Epidemiological, clinical, and therapeutic features of typhoid intestinal perforation in a rural environment of Burkina Faso.
The aim of this study was to describe the epidemiological, clinical, and therapeutic features of ileal perforation due to typhoid fever at the regional hospital of Tenkodogo (Burkina Faso). This cross-sectional study examined the records over a 5-year period of all patients treated for typhoid ileal perforation. Ileal perforation was diagnosed intraoperatively, and its typhoid origin determined according to the following criteria : background signs of typhoid fever, location of the perforation on the antimesenteric edge of the terminal ileum, and a positive Widal-Felix serology. The study included 216 patients. Their mean age was 13.8 years, and 63.4% were male. The average time to consultation was 11 days. Clinical signs were mainly abdominal pain, vomiting, and abdominal tenderness. Anemia was observed in 135 patients (62.5%). All patients underwent laparotomy. Three procedures for treating surgical perforation were used : excision and suture of the perforation in 86 patients (39.8%), ileal resection with anastomosis in 98 (45.4%), and ileostomy with subsequent recovery in 32 (14.8%). The average length of hospital stay was 16.1 days. Postoperative complications occurred in 156 patients (72.2%). Thirty-seven patients died, for a mortality rate of 17.1 %. Ileal perforations due to typhoid fever are the main cause of peritonitis in rural areas of Burkina Faso. Patients are relatively young, and most are anemic at admission. Morbidity and mortality are significant.


Nucleotide sequence of the glycoprotein gene of viral haemorrhagic septicaemia (VHS) viruses from different geographical areas: a link between VHS in farmed fish species and viruses isolated from North Sea cod (Gadus morhua L.).
RT-PCR methods have been applied to the detection and sequencing of the glycoprotein gene of viral haemorrhagic septicaemia virus (VHSV), the rhabdovirus which causes viral haemorrhagic septicaemia (VHS) in farmed salmonid fish. Phylogenetic analysis of a 360 nt region of the glycoprotein gene from a range of marine and fresh water VHSV isolates identified three genogroups, I-III. Significantly, two virus isolates recovered from ulcerated North Sea cod caught off the Shetland Islands, and an isolate recovered from diseased turbot farmed on the island of Gigha, Scotland were assigned to the same genogroup. Moreover, a virus isolated from diseased turbot farmed on the Baltic Sea coast shared 99.4% nucleotide sequence similarity with a virus associated with a VHS outbreak in rainbow trout. This is the first time that a genetic link between a VHS outbreak and natural VHSV infections of marine fish species has been demonstrated.


Purification and some properties of a medium-chain acyl-thioester hydrolase from lactating-rabbit mammary gland which terminates chain elongation in fatty acid synthesis.
1. An acyl-thioester hydrolase was isolated from the cytosol of lactating-rabbit mammary gland. The purified enzyme terminates fatty acid synthesis at medium-chain (C8:0-C12:0) acids when it is incubated with fatty acid synthetase and rate-limiting concentrations of malonyl-CoA. These acids are characteristic products of the lactating gland. 2. The mol.wt. of the enzyme is 29000+/-500 (mean+/-S.D. of three independent preparations), as estimated by polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. 3. The enzyme also hydrolyses acyl-CoA esters of chain lengths C10:0-C16:0 when these are used as model substrates. The greatest activity was towards dodecanoyl-CoA, and the three preparations had specific activities of 305, 1130 and 2010 nmol of dodecanoyl-CoA hydrolysed/min per mg of protein when 56muM substrate was used. 4. The way in which this enzyme controls the synthesis of medium-chain fatty acids by fatty acid synthetase is briefly discussed.


Role of cholesterol ester mass in regulation of secretion of ApoB100 lipoprotein particles by hamster hepatocytes and effects of statins on that relationship.
Our understanding of the factors that regulate the secretion of apoB100 lipoproteins remains incomplete with considerable debate as to the role, if any, for cholesterol ester in this process. This study examines this issue in primary cultures of hamster hepatocytes, a species in which both cholesterol and apoB100 metabolism are very similar to man. Addition of oleate to medium increased the mass of triglyceride and cholesterol ester within the hepatocyte and also increased the secretion of triglycerides, cholesterol ester, and apoB100 into the medium. Next, the responses of hamster hepatocytes to addition of either an HMG-CoA reductase inhibitor (lovastatin) or an acyl-CoA cholesterol acyltransferase inhibitor (58-035) to the medium, with or without added oleate, were determined. Effects of either agent were only evident in the oleate-supplemented medium in which cholesterol ester mass had been increased above basal. If oleate was not added to the medium, neither agent reduced apoB100 secretion; equally important, over the 24-hour incubation, neither agent, at the concentration used, produced any detectable change in intracellular cholesterol ester mass. However, in contrast to the estimates of mass, which were unchanged, under the same conditions radioisotopic estimates of cholesterol ester synthesis were markedly reduced. Any conclusion as to the relation of cholesterol ester mass to apoB100 secretion would therefore depend on which of the 2 methods was used. Overall, the data indicate a close correlation between the mass of cholesterol ester within the hepatocyte and apoB100 secretion from it and they go far to explain previous apparently contradictory data as to this relation. More importantly, though, taken with other available data, they indicate that the primary response of the liver to increased delivery of lipid is increased secretion rather than decreased uptake. These results point, therefore, to a hierarchy of hepatic responses to increased flux of fatty acids and increased synthesis of cholesterol that in turn suggests a more dynamic model of cholesterol homeostasis in the liver than has been appreciated in the past.


Case Report: Unilateral Hemispheric Hemorrhage with Bilateral Ptosis and Upgaze Palsy.
Determining the anatomic location of insult in cases of concurrent bilateral upgaze palsy with bilateral ptosis can be challenging due to the various overlapping pathways and shared functions. It is more commonly related to bilateral oculomotor nerve palsies and myasthenia gravis. However, the possibility of unilateral cerebrovascular events may be overlooked due to the lack of laterality of disease manifestations. This report documents the uncommon presentation of bilateral ptosis and upgaze palsy in unilateral hemispheric hemorrhage with the corresponding clinical and anatomical review. A 46-year-old gentleman presented to the emergency department with left-sided hemiplegia, concurrent bilateral ptosis, and upgaze palsy. He was found to have acute hemorrhagic stroke secondary to significantly elevated blood pressure. Computed tomography of the brain revealed acute extensive intraparenchymal hemorrhage involving the right basal ganglia, frontal lobe, and temporal lobe. There was an extension of hemorrhage into the third ventricle and subarachnoid extension to the Sylvian fissure with obstructive hydrocephalus. An emergency right craniotomy was performed to evacuate the blood clot, and the hydrocephalus subsequently resolved. Post-operatively, bilateral ptosis and upgaze palsy improved, and then resolved. Acute bilateral ptosis and upgaze palsy suggest the possibility of unilateral hemispheric hemorrhage, even though there is no direct involvement of the brainstem and its nuclei.


Cell clustering mediated by the adhesion protein PVRL4 is necessary for α6β4 integrin-promoted ferroptosis resistance in matrix-detached cells.
Ferroptosis is an iron-dependent form of programmed cell death characterized by the accumulation of lipid-targeting reactive oxygen species that kill cells by damaging their plasma membrane. The lipid repair enzyme GSH peroxidase 4 (GPX4) protects against this oxidative damage and enables cells to resist ferroptosis. Recent work has revealed that matrix-detached carcinoma cells can be susceptible to ferroptosis and that they can evade this fate through the signaling properties of the α6β4 integrin, which sustains GPX4 expression. Although these findings on ferroptosis are provocative, they differ from those in previous studies indicating that matrix-detached cells are prone to apoptosis via a process referred to as anoikis. In an effort to reconcile these discrepant findings, here we observed that matrix-detached epithelial and carcinoma cells cluster spontaneously via a mechanism that involves the cell adhesion protein PVRL4 (also known as Nectin-4). We found that this clustering process allows these cells to survive by stimulating a PVRL4/α6β4/Src signaling axis that sustains GPX4 expression and buffers against lipid peroxidation. In the absence of α6β4, PVRL4-mediated clustering induced an increase in lipid peroxidation that was sufficient for triggering ferroptosis. When the clustering was inhibited, single cells did not exhibit a significant increase in lipid peroxidation in the absence of α6β4, and they were more susceptible to apoptosis than to ferroptosis. These results indicate that ferroptosis induction depends on cell clustering in matrix-detached cells that lack α6β4 and imply that the fate of matrix-detached cells can be determined by the state of their cell-cell interactions.


Identification of intratumour low frequency microvascular components via BOLD signal fractal dimension mapping.
Typical clinical evaluation of the tumour microvascular environment is performed by dynamic contrast enhanced MRI (dceMRI). However, this approach has been defined by numerous mathematical models each with their own physiologic assumptions which often leads to inconclusive results in the assessment of microstructure. Alternatively, Blood Oxygen Level Dependent (BOLD) Magnetic Resonance Imaging (MRI) is already known to be sensitive to the microvascular environment through fluctuation in the oxyhemoglobin to deoxyhemoglobin ratio. Consequently, quantification of the BOLD signal's temporal complexity using a fractal dimension index allows maps to be generated that are physiologically distinctive in nature and allow potential insight into tumour microvasculature with no a priori assumptions as in dceMRI. Here, using rectal carcinoma as an example, we present this novel approach to tumour microvascular evaluation using fractal dimension parametric mapping.


Interpreting the significance of changes in health-related quality-of-life scores.
To determine the significance to patients of changes in health-related quality-of-life (HLQ) scores assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). A subjective significance questionnaire (SSQ), which asks patients about perceived changes in physical, emotional, and social functioning and in global quality of life (global QL) and the QLQ-C30 were completed by patients who received chemotherapy for either breast cancer or small-cell lung cancer (SCLC). In the SSQ, patients rated their perception of change since the last time they completed the QLQ-C30 using a 7-category scale that ranged from "much worse" through "no change" to "much better." For each category of change in the SSQ, the corresponding differences were calculated in QLQ-C30 mean scores and effect sizes were determined. For patients who indicated "no change" in the SSQ, the mean change in scores in the corresponding QLQ-C30 domains was not significantly different from 0. For patients who indicated "a little" change either for better or for worse, the mean change in scores was about 5 to 10; for "moderate" change, about 10 to 20; and for "very much" change, greater than 20. Effect sizes increased in concordance with increasing changes in SSQ ratings and QLQ-C30 scores. The significance of changes in QLQ-C30 scores can be interpreted in terms of small, moderate, or large changes in quality of life as reported by patients in the SSQ. The magnitude of these changes also can be used to calculate the sample sizes required to detect a specified change in clinical trials.


