Self-association of block copoly(oxyalkylene)s in aqueous solution. Effects of composition, block length and block architecture.
The article deals with the association behaviour in dilute aqueous solution of block copoly(oxyalkylene)s in which hydrophilic poly(ethylene oxide) is combined with hydrophobic poly(propylene oxide), poly(1,2-butylene oxide) or poly(styrene oxide). Polymers with three simple architectures are considered, i.e. copolymers of type EmAn, EmAnEm and AnEmAn, where E denotes an oxyethylene unit, A denotes a hydrophobic oxyalkylene unit, and the subscripts m and n denote number-average block lengths in repeat units. The aim is to examine how composition, block length and block architecture govern two fundamental properties, critical micelle concentration (cmc) and micelle association number (N), for systems which are in dynamic equilibrium. Copolymers with properties known to be greatly affected by heterogeneity in composition are excluded from consideration. A uniform pattern of behaviour emerges when log(cmc) is plotted against reduced hydrophobic block length (x), consistent with the micellisation equilibrium changing from one between unimers and multimolecular micelles at low values of x, to one between unimolecular micelles and multimolecular micelles at high values of x. Support for this model is provided by the enthalpy of micellisation, values of which fall effectively to zero as x is increased. Values of the micelle association number are used to define a critical hydrophobic block length for micellisation (n(cr)) for each class of diblock copolymers, values of which apply equally well to the half-length of the central block of corresponding EmAnEm triblock copolymers. Given these values, and irrespective of block architecture, the overall scaling law for the weight-average association number of the micelles is shown to be Nw = n'(1.07)m(-0.63) where m is the length (or half-length) of the hydrophilic block, and n' is the effective length of the hydrophobic block, equal to its length (or half-length) minus the critical length, i.e. n' = n-n(cr).


Corresponding measurements of delayed luminescence and impedance spectroscopy on acupuncture points.
Measurements of impedance spectroscopy and delayed luminescence have been performed on the acupuncture points PC4 and PC8 and other two control points of ten volunteers. The results show that there is a highly significant difference between the imaginary parts of the impedance of the acupunctural points and that of the control points. The same difference has not be observed in the values of the total number of counts of delayed luminescence. However a relationship has been detected between the imaginary part of the impedance of PC8 point and the total number of delayed luminescence counts, similar to that one found before for collagen, and it has been seen that the temporal dynamics of the two phenomena measured on one control points are similar. In particular, these final results confirm the close connection between the delayed luminescence and the dielectric properties of biological tissues.


Analysis of N-cadherin function in limb mesenchymal chondrogenesis in vitro.
During embryonic limb development, cartilage formation is presaged by a crucial mesenchymal cell condensation phase. N-Cadherin, a Ca2+ -dependent cell-cell adhesion molecule, is expressed in embryonic chick limb buds in a spatiotemporal pattern suggestive of its involvement during cellular condensation; functional blocking of N-cadherin homotypic binding, by using a neutralizing monoclonal antibody, results in perturbed chondrogenesis in vitro and in vivo. In high-density micromass cultures of embryonic limb mesenchymal cells, N-cadherin expression level is high during days 1 and 2, coincident with active cellular condensation, and decreases upon overt chondrogenic differentiation from day 3 on. In this study, we have used a transfection approach to evaluate the effects of gain- and loss-of-function expression of N-cadherin constructs on mesenchymal condensation and chondrogenesis in vitro. Chick limb mesenchymal cells were transfected by electroporation with recombinant expression plasmids encoding wild-type or two mutant extracellular/cytoplasmic deletion forms of N-cadherin. Expression of the transfected N-cadherin forms showed a transient profile, being high on days 1-2 of culture, and decreasing by day 3, fortuitously coincident with the temporal profile of endogenous N-cadherin gene expression. Examined by means of peanut agglutinin (PNA) staining for condensing precartilage mesenchymal cells, cultures overexpressing wild-type N-cadherin showed enhanced cellular condensation on culture days 2 and 3, whereas expression of the deletion mutant forms (extracellular/cytoplasmic) of N-cadherin resulted in a decrease in PNA staining, suggesting that a complete N-cadherin protein is required for normal cellular condensation to occur. Subsequent chondrogenesis was also affected. Cultures overexpressing the wild-type N-cadherin protein showed enhanced chondrogenesis, indicated by increased production of cartilage matrix (sulfated proteoglycans, collagen type II, and cartilage proteoglycan link protein), as well as increased cartilage nodule number and size of individual nodules, compared with control cultures and cultures transfected with either of the two mutant N-cadherin constructs. These results demonstrate that complete N-cadherin function, at the levels of both extracellular homotypic binding and cytoplasmic linkage to the cytoskeleton by means of the catenin complex, is required for chondrogenesis by mediating functional mesenchymal cell condensation.


In vivo wear of enamel by a lithia disilicate-based core ceramic used for posterior fixed partial dentures: first-year results.
This study aimed (1) to test the hypothesis that no significant relationship exists between the magnitude of occlusal clenching force and wear rates of enamel opposing a new core ceramic (e.max Press, Ivoclar Vivadent) used in posterior fixed partial dentures (FPDs); and (2) to test the hypothesis that mean annual enamel wear by an experimental core ceramic is comparable to the mean annual enamel wear by enamel of 38 microm. Baseline data were obtained for patients in addition to preliminary impressions of maxillary and mandibular teeth. Thirty ceramic FPDs were processed from a new core ceramic (e.max Press) that was hot pressed and glazed. Patients were recalled 1 year after cementation and evaluated using clinical criteria that included wear assessment of opposing teeth. Impressions were made of the opposing teeth with polyvinylsiloxane impression material and photographs were taken of intraoral occlusal contacts marked with articulating ribbon. Baseline casts and casts made at each recall exam of opposing dentitions were scanned using a 3-dimensional laser scanner (Laserscan 3D, Willytec) and evaluated for wear. A total of 21 occlusal surfaces were analyzed for the presence of wear. Statistical analysis using a linear and quadratic model revealed no significant relationship between occlusal forces and wear rate assuming either a linear model (R2 = 0.018) or a quadratic model (R2 = 0.023). The maximum annual wear of enamel by the glazed core ceramic (e.max Press) was 88.3 microm, which is significantly greater than the annual enamel-by-enamel wear of 38 microm (P < .0001). Further analysis with a larger sample size is needed to determine the relationship between occlusal clenching force and wear rate and the influence of other factors that cause increased wear of enamel by opposing ceramic restorations.


Ultrasound diagnosis and clinicopathological traits of female genital system malignant lymphomas.
This study investigated the clinicopathological traits and ultrasound features (including 2-dimensional and color Doppler ultrasound) of female genital system malignant lymphomas and explored the diagnostic performance of ultrasonography in this disease.Cases of female pelvic lymphoma diagnosed and treated at our hospital between July 2009 and July 2019 were included in this study. Pathological data and ultrasonic manifestations were assessed retrospectively to summarize the clinical traits and ultrasonic features of female genital system lymphoma (FGSL). Based on the results, recommendations for ultrasonography-based diagnosis of this disease are proposed.During the 10-year study period, 20 female patients were diagnosed with malignant lymphomas in the pelvic cavity based on postoperative pathology tests. The age of the patients ranged from 11 to 83 years, and no patients demonstrated specific clinical traits; however, examination of tumor biomarkers revealed that certain patients had elevated levels of CA125. Twenty-eight lesions were identified in the 20 patients, including 24 involving the reproductive system. The primary ultrasonic manifestations were hypoechoic or extremely hypoechoic solid lesions that were relatively large in size, had a relatively regular shape, and had clear boundaries. Certain patients had concurrent ascites, and although some lesions lacked blood supply, most lesions had medium to abundant blood flow, which was largely characterized by low resistance. Almost none of the lesions were definitively diagnosed preoperatively.Diagnosing malignant lymphomas in the female genital tract remains a considerable clinical challenge. Although certain clinical traits and ultrasonic features are associated with this disease and color Doppler ultrasonography might provide vital information indicating the presence of lymphoma, the final diagnosis depends on the clinical and pathological test results of the patients.


Role of oxysterol binding protein in hepatitis C virus infection.
Hepatitis C virus (HCV) RNA genome replicates within the ribonucleoprotein (RNP) complex in the modified membranous structures extended from endoplasmic reticulum. A proteomic analysis of HCV RNP complexes revealed the association of oxysterol binding protein (OSBP) as one of the components of these complexes. OSBP interacted with the N-terminal domain I of the HCV NS5A protein and colocalized to the Golgi compartment with NS5A. An OSBP-specific short hairpin RNA that partially downregulated OSBP expression resulted in a decrease of the HCV particle release in culture supernatant with little effect on viral RNA replication. The pleckstrin homology (PH) domain located in the N-terminal region of OSBP targeted this protein to the Golgi apparatus. OSBP deletion mutation in the PH (DeltaPH) domain failed to localize to the Golgi apparatus and inhibited the HCV particle release. These studies suggest a possible functional role of OSBP in the HCV maturation process.


The impact of material surface roughness and temperature on the adhesion of Legionella pneumophila to contact surfaces.
The adhesion of bacterial cells to various surfaces is based on physical and chemical interactions between the micro-organisms and the surfaces. The main purpose of this research is to determine the effect of material roughness and incubation temperature on the adhesion of bacteria. To determine the adhesion of the bacterial strain of Legionella pneumophila ATCC 33153 to the glass coupons, a spectrophotometric method of measuring the optical density of crystal violet dye that is released from pre-stained bacterial cells attached to the test surface was used. The intensity of adhesion is in positive correlation to the increase in surface roughness (p < 0.05). The adhesion is the greatest at an optimal temperature of 36 °C, whereas the temperature of 15 °C has a bacteriostatic effect and the temperature of 55 °C a bactericidal effect.


Nasopharyngeal rhabdomyosarcoma presenting as a breast mass.
We describe a 13-year-old girl with a primary nasopharyngeal rhabdomyosarcoma presenting with an isolated breast metastasis and no other evidence of distant metastatic spread. Only seven cases have been previously reported, and in all these cases the primary tumor was located either on an extremity or the buttock, and in six the disease was widely disseminated at diagnosis.


