Opioid Use After ICU Admission Among Elderly Chronic Opioid Users in Ontario: A Population-Based Cohort Study.
Critical illness is often associated with painful procedures and prolonged opioid infusions, raising the concern that chronic opioid users may be exposed to escalating doses that are continued after hospital discharge. We sought to assess patterns of opioid use after intensive care among elderly patients identified as chronic opioid users prior to hospitalization. Population-based cohort study. All adult ICUs in the province of Ontario, Canada. Elderly patients (> 65 yr) admitted to ICUs between April 2002 and March 2015 who also survived to day 180 after hospital discharge, identified as chronic opioid users prior to hospitalization. Chronic opioid use in the year before hospital admission, as well as a filled opioid prescription with a duration covering the day of hospital admission. The primary outcome was the proportion of patients who filled an opioid prescription with a duration covering day 180 after hospital discharge; secondary outcome was the difference in morphine equivalent daily dosage at day 180 after discharge compared with the amount prescribed prior to hospital admission. Of 496,985 elderly admissions to ICUs, 19,584 (3.9%) were chronic opioid users before hospitalization who also survived to day 180 after hospital discharge. The median daily dose of opioid prescriptions filled before hospital admission was 32.1 mg morphine equivalent (interquartile range, 17.5-75.0 mg morphine equivalent). Among these survivors, 63.3% had at least one opioid prescription filled with a duration covering day 180; 22.0% had filled prescriptions for a higher daily morphine equivalent dose compared with prehospitalization, 19.8% were unchanged, 21.5% had a lower dose, and 36.7% had no prescription filled. The majority of reduction was in prescriptions for codeine and oxycodone. Among chronic opioid users, hospitalization with critical illness was not associated with substantial increases in opioids prescribed in the 6 months following hospitalization.


Macular abnormalities in papilledema from pseudotumor cerebri.
Three young women with papilledema secondary to pseudotumor cerebri evolved mottled macular pigmentation with preservation of normal visual acuity. Choroidal folds or macular star figures were observed. These macular changes could represent the sequelae of either macular edema or a mechanical disruption of the retinal pigment epithelium. The mechanism of choroidal folds in papilledema remains uncertain.


Group visits hold great potential for improving diabetes care and outcomes, but best practices must be developed.
A diagnosis of diabetes can require multiple changes in a person's behavior, diet, and lifestyle. Efforts to sustain these changes and manage this complex chronic disease can be difficult. Group visits, in which several patients meet together with a primary care provider and transdisciplinary team, have tremendous potential to improve health care quality, cost, and access. When group-based diabetes self-management education and a primary care visit occur within a single appointment, people with the disease can address multiple needs in one visit and take advantage of peer groups for support and motivation. A review of the literature demonstrates that the efficacy of group visits has a promising evidence base-but more needs to be learned about optimal group size and aspects of the model that should be standardized. An important first step is introducing a procedural code for group visits, so that providers and researchers can better track the efficacy of the group-visit model and develop best practices before the model is adopted systemwide.


Physiological integration in the clonal perennial herb Trifolium repens L.
Translocation of 14C-labelled carbohydrates between the parent stolon and branches, and among branches, of Trifolium repens plants was investigated in two glasshouse experiments to determine patterns of physiological organisation in this clonal species. Differential defoliation treatments were applied to the parent stolon and/or branches to test the sensitivity of translocation to the short-term carbon needs of defoliated sinks. Strong reciprocal exchange of carbohydrate between the parent stolon and branches was observed, with 18 41% of the 14C exported from leaves on the parent stolon moving to branches, while branches simulta-neously exported 25% (for old source branches) to 54% (for young source branches) of the 14C they assimilated to the parent plant, including translocation to other branches. Branch-to-branch translocation occurred both acropetally and basipetally. Parent-to-branch, branch-to-parent and branch-to-branch carbon fluxes all increased in response to defoliation of the sink, at the expense of carbon supply to stolon tissue or roots of the source module. Reduced export to stolon tissue of the parent axis played a major role in facilitating C reallocation from leaves on the parent stolon to defoliated branches. The observed patterns of C allocation and translocation could be adequately explained by accepted source-sink theory, and are consistent with a high degree of intra-plant physiological integration in resource supply and utilisation. This information provides mechanistic explanations for aspects of the growth dynamics and ecological interactions of T. repens in the patchy environment of a grazed pasture.


Differences of chronological seasonality in drug overdose.
To investigate the association between seasonality and intentional drug overdose (IDO), a commonly seen method of self-harm in daily emergency medicine practice. Cases of IDO were retrospectively selected using the International Classification of Diseases (ICD)-10 coding system (codes T36-T50), in patients who attended the Emergency Department of MacKay Memorial Hospital between January 2018 and August 2019. Data regarding age, sex, arrival time, marital status, vital signs, comorbidities, psychiatric history, social conflicts, substance of overdose, and length of hospital stay by season, were analysed using Student's t-test and χ2-test. Of all included cases (n = 196), IDO occurred most frequently in spring (32.1%), particularly in male patients (28/49 male cases). First-time IDO occurred most frequently in spring (51/133 first-time cases) and most spring cases were first-time IDO (51/63 spring cases). Repeat IDO occurred most frequently in autumn (20/63 repeat cases). Female conflict with father and/or boyfriend, and personality disorder in patients who overdosed, showed seasonality with a spring peak. Hospital admission rate was highest in winter (10/45 winter cases [22.2%]). Episodes of IDO exhibited seasonality, with a spring peak, particularly for male patients, female patients in conflict with father and/or boyfriend, and those with personality disorder. Clinicians should pay close attention to the abovementioned patient groups.


Mechanism of renal potassium conservation in the rat.
The mechanisms responsible for renal potassium (K) conservation during dietary potassium deficiency are poorly understood. This study was undertaken to investigate the time course of potassium conservation as well as the roles of distal sodium (Na) delivery, the distal delivery or sodium plus a nonpermeable anion, mineralocorticoid hormone, renal tissue potassium content, and Na-K-ATPase activity in renal potassium conservation. After 72 hours of a low-potassium diet, basal potassium excretion was negligible. After 24 hours, and even more so after 72 hours of potassium restriction, the kaliuretic response to increasing distal delivery of sodium or sodium plus a nonpermeable anion was impaired. After 24 hours of a low-potassium diet, plasma aldosterone levels fell from 180 +/- 25 to 32 +/- 9 pg/ml (P less than 0.001). Mineralocorticoid hormone given in the first 24 hours of a low-potassium diet resulted in a greater potassium loss (1564 +/- 125 muEq) than it did in controls on the same diet not receiving mineralocorticoid hormone (1032 +/- 83 muEq, P less than 0.005). In contrast, after 72 hours of diet, large doses of mineralocorticoid hormone failed to cause a kaliuresis in either anesthetized or conscious rats. After both 24 and 72 hours, outer medullary Na-K-ATPase was increased. At 72 hours, cortical, medullary, and papillary tissue potassium concentrations were significantly depressed. Acute administration of potassium repleted tissue potassium levels and restored basal and saline-stimulated potassium excretion to normal. Although potassium excretion was markedly depressed after 24 hours of the low-potassium diet, 42K microinjection studies of the distal nephron did not suggest any increase in potassium reabsorption. Following 72 hours of diet, potassium reabsorption increased significantly from 26 +/- 2% to 41 +/- 2% (P less than 0.001). We conclude that renal potassium conservation is at first primarily related to a decrease in potassium secretion, which is most likely mediated by falling levels of mineralocorticoid hormone. After 72 hours of the potassium-deficient diet, however, potassium conservation becomes independent of mineralocorticoid hormone, distal delivery of sodium, and Na-K-ATPase. The decreased tissue potassium content appears to be the primary mediator of both the increase in potassium reabsorption by the distal nephron and of renal potassium conservation at this time.


Diagnosis of arteriovenous malformation of the internal iliac vessels by color Doppler ultrasonography: A case report.
A 13-year-old girl was admitted to the hospital because of cardiomegaly found incidentally at regular medical checkup at her school. Although dilated cardiomyopathy was suspected, the girl showed no symptoms. chest x-ray film showed cardiomegaly (cardiothoracic ratio, 67%), and echocardiogram demonstrated a dilatation of the left ventricle without thinning of the wall. While contraction was diffusely decreased, estimated cardiac output was increased to 13l/minute. Abdominal ultrasonography conducted to clarify the cause of this high output showed a multicystic lesion (8×6×4 cm) at the back of the left common iliac artery. Color Doppler ultrasonography revealed abundant blood flow within the lesion, establishing the diagnosis of arteriovenous malformation. Aortography delineated the arteriovenous malformation being supplied from the left internal iliac artery and from the left third and fourth lumbar arteries and drainage into the left common iliac vein and the right internal iliac vein. Although it did not show the precise location of the feeding and draining vessels, color Doppler ultrasonography was useful for the diagnosis of arteriovenous malformation.


An Innovative Nurse Staffing Model: Nurses Are Happy2Help and Strike the Right Balance.
The aim of this study was to develop a flexible nurse reallocation solution. Successful nurse reallocation supports appropriate staffing and may enhance workforce flexibility. An innovative program incentivizing regular nursing staff to volunteer for extra shifts systemwide was implemented at a large healthcare organization. Nurses' perceptions of appropriate staffing improved, and nursing care quality was not compromised. The program primed the organization to respond to the pandemic. The staffing model has been sustained for 3+ years.


The biogenic amine tryptamine, unlike β-phenylethylamine, shows in vitro cytotoxicity at concentrations that have been found in foods.
β-phenylethylamine and tryptamine are biogenic amines (BA) often found in foods. In general, BA are assumed to be toxic and their accumulation in food is not recommended. However, present knowledge regarding the toxicity of β-phenylethylamine and tryptamine is limited; more information is needed if qualitative and quantitative risk assessments of foods are to be successfully conducted. This study describes a real-time analysis of β-phenylethylamine and tryptamine toxicity on a human intestinal epithelial cell line. Both BA caused cell necrosis and apoptosis, although the former was the main mode of action of β-phenylethylamine, and the latter the main mode of action of tryptamine. Only tryptamine was cytotoxic at concentrations found in BA-rich foods. The results presented in this work may contribute to establish legal limits for β-phenylethylamine and tryptamine in food.


