Presence of diverse Candidatus Methylomirabilis oxyfera-like bacteria of NC10 phylum in agricultural soils.
To better explore the distribution and diversity of Candidatus Methylomirabilis oxyfera (M. oxyfera)-like bacteria of NC10 phylum in soil environments. The vertical distribution and diversity of NC10 phylum bacteria were investigated in an agricultural field (surface layer, 0-10 cm; subsurface layer, 20-30 cm; deep layers, 50-60 and 90-100 cm) by using Illumina-based 16S rRNA (V3-V4 region) gene sequencing of soil DNA samples and quantitative PCR assays. It was found that the NC10-related reads accounted for 0·8-4·5% of the 16S rRNA pool in each examined core sample, with greater percentage being observed in deep soils than in surface soils and subsurface soils. The recovered NC10-related reads showed 85·1-96·9% identity to the 16S rRNA gene of M. oxyfera. A high diversity of NC10 phylum bacteria was observed in the examined soil cores. A total of 115 operational taxonomic units (OTU) were detected based on 3% sequence divergence in the recovered 16S rRNA genes. Phylogenetic analysis showed that four distinct groups of NC10 phylum bacteria (groups A, B, C and D) were present in the examined soil cores, with group B members being the dominant bacteria. The group A members, which are identified as the dominant bacteria responsible for anaerobic methane oxidation (AMO) coupled to nitrite reduction, can mainly be detected at 50-60 cm. Quantitative PCR further confirmed the presence of NC10 phylum bacteria, ranging from 3·8 × 10(6) to 9·3 × 10(6) copies g(-1) soil. The results showed the presence of diverse NC10 phylum bacteria in agricultural soils by using Illumina-based 16S rRNA gene sequencing and qPCR assays. The greatest level of diversity of NC10 phylum bacteria was reported to date in this study, which improved our understanding of the distribution of NC10 phylum bacterial communities in soil environments.


Characterization of the somatogenic receptor in rat liver. Hydrodynamic properties and affinity cross-linking.
Rat liver somatogenic receptors have been characterized by gel permeation chromatography, sucrose density gradients in H2O and D2O, and affinity cross-linking using 125I-bovine growth hormone (bGH) as a specific somatogenic receptor ligand. Cross-linking of 125I-bovine growth hormone to a Triton X-100-treated low density fraction isolated from livers of late pregnant rats followed by sodium dodecylsulfate-polyacrylamide gel electrophoresis under reducing conditions showed three major binders with Mr 95,000, 86,000, and 43,000 and a minor binder of Mr 55,000, after correction for bound ligand assuming a 1:1 binding ratio of ligand-receptor. The Mr 86,000, 55,000, and 43,000 species were recovered in the detergent-soluble supernatant after high-speed centrifugation, whereas the Mr 95,000 species remained Triton X-100 insoluble. Detergent-soluble 125I-bGH-receptor complexes were further analyzed by sedimentation into sucrose density gradients. The sedimentation coefficient was S20,w = 5.2 S and the partial specific volume v = 0.72 ml/g. Gel permeation chromatography on a Sepharose S-400 column indicated a Stokes radius of 61 A for the 125I-bGH-receptor-Triton X-100 complex. Based on these figures, the molecular weight of the complex was calculated as 131,100. The molecular weight of the ligand-free receptor-Triton X-100 complex was calculated as Mr 109,100. Affinity cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the 61 A peak from Sephacryl S-400 chromatography (cf. above) showed two binding entities, one major and one minor with Mr values 86,000 and 43,000, respectively, in the absence of reductant. When electrophoresis was run in the presence of reductant the Mr 43,000 species was the major binding entity. Furthermore, two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis (first dimension, nonreducing and second dimension, reducing) showed that a disulfide-linked binder at Mr 43,000 is contained within the Mr 86,000 species. As with pregnant rats, female and male rats both showed 125I-bovine growth hormone binders of Mr 95,000, 84,000, 55,000, 43,000, and additionally an Mr 35,000 binder.


Long-Term Postoperative Cone-Beam Computed Tomography Analysis of Secondary Bone Grafting in 79 Patients With Unrepaired Alveolar Clefts.
This study used cone-beam computed tomography (CBCT) analysis to assess the long-term radiographic outcomes of early secondary alveolar bone grafting. The most recent postoperative CBCT scans of 79 alveolar cleft patients who underwent anterior iliac crest bone grafting by a single surgeon over a 6-year period and met all inclusion criteria were analyzed using a modified assessment tool. Clefts were measured vertically, horizontally, and superiorly in terms of nasal support and then assigned corresponding scores of 0 to 4 to help determine radiographic success. The sites were deemed poor (score of 0 or 1), acceptable (score ≥ 2), or favorable (score ≥ 3). Similarly, overall clefts (vertical plus horizontal scores) were classified as poor (score of 0 to 3), acceptable (score ≥ 4), or favorable (score ≥ 5). Statistical analysis was used to characterize patient demographic characteristics, to perform subgroup comparisons, and to identify factors specifically predictive of favorable outcomes. The study included 79 patients with a total of 105 clefts. Male patients comprised 60.8% of patients, and 32.9% of patients had a bilateral cleft. The average age at the time of surgery was 8 years 0 months, and the average time until the most recent postoperative CBCT scan was 2 years 8 months. The average scores were as follows: vertical, 2.9 (maximum score possible, 4); horizontal, 3.1 (maximum score possible, 4); nasal support, 2.7 (maximum score possible, 4); and overall cleft, 6.0 (maximum score possible, 8). All 79 patients were discharged on postoperative day 1, and the regraft rate was 0%. Multivariate analysis showed that younger patients had a significantly higher chance of achieving favorable results in terms of vertical scores (P = .0081) and overall cleft scores (P = .0204). The association between younger age and horizontal scores was marginally significant (P = .0667), but no significant association was found between age and nasal support. Younger patients have improved long-term radiographic success with grafted alveolar clefts. This finding supports performing anterior iliac crest bone grafting at a younger age in cleft lip patients.


Lead contamination of the mining and smelting district in Mitrovica, Kosovo.
Lead contamination in topsoil of the mining and smelting area of Mitrovica, Kosovo, was investigated for total concentrations and chemical fractions by sequential extraction analysis, mineralogical fractions by X-ray diffraction (XRD) and scanning electron microscopy with energy-dispersive X-ray spectrometer (SEM-EDX). The study revealed that all samples contained Pb exceeding USEPA standard of 400 mg kg-1. The highest total concentration of Pb (125,000 mg kg-1) was the soil from the former smelter. Sequential extraction results showed that the predominant form of Pb was associated with Fe-Mn oxide-bound fraction which ranged from 45.37 to 71.61% of total concentrations, while carbonate and silicate Pb-binding fractions were dominant when physical measurements (XRD and SEM-EDX) were applied. Application of Pb isotope ratios (206Pb/207Pb and 208Pb/206Pb), measured by inductively coupled plasma mass spectrometry, identified that Pb contamination is originated from similar anthropogenic source. The results reflected that the Pb contamination in the soil of this area is serious. In order to provide proper approaches on remediation and prevention of health impacts to the people in this area, a continuous monitoring and health risk assessment are recommended.


Enhancement of the fluorescence properties of double stranded DNA templated copper nanoparticles.
The weak fluorescence emission from dsDNA templated copper nanoparticles necessitates the use of high-end detectors like photomultiplier tubes for their detection. This sets limitations on their applicability to in-situ analyte detection and point-of-care applications which utilize comparatively low cost and less sensitive detectors. In this article, a technique to improve the fluorescence properties of copper nanoparticles templated on dsDNA is reported. The fluorescence enhancement is achieved by introducing a modification in the conventional synthesis technique by using a combination of sodium ascorbate and Taq buffer. When compared to the existing methods, the proposed method achieves 11 times higher fluorescence signal intensity from the dsDNA templated copper nanoparticles and 4 times faster attainment of maximum fluorescence signal. The effect of the ionic strength of the individual constituent components of Taq buffer on the fluorescence emission from the copper nanoparticles is also studied here. The utility of this enhancement strategy for analyte measurement is demonstrated with the example of melamine detection from milk samples. A linear relationship was observed between the fluorescence intensity from the copper nanoparticles and the concentration of melamine in the range from 0.5 ppm to 100 ppm (R2 = 0.9919), with a limit of detection of 0.1 ppm. The reported fluorescence enhancement technique also results in 2.95 times improved sensitivity of detection when compared to the conventional technique.


Detection of pepsinogen in the neonatal lung and stomach by immunohistochemistry.
Evaluate the hypothesis that the same pepsinogen C molecule produced in the stomach is also produced by the lung. Pulmonary and gastric tissues collected postmortem were immunohistochemically stained for pepsinogen C and pepsinogen A. Sixteen patients with diverse causes of death were evaluated. Gestational age at birth ranged between 21 and 37 weeks. Pepsinogen A was detected in 12 of the 13 stomach sections, mainly in the chief cells, but not in any lung sections. Pepsinogen C was detected in all stomach sections in chief and mucus cells and in 9 of the 16 lung sections, mainly in type II pneumocytes. Pepsinogen C was not detected in the 3 lung cases with a gestational age <23 weeks. The same pepsinogen C molecule is produced in the stomach and in the lung. These findings potentially affect previous study results that used an enzymatic pepsin detection assay to evaluate for and associate gastroesophageal reflux disease with other morbidities.


Chiral Lewis acid catalyzed resolution of racemic enol ester epoxides. Conversion of both enantiomers of an enol ester epoxide to the same enantiomer of acyloxy ketone.
This paper describes an efficient kinetic resolution of racemic enol ester epoxides via a chiral Lewis acid catalyzed rearrangement. Both enantiomerically enriched enol ester epoxides and alpha-acyloxy ketones can be obtained through this resolution. A positive nonlinear effect is observed in this process. By taking advantage of the mechanistic duality in acid-catalyzed enol ester epoxide rearrangement, we can completely convert a racemic enol ester epoxide into an enantiomerically enriched alpha-acyloxy ketone by treatment with a catalytic amount of a chiral Lewis acid followed by a catalytic amount of an achiral protic acid.


Peptides derived from a soluble molecule of the human leukocyte antigen (HLA) class I cause apoptosis in gastric cancer cell lines.
We have reported that the levels of the soluble molecule of the human leukocyte antigen class I (sHLA-I) in patients with advanced gastric cancer were significantly lower than those in patients with cancer in the early stages. However, the effect of sHLA-I on gastric cancer cells has not been elucidated. Using human gastric cancer cell lines, MKN28, MKN45, and MKN74, we evaluated the effects of sHLA-I on cell growth, DNA synthesis, and apoptosis induction. Three types of synthesized peptides derived from HLA-I were also examined for their capacity to induce apoptosis. sHLA-I and a synthesized peptide, nos. 220-232 of the alpha3 domain of HLA-B7, caused cell growth inhibition by inducing apoptosis in human gastric cancer cells. This peptide also inhibited the in vivo growth of cancer dissemination caused by an intraperitoneal injection of MKN45 into severe combined immunodeficient mice. In conclusion, sHLA-I and the peptides derived from HLA-I cause apoptosis in human gastric cancer cell lines.


