The activation of factor X by hepatocyte plasma membranes.
Synthesis and secretion of blood coagulation factor X was studied during incubations of hepatocytes prepared by perfusion of rat livers with collagenase. The apparent molecular weight of factor X isolated from the incubation medium was about 14,000 less than factor X isolated from rat plasma. The extracellular form of factor X was a two-chain polypeptide and the observed difference in molecular weight was reflected in the heavy chain. Since these properties were more characteristic of factor Xa than factor X, experiments were designed to determine if factor X activation occurred during the incubations. Clotting factor assays indicated that factor X secreted by hepatocytes was present as factor Xa. Also, when purified plasma factor X was added to incubations of hepatocytes the added factor X was converted to factor Xa. Plasma membranes prepared from isolated hepatocytes or from liver homogenates contained an enzyme that converted factor X to factor Xa in a calcium-dependent reaction. The results suggest that the activity is due to the presence of thromboplastin (tissue factor) and factor VII in the membrane preparations.


Effect of parathyroid hormone on phospholipid metabolism in osteoblast-like rat osteogenic sarcoma cells.
Previous results have shown that 1,25-dihydroxycholecalciferol [1,25(OH)2D3] enhances the synthesis of phosphatidylserine (PS) and suppresses the synthesis of phosphatidylethanolamine (PE) in osteoblast-like rat osteogenic sarcoma UMR 106 cells [Matsumoto, Kawanobe, Morita & Ogata (1985) J. Biol. Chem. 260, 13704-13709]. In the present study, the effect of parathyroid hormone (PTH) on phospholipid metabolism is examined by using these cells. Treatment of UMR 106 cells with human PTH-(1-34)-peptide suppresses the synthesis of phosphatidylethanolamine in a dose- and time-dependent manner without affecting the synthesis of PS. The maximal effect on PE synthesis is obtained with 2.4 nM-human PTH-(1-34)-peptide when the cells are treated for 48 h or longer. In addition, when human PTH-(1-34)-peptide is added together with the maximal dose of 1,25(OH)2D3, there is a further decline in PE synthesis, whereas the stimulation of PS synthesis by 1,25(OH)2D3 is not altered. Because methylation of PE is suggested to affect hormone receptor-adenylate cyclase coupling, the observed change in PE metabolism by PTH and 1,25(OH)2D3 may be, at least in part, involved in the development of desensitization phenomenon to PTH in these cells.


A curious abnormally developed embryo of the pill millipede Glomeris marginata (Villers, 1789).
This paper reports on an abnormally developed embryo (ADE) of the common pill millipede Glomeris marginata. This ADE represents a modified case of Duplicitas posterior, in which two posterior ends are present, but only one anterior end. While the major posterior germ band of the embryo appears almost normally developed, the minor posterior germ band is heavily malformed, has no clear correlation to the single head, little or no ventral tissue, and a minute amount of yolk. The anterior end of the minor germ band is fused to the ventral side of the major germ band between the first and second trunk segment. At least one appendage of the second trunk segment appears to be shared by the two germ bands. Morphology and position of the minor germ band suggest that the ADE may be the result of an incorrectly established single cumulus [the later posterior segment addition zone (SAZ)]. This differs from earlier reports on Duplicitas posterior type ADEs in Glomeris marginata that are likely the result of the early formation of two separate cumuli.


[LAI-based regional winter wheat yield estimation by remote sensing].
By using retrieved LAI from remotely-sensed imagery, this paper studied the regional winter wheat yield estimation in Huanghuaihai Plain of North China. In order to improve the quality of remotely sensed data for winter wheat yield estimation, a Savitzky-Golay filter was used to smooth the MODIS-NDVI time series data to reduce the cloud contamination and remove the abnormal data. Then, a Gaussian model was used to simulate the daily crop LAI which was corrected by interpolating the measured LAI to get the average LAI values for each phenological stage. Using these LAI data, the relationships between LAI and crop yield at the main phenological stages of winter wheat was established. After optimizing the yield estimation model, the optimal time period and the best model parameters for winter wheat yield estimation in the study area were selected out. Finally, the established model was applied to estimate winter wheat yield based on the retrieved LAI from MODIS-NDVI, and the model accuracy was tested. Through the comparison of the predicted yield with the measured yield in the field, the mean relative error was 1.21%, and the RMSE was 257.33 kg x hm(-2). The model and the method proposed in this study were promising, and could help to get the accurate estimated yield of winter wheat in about 20-30 days ahead of the harvest.


Effect of epidermal growth factor receptor internalization on regulation of the phospholipase C-gamma1 signaling pathway.
The epidermal growth factor receptor (EGFR) ligands, epidermal growth factor (EGF), and transforming growth factor-alpha (TGFalpha) elicit differential postendocytic processing of ligand and receptor molecules, which impacts long-term cell signaling outcomes. These differences arise from the higher affinity of the EGF-EGFR interaction versus that of TGFalpha-EGFR in the acidic conditions of sorting endosomes. To determine whether EGFR occupancy in endosomes might also affect short-term signaling events, we examined activation of the phospholipase C-gamma1 (PLC-gamma1) pathway, an event shown to be essential for growth factor-induced cell motility. We found that EGF continues to stimulate maximal tyrosine phosphorylation of EGFR following internalization, while, as expected, TGFalpha stimulates markedly less. The resulting higher level of receptor activation by EGF, however, did not yield higher levels of phosphatidylinositol (4,5)-bisphosphate (PIP2) hydrolysis over those stimulated by TGFalpha. By altering the ratio of activated receptors between the cell surface and the internalized compartment, we found that only cell surface receptors effectively participate in PLC function. In contrast to PIP2 hydrolysis, PLC-gamma1 tyrosine phosphorylation correlated linearly with the total level of Tyr(P)-EGFR stimulated by either ligand, indicating that the functional deficiency of internal EGFR cannot be attributed to an inability to interact with and phosphorylate signaling proteins. We conclude that EGFR signaling through the PLC pathway is spatially restricted at a point between PLC-gamma1 phosphorylation and PIP2 hydrolysis, perhaps because of limited access of EGFR-bound PLC-gamma1 to its substrate in endocytic trafficking organelles.


[6]-Gingerol suppresses colon cancer growth by targeting leukotriene A4 hydrolase.
[6]-Gingerol, a natural component of ginger, exhibits anti-inflammatory and antitumorigenic activities. Despite its potential efficacy in cancer, the mechanism by which [6]-gingerol exerts its chemopreventive effects remains elusive. The leukotriene A(4) hydrolase (LTA(4)H) protein is regarded as a relevant target for cancer therapy. Our in silico prediction using a reverse-docking approach revealed that LTA(4)H might be a potential target of [6]-gingerol. We supported our prediction by showing that [6]-gingerol suppresses anchorage-independent cancer cell growth by inhibiting LTA(4)H activity in HCT116 colorectal cancer cells. We showed that [6]-gingerol effectively suppressed tumor growth in vivo in nude mice, an effect that was mediated by inhibition of LTA(4)H activity. Collectively, these findings indicate a crucial role of LTA(4)H in cancer and also support the anticancer efficacy of [6]-gingerol targeting of LTA(4)H for the prevention of colorectal cancer.


Visualization of receptor-mediated endocytosis in yeast.
We studied the ligand-induced endocytosis of the yeast alpha-factor receptor Ste2p by immuno-electron microscopy. We observed and quantitated time-dependent loss of Ste2p from the plasma membrane of cells exposed to alpha-factor. This ligand-induced internalization of Ste2p was blocked in the well-characterized endocytosis-deficient mutant sac6Delta. We provide evidence that implicates furrow-like invaginations of the plasma membrane as the site of receptor internalization. These invaginations are distinct from the finger-like plasma membrane invaginations within actin cortical patches. Consistent with this, we show that Ste2p is not located within the cortical actin patch before and during receptor-mediated endocytosis. In wild-type cells exposed to alpha-factor we also observed and quantitated a time-dependent accumulation of Ste2p in intracellular, membrane-bound compartments. These compartments have a characteristic electron density but variable shape and size and are often located adjacent to the vacuole. In immuno-electron microscopy experiments these compartments labeled with antibodies directed against the rab5 homologue Ypt51p (Vps21p), the resident vacuolar protease carboxypeptidase Y, and the vacuolar H+-ATPase Vph1p. Using a new double-labeling technique we have colocalized antibodies against Ste2p and carboxypeptidase Y to this compartment, thereby identifying these compartments as prevacuolar late endosomes.


Gait analysis after total knee replacement for degenerative arthritis.
Using quantitative gait analysis and clinical evaluation, the functional results of 18 total knee replacement (TKR) in 13 patients who had osteoarthritis were evaluated. Nine knees each were replaced by Insall-Burnstein (I/B) posterior stabilized design or Miller-Galante (M/G) prosthesis. The former was fixed by cement and needed to sacrifice posterior cruciate ligament (PCL), while the latter was inserted without cement, and PCL could be reserved. The follow-up period ranged from 21 to 77 months. At the final follow-up, the overall functional knee score was 94.1 points (I/B 95.0 versus M/G 92.2). The average active knee flexion was 109.7 degrees (I/B 116.4 degrees versus M/G 102.9). For gait analysis, three cameras synchronized with 2 AMTI force plates were connected to the VICON system to provide kinetic and kinematic data during level walking. The data were compared with the non-operated side; and with younger subjects as normal control. They were supposed to possess normal knee functions. In patients after knee prosthesis, they tended to have slower velocity, shorter step length and less cadence. They also showed shorter swing and longer stance phases. In the M/G knee ground, the duration for double-limb support was longer, but shorter for single-limb support. The angles of knee flexion-extension of both prosthetic groups became narrower. Their ground reaction forces in both vertical and medio-lateral directions were larger than in the control groups, probably due to quadriceps dysfunction and subtle imbalance of the soft tissue-prosthesis complex around the joint.(ABSTRACT TRUNCATED AT 250 WORDS)


