Many-body calculations of low-energy eigenstates in magnetic and periodic systems with self-healing diffusion Monte Carlo: steps beyond the fixed phase.
The self-healing diffusion Monte Carlo algorithm (SHDMC) [F. A. Reboredo, R. Q. Hood, and P. R. C. Kent, Phys. Rev. B 79, 195117 (2009); F. A. Reboredo, ibid. 80, 125110 (2009)] is extended to study the ground and excited states of magnetic and periodic systems. The method converges to exact eigenstates as the statistical data collected increase if the wave function is sufficiently flexible. It is shown that the dimensionality of the nodal surface is dependent on whether phase is a scalar function or not. A recursive optimization algorithm is derived from the time evolution of the mixed probability density, which is given by an ensemble of electronic configurations (walkers) with complex weight. This complex weight allows the phase of the fixed-node wave function to move away from the trial wave function phase. This novel approach is both a generalization of SHDMC and the fixed-phase approximation [G. Ortiz, D. M. Ceperley, and R. M. Martin, Phys Rev. Lett. 71, 2777 (1993)]. When used recursively it simultaneously improves the node and the phase. The algorithm is demonstrated to converge to nearly exact solutions of model systems with periodic boundary conditions or applied magnetic fields. The computational cost is proportional to the number of independent degrees of freedom of the phase. The method is applied to obtain low-energy excitations of Hamiltonians with magnetic field. Periodic boundary conditions are also considered optimizing wave functions with twisted boundary conditions which are included in a many-body Bloch phase. The potential applications of this new method to study periodic, magnetic, and complex Hamiltonians are discussed.


Reliability of dose volume constraint inference from clinical data.
Dose volume histogram points (DVHPs) frequently serve as dose constraints in radiotherapy treatment planning. An experiment was designed to investigate the reliability of DVHP inference from clinical data for multiple cohort sizes and complication incidence rates. The experimental background was radiation pneumonitis in non-small cell lung cancer and the DVHP inference method was based on logistic regression. From 102 NSCLC real-life dose distributions and a postulated DVHP model, an 'ideal' cohort was generated where the most predictive model was equal to the postulated model. A bootstrap and a Cohort Replication Monte Carlo (CoRepMC) approach were applied to create 1000 equally sized populations each. The cohorts were then analyzed to establish inference frequency distributions. This was applied to nine scenarios for cohort sizes of 102 (1), 500 (2) to 2000 (3) patients (by sampling with replacement) and three postulated DVHP models. The Bootstrap was repeated for a 'non-ideal' cohort, where the most predictive model did not coincide with the postulated model. The Bootstrap produced chaotic results for all models of cohort size 1 for both the ideal and non-ideal cohorts. For cohort size 2 and 3, the distributions for all populations were more concentrated around the postulated DVHP. For the CoRepMC, the inference frequency increased with cohort size and incidence rate. Correct inference rates >[Formula: see text] were only achieved by cohorts with more than 500 patients. Both Bootstrap and CoRepMC indicate that inference of the correct or approximate DVHP for typical cohort sizes is highly uncertain. CoRepMC results were less spurious than Bootstrap results, demonstrating the large influence that randomness in dose-response has on the statistical analysis.


Enhancing computer self-efficacy and attitudes in multi-ethnic older adults: a randomised controlled study.
Several studies have documented the health-related benefits of older adults' use of computer technology, but before they can be realised, older individuals must be positively inclined and confident in their ability to engage in computer-based environments. To facilitate the assessment of computer technology attitudes, one aim of the longitudinal study reported in this paper was to test and refine a new 22-item measure of computer technology attitudes designed specifically for older adults, as none such were available. Another aim was to replicate, on a much larger scale, the successful findings of a preliminary study that tested a computer technology training programme for older adults (Laganà 2008). Ninety-six older men and women, mainly from non-European-American backgrounds, were randomly assigned to the waitlist/control or the experimental group. The same six-week one-on-one training was administered to the control subjects at the completion of their post-test. The revised (17-item) version of the Older Adults' Computer Technology Attitudes Scale (OACTAS) showed strong reliability: the results of a factor analysis were robust, and two analyses of covariance demonstrated that the training programme induced significant changes in attitudes and self-efficacy. Such results encourage the recruitment of older persons into training programmes aimed at increasing computer technology attitudes and self-efficacy.


[Delayed exacerbation of cervical myelopathy in a case of juvenile muscular atrophy of unilateral distal upper extremity].
We reported a case in which cervical myelopathy exacerbated 20 years after the stabilization of juvenile muscular atrophy of unilateral distal upper extremity. The patient presented progressive weakness in the right proximal upper extremity and spastic paraparesis in addition to the long-lasting muscular atrophy of right distal upper extremity. Plain x-ray showed severe cervical spondylosis with kyphosis of the cervical spine. Dynamic study on MRI disclosed cervical spinal cord atrophy and compression enhanced in both flexion and extension position of the neck. Malalignment (kyphosis) and severe spondylotic change of the cervical spine seemed to affect the spinal cord with little functional reservoir, manifesting the delayed exacerbation of myelopathy. We conclude that malalignment and subsequent spondylotic change of the cervical spine would be significant factors to determine the long term prognosis of patients with juvenile muscular atrophy of unilateral distal upper extremity.


Increased histone acetylation and deacetylation in rat ascites hepatoma cells.
Rates of histone acetylation and deacetylation in nuclei from fetal, adult, and two kinds of neoplastic rat hepatocytes were examined. Histone acetylation in isolated nuclei was measured in the presence of 6 mM sodium n-butyrate, a potent inhibitor of deacetylase, and in the absence of the inhibitor. The deacetylase activity was estimated from the difference between the rates with or without the inhibitor. Both histone acetylation and deacetylation in nuclei from hepatoma cells (AH 66 cells) occurred two times faster than those of nuclei from fetal and adult livers regardless of alpha-fetoprotein production. This increased acetylation and deacetylation in hepatoma cells may be ascribed to either the increased activities of the enzymes or the increased accessibility of histone to the enzymes in the chromatin. Autoradiographic analysis of acetylated histones showed that all of the internal histones of the nucleosomes were acetylated and that apparent difference was found in the pattern of acetylated fractions between hepatoma nuclei and normal liver cell nuclei.


FBXO43 increases CCND1 stability to promote hepatocellular carcinoma cell proliferation and migration.
Abnormal expression of E3 ubiquitin ligase plays an important role in the development and progression of hepatocellular carcinoma (HCC), although the mechanism has remained elusive. This study aimed to investigate the biological function and potential mechanism of FBXO43 in HCC. FBXO43 expression in tissues and cells were detected by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC). The Kaplan-Meier method and Cox regression analysis were used to explore the correlation between the expression level of FBXO43 and the clinical survival. MTT assay, EdU incorporation, colony formation, Transwell, and wound healing assays were performed to evaluate the function of FBXO43 in cell proliferation and migration in vitro. The interaction between FBXO43 and cyclin D1 (CCND1) was assessed by co-immunoprecipitation (Co-IP) assay and in vivo ubiquitination assay. We found that FBXO43 was upregulated in HCC patient tissues and positively associated with poor clinicopathological features. Meanwhile, HCC patients with high expression of FBXO43 had shorter overall survival (OS) and disease-free survival (DFS). Furthermore, knockdown of FBXO43 inhibited HCC cell proliferation, migration and epithelial-mesenchymal transition (EMT) in HCC cells. Mechanistically, FBXO43 interacted with CCND1 and promoted its stability by polyubiquitination, leading to HCC cell proliferation, migration and EMT. Functional rescue experiments demonstrated that knockdown of CCND1 blocks FBXO43-mediated cell proliferation and metastasis. FBXO43, as an independent prognostic biomarker, promotes HCC cell proliferation, metastasis and EMT by stability of CCND1, which provides a new potential strategy for HCC treatment by targeting FBXO43-CCND1 axis.


Inertial measurement unit sensor-based gait analysis in adults and older adults: A cross-sectional study.
Gait assessment has been used in a wide range of clinical applications, and gait velocity is also a leading predictor of disease and physical functional aspects in older adults. The study aim to examine the changes in IMU-based gait parameters according to age in healthy adults aged 50 and older, to analyze differences between aging patients. A total of 296 healthy adults (65.32 ± 6.74 yrs; 83.10 % female) were recruited. Gait assessment was performed using an IMU sensor-based gait analysis system, and 3D motion information of hip and knee joints was obtained using magnetic sensors. The basic characteristics of the study sample were stratified by age category, and the baseline characteristics between the groups were compared using analysis of variance (ANOVA). Pearson's correlation analysis was used to analyze the relationship between age as the dependent variable and several measures of gait parameters and joint angles as independent variables. The results of this study found that there were significant differences in gait velocity and both terminal double support in the three groups according to age, and statistically significant differences in the three groups in hip joint angle and knee joints angle. In addition, it was found that the gait velocity and knee/hip joint angle changed with age, and the gait velocity and knee/hip joint angle were also different in the elderly and adult groups. We found changes in gait parameters and joint angles according to age in healthy adults and older adults and confirmed the difference in gait velocity and joint angles between adults and older adults.


Facile Synthesis of gC3N4-Exfoliated BiFeO3 Nanocomposite: A Versatile and Efficient S-Scheme Photocatalyst for the Degradation of Various Textile Dyes and Antibiotics in Water.
Water pollution engendered from textile dyes and antibiotics is a globally identified precarious concern that is causing dreadful risks to human health as well as aquatic lives. This predicament is escalating the quest to develop competent photocatalysts that can degrade these water pollutants under solar light irradiation. Herein, we report an efficient photocatalyst comprising a hierarchical structure by integrating the layered graphitic carbon nitride (gC3N4) with nanoflakes of exfoliated BiFeO3. The coexistence of these two semiconducting nanomaterials leads to the formation of an S-scheme heterojunction. This nanocomposite demonstrated its excellent photocatalytic activity toward the degradation of several textile dyes (Yel CL2R, Levasol Yellow-CE, Levasol Red-GN, Navy Sol-R, Terq-CL5B) and various antibiotics (such as tetracycline hydrochloride (TCH), ciprofloxacin (CPX), sulfamethoxazole (SMX), and amoxicillin (AMX)) under the simulated solar light irradiation. As this photocatalyst exhibits its versatile activity toward the degradation of several commercial dyes as well as antibiotics, this work paves the path to develop a reasonable, eco-benign, and highly efficient photocatalyst that can be used in the practical approach to remediate environmental pollution.


