Assessment of risk of ALS conferred by the GGGGCC hexanucleotide repeat expansion in C9orf72 among first-degree relatives of patients with ALS carrying the repeat expansion.
We aimed to estimate the age-related risk of ALS in first-degree relatives of patients with ALS carrying the C9orf72 repeat expansion. We included all patients with ALS carrying a C9orf72 repeat expansion in The Netherlands. Using structured questionnaires, we determined the number of first-degree relatives, their age at death due to ALS or another cause, or age at time of questionnaire. The cumulative incidence of ALS among first-degree relatives was estimated, while accounting for death from other causes. Variability in ALS risk between families was evaluated using a random effects hazards model. We used a second, distinct approach to estimate the risk of ALS and FTD in the general population, using previously published data. In total, 214 of the 2,486 (9.2%) patients with ALS carried the C9orf72 repeat expansion. The mean risk of ALS at age 80 for first-degree relatives carrying the repeat expansion was 24.1%, but ranged between individual families from 16.0 to 60.6%. Using the second approach, we found the risk of ALS and FTD combined was 28.7% (95% CI 17.8%-54.3%) for carriers in the general population. On average, our estimated risk of ALS in the C9orf72 repeat expansion was lower compared to historical estimates. We showed, however, that the risk of ALS likely varies between families and one overall penetrance estimate may not be sufficient to describe ALS risk. This warrants a tailor-made, patient-specific approach in testing. Further studies are needed to assess the risk of FTD in the C9orf72 repeat expansion.


Shear induced drainage in foamy yield-stress fluids.
Shear induced drainage of a foamy yield-stress fluid is investigated using MRI techniques. Whereas the yield stress of the interstitial fluid stabilizes the system at rest, a fast drainage is observed when a horizontal shear is imposed. It is shown that the sheared interstitial material behaves as a viscous fluid in the direction of gravity, the effective viscosity of which is controlled by shear in transient foam films between bubbles. Results provided for several bubble sizes are not captured by the R2 scaling classically observed for foams. Furthermore, foam films are found to be responsible for the unexpected arrest of drainage, thus trapping irreversibly a significant amount of interstitial liquid.


Evaluation of two main RNA-seq approaches for gene quantification in clinical RNA sequencing: polyA+ selection versus rRNA depletion.
To allow efficient transcript/gene detection, highly abundant ribosomal RNAs (rRNA) are generally removed from total RNA either by positive polyA+ selection or by rRNA depletion (negative selection) before sequencing. Comparisons between the two methods have been carried out by various groups, but the assessments have relied largely on non-clinical samples. In this study, we evaluated these two RNA sequencing approaches using human blood and colon tissue samples. Our analyses showed that rRNA depletion captured more unique transcriptome features, whereas polyA+ selection outperformed rRNA depletion with higher exonic coverage and better accuracy of gene quantification. For blood- and colon-derived RNAs, we found that 220% and 50% more reads, respectively, would have to be sequenced to achieve the same level of exonic coverage in the rRNA depletion method compared with the polyA+ selection method. Therefore, in most cases we strongly recommend polyA+ selection over rRNA depletion for gene quantification in clinical RNA sequencing. Our evaluation revealed that a small number of lncRNAs and small RNAs made up a large fraction of the reads in the rRNA depletion RNA sequencing data. Thus, we recommend that these RNAs are specifically depleted to improve the sequencing depth of the remaining RNAs.


Resolution and absolute configuration assignment of a natural racemic chromane from Peperomia obtusifolia (Piperaceae).
The resolution of the natural racemic chromane 3,4-dihydro-5-hydroxy-2,7-dimethyl-8-(3''-methyl-2''-butenyl)-2-(4'-methyl-1',3'-pentadienyl)-2H-1-benzopyran-6-carboxylic acid (1) isolated from the leaves of Peperomia obtusifolia has been accomplished using stereoselective HPLC. The absolute configuration of the resolved enantiomers was determined by the analysis of optical rotations and CD spectra. The finding of a racemic mixture instead of an enantiomerically pure metabolite raises questions about the final steps in the biosynthesis of this class of natural products, suggesting that the intramolecular chromane ring formation step may not be enzymatically controlled at all in P. obtusifolia.


[Metabolic syndrome and other factors cardiovascular risk in workers of a plant of vinyl polychloride].
To establish the prevalence of Metabolic Syndrome and other factors of cardiovascular risk in a population of masculine workers of the operative area of the plant of vinyl poly chloride of a petrochemical complex, in the occident of Venezuela. An analytical cross sectional study was performed in 84 workers, they was determined size, weight, arterial pressure, abdominal circumference, body mass index, smoke, alcoholic habits and medicaments consumption. Additionally, 10 ml fasting venous blood sample was taken to determine glycemia, total cholesterol, HDL-C, LDL-C and VLDL-C. The diagnosis of the metabolic syndrome was carried out under the approaches of NCEP/ATP III criteria's. The prevalence of metabolic syndrome was of 27 cases (32 ,1 %), 21 cases (77,7 %) in ages among 26-40 years. The alcohol consumption (91 ,6 %), LDL-C (64,3 %), high systolic arterial pressure (59,5 %), obesity (56,6 %) and high triglycerides (55,9 %) were the principal's cardiovascular factors risk detected. The biochemical parameters were significantly higher in the men with clinical diagnosis of metabolic syndrome in comparison with those that didn't present the syndrome (p < 0.05). To weigh that the prevalence of metabolic syndrome was not so high, the factors of cardiovascular risk in an individual way were high, considering that the hard-working population is young is necessary to implement programs of prevention and changes of lifestyles to minimize the risk of coronary illness and vascular brain that lead to labour s disability.


Photoprotection of ultraviolet-B filters: Updated review of endocrine disrupting properties.
The Ultraviolet (UV) radiation is emitted by the sun and is part of the electromagnetic spectrum. There are three types of UV rays (UV-A, UV-B and UV-C), however only UV-A and UV-B have biologic effects in humans, with UV-B radiation being primarily responsible for these effects. Among the measures of photoprotection advised by the health authorities, the topical application of sunscreens (containing UV-B filters) is the preferred worldwide. Currently, octylmethoxycinnamate (OMC) is the most commonly used UV-B filter in sunscreens. Their application has proven to be effective in preventing burns, but its efficiency against melanoma continues under intense controversy. Studies have shown that OMC behaves like an endocrine disruptor, altering the normal functioning of organisms. However, few studies have evaluated their multiple hormonal activities. Some studies suggest that the OMC exerts an estrogenic, anti-androgenic, anti-progestenic and anti-thyroid activity. But, through what mechanisms? In humans, few studies were performed, and some questions remain unclear. Thus, the purpose of this review is to present the multiple hormonal activities established for the OMC, making a critical analysis and relationship between the effects in cells, animals and humans.


Malignant mesodermal mixed tumor of the ureter.
Malignant mesodermal mixed tumor comprised of epithelial and nonepithelial components is rarely encountered in the urological field. Only 6 cases of malignant mesodermal mixed tumor of the ureter have previously been reported in the literature. We recently encountered a 7th case of malignant mesodermal mixed tumor of the ureter and describe the case in detail. The etiology of malignant mesodermal mixed tumor is also discussed.


Risk of Malignancy in Thyroid Incidentaloma is Not Increased in Overweight or Obese Patients, but in Young Patients.
Thyroid incidentaloma is defined as an unsuspected, asymptomatic thyroid lesion that is discovered on an imaging study or during an operation unrelated to the thyroid gland. We aim to evaluate the relationship between overweight or obese and risk of malignancy in patients with thyroid incidentaloma detected by F18-flurodeoxyglucose positron emission tomography/computed tomography and factors to predict risk of malignancy in thyroid incidentaloma. From January 2010 to December 2013, a total of 238 patients were eligible for this study. Using the Bethesda system for reporting thyroid cytopathology, categories I-III were defined as a nonmalignancy and categories V-VI were defined as a malignancy. When patients with body mass index (BMI) of less than 23 and 23 or more were divided into two groups of normal and overweight or obese, risk of malignancy of thyroid incidentaloma was not significantly different between two groups (P = 0.1812). In logistic regression analysis, age was the only variable that showed a significant association with malignancy of thyroid incidentaloma (odds ratio 0.9608, P = 0.0021). However, none of sex, height, weight, and BMI was predictor of malignancy of thyroid incidentaloma. We demonstrated that being overweight or obese did not increase rate of malignancy in patients with thyroid incidentaloma.


Conserved codon composition of ribosomal protein coding genes in Escherichia coli, Mycobacterium tuberculosis and Saccharomyces cerevisiae: lessons from supervised machine learning in functional genomics.
Genomics projects have resulted in a flood of sequence data. Functional annotation currently relies almost exclusively on inter-species sequence comparison and is restricted in cases of limited data from related species and widely divergent sequences with no known homologs. Here, we demonstrate that codon composition, a fusion of codon usage bias and amino acid composition signals, can accurately discriminate, in the absence of sequence homology information, cytoplasmic ribosomal protein genes from all other genes of known function in Saccharomyces cerevisiae, Escherichia coli and Mycobacterium tuberculosis using an implementation of support vector machines, SVM(light). Analysis of these codon composition signals is instructive in determining features that confer individuality to ribosomal protein genes. Each of the sets of positively charged, negatively charged and small hydrophobic residues, as well as codon bias, contribute to their distinctive codon composition profile. The representation of all these signals is sensitively detected, combined and augmented by the SVMs to perform an accurate classification. Of special mention is an obvious outlier, yeast gene RPL22B, highly homologous to RPL22A but employing very different codon usage, perhaps indicating a non-ribosomal function. Finally, we propose that codon composition be used in combination with other attributes in gene/protein classification by supervised machine learning algorithms.


