Nanoplastics enhance the intestinal damage and genotoxicity of sulfamethoxazole to medaka juveniles (Oryzias melastigma) in coastal environment.
Antibiotics and nanoplastics are widely detected in the coastal ecosystem. However, the transcriptome mechanism elucidating the effect of antibiotics and nanoplastics co-exposure on the gene expression of aquatic organisms in coastal environment is still unclear. Here, single and joint effects of sulfamethoxazole (SMX) and polystyrene nanoplastics (PS-NPs) on the intestinal health and gene expression of medaka juveniles (Oryzias melastigma), which live in coastal environment, were investigated. The SMX and PS-NPs co-exposure decreased intestinal microbiota diversity compared to the PS-NPs, and caused more adverse effect on the intestinal microbiota composition and intestinal damage compared to the SMX, indicating that PS-NPs might enhance the toxicity of SMX on the medaka intestine. The increased abundance of Proteobacteria in the intestine was observed in the co-exposure group, which might induce the intestinal epithelium damage. In addition, the differentially expressed genes (DEGs) were mainly involved in the drug metabolism-other enzymes, drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450 pathways in visceral tissue after the co-exposure. The expression of the host immune system genes (e.g., ifi30) could be associated with the increased pathogens in intestinal microbiota. This study is useful for understanding the toxicity effect of antibiotics and NPs on aquatic organisms in coastal ecosystem.


Diffuse adherence of enteropathogenic Escherichia coli strains.
For the identification and characterization of the factor(s) responsible for the diffuse adherence (DA) pattern of enteropathogenic Escherichia coli strains, E. coli strain 2787 isolated from a case of infantile diarrhoea was employed. A plasmid-derived 11-kb fragment was cloned into pBR322. The recombinant plasmid pIB6 was shown to confer the diffuse adherence phenotype on different E. coli K12 strains as well as pIB4, a plasmid with a 9.2-kb insert. The DNA fragment necessary for the expression of the DA phenotype could be reduced to 6.0 kb. Antiserum obtained against pIB4-encoded proteins recognized a surface-associated protein of about 100 kDa in Western blotting. The isolated 100-kDa protein was found to bind to HeLa cells. The antiserum against C600(pIB4) inhibits adherence of E. coli 2787 and C600(pIB6) to HeLa cells. For this reason, the protein is called adhesin involved in diffuse adherence (AIDA-I).


Adults living with irritable bowel syndrome (IBS): A qualitative systematic review.
To consolidate existing qualitative studies which examined the experiences and needs of adults living with IBS, and to gather a holistic insight for future directions and avenues to support these adults. A qualitative systematic review was conducted and six databases were searched for qualitative studies, beginning from each database's inception to July 2020. The qualitative data were meta-synthesised and thematic analysis was adopted. Any discrepancies that arose were discussed between the reviewers until a consensus was reached throughout the process of data screening, selection, critical appraisal and synthesis. Seventeen studies with a total of 299 adults diagnosed with IBS were included. Four themes were identified: (1) physical, psychological, and social consequences; (2) impact of IBS on working adults; (3) dealing with IBS; and (4) sources of support and support needs. Future research across geographically diverse locations are needed to gather a thorough perspective of the experiences and needs of adults living with IBS. The development and evaluation of technology-based, trained peer-led volunteers, and interventions that adopt mindfulness, active coping strategies, cognitive behavioural therapy and acceptance, and commitment therapy are needed. Ultimately, the collaboration between the relevant stakeholders is essential for standardised instruments and materials for accurate testing, diagnosis, assessment, treatment and management of IBS.


Reproducibility Starts from You Today.
Who hasn't yet heard about the debates on research reproducibility, or, perhaps even more, about the research reproducibility crisis? There have been numerous papers in the past several years discussing reproducibility issues in research. In addition, funders, publishers, and research institutions followed policies aiming at increasing research reproducibility. But what does it mean in practice for research to be reproducible? And where does one start in this flood of information, tools, and requirements? In this article, we aim to help researchers improve the reproducibility of their work by providing simple tips and good practices that can be readily applied at different stages of the research life cycle. Reproducibility starts from you. Today!


Biliary excretion of iron and ferritin in idiopathic hemochromatosis.
The role of biliary excretion of iron and ferritin in iron overload was studied and evaluated. Ten patients with idiopathic hemochromatosis and two groups of controls (14 gallstone patients and 16 healthy subjects) were included. Liver tissue (obtained by percutaneous or operative biopsy) was investigated with light microscopy and transmission electron microscopy in combination with x-ray microanalysis. Fasting bile samples were obtained through duodenal aspiration or at cholecystectomy. Iron was determined in liver tissue and bile using atomic absorption spectroscopy, and ferritin was determined in serum and bile with a radioimmunoassay technique. All patients with hemochromatosis had iron-positive staining as seen in light microscopy. Electron microscopy showed iron-containing proteins in the lysosomes and cytosol of liver parenchymal cells, and this observation was supported by x-ray microanalysis. Hepatic iron concentration was increased about eightfold in the patients with hemochromatosis (p less than 0.001). Biliary iron concentration, expressed per millimole of bile acid, was increased about twofold (p less than 0.05) and biliary ferritin concentration about fivefold (p less than 0.001) in hemochromatosis. Four of the patients with hemochromatosis were reexamined after completed treatment with venesection; this resulted in normalized biliary concentrations of iron and ferritin. We conclude that biliary secretion of ferritin occurs in humans and that both iron and ferritin excretion are enhanced in hepatic iron overload. The apparently limited capacity of biliary iron excretion may be of importance for the hepatic iron accumulation in hemochromatosis.


Oscillatory coupling in writing and writer's cramp.
Writing is a highly skilled and overlearned movement. In patients suffering from writer's cramp, a focal task-induced dystonia, writing is impaired or even impossible due to involuntary muscle contractions and abnormal posture, which occur as soon as the person picks up a pen or within writing a few words. The underlying pathophysiological mechanisms of this movement disorder are not fully understood up to now. The aim of the present study was to unravel the oscillatory network underlying physiological writing in healthy subjects and dystonic writing in writer's cramp patients. Using whole-head magnetoencephalography (MEG) and the analysis tool dynamic imaging of coherent sources (DICS) we studied oscillatory neural coupling during writing in eleven healthy subjects and eight patients suffering from writer's cramp. Simultaneous recording of brain activity with MEG and activity of forearm and hand muscles with surface electromyography (EMG) was performed while subjects were writing for five minutes with their dominant right hand. Applying DICS sources of strongest cerebro-muscular coherence and cerebro-cerebral coherence during writing were identified, which consistently included six brain areas in both, the control subjects and the patients: contralateral and ipsilateral sensorimotor cortex, ipsilateral cerebellum, contralateral thalamus, contralateral premotor and posterior parietal cortex. Coherence between cortical sources and muscles appeared primarily in the frequency of writing movements (3-7 Hz) while coherence between cerebral sources occurred primarily around 10 Hz (8-13 Hz). Interestingly, consistent coupling between both sensorimotor cortices was observed in patients only, whereas coupling between ipsilateral cerebellum and the contralateral posterior parietal cortex was found in control subjects only. These results are consistent with the often described bilateral pathophysiology and impaired sensorimotor integration in writer's cramp patients.


A review on circular RNAs and bacterial infections.
Bacterial infections and related diseases have been a major burden on social public health and economic stability around the world. However, the effective diagnostic methods and therapeutic approaches to treat bacterial infections are still limited. As a group of non-coding RNA, circular RNAs (circRNAs) that were expressed specifically in host cells and played a key regulatory role have the potential to be of diagnostic and therapeutic values. In this review, we systematically summarize the role of circRNAs in common bacterial infections and their potential roles as diagnostic markers and therapeutic targets.


Electron irradiation of conjunctival lymphoma--Monte Carlo simulation of the minute dose distribution and technique optimization.
External beam radiotherapy is the only conservative curative approach for Stage I non-Hodgkin lymphomas of the conjunctiva. The target volume is geometrically complex because it includes the eyeball and lid conjunctiva. Furthermore, the target volume is adjacent to radiosensitive structures, including the lens, lacrimal glands, cornea, retina, and papilla. The radiotherapy planning and optimization requires accurate calculation of the dose in these anatomical structures that are much smaller than the structures traditionally considered in radiotherapy. Neither conventional treatment planning systems nor dosimetric measurements can reliably determine the dose distribution in these small irradiated volumes. The Monte Carlo simulations of a Varian Clinac 2100 C/D and human eye were performed using the penelope and penEasyLinac codes. Dose distributions and dose volume histograms were calculated for the bulbar conjunctiva, cornea, lens, retina, papilla, lacrimal gland, and anterior and posterior hemispheres. The simulated results allow choosing the most adequate treatment setup configuration, which is an electron beam energy of 6 MeV with additional bolus and collimation by a cerrobend block with a central cylindrical hole of 3.0 cm diameter and central cylindrical rod of 1.0 cm diameter. Monte Carlo simulation is a useful method to calculate the minute dose distribution in ocular tissue and to optimize the electron irradiation technique in highly critical structures. Using a voxelized eye phantom based on patient computed tomography images, the dose distribution can be estimated with a standard statistical uncertainty of less than 2.4% in 3 min using a computing cluster with 30 cores, which makes this planning technique clinically relevant.


Nosocomial spread of a Staphylococcus hominis subsp. novobiosepticus strain causing sepsis in a neonatal intensive care unit.
From 2002 to 2003, 32 isolates of Staphylococcus hominis subsp. novobiosepticus (SHN) were recovered from 21 patients, 18 of whom were neonates, with 13 considered to have late-onset SHN sepsis. All isolates from neonates had an indistinguishable pulsed-field gel electrophoresis pattern. Our data support SHN as an important nosocomial pathogen in neonates.


Feeding behaviors among incident cases of schizophrenia in a psychiatric hospital: Association with dimensions of psychopathology and social support.
Despite early description by Eugen Bleuler of abnormal feeding behaviors among patients with schizophrenia, it has remained poorly studied and understood by clinicians. The present study sought to describe the various eating behaviors among incident cases of schizophrenia and its relationship with the dimensions of psychopathology and perceived social support. This study elicited information on the feeding behavior of 206 incident cases of schizophrenia being followed up for various nutritional outcomes. Feeding behavior, dimensions of psychopathology and perceived social support were measured using literature based researchers' constructed nutritional questions, Positive and Negative Symptoms Scale (PANSS), and Multi-dimensional Scale of Perceived Social Support (MSPSS), respectively. Relationship between food refusal and dimensions of psychopathology as well as perceived social support were tested using independent t-test. Food refusal was seen in 56.5% of the patients, with 32.5% of it attributed to suspiciousness. Of the 13.2% with Inappropriate feeding behavior, 46.4% and 14.3% were related to abnormal food preparation and pica, respectively. Food refusal was significantly associated with positive symptoms dimension and general psychopathology (p < 0.05). Our findings show that subtle feeding abnormalities occur among schizophrenia patients and this is related to positive symptoms dimension and poor perceived social support.