Polymorphisms in the folate-metabolizing genes MTR, MTRR, and CBS and breast cancer risk.
Alterations in the nucleotide sequences of folate-metabolizing genes can increase the risk of malignant transformation. The aim of our study was to investigate the association of three single-nucleotide polymorphisms (SNPs) in the folate-metabolizing genes - A2756G MTR, A66G MTRR, and 844ins68 CBS - which have putative functional significance in breast cancer risk. The allele and genotype frequencies of the SNPs were determined in a case group (840 women with sporadic breast cancer) and a control group (770 women). No statistically significant association of studied SNPs with breast cancer was revealed. A meta-analysis, which included data obtained from the literature and the present research, did not reveal any statistically significant associations of these SNPs with breast cancer. The results obtained provide evidence that these SNPs are not involved in the development of breast cancer.


The adenylate cyclase-activating activity of cholera toxin is not associated with a nicotinamide--adenine dinucleotide glycohydrolase activity.
The NAD+ glycohydrolase activity of cholera-toxin samples can be separated from their adenylate cyclase-activating activity by polyacrylamide-gel electrophoresis and is inhibited by sodium dodecyl sulphate (which does not inhibit the action of toxin on cells), but not by antibodies to pure toxin. It is therefore probably not a true property of the toxin.


Alkalinization increases penetration of lidocaine across the human cornea.
To test the hypothesis that corneal permeability of lidocaine complies with the principle of nonionic diffusion. Department of Ophthalmology and Institute of Pharmacology, Vienna, Austria. Human corneas, mounted in an in vitro perfusion system under short-circuit conditions, were exposed on the epithelial (tear) side to lidocaine 4% in a buffered solution of pH 5 or pH 7. The endothelial bathing solutions had a constant pH of 7.4. Both solutions were adjusted to an osmolarity of 290 mOsm/L. The lidocaine permeability of the isolated corneas was assessed from the fluxes of 14C-labeled lidocaine across the tissue, measured at 15-minute intervals for 180 minutes, and corrected for the unidirectional fluxes of 3H-polyethylene glycol, a marker for the extracellular pathway. The corneal tissue content of lidocaine was estimated from the time span until the unidirectional lidocaine fluxes across the cornea reached a steady state. The mean transcorneal fluxes of lidocaine in the steady state (90 to 180 minutes) were 72% higher at pH 7 than at pH 5 (101 mmol/min +/- 37 (SD) versus 59 +/- 34 nmol/min.cornea; P <.002). The corneal content of lidocaine in the steady state was 65% higher at pH 7 than at pH 5 (2.8 +/- 0.9 micromol/cornea versus 1.7 +/- 1.2 micromol/cornea; not significant). A shift in solution pH from 5 to 7 significantly increased the corneal permeability of topically applied lidocaine. Alkaline pH-adjustment of topical lidocaine solutions is easy to perform by adding sodium bicarbonate. The main clinical advantages of anesthetic solutions buffered at pH 7 are increased penetration rates, effectiveness, prolonged action time, and a reduction in local irritation and lacrimation.


Health-related quality of life profiles in adolescents and young adults with chronic conditions.
To assess health-related quality of life (HRQOL) among adolescents and young adults (AYAs) with chronic conditions. AYAs (N = 872) aged 14-20 years completed NIH's Patient-Reported Outcomes Measurement Information System® (PROMIS®) measures of physical function, pain interference, fatigue, social health, depression, anxiety, and anger. Latent profile analysis (LPA) was used to group AYAs into HRQOL profiles using PROMIS T-scores. The optimal number of profiles was determined by model fit statistics, likelihood ratio test, and entropy. Multinomial logistic regression models were used to examine how LPA's HRQOL profile membership was associated with patient demographic and chronic conditions. The model prediction accuracy on profile membership was evaluated using Huberty's I index with a threshold of 0.35 for good effect. A 4-profile LPA model was selected. A total of 161 (18.5%), 256 (29.4%), 364 (41.7%), and 91 (10.4%) AYAs were classified into Minimal, Mild, Moderate, and Severe HRQOL Impact profiles. AYAs in each profile had distinctive mean scores with over a half standard deviation (5-points in PROMIS T-scores) of difference between profiles across most HRQOL domains. AYAs who were female or had conditions such as mental health condition, hypertension, and self-reported chronic pain were more likely to be in the Severe HRQOL Impact profile. The Huberty's I index was 0.36. Approximately half of AYAs with a chronic condition experience moderate to severe HRQOL impact. The availability of risk prediction models for HRQOL impact will help to identify AYAs who are in greatest need of closer clinical care follow-up.


LncRNA LINC00467 contributes to osteosarcoma growth and metastasis through regulating HMGA1 by directly targeting miR-217.
Osteosarcoma (OS) is a common primary bone tumor. Despite multiple treatment strategies have made great progress, the overall clinical outcome of OS patients is frustrating. Long non-coding RNA (lncRNA) LINC00467 has been reported in several cancers, while the research of the role of LINC00467 in OS is limited. The aim of this study was to figure out the potential mechanism of LINC00467 in OS. The expression levels of LINC00467, microRNA-217 (miR-217) and high mobility group A1 (HMGA1) were quantified by reverse transcription quantitative polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8), flow cytometry and transwell assay were performed to detect cell proliferation, apoptosis, migration and invasion, respectively. The protein levels of HMGA1, B-cell lymphoma-2 (Bcl-2), Bax, Cleaved Caspase-3 (C-Caspase 3), E-cadherin, N-cadherin and vimentin were measured by Western blot assay. Online software starbase was used to predict the binding sites of miR-217. Luciferase report assay and RNA Binding Protein Immunoprecipitation (RIP) assay were carried out for detecting the interaction between miR-217 and LINC00467 or HMGA1. The expression of LINC00467 and HMGA1 was increased in OS tissues and cells, while miR-217 expression was reduced. High expression of HMGA1 led to the poor overall survival. Down-regulation of LINC00467 or up-regulation of miR-217 could accelerate cell apoptosis, and slump cell proliferation, migration, invasion and EMT. However, miR-217 under-expression or HMGA1 over-expression could rescue these effects. Moreover, it was indicated that LINC00467 directly targeted miR-217 and HMGA1 was a target of miR-217. LINC00467 promoted cell proliferation, migration, invasion and EMT, and suppressed cell apoptosis by up-regulating HMGA1 via targeting miR-217.


Effective Modulation of Exciton Binding Energies in Polymorphs of a Small-Molecule Acceptor for Organic Photovoltaics.
The operation mechanisms and energy losses for organic solar cells are essentially determined by the exciton binding energies (Eb) of organic active materials. Because the factor of chemical modifications is precluded, polymorphisms featuring different packing motifs of the same molecular structures provide an ideal platform for revealing the influence of solid-state packing. Herein, we have calculated the Eb values in three different cystal phases of a representative acceptor-donor-acceptor molecular acceptor (IDIC) by the self-consistent quantum mechanics/embedded charge approach. The results show that the differences of mere molecular packing modes can result in a substantial change in Eb of ≤50%, in the range of 0.21-0.34 eV among the three IDIC crystal phases. Moreover, a higher backbone packing dimensionality is found to be beneficial for obtaining a smaller Eb. This indicates that polymorph engineering is an effective way to reduce Eb toward low-energy-loss organic solar cells.


ER morphology and endo-lysosomal crosstalk: Functions and disease implications.
The endoplasmic reticulum (ER) is a continuous endomembrane system comprising the nuclear envelope, ribosome-studded sheets, dense peripheral matrices, and an extensive polygonal network of interconnected tubules. In addition to performing numerous critical cellular functions, the ER makes extensive contacts with other organelles, including endosomes and lysosomes. The molecular and functional characterization of these contacts has advanced significantly over the past several years. These contacts participate in key functions such as cholesterol transfer, endosome tubule fission, and Ca2+ exchange. Disruption of key proteins at these sites can result in often severe diseases, particularly those affecting the nervous system.


Fundamentals of computerised data acquisition in the human performance laboratory.
Researchers of the future will depend upon computer technology to address questions that previously could not be answered using traditional methods of data acquisition. Recent advances in computer design and software availability have eliminated many of the limitations previously associated with computer use in the laboratory setting. Although computerisation facilitates the acquisition of laboratory data, identification of errors introduced into the measurement is often more difficult. The laboratory computer is only one component of an automated data acquisition system. A system designed to collect physiological data comprises several primary components, including: (a) sensing element; (b) signal amplification/conditioning circuits; (c) analogue display; (d) computer interface; (e) laboratory computer; and (f) acquisition software. The acquisition and conditioning of analogue signals is accomplished using traditional laboratory procedures familiar to the researcher. Converting this analogue signal into a digital format used by the computer, however, represents new techniques. Fundamentals of computerised data acquisition are discussed. An understanding of how an automated data acquisition system is configured and the techniques used to transform the values will assist the user in identifying sources of error introduced into the measurement. Additionally, familiarization with the methods of computerisation will provide insight into future applications of computer technology in the human performance laboratory.


The influence of sediment composition and leaf litter on the distribution of tubificid worms (Oligochaeta) : A field and laboratory study.
The horizontal distribution of three species of tubificid worm (Tubifex tubifex, Limnodrilus hoffmeisteri and L. udekemianus in the sediment of a small stream was examined. Worm distribution was most strongly correlated with the distribution of leaf litter. This relationship was examined in the laboratory by means of choice chambers. It was concluded that; 1) the addition, to an inorganic substratum, of conditioned leaf material, enhanced its attractiveness to the worms; 2) a combination of silt-clay and leaf material was preferred by the worms to mixtures of leaf material and coarser inorganic substrata 3) some leaf species were more attractive to the worms than others; 4) there were differences between the worm species in their preferences for the various leaf species; 5) none of the three tubificid species was exclusively associated with its preferred leaf species; 6) worms would switch to less attractive leaf species if preferred alternatives were unavailable; 7) leaf material only attracted the worms once it had become conditioned; 8) this appeal was lost when the leaves were autoclaved; and 9) substratum choice was independent of worm size.We believe the worms were attracted to the leaves because the associated microfloras provided a concentration of bacterial food. Differences between the three tubificid species in their preferences for the various leaf species probably reduced trophic competition.


High throughput qualitative analysis of polyphenols in tea samples by ultra-high pressure liquid chromatography coupled to UV and mass spectrometry detectors.
The analysis of polyphenols in tea extracts is important due to their potential health benefits. Therefore, efficient and high throughput analytical methods have been developed for the separation of seven predominant polyphenols, also known as catechin derivatives, present in tea extracts. Columns packed with sub-2-μm particles operating at elevated pressure (UHPLC strategy) were selected to improve chromatographic performance. The potential of UHPLC-UV was demonstrated with baseline resolution of all standard catechins in only 30 s using a 50-mm column packed with 1.7-μm particles. When dealing with real samples such as tea extracts, however, longer columns of up to 150 mm in length were employed to enhance the separation of catechin derivatives and other constituents within the tea samples while maintaining an acceptable analysis time. Two strategies based on 2-D experiments were proposed to clearly identify catechins. Firstly, a liquid-liquid extraction procedure was added prior to the UHPLC-UV analysis to decrease the complexity of the sample. Secondly, UHPLC was coupled to ESI-MS/MS to attain sufficient sensitivity and selectivity between catechin derivatives and other constituents of tea extract. These two strategies were found extremely promising as a clear discrimination of catechins from the matrix could be attained.


