Solvent specified conformation in poly(alpha-L-glutamic acid) thin films.
The ability to control conformational properties of polypeptides in their films is of considerable interest for many possible applications of these materials. By rational choice of the solvent system for film fabrication, control over the conformation of the main chain, the intermolecular hydrogen bonding in the side chain is easily achieved in poly(alpha-L-glutamic acid) (PLGA) thin films. The spectral data from circular dichromism (CD), FT-IR, and solid state (13)C NMR spectroscopies suggest that the beta-sheet conformation is dominant in PLGA films cast from trifluoroacetic acid (TFA) solution, whereas the right-handed alpha-helix is dominant in those cast from pyridine or DMF solution. In comparison with films cast from TFA solutions, the films fabricated from pyridine or DMF solutions exhibit strong intermolecular hydrogen bondings between -COOH groups and have a more ordered arrangement of side chains. Moreover, the extent of alpha-helix conformation of the PLGA backbone in films cast from pyridine or DMF solution is several times higher than that observed in the PLGA powder precipitated from aqueous solution at pH 4. All spectroscopic studies indicate clearly that the solvents (used for casting these films) play a crucial role in directing the organization of PLGA in these thin films.


Rauwolfia vomitoria Extract Represses Colorectal Cancer Cell Autophagy and Promotes Apoptosis.
Colorectal cancer (CRC) is one of the most frequent digestive tract tumors in the world with an increasing incidence. Currently, surgical resection and chemotherapy are the main therapeutic options; however, their effects are limited by various adverse reactions. Rauwolfia vomitoria extract (Rau) has been shown to repress the progression of multiple human cancers; however, whether Rau plays a role in CRC remains undetermined. Influences of Rau treatment on HCT-116 and LoVo cells were estimated via MTT and colony formation experiments. Flow cytometry analysis was adopted to evaluate the apoptosis rate of HCT-116 and LoVo cells. Apoptosis-related proteins (Bcl-2, Bax, and caspase-3) and autophagy-related proteins (LC3 and P62) were assessed by Western blotting. Effects of Rau on autophagy of HCT-116 and LoVo cell were evaluated through GFP-LC3 analysis. In vivo xenograft tumor assay was conducted to further examine the role of Rau in CRC tumor growth. Rau remarkably repressed HCT-116 and LoVo cell viability and promoted HCT-116 and LoVo cell apoptosis in vitro in a dose-dependent manner. Rau increased the expression of caspase-3 and Bax and decreased the expression of Bcl-2 in HCT-116 and LoVo cells. Moreover, Rau was demonstrated to decrease the LC3||/LC3| ratio and increase the level of P62 in HCT-116 and LoVo cells. In addition, we found that Rau repressed xenograft tumor growth and also repressed autophagy in vivo. Our findings revealed that Rau repressed CRC cell viability and autophagy in vitro and in vivo, suggesting that Rau might be a potent therapeutic agent of CRC.


Early Life Protein Intake: Food Sources, Correlates, and Tracking across the First 5 Years of Life.
High consumption of protein has been associated with accelerated growth and adiposity in early childhood. To describe intake, food sources, correlates, and tracking of protein in young children. Secondary analysis of Melbourne Infant Feeding Activity and Nutrition Trial (InFANT). Dietary data were collected using three 24-hour dietary recalls at ages 9 and 18 months as well as 3.5 and 5 years. First-time mothers and their child (n=542) participated in an 18-month intervention to prevent childhood obesity and the cohort was followed-up with no intervention when children were aged 3.5 and 5 years. Protein intake, food sources, correlates, and tracking of protein. Child and maternal correlates of protein intake were identified using linear regression and tracking of protein intake was examined using Pearson correlations of residualized protein scores between time points. Mean protein (grams per day) intake was 29.7±11.0, 46.3±11.5, 54.2±13.8, and 60.0±14.8 at 9 and 18 months and 3.5 and 5 years, respectively. Protein intakes at all ages were two to three times greater than age-appropriate Australian recommendations. The primary source of protein at 9 months was breast/formula milk. At later ages, the principal sources were milk/milk products, breads/cereals, and meat/meat products. Earlier breastfeeding cessation, earlier introduction of solids, high dairy milk consumption (≥500 mL), and high maternal education were significant predictors of high protein intake at various times (P<0.05). Slight tracking was found for protein intakes at 9 months, 18 months, and 5 years (r=0.16 to 0.21; P<0.01). This study provides unique insights into food sources and correlates of young children's high protein intakes, and confirms that early protein intakes track slightly up to age 5 years. These finding have potential to inform nutrition interventions and strategies to address high protein intakes and protein-related obesity risk.


Non-linear analysis for the sleepy drivers problem.
The problem addressed in this work is sleepiness during driving, which often leads to accidents in the streets. Experiments with sleepy drivers took place and the EEG data were analysed in terms of non-linear methods. Sample entropy and phase synchronization variations were investigated within the signal sections corresponding to "driving events", i.e. driving mistakes or loss of control, as well as to periods of drowsiness and sleepiness, as compared to the periods of normal driving. Decreased sample entropy, indicating loss of complexity, and an increased phase synchronisation have been found in the preliminary study presented. The results are encouraging towards developing an alerting system for predicting and preventing driving accidents.


Intra-specific leaf trait variability of F. sylvatica, Q. petraea and P. abies in response to inter-specific competition and implications for forest functioning.
Variability in functional traits (FT) is increasingly used to understand the mechanisms behind tree species interactions and ecosystem functioning. In order to explore how FT differ due to interactions between tree species and its influence on stand productivity and other ecological processes, we examined the effects of tree species composition on the intra-specific variability of four widely measured FT: specific leaf area, leaf nitrogen content, leaf angle and stomatal conductance response to vapor pressure deficit. This study focused on three major central European tree species: European beech (Fagus sylvatica L.), Sessile oak (Quercus petraea Liebl.) and Norway spruce (Picea abies [L.] H. Karst.). Each species was examined in monoculture and two-species mixtures in the 13-year-old tree biodiversity experiment BIOTREE-Kaltenborn. Trait distributions and linear mixed models were used to analyze the effect of species mixing, tree size and stand variables on the intra-specific FT variability. A significant effect of branch height on most traits and species indicated a vertical gradient of foliar trait frequently related to light availability. Beech and oak showed a high overall trait variability and sensitivity to species mixing and stand basal area, while the trait variability of spruce was limited. Greater shifts in trait distributions due to mixing were found in specific leaf area for oak and leaf nitrogen content for beech. Thus intra-specific variability of key leaf traits was already influenced at this young development stage by inter-specific interactions. Finally, we used the 3-PG (Physiological Processes Predicting Growth) process-based forest growth model to show that the measured intra-specific variability on single FT values could influence stand productivity, light absorption and transpiration, although the net effect depends on the considered trait and the species composition of the mixture. The results of this study will aid better understanding of the effects of inter-specific competition on intra-specific FT variability, which has implications for the parameterization of process-based forest growth models and our understanding of ecosystem functioning.


Long Non-Coding RNA-ATB Attenuates the Angiotensin II-Induced Injury of Vascular Endothelial Cell.
Long noncoding RNA activated by transforming growth factor-II (lncRNA-ATB) has been reported to have critical roles in carcinogenesis and progression of several cancers. However, the expression and biological roles of lncRNA-ATB in cardiovascular disease are still unclear. This study aimed to investigate the role of lncRNA-ATB expression in endothelial cell injury. Angiotensin II (Ang II)-induced damage to endothelial cells (ECs) plays a crucial role in the research of cardiovascular disease; it is used to treat human umbilical vein endothelial cell (HUVECs) at different concentrations. qRT-PCR is used to identify the expression of lncRNA-ATB in HUVECs. CCK-8 assay and flow cytometry analysis are performed to assess cell viability and apoptosis of HUVECs. Ang II treatment down-regulated the lncRNA-ATB level in HUVECs. Meanwhile, both knockdown of lncRNA-ATB and Ang II treatment impaired the viability, and increased apoptosis rate of cells. Furthermore, overexpression of lncRNA-ATB inhibited cell apoptosis and repaired cell viability in HUVECs. The findings indicated that lncRNA-ATB might be associated with the development of the cardiovascular disease.


[Esophageal atresia with distal tracheo-esophageal fistula. Evolution of the treatment in the period of 1955-2000 at the Anna Meyer Children's Hospital of Florence].
Over the past decades the esophageal atresia (EA) has represented the greatest challenging malformation encountered by the pediatric surgeon. Since then, there have been considerable advancements in the treatment of EA. In this paper the experience at the "Anna Meyer Children's Hospital of Florence" in regards to the surgical treatment of the EA from 1955 to present day is reported, so that the analysis of the various medical and surgical choices followed by the authors and their predecessors in this long period, can be an important learning tool for the EA management. From 1955 to 2000, 223 newborns affected by EA with tracheoesophageal fistula (TEF) have been operated on out of a total of 250 cases of EA. Our experience has been subdivided into periods on the basis of homogeneous medical and surgical treatment adopted in that determined time. We have analyzed particularly the data of the last period 1995-2000, where there has been a well standardized protocol of treatment from the medical, surgical and intensive care points of view. The mortality rate has decreased from 44.8 to 3.4% with a significant reduction (p<0.001) between the years 1979-1983 and 1984-2000, due to the introduction of a perioperative treatment in the newborn intensive care unit. Moreover, a significant correlation (p<0.05) has been shown between low birthweight and associated malformations, two risk factors that however do not negatively influence the results of the treatment in the last period 1995-2000. A full integration between the surgeon and neonatologist is necessary in order to guarantee a good result. The risk connected to EA is not as much the surgical procedure as the presence or absence of associate malformations that are undetected in the prenatal diagnosis. It is suggested that, in order to further reduce the mortality and morbidity rate after EA correction, the number of prenatal diagnoses should be increased.