Effect of prophylactic dalteparin on anti-factor Xa levels in morbidly obese patients after bariatric surgery.
There are limited data on appropriate dosing of low-molecular-weight heparins (LMWH) for venous thromboembolism (VTE) prophylaxis in bariatric surgery. The objective of this study was to describe the postoperative effects of LMWH dalteparin on anti-factor Xa (AFXa) level in morbidly obese patients undergoing bariatric surgery. This was a retrospective study. Morbidly obese patients (BMI >or= 40 kg/m(2) or BMI > 35 kg/m(2) with at least one significant co-morbidity) received subcutaneous dalteparin 7,500 IU daily during the postoperative period after biliopancreatic derivation with duodenal switch. AFXa level was measured 4 h after the fourth dalteparin administration. One hundred and thirty-five patients with a mean BMI of 53.7 kg/m(2) were included into this study. Only 60% of patients had targeted AFXa levels (0.2-0.5 UI/ml). There was a statistical difference in body weight between individuals with sub-target AFXa levels and those with values over target (159.4 +/- 35.8 vs. 134.6 +/- 24.2, p = 0.0310). There were three haemorrhages documented. These events were not associated with elevated AFXa values. These findings indicate that the 7,500 IU dalteparin dosage is appropriate for the majority of morbidly obese patients undergoing bariatric surgery. The present study, however, suggests that this dose might not be sufficient for patient with a very high body weight.


Physical and mechanical properties of elastomers in orthodontic positioners.
Elastomers for conventional Kesling-type tooth positioners are relatively inelastic and are primarily indicated as finishing devices. However, new materials, first described in the Japanese literature, with claims of a greater range of tooth movement warrant a comparison with conventional materials. Physical and mechanical property testing of positioner elastomers has not been reported in the orthodontic literature. This investigation compared properties of a high temperature vulcanizing (HTV) Japanese silicone (Orthocon) to three traditional polyurethane and vinyl-based polymers and five experimental silicone elastomers. Fourier transform infrared spectroscopy established the definitive chemical composition of the urethane and vinyl materials obtained from a commercial positioner laboratory. Tear strength, tensile strength, tensile stress at selected elongations, and ultimate elongation of all materials were evaluated at 37 degrees C in an aqueous environment. Hardness and water sorption values also were determined and an in vitro force measurement apparatus was fabricated to determine force levels exerted by positioner materials at low displacements. Orthocon was statistically different (Duncan's multiple range test, p less than 0.05) from the traditional commercial urethane and vinyl materials. Orthocon had lower tear strength than the traditional materials. It also demonstrated lower stress values below 100% elongation. The parameters of tensile stress at 50% elongation and ultimate elongation were statistically identical for Orthocon and one experimental silicone material.


Clomiphene therapy in epileptic women with menstrual disorders.
We studied the effects of clomiphene therapy on seizure frequency in 12 women who had clinical and EEG features of complex partial seizures as well as menstrual disorders with reproductive endocrine abnormalities. Ten of the 12 women improved (p less than 0.05); all ten developed normal cycles. The two women who did not improve continued to have irregular prolonged cycles. Average monthly seizure frequency for the entire group declined by 87% (p less than 0.01). Both complex partial and secondary generalized seizures decreased. During the investigation, one unwanted pregnancy occurred, two women developed severe abdominal pain with ultrasound-documented ovarian cysts, and three experienced breast tenderness and pelvic cramps.


Response of engineered cartilage to mechanical insult depends on construct maturity.
Injury to articular cartilage leads to degenerative changes resulting in a loss of mechanical and biochemical properties. In engineered cartilage, the injury response of developing constructs is unclear. To characterize the cellular response of tissue-engineered constructs cultured in chemically-defined medium after mechanical insult, either by compression-induced cracking, or by cutting, as a function of construct maturity. Primary immature bovine articular chondrocytes (4-6 weeks) were encapsulated in agarose hydrogel (2%, 30 millioncells/mL) and cultured in chemically-defined medium supplemented with Transforming growth factor (TGF)-β3 (10ng/mL, first 2 weeks). At early (5 days) and late (35 days) times in culture, subsets of constructs were exposed to mechanical overload to produce a crack in the tissue or were exposed to a sharp wound with a perpendicular cut. Constructs were returned to culture and allowed to recover in static conditions. Mechanical and biochemical properties were evaluated at 2-week intervals to day 70, and cellular viability was assessed at 2-week intervals to day 85. Constructs injured early in culture recovered their mechanical stiffness back to control values, regardless of the mode of injury. Later in culture, when constructs exhibited properties similar to those of native cartilage, compression-induced cracking catastrophically damaged the bulk matrix of the tissue and resulted in permanent mechanical failure with persistent cell death. No such detrimental outcomes were observed with cutting. Biochemical content was similar across all groups irrespective of mode or time of injury. Unlike native cartilage, engineered cartilage constructs exhibit a reparative capacity when the bulk integrity of the developing tissue is preserved after injury.


Clinical Implications of Dystonia as a Neural Network Disorder.
Isolated dystonia is a neurological disorder of diverse etiology, multifactorial pathophysiology, and wide spectrum of clinical presentations. We review the recent neuroimaging advances that led to the conceptualization of dystonia as a neural network disorder and discuss how current knowledge is shaping the identification of biomarkers of dystonia and the development of novel pharmacological therapies.


Statin-macrolide interaction risk: a population-based study throughout a general practice database.
The myopathy risk associated with statin use increases in case of concomitant prescription of certain drugs, such as cytochrome P(450) (CYP) system inhibitors (i.e., macrolides). The aim of this study was to assess whether concurrent statin/macrolide prescriptions at high interaction risk are commonly written in a general practice setting. For this study, 156 general practitioners (GPs) with a patient population of almost 200,000 individuals, and participating in the Arianna database set up by "Caserta-1" Local health-Service Agency (ASL), were recruited. Within such a study sample, subjects receiving at least one statin/macrolide concomitant prescription during the year 2003 were identified. Sensitivity analysis was performed to assess the time distribution of high-risk macrolide prescriptions written within +/-10 days from the statin prescription date. Among 190,124 patients included in the study, 7,176 (3.8%) received at least one statin prescription during the observation period. Of these, 228 (3.2%) were occasionally co-prescribed with any macrolide on the same date, in 153 cases (2.1% of statin users) the macrolide being of high interaction risk. In particular, 2.1% (55) of simvastatin users and 2.2% (64) of patients on atorvastatin were prescribed with high-risk macrolide on the same date versus 0.6% and 1.8% of patients prescribed with fluvastatin and pravastatin, respectively. Concerning GPs, 99 (63.5%) co-administered statin and macrolide at high interaction risk at least once. Most GPs occasionally prescribed statin/macrolide at high interaction risk on the same date, despite the availability of therapeutic alternatives. Prevention strategies targeted to increase awareness of health professionals about the interaction risks of widely prescribed drugs are needed.


The tragedy of San Juanico--the most severe LPG disaster in history.
During the early morning of Monday, 19 November 1984, one of the largest disasters in industrial history occurred in the Mexico City Area, causing the greatest rescue effort to assist population in an emergency ever undertaken. The tragic catastrophe started in a large LPG (Liquid Petroleum Gas) storage and distribution centre in San Juan Ixhuatepec, 20 km north of Mexico City. The facilities, owned by the Pemex State Oil Company, consisted of six spherical storage tanks (four with a volume of 1600 m3 and two with a volume of 2400 m3) and 48 horizontal cylindrical bullet tanks of different sizes. At the time of the disaster the storage tanks contained 11,000 m3 of a mixture of propane and butane. The inhabitants of San Juan Ixhuatepec numbered about 40,000, and a further 60,000 lived in the hills surrounding the village. The majority were poor country people living in one-story houses constructed of concrete pillars filled in with bricks and with roofs of iron sheets. The disaster started due to LPG leakage, probably a pipe leakage or rupture due to excess pressure. A vapour cloud built up and was slowly moved by the north-east wind towards the ground-placed flare pit located in the western part of the plant. The vapour cloud was ignited around 5:40 a.m. and was followed by an extensive fire at the plant area. The first explosion was registered on the seismograph at the University of Mexico at 05 h 44 min 52 s and was followed by a dozen explosions within the next hour, some of them of BLEVE type (Boiling Liquid Expanding Vapour Explosion) due to rupture of one or more storage tanks. Two of the explosions had an intensity of 0.5 on the Richter scale. Unburned and burning gas entered the houses south of the plant area and set fire to everything. Blast waves from the explosions not only destroyed a number of houses but also shifted several cylindrical tanks from their supports and added more gas to the fire. The smaller spheres and some of the cylinders exploded and fragments and even whole cylinders weighing around 30 tons, were scattered over distances ranging from a few to up to 1200 m.


New technique for superior guiding catheter support during advancement of a balloon in coronary angioplasty: the anchor technique.
To get superior guiding catheter support, we tried a new method called the anchor technique. By inflating a balloon in a nontarget vessel and holding its shaft with backward force while advancing another balloon, the anchor effect for the guiding catheter could be obtained and it appeared to be helpful for a balloon or a stent to cross the target lesion.


Efficient Inference in Structured Spaces.
Whittington et al. demonstrate how network architectures defined in a spatial context may be useful for inference on different types of relational knowledge. These architectures allow for learning the structure of the environment and then transferring that knowledge to allow prediction of novel transitions.