The provision of toys to pigs can improve the human-animal relationship.
It is now widely recognised that a positive human-animal relationship is beneficial not only for farm animals' welfare but also for productivity and the quality of products. A better understanding of animal emotions is an important goal in disciplines ranging from neuroscience to animal welfare science, but few reliable tools exist for measuring these emotions. In this study, whether the provision of toys to solicit play behaviour in pigs is associated with a change in the human-animal relationship and the emotional state of pigs was investigated. We involved a group of sixteen mini-pigs housed in an experimental setting and the use of a preliminary test called the 'strange person' test. After a Control and a Play session (with medium-sized dog toys, balls with ropes), the strange person test was performed. During the test, a person wearing a colourful overall, a hood, a mask, gloves and boots (unknown person with an odd appearance) entered the pen, where 2 mini-pigs were housed, for a 2-min video recording. The strange person test results after the Play and Control sessions were compared. The results showed that the latency to approach the person (duration in seconds) and the duration for which the pig was distant from the strange person (duration in seconds) were significantly lower after the Play session than after the Control session (Degrees of Freedom =30; Statistic of the F test =39.1; p < 0.0001 and Degrees of Freedom =15; Statistic of the F test =54.3; p < 0.0001, respectively). The duration of direct contact (duration in seconds) (Degrees of Freedom =15; Statistic of the F test =14.8; p = 0.002), the need to separate the pig from the strange person (frequency) (Degrees of Freedom =30; Statistic of the F test =9.3; p = 0.005) and the duration of tail movement (duration in seconds) (Degrees of Freedom =15; Statistic of the F test =12.6; p = 0.003) were all significantly higher after the Play sessions than after the Control sessions. Overall, the results suggest a change in the human-animal relationship after the Play sessions: the pigs seemed to be less fearful and more inclined to interact with the strange person, showing a more positive emotional state. This preliminary study suggests that the provision of toys, and more precisely, the opportunity to perform object play behaviour, and sometimes, spontaneously, social play behaviour, can improve the human-animal relationship. Additional research to explore this topic thoroughly may yield interesting results because a positive emotional state of the animals and a good human-animal relationship are essential to ensure good quality of life of farm animals.


Depression preceding choreiform movements in Huntington's Disease: a case study.
Huntington's Disease (HD) is a progressive neurological disorder whose cardinal features are involuntary movements and cognitive decline. Severe emotional and/ or psychiatric disturbances are common features of the mental deterioration. When the emotional disturbance precedes the development of the movement disorder, HD is often misdiagnosed as a psychiatric condition. The present case study taken from the University of Texas Neuropathology Museum illustrates these issues. The patient was diagnosed and treated for depression for over a decade before the behavioral and neurological deterioration progressed to the point that an HD diagnosis could be made. Only with the detection of a positive family history and the onset of the hallmark choreiform movements was the final diagnosis of HD made. The patient's behavioral features are presented and current pathological and neuropsychological findings in HD are reviewed and discussed.


Artificial intelligence in gastroenterology: A state-of-the-art review.
The development of artificial intelligence (AI) has increased dramatically in the last 20 years, with clinical applications progressively being explored for most of the medical specialties. The field of gastroenterology and hepatology, substantially reliant on vast amounts of imaging studies, is not an exception. The clinical applications of AI systems in this field include the identification of premalignant or malignant lesions (e.g., identification of dysplasia or esophageal adenocarcinoma in Barrett's esophagus, pancreatic malignancies), detection of lesions (e.g., polyp identification and classification, small-bowel bleeding lesion on capsule endoscopy, pancreatic cystic lesions), development of objective scoring systems for risk stratification, predicting disease prognosis or treatment response [e.g., determining survival in patients post-resection of hepatocellular carcinoma), determining which patients with inflammatory bowel disease (IBD) will benefit from biologic therapy], or evaluation of metrics such as bowel preparation score or quality of endoscopic examination. The objective of this comprehensive review is to analyze the available AI-related studies pertaining to the entirety of the gastrointestinal tract, including the upper, middle and lower tracts; IBD; the hepatobiliary system; and the pancreas, discussing the findings and clinical applications, as well as outlining the current limitations and future directions in this field.


Transcription Factor 2I Regulates Neuronal Development via TRPC3 in 7q11.23 Disorder Models.
Williams syndrome (WS) and 7q11.23 duplication syndrome (Dup7q11.23) are neurodevelopmental disorders caused by the deletion and duplication, respectively, of ~ 25 protein-coding genes on chromosome 7q11.23. The general transcription factor 2I (GTF2I, protein TFII-I) is one of these proteins and has been implicated in the neurodevelopmental phenotypes of WS and Dup7q11.23. Here, we investigated the effect of copy number alterations in Gtf2i on neuronal maturation and intracellular calcium entry mechanisms known to be associated with this process. Mice with a single copy of Gtf2i (Gtf2i+/Del) had increased axonal outgrowth and increased TRPC3-mediated calcium entry upon carbachol stimulation. In contrast, mice with 3 copies of Gtf2i (Gtf2i+/Dup) had decreases in axon outgrowth and in TRPC3-mediated calcium entry. The underlying mechanism was that TFII-I did not affect TRPC3 protein expression, while it regulated TRPC3 membrane translocation. Together, our results provide novel functional insight into the cellular mechanisms that underlie neuronal maturation in the context of the 7q11.23 disorders.


Rotating fullerene chains in carbon nanopeapods.
The rotation of fullerene chains in SWNT peapods is studied using low-voltage high resolution transmission electron microscopy. Anisotropic fullerene chain structures (i.e., C300) are formed in situ in carbon nanopeapods via electron beam induced coalescence of individual fullerenes (i.e., C60). A low electron accelerating voltage of 80 kV is used to prevent damage to the SWNT. The large asymmetric C300 fullerene structure exhibits translational motion inside the SWNT and unique corkscrew like rotation motion. Another asymmetric fullerene chain containing mixed fullerene species is prepared by fusing smaller C60 fullerenes to a larger Sc@C82 fullerene, and this also exhibits corkscrew rotational motion. Chains of Sc3C2@C80 in SWNT peapods adopt a zigzag packing structure, and the entire zigzag chain rotates inside the SWNT to induce structural modifications to the SWNT diameter and cross-sectional shape of the SWNT. The expansion and contraction of the diameter of the SWNT is measured as 17%, demonstrating nanoactuation behavior in carbon nanopeapods.


Prevalence and significance of MEFV gene mutations in patients with gouty arthritis.
Gouty arthritis is a chronic erosive autoinflammatory disease. Pyrin has anti-inflammatory effects in the regulation of inflammasome and is encoded by the MEFV gene. The relationship between different rheumatic diseases and the MEFV gene mutations was demonstrated. The aim of this study was to determine the frequency of MEFV gene mutations in patients with gouty arthritis and identify a possible correlation with disease phenotype. Ninety-three patients with gouty arthritis and 102 healthy controls, compatible with age, gender and ethnicity, were included in the study. MEFV gene mutations were investigated by PCR method. Out of 93 patients with gouty arthritis, 36 (38.7 %) showed MEFV gene mutations carriage, whereas 20.6 % in healthy control group. Distribution of mutations identified in patients with gouty arthritis was as; R202Q in 18 (19.3 %), E148Q in 5 (5.4 %), K695R in 4 (4.3 %), M680I in 2 (2.1 %), V726A in 2 (2.1 %), P369S in 2 (2.1 %), R408Q in 2 (2.1 %), M694 V in 1 (1.1 %), respectively. Three patients were identified with compound heterozygosity. Distribution of MEFV gene mutations carriage in healthy controls was; E148Q in 11 (10.7 %), M694 V in 2 (1.9 %), M694I in 1 (0.9 %), M680I in 2 (1.9 %), V726A in 1 (0.9 %), A744S in 1 (0.9 %), K695R in 2 (1.9 %), and P369S in 1 (0.9 %) patients, respectively. Higher MEFV gene mutations carrier frequency was observed in patients with gouty arthritis, compared with the control group (p = 0.009). Heterozygous R202Q was the most common mutation detected in patients with gouty arthritis, while heterozygous E148Q in healthy control group. Statistically significant difference was not detected between clinical findings of gouty arthritis and the MEFV gene mutations (p > 0.05). We determined higher prevalence of MEFV gene mutations in patients with gouty arthritis compared with the healthy control group. The most frequently detected mutation was heterozygous R202Q, whereas E148Q in healthy controls. High carriage rates of MEFV gene mutations in gouty arthritis suggest that it may play an important role in the pathogenesis of the disease and predisposition to the disease.


Erythrocyte aggregation tendency and cellular properties in horse, human, and rat: a comparative study.
Horse blood has a higher tendency to form red blood cell (RBC) aggregates compared with human blood, with this enhanced aggregation previously attributed to differences in plasma factors. Our results confirm this observation and further indicate that washed horse RBC also have a significantly higher aggregation tendency in dextran 70 solutions (i.e., horse RBC have a higher "aggregability"). In contrast, the aggregation tendency of rat RBC, both in autologous plasma and in dextran 70, is significantly less compared with human and horse RBC. Other rheological findings for horse and rat RBC include smaller changes in RBC deformation indexes over the same shear stress range and a lower RBC shape recovery time constant. Rat RBC also had higher two-phase aqueous polymer partition coefficients, suggesting a higher surface charge. Membrane protein analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed marked differences: 1) band 4.2 protein was lacking in horse RBC membranes, and 2) carbohydrate groups have different distributions in human, rat, and horse RBC, as indicated by different patterns in periodic acid-Schiff-stained protein bands. Our results clearly indicate significant differences in RBC aggregability among the three species and indicate that cellular factors contribute importantly to these differences. Furthermore, they suggest that systematic studies of blood and RBC from different species should provide insight into the mechanism(s) of RBC aggregation.


LPTA: location predictive and time adaptive data gathering scheme with mobile sink for wireless sensor networks.
This paper exploits sink mobility to prolong the lifetime of sensor networks while maintaining the data transmission delay relatively low. A location predictive and time adaptive data gathering scheme is proposed. In this paper, we introduce a sink location prediction principle based on loose time synchronization and deduce the time-location formulas of the mobile sink. According to local clocks and the time-location formulas of the mobile sink, nodes in the network are able to calculate the current location of the mobile sink accurately and route data packets timely toward the mobile sink by multihop relay. Considering that data packets generating from different areas may be different greatly, an adaptive dwelling time adjustment method is also proposed to balance energy consumption among nodes in the network. Simulation results show that our data gathering scheme enables data routing with less data transmission time delay and balance energy consumption among nodes.