Retinal pigment epithelium-secretome: A diabetic retinopathy perspective.
Diabetic retinopathy is a major complication of diabetes mellitus that can lead to retinal vascular abnormalities and visual impairment. While retinal endothelial pathology is well studied, retinal pigment epithelium (RPE) layer modifications and the patho-physiological regulations are not widely understood. The RPE is a highly specialized pigmented layer regulating not only physiological functions such as transport of nutrients, ions, absorption of light, phagocytosis of photoreceptor membranes, but also secretion of a number of cytokines, chemokines, angiogenic and anti-angiogenic factors. The RPE secretome, though crucial in health and disease, remains elusive in diabetic retinopathy. A knowledge of these secreted factors would help explain and correlate the clinical phase of the disease aiding in improved disease management. A comprehensive knowledge of the secreted factors of the RPE is a potential tool for understanding the differential treatment regime of early diabetic retinopathy, diabetic proliferative retinopathy and diabetic macular edema. In this review, we have delineated the importance of factors secreted by the retinal pigment epithelium and its regulation in the pathogenesis of diabetic retinopathy.


Spontaneous perforation of choledochal cyst: a study of 13 cases.
Of the 187 cases of infantile choledochal cyst treated at our hospitals, we encountered 13 with spontaneous perforation. All cases were under 4 years old. Eight cases were found to have biliary peritonitis and 5 had a sealed perforation. The shape of the extrahepatic bile duct was cystic in 8 and fusiform in 5. The cyst wall around the perforation was filmy and bile was found to be oozing through the thinned wall. Nine perforations were single while 4 cases had multiple perforations. Four of 17 perforations occurred in the posterior part of the cyst wall. Only 1 case of perforation was associated with protein plugs in a common channel, while 7 of the 10 cases of choledochal cyst requiring percutaneous biliary drainage due to signs of raised intrabiliary pressure were found to have protein plugs. We consider that spontaneous perforation of a choledochal cyst is not rare in infancy. The etiology of a perforation must be epithelial irritation of the biliary tract due to refluxed pancreatic juice caused by pancreatico-biliary malunion associated with mural immaturity due to infancy, rather than an abnormal rise in ductal pressure or congenital mural weakness at a certain point.


Oxygen sensitivity of the nifLA promoter of Klebsiella pneumoniae.
Oxygen sensitivity of the nifLA promoter of Klebsiella pneumoniae has been demonstrated. Studies on the oxygen regulation of nifB-lacZ and nifH-lacZ fusions in the presence of the nifLA operon, which contains either an intact or a deleted nifL gene, indicate that possibly both the nifL promoter and the nifL product are responsible for nif repression by oxygen.


SUMOylation code in cancer development and metastasis.
Protein modification by small ubiquitin-like modifier (SUMO) controls diverse cellular functions of protein targets including transcription factors and coregulators mainly in the nucleus and participates in maintaining cellular homeostasis. In addition, SUMO system plays important roles in DNA damage repair and maintaining genome integrity. Thus, in some cases, the loss of control on SUMOylation or deSUMOylation processes causes a defect in maintaining homeostasis and hence gives a cue to cancer development. Furthermore, recent study showed that SUMO system is also involved in cancer metastasis. In this review, we will summarize and discuss the possible role of SUMO system in cancer development and metastasis.


Algorithm for the multi-parameter analysis of nystagmus using a digital computer.
A computer program for analyzing nystagmus has been developed and can be used on a small laboratory digital computer. The algorithm accepts digitized data and looks for the minimum and maximum (minmax) points of the nystagmus waveform. These points in turn are used to define seven descriptive parameters of nystagmus, including the amplitude, duration, and velocity of the slow and fast phases, and the frequency. The algorithm uses three user-adjusted criteria for accepting or rejecting minmax points. The treatment of noisy or irregular data can be improved by adjusting the values of these criteria.


Impaired ability of Cftr knockout mice to control lung infection with Pseudomonas aeruginosa.
The present study was aimed at investigating the innate susceptibility of C57BL/6-Cftrunc/Cftrunc knockout [B6-Cftr (-/-)] mice to pulmonary infection with Pseudomonas aeruginosa. Our results indicate that 58.4% of B6-Cftr (-/-) mice died within 6 d following lung infection with 10(5) P. aeruginosa entrapped in agar beads, whereas only 12.1% of B6-Cftr (+/+) mice died over the same period of time. Moreover, the number of bacteria recovered from the lungs of B6-Cftr (-/-) mice 3 and 6 d after infection was significantly higher than that observed in their littermate controls. No correlation was found between the weight or age of the animals and the number of viable bacteria recovered from the lungs of mice. Histopathological examination of lung sections from P. aeruginosa-infected mice revealed that the infection results in a severe bronchopneumonia. Both B6-Cftr (-/-) knockout mice and their littermate controls developed similar lung pathology during the course of infection. Overall, results reported in the present study suggest that a defect at the Cftr locus leads to an exacerbation of P. aeruginosa lung infection resulting in a dramatically increased mortality rate and higher bacterial load.


Application of ELISA and ELADA assay (double substrate immunoassay) to red blood cell antigens.
A double substrate immunoassay has been developed that allows simultaneous quantitation and localization of red blood cell surface antigens. The assay can be used to quantitate surface antigens, or the titer of antisera specific to cell-surface antigens, on the red blood cell. The assay has been adapted to the study of both D antigen and erythrocyte membrane (EM) antigen, which were found to be uniformly dispersed over the surface of the cell. The number of EM antigens per cell appeared to be approximately twenty times that of the D antigen. For typing antisera, this assay makes it feasible to express antibodies in absolute units (microgram antibody) rather than conventional dilution titers, and thus offers a simpler means of rapidly comparing antisera.


Bioprospection of cold-adapted yeasts with biotechnological potential from Antarctica.
The aim of this study was to investigate the ability to produce extracellular hydrolytic enzymes at low temperature of yeasts isolated from 25 de Mayo island, Antarctica, and to identify those exhibiting one or more of the evaluated enzymatic activities. A total of 105 yeast isolates were obtained from different samples and 66 were identified. They belonged to 12 basidiomycetous and four ascomycetous genera. Most of the isolates were ascribed to the genera Cryptococcus, Mrakia, Cystobasidium, Rhodotorula, Gueomyces, Phenoliferia, Leucosporidium, and Pichia. Results from enzymes production at low temperatures revealed that the Antarctic environment contains metabolically diverse cultivable yeasts, which represent potential tools for biotechnological applications. While most the isolates proved to produce 2-4 of the investigated exoenzymes, two of them evidenced the six evaluated enzymatic activities: Pichia caribbica and Guehomyces pullulans, which were characterized as psycrotolerant and psycrophilic, respectively. In addition, P. caribbica could assimilate several n-alkanes and diesel fuel. The enzyme production profile and hydrocarbons assimilation capacity, combined with its high level of biomass production and the extended exponential growth phase make P. caribbica a promising tool for cold environments biotechnological purposes in the field of cold-enzymes production and oil spills bioremediation as well.


Theoretical prediction of pKa values for methacrylic acid oligomers using combined quantum mechanical and continuum solvation methods.
The acidity constant pKa for polymeric organic acid is expected to be different from its corresponding monomer value due to the change of chemical environment upon polymerization. Thermodynamic cycles were used to determine the free-energy changes for the proton dissociation processes in aqueous solution and the corresponding pKa values for monomer methacrylic acid and several similar carboxylic acids. First-principles calculations and continuum solvation model were used to determine the gas-phase and solvation free energies, respectively. A protocol was developed to use the efficient density functional calculations with B3LYP functional instead of the demanding CBS-QB3 method to determine the gas-phase free energies with relative high accuracy, thus enabling the determination of pKa values for the short oligomers of methacrylic acid. The predicted pKa values for the dimer and trimer of methacrylic acid are higher by about 0.8 pKa units than the predicted monomer value.


Post-impact assessment of oil pollution in Agbada west plain of Niger Delta, Nigeria: field reconnaissance and total extractable hydrocarbon content.
Typical post-impact assessment of an oil-spill-impacted site in Agbada west plain of the Niger Delta basin of Nigeria was carried out 13 months after recorded incidence of spillage, using empirical indices of reconnaissance and extractable hydrocarbon content. Field-reconnaissance surveys revealed lower species' numbers and diversity of surface and subterranean flora and fauna. The presence and absence of such plant species as Elaeis guineensis, Musanga cecropiodes, and Andropogon gayanus, as well as animal species like earthworms and nematodes in sampled plots, corroborated the evidence provided by the total extractable hydrocarbon content (of (2.53+/-0.43)x10(2) mg/kg and (2.00+/-0.76)x10(2) mg/kg at surface and subsurface depths, resp.) on the level of degradation and/or regeneration at the polluted site. The most important evidence that oiling must have been responsible, at least in part, for the reduction in species' number and diversity was provided by the plant cover, Andropogan gayanus, which occurred at a lower density of 0.9 plants/m2 in the oil-impacted plots and 14.00 plants/m2 in the unimpacted reference plots of an adjacent, geographically similar area. The presence of this species on site thus presented a significant difference (P<0.05) of over 85%, and indicated exhaustion or impoverishment of impacted soils. Elaeis guineensis, with a population density of 0.1 stands/m2, provided evidence of past cultivation on site, while species like Musanga cecropioides, with a density of 0.5 stands/m2, at the unimpacted site, confirmed the abandonment of the farmstead over a long period of time. For the fauna, the most sensitive indicator of hydrocarbon toxicity was provided by nematode Xiphinema sp. that were completely absent in the oil-impacted site.


Evidence-based treatment of atopic dermatitis with topical moisturizers.
Skin barrier restoration represents the mainstay of the treatment of atopic dermatitis and the use of moisturizers is recommended by several international guidelines. The aim of the study was to investigate through an evidence-based medicine analysis the effectiveness and safety of different moisturizing products available for a non-pharmacological treatment of atopic dermatitis. A total of 92 randomized controlled trials (RCTs) have been identified and analyzed. The results confirm the presence of a reasonable number of studies highlighting moisturizers safety and effectiveness in the treatment of atopic dermatitis by improving disease severity, increasing the time of relapse and reducing the time of flares. Moisturizers containing urea, glycerin or glycyrrhetinic acid seem to show the greater evidence of efficacy being supported by more clinical trials. Among the existing moisturizers, those containing a single agent generally work although the heterogeneity of RCTs does not allow reaching more definitive conclusions. Moisturizers made of a mixture of substances seem to be more effective thanks to the presence of different active substances that may exert a synergistic effect. A meta-analysis of 4 RCTs confirms the efficacy of a medical device containing glycyrrhetinic acid, hyaluronic acid, shea butter, telmesteine, and vitis vinifera in the treatment of atopic dermatitis.