Extreme intra-familial variability of congenital central hypoventilation syndrome: a case series.
Congenital central hypoventilation syndrome is an autosomal dominant disorder that classically presents as sudden death in infancy secondary to central hypoventilation. Most cases are caused by polyalanine repeat mutations in the paired-like homeobox 2B gene, PHOX2B. More severe disease is typically associated with nonpolyalanine repeat mutations. We report the case of a family with nonpolyalanine repeat mutations that uncharacteristically has many individuals who were mildly symptomatic and only diagnosed after genetic testing. We highlight the highly variable clinical presentation of this condition and the need for clinicians to remain vigilant. We identified 10 individuals in a large extended Caucasian family of German and Austrian background with congenital central hypoventilation syndrome.Case 1: A 16-year old male proband presented for reproductive counseling. He had a previous history of apneic spells and Hirschsprung disease in the neonatal period. A PHOX2B nonpolyalanine repeat mutation was identified in the proband and used to screen his extended family.Cases 2 to 10: Several mildly symptomatic family members (males aged 5, 13, 42 and 80 years; females aged 28, 44, 46 and 48 years) spanning four generations were identified after genetic screening. A newborn boy from this family was also recently diagnosed with Hirschsprung disease and went on to have an abnormal sleep study. In this report, we highlight the significant phenotypic variability of congenital central hypoventilation syndrome, previously thought to be a rare genetic condition. Given the extreme clinical variability, it is possible that the prevalence of congenital central hypoventilation syndrome in the general population is much higher than previous estimates. This is of major importance to all clinicians who will need to maintain a high index of suspicion for this not so rare and highly clinically variable genetic condition that spans all ages. As the familial mutation has been identified, presymptomatic and prenatal diagnostic testing are available options for family members.


Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells.
Chemotherapeutics represent the main approach for the treatment of leukemia. However, the occurrence of adverse side effects and the complete lack of effectiveness in some cases make it necessary to develop new drugs. As part of our screening program to evaluate the potential chemotherapeutic effect of natural coumarins, we investigated the anti-leukemic activities of a series of six prenylated coumarins isolated from the stem bark of Toddalia asiatica (Rutaceae). Among these, 6-(3-methyl-2-butenyl)-5,7-dimethoxycoumarin (toddaculin) displayed the most potent cytotoxic and anti-proliferative effects in U-937 cells. To determine whether these effects resulted from induction of cell death or differentiation, we further evaluated the expression of several apoptosis and maturation markers. Interestingly, while toddaculin at 250 μM was able to induce apoptosis in U-937 cells, involving decreased phosphorylation levels of ERK and Akt, 50 μM toddaculin exerted differentiating effects, inducing both the capacity of U-937 cells to reduce NBT and the expression of differentiation markers CD88 and CD11b, but no change in p-Akt or p-ERK levels. Taken together, these findings indicate that toddaculin displays a dual effect as a cell differentiating agent and apoptosis inducer in U-937 cells, suggesting it may serve as a pharmacological prototype for the development of novel anti-leukemic agents.


Granulomatous Inflammation of the Penis and Scrotum Following Application of Topical Cream.
Granulomas are collections of histiocytes that develop as an inflammatory response to bacterial and fungal infections, as well as foreign substances. We discuss here the case of a 49-year-old male who presented with a penile and scrotal mass with granulomatous inflammation, after application of a topical cream for enhancement of erectile function. While granuloma formation can often be seen with penile injections, this case presents the rare development of a foreign body granuloma after topical cream application on the penis and scrotum.


Identification of the N-acetyl-D-glucosamine-inducible element in the promoter of the Trichoderma atroviride nag1 gene encoding N-acetyl-glucosaminidase.
We have investigated the regulation by N-acetyl-glucosamine of the nag1 gene of the mycoparasitic biocontrol fungus Trichoderma atroviride (= T. harzianum P1), which encodes a 73-kDa N-acetyl-beta-D-glucosaminidase. The use of translational fusions revealed that a 290-bp fragment of the 5' regulatory region of nag1 is sufficient to confer inducibility on the Aspergillus niger goxA gene. The region between positions -150 and -290, upstream of the nag1 coding region, was investigated using in vivo methylation protection analysis and electrophoretic mobility shift assays (EMSAs). Two neighbouring regions that interacted with regulatory proteins were identified, and bases essential for these interactions were determined in vitro. These data reveal protein binding to a CCCCT element at -240, a CCAGN(13)CTGG motif at -284, and a CCAAT-box which is present in the spacer of the latter motif. Evidence for the binding of a Hap2/3/5 complex to this CCAAT motif is presented. Protein binding to all three motifs was constitutive, and no differences were observed between induced and non-induced cultures. Mutation of either the CCAGN(13)CTGG or the AGGGG motif resulted in loss of inducibility of nag1 expression by N-acetyl-D-glucosamine in vivo.


The possible involvement of both calcium and cyclic AMP in the dopaminergic inhibition of prolactin secretion.
Dopamine inhibited basal, TRH-, IBMX- and A23187-stimulated prolactin secretion from rat anterior pituitary cells. However, dopamine did not inhibit prolactin secretion stimulated by elevated K+ concentrations. These data are interpreted in terms of dopaminergic inhibition of both cyclic AMP production and Ca2+ influx through agonist-, but not voltage-, dependent Ca2+ channels.


Computational model of the jamming avoidance response in the electric fish Gymnotus carapo.
The unperturbed electric organ discharges of Gymnotus carapo fish are highly periodic with interpulse intervals around 40 ms. The 'jamming avoidance response' happens when fish interact and is a transitory interval shortening in the fish with the faster discharge that decreases the likelihood that pulses from it and the other fish will coincide. Our model's basic components match certain experimentally demonstrated facts. First, recurrence equations reproduce the periodic unperturbed discharges. Secondly, when an isolated pulse arrives, the two intervals following that with the pulse are shortened by amounts that decrease up to a minimum and then increase. Simulations demonstrated that this model reproduces satisfactorily the jamming avoidance response. Two additional conditions were demonstrably necessary: (i) one was that every pulse arrive within the hot cophase window (and not elsewhere); (ii) the other condition was that, along successive pulses, the respective cophases decrease by moderate amounts. In short, we conclude that the fish's jamming avoidance response can involve the simple computational rules implied by the proposed equations.


Estimating urban residential building-related energy consumption and energy intensity in China based on improved building stock turnover model.
Accurate estimation of urban residential building-related energy consumption (URBEC) and energy intensity per unit floor area at the national level has significant implications for the analysis of carbon emission peaks. However, reliable data on China's building floor space (BFS) are lacking, resulting in unclear energy intensity levels. This study proposes a China BFS estimation method (CBFSEM) based on improved building stock turnover model. Using CBFSEM, it estimates the BFS of historic urban dwelling stock, the demolished and newly built dwelling from 2000 to 2015. It then estimates the corresponding energy consumption and intensity based on the obtained urban residential BFS data. Results showed that total URBEC in China increased dramatically from 217.1 Mtce in 2000 to 417.2 Mtce in 2015 with an average annual growth rate of 4.45%. China's total dwelling stock almost doubled, from 10.6 billion m2 in 2000 to 27.4 billion m2 in 2015 with an annual growth rate of 6.56%. The operational energy consumption accounted for approximately 70% of total URBEC and the building material production energy intensity was the highest in total URBEC, >60 kgce/m2. A comparison with the China Population Census showed that the deviations were well below 8%, which indicated the reliability of the CBFSEM and the estimated results. In general, this study fills the gap in available data and addresses the shortage of estimation methods for BFS and energy intensity. It also provides the government with technical support and scientific evidence to promote building energy efficiency.


Novel substituted (pyridin-3-yl)phenyloxazolidinones: antibacterial agents with reduced activity against monoamine oxidase A and increased solubility.
Oxazolidinones represent a new and promising class of antibacterial agents. Current research in this area is mainly concentrated on improving the safety profile and the antibacterial spectrum. Oxazolidinones bearing a (pyridin-3-yl)phenyl moiety (e.g., 3) generally show improved antibacterial activity compared to linezolid but suffer from potent monoamine oxidase A (MAO-A) inhibition and low solubility. We now disclose the finding that new analogues of 3 with acyclic substituents on the pyridyl moiety exhibit excellent activity against Gram-positive pathogens, including linezolid-resistant Streptococcus pneumoniae. Generally, more bulky substituents yielded significantly reduced MAO-A inhibition relative to the unsubstituted compound 3. The MAO-A SAR can be rationalized on the basis of docking studies using a MAO-A/MAO-B homology model. Solubility was enhanced with incorporation of polar groups. One optimized analogue, compound 13, showed low clearance in the rat and efficacy against S. pneumoniae in a mouse pneumonia model.


Comparing risk-prediction methods using administrative or clinical data in assessing excess in-hospital mortality in patients with acute myocardial infarction.
To compare results of statistical process-control analyses of in-hospital deaths of patients with acute myocardial infarction by using either administrative or clinical data sources and prediction models, and to assess variation in results according to selected patient characteristics. Retrospective, cross-sectional study comparing variable life-adjusted display (VLAD) curves derived by using administrative or clinical prediction models applied to a single patient sample. Data from 467 consecutive patients admitted to a tertiary hospital in Queensland, between 1 July 2003 and 31 March 2006, with a coded discharge diagnosis of acute myocardial infarction. Statistical estimates of cumulative lives gained or lost in excess of those predicted at the end of the study period. The two prediction models, when applied to all patients, generated almost identical VLAD curves, showing a steadily increasing excess mortality over the study period, culminating in an estimated 11 excess deaths. Risk estimates for individual patients from each model were significantly correlated (r = 0.46, P < 0.001). After exclusion of misclassified cases, out-of-hospital cardiac arrests and deaths within 30 minutes of presentation, replotting the curves reversed the mortality trend and yielded, depending on the model, a net gain of three or seven lives. After further exclusion of transfers in from other hospitals and patients whose care had a palliative or conservative intent, the net gain increased to seven or 10 lives. Appropriate patient selection is more important than choice of dataset or risk-prediction model when statistical process-control methods are used to flag unfavourable mortality trends suggestive of suboptimal hospital care.


