must decussate in both the caudal pons and in the medulla. The finding of diffuse pathways from the pneumotaxic center to the medullary respiratory regions has implications for previous studies which reported a variety of respiratory patterns following a brain stem transection at the pontomedullary junction.


Irreducible compound dorsal dislocations of the proximal interphalangeal joint of the finger.
Three cases of compound irreducible dorsal dislocation of the proximal interphalangeal joint of the finger are reported. The probable mechanism is discussed. The findings warrant the description "volar capsular boutonnière" as the condyles of the proximal phalanx buttonhole, through the volar structures. Open reduction combined with debridement, is the treatment for such compound irreducible dorsal dislocations. Dislocation of the proximal interphalangeal joints of the fingers are common and can usually be reduced by simple traction. Occasionally reduction by closed methods is unsuccessful because of interposition of volar or dorsal soft tissue structures (Lamb 1981). This study reports three cases of compound dorsal dislocation of the proximal interphalangeal joint with volar soft tissue interposition. Such lesions are sparsely mentioned in text books on fractures and hand injuries and hitherto only a few cases have been published (Lamb 1981, Bunnell 1956).


Hippocampal GABAergic interneurons coexpressing alpha7-nicotinic receptors and connexin-36 are able to improve neuronal viability under oxygen-glucose deprivation.
The hippocampal interneurons are very diverse by chemical profiles and rather inconsistent by sensitivity to CI. Some hippocampal GABAergic interneurons survive certain time after ischemia while ischemia-sensitive interneurons and pyramidal neurons are damaged. GABAergic signaling, nicotinic receptors expressing α7-subunit (α7nAChRs(+)) and connexin-36 (Cx36(+), electrotonic gapjunctions protein) contradictory modulate post-ischemic environment. We hypothesized that hippocampal ischemia-resistant GABAergic interneurons coexpressing glutamate decarboxylase-67 isoform (GAD67(+)), α7nAChRs(+), Cx36(+) are able to enhance neuronal viability. To check this hypothesis the histochemical and electrophysiological investigations have been performed using rat hippocampal organotypic culture in the condition of 30-min oxygen-glucose deprivation (OGD). Post-OGD reoxygenation (4h) revealed in CA1 pyramidal layer numerous damaged cells, decreased population spike amplitude and increased pair-pulse depression. In these conditions GAD67(+) interneurons displayed the OGD-resistance and significant increase of GABA synthesis/metabolism (GAD67-immunofluorescence, mitochondrial activity). The α7nAChRs(+) and Cx36(+) co-localizations were revealed in resistant GAD67(+) interneurons. Under OGD: GABAA-receptors (GABAARs) blockade increased cell damage and exacerbated the pair-pulse depression in CA1 pyramidal layer; α7nAChRs and Cx36-channels separate blockades sufficiently decreased cell damage while interneuronal GAD67-immunofluorescence and mitochondrial activity were similar to the control. Thus, hippocampal GABAergic interneurons co-expressing α7nAChRs and Cx36 remained resistant certain time after OGD and were able to modulate CA1 neuron survival through GABAARs, α7nAChRs and Cx36-channels activity. The enhancements of the neuronal viability together with GABA synthesis/metabolism normalization suggest cooperative neuroprotective mechanism that could be used for increase in efficiency of therapeutic strategies against post-ischemic pathology.


X-ray Thomson scattering in warm dense matter at low frequencies.
The low-frequency portion of the x-ray Thomson scattering spectrum is determined by electrons that follow the slow ion motion. This ion motion is characterized by the ion-ion dynamic structure factor, which contains a wealth of information about the ions, including structure and collective modes. The frequency-integrated (diffraction) contribution is considered first. An effective dressed-particle description of warm dense matter is derived from the quantum Ornstein-Zernike equations, and this is used to identify a Yukawa model for warm dense matter. The efficacy of this approach is validated by comparing a predicted structure with data from the extreme case of a liquid metal; good agreement is found. A Thomas-Fermi model is then introduced to allow the separation of bound and free states at finite temperatures, and issues with the definition of the ionization state in warm dense matter are discussed. For applications, analytic structure factors are given on either side of the Kirkwood line. Finally, several models are constructed for describing the slow dynamics of warm dense matter. Two classes of models are introduced that both satisfy the basic sum rules. One class of models is the "plasmon-pole"-like class, which yields the dispersion of ion-acoustic waves. Damping is then included via generalized hydrodynamics models that incorporate viscous contributions.


Local administration of WP9QY (W9) peptide promotes bone formation in a rat femur delayed-union model.
The WP9QY peptide (W9) consists of nine amino acids. It binds to RANKL and blocks RANKL-induced increases in bone resorption and osteoclastogenesis. W9 has a unique effect on the coupling mechanism between osteoclasts and osteoblasts, which promotes bone formation while working to suppress bone resorption. In this study, with the aim of clinical application of W9 for fracture treatment, we aimed to clarify the bone repair-promoting effect of W9 when administered locally to a rat femur model of delayed union. Using Sprague-Dawley rats, a model of delayed union was created in the right femur by cauterizing the periosteum. Injection of W9 (1 mg in 100 μl) or phosphate-buffered saline (PBS) (100 μl) at the fracture site was performed at the operation and every week thereafter until death (sacrifice). The bone union rate was 14% in the PBS group and 57% in the W9 group at 8 weeks postoperatively. The X-ray score of the W9 group was significantly higher than that of the PBS group at 8 weeks postoperatively. When bone morphometry was analyzed by micro-computed tomography (CT), total callus volume (TV) and mineralized callus bone volume (BV) were measured. TV showed no significant difference between the two groups, but BV/TV was significantly higher in the W9 group. This finding suggests that local administration of W9 can promote bone maturation from callus and can be considered to contribute to fracture healing. These results reveal that W9 has an effect on fractures of promoting healing and could be applied as a fracture treatment.


Parent coping behaviors, parent functioning, and infant temperament characteristics.
This study focuses on the relationship between parent coping behaviors, parent functioning, and infant temperament characteristics. One hundred mothers and fathers of two-to three-month-old infants answered a 154-item self-administered questionnaire. The following three parent-coping behavior patterns emerged: (1) seeking social support and self-development; (2) maintaining family integrity; and (3) being religious, thankful, and content. Parents who were depressed, anxious, and had somatic complaints perceived social support and self-development as more helpful and were less focused on maintaining family integrity. Parents who perceived their infant as having a more smiling, laughing temperament, and as a child who cries less, used coping behaviors designed to maintain family integrity; they were more religious, thankful, and content. Parents who were depressed and parents who were anxious saw their infants as less soothable and more distressed when faced with limitations.


Reproductive ecology of the carnivorous plant Pinguicula moranensis (Lentibulariaceae).
The interaction of plants with pollinators can be a determinant of their reproductive fitness. However, information about the pollination biology of carnivorous plants is scarce. To increase knowledge of reproductive ecology of carnivorous plants we focused on Pinguicula moranensis. Specifically, based on the presence of large, zygomorphic and spurred flowers, we predicted higher reproductive fitness in cross-pollinated than in self-pollinated flowers. Within a plot of 51 m2 we characterised the reproductive phenology, including flower lifespan and stigmatic receptivity. We identified pollinators and their movement patterns within the plot. Breeding system was experimentally evaluated using hand-pollination (i.e. autonomous, self- and cross-pollination). Flowers of P. moranensis were visited by long-tongued pollinators, mainly members of the Lepidoptera. Hand-pollination experiments confirmed our prediction and suggest that flower traits might favour cross-pollination. We mainly discuss the implications of the patchy distribution of plants and behaviour of pollinators on gene movement in this plant species, as pollination between genetically related individuals could be occurring.


The pattern of growth and growth retardation of patients with hypophosphataemic vitamin D-resistant rickets: a longitudinal study.
Growth in height of 16 patients (5 boys and 11 girls) with hypophosphataemic rickets (HR) was studied in a longitudinal survey. The data shortly before and during puberty were analysed on the basis of Preece Baines curves, fitted to the original data; for the analysis at the age of 5 years, the original data were used. It appeared that the overall shape of the individual and average growth pattern could be adequately described by the Preece Baines method. The results further showed that from the age of 5 years onwards, average height was approximately two standard deviations below the normal mean for Dutch children. The patients showed a normal pubertal growth spurt which was, in general, insufficient to restore the growth retardation already established before adolescence. The four children who did show catch-up growth between the age of 5 years and adulthood had minimal rachitic lesions. The greater impact of the disease on growth in early childhood than on adolescent growth could be explained by the fact that HR mainly affects the growth of the legs, the major contributor to body size in early childhood. Finally, it was found that the difference between bone age, as determined by the Tanner Whitehouse (TW2)-method, and chronological age was not significant and the adult height in all patients except two could be adequately predicted from bone age and height.