A novel bit-quad-based Euler number computing algorithm.
The Euler number of a binary image is an important topological property in computer vision and pattern recognition. This paper proposes a novel bit-quad-based Euler number computing algorithm. Based on graph theory and analysis on bit-quad patterns, our algorithm only needs to count two bit-quad patterns. Moreover, by use of the information obtained during processing the previous bit-quad, the average number of pixels to be checked for processing a bit-quad is only 1.75. Experimental results demonstrated that our method outperforms significantly conventional Euler number computing algorithms.


Diet, obesity and obesogenic trends in two generations of Swedish women.
Secular trends in obesity and related lifestyle factors are reported in two generations of 38- and 50-year old Swedish women. Specifically, we describe changes in obesity and fat patterning, while examining concurrent shifts in factors that are proposed to be causally related to the modern obesity epidemic. A total of 1,270 women aged 38 or 50 were selected from population registries and examined in 1968/69 (born 1930 or 1918) or 2004/05 (born 1966 or 1954). Anthropometric methods and lifestyle questions were unchanged between earlier and later surveys. Dietary comparisons were based on 24-h recall, with additional questions about usual alcohol and salt consumption patterns. In subgroups, 24-h urinary sodium was determined. Weight, height, waist circumference, waist-hip ratio, triceps and subscapular skinfold measures were all significantly higher in later-born cohorts, although BMI and obesity were not significantly changed. Higher sodium excretion was observed among later-born sub-groups, consistent with reports of increasing salt preference. Lower proportions of energy as fat and sucrose, but higher carbohydrate, protein and fiber concentrations were reported by later-born cohorts. There were shifts towards increased frequency of wine and liquor consumption, but decreased beer. Leisure time physical activity and perceived stress levels both increased significantly over 36 years. A number of anthropometric and lifestyle differences between two generations of Swedish women were observed. Increases in subcutaneous and abdominal fatness were detected without significantly increasing BMI. While some aspects of diet showed improvement, increases in salt preference and sodium excretion are cause for concern.


Glutathione S-transferase omega 2 regulates cell growth and the expression of E-cadherin via post-transcriptional down-regulation of β-catenin in human esophageal squamous cells.
Glutathione S-transferase omega 2 (GSTO2), which belongs to the superfamily of GST omega class, lacks any appreciable GST activity. Although GSTO2 exhibits thioltransferase and glutathione dehydrogenase activities, its precise expression and physiological functions are still unclear. In the present study, we found that GSTO2 is exclusively expressed in the basal cell layer in Ki67-negative non-proliferative cells in the human esophageal mucosa. GSTO2 overexpression in esophageal squamous cell carcinoma (ESCC) cell lines inhibited cell growth and colony formation, and GSTO2-transfected cells formed smaller tumors in nude mice compared with mock-transfected cells. Interestingly, GSTO2 induction suppressed the expressions of E-cadherin and β-catenin at the cell-cell contact site. We quantified the phosphorylation levels of key proteins of MAPK signaling pathway and identified phosphorylation of p38. Additionally, HSP27, a downstream molecule of p38, was accelerated in GSTO2-transfected cells, unlike in mock-transfected cells. When GSTO2-transfected cells were treated with a p38 inhibitor, the expression of β-catenin and the membrane localization of E-cadherin was recovered. We next examined GSTO2 expression in 61 ESCC tissues using quantitative reverse transcription polymerase chain reaction and immunostaining. The results showed that GSTO2 mRNA and protein were significantly reduced in ESCC compared with normal tissues. When human ESCC cell lines were treated with 5-aza-2'-deoxycytidine, a DNA-methyltransferase inhibitor, GSTO2 transcription was induced, suggesting that aberrant hypermethylation is the cause of the down-regulated expression. Our results indicate that GSTO2 expression inhibits the membrane localization of E-cadherin, probably by modulation of the p38 signaling pathway. Down-regulation of GSTO2 by DNA hypermethylation contributes to the growth and progression of ESCC.


Correlation between serum magnesium levels and hepatic encephalopathy in immediate post liver transplantation period.
Liver transplantation is a complex procedure that interferes with multiple body functions and can cause several complications. Studies have shown varying incidences of neurological complications (8% to 47%) including encephalopathy, as well as cerebrovascular problems, infections, and neurotoxicity induced by immunosuppressive drugs. The majority of these cases occur in the first week after surgery. We sought to evaluate the correlation between serum magnesium levels and the development of encephalopathy in the immediate posttransplantation period. We collected data from patients undergoing liver transplantation, both donors and recipients, from 2007 to 2009. Magnesium levels during the first week of hospitalization were compared to reference laboratory results. The West Haven criteria were used to classify whether if the patient experienced encephalopathy. Only the level of magnesium posttransplantation represented a risk for encephalopathy (P = .049). Lower magnesium levels increased the risk of encephalopathy (relative risk = 3.718; 95% confidence interval: 1.001-13.699). We verified the importance of low levels of magnesium as a predictive factor to increase the occurrence of encephalopathy after liver transplantation.


Microbial transformations of steroids--III. Transformation of progesterone by Sepedonium ampullosporum.
The 16 alpha-steroid hydroxylating fungus Sepedonium ampullosporum (CMI strain 203 033) transformed progesterone into 16 alpha-hydroxyprogesterone and four other major metabolites which have not been reported previously for this organism, 6 beta-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, 16 alpha-hydroxyandrostenedione and 16-oxotestosterone (16-ketotestosterone). Among the minor metabolites we have been able to identify 15 alpha-hydroxyprogesterone. This compound has not been reported for S. ampullosporum. The conditions used for transformation had comparatively little effect on the relative proportions of products formed, 16 alpha-hydroxyprogesterone always being the predominant metabolite, but had a major effect on the total yields of metabolites isolatable. These findings suggest that one or more constitutive enzyme systems were responsible for the transformations.


Effect of moxonidine on blood pressure and sympathetic tone in conscious spontaneously hypertensive rats.
The effects of moxonidine on blood pressure, heart rate and sympathetic tone were studied in conscious spontaneously hypertensive rats. Intravenous moxonidine (80 nmol) transiently increased blood pressure without affecting heart rate or splanchnic nerve activity. Moxonidine (20-80 nmol) given into the fourth cerebral ventricle dose-dependently lowered mean arterial pressure, heart rate and sympathetic outflow (maximally by 60 +/- 3 mm Hg, 148 +/- 10 beats min(-1) and 15 +/- 3 microV). Moxonidine was more effective by this route than after the injection into the lateral ventricle. Clonidine (20-80 nmol) produced an initial pressor response after both intracerebroventricular routes of administration. A decrease in blood pressure was observed only when clonidine was given into the fourth ventricle. Clonidine decreased heart rate and splanchnic nerve activity similarly like moxonidine when the substances were given into the fourth ventricle. The data imply that the hypotensive effect of moxonidine is related to central sympathoinhibition. The main site of this action appears to be in the brainstem region.


Prochlorococcus have low global mutation rate and small effective population size.
Prochlorococcus are the most abundant free-living photosynthetic carbon-fixing organisms in the ocean. Prochlorococcus show small genome sizes, low genomic G+C content, reduced DNA repair gene pool and fast evolutionary rates, which are typical features of endosymbiotic bacteria. Nevertheless, their evolutionary mechanisms are believed to be different. Evolution of endosymbiotic bacteria is dominated by genetic drift owing to repeated population bottlenecks, whereas Prochlorococcus are postulated to have extremely large effective population sizes (Ne) and thus drift has rarely been considered. However, accurately extrapolating Ne requires measuring an unbiased global mutation rate through mutation accumulation, which is challenging for Prochlorococcus. Here, we managed this experiment over 1,065 days using Prochlorococcus marinus AS9601, sequenced genomes of 141 mutant lines and determined its mutation rate to be 3.50 × 10-10 per site per generation. Extrapolating Ne additionally requires identifying population boundaries, which we defined using PopCOGenT and over 400 genomes related to AS9601. Accordingly, we calculated its Ne to be 1.68 × 107, which is only reasonably greater than that of endosymbiotic bacteria but surprisingly smaller than that of many free-living bacteria extrapolated using the same approach. Our results therefore suggest that genetic drift is a key driver of Prochlorococcus evolution.


High-speed identification system for fresh tea leaves based on phenotypic characteristics utilizing an improved genetic algorithm.
High-quality tea requires leaves of similar size and tenderness. The grade of the fresh leaves determines the quality of the tea. The automated classification of fresh tea leaves improves resource utilization and reduces manual picking costs. The present study proposes a method based on an improved genetic algorithm for identifying fresh tea leaves in high-speed parabolic motion using the phenotypic characteristics of the leaves. During parabolic flight, light is transmitted through the tea leaves, and six types of fresh tea leaves can be quickly identified by a camera. The influence of combinations of morphology, color, and custom corner-point morphological features on the classification results were investigated, and the necessary dimensionality of the model was tested. After feature selection and combination, the classification performance of the Naive Bayes, k-nearest neighbor, and support vector machine algorithms were compared. The recognition time of Naive Bayes was the shortest, whereas the accuracy of support vector machine had the best classification accuracy at approximately 97%. The support vector machine algorithm with only three feature dimensions (equivalent diameter, circularity, and skeleton endpoints) can meet production requirements with an accuracy rate reaching 92.5%. The proposed algorithm was tested by using the Swedish leaf and Flavia data sets, on which it achieved accuracies of 99.57% and 99.44%, respectively, demonstrating the flexibility and efficiency of the recognition scheme detailed in the present study. This research provides an efficient tea leaves recognition system that can be applied to production lines to reduce manual picking costs. © 2022 Society of Chemical Industry.


Shear-horizontal waves in a rotated Y-cut quartz plate in contact with a viscous fluid.
We study shear-horizontal (SH) waves in a crystal plate of rotated Y-cut quartz in contact with a semi-infinite viscous fluid. The crystal plate and the fluid are governed by the equations of anisotropic elasticity and the theory of Newtonian fluids. A transcendental equation that determines the dispersion relations of the waves is obtained. Approximate analytical solutions to the equation are presented for the case of low viscosity fluids and the case of long waves whose wavelength is much larger than the plate thickness. The effects of the fluid viscosity and density on the dispersion relations of the waves are examined. The results obtained are fundamental and useful to the understanding and design of acoustic wave fluid sensors for measuring fluid viscosity or density.


