Maize glutathione-dependent formaldehyde dehydrogenase cDNA: a novel plant gene of detoxification.
We have previously shown that intact plants and cultured plant cells can metabolize and detoxify formaldehyde through the action of a glutathione-dependent formaldehyde dehydrogenase (FDH), followed by C-1 metabolism of the initial metabolite (formic acid). The cloning and heterologous expression of a cDNA for the glutathione-dependent formaldehyde dehydrogenase from Zea mays L. is now described. The functional expression of the maize cDNA in Escherichia coli proved that the cloned enzyme catalyses the NAD(+)- and glutathione (GSH)-dependent oxidation of formaldehyde. The deduced amino acid sequence of 41 kDa was on average 65% identical with class III alcohol dehydrogenase from animals and less than 60% identical with conventional plant alcohol dehydrogenases (ADH) utilizing ethanol. Genomic analysis suggested the existence of a single gene for this cDNA. Phylogenetic analysis supports the convergent evolution of ethanol-consuming ADHs in animals and plants from formaldehyde-detoxifying ancestors. The high structural conservation of present-day glutathione-dependent FDH in microorganisms, plants and animals is consistent with a universal importance of these detoxifying enzymes.


Influence of endoscopists' expertise level on clinical outcomes after bridge-to-surgery stenting in obstructive colorectal cancer.
This study aimed to investigate the effect of stenting-related factors, including endoscopists' expertise, on clinical outcomes after bridge-to-surgery (BTS) stenting for obstructive colorectal cancer (CRC). We analyzed BTS stenting-related factors, including stenting expertise and the interval between stenting and surgery, in 233 patients (63 [13] years, 137 male) who underwent BTS stenting for obstructive CRC. We evaluated the influence of these factors on post-BTS stenting clinical outcomes such as stent-related complications and cancer recurrence. The interval between stenting and surgery was ≤ 7 days in 79 patients (33.9%) and > 7 days in 154 patients (66.1%). BTS stenting was performed by endoscopists with ≤ 50, 51-100, and > 100 prior stenting experiences in 94, 43, and, 96 patients, respectively. The clinical success rate of BTS stenting was 93.1%. Stent-related and postoperative complications developed in 19 (8.2%) and 20 (8.6%) patients, respectively. Cancer recurrence occurred in 76 patients (32.6%). Short BTS interval of ≤ 7 days increased the risk of postoperative complications (odds ratio [OR], 2.61 [1.03-6.75]; P = 0.043). Endoscopists' stenting experience > 100 showed greater clinical success of stenting (OR, 5.50 [1.45-28.39]; P = 0.021) and fewer stent-related complications (OR, 0.26 [0.07-0.80]; P = 0.028) compared with stenting experience ≤ 50. BTS stenting-related factors did not affect long-term oncological outcomes. Greater expertise of endoscopists was associated with better short-term outcomes, including high stenting success rate and low rate of stent-related complications after BTS stenting for obstructive CRC. An interval of > 7 days between BTS stenting and surgery was required to decrease postoperative complications.


Observations on the male nucleus during fertilization in the fern Pteridium aquilinum.
Fertilization of eggs of Pteridium under controlled conditions has revealed that archegonia containing viable eggs require more than 30 min flooding before opening. Syngamy appears to take place by an engulfing action, and no evidence was found of a 'membrane-fusion' kind of conjugation. Although the gametic nucleus lacks a recognizable envelope, as soon as it comes into contact with the female cytoplasm an envelope is reconstituted from an opaque layer at the surface of its chromatin. This membrane also undergoes growth, the outer layer extending into the cytoplasm and surrounding spermatozoid mitochondria. The male envelope remains distinct from the female, and lacks evaginations and well defined pores. The male nucleus lies in irregular loops within a funnel, filled with egg cytoplasm, formed by the microtubular ribbon of the gamete. The mouth of the funnel is bordered by the multi-layered structure. Karyogamy is initiated at the anterior end of the male nucleus, the orifice connecting the 2 nuclei widening from about 0-1 to 2 mum in diameter during fusion. The contents of the male nucleus flow through the mouth of the funnel into the female, the chromatin relaxing locally, but retaining a rod-like form. The envelope of the male nucleus is probably resorbed at the site of junction. There is no evidence that it contributes significantly to the envelope of the zygotic nucleus.


Effect of combined actions of hip adduction/abduction on the force generation and maintenance of pelvic floor muscles in healthy women.
Pelvic floor muscle (PFM) force and coordination are related to urinary incontinence severity and to sexual satisfaction. Health professionals frequently combine classic PFM exercises with hip adduction/abduction contraction to treat these disorders, but the real benefits of this practice are still unknown. Based on a theoretical anatomy approach whereby the levator ani muscle is inserted into the obturator internus myofascia and in which force generated by hip movements should increase the contraction quality of PFMs, our aim was to investigate the effects of isometric hip adduction and abduction on PFM force generation. Twenty healthy, nulliparous women were evaluated using two strain-gauge dynamometers (one cylinder-like inside the vaginal cavity, and the other measuring hip adduction/abduction forces around both thighs) while performing three different tasks: (a) isolated PFM contraction; (b) PFM contraction combined with hip adduction (30% and 50% maximum hip force); and (c) PFM contraction combined with hip abduction (30% and 50% maximum hip force). Data were sampled at 100Hz and subtracted from the offset if existent. We calculated a gradient between the isolated PFM contraction and each hip condition (Δ Adduction and Δ Abduction) for all variables: Maximum force (N), instant of maximum-force occurrence (s), mean force in an 8-second window (N), and PFM force loss (N.s). We compared both conditions gradients in 30% and 50% by paired t-tests. All variables did not differ between hip conditions both in 30% and 50% of maximum hip force (p>.05). PFM contraction combined with isometric hip abduction did not increase vaginal force in healthy and nulliparous women compared to PFM contraction combined with isometric hip adduction. Therefore, so far, the use of hip adduction or abduction in PFM training and treatments are not justified for improving PFM strength and endurance.


Comparison of once- with twice-daily dosing of fluticasone propionate in mild and moderate asthma.
Two 12-week, randomized, double-blind, parallel-group studies were performed to compare the efficacy and safety of once- and twice-daily dosing of fluticasone propionate (FP) in the treatment of mild to moderate asthma, considered to require the equivalent of either 200 or 500 microg of FP daily. In study A, 461 patients with asthma received FP either 200 microg once daily or 100 microg twice daily. In study B, 443 patients with asthma received FP, either 500 microg once daily or 250 microg twice daily. In both studies, regardless of the treatment regimen to which patients were randomly assigned, small improvements over baseline were observed in morning peak expiratory flows (PEF) and forced expiratory volume in 1 s (FEV1) following 12 weeks of treatment. In study A, the mean morning PEF improved by 2.4% and 4.3% (once daily versus twice daily, P=0.008). In study B, the mean morning PEF improvement was 0.2% and 3.7% (once daily versus twice daily, P<0.001). For both studies, the increases observed in FEV1 were not significantly different between the two groups (P = not significant). The incidence of exacerbations of asthma and related events was 13% and 5%, respectively, in the patients with mild asthma for the once-daily group versus the twice-daily group; these exacerbations were 12% and 10%, respectively, in patients with moderate asthma. Otherwise, the incidence and types of adverse events were comparable for the two treatment regimens. Although twice-daily dosing demonstrated small but statistically significant improvements over once-daily dosing, patients of both groups generally maintained a good level of asthma control on both regimens according to current treatment guidelines. Twice-daily dosing of FP is more effective than once-daily dosing, although the latter can maintain asthma control in most patients.


Rates of pinocytic capture of simple proteins by rat yolk sacs incubated in vitro.
The rates of pinocytic uptake of a number of small 125I-labelled simple proteins (insulin, ribonuclease A and lysozyme) by rat yolk sacs incubated in vitro were determined both before and after treating these proteins with reagents that are known to increase the rate of capture of 125I-labelled bovine serum albumin. Uptake of the untreated forms of all three proteins was extremely rapid, indicating that adsorptive pinocytosis is the principal mechanism by which yolk-sac cells capture these simple proteins, but these rates show no simple correlation with molecular charge. In contrast with albumin, the rates of uptake of treated proteins were either unchanged or lower than that of the corresponding untreated protein preparations; polymeric forms of 125I-labelled lysozyme larger than dimers were ingested at rates significantly lower than that of the monomer.


Cognitive deficits and altered functional brain network organization in pediatric brain tumor patients.
Survivors of pediatric brain tumors experience significant cognitive deficits from their diagnosis and treatment. The exact mechanisms of cognitive injury are poorly understood, and validated predictors of long-term cognitive outcome are lacking. Resting state functional magnetic resonance imaging allows for the study of the spontaneous fluctuations in bulk neural activity, providing insight into brain organization and function. Here, we evaluated cognitive performance and functional network architecture in pediatric brain tumor patients. Forty-nine patients (7-18 years old) with a primary brain tumor diagnosis underwent resting state imaging during regularly scheduled clinical visits. All patients were tested with a battery of cognitive assessments. Extant data from 139 typically developing children were used as controls. We found that obtaining high-quality imaging data during routine clinical scanning was feasible. Functional network organization was significantly altered in patients, with the largest disruptions observed in patients who received propofol sedation. Awake patients demonstrated significant decreases in association network segregation compared to controls. Interestingly, there was no difference in the segregation of sensorimotor networks. With a median follow-up of 3.1 years, patients demonstrated cognitive deficits in multiple domains of executive function. Finally, there was a weak correlation between decreased default mode network segregation and poor picture vocabulary score. Future work with longer follow-up, longitudinal analyses, and a larger cohort will provide further insight into this potential predictor.


It's a MALDI but it's a goodie: MALDI-TOF mass spectrometry for microbial identification.
The last few years have witnessed a revolution in the diagnostic microbiology laboratory with the emergence of matrix assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) as an indispensible tool in microbial identification. In many laboratories this has superseded biochemical profiling. A mass spectrum is acquired from an unknown micro-organism and this proteomic fingerprint is then compared with a database of reference spectra to ascertain the likely genus and species identity. The reproducibility of this method is facilitated by the analysis of continually produced, highly abundant proteins (mainly ribosomal proteins) in the mass range 2000 to 20 000 Da. MALDI-TOF MS is reliable and rapid and has the ability to determine the identity of an isolate from culture in a matter of minutes rather than the hours or days required by more traditional methods. In addition to microbial identification of cultured isolates, work is underway to extend the utility of MALDI-TOF MS to include bacterial identification directly from clinical samples as well as providing timely information regarding antibiotic resistance and typing of different micro-organisms.