[Quantitative fluorescence characterization of organic matter stability during chicken manure composting].
Due to its high sensitivity, good selectivity and nondestructive nature, fluorescence spectroscopy was widely applied to characterize the nature of dissolved organic matter (DOM) from different source since the last decade. In the present study, dissolved organic matter (DOM) extracted from chicken manure samples during composting progress was quantitatively characterized by fluorescence analysis techniques and mathematical analysis methods. The results showed that, the ratio between the fluorescence intensities at 330 nm (humic-like matter) and 280 nm(protein-like matter) (I330/I280) in synchronous-scan excitation mode spectra, the area of a fluorescence spectrum obtained by excitation at the blue wavelength of 465 nm(A470-640), and the ratio between the area of the last quarter (435-480 nm) and the area of the first quarter (300-345 nm) of the emission spectrum (A435-480 nm/A300-345 nm) by exciting the sample with ultraviolet radiation of 240 nm, all increased during composting, and the humification degree of compost increased as well. Three-dimensional excitation emission matrix fluorescence spectroscopy showed that the intensity of protein-like matter decreased during composting progress and diminished at the end, while that of fulvic-like matter increased all the time. The ratio between the intensity of the ultraviolet fulvic-like fluorescence (Peak A) and that of the visible fulvic-like fluorescence gamma (A, C) showed an overall significant downward trend during composting, but fluctuated in the progress. The correlation analysis showed that, I330/I280, A470-640 and A435-480 nm/A300-345 nm were all significant correlative, while gamma (A, C) was not correlative with the above-mentioned three parameters at 0. 05 level due to effect by other factors. The results show that, I330/I280, A470-640 and A435-480 nm/A300-345 nm can be effectively used in the process of the evaluation of humification degree during composting.


Perioperative Outcomes After Cervical Laminoplasty Versus Posterior Decompression and Fusion: Analysis of 779 Patients in the ACS-NSQIP Database.
Retrospective cohort study. To compare the short-term outcomes for patients undergoing cervical laminoplasty versus posterior decompression and fusion for multilevel cervical pathology. There are conflicting data regarding the merits of cervical laminoplasty and posterior decompression and fusion for the treatment of multilevel cervical pathology. Patients who underwent cervical laminoplasty or posterior decompression and fusion were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2010 to 2012. Baseline patient characteristics were compared using bivariate logistic regression. Propensity-adjusted multivariate regressions were performed to assess differences in postoperative length of stay, adverse events, and 30-day readmission. A total of 779 patients were included in this study: 437 (56.1%) underwent cervical decompression and fusion and 342 (43.9%) underwent cervical laminoplasty. Decompression and fusion patients were found to be more comorbid at baseline than laminoplasty patients based on increased American Society of Anesthesiologists scores and Charlson Comorbidity Index.Propensity-adjusted multivariate analysis was used to control for differences in baseline patient characteristics, and found that compared with laminoplasty patients, decompression and fusion patients had increased length of stay (+1.2 d, P<0.001), greater rates of any adverse event (OR=1.7, P=0.018), and were more likely to be readmitted (OR=2.3, P=0.028). Posterior cervical decompression and fusion patients were found to have moderately worse short-term outcomes than laminoplasty patients. The information provided here can be used to inform patients and surgeons about the likely perioperative experience after they have made the decision to pursue 1 of these 2 procedures.


MRI-based comprehensive analysis of vascular anatomy and hemodynamics.
Standardized methods for mapping the complex blood flow in vessels are essential for processing the large data volume acquired from 4D Flow MRI. We present a method for systematic and efficient analysis of anatomy and flow in large human blood vessels. To attain the best outcomes in cardiac surgery, vascular modifications that lead to secondary flow patterns such as vortices should be avoided. In this work, attention was paid to the undesired cancelation of vortices with opposite directions of rotation, known as Dean flow patterns, using hemodynamic parameters such as circulation and helicity density. Our approach is based on the multiplanar reconstruction (MPR) of a multi-dimensional feature-space along the blood vessel's centerline. Hemodynamic parameters and anatomic information were determined in-plane from the reconstructed feature-space and from the blood vessel's centerline. A modified calculation of circulation and helicity density and novel parameters for quantifying Dean flow were developed. To test the model performance, we applied our methods to three test cases. Comprehensive information on position, magnitude and interrelation of vascular anatomy and hemodynamics were extracted from 4D Flow MRI datasets. The results show that the Dean flow patterns can be efficiently assessed using the novel parameters. Our approach to comprehensively and simultaneously quantify multiple parameters of vascular anatomy and hemodynamics from 4D Flow MRI provides new insights to map complex hemodynamic conditions.


Effects of metronidazole and oligofructose on faecal concentrations of sulphate-reducing bacteria and their activity in human volunteers.
Sulphate-reducing bacteria (SRB) have been implicated in the aetiology of ulcerative colitis. Sulphide produced from reduction of sulphate by SRB is highly toxic to colonocytes and can impair their metabolic function. The aim of this study was to investigate the modulation of the colonic bacterial flora using metronidazole and the prebiotic oligofructose on the concentration and activity of SRB. Healthy volunteers were randomly allocated to take metronidazole (5 days), oligofructose (12 days) or both metronidazole (5 days) and oligofructose (12 days). At days 0, 5, 12 and 19, stool samples were cultured, and their pH measured; concentrations of sulphate, hydrogen sulphide, short-chain fatty acids (SCFAs) were measured and the sulphate reduction rates (SRRs) determined. In SRB-positive volunteers (n=16) faecal SRB concentrations fell with metronidazole (95% CI, 2.19, 3.36 p<0.0001) even when combined with oligofructose (95% CI 2.32, 4.01 p<0.0001). Faecal anaerobe concentrations fell with metronidazole and bifidobacterial concentrations rose with oligofructose irrespective of SRB status. Faecal SRRs fell with metronidazole irrespective of the presence of faecal SRB (95% CI 29.0, 56.1 p<0.0001). No changes in faecal sulphate concentrations were seen. Faecal hydrogen sulphide concentrations fell with oligofructose in SRB-positive volunteers (95% CI 0.14, 0.53 p=0.002). Faecal SCFA concentrations fell with metronidazole (-103.7, -19.6, p=0.007) and rose with oligofructose (9.9, 83.1 p=0.016). The study shows that metronidazole, but not oligofructose, reduced the concentration and activity of faecal SRB. This reduction had no impact on faecal concentrations of sulphate and hydrogen sulphide, suggesting that other methods of hydrogen sulphide production are more important. Oligofructose causes a reduction in faecal hydrogen sulphide, and an increase in SCFA concentrations may thus have a therapeutic role in patients with ulcerative colitis.


Iron, Copper, and Zinc Homeostasis: Physiology, Physiopathology, and Nanomediated Applications.
Understanding of how the human organism functions has preoccupied researchers in medicine for a very long time. While most of the mechanisms are well understood and detailed thoroughly, medicine has yet much to discover. Iron (Fe), Copper (Cu), and Zinc (Zn) are elements on which organisms, ranging from simple bacteria all the way to complex ones such as mammals, rely on these divalent ions. Compounded by the continuously evolving biotechnologies, these ions are still relevant today. This review article aims at recapping the mechanisms involved in Fe, Cu, and Zn homeostasis. By applying the knowledge and expanding on future research areas, this article aims to shine new light of existing illness. Thanks to the expanding field of nanotechnology, genetic disorders such as hemochromatosis and thalassemia can be managed today. Nanoparticles (NPs) improve delivery of ions and confer targeting capabilities, with the potential for use in treatment and diagnosis. Iron deficiency, cancer, and sepsis are persisting major issues. While targeted delivery using Fe NPs can be used as food fortifiers, chemotherapeutic agents against cancer cells and microbes have been developed using both Fe and Cu NPs. A fast and accurate means of diagnosis is a major impacting factor on outcome of patients, especially when critically ill. Good quality imaging and bed side diagnostic tools are possible using NPs, which may positively impact outcome.


Effect of sitagliptin on glucose control in type 2 diabetes mellitus after Roux-en-Y gastric bypass surgery.
The present study was a 4-week randomized trial to assess the efficacy and safety of sitagliptin, a dipeptidyl-peptidase-4 inhibitor, in persistent or recurring type 2 diabetes after Roux-en-Y gastric bypass surgery (RYGB). Participants (n = 32) completed a mixed meal test (MMT) and self-monitoring of plasma glucose (SMPG) before and 4 weeks after randomization to either sitagliptin 100 mg daily or placebo daily. Questionnaires were administered to assess gastrointestinal discomfort. Outcome variables were glucose, active glucagon-like peptide-1 and β-cell function during the MMT, and glucose levels during SMPG. Age (56.3 ± 8.2 years), body mass index (34.4 ± 6.7 kg/m2 ), glycated haemoglobin (7.21 ± 0.77%), diabetes duration (12.9 ± 10.0 years), years since RYGB (5.6 ± 3.3 years) and β-cell function did not differ between the placebo and sitagliptin groups at pre-intervention. Sitagliptin was well tolerated, decreased postprandial glucose levels during the MMT (from 8.31 ± 1.92 mmol/L to 7.67 ± 1.59 mmol/L, P = 0.03) and mean SMPG levels, but had no effect on β-cell function. In patients with diabetes and mild hyperglycemia after RYGB, a short course of sitagliptin provided a small but significant glucose-lowering effect, with no identified improvement in β-cell function.


The strength characteristics of internal and external rotator muscles in professional baseball pitchers.
The purpose of this study was to establish a data base regarding the isokinetic muscular performance characteristics of the external/internal rotator muscles of professional baseball pitchers. One hundred fifty healthy professional baseball pitchers were evaluated by use of a Biodex isokinetic dynamometer. The subjects tested had a mean age of 23.4 years and a mean body weight of 199 pounds. Isokinetic tests were performed concentrically at 180 and 300 deg/sec for both the throwing and nonthrowing shoulders. Testing procedures regarding positioning and stabilization followed established guidelines. The testing protocol and actual test repetitions were standardized for each subject. Statistical analysis was performed using the Pearson Product Moment Correlation and paired t-tests. Determination of the correlation coefficient was made at the P < 0.05 level of significance. Test results for bilateral comparison of mean peak torque for the throwing and nonthrowing shoulders indicated no statistically significant difference between the internal rotators at both test speeds, or for the external rotators at 300 deg/sec. There was a significant statistical difference at the 180 deg/sec test speed for the external rotators. The external/internal rotator strength ratio indicated a 65% ratio at 180 deg/sec and a 61% ratio at 300 deg/sec. Data were also collected for mean peak torque/body weight ratios of the throwing shoulder to establish a data base in professional throwers. This study offers clinical relevance in establishing a muscle performance profile for the professional thrower. This data base can therefore be used as criteria that should be met before an injured pitcher can be returned to throwing at the professional baseball level.