Store depletion induces Gαq-mediated PLCβ1 activity to stimulate TRPC1 channels in vascular smooth muscle cells.
Depletion of sarcoplasmic reticulum (SR) Ca(2+) stores activates store-operated channels (SOCs) composed of canonical transient receptor potential (TRPC) 1 proteins in vascular smooth muscle cells (VSMCs), which contribute to important cellular functions. We have previously shown that PKC is obligatory for activation of TRPC1 SOCs in VSMCs, and the present study investigates if the classic phosphoinositol signaling pathway involving Gαq-mediated PLC activity is responsible for driving PKC-dependent channel gating. The G-protein inhibitor GDP-β-S, anti-Gαq antibodies, the PLC inhibitor U73122, and the PKC inhibitor GF109203X all inhibited activation of TRPC1 SOCs, and U73122 and GF109203X also reduced store-operated PKC-dependent phosphorylation of TRPC1 proteins. Three distinct SR Ca(2+) store-depleting agents, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, cyclopiazonic acid, and N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamineed, induced translocations of the fluorescent biosensor GFP-PLCδ1-PH from the cell membrane to the cytosol, which were inhibited by U73122. Knockdown of PLCβ1 with small hairpin RNA reduced both store-operated PLC activity and stimulation of TRPC1 SOCs. Immunoprecipitation studies and proximity ligation assays revealed that store depletion induced interactions between TRPC1 and Gαq, and TRPC1 and PLCβ1. We propose a novel activation mechanism for TRPC1 SOCs in VSMCs, in which store depletion induces formation of TRPC1-Gαq-PLCβ1 complexes that lead to PKC stimulation and channel gating.


Sucralfate versus placebo in reflux esophagitis. A double-blind multicenter study.
The healing capacity and symptom relief were studied in 138 patients with symptomatic endoscopically verified reflux esophagitis treated with sucralfate (n = 69) or placebo (n = 69), 1 g four times daily (granules suspended in half a glass of water), for at most up to 12 weeks. The reflux esophagitis (modified Savary-Miller scale) was distributed with 71 patients having grade 1, 39 patients having grade 2 or 3, and 28 patients having grade 4. All patients were told to follow the antireflux regimen. Antacid tablets were supplied, to be used only for the relief of severe pain, and were counted. The esophageal lesions were completely healed in 42% (sucralfate) and 35% (placebo) after 6 weeks of treatment (NS). Corresponding cumulative healing rates at 12 weeks of treatment were 54% and 41% (NS), respectively. The symptom improvement, however, was significantly better in the sucralfate group after 3 weeks of treatment. The results indicate a symptomatic benefit of sucralfate in reflux esophagitis.


In vivo evaluation of polyurethanes based on novel macrodiols and MDI.
A series of novel polyurethane elastomers based on methylenediphenyl diisocyanate, 1,4-butanediol and the macrodiols, poly(hexamethylene oxide), poly(octamethylene oxide), and poly(decamethylene oxide) were implanted subcutaneously in sheep for periods of 3 and 6 months. The specimens that were subjected to 3 months of implantation were strained to 250% of their resting length, while those implanted for 6 months had no applied external strain. SEM examination of the explanted specimens revealed that the novel materials displayed resistance to environmental stress cracking. Proprietary materials, Pellethane 2363-80A, Biomer and Tecoflex EG-80A, which had been implanted under identical conditions, showed evidence of significant stress cracking. The extent of stress cracking in the 3-month strained experiment was similar to that from the 6-month unstrained experiment. Stress cracking was also observed in Pellethane 2363-55D, when implanted for 6 months (unstrained). Neither changes in molecular weight nor in tensile properties provided a clear indication of early susceptibility to degradation by environmental stress cracking.


The arterial blood supply for the synovial tendon sheaths of the hand.
The blood supply for the synovial tendon sheaths of the hand was carefully investigated. We show that the origin of those arteries, supplying the synovial tendon-sheaths of the Mm. flexor pollicis longus, flexor digitorum superficialis and profundus, lies in the Canalis carpi. We also describe that the branches of the Aa. digitales palmares propriae arise independently. We emphasize that the terminal branches of the A. interossea posterior and the Rete carpi dorsalis form an arterial network on the synovial tendon sheaths of the Dorsum manus. The synovial membranes of the proximal joints of the fingers receive an ample blood supply from the Rami ascendentes of the Aa. metacarpeae palmares and the Aa. digitales palmares propriae (Aa. recurrentes).


Christianity in India: a temporal-spatial view.
The author "attempts to analyse the spatial diffusion of Christianity in India from the earliest times to the present." Consideration is given to the history of Christianity, its diffusion throughout the country, the response of different social groups to Christianity, and the impact of British colonial rule on the growth of the religion. It is concluded that the "distribution of Christians in the country is highly uneven and is associated with the vast historic, socio-economic and political diversity of various parts of the country." Data are from official and other published sources.


Recommendations for the use of antiretroviral therapy in adults living with HIV in Singapore.
Since the advent of combination antiretroviral therapy (ART), the mortality attributable to HIV infection has been reduced by 80%. Newer antiretroviral agents are highly efficacious, have minimal side effects as compared to older drugs, and can be formulated as combination tablets, which reduces patients' pill burden. Despite these advances, 680,000 people died of AIDS-related illnesses worldwide in 2020. The National ART and Monitoring Recommendations by the National HIV Programme are created to guide physicians on the prescribing of ART based on the patients' needs. These recommendations are based on international guidelines and tailored to the local context and unique domestic considerations. It is hoped that with the publication of these recommendations, the care of people living with HIV can be enhanced, bringing us closer to the ending of HIV in our lifetime.


[The shoe industry: from productive reality to risk individualization].
This article describes in detail each stage of the shoe manufacturing process: design, cutting and shearing, sewing and trimming, assemblage, sole preparation, finishing, packaging and stocking, shoe manufacturing with synthetic materials. It will then discuss new technologies and their impact on the improvement of the worker's health, safety and convenience. A definition of the shoe parts and of the materials and machinery employed in its production will be provided, as well as a synthesis of the occupational hazards involved in each department. Although dealing with competitors who can take advantage of low-cost production and lack of concern for labour protection and environmental issues, the industry should always take great care of topics such as innovation and automation, but also workplace health and safety, while pushing the limits of that technological advance which companies have to face.


A Novel, Inexpensive Method to Monitor, Record, and Analyze Breathing Behavior During Normobaric Hypoxia Generated by the Reduced Oxygen Breathing Device.
Since hypoxia remains one of the most important physiological hazards the aviation environment poses, military aviators are trained to recognize symptoms of hypoxia in order to implement appropriate safety procedures and countermeasures when hypoxia occurs. A widely used commercial instrument for hypoxia training, demonstration, and research is the Reduced Oxygen Breathing Device (ROBD). Here we describe a novel, inexpensive method to use the ROBD's breathing loop pressure (BLP) to measure respiration rate, a critically important response parameter for hypoxia. The ROBD can be controlled by a computer to export several variables including BLP, via the ROBD's RS232 port. An archived database was reanalyzed to assess the BLP data. New instrumentation added independent measures of respiration and expired oxygen and carbon dioxide; these measures were integrated with the ROBD output. Analysis of the archived data showed that the BLP reflected realistic breathing patterns. The new instrumentation integrated well with the ROBD, and independently supported the potential of the BLP as a valid measure of respiration. The ROBD's BLP data may provide a basis for a reliable, sensitive measure of respiration that is available at no additional cost.


Controversies in the evaluation and management of chronic cough.
Chronic cough that cannot be explained after basic evaluation is a common reason for patients to be referred to respiratory outpatient clinics. Asthma, gastroesophageal reflux, and upper airway disorders frequently coexist with chronic cough. There is some controversy as to whether these conditions are causes or aggravants of cough. Heightened cough reflex sensitivity is an important feature in most patients. There is good evidence that it is reversible when associated with upper respiratory tract infection, angiotensin-converting enzyme inhibitor medications, and chronic cough associated with eosinophilic airway inflammation. In many patients, heightened cough reflex sensitivity is persistent and their cough is unexplained. There are few therapeutic options for patients with unexplained chronic cough. There is a pressing need to understand the genetic, molecular, and physiological basis of unexplained chronic cough and to develop novel antitussive drugs that down-regulate cough reflex sensitivity.


Serum thyroglobulin adds no additional value to ultrasonographic features in a thyroid malignancy.
We investigated the adjunctive role of preoperative serum thyroglobulin (Tg) in the diagnosis of thyroid nodules. A retrospective study was performed on 374 thyroid nodules (363 benign and 11 malignant) in 360 patients (296 women and 64 men; mean age, 50.1 years; range, 16-86 years) between December 2010 and July 2011. We evaluated clinicopathologic characteristics of patients and ultrasonographic (US) features of the lesions including presurgical Tg levels. Univariate and multivariate analysis were used to determine independent predictors of malignancy. Serum Tg was positively correlated with nodule size and thyroid volume (P < 0.001). There was no difference in serum Tg levels between malignant and benign nodules. Suspicious US features of thyroid nodules were the only independent predictors of malignancy (P< 0.001). Preoperative serum Tg was not useful in differentiating thyroid cancer from benign nodules. Suspicious US features were the only predicting factors for malignancy.


Insulin and glucose mediate opposite intracellular ionized magnesium variations in human lymphocytes.
Insulin is capable of increasing intracellular magnesium, although very little is known about the effect of insulin on the biologically active fraction of magnesium, i.e. the ionized quota (Mg(i)(2+)), its interactions with glucose, and the cellular mechanisms involved in these processes. We studied the interactions of the effects of insulin and glucose on intracellular ionized magnesium in human lymphocytes. Mg(i)(2+) was measured using a fluorimetric method and the Mg(2+)-sensitive dye, furaptra. We found that insulin significantly increases the Mg(i)(2+)(without insulin 227 +/- 14 microM, with 10 microU/ml, insulin 301 +/- 30 microM, P<0.0001, n = 12) in a dose-dependent manner in all three glucose concentrations tested (5, 7 and 15 mmol/l). The half-maximal effect of insulin was approximately 0.8 microU/ml. Glucose and insulin showed opposite effects in their ability to modify Mg(i)(2+) in lymphocytes. Inhibitors of the membrane Na(+)- Mg(2+) transport system and of phosphatidylinositol (PI) 3-kinase abolish the insulin-mediated increase of Mg(i)(2+), thus suggesting that insulin is capable of increasing Mg(i)(2+) by modulating the activity of this transport system, possibly through the mediation of PI 3-kinase activation. Taking into account the relationship between insulin and glucose plasma levels and their opposing effects on Mg(i)(2+), this mechanism may represent the two limbs of a biphasic regulatory system of Mg(i)(2+) in both physiological and pathological conditions.