In vivo measurement of the elastic properties of pelvic floor muscles in pregnancy using shear wave elastography.
We aimed to investigate changes in the elastic properties of levator ani muscle (LAM) and external anal sphincter (EAS) during pregnancy using shear wave elastography (SWE). Our secondary objective was to examine the association between the elastic properties of pelvic floor muscles (PFM) and perineal tears at childbirth. This was a prospective monocentric study, including nulliparous women. Three visits were planned (14-18, 24-28, and 34-38 weeks) with a SWE assessment of the LAM and EAS at rest and during Valsalva maneuver. Then, we collected data about the delivery's characteristics. Assessments were performed using an Aixplorer V12® device (SL 18-5 linear probe) using a transperineal approach, reporting the shear modulus in kPa. We looked for changes in PFM's elastic properties during pregnancy using one-way ANOVA for repeated measures. We compared the mean shear modulus in late pregnancy for each muscle and condition between women with an intact perineum at delivery and those with a perineal tear using Student's t test. Forty-seven women were considered. Forty-five women had vaginal delivery of which 38 (84.4%) had perineal tears. We did not report any significant changes in the elastic properties of PFM during pregnancy. Women with an intact perineum at delivery had a stiffer EAS at Valsalva maneuver in late pregnancy (27.0 kPa vs. 18.2 kPa; p < 0.005). There were no significant changes in the elastic properties of the PFM in pregnancy. Stiffer EAS in late pregnancy appears to be associated with a lower incidence of perineal tears.


beta-Lactamase production and genetic location in Staphylococcus aureus: introduction of a beta-lactamase plasmid in strains of phage group II.
Staphylococcus aureus strains of phage group II have increased in frequency in hospital-acquired infections during recent years. A total of 184 penicillin resistant group II strains from bacteraemia cases in the years 1961-1990 were analysed for the amount of beta-lactamase produced and the location of the beta-lactamase gene. Until 1977 all strains investigated had a chromosomally located beta-lactamase gene, but since then a 21 kb beta-lactamase plasmid has increased in occurrence among group II strains, especially among those strains typable only at high phage concentrations [100 x Routine Test Dilution (RTD) and 1000 x RTD]. In 1990, 84% of the group II strains contained this plasmid. Plasmid-containing strains produced more beta-lactamase than strains without the plasmid. S. aureus strains of the 94,96 complex, which since 1984 have decreased in frequency from 18 to 9% in 1993, have remained high producers of beta-lactamase.


Glycan conformational change in mesomorphic structures of ternary systems: liposaccharide/phospholipid/water.
An amphipatic liposaccharide, beta 16, has been synthesized by condensation of the glycoamino acid beta of ovomucoid with the palmitic acid to serve as a model on which the properties of the saccharide chains can be studied. This paper reports the ternary system beta 16/dipalmitoylphosphatidylcholine (DPPC)/water. Using X-ray diffraction and freeze-fracture electron microscopy, it was shown that the ternary system exhibits mesomorphic structures in the temperature range over which the aliphatic chains of the DPPC are in a liquid-like conformation. A phase diagram of the system was drawn at 75 degrees C in terms of the water concentration and of the beta 16 content. As the molar fraction in beta 16 increases from about 0.08 to 1, the ternary system displays successively two lamellar structures analogous to that exhibited by the system DPPC/H2O, then a hexagonal structure similar to that exhibited by the system beta 16/H2O. The two types of lamellar structure were shown to differ by the T or Y conformation adopted by their saccharide chains.


A growth and biochemistry of ten high yielding genotypes of Pakistani rice (Oryza sativa L.) at maturity under elevated tropospheric ozone.
Experimental studies were conducted to estimate the possible damage caused to ten rice (Oryza sativa L.) genotypes of Pakistan by tropospheric ozone. The experimental site is located at 31.4504° N and 73.1350° E, at an altitude of 184 m.a.s level with an average annual rainfall of 784 mm. A suitable and agile method was adopted to assess tolerance and susceptibility in rice genotypes at an early growth stage. Genotype Injury response, growth and biochemical parameters were measured to estimate possible effects of ozone, which was subsequently proclaimed as a criterion for ozone tolerance. Rice genotypes were subjected to ozone concentrations of 70 pbb (Current ambient) and 120 pbb (expected in near future) under a polytunnel. The findings indicated that ozone, an atmospheric pollutant, substantially harmed crop growth and metabolism, as well as inflicted a specific type of foliar injury that caused early leaf senescence. Rice genotype IR-9 followed by Punjab-Basmati and Ksk-434 appeared to be the most susceptible, whereas Basmati-515 followed by Basmati 2000 and super-Basmati were found to be Ozone-tolerant. Plant genotypes grown under elevated ozone showed 13.45% and 11.35% reduction in total root and shoot dry weight, and 25.54% and 6.6% decrease in plant leaf area and plant total length respectively compared to the control group. A significant interaction between treatment × chemical components and growth parameters was also found. The Present study confirms a direct relationship between visual response and growth as well as biochemical parameters. Declared results were statistically analyzed by using analysis of variance at confidence level of p < 0.05.


The little (lit) mutation cosegregates with the growth hormone releasing factor receptor on mouse chromosome 6.
The little (lit) autosomal recessive mutation in the mouse causes dwarfism due to isolated growth hormone deficiency. The in vitro physiology of pituitary growth hormone release in lit/lit animals suggests that an abnormality in the growth hormone releasing factor (GRF) receptor (Ghrfr) is a very likely candidate for the lit mutation. We mapped Ghrfr to the region around lit on Chromosome (Chr) 6 in 100 chromosomes of an FVB x Czech II interspecific backcross. Molecular markers were Neuropeptide Y (Npy), homeobox (Hoxa2), immunoglobulin kappa chain (Igk), wingless-related MMTV integration site (Wnt-2), cystic fibrosis (Cftr), carboxypeptidase A (Cpa), and Ghrfr. Map order and distances were as follows: Cen-II-Wnt-2-(0 cM)-Cftr-(6.0 cM)-Cpa-(8.0 cM)-Npy-(1.0 cM)-Hoxa2-(3.0 cM)-Ghrfr-(2.0 cM)-Igk. We mapped lit (by phenotype) relative to Hoxa2 and Igk on 72 F2 chromosomes of offspring of a B6CZ lit/ + x B6FVB lit/ + intercross and 18 chromosomes of offspring of a B6FVB lit/ + intercross. Map order and distances were as follows: Hoxa2-(2.1 cM)-lit/Ghrfr-(3.7 cM)-Igk. No recombinations between lit and Ghrfr were detected. Thus, Ghrfr maps to mouse Chr 6 and may be allelic with lit. Amplification of a short segment at the 3' end of the Ghrfr mRNA by reverse transcription coupled to the polymerase chain reaction showed a greatly diminished level of GRF receptor mRNA in the pituitaries of lit/lit mice as compared with lit/ + controls. Low level of message could reflect a primary molecular defect or be due to secondary hypoplasia of somatotropes.(ABSTRACT TRUNCATED AT 250 WORDS)


Indole-3-carbinol activates the ATM signaling pathway independent of DNA damage to stabilize p53 and induce G1 arrest of human mammary epithelial cells.
The phytochemical indole-3-carbinol (I3C), from cruciferous vegetables such as broccoli, has been shown to elicit a potent anti-proliferative response in human breast cancer cell lines. Treatment of the immortalized human mammary epithelial cell line MCF10A with I3C induced a G1 cell cycle arrest, elevated p53 tumor suppressor protein levels and stimulated expression of downstream transcriptional target, p21. I3C treatment also elevated p53 levels in several breast cancer cell lines that express mutant p53. I3C did not arrest MCF10A cells stably transfected with dominant-negative p53, establishing a functional requirement for p53. Cell fractionation and immunolocalization studies revealed a large fraction of stabilized p53 protein in the nucleus of I3C-treated MCF10A cells. With I3C treatment, phosphatidyl-inositol-3-kinase family member ataxia telangiectasia-mutated (ATM) was phosphorylated, as were its substrates p53, CHK2 and BRCA1. Phosphorylation of p53 at the N-terminus has previously been shown to disrupt the interaction between p53 and its ubiquitin ligase, MDM2, and therefore stabilizing p53. Coimmunoprecipitation analysis revealed that I3C reduced by 4-fold the level of MDM2 protein that associated with p53. The p53-MDM2 interaction and absence of p21 production were restored in cells treated with I3C and the ATM inhibitor wortmannin. Significantly, I3C does not increase the number of 53BP1 foci or H2AX phosphorylation, indicating that ATM is activated independent of DNA double-strand breaks. Taken together, our results demonstrate that I3C activates ATM signaling through a novel pathway to stimulate p53 phosphorylation and disruption of the p53-MDM2 interaction, which releases p53 to induce the p21 CDK inhibitor and a G1 cell cycle arrest.


Screening and identification of host proteins interacting with Toxoplasma gondii SAG2 by yeast two-hybrid assay.
The identification of receptors or binding partners of Toxoplasma gondii from humans is an essential activity. Many proteins involved in T. gondii invasion have been characterized, and their contribution for parasite entry has been proposed. However, their molecular interactions remain unclear. Yeast two-hybrid (Y2H) experiment was used to identify the binding partners of surface antigens of T. gondii by using SAG2 as bait. Colony PCR was performed and positive clones were sent for sequencing to confirm their identity. The yeast plasmids for true positive clones were rescued by transformation into E. coli TOP 10F' cells. The interplay between bait and prey was confirmed by β-galactosidase assay and co-immunoprecipitation experiment. We detected 20 clones interacting with SAG2 based on a series of the selection procedures. Following the autoactivation and toxicity tests, SAG2 was proven to be a suitable candidate as a bait. Thirteen clones were further examined by small scale Y2H experiment. The results indicated that a strong interaction existed between Homo sapiens zinc finger protein and SAG2, which could activate the expressions of the reporter genes in diploid yeast. Co-immunoprecipitation experiment result indicated the binding between this prey and SAG2 protein was significant (Mann-Whitney U-test: Z = -1.964, P = 0.05). Homo sapiens zinc finger protein was found to interact with SAG2. To improve the understanding of this prey protein's function, advanced investigations need to be carried out.


Electrochemical detection of insertion/deletion mutations based on enhanced flexibility of bulge-containing duplexes on electrodes.
Ferrocene-modified DNA probes formed fully matched duplexes and bulge-containing ones with wild-type and insertion/deletion-type complements of clinical importance, respectively. Cyclic voltammetry measurements revealed that the bulge-containing duplexes showed an increased flexibility compared to the fully matched duplexes. The difference in the bending elasticity could be read out electrochemically by square wave voltammetry.


Stereospecific deuteration of alpha-furanosyl azomycin nucleosides: a model reaction for tritium radiolabeling.
Stereospecific synthesis of 1-alpha-d-(2-deuteroribofuranosyl)-2-nitroimidazole (2'-[(2)H]-alpha-AZR) is reported. This, deuteration was independent of the configuration of C-2' -OH group (arabinose or ribose) in sugar moiety of starting molecules. Slightly better yield (>37%) of the deuterated product, 6, from arabinosyl precursor in comparison to corresponding ribose precursor (29%) was obtained which may reflect better stereochemical availability of C-2' -OH in arabinose during oxidation.