[The value of fractionated exhaled nitric oxide in the diagnosis of asthma-chronic obstructive pulmonary disease overlap syndrome].
Objective: To explore the diagnostic value of fractionated exhaled nitric oxide (FeNO) measurement in patients with asthma-chronic obstructive pulmonary disease(COPD) overlap syndrome (ACOS). Methods: Eighty-one patients with ACOS, 76 patients with asthma, 82 patients with COPD and 39 healthy non-smoking subjects were recruited in the study. Naku Lun breath analyzer was used to measure the level of FeNO in the 4 groups. Pulmonary function was also measured. The ROC curve was used to differentiate ACOS from patients with COPD. The correlation between FeNO and lung function was analyzed with Pearson correlation analysis. Results: The levels of FeNO in asthmatic group, COPD group, ACOS group and healthy group were (102.3±8.2)×10(9,) (23.7±0.6)×10(9,) (50.2±3.2)×10(9,) and (18.5±7.1)×10(9) respectively. Among the former 3 groups, the differences of FeNO were statistically significant (P<0.05). FeNO>29×10(9) was the best cutoff point to differentiate ACOS from COPD; the sensitivity was 80%, specificity was 73%, positive predictive value was 75%, and negative predictive value and accuracy was 79% and 77%. There was no correlation between FeNO and FEV(1)% or FEV(1)/FVC in ACOS, COPD and asthma groups (r=0.12, 0.11, P>0.05; r=0.11, 0.03, P>0.05; r=0.06, 0.08, P>0.05). Conclusion: FeNO is a good marker to help clinicians differentiate ACOS from COPD. FeNO>29×10(9) was the best cutoff point for the identification of patients with ACOS from COPD.


Kinetics of α-glucosidase inhibition by different fractions of three species of Labiatae extracts: a new diabetes treatment model.
Glucosidases are a group of enzymes playing crucial roles in digestion of carbohydrates. Glucosidase inhibitors can reduce carbohydrate digestion rate and have the potential to prevent development of type 2 diabetes. The Labiatae is one of the largest plant families grown globally and many studies that have isolated new pharmaceutical compounds. In folk medicine, some of Labiatae plants such as Zataria multiflora Boiss, Salvia mirzayanii Rech. F. & Esfand, and Otostegia persica Boiss are consumed for the treatment of diabetes. This study investigates the inhibitory effects of different fractions of three mentioned species extracts on α-glucosidase. Ethanol extracts of these plants leaves were fractionated using petroleum ether, chloroform, ethyl acetate, and n-butanol solutions. The duration of this study was 12 months. To measure enzyme inhibition, 5 μL of the enzyme, 20 μL of substrate and samples were used and for evaluation mode of inhibition, constant amounts of α-glucosidase were incubated with rising concentrations of substrate (PNPG). The results revealed that the ethyl acetate fraction of Zataria multiflora (IC50 = 0.35 ± 0.01 mg/mL) and petroleum ether fraction of Salvia mirzayanii (IC50 = 0.4 ± 0.11 mg/mL) were the most potent inhibitors of α-glucosidase in comparison with the other samples and acarbose as the standard (IC50 = 7 ± 0.19 mg/mL). All of the samples exhibited noncompetitive-uncompetitive inhibition. It can be inferred from this study that α-glucosidase inhibitory potential of the studied extracts may be a marker of antidiabetic potential of these extracts.


Orbital pseudotumor: clinical features and outcomes.
To describe the clinical characteristics of orbital pseudotumor, a retrospective analysis was performed on patients with orbital pseudotumor at Siriraj Hospital for ten years. Forty-nine patients (24 males and 25 females; 62 eyes) with a mean age of 43.75 years were included (a mean follow-up of 25 months). Thirty-six patients (73.5%) had unilateral disease. The clinical features were proptosis (79.6%), ocular motor deficit (61.2%), pain (51%), lid swelling or lid mass (44.9%), ptosis (24.5%), and chemosis (18.4%). The most common presenting sign was proptosis (49%). All were treated with corticosteroids with clinical improvement in 40 (81.6%) patients. Ten (83.3%) of 12 patients with visual loss improved with mean recovery time of 10.3 days. Ocular motility recovered in 24 (80%) patients, occurring an average of 17.8 days after initiation of therapy. It is concluded that the clinical features of orbital pseudotumor are varied. Most patients were improved with corticosteroids treatment.


Influence of Systematic Errors in Reference States on Image Quality and on Stability of Derived Information for dc Optical Imaging.
Optical measurements of tissue can be performed in discrete, time-averaged, and time-varying data collection modes. This information can be evaluated to yield estimates of either absolute optical coefficient values or some relative change in these values compared with a defined state. In the case of time-varying data, additional analysis can be applied to define various dynamic features. Here we have explored the accuracy with which such information can be recovered from dense scattering media using linear perturbation theory, as a function of the accuracy of the reference medium that serves as the initial guess. Within the framework of diffusion theory and a first-order solution, we have observed the following inequality regarding the sensitivity of computed measures to inaccuracy in the reference medium: Absolute measures ? relative measures > dynamic measures. In fact, the fidelity of derived dynamic measures was striking; we observed that accurate measures of dynamic behavior could be defined even if the quality of the image data from which these measures were derived was comparatively modest. In other studies we identified inaccuracy in the estimates of the reference detector values, and not to corresponding errors in the image operators, as the primary factor responsible for instability of absolute measures. The significance of these findings for practical imaging studies of tissue is discussed.


[Hepatitis C virus infection in renal-transplant patients].
Chronic hepatitis C virus (HCV) infection is the first cause of liver disease after renal transplantation. The prevalence of HCV infection in dialysis and in renal-transplant patients remains high. Mortality of HCV-positive renal-transplant patients is higher than that of HCV-negative ones. Liver disease and sepsis seem to be the main causes of death. Graft survival is also lower in HCV-positive renal-transplant patients. This seems to be due in part to the occurrence of de novo glomerulopathy. The effect of HCV infection upon liver fibrosis in renal-transplant patients receiving immunosuppressive treatment remains controversial. To date, there is no efficient treatment of HCV infection after renal transplantation. Consequently, it is mandatory to treat by alpha-interferon all HCV-positive/RNA-positive dialysis patients waiting for renal transplantation.


Gene-environment interdependence.
Behavioural genetics was initially concerned with partitioning population variance into that due to genetics and that due to environmental influences. The implication was that the two were separate and it was assumed that gene-environment interactions were usually of so little importance that they could safely be ignored. Theoretical considerations suggested that that was unlikely to be true and empirical findings are now accumulating on the demonstrated and replicated biological interactions between identified common single genetic variants and the operation of environmentally mediated risks. The paper outlines the evidence and considers why it is changing concepts in ways that matter.


Symptoms associated with finding colorectal cancer during colonoscopy.
Patients with an increased risk of having colorectal cancer (CRC) should have priority on the colonoscopy list. To investigate whether presenting symptoms of patients referred for colonoscopy could help in identifying patients with an increased risk of CRC. Between February 2007 and November 2010, random outpatients referred for colonoscopy were asked to fill out a questionnaire with respect to symptoms for which the colonoscopy was performed. Informed consent was obtained to review the colonoscopy and histology reports. Multivariate logistic regression was performed to identify predictors for CRC. In total, 1458 (21%) patients returned the questionnaire, of whom 925 (63.4%) had undergone previous sigmoidoscopy or colonoscopy. CRC was detected in 41 patients (2.8%). Age over 50 years [adjusted odds ratio (aOR) 3.00; 95% confidence interval (CI) 1.30-6.91] and presenting symptoms of rectal blood loss (aOR 4.62; 95% CI 2.31-9.22) and a change in bowel habits (aOR 3.33; 95% CI 1.50-7.40) were associated independently with an increased risk of finding CRC. Previous sigmoidoscopy or colonoscopy (aOR 0.24; 95% CI 0.12-0.49) and fatigue as presenting symptoms (aOR 0.22; 95% CI 0.09-0.56) were associated with a decreased risk of CRC. Weight loss, self-reported anemia, and abdominal pain were not associated with CRC in this study. Patients presenting with rectal blood loss, change in bowel habits, and those older than 50 years of age have an increased risk of a finding of CRC during colonoscopy. We recommend that these risk groups should be prioritized on the colonoscopy list over patients who have undergone a previous endoscopy or who are presenting with fatigue.


[Problematics of fungal infections in the ear].
Fungal infections of the ear are recognised quite rarely, but they make sometimes, for many reasons, very important diagnostic-therapy issue. Cantagion may developes in every elements of the ear, ranging from external ear (external canal ear, sometimes auricle), middle ear (every pneumatic structure) to iner ear (extra ordinary rarely). Every states, which weaken general and punctual immunity (like immunosupression, chemo-sterydotherapy, blood disease, pregnancy and HIV) are circles, which give facilities to invansion. After penetrated organism, course of infections, in case of type of patogens, trim of the patient and localization, can have without symptoms, sharp, chronic or fulminant shape. For the sake of morphological differentiation fungal, in their developing cycle, treatment mycosis recommends serious difficulty, extra factor, which impeds therapy, is a must of prolongely antifungal treatment and repeated (to total elimination) remove hyphae from ear, which stay sometimes even for week. Progress of the mycotic infections ear, remain bacterial infections and is often reason of bad diagnosis and incorrect treatment.