Knowledge, attitude and practice towards antenatal physical exercise among pregnant women in Ethiopia: A systematic review and meta-analysis.
Physical activity and exercise during pregnancy have paramount importance for both the mother and fetus. Regardless of the benefits of exercise during pregnancy, significant proportion of women usually opt sedentary lifestyle during pregnancy. The aim of this systematic review and meta-analysis is to synthesis evidences on knowledge, attitude, and practice towards antenatal physical exercise among pregnant women in Ethiopia. The systematic review and meta-analysis was conducted on knowledge, attitude, practice, and associated factors towards antenatal physical exercise among pregnant women in Ethiopia. The systematic review and meta-analysis protocol was registered on PROSPERO website with registration number CRD42023444723. Articles were searched on international databases using medical subject heading and keywords. After ensuring eligibility, data were extracted using Microsoft excel and imported to STATA 17 for analysis. Cochran Q test and I2 statistics were used to check presence of heterogeneity. Weighted Inverse variance random effect model was used to estimate the pooled level of knowledge, attitude, and practice on antenatal physical exercise among pregnant women in Ethiopia. Funnel plot and egger's test were used to check presence of publication bias. A total of 11 studies were included in this systematic review and meta-analysis. The pooled prevalence of adequate knowledge, favorable attitude and good practice towards antenatal physical exercise were 46.04% with 95% CI (44.45%-47.63%), 43.71%, 95% CI (41.95%-45.46%) and 34.06, 95% CI (20.04%-48.08%) respectively. Good knowledge AOR 2.38 95% CI(1.80-3.14), unfavorable attitude AOR 0.43 95% CI (0.32-0.58), having no pre-pregnancy habit of physical exercise AOR 0.44 95 CI (0.24-0.79) and having diploma or above education status AOR 3.39 95% CI (1.92-5.98) were significantly associated with practice of antenatal physical exercise. The level of knowledge, attitude and practice towards antenatal physical exercise among pregnant women was far below the recommended level in Ethiopia. Knowledge, attitude, education status and pre-pregnancy habit of physical exercise were significantly associated factors with antenatal physical exercise practice. It is highly essential to disseminate health information on the benefits of antenatal physical exercise for all pregnant women during antenatal care contacts.


Local Ties, Trans-Local Ties, and Substance Use among Rural-to-Urban Migrants in China.
China has witnessed unprecedented rural-to-urban migration since the early 1980s. While trying to assimilate into the city, rural-to-urban migrants still maintain close ties with their home communities. This study examines how local ties and trans-local ties of rural-to-urban migrants affect their alcohol and tobacco use. Data were obtained from the 2016 and 2018 China Labor-force Dynamics Survey, a nationally representative sample of adults aged over 15 in 29 provinces in China. Participants included 1426 rural-to-urban migrant workers and 6438 urban residents in China. We found that compared to urban natives, rural-to-urban migrants had higher tobacco use prevalence (logit = 0.19, 95% CI = [0.03, 0.35]; p < 0.05) and more frequent alcohol use (logit = 0.27, 95% CI = [0.11, 0.42]; p < 0.001) after adjusting for sociodemographic characteristics. Migrants with more local social ties engaged in more frequent drinking (having >10 local friends vs. having 0 local friends: logit = 0.58, [0.10, 1.06], p < 0.05), whereas trans-local ties were not a significant correlate. In contrast, migrants who returned to their hometown more times (an indicator of trans-local ties) were more likely to be current tobacco users (logit = 0.01, 95% CI = [0.00, 0.02], p < 0.01) after adjusting for sociodemographic variables. These findings extended the research on social networks and health behaviors by identifying how local and trans-local ties differentially affected the vulnerabilities of tobacco and alcohol use among rural-to-urban migrants in China. The findings suggested that policies and interventions on reducing migrants' health risk behaviors should focus on the role of different types of social ties.


Antidepressant use in patients with meningioma: is there an association with tumor recurrence?
OBJECTIVE With increasing general use of antidepressants (ADs), multiple studies have noted a small protective effect of ADs for patients with glioma, but their impact on meningioma has not been established. This study aims to evaluate the role of ADs in the context of additional clinical factors in relation to long-term risk of meningioma recurrence. METHODS One hundred five patients with an intracranial meningioma presenting from 2011-2014 with at least 3 years of follow-up (median 4.2 years) after resection were reviewed. AD use along with demographics, tumor characteristics, and outcomes were recorded. Multivariate logistic regression was used to analyze the association of AD use with tumor recurrence, including other clinical measures significantly associated with recurrence as covariates. RESULTS Twenty-nine patients (27.4%) were taking ADs (27 selective serotonin reuptake inhibitors, 2 norepinephrine-dopamine reuptake inhibitors) prior to tumor recurrence. Their tumors largely affected the frontal (31.0%) or parietal lobe (17.2%) and were located in convexity, parasagittal, or falcine (CPF) areas more frequently than skull base areas relative to the tumors of non-AD users (p = 0.035). AD use was found to be an independent predictor of recurrence, in addition to subtotal resection and WHO grade II/III classification (p values < 0.05). The median time from AD prescription to tumor recurrence was 36.6 months (interquartile range [IQR] = 20.9-62.9 months) and median length of AD use was 41.4 months (IQR = 24.7-62.8 months). CONCLUSIONS AD use was an independent predictor of meningioma recurrence. This association may be due to mood or affective changes caused by tumor location in CPF regions that may be a sign of early recurrence. The finding calls attention to AD use in the management of patients with meningioma, and warrants further exploration of an underlying relationship.


Pharmacological Potential of Betulin as a Multitarget Compound.
Betulin is a natural triterpene, usually from birch bark, known for its potential wound-healing properties. Despite having a wide range of pharmacological targets, no studies have proposed betulin as a multitarget compound. Betulin has protective effects against cardiovascular and liver diseases, cancer, diabetes, oxidative stress, and inflammation. It reduces postprandial hyperglycemia by inhibiting α-amylase and α-glucosidase activity, combats tumor cells by inducing apoptosis and inhibiting metastatic proteins, and modulates chronic inflammation by blocking the expression of proinflammatory cytokines via modulation of the NFκB and MAPKs pathways. Given its potential to influence diverse biological networks with high target specificity, it can be hypothesized that betulin may eventually become a new lead for drug development because it can modify a variety of pharmacological targets. The summarized research revealed that the diverse beneficial effects of betulin in various diseases can be attributed, at least in part, to its multitarget anti-inflammatory activity. This review focuses on the natural sources, pharmacokinetics, pharmacological activity of betulin, and the multi-target effects of betulin on signaling pathways such as MAPK, NF-κB, and Nrf2, which are important regulators of the response to oxidative stress and inflammation in the body.


Meat and dairy consumption and subsequent risk of prostate cancer in a US cohort study.
To evaluate the association of meat and dairy food consumption with subsequent risk of prostate cancer. In 1989, 3,892 men 35+ years old, who participated in CLUE II study of Washington County, MD, completed an abbreviated Block food frequency questionnaire. Intake of meat and dairy related foods was calculated using consumption frequency and portion size. Incident prostate cancer cases (n = 199) were ascertained through October 2004. Cox proportional hazards regression was used to calculate hazard ratios (HR) of total and advanced (SEER states three and four; n = 54) prostate cancer and 95% confidence intervals (CI) adjusted for age, BMI at age 21, and intake of energy, saturated fat, and tomato products. Intakes of total mean (HR = 0.90, 95% CI 0.60-1.33, comparing highest to lowest tertile) and red meat (HR = 0.87, 95% CI 0.59-1.32) were not statistically significantly associated with prostate cancer. However, processed meat consumption was associated with a non-statistically significant higher risk of total (5+ vs. < or =1 servings/week: HR = 2.24; 95% CI 0.90-5.59) prostate cancer. There was no association across tertiles of dairy or calcium with total prostate cancer, although compared tp < or =1 servings/week consumption of 5+ servings/week of dairy foods was associated with an increased risk of prostate cancer (HR = 1.65, 98% CI 1.02-2.66). Overall, consumption of processed meat, but not total meat or red meat, was associated with a possible increased risk of total prostate cancer in this prospective study. Higher intake of dairy foods but not calcium was positively associated with prostate cancer. Further investigation into the mechanisms by which processed meat and dairy consumption might increase the risk of prostate cancer is suggested.


[The receptor theory of atherosclerosis].
Lipopolysaccharides of Gram-negative bacteria can interact with Toll-like receptor 4 (TLR4) and induce atheroma formation. The risk of atherosclerosis is decreased in case of TLR4 mutation. Other bacterial ligands and endogenous ligands of TLRs can also be involved in induction of atherogenesis. The general concept of atherosclerosis pathogentsis is presented. According to this concept atherogenesis can be initiated by some reactions resulting from interaction of exogenous and endogenous microbial ligands with Toll-like receptors.


Shoot, shovel and shut up: cryptic poaching slows restoration of a large carnivore in Europe.
Poaching is a widespread and well-appreciated problem for the conservation of many threatened species. Because poaching is illegal, there is strong incentive for poachers to conceal their activities, and consequently, little data on the effects of poaching on population dynamics are available. Quantifying poaching mortality should be a required knowledge when developing conservation plans for endangered species but is hampered by methodological challenges. We show that rigorous estimates of the effects of poaching relative to other sources of mortality can be obtained with a hierarchical state-space model combined with multiple sources of data. Using the Scandinavian wolf (Canis lupus) population as an illustrative example, we show that poaching accounted for approximately half of total mortality and more than two-thirds of total poaching remained undetected by conventional methods, a source of mortality we term as 'cryptic poaching'. Our simulations suggest that without poaching during the past decade, the population would have been almost four times as large in 2009. Such a severe impact of poaching on population recovery may be widespread among large carnivores. We believe that conservation strategies for large carnivores considering only observed data may not be adequate and should be revised by including and quantifying cryptic poaching.


[The genetics and selection of microorganisms].
Results of investigations in genetics and selection of bacteria, streptomycetes and fungi obtained at the Department of Genetics of Microorganisms for the recent 35 years are presented in the review.