Development of an endothelial cell-restricted transgenic reporter rat: a resource for physiological studies of vascular biology.
Here, we report the generation of a Cre-recombinase (iCre) transgenic rat, where iCre is driven using a vascular endothelial-cadherin (CDH5) promoter. The CDH5 promoter was cloned from rat pulmonary microvascular endothelial cells and demonstrated ~60% similarity to the murine counterpart. The cloned rat promoter was 2,508 bp, it extended 79 bp beyond the transcription start site, and it was 22,923 bp upstream of the translation start site. The novel promoter was cloned upstream of codon-optimized iCre and subcloned into a Sleeping Beauty transposon vector for transpositional transgenesis in Sprague-Dawley rats. Transgenic founders were generated and selected for iCre expression. Crossing the CDH5-iCre rat with a tdTomato reporter rat resulted in progeny displaying endothelium-restricted fluorescence. tdTomato fluorescence was prominent in major arteries and veins, and it was similar in males and females. Quantitative analysis of the carotid artery and the jugular vein revealed that, on average, more than 50% of the vascular surface area exhibited strong fluorescence. tdTomato fluorescence was observed in the circulations of every tissue tested. The microcirculation in all tissues tested displayed homogenous fluorescence. Fluorescence was examined across young (6-7.5 mo), middle (14-16.5 mo), and old age (17-19.5 mo) groups. Although tdTomato fluorescence was seen in middle- and old-age animals, the intensity of the fluorescence was significantly reduced compared with that seen in the young rats. Thus, this endothelium-restricted transgenic rat offers a novel platform to test endothelial microheterogeneity within all vascular segments, and it provides exceptional resolution of endothelium within-organ microcirculation for application to translational disease models.NEW & NOTEWORTHY The use of transgenic mice has been instrumental in advancing molecular insight of physiological processes, yet these models oftentimes do not faithfully recapitulate human physiology and pathophysiology. Rat models better replicate some human conditions, like Group 1 pulmonary arterial hypertension. Here, we report the development of an endothelial cell-restricted transgenic reporter rat that has broad application to vascular biology. This first-in-kind model offers exceptional endothelium-restricted tdTomato expression, in both conduit vessels and the microcirculations of organs.


Management of uterine fibroids in pregnancy: recent trends.
The review analyzes how fibroids may influence pregnancy and how myomas may be modified by pregnancy. The most important clinical aspect concerns the impact of myoma on pregnancy and the possibility of a well tolerated surgical treatment for the mother and her fetus, preserving maternal reproductive capacity. Fibroids significantly increase in size during early pregnancy and then decrease in the third trimester. Although most women with uterine fibroids have a regular pregnancy, data from the literature suggest that they may have a higher risk of fertility problems and pregnancy complications. Myomectomy can increase the rate of pregnancy in women with infertility, attempting to restore a normal anatomy and reduce uterine contractility and local inflammation associated with the presence of fibroids, improving the blood supply. Current evidence does not suggest routine myomectomy during pregnancy or at the cesarean birth, as fibroids-related complications are rare and may be overcome by the risks of surgery. However, in selected cases, myomectomy is a feasible and safe technique and associated to a good outcome.The diagnosis of myomas in pregnancy may require attention for the adequate management to preserve maternal and fetal well-being.


Significance of p53 expression in ovarian tumors and its correlation to the morphological differentiation.
Cancer of breast and cervix reign supreme among the fatal diseases in women globally. Interestingly the ovarian cancer has the highest mortality rate. This is attributed to its late clinical presentation and delayed diagnosis. The expression of p53 throws light on the prognosis of ovarian tumors. The surface epithelial tumors, especially the serous cystadenocarcinoma and non Hodgkin lymphoma of ovary where in the expression p53 was high compared to the benign and borderline tumors. Further the expression of p53 in tumors arising from germinal cells, sex-cord stromal cells are observed to be very low. The expression of p53 and its correlation to the morphology enhances the prognostic significance.


Organizing training workshops on gene literature retrieval, profiling, and visualization for early career researchers.
Early-career researchers must acquire the skills necessary to effectively search and extract information from biomedical literature. This ability is for instance crucial for evaluating the novelty of experimental results, and assessing potential publishing opportunities. Given the rapidly growing volume of publications in the field of biomedical research, new systematic approaches need to be devised and adopted for the retrieval and curation of literature relevant to a specific theme. In this context, we present a hands-on training curriculum aimed at retrieval, profiling, and visualization of literature associated with a given topic. The curriculum was implemented in a workshop in January 2021. Here we provide supporting material and step-by-step implementation guidelines with the ISG15 gene literature serving as an illustrative use case. Workshop participants can learn several skills, including: 1) building and troubleshoot PubMed queries in order to retrieve the literature associated with a gene of interest; 2) identifying key concepts relevant to given themes (such as cell types, diseases, and biological processes); 3) measuring the prevalence of these concepts in the gene literature; 4) extracting key information from relevant articles, and 5) developing a background section or summary on the basis of this information. Finally, trainees can learn to consolidate the structured information captured through this process for presentation via an interactive web application.


Curcumin Regulates Anti-Inflammatory Responses by JAK/STAT/SOCS Signaling Pathway in BV-2 Microglial Cells.
Microglia play important physiological roles in central nervous system (CNS) homeostasis and in the pathogenesis of inflammatory brain diseases. Inflammation stimulates microglia to secrete cytokines and chemokines that guide immune cells to sites of injury/inflammation. Neuroinflammation is also strongly implicated in the pathogenesis of a number of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, for which nutritional intervention could represent a benefit due to a lack of clinically efficacious drugs. To this end, the anti-inflammatory mechanisms of several phytochemicals, including curcumin, have been extensively studied. The present experiments show that the administration of curcumin is able to increase the production of the anti-inflammatory cytokines, IL-4 and IL-10, in murine BV-2 microglial cells treated with lipopolysaccharide (LPS). Consistent with these data, curcumin stimulation upregulates the expression of Suppressors of cytokine signaling (SOCS)-1, whereas phosphorylation of the JAK2 and STAT3 was reduced. Taken together, these results provide evidence that curcumin is able to regulate neuroinflammatory reactions by eliciting anti-inflammatory responses in microglia through JAK/STAT/SOCS signaling pathway modulation.


Effects of Transcranial Direct Current Stimulation on Upper Limb Muscle Strength and Endurance in Healthy Individuals: A Systematic Review and Meta-Analysis.
Whether transcranial direct current stimulation (tDCS) can improve upper limb muscle strength and endurance in healthy subjects is still controversial. This article reviews the relevant literature on the use of tDCS to improve upper limb muscle strength and endurance in healthy individuals. We systematically searched the Cochrane Library, PubMed, EMBASE, and the Web of Science until September 4, 2021. Randomized parallel or crossover experimental studies on the effects of tDCS on upper limb muscle strength and endurance in healthy individuals were included. Review Manager 5.3 software was used to evaluate methodological quality and analyze the combined effect of the included literature. Twelve studies (189 participants) were included in the qualitative synthesis, and nine studies (146 participants) were included in the meta-analysis. Compared with the control group, the tDCS intervention had no significant effect on improving upper limb muscle strength [I2 = 0%, 95% CI (-0.79, 0.23), p = 0.98, MD = 0.01]. In this analysis, tDCS had a significant heterogeneity (I2 = 87%) in improving upper limb muscle endurance compared with the control group. After the subgroup analysis and the sensitivity analysis, the source of heterogeneity was excluded. The final results showed that tDCS had a significant effect on improving upper limb muscle endurance [I2 = 0%, 95% CI (1.91, 4.83), p < 0.00001, MD = 3.37]. tDCS has no significant effect on improvement of upper limb muscle strength, but has a significant effect on improving upper limb endurance performance (especially on the non-dominant side).


Extended Car-Parrinello molecular dynamics and electronic g-tensors study of benzosemiquinone radical anion.
Car-Parrinello molecular dynamics simulations of benzoquinone and benzosemiquinone radical anion in both aqueous solution and the gas phase have been carried out at ambient conditions. Hydrogen bonding is considerably more extensive to the anionic than to the neutral aqueous system. In addition to the conventional hydrogen bonding to the carbonyl oxygen atoms, T-stacked hydrogen bonding to the pi-system is statistically and energetically significant for the semiquinone anion but not for the neutral quinone. EPR g-tensors have been calculated at DFT level for snapshots taken at regular intervals from the gas-phase and solution semiquinone anion trajectories. Different criteria for extraction of semiquinone/water clusters from the solution trajectory give insight into the effects of different interactions on the g-tensor, as does correlation of the g-tensor with statistically significant hydrogen-bond configurations identified along the trajectories. Comparison of gas-phase and solution results indicates opposite directions of direct electronic and indirect structural influences of hydrogen bonding on g-tensors. Short-time oscillations in g(x) along the trajectory are due mainly to C-O bond vibrations.


Influence of biochemical alterations on arterial stiffness in patients with end-stage renal disease.
The incremental elastic modulus of the common carotid and radial arteries is increased in patients with end-stage renal disease (ESRD), independently of blood pressure, wall stress, and the presence of atherosclerotic alterations. Whether biochemical factors may be involved in the arterial changes and related to renal dysfunction remain largely ignored. To assess this question, we measured aortic (carotid-femoral), upper-limb (carotid-radial), and lower-limb (femoral-tibial) pulse wave velocity (PWV) in 74 ESRD patients undergoing hemodialysis in comparison with 57 control subjects similar in age, sex ratio, and mean blood pressure. We evaluated arterial blood pressure by sphygmomanometry, aortic calcifications and cardiac mass by echography, and routine biochemical parameters, total plasma homocysteine, and plasma endothelin levels by standard techniques. In the population of patients with ESRD, on the basis of multiple stepwise regression analysis, aortic PWV was positively and independently correlated with systolic blood pressure (P<.0001), age (P<.0001), prevalence of aortic calcification (P=.0004), and the prevalence of diabetes mellitus (P=.0043). Upper-limb PWV was influenced exclusively by mean blood pressure (P<.0001). Lower-limb PWV was positively and independently correlated with plasma total homocysteine (P=.0004) and plasma endothelin (P=.0187) only. At any vascular site, PWV was not independently correlated with tobacco consumption; plasma levels of cholesterol, triglyceride, fibrinogen, or hemoglobin; body mass index; or the presence of bilateral nephrectomy. Finally, plasma homocysteine was independently correlated with cardiac mass (P=.0022). This study provides evidence that in ESRD patients, the stiffness of the arterial wall and cardiac mass are strongly influenced by biochemical factors related to the kidney alterations and are independent of age and blood pressure level. Increased plasma endothelin and homocysteine may be specifically involved in the vascular damage of lower limbs.