ACTH and adrenal aerobic glycolysis. I: Effects of O-nitrophenylsulphenyl and other ACTH analogues, vasoactive intestinal peptide and human parathyroid hormone(1-34) on lactic acid, steroid and cyclic AMP production by mouse adrenocortical cells.
The structural requirements in the ACTH molecule for evocation of the glycolytic response in suspensions of mouse adrenal cells were investigated by examining the effects of analogues containing modifications at positions 8, 9 and 10 and of peptides containing homologies with the amino-terminal segment of ACTH. Introduction of a nitrophenylsulphenyl (NPS) group into the tryptophan moiety at position 9 of ACTH(1-24) greatly reduced both the potency and the capacity for maximal glycolytic response. It also virtually abolished cyclic AMP formation. In contrast, the capacity for a maximal steroidogenic response remained unimpaired in the NPS derivative, although steroidogenic potency was reduced to 0.4% of that of ACTH(1-24). Replacement of the tryptophan moiety with phenylalanine had intermediate inhibitory effects on glycolysis and steroid output; replacement with alanine virtually abolished both these responses. Replacement of arginine in position 8 with lysine in the Phe9 analogue caused a fifty-fold increase in glycolytic potency, but rendered it steroidogenically inactive. Cyclic AMP production was abolished in the Ala9 analogue and greatly impaired in the Phe9 and Lys8,Phe9 analogues. Replacement of the glycine moiety in position 10 with L-alanine, D-alanine, beta-alanine or alpha-aminoisobutyric acid had little or no effect on steroidogenic or glycolytic capacity, although potency was reduced with all substitutions excepting L-alanine.(ABSTRACT TRUNCATED AT 250 WORDS)


Microdebrider removal of tracheal papilloma via tracheostomy in the child with an obliterated larynx.
In children, recurrent respiratory papillomatosis is the most common benign neoplasm of the airway. The disease frequently involves the larynx and may spread to extralaryngeal sites. Use of a microdebrider has been suggested as a safe and low-cost technique which reduces operating time, compared with laser removal of laryngeal lesions. We describe a technique for using a microdebrider to remove tracheal papillomas when the larynx is obliterated with the disease.


Image Haze Removal via Reference Retrieval and Scene Prior.
Photography of hazy scene typically suffers from low-contrast which degrades the visibility of the scene. The performance of single-image dehazing methods is limited by the priors or constraints. In this paper, we present an effective method for haze removal, which utilizes its retrieved correlated haze-free images as external information. The correlated haze-free images are with scene prior offering scene structure and local high frequency information for dehazing, although variations in viewpoints, scales, and illumination conditions exist. To utilize those reference more effectively, global geometric registration and local block matching toward the hazy input are performed to reinforce the spatial correlations. Based on the registration, different kinds of external information are estimated. In addition, we combine that additional external information with internal constraint and regularization for estimating scene transmission map. Experiments demonstrate that our approach can produce dehazing results with better visual quality compared with other state-of-the-art methods.


Gender-specific prediction of cardiac disease: importance of risk factors and exercise variables.
Current guidelines recommend targeting the intensity of preventive cardiovascular interventions to the level of the patient's risk, which is usually obtained from a global risk score such as the Framingham equations. However, a large proportion of asymptomatic U.S. women (approximately 80-90%) are classified as low risk by the Framingham score, although they have a 1 in 2 chance of dying from cardiovascular disease (CVD) during their lifetime. A promising avenue for improving CVD risk stratification has come from recent studies evaluating the prognostic value of exercise testing in asymptomatic populations using test variables that are not related to exercise-induced ST-segment depression. In particular, it has been shown that 2 easily obtained noninvasive measures, low exercise capacity and slow heart rate recovery, have been linked to increased CVD and all-cause death in both women and men. These 2 simple yet powerful measures of risk that are readily available are useful tools for the practicing cardiologist who desires more accurate assessment of risk in a female patient, particularly if she is deemed as intermediate risk by the Framingham score. In addition, both exercise capacity and heart rate recovery are at least partially modifiable by regular physical activity. Exercise recommendations of at least 30 minutes of moderate physical activity most days of the week have been associated with 30% to 50% reductions in coronary events and coronary mortality and should be recommended to all patients regardless of their Framingham risk score.


Purification of Trichinella spiralis tubulin: comparison of several analytic procedures.
This study compares the purity indices found after purifying tubulin obtained from the nematode parasite Trichinella spiralis, using different chromatographic and electrophoretic methods. Affinity chromatography, using monoclonal antibodies anti-alpha and anti-beta-tubulin fixed to activated Sepharosa 4B-CNBr, yields a tubulin purity of 15%. In contrast, by means of interchange-anionic chromatography using a column of DEAE-Sephadex-A50, we obtained an increase in purity of up to 75%. Finally, with the combined application of preparative electrophoresis and electroelution of proteins in polyacrylamide gels with SDS, we obtained the best results with a purity reaching 90%.


Changing demand for mental health services in the emergency department of a public hospital.
Deinstitutionalization and mainstreaming may have contributed to increased attendance in public emergency departments by people with mental health problems. This study describes changing patterns of attendances by patients with mental health problems to the emergency department (ED) of a public teaching hospital in Adelaide, South Australia. Records from a 10-year period from the ED were examined to identify changes in the number of, and diagnoses for, patients attending for primarily mental health concerns. Admission rates, detention and length of stay (LOS) were also examined in an attempt to identify trends. A tenfold increase in the number of patients attending the ED with primarily mental health problems has occurred over the 10-year period. This is within the context of relatively stable total ED presentations. The increase has been observed in all diagnostic categories although the greatest increase, by percentage, has been for psychotic disorders. A lesser increase was observed for patients presenting with overdose. People presenting with psychotic disorders are also more likely to be detained and admitted. LOS in the ED has also increased along with increasing demand. Reasons for the increased demand are likely multifactorial. While deinstitutionalization and mainstreaming have contributed, the closure of the ED at the local psychiatric hospital does not account entirely for the change. Insufficient community-based mental health services may also contribute to the reasons why people present to the ED and lack of inpatient beds contributes to the increasing LOS experienced in the ED.


Endothelial function predicts progression of carotid intima-media thickness.
Endothelial dysfunction develops early and has been shown to predict the development of clinical complications of atherosclerosis. However, the relationship between early endothelial dysfunction and the progression of arterial disease in the general population is unknown. We investigated endothelial dysfunction, risk factors, and progression of carotid intima-media thickness (cIMT) in late-middle-aged individuals at low to intermediate cardiovascular risk in a prospective study between 1997 and 2005. Brachial artery flow-mediated dilatation and cIMT were measured in 213 nonsmoking British civil servants recruited from a prospective cohort (Whitehall II study). Participants (age, 45 to 66 years) were free of clinical cardiovascular disease and diabetes mellitus. Risk factors and Framingham Risk Score were determined at baseline. cIMT was repeated 6.2+/-0.4 years later. At baseline, age, blood pressure, low-density lipoprotein cholesterol, and Framingham Risk Score correlated with cIMT. However, only flow-mediated dilatation, not risk factors or Framingham Risk Score, was associated with average annual progression of cIMT. This relationship remained significant after adjustment for risk factors whether entered as separate variables or as Framingham Risk Score. Further adjustment for waist circumference, triglycerides, and employment grade had no significant effect. Systemic endothelial function was associated with progression of preclinical carotid arterial disease over a 6-year period and was more closely related to cIMT changes than conventional risk factors. Thus, the relationship between endothelial dysfunction and adverse outcome is likely to be due not only to destabilization of established disease in high-risk populations but also to its impact on the evolution of the atherosclerotic substrate. Flow-mediated dilatation testing provides an integrated vascular measure that may aid the prediction of structural disease evolution and represents a potential short- to intermediate-term outcome measure for evaluation of preventive treatment strategies.


[Role of ciclesonide in asthma therapy].
Ciclesonide is a modern inhaled corticosteroid registered for asthma treatment. It is delivered as an inactive prodrug and undergoes conversion to an active metabolite in the lungs. Ciclesonide has been formulated as an aerosol solution in a metered dose inhaler with hydrofluoralkane which characterizes a high deposition rate over 50%. Lots of clinical trials show that ciclesonide is effective in asthma control in a wide range of doses from 40 do 1280 mug/day in a dose-dependent manner. It reduces the need for systemic corticosteroids. Due to the unique pharmacokinetics, ciclesonide has a favorable safety profile both in the low and in the high doses. It is recommended by GINA in every case when the glucocorticosteroids are indicated, as a drug with reduced local and systemic side effects. This article is a review of clinical trials on efficacy and safety of ciclesonide as the resume of authors' clinical experience.


Effect of calcium on the recovery and distribution of DNA polymerase alpha from cultured human cells.
It was recently reported (Lynch, W. E., Surrey, S., and Lieberman, I. (1975) J. Biol. Chem. 250, 8179-8183) that the extraction of regenerating rat liver in solutions of isotonic sucrose containing 4 mM CaCl2 leads to almost quantitative recovery of DNA polymerase alpha (Weissbach, A., Baltimore, D., Bollum, F., Gallo, R., and Korn, D. (1975) Science 190, 401--402) activity in the purified nuclear compartment. Our application of this method to the isolation of the DNA polymerase activities activities from cultured human epithelial and lymphoblastoid cells has led to substantially different results. We have observed that the inclusion of Ca2+ in either isotonic sucrose or hypotonic aqueous extraction media leads to the irreversible inactivation of the majority, cytoplasmic fraction of DNA polymerase alpha activity and is without quantitative effect on the recovery of the nuclear fraction of this activity.