[Effects of a regional intervention to promote asthma guidelines implementation].
Despite of asthma guidelines existing for years, secondary data analysis shows insufficient medical care of asthmatics in Germany. The aim of the present study was to improve asthma guideline adherence by promoting guidelines implementation. We analyzed prospectively pre- and post-interventional medical care of a sample of 127 asthmatics who were recruited by physicians working in ambulatory care and in hospitals of the Region Neckar-Alb, Germany. Data came primarily from patient interviews by phone. Our intervention to promote guidelines implementation consisted of following methods: 1. analyzing regional asthma care followed by a feedback performance report to physicians; 2. delivering asthma patient diaries and peak flow meters to study patients; 3. developing and adapting regionally asthma guidelines for adult asthmatics in the Region of Neckar-Alb; 4. promoting guidelines utilization by publishing the adapted guidelines in a scientific journal, direct mailing of a short version to the practitioners, and boosting the guidelines at regional CE meetings; 5. reanalyzing asthma care of the study cohort and the implementation of the guidelines 13 months after the beginning of the intervention. We studied the effect of the intervention using a qualitative model comprising 18 quality indicators measuring the proportion of patients who were treated in accordance to the guidelines. To compare pre- and post-interventional proportions we used the McNemar test for statistical analysis. The proportion of asthmatics treated in accordance to the guidelines improved significantly from 48 % to 57 %. The increase was mainly due to an improvement of guidelines adherence within the field of promoting asthma self-management and continuous monitoring of patients (42 % pre- and 57 % post-intervention), whereas guidelines adherence in pharmacotherapy improved only from 53 % to 56 %. The proportion of asthmatics treated in accordance to guidelines can be improved by using a multifaceted regional approach to promote guidelines implementation.


DFT calculation in design of near-infrared absorbing nitrogen-doped graphene quantum dots.
The near-infrared light (NIR) absorption of nitrogen-doped graphene quantum dots (NGQDs) containing different N-doping sites is systematically investigated with density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations with Perdew-Burke-Ernzerhof (PBE) functionals. The results show that the ultra-small HOMO-LUMO gaps (0.3-1.0 eV) of various N-doping structures (graphitic, amino, and pyridinic at center, and graphitic at edge) are attributed to the spin-polarization of the energy states, which effectively enhances the NIR absorption for NGQDs. Overall, the graphitic N-doping structure exhibits the best NIR absorption. Moreover, the electron attraction effect of the different N-sites is found to be crucial for the LUMO level, where stronger electron attraction lowers the LUMO energy. This work provides critical insight in further design of NGQDs for NIR absorption.


Effect of biodiesel-derived raw glycerol on 1,3-propanediol production by different microorganisms.
The microbial production of 1,3-propanediol (1,3-PD) from raw glycerol, a byproduct of biodiesel production, is economically and environmentally advantageous. Although direct use of raw glycerol without any pretreatment is desirable, previous studies have reported that this could cause inhibition of microbial growth. In this study, we investigated the effects of raw glycerol type, different microorganisms, and pretreatment of raw glycerol on the production of 1,3-PD. Raw glycerol from waste vegetable-oil-based biodiesel production generally caused more inhibition of 1,3-PD production and microbial growth compared to raw glycerol from soybean-oil-based biodiesel production. In addition, two raw glycerol types produced from two biodiesel manufacturers using waste vegetable oil exhibited different 1,3-PD production behavior, partially due to different amounts of methanol included in the raw glycerol from the two biodiesel manufacturers. Klebsiella strains were generally resistant to all types of raw glycerol while the growth of Clostridium strains was variably inhibited depending on the type of raw glycerol. The 1,3-PD production of the Clostridium strains using acid-pretreated raw glycerol was significantly enhanced compared to that with raw glycerol, demonstrating the feasibility of using raw glycerol for 1,3-PD production by various microorganisms.


Beyond the symptoms: Personalizing giant cell arteritis care through multidimensional patient reported outcome measure.
Giant Cell Arteritis (GCA) is the commonest form of systemic vasculitis in people over the age of 50. Published research highlighted the lack of a disease-specific patient reported outcomes (PROMs) for GCA. To assess the validity, reliability and responsiveness to change of a devised disease specific patient self-reported outcome measures questionnaire for Giant Cell Arteritis (GCA). The GCA-PROMs was conceptualized based on frameworks outlined in the OMERACT developed core set of Outcome Measures for Large-Vessel Vasculitis and the guiding principles of the FDA guidance. Initially, cognitive interviews were conducted to identify item pool of questions. Item selection and reduction was achieved based on patients as well as an interdisciplinary group of specialists. Rasch and internal consistency reliability analyses were implemented. A total of 54 GCA patients completed the questionnaire. The GCA-PROMs questionnaire was reliable as demonstrated by a high standardized alpha (0.878-0.983). Content construct assessment of the GCA-PROMs functional disability and QoL revealed significant correlation (p< 0.01) with both HAQ and EQ-5D. Changes in functional disability, QoL showed significant (p< 0.01) variation with diseases activity status in response to therapy. The developed GCA-PROMs questionnaire is a reliable and valid instrument for assessment of GCA patients. A stratified treatment regimen depending on the individual patient's risk factors as well as preferences and associated comorbidities is the best approach to tailored patient management.


Consumption of high-oleic acid ground beef increases HDL-cholesterol concentration but both high- and low-oleic acid ground beef decrease HDL particle diameter in normocholesterolemic men.
On the basis of previous results from this laboratory, this study tested the hypothesis that ground beef high in MUFA and low in SFA would increase the HDL-cholesterol (HDL-C) concentration and LDL particle diameter. In a crossover dietary intervention, 27 free-living normocholesterolemic men completed treatments in which five 114-g ground beef patties/wk were consumed for 5 wk with an intervening 4-wk washout period. Patties contained 24% total fat with a MUFA:SFA ratio of either 0.71 (low MUFA, from pasture-fed cattle) or 1.10 (high MUFA, from grain-fed cattle). High-MUFA ground beef provided 3.21 g more 18:1(n-9), 1.26 g less 18:0, 0.89 g less 16:0, and 0.36 g less 18:1(trans) fatty acids per patty than did the low-MUFA ground beef. Both ground beef interventions decreased plasma insulin and HDL(2) and HDL(3) particle diameters and increased plasma 18:0 and 20:4(n-6) (all P ≤ 0.05) relative to baseline values. Only the high-MUFA ground beef intervention increased the HDL-C concentration from baseline (P = 0.02). The plasma TG concentration was positively correlated with the plasma insulin concentration (r = 0.40; P < 0.001) and negatively correlated with HDL-C (r = -0.47; P < 0.001) and plasma 18:0 (r = -0.24; P < 0.01). Plasma insulin and HDL diameters were not correlated (r = 0.01; P > 0.50), indicating that reductions in these measures were not coordinately regulated. The data indicate that dietary beef interventions have effects on risk factors for cardiovascular disease that are independent (insulin, HDL diameters) and dependent (HDL-C) on beef fatty acid composition.


Split-belt treadmill stepping in infants suggests autonomous pattern generators for the left and right leg in humans.
The behavior of the pattern generator for walking in human infants (7-12 months of age) was studied by supporting the infants to step on a split-belt treadmill. The treadmill belts could be run at the same speed (tied-belt), different speeds, or in different directions (split-belt). We determined whether the legs could operate independently under these conditions, as demonstrated by taking different numbers of steps or by stepping in different directions. Video, surface electromyography, electrogoniometry, and force platform data were recorded. The majority of infants who could step under tied-belt conditions also stepped under split-belt conditions. During forward stepping at low speed differentials between the two belts (ratio, <4), infants adopted a step cycle duration that was intermediate between that expected from tied-belt stepping at each of the speeds. At large speed differentials between the two belts (ratio, 7-22), the infants took extra steps on the fast leg during the stance phase on the slow leg. When the two belts ran in opposite directions, one leg stepped forward, and the other stepped backward. During all forms of stepping, the legs maintained a reciprocal relationship, so that swing phase occurred in one leg at a time. Timing of muscle activity suggests a strong inhibition between the flexor-generating centers on each side and a weaker inhibition between the extensor-generating centers. The stepping behavior resembled that reported for other animals under similar conditions, suggesting that the pattern generator for each limb is autonomous but interacts with its counterpart for the contralateral limb.


"I guess you can interpret it in a number of ways like kind of a milder or the mildest form of dementia?": Multi-stakeholder perceptions of cognitive impairment.
Mild cognitive impairment (MCI) has a high prevalence and is a risk factor for dementia. Furthering understanding of MCI has been identified as a public health priority. This research aimed to explore views about the causes of cognitive impairment and identify associations between cognitive impairment, dementia, and normative ageing. Semi-structured qualitative interviews were conducted with 22 participants with different stakeholder perspectives on the area of MCI in England, and analysed thematically. Our analysis focuses on two main themes: 1) causes of cognitive impairment, and 2) ageing, dementia, and dying. Most participants viewed cognitive impairment as a transitional state between normative ageing and dementia. Participants expressed their fear of cognitive impairment and dementia, and made clear links between cognitive impairment and dying. Participants also showed an awareness of the links between lifestyle factors and cognitive health. However, linkage between lifestyle and cognition was discussed only when explicitly asked, suggesting that this was not especially salient for participants when considering the causes and risk factors for cognitive impairment. The results of this study highlight key areas for future public health initiatives, such as a focus on the multitude of benefits offered by adopting a healthy diet and physical exercise in reducing risk of cognitive impairment.