Rifampicin-associated segmental necrotizing glomerulonephritis in staphylococcal endocarditis.
Segmental necrotising glomerulonephritis has been reported as complication of rifampicin therapy in patients receiving treatment for tuberculosis. Changing epidemiology of infections such as infective endocarditis (IE) has led to an increase in the use of rifampicin for Staphylococcal infections. We describe a case of a patient with Staphylococcal IE who developed acute renal failure secondary to a segmental necrotising glomerulonephritis while being treated with rifampicin, and review the literature regarding this complication of rifampicin therapy.


Rapid assessment of Ebola infection prevention and control needs--six districts, Sierra Leone, October 2014.
As of October 31, 2014, the Sierra Leone Ministry of Health and Sanitation had reported 3,854 laboratory-confirmed cases of Ebola virus disease (Ebola) since the outbreak began in May 2014; 199 (5.2%) of these cases were among health care workers. Ebola infection prevention and control (IPC) measures are essential to interrupt Ebola virus transmission and protect the health workforce, a population that is disproportionately affected by Ebola because of its increased risk of exposure yet is essential to patient care required for outbreak control and maintenance of the country's health system at large. To rapidly identify existing IPC resources and high priority outbreak response needs, an assessment by CDC Ebola Response Team members was conducted in six of the 14 districts in Sierra Leone, consisting of health facility observations and structured interviews with key informants in facilities and government district health management offices. Health system gaps were identified in all six districts, including shortages or absence of trained health care staff, personal protective equipment (PPE), safe patient transport, and standardized IPC protocols. Based on rapid assessment findings and key stakeholder input, priority IPC actions were recommended. Progress has since been made in developing standard operating procedures, increasing laboratory and Ebola treatment capacity and training the health workforce. However, further system strengthening is needed. In particular, a successful Ebola outbreak response in Sierra Leone will require an increase in coordinated and comprehensive district-level IPC support to prevent ongoing Ebola virus transmission in household, patient transport, and health facility settings.


Bayesian Estimation of CBF Measured by DSC-MRI in Patients with Moyamoya Disease: Comparison with 15O-Gas PET and Singular Value Decomposition.
CBF analysis of DSC perfusion using the singular value decomposition algorithm is not accurate in patients with Moyamoya disease. This study compared the Bayesian estimation of CBF against the criterion standard PET and singular value decomposition methods in patients with Moyamoya disease. Nineteen patients with Moyamoya disease (10 women; 22-52 years of age) were evaluated with both DSC and 15O-gas PET within 60 days. DSC-CBF maps were created using Bayesian analysis and 3 singular value decomposition analyses (standard singular value decomposition, a block-circulant deconvolution method with a fixed noise cutoff, and a block-circulant deconvolution method that adopts an occillating noise cutoff for each voxel according to the strength of noise). Qualitative and quantitative analyses of the Bayesian-CBF and singular value decomposition-CBF methods were performed against 15O-gas PET and compared with each other. In qualitative assessments of DSC-CBF maps, Bayesian-CBF maps showed better visualization of decreased CBF on PET (sensitivity = 62.5%, specificity = 100%, positive predictive value = 100%, negative predictive value = 78.6%) than a block-circulant deconvolution method with a fixed noise cutoff and a block-circulant deconvolution method that adopts an oscillating noise cutoff for each voxel according to the strength of noise (P < .03 for all except for specificity). Quantitative analysis of CBF showed that the correlation between Bayesian-CBF and PET-CBF values (ρ = 0.46, P < .001) was similar among the 3 singular value decomposition methods, and Bayesian analysis overestimated true CBF (mean difference, 47.28 mL/min/100 g). However, the correlation between CBF values normalized to the cerebellum was better in Bayesian analysis (ρ = 0.56, P < .001) than in the 3 singular value decomposition methods (P < .02). Compared with previously reported singular value decomposition algorithms, Bayesian analysis of DSC perfusion enabled better qualitative and quantitative assessments of CBF in patients with Moyamoya disease.


Aortic valve disease: preventable or inevitable?
Calcific aortic valve stenosis is the most frequent valve disease and the most common cause of aortic valve replacement in the western world, concomitant with aging of the general population and habitual consumption of a high-calorie diet. For years it was considered to be a passive wear and tear process but now it is recognized as an active process similar to atherosclerosis with involvement of several mediators, such as adhesion molecules, TGFs, cathepsin enzymes and bone regulatory proteins. As conviction grew that aortic stenosis has a genesis similar to atherosclerosis, the hypothesis that statins might be able to alter the progression of the disease also grew. Various retrospective studies confirmed the benefits of statin use at an earlier stage of the disease, but some disappointing results were demonstrated by randomized clinical trials.


What determines the basal rate of metabolism?
The basal rate of metabolism (BMR) is the most reported estimate of energy expenditure in endotherms. Its principal determinant is body mass, but BMR also correlates with a variety of behavioral and ecological factors that do not determine basal rate: they are byproducts of the mechanisms that are its determinate. In mammals, mass-independent BMR increases when muscle mass is >40% of total body mass and BMR is then ≥100% of the value expected from body mass. Mammals with muscle masses <30% of body mass have lower BMRs, a diminished capacity to regulate body temperature and often have reduced activity levels. At muscle masses <42% of body mass, birds have body temperatures and basal rates higher than mammals with the same muscle mass. Their high basal rates derive from fast blood flow and increased mitochondrial density in their pectoral muscles. These enhancements also occur in the flight muscles of bats. Oxygen transport to the pectoral muscles of birds is facilitated by an increase in heart mass and hematocrit. This arrangement avoids transporting a large muscle mass to fuel flight, thereby reducing the cost of flight. Pectoral muscle masses <9% of body mass correlate with a flightless condition in kiwis, rails and ducks but some fruit pigeons have BMRs as low as those measured in kiwis, while remaining volant. The mass-independent BMRs of endotherms principally reflect changes of muscle activity and mass. An increase in muscle mass may have contributed to the evolution of endothermy.


Mode of inactivation of probiotic bacteria affects interleukin 6 and interleukin 8 production in human intestinal epithelial-like Caco-2 cells.
Five lactic acid bacteria and two bifidobacteria strains were heat or irradiation inactivated. Inactivated cultures were evaluated for their effects on cytokines interleukin (IL) 6 and IL-8 production in human intestinal-like Caco-2 cells. For both heat- and irradiation-inactivated cultures, production of IL-6 and IL-8 was dependent on the specific microorganism. However, with all of the cultures, both IL-6 and IL-8 production was significantly higher (P < 0.05) in Caco-2 cells that were treated with heat-inactivated probiotic bacteria compare to the irradiation-inactivated bacteria. In the majority of the cases, heat-inactivated bacteria induced IL-6 and IL-8 production, whereas irradiation-inactivated bacteria attenuated both cytokine production. Our results indicate that the same probiotic bacteria used in the same cell culture could provide opposite cytokine production and immune modulation results based on its mode of inactivation; therefore, it is important to describe inactivation methods and conditions in detail when characterizing probiotic effects.


Risk Assessment and Regulation Algorithm for Financial Technology Platforms in Smart City.
The informatization of cities has been further promoted, and the construction of smart cities supported by technological innovation has been upgraded. The financial industry and data are closely related. Whether the financial industry can make good use of new information technology is the key to its successful transformation. The development of smart cities has a significant effect on the development of people's livelihood, the process of urbanization, the use of technology, the solution of urban problems, and the improvement of economic levels. This also provides a good choice for the development of cities in each country. For better development, it needs technical support. Therefore, it is very important to improve the technical level. This research mainly discusses the risk assessment and regulation algorithms of financial technology platforms in smart cities. This study divides the risk decision channels into two paths based on the smart city theory, considers the internal risk factors and external risk factors of the robo-advisory service platform from the three perspectives of platform characteristics, corporate characteristics, and investor characteristics and exploring the construction of a robo-advisory service platform risk prediction model based on the machine learning perspective. The design and implementation of a personalized financial investment prototype system, a Python-based web development framework Django, and a variety of toolkits have realized a B/S architecture robo-advisor. Among them, the function of buying and selling ETF and the trend recording function after buying are realized by simulating the transaction data collected by the data collection module. The study found that the key potential characteristics that constitute platform risks are mainly the listing year of the background company, the age of the platform, the investment threshold, and the search index. To a certain extent, this provides data support for investors and regulatory authorities to evaluate platform capabilities and platform selection. Investors should comprehensively consider platform qualifications when making platform decisions and pay attention to information such as the age of listing of companies with platform background, platform age, and investment thresholds. Only when the quality of people is improved, the quality of the population of this city improves, so that the development of the city has a broad room for growth. The accuracy of the similar formula calculation method in the big data proposed in this study reached 88%. This research provides new ideas for perfecting the black box regulatory system of robo-advisory algorithms.


Urokinase-immobilization suppresses inflammatory responses to polyurethane tubes implanted in rabbit muscles.
Urokinase and plasmin appear to have antiinflammatory activity in some injury models, and urokinase immobilization has been clinically used to prevent thrombus formation in various implants, including intravenous indwelling catheters and subcutaneous drainage tubes. In the present study, polyurethane tubes were embedded in rabbit muscle for 3 months and the effect of urokinase immobilization on inflammatory responses to the implanted tubes was studied at 1 week, 1 month, and 3 months. Mononuclear leukocyte accumulation occurred around implanted polyurethane tubes and peaked after 1 month, but was reduced significantly by urokinase immobilization. The treatment also lessened as well as delayed eosinophil accumulation, but did not affect fibrosis caused by implanted tubes. These results indicate suppressive effects of urokinase immobilization on polyurethane-elicited inflammatory responses and suggest that an approach to develop persistently active urokinase immobilization is rational for successful long-term device implantation.