Recognition and management of excessive sleepiness in the primary care setting.
Excessive sleepiness often goes unrecognized in the primary care setting despite its high prevalence and deleterious effects on both individual and public safety. Patients with neurologic and psychiatric illnesses, as well as those with acute and chronic medical conditions, plus those with sleep disorders, often have symptoms of excessive sleepiness, tiredness, and fatigue. Recognition and prompt treatment of these symptoms are important, even though their etiology may not be immediately understood. This review focuses on the underlying causes, consequences, identification, and treatment of excessive sleepiness. A search of the literature to 2007 was performed using the PubMed search engine. English-language articles were identified using the following search terms: excessive sleepiness, fatigue, circadian rhythm, obstructive sleep apnea, shift work disorder, narcolepsy, drowsy driving, and wakefulness. Additional references were identified through bibliography reviews of relevant articles. Current assessments of the prevalence, consequences, and etiologies of excessive sleepiness, with leading treatment strategies, were extracted, reviewed, and summarized to meet the objectives of this article. Excessive sleepiness is associated with a wide range of medical, neurologic, and psychiatric disorders frequently seen in primary care practice. Excessive sleepiness is a serious, debilitating, potentially life-threatening condition, yet also treatable, and it is important to initiate appropriate intervention as early as possible. Physicians should place increasing emphasis on the substantial benefits that accompany improvements in wakefulness.


Diabetes care in Switzerland: good, but perfectible: a population-based cross-sectional survey.
While Switzerland invests a lot of money in its healthcare system, little is known about the quality of care delivered. The objective of this study was to assess the quality of care provided to patients with diabetes in the Canton of Vaud, Switzerland. Cross-sectional study of 406 non-institutionalized adults with type 1 or 2 diabetes. Patients' characteristics, diabetes and process of care indicators were collected using a self-administered questionnaire. Process indicators (past 12 months) included HbA1C check among HbA1C-aware patients, eye assessment by ophtalmologist, microalbuminuria check, feet examination, lipid test, blood pressure and weight measurement, influenza immunization, physical activity recommendations, and dietary recommendations. Item-by-item (each process of care indicator: percentage of patients having received it), composite (mean percentage of recommended care: sum of received processes of care / sum of possible recommended care), and all-or-none (percentage of patients receiving all specified recommended care) measures were computed. Mean age was 64.4 years; 59% were men. Type 1 and type 2 diabetes were reported by 18.2% and 68.5% of patients, respectively, but diabetes type remained undetermined for almost 20% of patients. Patients were treated with oral anti-diabetic drugs (50%), insulin (23%) or both (27%). Of 219 HbA1C-aware patients, 98% reported ≥ one HbA1C check during the last year. Also, ≥94% reported ≥ one blood pressure measurement, ≥ one weight measurement or lipid test, and 68%, 64% and 56% had feet examination, microalbuminuria check and eye assessment, respectively. Influenza immunization was reported by 62% of the patients.The percentage of patients receiving all processes of care ranged between 14.2%-16.9%, and 46.6%-50.7%, when considering ten and four indicators, respectively. Ambulatory care utilization showed little use of multidisciplinary care, and low levels of participation in diabetes-education classes. While routine processes-of-care were performed annually in most patients, diabetes-specific risk screenings, influenza immunization, physical activity and dietary recommendations were less often reported; this was also the case for multidisciplinary care and participation in education classes. There is room for diabetes care improvement in Switzerland. These results should help define priorities and further develop country-specific chronic disease management initiatives for diabetes.


Multiscale modeling of damaged surface topology in a hypersonic boundary.
In this work, we used molecular dynamics (MD) to perform trajectory simulations of ice-like argon and amorphous silica aggregates on atomically smooth highly ordered pyrolytic graphite (HOPG) and a comparatively rougher quartz surface. It was found that at all incidence velocities, the quartz surface was stickier than the HOPG surface. The sticking probabilities and elastic moduli obtained from MD were then used to model surface evolution at a micron length scale using kinetic Monte Carlo (kMC) simulations. Rules were derived to control the number of sites available for the process execution in kMC to accurately model erosion of HOPG by atomic oxygen (AO) attack and ice-nucleation on surfaces. It was observed that the effect of defects was to increase the material erosion rate, while that of aggregate nucleation was to lower it. Similarly, simulations were performed to study the effects of AO attack and N2 adsorption-desorption on surface evolution and it was found that N2 adsorption-desorption limits the surface available for erosion by AO attack.


Semi-automated screening of biomedical citations for systematic reviews.
Systematic reviews address a specific clinical question by unbiasedly assessing and analyzing the pertinent literature. Citation screening is a time-consuming and critical step in systematic reviews. Typically, reviewers must evaluate thousands of citations to identify articles eligible for a given review. We explore the application of machine learning techniques to semi-automate citation screening, thereby reducing the reviewers' workload. We present a novel online classification strategy for citation screening to automatically discriminate "relevant" from "irrelevant" citations. We use an ensemble of Support Vector Machines (SVMs) built over different feature-spaces (e.g., abstract and title text), and trained interactively by the reviewer(s). Semi-automating the citation screening process is difficult because any such strategy must identify all citations eligible for the systematic review. This requirement is made harder still due to class imbalance; there are far fewer "relevant" than "irrelevant" citations for any given systematic review. To address these challenges we employ a custom active-learning strategy developed specifically for imbalanced datasets. Further, we introduce a novel undersampling technique. We provide experimental results over three real-world systematic review datasets, and demonstrate that our algorithm is able to reduce the number of citations that must be screened manually by nearly half in two of these, and by around 40% in the third, without excluding any of the citations eligible for the systematic review. We have developed a semi-automated citation screening algorithm for systematic reviews that has the potential to substantially reduce the number of citations reviewers have to manually screen, without compromising the quality and comprehensiveness of the review.


United European Gastroenterology Week scientific abstracts and their progression to full publication.
Abstracts presentations at scientific meetings enable rapid dissemination of novel research. The percentage of abstracts that proceed to full publication from differing medical specialties is highly variable. This study aims to evaluate the outcomes of abstracts presented at the United European Gastroenterology Week (UEGW). All abstracts presented at UEGW between 2009 and 2011 were assessed. Cross-referencing of the first author, senior author and at least one keyword of the abstract was performed using PubMed and EMBASE databases. Abstracts and possible resultant full publications were then examined in tandem to ensure that they represented the same study. Data were also collected on lag time to publication, journal impact factors, country of the author and factors influencing subsequent publication. A total of 6785 abstracts (1438 oral and 5347 poster presentations) were presented during the period assessed. Of these, 2099 (30.9%) proceeded to full publication in indexed journals. Oral abstract presentations were most likely to proceed to full publication compared with poster presentations (odds ratio: 1.38, 95% confidence interval: 1.22-1.56) and were more likely to achieve publication in higher impact journals (median impact factor 4.78 vs. 2.89, P<0.0005). The median lag time to full publication was 15 (IQR: 7-15) months. The Netherlands had the highest United European Gastroenterology abstract conversion rate to full publication (46.8%). This is the first study to assess the publication rates of UEGW. Findings are favourable with similar studies from other societies.


Peak flow variation in childhood asthma: relationship to symptoms, atopy, airways obstruction and hyperresponsiveness. Dutch CNSLD Study Group.
Although home recording of peak expiratory flow (PEF) is considered useful in managing asthma, little is known about the relationship of PEF variation to other indicators of disease activity. We examined the relationship of PEF variation, expressed in various ways, to symptoms, atopy, level of lung function, and airways hyperresponsiveness in schoolchildren with asthma. One hundred and two asthmatic children (aged 7-14 yrs) recorded symptoms and PEF (twice daily) in a diary for 2 weeks after withdrawal of all anti-inflammatory maintenance medication. PEF variation was expressed as amplitude % mean, as standard deviation and coefficient of variation of all recordings, and as low % best (lowest PEF as percentage of the highest of all values). Atopy and level of forced expiratory volume in one second (FEV1) % predicted were not significantly related to PEF variation. The provocative dose of histamine causing a 20% fall in FEV1 (PD20) and symptom scores were significantly, but weakly, related to PEF variation. The index, low % best, proved easy to calculate and effective in identifying a short-term episode of reduced PEF. We conclude that peak expiratory flow variation in children with stable, moderately severe asthma is significantly, but weakly, related to symptoms and airways hyperresponsiveness. These three phenomena, therefore, all provide different information on the actual disease state. Expressing peak expiratory flow variation as low % best is easy to perform and appears to be clinically relevant.


Synthesis, biological evaluation, and radioiodination of halogenated closo-carboranylthymidine analogues.
The synthesis and initial biological evaluation of 3-carboranylthymidine analogues (3CTAs) that are (radio)halogenated at the closo-carborane cluster are described. Radiohalogenated 3CTAs have the potential to be used in the radiotherapy and imaging of cancer because they may be selectively entrapped in tumor cells through monophosphorylation by human thymidine kinase 1 (hTK1). Two strategies for the synthesis of a (127)I-labeled form of a specific 3CTA, previously designated as N5, are described: (1) direct iodination of N5 with iodine monochloride and aluminum chloride to obtain N5-(127)I and (2) initial monoiodination of o-carborane to 9-iodo-o-carborane followed by its functionalization to N5-(127)I. The former strategy produced N5-(127)I in low yields along with di-, tri-, and tetraiodinated N5 as well as decomposition products, whereas the latter method produced only N5-(127)I in high yields. N5-(127)I was subjected to nucleophilic halogen- and isotope-exchange reactions using Na(79/81)Br and Na(125)I, respectively, in the presence of Herrmann's catalyst to obtain N5-(79/81)Br and N5-(125)I, respectively. Two intermediate products formed using the second strategy, 1-(tert-butyldimethylsilyl)-9-iodo-o-carborane and 1-(tert-butyldimethylsilyl)-12-iodo-o-carborane, were subjected to X-ray diffraction studies to confirm that substitution at a single carbon atom of 9-iodo-o-carborane resulted in the formation of two structural isomers. To the best of our knowledge, this is the first report of halogen- and isotope-exchange reactions of B-halocarboranes that have been conjugated to a complex biomolecule. Human TK1 phosphorylation rates of N5, N5-(127)I, and N5-(79/81)Br ranged from 38.0% to 29.6% relative to that of thymidine, the endogenous hTK1 substrate. The in vitro uptake of N5, N5-(127)I, and N5-(79/81)Br in L929 TK1(+) cells was 2.0, 1.8, and 1.4 times greater than that in L929 TK1(-) cells.


[Antioxidants in the prevention and treatment of cerebral arteriosclerosis].
In animals with peroxide model of atherosclerosis and patients with cerebral atherosclerosis, the protecting effects of antioxidants were studied. These were shown to inhibit both humoral and local manifestations of experimental atherosclerosis. In the patients, lipid levels were lowered with peroxidation indices returning to normal levels and clinical state simultaneously improving.