Levocetrizine attenuates cyclophosphamide-induced lung injury through inhibition of TNF-α, IL-1β, TGF-β and MMP-9.
Cyclophosphamide (CP) is an antineoplastic drug commonly used worldwide. Despite its spread, it causes fatal organ toxicity. Lung toxicity is a serious side effect of CP. Actually, in the past three years the world has been facing an un-predicted crisis following COVID-19 pandemic and the associated high-mortality rates attributed to respiratory distress. Accordingly; this study aimed to probe the potential prophylactic role of levocetrizine against CP-induced lung injury. Animals were allocated into three sets; control; CP and CP/Levo. CP was intraperitoneally injected in rats 150 mg/kg once on day 7. Levocetrizine was given orally for 14 days starting 7 days before CP injection. On the last day, all rats were sacrificed and lung tissues were kept for analysis. CP significantly elevated lung/body weight index, inflammatory cell counts, LDH, total protein, TNF-α, IL-1β, TGF-β and histamine levels in bronchoalveolar lavage (BAL). Moreover, it markedly increased expression of MMP-9 and contents of MDA, hydroxyproline, collagen and NOx besides decreasing GSH level and SOD activity in lung tissues. These biochemical results were further confirmed by histopathological examination. In contrast, treatment with levocetrizine significantly attenuated CP-induced pathological alterations. These findings propose that levocetrizine can attenuate CP-induced lung injury via exerting antioxidant, anti-inflammatory and anti-fibrotic effects.


Impact of Multifocality on the Recurrence of Papillary Thyroid Carcinoma.
The incidence of thyroid cancer has dramatically increased over the last few decades, and up to 60% of patients have multifocal tumors. However, the prognostic impact of multifocality in patients with papillary thyroid carcinoma (PTC) remains unestablished and controversial. We evaluate whether multifocality can predict the recurrence of PTC. A total of 1249 patients who underwent total thyroidectomy for PTC at the Ewha Medical Center between March 2012 and December 2019 were reviewed. In this study, multifocality was found in 487 patients (39.0%) and the mean follow-up period was 5.5 ± 2.7 years. Multifocality was associated with high-risk features for recurrence, including extrathyroidal extension, lymph node metastasis, and margin involvement. After adjustment of those clinicopathological features, 10-year disease-free survival was 93.3% in patients with multifocal tumors, whereas those with unifocal disease showed 97.6% (p = 0.011). Multivariate Cox regression analysis indicated that male sex (HR 2.185, 95% CI 1.047-4.559), tumor size (HR 1.806, 95% CI 1.337-2.441), N1b LN metastasis (HR 3.603, 95% CI 1.207-10.757), and multifocality (HR 1.986, 95% CI 1.015-3.888) were independent predictors of recurrence. In conclusion, multifocality increased the risk of recurrence in patients with PTC. Patients with multifocal PTCs may need judicious treatment and follow-up approaches.


Retrograde myotomy: a variation in per oral endoscopic myotomy (POEM) technique.
Per oral endoscopic myotomy (POEM) has evolved as a novel therapeutic option for the treatment of esophageal motility disorders such as achalasia. The originally described dissection technique involves cutting the inner circular esophageal muscle fibers in an antegrade fashion. We have modified this technique by commencing the muscular division at the most distal aspect of the submucosal tunnel and continuing the dissection in a retrograde fashion. We present our initial series of patients performed using this modified technique. We retrospectively reviewed our prospectively collected database. Peri- and postoperative data were collected and analyzed. POEM procedures were performed in a near-identical manner as previously published. Retrograde myotomy was performed on five patients with a diagnosis of achalasia. Four had a history of prior treatment including balloon dilation, with one of these having a prior surgical myotomy. Retrograde POEM procedures were performed with trace blood loss and without any complications. Mean operative time was 85 min. All patients had normal esophagram studies, and diets were advanced as per protocol. POEM was developed as a minimally invasive method for the treatment of achalasia. Our retrograde dissection modification allows the most critical portion of the case, namely division of the lower esophageal and upper gastric circular muscle fibers, to be performed earlier in the case. This ensures adequate dissection of the primary site of esophageal dysfunction should problems arise during the procedure. The modification is straightforward, without the need for additional training or equipment, and appears to provide a more rapid myotomy with less charring in this small cohort of patients.


Frequency and determinants of residents' narrative feedback on the teaching performance of faculty: narratives in numbers.
Physicians involved in residency training often receive feedback from residents on their teaching. Research shows that learners value narrative feedback, but knowledge of the frequency and determinants of narrative feedback in teaching performance evaluation is lacking. This study aims to identifythe frequency with which residentsgave positive comments and suggestions for improvement to faculty, and the factors influencing that frequency. From September 2008 through May 2010, the authors collected data, using a validated formative feedback system (System for Evaluation of Teaching Qualities). The authors used univariate and multivariable analysis to investigate the associations between participants' characteristics, including faculty members' teaching performance, and the frequency of the two types of narrative comments. In total, 659 residents (79% of 839) completed 6,216 evaluations on 917 faculty (95% of 964), resulting in 11,574 positive comments and 4,870 suggestions for improvement. On average, faculty members received 13 positive comments and 5 suggestions for improvement. Multivariable analysis showed that higher teaching performance was associated with higher numbers of positive comments (regression coefficient 0.538; 95% confidence interval: 0.464 to 0.613) and with lower numbers of suggestions for improvement (-0.802; -0.911 to -0.692), both P < .0001. Nonacademic hospitals, participation in teacher training, and female residents' evaluation were statistically significant determinants of receiving more narrative feedback. Residents provided narrative feedback that paralleled and elaborated on quantitative evaluations they provided; therefore, faculty would be wise to attend to narrative feedback. Analysis of the quality of narrative feedback is needed to understand its effectiveness.


[Legionnaires' disease in travellers].
The outbreak of pneumonia involving delegates to the 1976 American Legion convention at a Philadelphia hotel was the first example of travel-associated legionnaires' disease. Travel is now well known as a common risk factor for legionnaires' disease. This travel-associated disease is a preoccupation among European countries because of morbidity among citizens of the European Union. The definition of the case of legionellosis is a patient who presents an acute lower respiratory tract infection with focal signs of pneumonia and/or radiological features, and microbiological evidence of Legionella infection. A case is considered to be travel associated if the patient has spent one or more nights away from home during the ten days before becoming ill. An European Surveillance Scheme for Travel-Associated Legionnaires' Disease was established in 1987 to identify clusters and outbreaks of cases of the disease. This group centralizes the case reports of twenty-nine collaborating centres in twenty-five countries. Outbreaks of legionnaires' disease were described in hotels, camps or cruise ships. In 1996, the number of travel-associated cases of legionnaires' disease represented 16% of the total number cases. The increase of the number of reported cases may reflect improved surveillance and increased ascertainment. In Europe in 1996, the diagnosis of legionellosis was confirmed by detection of Legionella pneumophila sero-group 1 antigen in urine (36%), seroconversion (fourfold rise in antibody titre, 33%) and culture of the organism (16%). Fifteen per cent of legionellosis was diagnosed by the identification of a single high antibody titre. In France a coordination between Public Health Institutions (Réseau National de Santé Public and DDASS), clinicians, laboratories and National Reference Center was established to improve prevention and control of legionnaires' disease outbreaks. Legislation obliges to report each case. When more two cases in the same area are notified an epidemiological investigation must be done. The knowing of the source of the contamination and its eradication allows to prevent new cases and outbreaks. Outbreaks of Legionnaires' disease are even now mediatic and this fact leads to maintain attention for the quality of diagnosis and epidemiology investigation due to touristic and economic consequences for the implicated countries.


Determinants of breastfeeding initiation within the first hour of life in a Brazilian population: cross-sectional study.
Breastfeeding within the first hour of life is a potential mechanism for health promotion. The purpose of this study was to evaluate the prevalence of breastfeeding initiation within the first hour of life in Feira de Santana, Bahia, Brazil, between 2004 and 2005, and investigate the influence of maternal, child and prenatal factors on this practice. This is a cross-sectional study extracted from the results of a contemporary cohort conducted in 10 maternity hospitals in the city of Feira de Santana, Bahia, Brazil. A group of 1,309 mother-child pairs was included in the study. Information about mother's and baby's characteristics, pregnancy, birth, and time of breastfeeding initiation was collected in the first 72 hours after delivery, through interview with mothers and hospital records. The data gathered were stored and analyzed using the SPSS 16.0 and R 8.0. The chi-square test and binary logistic regression analysis were used to examine the relationship between breastfeeding within the first hour and different variables. 47.1% of the mothers initiated breastfeeding within the first hour after birth. Early initiation of breastfeeding was associated with birth at full term pregnancy (adjusted Prevalence Ratio 1.43; 95% confidence interval 1.10 to 2.00), mothers who received prenatal guidance regarding the advantages of breastfeeding (aPR1.23; 95% CI 1.11 to 1.41) and vaginal delivery (aPR 2.78; 95% CI 2.38 to 3.23). In order to improve the rates of breastfeeding within the first hour of life, health care professionals must promote the factors favoring this practice such as prenatal guidance regarding the advantages of breastfeeding, vaginal delivery and full term birth, and stimulate this practice in vulnerable situations such as mothers with cesarean section and preterm birth.


An unusual internal carotid artery compression as a possible cause of Eagle syndrome - A novel hypothesis and an innovative surgical technique.
Eagle syndrome (ES) is a rare symptomatic condition generally caused by an elongated styloid process (SP) or calcification of the stylohyoid complex. On the diagnosis is made, its treatment remains subjective since the indications for surgical intervention are still not standardized. Although styloidectomy is the surgical treatment of choice, no consensus exists regarding the transcervical or/and transoral route. Here, we report our experience in a patient with bilateral internal carotid artery (ICA) dissection caused by ES, who underwent innovative surgical technique. A 53-year-old man, with the right-sided middle cerebral artery acute stroke, underwent computed tomography angiography 3 days after a successful endovascular treatment. The study showed a bilateral ICA dissection with bilateral hypertrophic SPs and a close relationship of ICAs with both SPs anteriorly and C1 transverse process posteriorly. Considering the occurrence of ICA compression by a styloid/C1 transverse process juxtaposition, the patient underwent the left partial C1 transversectomy by an extraoral approach. A temporary paresis of the ipsilateral lower lip lasted 1 month, with a partial remission after 3 months. The patient reported significant improvement of symptoms with a good esthetics and functional outcome. A styloid/C1 transverse process juxtaposition should be considered as an alternative pathogenetic mechanism in vascular ES. When a posterior ICA compression by C1 transverse process is present, a bone reshaping of C1 rather than a conventional styloidectomy can be considered an efficacious treatment which allows a good preservation of the styloid muscles and ligaments.