Cationic core-shell nanoparticles with carmustine contained within O⁶-benzylguanine shell for glioma therapy.
The application of carmustine (BCNU) for glioma treatment is limited due to its poor selectivity for tumor and tumor resistance caused by O⁶-methylguanine-DNA-methyl transferase (MGMT). To improve the efficacy of BCNU, we constructed chitosan surface-modified poly (lactide-co-glycolides) nanoparticles (PLGA/CS NPs) for targeting glioma, loading BCNU along with O⁶-benzylguanine (BG), which could directly deplete MGMT. With core-shell structure, PLGA/CS NPs in the diameter around 177 nm showed positive zeta potential. In vitro plasma stability of BCNU in NPs was improved compared with free BCNU. The cellular uptake of NPs increased with surface modification of CS and decreasing particle size. The cytotoxicity of BCNU against glioblastoma cells was enhanced after being encapsulated into NPs; furthermore, with the co-encapsulation of BCNU and BG into NPs, BCNU + BG PLGA/CS NPs showed the strongest inhibiting ability. Compared to free drugs, PLGA/CS NPs could prolong circulation time and enhance accumulation in tumor and brain. Among all treatment groups, F98 glioma-bearing rats treated with BCNU + BG PLGA/CS NPs showed the longest survival time and the smallest tumor size. The studies suggested that the co-encapsulation of BCNU and BG into PLGA/CS NPs could remarkably enhance the efficacy of BCNU, accompanied with greater convenience for therapy.


Chronic mercury at low doses impairs white adipose tissue plasticity.
The toxic effects of mercury (Hg) are involved in homeostasis of energy systems such as lipid and glucose metabolism, and white adipose tissue dysfunction is considered as a central mechanism leading to metabolic disorders. The aim of this study was to determine the effects of chronic inorganic Hg exposure at low doses on the lipid and glycemic metabolism. Male Wistar rats were divided into two groups and treated for 60 days with: saline solution, i.m. (Untreated) and mercury chloride, i.m. - 1st dose 4.6 μg/kg, subsequent doses 0.07 μg/kg/day - (Mercury). Histological analyses, Hg levels measurement and GRP78, CHOP, PPARα, PPARγ, leptin, adiponectin and CD11 mRNA expressions were performed in epididymal white adipose tissue (eWAT). Glucose, triglycerides, total cholesterol and insulin plasma levels were also measured. Hg exposure reduced the absolute and relative eWAT weights, adipocyte size, plasma insulin levels, glucose tolerance, antioxidant defenses and increased plasma glucose and triglyceride levels. In addition, CHOP, GRP78, PPARα, PPARγ, leptin and adiponectin mRNA expressions were increased in Hg-treated animals. No differences in Hg concentration were found in eWAT between the untreated and Hg groups. These results suggest that the reduction in adipocyte size is related to the impaired antioxidant defenses, endoplasmic reticulum (ER) stress, the disrupted PPARs and adipokines mRNA expression induced by the metal in eWAT. These disturbances possibly induced a decrease in circulating insulin levels, an imbalance between lipolysis and lipogenesis mechanisms in eWAT, with an increase in fatty acids mobilization, a reduction in glucose uptake and an activation of pro-apoptotic pathways, leading to hyperglycemia and hyperlipidemia. Hg is a powerful environmental WAT disruptor that influences signaling events and impairs metabolic activity and hormonal balance of adipocytes.


Functional characterization of the human dopamine D4.2 receptor using vaccinia virus as an expression system.
Recombinant vaccinia viruses harboring the human dopamine D4 receptor cDNA containing two 48 base pair-repeats (D4.2) or the rat dopamine D2 short (D2s) receptor cDNA were used to infect rat-1 fibroblasts. Heterologous expression of both dopamine receptors was demonstrated in binding assays. The affinity constants of these receptors were consistent with values previously reported, including D4.2's higher affinity for the antipsychotic clozapine and raclopride's selectivity for D2 receptors. In the presence of 200 microM 5'-guanylyl-imidodiphosphate (Gpp[NH]p) both receptors exhibited reduced affinities for dopamine. Furthermore, when rat-1 cells were infected with the D2s or the D4.2 recombinant vaccinia viruses and exposed to dopamine agonists, the inhibition of adenylyl cyclase activity was prevented in pertussis toxin-treated cells. This study demonstrates the utility of recombinant receptor-vaccinia viruses in studies of expression, pharmacology and functional coupling of inhibitory G protein-coupled receptors.


Immune checkpoint inhibitor-related adverse cardiac events in patients with lung cancer: a systematic review and meta-analysis.
Although people are more and more aware of the cardiotoxicity caused by immune checkpoint inhibitors (ICIs) in the treatment of lung cancer, its incidence rate has not been systematically analyzed. This study aims to evaluate the incidence of cardiotoxicity related to the ICI therapies for lung cancer, so as to enhance clinicians' attention to cardiotoxicity, implement proper prevention and intervention for high-risk patients, and minimize the risk of cardiac dysfunction during and after completion of therapy. We conducted a systematic literature search for relevant publications in PubMed and Scopus from inception to 19 April 2022. Pooled incidence and risk ratios with 95% confidence intervals (95% CIs) for cardiotoxicity events were calculated. A total of 37 studies covering 38 trials, including 14,342 patients, were identified. The pooled risk ratios of incidence of any cardiac AEs were 1.944 [95% CI 0.8-4.725] (Single ICI versus chemotherapy), 1.677 [95% CI 1.065-2.64] (Single ICI plus chemotherapy versus chemotherapy), and 0.478 [95% CI 0.127-1.798] (Single ICI versus Dual ICI). The incidence of myocarditis and arrhythmia were 0.003[95%CI 0.002-0.006] and 0.014[95%CI 0-0.037], respectively. Single ICI did not increase the risk of cardiotoxicity compared with chemotherapy, and single ICI plus chemotherapy increased the risk of cardiotoxicity by 67% compared with chemotherapy alone. Combination immunotherapy did not increase the risk of cardiotoxicity compared with single ICI.


Relationships between the physiological characteristics and pathogenicity of Nocardia brasiliensis.
The analysis of 19 physiological properties of 28 strains of Nocardia brasiliensis isolated from soil reveal differences which could be of great value in distinguishing pathogenic from nonpathogenic strains.


Organic zinc and manganese and 25-hydroxycholecalciferol improves eggshell thickness in late-phase laying hens.
The aim of this study was to evaluate the effects of organic micromineral zinc (Zn) and manganese (Mn) and 25-hydroxycholecalciferol supplementation in late-phase laying hens' diets on performance, egg quality, lipid stability of fresh and stored eggs, and bone quality. The treatments were a basal diet and diets supplemented with 32 mg Zn-Met/kg diet; 26 mg Mn-Met/kg diet; 32 mg Zn-Met/kg diet and 26 mg Mn-Met/kg diet; 1500 IU 25-hydroxycholecalciferol/kg diet; 32 mg Zn-Met/kg diet; 26 mg Mn-Met/kg diet; and 1500 IU 25-hydroxycholecalciferol/kg diet. On performance, the birds supplemented with organic manganese had the lowest feed intake. Regarding egg quality, the birds supplemented with Zn-Met and Mn-Met, with 25-hydroxycholecalciferol alone, and with Zn-Met, Mn-Met and 25-hydroxycholecalciferol presented a greater eggshell thickness than those receiving the basal diet. Lipid stability of the yolk varied only according to storage time. No effect of supplementation was observed on bone quality. Supplementation with Zn-Met and Mn-Met, or associated with 25-hydroxycholecalciferol, or 25-hydroxycholecalciferol alone, improved eggshell thickness in aged white layers. However, the associated or isolated supplementation with these nutrients did not influence performance, lipid stability of fresh and stored egg yolk or bone quality.


Plant Genome Evolution: Meat Lovers Expanded Gene Families for Carnivory and Dropped the Rest.
Every textbook says that land plants are primary producers and, as such, are eaten. A couple of plants, however, refuse to stay within the boundaries of their trophic level - the carnivorous plants. Now, a new genomic study pinpoints the genetic chassis that underpins carnivory in Venus flytrap, waterwheel plant, and sundew.


In vivo tumor transfection mediated by polyplexes based on biodegradable poly(DMAEA)-phosphazene.
In recent years, increasing interest is being paid to the design of transfectants based on non-toxic and biodegradable polymers for gene therapy purposes. We recently reported on a novel, biodegradable polymer, poly(2-dimethylamino ethylamino)phosphazene (p(DMAEA)-ppz) for use in non-viral gene delivery. In this study, the biodistribution and in vivo transfection efficiency of polyplexes composed of plasmid DNA and p(DMAEA)-ppz were investigated after intravenous administration in tumor bearing mice. Data were compared with those of polyplexes based on the non-biodegradable polyethylenimine (PEI 22kDa). Both polyplex systems were rapidly cleared from the circulation (<7% ID, at 60 min after administration) and showed considerable disposition in the liver and the lung, all in line with earlier work on cationic polyplex systems. The lung disposition is attributed to aggregates formed by interaction of the polyplexes with blood constituents. Redistribution of the polyplexes from the lung was observed for both polyplex formulations. Importantly, both polyplex systems showed a substantial tumor accumulation of 5% and 8% ID/g for p(DMAEA)-ppz and PEI22 polyplexes, respectively, at 240 min after administration. The tumor disposition of the p(DMAEA)-ppz and PEI22 polyplexes was associated with considerable expression levels of the reporter gene. In contrast to PEI22 polyplexes, p(DMAEA)-ppz polyplexes did not display substantial gene expression in the lung or other organs (organ gene expression<1/100 of tumor gene expression). The observed preferential tumor gene expression mediated by the p(DMAEA)-ppz polyplexes enables the application of this polymer to deliver therapeutic genes to tumors.


Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide.
While lenalidomide (LEN) shows high efficacy in myelodysplastic syndromes (MDS) with del[5q], responses can be also seen in patients presenting without del[5q]. We hypothesized that improved detection of chromosomal abnormalities with new karyotyping tools may better predict response to LEN. We have studied clinical, molecular and cytogenetic features of 42 patients with MDS, myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes and secondary acute myeloid leukemia (sAML) without del[5q] by metaphase cytogenetics (MC) who underwent therapy with LEN. Fluorescence in situ hybridization (FISH) or single nucleotide polymorphism array (SNP-A)-based karyotyping marginally increased the diagnostic yield over MC, detecting 2/42 (4.8%) additional cases with del[5q], one of whom were responded to LEN. Responses were more often observed in patients with a normal karyotype by MC (60% vs abnormal MC; 17%, p = .08) and those with gain of chromosome 8 material by either of all 3 karyotyping methods (83% vs all other chromosomal abnormalities; 44% p = .11). However, 5 out of those 6 patients received combined LEN/AZA therapy and it may also suggest those with gain of chromosome 8 material respond well to AZA. The addition of FISH or SNP-A did not improve the predictive value of normal cytogenetics by MC. Mutational analysis of TET2, UTX, CBL, EZH2, ASXL1, TP53, RAS, IDH1/2, and DNMT-3A was performed on 21 of 41 patients, and revealed 13 mutations in 11 patients, but did not show any molecular markers of responsiveness to LEN. Normal karyotype and gain of chromosome 8 material was predictive of response to LEN in non-del[5q] patients with myeloid malignancies.


Out on the farm with DNA vaccines.
DNA vaccination is a rapidly developing technology that offers new approaches for the prevention of disease. This technology may permit the production of new vaccines against diseases that have no current vaccine, as well as allowing the development of improved vaccines to replace existing products. We describe how DNA vaccination is being developed for use in commercial animal production, with an emphasis on viral diseases, and discuss the existing hurdles to its development and use.


The energy budget of two sympatric Daphnia species in Lake Constance: productivity and energy residence times.
Two Daphnia species, D. hyalina and D. galeata, are living in Lake Constance. Both populations show logistic growth, with the phase of exponential increase in May and the phase of steady state during the summer. In spring, food is not limited and both daphnids reveal an 'exploitative' strategy: females mature early, primiparae are small, egg weights are small, but clutch sizes are large. From June on, when food limiting conditions prevail, D. hyalina starts to migrate vertically with a diurnal rhythm whereas D. galeata keeps on living in the epilimnion over the whole season. The differing thermal environments of the populations lead to short generation times (age of first reproduction) of 11 days for D. galeata in mid-summer, and to 47 days (July) for D. hyalina. The annual production (P) of D. hyalina and D. galeata were 18 and 24 g DW/m2, respectively. The average standing stocks (B) were 1.6 and 0.9 g DW/m2. This corresponds to turnover rates of 11 x and 27 x per season (200 days), and to turnover times of 18 days and 7.5 days, respectively. From 1980 to 1982 the cumulative annual primary production (PPR) varied between 260 and 330 g C/m2. The common productivity (P) of the functional component 'Daphnia' (=sum of both Daphnia species) followed the PPR, but the Daphnia stading stock was constant at 2.5 g DW/m2. The increase of secondary production (P) was a consequence of a shift in abundance between the two Daphnia species: at low PPR, D. hyalina was 4 x more abundant, but at high PPR, the two species were equally abundant. Such internal regulatory mechanism within a system component is in accordance with the hypothesis of Cheslak and Lamarra (1981): increase of 'energy residence time' (B/R) with declining nutrients and increasing strength of competitive interrelationships within a given functional component of an ecosystem.


Narrowing the Relationship between Human CCR5 Gene Polymorphisms and Chagas Disease: Systematic Review and Meta-Analysis.
Our aim was to carry out a qualitative and quantitative synthesis of the influence of CCR5 genetic variants on Chagas disease (CD) through a systematic review. A total of 1197 articles were analyzed, and eleven were included in the review. A meta-analysis was conducted along with principal component analyses (PCAs). The polymorphisms found were analyzed using the SNP2TFBS tool to identify possible variants that influence the interaction with gene binding sites. Eleven studied variants were identified: rs2856758, rs2734648, rs1799987, rs1799988, rs41469351, rs1800023, rs1800024, Δ32/rs333, rs3176763, rs3087253 and rs11575815. The studies analyzed were published between 2001 and 2019, conducted in Argentina, Brazil, Spain, Colombia and Venezuela, and included Argentine, Brazilian, Colombian, Peruvian and Venezuelan patients. Eight polymorphisms were subjected to the meta-analysis, of which six were associated with the development of the cardiac form of CD: rs1799987-G/G and G/A in the dominance model and G/G in the recessiveness model; rs2856758-A/G in the codominance model; rs2734648-T/T and T/G in the dominance model; rs1799988-T/T in both the codominance and recessiveness models; rs1800023-G allele and the G/G genotype in the codominance and recessiveness models, and the G/G and G/A genotypes in the dominance model; and rs1800024-T allele. The PCA analyses were able to indicate the relationships between the alleles and the genotypes of the polymorphisms. The SNP2TFBS tool identified rs1800023 as an influencer of the Spi1 transcription factor (p < 0.05). A correlation was established between the alleles associated with the cardiac form of CD in this review, members of the C haplotype of the gene (HHC-TGTG), and the cardiac form of CD.


Predictors of severe sepsis not clinically apparent during the first twenty-four hours of hospitalization in children with cancer, neutropenia, and fever: a prospective, multicenter trial.
Severe sepsis is not clinically apparent during the first 24 hours of hospitalization in most children with cancer and febrile neutropenia (FN), delaying targeted interventions that could impact mortality. The aim of this study was to prospectively evaluate biomarkers obtained within 24 hours of hospitalization as predictors of severe sepsis before it becomes clinically evident. Children with cancer, admitted with FN at high risk for an invasive bacterial infection in 6 public hospitals in Santiago, Chile, were monitored throughout their clinical course for occurrence of severe sepsis. Clinical, demographic and 6 biomarkers [eg, blood urea nitrogen, serum glucose, lactic dehydrogenase, serum C-reactive protein (CRP), interleukin (IL)-8, and procalcitonin] were obtained at the time of admission and after 24 hours. Biomarkers independently associated with severe sepsis diagnosed after the first 24 hours of hospitalization were identified by logistic regression analysis. A total of 601 high risk FN episodes were enrolled between June 2004 and October 2006; 151 (25%) developed severe sepsis of which 116 (77%) were not clinically apparent during the first 24 hours of hospitalization. Risk factors for severe sepsis were age > or =12 years [odds ratio (OR): 3.85; 95% confidence interval (CI): 2.41-6.15], admission CRP > or =90 mg/L (OR: 2.03; 95% CI: 1.32-3.14), admission IL-8 > or =200 pg/mL (OR: 2.39; 95% CI: 1.51-3.78), 24-hour CRP > or =100 mg/L (OR: 3.06; 95% CI: 1.94-4.85), and 24-hour IL-8 > or =300 pg/mL (OR: 3.13; 95% CI 1.92-5.08). Age > or =12 years and admission or 24-hour values of CRP > or =90/100 mg/L and IL-8 > or =200/300 pg/mL are predictors of sepsis not clinically apparent during the first 24 hours of hospitalization.


Extremely low frequency electromagnetic field sensitizes cisplatin-resistant human ovarian adenocarcinoma cells via P53 activation.
In the following study, extremely low frequency electromagnetic fields (EL-EMF) radiation was used to restore sensitivity in the cisplatin-resistant A2780 ovarian cancer cells. For this purpose A2780 cells were treated with different doses of cisplatin and EL-EMF (50 Hz, 200 gauss, and 2 h) alone. Cytotoxicity was the measurement using MTT assay. After calculating IC50 for cisplatin (90 µg/ml) a lower concentration from IC50 (30 and 60 µg/ml) was used to be combined with EL-EMF. We compare the effects of each cisplatin, EL-EMF and combination groups using acridine orange-propidium iodide (AO/PI) and DAPI staining, caspase 3/9 activation assay and Annexin/PI assay. We also assessed changes in P53 and Matrix metalloproteinases 2 (MMPs) gene expression with semi-quantitative RT-PCR. Results indicated an EL-EMF-dependent proliferative decrease which was found <10 %, and occurred independently of cisplatin. The decreased proliferation rate for 30 and 60 µg/ml cisplatin was about 20 and 40 %, respectively, while for synergistic groups 30 and 60 µg/ml cisplatin with 2 h EL-EMF exposer, showed 47 and 71 % decrease in viability in rats. DAPI staining indicated that chromatin break down significantly increased in synergistic groups. Acridine orange staining also confirmed MTT assay results. Caspase activity significantly increased in the combined groups. Semi-quantitative RT-PCR showed that in synergistic groups of cisplatin and EL-EMF, expression of P53 was increased but the expression level of MPP-2 gene decreased. Results from this study showed that changes generated by the non-invasive EL-EMF can make resistant cells sensitive to cisplatin.


[Content and transportation of Ca(2+) to hepatocytes and lipid content of liver cell membrane structure in experimental diabetes in the rat].
It is proved that at experimental diabetes the calcium content in hepatocytes is disturbed. This disorder is mostly shown in increase of calcium content in hepatocytes and in decrease of accumulation of these ions in mitochondrias. One of the possible reasons of changes at this pathology is the change of lipid content of hepatocytes, mitochondrias and microsomes. It is proved that the in vitro model systems Ca ions inhibits the synthesis of 25-hydroxyvitamin D3 by hepatocytes.


The effect of deglycosylated human chorionic gonadotropin on corpora luteal function in healthy women.
Fourteen healthy young women were studied through a control and a treatment menstrual cycle in two series of experiments. In the first series, they were given one of four doses of deglycosylated human chorionic gonadotropin (hCG) as a 24-hour infusion during the mid-luteal phase of the cycle. In these studies, there were no significant alterations of the length of the luteal phase of the treatment cycle, and there was no decrease in serum progesterone (P) during the infusion. In fact, serum P increased during the infusion. In the second series of studies, five subjects were given a 48-hour infusion of normal saline during the control cycle, and a 48-hour infusion of deglycosylated alpha-intact beta-hCG during the treatment cycle, both being administered during the mid-luteal phase. Treatment did not alter luteal phase duration and, again, increased serum P. It is concluded that deglycosylated preparations of hCG are not clinically useful as luteinizing hormone antagonists, probably because of residual agonist activity.


Comparison of effects of OSA treatment by MAD and by CPAP on cardiac autonomic function during daytime.
The present study compared the effects of mandibular advancement therapy (MAD) with continuous positive airway pressure therapy (CPAP) on daytime cardiac autonomic modulation in a wide range of obstructive sleep apnea (OSA) patients under controlled conditions in a randomized, two-period crossover trial. Forty OSA patients underwent treatment with MAD and with CPAP for 12 weeks each. At baseline and after each treatment period, patients were assessed by polysomnography as well as by a daytime cardiac autonomic function test that measured heart rate variability (HRV), continuous blood pressure (BP), and baroreceptor sensitivity (BRS) under conditions of spontaneous breathing, with breathing at 6, 12, and 15/min. Both CPAP and MAD therapy substantially eliminated apneas and hypopneas. CPAP had a greater effect. During daytime with all four conditions of controlled breathing, three-minute mean values of continuous diastolic BP were significantly reduced for both MAD and CPAP therapy. At the same time, selective increases due to therapy with MAD were found for HRV high frequency (HF) values. No changes were observed for BRS in either therapy mode. These findings indicate that both MAD and CPAP result in similar beneficial changes in cardiac autonomic function during daytime, especially in blood pressure. CPAP is more effective than MAD in eliminating respiratory events.