Crystallization and characterization of the dehydrogenase domain from rat peroxisomal multifunctional enzyme type 1.
Peroxisomal multifunctional enzyme type 1 from rat (perMFE-1) is a monomeric multidomain protein shown to have 2-enoyl-CoA hydratase/Delta(3)-Delta(2)-enoyl-CoA isomerase and (3S)-hydroxyacyl-CoA dehydrogenase domains followed by a C-terminal extension of 130 amino acids with unknown function apart from being a carrier of the peroxisomal targeting signal type 1. The truncated perMFE-1 without the N-terminal hydratase/isomerase domain (perMFE-1DH; residues 260-722) was overexpressed as an enzymatically active recombinant protein, purified and characterized. Using (3S)-hydroxydecanoyl-CoA as a substrate, the specific enzymatic activity of perMFE-1DH was determined to be 2.2 micromol min(-1) mg(-1), comparable with that of perMFE-1 purified from rat liver (2.8 micromol min(-1) mg(-1)). The protein was crystallized in the apo form by the hanging-drop method and a complete data set to 2.45 A resolution was collected using a rotating-anode X-ray source. The crystals have primitive tetragonal symmetry, with unit-cell parameters a = b = 125.9, c = 60.2 A.


Carbon-nitrogen trading in symbiotic nodules depends on magnesium import.
Symbiotic nitrogen fixation provides large amounts of nitrogen for global agricultural systems with little environmental or economic costs. The basis of symbiosis is the nutrient exchange occurring between legumes and rhizobia, but key regulators controlling nutrient exchange are largely unknown. Here, we reveal that magnesium (Mg), an important nutrient factor that preferentially accumulates in inner cortical cells of soybean nodules, shows the most positive correlation with nodule carbon (C) import and nitrogen (N) export. We further identified a pair of Mg transporter genes, GmMGT4 and GmMGT5, that are specifically expressed in the nodule cortex, modulating both nodule Mg import and C-N transport processes. The GmMGT4&5-dependent Mg import activates the activity of a plasmodesmata-located β-1,3-glucanase GmBG2 and consequently keeps plasmodesmata permeable for C-N transport in nodule inner cortical cells. Our studies discovered an important regulating pathway for host plants fine-tuning nodule C-N trading to achieve optimal growth, which may be helpful for optimizing nutrient management for soybean production.


[Vegetation diversity of wild Chinese alligator (Alligator sinensis) habitats].
In June and July of 2003, a field survey on the vegetation of 22 Chinese alligator habitats distributed in Nanling county, Jingxian county, Guangde county, Langxi county and Xuancheng city of Anhui province was conducted, and the plant species of the habitats were recorded and analyzed. The results showed that the vegetation of the whole habitats was secondary, and there were 294 species vascular plants, belonging to 92 families. Pteioblastus amarus shrubbery could be found in all sites, and part differences of the vegetation consisted in different habitats. The relationship between Chinese alligator and habitat vegetation was also analyzed. All of these could offer some basic botanical data for the further protection of the Chinese alligator.


Inhibition of experimental metastasis by an alpha-glucosidase inhibitor, 1,6-epi-cyclophellitol.
Isolated from a culture filtrate of Phellinus sp., cyclophellitol is a specific inhibitor of beta-glucosidase, but unlike castanospermine, it does not inhibit experimental metastasis. However, its structural analogue, 1,6-epi-cyclophellitol, inhibited alpha-glucosidase as well as beta-glucosidase, and inhibited experimental metastasis. 1,6-Epi-cyclophellitol depressed alpha-glucosidase activity in cultured B16/F10 cells after 48 h of incubation. Preincubation of B16/F10 cells for 48 h with 1,6-epi-cyclophellitol inhibited invasion of the cells in a Boyden chamber assay at the doses effective in inhibiting alpha-glucosidase in situ. Pulmonary metastasis of B16/F10 cells in mice was inhibited by pretreatment of the cells with 1,6-epi-cyclophellitol in culture. The inhibitor reduced the collagen type I- and IV-mediated attachment of the cells, whereas it had no effect on laminin-mediated attachment. These results suggest that alpha-glucosidase in tumor cells is essential for the metastatic process through the cellular interaction with collagen type I and IV.


The neuroecology of dimethyl sulfide: a global-climate regulator turned marine infochemical.
Information transfer influences food-web dynamics in the marine environment, but infochemicals involved in these processes are only beginning to be understood. Dimethylsulfoniopropionate (DMSP) is produced by phytoplankton and other marine algae, and has been studied primarily in the context of sulfur cycling and regulation of global climate. My laboratory has been investigating DMSP and its breakdown product, dimethyl sulfide as infochemicals associated with trophic interactions in marine habitats, including sub-Antarctic and coral reef ecosystems. Using a neuroecological approach, our work has established that these biogenic sulfur compounds serve as critical signal molecules in marine systems and provides us with a more mechanistic understanding of how climate change may impact information transfer within marine food webs.


Strategic Task and Break Timing to Reduce Ultraviolet Radiation Exposure in Outdoor Workers.
Objectives: Public health messaging about sun avoidance strategies is often not practical for outdoor workers. The objective of this study was to use personal monitoring data to determine when peak UVR exposure occurs for outdoor workers, estimate how much UVR could be reduced by altering the timing of shady tasks or breaks during peak exposure times, and descriptively compare these to peak periods of ambient UVR. Ultimately, we aim to provide evidence-based sun avoidance recommendations for outdoor workers in British Columbia, Canada. Methods: UVR exposure data [standard erythemal dose (SED)] were collected during the 2013 summer months in Vancouver, using personal electronic dosimeters that sampled once per minute for an average of 4.4 working days (range: 1-7 days). Mixed-effect models were used to estimate the 60-, 30-, and 15-min time intervals at which maximum exposure occurred for the months of July and August. Using these time intervals, UVR exposure during peak periods was summarized as SED and as a percentage of the total daily exposure. Ambient UVR was also collected using data from the nearest Brewer spectrophotometer station and parallel analyses were conducted. Results: There were 73 workers and 321 participant-days available for analysis. Models indicated that periods of maximum exposure for 15-, 30-, and 60-min intervals began at 12:28, 12:17 pm, and 11:52 am, respectively, for sunny days in July. These periods were similar in August. The median exposure during these time periods and the potential for reducing UVR was 0.03 SED (2.8% potential daily exposure reduction), 0.09 SED (7.1%), and 0.18 SED (15.9%), respectively. However, there was a large range in exposure estimates as some workers experienced up to 84.8% of their exposure in the peak 60-min interval. Conclusion: Skin cancer prevention messaging does not include practical messages for outdoor workers and providing times of peak UVR help to identify times when the greatest reductions in exposure can occur. Prevention measures including shady breaks, increased sun protection, and task reorganization during these peak times are recommended during these peak times to reduce UVR exposure among those at highest risk.


Dual effects of gadodiamide injection in depiction of the region of myocardial ischemia.
The high safety index of the nonionic magnetic resonance (MR) contrast agent gadodiamide injection permits a wide dose range without induction of hemodynamic effects. The wide dose range might confer a diagnostic advantage by providing both T1 enhancing and magnetic susceptibility effects for demarcating pathologic regions. The dual utility of this contrast agent for T1 and T2 enhancement in creating differential contrast between normal and acutely ischemic myocardium was explored. MR imaging was initiated 20-40 minutes after occlusion of the left coronary artery in two groups of rats: Group 1 (n = 8) received 0.3 mmol/kg gadodiamide injection before and after acquisition of T1-weighted images; group 2 (n = 10) received 0.5 mmol/kg before and after acquisition of T2-weighted images. Postcontrast T1-weighted images showed clear delineation of the ischemic region as a relatively low-signal-intensity area for 15 minutes. On postcontrast T2-weighted images, the ischemic region appeared as a relatively high-signal-intensity area for 60 minutes. These effects were obtained with doses of gadodiamide injection that have safety indexes greater than those of gadopentetate dimeglumine.


Growing pains: can any willing provider laws overcome the challenges of the teenage years?
Any willing provider laws were first enacted in the late 1980's as a way to combat the exclusion of providers from insurer and Health Maintenance Organization (HMO) network panels. Generally, the laws provided that insurers and managed care organizations had to admit to their provider panels any provider who was willing to accept the entity's terms and conditions for participation. These laws face two significant challenges today: how to overcome Employee Retirement Income Security Act (ERISA) preemption and the fact that the legislatures either failed to put limits on the terms and conditions that could be imposed or did not define what reasonable terms and conditions were. This article gives a basic overview of any willing provider laws, the ERISA statutory and case law that affects them, and the current problem of what terms and conditions imposed upon providers can be considered reasonable. It also summarizes many of the current any willing provider laws and notes which laws among those listed have been held by courts to be preempted by ERISA. Efforts have been taken to make this article current and accurate; however, they should not be construed as legal advice or an opinion on specific situations. Because of the rapid pace with which these laws and the cases affecting them change, you should consult an attorney concerning the existence and validity of any willing provider and similar laws in your state.


[Tissue cultivation of tiller buds of Epimedium wushanense].
To established the rapid tissue propagation system of Epimedium wushanense, in order to provide theoretical basis for industrialized seed cultivation. Tiller buds E. wushanense were used as explants, with MS, B5, WPM as basic media, and added with different concentrations of plant growth regulators such as 6-BA, NAA and GA3, in order to conduct a systematic study on induction and propagation conditions for tiller buds. The suitable method for sterilizing bud was to disinfect with 75% ethanol for 30 s, and then treated with 0.1% HgCl2 for (4 + 2) min for consecutively twice, which could control the pollution rate below 5% and the survival rate above 75%. The optimal medium for bud induction was WPM + 6-BA 2.0 mg x L(-1) + NAA 0.1 mg x L(-1) + GA3 0.5 mg x L(-1), with the induction rate of 75.5%; meanwhile, the basic medium and 6-BA showed significant effect on the induction rate. The propagation medium suitable for buds was MS +6-BA 2.0 mg x L(-1) + NAA 0.5 mg x L(-1), with the propagation rate of 3.3. The optimal growth of rooting medium was 1/2 WPM + IBA 0.5 mg x L(-1) + activated carbon which (0.05%), with the rooting rate of 90%, three to six strong seedlings in each plant. The disinfection method suitable for tiller buds and the medium combination suitable for induction, propagation and rooting of adventitious buds are screened out to establish the rapid cultivation system for tiller buds of E. wushanense.