Breathe Soft, What Bugs through Early Windows Break?
In this issue of Cell Host & Microbe, Teo et al. (2018) explore the development of the upper airway microbiota over the first 5 years of life and provide evidence for a "critical window" of microbial exposure that contributes to chronic wheezing, a precursor to asthma.


An unusual WPW syndrome: What is the preexcitation variant?
A 15-year-old female with WPW syndrome and normal heart underwent an electrophysiology study for paroxysmal palpitations and syncope. Intravenous adenosine produced an unexpected response of QRS changes and advanced AV block. During isoproteronol infusion, short-lasting and poorly tolerated wide QRS tachycardia was inducible, but pacing maneuvers were not feasible during tachycardia to determine its definitive mechanism. However, various electrophysiologic phenomena including adenosine response, junctional beats pattern, and multisite atrial pacing were helpful to overcome the diagnosis challenges. Finally, careful evaluation of tachycardia features and the comprehensive electrophysiology study were crucial to establish presence of unusual preexcitation variants, and thus to guide successful catheter ablation of the arrhythmic substrate.


Achieving Highly Efficient Warm-White Light Emission in All-Inorganic Copper-Silver Halides via Structural Regulation.
Single-component metal halides with white light emission are highly attractive for solid-state lighting applications, but it is still challenging to develop all-inorganic lead-free metal halides with high white-light emission efficiency. Herein, by rationally introducing silver (Ag) into zero-dimensional (0D) Cs3 Cu2 Br5 as new structural building unit, a one-dimensional (1D) bimetallic halide Cs6 Cu3 AgBr10 is designed that emits strong warm-white light with an impressive photoluminescence quantum yield (PLQY) of 94.5% and excellent stability. This structural transformation lowers the conduction band minimum while maintaining the localized nature of the valence band maximum, which is crucial in expanding the excitation spectrum and obtaining efficient self-trapped excitons (STEs) emission simultaneously. Detailed spectroscopy studies reveal that the white-light originates from triplet STEs emission, which can be remarkably improved by weakening the strong electron-phonon coupling and thus suppressing phonon-induced non-radiative processes. Moreover, the interesting temperature-dependent emission behavior, together with self-absorption-free property, make Cs6 Cu3 AgBr10 as sensitive luminescent thermometer and high-performance X-ray scintillator, respectively. These findings demonstrate a general approach to achieving effective single-component white-light emitters based on lead-free, all-inorganic metal halides, thereby opening up a new avenue to explore their versatile applications such as lighting, temperature detection and X-ray imaging.


Cross-sectional observational study protocol: missing microbes in infants born by caesarean section (MiMIC): antenatal antibiotics and mode of delivery.
The intestinal microbiome in early life plays a major role in infant health and development. Factors like antibiotic exposure, breast/formula feeding and mode of delivery are known to affect the microbiome. The increasing occurrence of caesarean section (C-section) deliveries and antibiotic exposure warrants further insight into the potential missing microbes in those infants. The study objective is to study the effect of maternal antibiotic administration during pregnancy and/or C-section mode of delivery on the development of the infant's intestinal microbiome until the age of 2 years. A single site, cross-sectional observational study of C-section and vaginally delivered infants being either exposed to maternal antibiotic treatment or not during the third trimester of pregnancy. Throughout the nine visits, stool, urine, saliva, hair, breast milk and vaginal swabs will be collected from either mother and/or infant for microbiome and metabolomic analysis. The protocol was approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals. The trial has been registered at ClinicalTrials.gov.The findings from this study will be disseminated in peer-reviewed journals, during scientific conferences, and directly to the study participants. Sequencing data will be deposited in public databases. NCT04134819.


Psilocybin intoxication did not affect daytime or sleep-related declarative memory consolidation in a small sample exploratory analysis.
Psilocybin is investigated as a fast-acting antidepressant used in conjunction with psychotherapy. Intact cognitive functions, including memory, are one of the basic conditions of effective psychedelic-assisted therapy. While cognitive and memory processing is attenuated on various domains during psilocybin intoxication, the effect of psilocybin on the consolidation of memories learned outside of acute intoxication is not known. Thus the main aim of the current study was to test the effects of psilocybin on (A) memory consolidation of previously learned material just after the psilocybin session and (B) on overnight memory consolidation the night just after the psilocybin session. 20 healthy volunteers (10 M/10F) were enrolled in a placebo-controlled, double-blind, cross-over design. Effects on declarative memory consolidation in condition (A) The Groton Maze Learning Task and Rey Auditory Verbal Learning Test were used, and for (B) the Pair Associative Learning Test was used. We did not find psilocybin to improve memory consolidation. At the same time, we did not find psilocybin to negatively affect memory consolidation in any of the tests used. This evidence adds to the safety profile for the use of psilocybin.


Association of daily sleep duration with the incident dementia by serum soluble TREM2 in a community.
Little is known about the influence of serum level of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), which is a soluble type of an innate immune receptor expressed on the microglia, on the association of the daily sleep duration with the risk of dementia. A total of 1230 Japanese community-residents aged 60 and older without dementia were followed prospectively for 10 years (2002-2012). Serum sTREM2 levels were divided into two groups using the median value (334.8 pg/ml). Self-reported daily sleep duration was grouped into three categories of <5.0, 5.0-7.9, and ≥8.0 h. A Cox proportional hazards model was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) of daily sleep duration on the risk of dementia according to serum sTREM2 levels. During the follow-up, 262 subjects developed dementia. In subjects with low serum sTREM2 levels, subjects with ≥8.0 h of daily sleep had a significantly greater risk of dementia (multivariable-adjusted HR 2.05 [95% CI 1.32-3.19]) than those with 5.0-7.9 h of daily sleep, but those with <5.0 h did not. In contrast, the risk of dementia increased significantly in subjects with both <5.0 (1.95 [1.03-3.68]) and ≥8.0 h of daily sleep (1.48 [1.06-2.07]) in the subjects with high serum sTREM2 levels. The influence of daily sleep duration on risk of dementia differed according to serum sTREM2 levels in the older Japanese population. Short daily sleep may be associated with greater risk of dementia only in subjects with a high serum sTREM2 level.


Advanced inorganic lithium metasilicate binder for high-performance silicon anode.
Silicon (Si) is considered a high-capacity anode material with potential for next-generation lithium-ion batteries. However, the commercial application of Si anode is seriously hindered by huge volume variation (>300%) and limited Li+ diffusion ability. Herein, lithium metasilicate (LS), a novel inorganic binder, was innovatively developed to accommodate these challenges. Favorable compatibility is observed between the LS binder and Si nanoparticles (SiNPs) due to the existence of Si element within the LS skeleton. The interaction of the LS binder and SiNPs leads to a strong adhesion effect, enhancing the cycling stability of Si anode. The Si electrode with the LS binder presented an average discharge capacity of 2123 mAh/g at 0.84 A/g after 100 cycles. Furthermore, the presence of the Li+ transport channel within the LS binder enhances Li+ diffusion ability within Si anode. As a result, the average discharge capacity reaches 663 mAh/g at 8.4 A/g. This work thus explored new inorganic binder design approaches for Si anode, contributing to the advancement of high-performance Si anode.


A validated stability-indicating LC method for estimation of etoposide in bulk and optimized self-nano emulsifying formulation: Kinetics and stability effects.
The present investigation was aimed to establish a validated stability-indicating liquid chromatographic method for the estimation of etoposide (ETP) in bulk drug and self-nano emulsifying formulation. ETP was successfully separated from the degradation products formed under stress conditions on LiChrospher 100 C18 reverse-phase column (a 250 mm × 4.6 mm i.d., 5-μm particle size) using 55:45 (v/v) acetonitrile-phosphate buffer saline (pH 4.5) as the mobile phase, at a flow rate of 1.0 mL min(-1) and detection at 283 nm. The response was a linear function of analyte concentration (R(2) > 0.9997) over the concentration range of 0.05-50 μg mL(-1). The method was validated for precision, accuracy, robustness, sensitivity and specificity. The % recovery of ETP at three different levels (50%, 100% and 150%) ranged between 93.84% and 100.06% in optimized self-nano emulsifying formulation, Etosid® soft-gelatin capsule and Fytosid® injection. First-order degradation kinetics of ETP were observed under acidic and alkaline conditions. The method was also applied for the stability assessment of self-nano emulsifying formulation under accelerated conditions, the formulation was found to be stable at all storage conditions with the shelf-life of 2.37 years at 25 °C. The method holds promise for routine quality control of ETP in bulk, pharmaceutical formulations as well as in stability-indicating studies.


Thirty-Day Outcomes After Bilateral Total Hip Arthroplasty in a Nationwide Cohort.
Approximately 42% of patients with end-stage osteoarthritis have bilateral disease. Although bilateral total hip arthroplasty (THA) is physiologically demanding, certain patients may benefit from simultaneous rather than staged bilateral procedures. This study examines the intraoperative differences and 30-day outcomes in patients receiving bilateral THA compared with those who underwent unilateral THA. Patients undergoing THA were selected from the National Surgical Quality Improvement Program database from 2008 to 2015. Patients were selected according to those with primary and concurrent coding for Current Procedural Terminology 27130. Thirty-day complications were recorded, and multivariate analyses were performed to determine whether concurrent THA was a risk factor for poor outcomes. A total of 97,804 patients and 587 patients who underwent unilateral and bilateral THA, respectively, were identified. Patients who underwent bilateral procedures were younger (57.3 vs 64.6 years, P < .001), were of lower body mass index (29.2 vs 30.2, P < .001), and had fewer comorbidities than patients who underwent unilateral procedures. Length of stay was not increased for bilateral recipients (3.13 vs 2.93 days, P = .308), although fewer were discharged to home (62.8% vs 77.6%, P < .001). The bilateral recipients required postoperative transfusions at a higher rate (29.8% vs 10.9%, P < .001) and had an increased incidence of deep wound infections on univariate analysis (1.2% vs 0.3%, P = .002). There was no increased risk of superficial infection, medical complications, or thromboembolic events for the bilateral cohort. Although bilateral THA recipients are younger with fewer preoperative comorbidities, bilateral THA is associated with an increased rate of transfusion in a nationwide setting. With this knowledge, specific interventions should be instituted to target these procedure-specific risks.