Assessment of suitable cultivation region for Pepino (Solanum muricatum) under different climatic conditions using the MaxEnt model and adaptability in the Qinghai-Tibet plateau.
Pepino (Solanum muricatum), a member of the Solanaceae family originating from South America, is cultivated globally. However, the cultivation range and suitable habitat of Pepino have not been extensively studied, which hampers the further development of its cultivation industry. Therefore, we aimed at enrich and expand the planting scope of Pepino. Currently, the main cultivation areas of Pepino in China are the Yunnan-Guizhou Plateau and the Loess Plateau, where the altitude is above 1000 m. In this study, ArcGIS combined with the MaxEnt model was used for prediction, whose area under curve value was 0.949. The main climatic factors affecting the distribution of Pepino are temperature seasonality, annual means temperature, mean temperature of the coldest quarter, elevation, isothermality, and the climate factors, and their cumulative contribution rate of 87.6%. Pepino's main potential distribution areas are located in Yunnan-Guizhou Plateau, Yunnan Province, Hexi Corridor of Loess Plateau, and low altitude areas of Qinghai-Tibet Plateau. The main distribution ranges from 1000 to 2000 m above sea level, and the total suitable area accounts for 20.09% of China's total land area. The prediction results reveal an expanded potential area for Pepino, with no significant migration in the central region of the main potential distribution area by 2050 and 2070. No studies have been conducted on the open-area cultivation of Pepino in northern China. Our findings revealed that the yield and quality in the four experimental sites and final actual cultivation conditions were consistent with the predicted results of MaxEnt. The yiel d per plant in Xunhua and Minhe was significantly different from that in Xining, which was low, and that in Minhe was the highest. Overall, the fruit quality in the Xining region was the lowest among the three regions, which was related to the climatic differences in each region. These results align with the predicted outcomes, indicating that Xining is the least suitable area. Further, these data verify the accuracy of the prediction results. The climate data of the four regions were analyzed simultaneously to elucidate the influence of different climate conditions on the growth of Pepino. Our findings are of considerable significance for introducing characteristic horticultural crops in the Qinghai-Tibet Plateau and using the MaxEnt model to predict the cultivation range of crops.


Molecular Morphology and Function of Stromal Cells.
The term "stromal cells" refers to a highly heterogeneous class of connective tissue cells that build the infrastructure of any organ and fulfill a variety of fundamental roles in health and disease [...].


Synthesis and structure-activity relationships of imidazo[1,2-a]pyrimidin-5(1H)-ones as a novel series of beta isoform selective phosphatidylinositol 3-kinase inhibitors.
A series of PI3K-beta selective inhibitors, imidazo[1,2-a]-pyrimidin-5(1H)-ones, has been rationally designed based on the docking model of the more potent R enantiomer of TGX-221, identified by a chiral separation, in a PI3K-beta homology model. Synthesis and SAR of this novel chemotype are described. Several compounds in the series demonstrated potent growth inhibition in a PTEN-deficient breast cancer cell line MDA-MB-468 under anchorage independent conditions.


[Is surgery likely to be successful as a treatment for traumatic lesions of the superficial radial nerve?].
In the last 10 years 22 patients with lesions of the superficial branch of the radial nerve have been treated surgically in our neurosurgical department. The patients' main complaints were burning pain and paraesthesia in the region supplied by the superficial branch of the radial nerve. In most cases the lesion was due to tendolysis performed earlier to treat de Quervain tendovaginitis stenosans. In 8 cases external neurolysis was done with conservation of continuity; in 4 cases the nerve was reconstructed after resection of the neuroma (end-to-end-suture or implantation of a vicryl conduit); and in 10 cases the neuroma was resected and transposition of the proximal nerve end was performed. Nineteen patients were available for evaluation of the postoperative results, after an average follow-up of 51 months. Surprisingly, only 5 reported good subjective improvement of pain after surgery. Seven patients reported an unchanged status postoperatively, and in 1 case the pain was even worse after the surgical intervention. Satisfactory results (complete or partial pain relief in 75% of cases) was found to have been achieved in the subgroup of patients treated by resection of the neuroma of the superficial branch of the radial nerve and transposition of the nerve stump. In conclusion, we recommend caution when surgical interventions are considered for traumatic lesions of the superficial radial nerve, because the prospects of success are limited. In addition, we do not consider nerve reconstruction desirable in these circumstances.


Eukaryotic transcription factors.
Recently determined high-resolution structures of eukaryotic transcription factors have illuminated the enzymatic mechanism underlying transcription. Progress has been made in characterising protein-protein interactions between negative cofactors and general transcription factors, and between transrepression domains and corepressors. Structures of sequence-specific transcription factors have revealed further versatility in the mode of interaction with DNA and several have provided new insights into the molecular basis of human disease.


[Vertebro-basilar dissecting aneurysm : an anatomo-clinical case study fibrodysplasia of the left vertebral artery (author's transl)].
A new anatomo-clinical case of vertebro-basilar dissecting aneurysm in a 43 year old woman is reported. The originality of this study comes from the autopsic discovery of an intimal fibro-dysplasia at the origin of the dissection in the left vertebral artery. The authors also included anatomoclinical and pathogenic comments about both the lesions discussed.


Preparation of a polypyrrole-polyvinylsulphonate composite film biosensor for determination of phenol based on entrapment of polyphenol oxidase.
Abstract: In this paper, a novel amperometric phenol biosensor with immobilization of polyphenol oxidase (tyrosinase) on electrochemically polymerized polypyrrole-polyvinylsulphonate (PPy-PVS) film has been accomplished via the entrapment technique on the surface of a platinum electrode. The amperometric determination is based on the electrochemical reduction of quinon generated in the enzymatic reaction of phenol. The effects of pH and temperature were investigated and optimum parameters were found to be 8.0 and 30 °C, respectively. The linear working range of the electrode was 1.0 × 10(-7) - 5.0 × 10(-6) M. The storage stability and operation stability of the enzyme electrode were also studied.


Associations Between Autism Spectrum Quotient and Integration of Visual Stimuli in 9-year-old Children: Preliminary Evidence of Sex Differences.
The dorsal stream vulnerability hypothesis posits that the dorsal stream, responsible for visual motion and visuo-motor processing, may be particularly vulnerable during neurodevelopment. Consistent with this, autism spectrum disorder (ASD) has been associated with deficits in global motion integration, though deficits in ventral stream tasks, such as form identification, have also been reported. In the current study, we examined whether a similar pattern of results is found in a cohort of 381 children born with neurodevelopmental risk factors and exhibiting a wide spectrum of caregiver-reported autistic traits. We examined the associations between global motion perception, global form perception, fine motor function, visual-motor integration, and autistic traits (autism spectrum quotient, AQ) using linear regression, accounting for possible interactions with sex and other factors relevant to neurodevelopment. All assessments of dorsal stream function were significantly associated with AQ such that worse performance predicted higher AQ scores. We also observed a significant sex interaction, with worse global form perception associated with higher AQ in boys (n = 202) but not girls (n = 179). We found widespread associations between dorsal stream functions and autistic traits. These associations were observed in a large group of children with a range of AQ scores, demonstrating a range of visual function across the full spectrum of autistic traits. In addition, ventral function was associated with AQ in boys but not girls. Sex differences in the associations between visual processing and neurodevelopment should be considered in the designs of future studies.


Clinical significance and pathogenesis of viral respiratory infections.
Viral respiratory tract infections, also known as colds, are the most common infection in humans. The majority of these infections are caused by rhinoviruses. Rhinovirus deposition in the nose or the eye initiates infection. The virus attaches to the host cell intercellular adhesion molecule-1 (ICAM-1) receptors in the back of the throat. Subsequent viral replication triggers the release of inflammatory mediators and activation of neurogenic pathways, which lead to symptoms. Symptoms occur within 10 to 16 hours after virus entry into the nose and peak on days 2 to 3 of infection. Symptom duration is typically 1 week, although 25% of cases last longer. Understanding the chronology of these events is important in the timing of treatment. Because of the rapidity of symptom onset, early treatment is the key to reducing viral replication and illness. Also, early treatment may reduce the risk of transmission.


Cost-effectiveness of osteoporosis interventions for 'incidental' vertebral fractures.
Vertebral fractures detected "incidentally" by chest radiograph usually do not trigger osteoporosis treatment in older patients. In a 3-arm controlled trial we reported that both physician-directed and enhanced (physician plus patient activation) interventions increased treatment rates more than 10-fold (15%-20% absolute increases) compared with usual care; the cost-effectiveness of these interventions is unknown. Incremental cost-effectiveness of these 2 interventions compared with usual care was assessed using a Markov decision-analytic model, populated with 1-year outcomes data and direct intervention costs from the trial. Costs were expressed in 2009 Canadian dollars and effectiveness based on quality-adjusted life years (QALYs) gained. The perspective was health care payer; horizon was projected lifetime; costs and benefits were discounted at 3%; and deterministic and probabilistic sensitivity analyses were conducted. Per patient, the physician and enhanced interventions cost $34 and $42, respectively. Compared with usual care, for every 1000 patients exposed to the physican intervention there were 4 fewer fractures, 8 more QALYs gained, and $282,000 saved. Compared with physician interventions, for every 1000 patients exposed to enhanced interventions there were 6 fewer fractures, 6 more QALYs gained, and $339,000 saved. Both interventions dominated usual care and were cost-effective in ~80% of 10,000 probabilistic simulations. Although the enhanced intervention cost $8 more per patient, it still dominated the physician intervention and usual care, and was the most economically attractive option. Pragmatic and inexpensive interventions directed at patients with incidentally detected vertebral fractures and their physicians are highly cost-effective at improving osteoporosis treatment, and in most circumstances also are cost-saving.