Activation of the knirps locus links patterning to morphogenesis of the second wing vein in Drosophila.
The adjacent knirps (kni) and knirps-related (knrl) genes encode functionally related zinc finger transcription factors that collaborate to initiate development of the second longitudinal wing vein (L2). kni and knrl are expressed in the third instar larval wing disc in a narrow stripe of cells just anterior to the broad central zone of cells expressing high levels of the related spalt genes. Here, we identify a 1.4 kb cis-acting enhancer element from the kni locus that faithfully directs gene expression in the L2 primordium. We find that three independent ri alleles have alterations mapping within the L2-enhancer element and show that two of these observed lesions eliminate the ability of the enhancer element to direct gene expression in the L2 primordium. The L2 enhancer can be subdivided into distinct activation and repression domains. The activation domain mediates the combined action of the general wing activator Scalloped and a putative locally provided factor, the activity of which is abrogated by a single nucleotide alteration in the ri(53j) mutant. We also find that misexpression of genes in L2 that are normally expressed in veins other than L2 results in abnormal L2 development. These experiments provide a mechanistic basis for understanding how kni and knrl link AP patterning to morphogenesis of the L2 vein by orchestrating the expression of a selective subset of vein-promoting genes in the L2 primordium.


Temporal evolution of copper distribution in soil fractions, influence of soil pH and organic carbon level on copper distribution.
The present paper deals with the temporal evolution, over 6 years, of copper distribution in soil fractions using a sequential extraction procedure isolating five soil fractions which are operationally defined but commonly identified as : F1 = exchangeable metals, F2 = metals bound to organic matter, F3 = metals bound to manganese oxides, = metals bound to iron oxides and F5 = the residual fraction. The soil studied was a silty agricultural soil whose four plots were deliberately enriched with copper sulphate in October 1992 and one of them was also enriched with organic matter, another one with lime and the last one with both organic matter and lime. The great advantage of such an experimental procedure was that the five plots represent the same soil and thus had the same soil texture. It was then possible to fully describe anthropogenic copper behaviour, and to describe clearly the influence of pH and organic carbon level on copper distribution. Furthermore, the plots were subjected to natural climatic conditions allowing a temporal study of copper distribution under natural conditions. The total Cu level as well as Cu-F3 and Cu-F4 were clearly decreasing with time. Copper concentration in artificially defined soil fractions were described with multiple regression equations with the variable total copper content (TCu) and with the variables soil pH and soil organic carbon level when required. Cu-F1 and Cu-F2 depended on soil pH and soil organic carbon level, while Cu-F3 depended only on TCu. Copper level bound to iron oxides depended on soil pH.


Lysinuric protein intolerance mutation is expressed in the plasma membrane of cultured skin fibroblasts.
Lysinuric protein intolerance (LPI) is an autosomal recessive phenotype consistent with impaired transport of cationic amino acids at the basolateral membrane of intestinal and renal epithelia. On the assumption that the basolateral membrane of epithelial cells and plasma membrane of parenchymal cells are functional analogues, we studied transport of cationic amino acids by cultured skin fibroblasts from LPI and control subjects matched for age, sex, and site of biopsy. We measured Na+-independent transport of radiolabeled lysine, arginine, ornithine, and homoarginine on system y+, the carrier with preference for cationic amino acids, and leucine transport on system L (as the internal control). LPI cells had increased net uptake of cationic amino acids (nmol/mg of protein) relative to leucine. LPI cells also maintained increased steady-state intracellular pools of cationic amino acids. Neither increased metabolic utilization nor increased pool size were responsible for high uptake of cationic amino acids in LPI cells. We then measured trans-stimulated efflux of homoarginine as a specific test of system y+ activity. Homoarginine efflux was significantly impaired in LPI cells (P less than 0.05), whereas leucine efflux was similar in LPI and control cells. Percent trans-stimulation of homoarginine efflux was 1.0 +/- 0.5% in homozygous LPI cells, 10 +/- 0.5% in heterozygous cells, and 22 +/- 0.5% in control cells indicating a gene-dosage effect. The LPI mutation affects system y+ asymmetrically, selectively impairing efflux in fibroblast plasma membrane. To our knowledge, this appears to be the first demonstration that the skin fibroblast can be used to study a corresponding transport defect in intestinal and renal membranes.


Kinetic analysis of one-step solid-state reaction for Li4Ti5O12/C.
The kinetics of one-step solid-state reaction of Li(4)Ti(5)O(12)/C in a dynamic nitrogen atmosphere was first studied by means of thermogravimetric-differential thermal analysis technique at five different heating rates. According to the double equal-double steps method, the Li(4)Ti(5)O(12)/C solid-state reaction mechanism could be properly described as the Jander equation, which was a three-dimensional diffusion with spherical symmetry, and the reaction mechanism functions were listed as follows: f(α) = (3)/(2)(1 - α)(2/3)[1 - (1 - α)(1/3)](-1), G(α) = [1 - (1 - α)(1/3)](2). In FWO method, average activation energy, frequency factor, and reaction order were 284.40 kJ mol(-1), 2.51 × 10(18) min(-1), and 1.01, respectively. However, the corresponding values in FRL method were 271.70 kJ mol(-1), 1.00 × 10(17) min(-1), and 0.96, respectively. Moreover, the values of enthalpy of activation, Gibbs free energy of activation, and entropy of activation at the peak temperature were 272.06 kJ mol(-1), 240.16 kJ mol(-1), and 44.24 J mol(-1) K(-1), respectively.


Pain and risk of completed suicide in Japanese men: a population-based cohort study in Japan (Ohsaki Cohort Study).
Unrelieved pain is a major factor that influences suicide risk among terminally ill patients, but little is known about the relationship between pain and the risk of completed suicide in the general population. We prospectively examined the association between self-reports of pain and subsequent risk of completed suicide in 26,481 men aged 40 to 79 years from the Ohsaki National Health Insurance Cohort study, a population-based, prospective cohort study initiated in 1994. On the basis of a five-item questionnaire on pain, individuals were classified as having no pain, very mild pain, mild pain, or moderate or severe pain. Completed suicide cases were documented from 1995 to 2001. During 131,027 person-years, 64 completed suicides were documented. After adjustment for covariates, the risk for completed suicide was significantly higher in the subjects with more pain. Multivariate hazard ratios (95% confidence intervals) relative to the subjects who had no pain were 1.36 (0.67-2.75), 2.11 (1.02-4.33), and 2.93 (1.34-6.42) in the subjects who had very mild pain, mild pain, and moderate or severe pain, respectively (P for trend=0.004). Stratified analysis showed that the positive association between pain and suicide risk was robust in the subjects with good health, low stress, adequate sleep, good physical activity, and no history of chronic diseases. Our results suggest that pain is associated with an increased risk of completed suicide among Japanese men. The association was consistently observed among apparently healthy subjects.


Spin-Dependent Tunneling Barriers in CoPc/VSe2 from Many-Body Interactions.
Mixed-dimensional magnetic heterostructures are intriguing, newly available platforms to explore quantum physics and its applications. Using state-of-the-art many-body perturbation theory, we predict the energy level alignment for a self-assembled monolayer of cobalt phthalocyanine (CoPc) molecules on magnetic VSe2 monolayers. The predicted projected density of states on CoPc agrees with experimental scanning tunneling spectra. Consistent with experiment, we predict a shoulder in the unoccupied region of the spectra that is absent from mean-field calculations. Unlike the nearly spin-degenerate gas-phase frontier molecular orbitals, the tunneling barriers at the interface are spin-dependent, a finding of interest for quantum information and spintronics applications. Both the experimentally observed shoulder and the predicted spin-dependent tunneling barriers originate from many-body interactions in the interface-hybridized states. Our results showcase the intricate many-body physics that governs the properties of these mixed-dimensional magnetic heterostructures and suggests the possibility of manipulating the spin-dependent tunneling barriers through modifications of interface coupling.


Well-woman care among obstetrician-gynecologists: opportunity for preconception care.
To describe the practices of obstetrician-gynecologists who provide routine gynecological care and assess the relative importance of well-woman care to their training and practices. A questionnaire was mailed to 1000 members of the American College of Obstetricians and Gynecologists, of whom 600 participated in the Collaborative Ambulatory Research Network. The response rate was 57%. Of these, 403 respondents providing routine obstetric and gynecologic care (OB&Gyn) are included. Obstetricians-gynecologists spend the majority of their time on labor/delivery (22%) followed by well-woman care (14%). It was found that 26% of the respondents rarely or never discuss sexual abuse or domestic violence with non-pregnant patients and only 19% always discuss folic acid with non-pregnant patients during well-woman care. Most (71%) say that 50% or more of their pregnant patients initially contact them once they are pregnant. Respondents rated their training in well-woman care least strong of several areas listed. Obstetrician-gynecologists devote a substantial proportion of work time to providing well-woman care, though some important topics are not addressed and training in this area was rated least strong.


Effect of alkali metal cations on slow inactivation of cardiac Na+ channels.
Human heart Na+ channels were expressed transiently in both mammalian cells and Xenopus oocytes, and Na+ currents measured using 150 mM intracellular Na+. The kinetics of decaying outward Na+ current in response to 1-s depolarizations in the F1485Q mutant depends on the predominant cation in the extracellular solution, suggesting an effect on slow inactivation. The decay rate is lower for the alkali metal cations Li+, Na+, K+, Rb+, and Cs+ than for the organic cations Tris, tetramethylammonium, N-methylglucamine, and choline. In whole cell recordings, raising [Na+]zero from 10 to 150 mM increases the rate of recovery from slow inactivation at -140 mV, decreases the rate of slow inactivation at relatively depolarized voltages, and shifts steady-state slow inactivation in a depolarized direction. Single channel recordings of F1485Q show a decrease in the number of blank (i.e., null) records when [Na+]0 is increased. Significant clustering of blank records when depolarizing at a frequency of 0.5 Hz suggests that periods of inactivity represent the sojourn of a channel in a slow-inactivated state. Examination of the single channel kinetics at +60 mV during 90-ms depolarizations shows that neither open time, closed time, nor first latency is significantly affected by [Na+]0. However raising [Na+]0 decreases the duration of the last closed interval terminated by the end of the depolarization, leading to an increased number of openings at the depolarized voltage. Analysis of single channel data indicates that at a depolarized voltage a single rate constant for entry into a slow-inactivated state is reduced in high [Na+]0, suggesting that the binding of an alkali metal cation, perhaps in the ion-conducting pore, inhibits the closing of the slow inactivation gate.