Synchrotron tomography applications in agriculture and food sciences research: a review.
Synchrotron imaging is widely used for research in many scientific disciplines. This article introduces the characteristics of synchrotron X-ray imaging and its applications in agriculture and food science research. The agriculture and food sector are a vast area that comprises of plants, seeds, animals, food and their products; soils with thriving microbial communities; and natural resources such as water, fertilizers, and organic matter. These entities have unique internal features, structures and compositions which differentiate them from each other in varieties, species, grades, and types. The use of a bright and tuneable monochromatic source of synchrotron imaging techniques enables researchers to study the internal features and compositions of plants, seeds, soil and food in a quick and non-destructive way to enhance their use, conservation and productivity. Synchrotron's different X-ray imaging techniques offer a wide domain of applications, which make them perfect to enhance the understanding of structures of raw and processed food products to promote food safety and security. Therefore, this paper summarizes the results of major experiments carried out with seeds, plants, soil, food and relevant areas of agricultural sciences with more emphasis on two synchrotron X-ray imaging techniques: absorption and phase-contrast imaging and computed tomography.


The use of preoperative intra-aortic balloon pump in open heart surgery.
Intra-aortic balloon pump (IABP) therapy before open heart surgery has been suggested for ''high risk'' patients. Records from patients undergoing open heart surgery at our institution between June 1999 and February 2002 were reviewed. Indication for IABP insertion was severely impaired left ventricular function, acute myocardial infarction (MI) or unstable angina. Fifty-five patients were included in the study: 41 male, 14 female, age 64+/-9 years. Fifty-one (92.7%) required coronary artery bypass brafting (CABG) alone or as a combined procedure, 2 (3.6%) required mitral valve surgery, and 2 (3.6%) needed more complex cardiac procedures. Thirty-two patients (58%) underwent emergency cardiac surgery and 11 patients (20%) suffered from acute preoperative MI. The overall 30 days mortality was 9%. Mean intensive care unit (ICU) stay was 6+/-8 days. Four patients (7.2%) developed postoperative renal failure requiring temporary hemodialysis. Three patients (5.4%) developed IABP related peripheral vascular complications. Perioperative morbidity and mortality is increased despite preoperative IABP, particularly in patients with acute MI. In contrast to studies not using this approach, preoperative IABP reduces morbidity and mortality of high risk patients. IABP related complications are low. Our data suggest that high risk patients profit from preoperative IABP therapy, however, prospective studies are needed to confirm these findings.


6-beta-Iodopenicillanate as a probe for the classification of beta-lactamases.
An inactivator of serine beta-lactamases, 6 beta-iodopenicillanate, can be utilized as a probe in the classification of beta-lactamases. It is a substrate for class-B Zn2+-containing beta-lactamase II. Although it inactivates enzymes from both classes A and C, it is much more efficient for the former group, with which it sometimes interacts following a branched pathway. On the basis of these observations, predictions are made concerning the class to which several enzymes belong.


Plasma exchange in pemphigus. Uncontrolled study of ten patients.
Plasma exchange, together with oral immunosuppressive drugs and various doses of adrenal steroids, were used in the treatment of ten patients with pemphigus. Initially plasma exchange decreased the intercellular antibody (IC Ab) level in all patients and induced a clinical improvement in the conditions of eight of ten patients. This improvement was sustained for the six patients who received simultaneously 0.5 mg/kg/day or more of prednisone. Among the eight patients, four previously corticoresistant patients had perfect control of their disease. Conversely the other four patients, treated with low doses of prednisone, experienced a posttreatment rebound in IC Ab level and showed no or only transient clinical improvement. Plasma exchange may be useful in bringing corticoresistant pemphigus under control but it is not to be used without accompanying high doses of adrenal steroids.


Green synthesis of Ag/TiO2 composite coated porous vanadophosphates with enhanced visible-light photo-degradation and catalytic reduction performance for removing organic dyes.
As environmental pollution and energy shortages have become global concerns, the construction of highly efficient catalysts using facile and green methods remains a long-term goal. In the present study, we proposed a facile catalyst preparation method in which Ag/TiO2 composites were coated on the surface of the porous pure inorganic crystalline vanadium phosphates (VPO) by a one-step strategy. More importantly, the in situ reduction of Ag nanoparticles was achieved at room temperature without severe conditions or hydrogen atmosphere in which the porous VPO was employed as the reductant. The prepared Ag/VPO@TiO2 composites act as a class of efficient bifunctional catalysts for visible light photodegradation of MB molecules and catalytic reduction of p-nitrophenol (4-NP). Among these samples, the 6.82%Ag/VPO@TiO2 composite exhibited a superior photocatalytic activity in the degradation of MB and an ultrafast reduction rate for 4-NP of about 0.1 mM/40 s. The photocatalytic mechanistic studies revealed that the encapsulated VPO with a narrow band gap not only efficiently enhances the photosensitivity of the TiO2 but also largely facilitates the photogenerated charge separation. The subsequent deposition of Ag NPs is able to further promote electron transfer ability, which leads to the higher photocatalytic activity. Moreover, the contact of Ag NPs with the surface of semiconductor TiO2 can result in an electron-enhanced area in their interface that could effectively facilitate the uptake of electrons by the 4-NP molecules and then improve the reduction activity.


Determination of ethanol in breath for legal purposes using a five-filter infrared analyzer: studies on response to volatile interfering substances.
The analysis of ethanol in exhaled breath is widely accepted and used worldwide for legal purposes to gather evidence of alcohol-impaired driving. Most evidential breath-alcohol instruments incorporate infrared (IR) spectroscopy as the analytical principle focusing on C-H or C-O stretching frequencies in ethanol molecules. The instrument approved for legal purposes in Sweden is called Evidenzer and is equipped with five infrared filters of which four are used for identification and quantification of ethanol and the fifth is a reference filter. The response of Evidenzer was tested against 21 volatile organic compounds (VOCs), and the instrument was programmed to deduct any bias caused by these VOCs if present in a sample of breath. If the amount deducted exceeds a certain threshold value, the entire test is aborted. Whenever this happens, the police request a specimen of venous blood for analysis by gas chromatography. Of a total of 24 072 drunken drivers, the evidential breath-alcohol test was aborted on 27 occasions (0.11%) because an interfering substance was present above the critical threshold. The VOCs most commonly identified in blood were acetone, isopropanol and/or methyl ethyl ketone (MEK). Elevated levels of acetone and isopropanol might arise during ketogenesis in people suffering from diabetes, or in those who eat low carbohydrate diets. High concentrations of acetone and MEK are probably caused by people drinking a technical alcohol product (T-Red), which is available in Sweden and is denatured with these agents. This study confirms that relatively few apprehended drivers in Sweden have elevated concentrations of VOCs in breath other than ethanol. Even the aborted breath tests, to a large extent, contained ethanol above the legal limit for driving.


Effects of glucagon on cardiac chronotropic response to vagal stimulation in the dog.
Glucagon accelerates the heart independent of sympathetic nervous system stimulation. The effect of glucagon on the chronotropic responses to repetitive bursts of vagal stimulation was determined in open-chest anesthesized dogs. When the cervical vagi were stimulated at constant frequencies, the change in heart rate was not affected by glucagon administration, i.e., no vagolytic effect caused by glucagon was apparent. Thus glucagon did not alter the reaction of acetylcholine with cardiac postsynaptic receptors. When the vagi were stimulated intermittently with one short burst of vagal stimuli delivered each cardiac cycle, the resultant heart period was dependent on the time of vagal stimulus delivery. Both maximum and minimum cardiac cycle lengths obtained during phasic vagal stimulation were decreased by glucagon. As it has been previously demonstrated that vagal impulses to the heart tend to be clustered during certain times of the cardiac cycle, by accelerating the heart glucagon may shift the cardiac response to vagal stimulation.


Irritable mood in adult major depressive disorder: results from the world mental health surveys.
Although irritability is a core symptom of DSM-IV major depressive disorder (MDD) for youth but not adults, clinical studies find comparable rates of irritability between nonbipolar depressed adults and youth. Including irritability as a core symptom of adult MDD would allow detection of depression-equivalent syndromes with primary irritability hypothesized to be more common among males than females. We carried out a preliminary examination of this issue using cross-national community-based survey data from 21 countries in the World Mental Health (WMH) Surveys (n = 110,729). The assessment of MDD in the WHO Composite International Diagnostic Interview includes one question about persistent irritability. We examined two expansions of the definition of MDD involving this question: (1) cases with dysphoria and/or anhedonia and exactly four of nine Criterion A symptoms plus irritability; and (2) cases with two or more weeks of irritability plus four or more other Criterion A MDD symptoms in the absence of dysphoria or anhedonia. Adding irritability as a tenth Criterion A symptom increased lifetime prevalence by 0.4% (from 11.2 to 11.6%). Adding episodes of persistent irritability increased prevalence by an additional 0.2%. Proportional prevalence increases were significantly higher, but nonetheless small, among males compared to females. Rates of severe role impairment were significantly lower among respondents with this irritable depression who did not meet conventional DSM-IV criteria than those with DSM-IV MDD. Although limited by the superficial assessment in this single question on irritability, results do not support expanding adult MDD criteria to include irritable mood.


Methodological Issues in Randomized Clinical Trials for Prodromal Alzheimer's and Parkinson's Disease.
Alzheimer's disease (AD) and Parkinson's disease (PD) are the first and second most common neurodegenerative disorders, respectively. Both are proteinopathies with inexorable courses and no approved disease-modifying therapies. A substantial effort has been made to identify interventions that could slow down the progression of AD and PD; to date, with no success. The advances in biomarker research improved the identification of individuals at risk for these disorders before symptom onset, recognizing the pre-clinical stage, in which there is abnormal protein accumulation but no clinical symptoms of the disease, and the prodromal stage, in which mild symptoms are present but the clinical diagnostic criteria for disease cannot be fulfilled. The ability to detect pre-clinical and prodromal stages of these diseases has encouraged clinical trials for disease-modification at earlier phases, seeking to slow or prevent phenoconversion into clinical disease. Clinical trials at these stages have several challenges, such as the identification of the eligible population, the appropriate choice of biomarkers, the definition of clinical endpoints, the duration of follow-up, and the statistical analysis. This article aims to discuss some of the methodological challenges in the design of trials for pre-clinical and prodromal phases of AD and PD, to critically review the recent studies, and to discuss methodological approaches to mitigate these challenges in trial design.