Membrane binding and conformational properties of peptides representing the NH2 terminus of influenza HA-2.
Synthetic peptides representing amino acid residues 1-16 and 1-20, a proposed fusogenic region of the HA-2 subunit of influenza virus hemagglutinin, bind to phosphatidylcholine vesicles with submicromolar dissociation constants. The 1-20, but not the 1-16, peptide appears to adopt a helical conformation when bound to vesicles and cooperatively promotes vesicle fusion.


On-Site Monitoring of Postoperative Bile Leakage Using Bilirubin-Inducible Fluorescent Protein.
Bile leakage is the most common postoperative complication associated with hepatobiliary and pancreatic surgery. Until now, however, a rapid, accurate diagnostic method for monitoring intraoperative and postoperative bile leakage had not been established. Bilirubin levels in drained abdominal fluids collected from 23 patients who had undergone hepatectomy (n = 22) or liver transplantation (n = 1) were measured using a microplate reader with excitation/emission wavelengths of 497/527 nm after applying 5 µM of UnaG to the samples. UnaG was also sprayed directly on hepatic raw surfaces in swine hepatectomy models to identify bile leaks by fluorescence imaging. The bilirubin levels measured by UnaG fluorescence imaging showed favorable correlations with the results of the conventional light-absorptiometric methods (indirect bilirubin: rs = 0.939, p < 0.001; direct bilirubin: rs = 0.929, p < 0.001). Approximate time required for bilirubin measurements with UnaG was 15 min, whereas it took about 40 min with the conventional method at a hospital laboratory. Following administration of UnaG on hepatic surfaces, the fluorescence imaging identified bile leaks not only on the resected specimens but also in the abdominal cavity of the swine hepatectomy models. Fluorescence imaging techniques using UnaG may enable real-time identification of bile leaks during hepatectomy and on-site rapid diagnosis of bile leaks after surgery.


Incidence and predictors of positive and negative effects of BRCA1/2 genetic testing on familial relationships: a 3-year follow-up study.
Little is known about the long-term impact of BRCA1/2 testing on the relationships between family members. We assessed the incidence of positive and negative family relationship effects of BRCA1/2 testing in the 3 years after result disclosure and identified predictors of these effects. A total of 485 women and 67 men who had undergone BRCA1/2 testing were asked 3 years later whether having been tested had improved and/or disrupted relationships with their relatives. The associations with sociodemographic, medical, and psychosocial characteristics were assessed. Globally, 85.1% did not report any positive or negative effects of genetic testing on family relationships. Positive and negative effects were reported by 13.2% and 3.7% of participants, respectively. Reporting positive relationship effects was associated with older age, intolerance for uncertainty, cancer-specific distress, and more social support. Low education, positive attitude toward prophylactic mastectomy, and low social support increased the likelihood of negative effects. Our findings do not support the belief that family relationships are frequently disrupted by BRCA1/2 testing. Understanding that most family relationships are unchanged long term by genetic testing may help genetic service providers encourage those considering testing to overcome hesitancy related to potential difficulties of communicating results to relatives.


Routine glucose assessment in the emergency department for detecting unrecognised diabetes: a cluster randomised trial.
To determine whether routine blood glucose assessment of patients admitted to hospital from emergency departments (EDs) results in higher rates of new diagnoses of diabetes and documentation of follow-up plans. Cluster randomised trial in 18 New South Wales public district and tertiary hospitals, 31 May 2011 - 31 December 2012; outcomes follow-up to 31 March 2016. Patients aged 18 years or more admitted to hospital from EDs. Routine blood glucose assessment at control and intervention hospitals; automatic requests for glycated haemoglobin (HbA1c ) assessment and notification of diabetes services about patients at intervention hospitals with blood glucose levels of 14 mmol/L or more. New diagnoses of diabetes and documented follow-up plans for patients with admission blood glucose levels of 14 mmol/L or more. Blood glucose was measured in 133 837 patients admitted to hospital from an ED. The numbers of new diabetes diagnoses with documented follow-up plans for patients with blood glucose levels of 14 mmol/L or more were similar in intervention (83/506 patients, 16%) and control hospitals (73/278, 26%; adjusted odds ratio [aOR], 0.83; 95% CI 0.42-1.7; P = 0.61), as were new diabetes diagnoses with or without plans (intervention, 157/506, 31%; control, 86/278, 31%; aOR, 1.51; 95% CI, 0.83-2.80; P = 0.18). 30-day re-admission (31% v 22%; aOR, 1.34; 95% CI, 0.86-2.09; P = 0.21) and post-hospital mortality rates (24% v 22%; aOR, 1.07; 95% CI, 0.74-1.55; P = 0.72) were also similar for patients in intervention and control hospitals. Glucose and HbA1c screening of patients admitted to hospital from EDs does not alone increase detection of previously unidentified diabetes. Adequate resourcing and effective management pathways for patients with newly detected hyperglycaemia and diabetes are needed. Australian New Zealand Clinical Trials Registry, ACTRN12611001007921.


The effect of additional autopolyploidization in a slow growing cellulase hyperproducer of Trichoderma.
M14-2 is a cellulase hyperproducer derived from Trichderma reesei QM 6a, but with a growth rate lower than that of the original strain. When M14-2 was autopolyploidized followed by haploidization and selection, the strain with both a higher cellulase productivity per mycelia and a higher growth rate could be obtained as M14-2B. This strain seemed to be constructed using gene sources amplified by additional autopolyploidization.


Biomechanical effects of sensorimotor orthoses in adults with Charcot-Marie-Tooth disease.
Charcot-Marie-Tooth disease is an inherited neuropathy causing progressive weakness, foot deformity and difficulty walking. Clinical anecdotes suggest orthoses designed on the 'sensorimotor' paradigm are beneficial for improving gait in Charcot-Marie-Tooth disease. Investigate the effect of sensorimotor orthoses on in-shoe and lower limb biomechanics in adults with Charcot-Marie-Tooth disease. Randomised, repeated-measures, exploratory study. Eight males and two females with Charcot-Marie-Tooth disease aged 31-68 years fitted with pedorthic shoes and custom-made sensorimotor orthoses were randomly tested at baseline and after 4 weeks of adaptation. In-shoe three-dimensional multi-segment foot and lower limb kinematics and kinetics were collected as were plantar pressures, electromyography and self-reported comfort, stability, cushioning and preference. Compared to the shoe only condition, sensorimotor orthoses increased midfoot eversion and plantarflexion, increased ankle eversion and produced small but significant changes at the knee and hip indicating increased internal rotation. The orthoses increased medial ground reaction forces and increased pressure at the heel, midfoot and toes. There were minimal effects on electromyography. The sensorimotor orthoses were rated higher for comfort, cushioning, stability and preference. Sensorimotor orthoses produced changes in kinematic, kinetic and pressure variables in adults with Charcot-Marie-Tooth disease and were regarded as more comfortable, cushioned and stable during walking. In this study, the walking ability of patients with Charcot-Marie-Tooth disease improved with the use of foot orthoses designed according to the sensorimotor paradigm. However, the mechanism of action appears to be primarily mechanical in origin. Randomised controlled trials are necessary to evaluate the long-term patient-reported outcomes of sensorimotor orthoses.


Anterior Lumbar Interbody Fusion May Provide Superior Decompression of the Foraminal Space Compared with Direct Foraminotomy: Biomechanical Cadaveric Study.
The objective of this cadaveric biomechanical study was to compare the area of the foraminal space during motion in the intact condition, after direct decompression via foraminotomy, and after indirect decompression via anterior lumbar interbody spacer insertion. Eight (8) L5-S1 cadaver specimens were used for testing. Each specimen was tested in the intact state, after posterior foraminotomy, and after standalone anterior lumbar interbody fusion (ALIF). Each specimen was 3-dimensional imaged under neutral loading, flexion, and extension. The 3-dimensional images were analyzed for changes in the foraminal area under each loading scenario. A repeat-measures design was used. Outcome measures from testing included the frequency in which an increase in cross-sectional area was observed, as well as the percent increase of the foraminal area for each surgical group and loading direction. Direct foraminotomy and ALIF maintained the foraminal space during initial distraction under no loading with areas 99.7% and 96.5% of the native foraminal area, respectively (P = 0.955 and P = 0.455). Direct foraminotomy increased the foraminal area significantly during flexion to 112.2% of the area before motion (P = 0.008) while ALIF did not. Direct foraminotomy significantly decreased the foraminal area during extension to 89.2% of the area before motion (P = 0.006). ALIF, however, maintained its initial distraction during extension with 98.2% of the area before motion (P = 0.808). ALIF maintains the foraminal area in extension while direct posterior foraminotomy does not.


Cell cycle inhibition therapy that targets stathmin in in vitro and in vivo models of breast cancer.
Stathmin is the founding member of a family of microtubule-destabilizing proteins that have a critical role in the regulation of mitosis. Stathmin is expressed at high levels in breast cancer and its overexpression is linked to disease progression. Although there is a large body of evidence to support a role for stathmin in breast cancer progression, the validity of stathmin as a viable therapeutic target for breast cancer has not been investigated. Here, we used a bicistronic adenoviral vector that co-expresses green fluorescent protein and a ribozyme that targets stathmin messenger RNA in preclinical breast cancer models with different estrogen receptor (ER) status. We examined the effects of anti-stathmin ribozyme on the malignant phenotype of breast cancer cells in vitro and in xenograft models in vivo both as a single agent and in combination with chemotherapeutic agents. Adenovirus-mediated gene transfer of anti-stathmin ribozyme resulted in a dose-dependent inhibition of proliferation and clonogenicity associated with a G2/M arrest and increase in apoptosis in both ER-positive and ER-negative breast cancer cell lines. This inhibition was markedly enhanced when stathmin-inhibited breast cancer cells were exposed to low concentrations of taxol, which resulted in virtually complete loss of the malignant phenotype. Interestingly, breast cancer xenografts treated with low doses of anti-stathmin therapy and taxol showed regression in a majority of tumors, while some tumors stopped growing completely. In contrast, combination of anti-stathmin ribozyme and adriamycin resulted in only a modest inhibition of growth in vitro and in breast cancer xenografts in vivo. Although inhibition of tumor growth was observed in both the combination treatment groups compared with groups treated with single agent alone, combination of anti-stathmin therapy and taxol had a more profound inhibition of tumorigenicity, as both agents target the microtubule pathway. Clinically, these findings are highly relevant because taxol is one of the most active chemotherapeutic agents in breast cancer. These studies provide the proof-of-principle that stathmin provides an attractive molecular target, which could serve as a primary focus of novel approaches to breast cancer.