[Anatomical study of the lumbar multifidus muscle and its innervation in human adults and fetuses].
The lumbar multifidus muscle was dissected with particular reference to its innervation in 10 Japanese adults and 10 fetuses from 5 to 10 months old. The results were as follows: 1) The multifidus muscle attached to the spinous process of a lumbar vertebra was segmentally innervated by the medial branch of the dorsal ramus of the lumbar nerve on a level with the spinous process. 2) The motor point of the nerve innervating the multifidus muscle in adults was slightly ventro-caudal to that portion of the lumbar spinous process with muscle attached. 3) The multifidus muscle in fetuses was thinner and flatter than that in adults. The motor point of the nerve innervating this muscle was slightly caudal at the lateral margin of the muscle to that portion of the lumbar spinous process with the muscle attached. These differences can be attributed to the fact that muscles used to oppose gravity are undeveloped in fetuses. 4) There was variation in 5 fascicles in total, in which the medial branch of the dorsal ramus of a lumbar nerve entered the multifidus muscle originating at the spinous process of a lower lumbar vertebra.


Normal proximal and delayed distal conduction in the pudendal nerves of patients with idiopathic (neurogenic) faecal incontinence.
The latency of the response in the external anal sphincter muscle following transcutaneous stimulation of the cauda equina at the L1 vertebral level was measured in nine women with neurogenic faecal incontinence (mean 7.3 SD 0.7 ms) and 11 normal subjects (mean 5.6 SD 0.6 ms) (p = 0.01). There was no difference in conduction velocity between the L1 and L4 vertebral levels thus supporting the suggestion that conduction delay in faecal incontinence occurs distally.


Enhanced production of 6-aminopenicillanic acid in aqueous methyl isobutyl ketone system with immobilized penicillin G acylase.
Enzymatic hydrolysis of penicillin G for production of 6-amino-penicillanic-acid (6-APA) was achieved by using penicillin G acylase as catalyst in an aqueous-methylisobutyl ketone (MIBK) system. The optimization was carried out and it was found that the best conversion was improved 10% more than the aqueous system, which was obtained at the conditions: initial pH 8.0, 5.0% (W/V) substrate (penicillin G), and temperature at 35 degrees C, and the ratio of aqueous and organic phase was 3:1. The stability of the biocatalyst was studied at the operational conditions. After 5 cycles of semi-batch reactions, the residual activity of penicillin G acylase was 69.2% of the initial activity. There was no apparent loss of the yield of product. This process has a potential application in the industrial scale production of 6-APA because it simplifies the process effectively.


Proconvulsant potential of cyproheptadine in experimental animal models.
In epileptic patients cyproheptadine is frequently prescribed as an appetite stimulant for the treatment of anorexia associated with anti-epileptic drugs and for the management of 'serotonin syndrome' in depressed epileptic patients. However, the study of serotonergic and histaminergic pathway shows that the decreased neurotransmission of serotonin and histamine in the brain reduces seizures threshold. Since, cyproheptadine interferes with these pathways via antagonizing subtypes of 5-HT(1/2) receptors and H(1) receptor, therefore the present study was undertaken to investigate its effect on seizures threshold, so as to substantiate its use in epileptics. In the present study convulsions were induced in mice by, maximum electroshock (MES), picrotoxin, and pentylenetetrazol (PTZ). Cyproheptadine (4 mg/kg, i.p.) was administered per se and along with clinically used anti-epileptic drugs (phenytoin 25 mg/kg, i.p. and diazepam 5 mg/kg, i.p.) in different groups of mice, onset and extent of convulsions in these groups were compared with that of vehicle control and anti-epileptics per se treated groups. Percentage mortality in all groups was also determined. Results depicted a significant increase in duration of tonic hind limb extension in MES and decrease in latency to clonic convulsions induced by PTZ and picrotoxin in cyproheptadine treated groups (per se and along with anti-epileptics), as compared to vehicle control and anti-epileptics per se treated groups respectively. Percentage mortality was also increased with cyproheptadine treatment. Therefore it is concluded that cyproheptadine pretreatment reduces threshold, increases severity of seizures and decreases the efficacy of clinically used anti-epileptic drugs in experimental animal models of convulsions.


The Impact of Mixed Dentition Malocclusion on the Oral Health-Related Quality of Life for Children and Their Families: A Case-Control Study.
Objective: The aim of this study was to investigate the relation between malocclusion in mixed dentition and its impact on the oral health-related quality of life OHRQoL of children and their families as well to determine if there were any reported differences in OHRQoL due to malocclusion severity. Study design: A total of 144 subjects, which included 70 children (aged 8-10 years) and their parents, were recruited on the basis of predetermined criteria and divided into the following groups: children with malocclusion (case group) and children without malocclusion (control group). The OHRQoL was assessed using the Child Perceptions Questionnaire (CPQ8-10) and the Family Impact Scale (FIS). The severity of malocclusion was assessed using the Dental Aesthetic Index. The specific types of malocclusions (anterior open bite, anterior/ posterior crossbite and overjet) and their severity were considered for the statistical analyses by applying the Mann-Whitney and Kruskal-Wallis tests, respectively, with a set at p<0.05. Results: The CPQ8-10 and FIS scores demonstrated higher impact on OHRQoL in the case group (p<0.01). There were no reported differences in OHRQoL according to the dental aesthetic index severity (p>0.05) and no differences between specific types of malocclusion (p>0.05) Conclusions: Mixed dentition malocclusion impacted the oral-health quality of life for children and their families independently of the severity.


Loss of phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (Pip5k1c) in mesenchymal stem cells leads to osteopenia by impairing bone remodeling.
Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (Pip5k1c) is a lipid kinase that plays a pivotal role in the regulation of receptor-mediated calcium signaling in multiple tissues; however, its role in the skeleton is not clear. Here, we show that while deleting Pip5k1c expression in the mesenchymal stem cells using Prx1-Cre transgenic mice does not impair the intramembranous and endochondral ossification during skeletal development, it does cause osteopenia in adult mice, but not rapidly growing young mice. We found Pip5k1c loss dramatically decreases osteoblast formation and osteoid and mineral deposition, leading to reduced bone formation. Furthermore, Pip5k1c loss inhibits osteoblastic, but promotes adipogenic, differentiation of bone marrow stromal cells. Pip5k1c deficiency also impairs cytoplasmic calcium influx and inactivates the calcium/calmodulin-dependent protein kinase, which regulates levels of transcription factor Runx2 by modulating its stability and subsequent osteoblast and bone formation. In addition, Pip5k1c loss reduces levels of the receptor activator of nuclear factor-κB ligand, but not that of osteoprotegerin, its decoy receptor, in osteoblasts in bone and in sera. Finally, we found Pip5k1c loss impairs the ability of bone marrow stromal cells to support osteoclast formation of bone marrow monocytes and reduces the osteoclast precursor population in bone marrow, resulting in reduced osteoclast formation and bone resorption. We conclude Pip5k1c deficiency causes a low-turnover osteopenia in mice, with impairment of bone formation being greater than that of bone resorption. Collectively, we uncover a novel function and mechanism of Pip5k1c in the control of bone mass and identify a potential therapeutic target for osteoporosis.


Methanosarcina acetivorans contains a functional ISC system for iron-sulfur cluster biogenesis.
The production of methane by methanogens is dependent on numerous iron-sulfur (Fe-S) cluster proteins; yet, the machinery involved in Fe-S cluster biogenesis in methanogens remains largely unknown. Methanogen genomes encode uncharacterized homologs of the core components of the ISC (IscS and IscU) and SUF (SufBC) Fe-S cluster biogenesis systems found in bacteria and eukaryotes. Methanosarcina acetivorans contains three iscSU and two sufCB gene clusters. Here, we report genetic and biochemical characterization of M. acetivorans iscSU2. Purified IscS2 exhibited pyridoxal 5'- phosphate-dependent release of sulfur from L-cysteine. Incubation of purified IscU2 with IscS2, cysteine, and iron (Fe2+) resulted in the formation of [4Fe-4S] clusters in IscU2. IscU2 transferred a [4Fe-4S] cluster to purified M. acetivorans apo-aconitase. IscU2 also restored the aconitase activity in air-exposed M. acetivorans cell lysate. These biochemical results demonstrate that IscS2 is a cysteine desulfurase and that IscU2 is a Fe-S cluster scaffold. M. acetivorans strain DJL60 deleted of iscSU2 was generated to ascertain the in vivo importance of IscSU2. Strain DJL60 had Fe-S cluster content and growth similar to the parent strain but lower cysteine desulfurase activity. Strain DJL60 also had lower intracellular persulfide content compared to the parent strain when cysteine was an exogenous sulfur source, linking IscSU2 to sulfur metabolism. This study establishes that M. acetivorans contains functional IscS and IscU, the core components of the ISC Fe-S cluster biogenesis system and provides the first evidence that ISC operates in methanogens.


Ten key considerations for the successful optimization of large-scale health information technology.
Implementation and adoption of complex health information technology (HIT) is gaining momentum internationally. This is underpinned by the drive to improve the safety, quality, and efficiency of care. Although most of the benefits associated with HIT will only be realized through optimization of these systems, relatively few health care organizations currently have the expertise or experience needed to undertake this. It is extremely important to have systems working before embarking on HIT optimization, which, much like implementation, is an ongoing, difficult, and often expensive process. We discuss some key organization-level activities that are important in optimizing large-scale HIT systems. These include considerations relating to leadership, strategy, vision, and continuous cycles of improvement. Although these alone are not sufficient to fully optimize complex HIT, they provide a starting point for conceptualizing this important area.


Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers.
The importance of prostaglandin E(2) in various pathophysiological events emphasizes the necessity of understanding the role of PGE synthases (PGESs) in vivo. However, there has been no report on the functional relevance of microsomal PGES-1 (mPGES-1) to the physiological healing processes of gastric ulcers, or to angiogenesis, which is indispensable to the healing processes. In this report, we tested whether mPGES-1 plays a role in the healing of gastric ulcers and in the enhancement of angiogenesis using mPGES-1 knockout mice (mPGES-1 KO mice) and their wild-type (WT) counterparts. Gastric ulcers were induced by the serosal application of 100% acetic acid, and the areas of the ulcers were measured thereafter. mPGES-1 together with cyclooxygenase-2 were induced in the granulation tissues compared with normal stomach tissues. The healing of acetic acid-induced ulcers was significantly delayed in mPGES-1 KO mice compared with WT. This was accompanied with reduced angiogenesis in ulcer granulation tissues, as estimated by CD31 mRNA levels determined by real-time PCR and the microvessel density in granulation tissues. The mRNA levels of proangiogenic growth factors, such as transforming growth factor-β, basic fibroblast growth factor, and connective tissue growth factor in ulcer granulation tissues determined were reduced in mPGES-1 KO mice compared with WT. The present results suggest that mPGES-1 enhances the ulcer-healing processes and the angiogenesis indispensable to ulcer healing, and that a selective mPGES-1 inhibitor should be used with care in patients with gastric ulcers.