Electrocardiographic changes during continuous intravenous application of bupivacaine in neonatal pigs.
It is controversial as to whether T-wave elevation is caused by local anaesthetics, epinephrine, or their combination. It has been shown that T-elevation after intravascular injection of a small bupivacaine test dose is caused by epinephrine and not by bupivacaine. The aim of this study was to investigate ECG changes with higher doses of i.v. bupivacaine. Thirty neonatal pigs were anaesthetized with sevoflurane and their tracheas intubated and artificially ventilated. Under steady-state conditions, bupivacaine was continuously infused (flow rate 3.2 ml kg(-1) min(-1)) by a syringe infusion pump through a central venous catheter. Group 1 received bupivacaine 0.125%, Group 2 bupivacaine 0.5%. The ECG was continuously printed and subsequently analysed for alterations in heart rate, ventricular de- and repolarization, and arrhythmias at 1.25, 2.5, and 5 mg kg(-1) bupivacaine infused. Sinus rhythm persisted in all pigs. Heart rate decreased progressively in both groups, but this was significantly more pronounced in Group 1. T-wave elevation occurred in 40% and 0% (Groups 1 and 2) at 1.25 mg kg(-1), in 80% and 0% at 2.5 mg kg(-1), and in 93% and 80% at 5 mg kg(-1) bupivacaine infused. There were significant differences between the two groups at 1.25 and 2.5 mg kg(-1) infused. Higher doses of i.v. infused bupivacaine can cause T-elevation. With slower injection technique, T-elevation can already be detected at lower bupivacaine doses administered.


RNase E, the major player in mRNA degradation, is down-regulated in Escherichia coli during a transient growth retardation (diauxic lag).
The endoribonuclease RNase E plays a major part in mRNA degradation in Escherichia coli in addition to its role in processing rRNA. RNase E is encoded by an essential gene, rne, also known as ams and hmp, which is autoregulated post-transcriptionally. Here we report a transient decrease in the steady state level of the full-length rne transcript and a corresponding decline in the amount of the protein and enzymatic activity. During this period an mRNA fragment, lacking an intact 5' end, accumulates. This down-regulation of RNase E occurs under aerobic growth conditions in rich medium during a short diauxic lag in mid-exponential phase; it most likely reflects an exhaustion of a not yet identified medium compound which is followed by switching on a new metabolic pathway. During this lag, the levels of bulk protein are maintained. Our results suggest that a transient drop in the intracellular RNase E level is a means of cells to retard mRNA turnover in a period of adjustment to medium utilization. Furthermore, the here described regulation of the rne transcript and its cognate gene product seems to occur by an RNase E-independent mechanism responsive to changes in growth conditions.


Psychological outcomes in long-term survivors of childhood leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma: a report from the Childhood Cancer Survivor Study.
To evaluate and compare psychological outcomes in long-term survivors of pediatric leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma and sibling controls. Adult survivors of childhood leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma (N = 5736) and sibling controls (N = 2565) were administered a long-term follow-up questionnaire allowing assessment of symptoms associated with depression and somatic distress. The majority of respondents in this study did not demonstrate symptomatology indicative of depression or somatic distress. Survivors, however, were significantly more likely than sibling controls to report symptoms of depression and somatic distress. Women were significantly more likely to indicate symptoms of depression and somatic distress than were men; however, this difference did not vary by survivor/sibling status. Similarly, socioeconomic (SES) variables predicted symptomatic levels of depression and somatic distress for both survivors and siblings, and these effects did not vary by survivor/sibling status. Among leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma survivors, in addition to gender and SES, the only treatment variable that predicted scores indicating depressive symptomatology was exposure to intensive chemotherapy. Exposure to intensive chemotherapy also predicted scores indicative of somatic distress symptoms. No other medical variables, including diagnostic category, age at diagnosis, time since diagnosis, and duration of treatment, predicted symptomatic scores for depression and somatic distress. This large, sibling-controlled, multisite study of young adult survivors of childhood leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma found that survivors had significant increased risk for reporting symptoms of depression and somatic distress and that intensive chemotherapy added to this risk. However, being a cancer survivor did not compound the effects of gender and SES variables on the 2 outcomes measured. The ability of SES, gender, and treatment-related variables to predict psychological symptoms in this cohort of childhood survivors and sibling controls calls for future research into varied biological and psychosocial pathways by which cancer influences future psychosocial functioning.


Packet Fragmentation and Reassembly in Molecular Communication.
This paper describes packet fragmentation and reassembly to achieve reliable molecular communication among bionanomachines. In the molecular communication described in this paper, a sender bionanomachine performs packet fragmentation, dividing a large molecular message into smaller pieces and embedding into smaller molecular packets, so that molecular packets have higher diffusivity to reach the receiver bionanomachine. The receiver bionanomachine then performs packet reassembly to retrieve the original molecular message from a set of molecular packets that it receives. To examine the effect of packet fragmentation and reassembly, we develop analytical models and conduct numerical experiments. Numerical results show that packet fragmentation and reassembly can improve the message delivery performance. Numerical results also indicate that packet fragmentation and reassembly may degrade the performance in the presence of drift in the environment.


New real-time interactive cardiac magnetic resonance imaging system complements echocardiography.
We conducted an initial clinical trial of a newly developed cardiac magnetic resonance imaging (CMRI) system. We evaluated left ventricular (LV) function in 85 patients to compare the clinical utility of the CMRI system with echocardiography, the current noninvasive gold standard. Conventional CMRI systems require cardiac-gating and respiratory compensation to synthesize a single image from data acquired over multiple cardiac cycles. In contrast, the new CMRI system allows continuous real-time dynamic acquisition and display of any scan plane at 16 images/s without the need for cardiac gating or breath-holding. A conventional 1.5T Signa MRI Scanner (GE, Milwaukee, Wisconsin) was modified by the addition of an interactive workstation and a bus adapter. The new CMRI system underwent clinical trial by testing its ability to evaluate global and regional LV function. The first group (A) consisted of 31 patients with acceptable echocardiography image quality. The second group (B) consisted of 31 patients with suboptimal echocardiography image quality. The third group (C) consisted of 29 patients with severe lung disease or congenital cardiac malformation who frequently have suboptimal echo study. Two independent observers scored wall motion and image quality using the standard 16-segment model and rank-order analysis. CMRI evaluation was complete in less than 15 min. In group A, no significant difference was found between ECHO and CMRI studies (p = NS). In group B, adequate visualization of wall segments was obtained 38% of the time using ECHO and 97% of the time using CMRI (p < 0.0001). When grouped into coronary segments, adequate visualization of at least one segment occurred in 18 of 30 patients (60%) with ECHO and in all 30 patients (100%) with CMRI (p < 0.0001). In group C, adequate visualization of the wall segments was obtained in 58% (CI 0.53-0.62) of the time using echocardiography and 99.7% (CI 0.99-1.0) of the time using CMRI (p < 0.0001). The new CMRI system provides clinically reliable evaluation of LV function and complements suboptimal echocardiography. In comparison with the conventional CMRI, the new CMRI system significantly reduces scan time, patient discomfort and associated cost.


Inhibitor of adenosine 3':5'-monophosphate-dependent protein kinase blocks presynaptic facilitation in Aplysia.
Sensitization of the gill withdrawal reflex results from presynaptic facilitation at the excitatory synapses made by sensory neurons on gill motor neurons. Facilitation is accompanied by an increase in the duration of the action potential in sensory cells because of the depression of a K+ current. This results in an increasd influx of CA2+ and a greater release of transmitter from sensory neurons. There is evidence that serotonin is the facilitating transmitter and that the depression of the K+ current by serotonin mediated by cAMP-dependent protein phosphorylation. To test further the role of the cAMP-dependent protein kinase and of protein phosphorylation in sensitization, we have attempted to prevent or reverse the development of the electrophysiological correlates that accompany sensitization. We have pressure-injected sensory neurons with a specific and a stable protein inhibitor of the cAMP-dependent protein kinase both before and after the application of serotonin or the activation of the facilitator neurons. The increase in spike broadening that accompanies facilitation was prevented or diminished by injection of the inhibitor. Moreover, injection of the inhibitor could reverse fully the developed spike broadening produced by prior application of serotonin. These observations strenthen the evidence for the involvement of protein phosphorylation in presynaptic facilitation. Phosphorylation of the substrate protein evidently is quite labile and does not persist after the kinase is inhibited. Thus, the time course of short term sensitization appears to be determined by an active kinase. We think that it is likely that the mechanism for maintaining the kinase in an active form resides in the slow decay of the cAMP produced by the action of serotonin or the facilitator neurons on the sensory cells.


Prognostic value of axillary lymph node metastases in invasive lobular breast carcinoma.
Axillary lymph node involvement is a well-established prognostic factor for recurrence in breast cancer, specifically the number of nodes affected and the ratio of the number of affected nodes to the number of harvested nodes for non-specific invasive breast cancer (invasive ductal carcinoma). However, there is limited information on the impact of lymph node involvement in the case of invasive lobular carcinoma. our study aimed to evaluate the prognostic impact of lymph node involvement on overall survival and distant metastatic-free survival according to the number of nodes affected and the ratio of positive nodes (LNR) for patients managed for invasive lobular carcinoma. This is a monocentre, comparative, observational study of patients managed for invasive lobular carcinoma at the Gynaecology Department of the University Hospital Center of Tours between January 1, 2007 and December 31, 2018. The LNR cut-off values used were: low risk if LNR ≤ 0.2; intermediate risk if LNR > 0.2 and ≤ 0.65, and high risk for LNR >0.659. Our study demonstrated a significant difference in overall survival and distant metastasis free survival (p < 0.0001). The 5-years Overall survival was 94 % for N0 patients, 92.4 % for low-risk patients, 85.6 % for intermediate-risk patients and 58.5 % for high-risk patients. The 5-year distant metastasis-free survival was 98.2 % for N0 patients, 95.9 % for low-risk patients, 80.1 % for intermediate-risk patients, and 60.3 % for high-risk patients. Multivariate analysis identified age, invasive lobular histologic type, presence of clinical inflammation, and intermediate and high risk classes of LNR ratio as independent factors affecting overall survival. For metastatic-free survival, the presence of clinical inflammation, the presence of LVSI and the low, intermediate, or high-risk classes of LNR ratio were identified as independent factors. However, age and invasive lobular histologic type did not appear to be independent factors affecting metastatic-free survival. Our study highlights the significant prognostic impact of lymph node involvement in patients with invasive lobular carcinoma. The LNR ratio can be used as a reliable predictor of overall survival and metastatic-free survival in these patients.