Os-odontoideum leading to atlanto-axial instability--report of surgery in four cases.
Os odontoideum can lead to atlantoaxial instability, which can be either reducible or a fixed dislocation. We present surgical management in four patients with os odontoideum at our center. Two of these had reducible dislocations and were managed by posterior transarticular screw fixation. Other two had fixed dislocations necessitating posterior decompression and occipitocervical fixation.


Use of radiographic features in COVID-19 diagnosis: Challenges and perspectives.
The rapid surge and wide spread of the coronavirus disease-2019 (COVID-19) overshadows the entire medical industries worldwide. The stringent medical resources hinder the diagnostic capacity globally, while 84 000 of new cases confirmed within a single day of April 14, 2020. Real-time reverse-transcription polymerase chain reaction (RT-PCR) with is the current first-line diagnosis, but the false-negative rate remains concerned. Radiographic technologies and tools, including computed tomography (CT) and chest X-ray, were applied for initial screening and follow-up, from which the tools provide detail diagnosis with specific pathologic features for staging and treatment arrangement. Although the radiographic imaging is found less sensitive, numerous CT-positive patients were not screened out by RT-PCR initially and later confirmed as COVID-19 positive. Besides, the shortage of sampling kits and the longer turn-over time of PCR examinations in some areas were noticed due to logistic issues and healthcare burden. In this review, we will discuss the challenges and the future perspectives of using radiographic modalities for COVID-19 diagnosis in view of securing human lives amid the crisis.


Economic burden from smoking-related diseases in Thailand.
To assess economic burden attributable to smoking in Thailand in 2009. A prevalence-based, disease-specific cost of illness approach was used to estimate the direct medical costs, indirect medical costs, productivity loss due to premature deaths and absenteeism caused by smoking-related diseases. Direct healthcare costs were obtained from the inpatient and outpatient charge database at the National Health Security Office and the Central Office for Healthcare Information. Indirect healthcare costs were obtained from the Health and Welfare Survey. The household Socioeconomic Survey provided data on income of the population. Costs were estimated for 7 disease groups, namely, lung cancer, chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD), upper aerodigestive tract cancer, other cancer, other respiratory diseases and other medical conditions. Smoking Attributable Fractions were derived from the 2009 Thai Burden of Disease study. Total economic burden of smoking amounted to 74.88 billion Thai Baht (THB) (95% CI 74.59 to 75.18) (US$2.18, 95% CI US$2.17 to US$2.19 billion). Of this, most of the burden resulted from productivity loss 62.24 billion THB (95% CI 62.05 to 62.44) (US$1.81, 95% CI US$1.81 to US$1.82 billion). Total medical cost was 12.64 billion THB (12.44 to 12.85) (US$0.37, 95% CI US$0.36 to US$0.37 billion). Excluding other medical conditions, the direct healthcare costs were highest for CVD, followed by COPD and other respiratory diseases, respectively. All together, the total cost of smoking accounted for 0.78% (95% CI 0.78% to 0.79%) of the national gross domestic product and about 18.19% (95% CI 18.12% to 18.27%) of total health expenditure. The total economic loss from smoking-related diseases highlights the significant loss to the society, health sector and the country's economy. Such information is crucial for informing national public health policy, particularly when a conflict arises between the economy and health.


Acute duodenal intramural hematoma complicated by acute pancreatitis-a rare complication of endoscopic epinephrine injection therapy.
Intramural duodenal hematoma (IDH) is a rare complication in endoscopic management of ulcer hemorrhage. Usually noted in cases of blunt abdominal trauma, non-traumatic IDHs have been reported in individuals on anticoagulation, with blood disorders, pancreatic diseases and in endoscopic procedures such as biopsy, sclerotherapy and argon plasma coagulation. Patients may be asymptomatic or present with acute blood loss anemia, abdominal pain or vomiting. We report a case of an 83-year-old man with melena and syncope who underwent endoscopy for bleeding ulcer control and subsequently developed acute pancreatitis due to an acute IDH. Computed tomography (CT) scan confirms the diagnosis. Most cases are conservatively managed however when unsuccessful, laparoscopic surgical drainage or ultrasound or CT guided drainage can be performed.


Characterization and Biological Evaluation of Propolis from Poland.
In this study, we assessed the therapeutic potential of propolis from Poland and performed chemical analysis by GC-MS, as well as determined its botanical origin. Chemical constituents typical for bud exudates of Populusnigra (section Aigeiros) were determined, however, glycerol esters of phenolic acids, as well as unusually high amounts of p-coumaric and ferulic acid and their benzyl esters, were also detected. These constituents are characteristic for buds of Populustremula (section Leuce). We also evaluated the antiproliferative effect of propolis extracts against nine human cancer cell lines. Additionally, promising antibacterial activity of the dichloromethane extract (Minimal Inhibitory Concentration MIC values of 0.95-1.24 mg/mL), as well as a moderate antifungal activity (MIC values of 1.25-1.40 mg/mL), was noticed. Propolis from Poland appeared as a rich source of antibacterial and antiproliferative compounds and this confirmed that it is a valuable natural product with the potential to improve human health.


A rare sequel following cornual ectopic pregnancy: a case report.
One of the major concerns following cornual ectopic pregnancy, as shown in this case, is uterine rupture in future pregnancies. Uterine rupture has been described at 20 weeks gestation in a woman who had a cornual pregnancy treated by salpingectomy at 24 weeks, and as such it has been suggested by some experts that suturing the uterine wall to reinforce the defective area is advisable. Conversely, term deliveries have been described in patients with laparoscopic treatment of cornual pregnancies without reinforcing sutures. There is general agreement that suturing the uterine wall should be performed in cases where the cornual pregnancy sac extends into the endometrial cavity. Long-term follow-up of patients treated with cornual pregnancies with endometrial involvement may reveal the optimum treatment technique. In addition to surgical technique, patient counselling and appropriate debriefing regarding increasing interpregnancy interval is paramount in reducing maternal and fetal morbidity. Proper documentation in operative notes is vitally important for future reference.


Comparison of the qualified occupational physician systems in the United Kingdom and Japan.
The British educational system of occupational medicine was compared to the Japanese system. Furthermore, a comparison was carried out between the certified occupational physician (COP) recognized by the Japan Society for Occupational Health in Japan and the Associateship of the Faculty of Occupational Medicine (AFOM) by the Faculty of Occupational Medicine (FOM) which is a part of the Royal College of Physicians in the United Kingdom. Judging from the comparison of the minimum total training period, the clinical training period, the occupational health training period, the method of examination and the success rate between COP and AFOM, it is suggested that the British system of occupational physicians may be better as a training system for occupational medicine and may regard occupational clinical training as more important than the Japanese system does. A comparison of a Diploma in Occupational Medicine (Dip Occ Med) approved by the FOM and the certification of occupational physicians by the Japan Medical Association has shown that the former has an examination but there is no test system in the latter. It should be discussed whether an examination system for the certification of occupational physicians should be introduced into the Japanese system in the near future.


[Using ROC curves in clinical investigation: theoretical and practical issues].
Numerous diagnostic tests report their results quantitatively, using continuous scales. Receiver operating characteristic curve (ROC) analysis provides a statistical method for the assessment of the diagnostic accuracy of these tests, being used for three specific purposes: determine of the cutoff value with the highest sensitivity and specificity, evaluate the discriminative capacity of the diagnostic test, in other words, its ability to differentiate healthy versus sick individuals, and compare the discriminative capacity of two or more diagnostic tests that express their results as continuous scales. Based on a real clinical investigation, this article illustrates theoretical aspects regarding the construction of ROC curves, being its objective to help readers and investigators interpret correctly their results.


Haemobilia due to hepatic artery pseudoaneurysm.
An 83-year-old woman with a history of hepaticoduodenostomy 20 years ago was admitted with upper gastrointestinal bleeding. Emergency upper gastrointestinal endoscopy revealed multiple blood clots over the stomach and first and second parts of the duodenum. The cannulation of the biliary tree with a flexible end-viewing endoscope exposed the presence of blood clot inside biliary lumen and a semipedunculated polyp which, at first, appeared to be the cause of haemorrhage. A few days after polypectomy, patient was discharged home, however, was admitted again with massive bleeding and selective angiography demonstrated a pseudoaneurysm of left hepatic artery. Angioembolisation was performed and haemorrhage was stopped afterwards.


A polymorphism in the microsomal triglyceride transfer protein can predict the response to antiviral therapy in Egyptian patients with chronic hepatitis C virus genotype 4 infection.
A polymorphism in the microsomal triglyceride transfer protein (MTP) is associated with hepatic fibrosis, and carriers showed higher levels of steatosis, higher levels of hepatitis C virus (HCV) RNA and advanced fibrosis. The aim of this study was to study MTP expression pattern in HCV patients and impact of the MTP polymorphism on the response to antiviral therapy. One hundred consecutive naive HCV genotype 4 patients were recruited to receive antiviral therapy, and 40 control subjects were also recruited. Demographic, laboratory, and histopathology data were collected. DNA was isolated, and the samples were subjected to polymerase chain reaction analysis and genotyping for MTP by restriction fragment length polymorphism analysis. Patients and controls were age- and sex-matched (male/female, 56/44, age, 39.2±7.8 years for patients with HCV; male/female, 18/22, age, 38.1±8.1 years for controls). MTP single nucleotide polymorphisms (SNPs) (GG, GT, TT) and alleles (G, T) in the patients versus the controls were 70%, 21%, 9% & 80.5%, 19.5% versus 10%, 87.5%, 2.5% & 53.8%, 46.3%, respectively (p=0.0001). The sustained viral response (SVR) of the patients was 60%. SNPs in MTP genotypes (GG, GT, and TT) and alleles (G and T) in the responders and nonresponders were 71.7%, 25%, 3.3% & 84.2%, 15.8% versus 67.5%, 15%, 17.5% & 75%, 25% (p=0.038 and p=0.109, respectively). A multivariate analysis showed that the GT genotype was an independent predictor of SVR (area under the curve 90% and p=0.0001). MTP could be a new predictor for SVR to antiviral therapy in patients with HCV genotype 4 infection.