The staying power of adhesion-associated antioxidant activity in Mytilus californianus.
The California mussel, Mytilus californianus, adheres in the highly oxidizing intertidal zone with a fibrous holdfast called the byssus using 3, 4-dihydroxyphenyl-l-alanine (DOPA)-containing adhesive proteins. DOPA is susceptible to oxidation in seawater and, upon oxidation, loses adhesion. Successful mussel adhesion thus depends critically on controlling oxidation and reduction. To explore how mussels regulate redox during their functional adhesive lifetime, we tracked extractable protein concentration, DOPA content and antioxidant activity in byssal plaques over time. In seawater, DOPA content and antioxidant activity in the byssus persisted much longer than expected-50% of extractable DOPA and 30% of extractable antioxidant activity remained after 20 days. Antioxidant activity was located at the plaque-substrate interface, demonstrating that antioxidant activity keeps DOPA reduced for durable and dynamic adhesion. We also correlated antioxidant activity to cysteine and DOPA side chains of mussel foot proteins (mfps), suggesting that mussels use both cysteine and DOPA redox reservoirs for controlling interfacial chemistry. These data are discussed in the context of the biomaterial structure and properties of the marine mussel byssus.


Co-infection with Legionella pneumophila and Pneumocystis carinii in a patient with chronic lymphocytic leukemia.
A patient with chronic lymphocytic leukemia was found to have pneumonitis caused by a simultaneous Pneumocystis carinii and Legionella pneumophila infection. Although both microorganisms frequently cause pulmonary infections in immunocompromised patients, co-infection has not been reported. This patient responded to antimicrobial therapy, but superinfection with Candida albicans led to his death. As there are numerous infective and noninfective causes of pneumonia in such patients, this case illustrates that the identification of a single etiologic agent does not obviate the search for other potential causes.


Targeting Soluble Epoxide Hydrolase and Cyclooxygenases Enhance Joint Pain Control, Stimulate Collagen Synthesis, and Protect Chondrocytes From Cytokine-Induced Apoptosis.
Objective: To determine the symptomatic and disease-modifying capabilities of sEH and COX inhibitors during joint inflammation. Methods: Using a blinded, randomized, crossover experimental design, 6 adult healthy horses were injected with lipopolysaccharide (LPS; 3 μg) from E. coli in a radiocarpal joint and concurrently received the non-selective cyclooxygenase (COX) inhibitor phenylbutazone (2 mg/kg), the sEH inhibitor t-TUCB (1 mg/kg) or both (2 mg/kg phenylbutazone and 0.1, 0.3, and 1 mg/kg t-TUCB) intravenously. There were at least 30 days washout between treatments. Joint pain (assessed via inertial sensors and peak vertical forces), synovial fluid concentrations of prostanoids (PGE2, TxB2), cytokines (IL-1β, IL-6, TNF-α) and biomarkers of collagen synthesis (CPII) and degradation (C2C) were measured at pre-determined intervals over a 48-h period. The anti-apoptotic effect of COX and sEH inhibitors was determined via ELISA technique in primary equine chondrocytes incubated with TNF-α (10 ng/ml) for 24 h. Apoptosis was also determined in chondrocytes incubated with sEH-generated metabolites. Results: Combined COX and sEH inhibition produced significantly better control of joint pain, prostanoid responses, and collagen synthesis-degradation balance compared to each compound separately. When administered separately, pain control was superior with COX vs. sEH inhibition. Cytokine responses were not different during COX and/or sEH inhibition. In cultured chondrocytes, sEH inhibition alone or combined with COX inhibition, but not COX inhibition alone had significant anti-apoptotic effects. However, sEH-generated metabolites caused concentration-dependent apoptosis. Conclusions: Combined COX and sEH inhibition optimize pain control, attenuate loss of articular cartilage matrix during joint inflammation and cytokine-induced chondrocyte apoptosis.


Decisional processing in paranoid and non-paranoid schizophrenics.
40 schizophrenic subjects, divided into paranoid/non-paranoid categories and 14 normal controls were presented a task which involved making "same-different" judgments during random presentations of a series of visual comparison stimuli with a standard which represented the midpoint of the stimulus continuum. Using Sternberg's Choice RT paradigm for studying the locus of cognitive deficit, difficulty at the response-selection stage was manipulated while holding other stages constant. It was predicted that paranoids would have shorter RTs at easy decision points and longer RTs at difficult decision points relative to non-paranoids. The directions of the differences were as predicted but did not attain statistical significance. Both schizophrenic groups, compared to normals, made significantly fewer "same" responses on those trials where the comparison and standard were most similar.


Amphotericin B delays both scrapie agent replication and PrP-res accumulation early in infection.
Amphotericin B delays the onset of clinical symptoms in hamsters infected with scrapie agent strain 263K. Here we show that accumulation of a scrapie-specific isoform of the prion protein (PrP-res) and agent replication were delayed early in amphotericin B-treated animals. By 8 weeks postinfection, only untreated animals exhibited clinical symptoms of scrapie infection whereas PrP-res levels and titers were similar in treated and untreated animals. This suggests that although PrP-res accumulation and agent replication are linked, they are not the sole factors required for the onset of clinical disease.


The definition, prevalence, and risk factors for stress urinary incontinence.
Stress urinary incontinence (SUI) has an observed prevalence of between 4% and 35%. Whereas the clinical definition of SUI has been established by the International Continence Society, the epidemiologic definition has not been established, leading to a broad disparity in reported prevalence rates. Numerous risk factors for SUI have been identified. Aging, obesity, and smoking appear to have consistent causal relationships with the condition, whereas the roles of pregnancy and childbirth remain controversial. The prevalence of many of these risk factors is increasing in the adult female population of the United States. These population changes, combined with increasing physician awareness and the availability of nonsurgical therapy, will likely increase the number of women receiving care for SUI over the next 3 decades.


TRIM5 Retroviral Restriction Activity Correlates with the Ability To Induce Innate Immune Signaling.
Host restriction factor TRIM5 inhibits retroviral transduction in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. However, the restriction mechanism may not be that simple since TRIM5 E3 ubiquitin ligase activity, the proteasome, autophagy, and TAK1-dependent AP-1 signaling have been suggested to contribute to restriction. Here, we show that, among a panel of seven primate and Carnivora TRIM5 orthologues, each of which has potential for potent retroviral restriction activity, all activated AP-1 signaling. In contrast, TRIM family paralogues most closely related to TRIM5 did not. While each primate species has a single TRIM5 gene, mice have at least seven TRIM5 homologues that cluster into two groups, Trim12a, -b, and -c and Trim30a, -b, -c, and -d. The three Trim12 proteins activated innate immune signaling, while the Trim30 proteins did not, though none of the murine Trim5 homologues restricted any of a panel of cloned retroviruses. To determine if any mouse TRIM5 homologues had potential for restriction activity, each was fused to the human immunodeficiency virus type 1 (HIV-1) CA binding protein cyclophilin A (CypA). The three Trim12-CypA fusions all activated AP-1 and restricted HIV-1 transduction, whereas the Trim30-CypA fusions did neither. AP-1 activation and HIV-1 restriction by the Trim12-CypA fusions were inhibited by disruption of TAK1. Overall then, these experiments demonstrate that there is a strong correlation between TRIM5 retroviral restriction activity and the ability to activate TAK1-dependent innate immune signaling. The importance of retroviruses for the evolution of susceptible host organisms cannot be overestimated. Eight percent of the human genome is retrovirus sequence, fixed in the germ line during past infection. Understanding how metazoa protect their genomes from mutagenic retrovirus infection is therefore of fundamental importance to biology. TRIM5 is a cellular protein that protects host genome integrity by disrupting the retroviral capsid as it transports viral nucleic acid to the host cell nucleus. Previous data suggest that innate immune signaling contributes to TRIM5-mediated restriction. Here, we show that activation of innate immune signaling is conserved among primate and carnivore TRIM5 orthologues and among 3 of the 7 mouse Trim5 homologues and that such activity is required for TRIM5-mediated restriction activity.


[Expression and clinical significance of type-1 blood group antigens (Lea, Leb, CA19-9) in colorectal cancer--comparison with CEA].
The immunohistochemical analysis using the monoclonal antibodies to the blood group associated antigens Lea, Leb, CA19-9, and CEA, were performed on the tissues of the colorectal cancers, adenomas, normal mucosae and distant metastatic lesions, to determine whether the given degree of expression have some relation to the prognosis of patients or the potential of metastasis. We also analysed the serum levels of CA19-9 and CEA by RIA and compared them with the results of immunopathology. The more pronounced expression of CEA, Lea, Leb, and CA19-9 was observed in proportion to the progress of the cancer. In those cases of immunohistochemically Lea negative results in tissues, CA19-9 was not detected either in the serum level nor in tissue sections, therefore all cases of Lea negative results were eliminated in the evaluation of the clinical significance of CA19-9. Positive expression of CA19-9 in tissue of cancer indicated a poor prognosis of the patient and high risk of distant metastasis. Higher intensity of staining was observed in hepatic metastasis, in comparison with the primary lesion. These studies demonstrated that immunohistochemical analysis of CA19-9 and blood group antigens in useful tool for evaluation of prognosis and risk of metastasis in colorectal cancer.


