Organization and characterization of the capsule biosynthesis locus of Streptococcus pneumoniae serotype 9V.
The capsular polysaccharide (CPS) synthesis locus of Streptococcus pneumoniae serotype 9V was amplified by long-range PCR and sequenced. The locus was 17368 bp in size and contained 15 ORFs. The genetic organization of the cluster shared many features with other S. pneumoniae capsule loci, including the presence of four putative regulatory genes at the 5' end. Comparative sequence analyses allowed putative functions to be assigned to each of the gene products. The ORFs appeared to encode, besides the four regulatory genes, five glycosyltransferases, two O-acetyltransferases, an N-acetylglucosamine 2-epimerase, a glucose 6-dehydrogenase, an oligosaccharide transporter protein and a polysaccharide repeating unit polymerase. These functions covered the steps proposed in the CPS biosynthesis of serotype 9V. TLC of carbohydrate intermediates formed after incubation of bacterial membrane preparations with 14C-labelled precursors demonstrated that the fifth ORF (cps9vE) encoded a UDP-glucosyl-1-phosphate transferase. This function was confirmed with the help of a cps9vE mutant that carried a deletion of a guanine residue located adjacent to a stretch of adenines. The identification and characterization of the serotype 9V locus is a major step in unravelling the 9V capsule biosynthesis pathway and broadens the insight into the genetic diversity of the S. pneumoniae capsule loci.


Adult or not? Accuracy of Cameriere's cut-off value for third molar in assessing 18 years of age for legal purposes.
The discovery of reliable means to determine the age of an individual is a fundamental objective in forensic medicine, in consideration of the constant increase of illegal immigration into the European community. In 2008 Cameriere et al. developed a method based on the relationship between age and the third molar index (I3m), which assesses the degree of maturation of the third molar through measurements made on orthopantomography. The purpose of this work was to test the accuracy of Cameriere's cut-off for I3m as a tool to assess full age (18) on a new sample of living subjects. Orthopantomographs of 287 Italian living subjects aged between 13 and 22 years have been randomly selected and included in the study. Identification number, gender, date of birth and date of execution of the radiograph were recorded for each patient on a Microsoft Excel® spreadsheet. Radiographs were digitalized and analyzed using a computerized image-processing program (Adobe® Photoshop® CS4). The results show that the sensitivity of the test was 84.1% and the specificity was 92.5%. The estimated post-test probability was 90.1%, with a confidence interval of 95% (83.6%, 95.2%). Thus, the probability that a person being positive to the test has 18 or more years of age was 90.1%. The results highlight the contribution of Cameriere's cut-off value for the I3m in the assessment of full age, always remembering that the simultaneous employment of previously introduced complementary methods is essential for the purpose.


Evaluation of the Role of Propolis and a New Herbal Ointment in Promoting Healing of Traumatic Oral Ulcers: An Animal Experimental Study.
Most of the currently used medications for the treatment of oral ulcers focus primarily on providing symptomatic relief and preventing secondary infections. Not much attention has been paid in the past on agents that can promote healing of these lesions. In the current study, we have tested and compared the efficacy of such wound healing promoting agents i.e. Propolis (product obtained from Bees) and a newly developed herbal ointment (containing extracts of Azadirachta indica (Neem), Linum usitatissimum L.(Linseed) oil, and resin of Shorea robusta) in experimental rabbits. Traumatic oral ulcers were inflicted in experimental rabbits (New Zealand white) with the help of a punch biopsy instrument. The animals were then divided into three groups each group consisted of 12 animals (n = 12), Group I was the untreated control group and Group II was topically treated with nonalcohol extract of propolis and Group III was treated with newly developed herbal ointment. Histological healing scores of the ulcers were evaluated on day 7 and day 14. Data were statistically analyzed using descriptive and inferential statistic methods. In Group III treated with newly developed herbal ointment, significantly higher healing scores, in comparison to the untreated control group (Group I) and propolis (Group II) was observed on day 7 and 14. Improved healing scores in prapolis-treated group were observed than the untreated control group. However, the difference was not statistically significant on both day 7 and day 14. With the newly developed herbal ointment, superior healing of traumatic oral ulcers was observed.


[Post-primary functional soft tissue coverage after extensive muscle-/soft tissue loss of the upper extremity].
Two cases of severe contusion/avulsion injuries of the upper extremity with involvement of the neuro-vascular structures and extensive muscle necrosis after post-ischemic syndrome (PIS) are demonstrated. The concept of early post-primary soft tissue coverage and the opportunity of a simultaneous "functional" soft-tissue replacement with pedicled neuro-vascular myocutaneous island flaps is elucidated.