[Defects in the prostaglandin system. IX. Lipoxygenase defect of thrombocytes in a patient with polycythemia vera].
Patients with the myeloproliferative syndrome (MPS) often show morphological and functional platelet abnormalities and an increased incidence of lowered cyclooxygenase- and/or lipoxygenase activity. We present the case history of a 68-year-old male patient with polycythaemia vera in whom an absolute absence of platelet lipoxygenase activity has been detected for the first time in the literature.


Simultaneous multiplexed materials characterization using a high-precision hard X-ray micro-slit array.
The needs both for increased experimental throughput and for in operando characterization of functional materials under increasingly realistic experimental conditions have emerged as major challenges across the whole of crystallography. A novel measurement scheme that allows multiplexed simultaneous measurements from multiple nearby sample volumes is presented. This new approach enables better measurement statistics or direct probing of heterogeneous structure, dynamics or elemental composition. To illustrate, the submicrometer precision that optical lithography provides has been exploited to create a multiplexed form of ultra-small-angle scattering based X-ray photon correlation spectroscopy (USAXS-XPCS) using micro-slit arrays fabricated by photolithography. Multiplexed USAXS-XPCS is applied to follow the equilibrium dynamics of a simple colloidal suspension. While the dependence of the relaxation time on momentum transfer, and its relationship with the diffusion constant and the static structure factor, follow previous findings, this measurements-in-parallel approach reduces the statistical uncertainties of this photon-starved technique to below those associated with the instrument resolution. More importantly, we note the potential of the multiplexed scheme to elucidate the response of different components of a heterogeneous sample under identical experimental conditions in simultaneous measurements. In the context of the X-ray synchrotron community, this scheme is, in principle, applicable to all in-line synchrotron techniques. Indeed, it has the potential to open a new paradigm for in operando characterization of heterogeneous functional materials, a situation that will be even further enhanced by the ongoing development of multi-bend achromat storage ring designs as the next evolution of large-scale X-ray synchrotron facilities around the world.


Parametric study of acoustically-driven microbubble cavitations in a sonochemical reactor.
The bubble cavitation along a solid wall is investigated with a three-dimensional model based on the indirect boundary element method. Kinetic energy and Kelvin impulse are calculated in order to quantify the strength of cavitation. The influences of acoustic wave amplitude and frequency and liquid properties on the strength of cavitation are investigated. This study was carried out in order to better understand the relation between microscale processes and macroscale parameters in a sonochemical reactor used for impregnation of fabrics with nanoparticles.


Androgen receptor in the rat brain--assays and properties.
The existence and relevance of an androgen receptor in the developing brain has been a matter of controversy. We here describe both sucrose density gradient and hydroxylapatite assays which clearly define a distinct androgen receptor in the 24-day-old rat hypothalamus, amygdala and preoptic region, but not in the cortex. This receptor has considerable affinity for estradiol-17beta, thus perhaps accounting for some uncertainty about its nature, but none for diethylstilbestrol or other estrogens, antiestrogens or glucocorticoids. Its Kd for both dihydrotestosterone and testosterone is about 1 X 10(-9) M and for estradiol about 2 X 10(-8) M. Its properties are generally consistent with those of androgen receptor reported for other tissues.


Enhancer-specified GFP-based FACS purification of human spinal motor neurons from embryonic stem cells.
Human embryonic stem (hES) cells may generate all major somatic cell types, yet no neuronal subtype has yet been specifically generated in useful purity from hES culture. We report here the selective induction and isolation of functional spinal motor neurons (MNs) from human ES cells. hES cells of the H1 line were transfected with plasmids encoding GFP placed under the control of an MN-specifying enhancer within the 5'-regulatory region of the gene encoding the transcription factor Hb9 and treated with sonic hedgehog (Shh) and retinoic acid (RA). As MNs were induced under the influence of Shh and RA, they activated Hb9-driven GFP expression, permitting their isolation by fluorescence-activated cell sorting (FACS). The MNs thereby generated and isolated became cholinergic and achieved functional maturation in vitro, as evidenced by their fast sodium currents and action potentials on whole-cell patch-clamp and alpha-bungarotoxin-identified clustering of AChR receptors on co-cultured skeletal myoblasts. The serial combination of these two approaches, motor neuron phenotypic induction followed by Hb9 enhancer-based FACS, permitted the high-efficiency induction and isolation of functional motor neurons from hES cells. These results suggest the utility of promoter/enhancer-based FACS for the isolation of specific phenotypes from hES cell populations as a means of purifying clinically appropriate vectors for cell therapy.


Bone formation within the articular cartilage of the lateral compartment of varus osteoarthritic knees.
One of the causes of failure after unicompartmental knee arthroplasty (UKA) for varus osteoarthritis is the progression of osteoarthritis in the lateral compartment. Bone formation within the articular cartilage has been reported as a possible cause of the deterioration of the osteoarthritis. However, its prevalence and histology are still uncertain. The purpose of the current study is to investigate bone pieces obtained from the lateral compartment of the knee during total knee arthroplasty (TKA) radiographically and histopathologically, and to examine the bone formation within the articular cartilage in detail. Thirty-four consecutive patients, who underwent TKA for varus osteoarthritis of the knee, were included in this study. There were 6 males and 28 females and the mean age at the surgery was 74 years (range 63-85 years). Fifty-seven and 99 sagittal slabs were acquired from the resected bone pieces of the distal lateral femoral condyle and lateral tibial plateau, respectively. These slabs were investigated by soft X-ray radiographs and histopathological analyses stained with hematoxylin-eosin and elastica-Masson. On soft X-ray radiographs, bone formation (in which bone trabeculae were clearly detected) within the articular cartilage was observed in 8 (14.0%) of 57 femoral slabs and 7 (7.1%) of 99 tibial slabs. Histopathological analyses revealed that the bone which had formed comprised normal trabeculae and fatty marrow. There was rich vascularity in the cartilage around the formed bone. The current study is the first to describe the prevalence, location, and histopathological findings of bone formation within the articular cartilage of the lateral compartment of varus osteoarthritic knees. Since the thickness of the cartilage covering the bone formation is less than that without it, it may result in the deterioration of the lateral compartment after UKA.


Telemedicine and remote monitoring in cystic fibrosis.
Guidelines for cystic fibrosis (CF) care recommend multidisciplinary teams see patients at least quarterly with frequent measurement of spirometry and collection of respiratory cultures. This can be burdensome for people with CF, particularly if they live far from a specialized care center. This has led to an interest in telehealth coupled with remote monitoring. We review the recent literature on these topics for people with CF. The COVID-19 pandemic accelerated a move toward remote delivery of CF care and multiple recent publications have reported on the feasibility of telehealth, remote spirometry, remote collection of respiratory cultures, adherence monitoring, cough assessment, symptom monitoring and activity tracking. Useful data can be obtained and both clinicians and patients have favorable opinions about remote delivery of healthcare, though the impact on clinical outcomes is not yet known. Telehealth and remote monitoring for people with CF is feasible and has grown in use, though it is too early to know how prominently these approaches will fit into routine care for CF.


Pneumococcal polysaccharide vaccination in allogeneic hematopoietic stem cell transplantation recipients: a prospective single-center study.
Few studies have evaluated the response of allogeneic hematopoietic stem cell transplantation [allo-HSCT] recipients to pneumococcal polysaccharide vaccine-23 [PPSV23] in the modern transplant era when more elderly patients undergo allo-HSCT. We administered a single dose of PPSV23 to 30 allo-HSCT recipients and evaluated serotype-specific antibody responses using IgG measured by enzyme-linked immunosorbent assay and opsonophagocytic assay [OPA] titers in a multiplexed opsonophagocytic killing assay. The median patient age was 54 years [range, 23-68], and the interval from allo-HSCT to vaccination was 756 days [range, 389-1903]. No severe adverse effects were observed. The median positive response rates at 1 month and 1 year post-vaccination for the 7 serotypes measured by IgG were the same at 43% [range, 33-57], while those for 8 serotypes measured by OPA were 72% [range, 55-86] and 55% [range, 52-62], respectively. Peripheral blood stem cell transplantation improved vaccine response based on OPA titers at 1 month post-vaccination. During the median follow-up period of 1135 days post-vaccination, one patient developed pneumococcal bacteremia at 998 days. Our study suggests that PPSV23 vaccination in allo-HSCT recipients is safe and may result in a serological response.


Injuries in elite motorcycle racing in Japan.
To investigate the incidence and pattern of injuries, relative risks, and factors affecting incidence among elite motorcycle competitors in Japan. A total of 117 elite motorcycle competitors including 36 road racers, 60 motocross racers, and 21 trial bike riders completed a questionnaire about injuries. Sixty major injuries (25 in road racing, 32 in motocross, and three in trial bike riding) were reported. The most common injuries were fractures (45), followed by ligament injuries (8), dislocations (5), and soft tissue injuries (2). The overall injury rate was 22.4 per 1000 hours, and the death rate was zero. There was no significant correlation between risk of injury and age, experience, or accumulated competition points. Injury rates in competitions such as road racing and motocross are high, and therefore additional safety measures are needed to protect competitors from injury.


Microbiome analysis in women with endometriosis: Does a microbiome exist in peritoneal fluid and ovarian cystic fluid?
To investigate the relationship between the microbiome of the female genital tract and endometriosis. This prospective cohort study included 36 women who underwent laparoscopic surgery for ovarian tumor from July 2019 to April 2020. Of them, 18 had endometriosis, and 18 did not have endometriosis. Vaginal secretions, endometrial fluid, peritoneal fluid, and ovarian cystic fluid were collected during surgery. Next-generation sequencing of bacterial 16S rRNA was performed to characterize the microbiome. Specific microbiomes were not detected in either peritoneal fluid or ovarian cystic fluid regardless of the presence or absence of endometriosis and the type of cyst. When the cutoff value of infectious bacterial abundance in the vagina was set as 64.3%, there were many cases more than a cutoff value in the endometriosis group significantly (p = 0.01). When the cutoff value of infectious bacterial abundance in the endometrium was set as 18.6%, there were many cases more than a cutoff level in the endometriosis cases significantly (p = 0.02). Peritoneal fluid and ovarian cystic fluid are almost sterile, although dysbiosis may occur in the vaginal and endometrial microbiome in women with endometriosis.