Effects of Glucose and Starch on Lactate Production by Newly Isolated Streptococcus bovis S1 from Saanen Goats.
When ruminants are fed high-concentrate diets, Streptococcus bovis proliferates rapidly and produces lactate, potentially causing rumen acidosis. Understanding the regulatory mechanisms of the metabolism of this species might help in developing dietary strategies to alleviate rumen acidosis. S. bovis strain S1 was newly isolated from the ruminal fluid of Saanen dairy goats and then used to examine the effects of glucose and starch on bacterial metabolism and gene regulation of the organic acid-producing pathway in cultures at a pH of 6.5. Glucose or starch was added to the culture medium at 1 g/liter, 3 g/liter (close to a normal range in the rumen fluid), or 9 g/liter (excessive level). Lactate was the dominant acid produced during the fermentation, and levels increased with the amount of glucose or starch in a dose-dependent manner (P < 0.001). The production of formate and acetate in the fermentation media fluctuated slightly with the dose but accounted for small fractions of the total acids. The activities of lactate dehydrogenase (LDH) and α-amylase (α-AMY) increased with the starch dose (P < 0.05), but the α-AMY activity did not change with the glucose dose. The relative expression levels of the genes ldh, pfl (encoding pyruvate formate lyase), ccpA (encoding catabolite control protein A), and α-amy were higher at a dose of 9 g/liter than at 1 g/liter (P < 0.05). Expression levels of pfl and α-amy genes were higher at 3 g/liter than at 1 g/liter (P < 0.05). The fructose 1,6-diphosphate (FDP) concentration tended to increase with the glucose and starch concentrations. In addition, the S. bovis S1 isolate fermented glucose much faster than starch. We conclude that the quantities of glucose and soluble starch had a major effect on lactate production due to the transcriptional regulation of metabolic genes. This work used a newly isolated S. bovis strain S1 from the rumen fluid of Saanen goats and examined the effects of glucose and soluble starch on organic acid patterns, enzyme activity, and expression of genes for in vitro fermentation. It was found that lactate was the dominant product from S. bovis strain S1, and the quantities of both glucose and starch in the medium were highly correlated with lactate production and with the corresponding changes in associated enzymes and genes. Therefore, manipulating the metabolic pathway of S. bovis to alter the dietary level of readily fermentable sugar and carbohydrates may be a strategy to alleviate rumen acidosis.


uPA, tPA and PAI-1 mRNA expression in periretinal membranes.
Formation of periretinal membranes occurs in proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR) and includes cell migration, proliferation, extracellular matrix formation and tissue contraction, processes in which plasminogen activation (PA) system is involved. Twenty PVR, PDR or pucker membranes were examined to identify the cells with cell specific markers and to detect the expression of urokinase (uPA), tissue-type plasminogen activator (tPA) or plasminogen activator inhibitor-1 (PAI-1) by in situ hybridization and by immunohistochemistry. In PVR, uPA, tPA and PAI-1 were expressed by retinal pigment epithelial (RPE) cells, macrophages or retinal glial cells. In PDR, PA components were also expressed by endothelial cells. Semiquantitative analysis in in situ hybridization and immunohistochemistry results demonstrated no notable differences in uPA, tPA or PAI-1 expression between PDR and PVR membranes. We conclude that local proteolytic activation is involved in extracellular matrix production both in diabetic and non-diabetic membranes.


Outbreaks of pseudo-infection with Cyclospora and Cryptosporidium--Florida and New York City, 1995.
Efforts to expand the scope of surveillance and diagnostic testing for emerging infectious diseases also may increase the potential for identifying pseudo-outbreaks (i.e., increases in incidence that may result from enhanced surveillance) and outbreaks of pseudo-infection (i.e., clusters of false-positives for infection). This report describes the investigations of outbreaks of pseudo-infection with Cyclospora in Florida and Cryptosporidium in New York City in 1995 after health departments in those jurisdictions had initiated surveillance for these emerging organisms. These investigations emphasize 1) the need for laboratory training in the identification of emerging pathogens and 2) the importance of confirmation by reference laboratories as an early step in the investigation of any apparent outbreak caused by an emerging pathogen.


Transportable Optical Lattice Clock with 7×10^{-17} Uncertainty.
We present a transportable optical clock (TOC) with ^{87}Sr. Its complete characterization against a stationary lattice clock resulted in a systematic uncertainty of 7.4×10^{-17}, which is currently limited by the statistics of the determination of the residual lattice light shift, and an instability of 1.3×10^{-15}/sqrt[τ] with an averaging time τ in seconds. Measurements confirm that the systematic uncertainty can be reduced to below the design goal of 1×10^{-17}. To our knowledge, these are the best uncertainties and instabilities reported for any transportable clock to date. For autonomous operation, the TOC has been installed in an air-conditioned car trailer. It is suitable for chronometric leveling with submeter resolution as well as for intercontinental cross-linking of optical clocks, which is essential for a redefinition of the International System of Units (SI) second. In addition, the TOC will be used for high precision experiments for fundamental science that are commonly tied to precise frequency measurements and its development is an important step to space-borne optical clocks.


Early high-dose vitamin C in post-cardiac arrest syndrome (VITaCCA): study protocol for a randomized, double-blind, multi-center, placebo-controlled trial.
High-dose intravenous vitamin C directly scavenges and decreases the production of harmful reactive oxygen species (ROS) generated during ischemia/reperfusion after a cardiac arrest. The aim of this study is to investigate whether short-term treatment with a supplementary or very high-dose intravenous vitamin C reduces organ failure in post-cardiac arrest patients. This is a double-blind, multi-center, randomized placebo-controlled trial conducted in 7 intensive care units (ICUs) in The Netherlands. A total of 270 patients with cardiac arrest and return of spontaneous circulation will be randomly assigned to three groups of 90 patients (1:1:1 ratio, stratified by site and age). Patients will intravenously receive a placebo, a supplementation dose of 3 g of vitamin C or a pharmacological dose of 10 g of vitamin C per day for 96 h. The primary endpoint is organ failure at 96 h as measured by the Resuscitation-Sequential Organ Failure Assessment (R-SOFA) score at 96 h minus the baseline score (delta R-SOFA). Secondary endpoints are a neurological outcome, mortality, length of ICU and hospital stay, myocardial injury, vasopressor support, lung injury score, ventilator-free days, renal function, ICU-acquired weakness, delirium, oxidative stress parameters, and plasma vitamin C concentrations. Vitamin C supplementation is safe and preclinical studies have shown beneficial effects of high-dose IV vitamin C in cardiac arrest models. This is the first RCT to assess the clinical effect of intravenous vitamin C on organ dysfunction in critically ill patients after cardiac arrest. ClinicalTrials.gov NCT03509662. Registered on April 26, 2018. https://clinicaltrials.gov/ct2/show/NCT03509662 European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL.


Effects of circadian clock genes and health-related behavior on metabolic syndrome in a Taiwanese population: Evidence from association and interaction analysis.
Increased risk of developing metabolic syndrome (MetS) has been associated with the circadian clock genes. In this study, we assessed whether 29 circadian clock-related genes (including ADCYAP1, ARNTL, ARNTL2, BHLHE40, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, GSK3B, HCRTR2, KLF10, NFIL3, NPAS2, NR1D1, NR1D2, PER1, PER2, PER3, REV1, RORA, RORB, RORC, SENP3, SERPINE1, TIMELESS, TIPIN, VIP, and VIPR2) are associated with MetS and its individual components independently and/or through complex interactions in a Taiwanese population. We also analyzed the interactions between environmental factors and these genes in influencing MetS and its individual components. A total of 3,000 Taiwanese subjects from the Taiwan Biobank were assessed in this study. Metabolic traits such as waist circumference, triglyceride, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and fasting glucose were measured. Our data showed a nominal association of MetS with several single nucleotide polymorphisms (SNPs) in five key circadian clock genes including ARNTL, GSK3B, PER3, RORA, and RORB; but none of these SNPs persisted significantly after performing Bonferroni correction. Moreover, we identified the effect of GSK3B rs2199503 on high fasting glucose (P = 0.0002). Additionally, we found interactions among the ARNTL rs10832020, GSK3B rs2199503, PER3 rs10746473, RORA rs8034880, and RORB rs972902 SNPs influenced MetS (P < 0.001 ~ P = 0.002). Finally, we investigated the influence of interactions between ARNTL rs10832020, GSK3B rs2199503, PER3 rs10746473, and RORB rs972902 with environmental factors such as alcohol consumption, smoking status, and physical activity on MetS and its individual components (P < 0.001 ~ P = 0.002). Our study indicates that circadian clock genes such as ARNTL, GSK3B, PER3, RORA, and RORB genes may contribute to the risk of MetS independently as well as through gene-gene and gene-environment interactions.


Links Between Genetic Groups, Host Specificity, and Ergot-Alkaloid Profiles within Claviceps purpurea (Fr.) Tul. on Slovenian Grasses.
In the present study, the genetic relationships and ergot-alkaloid production of the fungus Claviceps purpurea on grasses were investigated, to determine any associations between grass host specificity, ergot-alkaloid production, and geographic origin. C. purpurea sclerotia were obtained from wild and cultivated grasses along a 300-km climatic gradient, from sub-Mediterranean to continental climates. Twenty-one infected grass samples provided 39 sclerotia for analysis of the ergot alkaloids ergometrine, ergosine, ergotamine, ergocornine, ergocryptine, and ergocristine, and their "-inine" epimers, using liquid chromatography-tandem mass spectrometry. C. purpurea ribosomal DNA underwent molecular classification to determine any grass host or geographic specificity of ergot-alkaloid composition for the different operational taxonomic units. Molecular analysis of sclerotia ribosomal DNA showed three genetic groups, with some associations with specific grass host taxonomic groups. The ergot-alkaloid composition data were in agreement with the data obtained by molecular methods. The most frequent ergot-alkaloid epimers were ergocristine, and ergosine. The total ergot-alkaloid concentrations in sclerotia varied from 59 to 4,200 mg kg-1, which corresponds to 0.059 to 4.2 mg kg-1 in animal feed (assuming ergot alkaloids at 1,000 mg kg-1 sclerotia). Therefore, grasses can be associated with significant levels of ergot alkaloids. In addition, the ergot-alkaloid compositions of C. purpurea sclerotia can be different for infections with different C. purpurea genetic groups, because these show different ergot-alkaloid compositions.


Lack of mutations in the TSHr and Gsalpha genes in TSHr antibody negative Graves' disease.
The aim of this study was to investigate whether TSHr antibody negative Graves' disease is associated with somatic mutations in the TSHr or Gsalpha genes and whether histopathologically defined thyroid lesions, i.e., hyperfunctioning adenoma, non-functioning follicular adenomas, or nodules in toxic and non-toxic multinodular goiters are associated with such mutations. No mutations but three germ-line polymorphisms were found in patients with TSHr antibody negative Graves' disease. The three polymorphisms are expected to have no or only minor effects on the signaling properties, and is not associated with altered antigenecity imposed by such mutations. Two heterozygous somatic TSHr mutations were found in two hyperfunctioning adenomas and in two toxic multinodular goiters. The lack of TSHr and Gsalpha mutations in TSHr antibody negative Graves' disease patients indicates that such mutations are neither primary nor secondary events in this disease. The results also confirm that somatic gain-of-function TSHr mutations are present in hyperfunctioning follicular adenomas and goiters, but not in non-functioning thyroid lesions.


[Pitfalls in medical expert evaluation. Of "credible" probands and "convincing" experts].
Periodical reading of medical expert opinions reveals deficient assessment-knowledge on the part of German physicians. Six characteristic cases are presented and discussed. The instructive examples show how careless doctors risk their reputation. Inadequate expert opinions are useless. Courts cannot judge correctly, administrations cannot decide in time, insurance companies cannot regulate reasonably. Finally inferior assessments harm more than they serve--especially the doctor's reputation.