Patterns of Heart Failure Dyadic Illness Management: The Important Role of Gender.
The ways in which patients with heart failure (HF) and their care partners work together to manage HF are often overlooked. The aim of this study was to identify and compare different patterns of HF dyadic illness management. This was a secondary analysis of data on HF dyads. Heart failure management was measured using patient and care partner versions of the Self-Care of HF Index and European HF Self-care Behavior Scale. Latent class modeling was used to identify patterns of HF dyadic management. The mean age of the 62 patients and their care partners was 59.7 ± 11.8 and 58.1 ± 11.9 years, respectively. A majority of patients (71.0%) had class III/IV HF, and a majority of the couples (95.2%) were married. Two distinct dyadic patterns were observed, 1 collaborative management type (n = 42, 67.7%) and 1 autonomous management type (n = 20, 32.3%). Dyads in the autonomous pattern were mostly female patients with male care partners; patients in this pattern also were more anxious and depressed, and reported worse relationship quality compared with collaborative dyads. There is an engendered spectrum of collaboration in how HF patient-care partner dyads work together to manage HF that needs to be considered in clinical care and research.


Genetic and environmental influences on psychological distress in the population: General Health Questionnaire analyses in UK twins.
The General Health Questionnaire (GHQ) is the most popular screening instrument for detecting psychiatric disorders in community samples. Using longitudinal data of a large sample of UK twin pairs, we explored (i) heritabilities of the four scales and the total score; (ii) the genetic stability over time; and (iii) the existence of differential heritable influences at the high (ill) and low (healthy) tail of the distribution. At baseline we assessed the GHQ in 627 MZ and 1323 DZ female pairs and at a second occasion (3.5 years later) for a small subsample (90 MZ and 270 DZ pairs). Liability threshold models and raw ordinal maximum likelihood were used to estimate twin correlations and to fit longitudinal genetic models. We estimated extreme group heritabilities of the GHQ distribution by using a model-fitting implementation of the DeFries-Fulker regression method for selected twin data. Heritabilities for Somatic Symptoms, Anxiety, Social Dysfunction, Depression and total score were 0.37, 0.40, 0.20, 0.42 and 0.44, respectively. The contribution of shared genetic factors to the correlations between time points is substantial for the total score (73%). Group heritabilities of 0.48 and 0.43 were estimated for the top and bottom 10% of the total GHQ score distribution, respectively. The overall heritability of the GHQ as a measure of psychosocial distress was substantial (44%), with all scales having significant additive genetic influences that persisted across time periods. Extreme group analyses suggest that the genetic control of resilience is as important as the genetic control of vulnerability.


Mevalonate metabolism: role of kidneys.
More than one-half of the amount of mevalonate that is metabolized by pathways not leading to sterols is accounted for by the action of the kidneys. Conversion of mevalonate in vivo to squalene and sterols in the kidneys is confined almost entirely to the proximal and distal convoluted tubules in the cortex. More sterol than squalene is synthesized from mevalonate not only in the liver but also in the kidney.


[Evaluation of the value of ultrasound-guided core needle biopsy in the diagnosis of breast lesions].
To investigate the accuracy, consistency and related affecting factors in pathological results of breast lesions diagnosed by ultrasound-guided core needle biopsy (CNB) and conventional excision histopathology. The clinical data of 177 consecutive cases of breast lesions examined by ultrasound-guided CNB and subsequently excised were reviewed from Jan. 2003 to Nov. 2009. The agreement of pathological diagnosis between the CNB and subsequent excision pathology was analyzed. There were 136 cancers in the final diagnosis after surgical excision among 386 breast lesions and 129 of them were diagnosed by CNB. The sensitivity (true positive) of CNB was 94.9%, false negative rate was 5.1%, specificity (true negative) was 100%, false positive rate 0, Youden's index was 0.949, and positive predictive value and negative predictive value were 100% and 85.4%, respectively. Condensation rate was 96.0% and Kappa value was 0.895. Ultrasound-guided CNB with histopathological assessment is accurate in diagnosis of breast lesions and has a great consistency with conventional excision pathology. It is a reliable method for the diagnosis of breast lesions to avoid an over-reliance on excision pathological examination.


Spatiotemporal slope stability analytics for failure estimation (SSSAFE): linking radar data to the fundamental dynamics of granular failure.
Impending catastrophic failure of granular earth slopes manifests distinct kinematic patterns in space and time. While risk assessments of slope failure hazards have routinely relied on the monitoring of ground motion, such precursory failure patterns remain poorly understood. A key challenge is the multiplicity of spatiotemporal scales and dynamical regimes. In particular, there exist a precursory failure regime where two mesoscale mechanisms coevolve, namely, the preferred transmission paths for force and damage. Despite extensive studies, a formulation which can address their coevolution not just in laboratory tests but also in large, uncontrolled field environments has proved elusive. Here we address this problem by developing a slope stability analytics framework which uses network flow theory and mesoscience to model this coevolution and predict emergent kinematic clusters solely from surface ground motion data. We test this framework on four data sets: one at the laboratory scale using individual grain displacement data; three at the field scale using line-of-sight displacement of a slope surface, from ground-based radar in two mines and from space-borne radar for the 2017 Xinmo landslide. The dynamics of the kinematic clusters deliver an early prediction of the geometry, location and time of failure.


Winter peak of respiratory syncytial virus in Islamabad.
A study was carried out on 391 cases of bronchiolitis and pneumonia from different paediatric units in Rawalpindi/Islamabad, Pakistan. A clear winter spike of respiratory syncytial virus (RSV) was noted. It was found that there was a substantial increase of 30-50% in the positivity of RSV from December to February.


Colchicine myopathy and neuropathy.
Although colchicine has been used for centuries, its neuromuscular toxicity in humans is largely unrecognized. In this report we describe a characteristic syndrome of myopathy and neuropathy and present 12 new cases of the condition. Colchicine myopathy may occur in patients with gout who take customary doses of the drug but who have elevated plasma drug levels because of altered renal function. It usually presents with proximal weakness and always presents with elevation of serum creatine kinase; both features remit within three to four weeks after the drug is discontinued. The accompanying axonal polyneuropathy is mild and resolves slowly. Electromyography of proximal muscles shows a myopathy that is marked by abnormal spontaneous activity. Because of these features, colchicine myoneuropathy is usually misdiagnosed initially, either as probable polymyositis or as uremic neuropathy. The myopathy is vacuolar, marked by accumulation of lysosomes and autophagic vacuoles unrelated to necrosis or to the mild denervation in distal muscles. The morphologic changes in muscle suggest that the pathogenesis involves disruption of a microtubule-dependent cytoskeletal network that interacts with lysosomes. Correct diagnosis may save patients with this disorder from inappropriate therapy.


Correlating IgE reactivity with three-dimensional structure.
This Commentary discusses the work of Neudecker et al. in this issue of the Biochemical Journal in which site-directed mutagenesis and NMR spectroscopy have been used to analyse in detail the IgE-binding capacity of two cross-reactive allergens: Apg1.0101 from celery ( Apium graveolens ) and Pru av 1 from cherry ( Prunus avium ), which are both members of the pathogenesis-related allergen family. The study, showing that the IgE-binding epitopes are highly patient specific, will have a profound impact on our understanding of conformational IgE-binding epitopes, raising serious questions about the therapeutic usefulness of conventional site-directed-mutagenic approaches for the production of hypo-allergenic protein variants.


Menstrual cycle dysfunction associated with neurologic and psychiatric disorders: their treatment in adolescents.
Epilepsy, bipolar disorder, and migraines are common disorders that are often associated with disturbances in menstrual function in adolescent girls. Women with untreated epilepsy are more likely to have irregular menstrual cycles than are nonepileptic controls, indicating that the disease itself plays a role in the etiology of these reproductive abnormalities. In addition, many girls with these disorders require chronic maintenance treatment with agents that may perturb the hypothalamic-pituitary-ovarian axis. Valproate is a highly effective antiepileptic drug used widely to treat epilepsy, bipolar disorder, and migraines. Valproate induces features of the polycystic ovary syndrome (PCOS) in approximately 7% of women. Girls with epilepsy, and possibly bipolar disorder, appear particularly susceptible to developing PCOS features on valproate, perhaps on account of the relative immaturity of their hypothalamic-pituitary-ovarian axes. Antipsychotics are highly effective drugs used widely to treat adolescents with bipolar disorder, psychotic disorders, and behavioral disturbances. Some, but not all of the antipsychotic, induce hyperprolactinemia, which may result in oligo- or amenorrhea. Prolonged amenorrhea in association with hyperprolactinemia incurs significant risks for bone health in adolescent girls. Because of the potential reproductive health risks associated with use of specific antiepileptic drugs and selective antipsychotics, these agents are vital treatments for adolescents with severe illnesses. Use of these agents should be considered and weighed against the risk of using alternative agents, which have their own side effects, or not treating these serious neurologic and psychiatric disorders.


The TCR γδ repertoire and relative gene expression characteristics of T-ALL cases with biclonal malignant Vδ1 and Vδ2 T cells.
Despite significant improvement in our understanding of T-cell acute lymphoblastic leukemia (T-ALL) biology and pathogenesis, many questions remain unanswered. In previous studies, we found a T-ALL case with two malignant T-cell clones with Vδ1Dδ2Dδ3Jδ1 and Vδ2Dδ3Jδ2 rearrangements. In this study, we further characterized T-ALL cases with two malignant clones containing Vδ1Dδ3Jδ1 and Vδ2Dδ1Jδ1 rearrangements using fine-tiling array comparative genomic hybridization, ligation-mediated polymerase chain reaction (LM-PCR), sequencing, and reverse transcription polymerase chain reaction (RT-PCR) analysis. We further analyzed the distribution and clonality of the T-cell receptor (TCR) Vγ and Vδ subfamily T cells in the two T-ALL cases by RT-PCR and GeneScan. Monoclonal Vδ1 and Vδ2 subfamilies were confirmed in both samples, the Vδ3 through Vδ7 subfamilies could not be detected in the T-ALL samples, whereas the oligoclonal Vδ8 subfamily could be identified. Based on the clinical finding that both of the T-ALL cases with two malignant T-cell clones had a poor outcome, we attempted to compare the expression pattern of genes related to T-cell activation and proliferation between cases with the malignant Vδ1 and Vδ2 T-cell clones and T-ALL cases with a mono-malignant Vα T-cell clone. We selected two T-ALL cases with VαJα rearrangements and analyzed the expression level of Notch1, TAL1, and the CARMA-BCL10-MALT-A20-NF-κB pathway genes by real-time PCR. A20 had significantly higher expression in the biclonal compared with the monoclonal T-ALL group (p=0.0354), and there was a trend toward higher expression for the other genes in the biclonal group with the exception of TAL1, although the differences were not statistically significant. In conclusion, we identified two T-ALL cases with biclonal malignant T-cell clones and described the characteristics of the biclonal T-ALL subtype and its gene expression pattern. Thus, our findings may improve the understanding of biclonal T-ALL.