Commoning the governance: a review of literature and the integration of power.
The concept of commoning is continuing to gain scholarly interest, with multiple definitions and interpretations across different research communities. In this article, we define commoning as the actions by groups with shared interests towards creating shared social and relational processes as the basis of governance strategy. Perhaps it can be more simply defined as collective ways of relating and governing. This article addresses two specific gaps in the commoning literature: (1) to bridge disparate strands of literature on commoning by briefly reviewing each and arguing for integration through epistemic pluralism, and (2) to explicitly examine how power is manifest in commoning processes by bringing in a framework on power (i.e., power over, power with, power to, power within) to understand the links between power and commoning governance processes in two case studies. The two cases are tourism governance on Gili Trawangan, Indonesia and aquatic food production systems in Bulacan, Philippines. We preface this analysis with the argument that power is an integral part of the commoning concept, but that it has yet to be analytically integrated to applications of the broader institutional analysis and development framework or within the networks of action situations approach. We argue that by making explicit how an analysis of power can be coupled to a network of action situations analysis in a qualitative way, we are advancing a key feature of the commoning concept, which we introduce as rooted in epistemic and analytical pluralism in the analysis of governance. In the discussion, we expand on how each case study reveals each of the four power dynamics, and how they improve the understanding of commoning as a pluralistic and perhaps bridging analytical concept.


Retrospective and integrative analyses of molecular characteristics and their specific imaging parameters in pediatric grade 1 gliomas.
Pediatric low-grade gliomas (PLGG) are the most common brain tumors diagnosed during childhood and represent a heterogeneous group associating variable molecular abnormalities. To go further and develop specific statistical patterns between tumor molecular background, imaging features, and patient outcome, a retrospective study was performed in a group of non-neurofibromatosis type 1 (non-NF1) grade 1 PLGGs. Seventy-eight children, followed from 2004 to 2017, were retrospectively reported. In this population, we analyzed radiological and molecular parameters. Their therapeutic management comprised surgery or surgery plus chemotherapies. Considering all 78 patients, 59 had only a surgical removal and 19 patients were treated with postoperative chemotherapy. Twelve progressions were reported in the partially resected and chemotherapeutic groups, whereas four deaths occurred only in the highly treated patients. As expected, in the global cohort, PLGG with BRAF p.V600E and/or CDKN2A loss exhibited poor outcomes and we evidenced significant associations between those molecular characteristics and their imaging presentation. In the chemo-treated patients, when associating initial and 6-month magnetic resonance imaging (MRI) parameters to the molecular features, the good risk situations were significantly linked to the presence of a large tumor cyst at diagnosis and the appearance during treatment of a higher cystic proportion that we called cystic conversion. So, additionally to the presence of BRAF p.V600E or CDKN2A deletion in grade 1 PLGGs, the absence on diagnostic MRI of cystic parts and/or cystic conversion at 6-month chemotherapy were significantly linked to a worst prognosis and response to treatment. These imaging features should be considered as prognostic markers in future PLGG studies.


Inhibition of gecko GSK-3β promotes elongation of neurites and oligodendrocyte processes but decreases the proliferation of blastemal cells.
GSK-3β signaling is involved in regulation of both neuronal and glial cell functions, and interference of the signaling affects central nervous system (CNS) development and regeneration. Thus, GSK-3β was proposed to be an important therapeutic target for promoting functional recovery of adult CNS injuries. To further clarify the regulatory function of the kinase on the CNS regeneration, we characterized gecko GSK-3β and determined the effects of GSK-3β inactivation on the neuronal and glial cell lines, as well as on the gecko tail (including spinal cord) regeneration. Gecko GSK-3β shares 91.7-96.7% identity with those of other vertebrates, and presented higher expression abundance in brain and spinal cord. The kinase strongly colocalized with the oligodendrocytes while less colocalized with neurons in the spinal cord. Phosphorylated GSK-3β (pGSK-3β) levels decreased gradually during the normally regenerating spinal cord ranging from L13 to the 6th caudal vertebra. Lithium injection increased the pGSK-3β levels of the corresponding spinal cord segments, and in vitro experiments on neurons and oligodendrocyte cell line revealed that the elevation of pGSK-3β promoted elongation of neurites and oligodendrocyte processes. In the normally regenerate tails, pGSK-3β kept stable in 2 weeks, whereas decreased at 4 weeks. Injection of lithium led to the elevation of pGSK-3β levels time-dependently, however destructed the regeneration of the tail including spinal cord. Bromodeoxyuridine (BrdU) staining demonstrated that inactivation of GSK-3β decreased the proliferation of blastemal cells. Our results suggested that species-specific regulation of GSK-3β was indispensable for the complete regeneration of CNS.


A quackery with a difference-new medical pluralism and the problem of 'dangerous practitioners' in the United Kingdom.
The figure of the 'miracle cure'-peddling quack pretending spectacular properties for worthless tonics is iconic. From their 19th century traveling wagon shows to their 21st century Internet spam scams, hucksters and cranks have been consistently targeted by health authorities as a danger to public health. Yet, in this paper, I argue that this is only one form that the problem of 'quackery' has taken in the past two centuries or so in the United Kingdom. Just as Roy Porter showed how the mid-19th century professionalization of medicine gave rise to a 'quackery with a difference' as a whole range of new medical movements-homoeopathy, hydropathy, medical botany, mesmerism-actively denounced allopathic or modern medicine, I will suggest that the late 20th century birth of 'complementary and alternative medicine' (CAM) has resulted in yet another transformation in quackery. By examining the ways in which regulatory authorities in the UK have come to address what is invariably described as a 'growing interest in CAM', I will show how the problem of quackery today is increasingly located in an ethical field of practitioner competency, qualifications, conduct, responsibility and personal professional development, almost (but not quite) regardless of the form of therapy in question.


Motion compensated cine CMR of the fetal heart using radial undersampling and compressed sensing.
To develop and evaluate a reconstruction framework for high resolution time-resolved CMR of the fetal heart in the presence of motion. Data were acquired using a golden angle radial trajectory in seven fetal subjects and reconstructed as real-time images to detect fetal movement. Data acquired during through-plane motion were discarded whereas in-plane motion was corrected. A fetal cardiac gating signal was extracted to sort the corrected data by cardiac phase, allowing reconstruction of cine images. The quality of motion corrected images and the effect of data undersampling were quantified using separate expressions for spatial blur and image error. Motion corrected reordered cine reconstructions (127 slices) showed improved image quality relative to both uncorrected cines and corresponding real-time images across a range of root-mean-squared (RMS) displacements (0.3-3.7 mm) and fetal heart rates (119-176 bpm). The relative spatial blur between cines with and without motion correction increased with in-plane RMS displacement leading to an effective decrease in the effective spatial resolution for images without motion correction. Image error between undersampled and reference images was less than 10% for reconstructions using 750 or more spokes, yielding a minimum acceptable scan time of approximately 4 s/slice during quiescent through plane motion. By rejecting data corrupted by through-plane motion, and correcting data corrupted by in-plane translation, the proposed reconstruction framework accounts for common sources of motion artifact (gross fetal movement, maternal respiration, fetal cardiac contraction) to produce high quality images of the fetal heart.


Morbid obesity increases the failure rate of sentinel lymph node mapping for endometrial carcinoma.
The goal of this study was to examine the relationship between body mass index (BMI) and the success rate of sentinel lymph node (SLN) mapping using indocyanine green and near-infrared imaging. Sentinel lymph node mapping is recommended for patients with endometrial carcinoma to reduce the rate of full lymphadenectomy and its associated morbidity such as lymphedema. A retrospective review was conducted of robotic hysterectomy procedures for patients with a coded diagnosis of endometrial cancer and a cost code for indocyanine green discharged between March, 2016 and August, 2019. Preoperative characteristics included age, BMI, and number of prior abdominal surgeries (includes cervical, adnexal, uterine or rectal procedures, caesarian section, or appendectomy). Intra and postoperative characteristics included procedure time (incision to close), estimated blood loss, the American Society of Anesthesiologists (ASA) physical status classification, uterine weight, uterine diameter, FIGO Grade, myometrial depth, and depth of myometrial invasion. SLN and non-SLN number, location, and pathology were recorded. The primary outcome was the bilateral success rate for SLN mapping. Patients with class III obesity (BMI > 40) were found to have a significantly lower success rate for SLN mapping when compared with all other BMI categories (54.1% vs. 76.1%, respectively, p < 0.01).


Cathepsin H: Molecular characteristics and clues to function and mechanism.
Cathepsin H (CatH) is a lysosomal cysteine protease with a unique aminopeptidase activity that is extensively expressed in the lung, pancreas, thymus, kidney, liver, skin, and brain. Owing to its specific enzymatic activity, CatH has critical effects on the regulation of biological behaviours of cancer cells and pathological processes in brain diseases. Moreover, a neutral pH level is optimal for CatH activity, so it is expected to be active in the extra-lysosomal and extracellular space. In the present review, we describe the expression, maturation, and enzymatic properties of CatH, and summarize the available experimental evidence that mechanistically links CatH to various physiological and pathological processes. Finally, we discuss the challenges and potentials of CatH inhibitors in CatH-induced disease therapy.


Long-term complications in two patients after aortoaortic bypass for midaortic syndrome.
The midaortic syndrome (MAS) refers to descending thoracic and abdominal aortic coarctation, which is rare and most common in the pediatric population. Open surgical repair, often with aortoaortic bypass, remains a highly effective treatment and is traditionally thought to be definitive despite concerns over patient growth postoperatively. This article presents 2 cases of MAS treated with aortoaortic bypass who developed long-term complications, one related to patient growth and the other to graft-enteric fistula. Consideration must be given to patient growth at operation for MAS, and long-term follow-up is necessary to identify other complications.


Increased plasma melatonin in presymptomatic Huntington disease sheep (Ovis aries): Compensatory neuroprotection in a neurodegenerative disease?
Melatonin is a pleiotrophic hormone, synthesised primarily by the pineal gland under the control of the suprachiasmatic nuclei (SCN). It not only provides a hormonal signal of darkness but also has neuroprotective properties. Huntington's disease (HD) is a progressive neurodegenerative disorder characterised by abnormal motor, cognitive and psychiatric symptoms. There is growing evidence, particularly from animal models, that circadian rhythms may also be disturbed in HD. We measured two circadian-regulated hormones, melatonin and cortisol, in plasma samples collected around-the-clock from normal and presymptomatic transgenic HD sheep (Ovis aries) at 5 and 7 years of age, to assess SCN-driven rhythms and the effect of genotype, sex and age. Melatonin-related precursors and metabolites (tryptophan, serotonin, kynurenine) were also measured by liquid chromatography (LC)-mass spectrometry (MS). At 5 years of age in both rams and ewes, plasma melatonin levels were significantly elevated in HD sheep. In ewes measured 2 years later, there was still a significant elevation of nocturnal melatonin. Furthermore, the daytime baseline levels of melatonin were significantly higher in HD sheep. Since increased melatonin could have global beneficial effects on brain function, we suggest that the increased melatonin measured in presymptomatic HD sheep is part of an autoprotective response to mutant huntingtin toxicity that may account, at least in part, for the late onset of disease that characterises HD.