Slr1293 in Synechocystis sp. strain PCC 6803 Is the C-3',4' desaturase (CrtD) involved in myxoxanthophyll biosynthesis.
When grown at high light intensity, more than a quarter of the total carotenoids in the unicellular cyanobacterium Synechocystis consists of myxoxanthophyll, a polar carotenoid glycoside. The biosynthetic pathway of myxoxanthophyll is unknown but is presumed to involve a number of enzymes, including a C-3',4' desaturase required to add one double bond to generate 11 conjugated double bonds in the monocyclic myxoxanthophyll. A candidate for this desaturase is Slr1293, which was identified by genome similarity searching. To determine whether Slr1293 is a desaturase recognizing neurosporene and lycopene, slr1293 was expressed in Escherichia coli strains accumulating neurosporene or lycopene. Confirming such a desaturase function for Slr1293, these E. coli strains accumulated 3',4'-didehydroneurosporene and 3',4'-didehydrolycopene, respectively. Indeed, deletion of slr1293 in Synechocystis provides further evidence that Slr1293 is a desaturase recognizing neurosporene: In the slr1293 deletion mutant, neurosporene was found to accumulate and was further processed to produce neurosporene glycoside. Neurosporene hereby becomes a primary candidate to be the branch point molecule between carotene and myxoxanthophyll biosynthesis in this cyanobacterium. The slr1293 gene was concluded to encode a C-3',4' desaturase that is essential for myxoxanthophyll biosynthesis, and thus it was designated as crtD. Furthermore, as Slr1293 appears to recognize neurosporene and to catalyze the first committed step on the myxoxanthophyll biosynthesis pathway, Slr1293 plays a pivotal role in directing a portion of the precursor pool for carotenoid biosynthesis toward myxoxanthophyll biosynthesis in Synechocystis sp. strain PCC 6803.


Job demands and pesticide exposure among immigrant Latino farmworkers.
The goal of this study was to understand the potential threat of job stressors to farmworker health. To accomplish this goal we studied pesticide exposure, an issue with immediate and long-term health consequences, and predictions from the Demands-Control model of occupational stress. Longitudinal, self-report data and urine samples were collected at monthly intervals from a cohort of Latino farmworkers (N = 287) during the 2007 agricultural season. The primary hypothesis was that greater exposure to psychological demands, physical exertion, and hazardous work conditions are associated with greater odds of detecting dialkylphosphate (DAP) urinary pesticide metabolites, biomarkers indicating exposure to pesticides. Contrary to this hypothesis, results indicated that none of the elements of the Demands-Control model were independently associated with detection of DAP urinary pesticide metabolites. However, analyses produced several interaction effects, including evidence that high levels of control may buffer the effects of physical job demands on detection of DAP urinary pesticide metabolites.


Expression and regulatory effects on cancer cell behavior of NELL1 and NELL2 in human renal cell carcinoma.
Neural epidermal growth factor-like like (NELL) 1 and 2 constitute a family of multimeric and multimodular extracellular glycoproteins. Although the osteogenic effects of NELL1 and functions of NELL2 in neural development have been reported, their expression and functions in cancer are largely unknown. In this study, we examined expression of NELL1 and NELL2 in renal cell carcinoma (RCC) using clinical specimens and cell lines. We show that, whereas NELL1 and NELL2 proteins are strongly expressed in renal tubules in non-cancerous areas of RCC specimens, their expression is significantly downregulated in cancerous areas. Silencing of NELL1 and NELL2 mRNA expression was also detected in RCC cell lines. Analysis of NELL1/2 promoter methylation status indicated that the CpG islands in the NELL1 and NELL2 genes are hypermethylated in RCC cell lines. NELL1 and NELL2 bind to RCC cells, suggesting that these cells express a receptor for NELL1 and NELL2 that can transduce signals. Furthermore, we found that both NELL1 and NELL2 inhibit RCC cell migration, and NELL1 further inhibits RCC cell adhesion. These results suggest that silencing of NELL gene expression by promoter hypermethylation plays roles in RCC progression by affecting cancer cell behavior.


Sleep disturbances in Parkinson's disease.
Sleep disturbances are very common in patients with PD and are associated with a variety of negative outcomes. The evaluation of sleep disturbances in these patients is complex, as sleep may be affected by a host of primary sleep disorders, other primary medical or psychiatric conditions, reactions to medications, aging or the neuropathophysiology of PD itself. In this article, we review the evaluation of the common disturbances of sleep seen in PD. This includes the primary sleep disorders, the interaction of depression and insomnia, the impact that medications for PD have on sleep, as well as the role of factors such as nocturia, pain, dystonia, akinesia, difficulty turning in bed, and vivid dreaming. The treatment of sleep disturbances in PD is largely unstudied but recommendations based on clinical experience in PD and research studies in other geriatric populations can be made. Important principles include, diagnosis, treating the specific sleep disorder or co-occurring disorder, and control of the motor aspects of PD.


[The natural course of a complete atrioventricular block].
The natural disease course is analyzed in 311 patients with atrioventricular blockade admitted for surgical treatment to the Leningrad Center of Arrhythmia Surgery and Cardiac Pacing. It has been discovered that, as a rule, Morgagni-Adams-Stokes (MAS) attacks do not occur for over 2-3 years after their onset, which determines to a considerable measure the patients: life expectancy. The authors hold that the very first Mas attack which may occur in a patient with atrioventricular blockade is an absolute indication for implantation of a permanent cardiac pacemaker. If the permanent cardiac pacemaker was established, 1-, 3-, 5-, 7- and 8-year survival rates were, respectively, 91.1, 85.8, 77.3, 63.2, and 60.8%.


How genetic and environmental variance in personality traits shift across the life span: Evidence from a cross-national twin study.
Decades of research have shown that about half of individual differences in personality traits is heritable. Recent studies have reported that heritability is not fixed, but instead decreases across the life span. However, findings are inconsistent and it is yet unclear whether these trends are because of a waning importance of heritable tendencies, attributable to cumulative experiential influences with age, or because of nonlinear patterns suggesting Gene × Environment interplay. We combined four twin samples (N = 7,026) from Croatia, Finland, Germany, and the United Kingdom, and we examined age trends in genetic and environmental variance in the six HEXACO personality traits: Honesty-Humility, Emotionality, Extraversion, Agreeableness, Conscientiousness, and Openness. The cross-national sample ranges in age from 14 to 90 years, allowing analyses of linear and nonlinear age differences in genetic and environmental components of trait variance, after controlling for gender and national differences. The amount of genetic variance in Extraversion, Agreeableness, and Openness followed a reversed U-shaped pattern across age, showed a declining trend for Honesty-Humility and Conscientiousness, and was stable for Emotionality. For most traits, findings provided evidence for an increasing relative importance of life experiences contributing to personality differences across the life span. The findings are discussed against the background of Gene × Environment transactions and interactions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Minimally invasive surgery for achalasia: an 8-year experience with 168 patients.
Seven years ago, the authors reported on the feasibility and short-term results of minimally invasive surgical methods to treat esophageal achalasia. In this report, they describe the evolution of the surgical technique and the clinical results in a large group of patients with long follow-up. Between January 1991 and October 1998, 168 patients (96 men, 72 women; mean age 45 years, median duration of symptoms 48 months), who fulfilled the clinical, radiographic, endoscopic, and manometric criteria for a diagnosis of achalasia, underwent esophagomyotomy by minimally invasive techniques. Forty-eight patients had marked esophageal dilatation (diameter >6.0 cm). Thirty-five patients had a left thoracoscopic myotomy, and 133 patients had a laparoscopic myotomy plus a partial fundoplication. Follow-up to October 1998 was complete in 145 patients (86%). Median hospital stay was 72 hours for the thoracoscopic group and 48 hours for the laparoscopic group. Eight patients required a second operation for recurrent or persistent dysphagia, and two patients required an esophagectomy. There were no deaths. Good or excellent relief of dysphagia was obtained in 90% of patients (85% after thoracoscopic and 93% after laparoscopic myotomy). Gastroesophageal reflux developed in 60% of tested patients after thoracoscopic myotomy and in 17% after laparoscopic myotomy plus fundoplication. Laparoscopic myotomy plus fundoplication corrected reflux present before surgery in five of seven patients. Patients with a dilated esophagus had excellent relief of dysphagia after laparoscopic myotomy; none required an esophagectomy. Minimally invasive techniques provided effective and long-lasting relief of dysphagia in patients with achalasia. The authors prefer the laparoscopic approach for three reasons: it more effectively relieved dysphagia, it was associated with a shorter hospital stay, and it was associated with less postoperative reflux. Laparoscopic Heller myotomy and partial fundoplication should be considered the primary treatment for esophageal achalasia.


Evaluation of the performance of a shearing interferometer in strong scintillation in the absence of additive measurement noise.
A simulation study is presented that evaluates the ability of a unit-shear, shearing interferometer to estimate a complex field resulting from propagation through extended turbulence. Performance is defined in terms of the Strehl ratio achieved when the estimate of the complex field obtained from reconstruction is used to correct the distorted wave front presented to the wave-front sensor. A series of evaluations is performed to identify the strengths and weaknesses of the shearing interferometer in the two-dimensional space of the Fried parameter r0 and the Rytov number. The performance of the shearing interferometer is compared with that of a Hartmann sensor in the Fried and Hutchin geometries. Although the effects of additive measurement noise (such as read noise, shot noise, amplifier noise) are neglected, the fundamental characteristics of the measurement process are shown to distinguish the performance of the various wave-front sensors. It is found that the performance of a shearing interferometer is superior to that of a Hartmann sensor when the Rytov number exceeds 0.2.


Phenylethanolamine N-methyltransferase-containing neurons in rat retina: immunohistochemistry, immunochemistry, and molecular biology.
We sought to characterize in detail neurons in rat retina that contain phenylethanolamine N-methyltransferase (PNMT), the epinephrine biosynthetic enzyme. Cell bodies and processes of PNMT-containing neurons in retina were identified by immunohistochemistry. The coexistence of other catecholamine biosynthetic enzymes in the same cells was also investigated. Biochemical, molecular biological and immunochemical methods were applied to determine whether retinal PNMT is similar to the adrenal enzyme, since regulation of PNMT in retina and adrenal appears to be different. The results show that there are two types of PNMT-containing cells: those containing PNMT exclusively and those containing PNMT with two other catecholamine-synthesizing enzymes, tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC), but not dopamine beta-hydroxylase (DBH). PNMT-only cell bodies are localized in the inner nuclear layer (INL) and the ganglion cell layer (GCL). Their processes are observed in outer and inner strata of the inner plexiform layer (IPL). Only a small fraction of PNMT neurons in INL also contain TH and AADC. These cells send their processes to the adjacent stratum of the IPL. Antibodies to bovine adrenal DBH, however, fail to localize DBH in any rat retinal cells. Immunochemical titration shows that PNMT from both retina and adrenal gland has the same immunoreactivity. Furthermore, a PNMT-cDNA probe hybridizes equally with PNMT-mRNA isolated from both the retina and the adrenal gland. These results indicate that PNMT is identical in these tissues.