Treatment of taste and odor material by oxidation and adsorption.
Massive blooms of blue-green algae in reservoirs produce the musty-earthy taste and odor, which are caused by compounds such as 2-MIB and geosmin. 2-MIB and geosmin are rarely removed by conventional water treatment. Their presence in the drinking water, even at low levels (ng/L), can be detected and it creates consumer complaints. So those concentrations have to be controlled as low as possible in the drinking water. The removals by oxidation (O3, Cl2, ClO2) and adsorption (PAC, filter/adsorber) were studied at laboratory and pilot plant (50 m3/d) to select suitable 2-MIB and geosmin treatment processes. The following conclusions were derived from the study. Both of the threshold odor levels for 2-MIB and geosmin appeared to be 30 ng/L as a consequence of a lab test. For any given PAC dosage in a jar-test, removal efficiencies of 2-MIB and geosmin were increased in proportion to PAC dosage and were independent of their initial concentration in raw water for the tested PAC dosages. In comparison of geosmin with 2-MIB, the adsorption efficiency of geosmin by PAC was superior to that of 2-MIB. The required PAC dosages to control below the threshold odor level were 30 mg/L for geosmin and 50 mg/L for 2-MIB at 100 ng/L of initial concentration. Removal efficiencies of odor materials by Cl2, ClO2, and O3 were very weak under the limited dosage (1.5 mg/L), however increased ozone dosage (3.8 mg O3/L) showed high removal efficiency (84.8% for 2-MIB) at contact time 6.4 minutes. According to the initial concentrations of 2-MIB and geosmin, their removal efficiencies by filter/adsorber differed from 25.7% to 88.4%. For all those, however, remaining concentrations of target materials in finished waters were maintained below 30 ng/L. The longer run-time given for the filter/adsorber, the higher the effluent concentration generated. So it is necessary that the run-time of the filter/adsorber be decreased, when 2-MIB or geosmin occurs in raw water.


Interconnection between Mixed-Handedness, Digit Ratios and Hand and Foot Minor Anomalies in Predicting Schizophrenia.
According to the neurodevelopmental theory, brain structuring early markers could be seen in different body parts as minor physical anomalies. Alongside minor physical anomalies, handedness and index to ring finger ratio are brain development indicators, specifically brain lateralization. Studies are consentient about the association of these findings with schizophrenia, though there is inconsistency about individual anatomical regions' contribution. We proposed that handedness in combination with morphological indicators of early brain development could be sensitive and specific in predicting schizophrenia status. Within the list for the assessment of schizophrenia patients and normal controls of the Caucasian race were seven categorical minor physical anomalies of hand and feet, handedness, and index to ring finger ratio. In this cross-sectional study the examinees were recruited from January 2012 to December 2015. Forced-entry binary logistic regression model correctly classified 86.5% of patients and 99.2% of the comparison subjects with a 92.8% overall accuracy. Mixed-handedness, hyperconvex fingernails, big gap between 1st and 2nd toe, and partial syndactyly of 2nd and 3rd toe made a significant independent contribution to the patient-control prediction group status. Furthermore, these items showed a significant correlation with the predictors of the head from the previous study. Briefly, the limb components, assessed independently of other body regions, proved to be worthy as schizophrenia predictors.


Value of routine early post-operative computed tomography in determining short-term functional outcome after drainage of chronic subdural hematoma: An evaluation of residual volume.
Computed tomography (CT) scans are widely used in managing chronic subdural hematoma (CSDH). Factors that determine early post-operative volume have not been examined. The value of routine early post-operative residual volume have not been evaluated. Our study aims to compare pre-operative and early post-operative CT findings to determine the factors affecting residual hematoma and evaluate if early post-operative CT scans are useful in the management of CSDH. Forty-three patients who underwent burr hole drainage of unilateral CSDH from August 2006 to January 2013 and had routine post-operative CT scans within 48 hours of surgery were selected. Data regarding age, sex, neurological deficit, Glasgow Coma Scale (GCS), pre-existing medical conditions, use of antiplatelets or anticoagulation, operative time, usage of drains, and number of burr holes were obtained. The pre-operative CSDH volume, CSDH density, and midline shift were measured. Residual volume was calculated from early post-operative CT scans. Clinical outcome was evaluated with Glasgow Outcome Scale (GOS) at the time of discharge. Statistical analysis was performed to look for correlation between the pre-operative factors and residual volume, and the residual volume and GOS. Pre-operative volume was found to correlate significantly with post-operative residual volume. There was no significant correlation between all other pre-operative factors and residual volume. There was also no correlation between residual volume and GOS at discharge. Routine post-operative CT brain for burr hole drainage of CSDH may be unnecessary in view of the good predictive value of pre-operative volume, and also because it is not predictive of the clinical outcome.


Combination treatment with infliximab and leflunomide in patients with active rheumatoid arthritis: safety and efficacy in an open-label clinical trial.
To assess the safety and efficacy of combination therapy with infliximab and leflunomide in adults with active rheumatoid arthritis (RA) despite leflunomide therapy. Adult patients with active RA who had received leflunomide for at least 16 weeks were eligible for this 30-week, open-label trial. All patients received ongoing oral leflunomide (20 mg/day) and 3 mg/kg infliximab administered IV at weeks 0, 2, 6, 14, and 22. The primary end point was the percentage of patients with adverse events that led to patient withdrawal and were at least possibly related to treatment. Descriptive evaluations of efficacy and other safety assessments were performed. Twelve out of 70 patients (17.1%; upper 90% CI 24.5%) withdrew due to treatment-related adverse events. Adverse events were reported in 69 of 72 patients (95.8%); the most common were nasopharyngitis, diarrhea, and pruritus. Serious adverse events occurred in 16 out of 72 patients (22.2%). Significant improvements were observed in efficacy assessments, including Disease Activity Score 28 (DAS28) and pain. At end point, 19.4% of the patients showed a good improvement in DAS28 score and 46.3% had a moderate improvement. American College of Rheumatology (ACR) 20, 50, and 70 responses were achieved by 47.1%, 21.4%, and 12.9% of the patients, respectively. The combination of infliximab and leflunomide neither increased the rate of toxicities nor resulted in unexpected adverse events. Treatment-related withdrawals occurred at an acceptable frequency. Patients experienced clinically significant improvements. Treatment with infliximab plus leflunomide benefits the majority of patients, but monitoring of adverse events is required.


Sub-fossil Chironomidae (Diptera) from lake sediments in Central America: a preliminary inventory.
The chironomid diversity of Central America is virtually underestimated and there is almost no knowledge on the chironomid remains accumulated in surface sediments of lakes. Thus, in the present study we provide information on the larval sub-fossil chironomid fauna from surface sediments in Central American lakes for the first time. Samples from 27 lakes analysed from Guatemala, El Salvador and Honduras yielded a total of 1,109 remains of four subfamilies. Fifty genera have been identified, containing at least 85 morphospecies. With 45 taxa, Chironominae were the most specious and also most abundant subfamily. Tanypodinae with 14 taxa dominated in about one third of the sites. Orthocladiinae were presented by 24 taxa, but were recorded in 9 sites, being dominant in only one site. Podonominae were collected only in one locality. Head capsules of Heterotrissocladius found in the high elevation lake Magdalena, Guatemala, represent a first record for the Neotropical region. Both relative abundance and species richness of Chironominae and Orthocladiinae showed significant relationship to elevation, while Tanypodinae were indifferent. Hopefully, the list of taxa provided by our study will be a base line for future limnological and paleolimnological investigations using chironomid remains in the region.


[Primary ovarian squamous cell carcinoma: clinicopathological features and prognostic analysis of fifteen cases].
Objective: To assess the clinical features and treatment outcomes in patients with primary ovarian squamous cell carcinoma (POSCC). Methods: Fifteen patients with primary ovarian squamous cell carcinoma diagnosed from January 2009 to December 2018 in Cancer Hospital of the University of Chinese Academy of Sciences were collected. The expression of p16, hMLH1, hMSH2, hMSH6 and PMS2 in POSCC was detected by immunohistochemistry, and the status of high-risk human papillomavirus (HPV) by RNAscope test. Results: Squamous cell carcinoma with different degrees of differentiation was found in 15 cases, including three cases with high differentiation and 12 cases with medium to low differentiation. There were four cases with in situ squamous cell carcinoma, four cases with teratoma, one case with endometrial carcinoma/atypical hyperplasia, and one case with endometriosis. p16 was expressed in five cases (5/15), indicating coexisting high-risk HPV infection. There was no high-risk HPV infection in the remaining 10 cases, and p16 staining was negative. There was no deficient mismatch repair protein in all cases. The overall survival time (P=0.038) and progression free survival (P=0.045) of patients with high-risk HPV infection were longer than those without HPV infection. Conclusions: POSCC is more commonly noted in postmenopausal women and often occurs unilaterally. Elevated serological indexes CA125 and SCC are the most common finding. Morphologically, the tumors show variable degrees of differentiation, but the current data suggest that the degree of differentiation cannot be used as an independent prognostic index. High-risk HPV infection may be associated with the occurrence of POSCC, and that the prognosis of POSCC patients with HPV infection is better than that of patients without infection.


The nonerythropoietic component of early bilirubin.
The early labeled bilirubin consists of two primary components. The more rapidly synthesized of the two is independent of erythropoiesis (nonerythropoietic), whereas the second fraction is related to red cell production (erythyropoietic). The present studies concern the origin of the nonerythropoietic component. The nonerythropoietic, early labeled bilirubin was studied in bile fistula rats with (delta ALA)-4-(14)C delta aminolevulinic acid and glycine-2-(14)C as precursors. That nephrectomy did not reduce the size of this component despite the large and rapidly turning over pool of renal heme suggests that this pool may be of minor importance in its production. Intoxication with lead to a level that reduced hepatic heme synthesis was associated with a decrease in early bilirubin formation. The synthesis of this bilirubin was assessed in animals with phenobarbital-induced heme protein and cycloheximide-suppressed protein synthesis. Rats pretreated with phenobarbital at a dose level of 60 mg/kg with induction of cytochrome P-450 synthesis showed a minor increase in early labeling when glycine-2-(14)C but not when delta ALA-4-(14)C was used as precursor. Rats given cycloheximide at a dose level that markedly reduced hepatic protein and cytochrome P-450 synthesis but allowed heme synthesis to continue at 60% of its pretreatment level synthesized normal or increased amounts of early bilirubin from delta ALA-4-(14)C. Allylisopropylacetamide intoxication caused little change in early bilirubin formation, whereas aminotriazole given at a time after maximal hepatic heme labeling produced a small but significant increase in the appearance of labeled bilirubin. These findings indicate that early bilirubin production is little influenced by increased hepatic porphyrin synthesis or by changes in the rapidly turning over heme protein P-450. A minimal increase attends catalase inactivation by aminotriazole. Normal or increased synthesis takes place in the presence of suppression of protein synthesis. This finding suggests that the nonerythropoietic early bilirubin may itself consist of two subcomponents. The first of these may arise from free tissue heme or its precursors, and the second may derive from the turnover of the heme proteins. The first subcomponent may serve as a regulatory mechanism for the removal of heme synthesized in excess of its protein acceptor. A composite scheme is proposed for the origin of the total early bilirubin from heme compartments in tissue and marrow.