Accuracy of pulse oximetry during intense exercise under severe hypoxic conditions.
There is a growing need to measure arterial oxygen saturation with a non-invasive method during heavy exercise under severe hypoxic conditions. Although the accuracy of pulse oximetry has been challenged by several authors, it has not been done under extreme conditions. The purpose of this study was to evaluate the accuracy of a pulse oximeter (Satllite. Datex, Finland) during exercise under hypoxic conditions where arterial oxygen saturation was below 75%, simulating exercise at extreme altitude. Ten healthy non-smoking men performed two exercise studies of 30 min under normoxia and under hypoxia on two consecutive days. The exercise intensity was 80% of maximal O2 consumption of VO2max. Arterial oxygen saturation measured by pulse oximetry was corrected (SpO2[corr]) according to previously published equations and was compared to arterial oxygen saturation (SaO2) in blood samples taken simultaneously from the radial artery. Reference arterial saturation values ranged from 57.2 to 97.6% for the whole data set. This data set was split according to low (SaO2 < or = 75%) and high (SaO2 > 75%) SaO2 values. The error of pulse oximetry (SpO2[corr]-SaO2) was 2.05 (0.87)% [mean (SD)] and 1.80 (1.81)% for high and low SaO2 values, respectively. SpO2[corr] and SaO2 were highly correlated (r = 0.93, SEE = 1.81) for low values. During high-intensity constant workload under severe hypoxic conditions, once corrected, pulse oximetry provides an estimate of SaO2 with a mean error of 2%. Thus, the correction previously described for SpO2 values above 75% saturation applies also to SpO2 values in the range of 57-75% during exercise under hypoxic conditions.


Pharmacological preconditioning of ischemic heart disease by low-dose dipyridamole.
Fourteen patients affected with coronary artery disease underwent two consecutive dipyridamole echocardiographic stress tests, in basal conditions and after repeated low doses of intravenous dipyridamole, following the observation that pulse increases in adenosine plasma levels due to repeated intravenous administration of dipyridamole mimic the mechanism of ischemic preconditioning. Echocardiographic, electrocardiographic, haemodynamic parameters, and adenosine plasma levels were measured. After the second test, six patients were completely negative, and in those eight still positive the onset of dyssynergy was delayed.


Mutational analysis of FUS gene and its structural and functional role in amyotrophic lateral sclerosis 6.
Amyotrophic lateral sclerosis 6 (ALS6) is an autosomal recessive disorder caused by heterozygous mutation in the Fused in Sarcoma (FUS) gene. ALS6 is a neurodegenerative disorder, which affects the upper and lower motor neurons in the brain and spinal cord, resulting in fatal paralysis. ALS6 is caused by the genetic mutation in the proline/tyrosine-nuclear localization signals of the Fused in sarcoma Protein (FUS). FUS gene also known as TLS (Translocated in liposarcoma), which encodes a protein called RNA-binding protein-Fus (FUS), has a molecular weight of 75 kDa. In this analysis, we applied computational approach to filter the most deleterious and neurodegenerative disease of ALS6-associated mutation on FUS protein. We found H517Q as most deleterious and disease associated using PolyPhen 2.0, I-Mutant 3.0, SIFT, SNPs&GO, PhD-SNP, Pmut, and Mutpred tools. Molecular dynamics simulation (MDS) approach was conducted to investigate conformational changes in the mutant protein structure with respect to its native conformation. MDS results showed the flexibility loss in mutant (H517Q) FUS protein. Due to mutation, FUS protein became more rigid in nature and might alter the structural and functional behavior of protein and play a major role in inducing ALS6. The results obtained from this investigation would help in the field of pharmacogenomics to develop a potent drug target against FUS-associated neurodegenerative diseases.


A crystal milestone: the structure of regulated Src.
The viral and cellular forms of the Src protein tyrosine kinases take a prototypic role in oncology and signal transduction research, by virtue of being holders of an impressive number of 'firsts'. Our understanding of the biochemistry and physiology of Src has therefore always been used as a reference for our general advancement in the field of protein phosphorylation and growth control. The recent solution of the crystal structure of two members of the Src family represents a milestone in these disciplines and, as usual, provides a general lookout post for developments to come.


UCP-3 expression in skeletal muscle: effects of exercise, hypoxia, and AMP-activated protein kinase.
Uncoupling protein 3 (UCP-3), a member of the mitochondrial transporter superfamily, is expressed primarily in skeletal muscle where it may play a role in altering metabolic function under conditions of fuel depletion caused, for example, by fasting and exercise. Here, we show that treadmill running by rats rapidly (30 min) induces skeletal muscle UCP-3 mRNA expression (sevenfold after 200 min), as do hypoxia and swimming in a comparably rapid and substantial fashion. The expression of the mitochondrial transporters, carnitine palmitoyltransferase 1 and the tricarboxylate carrier, is unaffected under these conditions. Hypoxia and exercise-mediated induction of UCP-3 mRNA result in a corresponding four- to sixfold increase in rat UCP-3 protein. We treated extensor digitorum longus (EDL) muscle with 5'-amino-4-imidazolecarboxamide ribonucleoside (AICAR), a compound that activates AMP-activated protein kinase (AMPK), an enzyme known to be stimulated during exercise and hypoxia. Incubation of rat EDL muscle in vitro for 30 min with 2 mM AICAR causes a threefold increase in UCP-3 mRNA and a 1.5-fold increase of UCP-3 protein compared with untreated muscle. These data are consistent with the notion that activation of AMPK, presumably as a result of fuel depletion, rapidly regulates UCP-3 gene expression.


Recurrence of spontaneous versus medically indicated preterm birth.
Despite the increased tendency of preterm birth to recur, little is known with regard to recurrence risks for spontaneous and medically indicated preterm birth as well as recurrence risks in relation to severity of preterm birth. We examined the recurrence of spontaneous and medically indicated preterm birth. A population-based, retrospective cohort study of births in Missouri (1989 to 1997) was carried out with analyses restricted to women who delivered their first 2 consecutive singleton live births (n = 154,809). Women who experienced spontaneous onset of labor and subsequently delivered preterm (less than 35 weeks) were classified as spontaneous preterm birth. Medically indicated preterm birth included women who delivered preterm through a labor induction or a prelabor cesarean delivery. Risk and odds ratio of preterm birth recurrence were derived from fitting multivariate conditional logistic regression models after adjusting for potential confounders. If the first pregnancy resulted in a spontaneous preterm birth, then affected women were more likely to deliver preterm spontaneously (adjusted odds ratio 3.6, 95% confidence interval 3.2, 4.0) and also as a medically indicated preterm birth (odds ratio 2.5, 95% confidence interval 2.1, 3.0) in the second birth. Similarly, if the first pregnancy resulted in a medically indicated preterm birth, affected women were 10.6-fold (95% confidence interval 10.1, 12.4) more likely to deliver preterm because of medical indications in the second pregnancy as well as preterm spontaneously (odds ratio 1.6, 95% confidence interval 1.3, 2.1). The greatest risk of recurrence of preterm birth in the second pregnancy tended to occur around the same gestational age as preterm birth in the first pregnancy, regardless of the clinical subtype. The observation that spontaneous preterm birth is not only associated with increased recurrence of spontaneous but also medically indicated preterm birth and vice versa, suggests that the 2 clinical subtypes may share common etiologies.


Assessment of factors influencing blood pressure control in a managed care population.
We attempted to determine the percentage of patients meeting Health Plan Employer Data Information Set (HEDIS) criteria for blood pressure control (< or = 140/90 mm Hg), to identify factors contributing to differences in blood pressure control among those who met HEDIS criteria and those who did not, and to assess compliance with blood pressure management recommendations established by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) for diabetes mellitus and myocardial infarction. In this retrospective analysis, we randomly selected 502 patient records from three primary care clinics in southeast Michigan. All patients were commercial members of one health maintenance organization, 74% of whom met HEDIS criteria for blood pressure control. These patients took fewer blood pressure drugs throughout the year (p=0.023) and had lower antihypertensive drug costs than those who did not achieve HEDIS blood pressure goals (p=0.016). According to JNC-VI criteria, 46% of diabetic patients were at their blood pressure goal of below 130/85 mm Hg and 71.6% were managed with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Eighty-five percent of patients were taking beta-blockers after myocardial infarction. The percentage of patients achieving target blood pressure exceeded the national average and was associated with few antihypertensive drugs and low drug cost. Effective and appropriate management of blood pressure in people with diabetes remains a challenge.