Comparison of MRI Activity Scoring Systems and Features for the Terminal Ileum in Patients With Crohn Disease.
The purpose of this study was to evaluate four previously validated MRI activity scoring systems for diagnosis and grading of Crohn disease (CD) in the terminal ileum against an endoscopic and histopathologic reference standard. Ethics approval and written informed consent were obtained. Subjects with known or suspected CD were prospectively recruited between December 2011 and August 2014. Each patient underwent MRI and ileocolonoscopy with terminal ileum biopsies. Four MRI scoring systems (Magnetic Resonance Index of Activity [MaRIA], Clermont score, London score, and Crohn disease MRI Index) and component features were applied by two observers and correlated to the Crohn disease endoscopic index of severity (CDEIS, 0-44) and histopathologic endoscopic acute inflammation score (0-6). Interobserver agreement (weighted kappa and intraclass correlation coefficient [ICC]) and diagnostic accuracy for active and ulcerating endoscopic or histopathologic disease were evaluated. Ninety-eight patients (median age, 32 years old; 55 women, 43 men) were included. All four scoring systems showed good interobserver agreement (ICC = 0.70-0.78), moderate-to-strong correlation to CDEIS (r = 0.57-0.67) and weak-to-moderate correlation to endoscopic acute inflammation score (r = 0.38-0.49). Scoring systems' diagnostic accuracy for active and ulcerating endoscopic disease ranged from 73% to 78% and 71% to 76%, respectively, whereas for active histopathologic disease accuracy ranged from 65% to 72%. Between the scoring systems, no significant differences were found for both observers regarding interobserver agreement, correlation coefficients, and diagnostic accuracy. All scoring systems were comparable in terms of interobserver agreement, correlation to the endoscopic and histopathologic reference standard, and diagnostic accuracy. The London score, MaRIA, and Clermont score have the additional benefit of having validated cutoff values for both active and ulcerating endoscopic disease.


The RNASeq-er API-a gateway to systematically updated analysis of public RNA-seq data.
The exponential growth of publicly available RNA-sequencing (RNA-Seq) data poses an increasing challenge to researchers wishing to discover, analyse and store such data, particularly those based in institutions with limited computational resources. EMBL-EBI is in an ideal position to address these challenges and to allow the scientific community easy access to not just raw, but also processed RNA-Seq data. We present a Web service to access the results of a systematically and continually updated standardized alignment as well as gene and exon expression quantification of all public bulk (and in the near future also single-cell) RNA-Seq runs in 264 species in European Nucleotide Archive, using Representational State Transfer. The RNASeq-er API (Application Programming Interface) enables ontology-powered search for and retrieval of CRAM, bigwig and bedGraph files, gene and exon expression quantification matrices (Fragments Per Kilobase Of Exon Per Million Fragments Mapped, Transcripts Per Million, raw counts) as well as sample attributes annotated with ontology terms. To date over 270 00 RNA-Seq runs in nearly 10 000 studies (1PB of raw FASTQ data) in 264 species in ENA have been processed and made available via the API. The RNASeq-er API can be accessed at http://www.ebi.ac.uk/fg/rnaseq/api . The commands used to analyse the data are available in supplementary materials and at https://github.com/nunofonseca/irap/wiki/iRAP-single-library . firstname.lastname@example.com ; firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Sequential development of embryoblast-like memory entities in human cancer tissues: an evolutionary self-repair structure with pluripotentiality.
Hidden collective organization of cancer cells can partially or completely return to embryoid genotype-phenotype with the plasticity to transform their morphology on cell embryoblast-like memory entities by expression of dormant genes that arise from embryogenesis. After hundreds of driver mutations, cancer cells gain new abilities or attributes and recapitulate early stages of embryogenesis. Our findings document how malignant tissues reactivated ancestral storage memory and elaborate inside tumor glands spiral-pyramidal-fractal chiral crystals (Tc) as geometric attractor proteins and biomimicry the primitive cellular blastocyst embryoblast fluid-filled cavity. The resultant evolutionary embryoblast-like entity has higher survivability and spatial cephalic-caudal growth organization with pluripotentiality that carry the correct DNA instructions to repair, and regenerate. The isolation and manipulation of these order structures can guide and control the regenerative pathway mechanism in human tumors as follows: modify and reprogram the phenotype of the tumor where these entities are generated, establish a reverse primordial microscopic mold to use the swirlonic collective behavior of cellular building blocks to regenerate injured tissues, convert cancer cells to a normal phenotype through regeneration using the organizational level and scale properties of reverse genetic guidance, global control of mitotic activity and morphogenetic movements avoiding their spread and metastasis, determining a better life prognosis for patients who incubate these entities in their tumors compared to those who do not express them. An emergent self-repair order structure, biological template can develop targeted therapeutic alternatives not only in cancer but also in treatment of autoimmune, viral diseases, and in regenerative medicine and rejuvenation.


Chronic cryptococcal meningitis: a new experimental model in rabbits.
This paper describes the salient features of a new model for chronic cryptococcal meningitis in cortisone-treated rabbits. Normal rabbits soon recovered after intracisternal inoculation of Cryptococcus neoformans, but cortisone-treated animals developed chronic progressive meningitis that was fatal in 2-12 weeks. Incidence and severity of infection was related to cortisone dose, not to inoculum size. The number of mononuclear cells that migrated into the subarachnoid spaces and cerebrospinal fluid of infected rabbits was strikingly reduced by cortisone treatment. Rabbits with cryptococcal meningitis were febrile; their high body temperature did not confer resistance to this infection. Cortisone-treated rabbits provide a new and expedient laboratory model for cryptococcal disease. Potential applications include study of the pathogenesis of cryptococcosis, investigation of the immunobiology of the CNS in chronic meningitis, and in vivo evaluation of newer anticryptococcal treatment regimens.


Accuracy in core biopsy of the prostate. An autopsy study.
In this autopsy study the predictive values of positive and negative tests of core biopsies of the prostate were investigated. Core biopsies, which were performed after evisceration, were compared with macroscopic and microscopic findings of the entire prostatic gland. Of 107 investigated patients, 100 contained prostatic tissue in the core biopsies. In 11 patients the core biopsies contained carcinoma. All these patients had carcinoma in the tissue sections from the prostate. In 89 patients the core biopsy did not contain carcinoma. 88 of these patients had no carcinoma in the tissue sections from the entire specimens. However, in 1 patient a highly differentiated acinar adenocarcinoma was found. From these results the predictive value of a positive test is 11/11 = 100%, and the predictive value of a negative test is 88/89 = 98.5%. Core biopsy is a suitable method in diagnosing prostatic diseases and gives a very high accuracy when the core biopsy contains prostatic tissue.


New High-Throughput Screening Identifies Compounds That Reduce Viability Specifically in Liver Cancer Cells That Express High Levels of SALL4 by Inhibiting Oxidative Phosphorylation.
Some oncogenes encode transcription factors, but few drugs have been successfully developed to block their activity specifically in cancer cells. The transcription factor SALL4 is aberrantly expressed in solid tumor and leukemia cells. We developed a screen to identify compounds that reduce the viability of liver cancer cells that express high levels of SALL4, and we investigated their mechanisms. We developed a stringent high-throughput screening platform comprising unmodified SNU-387 and SNU-398 liver cancer cell lines and SNU-387 cell lines engineered to express low and high levels of SALL4. We screened 1597 pharmacologically active small molecules and 21,575 natural product extracts from plant, bacteria, and fungal sources for those that selectively reduce the viability of cells with high levels of SALL4 (SALL4hi cells). We compared gene expression patterns of SALL4hi cells vs SALL4-knockdown cells using RNA sequencing and real-time polymerase chain reaction analyses. Xenograft tumors were grown in NOD/SCID gamma mice from SALL4hi SNU-398 or HCC26.1 cells or from SALL4lo patient-derived xenograft (PDX) cells; mice were given injections of identified compounds or sorafenib, and the effects on tumor growth were measured. Our screening identified 1 small molecule (PI-103) and 4 natural compound analogues (oligomycin, efrapeptin, antimycin, and leucinostatin) that selectively reduced viability of SALL4hi cells. We performed validation studies, and 4 of these compounds were found to inhibit oxidative phosphorylation. The adenosine triphosphate (ATP) synthase inhibitor oligomycin reduced the viability of SALL4hi hepatocellular carcinoma and non-small-cell lung cancer cell lines with minimal effects on SALL4lo cells. Oligomycin also reduced the growth of xenograft tumors grown from SALL4hi SNU-398 or HCC26.1 cells to a greater extent than sorafenib, but oligomycin had little effect on tumors grown from SALL4lo PDX cells. Oligomycin was not toxic to mice. Analyses of chromatin immunoprecipitation sequencing data showed that SALL4 binds approximately 50% of mitochondrial genes, including many oxidative phosphorylation genes, to activate their transcription. In comparing SALL4hi and SALL4-knockdown cells, we found SALL4 to increase oxidative phosphorylation, oxygen consumption rate, mitochondrial membrane potential, and use of oxidative phosphorylation-related metabolites to generate ATP. In a screening for compounds that reduce the viability of cells that express high levels of the transcription factor SALL4, we identified inhibitors of oxidative phosphorylation, which slowed the growth of xenograft tumors from SALL4hi cells in mice. SALL4 activates the transcription of genes that regulate oxidative phosphorylation to increase oxygen consumption, mitochondrial membrane potential, and ATP generation in cancer cells. Inhibitors of oxidative phosphorylation might be used for the treatment of liver tumors with high levels of SALL4.