Antimicrobial activity of silver nanoparticles encapsulated in poly-N-isopropylacrylamide-based polymeric nanoparticles.
In this study, we analyzed the antimicrobial activities of poly-N-isopropylacrylamide (pNIPAM)-based polymeric nanoparticles encapsulating silver nanoparticles (AgNPs). Three sizes of AgNP-encapsulating pNIPAM- and pNIPAM-NH2-based polymeric nanoparticles were fabricated. Highly stable and uniformly distributed AgNPs were encapsulated within polymeric nanoparticles via in situ reduction of AgNO3 using NaBH4 as the reducing agent. The formation and distribution of AgNPs was confirmed by UV-visible spectroscopy, transmission electron microscopy, and inductively coupled plasma optical emission spectrometry, respectively. Both polymeric nanoparticles showed significant bacteriostatic activities against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria depending on the nanoparticle size and amount of AgNO3 used during fabrication.


Measurement of three-dimensional track profiles on CR-39s based on the photometric stereo method.
To obtain more information about incident particles, a new method for measuring three-dimensional track profiles formed on CR-39s based on the photometric stereo method was developed. A new optical microscope system with 16 lasers and a complementary metal-oxide-semiconductor camera was built to automatically capture the reflecting track images illuminated by the laser beams from different angles, and the track profiles were three-dimensionally reconstructed using a self-developed software. To verify the reconstruction results of the track profiles, both the openings and depth were measured with an atomic force microscope. The results showed that the relative deviations between the two methods of the openings were about 5.5% and the deviations of the depth were about 8.0%. At present, the reconstruction speed of a three-dimensional track profile is a factor of 400 greater than that of the atomic force microscope. The new method shows great potential for rapid reconstruction of numerous track morphologies. It is expected to be helpful for further studies on the energy and angle discrimination of incident particles in the field of nuclear measurements.


Folding of the disulfide-bonded beta-sheet protein tendamistat: rapid two-state folding without hydrophobic collapse.
We investigated the reversible folding and unfolding reactions of the small 74 amino acid residue protein tendamistat. The secondary structure of tendamistat contains only beta-sheets and loop regions and the protein contains two disulfide bonds. Fluorescence-detected refolding kinetics of tendamistat (disulfide bonds intact) comprise of a major rapid fast reaction (tau = 10 ms in water) and two minor slow reactions. In the fast reaction 80% of the unfolded molecules are converted to native protein. The two slow reactions are part of a parallel slow folding pathway. On this pathway the rate-limiting step in the formation of native molecules is cis to trans isomerization of at least one of the three trans Xaa-Pro peptide bonds. This reaction is catalyzed efficiently by the enzyme peptidyl-prolyl cis-trans isomerase. Comparison of kinetic data with equilibrium unfolding transitions shows that the fast folding pathway follows a two-state process without populated intermediate states. Additionally, various sensitive tests did not detect any rapid chain collapse during tendamistat folding prior to the acquisition of the native three-dimensional structure. These results show that pre-formed disulfide bonds do not prevent efficient and rapid protein folding.


Predictive value of initial FDG-PET features for treatment response and survival in esophageal cancer patients treated with chemo-radiation therapy using a random forest classifier.
In oncology, texture features extracted from positron emission tomography with 18-fluorodeoxyglucose images (FDG-PET) are of increasing interest for predictive and prognostic studies, leading to several tens of features per tumor. To select the best features, the use of a random forest (RF) classifier was investigated. Sixty-five patients with an esophageal cancer treated with a combined chemo-radiation therapy were retrospectively included. All patients underwent a pretreatment whole-body FDG-PET. The patients were followed for 3 years after the end of the treatment. The response assessment was performed 1 month after the end of the therapy. Patients were classified as complete responders and non-complete responders. Sixty-one features were extracted from medical records and PET images. First, Spearman's analysis was performed to eliminate correlated features. Then, the best predictive and prognostic subsets of features were selected using a RF algorithm. These results were compared to those obtained by a Mann-Whitney U test (predictive study) and a univariate Kaplan-Meier analysis (prognostic study). Among the 61 initial features, 28 were not correlated. From these 28 features, the best subset of complementary features found using the RF classifier to predict response was composed of 2 features: metabolic tumor volume (MTV) and homogeneity from the co-occurrence matrix. The corresponding predictive value (AUC = 0.836 ± 0.105, Se = 82 ± 9%, Sp = 91 ± 12%) was higher than the best predictive results found using the Mann-Whitney test: busyness from the gray level difference matrix (P < 0.0001, AUC = 0.810, Se = 66%, Sp = 88%). The best prognostic subset found using RF was composed of 3 features: MTV and 2 clinical features (WHO status and nutritional risk index) (AUC = 0.822 ± 0.059, Se = 79 ± 9%, Sp = 95 ± 6%), while no feature was significantly prognostic according to the Kaplan-Meier analysis. The RF classifier can improve predictive and prognostic values compared to the Mann-Whitney U test and the univariate Kaplan-Meier survival analysis when applied to several tens of features in a limited patient database.


Effects of general anesthetics and pressure on mammalian excitatory receptors expressed in Xenopus oocytes.
The effects of general anesthetics and pressure on receptors from the mammalian central nervous system have been investigated using oocyte expression techniques. Poly A+ mRNA extracted from rat whole brain was injected into mature Xenopus oocytes producing depolarizing responses to the fast excitatory neurotransmitters NMDA and kainate and the inhibitory neurotransmitters GABA and glycine. An apparatus was constructed to allow agonist dose-response curves to be determined at high pressures using voltage-clamped oocytes. This was used to investigate the excitatory transmitter kainate. It was found that anesthetics depress the current induced by kainate whereas pressure does not appear to affect the responses associated with this transmitter. Furthermore it was found that pressure does not reverse (or modify in any way) the changes in response brought about by application of anesthetics.


A Graphic Encoding Method for Quantitative Classification of Protein Structure and Representation of Conformational Changes.
In order to successfully predict a proteins function throughout its trajectory, in addition to uncovering changes in its conformational state, it is necessary to employ techniques that maintain its 3D information while performing at scale. We extend a protein representation that encodes secondary and tertiary structure into fix-sized, color images, and a neural network architecture (called GEM-net) that leverages our encoded representation. We show the applicability of our method in two ways: (1) performing protein function prediction, hitting accuracy between 78 and 83 percent, and (2) visualizing and detecting conformational changes in protein trajectories during molecular dynamics simulations.


A Social Media-Based Acute Alcohol Consumption Behavior (NekNomination): Case Series in Italian Emergency Departments.
NekNomination, also known as NekNominate, Neck and Nominate, or Neck Nomination, is a social network-based drinking game which is thought to have originated in Australia and spread all over the world between 2013 and 2014. Individuals record videos of themselves while rapidly drinking excessive quantities of alcoholic drinks (necking) and then nominate friends to outdo them within 24 hours; the videos are then posted on social media such as Facebook or YouTube. The consequences of this drinking game have been very dangerous; at least 5 people under age 30 years have died after drinking deadly cocktails, and many others have suffered from alcohol intoxication. The goal of the research is to evaluate data about clinically important acute alcohol intoxication among teenagers and young adults and inform and educate the general public, especially parents, teachers, and health workers, about the spreading craze of dangerous Internet-related behavior among today's teenagers and young people up to the age of 23 years. Patients aged 15 to 23 years with acute alcohol intoxication who came to the emergency department (ED) of 2 major hospitals in Italy from January 1, 2011, to June 30, 2014, were included in this study. Data were retrieved from prehospital and intrahospital medical records and included personal information, methods of intoxication, triage color code, date and time of access to the ED, any relevant signs and symptoms, blood alcohol concentration, and diagnosis at discharge. A total of 450 young patients (male 277/450, 61.5%, female 173/450, 38.5%; age 15 to 16 years 15/450, 3.3%, age 17 to 18 years 184/450, 40.9%, age 19 to 23 years 251/450, 55.8%) were recruited. The causes of intoxication were happy hour, binge drinking, NekNominate, eyeballing, other alcoholic games, or a mix of them. Happy hour was found to be more common among the older patients, whereas NekNominate accounted for almost half of the youngest group of hospitalizations. Eyeballing occurred in 1.6% (7/450) of cases; binge drinking and other alcoholic games caused 23.3% (105/450) and 23.8% (107/450) of hospitalizations, respectively. On admission, 44.2% (199/450) of patients were assigned a red or yellow color code requiring immediate medical attention; about 14% of them required additional medical assistance (after being in the ED) or hospitalization, some in semi-intensive care units. Our study shows that the increased numbers of hospitalizations due to alcohol intoxication in the adolescent age group, as a consequence of NekNominate or other drinking games, is alarming and represents a serious public health issue. The potential markers of improper use of social networks must be clearly identified, including categories at risk of alcohol abuse, in order to develop intervention and prevention strategies in terms of education and awareness, which may help in averting potentially fatal episodes.


Investigative cases and student outcomes in an upper-division cell and molecular biology laboratory course at a minority-serving institution.
Active-learning strategies are increasingly being integrated into college-level science courses to make material more accessible to all students and to improve learning outcomes. One active-learning pedagogy, case-based learning (CBL), was developed as a way to both enhance engagement in the material and to accommodate diverse learning styles. Yet, adoption of CBL approaches in undergraduate biology courses has been piecemeal, in part because of the perceived investment of time required. Furthermore, few CBL lesson plans have been developed specifically for upper-division laboratory courses. Here, we describe four cases that we developed and implemented for a senior cell and molecular biology laboratory course at San Francisco State University, a minority-serving institution. To evaluate the effectiveness of these modules, we used both written and verbal assessments to gauge learning outcomes and attitudinal responses of students over two semesters. Students responded positively to the new approach and seemed to meet the learning goals for the course. Most said they would take a course using CBL again. These case modules are readily adaptable to a variety of classroom settings.