Genetic screening for the protective antigenic targets of BCG vaccination.
Bovine tuberculosis is an important animal health problem and the predominant cause of zoonotic tuberculosis worldwide. It results in serious economic burden due to losses in productivity and the cost of control programmes. Control could be greatly improved by the introduction of an efficacious cattle vaccine but the most likely candidate, BCG, has several limitations including variable efficacy. Augmentation of BCG with a subunit vaccine booster has been shown to increase protection but the selection of antigens has hitherto been left largely to serendipity. In the present study, we take a rational approach to identify the protective antigens of BCG, selecting a BCG transposon mutant library in naïve and BCG-vaccinated cattle. Ten mutants had increased relative survival in vaccinated compared to naïve cattle, consistent with loss of protective antigen targets making the mutants less visible to the BCG immune response. The immunogenicity of three putative protective antigens, BCG_0116, BCG_0205 (YrbE1B) and BCG_1448 (PPE20) was investigated using peptide pools and PBMCs from BCG vaccinated cattle. BCG vaccination induced PBMC to release elevated levels of IP10, IL-17a and IL-10 in response to all three antigens. Taken together, the data supports the further study of these antigens for use in subunit vaccines.


The Application of Ibadah (Worship) in Counseling: Its Importance and Implications to Muslim Clients.
Ibadah is one of the important components in Islamic teachings other than aqidah (belief) and akhlaq (moral). Its importance is determined through the purpose for creation of humans, namely to be devoted to Allah. In the context of counseling discipline, however, the element of ibadah or worship (submission) of Allah is not applied in the counseling process and is not recognized as one of the spiritual therapies able to help the client know his true potential in decision-making and problem-solving. Hence, the purpose of this study is to determine the importance of applying ibadah in counseling and its implications to the client. This study selects survey research as the method to collect data from clients. A set of questionnaire instruments was constructed and distributed to 30 clients selected through convenience sampling. Data obtained from research questionnaire are then analyzed using descriptive statistical technique. Research outcome finds that application of ibadah is very important in counseling and has four implications for the client: the client is able to control his behavior, gain peace of mind, control his emotions and becomes increasingly diligent in ibadah.


In vitro and in vivo study in rats of rectal suppositories containing furosemide.
The aim of our experimental work was to formulate furosemide-containing rectal suppositories, to study drug release with in vitro membrane diffusion examinations and to increase drug liberation with the use of non-ionic surfactants (Solutol HS 15, Cremophor RH 60, Montanox 60 DF), which were incorporated in the suppository base in various concentrations. Suppocire AS2X proved to be the best suppository base (diffused drug: 69.78%). The use of 1% Cremophor RH 60 additive with the Witepsol H 15 base increased the quantity of the diffused drug from 62 to 75%. The membrane diffusion examinations were followed by studying the influence of suppository bases and additives exerted on the actual diuretic effect in Sprague-Dawley male rats. Once again the Suppocire AS2X suppository base gave the best results compared to the control; the quantity of the animals' urine showed a fourfold increase. Used with the Witepsol H 15 base, even 1% of all the three additives resulted in a considerable increase of diuretic effect, so their use proved to be advantageous. The comparison of the membrane diffusion examinations with the in vivo diuretic effect reveals that in vitro drug release and the pharmacological effect usually showed the same tendency, that is a greater extent of in vitro furosemide release was associated with a greater quantity of rat urine.


Genomic characterization of Ralstonia solanacearum phage phiRSB1, a T7-like wide-host-range phage.
PhiRSB1 is a wide-host-range, T7-like bacteriophage that infects and efficiently lyses the phytopathogenic bacterium Ralstonia solanacearum. The phiRSB1 genome comprises 43,079 bp of double-stranded DNA (61.7% G+C) with 325-bp terminal repeats and contains 47 open reading frames. Strong activity of tandem early promoters and wide specificity of phage promoters of phiRSB1 were demonstrated.


Carbonylative cross-coupling of ortho-disubstituted aryl iodides. convenient synthesis of sterically hindered aryl ketones.
A mild and general protocol for the carbonylative cross-coupling of sterically hindered ortho-disubstituted aryl iodides is reported. Carbonylative Suzuki-Miyaura couplings of a variety of aryl boronic acids provide an array of substituted biaryl ketones in modest to excellent yield. A carbonylative Negishi coupling that utilizes alkynyl nucleophiles is also described.


Acrolein and cell cycle.
Acrolein, a potent cilioinhibitor of cigarette smoke was tested on synchronously dividing cultures. Mitosis could be blocked whenever the addition of acrolein was made during the cell cycle but this effect was totally reversible (between 0.06 microgram/ml to 1 microgram/ml). Nucleic acid syntheses were more affected than protein syntheses but the syntheses were only delayed and they resumed simultaneously during the same cycle.


Epigenetic inactivation of the extracellular matrix metallopeptidase ADAMTS19 gene and the metastatic spread in colorectal cancer.
ADAMTS19 encodes a member of the ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) protein family with emerging roles in carcinogenesis and metastasis. ADAMTS shares several distinct protein modules including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. In a previous work, we found ADAMTS19 frequently hypermethylated in colorectal cancer (CRC). We explored the association of methylation with tumor genotype and phenotype. The methylation status of the CpG island in the promoter of ADAMTS19 was determined in 252 colorectal, 65 pancreatic, 33 breast and 169 ovarian primary tumors, 70 CRC metastases, and 10 CRC cell lines. Tumor-specific methylation of ADAMTS19 was significantly more frequent in gastrointestinal than in gynecological cancers (odds ratio (OR) = 2.9, confidence interval (CI) = (1.9-4.7), p = 5.2 × 10(-7)) and was independent of the methylation of adjacent loci in CRC. Hypermethylation associated with CRC with mutated BRAF oncogene (OR = 10.1, CI = (3.1-42.9), p = 6.3 × 10(-6)) and with the mucinous phenotype in CRC (OR = 2.1, CI = (1.1-4.1), p = 0.023) and ovarian cancer (OR = 60, CI = (16-346), p = 4 × 10(-16)). Methylation was significantly more frequent in CRC metastases homing to the ovary and omentum than in those homing to the liver and lung (OR = 6.1, CI = (1.8-22.2), p = 0.001). Differentiating local from distant metastatic spread, methylation negatively associated with tumor progression (p = 0.031) but positively with depth of invasion (p = 0.030). Hypermethylation associated with transcriptional repression in CRC cell lines, and treatment with 5'-AZA-2'-deoxycytidine led to reactivation of mRNA expression. shRNA-mediated silencing of ADAMTS19 had no effect on the in vitro proliferation rate of CRC cells but significantly diminished their collective migration speed (56 %, p = 3.3 × 10(-4)) and potential to migrate in collagen I (64 %, p = 4.3 × 10(-10)). Our results highlight the frequent involvement of ADAMTS19 epigenetic silencing in CRC and mucinous ovarian cancer. The mechanistic preferences for the target organ of metastatic spread may lead to the development of diagnostic CRC biomarkers. The association with the mucinous phenotype also may have diagnostic applications for ovarian cancer.


Biochar as a potential strategy for remediation of contaminated mining soils: Mechanisms, applications, and future perspectives.
Soil heavy metal contamination caused by mining activities is a global issue. These heavy metals can be enriched in plants and animals through the food chain, and eventually transferred to the human system and threatening public health. Biochar, as an environmentally friendly soil remediation agent, can effectively immobilize heavy metals in soil. However, most researchers concern more about the remediation effect and mechanism of biochar for industrial and agricultural contaminated soil, while related reviews focusing on mining soil remediation are limited. Furthermore, the remediation effect of soil in mining areas is affected by many factors, such as physicochemical properties of biochar, pyrolysis conditions, soil conditions, mining environment and application method, which can lead to great differences in the remediation effect of biochar in diverse mining areas. Therefore, it is necessary to systematically unravel the relevant knowledge of biochar remediation, which can also provide a guide for future studies on biochar remediation of contaminated soils in mining areas. The present paper first reviews the negative effects of mining activities on soil and the advantages of biochar relative to other remediation methods, followed by the mechanism and influencing factors of biochar on reducing heavy metal migration and bioavailability in mining soil were systematically summarized. Finally, the main research directions and development trends in the future are pointed out, and suggestions for future development are proposed.


Design of a long-term antipsychotic in situ forming implant and its release control method and mechanism.
Two kinds of in situ forming implants (ISFIs) of atypical antipsychotics, risperidone and its 9-hydroxy active metabolite, paliperidone, using poly(lactide-co-glycolide)(PLGA) as carrier, were investigated. Significant difference was observed in the solution-gel transition mechanism of the two systems: homogeneous system of N-methyl-2-pyrrolidone (NMP) ISFI, in which drug was dissolved, and heterogeneous system of dimethyl sulfoxide (DMSO) ISFI, in which drug was dispersed. Fast solvent extractions were found in both systems, but in comparison with the high drug release rate from homogeneous system of drug/polymer/NMP, a fast solvent extraction from the heterogeneous system of drug/polymer/DMSO was not accompanied by a high drug release rate but a rapid solidification of the implant, which resulted in a high drug retention, well-controlled initial burst and slow release of the drug. In vivo study on beagle dogs showed a more than 3-week sustained release with limited initial burst. Pharmacologic evaluation on optimized paliperidone ISFIs presented a sustained-suppressing effect from 1 day to 38 day on the MK-801 induced schizophrenic behavior mice model. A long sustained-release antipsychotic ISFI of 50% drug loading and controlled burst release was achieved, which indicated a good potential in clinic application.