Quantification of myocardial deformation in patients with Fabry disease by cardiovascular magnetic resonance feature tracking imaging.
Cardiac involvement is a major contributor of morbidity and mortality in Fabry disease (FD). Early detection and accurate evaluation of the disease progression is important in management. Cardiovascular magnetic resonance (CMR) derived feature fracking (FT) is a validated quantitative method of assessing myocardial deformation which may reflect early changes of myocardial function and track disease severity. We sought to evaluate the utility of CMR-FT as a measure of myocardial dysfunction in FD. Twenty FD patients (12 males, 40.8±14.9 years) and 20 age and sex matched healthy controls (10 males, 40.5±7.2 years) were prospectively enrolled. Subjects underwent CMR including cine, pre-/post-contrast T1 mapping and late gadolinium enhancement (LGE). FD patients were divided into three groups; group 1: patients without left ventricular hypertrophy (LVH) and LGE negative; group 2: patients with LVH positive, LGE either positive or negative; group 3: patients with LGE positive, LV wall thinning and heart failure. FT derived strain indices were measured and its associations with other processes were investigated. In FD patients, 14 (70%) had LVH and 4 (20%) had LGE. Compared with normal controls, LV global longitudinal strain (GLS) were reduced significantly in all three Fabry groups (all P<0.05), global circumferential strain (GCS) were reduced only in group 2 and group 3 (P<0.05). Among three FD groups, there were significant differences of LV GLS, GCS, native T1 value and extracellular volume fraction (ECV) (all P<0.01), group 1 had mild LV strain indices impairment, group 3 had the most severe LV strain indices. When compared between FD subgroups, GLS and GCS showed significant difference between each two groups (all P<0.05). There were weak correlations between the LV functional parameters (ejection fraction, LV mass index), maximal wall thickness, T1 mapping indices (native T1, ECV) and LV strain indices. The strongest relation was between global longitudinal early diastolic strain rate and native T1 value (r=0.783, P<0.01). CMR strain imaging identifies myocardial deformation in FD in different stages. Strain imaging can track disease severity and may be an alternative method for follow-up of FD patients.


The 'prediction imperative' as the basis for self-awareness.
Here, we propose that global brain function is geared towards the implementation of intelligent motricity. Motricity is the only possible external manifestation of nervous system function (other than endocrine and exocrine secretion and the control of vascular tone). The intelligence component of motricity requires, for its successful wheeling, a prediction imperative to approximate the consequences of the impending motion. We address how such predictive function may originate from the dynamic properties of neuronal networks.


Comparison of aerosol and intranasal challenge in a mouse model of allergic airway inflammation and hyperresponsiveness.
The aim was to optimize antigen challenge for induction of airway hyperresponsiveness (AHR) and inflammation in BALB/c mice sensitized to ovalbumin (OVA). Comparisons were made between mice challenged with OVA either as an aerosol or intranasally. The protocol that induced maximal AHR in BALB/c mice was thereafter tested in C57BL/6 mice. Methacholine responsiveness was measured using the flexiVent® system to assess AHR. Inflammatory responses were investigated by histology and cell counts in bronchoalveolar lavage (BAL) fluid. 48 h after challenge with 1 or 6% OVA aerosols, there were similar increments in AHR and BAL cells, predominantly eosinophils. When comparing the effect of 1% OVA aerosol on AHR and cell infiltration at 24 and 48 h after challenge, the responses were similar. At 24 h, intranasal OVA administration (20-200 μg) caused a dose-dependent increase in AHR. BAL cells were increased by all intranasal OVA doses and to a greater extent than after 1% OVA aerosol challenge but without any dose dependency. Histological examination confirmed that there was an increase of eosinophils in lung tissue following either challenge. In C57BL/6 mice, baseline tissue elastance was the only functional outcome that was increased after intranasal OVA challenge. Even though the AHR response was negligible in C57BL/6 mice, a similar infiltration of BAL cells was observed in both strains. Intranasal challenge was more effective than aerosol challenge at inducing both AHR and airway inflammation in BALB/c mice. Although intranasal challenge caused airway inflammation in C57BL/6 mice, this strain is not optimal for studying AHR.


Effects of Promoting Long-term, Exclusive Breastfeeding on Adolescent Adiposity, Blood Pressure, and Growth Trajectories: A Secondary Analysis of a Randomized Clinical Trial.
Evidence that breastfeeding reduces child obesity risk and lowers blood pressure (BP) is based on potentially confounded observational studies. To investigate the effects of a breastfeeding promotion intervention on adiposity and BP at age 16 years and on longitudinal growth trajectories from birth. Cluster-randomized Promotion of Breastfeeding Intervention Trial. Belarusian maternity hospitals and affiliated polyclinics (the clusters) were allocated into intervention (n = 16) or control arms (n = 15) in 1996 and 1997. The trial participants were 17 046 breastfeeding mother-infant pairs; of these, 13 557 children (79.5%) were followed up at 16 years of age between September 2012 and July 2015. Breastfeeding promotion, modeled on the Baby-Friendly Hospital Initiative. Body mass index (BMI, calculated as weight in kilograms divided by height in meters squared); fat and fat-free mass indices and percentage of body fat from bioimpedance; waist circumference; overweight and obesity; height; BP; and longitudinal growth trajectories. The primary analysis was modified intention-to-treat (without imputation for losses to follow-up) accounting for within-clinic clustering. We examined 13 557 children at a median age of 16.2 years (48.5% were girls). The intervention substantially increased breastfeeding duration and exclusivity compared with the control arm (exclusively breastfed: 45% vs 6% at 3 months, respectively). Mean differences at 16 years between intervention and control groups were 0.21 (95% CI, 0.06-0.36) for BMI; 0.21 kg/m2 (95% CI, -0.03 to 0.44) for fat mass index; 0.00 kg/m2 (95% CI, -0.21 to 0.22) for fat-free mass index; 0.71% (95% CI, -0.32 to 1.74) for percentage body fat; -0.73 cm (-2.48 to 1.02) for waist circumference; 0.05 cm (95% CI, -0.85 to 0.94) for height; -0.54 mm Hg (95% CI, -2.40 to 1.31) for systolic BP; and 0.71 mm Hg (95% CI, -0.68 to 2.10) for diastolic BP. The odds ratio for overweight/obesity (BMI ≥85th percentile vs <85th percentile) was 1.14 (95% CI, 1.02-1.28) and the odds ratio for obesity (BMI ≥95th percentile vs <95th percentile) was 1.09 (95% CI, 0.92-1.29). The intervention resulted in a more rapid rate of gain in postinfancy height (1 to 2.8 years), weight (2.8 to 14.5 years), and BMI (2.8 to 8.5 years) compared with the control arm. The intervention had little effect on BMI z score changes after 8.5 years. A randomized intervention that increased the duration and exclusivity of breastfeeding was not associated with lowered adolescent obesity risk or BP. On the contrary, the prevalence of overweight/obesity was higher in the intervention arm. All mothers initiated breastfeeding, so findings may not apply to comparisons of the effects of breastfeeding vs formula feeding. isrctn.org: ISRCTN37687716; and clinicaltrials.gov: NCT01561612.


Effective prophylactic therapy for cyclic vomiting syndrome in children using amitriptyline or cyproheptadine.
To evaluate our experience using the antimigraine prophylactic drugs, amitriptyline and cyproheptadine, for the prophylactic management of cyclic vomiting syndrome (CVS) in children. Twenty-seven patients (16 males) ranging in age from 2 to 16 years at diagnosis, fulfilling the diagnostic criteria for CVS and treated prophylactically with either amitriptyline (22) or/and cyproheptadine (6) were identified through retrospective chart review. Individual patient data were corroborated by the attending physician and/or interviews with patients and families. Minimum follow-up time before entry into the study group was 5 months. Patients were stratified according to three treatment outcomes: 1) complete response-no attacks, 2) partial response-50% or greater reduction in frequency of attacks, and 3) no response-less than 50% decrease in frequency of attacks. Of the 22 patients treated with amitriptyline, 16 (73%) had a complete response while 4 (18%) had a partial response. Of the 6 patients treated with cyproheptadine, 4 (66%) had a complete response and 1 (17%) had a partial response. Thus, 91% of the amitriptyline group and 83% of the cyproheptadine group had at least a partial response to therapy. No patients experienced significant side effects to either medication. The antimigraine prophylactic drugs, amitriptyline and cyproheptadine, represent effective prophylactic agents for the management of CVS in the vast majority of patients fulfilling the diagnostic criteria for this syndrome.


Managing Mental Health Disorders Resulting from Trauma through Yoga: A Review.
There are many and varied types of trauma. The extent to which trauma influences the mental health of an individual depends on the nature of trauma, as well as on the individual's coping capabilities. Often trauma is followed by depression, anxiety, and PTSD. As the pharmacological remedies for these conditions often have undesirable side-effects, nonpharmacological remedies are thought of as a possible add-on treatment. Yoga is one such mind-body intervention. This paper covers eleven studies indexed in PubMed, in which mental health disorders resulting from trauma were managed through yoga including meditation. The aim was to evaluate the use of yoga in managing trauma-related depression, anxiety, PTSD and physiological stress following exposure to natural calamities, war, interpersonal violence, and incarceration in a correctional facility. An attempt has also been made to explore possible mechanisms underlying benefits seen. As most of these studies were not done on persons exposed to trauma that had practiced yoga, this is a definite area for further research.


'Searching for a "generalized social agent" to predict Namibians' intentions to prevent sexual transmission of HIV.
Debate surrounds the definition, measurement and utility of subjective norms (theory of reasoned action, Fishbein & Ajzen, 1975; Ajzen & Fishbein, 1980). Scholars propose alternative concepts including descriptive norms and injunctive norms (Cialdini et al., 1990), enabling factors and social embeddedness (e.g. Barrera, 1986), and betweenness to others in a network (Wasserman & Faust, 1994) to explain social influences on willingness to perform a behaviour. This study explores the relative utility and comparability of different social concepts in understanding Namibians' intentions (n=1200) to abstain from sex or to be faithful to one sexual partner. Neither subjective norms nor the five other concepts consistently predict either intentions, although they account for 21% of variance in intentions to abstain and 24% of intentions to have one sexual partner in one region. Conflicting relationships between injunctive and subjective norms exist; stigma surrounding HIV prevention provides some explanation. Campaigns designed to alter norms may benefit from altering stigma simultaneously.