Chemoprevention of colorectal cancer by black raspberry anthocyanins involved the modulation of gut microbiota and SFRP2 demethylation.
Freeze-dried black raspberry (BRB) powder is considered as a potential cancer chemopreventive agent. In this study, we fed azoxymethane (AOM)/dextran sodium sulfate (DSS)-treated C57BL/6J mice with a diet containing BRB anthocyanins for 12 weeks, and this led to a reduction in colon carcinogenesis. These animals had consistently lower tumor multiplicity compared with AOM/DSS-treated mice not receiving BRB anthocyanins. In AOM/DSS-treated mice, the number of pathogenic bacteria, including Desulfovibrio sp. and Enterococcus spp., was increased significantly, whereas probiotics such as Eubacterium rectale, Faecalibacterium prausnitzii and Lactobacillus were dramatically decreased, but BRB anthocyanins supplement could reverse this imbalance in gut microbiota. BRB anthocyanins also caused the demethylation of the SFRP2 gene promoter, resulting in increased expression of SFRP2, both at the mRNA and protein levels. Furthermore, the expression levels of DNMT31 and DNMT3B, as well as of p-STAT3 were downregulated by BRB anthocyanins in these animals. Taken together, these results suggested that BRB anthocyanins could modulate the composition of gut commensal microbiota, and changes in inflammation and the methylation status of the SFRP2 gene may play a central role in the chemoprevention of CRC.


Multimodality Treatment Outcome of Hepatoblastoma in a Resource Limited Country.
Our objective is to review the records of management of hepatoblastoma (HB) at the Paediatric Haematology and Oncology (PHO) department in the Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2004 to December 2012. This is a retrospective study of clinical, radiological and pathological data of hepatoblastoma patients treated at our institution. Thirteen patients were treated for HB between 2004 and 2012. The records of clinical presentations, chemotherapy tolerance and response, surgical procedure undertaken, and complications were analyzed. Median age of the study population was 12 months (3-60 months) and male: female was 3.3:1. Nine patients were treated with neoadjuvant chemotherapy consists of cisplatin and adriamycin. Primary surgery was done in four patients. Extent of hepatic resection in the operated patients varied. Mixed type was the predominant histopathological diagnosis. Adjuvant chemotherapy was well tolerated with no morbidity or mortality. Five-year event-free survival (EFS) and overall survival (OS) of all the 13 patients is 76.9%. All the nine patients who could complete multimodality treatment are alive with no evidence of disease or complications with median follow-up of 63 months (46-122 months). Treatment of HB with multidisciplinary approach was well tolerated. OS and EFS of patients were comparable with published studies.


Novel perspectives on gastrointestinal stromal tumors (GISTs).
Since they were described, gastrointestinal stromal tumors (GISTs) are, for pathologists and not only for them, a subject of controversy regarding histological origin, differentiation, nomenclature, malignant potential and prognosis. Before 1998, there were no certainties that GISTs were fundamentally different from other types of abdominal cancers in the big family of mesenchymal tumors. Before the discovery of KIT gene mutations, GISTs were most often classified as leiomyoma, leiomyosarcoma, leiomyoblastoma, and gastrointestinal autonomic nerve tumor. When a tumor is discovered, the first data obtained are initially assessed by one or more imaging tests, such as an ultrasound, computed tomography scan or magnetic resonance imaging. The imaging results define the size of the lesion and its anatomic location, which in the case of GIST is usually within the wall of the stomach or intestine. Depending on the experience of the medical team - radiologist, gastroenterologist or surgeon - reviewing the imagistic tests and correlating them with the general patient profile, the differential diagnostic is reduced and GIST may become the main suspect.


Biogenesis, Mode of Action and the Interactions of Plant Non-Coding RNAs.
The central dogma of genetics, which outlines the flow of genetic information from DNA to RNA to protein, has long been the guiding principle in molecular biology. In fact, more than three-quarters of the RNAs produced by transcription of the plant genome are not translated into proteins, and these RNAs directly serve as non-coding RNAs in the regulation of plant life activities at the molecular level. The breakthroughs in high-throughput transcriptome sequencing technology and the establishment and improvement of non-coding RNA experiments have now led to the discovery and confirmation of the biogenesis, mechanisms, and synergistic effects of non-coding RNAs. These non-coding RNAs are now predicted to play important roles in the regulation of gene expression and responses to stress and evolution. In this review, we focus on the synthesis, and mechanisms of non-coding RNAs, and we discuss their impact on gene regulation in plants.


Both core- and shell-cross-linked nanogels: photoinduced size change, intraparticle LCST, and interparticle UCST thermal behaviors.
New thermal- and photoresponsive core-shell nanogel particles were obtained from self-assembly in aqueous solution of a double-hydrophilic block copolymer (DHBCP) of which the two blocks could be photo-cross-linked via the reversible photodimerization and photocleavage of coumarin moieties. The diblock copolymer, consisting of poly[N,N-dimethylacrylamide-co-4-methyl-[7-(methacryloyl)oxyethyloxy]coumarin] and poly[N-isopropylacrylamide-co-4-methyl-[7-(methacryloyl)oxyethyloxy]coumarin] (P(DMA-co-CMA)-b-P(NIPAM-co-CMA)), was synthesized by using reversible addition-fragmentation chain transfer (RAFT) polymerization. At T > LCST of the P(NIPAM-co-CMA) block, core-shell micelles were formed and UV light irradiation at λ > 310 nm resulted in cross-linking of both the micelle core of P(NIPAM-co-CMA) and the micelle shell of P(DMA-co-CMA); subsequent cooling of the solution to T < LCST gave rise to water-soluble, swollen nanogel particles. Upon UV light irradiation at λ < 260 nm, the decrease of cross-linking density could increase the swelling of nanogel particles by ∼23% in diameter. By alternating irradiation with the different wavelengths, the average hydrodynamic diameter of nanogel particles was tunable between ∼58 and ∼47 nm. Interestingly, upon further cooling of the solution, aggregation occurred for nanogel particles with a moderate cross-linking density (10%-40% dimerization of coumarin moieties). Therefore, such core- and shell-cross-linked nanogel could display both "intraparticle" LCST (solubility of polymer chains forming the core) and "interparticle" UCST (solubility of particles). The possible mechanism and the effect of dimerization degree on the UCST behavior were discussed.


Risk factors for impaired length growth in early life viewed in terms of the infancy-childhood-puberty (ICP) growth model.
A difference in length or height growth is observed between populations in developing and developed countries and, within a country, between well-off and poor subpopulations. The aim of this community-based study was to identify possible risk factors for growth stunting in early life using the infancy-childhood-puberty (ICP) growth model. A periurban slum, a village and an urban slum, plus a local control group in Lahore, Pakistan, were investigated. In total, there were 425 infants born from September 1984 to March 1987 in the study. Children were followed from birth to 24 months and anthropometric data were recorded at each examination. A well-designed questionnaire was used to collect background information to identify risk factors for growth faltering over this period. The age at onset of the childhood component was determined individually using the ICP growth model. A late onset was defined as onset after 12 months. Univariate odds ratio analysis identified 20 significant risk factors for a delayed childhood onset in the total sample. Backward logistical analysis showed that only six variables were significant, i.e. small number of rooms in a household, episode(s) of diarrhoeal diseases, poor house structure, low body mass index, early end of breastfeeding and birth in warm season. Stratified analysis showed that episode(s) of diarrhoeal diseases and birth in warm season were the only significant risk factors in the two poor areas. This study also found that the impact of diarrhoeal diseases on length growth persisted after allowing for birth season. Seasonal variation in length growth was seen in the age at onset of the childhood component. General socioeconomic status was found to be a risk factor for growth faltering in early life. Diarrhoeal diseases and being born in a warm season are particular risk factors for growth faltering in early life.


Structure of human promyeloperoxidase (proMPO) and the role of the propeptide in processing and maturation.
Myeloperoxidase (MPO) is synthesized by neutrophil and monocyte precursor cells and contributes to host defense by mediating microbial killing. Although several steps in MPO biosynthesis and processing have been elucidated, many questions remained, such as the structure-function relationship of monomeric unprocessed proMPO versus the mature dimeric MPO and the functional role of the propeptide. Here we have presented the first and high resolution (at 1.25 Å) crystal structure of proMPO and its solution structure obtained by small-angle X-ray scattering. Promyeloperoxidase hosts five occupied glycosylation sites and six intrachain cystine bridges with Cys-158 of the very flexible N-terminal propeptide being covalently linked to Cys-319 and thereby hindering homodimerization. Furthermore, the structure revealed (i) the binding site of proMPO-processing proconvertase, (ii) the structural motif for subsequent cleavage to the heavy and light chains of mature MPO protomers, and (iii) three covalent bonds between heme and the protein. Studies of the mutants C158A, C319A, and C158A/C319A demonstrated significant differences from the wild-type protein, including diminished enzymatic activity and prevention of export to the Golgi due to prolonged association with the chaperone calnexin. These structural and functional findings provide novel insights into MPO biosynthesis and processing.


Effect of high cell density on the growth properties of tumor cells: a role in tumor cytotoxicity of chemotherapeutic drugs.
The aim of this study was to understand the role of tumor progression in the growth properties of tumor cells and their susceptibility to the cytotoxicity of chemotherapeutic drugs. A murine transplantable T cell lymphoma of spontaneous origin, designated as Dalton's lymphoma, was used as a model tumor for this investigation. Tumor cells were harvested from the early (5 days after tumor transplantation) and late tumor-bearing stages (17 days after tumor transplantation), with or without in-vivo administration of the chemotherapeutic drugs, cisplatin or doxorubicin. Tumor cells harvested at the late tumor-bearing stages showed a higher proliferative ability in vitro. Tumor progression was found to be associated with a decline in the tumor cytotoxicity of the chemotherapeutic drugs. Similar results were also obtained when tumor cells were cultured at low (10(5) cells/ml) and high (10(9) cells/ml) cell densities in vitro in medium alone or in one containing the chemotherapeutic drugs. An increase in the expression of heat shock protein (Hsp70), vascular endothelial growth factor, interleukin-2 receptor and interleukin-2 proteins along with an inhibition in the expression of caspase-activated DNase and p53 proteins was observed during the late tumor-bearing stage and also in the Dalton's lymphoma cells when cultured in vitro at a higher cell density. The ascitic fluid obtained from the late tumor-bearing stage and the culture supernatant of tumor cells incubated in vitro at high cell density showed high levels of cell growth-regulating cytokines: interleukin-1, interleukin-2, interferon-gamma, vascular endothelial growth factor, tumor growth factor-beta and interleukin-10. In-vivo administration of cisplatin in tumor-bearing mice at the late tumor-bearing stage did not alter the level of these cytokines in the ascitic fluid. In view of the results of this investigation, it is suggested that under high cellular density-associated environmental conditions the tumor cells alter their growth properties depending on an alteration in the expression of cell growth and apoptosis-regulating proteins. Tumor cells, thus, switch to a high level of proliferation, which renders them resistant to the cytotoxicity of chemotherapeutic drugs.