Mother-child interaction and resilience in children with early developmental risk.
Although prenatal and genetic factors make strong contributions to the emergence of intellectual disability (ID), children's early environment may have the potential to alter developmental trajectories and to foster resilience in children with early risk. The present study examined mother-child interaction and the promotion of competence in 50 children with early developmental delays. Three related but distinct aspects of mother-child interaction were considered: maternal technical scaffolding, maternal positive sensitivity, and mother-child dyadic pleasure. Children were classified as exhibiting undifferentiated delays at age 3, based upon performance on developmental assessments and the absence of known genetic syndromes. Mother-child interaction was assessed at age 4 through observational ratings of structured laboratory tasks, and through naturalistic home observations. ID was identified at age 5 using the dual criteria of clinically significant delays in cognitive functioning and adaptive behavior. Maternal technical scaffolding and dyadic pleasure each uniquely predicted reduced likelihood of later ID, beyond the contributions of children's early developmental level and behavioral functioning. Follow-up analyses suggested that mother-child interaction was primarily important to resilience in the area of adaptive behavior, with scaffolding and dyadic pleasure differentially associated with particular subdomains. Implications for theories of intellectual disability and for family-based early intervention and prevention efforts are discussed.


Misdiagnosis in vertebral osteomyelitis: problems and factors.
One hundred and one cases diagnosed with vertebral osteomyelitis were evaluated for misdiagnosis and both factors and outcomes of misdiagnosis were assessed. There were 67 patients with tuberculous spondylitis and 34 patients with pyogenic vertebral osteomyelitis. Misdiagnosis occurred in 33.7 per cent of the cases. The average delayed diagnosis time was 2.6 months (range, 0.2 to 12). Age between 60 to 70 years was the most frequent group for misdiagnosis, while the most frequent area of misdiagnosis was the lumbar spine. Metastatic carcinoma, spinal stenosis, herniated nucleus palposus and back strain were common initial misdiagnoses. The factors, age group, absence of fever and positive straight leg raising test (SLRT) were associated with misdiagnosis in univariate analysis and multivariate analysis (odds ratio 3.40 (95%CI:1.07-11.94), 3.47 (95%CI:1.20-10.05), and 24.47 (95%CI:2.18-274.28), respectively) Misdiagnosis was statistically significantly associated with the result of treatment. This paper emphasizes that the elderly age group, absence of fever and positive SLRT are the independent factors which increase the risk of misdiagnosis of vertebral osteomyelitis.


A EuroPrevall review of factors affecting incidence of peanut allergy: priorities for research and policy.
Peanuts are extensively cultivated around the world, providing a foodstuff that is both cheap to produce and nutritious. However, allergy to peanuts is of growing global concern, particularly given the severity of peanut-allergic reactions, which can include anaphylaxis and death. Consequently, it is important to understand the factors related to the prevalence of peanut allergy in order to inform efforts to ameliorate or pre-empt the condition. In this article we review evidence for the relevance of factors hypothesized to have some association with allergy prevalence, including both genetic and environmental factors. Although our analysis does indicate some empirical support for the importance of a number of factors, the key finding is that there are significant data gaps in the literature that undermine our ability to provide firm conclusions. We highlight these gaps, indicating questions that need to be addressed by future research.


One- and two-dimensional Cd(II) coordination polymers constructed from 2-(2-methyl-1H-benzimidazol-1-yl)acetate ligands.
The one- and two-dimensional polymorphic cadmium polycarboxylate coordination polymers, catena-poly[bis[μ2-2-(2-methyl-1H-benzimidazol-1-yl)acetato-κ(3)N(3):O,O']cadmium(II)], [Cd(C10H9N2O2)2]n, and poly[bis[μ2-2-(2-methyl-1H-benzimidazol-1-yl)acetato-κ(3)N(3):O,O']cadmium(II)], also [Cd(C10H9N2O2)2]n, were prepared under solvothermal conditions. In each structure, each Cd(II) atom is coordinated by four O atoms and two N atoms from four different ligands. In the former structure, two crystallographically independent Cd(II) atoms are located on twofold symmetry axes and doubly bridged in a μ2-N:O,O'-mode by the ligands into correspondingly independent chains that run in the [100] and [010] directions. Chains containing crystallographically related Cd(II) atoms are linked into sheets via π-π stacking interactions. Sheets containing one of the distinct types of Cd(II) atom are stacked perpendicular to [001] and alternate with sheets containing the other type of Cd(II) atom. The second complex is a two-dimensional homometallic Cd(II) (4,4) net structure in which each Cd(II) atom is singly bridged to four neighbouring Cd(II) atoms by four ligands also acting in a μ2-N:O,O'-mode. A square-grid network results and the three-dimensional supramolecular framework is completed by π-π stacking interactions between the aromatic ring systems.


Zuclopenthixol acetate in viscoleo in acutely disturbed psychotic patients.
This report describes an open pilot study of ten acutely disturbed and agitated psychotic patients who received CPT-A zuclopenthixol injections. The dosage ranged from 50 mg to 100 mg. Sedative effects were noticed already after 2 hours, and the patients were all sleepy and sedated after 8 hours. There was a definite improvement in the CGI within 24 hours. The BPRS improved within 24 hours, having the greatest effect on activation, anxiety, depression, and hostile suspiciousness. These effects were sufficient to control these patients. The findings show a rapid onset of therapeutic effect, with no side effects, a duration of 2-3 days and a good local tolerability.


Safety studies of the oral rabies vaccine SAD B19 in striped skunk (Mephitis mephitis).
Safety of the modified live rabies virus vaccine, SAD B19, was studied in striped skunks (Mephitis mephitis). Seven skunks received 10(7.9) foci formatting units by direct oral administration. In four cages, a vaccinated animal was placed with a control animal, the other three vaccinated skunks were housed individually. Saliva and nasal swabs were collected 1, 2, 4, 24, 48, and 72 hr post-vaccination. From all vaccinated and control animals (n = 11) blood samples were collected 0, 28, 56, 84, and 296 days post-vaccination. Three of seven vaccinated skunks seroconverted. None of the control animals had detectable levels of rabies virus neutralizing antibodies. Also no vaccine virus was isolated from the nasal and saliva swabs collected from any animal. Thus, SAD B19 was innocuous for skunks in our study after direct oral administration at field concentration.


Rapid cerebral vasodilatation in brief hypoxia in anaesthetized animals.
In anaesthetized dogs, cats and rabbits, intracranial pressure was measured continuously during brief or transient hypoxia, induced by (a) lowering inspired O2 to 9--10% for 2--3 min, or (b) giving 2--3 breaths of nitrogen. In almost all instances there was an increase in i.c.p. which started in less than 20 s; this occurred with either spontaneous or controlled ventilation, and whether or not there was also a rise in arterial blood pressure; the time course was similar to that of the arterial chemoreceptor reflex responses of ventilation and blood pressure. Division bilaterally of the sinus and vagus nerves in six cats showed that the intracranial pressure response was not dependent on these chemoreceptor afferent pathways. The results suggest a rapid vasodilatation starting at a time when cerebral arterial oxygen tension is unlikely to be below 7 kPa (50 mmHg). The mechanism remains unexplained.


LC/MS/MS characterization of phenolic constituents in dried plums.
Dried plums are known as a healthy food in the West and used as medicine in India. They have been characterized by high concentrations of phenolic compounds, which are believed to play a crucial role in protection against various age-related diseases. Liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) with four different conditions was used to analyze the phytochemicals in commercial dried plums. The major components were neochlorogenic acid and cryptochlorogenic acid. Forty minor components were characterized by their MS/MS spectra and LC retention time. Six of them are novel ester isomers formed by two caffeic acids and one quinic acid. The diagnostic fragmentation patterns of different phenolics are presented on the basis of electrospray ionization (ESI) MS/MS data of components in dried plums and fourteen authentic standards.


Aggregation of Cricket Activity in Response to Resource Addition Increases Local Diversity.
Crickets are often found feeding on fallen fruits among forest litter. Fruits and other sugar-rich resources are not homogeneously distributed, nor are they always available. We therefore expect that crickets dwelling in forest litter have a limited supply of sugar-rich resource, and will perceive this and displace towards resource-supplemented sites. Here we evaluate how sugar availability affects cricket species richness and abundance in old-growth Atlantic forest by spraying sugarcane syrup on leaf litter, simulating increasing availability, and collecting crickets via pitfall trapping. We found an asymptotic positive association between resource addition and species richness, and an interaction between resource addition and species identity on cricket abundance, which indicates differential effects of resource addition among cricket species. Our results indicate that 12 of the 13 cricket species present in forest litter are maintained at low densities by resource scarcity; this highlights sugar-rich resource as a short-term driver of litter cricket community structure in tropical forests. When resource was experimentally increased, species richness increased due to behavioral displacement. We present evidence that the density of many species is limited by resource scarcity and, when resources are added, behavioral displacement promotes increased species packing and alters species composition. Further, our findings have technical applicability for increasing sampling efficiency of local cricket diversity in studies aiming to estimate species richness, but with no regard to local environmental drivers or species-abundance characteristics.


Energetics of underwater swimming with SCUBA.
Underwater swimming has unique features of breathing apparatus (SCUBA), thermal protective gear, and fins. The energy cost of underwater swimming is determined by the drag while swimming and the net mechanical efficiency. These are influenced by the cross-sectional area of the diver and gear and the frequency of the leg kick. The speeds that divers can achieve are relatively low, thus the VO(2) increases linearly with values of VO(2)*d(-1) of 30-50 l*km(-1)for women and men, respectively. Diving experience had little effect on VO(2) for women; however, male divers with experience had lower VO(2) than beginners. The location and density of the gear can alter the diver's attitude in the water and increase the energy cost of swimming by 30 percent at slow speeds. The type of fin used has an effect on the depth and frequency of the kick, thus on drag and efficiency, with a range of VO(2) from 25 to 50 l*km(-1). A large flexible fin had the lowest energy cost and a large rigid fin the highest. Adding extra air tanks or a dry suit increased the cost of swimming by 25 percent. The energy cost of underwater swimming is influenced by gender, gear and its placement, fin type, and experience of the diver.