Update in new anabolic therapies for osteoporosis.
Skeletal anabolic agents enhance bone formation, which is determined by the number and function of osteoblasts. Cell number is controlled by factors that regulate the replication, differentiation, and death of cells of the osteoblastic lineage, whereas cell function is controlled by signals acting on the mature osteoblast. Bone morphogenetic proteins (BMP) and Wnt induce the differentiation of mesenchymal cells toward osteoblasts, and IGF-I enhances the function of mature osteoblasts. The activity of BMP, Wnt, and IGF-I is controlled by proteins that, by binding to the growth factor or to its receptors, can antagonize its effects. Changes in the expression or binding affinity of these extracellular antagonists can be associated with increased or decreased bone formation and bone mass. Novel approaches to anabolic therapies for osteoporosis may include the use of factors with anabolic properties, or the neutralization of a growth factor antagonist. Selected approaches include the use of neutralizing antibodies to Wnt antagonists, the enhancement of BMP signaling by proteasome inhibitors, or the use of activin soluble receptors, IGF-I, or PTH analogs. An anabolic agent needs to be targeted specifically to the skeleton to avoid unwanted nonskeletal effects and ensure safety. Clinical trials are being conducted to test the long-term effectiveness and safety of novel bone anabolic agents.


[Legal aspects of epilepsy and coexisting psychiatric disorders].
Major advances in understanding the neurobiology of epilepsy have led to more precise diagnosis, early rational treatment with new drugs, useful new neurosurgical techniques, etc. This has led to significant control of seizures, a marked reduction in concurrent psychopathology, improved quality of life of the epileptic patient, the almost complete abolition of old-style institutions for these patients, etc. However in spite of greater scientific knowledge about epilepsy, this has not led to an equally great advance socially. Old-fashioned restrictions and limitations based on mistaken ideas as to the nature of epilepsy still remain. Epilepsy is still considered in the same light as the psychopathological disorders seen in some epileptics, as a result of different variables which are not necessarily related to seizures. Current legal rulings on epilepsy, with or without co-existing mental disorder, are reviewed in relation to their effect on driving motor vehicles, carrying out military service, the condition of minusvalia, the possibility of legal incompetence, and the nullity of marriage and of priesthood. It is concluded that although the limitations maintained by some statutory requirements are reasonable, it would be fairest to abolish restrictions which, in view of present scientific knowledge, are out of date and prevent the return to normal and full social integration which should prevail for people with epilepsy.


Simultaneous bilateral spontaneous pneumothorax observed during the administration of gefitinib for lung adenocarcinoma with multiple lung metastases.
A 41-year-old man with productive cough was admitted to our hospital. His chest roentgenogram showed multiple small nodules in the bilateral lung fields. The nodules were revealed as intrapulmonary metastases of the adenocarcinoma of the lung. Systemic chemotherapy with paclitaxel and carboplatin was not effective, and continuous oral gefitinib therapy was initiated. Twenty-one days later, spontaneous pneumothorax was found in the left lung, and four days after that, in the right lung as well. The extent of the pneumothorax was slight; therefore, he recovered without drainage within several days. Spontaneous pneumothorax, especially bilateral pneumothorax, is a rare complication of chemotherapy for lung cancer.


Titration of antiplatelet treatment in pregnant women at risk of preeclampsia.
We recruited 111 patients who were considered to be at significantly increased risk of preeclampsia on the basis of previous obstetric history or preexisting medical disorders. All patients were treated with low dose aspirin (75 mg/day) from the first occasion the patient attended the antenatal clinic, regardless of gestational age. If the maternal mean platelet volume (MPV) increased significantly (by > 0.8 fl) from the baseline, antiplatelet treatment was increased. Five pregnancies were lost during the second trimester and 106 of the treated patients had live infants. The incidence of neonatal death (3/106 infants) was much lower than in the previous pregnancies in these patients (32/134 infants). Patients who were treated from the first trimester of pregnancy (group A, 89 patients) did substantially better than those treated from the second trimester (group B, 17 patients) as assessed by the incidence of pre-eclampsia or intrauterine growth restriction (IUGR), gestational age and birthweight at delivery. These data suggest that longitudinal monitoring of the MPV may identify the women who could benefit from increased antiplatelet treatment, and that antiplatelet treatment may be more effective when initiated in the first trimester rather than later in pregnancy.


piggyBac is a flexible and highly active transposon as compared to sleeping beauty, Tol2, and Mos1 in mammalian cells.
A nonviral vector for highly efficient site-specific integration would be desirable for many applications in transgenesis, including gene therapy. In this study we directly compared the genomic integration efficiencies of piggyBac, hyperactive Sleeping Beauty (SB11), Tol2, and Mos1 in four mammalian cell lines. piggyBac demonstrated significantly higher transposition activity in all cell lines whereas Mos1 had no activity. Furthermore, piggyBac transposase coupled to the GAL4 DNA-binding domain retains transposition activity whereas similarly manipulated gene products of Tol2 and SB11 were inactive. The high transposition activity of piggyBac and the flexibility for molecular modification of its transposase suggest the possibility of using it routinely for mammalian transgenesis.


Pancreatic cancer stroma: controversies and current insights.
Pancreatic cancer is characterized by a dense stromal response. The stroma includes a heterogeneous mass of cells, including pancreatic stellate cells, fibroblasts, immune cells and nerve cells, as well as extracellular matrix proteins, cytokines and growth factors, which interact with the tumor cells. Previous research has indicated that stromal elements contribute to tumor growth and aggressiveness. However, recent studies suggest that some elements of the stroma may actually restrain the tumor. This review focuses on the complex interactions between the stromal microenvironment and tumor cells, discussing molecular mechanisms and potential future diagnostic and therapeutic approaches by targeting the stroma.


Probability of Alzheimer's disease based on common and rare genetic variants.
Alzheimer's disease, among other neurodegenerative disorders, spans decades in individuals' life and exhibits complex progression, symptoms and pathophysiology. Early diagnosis is essential for disease prevention and therapeutic intervention. Genetics may help identify individuals at high risk. As thousands of genetic variants may contribute to the genetic risk of Alzheimer's disease, the polygenic risk score (PRS) approach has been shown to be useful for disease risk prediction. The APOE-ε4 allele is a known common variant associated with high risk to AD, but also associated with earlier onset. Rare variants usually have higher effect sizes than common ones; their impact may not be well captured by the PRS. Instead of standardised PRS, we propose to calculate the disease probability as a measure of disease risk that allows comparison between individuals. We estimate AD risk as a probability based on PRS and separately accounting for APOE, AD rare variants and the disease prevalence in age groups. The mathematical framework makes use of genetic variants effect sizes from summary statistics and AD disease prevalence in age groups. The AD probability varies with respect to age, APOE status and presence of rare variants. In age group 65+, the probability of AD grows from 0.03 to 0.18 (without APOE) and 0.07 to 0.7 (APOE e4e4 carriers) as PRS increases. In 85+, these values are 0.08-0.6 and 0.3-0.85. Presence of rare mutations, e.g. in TREM2, may increase the probability (in 65+) from 0.02 at the negative tail of the PRS to 0.3. Our approach accounts for the varying disease prevalence in different genotype and age groups when modelling the APOE and rare genetic variants risk in addition to PRS. This approach has potential for use in a clinical setting and can easily be updated for novel rare variants and for other populations or confounding factors when appropriate genome-wide association data become available.


Age-related seasonal patterns of emergency department visits for acute asthma in an urban environment.
Asthma morbidity is greater in younger patients. The reasons are not fully understood, although identifying demographic patterns of seasonality may help determine causes and potential prevention. The objective of this study is to determine the relationship between age and seasonal asthma periodicity in patients presenting to the emergency department (ED). We conducted a retrospective study of ED visits from 1991 to 2000 in 11 municipal hospitals in New York City, with 911 receiving facilities. There were 673,141 patients who presented to the ED during the study period and had a primary diagnosis of acute asthma. Distinct seasonal patterns were observed, with the highest number of visits occurring in the fall and the fewest in the summer. Seasonal fluctuations of ED visits were highest in children aged 13 years or younger (coefficient of variation [CV] 37.8%; 95% confidence interval [CI] 37.5% to 38.1%), with a peak in CV occurring at approximately age 7 years (CV 43.3%; 95% CI 43.0% to 43.6%). Less variability was noted with increasing age, and the population aged 30 years and older appeared to be the least susceptible to seasonal influences (CV 11.7%; 95% CI 11.3% to 12.1%). Although the total number of asthma visits decreased by more than 30% from 1991 to 2000, the CVs for each year remained within a relatively narrow range of 24.2% to 30.5%. In an urban population, seasonal variability of asthma episodes requiring ED visits are closely linked to age, which may be important in understanding the causes of asthma and developing disease-management strategies for the prevention of asthma episodes.


Column experiment on activation aids and biosurfactant application to the persulphate treatment of chlorophene-contaminated soil.
An innovative strategy integrating the use of biosurfactant (BS) and persulphate activated by chelated iron for the decontamination of soil from an emerging pollutant chlorophene was studied in laboratory down-flow columns along with other persulphate activation aids including combined application of persulphate and hydrogen peroxide, and persulphate activation with sodium hydroxide. Although BS addition improved chlorophene removal by the persulphate treatment, the addition of chelated iron did not have a significant influence. Combined application of persulphate with hydrogen peroxide resulted in a significant (p≤.05) overall improvement of chlorophene removal compared with treatment with persulphate only. The highest removal rate (71%) of chlorophene was achieved with the base-activated persulphate, but only in the upper part (of 0.0-3.5 cm in depth) of the column. The chemicals at the applied dosages did not substantially influence the Daphnia magna toxicity of the effluent. Dehydrogenase activity (DHA) measurements indicated no substantial changes in the microbial activity during the persulphate treatment. The highest oxygen consumption and a slight increase in DHA were observed with the BS addition. The combined application of persulphate and BS at natural soil pH is a promising method for chlorophene-contaminated soil remediation. Hydroquinone was identified among the by-products of chlorophene degradation.