Cellular mechanisms of adaptive myelination: bridging the gap between animal studies and human cognition.
Voelker and colleagues propose that we may illuminate learning-associated phenomena such as generalization by considering white matter plasticity. Consistent with this idea, human neuroimaging studies reveal learning-induced changes in adult white matter. Animal studies reveal that some forms of learning induce, and are dependent on, generation of new oligodendrocytes. Nevertheless, it remains unclear which alterations to myelin structure are most relevant to learning, and humans and rodents may profoundly differ in their capacity for oligodendrogenesis in adulthood. A full understanding of these issues will be critical to appreciating the role of adaptive myelination in human neuroplasticity.


Proton MR spectroscopy of normal breasts: Association of risk factors for breast cancer with water and lipid composition of the breast.
To investigate the water and lipid composition of normal women breasts on proton MR spectroscopy ((1)H-MRS), and the association of breast cancer risk factors with (1)H-MRS parameters. Three groups of participants were included: group 1, women without a family history of breast cancer (n=49); group 2, women with at least one affected first-degree relative (n=77); group 3, contralateral normal breasts of women with newly diagnosed unilateral breast cancer (n=84). (1)H-MRS parameters were shown below: water fraction 1 (WF1)=(water integral)/(water integral+integral for methylene peak); lipid line width for methylene resonance (LW1) and lipid line width for methyl peaks (LW2) were measured. The association of breast cancer risk factors - age, breast density, body mass index (BMI), menopausal status, group with (1)H-MRS parameters - was analyzed by multiple linear regression. In age-adjusted multiple linear regression, breast density was positively associated with WF1 (P=0.009, 0.001, and <0.001 for groups 1, 2, and 3, respectively). BMI was inversely associated with LW1 in groups 1 (P=0.040) and 3 (P=0.005). In group 3, premenopausal breasts had lower LW2 than their postmenopausal counterparts (P=0.033). Group 3 had narrower LW2 than group 2 (P=0.007). The risk factors for breast cancer were associated with (1)H-MRS parameters.


[HTLV1 infection and pregnancy].
We report an epidemiological study with an analysis of the risk factors of the HTLV-1 seroprevalence in pregnant women and their children in the town of St Laurent du Maroni, French Guyana. HTLV-1 seroprevalence and risk associated factors were first studied in all the pregnant women having delivered at St. Laurent between July 1991 and June 1993. Then, a retrospective analysis was performed in the children, aged between 18 months and 12 years old, born from HTLV-1 infected mothers, focusing especially on the duration of breast feeding and the level of HTLV-1 anti body titers and proviral load. The global HTLV-1 seroprevalence was 4.4% (75/1727) but it was more prevalent among ethnic groups of African origin such as the Noir Marron population (5.5%) and Haitians (6.3%). In the Noir-Marron population, which represents 70% of the studied population, HTLV-1 seropositivity was associated with a maternal age of>35 years, prior miscarriage, prior cesarean section, parity>4, gravidity>6 and negative rhesus factor. After logistic regression, HTLV-1 seropositivity remained associated with gravidity>6 and negative rhesus factor. Out of the 216 children born from 81 HTLV-1 infected mothers, only 21 were found to be HTLV-1 seropositive, giving a crude HTLV-1 transmission rate of 9.7% while among the 180 breast-fed children 10.6% were HTLV-1 seropositive. HTLV-1 seropositivity in children was associated with elevated maternal anti HTLV-1 antibody titer, high maternal HTLV-1 proviral load and child's gender, girls being more frequently HTLV-1 infected than boys. HTLV-1 infection, which can be responsible for severe pathologies in adults (adult T cell leukemia and tropical spastic paraparesis/HTLV-1 associated myelopathy) should be screened during pregnancy in women originating from high HTLV-1 endemic areas, as for France, mainly the French West Indies, French Guyana and Intertropical Africa. In case of HTLV-1 seropositivity, mothers should be informed on the risk of transmission and promotion of bottle feeding of their children should be strongly proposed.


Circular RNA expression profiles during the differentiation of human umbilical cord-derived mesenchymal stem cells into cardiomyocyte-like cells.
So far, there were no reports on circular RNA (circRNA) expression profiles in the differentiation of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) into cardiomyocyte-like cells induced by 5-aza. In this study, hUCMSCs were isolated from umbilical cords and induced with 5-aza for 14 days. Immunofluorescence staining, real-time reverse transcription polymerase chain reaction (RT-PCR), and western blot of cardiac troponin I and α-sarcomeric actin on hUCMSCs between Days 14 and 0 were performed. The expression profile of circRNAs was analyzed by microarray and validated with RT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were performed to identify the functions of differentially expressed genes and related pathways. The connections between circRNAs and microRNAs were explored by using Cytoscape. The results showed that a total of 226 circRNAs were calculated as differentially expressed during the differentiation. Among them, 127 were upregulated and 99 were downregulated. We selected circRNAs that were upregulated by more than five-fold and downregulated by more than three-fold. Ultimately, 74 differentially expressed circRNAs that were highly conserved on Day 14 after induction compared to Day 0 were identified. Among them, 41 were upregulated and 33 were downregulated. Four upregulated circRNAs (circRNA_01536, circRNA_04411, circRNA_09169, and circRNA_09905) and four downregulated circRNAs (circRNA_00699, circRNA_01183, circRNA_01978, and circRNA_16804) were randomly confirmed by RT-PCR. GO analysis suggested a number of cell proliferation and differentiation related physiological processes and pathways, such as the Wnt signaling pathway and others. Network analysis uncovered three potential key circRNAs, that is, circRNA_05432, circRNA_08441, and circRNA_01536.


Digest: Does sexual conflict complicate a trade-off between fecundity and survival?
Why do some species exhibit apparently suboptimal combinations of life history traits? In a comparative study of lizard species, Reedy et al. test the idea that variation in the trade-off between fecundity and survival can be explained by sexual conflict. Their results show that degree of sexual conflict alone cannot explain this variation, and they found a positive correlation between trade-off optimality and the size of males relative to females. These findings suggest a more complicated picture of the fecundity-survival trade-off, possibly involving a third, unknown source of selective pressure.


Only-child and non-only-child exhibit differences in creativity and agreeableness: evidence from behavioral and anatomical structural studies.
Different family composition and size inevitably make only-children different from non-only-children. Previous studies have focused on the differences in behaviors, such as cognitive function and personality traits, between the only-child and the non-only-child. However, there are few studies that have focused on the topic of whether different family environments influence children's brain structural development and whether behavior differentially has its neural basis between only-child and non-only-child status. Thus, in the present study, we investigated the differences in cognition (e.g., intelligence and creativity) and personality and the anatomical structural differences of gray matter volume (GMV) using voxel-based morphometry (VBM) between only-children and non-only-children. The behavioral results revealed that only-children exhibited higher flexibility scores (a dimension of creativity) and lower agreeableness scores (a dimension of personality traits) than non-only-children. Most importantly, the GMV results revealed that there were significant differences in the GMV between only-children and non-only-children that occurred mainly in the brain regions of the supramarginal gyrus, which was positively correlated with flexibility scores; the medial prefrontal cortex (mPFC), which was positively correlated with agreeableness scores; and the parahippocampal gyrus. These findings may suggest that family environment (i.e., only-child vs. non-only-child), may play important roles in the development of the behavior and brain structure of individuals.


Bioresorbable β-TCP-FeAg nanocomposites for load bearing bone implants: High pressure processing, properties and cell compatibility.
In this paper, the processing and properties of iron-toughened bioresorbable β-tricalcium phosphate (β-TCP) nanocomposites are reported. β-TCP is chemically similar to bone mineral and thus a good candidate material for bioresorbable bone healing devices; however intrinsic brittleness and low bending strength make it unsuitable for use in load-bearing sites. Near fully dense β-TCP-matrix nanocomposites containing 30vol% Fe, with and without addition of silver, were produced employing high energy attrition milling of powders followed by high pressure consolidation/cold sintering at 2.5GPa. In order to increase pure iron's corrosion rate, 10 to 30vol% silver were added to the metal phase. The degradation behavior of the developed composite materials was studied by immersion in Ringer's and saline solutions for up to 1month. The mechanical properties, before and after immersion, were tested in compression and bending. All the compositions exhibited high mechanical strength, the strength in bending being several fold higher than that of polymer toughened β-TCP-30PLA nanocomposites prepared by the similar procedure of attrition milling and cold sintering, and of pure high-temperature sintered β-TCP. Partial substitution of iron with silver led to an increase in both strength and ductility. Furthermore, the galvanic action of silver particles dispersed in the iron phase significantly accelerated in vitro degradation of β-TCP-30(Fe-Ag) nanocomposites. After 1month immersion, the composites retained about 50% of their initial bending strength. In cell culture experiments, β-TCP-27Fe3Ag nanocomposites exhibited no signs of cytotoxicity towards human osteoblasts suggesting that they can be used as an implant material.