Therapeutic targeting of cellular stress responses in cancer.
Similar to bacteria, yeast, and other organisms that have evolved pathways to respond to environmental stresses, cancer cells develop mechanisms that increase genetic diversity to facilitate adaptation to a variety of stressful conditions, including hypoxia, nutrient deprivation, exposure to DNA-damaging agents, and immune responses. To survive, cancer cells trigger mechanisms that drive genomic instability and mutation, alter gene expression programs, and reprogram the metabolic pathways to evade growth inhibition signaling and immune surveillance. A deeper understanding of the molecular mechanisms that underlie the pathways used by cancer cells to overcome stresses will allow us to develop more efficacious strategies for cancer therapy. Herein, we overview several key stresses imposed on cancer cells, including oxidative, metabolic, mechanical, and genotoxic, and discuss the mechanisms that drive cancer cell responses. The therapeutic implications of these responses are also considered, as these factors pave the way for the targeting of stress adaption pathways in order to slow cancer progression and block resistance to therapy.


Parameters of the rectoanal inhibitory reflex in patients with idiopathic fecal incontinence and chronic constipation.
The rectoanal inhibitory reflex is a response of the internal anal sphincter to rectal distention, reflecting the functional nature of the anal sampling mechanism of rectal discrimination. The aim of this study was to assess the parameters of the rectoanal inhibitory reflex in healthy volunteers and incontinent and symptomatically constipated patients. The rectoanal inhibitory reflex was recorded in 42 patients using reproducible threshold volumes. Excitatory and inhibitory latencies, maximum excitatory and inhibitory pressures, amplitude, and slope of inhibition, slope and time of pressure recovery, and area under the inhibitory curve were estimated. Pudendal nerve terminal motor latency and endoanal magnetic resonance imaging were performed in all incontinent patients. Significant linear trends were found for most parameters at each sphincter level when analyzed. Recovery time and area under the inhibitory curve differed between the sphincter levels and patient groups, with the most rapid recovery occurring in the distal sphincter of incontinent patients (P < 0.001). These pressure findings were not accounted for by differences in excitation between patient groups. A coordinated response by the internal anal sphincter to rectal distention with recovery of anal pressure from the distal to the proximal sphincter is suggested. Continence may rely on the character of internal anal sphincter inhibition, and recovery and preoperative assessment of rectoanal inhibitory reflex parameters may be important for predicting functional result following low anastomosis.


The optimisation of radiological protection: broadening the process. ICRP publication 101. Approved by the Commission in September 2005.
The principle of optimisation of radiation protection is defined by the Commission as the source-related process to keep the magnitude of individual doses, the number of people exposed, and the likelihood of potential exposure as low as reasonably achievable below the appropriate dose constraints, with economic and social factors being taken into account. According to the revised recommendations of ICRP, this process of optimisation below constraint should be applied whatever the exposure situation; i.e. planned, emergency, and existing. The previous recommendations for the practical implementation of the optimisation process are still valid. It must be implemented through an ongoing, cyclical process that involves the evaluation of the exposure situation to identify the need for action, the identification of the possible protective options to keep the exposure as low as reasonably achievable, the selection of the best option under the prevailing circumstances, the implementation of the selected option through an effective optimisation programme, and regular review of the exposure situation to evaluate if the prevailing circumstances call for the implementation of corrective protective actions. However, the way in which the optimisation process should be implemented is now viewed more broadly to reflect the increasing role of individual equity, safety culture, and stakeholder involvement in our modern societies. This report is a consolidation and an evolution of the Commission's recommendations concerning the optimisation principle. After some background information on the foundation and evolution of the principle, this report describes the main characteristics of the process, addresses the issue of exposure distribution in that process, and provides the basic requirements for its application in operation and regulation. A description of decision-aiding techniques commonly used for practical implementation of the optimisation process is provided in Annex A.


Combining signal and sequence to detect RNA polymerase initiation in ATAC-seq data.
The assay for transposase-accessible chromatin followed by sequencing (ATAC-seq) is an inexpensive protocol for measuring open chromatin regions. ATAC-seq is also relatively simple and requires fewer cells than many other high-throughput sequencing protocols. Therefore, it is tractable in numerous settings where other high throughput assays are challenging to impossible. Hence it is important to understand the limits of what can be inferred from ATAC-seq data. In this work, we leverage ATAC-seq to predict the presence of nascent transcription. Nascent transcription assays are the current gold standard for identifying regions of active transcription, including markers for functional transcription factor (TF) binding. We combine mapped short reads from ATAC-seq with the underlying peak sequence, to determine regions of active transcription genome-wide. We show that a hybrid signal/sequence representation classified using recurrent neural networks (RNNs) can identify these regions across different cell types.


Probing spatial locality in ionic liquids with the grand canonical adaptive resolution molecular dynamics technique.
We employ the Grand Canonical Adaptive Resolution Simulation (GC-AdResS) molecular dynamics technique to test the spatial locality of the 1-ethyl 3-methyl imidazolium chloride liquid. In GC-AdResS, atomistic details are kept only in an open sub-region of the system while the environment is treated at coarse-grained level; thus, if spatial quantities calculated in such a sub-region agree with the equivalent quantities calculated in a full atomistic simulation, then the atomistic degrees of freedom outside the sub-region play a negligible role. The size of the sub-region fixes the degree of spatial locality of a certain quantity. We show that even for sub-regions whose radius corresponds to the size of a few molecules, spatial properties are reasonably reproduced thus suggesting a higher degree of spatial locality, a hypothesis put forward also by other researchers and that seems to play an important role for the characterization of fundamental properties of a large class of ionic liquids.


[Treatment of bilateral vocal cord paralysis: surgical technique and functional results].
The authors present possibilities of the surgical treatment in bilateral vocal cord paralysis. We described the technique of the operation which is being used in our department in such a cases. 13 patients were analyzed after operations (11 women, 2 men). Bilateral vocal cord paralysis was caused by thyroidectomy (11 cases), virus infection (1 case) and in the course of multiple sclerosis (1 case). Functional results were evaluated by subjective examination, indirect laryngoscopy, spirometry and video-laryngoscopy. The effects of the treatment were satisfied.


Low-Intensity Guided Help Through Mindfulness (LIGHTMIND): study protocol for a randomised controlled trial comparing supported mindfulness-based cognitive therapy self-help to supported cognitive behavioural therapy self-help for adults experiencing depression.
Depression has serious personal, family and economic consequences. It is estimated that it will cost £12.15 billion to the economy each year in England by 2026. Improving access to psychological therapies (IAPT) is the National Health Service talking therapies service in England for adults experiencing anxiety or depression. Over 1 million people are referred to IAPT every year, over half experiencing depression. Where symptoms of depression are mild to moderate, people are typically offered cognitive behavioural therapy (CBT) self-help (CBT-SH) supported by a psychological well-being practitioner. The problem is that over half of people who complete treatment for depression in IAPT remain depressed despite receiving National Institute of Health and Care Excellent recommended treatment. Furthermore, less than half of IAPT service users complete treatment. This study seeks to investigate the effectiveness of an alternative to CBT-SH. Mindfulness-based cognitive therapy (MBCT) differs from CBT in focus, approach and practice, and may be more effective with a higher number of treatment completions. This is a definitive randomised controlled trial comparing supported MBCT self-help (MBCT-SH) with CBT-SH for adults experiencing mild to moderate depression being treated in IAPT services. We will recruit 410 participants experiencing mild to moderate depression from IAPT services and randomise these to receive either an MBCT-based self-help workbook or a CBT-based self-help workbook. Participants will be asked to complete their workbook within 16 weeks, with six support sessions with a psychological well-being practitioner. The primary outcome is depression symptom severity on treatment completion. Secondary outcomes are treatment completion rates and measures of generalized anxiety, well-being, functioning and mindfulness. An exploratory non-inferiority analysis will be conducted in the event the primary hypothesis is not supported. A semi-structured interview with participants will guide understanding of change processes. If the findings from this randomised controlled trial demonstrate that MBCT-SH is more effective than CBT-SH for adults experiencing depression, this will provide evidence for policy makers and lead to changes to clinical practice in IAPT services, leading to greater choice of self-help treatment options and better outcomes for service users. If the exploratory non-inferiority analysis is conducted and this indicates non-inferiority of MBCT-SH in comparison to CBT-SH this will also be of interest to policy makers when seeking to increase service user choice of self-help treatment options for depression. Current Controlled Trial registration number: ISRCTN 13495752. Registered on 31 August 2017 (www.isrctn.com/ISRCTN13495752).


mRNA expression of components of the IGF system and of GH and insulin receptors in ovaries of broiler breeder hens fed ad libitum or restricted from 4 to 16 weeks of age.
An evaluation of the insulin-like growth factors (IGF) system in the ovaries of heavy breeder hens during the growing phase was performed to measure the effect of feed restriction. The transcripts of IGF-I, IGF-II, IGF receptor (IGF-R), two IGF binding proteins (IGFBP-2 and IGFBP-5), GH receptor (GH-R) and insulin receptor (I-R) were measured by RT-PCR at 4, 8, 12 and 16 weeks of age in the ovaries of ad libitum fed and feed restricted hens. The transcripts of all genes screened were detected in all feed regime groups and at all ages sampled. However, no significant overall effects of feed restriction on these transcripts were found despite the marked difference in body growth (200% at 16 weeks of age). Similarly there were no significant age effects except for the expression of GH-R-that showed a decrease after 8 weeks of age (P<0.01). Although feed restriction seems to have a relatively limited effect on the expression of these components of the ovarian IGF system in juveniles, a more detailed determination is necessary to determine possible changes nearer to sexual maturity (16 weeks of age onwards). It is concluded that components of the IGF system, GH or insulin may not be involved in the mechanisms that, through restricted feeding, alter ovarian development and function during growth to enable better reproductive performance during lay.