The challenge in detecting risk areas of snakebite when case rates are low: the case of Amazonian coral snakes.
Identifying risk areas for envenomation by animals is relevant for public health, such as strategic distribution of antivenoms. Coral snakes are highly diverse in the Amazon, inhabit natural and human-modified environments, and the outcome of the cases tends to be serious and potentially lethal due to their neurotoxic venom. By integrating species' geographical records and environmental variables, we used species distribution modeling to predict the distribution of coral snake species in the Brazilian Amazonia. We analyzed the relationship between the predicted distribution of coral snake species, along with envenomation data in the region, to propose actions to reduce the number of cases and to provide tools for a better policy of public health. We conclude that the entire Amazon shows high environmental suitability for coral snakes, and such suitability explains little about the incidence of cases. This is probably due to the low human density in the Amazon and to coral snake traits such as secretive habits and non-agressive behavior. Differently from other venomous snakes, the scenario regarding coral snakebites precludes the detection of prominent geographical areas of concern and demands a broad and equitable availability of health centers throughout Amazonia and along other areas of occurrence of the genus Micrurus.


Comparison of robotic versus laparoscopic skills: is there a difference in the learning curve?
To evaluate the learning curve between robot-assisted and manual laparoscopic suturing, as well as to assess other skills. Laparoscopic reconstructive procedures have been limited by instrumentation, small working spaces, and fixed angles at the trocar level to place sutures. Robot-assisted laparoscopic suture placement may provide one means of increasing dexterity and facilitating laparoscopic reconstructive procedures. Eight physicians participated in this study. A series of five trials were performed to assess dexterity (task 1) and free-hand suturing (task 2). Each task was performed using robot-assisted and manual laparoscopy. The participants were categorized as novice and experienced laparoscopists. Task 1 involved passing sutures through the eye of seven needles positioned 1 cm apart in a P configuration. Task 2 involved tying one surgeon's knot, followed by two subsequent knots. The average time for trials 1 and 5 of task 1, robot-assisted laparoscopy, was 242.6 and 101.8 seconds, respectively (P <0.001). Both groups demonstrated a statistically significant difference (P <0.001) between the first and last trial. The average time for trials 1 and 5 of task 1, manual laparoscopy, was 205.3 and 169 seconds, respectively. The differences in the learning curves for robot-assisted and manual laparoscopy were statistically significant in favor of robotic assistance. Manual laparoscopic suturing did not demonstrate as much of a difference for the experienced surgeon. Overall, the difference in improvement between robot-assisted and manual laparoscopy was not statistically significant. Robot-assisted laparoscopic allows suturing and dexterity skills to be performed quicker than does manual laparoscopy.


[Intraperitoneal chemo-hyperthermia in the treatment of peritoneal carcinomatosis of ovarian origin. Initial cases, physiopathologic data].
The authors report the first results using intraperitoneal hyperthermic chemotherapy with mitomycin C or cisplatinum with protective hypothermia up to 32 degrees C in four cases of peritoneal carcinomatosis secondary to cancer of the ovary which was resistant to conventional treatment. They were stage III and IV in the FIGO classification. There were no post-operative complications. Two patients are still alive 4 and 6 months after intraperitoneal hyper-chemotherapy. Hypothermia has its own action of destroying tumour cells and potentiates the effects of chemotherapy. We have, following the work of the japanese, devised a therapeutic regime combining chemotherapy and intraperitoneal hyperthermia.


Interventions to reduce pedestrian road traffic injuries: A systematic review of randomized controlled trials, cluster randomized controlled trials, interrupted time-series, and controlled before-after studies.
Road traffic injuries are among the top ten causes of death globally, with the highest burden in low and middle-income countries, where over a third of deaths occur among pedestrians and cyclists. Several interventions to mitigate the burden among pedestrians have been widely implemented, however, the effectiveness has not been systematically examined. To assess the effectiveness of interventions to reduce road traffic crashes, injuries, hospitalizations and deaths among pedestrians. We considered studies that evaluated interventions to reduce road traffic crashes, injuries, hospitalizations and/or deaths among pedestrians. We considered randomized controlled trials, interrupted time-series studies, and controlled before-after studies. We searched MEDLINE, EMBASE, Web of Science, WHO Global Health Index, Health Evidence, Transport Research International Documentation and ClinicalTrials.gov through 31 August 2020, and the reference lists of all included studies. Two reviewers independently screened titles and abstracts and full texts, extracted data and assessed the risk of bias. We summarized findings narratively with text and tables. A total of 69123 unique records were identified through the searches, with 26 of these meeting our eligibility criteria. All except two of these were conducted in high-income countries and most were from urban settings. The majority of studies observed either a clear effect favoring the intervention or an unclear effect potentially favoring the intervention and these included: changes to the road environment (19/27); changes to legislation and enforcement (12/12); and road user behavior/education combined with either changes to the road environment (3/3) or with legislation and enforcement (1/1). A small number of studies observed either a null effect or an effect favoring the control. Although the highest burden of road traffic injuries exists in LMICs, very few studies have examined the effectiveness of available interventions in these settings. Studies indicate that road environment, legislation and enforcement interventions alone produce positive effects on pedestrian safety. In combination with or with road user behavior/education interventions they are particularly effective in improving pedestrian safety.


Nuclease resistant circular DNAs copurify with infectivity in scrapie and CJD.
In transmissible encephalopathies (TSEs), it is commonly believed that the host prion protein transforms itself into an infectious form that encodes the many distinct TSE agent strains without any nucleic acid. Using a Ф29 polymerase and chromatography strategy, highly infectious culture and brain preparations of three different geographic TSE agents all contained novel circular DNAs. Two circular "Sphinx" sequences, of 1.8 and 2.4 kb, copurified with infectious particles in sucrose gradients and, as many protected viruses, resisted nuclease digestion. Each contained a replicase ORF related to microviridae that infect commensal Acinetobacter. Infectious gradient fractions also contained nuclease-resistant 16 kb mitochondrial DNAs and analysis of >4,000 nt demonstrated a 100% identity with their species-specific sequences. This confirmed the fidelity of the newly identified sequences detailed here. Conserved replicase regions within the two Sphinx DNAs were ultimately detected by PCR in cytoplasmic preparations from normal cells and brain but were 2,500-fold less than in parallel-infected samples. No trace of the two Sphinx replicases was found in enzymes, detergents, or other preparative materials using exhaustive PCR cycles. The Sphinx sequences uncovered here could have a role in TSE infections despite their apparently symbiotic, low-level persistence in normal cells and tissues. These, as well as other cryptic circular DNAs, may cause or contribute to neurodegeneration and infection-associated tumor transformation. The current results also raise the intriguing possibility that mammals may incorporate more of the prokaryotic world in their cytoplasm than previously recognized.


Platelet microparticles: a new player in malaria parasite cytoadherence to human brain endothelium.
Cerebral malaria (CM) is characterized by accumulation of circulating cells within brain microvessels, among which platelets play an important role. In vitro, platelets modulate the cytoadherence of Plasmodium falciparum-parasitized red blood cells (PRBCs) to brain endothelial cells. Here we show for the first time that platelet microparticles (PMPs) are able to bind to PRBCs, thereby transferring platelet antigens to the PRBC surface. This binding is largely specific to PRBCs, because PMPs show little adherence to normal red blood cells. PMP adherence is also dependent on the P. falciparum erythrocyte membrane protein 1 variant expressed by PRBCs. PMP binding to PRBCs decreases after neutralization of PRBC surface proteins by trypsin or after treatment of PMPs with a mAb to platelet-endothelial cell adhesion molecule-1 (CD31) and glycoprotein IV (CD36). Furthermore, PMP uptake is a dynamic process that can be achieved by human brain endothelial cells (HBECs), inducing changes in the endothelial phenotype. Lastly, PMPs dramatically increase PRBC cytoadherence to HBECs. In conclusion, our study identifies several mechanisms by which PMPs may participate in CM pathogenesis while interacting with both PRBCs and HBECs. PMPs thereby provide a novel target for antagonizing interactions between vascular cells that promote microvascular sludging and blood brain barrier alteration during CM.


The Curious Case of the Nidovirus Exoribonuclease: Its Role in RNA Synthesis and Replication Fidelity.
Among RNA viruses, the order Nidovirales stands out for including viruses with the largest RNA genomes currently known. Nidoviruses employ a complex RNA-synthesizing machinery comprising a variety of non-structural proteins (nsps). One of the postulated drivers of the expansion of nidovirus genomes is the presence of a proofreading 3'-to-5' exoribonuclease (ExoN) belonging to the DEDDh family. ExoN may enhance the fidelity of RNA synthesis by correcting nucleotide incorporation errors made by the RNA-dependent RNA polymerase. Here, we review our current understanding of ExoN evolution, structure, and function. Most experimental data are derived from studies of the ExoN domain of coronaviruses (CoVs), which were triggered by the bioinformatics-based identification of ExoN in the genome of severe acute respiratory syndrome coronavirus (SARS-CoV) and its relatives in 2003. Although convincing data supporting the proofreading hypothesis have been obtained, from biochemical assays and studies with CoV mutants lacking ExoN functionality, the features of ExoN from most other nidovirus families remain to be characterized. Remarkably, viable ExoN knockout mutants were obtained only for two CoVs, mouse hepatitis virus (MHV) and SARS-CoV, whose RNA synthesis and replication kinetics were mildly affected by the lack of ExoN function. In several other CoV species, ExoN inactivation was not tolerated, and knockout mutants could not be rescued when launched using a reverse genetics system. This suggests that ExoN is also critical for primary viral RNA synthesis, a property that poorly matches the profile of an enzyme that would merely boost long-term replication fidelity. In CoVs, ExoN resides in a bifunctional replicase subunit (nsp14) whose C-terminal part has (N7-guanine)-methyltransferase activity. The crystal structure of SARS-CoV nsp14 has shed light on the interplay between these two domains, and on nsp14's interactions with nsp10, a co-factor that strongly enhances ExoN activity in vitro assays. Further elucidation of the structure-function relationships of ExoN and its interactions with other (viral and/or host) members of the CoV replication machinery will be key to understanding the enzyme's role in viral RNA synthesis and pathogenesis, and may contribute to the design of new approaches to combat emerging nidoviruses.