Insertion sequence ISEcp1B is involved in expression and mobilization of a bla(CTX-M) beta-lactamase gene.
The genetic structures (ca. 10-kb DNA fragment) surrounding the plasmid-borne extended-spectrum beta-lactamase bla(CTX-M-19) gene in a Klebsiella pneumoniae clinical isolate were determined. This beta-lactamase gene was part of a 4,797-bp transposon inserted inside orf1 of Tn1721. Inside this transposon, bla(CTX-M-19) was bracketed upstream and downstream by insertion sequences ISE cp1B and IS903D, respectively, and further downstream by a truncated gene encoding an outer membrane protein for iron transport. The single-copy ISEcp1B element was probably involved alone in the mobilization process that led to a 5-bp duplication at the target site of the transposed fragment. This mobilization event probably involved one inverted repeat of ISE cp1B and a second sequence farther away, resembling its second inverted repeat. Additionally, ISEcp1B provided -35 and -10 promoter sequences, contributing to the high-level expression of the bla(CTX-M-19) gene. Southern blot analysis failed to identify a reservoir of ISEcp1-like sequences among a series of gram-negative and gram-positive bacterial species usually found in the skin and intestinal human floras. The ability of ISEcp1-like elements to mobilize and to promote the expression of beta-lactamase genes may explain, in part, the current spread of CTX-M-type enzymes worldwide.


Social Communication Coaching Smartglasses: Well Tolerated in a Diverse Sample of Children and Adults With Autism.
Augmented reality (AR) smartglasses are an emerging technology that is under investigation as a social communication aid for children and adults with autism spectrum disorder (ASD) and as a research tool to aid with digital phenotyping. Tolerability of this wearable technology in people with ASD is an important area for research, especially as these individuals may experience sensory, cognitive, and attentional challenges. The aim of this study was to assess the tolerability and usability of a novel smartglasses system that has been designed as a social communication aid for children and adults with autism (the Brain Power Autism System [BPAS]). BPAS runs on Google Glass Explorer Edition and other smartglasses, uses both AR and affective artificial intelligence, and helps users learn key social and emotional skills. A total of 21 children and adults with ASD across a spectrum of severity used BPAS for a coaching session. The user's tolerability to the smartglasses, user being able to wear the smartglasses for 1 minute (initial tolerability threshold), and user being able to wear the smartglasses for the entire duration of the coaching session (whole session tolerability threshold) were determined through caregiver report. Of 21 users, 19 (91%) demonstrated tolerability on all 3 measures. Caregivers reported 21 out of 21 users (100%) as tolerating the experience, while study staff found only 19 out of 21 users managed to demonstrate initial tolerability (91%). Of the 19 users who demonstrated initial tolerability, all 19 (100%) were able to use the smartglasses for the entire session (whole session tolerability threshold). Caregivers reported that 19 out of 21 users (91%) successfully used BPAS, and users surpassed caregiver expectations in 15 of 21 cases (71%). Users who could communicate reported BPAS as being comfortable (94%). This preliminary report suggests that BPAS is well tolerated and usable to a diverse age- and severity-range of people with ASD. This is encouraging as these devices are being developed as assistive technologies for people with ASD. Further research should focus on improving smartglasses design and exploring their efficacy in helping with social communication in children and adults with ASD.


Regional cerebral blood flow in vascular depression assessed by 123I-IMP SPECT.
As the prevalence of white matter hyperintensities detected on T2 weighted MRI scans in patients with late-onset depression is higher than that in nondepressed patients, the concept of"vascular depression" (VDep) was introduced in 1997. However, the pathology of vascular depression has not been clarified. This study examined the differences in functional imaging between vascular and non-vascular depression (non-VDep). We utilized (123)I-IMP single photon emission computed tomography (SPECT) to compare regional cerebral blood flows (rCBF) between 9 patients with VDep (Krishnan criteria) and 11 age- and sex-matched patients with non-VDep in both depressed and remitted states. In both VDep and non-VDep patients, mean rCBF increased significantly as depression improved, partially aided by changes in left anterior temporal blood flow. In addition, compared to non-VDep patients, the left anterior frontal rCBF for VDep patients was significantly lower in both depressed and remitted states. Left anterior temporal rCBF therefore appears to represent a state marker that increases as symptoms associated with late-onset depression improve, regardless of vascular changes. Furthermore, in VDep patients, left anterior frontal rCBF was low in both states compared to non-VDep patients, and might not only represent a trait marker, but also correlated with the duration of disease and likelihood of recurrence and relapse.


Economic evaluation of dialysis therapies.
The prevalence of chronic kidney disease and end-stage renal disease requiring dialysis therapy continues to increase worldwide, and despite technological advances, treatment remains resource intensive. Thus, the increasing burden of dialysis therapy on finite health-care budgets is an important consideration. The principles of allocative efficiency and the concept of 'opportunity cost' can be used to assess whether dialysis is economically justified; if dialysis is to be provided, cost-minimization and cost-utility analyses can be used to identify the most efficient dialysis modality. Existing studies have examined the cost, and where relevant the effectiveness, of the various currently available peritoneal dialysis and haemodialysis modalities. In this Review, we discuss variations in the intrinsic costs of the available dialysis modalities as well as other factors, such as variation by country, available health-care infrastructures, the timing of dialysis initiation and renal transplantation. We draw on data from robust micro-costing studies of the various dialysis modalities in Canada to highlight key issues.


Performance Analysis of Sphere Packed Aided Differential Space-Time Spreading with Iterative Source-Channel Detection.
The introduction of 5G with excessively high speeds and ever-advancing cellular device capabilities has increased the demand for high data rate wireless multimedia communication. Data compression, transmission robustness and error resilience are introduced to meet the increased demands of high data rates of today. An innovative approach is to come up with a unique setup of source bit codes (SBCs) that ensure the convergence and joint source-channel coding (JSCC) correspondingly results in lower bit error ratio (BER). The soft-bit assisted source and channel codes are optimized jointly for optimum convergence. Source bit codes assisted by iterative detection are used with a rate-1 precoder for performance evaluation of the above mentioned scheme of transmitting sata-partitioned (DP) H.264/AVC frames from source through a narrowband correlated Rayleigh fading channel. A novel approach of using sphere packing (SP) modulation aided differential space time spreading (DSTS) in combination with SBC is designed for the video transmission to cope with channel fading. Furthermore, the effects of SBC with different hamming distances d(H,min) but similar coding rates is explored on objective video quality such as peak signal to noise ratio (PSNR) and also the overall bit error ratio (BER). EXtrinsic Information Transfer Charts (EXIT) are used for analysis of the convergence behavior of SBC and its iterative scheme. Specifically, the experiments exhibit that the proposed scheme of error protection of SBC d(H,min) = 6 outperforms the SBCs having same code rate, but with d(H,min) = 3 by 3 dB with PSNR degradation of 1 dB. Furthermore, simulation results show that a gain of 27 dB Eb/N0 is achieved with SBC having code rate 1/3 compared to the benchmark Rate-1 SBC codes.


Detailed municipal solid waste composition analysis for Nur-Sultan City, Kazakhstan with implications for sustainable waste management in Central Asia.
A detailed characterization of municipal solid waste (MSW) beyond a standard compositional analysis may offer insights useful for improving waste management systems. The present paper contributes to the scarce literature in the field by presenting new data from a rapidly developing Central Asian city, the capital of Kazakhstan, Nur-Sultan. Three sampling campaigns (each 1 week long) have been conducted at the city landfill over a 1-year period (2018-2019), and a detailed characterization for selected waste components and sub-components has been performed. The major fractions of MSW were organics (46.3%), plastics (15.2%), paper (12.8%), and diapers (5.9%). The detailed composition analysis showed high LDPE (low-density polyethylene) content (5.5%) mostly comprised of plastic bags (4.5%), transparent glass (3.2%), pharmaceuticals (0.4%), and fine (i.e., < 12 mm) organic fraction content (29%). The MSW generation rate of Nur-Sultan was estimated as 1.47 kg capita-1 day-1 based on the field collection as well as literature data. Among sustainable waste management recommendations addressed for Nur-Sultan and applicable to other cities in Central Asia, composting is recommended due to high organics fraction in MSW and its great potential to reduce the landfilled waste volume and to help valorizing the waste.


Prevalence of being underweight and overweight and obesity at diagnosis in UK patients with childhood acute lymphoblastic leukaemia 1985-2002.
Being underweight or overweight and obesity at diagnosis may all worsen prognosis in childhood acute lymphoblastic leukaemia (ALL), although no studies have estimated the prevalence of an unhealthy weight status at diagnosis in large representative samples using contemporary definitions of weight status based on body mass index (BMI) for age. The present study comprised a retrospective study that aimed to estimate prevalence of being underweight and overweight and obesity at diagnosis for patients with childhood ALL on three successive UK treatment trials: UKALL X (1985-1990; n = 1033), UKALL XI (1990-1997; n = 2031), UKALL 97/99 (1997-2002; n = 898).The BMI for age was used to define weight status with both UK 1990 BMI for age reference data and the Cole-International Obesity Task Force (IOTF) definitions. The prevalence of being underweight was 6% in the most recent trial for which data were available. The prevalence of being overweight and obesity was 35% in the most recent trial when expressed using Cole-IOTF definitions and 41% when expressed relative to UK 1990 reference data. Even with highly conservative estimates, >40% of all UK patients with ALL were underweight, overweight or obese at diagnosis in the most recent trial for which UK data are available (UKALL 97/99, 1997-2002).


Radiation Shielding Tests of Crosslinked Polystyrene-b-Polyethyleneglycol Block Copolymers Blended with Nanostructured Selenium Dioxide and Boron Nitride Particles.
In this work, gamma-ray shielding features of crosslinked polystyrene-b-polyethyleneglycol block copolymers (PS-b-PEG) blended with nanostructured selenium dioxide (SeO2) and boron nitride (BN) particles were studied. This research details several radiation shielding factors i.e., mass attenuation coefficient (μm), linear attenuation coefficient (μL), radiation protection efficiency (RPE), half-value layer (HVL), tenth-value layer (TVL), and mean free path (MFP). The irradiation properties of our nanocomposites were investigated with rays from the 152Eu source (in the energy intervals from 121.780 keV to 1408.010 keV) in a high-purity germanium (HPGe) detector system, and analyzed with GammaVision software. Moreover, all radiation shielding factors were determined by theoretical calculus and compared with the experimental results. In addition, the morphological and thermal characterization of all nanocomposites was surveyed with various techniques i.e., nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM). Acceptable compatibility was revealed and observed in all nanocomposites between the experimental and theoretical results. The PS-b-PEG copolymer and nanostructured SeO2 and BN particles exerted a significant effect in enhancing the resistance of the nanocomposites, and the samples with high additive rates exhibited better resistance than the other nanocomposites. From the achieved outcomes, it can be deduced that our polymer-based nanocomposites can be utilized as a good choice in the gamma-irradiation-shielding discipline.