The association between suicidality and treatment with selective serotonin reuptake inhibitors in older people with major depression: a systematic review.
Suicide among the elderly is an emerging public health issue. In Australia, suicide is a leading cause of death, most notably amongst elderly men over the age of 75. Depression is one of the main causes of suicide in older people. Selective serotonin reuptake inhibitors are considered to be a safe pharmacological therapy in the management of depression in adults. The risk of suicidality/suicide associated with the use of antidepressants in older people is unclear. The objective of this review was to determine the association between treatment with selective serotonin reuptake inhibitors and suicidality/suicide in older people who suffer from major depression. Consideration was given to studies that included older people aged 60 years and over, regardless of gender or ethnic background, with Diagnostic and Statistical Manual of Mental Disorders Fourth Edition or equivalent diagnostic criteria for Major Depressive Disorder without psychotic features. Types of intervention(s)/phenomena of interest: The review considered treatments using any selective serotonin reuptake inhibitors medication. Comparators included placebo or a different class of antidepressants including monoamine oxidase inhibitors or tricyclic antidepressants. Types of studies: This review considered both experimental and observational study designs including randomized controlled trials, non-randomized controlled trials, prospective and retrospective cohort studies and case control studies. Types of outcomes: The primary outcome measures of interest in this systematic review were worsening or emergent suicidal ideation, attempted suicide and completed suicide. For this systematic review, the term 'suicide attempt' referred to potentially self-injurious behavior with a non-fatal outcome. A three-step search strategy was employed that aimed to locate both published and unpublished studies in the English language. An initial search in PubMed was followed by a second search using all identified keywords and index terms across multiple databases and grey literature sites. Finally, the reference list of all identified reports and articles were searched for additional studies. METHODOLOGICAL QUALITYÂ : Critical appraisal was undertaken by two independent reviewers using the standard critical appraisal instrument from the Joanna Briggs Institute Mata-Analysis of Statistical Assessment and Review Instrument. The McMaster Quality Assessment Scale for Harms was used to analyse reporting quality on suicide related harm. The primary data on the number of emergent or worsening of suicidal ideation, attempted suicide and completed suicides, in both arms of randomized controlled trials and observational studies was extracted using the standardized data extraction tool from the Joanna Briggs Institute Mata-Analysis of Statistical Assessment and Review Instrument. Baseline demographic data on each study was collected for presentation in tabular format. The data from randomized controlled trials and observational studies was pooled separately in statistical meta-analysis using RevMan V 5.1 software (The Cochrane Collaboration). Population demographic and other study characteristics were presented in tables and as a narrative summary. Following critical appraisal, eight randomized controlled trials and five observational studies (i.e. population cohort and retrospective case control studies) with data on suicide-related events were included in the systematic review. Based on the data on TRUNCATED AT 500 WORDS.


Sleep in children with autism spectrum disorders.
The amount of research conducted on sleep in children and adolescents has increased dramatically over the past decade due to the recognition that many children have significant sleep problems leading to daytime dysfunction. Approximately one third of typically developing children have sleep difficulties at some point, and a similar percentage of adolescents have impaired or insufficient sleep leading to daytime impairments. Sleep problems are known to occur at even greater rates in children with special needs, such as those with developmental disabilities, psychiatric conditions, and medical illnesses. The recognition that interventions can improve sleep and may result in better daytime functioning has fueled a growing interest in more fully characterizing the sleep problems in children with special needs. This article presents a discussion of the sleep problems experienced by children with one particular group of developmental disorders--the autism spectrum disorders.


Utility of NucleoCounter for the chondrocyte count in the collagenase digest of human native cartilage.
In cartilage tissue engineering, viable cell numbers should be correctly counted in the collagenase digest of the biopsied cartilage. However, this is a difficult task due to the presence of matrix debris, cell ghosts and their aggregates. To search for the correct cell counting method in this situation, we evaluated the utility of an automatic cell counting device, the NucleoCounter, and compared it with conventional staining using the LIVE/DEAD® kit. We first measured the cell numbers of a standard chondrocyte sample by the NucleoCounter, which showed a high accuracy (R(2) = 0.9999) and reproducibility (%CV: 2.00-8.66). We then calculated the cell numbers and viability in some collagenase digests of native cartilage using either the NucleoCounter or LIVE/DEAD® kit, revealing that the total cell numbers, viable ones and viability were highly correlated between them (R(2) = 0.9601, 0.9638 and 0.917, respectively). However, both the intrapersonal and interpersonal variabilities in the NucleoCounter was significantly decreased to about 1/20-1/5, compared to that of the LIVE/DEAD® kit. The NucleoCounter was regarded as a useful tool for simple, rapid, and highly reproducible cell counts, which may not only provide constant experimental data in a certain laboratory, but also contribute to the high reproducibility of the clinical results of cartilage tissue engineering among multiple institutions.


Potential patient screening for late-onset Pompe disease in suspected sleep apnea: a rationale and study design for a Prospective Multicenter Observational Cohort Study in Japan (PSSAP-J Study).
Pompe disease is an autosomal recessive disorder caused by deficiency of the acid α-glucosidase (GAA) enzyme. GAA deficiency induces progressive glycogen accumulation which leads to weakness of the respiratory muscle including the diaphragm. Pompe disease is one of the few myopathies, for which an established therapy is available. Thus, earlier detection of potential late-onset Pompe disease (LOPD) and earlier intervention would have a significant clinical impact. Our hypothesis is that sleep problems including sleep disordered breathing (SDB) and clinical symptoms may indicate an early stage of LOPD since decreased respiratory muscle activity generally first presents during sleep. Thus, the aims of this prospective, multicenter observational cohort study in Japan (PSSAP-J) are to demonstrate a higher prevalence of LOPD in a sleep lab-based population (primary outcome), and to identify predictive factors for LOPD from findings in diagnostic polysomnography (PSG) and clinical symptoms (secondary outcomes). The study design is a prospective multicenter observational cohort study. Consecutive patients who present to sleep labs due to suspected SDB for an overnight PSG will be enrolled. All patients will be measured for creatine kinase, GAA activity, and if necessary, genetic analysis of GAA. Furthermore, chest X-ray, pulmonary function test, and arterial blood gas analysis will be collected. Then, prevalence and specific findings of LOPD will be assessed. Congenital myopathy shows a shift from slow-deep to rapid-shallow breathing during transition from wakefulness to sleep accompanying a symptom of waking with gasping (actual further results are pending). The distribution in respiratory physiology between during wakefulness and sleep specific to LOPD may provide insights into early-stage detection. UMIN000039191, UMIN Clinical Trials Registry ( http://www.umin.ac.jp/ctr ).


Mutagenic effect of orally given AF-2 on embryonic cells in pregnant Syrian hamsters.
Pregnant hamsters were given various doses of AF-2 by stomach tube; then the cells of their embryos were isolated and cultured in normal medium. Chromosome preparations were made within 24 h after the start of primary culture, and examined for chromosomal aberrations. Marked chromosomal abnormalities were observed in cells of embryos of animals treated with AF-2 at over 20 mg/kg. Samples of surviving cells were also cultured in normal medium for 48 h, and then selected in medium containing 8AG or 6TG. This treatment with AF-2 caused marked dose-dependent induction of 8AG- or 6TG-resistant mutations: mutant colonies were even obtained after a single treatment with 2 mg of AF-2 per kg. These results show that this is a sensitive and useful mammalian system for detecting environmental mutagens.


A stochastic modelling approach to determine the effect of diverse Staphylococcus aureus strains on the economic and epidemiological outcomes of mastitis intervention strategies in dairy cattle.
Staphylococcus aureus (S. aureus) strains with considerable genetic and phenotypic differences have previously been identified. The economic and epidemiologic impact of S. aureus mastitis has been investigated, but none of these studies took differences between strains into account. Here we aimed to investigate how differences between S. aureus strains affect the economic and epidemiologic outcome of various intervention strategies against clinical and subclinical intramammary infections. Five S. aureus strains were modelled using a stochastic bio-economic model simulating a dairy herd of 200 cows using single-day time steps. The strain characteristics of the five simulated S. aureus strains (general, contagious, spill-over, clinical and persistent) were based on divergent phenotypes as described in literature. Outcomes of the model included incidence (both clinical and subclinical), number of antibiotic treatment days, number of culled cows, and net income. Intervention strategies against clinical and subclinical intramammary infections were based on (variations of) intramammary antibiotic treatment, testing, and culling. Both single and multiple pathogen (intramammary infection caused by S. aureus, Escherichia coli, and non-aureus staphylococci) scenarios were simulated to determine the effect of the five S. aureus strains on the impact of 19 different intervention strategies. The results showed that the incidence (both clinical and subclinical), number of treatment days, number of culled cows, and net income varied considerably for the different S. aureus strains. Comparison of the model outcomes within and between strains showed that for most intervention strategies the relative impact differed per strain. However, the intervention strategy with the best outcome for most variables and strains was the culling of cows with a recovery probability lower than 50%. This shows that the relative economic and epidemiologic impact of most of the modelled intervention strategies were strain-dependent, while some intervention strategies were not strain-dependent. From this, we conclude that, depending on the intervention strategy applied on a farm, it could be advantageous to type S. aureus to determine whether it would be economically and epidemiologically beneficial for the existing intervention strategy to be changed.


Development and validation of delirium prediction model for critically ill adults parameterized to ICU admission acuity.
Risk prediction models allow clinicians to forecast which individuals are at a higher risk for developing a particular outcome. We developed and internally validated a delirium prediction model for incident delirium parameterized to patient ICU admission acuity. This retrospective, observational, fourteen medical-surgical ICU cohort study evaluated consecutive delirium-free adults surviving hospital stay with ICU length of stay (LOS) greater than or equal to 24 hours with both an admission APACHE II score and an admission type (e.g., elective post-surgery, emergency post-surgery, non-surgical) in whom delirium was assessed using the Intensive Care Delirium Screening Checklist (ICDSC). Risk factors included in the model were readily available in electric medical records. Least absolute shrinkage and selection operator logistic (LASSO) regression was used for model development. Discrimination was determined using area under the receiver operating characteristic curve (AUC). Internal validation was performed by cross-validation. Predictive performance was determined using measures of accuracy and clinical utility was assessed by decision-curve analysis. A total of 8,878 patients were included. Delirium incidence was 49.9% (n = 4,431). The delirium prediction model was parameterized to seven patient cohorts, admission type (3 cohorts) or mean quartile APACHE II score (4 cohorts). All parameterized cohort models were well calibrated. The AUC ranged from 0.67 to 0.78 (95% confidence intervals [CI] ranged from 0.63 to 0.79). Model accuracy varied across admission types; sensitivity ranged from 53.2% to 63.9% while specificity ranged from 69.0% to 74.6%. Across mean quartile APACHE II scores, sensitivity ranged from 58.2% to 59.7% while specificity ranged from 70.1% to 73.6%. The clinical utility of the parameterized cohort prediction model to predict and prevent incident delirium was greater than preventing incident delirium by treating all or none of the patients. Our results support external validation of a prediction model parameterized to patient ICU admission acuity to predict a patients' risk for ICU delirium. Classification of patients' risk for ICU delirium by admission acuity may allow for efficient initiation of prevention measures based on individual risk profiles.