Eggshell calcification after intrathyroidal hemorrhage of retrosternal thyroid.
We report a rare event of old hemorrhage into a thyroid causing respiratory distress. A 67-year-old man with chronic cough and recent dysphagia was found to have a retrosternal mass extending into the visceral mediastinum on chest roentgenogram. A computed tomographic (CT) scan confirmed eggshell callcification, which was 53 x 53 x 80 mm in size a retrosternal thyroid mass and revealed significant tracheal deviation to the right due to an extensive mass surrounded by a calcificated capsule in the left lobe of the thyroid gland with extension to the upper mediastinum. He successfully underwent left lobectomy of the thyroid gland with sternotomy. The pathological examination revealed intrathyroidal hemorrhage of the thyroid gland with massive intracystic old bleeding.


Adsorption of molecular hydrogen on coordinatively unsaturated Ni(II) sites in a nanoporous hybrid material.
A porous hybrid inorganic/organic material, NaNi3(OH)(SIP)2 [SIP = 5-sulfoisophthalate][1], is shown to strongly bind molecular hydrogen at coordinatively unsaturated metal sites. A combination of H2 sorption isotherms, temperature programmed desorption, and inelastic neutron scattering spectroscopy show the existence of a considerable number of such strong binding sites in [1] along with other sites where hydrogen is more weakly physisorbed. The overall capacity for hydrogen of this material as well as the much stronger binding of hydrogen than in typical porous material represent an important step toward a possible utilization of porous media for hydrogen storage.


[Prevention of pregnancy with a low dosage 3-stage oral preparation].
A triphasic oral contraceptive pill was tested on fifty patients in 1200 cycles during two years. Side effects observed were minimal. The normal menstrual cycle was imitated extensively. Tests concerning lipid and protein metabolism and blood coagulation were performed. There were no significant changes. According to our data the triphasic contraceptive pill did not suggest any damaging effect on the endometrium.


Sequence and characterization of the Escherichia coli genome between the ndk and gcpE genes.
The region of the chromosome immediately upstream of the Escherichia coli gene gcpE has been cloned and sequenced. This region contains two functional open reading frames, orf 384 and orf 337, encoding proteins of 43,082 and 36,189 Da, respectively. Sequencing analysis (this paper) and the isolation of a DNA fragment containing a functional promoter (Talukder, A.A., Yanai, S., and Yamada, M. (1994) Biosci. Biotech. Biochem. 58, 117-120) indicate that orf 337 is in an operon with gcpE. The gene orf 384 is immediately downstream of the gene ndk, which encodes nucleoside diphosphate kinase.


Differential impacts of vaccine scandal by ethnic and socioeconomic factors: Evidence from China.
Widespread vaccination against important diseases plays a key role for global health security, particularly in the context of the COVID-19 pandemic. However, building and maintaining trust in immunization services remains challenging because of doubts about quality and safety of vaccines. China has periodically faced mounting pressure and even public outrage triggered by incidents of poor-quality vaccines. We aimed to evaluate the impact of the diphtheria, pertussis, and tetanus (DPT) vaccine scandal of 2018 in China and the ensuing misinformation on vaccination, and investigate differential responses to the scandal by ethnic and socioeconomic factors. With data from January 2017 to December 2018 in Sichuan province, China, we used a difference-in-differences (DID) method to compare the changes in the county-level monthly DPT vaccinations against the hepatitis B vaccinations, both before and after the DPT vaccine scandal. We found that the number of DPT vaccinations decreased by 14.0 percent in response to the vaccine scandal and ensuing misinformation. The number of vaccinations in minority regions, under-developed regions, and regions with poor medical resources decreased more than in non-minority regions, developed regions, and regions with good medical resources (24.5 versus 10.1 percent, 17.3 versus 8.3 percent, and 17.0 versus 8.7 percent, respectively). People did more online searching for "Substandard vaccine" and "DPT vaccine" after the scandal, with the socioeconomically advantaged group searching more compared with the socioeconomically disadvantaged group. The results suggest the urgent need to make true information about the vaccine easily accessible over the internet, especially for the socioeconomically disadvantaged groups. Our findings for China can also have implications for immunization service planning for better safeguarding public health in other countries, particularly developing ones.


Effect of computer game intervention on the attention capacity of mentally retarded children.
The low rate of understanding and the limited domain of attention are two important and distinctive characteristics of mental retardation. One of the important strategies to provide effective education for these subjects is to lessen the backgrounds and impacts of these affective factors. The aim of this research was to find the effect of computer games program on the amount of mentally retarded persons' attention. Sixty educable male mentally retarded subjects were selected from two 24-h care centres in Tehran. The Toulouse-Pieron Scale was used to determinate the subjects' attention at pre-post test. Members of the experimental group were subjected to 35 sets of computer games. After use of the sets of computer games, the attention scores of the subjects were assessed immediately after the intervention and 5 weeks later. The results showed that exactly after the intervention the average attention scores of the experimental group were significantly higher than those of the control group. But, 5 weeks after the intervention, there was actually no significant difference.


Ethical issues in a study of Internet use: uncertainty, responsibility, and the spirit of research relationships.
In this article we explore ethical issues arising in a study of home Internet use by low-income families. We consider questions of our responsibility as educational researchers and discuss the ethical implications of some unanticipated consequences of our study. We illustrate ways in which the principles of research ethics for use of human subjects can be ambiguous and possibly inadequate for anticipating potential harm in educational research. In this exploratory research of personal communication technologies, participants experienced changes that were personal and relational. These unanticipated changes in their way of being complicated our research relationships, testing the boundaries of our committment to the principle of trustworthiness and forcing us to reevaluate our responsibilities.


Gradation of the stress response in rainbow trout exposed to stressors of different severity: the role of brain serotonergic and dopaminergic systems.
After an intense acute stressor, fish develop a metabolic and behavioural response that usually lasts for several hours. Brain monoaminergic systems, particularly the serotonergic system, appear to play a key role in the central regulation of the stress response. However, the influence of stressor severity on brain monoaminergic systems and on the induced stress responses is yet poorly understood. We hypothesise that serotonergic system could have a direct role in the integration of sensory information during stressor exposure and in the organisation of the subsequent integrated stress response. According to our hypothesis, a low stressor intensity would induce a low response of brain serotonergic system and therefore stress responses of low magnitude and duration. To test this hypothesis, we exposed fish to handling disturbance for 5 s, 15 s or 3 min. We sampled fish at 0 (controls), 3, 15, 45 and 240 min after the start of the stress protocol. Brain levels of serotonin, dopamine and their respective main oxidative metabolites were quantified, along with plasma levels of stress markers (catecholamines, cortisol, glucose and lactate). Regarding stress markers, the 5-s and 15-s stress protocols induced similar and relatively low elevations in all parameters assessed. As expected, the 3-min protocol induced responses of a higher intensity and duration in all plasma parameters. Interestingly, the alterations of brain monoaminergic systems did not follow the same trend. The three stress protocols induced increases in the serotonergic activity in all brain regions analysed (hypothalamus, telencephalon and medulla oblongata), independently of the duration of the handling disturbance, whereas the effects on the dopaminergic system were minor and brain region-dependent. These data suggest that the brain serotonergic system, although likely involved in the recognition of the stressor stimuli, is not the only actor determining the magnitude and duration of the acute stress response in trout.


HIV-1 neutralizing monoclonal antibodies induced by a synthetic peptide.
We have developed a series of murine monoclonal antibodies to a region of the 120 kD envelope glycoprotein (gp120) of human immunodeficiency virus type 1 (HIV-1). This region has previously been implicated as a site for virus neutralization by antisera raised to recombinant proteins and by antibodies made to full-length gp120 purified from virus. The antigen employed was a synthetic peptide containing 15 amino acids, representing amino acid residues 308-322, RIQRGPGRAFVTIGK, of env gp120 (HTLV-IIIB isolate). Five of the monoclonal antibodies raised to this antigen have reactivity with gp120 from divergent strains of HIV-1 in Western blot assays. The two of these five which were tested with live cells infected with the divergent HIV-1 isolates IIIB, MN, and RF were specifically reactive by fluorescence analyses with cells infected with the MN and IIIB isolates. Four of the five monoclonal antibodies blocked the fusion of IIIB-infected cells with uninfected MOLT-4 target cells. The monoclonal antibody most reactive with MN-infected cells by fluorescence, #5025A, blocked the fusion of MN-infected cells with uninfected MOLT-4 cells. Four of the five monoclonal antibodies neutralized the IIIB isolate of HIV-1 in vitro, but none neutralized the MN or RF isolates at the levels of antibody tested (less than or equal to 50 micrograms/ml). Taken together these data indicate that monoclonal antibodies to the immunodominant neutralizing domain of HIV-1 gp120 display different levels of group reactivity depending on the assay system being examined.


Use of laryngeal mask airway for prolonged ventilatory support in a preterm newborn.
We present the case report of a preterm, low weight newborn with dysmorphic features and micrognathia in whom a laryngeal mask airway was inserted and maintained for 44 h for ventilatory support after several failed intubations. No complications associated with laryngeal mask airway use were apparent.


[Atypical risk factors of atherosclerosis in patients with hypothyroidism].
The non-traditional risk factors for atherosclerotic lesions of the cardiovascular system (C-reactive protein, uric acid, fibrinogen, homocysteine) in blood plasma of patients with manifestative hypothyroidism at the age of 23 to 73 years were assessed in the study. An increase in the average values of C-reactive protein was revealed in patients with hypothyroidism without arterial hypertension (AH), as well as under its presence, and increased BMI. Uric acid level also was increased with the combination of hypothyroidism and hypertension. Average level of fibrinogen was within the values of the control group and increased only in 23.4% of patients with hypothyroidism. Homocysteine content was elevated in 32% of patients and was not associated with the presence of AH. Increased levels of these markers of cardiovascular lesions risk coincided with the increased diameter of the common carotid artery.