A model balancing cooperation and competition can explain our right-handed world and the dominance of left-handed athletes.
An overwhelming majority of humans are right-handed. Numerous explanations for individual handedness have been proposed, but this population-level handedness remains puzzling. Here, we present a novel mathematical model and use it to test the idea that population-level hand preference represents a balance between selective costs and benefits arising from cooperation and competition in human evolutionary history. We use the selection of elite athletes as a test-bed for our evolutionary model and find evidence for the validity of this idea. Our model gives the first quantitative explanation for the distribution of handedness both across and within many professional sports. It also predicts strong lateralization of hand use in social species with limited combative interaction, and elucidates the absence of consistent population-level 'pawedness' in some animal species.


Induction of labour after fetal death: a randomized controlled trial of two prostaglandin regimens.
A total of 85 women with antepartum fetal death between 14 and 42 weeks gestation was randomly assigned to one of two regimens of intravenous infusion of the prostaglandin analogue 16-phenoxy-17, 18, 19, 20-tetranor-PGE2-methylsulphonamide (sulprostone) for inducing labour. Women received either 1 microgram/min until delivery or the commonly recommended treatment of 1500 micrograms in 8 h followed by another, identical course of treatment if delivery did not occur within 24 h. The 1 microgram/min dose schedule used half the amount of prostaglandin and resulted in statistically significantly fewer gastrointestinal side-effects compared with the conventional treatment. All women were delivered vaginally and there were no differences in induction-to-delivery intervals between the two treatments. Sulprostone infused at a rate of 1 microgram/min resulted in a 50% chance of being delivered within 12 h and a 90% chance of being delivered within 24 h, with an overall frequency of side-effects of 20%.


Conversion of Shigella flexneri serotype 2a to serotype Y in a shigellosis patient due to a single amino acid substitution in the protein product of the bacterial glucosyltransferase gtrII gene.
Conversion of serotype from 2a to Y was demonstrated with five Shigella flexneri isolates recovered from an infected patient. When introduced into the serotype Y isolate, the glucosyltransferase (gtr) II gene of the serotype 2a isolate is capable of inducing the conversion from serotype Y to 2a. In contrast, the gtrII of the serotype Y isolate lacks the capacity to change serotype, resulting from a Cys-->Tyr substitution in its predicted protein sequence. The protein product of the gtrII gene was detected. This is the first report of serotype conversion of S. flexneri in humans, and successful detection of the protein product from a gtr gene.


The effect of pain neurophysiology education on healthcare students' knowledge, attitudes and behaviours towards pain: A mixed-methods randomised controlled trial.
1) To investigate the effects of a brief pain neuroscience education (PNE) lecture on multi-disciplinary healthcare students' knowledge, attitudes and behaviours towards people with pain post intervention and at 6-months follow-up, 2) To explore students' perceptions of PNE. Mixed-methods randomized controlled trial. UK university. Thirty-seven students (30♀, mean age 30 years) from six healthcare disciplines. 70-min PNE lecture (intervention group) or a 70-min control education. 1) Knowledge: The Revised Pain Neurophysiology Quiz (RPNQ); 2) Attitudes: Health Care Providers' Pain and Impairment Relationship Scale (HC-PAIRS); 3) Behaviours: A case vignette to assess clinical recommendations; and 4) Thematic analysis of semi-structured interviews (n = 12). The intervention group increased knowledge compared to the control, post-intervention [mean difference 3.7 (95% CI, 2.4, 5.0), P < 0.001] but not at 6-months (0.1 (-1.1, 1.3), P = 0.860). Greater improvements in attitudes for the intervention group were seen post-intervention [-10.4 (-16.3, -4.6), P < 0.001] and at 6-months [-5.8 (-11.5, -0.2), P < 0.044]. There was no difference in behaviours between groups. Thematic analysis identified increased patient empathy, partial and patchy reconceptualisation of pain and increased confidence in recommending an active management programme following PNE. This study adds to existing knowledge by demonstrating that a 70-min PNE lecture can have a short-term effect on knowledge and positively shift attitudes towards people with pain in the short and medium-term. It also resulted in some students' reconceptualisation of pain, increased empathy, and confidence to recommend activity. The effect of PNE on clinical behaviours was unclear.


Multivariate Failure Times Regression with a Continuous Auxiliary Covariate.
How to take advantage of the available auxiliary covariate information when the primary covariate of interest is not measured is a frequently encountered question in biomedical study. In this paper, we consider the multivariate failure times regression analysis in which the primary covariate is assessed only in a validation set but a continuous auxiliary covariate for it is available for all subjects in the study cohort. Under the frame of marginal hazard model, we propose to estimate the induced relative risk function in the nonvalidation set through kernel smoothing method and then obtain an estimated pseudo-partial likelihood function. The proposed estimated pseudo-partial likelihood estimator is shown to be consistent and asymptotically normal. We also give an estimator of the marginal cumulative baseline hazard function. Simulations are conducted to evaluate the finite sample performance of our proposed estimator. The proposed method is illustrated by analyzing a heart disease data from Studies of Left Ventricular Dysfunction (SOLVD).


The actions of flunitrazepam (Rohypnol) on heart and respiratory rates and skin potential fluctuations during the sleep cycle in normal volunteers and neurotic patients with insomnia.
The actions of flunitrazepam (Rohypnol) were assessed on the sleep cycle, heart and respiratory rates and skin potential fluctuations of normal volunteers and neurotic patients with insomnia by means of all night recordings. The most conspicuous effect of flunitrazepam (2 mg p.o.) in the healthy subject's sleep cycle was an increase of the latency for the appearance of the first REM period. In the insomniacs the compounds was effective in inducing and maintaining sleep. Flunitrazepam diminished heart rates during the REM phases and significantly decreased the variability indices, this effect being more prominent in the normal subjects. Skin potential fluctuations during stages 2 and REM sleep were also decreased although tolerance developed rapidly in this connection.


Proof of concept and improvement of a triple chamber biosystem coupling anaerobic digestion, nitrification and mixotrophic endogenous denitrification for organic matter, nitrogen and sulfide removal from domestic sewage.
In this study, two versions of a triple chamber biosystem, coupling anaerobic digestion, nitrification and mixotrophic endogenous denitrification (ADNMED), were evaluated and compared. They were designed to maximize the use of endogenous electron donors produced by anaerobic digestion (residual organic matter and sulfide) to abate a portion of the influent nitrogen contained in domestic sewage while removing the inconvenience of effluent sulfide. The first version was able to abate 40% of the influent nitrogen but presented operational and hydrodynamic problems, which resulted in sulfide emissions. A modified second version was proposed, improving the first approach and achieving a nitrogen abatement of more than 60% and a sulfide-free effluent, complying with local emission standards. The results demonstrated that endogenous electron donors produced by anaerobic digestion should not be neglected, and a significant cost reduction in nitrogen removal from domestic sewage could be achieved by exploiting their potential with novel reactor configurations.


Evidence for mechanoreceptors in the muscular stomach of the chicken.
Single-fiber, vagal recordings were made from mechanoreceptors in the muscular stomach of the chicken. These receptors increased discharge frequency (i) during gentle compression of the wall of this organ and (ii) when coordinated contractions of the organ were induced pharmacologically.


Evidence for Clostridium perfringens enterotoxin (CPE) inducing a mitogenic and cytokine response in vitro and a cytokine response in vivo.
We investigated some immunogenic properties of Clostridium perfringens enterotoxin (CPE) in vitro using murine J774A macrophages (MPhi) and in vivo using Swiss Webster (SW) mice. CPE was a potent mitogen in vitro, where cell proliferation increased with CPE concentration. CPE was nonmitogenic when MPhi were concurrently incubated with CPE and interferon gamma (IFN-gamma). MPhi incubated in the presence of CPE induced the synthesis of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN-gamma), but not interleukin-2 (IL-2). In vivo, CPE induced a pro-inflammatory cytokine response with striking production of IFN-gamma, IL-1, and IL-6. Regardless of route of CPE entry, serum cytokine levels generally peaked within 1 h of administration and were maintained for 4-8 h. Although CPE engenders an intense immune response during toxicosis, the toxin does not appear to be a superantigen. Death from CPE-induced shock appears to result from various interrelating immunological mechanisms.


Degeneration patterns in the chicken central nervous system induced by ingestion of the organophosphorus delayed neurotoxin tri-ortho-tolyl phosphate. A silver impregnation study.
Exposure to certain organophosphorus compounds results in a neurological condition known as organophosphorus-induced delayed neurotoxicity (OPIDN). OPIDN is characterized clinically by an initial post-exposure delay period of 8-14 days after which signs of progressively developing ataxia and paralysis of the hindlimbs are observed. Although several studies have reported the presence of degeneration induced by organophosphorus delayed neurotoxins in specific central nervous system (CNS) structures, none have systematically examined CNS changes seen in the most frequently studied animal model for OPIDN--the domestic fowl. In the present study, we assessed the location and extent of anterograde degeneration in the chicken CNS following exposure to tri-o-tolyl phosphate (TOTP). All birds were dosed with 500 mg TOTP/kg body weight and killed after post-exposure periods of 1, 2, 3, or 4 weeks. The brains and spinal cords were processed with Fink-Heimer and Nissl stains. In the spinal cord, axon degeneration was noted in the fasciculus gracilis at cervical levels two weeks after exposure to TOTP. At 3 weeks, degeneration was also present in the cervical part of the dorsal spinocerebellar tract, in the lumbar part of the medial pontine-spinal tract, and in lamina VII in the lumbar ventral horn. In the medulla, moderate amounts of terminal and preterminal degeneration appeared at two weeks in the lateral vestibular, gracile, external cuneate, and lateral cervical nuclei. Lesser amounts of degeneration were noted in the solitary, inferior olivary, and raphae nuclei, in the medial, descending and lateral vestibular nuclei, and in the lateral paragigantocellular, gigantocellular, and lateral reticular nuclei. Fiber degeneration was also present in the medullary portions of the dorsal and ventral spinocerebellar tracts and spinal lemniscus. In the cerebellum, moderate amounts of terminal degeneration appeared in the deep cerebellar nuclei at one week while moderate mossy fiber degeneration was first noted in the granular layers of cerebellar folia I-V at 3 weeks. These results indicate (1) that, in the CNS, axonal and terminal degeneration resulting from TOTP intoxication appears to be confined to the spinal cord, medulla and cerebellum, (2) that the time of onset of degeneration in different fiber tracts and nuclei ranges from one to three weeks post-exposure, and (3) that the delay in the appearance of clinical signs of OPIDN is consistent with the delayed onset of degeneration in many of the affected CNS fiber systems.