Clinic and 24h blood pressure in elderly treated hypertensives with postural hypotension.
The objectives of this study were to determine the prevalence of, and factors associated with, postural hypotension (PH) in elderly treated hypertensive subjects, to examine the 24h BP profile in those subjects with and without PH and to determine the effects of antihypertensive treatment withdrawal on the prevalence and symptoms of PH. Eighty-six subjects (mean age +/- standard deviation 76 +/- 6 years) on antihypertensive drug therapy for > 6 months had three clinic BP measurements taken in supine and standing positions followed by 24h ambulatory BP monitoring. Forty-seven subjects underwent repeat BP measurement five weeks after withdrawal of antihypertensive medication and institution of standard nonpharmacological methods. Twenty-six (30%) of the 86 subjects exhibited PH (defined as SBP fall on standing > or = 20 mmHg) within three minutes of standing. Supine clinic and 24h SBP and DBP, age and presence of previous cardiovascular events were similar in the groups with and without PH. There was a significant correlation between the orthostatic BP fall for all subjects and day-night SBP difference (r = -0.30, P = 0.01) and urinary sodium:creatinine ratio (r = -0.33, P = 0.04). Multiple regression analysis revealed only the day-night SBP difference was a significant predictor of orthostatic BP change. In the PH group, 19 subjects had treatment withdrawn resulting in a reduction of 58% (P > 0.001) in those continuing to demonstrate PH. If indicated a trial of antihypertensive drug treatment withdrawal could reduce the risk of PH; the additional benefit of instituting nonpharmacological therapy in reducing BP and orthostatic hypotension warrants further assessment.


Evaluation of a perforated drug delivery system in mice for prolonged and constant release of a hydrophilic drug.
A drug delivery system (DDS) consisting of a perforated microtube (polyimide, inside diameter = 1.8 mm, tube length = 20 mm, hole size = 0.15 mm) was characterized in vitro and in vivo for its usefulness for long-term release of hydrophilic drugs at a constant rate. Sodium fluorescein mixed with stearic acid was used as the model drug. The DDS was packed with sodium fluorescein and stearic acid in ratios of 50:50, 40:60, and 25:75, respectively, and in vitro drug release studies were performed in saline. Linear release rates with R (2) > 0.9700 were obtained for all groups. Release rates of 1,077.3 ± 264.6, 342.6 ± 146.4, and 14.4 ± 7.0 μg/day for sodium fluorescein were obtained from the three groups, respectively. After monitoring the in vitro release of fluorescein for 11 days, 7 tubes from the 40:60 group were implanted subcutaneously in each individual mice to study the in vivo release of fluorescein from the tubes by measuring the fluorescein in the urine for 84 days. An initial rapid release during the first 4 days was followed by a near zero order fluorescence from the tubes (R (2) = 0.9870). Following completion of the study, the DDSs were retrieved for histology. Morphological analysis indicated no clinical adverse reaction at the site of device implantation specific to the device. The DDS was found to be biocompatible and capable of long-term constant release of a hydrophilic drug such as sodium fluorescein.


Recent advances towards identification of new drug targets for Mycobacterium tuberculosis.
Mycobacterium tuberculosis is a very successful pathogen that remains a leading infectious killer worldwide. The global situation has become precarious due to various factors such as the variable efficacy of the Bacille Calmette-Guerin (BCG) vaccine, drug resistance, delay in diagnosis, association with HIV, and other factors, creating a long-lasting reservoir of impending disease and infection. Surprisingly, no new drugs have been developed in the past 30 years. The release of the complete genome sequence of M. tuberculosis and the availability of advanced genetic tools have provided the powerful repertoire of potential drug targets that are now in hand and can be explored in a more rational and directional manner. In this review, the authors highlight some possible therapeutic targets in M. tuberculosis. The gene products involved in various processes, such as mycobacterial cell wall synthesis, ability to acquire or obtain essential nutrients, persistence, transcription regulation, energy metabolism and others, such as the PE-PGRS family and culture filtrate proteins, would be potential targets for the development of new drugs. Apart from these categories, the importance of signal transduction events in the virulence of mycobacteria is discussed in relation to their potential as therapeutic targets. The potential of all of these therapeutic targets should be investigated together with the potential of being able to synthesise future chemotherapeutic agents.


Scimitar syndrome in neonates: report of four cases and review of the literature.
Four neonates with scimitar syndrome are presented. Three of the cases had congenital cardiovascular abnormalities not usually regarded as part of the scimitar syndrome, namely, ventricular septal defect, abnormalities of the aortic arch, and abnormal relationship of the pulmonary arteries and bronchi. Review of the literature indicates that among subjects of all ages the incidence of additional congenital heart disease is 24%; in patients within the pediatric age group the incidence is about 36% and is highest (75%) among those subjects having diagnostic studies while neonates.


Mesenchymal stem cells support migration, extracellular matrix invasion, proliferation, and survival of endothelial cells in vitro.
We investigated effects of the paracrine factors secreted by human mesenchymal stem cells (hMSCs) on endothelial cell migration, extracellular matrix invasion, proliferation, and survival in vitro. Human mesenchymal stem cells were cultured as a monolayer or as three-dimensional aggregates in hanging drops (hMSC spheroids). We performed analysis of paracrine factors in medium conditioned by a monolayer of hMSCs and hMSC spheroids. Concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor, angiogenin, procathepsin B, interleukin (IL)-11, and bone morphogenic protein 2 were increased 5-20 times in medium conditioned by hMSC spheroids, whereas concentrations of IL-6, IL-8, and monocyte hemoattractant protein-1 were not increased. Concentrations of VEGF and angiogenin in medium conditioned by hMSC spheroids showed a weak dependence on the presence of serum, which allows serum-free conditioned medium with elevated concentrations of angiogenic cytokines to be obtained. Medium conditioned by hMSC spheroids was more effective in stimulation of umbilical vein endothelial cell proliferation, migration, and basement membrane invasion than medium conditioned by a monolayer of hMSCs. This medium also promotes endothelial cell survival in vitro. We suggest that culturing of hMSCs as three-dimensional cellular aggregates provides a method to concentrate proangiogenic factors secreted by hMSCs and allows for reduction of serum concentration in conditioned medium. Our data support the hypothesis that hMSCs serve as trophic mediators for endothelial cells. Disclosure of potential conflicts of interest is found at the end of this article.


Induced resistance to 6-methylpurine and cycloheximide in Tetrahymena. II. Variation within vegetative cultures of micronucleate T. thermophila and amicronucleate T. pyriformis.
Resistance to 6-methylpurine and cycloheximide has been induced in both the micronucleate species Tetrahymena thermophila and the amincronucleate species T. pyriformis. Resistance follows only after mutagen treatment and vegetative growth. The frequencies with which resistant variants are induced and the independence of mutagenesis and selection are demonstrated. All evidence is consistent with the hypothesis that macronuclear subunits are assorting in both species during vegetative growth to produce new phenotypes among subclones.


Lack of melatonin action on testosterone production by superfused rat interstitial cells.
The direct effect of increasing doses of melatonin (10(-8) to 10(-5) M) on testosterone production by superfused rat interstitial cells was studied. A constant basal testosterone output was observed for approximately 3 h after the initial high release. A continuous hypothalamo-pituitary stimulation induced a rapid testosterone response reaching peak values in 40-60 min, then decreasing progressively. Basal testosterone release was not modified by 20 or 140 min melatonin infusions. Furthermore, melatonin induced no alteration of the stimulative testosterone response when directly infusing the cells. This study demonstrates that melatonin in vitro has no direct effect on testosterone production by adult rat interstitial cells. It would seem, therefore, that the well known inhibitory influence of melatonin on rat reproductive function is not produced by a direct effect on Leydig cells.


Postexercise heart rate recovery accelerates in strength-trained athletes.
The left ventricle morphologically adapts to endurance exercise training (eccentric cardiac remodeling) and strength exercise training (concentric remodeling). In addition, the acceleration of vagally mediated heart rate (HR) recovery after exercise is one of the functional adaptations of the heart in endurance-trained humans. However, the effect of strength training on HR recovery is unclear. The purpose of this study was to investigate whether postexercise HR recovery accelerates in strength-trained athletes. Subjects were young strength-trained athletes (ST; N = 12), endurance-trained athletes (ET; N = 12), and age-matched sedentary control men (C; N = 12). HR and oxygen uptake were measured during submaximal exercise (cycling exercise, 40% maximal oxygen uptake for 8 min) and 30 s after the exercise (the postexercise period). Left ventricular end-diastolic dimension was higher in both types of athletes compared with C, but greater in ET than in ST (C, 4.3 +/- 0.1 cm; ET, 5.0 +/- 0.1 cm; ST, 4.8 +/- 0.1 cm). Left ventricular average wall thickness was greater in ST in comparison with ET, although it was higher in both trained men compared with C (C, 0.85 +/- 0.02 cm; ET, 0.90 +/- 0.02 cm; ST, 1.00 +/- 0.02 cm). The time constant of postexercise HR decay, an index of vagally mediated postexercise HR recovery, was lower in ST and ET compared with C (C, 94.4 +/- 9.2 s; ET, 65.9 +/- 4.3 s; ST, 69.1 +/- 4.0 s). Oxygen pulse was greater in ST and ET than in C (C, 9.4 +/- 0.6 mL per beat; ET, 13.0 +/- 0.9 mL per beat; ST, 12.8 +/- 0.4 mL per beat), and it results in increased oxygen debt for both types of athletes (C, 0.257 +/- 0.024 L; ET, 0.343 +/- 0.030 L; ST, 0.331 +/- 0.017 L). We did not find significant differences in these indices between ST and ET. These results suggest that the HR recovery immediately after exercise is accelerated in both strength- and endurance-trained athletes.