Susceptibility of Salmonella Biofilm and Planktonic Bacteria to Common Disinfectant Agents Used in Poultry Processing.
Poultry contaminated with Salmonella enterica subsp. enterica are a major cause of zoonotic foodborne gastroenteritis. Salmonella Heidelberg is a common serotype of Salmonella that has been implicated as a foodborne pathogen associated with the consumption of improperly prepared chicken. To better understand the effectiveness of common antimicrobial disinfectants (i.e., peroxyacetic acid [PAA], acidified hypochlorite [aCH], and cetylpyridinium chloride [CPC]), environmental isolates of nontyphoidal Salmonella were exposed to these agents under temperature, concentration, and contact time conditions consistent with poultry processing. Under simulated processing conditions (i.e., chiller tank and dipping stations), the bacteriostatic and bactericidal effects of each disinfectant were assessed against biofilm and planktonic cultures of each organism in a disinfectant challenge. Log reductions, planktonic MICs, and mean biofilm eradication concentrations were computed. The biofilms of each Salmonella isolate were more resistant to the disinfectants than were their planktonic counterparts. Although PAA was bacteriostatic and bactericidal against the biofilm and planktonic Salmonella isolates tested at concentrations up to 64 times the concentrations commonly used in a chiller tank during poultry processing, aCH was ineffective against the same isolates under identical conditions. At the simulated 8-s dipping station, CPC was bacteriostatic against all seven and bactericidal against six of the seven Salmonella isolates in their biofilm forms at concentrations within the regulatory range. These results indicate that at the current contact times and concentrations, aCH and PAA are not effective against these Salmonella isolates in their biofilm state. The use of CPC should be considered as a tool for controlling Salmonella biofilms in poultry processing environments.


Adequacy of recommended aminophylline loading doses in children.
The adequacy of a loading dose of aminophylline 6 mg/kg i.v. in hospitalized pediatric patients with reactive airway disease was studied. Children six months to 14 years of age were studied to determine their serum theophylline concentrations after they were given an aminophylline loading dose of 5-7 mg/kg i.v. and to see whether they had to receive additional bolus doses. Bolus doses were infused over 20-30 minutes and were followed by a continuous infusion. Additional bolus doses were administered if the patient's serum theophylline concentration and clinical condition indicated they were necessary. Data from two separate phases of the study were combined for analysis. Phase 1 was designed for estimating population pharmacokinetic values. Some 72% of the 64 patients studied had subtherapeutic serum theophylline concentrations (< 10 mg/L) within 5.5 hours of the loading dose, and 78% required at least one additional bolus dose. Males had significantly lower serum theophylline concentrations than females; of the patients with subtherapeutic concentrations, 67% were males. Patients five years of age or younger were more likely than older children to have subtherapeutic theophylline concentrations. A 6-mg/kg loading dose of i.v. aminophylline did not produce adequate serum theophylline concentrations or eliminate the need for a second bolus dose in most pediatric patients with acute exacerbations of asthma.


Pseudorheumatoid nodule: a variant of granuloma annulare?
We present an adult woman with subcutaneous nodules without any signs or symptoms of rheumatoid arthritis. These nodules are believed to be pseudorheumatoid nodules, which are considered a deep form of granuloma annulare. This case is unique because these are typically found in children and have rarely been reported in adults. These nodules are typically asymptomatic and do not require treatment. However, attempts have been made to treat them with intralesional corticosteroids, cryotherapy, or excision. Owing to the fact that this is considered a deep form of granuloma annulare, they are sometimes treated similarly with a combination of monthly rifampin, ofloxacin, and minocycline.


Multi-Walled Carbon Nanotubes as a Catalyst for Gas-Phase Oxidation of Ethanol to Acetaldehyde.
Multi-walled carbon nanotubes (CNTs) were directly used as a sustainable and green catalyst to convert ethanol into acetaldehyde in the presence of molecular oxygen. The C=O groups generated on the nanocarbon surface were demonstrated as active sites for the selective oxidation of ethanol to acetaldehyde. The transformation of disordered carbon debris on the CNT surface to ordered graphitic structures induced by thermal-treatment significantly enhanced the stability of the active C=O groups, and thus the catalytic performance. A high reactivity with approximately 60 % ethanol conversion and 93 % acetaldehyde selectivity was obtained over the optimized CNT catalyst at 270 °C. More importantly, the catalytic performance was quite stable even after 500 h, which is comparable with a supported gold catalyst. The robust catalytic performance displayed the potential application of CNTs in the industrial catalysis field.


Significance of exercise induced U wave inversion as a marker for coronary artery disease.
Exercise stress testing for detecting inducible ischaemia was first introduced in the 1950s and remained one of the only methods of stressing the heart for years to come. The presence of inducible ischaemia was assessed by ECG changes during exercise apart from other factors, namely, duration of exercise, blood pressure and heart rate response, metabolic equivalents achieved, etc. With the emergence of other tests to look for inducible ischaemia, for example, dobutamine stress echocardiography and myocardial perfusion scanning and also as the threshold for invasive evaluation has decreased, unusual and infrequently encountered ECG changes are not looked for during exercise stressing with the same degree of diligence. The authors describe below the case of a 49-year-old male whose left anterior descending artery stenosis was diagnosed on exercise stress test on the basis of a negative U wave.


[Effect of dialysis time in vivo on recovery of amino acids for micro-dialysis probe].
To investigate the variety of vitro recovery of amino acids for microdialysis probe after different dialysis time in vivo. Probes were dialyzed in the amino acids standard solutions with microdialysis system,amino acid standard solutions and the microdialysate of probe were detected by the method of precolumn derivation with HPLC-RF. After using different time of probe made by regenerated cellulose membrane, the vitro recoveries of Asp, Glu and GABA were not completely same (Asp: F=19.669, P=0.000; Glu: F=103.955, P=0.000; GABA: F=3.454, P=0.040); while the vitro recovery of Tau had no obvious difference(F=2.001, P=0.152). After using 6 h in vivo, recovery remain percentage (RRP) of Asp, Glu,Tau and GABA was 64.34 %, 67.36%, 103.11 % and 98.23 %, respectively, the recoveries of Asp, Glu decreased obviously (Asp: P < 0.01,Glu: P <0.05). After using 12 h in vivo, the RRP of Asp, Glu, Tau and GABA was 43.44 %, 24.42%, 77.45 % and 67.36 %, respectively, the recoveries of Asp, Glu and GABA decreased obviously (Asp: P < 0.001, Glu: P < 0.001, GABA: P < 0.05). After using 24 h in vivo, the RRP of Asp, Glu,Tau and GABA was 36.26 %, 12.24 %, 89.48 % and 71.35 %, respectively, the recoveries of Asp, Glu, GABA decreased obviously (Asp: P < 0.0001, Glu: P < 0.0001, GABA: P < 0.01). Dialysis in vivo could lead to the decline of recovery of probe, the decline is more obvious after longer dialysis. So when making brain dialysis experiments, the use time of probe should not be too long. To improve the validity of data, some calibration should be made on the recoveries of probe.


Crossed-antigenicity between the etiologic agents of lobomycosis and paraccocidioidomycosis evidenced by an immunoenzymatic method (PAP).
Lobomycosis or Keloidal blastomycosis and Paracoccidiodomycosis found in South American tropical regions are considered different mycoses from the clinical and mycological point of view. Very little is known about the immunology of Lobomycosis, since the etiological agent of this mycosis, Loboa loboi, is not cultured "in vitro". In order to overcome this difficulty, a rabbit Paracoccidioides brasiliensis, antiserum is usually used, since crossed-antigenicity between both fungi has been demonstrated by serological methods and immunofluorescence. In this paper, common antigens between Loboa loboi and Paracoccidiodes brasiliensis were detected by means of rabbit serum against a metabolic antigen from Paracoccidiodies brasiliensis and using a peroxidase-antiperoxidase (PAP) technique. This method provided retrospective studies on three cases studied by using histological material from Lobomycosis stocked for a long time. The antigenic relationship between both fungi was confirmed by our results based on biopsies from Keloidal blastomycosis and Paracoccidioidomycosis, by using the PAP method and a rabbit serum against a metabolic antigen from Paracoccidioides brasiliensis.


Interleukin-1 and interleukin-2 production by peripheral blood mononuclear cells of patients with rheumatoid arthritis.
Contradictory results have been reported concerning the secretion of interleukin-1 (IL-1) and interleukin-2 (IL-2) by mononuclear cells of rheumatoid arthritis (RA) patients. In the present study, peripheral blood mononuclear cells from 18 RA patients were stimulated in vitro to produce IL-1 and IL-2 and compared with monocytes of age-matched healthy control subjects. Endotoxin-stimulated monocytes of RA patients produced normal amounts of IL-1 compared with healthy controls (P = 0.5), whereas T-lymphocytes from the same patients produced decreased amounts of IL-2 compared with control T-lymphocytes (P less than 0.01). There was no difference in IL-1 or IL-2 production by mononuclear cells from patients with active or inactive disease. These findings could not be explained by concurrent therapy, and support the notion that defective immunoregulatory T-cell functions are involved in the pathogenesis of RA.


Obese Adolescents Show Reduced Cognitive Processing Speed Compared with Healthy Weight Peers.
Childhood obesity and obesity-associated diabetes and metabolic syndrome (MetS) continue to rise. Obesity has been linked to structural and functional brain abnormalities, particularly in the frontal lobe. One hundred sixty-two adolescents (aged 19.53 ± 1.53 years) underwent medical, neurocognitive, and brain magnetic resonance imaging assessments. Participants were either healthy weight (BMI <25.0 kg/m2 or BMI percentile <85%) or obese (BMI ≥30.0 kg/m2 or BMI percentile ≥95%). We evaluated frontal lobe cognitive functions and the size of the corpus callosum (CC). Groups differed on four measures of processing speed contained in four different cognitive tests, but not on executive function. A confirmatory factor analysis verified that the significant processing speed variables loaded on the same factor. We also found differences between the weight groups on the area of the anterior portion of the CC, but not the overall CC. Only the Controlled Oral Word Association Test (COWAT) was significantly correlated with the area of the anterior portion of the CC. In the obese group, 32.4% met criteria for MetS. No differences were found between obese participants with or without MetS and none of the MetS factors contributed consistently to cognitive performance. Obese adolescents show slower cognitive processing speed while maintaining equivalent performance on executive functioning compared with their healthy weight peers. The group differences in the anterior portion of the CC, responsible for frontal lobe interhemispheric communication, may in part explain our processing speed findings. Future studies should include a longitudinal design and diffusion tensor imaging to examine the integrity of white matter.