Maternal and neonatal complications in term breech delivered vaginally.
To evaluate the maternal and neonatal complications in terms of genital tract trauma to mother, perinatal mortality, Apgar score at 5 minutes and neonatal trauma in all singleton term breech cases delivered vaginally. Case series. Department of Obstetrics and Gynaecology, Bolan Medical Complex Hospital, Quetta, from May 2005 to March 2006. A 100 consecutive patients with singleton breech presentation, whether booked or unbooked, were admitted and delivered vaginally in hospital during the study period. They were studied for maternal and neonatal complications. Maternal complication included any genital tract trauma during delivery while neonatal complications were perinatal mortality, low Apgar score (less than eight at 5 minutes) and birth trauma. There were a total 3977 deliveries during this study period, 145 breech presentation (incidence 3.6%). Out of those, 100 were included in the study. All were unbooked cases, 87% were multigravida while 13% were primigravida. An Apgar score of eight was recorded in 87% babies while 10% had an Apgar score of less than eight after 5 minutes. There were 3 still births and one neonatal death. Aggregated perinatal mortality rate was 40/1000 live births. Only one baby had birth trauma (Erb's paralysis) during vaginal breech delivery. Ninety seven (97%) mothers had no complications while only 3 (3%) had complications. Out of these, one had cervical tear and 2 had vaginal tears. Offering a trial of vaginal breech delivery to strictly selected and well-counselled patients remains an appropriate option without compromising perinatal and maternal outcome. It also decreases the rate of operative delivery for this malpresentation.


Cornification (keratinization) in Basal cell carcinoma: a histopathological and immunohistochemical study of 16 cases.
The concept of keratotic BCC is obscure and not well-defined. To elucidate the histopathological and immunohistochemical properties of cornification in BCC and to clarify the concept of keratotic BCC, by careful examination of 600 BCC specimens, we selected 16 cases of BCC that showed cornification. We investigated the precise histopathological features of these 16 cases, and studied the immunohistochemical expression patterns of anticytokeratin (CK) antibodies (CKs 1, 10, 13, 14, 17) and other antibodies in these cornifying (keratotic) BCCs. We compared these data to those from normal adult hair follicles and three types of cornifying cysts (epidermal cyst, tricholemmal cyst and steatocystoma). Six types of cornification were observed in these BCCs; 1) infundibular type (4 cases) with thin laminated corneocytes expressing CKs 1 and 10, 2) tricholemmal (isthmus) type (9 cases) showing compact, homogenous cornified contents with CK 17 expression on the surrounding cells, 3) inner root sheath type (1 case) characterized by compact, blue-gray corneocytes lined by CK 13 positive-squamous cells with red trichohyalin granules, 4) sebaceous duct type (1 case) characterized by crenulated cornified cells expressing CK 17, 5) apocrine acrosyringium type (2 cases) characterized by small duct-like structures lined by eosinophilic cuticle expressing CEA, in association with keratohyaline granules, and 6) cornifying microcyst type (10 cases) characterized by micro and small cystic structures containing the debris of cornified cells, which was associated with the infundibular or tricholemmal type and could be classified as having the primitive features of the tricholemmal type of cornification. The tricholemmal type could be subdivided into two groups: one with keratohyaline granules and the other without keratohyaline granules, and the cornified contents in approximately 30% of the cornified areas in this type were positive for CK 17. The matrical type of cornification (seventh type) was not seen in our study. The examples described as "keratotic BCC" thus far were similar to BCCs with cornification of the tricholemmal (isthmus) or infundibular type. The cornification in BCCs could be classified into seven types. Excluding the cornifying microcyst type, the tricholemmal type is the most common type of cornification. This type will be abnormal and incomplete in attempts to cornify in the form of an isthmus, occasionally with concomitant exhibition of lower infundibular differentiation. The keratotic BCC is considered to be BCC with cornification of the tricholemmal (isthmus) or infundibular type.


EFFECT OF WORKING CONDITIONS AND NATURAL RADIOACTIVITY LEVELS ON OCCUPATIONAL DOSES TO WORKERS OF AN OLD MANGANESE MINE.
The aim of this work was to use RESRAD-Build model to predict the resulting external and internal radiological doses received by the workers of manganese mine located in Southern Sinai. In order to achieve that goal, measurement of the activity concentrations of natural radionuclides in rock samples collected from the inside gallery of such mine, using hyper pure germanium (HPGe) detector. Radon gas concentrations were also measured. The average activity concentrations of 238U, 226Ra, 232Th, 40K and 210Pb in rock samples were 207.3, 155.5, 59.7, 304.5 and 119.3 Bq kg-1, respectively. The average radon activity concentration was 1254.6 Bqm-3, which is equivalent to 0.135 WL. The radon concentration increases further as going deep inside the mine up to 6238 Bqm-3. RESRAD-Build model occupational effective dose equivalent (EDE) received by the workers, from natural radionuclides, dominated by 222Rn emanated from the parent nuclide 226Ra.There was good agreement between the occupational annual EDE calculated from the measured rock samples and that predicted by modeling, with estimated values of 83.8 and 82.1 mSvy-1, respectively. This radiological dose assessment indicated the predominance of internal pathways owing to radon decay products, in both cases (measured and modeled). The occupational radiological dose from the inhalation of radon and radon decay products resulted in a high lung cancer risk based on the current measurements and ventilation conditions within the mine.


Emerging Treatment Options of Regenerative Medicine in Severe Corona Virus/COVID 19 Infections.
COVID-19 pandemic has brought the whole world stand still, locked down in their homes, infecting more than 8 million people, and many thousands (449,182) -have lost their lives across the globe. Due to lack of any definitive medicine or vaccine, treatment options are supportive of oxygenation, antiviral, antiretroviral drugs, antibiotics, fluid/ electrolyte, mechanical ventilation with ICU (Intensive Care Unit) support, and chloroquine/hydroxychloroquine have been tried to fight this infection. However, mortality due to severe pneumonia, ARDS (Acute Respiratory Distress Syndrome), and multiorgan failure arising from the overactive immune response (storm) mediated by cytokines remains a treatment challenge in elderly and patients with severe medical comorbidities. Recently, anti-inflammatory, angiogenic, immune-modular, and healing properties of intravenous injections of culture derived stem cells have been proposed and shown to benefits in a small number of patients with severe COVID-19 infections. Based on previous experience with other viral infections, convalescent plasma, and serum transfusion are being used as a source of neutralizing antibody/factors to minimize the effects of inflammatory cytokines in this infection. Immunotherapy with purified monoclonal antibodies and conditioned serum with a mixture of unique cytokines are also being developed. Regenerative Medicine has emerged as a crucial adjuvant tool in promoting healing and early recovery in severe COVID-19 infections and other supportive treatments.


The Persian version of the Youth Psychopathic Traits Inventory-Short Version (YPI-S): A psychometric evaluation.
Studies on the psychopathy construct are mostly limited to Western cultures, and there is a lack of research in this area in non-Western countries, specifically in Iran. The present study aimed to examine the factor structure, internal consistency, and convergent validity of the Persian version of the Youth Psychopathic Traits Inventory-Short Version (YPI-S) with a sample of 668 school-attending adolescents in Iran (46% girls; Mage = 16.35). Confirmatory factor analysis supported the proposed three-factor model. While the internal consistency of some YPI-S scores was unsatisfactory, the YPI-S scores showed the expected relations with external correlates (e.g., aggression, hyperactivity), supporting the validity of YPI-S scores. The authors' results supported the YPI-S for assessing psychopathic traits in Iranian adolescents. The modification of the YPI-S factor structure, the low factor loadings of some YPI-S items, and the inadequate internal consistency of some YPI-S dimensions indicate cultural influences on the assessment of cross-cultural traits.


Endothelin modulates L-NG-nitroarginine-induced enhancement of vasoconstriction evoked by norepinephrine.
The interaction of endothelin-1 (ET-1), a novel vasoconstrictor peptide synthesized according to the encoded amino acid sequence, with L-NG-nitroarginine (NOARG), an L-arginine-reversible inhibitor of endothelium-derived relaxing factor (EDRF) on adrenergic receptors, was investigated. Male Sprague-Dawley rats were used in this study. Mesenteric arteries were isolated and perfused with Krebs-Ringer solution at a constant flow rate. The vasoconstrictor responses to exogenous norepinephrine were determined. Low concentrations of ET-1 (10(-11) and 10(-10) M) potentiated the pressor responses to norepinephrine without affecting the baseline perfusion pressure. Simultaneous NOARG (10(-5) M) infusion with ET-1 (10(-11) M) into the mesenteric arteries caused further enhancement of the pressor responses to exogenous norepinephrine (200 ng) without affecting the baseline perfusion pressure: 126 +/- 15% to 262 +/- 45% (p less than 0.05, vehicle control: 100%). This facilitatory effect of NOARG on the pressor response to norepinephrine was attenuated with L-arginine (10(-4) M) infusion, but not D-arginine. These results suggest that ET, one of the endothelium-derived vasoconstricting factors, interacts with EDRF to modulate the tone of resistance vessels.


Mosaic gene expression in nuclear transfer-derived embryos and the production of cloned transgenic pigs from ear-derived fibroblasts.
Genetically modified domestic animals have many potential applications ranging from basic research to production agriculture. One of the goals in transgenic animal production schemes is to reliably predict the expression pattern of the foreign gene. Establishing a method to screen genetically modified embryos for transgene expression before transfer to surrogates may improve the likelihood of producing offspring with the desired expression pattern. In order to determine how transgene expression may be regulated in the early embryo, we generated porcine embryos from two distinct genetically modified cell lines by using the nuclear transfer (NT) technique. Both cell lines expressed the enhanced green fluorescent protein (eGFP); the first was a fibroblast cell line derived from the skin of a newborn pig that expressed eGFP, whereas the second was a fetal derived fibroblast cell line into which the eGFP gene was introduced by a retroviral vector. The reconstructed embryos were activated by electrical pulses and cultured in NCSU23. Although the in vitro developmental ability of each group of NT embryos was not different, the eGFP expression pattern was different. All embryos produced from the transduced fetal cell line fluoresced, but only 26% of the embryos generated from the newborn cell line fluoresced, and among those that did express eGFP, more than half had a mosaic expression pattern. This was unexpected because the fetal cell line was not clonally selected, and each cell had potentially different sites of integration. Embryos generated from the newborn cell line were surgically transferred to five surrogate gilts. One gilt delivered four female piglets, all of which expressed eGFP, and all had microsatellites identical to the donor. Here we demonstrate that transgene expression in all the blastomeres of an NT embryo is not uniform. In addition, transgene expression in a genetically manipulated embryo may not be an accurate indicator of expression in the resulting offspring.