An evolutionary theory of large-scale human warfare: Group-structured cultural selection.
When humans wage war, it is not unusual for battlefields to be strewn with dead warriors. These warriors typically were men in their reproductive prime who, had they not died in battle, might have gone on to father more children. Typically, they are also genetically unrelated to one another. We know of no other animal species in which reproductively capable, genetically unrelated individuals risk their lives in this manner. Because the immense private costs borne by individual warriors create benefits that are shared widely by others in their group, warfare is a stark evolutionary puzzle that is difficult to explain. Although several scholars have posited models of the evolution of human warfare, these models do not adequately explain how humans solve the problem of collective action in warfare at the evolutionarily novel scale of hundreds of genetically unrelated individuals. We propose that group-structured cultural selection explains this phenomenon.


Effect of temperature shift on levels of acidic charge variants in IgG monoclonal antibodies in Chinese hamster ovary cell culture.
During the production of therapeutic monoclonal antibodies (mAbs), not only enhancement of mAb productivity but also control of quality attributes is critical. Charge variants, which are among the most important quality attributes, can substantially affect the in vitro and in vivo properties of mAbs. During process development for the production of mAbs in a Chinese hamster ovary cell line, we have observed that an improvement in mAb titer is accompanied by an increase in the content of acidic charge variants. Here, to help maintain comparability among mAbs, we aimed to identify the process parameters that controlled the content of acidic charge variants. First, we used a Plackett-Burman design to identify the effect of selected process parameters on the acidic charge variant content. Eight process parameters were selected by using a failure modes and effects analysis. Among these, temperature shift was identified from the Plackett-Burman design as the factor most influencing the acidic charge variant content. We then investigated in more detail the effects of shift temperature and temperature shift timing on this content. The content decreased with a shift to a lower temperature and with earlier timing of this temperature shift. Our observations suggest that Plackett-Burman designs are advantageous for preliminary screening of bioprocess parameters. We report here for the first time that temperature downshift is beneficial for effective control of the acidic peak variant content.


Genetic characterization of high-level gentamicin-resistant strains of Enterococcus faecalis in Iran.
The prevalence of resistance to high levels of gentamicin among 182 isolates of Enterococcus faecalis from 2 Iranian hospitals was 42%. Gentamicin resistance was associated with conjugative plasmids (>70 kb) in most strains. Fingerprinting using EcoRI and HindIII showed genetic variation among these plasmids and gave evidence of nosocomial outbreaks and persistence of infection in different wards of the study hospitals, as well as transfer of plasmids between genetically diverse isolates. Using EcoRI, hospital-based specific plasmid fingerprints were detected for the isolates that had previously proved to be unrelated by multilocus enzyme electrophoresis, suggesting the persistence of related plasmids at each hospital, though minor changes in these related plasmids could be detected with HindIII.


Tomato-oleoresin supplement prevents doxorubicin-induced cardiac myocyte oxidative DNA damage in rats.
Doxorubicin (DOX) is an efficient chemotherapeutic agent used against several types of tumors; however, its use is limited due to severe cardiotoxicity. Since it is accepted that reactive oxygen species are involved in DOX-induced cardiotoxicity, antioxidant agents have been used to attenuate its side effects. To determine tomato-oleoresin protection against cardiac oxidative DNA damage induced by DOX, we distributed Wistar male rats in control (C), lycopene (L), DOX (D) and DOX+lycopene (DL) groups. They received corn oil (C, D) or tomato-oleoresin (5mg/kg body wt. day) (L, DL) by gavage for a 7-week period. They also received saline (C, L) or DOX (4mg/kg body wt.) (D, DL) intraperitoneally at the 3rd, 4th, 5th, and at 6th week. Lycopene absorption was checked by HPLC. Cardiac oxidative DNA damage was evaluated by the alkaline Comet assay using formamidopyrimidine-DNA glycosylase (FPG) and endonuclease III (endo III). Cardiomyocyte levels of SBs, SBs FPG and SBs Endo III were higher in rats from D when compared to other groups. DNA damage levels in cardiomyocytes from DL were not different when compared to C and L groups. The viability of cardiomyocytes from D or DL was lower than C or L groups (p<0.01). Lycopene levels (mean+/-S.D.nmol/kg) in saponified hearts were similar between L (47.43+/-11.78) and DL (49.85+/-16.24) groups. Our results showed: (1) lycopene absorption was confirmed by its cardiac levels; (2) DOX-induced oxidative DNA damage in cardiomyocyte; (3) tomato-oleoresin supplementation protected against cardiomyocyte oxidative DNA damage.


Anti-inflammatory and antioxidant properties of jervine, a sterodial alkaloid from rhizomes of Veratrum album.
Veratrum, hellebore is an important plant species of the Liliaceae family and jervine is the characteristic steroidal alkaloid constituent of Veratrum album. In the current study, anti-inflammatory and antioxidant effects of jervine isolated from NH4OH-benzene extract of V. album rhizomes were investigated on CAR induced paw edema in rats. In inflammatory study, 50, 100, 200 and 400 mg/kg doses of jervine, 25 mg/kg doses of DIC and IND were orally administered, and the volume of the foots were measured up to their knee arthrosis by plethismometer. After one hour of the oral administration of the all treatments, 0.1 ml of CAR solution (1%) was injected into the foot of the all rat groups and the volume of the foots were measured during 5 h after CAR injection. GPx, SOD, GR, MPO, CAT enzymes activities and GSH, LPO levels of the supernatants of paw homogenates and inflammation biomarkers such as TNF-α and IL-1β in the rats serums were also estimated. According to the present results, jervine exerted 50.4-73.5% anti-inflammatory effects in carrageenan induced paw edema. Inflammation biomarkers such as TNF-α, IL-1β and MPO that increased by CAR injection were suppressed by the administrations of all doses of jervine, IND and DIC. In all paw tissues, LPO levels as indicator of oxidative tissue damage were found to be high in CAR-treated group and it was found to be decreased in all doses of jervine. Jervine, DIC and IND reduced the negative effects of CAR due to increasing effects on the SOD, CAT, GSH, GPx and GR antioxidants.


How do peers promote social inclusion of children with disabilities?A mixed-methods systematic review.
This mixed-methods systematic review synthesized findings from studies published between January 1, 2006 and July 31, 2018 on the social inclusion experiences of children with and without disabilities, as viewed from their own perspective, with a focus on how typically developing peers promote social inclusion. Forty-five studies met the inclusion criteria. Data from included studies were synthesized by means of content analysis. The findings detail the inner social inclusion experiences (e.g., feeling included, different) of children with disabilities and provide information regarding the influence of disability type (e.g., physical, social, affective) on typically developing peers' responses (e.g., acceptance vs. rejection), peers' explanations for social inclusion/exclusion, and peers' relationships with children with disabilities. Barriers to social inclusion, supports, as well as strategies used to promote social inclusion, as perceived by peers and children with disabilities, are also reported. The findings of this review provide evidence that despite society's efforts to promote social inclusion, children with disabilities continue to report feeling lonely and excluded, having limited contact socially outside of home, and encountering systemic barriers (e.g., bullying, discrimination). More research on the social inclusion experiences of children with disabilities beyond educational settings is needed, such as in the contexts of recreation and leisure, community, and employment. Implications for rehabilitation The perspectives of children with and without disabilities need to be integrated in activities and programs aimed at promoting social inclusion. Teaching social inclusion strategies to children with and without disabilities is needed to help them deal with barriers. In addition to educational settings, rehabilitation clinicians need to promote social inclusion strategies in other contexts such as recreation and leisure, community, and employment contexts.


Review article: the benefits of pharmacogenetics for improving thiopurine therapy in inflammatory bowel disease.
Thiopurines represent an effective and widely prescribed therapy in inflammatory bowel disease (IBD). Concerns about toxicity, mainly resulting from a wide inter-individual variability in thiopurine metabolism, restrict their use. Optimal thiopurine dosing is challenging for preventing adverse drug reactions and improving clinical response. To review efficacy and toxicity of thiopurines in IBD. To provide pharmacogenetic-based therapeutic recommendations. We conducted a query on PubMed database using 'inflammatory bowel disease', 'thiopurine', 'azathioprine', '6-mercaptopurine', 'TPMT', 'pharmacogenetics', 'TDM', and selected relevant articles, especially clinical studies. Thiopurine metabolism - key enzyme: thiopurine S-methyltransferase (TPMT) - modulates clinical response, as it results in production of the pharmacologically active and toxic metabolites, the thioguanine nucleotides (6-TGN). Adjusting dosage according to TPMT status and/or metabolite blood levels is recommended for optimising thiopurine therapy (e.g. improving response rate up to 30% or decreasing haematological adverse events of 25%). Other enzymes or transporters of interest, as inosine triphosphatase (ITPase), glutathione S-transferase (GST), xanthine oxidase (XO), aldehyde oxidase (AOX), methylene tetrahydrofolate reductase (MTHFR) and ATP-binding cassette sub-family C member 4 (ABCC4) are reviewed and discussed for clinical relevance. Based on the literature data, we provide a therapeutic algorithm for thiopurines therapy with starting dose recommendations depending on TPMT status and thereafter dose adjustments according to five metabolite profiles identified with therapeutic drug monitoring (TDM). This algorithm allows a dosage individualisation to optimise the management of patients under thiopurine. Furthermore, identification of new pharmacogenetic biomarkers is promising for ensuring maximal therapeutic response to thiopurines with a minimisation of the risk for adverse events.