Effects of intravenous administration of pentoxifylline in pancreatic ischaemia-reperfusion injury.
Therapeutic strategies to reduce the occurrence of pancreatic ischaemia-reperfusion (I-R) injury might improve outcomes in human pancreas and kidney transplantation. In addition to its haemorrheologic effects, pentoxifylline has an anti-inflammatory effect by inhibiting NF-κB activation. This group has previously demonstrated that pentoxifylline induces an anti-inflammatory response in acute pancreatitis and liver I-R models. This led to the hypothesis that pentoxifylline might reduce pancreatic and renal lesions and the systemic inflammatory response in pancreatic I-R injury. The aim of this experimental study was to evaluate the effect of pentoxifylline administration in a rat model of pancreatic I-R injury. Pancreatic I-R was performed in Wistar rats over 1 h by clamping the splenic vessels. The animals submitted to I-R were divided into two groups: Group 1 (n = 20, control) rats received saline solution administered i.v. at 45 min after ischaemia, and Group 2 (n = 20) rats received pentoxifylline (25 mg/kg) administered i.v. at 45 min after ischaemia. Blood samples were collected to enable the determination of amylase, creatinine, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10. Pancreatic malondialdehyde (MDA) content, pancreas histology and pulmonary myeloperoxidase (MPO) were also assessed. Significant reductions in serum TNF-α, IL-6 and IL-10 were observed in Group 2 compared with Group 1 (P < 0.05). No differences in pancreatic MDA content or serum amylase levels were observed between the two groups. The histologic score was significantly lower in pentoxifylline-treated animals, denoting less severe pancreatic histologic damage. Pentoxifylline administration reduced the systemic inflammatory response, the pancreatic histological lesion and renal dysfunction in pancreatic I-R injury and may be a useful tool in pancreas and kidney transplantation.


The Pedicled Anterolateral Thigh Flap for Donor Site Closure after a Large Superficial Circumflex Iliac Artery Perforator Flap Harvest.
The superficial circumflex iliac artery perforator (SCIP) flap is useful for covering defects in the extremities because its pedicle size can match many recipient options. However, when harvesting a large flap, skin grafting of the donor site is not highly recommended because of the mobility of the hip joint and occasional lymphorrhea. Here, we present a case of a successful reconstruction of a defect in the lower leg after sarcoma resection, using a large SCIP flap. A 58-year-old man underwent resection of a large soft tissue tumor in the lower leg, resulting in a 16 × 14 cm defect. A 25 × 14 cm SCIP flap was harvested from the groin, and the superficial circumflex iliac artery and the superficial circumflex iliac vein were anastomosed to the saphenous artery and the great saphenous vein, respectively, in an end-to-end fashion. For coverage of the groin donor site, a 25 × 8 cm pedicled anterolateral thigh (ALT) flap was harvested from the ipsilateral lateral thigh and was pulled through a subcutaneous tunnel to the groin. The additional operative time for pedicled ALT flap elevation and transfer was approximately 15 minutes. With this pedicled ALT flap, the donor site of the SCIP flap could be closed directly over a drain. The follow-up at 3 months showed complete survival of both flaps, and the patient was able to walk with a cane. The pedicled ALT flap allows for direct closure of the donor site after a large SCIP flap harvest.


Establishing Thermal Infusion Method for Stable Zinc Metal Anodes in Aqueous Zinc-Ion Batteries.
Metallic zinc (Zn) having low cost, high capacity, environmentally friendly features is considered to be an attractive anode material for aqueous energy storage devices. However, dendritic growth and severe side reactions restrict the development of Zn-metal anodes. Numerous 3D hosts are extensively explored to settle these issues, whereas the accessible prestoring of Zn metal into structured electrodes is challenging. Here, a thermal infusion strategy is first reported to create a stable composite Zn-based anode. Upon this melting-wetting-cooling process, the metallic Zn is densely and firmly encapsulated in the 3D skeleton, efficiently inhibiting the dendritic growth. Meanwhile, through in/ex situ tests, the formation of ZnO layer on the metallic Zn surface inhibits the hydrogen evolution reactions (1.8 mmol h-1 cm-2 ) and passivation during cycling. Consequently, the electrode enables a long-cycling life of over 1000 cycles at 10 mA cm-2 in a symmetrical cell. The pouch cells pairing this novel anode and LiMn2 O4 cathode maintain over 94 mAh g-1 capacity retention after 300 cycles. This research presents an innovative Zn anode structure and extendable prestoring metallic Zn method for aqueous Zn-ion batteries.


Nonconscious control of autonomic responses: a role for Pavlovian conditioning?
This paper reviews data demonstrating nonconscious control of autonomic responses and emotional processes. After briefly having considered theoretical attempts to encompass such processes within Pavlovian conditioning frameworks, it goes on the examine theories and evidence for nonconscious control of emotional processes. The phenomena covered include affective discrimination, neurophysiological mechanisms in the control of conditioned emotional responses, and attentional biases in anxiety disorders. The main section of the paper examines evidence for nonconscious, automatic control of autonomic responses. Such control is demonstrated by data on skin conductance responses to nonattended stimuli, by skin conductance responses in prosopagnosic patients, and by skin conductance responses to masked conditioned stimuli. There are also some data suggesting that responses can be learned to nonconsciously presented in stimuli. In the discussion, it is argued that controlled processing may be dissociated from awareness. That is to say, stimuli may be processed at a controlled level without being accessible for conscious awareness. The relevance of these findings for Pavlovian conditioning is discussed.


LOX-1: Implications in atherosclerosis and myocardial ischemia.
Understanding the pathophysiology of atherosclerosis is fundamental to the practice of cardiovascular medicine. Atherosclerosis is a multi-step cascade of accumulation of lipids and downstream changes that lead to a fibro-fatty plaque formation in the arterial intima. Multiple biochemical stimuli, cellular receptors and intra-cellular signals are implicated in this complex mechanism. Lectin-type oxidized LDL receptor-1 or LOX-1 is a type II membrane glycoprotein receptor which has emerged as an important effector of atherosclerosis. Hence, LOX-1 modification and its clinical consequences are of much interest in recent times.


Phosphorylation sites in ligand-induced and ligand-independent activation of the progesterone receptor.
Steroid hormone receptors are phosphoproteins that undergo hyperphosphorylation upon binding of hormone. The mechanism and the role of this reaction remain poorly understood. Two-dimensional analysis of ligand-free progesterone receptor (PR) tryptic digests showed the existence of seven main phosphopeptides. Incubation of the cells with the progestin R5020 led to a global increase in the levels of PR phosphorylation. However, the same phosphopeptides were seen, and their levels of labeling relative to each other were unchanged. A similar result was observed after incubation of cells with the antiprogestin RU486. The antiprogestin ZK98299 demonstrated only half of the activity of RU486 in terms of receptor hyperphosphorylation, but the same phosphopeptides, proportionally labeled to the same extent, were observed by chromatography electrophoresis. Ligand-induced DNA binding did not play a role in receptor hyperphosphorylation since the mutant delta 547-592, which is devoid of the first zinc finger region, exhibited the same phosphopeptides, labeled to the same extent, as did wild-type receptor after incubation of cells with hormone. These results suggest that the same kinase(s) act in vivo on ligand-free and on agonist or antagonist-bound progesterone receptor. Binding of different ligands produces different conformational changes in the ligand binding domain of the receptor which enhance, to varying extents, affinity of the receptor for the kinase(s). The DNA binding region also plays a role in the interaction with the kinase(s), although binding to DNA per se is not necessary for the hyperphosphorylation of the receptor to take place.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparative analysis of the human saliva microbiome from different climate zones: Alaska, Germany, and Africa.
Although the importance of the human oral microbiome for health and disease is increasingly recognized, variation in the composition of the oral microbiome across different climates and geographic regions is largely unexplored. Here we analyze the saliva microbiome from native Alaskans (76 individuals from 4 populations), Germans (10 individuals from 1 population), and Africans (66 individuals from 3 populations) based on next-generation sequencing of partial 16S rRNA gene sequences. After quality filtering, a total of 67,916 analyzed sequences resulted in 5,592 OTUs (defined at ≥97% identity) and 123 genera. The three human groups differed significantly by the degree of diversity between and within individuals (e.g. beta diversity: Africans > Alaskans > Germans; alpha diversity: Germans > Alaskans > Africans). UniFrac, network, ANOSIM, and correlation analyses all indicated more similarities in the saliva microbiome of native Alaskans and Germans than between either group and Africans. The native Alaskans and Germans also had the highest number of shared bacterial interactions. At the level of shared OTUs, only limited support for a core microbiome shared across all three continental regions was provided, although partial correlation analysis did highlight interactions involving several pairs of genera as conserved across all human groups. Subsampling strategies for compensating for the unequal number of individuals per group or unequal sequence reads confirmed the above observations. Overall, this study illustrates the distinctiveness of the saliva microbiome of human groups living under very different climatic conditions.


Myc-Associated Zinc Finger Protein Promotes Metastasis of Papillary Thyroid Cancer.
Myc-associated zinc finger protein (MAZ) plays a role in cancer progression and metastasis. However, the role and underlying molecular mechanism of MAZ in thyroid cancer have not yet been fully elucidated. This study aimed to explore the clinical significance of MAZ in thyroid cancer tissues, and clarify its mechanism in the occurrence and development of thyroid cancer. The expression level of MAZ protein in thyroid cancer tissues was detected by bioinformatics analysis and immunohistochemistry (IHC). The relationship between the expression level of MAZ and clinicopathological characteristics of thyroid cancer patients was analyzed by multivariate logistic regression analysis. Quantitative reverse-transcription polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression level of MAZ in thyroid cancer cell lines. After MAZ knockdown cell lines were constructed, wound healing and Transwell assays were used to detect the migratory and invasive abilities of cancer cells. The results of IHC showed that the expression level of MAZ protein in thyroid cancer tissues was higher than that in normal adjacent thyroid tissues (p < 0.05), which was consistent with the high expression level of MAZ in thyroid cancer tissues found in The Cancer Genome Atlas (TCGA) database. The results of multivariate logistic regression analysis indicated that the expression level of MAZ was correlated with tumor diameter and tumor capsule of thyroid cancer patients. Moreover, patients with the high MAZ expression level had shorter overall and disease-free survival compared with thyroid cancer patients with the low MAZ expression level (p < 0.05). Further cell function assays indicated that downregulation of MAZ expression level could inhibit the migration and invasion of thyroid cancer cell lines. Moreover, the expression level of epithelial-mesenchymal transition (EMT)-related factor fibronectin 1 (FN1) was obtained from the RNA-seq of MAZ knockdown in thyroid cancer cells. RT-qPCR confirmed that the expression level of FN1 was elevated in MAZ knockdown cell lines (p < 0.05). Bioinformatics analysis indicated that the expression level of FN1 was upregulated in thyroid cancer tissues and had a negative relationship with the expression level of MAZ, as evidenced by correlation analysis. A high expression level of MAZ in thyroid cancer tissues was associated with a poor prognosis of patients. MAZ could affect the progression of thyroid cancer by inducing the EMT process.