The evolutionary adaptation of HIV-1 to specific immunity.
Recent evidence of the evolutionary adaptation of HIV-1 to the specific immune system is reviewed. Longitudinal studies of patients show that a neutralizing antibody (NAb) response specific to autologous virus is detectable within 1-2 months of infection and that viral variants resistant to neutralization arise and spread in the viral population within the subsequent three months, and that this general pattern is repeated. There is strong evidence that amino acid replacements in gp120 glycan-binding motifs affect viral sensitivity to neutralization and are selected by NAbs. Longitudinal studies of humans have also provided good evidence of amino acid replacements in cytotoxic T lymphocyte (CTL) epitopes that allow the virus to escape detection by CTLs. But, the clearest evidence of adaptation to CTL surveillance at the molecular level comes from experiments with SIV-infected rhesus macaques. These show unequivocally that amino acid replacements in CTL epitopes are the result of positive selection and that these escape mutants have a lower class I major histocompatibility complex (MHC) binding affinity or are less likely to be recognized by CTLs than non-escape variants. To improve our ability to predict HIV's evolutionary responses to selection by the specific immune system it is suggested that future work focus on the details of the adaptive response to antibody surveillance, the temporal dynamics of specific immune responses, the relative importance of antibody and CTL selection, and the effects of superinfection, viral recombination, and viral protein functional constraints on immune escape.


Early prediction of treatment outcome in idiopathic membranous nephropathy.
Most patients with idiopathic membranous nephropathy have a benign course, but a minority develop severe persistent nephrotic syndrome or endstage renal failure. The disease appears to have an immunological basis and immunosuppression has been used with some benefit. Unfortunately, treatment can be toxic and not all patients respond. For this reason it would be useful to identify at an early stage those patients who might benefit from treatment. This information could be used to minimize the exposure of patients to unnecessary treatment toxicity. We studied a cohort of 128 patients over a 2-year period. A clear relationship exists between the early response to treatment at one month and the long-term outcome from treatment across a number of treatment types. Those patients who might benefit from treatment and those who are unlikely to benefit, can be clearly distinguished at an early stage.


Upregulation of amplified in breast cancer 1 contributes to pancreatic ductal adenocarcinoma progression and vulnerability to blockage of hedgehog activation.
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and devastating cancers without effective treatments. Amplified in breast cancer 1 (AIB1) is a member of the steroid receptor coactivator family that mediates the transcriptional activities of nuclear receptors. While AIB1 is associated with the initiation and progression of multiple cancers, the mechanism by which AIB1 contributes to PDAC progression remains unknown. In this study, we aimed to explore the role of AIB1 in the progression of PDAC and elucidate the underlying mechanisms. Methods: The clinical significance and mRNA level of AIB1 in PDAC were studied by database analysis. To demonstrate whether AIB1 mediates the malignant features of PDAC cells, namely, proliferation, migration, invasion, we performed real-time PCR and Western blot analysis, established xenograft models and used in vivo metastasis assay. With insights into the mechanism of AIB1, we performed RNA sequencing (Seq), ChIP-Seq, luciferase reporter assays and pull-down assays. Furthermore, we analyzed the relationship between AIB1 expression and its target expression in PDAC cells and patients and explored whether PDAC cells with high AIB1 levels are sensitive to inhibitors of its target. Results: We found that AIB1 was significantly upregulated in PDAC and associated with its malignancy. Silencing AIB1 impaired hedgehog (Hh) activation by reducing the expression of smoothened (SMO), leading to cell cycle arrest and the inhibition of PDAC cell proliferation. In addition, AIB1, via upregulation of integrin αv (ITGAV) expression, promoted extracellular matrix (ECM) signaling, which played an important role in PDAC progression. Further studies showed that AIB1 preferably bound to AP-1 related elements and served as a coactivator for enhancing the transcriptional activity of MafB, which promoted the expression of SMO and ITGAV. PDAC cells with high AIB1 levels were sensitive to Hh signaling inhibitors, suggesting that blocking Hh activation is an effective treatment against PDAC with high AIB1 expression. Conclusions: These findings reveal that AIB1 is a crucial oncogenic regulator associated with PDAC progression via Hh and ECM signaling and suggest potential therapeutic targets for PDAC treatment.


Alcohol as a risk factor for injury: lessons from French data.
The relationship between alcohol and injury is complex and the evidence level varies depending on the type of injury. The role of alcohol as a causal factor of traffic accidents is clear. There is less evidence concerning home and leisure injuries which include a wide range of accident causes and mechanisms. However, several studies dealing with specific injuries, such as drowning and fracture injuries in seniors, suggest a correlation between alcohol and the occurrence of injuries. Intentional injuries (violence, suicide) are complex and multifactorial phenomena. It is therefore more complicated to find the link between alcohol consumption and these kind of injuries. However, several physiological, psychological and social mechanisms are suggested to clarify this relationship. In conclusion, further data are needed to improve knowledge regarding the link between alcohol and injuries and, consequently, to implement preventive interventions. The collection of data on alcohol consumption at the moment of admission in emergency wards should be particularly promoted.


Transcriptional and Post-Transcriptional Regulation and Transcriptional Memory of Chromatin Regulators in Response to Low Temperature.
Chromatin regulation ensures stable repression of stress-inducible genes under non-stress conditions and transcriptional activation and memory of stress-related genes after stress exposure. However, there is only limited knowledge on how chromatin genes are regulated at the transcriptional and post-transcriptional level upon stress exposure and relief from stress. We reveal that the repressive modification histone H3 lysine 27 trimethylation (H3K27me3) targets genes which are quickly activated upon cold exposure, however, H3K27me3 is not necessarily lost during a longer time in the cold. In addition, we have set-up a quantitative reverse transcription polymerase chain reaction-based platform for high-throughput transcriptional profiling of a large set of chromatin genes. We find that the expression of many of these genes is regulated by cold. In addition, we reveal an induction of several DNA and histone demethylase genes and certain histone variants after plants have been shifted back to ambient temperature (deacclimation), suggesting a role in the memory of cold acclimation. We also re-analyze large scale transcriptomic datasets for transcriptional regulation and alternative splicing (AS) of chromatin genes, uncovering an unexpected level of regulation of these genes, particularly at the splicing level. This includes several vernalization regulating genes whose AS may result in cold-regulated protein diversity. Overall, we provide a profiling platform for the analysis of chromatin regulatory genes and integrative analyses of their regulation, suggesting a dynamic regulation of key chromatin genes in response to low temperature stress.


Men's attitudes toward breastfeeding: findings from the 2007 Texas Behavioral Risk Factor Surveillance System.
Past research on breastfeeding demonstrates that male partners' support is a significant factor in mothers' decisions to breastfeed. This study explored the diversity of men's opinions about breastfeeding, for the purpose of increasing breastfeeding support among men. This study used the Texas sample of the 2007 Behavioral Risk Factor Surveillance System (BRFSS) to examine whether men's attitudes toward breastfeeding varied by their demographic characteristics and whether fathers' breastfeeding attitudes were related to couples' choice of infant feeding method. Descriptive statistics and linear regression estimated the influence of each demographic characteristic on breastfeeding attitudes. Among a subsample of fathers, multinomial logistic regression analyzed the influence of men's breastfeeding attitudes on their choice of infant feeding method. Findings showed that Spanish-speaking Hispanic men were most likely to agree that breastfeeding had social limitations (e.g. interfere with social life) for mothers, yet they viewed public images of breastfeeding as more acceptable compared with other men. In comparison to U.S.-born men, foreign-born men were in greater agreement that employers should accommodate breastfeeding. Among fathers, support of public images of breastfeeding and attitudes toward employers' accommodations were positively associated with the choice to use breast milk. Men's ethnicity, country of origin, education level, and socioeconomic status all contribute to different norms and expectations about breastfeeding. Men's attitudes about public images of breastfeeding and employers' accommodations for breastfeeding mothers influence the choice of breast milk as the sole infant-feeding method.


Ribosomal and immune transcripts associate with relapse in acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura.
Approximately 40% of patients who survive acute episodes of thrombotic thrombocytopenic purpura (TTP) associated with severe acquired ADAMTS13 deficiency experience one or more relapses. Risk factors for relapse other than severe ADAMTS13 deficiency and ADAMTS13 autoantibodies are unknown. ADAMTS13 autoantibodies, TTP episodes following infection or type I interferon treatment and reported ensuing systemic lupus erythematosus in some patients suggest immune dysregulation. This cross-sectional study asked whether autoantibodies against RNA-binding proteins or peripheral blood gene expression profiles measured during remission are associated with history of prior relapse in acquired ADAMTS13-deficient TTP. Peripheral blood from 38 well-characterized patients with autoimmune ADAMTS13-deficient TTP in remission was examined for autoantibodies and global gene expression. A subset of TTP patients (9 patients, 24%) exhibited a peripheral blood gene signature composed of elevated ribosomal transcripts that associated with prior relapse. A non-overlapping subset of TTP patients (9 patients, 24%) displayed a peripheral blood type I interferon gene signature that associated with autoantibodies to RNA-binding proteins but not with history of relapse. Patients who had relapsed bimodally expressed higher HLA transcript levels independently of ribosomal transcripts. Presence of any one potential risk factor (ribosomal gene signature, elevated HLA-DRB1, elevated HLA-DRB5) associated with relapse (OR = 38.4; p = 0.0002) more closely than any factor alone or all factors together. Levels of immune transcripts typical of natural killer (NK) and T lymphocytes positively correlated with ribosomal gene expression and number of prior episodes but not with time since the most recent episode. Flow cytometry confirmed elevated expression of cell surface markers encoded by these transcripts on T and/or NK cell subsets of patients who had relapsed. These data associate elevated ribosomal and immune transcripts with relapse history in acquired, ADAMTS13-deficient TTP.