The Effectiveness of Unguided Internet-Based Cognitive Behavioral Therapy for Tinnitus for Patients with Tinnitus Alone or Combined with Hyperacusis and/or Misophonia: A Preliminary Analysis.
In the UK, audiologist-delivered cognitive behavioral therapy (CBT) is a key intervention to alleviate the distress caused by tinnitus and its comorbid hyperacusis. However, the availability of face-to-face CBT is limited, and such therapy involves significant costs. CBT provided via the internet provides a potential solution to improve access to CBT for tinnitus. The aim was to perform a preliminary assessment of the effect of a specific program of non-guided internet-based CBT for tinnitus, denoted iCBT(T), in alleviating the problems caused by tinnitus alone or tinnitus combined with hyperacusis. This was a retrospective cross-sectional study. The data for 28 people with tinnitus who completed the iCBT(T) program and answered a series of questions about their tinnitus and hearing status were included in the study. Twelve patients reported also having hyperacusis (including five also with misophonia). The iCBT(T) program has seven self-help modules. Anonymous data were collected retrospectively from patients' answers to the questions in the iCBT(T) initial and final assessment modules. Questionnaires administered within the iCBT(T) program were: 4C Tinnitus Management Questionnaire (4C), Screening for Anxiety and Depression in Tinnitus (SAD-T), and the CBT Effectiveness Questionnaire (CBT-EQ). Responses to the 4C showed a significant improvement from pre- to post-treatment, with a medium effect size. The mean improvement was similar for those with and without hyperacusis. Responses to the SAD-T questionnaire also showed a significant improvement from pre- to post-treatment with a medium effect size. The improvement was significantly greater for participants with tinnitus alone than for participants who also had hyperacusis. For both the 4C and the SAD-T, the improvements were not significantly related to age or gender. Participants' views of the effectiveness of the iCBT(T) program were assessed using the CBT-EQ. The mean score was 50 out of a maximum of 80, indicating moderately high effectiveness. CBT-EQ scores did not differ for those with and without hyperacusis. Based on this preliminary analysis, the iCBT(T) program showed promising result in improving the ability to manage tinnitus and decreasing symptoms of anxiety and depression. Future studies with larger samples and control group(s) are required to further assess various aspects of this program.


[Detection of hemoglobin abnormalities in 35,000 exchange students].
Distribution of abnormal hemoglobins and thalassemia worked out of 35,000 foreigners from 99 countries examined in Paris.


Targeted proteomics data interpretation with DeepMRM.
Targeted proteomics is widely utilized in clinical proteomics; however, researchers often devote substantial time to manual data interpretation, which hinders the transferability, reproducibility, and scalability of this approach. We introduce DeepMRM, a software package based on deep learning algorithms for object detection developed to minimize manual intervention in targeted proteomics data analysis. DeepMRM was evaluated on internal and public datasets, demonstrating superior accuracy compared with the community standard tool Skyline. To promote widespread adoption, we have incorporated a stand-alone graphical user interface for DeepMRM and integrated its algorithm into the Skyline software package as an external tool.


Foraging and predator avoidance: a test of a patch choice model with juvenile bluegill sunfish.
In situations where foraging sites vary both in food reward and predation risk, conventional optimal foraging models based on the criterion of maximizing net rate of energy intake commonly fail to predict patch choice by foragers. Recently, an alternative model based on the simple rule "when foraging, minimize the ratio of mortality rate (u) to foraging rate (f)" was successful in predicting patch preference under such conditions (Gilliam and Fraser 1987). In the present study, I compare the predictive ability of these two models under conditions where available patches vary both in predation hazard and foraging returns. Juvenile bluegill sunfish (Lepomis macrochirus) were presented with a choice between two patches of artificial vegetation differing in stem density (i.e. 100, 250, and 500 stems/m2) in which to forage. Each combination (100:250, 250:500, or 100:500) was presented in the absence, presence, and after exposure to a bass predator (Micropterus salmoides). Which patch of vegetation bluegills chose to forage in, and foraging rate within each patch were recorded. Independent measurements of bluegill foraging rate and risk of mortality in the three stem densities provided the data for predicting patch choice by the two models. With no predator, preference between plots was consistent with the maximize energy intake per unit time rule of conventional optimality models. However, with a predator present, patch preference switched to match a minimize u/f criterion. Finally, when tested shortly after exposure to a predator (i.e. 15 min), bluegill preference appeared to be in a transitional phase between these two rules. Results are discussed with respect to factors determining the distribution of organisms within beds of aquatic vegetation.


Concentration gradients for monoamine metabolites in lumbar cerebrospinal fluid.
Concentration gradients in lumbar cerebrospinal fluid (CSF) for the monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) were studied in 9 healthy controls and 47 neuropsychiatric patients without diseases causing disturbed CSF circulation. In a serial sampling of the first 24 ml of CSF, steep concentration gradients between the first (0-4th ml) and last (21st-24th ml) portions of CSF were found for HVA (99 +/- 59% increase; p < 0.001) and 5-HIAA (88 +/- 54% increase; p < 0.001), while the concentration gradient was slight for HMPG (11 +/- 7% increase; p < 0.001). The existence of marked concentration gradients for the monoamine metabolites HVA and 5-HIAA gives further evidence for an active transport system for these metabolites and indicates that the lumbar CSF-HVA and 5-HIAA levels reflect the dopamine and serotonin metabolism in the brain. Moreover, the existence of pronounced concentration gradients for HVA and 5-HIAA stresses the importance of making analyses on a standardized volume of CSF.


Mapping the Asthma Care Process: Implications for Research and Practice.
Whether people with asthma gain and maintain control over their condition depends not only on the availability of effective drugs, but also on multiple patient and health care professional (HCP) behaviors. Research in asthma rarely considers how these behaviors interact with each other and drug effectiveness to determine health outcomes, which may limit real-life applicability of findings. The objective of this study was to develop a logic process model (Asthma Care Model; ACM) that explains how patient and HCP behaviors impact on the asthma care process. Within a European research project on asthma (ASTRO-LAB), we reviewed asthma care guidelines and empirical literature, and conducted qualitative interviews with patients and HCPs. Findings were discussed with the project team and respiratory care experts and integrated in a causal model. The model outlines a causal sequence of treatment events, from diagnosis and assessment to treatment prescription, drug exposure, and health outcomes. The relationships between these components are moderated by patient behaviors (medication adherence, symptom monitoring, managing triggers, and exacerbations) and HCP behaviors (medical care and self-management support). Modifiable and nonmodifiable behavioral determinants influence the behaviors of patients and HCPs. The model is dynamic as it includes feedback loops of behavioral and clinical outcomes, which influence future patient and HCP decision making. Key evidence for each relationship is summarized to derive research priorities and clinical recommendations. The ACM model is of interest to both researchers and practitioners, and intended as a first version (ACM-v1) of a common framework for generating and translating research evidence in asthma care.


The increase in human antithrombin III tryptophan fluorescence produced by heparin.
The increase in fluorescence of human antithrombin III has been used to study the binding of a semi-synthetic heparin analogue. One molecule of heparin were found to bind with an association constant of 8.9 . 10(4) M-1. The intrinsic fluorescence of antithrombin III exhibits a fluorescence quantum yield of 0.17. Upon addition of heparin a marked increase in the protein fluorescence quantum yield is observed.


Pickering emulsions synergistically stabilized by sugar beet pectin and montmorillonite exhibit enhanced storage stability and viscoelasticity.
Sugar beet pectin (SBP) is a naturally occurring emulsifying type of pectin fabricated into nanocomposites with montmorillonite (MMT) and then introduced as a stabilizer for high internal phase emulsions (HIPEs). SBP-MMT composites performed well in emulsifying medium-chain triglyceride with an oil volume fraction (φ) of 0.1-0.85 and SBP/MMT mass ratios of 1:0.1-1:0.75. The two representative high internal phase emulsions stabilized by SBP-MMT composites at different SBP/MMT mass ratios exhibited good stability against creaming and coalescence. In these emulsion systems, SBP and MMT formed a network in the continuous phase that markedly improved the rheological properties, including the storage modulus (by 3 orders of magnitude). Confocal light scattering microscopy analysis indicated that a fraction of MMT could work synergistically with SBP in adsorbing on oil droplet surfaces, enhancing stability. SBP-MMT composites stabilized high internal phase emulsions destabilized after the freeze-thaw treatment (-40 °C for 20 h and 25 °C for 4 h) but could be facilely re-emulsified via high-speed shearing. The gastrointestinal digestion behaviors were also modified by stabilizing SBP and MMT. Overall, this work reveals a hitherto undocumented strategy for fabricating highly stable emulsions based on SBP-MMT composites which have huge prospects for application in the food and related industries.


Efficacy of Immune Checkpoint Inhibitors Is Modulated by Androgen Receptor.
Androgen receptor (AR) activity can alter T-cell function and modulate resistance to PD-1 inhibitors.


Efficacy of endoluminal interventional therapy in diabetic peripheral arterial occlusive disease: a retrospective trial.
The purpose of this study was to assess the efficacy of interventional therapy for peripheral arterial occlusive disease and the difference between diabetic patients and non-diabetic patients. 139 consecutive patients between September 2006 and September 2010 who underwent percutaneous lower extremity revascularization for arterial lesions were divided into diabetes group (n = 62) and non-diabetes group (n = 77). Before intervention, rest ankle brachial indexes and three dimensional computed tomography angiography from abdominal aorta to tiptoe were performed. The interventional treatments included angioplasty with or without stenting. The clinical outcomes included rest ankle-brachial indexes, primary patency rates, secondary patency rates and limb-salvage rates for 6-month, 12-month, 24-month and 36-month after treatment. The primary and secondary patency rates of all interventions and the limb-salvage rates of the patients are illustrated by Kaplan-Meier curves and compared by log-rank analysis. The interventional operation success rates were 98.4% (61/62) in diabetes group and 100% (77/77) in non-diabetes group. The re-interventional operation success rates were 85.7% (18/21) in diabetes group and 76.9% (20/26) in non-diabetes group. The mean value of ankle brachial indexes was significantly increased after intervention (0.397 ± 0.125 versus 0.779 ± 0.137, t = -25.780, P < 0.001) in diabetes group and (0.406 ± 0.101 versus 0.786 ± 0.121, t = -37.221, P < 0.001) in non-diabetes group. Perioperative 30-day mortality was 0%. Major complications included groin hematoma in 7.2%, and pseudoaneurysm formation 2.2%. In diabetes group, 6, 12, 24, and 36-month primary patency rates were 88.7% ± 4.0%, 62.3% ± 6.6%, 55.3% ± 7.0%, and 46.5% ± 7.5%; secondary patency rates were 93.5% ± 3.1%, 82.3% ± 5.1%, 70.8% ± 6.5%, and 65.7% ± 7%; limb-salvage rates were 95.2% ± 2.7%, 87.7% ± 4.4%, 85.5% ± 4.8%, and 81.9% ± 5.8%. In non-diabetes group, 6, 12, 24, and 36-month primary patency rates were 90.9% ± 3.3%, 71.8% ± 5.4%, 71.8% ± 5.4%, and 60.9% ± 6.2%; secondary patency rates were 96.1% ± 2.2%, 91.6% ± 3.3%, 82.7% ± 4.8%, and 71.8% ± 6.2%; limb-salvage rates were 97.4% ± 1.8%, 94.4% ± 2.7%, 90.6% ± 3.7%, and 83.1% ± 5.4%. The differences between two groups were not significant (P > 0.05). With a low risk of morbidity and mortality, the percutaneous revascularization accepted by patients does not affect ultimate necessary surgical revascularization and consequently should be considered as the preferred therapy for chronic lower extremity ischemia. The efficacy and prognosis of interventional therapy in diabetic patients is similar that in non-diabetic patients.