Nutritional supplement chromium picolinate generates chromosomal aberrations and impedes progeny development in Drosophila melanogaster.
Chromium picolinate, [Cr(pic)(3)], is a popular nutritional supplement found in a variety of consumer products. Despite its popularity, safety concerns over its use have arisen. The supplement has been shown to generate clastogenic damage, mitochondrial damage, oxidative damage, and mutagenic effects in cultured cells and oxidative DNA damage and lipid peroxidation in rats. Recently [Cr(pic)(3)] has been demonstrated to generate heritable genetic change and delays in progeny development in Drosophila melanogaster. Based on the damage to chromosomes of cultured cells and of animal models, similar chromosome damage appeared to be a likely source of the mutagenic effects of the supplement in Drosophila. The current three-part study examines the effects of several chromium-containing supplements and their components on hatching and eclosion rates and success of development of first generation progeny of adult Drosophila fed food containing these compounds. It further examines the effects of the compounds on longevity of virgin male and female adults. Finally, the chromosomes in the salivary glands of Drosophila late in the third instar larval stage, which were the progeny of Drosophila whose diets were supplemented with nutritional levels of [Cr(pic)(3)], are shown to contain on average over one chromosomal aberration per two identifiable chromosomal arms. No aberrations were observed in chromosomes of progeny of untreated flies. The results suggest that human consumption of the supplement should be a matter of concern and continued investigation to provide insight into the requirements of chromium-containing supplements to give rise to genotoxic effects.


Solid state characterization of dehydroepiandrosterone.
Three polymorphs (forms I-III), a monohydrate (form S2), and three new solvates [4:1 hydrate (form S1), monohydrate (form S3), and methanol half-solvate (form S4)] were isolated and characterized by X-ray powder diffractometry (XRPD), IR spectroscopy, differential scanning calorimetry (DSC), hot stage microscopy, solution calorimetry, and their dissolution rates. A new polymorph, designated as form V, melting at 146.5-148 degrees C, was observed by hot stage microscopy. Our results indicate that only forms I and S4 exhibit reproducible DSC thermograms. Five of the isolated modifications undergo phase transformation on heating, and their DSC thermograms are not reproducible. Interpretation of DSC thermograms was facilitated by use of hot stage microscopy. The identification of each modification is based on XRPD patterns (except forms S3 and S4, for which the XRPD patterns are indistinguishable) and IR spectra. In the IR spectra, a significant difference was observed in the OH stretching region of all seven modifications. In a purity determination study, 5% of a contaminant modification in binary mixtures of several modifications could be detected by use of XRPD. To obtain a better understanding of the thermodynamic properties of these modifications, a series of increasing heating rates and different pan types were used in DSC. According to Burger's rule, forms I-III are monotropic polymorphs with decreasing stability in the order form I > form II > form III. The melting onsets and heats of fusion for forms I-III are 149.1 degrees C, 25.5 kJ/mol; 140.8 degrees C, 24.6 kJ/mol; and 137.8 degrees C, 24.0 kJ/mol, respectively. For form III the heat of fusion was calculated from heat of solution and DSC data. In the case of form S1 the melting point, 127.2 degrees C, was obtained by DSC using a hermetically sealed pan. The relative stabilities of the six modifications stored under high humidity conditions were predicted to be, on the basis of the heat of solution and thermal analysis data, from S2 > form S3 > form S1 > form I > form II > form III. However, the results of the dissolution rate determination were inconsistent with the heat of solution data. The stable form I shows a higher initial dissolution rate than the metastable form II and unstable form III. All modifications were converted into the stable monohydrate, form S2, during the dissolution study, suggesting that the moisture level in solid formulations should be carefully controlled.


Neuropsychological test performance in Aruaco Indians: an exploratory study.
A sample of 20 right-handed Aruaco Indians (12 male, 8 female; age 8-30 years) from the Sierra Nevada de Santa Marta (Colombia) participated in this study. A brief neuropsychological test battery (visuoconstructive and visuoperceptual abilities, memory, ideomotor praxis, verbal fluency, spatial abilities, concept formation) was individually administered. In addition, a handedness questionnaire was included. In some neuropsychological tests performance was virtually perfect (Recognition of Overlapped Figures and Ideomotor Praxis Ability test), whereas performance in other tests was impossible (e.g., Block Design using a time limit). It was proposed that two types of variables were significantly affecting performance: (1) educational level; and (2) cultural relevance. Some tests appeared significant and meaningful whereas others were meaningless and even impossible to understand. The appropriateness of current neuropsychological instruments for cross-cultural assessment is discussed.


Long Non-Coding RNA CD27-AS1-208 Facilitates Melanoma Progression by Activating STAT3 Pathway.
Melanoma is the most lethal skin cancer that originates from epidermal melanocytes. Recently, long non-coding RNAs (lncRNAs) are emerging as critical regulators of cancer pathogenesis and potential therapeutic targets. However, the expression profile of lncRNAs and their role in melanoma progression have not been thoroughly investigated. Herein, we firstly obtained the expression profile of lncRNAs in primary melanomas using microarray analysis and unveiled the differentially-expressed lncRNAs compared with nevus. Subsequently, a series of bioinformatics analysis showed the great involvement of dysregulated lncRNAs in melanoma biology and immune response. Further, we identified lncRNA CD27-AS1-208 as a novel nuclear-localized factor with prominent facilitative role in melanoma cell proliferation, invasion and migration. Mechanistically, CD27-AS1-208 could directly interact with STAT3 and contribute to melanoma progression in a STAT3-dependent manner. Ultimately, the role of CD27-AS1-208 in melanoma progression in vivo was also investigated. Collectively, the present study offers us a new horizon to better understand the role of lncRNAs in melanoma pathogenesis and demonstrates that CD27-AS1-208 up-regulation contributes to melanoma progression by activating STAT3 pathway. Targeting CD27-AS1-208 in melanoma cells can be exploited as a potential therapeutic approach that needs forward validation in clinical trials in the future.


Expression of nitric oxide synthase-2 in cutaneous squamous cell carcinoma of the head and neck.
Nitric oxide (NO) has a pivotal role in angiogenesis. The expression of NO synthase (NOS2) is down-regulated in basal cell skin cancer but we know of no studies that have investigated its expression in the more aggressive squamous cell skin carcinoma. This immunohistochemical study assessed NOS2 expression in 37 cases of head and neck squamous cell skin carcinoma. NOS2 expression was located in cells of the basal cell layer of epidermis, but was significantly increased in tumour epithelium. No correlations were found between NOS2 expression and tumour size or degree of tumour differentiation. The raised NO concentrations in these tumours may provide one explanation for their more aggressive behaviour than that of the slower-growing basal cell carcinoma.


Impact of prenatal screening and diagnosis on the epidemiology of structural congenital anomalies.
To assess the impact of prenatal screening on the birth prevalence of three categories of structural congenital anomaly: abdominal wall defects (omphalocele and gastroschisis), renal agenesis/dysgenesis, and limb reduction defects. Glasgow, Scotland, United Kingdom. Data on the selected defects were obtained retrospectively from the population based Glasgow Register of Congenital Anomalies for the period 1980-91 inclusive. The register records all clinical or laboratory diagnoses of congenital anomaly in live births, stillbirths, and induced abortions occurring in women resident within the boundaries of the Greater Glasgow Health Board. The secular trends in the proportions of the defects diagnosed prenatally and terminated after screening, and in their prevalence at birth and during pregnancy, were examined. A total of 154,845 births were surveyed: 309 cases were identified in the selected anomaly categories. 83 cases of omphalocele/gastroschisis (5.4/10,000 births), 92 cases of renal agenesis/dysgenesis (5.9/10,000 births), and 134 cases of limb reduction defects (8.7/10,000 births) were found. Marked increases occurred over the study period in the proportions of cases diagnosed prenatally but not in the proportions terminated. The greatest difference between the prevalence at birth and during pregnancy was found for omphalocele. There were no significant secular trends in the prevalence of the selected defects. Prenatal screening has made a limited epidemiological impact on the prevalence of these defects. It has been moderately (but inconsistently) effective in the avoidance of births of infants with omphalocele/gastroschisis and renal agenesis/dysgenesis but not of limb reduction defects. Future efforts should be directed towards improving the technical aspects of the ultrasonographic detection of fetal abnormalities and exploring in detail, locally, the reasons for the varying pattern of decision making about termination of pregnancy among prospective parents.


Hepatocyte nuclear factor-4 is responsible for the liver-specific expression of the gene coding for hepatocyte growth factor-like protein.
In an attempt to understand the molecular mechanism regulating the expression of the gene coding for human hepatocyte growth factor-like protein/macrophage stimulating protein (HGFL), our laboratory has isolated and characterized approximately 4200 bp of the 5'-flanking region of the HGFL gene. To determine the location of sites which may be critical for the function of the HGFL gene promoter, we constructed a series of hybrid genes containing serial deletions of this region attached to the coding sequences for chloramphenicol acetyltransferase. Expression of these chimeric plasmids was examined by transient transfection of HepG2 and 293 cells. Our results suggest that the transcriptional activity of the HGFL promoter is modulated in HepG2 cells by one positive element at position -135 to -105 (-135/-105). In contrast, only background levels of chloramphenicol acetyltransferase expression have been detected in 293 cells. The -135/-105 region appears to bind a liver-specific transcription factor essential for expression of this gene. Gel mobility shift experiments with antibodies against hepatocyte nuclear factor-4 (HNF-4) and transactivation of the HGFL promoter by a HNF-4 cDNA expression vector suggest that HNF-4 binds to the -135/-105 region and is responsible for the liver-specific expression of HGFL.


Behaviour of pesticides in a water/sediment system under laboratory and field conditions.
Experiments were conducted in order to evaluate the behaviour of some pesticides commonly used in rice production. At a laboratory scale, but exposed to the environmental conditions, a known concentration of pesticides in water flowed through a cement channel over a sediment layer, at a constant flow rate. The collected water was homogenised and analysed by gas chromatography/HPLC to assess the concentration of each pesticide. Under these conditions, the reduction of each pestcide concentration in water depends on the nature of it and on the water flow rate. The lower the flow rate, the grater the reduction in the concentration of pesticides in the water that ran over the sediment layer. Experiments were also carried out under field conditions, using a 1200 m length, 2 m width and 0.3 m depth rice field channel. A pesticide mixture of known concentration was poured on the flowing water and mixed thoroughly. After the arrival of this contaminated water at preestablished sampling points down the stream, the concentration of each pesticide in water was determined. The longer the distance of the sampling points downstream from the starting point, the lower the pesticide concentration found. Only a few pesticides were detected at the 1200 m sampling point, but at very low concentration. The others were not detected. It was pointed out that the channel length was the most important factor in the reduction of the pesticide concentration in the flowing water. The influence of the flow rate on this reduction could not be clearly related as in the laboratory experiments.