SARS-CoV-2 Infection: Differences in Hematological Parameters Between Adults and Children.
Since December 2019, corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, posing a huge threat to human health, and the current epidemic prevention situation is still severe. Hematological parameters directly reflect the damage of SARS-CoV-2 to human blood cells, which can better assess the severity and prognosis of patients infected with COVID-19, but hematological parameters have some differences between adults and children. This article comprehensively reviews the differences in hematological parameters between adults and children after SARS-CoV-2 infection, and provides a reference for the diagnosis and treatment of COVID-19.


Cytoprotective effect against UV-induced DNA damage and oxidative stress: role of new biological UV filter.
The majority of chemical solar filters are cytotoxic, particularly on sensitive ocular cells (corneal and conjunctival cells). Consequently, a non-cytotoxic UV filter would be interesting in dermatology, but more especially in ophthalmology. In fact, light damage to the eye can be avoided thanks to a very efficient ocular antioxidant system; indeed, the chromophores absorb light and dissipate its energy. After middle age, a decrease in the production of antioxidants and antioxidative enzymes appears with accumulation of endogenous molecules that are phototoxic. UV radiations can induce reactive oxygen species formation, leading to various ocular diseases. Because most UV filters are cytotoxic for the eye, we investigated the anti-UV properties of Calophyllum inophyllum oil in order to propose it as a potential vehicle, free of toxicity, with a natural UV filter action in ophthalmic formulation. Calophyllum inophyllum oil, even at low concentration (1/10,000, v/v), exhibited significant UV absorption properties (maximum at 300nm) and was associated with an important sun protection factor (18-22). Oil concentrations up to 1% were not cytotoxic on human conjunctival epithelial cells, and Calophyllum inophyllum oil appeared to act as a cytoprotective agent against oxidative stress and DNA damage (85% of the DNA damage induced by UV radiations were inhibited with 1% Calophyllum oil) and did not induce in vivo ocular irritation (Draize test on New Zealand rabbits). Calophyllum inophyllum oil thus exhibited antioxidant and cytoprotective properties, and therefore might serve, for the first time, as a natural UV filter in ophthalmic preparations.


Mechanistic studies on the catalytic asymmetric Mannich-type reaction with dihydroisoquinolines and development of oxidative Mannich-type reactions starting from tetrahydroisoquinolines.
Detailed mechanistic studies on our recently reported asymmetric addition reactions of malonates to dihydroisoquinolines (DHIQs) catalyzed by chiral Pd(II) complexes were carried out. It was found that an N,O-acetal was generated in situ by the reaction of DHIQ with (Boc)2O, and cooperative action of the Pd(II) complex as an acid-base catalyst allowed the formation of a chiral Pd enolate and a reactive iminium ion via alpha-fragmentation. The iminium ion was also accessible via oxidation with DDQ as an oxidant, and a catalytic asymmetric oxidative Mannich-type reaction was achieved with tetrahydroisoquinolines (THIQs) as starting materials. This oxidation protocol was applicable to N-acryloyl-protected THIQs, allowing the efficient synthesis of optically active tetrahydrobenzo[a]quinolizidine derivatives via intramolecular Michael reaction.


Surveying and screening preschool language development in community-focused intervention programmes: a review of instruments.
Preschool language intervention has come increasingly to the fore with the development of community-focused interventions including Sure Start in the UK. Successful intervention methods may well be incorporated into mainstream service delivery, especially in areas of disadvantage. The question of whether such interventions will work and of their impact on children's language development has focused attention on measures of language. This paper distinguishes two reasons for measuring language development: (1) surveying language; and (2) screening language. It goes on to suggest a set of criteria for selecting instruments for these applications. The review includes a wide range of language assessment instruments for preschool children and examines those most likely to be suitable. It suggests a role for paraprofessionals in survey and screening and argues that this may be advantageous in terms of reaching families and thereby achieving high levels of coverage of a population group. Finally, there is a discussion of the implications of such measures in community-focused preschool interventions.


pH-responsive ion transport in polyelectrolyte multilayers of poly(diallyldimethylammonium chloride) (PDADMAC) and poly(4-styrenesulfonic acid-co-maleic acid) (PSS-MA) bearing strong- and weak anionic groups.
The layer-by-layer construction of interfacial architectures displaying stimuli-responsive control of mass transport is attracting increasing interest in materials science. In this work, we describe the creation of interfacial architectures displaying pH-dependent ionic transport properties which until now have not been observed in polyelectrolyte multilayers. We describe a novel approach to create pH-controlled ion-rectifying systems employing polyelectrolyte multilayers assembled from a copolymer containing both weakly and strongly charged pendant groups, poly(4-styrenesulfonic acid-co-maleic acid) (PSS-MA), alternately deposited with poly(diallyldimethylammonium chloride) (PDADMAC). The conceptual framework is based on the very contrasting and differential interactions of PSS and MA units with PDADMAC. In our setting, sulfonate groups play a structural role by conferring stability to the multilayer due to the strong electrostatic interactions with the polycations, while the weakly interacting MA groups remain "silent" within the film and then act as on-demand pH-responsive units. When these multilayers are combined with a strong cationic capping layer that repels the passage of cationic probes, a pH-gateable rectified transport of anions is observed. Concomitantly, we also observed that these functional properties are significantly affected when multilayers are subjected to extensive pH cycling as a consequence of irreversible morphological changes taking place in the film. We envision that the synergy derived from combining weak and strong interactions within the same multilayer will play a key role in the construction of new interfacial architectures displaying tailorable ion transport properties.


Electroless reduction of silver chloride precipitates for the preparation of highly sensitive substrates for surface-enhanced infrared absorption (SEIRA) measurements.
To prepare silver nanoparticles (AgNPs) on infrared-transmitting crystal for surface-enhanced infrared absorption (SEIRA) measurements, a new strategy is proposed and demonstrated using electroless reduction of preformed silver chloride (AgCl) particles. Silver chloride precipitates were formed using an additive of polyvinyl pyrrolidone (PVP) to vary the size and shape of the precipitates. After settling on germanium substrates, the preformed particles of AgCl were reduced electrolessly and spontaneously coagulated to AgNPs. The resulting AgNPs showed a multilayer structure, but the AgNPs were isolated, as shown by the lack of absorption-band distortion in the SEIRA measurements. Hence, the sensitivity and analyte-loading capacity for SEIRA measurements are improved significantly. To optimize the chemical deposition and electroless reduction method, we examined several parameters, including the concentrations of reagents during AgCl precipitation and the reaction time required in the deposition-reduction steps. We used para-nitrobenzoic acid (pNBA) to probe the intensity of the SEIRA effect for the prepared substrates. To better correlate the SEIRA performances with each variable, we examined the prepared substrates using a scanning electron microscope and SEIRA. The results indicate that two major morphologies of AgNPs are observed: nanoparticles and nanorods. The distributions of nanorods we observed were related to the procedures used to prepare the substrates. Based on SEIRA signals, we observed enhancement factors approaching three orders of magnitude compared to conventional transmission measurement. Also, based on the morphologies, the large signals were mainly caused by the formation of multilayers of non-percolated AgNPs.


Novel effects of diets enriched with corn oil or with an olive oil/sunflower oil mixture on vitamin K metabolism and vitamin K-dependent proteins in young men.
Little is known of how the fat components of diets influence the absorption and metabolism of vitamin K and the possible consequences to the synthesis of vitamin K-dependent (VKD) proteins in different target organs. We have evaluated the effects of two diets on circulating phylloquinone (K1) and triacylglycerols (TAG). One diet was enriched with corn oil (CO) (also rich in gamma-tocopherol) and the other with an olive/sunflower (O/SO) mixture (rich in alpha-tocopherol). Effects on gamma-carboxylation were assessed from coagulation assays and sensitive assays for undercarboxylated prothrombin (ucFII) and osteocalcin (ucOC). Total plasma matrix Gla-protein (MGP) was also measured. After an initial adjustment diet, 26 healthy young men were fed, in a crossover design, the O/SO or CO diet for 2 weeks. Mean intakes of K1 during consumption of adjustment, O/SO, and CO diets were 225 microg/day, 291 microg/day, and 291 microg/day, respectively. Mean fasting levels of TAG and K1 were both significantly reduced by the CO diet, but not by the O/SO diet. Neither diet reduced FII activity but ucFII became detectable in nine subjects, eight of whom showed this abnormality with both diets. The CO diet induced a rise in ucOC (P < 0.05), which was negatively correlated to ucFII (r = -0.71, P < 0.03). The CO but not O/SO diet induced a decrease of total circulating MGP. We conclude that both oils, notably CO, affected vitamin K absorption and/or metabolism which may increase the requirements for gamma-carboxylation. The mechanism is unclear but may result from interactions of vitamin K with PUFA and/or other lipid components such as vitamin E.


HPLC-ED determination of catecholamines and their metabolites in urine.
High performance liquid chromatography (HPLC) with electrochemical detection (ED) was applied for the monitoring of catecholamines (epinephrine - E, norepinephrine - NE, dopamine - DA) and their main metabolites (homovanillic acid - HVA, vanillylmandelic acid - VMA) in urine samples of patients with the pheochromocytoma diagnosis. Both amperometric and colorimetric detectors were tested for the clinical applications and the results were compared. The optimization of separation conditions was worked out, especially the effects of mobile phase compositions (pH, ionic strength, organic modifier and ion-pair agent concentrations). Dependences of capacity ratio values k' on all optimized components of the mobile phases were evaluated. Chromatographic conditions were optimized for the suitable chromatographic resolution (Rij > 1.25). Extraction recoveries for liquid-liquid and solid-phase extractions have been worked-out. Detection limits for catecholamines in urine were in the range of 0.3-0.6 ng/ml and 10-20 ng/ml for HVA, VMA using coulometric detector.