Oxidative damage to catalase induced by peroxyl radicals: functional protection by melatonin and other antioxidants.
Thermal decomposition by the azo initiator 2,2' azobis(2-amidinopropane) dihydrochloride (AAPH) has been widely used as a water-soluble source of free radical initiators capable of inducing lipid peroxidation and protein damage. Here, in a lipid-free system, AAPH alone (40 mM) rapidly induced protein modification and inactivation of the enzyme catalase (EC 1.11.1.6). Using SDS-PAGE, it was shown that protein band intensity is dramatically reduced after 4 h of incubation with AAPH, leading to protein aggregation. Several antioxidants including melatonin, glutathione (GSH) and trolox prevented catalase modification when used at a 250 microM concentration whereas ascorbate was only effective at 1 mM concentration. All the antioxidants tested reduced carbonyl formation although melatonin was the most effective in this regard. Enzyme inactivation caused by AAPH was also significantly reduced by the antioxidants and again melatonin was more efficient than the other antioxidants used in this study. Results shown here demonstrate that alkyl peroxyl radicals inactivate catalase and reduce the effectiveness of cells to defend against free radical damage; the damage to catalase can be prevented by antioxidants, especially melatonin.


Isolation of leptospires from a one week dead coypu (Myocastor coypus Molina).
The isolation of L. Interrogans from a one week dead coypu is reported. The isolate was identified as a pathogenic strain of leptospira belonging to the Icterohaemorrhagiae serogroup.


[The effect of stimulation of the orbitofrontal cortex on the activity of the bulbar respiratory neurons and on respiration in normal rats and in hypoxia].
Stimulation of the orbito-frontal cortex inhibited activity of bulbar expiratory, inspiratory and reticular (non-respiratory) neurons. The first phase of hypoxia generated facilitatory influence of cerebral activating structures, whereas the second phase led to a contrary effect (depression). Subcortical activating structures, however, retained some of their facilitatory influence thus maintaining the oxygen homeostasis of the organism.


Cloning and biochemical characterization of a glucosidase from a marine bacterium Aeromonas sp. HC11e-3.
By constructing the genomic library, a β-glucosidase gene, with a length of 2,382 bp, encoding 793 amino acids, designated bgla, is cloned from a marine bacterium Aeromonas sp. HC11e-3. The enzyme is expressed successfully in the recombinant host Escherichia coli BL21 (DE3) and purified using glutathione affinity purification system. It shows the optimal activity at pH 6, 55 °C and hydrolyzes aryl-glucoside specially. Ca(2+), Mn(2+), Zn(2+), Ba(2+), Pb(2+), Sr(2+) can activate the enzyme activity, whereas SDS, EDTA, DTT show slight inhibition to the enzyme activity. Homologous comparing shows that the enzyme belongs to glycosyl hydrolase family 3, exhibiting 46 % identity with a fully characterized glucosidase from Thermotoga neapolitana DSM 4359. Such results provide useful references for investigating other glucosidases in the glycosyl family 3 as well as developing glucosidases using in suitable industrial area.


New perspectives on the immunology of chronic mucocutaneous candidiasis.
Chronic mucocutaneous candidiasis is a primary immune deficiency presenting as an inability to clear fungal infections and consequently as persisting and recurring infections of the skin and mucous membranes with yeasts, mostly Candida albicans. Chronic mucocutaneous candidiasis is a heterogeneous clinical syndrome which usually presents in childhood and can have an autosomal recessive, dominant or sporadic mode of inheritance. Most chronic mucocutaneous candidiasis patients also develop accompanying endocrine and inflammatory disorders that suggest an underlying deregulation of the immune system. It has long been recognized that protection from mucocutaneous candidiasis relies on cell-mediated immunity and studies on animal models have highlighted the essential role of type 1 cytokines in protection against Candida spp. Recent data in patients with chronic mucocutaneous candidiasis have documented altered patterns of cytokine production in response to Candida spp. with decreased production of some but not all type 1 cytokines and increased levels of interleukin-10. The defect underlying altered cytokine production remains unknown but studies are in progress addressing the putative role of dendritic cells and pattern recognition receptors in directing cytokine responses. These novel insights into immune mechanisms responsible for protection against Candida spp. are opening new possibilities of immunomodulation and vaccination that could prove beneficial in the management of chronic mucocutaneous candidiasis.


Tim-4 Inhibits NLRP3 Inflammasome via the LKB1/AMPKα Pathway in Macrophages.
Nonalcoholic fatty liver disease (NAFLD), characterized by excessive inflammation and lipid deposition, is one of the most common metabolic liver diseases. The expression of NLRP3 inflammasome in macrophages is significantly increased in NAFLD, and its activation aggravates NAFLD greatly. Tim-4, as the phosphatidylserine (PS) receptor, is expressed highly in macrophages, and macrophage Tim-4 inhibits inflammation under various conditions of immune activation. However, the precise role of Tim-4 in NLRP3 inflammasome regulation and NAFLD pathogenesis remains completely unknown. Using NAFLD mice models, we confirmed that the expression of Tim-4 was increased in liver tissues by Western blot, real-time PCR, immunohistochemistry, and immunofluorescence, especially higher expression in liver macrophages, and Tim-4 knockout mice displayed more severe liver inflammation and hepatic steatosis than controls in NAFLD mice model. In vitro, we found that Tim-4 could inhibit NLRP3 inflammasome activation, and the inhibition was dependent on PS binding domain in the IgV domain. Mechanistically, Tim-4 induced the degradation of NLRP3 inflammasome components through activating AMPKα-mediated autophagy. Specifically, Tim-4 promoted AMPKα phosphorylation by interacting with LKB1 and AMPKα. In addition, PS binding motif was responsible for Tim-4-mediated AMPKα and LKB1 interaction. In conclusion, NAFLD microenvironments upregulate Tim-4 expression in macrophages, and elevated Tim-4, in turn, suppresses NLRP3 inflammasome activation by activating LKB1/AMPKα-mediated autophagy, thereby ameliorating the release of IL-1β and IL-18. Collectively, this study unveils the novel function of Tim-4 in suppressing NLRP3 inflammasome, which would shed new lights on intervention of NAFLD or inflammatory liver diseases by targeting Tim-4.


Congenital malaria--Nassau County, New York, 2004.
Human malaria is a parasitic disease caused by four distinct species of intraerythrocytic protozoa of the genus Plasmodium. The parasites are transmitted to persons by the bite of an infective female Anopheles mosquito and rarely through blood transfusion and congenital transmission. The majority of malarial infections reported in the United States are acquired abroad by recent immigrants or persons returning from areas where malaria is endemic. This report describes the first documented case of congenital malaria acquired in Nassau County, New York, which is the fifth case of congenital malaria reported in the United States since 2000. Health-care providers should consider malaria as a diagnosis in neonates and young infants, particularly those with fever, whose mothers emigrated from areas where malaria is endemic.


New evidence on the link between genes, psychological traits, and political engagement.
We investigate the link between genes, psychological traits, and political engagement using a new data set containing information on a large sample of young German twins. The TwinLife Study enables us to examine the predominant model of personality, the Big Five framework, as well as traits that fall outside the Big Five, such as cognitive ability, providing a more comprehensive understanding of the underpinnings of political engagement. Our results support previous work showing genetic overlap between some psychological traits and political engagement. More specifically, we find that cognitive ability and openness to experience are correlated with political engagement and that common genes can explain most of the relationship between these psychological traits and political engagement. Relationships between genes, psychological traits, and political engagement exist even at a fairly young age, which is an important finding given that previous work has relied heavily on older samples to study the link between genes, psychological traits, and political engagement.


Identification and characterization of N-acetylglucosamine-6-O-sulfate-specific beta1,4-galactosyltransferase in human colorectal mucosa.
6-Sulfo-sialyl Lewis X structure is attributable to recognition between lymphocytes and high endothelial venules. However, the biosynthetic pathway still remains unclear. We found that a beta-galactosyltransferase (betaGalT) in human colorectal mucosa preferentially acts on GlcNAc-6-O-sulfate (6S-GN). 6S-GN:beta4GalT was partially purified by UDP-hexanolamine-Sepharose and asialo-agalacto-ovomucin-Sepharose chromatographies. The optimum pH of this enzyme was found to be 6.5-7.5 and the Michaelis constants for 6S-GN and UDP-Gal were 0.43 mM and 16 microM, respectively. The enzymatic activity was dependent on divalent cations and the substrate specificity was not affected by alpha-lactalbumin. This is the first demonstration of the occurrence of 6S-GN:beta4GalT.