Altering equine corneal fibroblast differentiation through Smad gene transfer.
To explore the impact of equine corneal fibroblast (ECF) to myofibroblast (ECM) differentiation by altering the expression of the Smad genes either individually or in combination. Specifically, we sought to examine the ECF differentiation after (a) silencing of Smad2, 3, and 4 profibrotic genes individually and (b) overexpression of antifibrotic Smad7 gene and in a combination with pro- and antifibrotic Smad genes. Equine corneal fibroblast primary cultures were generated as previously described. ECFs were transfected with individual plasmids which silenced gene expression of either Smad2, 3, or 4 or in combination with a plasmid overexpressing Smad7 using Lipofectamine 2000™ or Lipofectamine BLOCK-iT™. Smad-transfected clones were then exposed to TGF-β1 to induce differentiation to myofibroblasts. Immunofluorescence and qRT-PCR techniques quantified levels of ECF differentiation to ECM by measuring alpha smooth muscle actin, a known marker of ECM transdifferentiation. Silencing of individual Smad2, 3, or 4 genes or overexpression of Smad7 showed significant inhibition of ECF transdifferentiation (73-83% reduction). Silencing of Smad2 showed the greatest inhibition of ECF transdifferentiation in (a) and was therefore utilized for the combination gene transfer testing. The combination gene transfer consisting of Smad7 overexpression and Smad2 silencing attenuated ECF differentiation significantly; however, the level was not significant compared to the overexpression of Smad7 individually. Using gene transfer technology involving profibrotic Smad silencing, antifibrotic Smad overexpression or its combination is a novel strategy to control TGF-β1-mediated fibrosis in equine fibroblasts. Combination gene therapy was not better than single gene therapy in this study.


Taxonomic clustering and frequency associations as features of semantic memory development in children with learning disabilities.
This study investigated taxonomic clustering and use of frequency associations as features in the semantic memory development of children with learning disabilities (LD). Free-recall organization of second- and sixth-grade children with and without LD was analyzed for two types of primary and secondary word lists: (a) items associated with frequency (FA), and (b) items related by category members (CM). In contrast to expected findings, younger, non-disabled children organized words categorically as proficiently as their older nondisabled peers, and the categorization abilities of children with LD were comparable to those of nondisabled subjects, with one exception: Subjects with LD showed less clustering for secondary FA. These results indicate that when individual child-generated word lists (i.e., meaningful and familiar words) are used, children with LD may not be impaired in their ability to recognize and utilize semantic structure to facilitate learning.


Application of An Improved HPLC-FL Method to Screen Serine Palmitoyl Transferase Inhibitors.
In this work, we reported the application and validation of an improved high-performance liquid chromatography method coupled with a fluorimetric detector (HPLC-FL) to screen the activity of two heterocyclic derivatives reported as serine palmitoyl transferase (SPT) inhibitors. The analytical conditions were optimized in terms of the derivatization procedure, chromatographic condition, extraction procedure, and method validation according to EMEA guidelines. Once fully optimized, the method was applied to assess the SPT-inhibitory activity of the above-mentioned derivatives and of the reference inhibitor myriocin. The obtained results, expressed as a percentage of residual SPT activity, were compared to those obtained with the reference radio immune assay (RIA). The good correlation between the two types of assay demonstrated that the improved HPLC-FL method is suitable for a preliminary and rapid screening of potential SPT-inhibitors.


ALDH1A1 Inhibits Chicken Preadipocytes' Proliferation and Differentiation via the PPARγ Pathway In Vitro and In Vivo.
ALDH1A1 (aldehyde dehydrogenase 1A1) is a crucial protein in retinoids' metabolism, and the lack of ALDH1A1 inhibits the fat deposition in mice. However, whether ALDH1A1 has a similar effect on chickens' fat-depot is still unknown. In this study, we investigate the role of ALDH1A1 in chickens' adipogenesis. The immortalized chicken preadipocyte 1 (ICP1) cell line and chicken primary preadipocytes isolated from abdominal fat were used to perform a series of experiments in vitro to elucidate the effects of ALDH1A1. In addition, lentivirus was used to verify the results of cell experiments in vivo. The data showed that overexpression of ALDH1A1 significantly weakened the proliferation of preadipocytes and suppressed the differentiation of preadipocytes through the PPARγ pathway, and the knockdown experiments had the opposite results. Moreover, chickens injected with overexpression lentivirus had higher abdominal fat percentage, a bigger size of lipid droplets, and higher triglyceride content in abdominal fat, and chickens injected with interfering lentivirus had the opposite situation. We proved that ALDH1A1 not only inhibited the proliferation and differentiation of chickens' preadipocytes in vitro, but also inhibited the fat-depot of chickens in vivo, which was completely opposite the function of ALDH1A1 in mice, indicating that ALDH1A1 may have a different mechanism that is still unknown.


Isothermal Microcalorimetry: Insight into the Impact of Crystallite Size and Agglomeration on the Lithiation of Magnetite, Fe3O4.
Magnetite, Fe3O4, holds significant interest as a Li-ion anode material because of its high theoretical capacity (926 mAh/g) associated with multiple electron transfers per cation center. Notably, both crystallite size and agglomeration influence ion transport. This report probes the effects of crystallite size (12 and 29 nm) and agglomeration on the reactions involved with the formation of the surface electrolyte interphase on Fe3O4. Isothermal microcalorimetry (IMC) was used to determine the parasitic heat evolved during lithiation by considering the total heat measured, cell polarization, and entropic contributions. Interestingly, the 29 nm Fe3O4-based electrodes produced more parasitic heat than the 12 nm samples (1346 vs 1155 J/g). This observation was explored using scanning electron microscopy (SEM) and X-ray fluorescence (XRF) mapping in conjunction with spatially resolved X-ray absorption spectroscopy (XAS). SEM imaging of the electrodes revealed more agglomerates for the 12 nm material, affirmed by XRF maps. Further, XAS results suggest that Li+ transport is more restricted for the smaller crystallite size (12 nm) material, attributed to its greater degree of agglomeration. These results rationalize the IMC data, where agglomerates of the 12 nm material limit solid electrolyte interphase formation and parasitic heat generation during lithiation of Fe3O4.


Kallikrein and renal enzyme excretion in rats.
Using the model of renal enzyme excretion in rats it was investigated whether a chemically defined kininogenase (kallikrein) exerts shock-inducing activity. Following i.p. injections of kallikrein in doses of 1000 or 7000 KU/kg body weight, an increase in urinary AP- and LAP-activities was encountered as well as an increase in creatinine excretion. These effects were attributable to increased diuresis and could not be related to any anaphylactoid activity (elicitation of vascular shock) of the injected enzyme preparation. According to these experimental results, kallikrein may not be considered as anaphylactoid drug, at least not in the rat.


Supporting therapy selection in computerized clinical guidelines by means of decision theory.
Supporting therapy selection is a fundamental task for a system for the computerized management of clinical guidelines (GL). The goal is particularly critical when no alternative is really better than the others, from a strictly clinical viewpoint. In these cases, decision theory appears to be a very suitable means to provide advice. In this paper, we describe how algorithms for calculating utility, and for evaluating the optimal policy, can be exploited to fit the GL management context.


Simulating the mechanism of antimicrobial lipopeptides with all-atom molecular dynamics.
The emergence of antibiotic resistant pathogens is one of the major medical concerns of the 21st century, prompting renewed interest in the development of novel antimicrobial compounds. Here we use microsecond-scale all-atom molecular dynamics simulations to characterize the structure, dynamics, and membrane-binding mechanism of a synthetic antimicrobial lipopeptide, C16-KGGK. Our simulations suggest that these lipopeptides prefer to aggregate in solution and alter the intrinsic order of the lipid bilayer upon binding. From these results and previous coarse-grained simulations, we have developed a simple model for the binding and insertion process for these lipopeptides.


Second-order axial color of thin lenses in air.
In present research, the influence of higher-order aberrations on the correction of secondary axial color is under investigation. Analytical solutions have so far been restricted to special cases and simple optical systems. Common theories require the tracing of rays of different wavelengths. Such numerical approaches do not support the comprehension of the underlying physical effects. In this paper, a formula for second-order axial color contributions is derived which is based on paraxial ray data for the reference wavelength only. Therefore, it allows the determination of second-order axial color in early paraxial design stages without further numerical ray trace. For systems of thin lenses in air, three second-order effects are identified and discussed using simple examples. A quantitative comparison with intrinsic secondary axial color is given.


Endocrine Surgical Procedures During COVID-19: Patient Prioritization and Time to Surgery.
We tracked endocrine surgery patients with treatment delays due to COVID-19 to investigate the relationship between physician assigned priority scoring (PAPS), the Medically Necessary, Time Sensitive (MeNTS) scoring system and delay to surgery. Patients scheduled for endocrine surgery or clinically evaluated during COVID-19-related elective surgery hold at our institution (2/26/20-5/1/20) were prospectively enrolled. PAPS was assigned based on categories of high, moderate, or low risk, consistent with the American College of Surgeons' priority system. MeNTS scores were calculated. The primary outcome was delay to surgery. Descriptive statistics were performed, and receiver operator characteristic (ROC) curves and area under the curve (AUC) values were calculated for PAPS and MeNTS. Of 146 patients included, 68% (n = 100) were female; the median age was 60 years (IQR:43,67). Mean delay to surgery was significantly shorter (P = 0.01) in patients with high PAPS (35 d), compared with moderate (61 d) and low (79 d) PAPS groups. MeNTS scores were provided for 105 patients and were analyzed by diagnosis. Patients with benign thyroid disease (n = 17) had a significantly higher MeNTS score than patients with thyroid disease which was malignant/suspicious for malignancy (n = 44) patients (51.5 versus 47.6, P = 0.034). Higher PAPS correlated well with a delay to surgery of <30 d (AUC: 0.72). MeNTS score did not correlate well with delay to surgery <30 d (AUC: 0.52). PAPS better predicted delay to surgery than MeNTS scores. PAPS may incorporate more complex components of clinical decision-making which are not captured in the MeNTS score.