Precision compression molding of glass microlenses and microlens arrays--an experimental study.
An innovative manufacturing process utilizing high-temperature compression molding to fabricate aspherical microlenses by using optical glasses, such as BK7, K-PG325, and soda-lime glass, is investigated. In a departure from conventional approaches, a unique hollow contactless mold design is adopted. Polished glass substrates and the mold assembly are heated above the glass transition temperature first, followed by initial forming, then annealing. The forming rate is controlled in real time to ensure mold position accuracy. Mold materials used include tungsten carbides, 316 stainless steel, 715 copper nickel, and aluminum alloys. The geometric control of the microlenses or microlens arrays can be precisely controlled by the forming temperature, forming speed, mold design, and annealing time.


PI3K induces B-cell development and regulates B cell identity.
Phosphoinositide-3 kinase (PI3K) signaling is important for the survival of numerous cell types and class IA of PI3K is specifically required for the development of B cells but not for T cell development. Here, we show that class IA PI3K-mediated signals induce the expression of the transcription factor Pax5, which plays a central role in B cell commitment and differentiation by activating the expression of central B cell-specific signaling proteins such as SLP-65 and CD19. Defective class IA PI3K function leads to reduction in Pax5 expression and prevents B cell development beyond the stage expressing the precursor B cell receptor (pre-BCR). Investigating the mechanism of PI3K-induced Pax5 expression revealed that it involves a network of transcription factors including FoxO1 and Irf4 that directly binds to the Pax5 gene. Together, our results suggest that PI3K signaling links survival and differentiation of developing B cells with B cell identity and that decreased PI3K activity in pre-B cells results in reduced Pax5 expression and lineage plasticity.


Multiply relapsing hairy cell leukemia responsive to repeated courses of rituximab: a case report.
While cladribine is a highly effective therapy for patients with symptomatic hairy cell leukemia (HCL), up to 37% of patients ultimately relapse and incompletely responding patients relapse more frequently. Rituximab is a monoclonal antibody against CD20 that has been shown to be effective in patients with relapsed HCL. We present an unusual case of successful multiple re-treatments with rituximab in a patient with heavily pre-treated HCL and briefly review the relevant literature.


Matrix Metalloproteinases Are Differentially Regulated and Responsive to Compression Therapy in a Red Duroc Model of Hypertrophic Scar.
Objective: Proteins of the matrix metalloproteinases family play a vital role in extracellular matrix maintenance and basic physiological processes in tissue homeostasis. The function and activities of matrix metalloproteinases in response to compression therapies have yet to be defined. Here, a swine model of hypertrophic scar was used to profile the transcription of all known 26 matrix metalloproteinases in scars treated with a precise compression dose. Methods: Full-thickness excisional wounds were created. Wounds underwent healing and scar formation. A subset of scars underwent 2 weeks of compression therapy. Biopsy specimens were preserved, and microarrays, reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry were performed to characterize the transcription and expression of various matrix metalloproteinase family members. Results: Microarray results showed that 13 of the known 26 matrix metalloproteinases were differentially transcribed in wounds relative to the preinjury skin. The predominant upregulation of these matrix metalloproteinases during early wound-healing stages declined gradually in later stages of wound healing. The use of compression therapy reduced this decline in 10 of the 13 differentially regulated matrix metalloproteinases. Further investigation of MMP7 using reverse transcription-polymerase chain reaction confirmed the effect of compression on transcript levels. Assessment of MMP7 at the protein level using Western blotting and immunohistochemistry was concordant. Conclusions: In a swine model of hypertrophic scar, the application of compression to hypertrophic scar attenuated a trend of decreasing levels of matrix metalloproteinases during the process of hypertrophic wound healing, including MMP7, whose enzyme regulation was confirmed at the protein level.


Lack of association between urotensin-II (UTS2) gene polymorphisms (Thr21Met and Ser89Asn) and migraine.
Migraine is a common neurovascular brain disorder with heterogeneous clinical presentation, including recurrent headache attacks. The pathophysiology of migraine is complex, and a number of genomic regions have been associated with the development of migraine. In this study, we analyzed the allele and genotype frequencies of the urotensin-II gene (UTS2) polymorphisms, Thr21Met and Ser89Asn, among Turkish patients with migraine. A total of 146 patients with migraine (14 with aura [MA group] and 132 without aura [MO group]) were genotyped for Thr21Met and Ser89Asn polymorphisms and compared with 154 age- and sex-matched healthy controls. The UTS2 gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No significant differences were observed in allele and genotype frequencies for Thr21Met and Ser89Asn polymorphisms between the patients with migraine and control group. Similarly, we did not observe significant differences in allele and genotype frequencies between MA and MO and control group. Moreover, the haplotype analysis showed no association between UTS2 gene haplotypes (MN, MS, TN, and TS) and migraine. In summary, Thr21Met and Ser89Asn polymorphisms of the UTS2 gene are not risk factors for migraine in our sample of Turkish migraine patients.


Enantioselective Radical Cyclization of Tryptamines by Visible Light-Excited Nitroxides.
Nitroxides can absorb both ultraviolet (UV) and visible light, and their electron can be excited from the π-bonding orbital to the antibonding π* orbital or the n-bonding orbital to the antibonding π* orbital, respectively. Despite the reported UV-induced hydrogen atom transfer (HAT) process, the potential of nitroxides for visible light-excited photosynthesis is underexplored. Here we demonstrate that nitroxide can convert indole to its radical through a visible light-induced HAT process. A chiral phosphoric acid-catalyzed cyclization of the in situ-formed imine radical, followed by trapping by another molecule of nitroxide, provides the product in high yield and enantioselectivity. To highlight the novelty and efficiency of this strategy, an asymmetric total synthesis of natural product (-)-verrupyrroloindoline was accomplished in 5 steps.


Laminin-derived peptide C16 regulates Tks expression and reactive oxygen species generation in human prostate cancer cells.
Laminin peptides influence cancer biology. We investigated the role of a laminin-derived peptide C16 regulating invadopodia molecules in human prostate cancer cells (DU145). C16 augmented invadopodia activity of DU145 cells, and stimulated expression Tks4, Tks5, cortactin, and membrane-type matrix metalloproteinase 1. Reactive oxygen species generation is also related to invadopodia formation. This prompted us to address whether C16 would induce reactive oxygen species generation in DU145 cells. Quantitative fluorescence and flow cytometry showed that the peptide C16 increased reactive oxygen species in DU145 cells. Furthermore, significant colocalization between Tks5 and reactive oxygen species was observed in C16-treated cells. Results suggested that the peptide C16 increased Tks5 and reactive oxygen species in prostate cancer cells. The role of C16 increasing Tks and reactive oxygen species are novel findings on invadopodia activity.


ACR Appropriateness Criteria® Suspected Upper Extremity Deep Vein Thrombosis.
This publication includes the appropriate imaging modalities to assess suspected deep vein thrombosis in the upper extremities. Ultrasound duplex Doppler is the most appropriate imaging modality to assess upper-extremity deep vein thrombosis. It is a noninvasive test, which can be performed at the bedside and used for serial evaluations. Ultrasound can also directly identify thrombus by visualizing echogenic material in the vein and by lack of compression of the vein walls from manual external pressure. It can indirectly identify thrombus from altered blood-flow patterns. It is most appropriate in the evaluation of veins peripheral to the brachiocephalic vein. CT venography and MR venography are not first-line imaging tests, but are appropriate to assess the central venous structures, or to assess the full range of venous structures from the hand to the right atrium. Catheter venography is appropriate if therapy is required. Radionuclide venography and chest radiography are usually not appropriate to assess upper-extremity deep vein thrombosis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Haemodynamics and blood flow measured using ultrasound imaging.
Visualization of, and measurements related to, haemodynamic phenomena in arteries may be made using ultrasound systems. Most ultrasound technology relies on simple measurements of blood velocity taken from a single site, such as the peak systolic velocity for assessment of the degree of lumen reduction caused by an arterial stenosis. Real-time two-dimensional (2D) flow field visualization is possible using several methods, such as colour flow, blood flow imaging, and echo particle image velocimetry; these have applications in the examination of the flow field in diseased arteries and in heart chambers. Three-dimensional (3D) and four-dimensional ultrasound systems have been described. These have been used to provide 2D velocity profile data for the estimation of volumetric flow. However, they are limited for haemodynamic evaluation in that they provide only one component of the velocity. The provision of all seven components (three space, three velocity, and one time) is possible using image-guided modelling, in which 3D ultrasound is combined with computational fluid dynamics. This method also allows estimation of turbulence data and of relevant quantities such as the wall shear stress.


Oxidative stress, micronutrients, diabetes mellitus and its complications.
Oxidative stress is defined as excessive production of reactive oxygen species (ROS) in the presence of diminished antioxidant substances. It has been shown that oxidative stress has an adverse effect on glucose metabolism. Development of the disabling chronic complications of diabetes mellitus (DM) has also been attributed to oxidative stress. The body's defence against oxidative stress is accomplished by interconnecting systems of antioxidant micronutrients (vitamins and minerals) and enzymes. While the vitamins act as donors and acceptors of ROS, minerals regulate activity of the enzymes. This review article is focused on the preventive and therapeutic roles of these antioxidant micronutrients in DM. Although there is scarcity of data from controlled studies, anecdotal reports indicate that the use of certain antioxidant vitamin and mineral supplements may be beneficial as an adjunct therapy in the management of DM and its complications. In particular, it has been reported that high doses of single micronutrient antioxidant supplements, such as vitamin E, may be beneficial to patients suffering from this disease. However, micronutrient antioxidants interact with each other in a biochemical chain of defence against free radicals, and the use of high doses of a single antioxidant poses potential risks because it could perturb the antioxidant-prooxidant balance. It has, therefore, been recommended that high doses of micronutrient antioxidant vitamins should be administered in combination rather than as single supplements. There are a growing number of preparations containing mixtures of antioxidant vitamins and/or trace elements. A particularly impressive supplement is a new formula called Akesis, which is a mixture of antioxidant vitamins and antidiabetic trace elements, adequately balanced with other vitamins and minerals that enhance metabolic processes.