Cellular automata modeling suggests symmetric stem-cell division, cell death, and cell drift as key mechanisms driving adult spinal cord growth in teleost fish.
Adult neurogenesis - the generation of neurons during adulthood - is intensively studied, yet little is known about its consequences at the tissue level. In the teleost fish Apteronotus leptorhynchus, morphometric analysis has revealed that the total number of cells in the spinal cord increases continuously throughout adulthood, driven by the activity of neurogenic stem/progenitor cells in both the ependymal layer at the central canal and in the radially located parenchyma. This net increase in cell numbers demonstrates cellular addition, as opposed to cellular turnover which appears to be the common outcome of adult neurogenesis in mammals. Grounded on a comprehensive set of quantitative data generated through high-resolution mapping of stem cells and their progeny, we constructed a cellular automata model of the stem-cell-driven growth of the spinal cord. Simulations based on this model suggest that three cellular mechanisms play a critical role for promoting sustained tissue growth and acquisition of correct form of the spinal cord, including the development of the ependymal layer and the parenchyma: the number of symmetric stem-cell divisions versus asymmetric divisions; the probability of the progeny of progenitor cells to undergo cell death; and the radial drifting of cells.


Nitric oxide bioavailability and its potential relevance to the variation in susceptibility to the renal and vascular complications in patients with type 2 diabetes.
We compared the renal and systemic vascular (renovascular) response to a reduction of bioavailable nitric oxide (NO) in type 2 diabetic patients without nephropathy and of African and Caucasian heritage. Under euglycemic conditions, renal blood flow was determined by a constant infusion of paraminohippurate and changes in blood pressure and renal vascular resistance estimated before and after an infusion of L-Ng-monomethyl-L-arginine. In the African-heritage group, there was a significant fall in renal blood flow (Delta-46.0 ml/min per 1.73 m(2); P < 0.05) and rise in systolic blood pressure (Delta 10.0 mmHg [95% CI 2.3-17.9]; P = 0.017), which correlated with an increase in renal vascular resistance (r(2) = 0.77; P = 0.004). The renal vasoconstrictive response associated with NO synthase inhibition in this study may be of relevance to the observed vulnerability to renal injury in patients of African heritage.


Microencapsulated VO(acac)2: preparation and use in allylic alcohol epoxidation.
[reaction: see text]. Microencapsulated VO(acac)2 [MC-VO(acac)2] has been prepared and screened with success as a catalyst for the epoxidation of allylic alcohols using tert-butyl hydroperoxide as oxidant. The reactions are run in hexane at room temperature. The MC-VO(acac)2 is reusable without significant loss of activity.


PDIA3 modulates genomic response to 1,25-dihydroxyvitamin D3 in squamous cell carcinoma of the skin.
An active form of vitamin D3 (1,25-dihydroxyvitamin D3) acts through vitamin D receptor (VDR) initiating genomic response, but several studies described also non-genomic actions of 1,25-dihydroxyvitamin D3, implying the role of PDIA3 in the process. PDIA3 is a membrane-associated disulfide isomerase involved in disulfide bond formation, protein folding, and remodeling. Here, we used a transcriptome-based approach to identify changes in expression profiles in PDIA3-deficient squamous cell carcinoma line A431 after 1,25-dihydroxyvitamin D3 treatment. PDIA3 knockout led to changes in the expression of more than 2000 genes and modulated proliferation, cell cycle, and mobility of cells; suggesting an important regulatory role of PDIA3. PDIA3-deficient cells showed increased sensitivity to 1,25-dihydroxyvitamin D3, which led to decrease migration. 1,25-dihydroxyvitamin D3 treatment altered also genes expression profile of A431ΔPDIA3 in comparison to A431WT cells, indicating the existence of PDIA3-dependent genes. Interestingly, classic targets of VDR, including CAMP (Cathelicidin Antimicrobial Peptide), TRPV6 (Transient Receptor Potential Cation Channel Subfamily V Member 6), were regulated differently by 1,25-dihydroxyvitamin D3, in A431ΔPDIA3. Deletion of PDIA3 impaired 1,25-dihydroxyvitamin D3-response of genes, such as PTGS2, MMP12, and FOCAD, which were identified as PDIA3-dependent. Additionally, response to 1,25-dihydroxyvitamin D3 in cancerous A431 cells differed from immortalized HaCaT keratinocytes, used as non-cancerous control. Finally, silencing of PDIA3 and 1,25-dihydroxyvitamin D3, at least partially reverse the expression of cancer-related genes in A431 cells, thus targeting PDIA3 and use of 1,25-dihydroxyvitamin D3 could be considered in a prevention and therapy of the skin cancer. Taken together, PDIA3 has a strong impact on gene expression and physiology, including genomic response to 1,25-dihydroxyvitamin D3.


Listeriolysin O: a phagosome-specific lysin.
Listeriolysin O (LLO) is a pore-forming toxin of the cholesterol-dependent cytolysin family and a primary virulence factor of the gram-positive, facultative intracellular pathogen Listeria monocytogenes. During the intracellular life cycle of L. monocytogenes, LLO is largely responsible for mediating rupture of the phagosomal membrane, thereby allowing the bacterium access to the host cytosol, its replicative niche. In the host cytosol, LLO activity is controlled at numerous levels to prevent perforation of the plasma membrane and loss of the intracellular environment. In this review, we focus primarily on the role of LLO in phagosomal escape and the multiple regulatory mechanisms that control LLO activity in the host cytosol.


Characterization of a novel and selective CB1 antagonist as a radioligand for receptor occupancy studies.
Obesity remains a significant public health issue leading to Type II diabetes and cardiovascular disease. CB1 antagonists have been shown to suppress appetite and reduce body weight in animal models as well as in humans. Evaluation of pre-clinical CB1 antagonists to establish relationships between in vitro affinity and in vivo efficacy parameters are enhanced by ex vivo receptor occupancy data. Synthesis and biological evaluation of a novel and highly selective radiolabeled CB1 antagonist is described. The radioligand was used to conduct ex vivo receptor occupancy studies.


Current evidence of rituximab in the treatment of multiple sclerosis.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system. The immunopathology of MS involves both T and B lymphocytes. Rituximab is one of the anti-CD20 monoclonal antibody therapies which deplete B-cells. Although some anti-CD20 therapies have been approved by the Food and Drug Administration for treatment of MS, rituximab is used off-label. Several studies have shown that rituximab has a good efficacy and safety in MS, including certain specific patient conditions such as treatment-naïve patients, treatment-switching patients, and the Asian population. However, there are still questions about the optimal dose and duration of rituximab in MS due to the different dosing regimens used in each study. Moreover, many biosimilars have become available at a lower cost with comparable physicochemical properties, pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity. Thus, rituximab may be considered as a potential therapeutic option for patients without access to standard treatment. This narrative review summarized the evidence of both original and biosimilars of rituximab in MS treatment including pharmacokinetics, pharmacodynamics, clinical efficacy, safety, and dosing regimen.


A synthetic lethal approach for compound and target identification in Staphylococcus aureus.
The majority of bacterial proteins are dispensable for growth in the laboratory but nevertheless have important physiological roles. There are no systematic approaches to identify cell-permeable small-molecule inhibitors of these proteins. We demonstrate a strategy to identify such inhibitors that exploits synthetic lethal relationships both for small-molecule discovery and for target identification. Applying this strategy in Staphylococcus aureus, we have identified a compound that inhibits DltB, a component of the teichoic acid D-alanylation machinery that has been implicated in virulence. This D-alanylation inhibitor sensitizes S. aureus to aminoglycosides and cationic peptides and is lethal in combination with a wall teichoic acid inhibitor. We conclude that DltB is a druggable target in the D-alanylation pathway. More broadly, the work described demonstrates a systematic method to identify biologically active inhibitors of major bacterial processes that can be adapted to numerous organisms.


A Novel MgO-CaO-SiO₂ System for Fabricating Bone Scaffolds with Improved Overall Performance.
Although forsterite (Mg₂SiO₄) possesses good biocompatibility and suitable mechanical properties, the insufficient bioactivity and degradability hinders its further application. In this study, a novel MgO-CaO-SiO₂ system was developed by adding wollastonite (CaSiO₃) into Mg₂SiO₄ to fabricate bone scaffolds via selective laser sintering (SLS). The apatite-forming ability and degradability of the scaffolds were enhanced because the degradation of CaSiO₃ could form silanol groups, which could offer nucleation sites for apatite. Meanwhile, the mechanical properties of the scaffolds grew with increasing CaSiO₃ to 20 wt %. It was explained that the liquid phase of CaSiO₃ promoted the densification during sintering due to its low melting point. With the further increase in CaSiO₃, the mechanical properties decreased due to the formation of the continuous filling phase. Furthermore, the scaffolds possessed a well-interconnected porous structure and exhibited an ability to support cell adhesion and proliferation.