High reactivity of nanosized niobium oxide cluster cations in methane activation: A comparison with vanadium oxides.
The reactions between methane and niobium oxide cluster cations were studied and compared to those employing vanadium oxides. Hydrogen atom abstraction (HAA) reactions were identified over stoichiometric (Nb2O5)N(+) clusters for N as large as 14 with a time-of-flight mass spectrometer. The reactivity of (Nb2O5)N(+) clusters decreases as the N increases, and it is higher than that of (V 2O5)N(+) for N ≥ 4. Theoretical studies were conducted on (Nb2O5)N(+) (N = 2-6) by density functional calculations. HAA reactions on these clusters are all favorable thermodynamically and kinetically. The difference of the reactivity with respect to the cluster size and metal type (Nb vs V) was attributed to thermodynamics, kinetics, the electron capture ability, and the distribution of the unpaired spin density. Nanosized Nb oxide clusters show higher HAA reactivity than V oxides, indicating that niobia may serve as promising catalysts for practical methane conversion.


Long non-coding RNA XIST promotes cell proliferation and migration through targeting miR-133a in bladder cancer.
The long non-coding RNA (lncRNA) X inactive specific transcript (XIST) has recently been reported to promote the malignant progression of bladder cancer through regulating several microRNAs (miRs), including miR-124, miR-139-5p and miR-200c. However, whether other miRs are also involved in this process has remained to be determined. The present study demonstrated that XIST was significantly upregulated in bladder cancer tissues compared with that in adjacent normal tissues. Furthermore, its expression was reduced in several common bladder cancer cell lines. High expression of XIST was significantly associated with tumour progression and poor prognosis of patients with bladder cancer. An in vitro experiment indicated that knockdown of XIST significantly reduced the proliferation and migration of bladder cancer cells. A luciferase assay suggested that XIST binds to its predicted binding site in miR-133a. In addition, it was identified that miR-133a was significantly downregulated in bladder cancer, and its expression levels were inversely correlated with those of XIST in bladder cancer tissues. Furthermore, loss- and gain-of-function experiments indicated that miR-133a acted as a downstream effector in XIST-mediated bladder cancer cell proliferation and migration. In conclusion, the present study demonstrates that XIST promotes bladder cancer cell proliferation and migration via targeting miR-133a and thus suggests that XIST may be used as a potential therapeutic target for bladder cancer.


Diaphragmatic discontinuity associated with perihepatic ascites: a sonographic refractive artifact.
Apparent discontinuity in the diaphragm frequently is seen in sonograms of the right upper quadrant in patients with perihepatic ascites. Using a fresh cadaveric liver and a linear reflector to simulate the diaphragm, we performed in vitro analysis and confirmed that the appearance of the diaphragm was artifactual; this was due to refraction of the sound beam at the interface between the liver and ascites. Knowledge of the typical sonographic appearance and location of this artifact should prevent diagnostic errors.


Septal hematoma due to stent implementation in the septal course of the left anterior descending artery.
The interventricular septal hematoma (IVSH) is a rare and potentially lethal finding. There are variously reported etiologies including instrumental damages during cardiac interventions. Although there are not enough studies available, conservative management is considered as a preferable approach in stable patients. A 45-year man smoker with the previous history of percutaneous coronary intervention (PCI), admitted with unstable angina in present visit. Coronary angiography showed significant in-stent restenosis (ISR) of the left anterior descending (LAD) artery stent. During our intervention for treatment of the ISR, the wire movement caused a diffuse dissection without any runoff, in the distal portion of the LAD. Therefore two stents were deployed in the dissected segment with a short overlapping segment. Unfortunately, the overlapping segment of these stents was located in the myocardial bridge segment. Therefore the contraction of the interventricular septum (IVS) caused a scissor-like movement of the stents, and they ruptured the LAD into the septum. Therefore, the contrast agent was accumulated in the IVS. Immediately, a graft stent was deployed in the overlapping segment of stents and perforation became sealed. In echocardiography, the IVS diameter increased to 30 mm. Since the patient was hemodynamically and electrically stable, he underwent conservative approach and after two months the septum returned to the normal size. During PCI on the LAD artery, the implantation of stents in the septal course with a short overlapping segment can result in coronary perforation, and therefore IVS hematoma by the scissor effect. Septal hematoma may cause life-threatening arrhythmias or ventricular septal rupture, but if it is asymptomatic or uncomplicated. Conservative management is the best strategy.


Arthrobacter sialophilus sp. nov.; a neuraminidase-producing coryneform.
A new species of Arthrobacter is described for which the name A. sialophilus is proposed. The organism was obtained by elective culture from soil using Collocalia mucoid, and can readily be induced in replacement minimal media with appropriate substrates, to form the enzyme neuraminidase. It undergoes sphere-rod-sphere morphogenesis, is gram-variable, non-motile, aerobic, catalase-positive, oxidase-negative, fails to release acid or gas from saccharides, has a GC content of 56.0 mol % and can grow at temperatures up to 45 degrees C. The peptidoglycan composition of its spherical form contains neither diaminopimelic acid nor arabinose as components, but does manifest the presence of glycine. Its generation time at 30 degrees C on tryptone-yeast extract medium is 1.6 h. Accessory growth factors do not appear to be required. The organism, though colorless in the dark, provides a bright yellow water-insoluble pigment after exposure to light. The foregoing combination of properties distinguishes this isolate from other well-described Arthrobacter spp.


A comparison for use in radiotherapy of neutron beams generated with 16 and 42 MeV deuterons on beryllium.
The physical and radiobiological properties of two neutron beams have been compared. The beams were generated by deuterons of 16 MeV at Hammersmith Hospital and 42 MeV at Harwell, in both cases falling on a Be/Cu target. The dose-rate and depth-dose characteristics at the higher energy were found to be superior to those at the lower energy. Collimation and shielding at the higher energy are facilitated by the greater degree of forward-peaking and by the fact that a higher dose-rate allows longer collimators to be used. Attenuation in iron was found to be similar at the two energies. The radiobiological properties of the two neutron beams are very similar. There is a difference of about 20 per cent in RBE for effects on mammalian tissues for doses between 300 and 2,000 rad of neutrons. The OER and the sparing effect of two large fractions are the same for the two beams.


Retrospective analysis of long-term adherence to and persistence with DPP-4 inhibitors in US adults with type 2 diabetes mellitus.
Patients with type 2 diabetes mellitus (T2DM) must remain adherent and persistent on antidiabetic medications to optimize clinical benefits. This analysis compared adherence and persistence among adults initiating dipeptidyl peptidase-4 inhibitors (DPP-4is), sulfonylureas (SUs), and thiazolidinediones (TZDs) and between patients initiating saxagliptin or sitagliptin, two DPP-4is. This retrospective cohort study utilized the US MarketScan(®) (Truven Health Analytics, Ann Arbor, MI, USA) Commercial and Medicare Supplemental health insurance claims databases. Adults aged ≥18 years with T2DM who initiated a DPP-4i, SU, or TZD from January 1, 2009 to January 31, 2012 were included. Patients must have been continuously enrolled for ≥1 year prior to and ≥1 year following initiation. Adherence was measured using proportion of days covered (PDC), with PDC ≥ 0.80 considered adherent. Persistence was measured as time to discontinuation, defined as last day with drug prior to a 60+ days gap in therapy. Multivariable logistic regression and Cox proportional hazards models compared the outcomes between cohorts, controlling for baseline differences. The sample included 238,372 patients (61,399 DPP-4i, 134,961 SU, 42,012 TZD). During 1-year follow-up, 47.3% of DPP-4i initiators, 41.2% of SU initiators, and 36.7% of TZD initiators were adherent. Adjusted odds of adherence were significantly greater among DPP-4i initiators than SU (adjusted odds ratio [AOR] = 1.678, P < 0.001) and TZD initiators (AOR = 1.605, P < 0.001). During 1-year follow-up, 55.0% of DPP-4i initiators, 47.8% of SU initiators, and 42.9% of TZD initiators did not discontinue therapy. Adjusted hazards of discontinuation were significantly greater for SU (adjusted hazard ratio [AHR] = 1.390, P < 0.001) and TZD initiators (AHR = 1.402, P < 0.001) compared with DPP-4i initiators. Saxagliptin initiators had significantly better adherence (AOR = 1.213, P < 0.001) compared with sitagliptin initiators, and sitagliptin initiators had significantly greater hazard of discontinuation (AHR = 1.159, P < 0.001). Results were similar over a 2-year follow-up. US adults with T2DM who initiated DPP-4i therapy, particularly saxagliptin, had significantly better adherence and persistence compared with patients who initiated SUs or TZDs.


New ent-kaurene-type diterpenoids possessing cytotoxicity from the New Zealand liverwort Jungermannia species.
Two new ent-kaurene-type and a new rearranged ent-kaurene-type diterpenoids possessing cytotoxicity against a human leukemia cell line have been isolated from the New Zealand liverwort Jungermannia species, together with previously known ent-kaurene-type diterpenoids. Their structures were established based on extensive NMR techniques.


Six-Month Chronic Toxicity Study of Tamarind Pulp (Tamarindus indica L.) Water Extract.
Tamarind water extract has been shown to demonstrate an anti-obesity effect. In this research, long-term use of tamarind pulp water extract safety was evaluated. Tamarind pulp was extracted by reflux method, followed by freeze-drying to obtain dry extract. Wistar rats were divided into six groups, with 20 animals of each sex per group. The control group and satellite control group received carboxymethylcellulose sodium (CMC-Na) 0.5% 1 mL/100 g bw (body weight) per day. Treatment groups received tamarind pulp extract at doses of 75, 200, 1000, satellite 1000 mg/kg bw per day for six months. After six months, control groups and the treatment group were sacrificed. Satellite groups were sacrificed one month later. Relative organ weights, hematology and clinical biochemistry profiles were determined. After six months, there were no significant change in body weight, hematologic, and clinical biochemistry profiles of the tested group. Body weight of male rats in the satellite 1000 mg/kg bw group was significantly increased in week 30 compared to the satellite control group (p < 0.05). The relative spleen weight of female rats of the 200 mg/kg bw group was reduced (p < 0.05). The relative kidney weight of male rats in the 1000 mg/kg bw group was increased (p < 0.05). This study showed that tamarind pulp extract was generally safe and well tolerated at the tested dose.