Long-term outcomes of intraoperative 5-fluorouracil versus intraoperative mitomycin C in primary trabeculectomy surgery.
To compare the long-term efficacy of intraoperative 5-fluorouracil (5-FU) and mitomycin C (MMC) in primary trabeculectomy. Comparative case series and extension of a prospective, randomized controlled trial. One hundred fifteen eyes of 103 subjects undergoing primary trabeculectomy with either intraoperative 5-FU or MMC. This study is an extension of a 12-month, prospective, double-masked, randomized trial that previously was reported. Subjects were randomized to receive either intraoperative 5-FU (50 mg/ml for 5 minutes) or MMC (0.2 mg/ml for 2 minutes) during primary trabeculectomy. Follow-up data were collected from patient medical records after informed consent was obtained from the study patient. Attempts were made to contact subjects who had been lost to follow-up, and some consented to reexamination. The primary measure was Kaplan-Meier survival function, with failure defined as intraocular pressure (IOP) of more than 21 mmHg or less than 6 mmHg on 2 consecutive visits, less than 20% reduction from baseline IOP, loss of light perception vision, or additional glaucoma surgery to lower IOP (except bleb revision). Secondary measures included IOP, number of glaucoma medications, visual acuity, additional surgeries, and number and type of complications. Mean follow up was 53.4+/-31.4 months (interquartile range, 34-82 months) in the 5-FU group and 45.3+/-28.0 months (interquartile range, 19-70 months) in the MMC group (P = 0.15, t test). Kaplan-Meier success was 0.83 at 3 years and 0.76 at 5 years in the 5-FU group and 0.79 at 3 years and 0.66 at 5 years in the MMC group (P = 0.18, log-rank test). Bleb leakage was the most common complication in each group and developed in approximately 4% of subjects in each group per year (P = 0.33, log-rank test). There were no significant differences between topical 5-FU and topical MMC in reducing IOP of eyes undergoing primary trabeculectomy. Both antifibrosis agents may contribute to the development of bleb leakage. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Neuromuscular Electrical Stimulation for Venous Thromboembolism Prophylaxis and Its Effects on Somatosensory-Evoked Potentials: A Pretrial Study of a New, U.S. Food and Drug Administration-Approved Device.
Neuromuscular electrical stimulation (NMES) has emerged as a viable alternative for venous thromboembolism prophylaxis. Electrical stimulation of the peroneal nerve using NMES may potentially interfere with somatosensory-evoked potential (SSEP) acquisition. This feasibility study evaluates a NMES device and its effect on SSEP acquisition as an initial step in a randomized clinical trial to assess NMES for intraoperative venous thromboembolism prophylaxis. Healthy volunteers underwent SSEP testing during NMES in an outpatient setting. Concurrently, SSEP recordings of the posterior tibial nerve with stimulation at each ankle were obtained in 3 conditions: sham, NMES in place but inactive; ipsi, NMES active on leg ipsilateral to SSEP acquisition; and contra, NMES active on the leg contralateral to SSEP acquisition. Nonparametric statistical methods, including repeated measures, were used for data analysis. Stimulation intensities on the left, right, and bilaterally did not differ (P ≥ 0.20). Strong positive correlations were noted between the ipsilateral geko stimulus pulse width and ipsilateral SSEP stimulation intensities (left: rs = 0.866, P = 0.001; right: rs = 0.877, P = 0.001). Women required significantly greater pulse width settings than men (P = 0.01). Finally, visual inspection of waveforms, as used during dynamic IONM, did not show any significant variations of P37 cortical waveforms during NMES. As a preliminary step to testing NMES intraoperatively for venous thromboembolism prophylaxis, interference with SSEP acquisition was investigated in the outpatient laboratory setting. Within a small sample of healthy volunteers, no significant changes were seen in P37 cortical latencies to suggest interference between the NMES device and SSEP waveforms.


The effects of cardiovascular risk factor combined anti-platelet therapy and the risk of cerebrovascular events in patients with T2DM in an urban community over 96-months follow-up: The Beijing communities diabetes study 19.
We investigated the prognostic significance of metabolic risk scores and aspirin with respect to cerebrovascular events. A total of 25 communities of diabetic patients were enrolled in Beijing Community Diabetes Study (BCDS) from 2008. 3413 patients with T2DM in BCDS have complete screening data, including blood glucose, blood pressure, lipid profiles and anti-platelet therapy, which were assigned metabolic score (MS) and add up to the total metabolic score (TMS). According to the total metabolic score (TMS), the patients were divided into four equal groups: Group 1 (24 < TMS < 40), Group 2 (40 < TMS < 47), Group 3 (47 < TMS < 55) and Group 4 (55 < TMS < 87). After 96 months, patients were followed-up to assess the long-term effects of the multifactorial interventions. During 96-months follow-up, a total of 91 cerebrovascular events occurred, including acute cerebral infarction, acute cerebral hemorrhage and transient ischemic attack (TIA). The incidence of cerebrovascular events was higher in the Group 4 than in the Group 1. In Cox multivariate analyses, there are significant differences in incidences of cerebral infarction events among the four groups during the 96-months follow-up. Cox proportional hazards analysis revealed that, HbA1c (p ≤ 0.001), systolic pressure (p ≤ 0.001), aspirin free treatment (P = 0.0023) are independent predictor for cerebrovascular events in diabetic patients. This study indicates that total metabolic score (TMS) influences the incidence of cerebrovascular events in diabetic patients. In addition to good control of blood glucose, blood pressure and lipid profiles, anti-platelet therapy is important for the prevention of cerebrovascular events in T2DM. ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.


Factors affecting the onset of deoxyribonucleic acid synthesis during wheat embryo germination. Study of the changes in DNA polymerases A, B and C and the pool of DNA precursors.
DNA synthesis starts about 12 h after water imbibition in wheat embryos. We have determined that noticeable amounts of labelled thymidine are found inside the embryo only after 6 hr of germination. DNA polymerase C from ungerminated wheat embryos decreased markedly in activity during the first hours of germination, whereas the activities of DNA polymerases A and B increased, having a maximum at about 15 h or germination. Serological evidence has suggested a clear antigenic relationship between DNA polymerases A and C. Although the pool of ATP increases rapidly after water imbibition, the increase in the pool of dNTP species was much slower.


Breaking the vicious circle of fear and avoidance in children with abdominal pain: A mediation analysis.
Exposure-based cognitive behavioral therapy via internet (Internet-CBT) has been shown to reduce symptoms and increase quality of life for children with functional abdominal pain disorders (FAPDs), but the mechanisms of change are unknown. The objective was to examine whether a change in symptom-specific fear and avoidance, i.e., gastrointestinal-specific anxiety (GI-anxiety) and gastrointestinal-specific avoidance (GI-avoidance), mediated changes in parent-reported abdominal symptoms for children receiving Internet-CBT compared with children receiving treatment as usual. A further aim was to assess if baseline levels of the proposed mediators moderated the mediation. Weekly assessments of child-reported mediators and parent-reported outcome from 90 children aged 8-12 who were included in a randomized controlled trial were used in univariate and multivariate growth models to test the direct effect of treatment on outcome and the indirect effects via mediators and moderated mediation. Treatment condition significantly predicted the slope of the mediators (a-path), in favor of Internet-CBT, and mediators were correlated with the outcome (b-path). The indirect effects of the mediators on the outcome (cross-product of the a and b-paths) were significantly different from zero for both GI-avoidance, ab = 1.43, 95%CI [0.42, 3.23]; and GI-anxiety ab = 1.58, 95%CI [0.43, 3.62]. Baseline levels of the proposed mediators moderated the size of the mediation. GI-anxiety and GI-avoidance were mediators of change in Internet-CBT and high levels of the mediators at baseline were associated with larger mediated effects. Healthcare professionals should be aware of, and inform families about, the potential benefits of reducing symptom-specific fear and avoidance.


The synthesis and reactivity of a molybdenum (IV) stretched-dihydrogen complex.
Reaction of [Mo(NPh)(PMe3)3(o-(Me3SiN)2C6H4)] (1) with molecular hydrogen (ca. 1 atm) at -10 degrees C in toluene-d8 results in the formation of dihydrogen complex [Mo(NPh)(PMe3)2(H2)(o-(Me3SiN)2C6H4)] (2) by 1H and 31P NMR spectroscopy. In solution at -50 degrees C 1 and 2 are present in a 1:3 ratio, respectively. The nature of dihydrogen ligand bonding in 2 was probed by T1 analysis and analysis of the JH-D coupling constant in the deuterium hydride isotopomer of 2 giving H-H distances of 1.18 A and 1.17 A, respectively. When allowed to warm to 30 degrees C, 2 reacts affording [Mo(NPh)(PMe3)3(o-(Me3SiN)(NH)C6H4)] (3) over a 1 h period. The X-ray structures of 1 and 3 are reported.


Comparison of heart rate and cardiac output of VVI pacemaker settings in patients with atrial fibrillation with bradycardia.
While most VVI pacemakers in bradycardic patients are set to a low limit of 60/min, the optimal lower limit rate for VVI pacemakers in atrial fibrillation has not been established. Although an increase in heart rate within the normal range in the setting of a VVI pacemaker might be expected to lead to an increase in cardiac output with the shortening of the diastolic time, the changes in cardiac output at different pacemaker settings have not been fully clarified. We included 11 patients with bradycardic atrial fibrillation who had VVI pacemakers implanted. Stroke volume was measured using the electrical cardiometry method (AESCULONⓇ mini; Osypka Medical) without pacing and at ventricular pacings of 60, 70, 80, and 90/min. Stroke volume decreased stepwise at ventricular pacing rates of 60, 70, 80, and 90/min (63.6 ± 11.2, 61.9 ± 10.6, 59.3 ± 12.2, and 57.5 ± 12.2 mL, p < .001), but cardiac output increased (3.81 ± 0.67, 4.33 ± 0.74, 4.74 ± 0.97, and 5.17 ± 1.09 L/min, p < .001). The rate of increase in cardiac output at a pacing rate of 70/min compared to 60/min correlated with left ventricular end-systolic volume (r = 0.711, p = .014). Cardiac output increased at a pacing rate of 70 compared to 60 in bradycardic atrial fibrillation patients, and the rate of increase in cardiac output was greater in those with larger left ventricular end-systolic volume.