Exposure and risk factors among elderly drivers: a case-control study.
To study the risk factors associated with exposure, aging, and other characteristics of elderly drivers, a case-control survey of 557 licensed drivers was conducted among residents of medium-sized, small towns and rural areas in Quebec, Canada. The subjects, aged 68 and over, were selected from the database of the provincial Automobile Insurance Board. The case group was chosen on the basis of performance, either accidents or violations, during the preceding three years. Cases were matched to a control group (blank file for the last three years) on a stratification basis (age, gender, region) in the proportion of two controls for one case. The survey which was conducted through a mail questionnaire achieved a participation rate of nearly 60%. The logistic regression method was used to assess the risk (odds ratios). The results of this study reveal that risk is proportional to the frequency of daily vehicle use or annual kilometrage. The hypothesis that elderly drivers who rarely expose themselves are at more risk is thus rejected. Vulnerable subgroups were the most elderly (> 77), city or suburban residents, the unmarried, and white collars (during active life).


Antimicrobial Stewardship at the Core of COVID-19 Response Efforts: Implications for Sustaining and Building Programs.
We describe traditional antimicrobial stewardship program (ASP) activities with a discussion of how these activities can be refocused in the setting of the COVID-19 pandemic. Additionally, we discuss possible adverse consequences of ASP attention diversion on COVID-19 response efforts and overall implications for future pandemic planning. We also discuss ASP in collaboration with other groups within health systems and how COVID-19 may affect these relationships long term. Despite the paucity of literature on Antimicrobial Stewardship and COVID-19, the potential contributions of ASPs during a pandemic are numerous. ASPs can develop strategies to identify patients with COVID-19-like-illness; this is particularly useful when these patients are missed at the time of health system entry. ASPs can also play a critical role in the management of potential drug shortages, developing local treatment guidelines, optimizing the use of antibiotics, and in the diagnostic stewardship of COVID-19 testing, among other roles. Importantly, it is often difficult to ascertain whether critically ill patients who are hospitalized with COVID-19 have concurrent or secondary bacterial infections-ASPs are ideally situated to help optimize antimicrobial use for these patients via a variety of mechanisms. ASPs are uniquely positioned to aid in pandemic response planning and relief efforts. ASPs are already integrated into health systems and play a key role in optimizing antimicrobial prescribing. As ASPs assist in COVID-19 response, understanding the role of ASPs in pandemic relief efforts may mitigate damage from future outbreaks.


Enhancing timeliness of drug overdose mortality surveillance: A machine learning approach.
Timely data is key to effective public health responses to epidemics. Drug overdose deaths are identified in surveillance systems through ICD-10 codes present on death certificates. ICD-10 coding takes time, but free-text information is available on death certificates prior to ICD-10 coding. The objective of this study was to develop a machine learning method to classify free-text death certificates as drug overdoses to provide faster drug overdose mortality surveillance. Using 2017-2018 Kentucky death certificate data, free-text fields were tokenized and features were created from these tokens using natural language processing (NLP). Word, bigram, and trigram features were created as well as features indicating the part-of-speech of each word. These features were then used to train machine learning classifiers on 2017 data. The resulting models were tested on 2018 Kentucky data and compared to a simple rule-based classification approach. Documented code for this method is available for reuse and extensions: https://github.com/pjward5656/dcnlp. The top scoring machine learning model achieved 0.96 positive predictive value (PPV) and 0.98 sensitivity for an F-score of 0.97 in identification of fatal drug overdoses on test data. This machine learning model achieved significantly higher performance for sensitivity (p<0.001) than the rule-based approach. Additional feature engineering may improve the model's prediction. This model can be deployed on death certificates as soon as the free-text is available, eliminating the time needed to code the death certificates. Machine learning using natural language processing is a relatively new approach in the context of surveillance of health conditions. This method presents an accessible application of machine learning that improves the timeliness of drug overdose mortality surveillance. As such, it can be employed to inform public health responses to the drug overdose epidemic in near-real time as opposed to several weeks following events.


Tourism crises and island destinations: Experiences in Penang, Malaysia.
Crisis management and tourism is attracting increasing attention as an industry practice and subject of academic enquiry, not least in South East Asia which has been affected by a number of severe crises in recent years. However, organisations are not always well prepared and response strategies can be deficient. The paper discusses issues of tourism crisis management with specific reference to the popular Malaysian destination of Penang. Findings are based on qualitative research consisting of semi-structured interviews with industry leaders from assorted sectors. Tourism in Penang emerges as vulnerable to regional and global events which act as a trigger for tourism crises, demanding a response in which various strategies are employed. The destination is also seen to recover fairly quickly from experiences of crises, but a well designed and formulated tourism crisis management plan under the stewardship of the public sector is necessary to mitigate further damage in the future.


Expression and function of NPSR1/GPRA in the lung before and after induction of asthma-like disease.
A genetic contribution to asthma susceptibility is well recognized, and linkage studies have identified a large number of genes associated with asthma pathogenesis. Recently, a locus encoding a seven-transmembrane protein was shown to be associated with asthma in founder populations. The expression of the protein GPRA (G protein-coupled receptor for asthma susceptibility) in human airway epithelia and smooth muscle, and its increased expression in a mouse model of asthma, suggested that a gain-of-function mutation in this gene increased the disease risk. However, we report here that the development of allergic lung disease in GPRA-deficient mice is unaltered. A possible explanation for this finding became apparent upon reexamination of the expression of this gene. In contrast to initial studies, our analyses failed to detect expression of GPRA in human lung tissue or in mice with allergic lung disease. We identify a single parameter that distinguishes GPRA-deficient and wild-type mice. Whereas the change in airway resistance in response to methacholine was identical in control and GPRA-deficient mice, the mutant animals showed an attenuated response to thromboxane, a cholinergic receptor-dependent bronchoconstricting agent. Together, our studies fail to support a direct contribution of GPRA to asthma pathogenesis. However, our data suggest that GPRA may contribute to the asthmatic phenotype by altering the activity of other pathways, such as neurally mediated mechanisms, that contribute to disease. This interpretation is supported by high levels of GPRA expression in the brain and its recent identification as the neuropeptide S receptor.


[Primary antiphospholipid syndrome and cerebrovascular disturbances].
Neurological, including cecbrovascular, disorders frequently emerge in primary antiphospholipid syndrome (PAS). Clinical peculiarities of PAS were studied in 113 patients with cerebrovascular disturbances. Its had mainly ischemic patogenesis. Structure of cerebrovascular disorders was as follows: stroke (33% cases), transient ischemic lesions (10%), its combination (57%), thrombosis of brain venous sinuses (3%), vascular dementia (27%). Besides it were found epileptic seizures, peripheral neuropathy, headache, chorea and some symptoms of myasthenia, parkinsonism, multiple sclerosis and psychotic disorders. In all cases antibodies to phospholipids have been detected. Secondary prophylaxis includes regular use of anticoagulants and small doses of aspiriny.


Otitis media as a sign of Wegener's granulomatosis in childhood.
Wegener's granulomatosis (WG) is a rare disease among paediatric patients. Chronic otitis media with or without facial nerve dysfunction is a known manifestation of the disease among adults. A case of a 15-year-old boy with WG, whose initial symptoms were acute otitis media and facial nerve paralysis, is presented. The otorhinolaryngological manifestations, as well as diagnostic and current treatment modalities in paediatric patients with WG, are discussed.


H2 consumption by anaerobic non-methanogenic mixed cultures.
The impact of H2 consumption, by homoacetogens, on the overall hydrogen yield in mixed culture fermentation is the focus of this study. Batch reactors were used to test the ability of anaerobic digested sludge, heat treated to eliminate methanogens, to produce and consume molecular hydrogen. The measured average hydrogen production rate from 4.2 g glucose/L was 44 +/- 4 mmol H2/L sludge . d, while the H2 consumption rate varied much more, in the range from 4 to 62 mmol H2/L sludge . d. Hydrogen consumption rate depends on acetic acid concentration, headspace H2 partial pressure and mass transfer rates. Different but relatively long lag-phases for hydrogen consumption were observed. It is concluded that homoacetogenesis can have a significant negative effect on bio-H2 production by mixed cultures, limiting the possibilities for sustainable solutions.


Laparoscopic and thoracoscopic partial hepatectomy for hepatocellular carcinoma.
Several trials have been reported examining laparoscopic liver resections for the treatment of various kinds of liver tumors. However, there are no detailed reports on the use of laparoscopic (LH) and thoracoscopic (TH) hepatectomy for the treatment of hepatocellular carcinoma (HCC). Eleven laparoscopic and thoracoscopic partial liver resections were attempted for treating HCC. The indications for performing a laparoscopic or thoracoscopic partial hepatectomy were as follows: (1) the tumor was located on the surface of the liver; (2) the tumor was less than 3 cm in diameter; and (3) the tumor was not located adjacent to any large vessels. A TH was performed if the tumor was located in segment 8; an LH was performed if the tumor was located in segment 3, 4, or 5. Hand-assisted operations were performed in two patients. The mean operating time was 186.1 +/- 44.0 minutes (range 130-310 minutes). The operative blood loss was 218.3 +/- 197.6 ml (range 20-650 ml). The mean postoperative hospital stay was 11.3 +/- 5.7 days (range 7-26 days). Two patients experienced postoperative complications (wound infection and ascites). No local recurrences have occurred to date. The overall 5-year survival rate and disease-free 5-year survival rate were 75.0% and 38.2%, respectively. Laparoscopic and thoracoscopic hepatic resections are less invasive than conventional surgical techniques and are useful for treating HCC in select patients.


[Auditory neuropathy (auditory neuropathy spectrum disorders): the approaches to diagnostics and rehabilitation].
Auditory neuropathies (auditory neuropathy spectrum disorders, ANSD) may be a consequence of dysfunction of inner hair cells and/or of synapses between these cells and auditory nerve fibers. Another cause of these disorders is supposed to be pathological changes in the auditory nerve itself. The outcome of the rehabilitative treatment of the patients presenting with this disorder depends on the quality of diagnosis and precise location of the pathological process. The present study involved 82 patients with auditory neuropathies. The audiological data obtained in the course of this work were compared with the results of other authors published during the recent years. The objective audiological examination included electrocochleography, registration of auditory brainstem response (ABR) and otoacoustic emission of short-latency and long-latency evoked auditory nerve action potentials. High-amplitude cochlear microphonic and transient evoked otoacoustic emission (TEOAE) potentials were recorded in 82 patients. In 17 (20.7%) patients, otoacoustic emission disappeared in the course of time even though the microphonic potential remained stable. It was shown that the results of electrical acoustic correction in the patients exhibiting long-latency evoked auditory action potentials and positive ABR to electrical stimulation (positive promontory test) were better than in the remaining cases. The outcome of cochlear implantation to a large extent depended on the localization of the pathological process. Specifically, the results of the treatment of the patients with high-amplitude summation potentials, prolonged latency, and positive auditory action potentials in response to electrical stimulation (typical of pre-synaptic localization of the pathological process) were better than in the patients with normal summation potentials, pathological auditory nerve action potentials, TEOAE, and negative ABR to electrical stimulation (indicative of post-synaptic localization of the pathological process). In the latter group of patients, the results of cochlear implantation were far from being satisfactory. It is concluded that additional information facilitating categorization of the pathological process can be obtained by the identification of the genetic mutations responsible for the development of auditory neuropathies.