Associations of Sleep Duration and Disturbances With Hypertension in Metropolitan Cities of Delhi, Chennai, and Karachi in South Asia: Cross-Sectional Analysis of the CARRS Study.
Sleep duration and disturbances may be risk factors for hypertension. Despite the high burden of hypertension in South Asia, little is known about this relationship in this region. We analyzed population-level cross-sectional data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) study that recruited representative samples of adults ≥ 20 years from three cities-Delhi, Chennai (India), and Karachi (Pakistan) during 2010-2011. We defined hypertension as self-reported treatment or measured blood pressure (BP) ≥140/90 mm Hg. Data on usual duration of sleep, insomnia, and snoring were collected using "The Sleep Habits Questionnaire" and excessive daytime sleepiness (EDS) using Epworth Sleepiness Score. Logistic and linear regression were done with hypertension and BP as outcome variables, respectively. Age, gender, education, wealth index, family history, and body mass index (BMI) were included as covariates. We used multiple imputation to account for missing variables. Prevalence of hypertension was 30.1%. The mean (SD) sleep duration was 7.3 (1.2) hours. Insomnia, snoring, and EDS were present in 13.6%, 28.7%, and 4.6%, respectively. Moderate and habitual snoring were associated with increased odds of hypertension (odds ratio [OR] = 1.18, 95% confidence interval [CI] [1.04 to 1.33] and 1.47 [1.29 to 1.67], respectively), after adjusting for covariates. Rare, occasional, and frequent insomnia were associated with increased hypertension (OR 1.41 [1.12 to 1.77], 1.39 [1.16 to 1.67], and 1.34 [1.09 to 1.65], respectively). Sleep duration and EDS were not associated with hypertension. Self-reported snoring and insomnia were associated with hypertension in South Asia. This relationship needs further exploration through robust longitudinal studies in this region.


Caregiving for Older Adults with Obesity in the United States.
To determine the difference in receipt of activity of daily living (ADL) assistance between obese and normal-weight older adults. Retrospective cohort study. National Health and Aging Trends Study, 2011-2015. U.S. adults aged 65 and older with ADL disability and a body mass index (BMI) of 18.5 kg/m2 or greater (N = 5,612) MEASUREMENTS: BMI was classified as normal weight (18.5-24.9 kg/m2 ), overweight (25.0-29.9 kg/m2 ), or obese (≥30.0 kg/m2 ). Primary outcome was self-reported receipt of help with specific ADLs. Models were adjusted for demographic characteristics (age, sex, race), degree of need (self-reported general health, severity of disability), household resources (income, marriage, people in household, number of children), and cognitive status (dementia, proxy respondent). Obese with disabilities had lower rates of receiving assistance with walking inside (odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.50-0.81), walking outside (OR = 0.76, 95% CI = 0.59-0.97), toileting (OR = 0.68, 95% CI = 0.52-0.89), and getting in and out of bed (OR = 0.67, 95% CI = 0.50-0.87) than normal-weight older adults after adjustment for respondent demographic characteristics. Level of need and cognitive status partially explained the associations. In fully adjusted models, older adults with obesity still had significantly lower odds of receiving assistance in getting in and out of bed than normal weight adults (OR = 0.69, 95% CI = 0.49-0.98). Older adults with obesity are less likely to receive assistance for ADL disabilities than their normal-weight counterparts-an important concern because of ongoing demographic changes in the United States.


Sarcoplasmic reticulum Ca(2+) pump mRNA stability in cardiac and smooth muscle: role of the 3'-untranslated region.
Stomach smooth muscle (SSM) and left ventricular muscle (LVM) express the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) pump gene SERCA2. Alternative splicing yields two major isoforms, SERCA2a in LVM and slow twitch muscle and SERCA2b in SSM and most other tissues. The splices have different 3'-untranslated regions (UTR) and also encode proteins that differ slightly in their COOH-terminal domains. SERCA2 transcription rates are similar in the two tissues, yet LVM has a much higher level of SERCA2 mRNA than SSM. To understand the control of SERCA2 RNA expression, we inhibited transcription and showed that the half-life of SERCA2 mRNA is significantly longer (P < 0.05) in primary cultures of LVM cells than in SSM cells. Nuclear SERCA2 mRNA levels were also higher in LVM than in SSM. In vitro decay assays using synthetic RNA corresponding to the 3'-UTR of SERCA2a and -2b showed that nuclear extracts produced a faster decay of SERCA2 RNA than cytoplasmic extracts and that nuclear extracts produced a faster decay of SERCA2b than -2a. This was also true when the full-length native mRNA was used instead of the 3'-UTR RNA, and SERCA2b decay by cytoplasmic extracts was faster for LVM than for SSM. We propose that nuclear decay is an initial step in the control of SERCA2 RNA abundance and that this control is maintained or modulated in the cytoplasm. We discuss how these control mechanisms may be part of a control switch in cardiac development and pathophysiology.


Concentrations of polychlorinated biphenyls in soil and indoor dust associated with electricity generation facilities in Lagos, Nigeria.
Concentrations of 7 indicator polychlorinated biphenyls (PCBs) were measured in dust and soil samples from 12 power stations collected over the two major seasons of the Nigerian climate. Median ƩPCB7 concentrations in soil ranged from 2 ng/g for power station A to 220 ng/g for power station I; while those in dust ranged from 21 ng/g for power station L to 2200 ng/g for power station I. For individual congeners, median PCB concentrations ranged from 3.8 ng/g for PCB 101 to 52 ng/g for PCB 180 in dust, and <0.07 ng/g for PCB 28 to 5.9 ng/g for PCB 153 in soil. The type of power station activity exerted a significant influence on concentrations of ΣPCB7 in dust and soil (generation > transmission > distribution). Congener patterns in dust and soil samples were compared using principal component analysis (PCA) with those in transformer oil samples from 3 of the power stations studied and with common PCB mixtures (Aroclors). This revealed congener patterns in soil were more closely related to that in the transformer oil than dust. Congener patterns in most samples were similar to Aroclor 1260. Concentrations of PCBs in soil samples close to the transformers significantly exceeded those in soil sampled further away.


Noradrenergic dysfunction in the prefrontal cortex in depression: an [15O] H2O PET study of the neuromodulatory effects of clonidine.
Noradrenergic dysfunction has been consistently implicated in depression. Much of the evidence, though, has been indirect, such as an attenuated growth hormone response to the alpha2-adrenoceptor agonist clonidine. To more directly examine central functioning of the noradrenergic system in depression, we have used [15O] H2O positron emission tomography (PET) to measure cerebral blood flow (rCBF) in combination with clonidine as a neuromodulatory probe. Subjects were six depressed and six healthy women, medication free and matched for age and phase of menstrual cycle. Two PET scans were acquired at baseline and two scans at 20 and 35 min following an intravenous clonidine infusion of 1.4 microg/kg while subjects performed a sustained attention task. The growth hormone response did not show a significant difference between groups. However, PET results revealed a difference in the right superior prefrontal cortex that was resolved as an interaction from decreased rCBF in healthy control subjects but increased rCBF in the depressed group, which was not accounted for by differences in task performance. This differential effect of clonidine in the right prefrontal cortex provides in vivo evidence of noradrenergic dysfunction in depression, which we postulate arises from functionally impaired presynaptic alpha2-adrenoceptors as well as regionally "supersensitive" postsynaptic cortical alpha2-adrenoceptors.


Structure determination of Nudaurelia capensis omega virus.
The structure of Nudaurelia capensis omega virus (NomegaV), a single-stranded RNA virus, was determined to 2.8 A resolution. Triclinic crystals (a = 413.6, b = 410.2, c = 419.7 A, alpha = 59.13, beta = 58.9, gamma = 64.0 degrees ) diffracted X-rays beyond 2.7 A resolution. The unit cell contained one icosahedral virus particle, providing 60-fold non-crystallographic symmetry (n.c.s.) and structural redundancy. The particle orientation in the unit cell was determined by self-rotation function analyses. Initial phases to 18 A resolution were derived from a hollow spherical model of 192 A outer radius and 139 A inner radius, filled with uniform electron density. Radii of the model were determined by maximizing the correlation of the model-based calculated data with the low-resolution X-ray diffraction and solution-scattering data. Phases were refined by 60-fold non-crystallographic electron-density averaging and extended in small steps to a resolution of 5 A. The phases obtained represented a mixture of four different phase sets, each consistent with the icosahedral symmetry constraints. The resulting electron density was not interpretable. A difference Fourier map computed with the native and an isomorphous heavy-atom derivative data sets and phases refined by real-space averaging was interpretable only if data within the 10 A resolution shell were used. Maps calculated with data significantly higher than 10 A resolution failed to display a constellation of heavy-atom sites consistent with the T = 4 icosahedral symmetry. Attempts to extend the phases beyond 10 A resolution, starting with either phases based on a model or single isomorphous replacement, were unsuccessful. Successful phase extension was achieved by computing the phases for the higher resolution reflections from a partial atomic model (poly gly) built into the averaged 10 A electron-density map. Phases from this model served as the starting point for n.c.s. phase refinement and extension to slightly higher resolution. The atomic model was improved at each extension interval and these phases were used for the subsequent phase calculation and extension. The entire polypeptide backbone corresponding to the NomegaV structure was built into the map at 4 A. The same procedure for phase refinement was used to extend the phases to 2.8 A in small increments of resolution. The overall molecular averaging R factor and correlation coefficient at 2.8 A resolution were 18.4% and 0.87, respectively.


Fibromyalgia syndrome pathology and environmental influences on afflictions with medically unexplained symptoms.
Fibromyalgia syndrome (FMS) is a clinical disorder predominant in females with unknown etiology and medically unexplained symptoms (MUS), similar to other afflictions, including irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), post-traumatic stress disorder (PTSD), Gulf War illness (GFI), and others. External environmental stimuli drive behavior and impact physiologic homeostasis (internal environment) via autonomic functioning. These environments directly impact the individual affective state (mind), which feeds back to regulate physiology (body). FMS has emerged as a complex disorder with pathologies identified among neurotransmitter and enzyme levels, immune/cytokine functionality, cortical volumes, cutaneous innervation, as well as an increased frequency among people with a history of traumatic and/or emotionally negative events, and specific personality trait profiles. Yet, quantitative physical evidence of pathology or disease etiology among FMS has been limited (as with other afflictions with MUS). Previously, our group published findings of increased peptidergic sensory innervation associated with the arterio-venous shunts (AVS) in the glabrous hand skin of FMS patients, which provides a plausible mechanism for the wide-spread FMS symptomology. This review focuses on FMS as a model affliction with MUS to discuss the implications of the recently discovered peripheral innervation alterations, explore the role of peripheral innervation to central sensitization syndromes (CSS), and examine possible estrogen-related mechanisms through which external and internal environmental factors may contribute to FMS etiology and possibly other afflictions with MUS.