Stage-specific gene expression during sexual development in Phytophthora infestans.
Eight genes that are upregulated during sexual development in the heterothallic oomycete, Phytophthora infestans, were identified by suppression subtractive hybridization. Two genes showed very low but detectable expression in vegetative hyphae and became induced about 40- to >100-fold early in mating, before gametangial initials appeared. The remaining six loci were not induced until later in mating, coincident with the formation of gametangia and oospores, with induction levels ranging from 60- to >100-fold. Five genes were single copy, and three were members of families. Sequence analysis revealed that the predicted products of three of the genes had similarity to proteins that influence RNA stability, namely a ribonuclease activator, the pumilio family of RNA-binding proteins and RNase H. The products of two other mating-induced genes resembled two types of Phytophthora proteins previously shown to elicit plant defence responses. Each mating-induced gene was also expressed in a self-fertile strain, which was shown to be a heterokaryon. However, quantitative and qualitative differences existed in their expression in normal matings and in the self-fertile heterokaryon. Besides the mating-induced genes, two extrachromosomal RNA elements were identified.


Molecular basis of the phenotypic variants arising from a Pseudoalteromonas lipolytica mutator.
Bacterial deficiencies in the DNA repair system can produce mutator strains that promote adaptive microevolution. However, the role of mutator strains in marine Pseudoalteromonas, capable of generating various gain-of-function genetic variants within biofilms, remains largely unknown. In this study, inactivation of mutS in Pseudoalteromonas lipolytica conferred an approximately 100-fold increased resistance to various antibiotics, including ciprofloxacin, rifampicin and aminoglycoside. Furthermore, the mutator of P. lipolytica generated variants that displayed enhanced biofilm formation but reduced swimming motility, indicating a high phenotypic diversity within the ΔmutS population. Additionally, we observed a significant production rate of approximately 50 % for the translucent variants, which play important roles in biofilm formation, when the ΔmutS strain was cultured on agar plates or under shaking conditions. Using whole-genome deep-sequencing combined with genetic manipulation, we demonstrated that point mutations in AT00_17115 within the capsular biosynthesis cluster were responsible for the generation of translucent variants in the ΔmutS subpopulation, while mutations in flagellar genes fliI and flgP led to a decrease in swimming motility. Collectively, this study reveals a specific mutator-driven evolution in P. lipolytica, characterized by substantial genetic and phenotypic diversification, thereby offering a reservoir of genetic attributes associated with microbial fitness.


The mechanism of template activation by exonuclease V.
In crude extracts from Escherichia coli cells the ATP-dependent exonuclease V was found to be most active in converting double-stranded DNA into a suitable template for DNA polymerase. This phenomenon was studied in some detail with isolated exonuclease V and T7 DNA polymerase. We found that, at ATP concentrations arount 1 mM, the exonuclease produces a broad spectrum of DNA fragments. One class of fragments is largely single stranded with hydrogen-bonded small primer sequences. These structures allow the synthesis of remarkably homogeneous polynucleotide strands by T7 DNA polymerase.


Epidemiology of unintentional childhood injuries in urban and rural areas of Nepal- A comparative study.
Unintentional injuries are one of the leading causes of ill health, disability & death among the children and young adults worldwide. As these injuries are strongly related to social determinants, the burden falls mainly upon the Low- and Middle-Income Countries (LMICs) like Nepal. Thus, the main objective was to explore the epidemiology of unintentional childhood injuries in urban and rural areas of Kavrepalanchok district. A cross sectional analytical study was done in Bethanchok rural municipality and Dhulikhel municipality of Kavrepalanchok district. The respondents were interviewed using a pretested semi-structured questionnaire. The details of injuries sustained within the past 12 months were included. A total of 667 children aged 1-16 years were surveyed, among which 26% from rural and 17.2% from urban areas had unintentional injuries in the past 12 months. Falls were the most common mode of injury in both the areas. Similarly, the proportion of burn was more in rural area (16.1%) whereas, Road Traffic Injuries were more in urban area (12.5%). Majority of the injuries occurred at home (54.5%) while the child was playing (64.1%). Factors like child's gender and place of residence affected the occurrence of unintentional injuries (p<0.05). Out of total injured children, 18 of them had not recovered and 11 were left with some form of permanent disability. As the rate and pattern of unintentional childhood injuries in the rural and urban area differ, the prevention strategies should focus on risk factors that apply to both the areas and awareness should be created among the parents and primary caregivers about the fact that childhood injuries are predictable and preventable.


Structurally stable but functionally disrupted marine microbial communities under a future climate change scenario: Potential importance for nitrous oxide emissions.
The blue mussel Mytilus edulis is a widespread and abundant bivalve species along the North Sea with high economic and ecological importance as an engineer species. The shell of mussels is intensively colonized by microbial organisms that can produce significant quantities of nitrous oxide (N2O), a potent greenhouse gas. To characterize the impacts of climate change on the composition, structure and functioning of microbial biofilms on the shell surface of M. edulis, we experimentally exposed them to orthogonal combinations of increased seawater temperature (20 vs. 23 °C) and decreased pH (8.0 vs. 7.7) for six weeks. We used amplicon sequencing of the 16S rRNA gene to characterize the alpha and beta diversity of microbial communities on the mussel shell. The functioning of microbial biofilms was assessed by measuring aerobic respiration and nitrogen emission rates. We did not report any significant impacts of climate change treatments on the diversity of mussel microbiomes nor on the structure of these communities. Lowered pH and increased temperature had antagonistic effects on the functioning of microbial communities with decreased aerobic respiration and N2O emission rates of microbial biofilms in acidified seawater compared to increased rates in warmer conditions. An overriding impact of acidification over warming was finally observed on N2O emissions when the two factors were combined. Although acidification and warming in combination significantly reduced N2O biofilm emissions, the promotion of aquaculture activities in coastal waters where shellfish do not normally occur at high biomass and density could nonetheless result in unwanted emissions of this greenhouse gas in a near future.


Correlations of total pelvic spongiosa volume with both anthropometric parameters and computed tomography-based skeletal size measurements.
Patient-specific dosimetry within the field of molecular radiotherapy continues to pose a challenge owing to the difficulty in predicting marrow toxicity. This study examined the correlation between total pelvic spongiosa volume (TPSV) and independent variables, which include both readily measured or calculated anthropometric parameters (AP), and image-based skeletal measurements requiring computed tomography (CT) images or skeletal radiographs. Fourteen (14) patients (5 male and 9 female) undergoing total hip arthroplasty (THA) were subjected to modified pelvic CT scans. These scans were utilized to estimate TPSV, which was comprised of the volumes of spongiosa within the L5 vertebra, os coxae, sacrum, and both proximal femurs. The APs investigated included total body height (TBH), total body mass (TBM), body mass index (BMI), body surface area (BSA), maximum effective mass (MEM), lean body mass (LBM), and fat-free mass (FFM). Skeletal measurements were also obtained from the CT images of the pelvic region. Correlation coefficients (r) were obtained for TPSV and each set of APs as well as each set of skeletal measurements. Total body height (r = 0. 80) and os coxae height (r = 0.83) had the highest correlation coefficients of all the APS and skeletal measurements, respectively. FFM (r = 0.50), LBM (r = 0.42), TBM (r = 0.11), and BSA (r = 0.11) did not correlate well with TPSV, which accounts for approximately 45% of total spongiosa seen throughout the skeleton at sites associated with active bone marrow. Skeletal height measurements appear to have a much higher correlation with TPSV than either their corresponding skeletal width measurements or parameters that are a function of an individual's TBM.


Pharmacokinetics and Pharmacodynamics of Minocycline against Acinetobacter baumannii in a Neutropenic Murine Pneumonia Model.
Multidrug-resistant (MDR) Acinetobacter baumannii is increasingly more prevalent in nosocomial infections. Although in vitro susceptibility of A. baumannii to minocycline is promising, the in vivo efficacy of minocycline has not been well established. In this study, the in vivo activity of minocycline was evaluated in a neutropenic murine pneumonia model. Specifically, we investigated the relationship between minocycline exposure and bactericidal activity using five A. baumannii isolates with a broad range of susceptibility (MIC ranged from 0.25 mg/liter to 16 mg/liter). The pharmacokinetics of minocycline (single dose of 25 mg/kg of body weight, 50 mg/kg, 100 mg/kg, and a humanized regimen, given intraperitoneally) in serum and epithelial lining fluid (ELF) were characterized. Dose linearity was observed for doses up to 50 mg/kg and pulmonary penetration ratios (area under the concentration-time curve in ELF from 0 to 24 h [AUCELF,0-24]/area under the concentration time curve in serum from 0 to 24 h [AUCserum,0-24]) ranged from 2.5 to 2.8. Pharmacokinetic-pharmacodynamics (PK-PD) index values in ELF for various dose regimens against different A. baumannii isolates were calculated. The maximum efficacy at 24 h was approximately 1.5-log-unit reduction of pulmonary bacterial burdens from baseline. The AUC/MIC ratio was the PK-PD index most closely correlating to the bacterial burden (r2 = 0.81). The required AUCELF,0-24/MIC for maintaining stasis and achieving 1-log-unit reduction were 140 and 410, respectively. These findings could guide the treatment of infections caused by A. baumannii using minocycline in the future. Additional studies to examine resistance development during therapy are warranted.


Experimental Colonization of Sand Flies (Lutzomyia longipalpis; Diptera: Psychodidae) by Bartonella ancashensis.
Background: Bartonella ancashensis is a recently described Bartonella species endemic to Peru, where it causes verruga peruana in humans. While the arthropod vector of B. ancashensis transmission is unknown, human coinfections with Bartonella bacilliformis suggest that phlebotomine sand flies are a vector. Materials and Methods: To address the hypothesis that sand flies are involved in the bacterium's transmission, Lutzomyia longipalpis sand flies were used as an infection model, together with green fluorescent protein-expressing B. ancashensis. Results: Results showed that bacterial infections were clearly established, limited to the anterior midgut of the female fly, and maintained for roughly 7 days. At 3-7 days postinfection, a prominent microcolony of aggregated bacteria was observed in the anterior midgut, immediately distal to the stomodeal valve of the esophagus. In contrast, eggs, diuretic fluid, feces, and other tissues were not infected. Conclusion: These results suggest that certain sand fly species within the endemic zone for B. ancashensis may play a role in the bacterium's maintenance and possibly in its transmission to humans.