Thymoquinone induces apoptosis of human epidermoid carcinoma A431 cells through ROS-mediated suppression of STAT3.
Black seed (Nigella sativa) oil has been used in various dermatological applications, and its major constituent, thymoquinone (TQ) has been shown to exhibit antiproliferative activity against various cancer cells. In this study, we tried to provide a mechanistic basis of apoptosis induced by TQ. Skin squamous carcinoma A431 cells were treated with TQ to monitor the apoptosis induced by TQ. Western blot analysis was performed to detect expression of apoptotic or anti-apoptotic proteins. Cell viability and apoptosis were measured by using the MTT test and FACS analysis, respectively. The induction of intracellular reactive oxygen species (ROS) by TQ was evaluated by 2',7'-dichlorofluorescein diacetate staining. In vivo xenograft study was followed to confirm the antiproliferative effect of TQ. Treatment of A431 cells with TQ-induced apoptosis, which was associated with the induction of p53 and Bax, inhibition of Mdm2, Bcl-2, and Bcl-xl expression, and activation of caspase-9, -7, and -3. TQ inhibited the constitutive phosphorylation and DNA binding activity of signal transducer and activator of transcription-3 (STAT3) in A431 cells by blocking the phosphorylation of the upstream kinase, Src. Moreover, the expression of STAT3 target gene products, cyclin D1 and survivin, was attenuated by TQ treatment. The generation of ROS was increased during TQ-induced apoptosis, and the pretreatment of N-acetyl cysteine, a ROS scavenger, reversed the apoptotic effect of TQ. In vivo study with NOD scid gamma (NSG) mice confirmed the inhibitory effect of TQ on the growth of A431 cells. Our results provide the first demonstration that TQ induces the apoptosis of A431 cells through generation of ROS and inhibition of STAT3 signaling.


Techno-functional and 3D shape analysis applied for investigating the variability of backed tools in the Late Middle Paleolithic of Central Europe.
In the Late Middle Paleolithic of Central Europe, two main cultural complexes have been distinguished: the Micoquian or Keilmessergruppe (KMG), and the Mousterian. Their differences mainly consist in the frequence of some retouched tools and the presence of bifacial technology. When these industries coexist, one element of discussion is the application of different concepts to manufacture tools with the same techno-functionality. This is particularly true for backed artifacts, such as Keilmesser (backed, asymmetrical bifacially-shaped knives) opposed to flake-tools equipped with a natural or knapped back. We conducted a techno-functional analysis of the backed tools from the G-Layer-Complex of Sesselfelsgrotte, one of the main Late Middle Paleolithic sequences in Central Europe, characterized by a combination of KMG and Mousterian aspects. In order to better understand the morpho-metrical data, 3D scans were used for recording technical features and performing semi-automatic geometric morphometrics. Results indicate that the techno-functional schemes of Keilmesser show a moderate variability and often overlap with the schemes of other typological groups. Within bifacial backed knives, a process of imitation of unifacial flake tools' functionaly was recognized particularly in the cutting edge manufacturing. Keilmesser proved to be the long-life, versatile version of backed flake-tools, also due to the recurrent valence as both tool and core. This is why Keilmesser represent an ideal strategic blank when a mobile and multi-functional tool is needed. Based on these data, it is assumed that the relationship between Mousterian and KMG is deeply rooted and the emergence of KMG aspects could be related to constrained situations characterizing the long cold stages of the Early Weichselian. A higher regional mobility caused by the comparably low predictability of resources characterized the subsistence tactics of Neanderthal groups especially at the borders of their overall distribution. For this reason, Keilmesser could have represented an ecological answer before possibly becoming a marker of cultural identity.


Clinical features and disability milestones in multiple system atrophy and progressive supranuclear palsy.
Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are an adult-onset progressive neurodegenerative disorder that are known to display diverse clinical features and disease progression. We aim to characterize the clinical features and disease progression in patients with MSA and PSP by using a number of relevant disability milestones in Koreans. Forty-one patients with MSA and 14 patients with PSP had been enrolled. The mean age at onset of MSA-C, MSA-P and PSP was 56.7 ± 7.8, 62.5 ± 8.0, 68.9 ± 6.1 years respectively. The most commonly reported symptom at disease onset is disequilibrium/dizziness in MSA-C, tremor in MSA-P and frequent falling in PSP. The mean duration of reaching milestones after disease onset in MSA-C were as followings: 20.8 (urinary incontinence), 22.9 (frequent falling), 27.8 (wheelchair bound), 31.8 (dysarthria) and 35.8 months (diagnosis). The mean duration of reaching milestones after disease onset were 22.0 (urinary incontinence), 32.6 (frequent falling and diagnosis), 41.2 (dysarthria), 61.4 months (wheelchair bound) in MSA-P and 16.8 (dysarthria), 21.6 (diagnosis), 21.7 (frequent falling), 24.0 months (wheel chair bound) in PSP. In the case of MSA, dizziness may occur for the first time. Thus, when the patient complains of non-specific dizziness, a follow-up examination to distinguish it from MSA can be helpful. There was a trend for patients with MSA-C to reach more disability milestones than in MSA-P and PSP before diagnosis. It may explain why patients with MSA-C are required more detail history taking and neurologic examination at an earlier stage.


DNA-binding-dependent androgen receptor signaling contributes to gender differences and has physiological actions in males and females.
We used our genomic androgen receptor (AR) knockout (ARKO) mouse model, in which the AR is unable to bind DNA to: 1) document gender differences between males and females; 2) identify the genomic (DNA-binding-dependent) AR-mediated actions in males; 3) determine the contribution of genomic AR-mediated actions to these gender differences; and 4) identify physiological genomic AR-mediated actions in females. At 9 weeks of age, control males had higher body, heart and kidney mass, lower spleen mass, and longer and larger bones compared to control females. Compared to control males, ARKO males had lower body and kidney mass, higher splenic mass, and reductions in cortical and trabecular bone. Deletion of the AR in ARKO males abolished the gender differences in heart and cortical bone. Compared with control females, ARKO females had normal body weight, but 14% lower heart mass and heart weight/body weight ratio. Relative kidney mass was also reduced, and relative spleen mass was increased. ARKO females had a significant reduction in cortical bone growth and changes in trabecular architecture, although with no net change in trabecular bone volume. In conclusion, we have shown that androgens acting via the genomic AR signaling pathway mediate, at least in part, the gender differences in body mass, heart, kidney, spleen, and bone, and play a physiological role in the regulation of cardiac, kidney and splenic size, cortical bone growth, and trabecular bone architecture in females.


Vortex assisted-ionic liquid dispersive liquid-liquid microextraction and spectrophotometric determination of quercetin in tea, honey, fruit juice and wine samples after optimization based on response surface methodology.
The aim of our study is to develop a new vortex assisted-ionic liquid dispersive liquid-liquid microextraction (VA-IL-DLLM) method for preconcentration and determination of the quercetin in tea, honey, fruit juice and wine samples by spectrophotometry. The method is based on pH sensitive ion-pair formation between quercetin and rhodamine B at pH 6.5 by donor-acceptor mechanism, and then dispersion of the complex in the fine-drops of ionic liquid (IL). In this context, the effects of pH, concentrations of ion-pairing reagent, the IL, vortex time and dispersive solvent type on the preconcentration process of quercetin were investigated using a 2-level-5-factor central composite half fraction design (CCD) as experimental design for response surface methodology (RSM). Quantitative model was developed to determine the quercetin in food samples, and it is verified by analysis of variance (ANOVA) at a 95% confidence level (P < 0.05). Response surface plots and contour plots obtained by the model are used to determine the interactions of experimental variables. After the optimization, calibration graph was obtained between 35 and 750 μg L-1 with the detection limit of 10.2 μg L-1. The recovery and relative standard deviations (RSD%) were in range of 94-104%, and in range of 2.5-4.2%, respectively. The accuracy and precision of the method were tested by the experimental studies such as recoveries, intermediate precision, trueness and expanded uncertainty. A comparison of the current results to those reported for other studies is also presented.


Quantal amplitude at the cone ribbon synapse can be adjusted by changes in cytosolic glutamate.
Vision is encoded at photoreceptor synapses by the number of released vesicles and size of the post-synaptic response. We hypothesized that elevating cytosolic glutamate could enhance quantal size by increasing glutamate in vesicles. We introduced glutamate (10-40 mM) into cone terminals through a patch pipette and recorded excitatory post-synaptic currents (EPSCs) from horizontal or OFF bipolar cells in the Ambystoma tigrinum retinal slice preparation. Elevating cytosolic glutamate in cone terminals enhanced EPSCs as well as quantal miniature EPSCs (mEPSCs). Enhancement was prevented by inhibiting vesicular glutamate transport with 1S,3R-1-aminocyclopentane-1,3-dicarboxylate in the patch pipette. A low affinity glutamate receptor antagonist, γD-glutamylglycine (1 mM), less effectively inhibited EPSCs evoked from cones loaded with glutamate than control cones indicating that release from cones with supplemental glutamate produced higher glutamate levels in the synaptic cleft. Raising presynaptic glutamate did not alter exocytotic capacitance responses and exocytosis was observed after inhibiting glutamate loading with the vesicular ATPase inhibitor, concanamycin A, suggesting that release capability is not restricted by low vesicular glutamate levels. Variance-mean analysis of currents evoked by flash photolysis of caged glutamate indicated that horizontal cell AMPA receptors have a single channel conductance of 10.1 pS suggesting that ~8.7 GluRs contribute to each mEPSC. Quantal amplitude at the cone ribbon synapse is capable of adjustment by changes in cytosolic glutamate levels. The small number of channels contributing to each mEPSC suggests that stochastic variability in channel opening could be an important source of quantal variability.