Genetic dissection of the outer membrane secretin PulD: are there distinct domains for multimerization and secretion specificity?
Linker and deletion mutagenesis and gene fusions were used to probe the possible domain structure of the dodecameric outer membrane secretin PulD from the pullulanase secretion pathway of Klebsiella oxytoca. Insertions of 24 amino acids close to or within strongly predicted and highly conserved amphipathic beta strands in the C-terminal half of the polypeptide (the beta domain) abolished sodium dodecyl sulfate (SDS)-resistant multimer formation that is characteristic of this protein, whereas insertions elsewhere generally had less dramatic effects on multimer formation. However, the beta domain alone did not form SDS-resistant multimers unless part of the N-terminal region of the protein (the N domain) was produced in trans. All of the insertions except one, close to the C terminus of the protein, abolished function. The N domain alone was highly unstable and did not form SDS-resistant multimers even when the beta domain was present in trans. We conclude that the beta domain is a major determinant of multimer stability and that the N domain contributes to multimer formation. The entire or part of the N domain of PulD could be replaced by the corresponding region of the OutD secretin from the pectate lyase secretion pathway of Erwinia chrysanthemi without abolishing pullulanase secretion. This suggests that the N domain of PulD is not involved in substrate recognition, contrary to the role proposed for the N domain of OutD, which binds specifically to pectate lyase secreted by E. chrysanthemi (V. E. Shevchik, J. Robert-Badouy, and G. Condemine, EMBO J. 16:3007-3016, 1997).


Sometimes it is better to wait: First Italian case of a newborn with transient abnormal myelopoiesis and a favorable prognosis.
Congenital leukemia is rare disease with an incidence of one to five cases per million births. Transient abnormal myelopoiesis (TAM), also called transient myeloproliferative disorder, is a pre-leukemia disorder that may occur in Down syndrome (DS) or non-DS infants. TAM may enter spontaneous remission; however, continual monitoring is required, as this disorder has been observed to develop into acute megakaryoblastic leukemia in 16-30% of cases. In the literature, 16 cases of TAM in non-DS infants have been reported. The case presented in the current study is, to the best of our knowledge, the first case of an Italian non-DS newborn presenting with clinical manifestations of acute leukemia at five days after birth, exhibiting a normal karyotype, trisomy 21 only in blast cells, and spontaneous remission. Chromosomal analyses on peripheral blood cells, bone marrow cells and dermal fibroblasts were conducted using a G-banding technique, and fluorescence in situ hybridization (FISH) was used to identify the critical regions of DS. Amplification of GATA binding protein 1 (GATA1) exon 2 genomic DNA was performed using polymerase chain reaction. Cytogenetic analysis of 50 peripheral blood cells and dermal fibroblasts from the patient revealed a normal karyotype: 46, XX. Conversely, cytogenetic analysis of the patient's bone marrow revealed an abnormal karyotype 47, XX+21. In order to investigate this result, FISH was performed, which identified the presence of three signals in 70% of the cells and two signals in 30% of bone marrow cells. GATA1 sequencing revealed the substitution of a single base (c.150delG) in exon 2. Seven months after the initial analysis, FISH and cytogenetic analyses of the stimulated/unstimulated peripheral blood cells and bone marrow cells were performed, revealing that each exhibited diploid signals, as observed in a normal karyotype.


Low concentrations of nitric oxide increase oxygen affinity of sickle erythrocytes in vitro and in vivo.
The hallmark of sickle cell disease (SCD) is the polymerization of deoxygenated sickle hemoglobin (HbS). In SCD patients, one strategy to reduce red blood cell (RBC) sickling is to increase HbS oxygen affinity. Our objective was to determine if low concentrations of nitric oxide (NO) gas would augment the oxygen affinity of RBCs containing homozygous HbS (SS). Blood containing normal adult hemoglobin (AA) or SS RBCs was incubated in vitro in the presence of varying concentrations of NO up to 80 ppm, and oxygen dissociation curves (ODCs) were measured. In addition, blood was obtained from three AA and nine SS volunteers, before and after breathing 80 ppm NO in air for 45 min, and the ODCs were measured. Exposure of SS RBCs to 80 ppm NO in vitro for 5 min or longer decreased the partial pressure of oxygen at which hemoglobin is 50% saturated with oxygen (P50), an average of 15% (4.8+/-1.7 mmHg mean+/-SE; P < 0.001). The increase in SS RBC oxygen affinity correlated with the NO concentration. The P50 of AA RBCs was unchanged (P > 0.1) by 80 ppm NO. In SS volunteers breathing 80 ppm NO for 45 min, the P50 decreased (P < 0.001) by 4.6+/-2.0 mmHg. 60 min after NO breathing was discontinued, the RBC P50 remained decreased in five of seven volunteers in whom the ODC was measured. There was no RBC P50 change (P > 0.1) in AA volunteers breathing NO. Methemoglobin (Mhb) remained low in all subjects breathing NO (SS Mhb 1.4+/-0.5%), and there was no correlation (r = 0.02) between the reduction in P50 and the change in Mhb. Thus, low concentrations of NO augment the oxygen affinity of sickle erythrocytes in vitro and in vivo without significant Mhb production. These results suggest that low concentrations of NO gas may offer an attractive new therapeutic model for the treatment of SCD.


Identification and distribution of mercury species in rat tissues following administration of thimerosal or methylmercury.
Methylmercury (Met-Hg) is one the most toxic forms of Hg, with a considerable range of harmful effects on humans. Sodium ethyl mercury thiosalicylate, thimerosal (TM) is an ethylmercury (Et-Hg)-containing preservative that has been used in manufacturing vaccines in many countries. Whereas the behavior of Met-Hg in humans is relatively well known, that of ethylmercury (Et-Hg) is poorly understood. The present study describes the distribution of mercury as (-methyl, -ethyl and inorganic mercury) in rat tissues (brain, heart, kidney and liver) and blood following administration of TM or Met-Hg. Animals received one dose/day of Met-Hg or TM by gavage (0.5 mg Hg/kg). Blood samples were collected after 6, 12, 24, 48, 96 and 120 h of exposure. After 5 days, the animals were killed, and their tissues were collected. Total blood mercury (THg) levels were determined by ICP-MS, and methylmercury (Met-Hg), ethylmercury (Et-Hg) and inorganic mercury (Ino-Hg) levels were determined by speciation analysis with LC-ICP-MS. Mercury remains longer in the blood of rats treated with Met-Hg compared to that of TM-exposed rats. Moreover, after 48 h of the TM treatment, most of the Hg found in blood was inorganic. Of the total mercury found in the brain after TM exposure, 63% was in the form of Ino-Hg, with 13.5% as Et-Hg and 23.7% as Met-Hg. In general, mercury in tissues and blood following TM treatment was predominantly found as Ino-Hg, but a considerable amount of Et-Hg was also found in the liver and brain. Taken together, our data demonstrated that the toxicokinetics of TM is completely different from that of Met-Hg. Thus, Met-Hg is not an appropriate reference for assessing the risk from exposure to TM-derived Hg. It also adds new data for further studies in the evaluation of TM toxicity.


Alzheimer neurofibrillary tangles contain phosphorylated and hidden neurofilament epitopes.
Three monoclonal antibodies to neurofilaments (RT97, BF10 and 147), two of which also recognised neurofibrillary tangles (RT97 and BF10), have all been shown to be specific for phosphorylated epitopes. Treatment of histological sections with alkaline phosphatase prior to immunostaining resulted in reduction of axonal neurofilament staining with all three whilst the neurofibrillary tangles staining with BF10 was unaffected. Antibody 147 was found to recognise weakly some neurofibrillary tangles following alkaline phosphatase treatment. The results presented confirm the presence of structurally abnormal but phosphorylated neurofilaments in neurofibrillary tangles.


From calcium to NF-kappa B signaling pathways in neurons.
NF-kappa B plays crucial roles in the nervous system, including potential roles in long-term responses to synaptic plasticity, pro- or antiapoptotic effects during developmental cell death, and neurodegenerative disorders. We report here the characterization of signaling pathways leading to the constitutive activation of NF-kappa B in primary cultures of neonatal cerebellar granule neurons, consecutive to calcium entry into the cytosol. We found that opening of calcium channels at the plasma membrane and at intracellular stores is indispensable for the basal NF-kappa B activity. We demonstrated further that three cellular sensors of the cytosolic Ca(2+) levels, calmodulin, protein kinases C (PKCs), and the p21(ras)/phosphatidylinositol 3-kinase (PI3K)/Akt pathway are simultaneously involved in the steps linking the Ca(2+) second messenger to NF-kappa B activity. Calmodulin triggers the activity of calcineurin, a phosphatase which plays a role in the basal NF-kappa B activity, while stimulation of both the calmodulin kinase II and Akt kinase pathways results in the up-regulation of the transcriptional potential of the p65 subunit of NF-kappa B. Finally, using pharmacological and molecular approaches, we analyze interactions between these three pathways at different levels and demonstrate a connection between PKCs and PI3K. All three components converge towards NF-kappa B, at the level of both nuclear translocation and transcriptional activity. These results stand in contrast to the situation in nonneuronal cells, which either do not respond to Ca(2+) or do not simultaneously activate all three cascades. By using a global approach in studying signaling pathways in neurons, these results provide further evidence to validate the concept of networks of transducing cascades, specific to cells and to physiological situations.


An active chromatin structure acquired by translocated c-myc genes.
We used general sensitivity to DNase I digestion to analyze the chromatin structure of c-myc genes in seven murine plasmacytomas. In every case, the 3' portion of c-myc juxtaposed with C alpha displayed a much more DNase I-sensitive chromatin structure than untranslocated c-myc or, in one case analyzed, the reciprocally translocated 5' portion. Our data suggest the presence of regulatory sequences near the C alpha gene segment.


The 3-Year Course of Multiple Substance Use Disorders in the United States: A National Longitudinal Study.
To examine the 3-year course of multiple co-occurring substance use disorders (SUDs) based on longitudinal survey data from a large, nationally representative sample. National estimates of the prevalence of DSM-IV SUDs were derived by analyzing data from structured, face-to-face diagnostic interviews as part of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), which collected data from a large, nationally representative sample of noninstitutionalized US adults at 2 waves (2001-2002 and 2004-2005; N = 34,653). US adults with multiple past-year SUDs at Wave 1 were substantially more likely than those with an individual past-year SUD or no SUD at Wave 1 to report at least 1 past-year SUD at Wave 2 (66.3% vs 46.0% vs 6.9%, respectively). There were several sociodemographic characteristics and psychiatric disorders (ie, male, younger age, never married, sexual minority identity, nicotine dependence, mood disorder, and personality disorder) associated with increased odds of developing multiple SUDs and having 3-year persistence of multiple SUDs. The majority of adults with multiple past-year SUDs had a lifetime personality disorder and did not utilize substance abuse treatment or other help-seeking. Multiple SUDs are associated with a more persistent 3-year course of disease over time relative to individual SUDs. Despite a more severe 3-year course and higher rates of comorbidity with other psychiatric disorders, the majority of US adults with multiple SUDs do not utilize substance abuse treatment or other help-seeking. Clinical assessments and the substance abuse literature tend to focus on drug-specific individual SUDs rather than considering the more complex multiple SUDs, which can be more challenging to treat.