Patterns of Substitution Rate Variation at Many Nuclear Loci in Two Species Trios in the Brassicaceae Partitioned with ANOVA.
There are marked variations among loci and among lineages in rates of nucleotide substitution. The generation time hypothesis (GTH) is a neutral explanation for substitution rate heterogeneity that has genomewide application, predicting that species with shorter generation times accumulate DNA sequence substitutions faster than species with longer generation times do since faster genome replication provides more opportunities for mutations to occur and reach fixation by genetic drift. Relatively few studies have rigorously evaluated the GTH in plants, and there are numerous alternative hypotheses for plant substitution rate variation. One major challenge has been finding pairs of closely related plant species with contrasting generation times and appropriate outgroup taxa that all also have DNA sequence data for numerous loci. To test for causes of rate variation, we obtained sequence data for 256 genes for Arabidopsis thaliana, normally reproducing every year, and the biennial Arabidopsis lyrata with three closely related outgroup taxa (Brassica rapa, Capsella grandiflora, and Neslia paniculata) as well as the biennial Brassica oleracea and the annual B. rapa lineage with the outgroup N. paniculata. A sign test indicated that more loci than expected by chance have faster rates of substitution on the branch leading to the annual than to the perennial for one three-species trio but not another. Tajima's 1D and 2D tests, and a likelihood ratio test that incorporated saturation correction, rejected rate homogeneity for up to 26 genes (up to 14 genes when correcting for multiple tests), consistently showing faster rates for the annual lineage in the Arabidopsis species trio. ANOVA showed significant rate heterogeneity between the Arabidopsis and Brassica species trios (about 6 % of rate variation) and among loci (about 26-32 % of rate variation). The lineage-by-locus interaction which would be caused by locus- and lineage-specific natural selection explained about 13 % of substitution rate variation in one ANOVA model using substitution rates from genes partitioned into odd and even codons but was not a significant effect without partitioned genes. Annual/perennial lineage and species trio by annual/perennial lineage each explained about 1 % of substitution rate variation.


Advances in the management of gout and hyperuricaemia.
An acute attack of gouty arthritis is one of the most painful experiences reported throughout medical history. Therefore it is paramount to initiate appropriate therapy quickly in order to terminate the acute phase. This goal can be achieved with non-steroidal anti-inflammatory agents, colchicine, or corticosteroid-based therapies. Rarely, because of contraindications to these agents, only symptomatic treatment can be given until the attack subsides. The next step is to lower the serum urate level below the limit of solubility (i.e., below 40.8 mmol/L, or 6.8mg/dL) which reduces recurrences and begins to return the total body urate pool to normal. This equally important goal can be achieved by uricosuric agents or xanthine oxidase inhibitors, although the latter is generally favored. Allopurinol is the agent most commonly preferred because of its safety profile and ease of use, but there are known serious allergic reactions and untoward side effects that occasionally require discontinuation. Febuxostat, a xanthine oxidase inhibitor, and pegylated uricase are new agents under development and may be beneficial in these situations or when other comorbid conditions prevent the use of conventional treatments. Alcohol and dietary consumption are also related to hyperuricemia and acute gout. Recently beer, wine, and liquor were studied and the risk of gout varied according to the alcohol ingested. Furthermore, recent data sheds light on important dietary modifications that may help in the treatment of gout, and dispels certain beliefs about protein ingestion and the occurrence of acute gout. As we learn more about the associated conditions of hypertriglyceridemia, hypertension, and the metabolic syndrome, it may allow the tailoring of medical regimens that directly prevent or reduce recurrent attacks of gouty arthritis. There are specific approved treatments for these common comorbidities that have parallel effects of lowering serum urate levels. These recent findings may be especially important for treating refractory cases. While patient education remains a cornerstone to ensure compliance, other quality indicators for the management of this disease have been reported and should guide the clinician in the treatment of gout and result in improved care.


A systematic drug repurposing approach to identify promising inhibitors from FDA-approved drugs against Nsp4 protein of SARS-CoV-2.
COVID-19 is caused by SARS-CoV-2 and responsible for the ongoing global pandemic in the world. After more than a year, we are still in lurch to combat and control the situation. Therefore, new therapeutic options to control the ongoing COVID-19 are urgently in need. In our study, we found that nonstructural protein 4 (Nsp4) of SARS-CoV-2 could be a potential target for drug repurposing. Due to availability of only the crystal structure of C-terminal domain of Nsp4 (Ct-Nsp4) and its crucial participation in viral RNA synthesis, we have chosen Ct-Nsp4 as a target for screening the 1600 FDA-approved drugs using molecular docking. Top 102 drugs were found to have the binding energy equal or less than -7.0 kcal/mol. Eribulin and Suvorexant were identified as the two most promising drug molecules based on the docking score. The dynamics of Ct-Nsp4-drug binding was monitored using 100 ns molecular dynamics simulations. From binding free energy calculation over the simulation, both the drugs were found to have considerable binding energy. The present study has identified Eribulin and Suvorexant as promising drug candidates. This finding will be helpful to accelerate the drug discovery process against COVID-19 disease.Communicated by Ramaswamy H. Sarma.


Perceptuomotor functioning in preschool children with symptoms of attention deficit hyperactivity disorder.
Given limited research on perceptual-motor functioning of preschool children with symptoms of ADHD, the purpose of this study was to compare the fine motor, gross motor, visuomotor, and oral-motor functioning of 49 4- to 6-yr.-old children with symptoms of Attention Deficit Hyperactivity Disorder and 48 typically developing children. Analysis showed scores of the ADHD group were significantly lower than those of the control group on all perceptuomotor measures. In addition, scores on all measures yielded significant correlations with scores on the Hyperactive-Inattentive scale of the Preschool Behavior Questionnaire. Regression analyses indicated that the scores of gross motor and visuomotor functioning were significant predictors of group classification (with and without ADHD). These findings extend the well documented findings of perceptuomotor deficits among school-age children with ADHD into the preschool period and emphasize the importance of early assessment and treatment of these deficits in young children with symptoms of ADHD.


Low temperature-induced viable but not culturable state of Ralstonia eutropha and its relationship to accumulated polyhydroxybutyrate.
The culturability of Escherichia coli, Ralstonia eutropha and Bacillus subtilis after incubation in phosphate-buffered saline at either 5°C or 30°C was determined. The culturability of B. subtilis showed little dependence on temperature. The culturability of E. coli rapidly decreased at 30°C but remained almost constant at 5°C. In contrast, the culturability of R. eutropha decreased by three orders of magnitude at 5°C within 24 h but only moderately decreased (one order of magnitude) at 30°C. Remarkably, prolonged incubation of R. eutropha at 30°C resulted in a full recovery of colony forming units in contrast to only a partial recovery at 5°C. Ralstonia eutropha cells at 30°C remained culturable for 3 weeks while culturability at 5°C constantly decreased. The effect of temperature was significantly stronger in a polyhydroxybutyrate-negative mutant. Our data show that accumulated polyhydroxybutyrate has a cold-protective function and can prevent R. eutropha entering the viable but not culturable state.


Oral administration of n-3 fatty acids positively affect the mucosal lesions after experimental ischemic enteritis in the rat.
The purpose of the study was to evaluate the effect of oral administration of n-3 polyunsaturated fatty acids in experimental ischemic enteritis in rats. Forty Wistar rats were submitted to control narrowing of the superior mesenteric artery and were divided in two groups: N3 polyunsaturated fatty acids, which received a high-molecular polymer solution of artificial total enteral nutrition enriched with n-3 fatty acids and CONTROL which received a high-molecular polymer solution of artificial total enteral nutrition. Reduction of the animals' body weight was observed in both groups, but there was no difference between the two groups. Regarding the level of cytokines interleukin (IL)-1b, IL-6, and tumor necrosis factor a (TNF-a) there was no statistically significant difference between the two groups. Ischemic lesions to the small bowel mucosa were observed in both groups. A statistically significant difference in the extent of intestinal lesions was observed between the two groups with the animals that received enteral nutrition enriched with n-3 fatty acid developing fewer lesions. Enteral nutrition enriched with n-3 polyunsaturated fatty acids reduces the mucosal lesions caused by mesenteric ischemia compared to standard enteral nutrition, by modifying the local, but not the systemic, immune, and inflammatory response.


Clustering Field-Based Maize Phenotyping of Plant-Height Growth and Canopy Spectral Dynamics Using a UAV Remote-Sensing Approach.
Phenotyping under field environmental conditions is often considered as a bottleneck in crop breeding. Unmanned aerial vehicle high throughput phenotypic platform (UAV-HTPP) mounted with multi-sensors offers an efficiency, non-invasive, flexible and low-cost solution in large-scale breeding programs compared to ground investigation, especially where measurements are time-sensitive. This study was conducted at the research station of the Xiao Tangshan National Precision Agriculture Research Center of China. Using the UAV-HTPP, RGB and multispectral images were acquired during four critical growth stages of maize. We present a method of extracting plant height (PH) at the plot scale using UAV-HTPP based on the spatial structure of the maize canopy. The core steps of this method are segmentation and spatial Kriging interpolation based on multiple neighboring maximum pixels from multiple plants in a plot. Then, the relationships between the PH extracted from imagery collected using UAV-HTPP and the ground truth were examined. We developed a semi-automated pipeline for extracting, analyzing and evaluating multiple phenotypic traits: canopy cover (CC), normalized vegetation index (NDVI), PH, average growth rate of plant height (AGRPH), and contribution rate of plant height (CRPH). For these traits, we identify genotypic differences and analyze and evaluate dynamics and development trends during different maize growth stages. Furthermore, we introduce a time series data clustering analysis method into breeding programs as a tool to obtain a novel representative trait: typical curve. We classified and named nine types of typical curves of these traits based on curve morphological features. We found that typical curves can detect differences in the genetic background of traits. For the best results, the recognition rate of an NDVI typical curve is 59%, far less than the 82.3% of the CRPH typical curve. Our study provides evidence that the PH trait is among the most heritable and the NDVI trait is among the most easily affected by the external environment in maize.