Association between ZFHX3 and PRRX1 Polymorphisms and Atrial Fibrillation Susceptibility from Meta-Analysis.
Atrial fibrillation (AF) is a common, sustained cardiac arrhythmia. Recent studies have reported an association between ZFHX3/PRRX1 polymorphisms and AF. In this study, a meta-analysis was conducted to confirm these associations. Objective and Methods. The PubMed, Embase, and Wanfang databases were searched, covering all publications before July 20, 2020. Overall, seven articles including 3,674 cases and 8,990 healthy controls for ZFHX3 rs2106261 and 1045 cases and 1407 controls for PRRX1 rs3903239 were included. The odds ratio (OR) (95% confidence interval (CI)) was used to assess the associations. Publication bias was calculated using Egger's and Begg's tests. We found that the ZFHX3 rs2106261 polymorphism increased AF risk in Asians (for example, allelic contrast: OR [95% CI]: 1.39 [1.31-1.47], P < 0.001). Similarly, strong associations were detected through stratified analysis using source of control and genotype methods (for example, allelic contrast: OR [95% CI]: 1.51 [1.38-1.64], P < 0.001 for HB; OR [95% CI]: 1.31 [1.21-1.41], P < 0.001 for PB; OR [95% CI]: 1.55 [1.33-1.80], P < 0.001 for TaqMan; and OR [95% CI]: 1.31 [1.21-1.41], P < 0.001 for high-resolution melt). In contrast, an inverse relationship was observed between the PRRX1 rs3903239 polymorphism and AF risk (C-allele vs. T-allele: OR [95% CI]: 0.83 [0.77-0.99], P=0.036; CT vs. TT: OR [95% CI]: 0.79 [0.67-0.94], P=0.006). No obvious evidence of publication bias was observed. In summary, our study suggests that the ZFHX3 rs2106261 and PRRX1 rs3903239 polymorphisms are associated with AF risk, and larger case-controls must be carried out to confirm the abovementioned conclusions.


Recent advances in assessment methods and mechanism of microbe-mediated chlorpyrifos remediation.
Chlorpyrifos (CP) is one of the Organophosphorus pesticides (OPs) primarily used in agriculture to safeguard crops from pests and diseases. The pervasive use of chlorpyrifos is hazardous to humans and the environment as it inhibits the receptor for acetylcholinesterase activity, leading to abnormalities linked to the central nervous system. Hence, there is an ardent need to develop an effective and sustainable approach to the on-site degradation of chlorpyrifos. The role of microbes in the remediation of pesticides is considered the most effective and eco-friendly approach, as they have strong degradative potential due to their gene and enzymes naturally adapted to these sites. Several reports have previously been published on exploring the role of microbes in the degradation of CP. However, detection of CP as an environmental contaminant is an essential prerequisite for developing an efficient microbial-mediated biodegradation method with less harmful intermediates. Most of the articles published to date discuss the fate and impact of CP in the environment along with its degradation mechanism but still fail to discuss the analytical portion. This review is focused on the latest developments in the field of bioremediation of CP along with its physicochemical properties, toxicity, fate, and conventional (UV-Visible spectrophotometer, FTIR, NMR, GC-MS, etc) and advanced detection methods (Biosensors and immunochromatography-based methods) from different environmental samples. Apart from it, this review explores the role of metagenomics, system biology, in-silico tools, and genetic engineering in facilitating the bioremediation of CP. One of the objectives of this review is to educate policymakers with scientific data that will enable the development of appropriate strategies to reduce pesticide exposure and the harmful health impacts on both Human and other environmental components. Moreover, this review provides up-to-date developments related to the sustainable remediation of CP.


ENG-releasing subdermal implants in postpartum teenagers - an open-label trial study protocol.
Higher than expected adolescent pregnancy high rates continue globally, with repeated unplanned pregnancy (UP) in this age group is a public health problem. In Brazil, 16% of pregnancies occur in adolescents under 18 years old, with high maternal morbidity and mortality rates in this age group. Effective and safe contraception is required to reduce UP rates. The objective of our study is to evaluate acceptance of etonogestrel (ENG)-releasing subdermal contraceptive implant after childbirth, before discharge, as well as clinical performance up to one year after placement. Comparison between teenagers who opt for ENG-implant versus other contraceptive methods after childbirth will be also evaluated, specifically regarding UP, continuation and discontinuation rates and reasons, body composition, pelvic ultrasound characteristics and user satisfaction. A non-randomized open-label trial will be conducted with teenagers after childbirth and followed up to one year at the Women's Hospital, University of Campinas (UNICAMP), Campinas, Brazil. The study group will consist of patients who accepted to use ENG-implant and placed before discharge. The comparison group will include adolescents who choose to use other contraceptive methods at the first postpartum visit (42 ± 3 days after childbirth). All women will follow-up at 40-60 days postpartum, as well as, at 6 and 12 months post-enrollment. Patient satisfaction, contraceptive effectiveness, reasons of discontinuation, continuation rate and body composition will be evaluated. Transvaginal ultrasound and electric bio impedance tests will be performed at all follow-up appointments. A 5% significance level was assumed, as well as, a sampling error (absolute) for 10% prevalence. The sample size was calculated at n = 100, obtaining an estimate of 50 to 70 adolescents who would accept the method offered, according to the prevalence and sample error assumed. Long-acting reversible contraceptive (LARC) methods include subdermal implants and intrauterine contraceptives, are considered first line contraception for teenagers. Immediate postpartum use is a safe option, which significantly reduces rates of repeated UP and all the undesirable consequences inherent to this process. This study was approved by the Ethics and Research Commission of UNICAMP (CAAE: 92869018.5.0000.5404) and the Brazilian Registry of Clinical Trials (REBEC): http://www.ensaiosclinicos.gov.br/rg/RBR-4z7bc6, (number 2.901.752).


Factor VIII mutated with Lys1813Ala within the factor IXa-binding region enhances intrinsic coagulation potential.
Factor VIII (FVIII) functions as a cofactor of FIXa for FX activation in the intrinsic tenase complex. The 1811-1818 region in the FVIII A3 domain was observed to contribute to FIXa binding, and the K1813A/K1818A mutant increased the binding affinity for FIXa. The current study aims to identify mutated FVIII protein(s) that increase FVIIIa cofactor activity in the 1811-1818 region. FVIII mutants with K1813A, K1818A, and K1813A/K1818A were expressed in baby hamster kidney cells and were followed by assessments using purified and global coagulation assays for mouse models with hemophilia A (HA). A surface plasmon resonance-based assay revealed that the Kd value of FVIII-K1813A for FIXa interaction was lower than that of the wild-type (WT) (3.9±0.7/6.3±0.3 nM). However, the Km value of FVIII-K1813A for FIXa on tenase activity was comparable with that of the WT, whereas the kcat of this mutant was significantly greater than that of the WT. Thrombin-catalyzed FVIII-K1813A activation was ∼1.3-fold more enhanced than that of the WT, and the spontaneous decay of activated FVIII-K1813A was ∼2.5-fold slower than that of WT. The heat stability assay revealed that the decay rate of FVIII-K1813A was ∼2.5-fold slower than that of WT. Thrombin generation assay and rotational thromboelastometry using blood samples from patients with HA demonstrated that the addition of FVIII-K1813A (0.5 nM) exhibited a coagulation potential compatible with that of WT (1 nM). In the tail clip assay of HA mice, FVIII-K1813A showed a two- to fourfold higher hemostatic potential than that of the WT. FVIII-K1813A, with higher a FIXa binding affinity, enhances the global coagulation potential because of the stability of FVIII/FVIIIa molecules.


Effects of vitamin D on inflammatory state in patients with chronic kidney disease: A controversial issue.
The anti-inflammatory effect of vitamin D in patients with chronic kidney disease (CKD) remains controversial. This study aimed to conduct a meta-analysis of randomized controlled trials to assess the anti-inflammatory effects of vitamin D in patients with CKD. We searched Embase, Science Citation Index, Medline, Cochrane Central Register of Controlled Trials, and Clinical Trial Registries for randomized controlled trials that comparing vitamin D with control groups for inflammatory markers in patients with CKD. Subgroup analysis was performed based on treatment duration (short-term treatment, long-term treatment), type of patients (predialysis CKD, dialysis, kidney transplant), 25(OH)D levels (25(OH)D deficiency or normal 25(OH)D), and methods of C-reactive protein (CRP) test (standard CRP test or high-sensitivity CRP [hs-CRP] test). Eighteen trials with 1834 patients were included in the present study. There were no significant differences between the vitamin D group and control group for CRP (WMD, -0.3 mg/L; 95% CI, -0.81 to 0.22, p = 0.26, I2 = 62%), interleukin-6 (IL-6) (WMD, -1.07 pg/ml; 95% CI, -2.44 to 0.30, p = 0.12, I2 = 52%), and tumor necrosis factor-α (TNF-α) (WMD, -0.00 pg/ml; 95% CI, -0.36 to 0.35, p = 0.99, I2 = 0%) in patients with CKD. Subgroup analysis showed vitamin D can improve hs-CRP, but not CRP. The rest of subgroups showed that no significant differences were observed between the vitamin D group and control group based on 25(OH)D levels, treatment duration, and predialysis CKD or dialysis patients. This meta-analysis demonstrates that vitamin D supplementation does not have anti-inflammatory effects in CKD patients. Well-designed randomized controlled trials with large samples are required to confirm this conclusion. It is still needed to find an effective treatment for inflammatory state in CKD.


Forensic entomology.
Necrophagous insects are important in the decomposition of cadavers. The close association between insects and corpses and the use of insects in medicocriminal investigations is the subject of forensic entomology. The present paper reviews the historical background of this discipline, important postmortem processes, and discusses the scientific basis underlying attempts to determine the time interval since death. Using medical techniques, such as the measurement of body temperature or analysing livor and rigor mortis, time since death can only be accurately measured for the first two or three days after death. In contrast, by calculating the age of immature insect stages feeding on a corpse and analysing the necrophagous species present, postmortem intervals from the first day to several weeks can be estimated. These entomological methods may be hampered by difficulties associated with species identification, but modern DNA techniques are contributing to the rapid and authoritative identification of necrophagous insects. Other uses of entomological data include the toxicological examination of necrophagous larvae from a corpse to identify and estimate drugs and toxicants ingested by the person when alive and the proof of possible postmortem manipulations. Forensic entomology may even help in investigations dealing with people who are alive but in need of care, by revealing information about cases of neglect.


Long-term Anticoagulation With Rivaroxaban for Preventing Recurrent VTE: A Benefit-Risk Analysis of EINSTEIN-Extension.
Short-term anticoagulant treatment for acute DVT or pulmonary embolism (PE) effectively reduces the risk of recurrent disease during the first 6 to 12 months of therapy. Continued anticoagulation often is not instituted because of the perception among physicians that the risk of major bleeding will outweigh the risk of new venous thrombotic episodes. The authors performed a benefit-risk analysis by using the randomized EINSTEIN-Extension trial, which compared continued rivaroxaban with placebo in 1,197 patients with symptomatic DVT or PE who had completed 6 to 12 months of anticoagulation and in whom physicians had equipoise with respect to the need for continued anticoagulation. One-year Kaplan-Meier rates and rate differences of recurrent VTE and major bleeding were calculated. Benefits and risks were assessed using rate differences scaled to a population size of 10,000 patients treated for 1 year. Recurrent VTE occurred in eight recipients of rivaroxaban and 42 patients receiving placebo. In a population of 10,000 patients treated for 1 year, rivaroxaban treatment would have resulted in 665 (95% CI, 246-1,084) fewer recurrent VTEs than would placebo (number needed to treat = 15). Major bleeding occurred in four (0.7%) and zero patients, respectively. Rivaroxaban treatment would have resulted in 68 (95% CI, 2-134) more major bleeding events than would placebo (number needed to harm = 147). Kaplan-Meier analysis showed early recurrent VTE reduction with rivaroxaban that continued to improve throughout treatment; major bleeding increased gradually, plateauing at approximately 100 days. A clinically important benefit and a favorable benefit-risk profile of continued rivaroxaban anticoagulation was observed. ClinicalTrials.gov; No.: NCT00439725; URL: www.clinicaltrials.gov.