The use of low molecular weight heparin in the initial management of patients with deep vein thrombosis.
Low molecular weight heparins (LMWH) have been found to be a safe and effective treatment for the prevention of venous thromboembolism. Recent clinical trials have further investigated the use of this class of drugs in the initial treatment of venous thromboembolism. The interest surrounding this new group of anticoagulants is sparked by the reduction in intensive resources required to safely administer this medication in comparison to the traditional treatment with heparin. Low molecular weight heparins do not require laboratory monitoring and can be given once or twice a day by subcutaneous injection, thereby allowing safe administration in the home. The potential cost savings incurred is timely in light of cost containment needs surrounding the current health care climate.


Fibronectin-adherent peripheral blood derived mononuclear cells as Paclitaxel carriers for glioblastoma treatment: An in vitro study.
Glioblastoma (GBM) represents the most aggressive malignant brain tumor in adults, with a risible median life expectancy despite gold standard treatment. Novel drug-delivery methods have been explored. Here we evaluated the possibility to use mononuclear cells (MCs) belonging to the monocytic-dendritic lineage as drug-carrier. MCs were obtained from 10 patients harboring a GBM, and from healthy volunteers, considered as controls. GBM tissue was also obtained from patients. MCs were cultured and the adherent population on fibronectin (FN-MCs), after immunocytochemistry and flow cytometry characterization, was loaded with Paclitaxel (FN-MCs-PTX). Antiproliferative and migration activity of FN-MCs-PTX was evaluated in two-dimensional (2D) and three-dimensional (3D) co-culture assays with red fluorescent U87 Malignant Glioma cells and primary GBM cells. Antiangiogenic properties of FN-MCs-PTX were tested on cultures with endothelial cells. Phenotypical characterization showed a high expression of monocytic-dendritic markers in GBM cells and FN-MCs. FN-MCs demonstrated to effectively uptake PTX and to strongly inhibit GBM growth in vitro (P <0.01). Moreover, tumor-induced migration of MCs, although partially affected by the PTX cargo, remained statistically significant when compared with unprimed cells and this was confirmed in a 3D Matrigel model (P <0.01) and in a Trans-well assay (P <0.01). FN-MCs-PTX also disclosed considerable antiangiogenic properties. Our results suggest that the fibronectin-adherent population of MCs isolated from peripheral blood can be an effective tool to inhibit GBM growth. Given the relative facility to obtain such cells and the short time needed for their culture and drug loading this approach may have potential as an adjuvant therapy for GBM.


The prediction of para-aortic lymph node metastasis in endometrioid adenocarcinoma of endometrium.
The aim of this study was to assess factors associated with para-aortic lymph node metastasis in endometrioid adenocarcinoma. The data of 157 patients with endometrioid adenocancer, who underwent staging surgery, was reviewed retrospectively. A total of 23 patients (14.6%) had pelvic and 19 patients (12.1%) had para-aortic lymph node metastasis; 21% (4/19) of the patients with para-aortic lymph node involvement did not have pelvic lymph node metastasis. Para-aortic lymph node involvement was significantly more common in the presence of LVSI and pelvic lymph node metastasis, and pelvic lymph node metastasis was the only independent risk factor for para-aortic lymph node involvement. The sensitivity and NPV of positive pelvic lymph node in the prediction of para-aortic lymph node metastasis were found to be 78.9% and 97%, respectively. The corresponding rates for obturator and/or external iliac lymph node were 63.1% and 95%, respectively. In conclusion, although pelvic lymph node metastasis is the only independent risk factor for para-aortic lymph node involvement, negative pelvic lymph node is not enough to omit para-aortic lymph node dissection. On the other hand, intraoperative frozen section examination of obturator and/or external iliac lymph node to omit para-aortic lymphadenectomy might be a good option for the patients who have high medical risks for surgery.


Taurolidine lock solution for catheter-related bloodstream infections in pediatric patients: A meta-analysis.
Infection is one of the most commonly described complications, and a major cause of morbidity and mortality in pediatric patients treated using central venous catheters (CVCs). Taurolidine lock solutions have been used to decrease catheter-related bloodstream infections (CRBSIs) in both adult and pediatric patients. The purpose of this study was to systematically search the literature and conduct a meta-analysis to determine the efficacy of taurolidine in reducing CRBSI in children. We conducted an electronic search of the PubMed, EMBASE, Cochrane Library, TRIP Database, CINAHL, and Google Scholar databases for articles published up to 1st November 2019. Eligible studies included randomized controlled trials (RCTs) comparing the effects of taurolidine with control for preventing CRBSI in pediatric patients. Four studies were included. Our results indicated a statistical significant reduction in the total number of CRBSI with taurolidine as compared to control (RR: 0.23; 95% CI:0.13, 0.40; I2 = 0%; P<0.00001). The pooled analysis also indicated a statistical significant reduction in the incidence of CRBSI (defined as the number of CRBSI events/1000 catheter days) in the taurolidine group (MD: -1.12; 95% CI:-1.54, -0.71; I2 = 1%; P<0.00001). The number of catheters removed due to infection or suspected infection was not significantly different between the two groups (RR: 0.68; 95% CI:0.22, 2.10; I2 = 56%; P = 0.50) (Fig 5). The quality of the included studies was not high. The use of taurolidine as a catheter locking solution may significantly reduce CRBSI in pediatric patients. However, the quality of current evidence is not high and further high-quality large scale RCTs are needed to corroborate our results.


In utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure: effects on fetal and adult cardiac gene expression and adult cardiac and renal morphology.
The mouse heart is a target of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during fetal development, and microarray analysis demonstrates significant changes in expression of cardiac genes involved in extracellular matrix (ECM) remodeling. We tested the hypothesis that developmental TCDD exposure would disrupt cardiac ECM expression and be associated with changes in cardiac morphology in adulthood. In one study, time-pregnant C57BL/6 mice were dosed with corn oil or 1.5, 3.0, or 6.0 microg TCDD/kg on gestation day (GD) 14.5 and sacrificed on GD 17.5, when changes in fetal cardiac mRNA expression were analyzed using quantitative PCR. TCDD induced mRNA expression of genes associated with ECM remodeling (matrix metalloproteinase 9 and 13, preproendothelin-1 [preproET-1]), cardiac hypertrophy (atrial natriuretic peptide, beta-myosin heavy chain, osteopontin), and aryl hydrocarbon receptor (AHR) activation (cytochrome P4501A1, AHR repressor). Further, all TCDD-induced changes required the AHR since gene expression was not altered in AHR knockout fetuses. In a second study, time-pregnant mice were treated with corn oil or 6.0 microg TCDD/kg on GD 14.5, and male offspring were assessed for changes in cardiac gene expression and cardiac and renal morphology at 3 months. All TCDD-induced changes in cardiac gene expression observed fetally, except for preproET-1, remained induced in the hearts of adult male offspring. Adult male offspring of TCDD-exposed dams also displayed cardiac hypertrophy, decreased plasma volume, and mild hydronephrosis. These results demonstrate that in utero and lactational TCDD exposures alter cardiac gene expression and cardiac and renal morphology in adulthood, which may increase the susceptibility to cardiovascular dysfunction.


Cilostazol-based triple versus potent P2Y12 inhibitor-based dual antiplatelet therapy in patients with acute myocardial infarction undergoing percutaneous coronary intervention.
Although potent P2Y12 inhibitor-based dual antiplatelet therapy (DAPT) has replaced clopidogrel-based therapy as the standard treatment in patients with acute myocardial infarction (AMI), there is a concern about the risk of bleeding in East Asian patients. We compared the efficacy and safety of cilostazol-based triple antiplatelet therapy (TAT) with potent P2Y12 inhibitor-based DAPT in Korean patients. A total of 4152 AMI patients who underwent percutaneous coronary intervention (PCI) in the Korea Acute Myocardial Infarction Registry were analyzed retrospectively. Patients were divided into two groups: the TAT group (aspirin + clopidogrel + cilostazol, n = 3161) and the potent DAPT group (aspirin + potent P2Y12 inhibitors [ticagrelor or prasugrel], n = 991). Major clinical outcomes at 30 days and 2 years were compared between the two groups using propensity score matching (PSM) analysis. After PSM (869 pairs), there were no significant differences between the two groups in the incidence of total death, cardiac death, myocardial infarction (MI), target vessel revascularization, stent thrombosis, and stroke at 30 days and 2 years. However, the Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding rates were significantly lower in the TAT group compared with the potent DAPT group at 2 years (6.4% vs. 3.6%, p = 0.006). In Korean AMI patients undergoing PCI, TAT with cilostazol was associated with lower bleeding than the potent P2Y12 inhibitor-based DAPT without increased ischemic risk. These results could provide a rationale for the use of TAT in East Asian AMI patients.


AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review.
The purpose of this Clinical Practice Update Expert Review is to provide clinicians with guidance on the diagnosis and management of atrophic gastritis, a common preneoplastic condition of the stomach, with a primary focus on atrophic gastritis due to chronic Helicobacter pylori infection-the most common etiology-or due to autoimmunity. To date, clinical guidance for best practices related to the diagnosis and management of atrophic gastritis remains very limited in the United States, which leads to poor recognition of this preneoplastic condition and suboptimal risk stratification. In addition, there is heterogeneity in the definitions of atrophic gastritis, autoimmune gastritis, pernicious anemia, and gastric neoplasia in the literature, which has led to confusion in clinical practice and research. Accordingly, the primary objective of this Clinical Practice Update is to provide clinicians with a framework for the diagnosis and management of atrophic gastritis. By focusing on atrophic gastritis, this Clinical Practice Update is intended to complement the 2020 American Gastroenterological Association Institute guidelines on the management of gastric intestinal metaplasia. These recent guidelines did not specifically discuss the diagnosis and management of atrophic gastritis. Providers should recognize, however, that a diagnosis of intestinal metaplasia on gastric histopathology implies the diagnosis of atrophic gastritis because intestinal metaplasia occurs in underlying atrophic mucosa, although this is often not distinctly noted on histopathologic reports. Nevertheless, atrophic gastritis represents an important stage with distinct histopathologic alterations in the multistep cascade of gastric cancer pathogenesis. The Best Practice Advice statements presented herein were developed from a combination of available evidence from published literature and consensus-based expert opinion. No formal rating of the strength or quality of the evidence was carried out. These statements are meant to provide practical advice to clinicians practicing in the United States. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Atrophic gastritis is defined as the loss of gastric glands, with or without metaplasia, in the setting of chronic inflammation mainly due to Helicobacter pylori infection or autoimmunity. Regardless of the etiology, the diagnosis of atrophic gastritis should be confirmed by histopathology. BEST PRACTICE ADVICE 2: Providers should be aware that the presence of intestinal metaplasia on gastric histology almost invariably implies the diagnosis of atrophic gastritis. There should be a coordinated effort between gastroenterologists and pathologists to improve the consistency of documenting the extent and severity of atrophic gastritis, particularly if marked atrophy is present. BEST PRACTICE ADVICE 3: Providers should recognize typical endoscopic features of atrophic gastritis, which include pale appearance of gastric mucosa, increased visibility of vasculature due to thinning of the gastric mucosa, and loss of gastric folds, and, if with concomitant intestinal metaplasia, light blue crests and white opaque fields. Because these mucosal changes are often subtle, techniques to optimize evaluation of the gastric mucosa should be performed. BEST PRACTICE ADVICE 4: When endoscopic features of atrophic gastritis are present, providers should assess the extent endoscopically. Providers should obtain biopsies from the suspected atrophic/metaplastic areas for histopathological confirmation and risk stratification; at a minimum, biopsies from the body and antrum/incisura should be obtained and placed in separately labeled jars. Targeted biopsies should additionally be obtained from any other mucosal abnormalities. BEST PRACTICE ADVICE 5: In patients with histology compatible with autoimmune gastritis, providers should consider checking antiparietal cell antibodies and anti-intrinsic factor antibodies to assist with the diagnosis. Providers should also evaluate for anemia due to vitamin B-12 and iron deficiencies. BEST PRACTICE ADVICE 6: All individuals with atrophic gastritis should be assessed for H pylori infection. If positive, treatment of H pylori should be administered and successful eradication should be confirmed using nonserological testing modalities. BEST PRACTICE ADVICE 7: The optimal endoscopic surveillance interval for patients with atrophic gastritis is not well-defined and should be decided based on individual risk assessment and shared decision making. A surveillance endoscopy every 3 years should be considered in individuals with advanced atrophic gastritis, defined based on anatomic extent and histologic grade. BEST PRACTICE ADVICE 8: The optimal surveillance interval for individuals with autoimmune gastritis is unclear. Interval endoscopic surveillance should be considered based on individualized assessment and shared decision making. BEST PRACTICE ADVICE 9: Providers should recognize pernicious anemia as a late-stage manifestation of autoimmune gastritis that is characterized by vitamin B-12 deficiency and macrocytic anemia. Patients with a new diagnosis of pernicious anemia who have not had a recent endoscopy should undergo endoscopy with topographical biopsies to confirm corpus-predominant atrophic gastritis for risk stratification and to rule out prevalent gastric neoplasia, including neuroendocrine tumors. BEST PRACTICE ADVICE 10: Individuals with autoimmune gastritis should be screened for type 1 gastric neuroendocrine tumors with upper endoscopy. Small neuroendocrine tumors should be removed endoscopically, followed by surveillance endoscopy every 1-2 years, depending on the burden of neuroendocrine tumors. BEST PRACTICE ADVICE 11: Providers should evaluate for iron and vitamin B-12 deficiencies in patients with atrophic gastritis irrespective of etiology, especially if corpus-predominant. Likewise, in patients with unexplained iron or vitamin B-12 deficiency, atrophic gastritis should be considered in the differential diagnosis and appropriate diagnostic evaluation pursued. BEST PRACTICE ADVICE 12: In patients with autoimmune gastritis, providers should recognize that concomitant autoimmune disorders, particularly autoimmune thyroid disease, are common. Screening for autoimmune thyroid disease should be performed.


Why does smoking so often produce dependence? A somewhat different view.
The usual explanation for why smoking produces dependence focuses on the effects of nicotine on dopamine and other neurobiological explanations. This review offers four somewhat different explanations: (1) nicotine can offer several psychopharmacological benefits at the age when such benefits are especially needed; (2) cigarettes provide for a rapid, frequent, reliable and easy-to-obtain reward; (3) nicotine is not intoxicating, allowing chronic intake; and (4) the long duration of the nicotine withdrawal syndrome effectively undermines cessation. This article reviews the evidence for the above views and the tobacco control activities these views suggest.


Update on mupirocin resistance.
Mupirocin inhibits the activity of bacterial isoleucyl-tRNA synthetase resulting in a decrease or cessation of protein synthesis. Expression of resistance in staphylococci has been divided arbitrarily into two groups, low level (minimum inhibitory concentrations [MIC] of between 8 and 256 mg/L) and high level (MICs of > or = 512 mg/L). Low level resistance is associated with spontaneous mutational events, while high level resistance is mediated by a large transferable plasmid. The introduction of a nasal formulation of mupirocin raises many issues concerning staphylococcal breakpoints, since 20,000 mg/L is applied to the mucosal surface to eradicate nasal colonisation with staphylococci, as opposed to eliminating infection. For several years after its introduction reports of resistance in staphylococci were rare. However, the contemporary literature indicates reports of resistance in select populations, particularly associated with dermatology patients. The overall rate of resistance for organisms isolated from the nares is currently unknown. The recent introduction of the E test combined with the 5 microgram screening disk may assist in determining resistance rates in large populations.


The association between social capital measures and self-reported health among Muslim majority nations.
Much evidence suggests that social capital (e.g. networks, trust, organizational memberships) has a significant effect on self-reported health. Previous research, however, has focused primarily on Western countries. The current research seeks to remedy this problem by investigating the association between multiple social capital indicators and subjective health in a novel empirical setting. The data come from the Comparative Values Survey of Islamic Countries (1999-2006) which consists of probabilistic samples from Muslim majority nations. Three-way multilevel analysis is used to examine the social determinants of health. Statistical results from hierarchical linear modeling shows that frequent contact with strong and intermediate ties (i.e. family members and friends, respectively) is significant, while interaction with weak ties (coworkers) has no association. General trust and trust in the central government are also significantly related to subjective health, as is trust in religious authority, albeit in an inverse way. This study calls for a more contingent view of the relationship between social capital and self-reported health. Future research needs to take this into consideration in hypothesizing and testing the potential health benefits of social capital.


Spectral characteristics and motion-compensated restoration of composite frames.
The practice of superimposing the fields of a frame is applied in various fields, for example, thermographic and biomedical imaging. The pictures obtained in this way, which are termed composite frames, are severely degraded if the scene's objects are not perfectly still. The restoration of composite frames affected by motion-induced blurring requires the ability to estimate the field displacement from composite frames. The frequency domain analysis of composite frames proposed in the paper suggests a displacement estimation technique of a phase-correlation type that can be applied to composite frames.


Uptake, distribution and binding of beryllium to organelles of the rat liver cell.
1. Male rats were injected intravenously with amounts ranging from 0.08 to 111.0mumoles of [(7)Be]beryllium sulphate/kg. body wt. The distribution in the rat and the subcellular distribution of beryllium in the liver were determined. 2. Within the entire dose range a higher specific activity of beryllium was present in a mitochondrial fraction containing the lysosomes. Purification of this fraction confirmed that beryllium is taken up by lysosomes. 3. With doses approaching the LD(50), beryllium was also found in increasing amounts to be present in the liver cell nuclei. Beryllium also showed affinity towards isolated cell nuclei in vitro. Evidence is presented that they have one class of binding sites for beryllium. Mitochondria have less affinity for beryllium. 4. No evidence could be obtained of an affinity of beryllium for DNA or RNA by fractionation of nuclei and dialysis experiments. 5. The presence of beryllium in liver cell nuclei may be relevant to the effects of beryllium on nuclear structure and function.


The Need for a Specific Noise Measurement for Population Exposed to Aircraft Noise during Night-time.
Most of subjective complaints about aircraft noise during night-time refers to sleep disruption. In order to protect populations who live around airports, it is of major importance to define levels of noise considered to be unacceptable during that particular time of the 24-hour period. In addition to an integrated indicator which describes the global noise exposure (Lden), the French authority on airport noise control (Autorite de Controle des Nuisances Sonores Aeroportuaires: ACNUSA) is considering the possibility of defining a maximum noise level [LAmax (1s)] that should not be exceeded at night (from 22.00 to 06.00) by any flying aircraft over residential areas. The main benefit of this single event indicator would be the identification of contravening vessels and application of possible penalty. It is believed that this type of sanction would help protecting sleep in highly noise-exposed areas.


Autodisplay: efficacious surface exposure of antigenic UreA fragments from Helicobacter pylori in Salmonella vaccine strains.
Live attenuated Salmonella strains expressing antigens of pathogens are promising oral vaccine candidates. There is growing evidence that the topology of expression of the foreign antigens can have a dramatic impact on the immunogenicity. We examined the potential of the AIDA-I (Escherichia coli adhesin involved in diffuse adherence) autotransporter domain to display antigenic fragments of the urease A subunit of Helicobacter pylori for the induction of a protective immune response. In the murine H. pylori model, protection is mainly mediated by CD4(+) T cells, and we therefore used the AIDA-I expression system to successfully express both nearly full-length UreA and defined T-helper-cell epitopes on the surface of an attenuated Salmonella enterica serovar Typhimurium vaccine strain. Surface exposure of the large UreA fragment or of one UreA T-cell epitope mediated a significant reduction in the level of H. pylori in immunized mice after challenge infection, whereas conventional cytoplasmic expression of UreA in Salmonella had no effect. These results support the concept that surface display increases the immunogenicity of recombinant antigens expressed on oral live vaccine carriers and further demonstrate the feasibility of immunizing against H. pylori with Salmonella vaccine strains expressing CD4(+) T-cell epitopes.