Differential effects of clorgyline on catecholamine and indoleamine metabolites in the cerebrospinal fluid of rhesus monkeys.
The effects of acute and chronic administration of clorgyline, an irreversible inhibitor of monoamine oxidase type A (MAO-A), on the deaminated metabolites of norepinephrine, dopamine and serotonin were examined in rhesus monkey cerebrospinal fluid (CSF). Acute clorgyline treatment resulted in highly significant, dose-dependent reductions in 3-methoxy-4-hydroxyphenylglycol (MHPG) of 50% (1 mg/kg) and 68% (2 mg/kg) compared to pretreatment values. Chronic clorgyline administration (0.25 to 0.5 mg/kg X 24 days) resulted in a 67% reduction in CSF MHPG. In contrast, the concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were less affected by acute clorgyline administration, being reduced significantly only after the 2 mg/kg dose, which lowered 5-HIAA 27% and HVA 48%. Chronic clorgyline treatment had no significant effect on the CSF concentrations of HVA and 5-HIAA. These data, which suggest that MAO-A inhibition by clorgyline in vivo is more closely associated with changes in the noradrenergic than the serotonergic or dopaminergic systems in nonhuman primates, are in general agreement with the effects of clorgyline on CSF and urinary biogenic amine metabolites in man. They differ from several in vitro studies which indicate a primary role of MAO-A in the metabolism of serotonin and of MAO-B in norepinephrine degradation in primate brain. The discrepancies may reflect modulating effects of synaptic feedback mechanisms on the actions of clorgyline in vivo or perhaps a failure of CSF metabolites to adequately reflect brain amine metabolism changes. The lack of change in platelet MAO-B activity during clorgyline treatment together with the minimal changes in HVA concentrations indicate that the selective inhibitory effects of clorgyline on MAO-A were maintained during chronic administration of low drug doses.


Predictive risk factors for early recurrence in patients with localized pancreatic ductal adenocarcinoma who underwent curative-intent resection after preoperative chemoradiotherapy.
The optimal surgical indication after preoperative chemoradiotherapy (CRT) remains a subject of debate for patients with pancreatic ductal adenocarcinoma (PDAC) because early recurrence often occurs even after curative-intent resection. The present study aimed to identify perioperative risk factors of early recurrence for patients with PDAC who underwent curative-intent resection after preoperative CRT. Two hundred three patients with PDAC who underwent curative-intent resection after preoperative CRT from February 2005 to December 2018 were retrospectively analyzed. The optimal threshold for differentiating between early and late recurrence was determined by the minimum p-value approach. Multivariate regression analysis was performed to identify predictive factors for early recurrence. In 130 patients who developed recurrence after resection, 52 who had an initial recurrence within 12 months were defined as the early recurrence group, and the remaining 78 were defined as the late recurrence group. The incidence of hepatic recurrence was significantly higher in the early recurrence group than in the late recurrence group (39.7 vs. 15.4%). The early recurrence group had significantly lower 3-year rates of post-recurrence and overall survival than the late recurrence group (4.0 and 10.7% vs. 9.8 and 59.0%, respectively). Serum level of CA19-9 before surgery ≥56.8 U/ml was identified as an independent risk factor for early recurrence (OR:3.07, 95%CI:1.65-5.73, p<0.001) and associated with a significantly higher cumulative incidence rate of hepatic recurrence and lower rates of recurrence-free and overall survival. Serum level of CA19-9 before surgery after preoperative CRT was a strong predictive factor for early recurrence.


Neonatal sucking as a clinical assessment tool: preliminary findings.
The sucking patterns of 42 healthy full-term and 44 preterm infants whose gestational age at birth was 30.9 +/- 2.1 weeks were compared using the Kron Nutritive Sucking Apparatus for a 5-minute period. The measured pressures were used to calculate six characteristics of the sucking response: maximum pressure generated, amount of nutrient consumed per suck, number of sucks per episode, the duration or width of each suck, the length of time between sucks, and the length of time between sucking episodes. The maximum pressure of the term infant (100.3 +/- 35) was higher, p less than .05, than the maximum pressure of the preterm infant (84 +/- 33). Term infants also consumed more formula per suck (45.3 +/- 20.3 vs. 37.6 +/- 15.9, p less than .05). In addition, they had more sucks/episode (13.6 +/- 8.7 vs. 7.7 +/- 4.1, p less than .001) and maintained the pressure longer for a wider suck width (0.49 +/- 0.1 vs. 0.45 +/- 0.08, p less than .05). Sucking profiles of the preterm infant are significantly different from the full-term infant. These sucking profiles can be developed as a clinically useful tool for nursing practice.


Heart rate variability can be used to estimate sleepiness-related decrements in psychomotor vigilance during total sleep deprivation.
To assess whether changes in psychomotor vigilance during sleep deprivation can be estimated using heart rate variability (HRV). HRV, ocular, and electroencephalogram (EEG) measures were compared for their ability to predict lapses on the Psychomotor Vigilance Task (PVT). Chronobiology and Sleep Laboratory, Duke-NUS Graduate Medical School Singapore. Twenty-four healthy Chinese men (mean age ± SD = 25.9 ± 2.8 years). Subjects were kept awake continuously for 40 hours under constant environmental conditions. Every 2 hours, subjects completed a 10-minute PVT to assess their ability to sustain visual attention. During each PVT, we examined the electrocardiogram (ECG), EEG, and percentage of time that the eyes were closed (PERCLOS). Similar to EEG power density and PERCLOS measures, the time course of ECG RR-interval power density in the 0.02-0.08-Hz range correlated with the 40-hour profile of PVT lapses. Based on receiver operating characteristic curves, RR-interval power density performed as well as EEG power density at identifying a sleepiness-related increase in PVT lapses above threshold. RR-interval power density (0.02-0.08 Hz) also classified subject performance with sensitivity and specificity similar to that of PERCLOS. The ECG carries information about a person's vigilance state. Hence, HRV measures could potentially be used to predict when an individual is at increased risk of attentional failure. Our results suggest that HRV monitoring, either alone or in combination with other physiologic measures, could be incorporated into safety devices to warn drowsy operators when their performance is impaired.


Response of soil microorganisms and enzymes to the foliar application of Helicur 250 EW fungicide on Horderum vulgare L.
The use of fungicides bears the risk of many undesirable outcomes that are manifested in, among other things, changes in the structure and activity of microorganisms. This study aimed at determining the effect of a Helicur 250 EW preparation, used to protect crops against fungal diseases, on the microbiological and biochemical activity of soil and on the development of Horderum vulgare L. The fungicide was sprayed on leaves of spring barley in the following doses (per active substance, i.e. tebuconazole, TEB): 0.046, 0.093, 0.139, 1.395, and 2.790 mg TEB plant-1. The following indices were analyzed in the study: index of microorganisms resistance (RS) to the effects of fungicide, microorganisms colony development index (CD), microorganisms ecophysiological diversity index (EP), genetic diversity of bacteria, enzymatic activity, and effect of the fungicide on spring barley development (IFH). The most susceptible to the effects of the fungicide turned out to be fungi. The metagenomic analysis demonstrated that the bacterial community differed in terms of structure and percentage contribution in the soil exposed to the fungicide from the control soil even at the Phylum level. However, Proteobacteria appeared to be the prevailing taxon in both soils. Bacillus arabhattai, B. soli, and B. simplex occurred exclusively in the control soil, whereas Ramlibacter tataounensis, Azospirillum palatum, and Kaistobacter terrae - exclusively in the soil contaminated with the fungicide. Helicur 250 EW suppressed activities of all soil enzymes except for arylsulfatase. In addition, it proved to be a strong inhibitor of spring barley growth and development.


A technique to salvage a single implant-supported fixed dental prosthesis having a nonretrievable implant screw fragment.
An implant screw fracture is one of the common problems associated with the implant components. In some situations, it may not be possible to retrieve the fractured implant screws. As a result, clinicians either remove the implant or the implant may need to be covered over with soft tissue. The salvage of an implant with a nonretrievable screw fragment may be highly beneficial to the patients. This report describes a technique to salvage an implant-supported single restoration that has a nonretrievable implant screw fragment.


Infant feeding practices in East Harlem.
Infant feeding practices among low-income infants in East Harlem were surveyed prior to undertaking a nutrition education program. Data were obtained from 24-hr. recalls on 153 infants seen in a well-baby clinic. Intakes of energy, protein, fat, ascorbic acid, iron, and sodium showed wide variations among infants of similar ages. Nutrient intakes were similar for black and Puerto Rican infants, although some ethnic differences were observed in the types of milk and solid foods consumed. Black infants received formula for a longer period, while Puerto Rican infants were transferred to whole cow's milk at a younger age. In contrast black infants were introduced to table foods earlier.


Clinical Correlates of Cerebrospinal Fluid 14-3-3 Protein in Non-Prion Rapid Progressive Dementia.
The 14-3-3 protein in cerebrospinal fluid (CSF) is a suitable biomarker for the diagnosis of Creutzfeldt-Jakob disease (CJD). However, it has also been detected in various non-prion-related rapidly progressive dementia (RPD), which affected its diagnostic performance and clinical utilization. To investigate the general disease distribution with positive 14-3-3 result and to evaluate the association between CSF 14-3-3 protein and the clinical features in patients with non-prion RPD. A total of 150 patients with non-prion RPD were enrolled. The clinical data were collected and CSF 14-3-3 test was performed for all patients. The distribution of various diseases with a positive 14-3-3 result was analyzed and the association of CSF 14-3-3 with clinical features was tested. The CSF 14-3-3 protein was detected in 23.3% of non-prion RPD patients, and the most frequent diagnoses were autoimmune encephalitis (22.9%) and neurodegenerative disease (22.9%). CSF 14-3-3 protein was more common in older patients (p = 0.028) and those presenting myoclonus (p = 0.008). In subgroup analysis, the positive 14-3-3 test was more common in neurodegenerative disease with a long time from the symptom onset to CSF 14-3-3 test (p = 0.014). CSF 14-3-3 protein could be detected in a broad spectrum of non-prion RPD. In particular, patients with autoimmune encephalitis and rapidly progressive neurodegenerative diseases and those with myoclonus have a greater likelihood of a positive 14-3-3 result. These results could help clinicians interpret the results of CSF 14-3-3 protein more reasonably.


Environmental endocrine disruptors and pregnane X receptor action: A review.
The pregnane X receptor (PXR) is a kind of orphan nuclear receptor activated by a series of ligands. Environmental endocrine disruptors (EEDs) are a wide class of molecules present in the environment that are suspected to have adverse effects on the endocrine system by interfering with the synthesis, transport, degradation, or action of endogenous hormones. Since EEDs may modulate human/rodent PXR, this review aims to summarize EEDs as PXR modulators, including agonists and antagonists. The modular structure of PXR is also described, interestingly, the pharmacology of PXR have been confirmed to vary among different species. Furthermore, PXR play a key role in the regulation of endocrine function. Endocrine disruption of EEDs via PXR and its related pathways are systematically summarized. In brief, this review may provide a way to understand the roles of EEDs in interaction with the nuclear receptors (such as PXR) and the related pathways.