Pre-procedural fasting in emergency sedation.
Emergency physicians frequently undertake emergency procedural sedation in non-fasted patients. At present, no UK guidelines exist for pre-procedural fasting in emergency sedation, and guidelines from the North American Association of Anesthesiologists (ASA) designed for general anaesthesia (GA) are extrapolated to emergency care. A systematic review of the literature was conducted with the aim of evaluating the evidence for risk of pulmonary aspiration during emergency procedural sedation in adults. All abstracts were read and relevant articles identified. Further literature was identified by hand-searching reference sections. Papers were objectively evaluated for relevance against pre-determined criteria. The risk of aspiration in emergency procedural sedation is low, and no evidence exists to support pre-procedural fasting. In several large case series of adult and paediatric emergency procedural sedation, non-fasted patients have not been shown to be at increased risk of pulmonary aspiration. There is only one reported case of pulmonary aspiration during emergency procedural sedation, among 4657 adult cases and 17 672 paediatric cases reviewed. Furthermore, ASA guidelines for fasting prior to GA are based on questionable evidence, and there is high-level evidence that demonstrates no link between pulmonary aspiration and non-fasted patients. There is no reason to recommend routine fasting prior to procedural sedation in the majority of patients at the Emergency Department. However, selected patients believed to be significantly more prone to aspiration may benefit from risk:benefit assessment prior to sedation.


Molecularly imprinted polymer for selective extraction of domoic acid from seafood coupled with high-performance liquid chromatographic determination.
In this work, a highly selective sample cleanup procedure that combining molecular imprinting technique (MIT) and solid phase extraction (SPE) was developed for the isolation of domoic acid (a fascinating marine toxin) from seafood samples. The molecular imprinting polymer (MIP) for domoic acid was prepared using 1,3,5-pentanetricarboxylic acid as the template molecule instead of domoic acid. 4-Vinyl pyridine was used as the functional monomer and ethylene glycol dimethacrylate was used as the cross-linking monomer. The obtained imprinted polymer showed high affinity to domoic acid and was used as selective sorbent for the SPE of domoic acid from seafood samples. An off-line molecularly imprinted solid phase extraction (MISPE) method followed by high-performance liquid chromatography (HPLC) with diode-array detection for the detection of domoic acid was also established. Good linearity was obtained from 0.5 mg L(-1) to 25 mg L(-1) (R(2)>0.99) with a quantitation limit of 0.1 mg L(-1), which was sufficient to determine domoic acid at the maximum level permitted by several authorities. The mean recoveries of domoic acid from mussel extracts were 93.4-96.7%. It was demonstrated that the proposed MISPE-HPLC method could be applied to direct determination of domoic acid from seafood samples.


Spin Andreev-like reflection in metal-Mott insulator heterostructures.
Using the time-dependent density-matrix renormalization group (tDMRG), we study the time evolution of electron wave packets in one-dimensional (1D) metal-superconductor heterostructures. The results show Andreev reflection at the interface, as expected. By combining these results with the well-known single-spin-species electron-hole transformation in the Hubbard model, we predict an analogous spin Andreev reflection in metal-Mott insulator heterostructures. This effect is numerically confirmed using 1D tDMRG, but it is expected to also be present in higher dimensions, as well as in more general Hamiltonians. We present an intuitive picture of the spin reflection, analogous to that of Andreev reflection at metal-superconductor interfaces. This allows us to discuss a novel antiferromagnetic proximity effect. Possible experimental realizations are discussed.


Continuation of deferiprone therapy in patients with mild neutropenia may not lead to a more severe drop in neutrophil count.
Approximately 6% of patients with thalassemia receiving deferiprone develop neutropenia. Present practice is to monitor absolute neutrophil count (ANC) weekly and to interrupt treatment at the first sign of neutropenia, lest continuation lead to progressive neutrophil reduction. In a 6-month study evaluating the safety and efficacy of a liquid form of deferiprone in 100 children, ANC was initially checked weekly for all patients. For individuals experiencing mild neutropenia, deferiprone was continued but monitoring was increased to daily until resolution. Therapy was to be suspended only if the episode was prolonged or if it worsened. Four patients experienced single episodes of mild neutropenia, and two others each experienced two episodes. All eight episodes resolved within 4-7 d despite continued therapy. (One patient later developed agranulocytosis and had treatment terminated.) This study showed that not all cases of mild neutropenia during deferiprone therapy develop into agranulocytosis, and suggests that many may not be caused by deferiprone. Transient declines in ANC to levels defined as neutropenic are common even in healthy individuals, particularly children; and it could be that the frequent monitoring of ANC mandated during deferiprone therapy may reveal cases of transient neutropenia that would otherwise have gone undetected and resolved on their own without clinical consequences. In patients with thalassemia, several factors increase the probability of a transient fall in ANC. These findings raise the question of whether deferiprone should be routinely stopped in cases of mild neutropenia, provided that such patients have their ANC monitored more frequently during the neutropenic episode.


Inflammation and cancer: a multifaceted link.
Mounting evidence indicates a link between inflammation and cancer. However, the molecular mechanism(s) remains unclear. Indeed, although preclinical and clinical studies suggest that chronic inflammation can promote cancer development, the role(s) of inflammation in the process is likely very complex and far to be completely understood. Inflammation can promote all stages of tumor development through multiple mechanisms which include enhanced proliferation and resistance to apoptosis of initiated cells, induction of DNA mutations, promotion of angiogenesis, invasion and metastasis. On the other hand, components of tumor microenviroment, including tumor cells themselves, may promote an inflammatory state by producing inflammatory mediators. Moreover, while chronic inflammation might promote tumor formation, acute inflammation might well hamper the process and is indeed used therapeutically to inhibit tumor formation. The present review briefly highlights the relationship between inflammation and tumorigenesis and discusses the possibility to develop chemoprevention and/or therapeutical approaches targeting components of the inflammatory responses.


[Evaluation of peripheral neuropathy in the patients with type 2 diabetes mellitus by laboratory examination: relationship between albuminuria and ankle-brachial index].
The aim of this study was to investigate the influence of peripheral neuropathy on laboratory examinations and to evaluate the relationship between nerve conduction velocity (NCV), albuminuria, and ankle-brachial index (ABI) results in patients with type 2 diabetes mellitus (DM). One hundred twenty-six patients with type 2 DM who had undertaken the nerve conduction study for an initial screening test of diabetic complications were included in our study. We divided patients to 4 groups according to the stage of microalbuminuria and ABI results. Two factors negative (2FN) group (n = 75), urinary albumin creatinine ratio (A/C) < 30 mg/gCr and ABI > or = 1.0; A/C group (n = 25), A/C > or = 30 mg/gCr and ABI > or = 1.0; ABI group (n = 14), A/C < 30 mg/gCr and ABI < 1.0; two factors positive (2FP) group (n = 12), A/C > or = 30 mg/gCr and ABI < 1.0. Neuropathy, retinopathy, hypertension, macroangiopathy, and hyperlipidemia were seen in 57.9%, 38.1%, 59.5%, 22.2%, and 56.3%, respectively. Lower leg NCV in 2FP group was significantly lower than other groups. Our study indicated that impaired diabetic peripheral neuropathy may be detected by combining decreased ABI with increased A/C results.


Identification and characterization of several new members of the ZIP family of metal ion transporters in Medicago truncatula.
To broaden our understanding of micronutrient metal transport in plants, we have identified cDNAs for six new metal transporters in the model legume Medicago truncatula. All of the predicted proteins have high similarity to the ZIP protein family, and have been designated MtZIP1, MtZIP3, MtZIP4, MtZIP5, MtZIP6, and MtZIP7. The six predicted proteins ranged from 350 to 372 amino acids in length; sequence analysis revealed that all proteins contained eight transmembrane domains and the highly conserved ZIP signature motif. Most of the proteins also exhibited a histidine-rich region in the variable sequence between transmembrane domains III and IV. When MtZIPs were transformed into appropriate metal-uptake defective yeast mutants and grown on metal-limited media, MtZIP1, MtZIP5, and MtZIP6 proteins restored yeast growth on Zn-limited media, MtZIP4 and MtZIP7 proteins restored yeast growth on Mn-limited media, and MtZIP3, MtZIP5, and MtZIP6 proteins restored yeast growth on Fe-limited media. Therefore, we conclude that these proteins function as metal transporters in Medicago truncatula. The expression pattern for each gene was studied by semi-quantitative RT-PCR in roots and leaves from plants grown under various metal supplies. MtZIP1 transcripts were only detected in Zn-deficient roots and leaves. MtZIP3 and MtZIP4 expression was down regulated in leaves from Mn- and Fe-deficient plants and appeared to be upregulated under Zn-deficient conditions in both roots and leaves. MtZIP5 was upregulated in leaves under Zn and Mn deficiency. The expression of MtZIP6 and MtZIP7 was unaffected by the metal supply, at least in root and leaf tissues. Characterizing these proteins in a single organism will allow us to understand the interplay between various ZIP genes, and the role they play in the regulation/execution of plant metal homeostasis.


Six-day dry immersion leads to downregulation of slow-fiber type and mitochondria-related genes expression.
The soleus muscle in humans is responsible for maintaining an upright posture and participating in walking and running. Under muscle disuse, it undergoes molecular signaling changes that result in altered force and work capacity. The triggering mechanisms and pathways of these changes are not yet fully understood. In this article, we aimed to detect the molecular pathways that are involved in the unloading-induced alterations in the human soleus muscle under 6-days of dry immersion. A 6-day dry immersion led to the downregulation of mitochondrial biogenesis and dynamics markers, upregulation of calcium-dependent CaMK II phosphorylation, enhanced PGC1α promoter region methylation, and altered muscle micro-RNA expression, without affecting p-AMPK content or fiber-type transformation.NEW & NOTEWORTHY Dry immersion dysregulates mitochondrial genes expression, affects mi-RNA expression and PGC1 promoter methylation.