Abiotic stress responsive rice ASR1 and ASR3 exhibit different tissue-dependent sugar and hormone-sensitivities.
The expression of the six rice ASR genes is differentially regulated in a tissue-dependent manner according to environmental conditions and reproductive stages. OsASR1 and OsASR3 are the most abundant and are found in most tissues; they are enriched in the leaves and roots, respectively. Coexpression analysis of OsASR1 and OsASR3 and a comparison of the cis-acting elements upstream of OsASR1 and OsASR3 suggested that their expression is regulated in common by abiotic stresses but differently regulated by hormone and sugar signals. The results of quantitative real-time PCR analyses of OsASR1 and OsASR3 expression under various conditions further support this model. The expression of both OsASR1 and OsASR3 was induced by drought stress, which is a major regulator of the expression of all ASR genes in rice. In contrast, ABA is not a common regulator of the expression of these genes. OsASR1 transcription was highly induced by ABA, whereas OsASR3 transcription was strongly induced by GA. In addition, OsASR1 and OsASR3 expression was significantly induced by sucrose and sucrose/glucose treatments, respectively. The induction of gene expression in response to these specific hormone and sugar signals was primarily observed in the major target tissues of these genes (i.e., OsASR1 in leaves and OsASR3 in roots). Our data also showed that the overexpression of either OsASR1 or OsASR3 in transgenic rice plants increased their tolerance to drought and cold stress. Taken together, our results revealed that the transcriptional control of different rice ASR genes exhibit different tissue-dependent sugar and hormone-sensitivities.


Whitham equations and phase shifts for the Korteweg-de Vries equation.
The semi-classical Korteweg-de Vries equation for step-like data is considered with a small parameter in front of the highest derivative. Using perturbation analysis, Whitham theory is constructed to the higher order. This allows the order one phase and the complete leading-order solution to be obtained; the results are confirmed by extensive numerical calculations.


Energy intake rates and nectar concentration preferences by hummingbirds.
In a series of daul choice tests with large volume feeders, rufous hummingbirds preferred sucrose concentrations near those that maximized their instantaneous rates of energy intake. As predicted on theoretical grounds, energy intake rates increased with increasing sucrose concentration to a maximum then decreased above this maximum. Earlier experimental studies suggested that hummingbirds always prefer the highest available concentration. Our results are consistent with the data of these studies, but by using a wider range of concentrations than previous workers, we found that the hummingbirds discriminated against very concentrated solutions.


Intertwined associations between oxytocin, immune system and major depressive disorder.
Major depressive disorder (MDD) is a prominent psychiatric disorder with a high prevalence rate. The recent COVID-19 pandemic has exacerbated the already high prevalence of MDD. Unfortunately, a significant proportion of patients are unresponsive to conventional treatments, necessitating the exploration of novel therapeutic strategies. Oxytocin, an endogenous neuropeptide, has emerged as a promising candidate with anxiolytic and antidepressant properties. Oxytocin has been shown to alleviate emotional disorders by modulating the hypothalamic-pituitary-adrenal (HPA) axis and the central immune system. The dysfunction of the immune system has been strongly linked to the onset and progression of depression. The central immune system is believed to be a key target of oxytocin in ameliorating emotional disorders. In this review, we examine the evidence regarding the interactions between oxytocin, the immune system, and depressive disorder. Moreover, we summarize and speculate on the potential roles of the intertwined association between oxytocin and the central immune system in treating emotional disorders.


Laparoscopic compared to open approach for distal gastrectomy may reduce pneumonia risk for patients with gastric cancer.
Whether laparoscopic approach to gastrectomy for gastric cancer (GC) reduces the risk of pneumonia remains unknown. In this study, we compared pneumonia outcomes for patients with GC who underwent either laparoscopic gastrectomy (LG) or open gastrectomy (OG). The ACS NSQIP database was queried to identify patients with GC who underwent LG or OG between Jan 2012 - Dec 2018. Outcomes were compared using regression models. A post-hoc analysis was performed for elderly patients. The study cohort included 2661 patients, 23.4 % undergoing LG. Laparoscopic approach lowered pneumonia risk (OR 0.47, p = .028) and reduced hospital length of stay, (5.3 vs 7.1 days, p < .001). Elderly patients undergoing LG demonstrated similar benefits. Risk factors for pneumonia included advanced age, dyspnea and weight-loss, whereas laparoscopic approach reduced this risk. LG in patients with GC has both statistically and clinically significant advantages over OG with respect to pneumonia. Further studies are needed to validate the relationship between postoperative pneumonia and surgical approach for gastrectomy.


Allograft Anterior Cruciate Ligament Reconstruction Fails at a Greater Rate in Patients Younger Than 34 Years.
To characterize the secondary anterior cruciate ligament (ACL) injury rates after primary allograft anterior cruciate ligament reconstruction (ACLR) and to identify the age cut-score at which the risk of allograft failure decreases. All patients who underwent primary ACLR within a single orthopaedic department between January 2005 and April 2020 were contacted at a minimum of 2 years post-ACLR to complete a survey regarding complications experienced post-surgery, activity level, and perceptions of knee health. Patients were excluded for incidence of previous ACLR (ipsilateral or contralateral) and/or age younger than 14 years. Relative proportions were calculated, binary regression analysis was performed, and receiver operating characteristic analysis was used to identify the threshold age for maximal sensitivity and specificity to predict high risk of allograft failure, defined as undergoing revision ACLR. Of the 939 surveys completed, 398 patients underwent primary allograft ACLR (mean age 39.5 years; range 16.0-66.1 years; 54.3% female). The secondary ACL injury rate was 11.6% (5.8% ipsilateral revision ACLR, 5.8% contralateral ACL injury). Male and female patients had similar revision (5.5% male, 6.0% female, P = .82) and contralateral ACL injury rates (6.6% male, 5.1% female, P = .52). Receiver operating characteristic analysis indicated that age ≤34 years was threshold for differentiating high risk of allograft failure (area under the curve 0.65, 95% confidence interval 0.55-0.76; P = .014). Patients aged ≤34 years had a greater secondary injury rate than patients >34 years (20.4% (10.2% revision ACLR, 10.2% contralateral ACL injury) versus 6.9% (3.5% revision ACLR, 3.5% contralateral ACL injury; P < .001). Binary regression analysis demonstrated that decreasing age was associated with increased risk of graft failure (χ2 = 7.9, P = .02.). Allograft ACLR showed similar failure rates between sexes but displayed suboptimal graft failure outcomes in younger and active patients. By age 34 years, the increased revision risk for younger patients diminished. Level IV, therapeutic case series.


Thoracoscopic excision of the sympathetic chain: an easy and effective treatment for hyperhidrosis in children.
Thoracoscopic sympathectomy (TS) is an effective treatment for hyperhidrosis. Various surgical approaches are described in the literature. We describe the technique of thoracoscopic excision of the sympathetic chain done exclusively in children younger than 13 years. All patients younger than 13 years who underwent TS from 2006 at a single institution were prospectively identified and fully evaluated with emphasis on demographic data, age, surgical management, complications and follow-up. All patients were contacted again at the end of 2009 to complete a follow-up questionnaire. Twelve patients underwent TS between 2006 and 2009. Age ranged from 6 to 13 years. This involved T2-T3 excision for nine patients with isolated palmar hyperhidrosis, and T2-T3-T4 excision for three with additional axillary hyperhidrosis. Six underwent bilateral TS at the same session and six underwent unilateral TS for the dominant side. Four of them had their contralateral operation performed 2-3 months later. Dry limbs were immediately achieved in all patients. Compensatory sweating (CS) was noted in eight patients. Complications included transient ptosis in two and mild recurrence in one. Thoracoscopic excision of the sympathetic chain is a simple and safe procedure that relieves hyperhidrosis in all cases and significantly improves the quality of life.


Hereditary spastic paraplegias: one disease for many genes, and still counting.
Hereditary spastic paraplegias (HSPs) are genetically heterogeneous Mendelian disorders characterized by spastic gait with stiffness and weakness in the legs and an associated plethora of neurological or extraneurological signs in "complicated" forms. Major advances have been made during the past two decades in our understanding of their molecular bases with the identification of a large number of gene loci and the cloning of a set of them. The combined genetic and clinical information obtained has permitted a new, molecularly-driven classification and an improved diagnosis of these conditions. This represents a prerequisite for better counseling in families and more appropriate therapeutic options. However, further heterogeneity is expected and new insight into the possible mechanisms anticipated.


Analysis of medical emergency team calls comparing subjective to "objective" call criteria.
To explore the reasons why nursing staff use the subjective "worried" Medical Emergency Team (MET) calling criterion and compare the outcomes of calls activated using the "worried" criterion with those calls activated using "objective" criteria such as vital sign abnormalities. A descriptive study of MET calls in six acute hospitals over a 12 months period. Outcomes for "objective" and "worried" calls were compared. The "worried" criterion was used to activate 29% of 3194 MET calls studied; it was the single most common reason for a MET call. Half (51.7%) of the "worried" calls were related to problems with Airway, Breathing, Circulation or Neurology. 'Breathing' problems accounted for the largest proportion (35.2%). A low oxygen saturation by pulse oximetry (SpO2) (n=249, 26.9%) and 'respiratory distress' (n=133, 14.4%) were the most common reasons for a "worried" call. Only 1.1% (10) of calls triggered by the "worried" criteria had cardiac arrest as an outcome compared with 170 calls (7.6%) for "objective" criteria. The proportion of patients who remained in a general ward area after MET calls was higher for the "worried" calls. The "worried" criterion was the most frequent reason for MET calls, implying a high degree of empowerment and independent action by nursing staff. Low SpO2 and respiratory distress were the most common causes for concern. There was a significant difference between MET calls triggered by "worried" criteria and "objective" criteria for outcomes immediately following MET (p < 0.001). Further assessment and refinement of MET triggers particularly in relation to respiratory distress and pulse oximetry may be needed.