π-Conjugated polymer anisotropic organogel nanofibrous assemblies for thermoresponsive photonic switches.
The present work demonstrates one of the first examples of π-conjugated photonic switches (or photonic wave plates) based on the tailor-made π-conjugated polymer anisotropic organogel. New semicrystalline segmented π-conjugated polymers are designed with rigid aromatic oligophenylenevinylene π-core and flexible alkyl chain along the polymer backbone. These polymers are found to be self-assembled as semicrystalline or amorphous with respect to the number of carbon atoms in the alkyl units. These semicrystalline polymers produce organogels having nanofibrous morphology of 20 nm thickness with length up to 5 μm. The polymer organogel is aligned in a narrow glass capillary, and this anisotropic gel device is further demonstrated as photonic switches. The glass capillary device behaves as typical λ/4 photonic wave plates upon the illumination of the plane polarized light. The λ/4 photonic switching ability is found to be maximum at θ = 45° angle under the cross polarizers. The orthogonal arrangements of the gel capillaries produce dark and bright spots as on-and-off optical switches. Thermoreversibility of the polymer organogel (also its xerogel) was exploited to construct thermoresponsive photonic switches for the temperature window starting from 25 to 160 °C. The organic photonic switch concept can be adapted to large number of other π-conjugated materials for optical communication and storage.


Differential Diagnosis of Cysts and Granulomas Supported by Texture Analysis of Intraoral Radiographs.
The aim of this study was to evaluate whether textural analysis could differentiate between the two common types of lytic lesions imaged with use of radiography. Sixty-two patients were enrolled in the study with intraoral radiograph images and a histological reference study. Full textural analysis was performed using MaZda software. For over 10,000 features, logistic regression models were applied. Fragments containing lesion edges were characterized by significant correlation of structural information. Although the input images were stored using lossy compression and their scale was not preserved, the obtained results confirmed the possibility of distinguishing between cysts and granulomas with use of textural analysis of intraoral radiographs. It was shown that the important information distinguishing the aforementioned types of lesions is located at the edges and not within the lesion.


Flow cytometric detection of unbalanced ram spermatozoa from heterozygous 1;20 translocation carriers.
Flow cytometric analysis of enzymatically decondensed, DAPI-stained spermatozoa was performed to confirm the suspected production of unbalanced spermatozoa in heterozygous rams carrying a 1;20 translocation. High-precision flow cytometry (coefficient of variation, 0.6-0.8%) with a PAS II flow cytometer depicted Y- and X-chromosome-bearing spermatozoa from three cytogenetically normal rams as two distinct peaks. The difference in DNA fluorescence intensity between the gonosomes averaged 4.8%. Analysis of sperm samples from three heterozygous 1;20 translocation carriers yielded histograms with five peak distributions. The individual peaks were attributed to spermatozoa with a normal, balanced, and unbalanced chromosomal status. Peaks within Y- and X-spermatozoa populations were distributed in a ratio of 1:2:1 and were almost completely separated, with a coefficient of variation of 0.5-0.6%. Owing to the relative size of the translocated chromosomal segment (2.4% of the total DNA content, as determined from the flow cytometric data), histograms with five instead of the expected six peaks were observed.


High-level ciprofloxacin resistance among hospital-adapted Enterococcus faecium (CC17).
Hospital-adapted Enterococcus faecium differ from their colonising variants in humans and animals by additional genomic content. Molecular typing based on multilocus sequence typing (MLST) allows allocation of isolates to specific clonal complexes (CCs), such as CC17 for hospital-adapted strains. Acquired ampicillin resistance is a specific feature of these hospital isolates, especially in Europe. A few recent reports have described acquired high-level ciprofloxacin resistance as a supposed feature of hospital-adapted E. faecium strains. In the present retrospective analysis, ciprofloxacin minimum inhibitory concentrations (MICs) of 609 clinical isolates from German hospital patients (1997-2007) were determined and a breakpoint for high-level resistance was deduced (>16mg/L). Acquired high-level ciprofloxacin resistance was distributed among isolates of 26 different MLST types (all CC17), indicating a wide prevalence of this acquired resistance trait among the hospital-adapted E. faecium population. High-level ciprofloxacin resistance was linked to gyrA and parC mutations in 98 investigated isolates. Eleven different allele types or combinations thereof were identified. Their allocation to specific MLST and pulsed-field gel electrophoresis (PFGE) types revealed differences in the emergence and spread of corresponding mutations and strains.


[Anterior cervical hypertrichosis: case report].
The non-syndromic anterior cervical hypertrichosis (OMIM N° 600457) is a genetic disorder characterized by a patch of hair at the level of the laryngeal prominence. We present a 12-year-old boy with anterior cervical hypertrichosis and mild generalized hypertrichosis. He has no neurological, ophthalmological or skeletal anomalies. The clinical follow up is 10 years.


Risk analysis systems for veterinary biologicals: a regulator's tool box.
Recent advances in biology and technology have significantly improved our ability to produce veterinary biologicals of high purity, efficacy and safety, virtually anywhere in the world. At the same time, increasing trade and comprehensive trade agreements, such as the Uruguay Round of the General Agreement on Tariffs and Trade (GATT: now the World Trade Organisation [WTO]), have put pressure on governments to use scientific principles in the regulation of trade for a wide range of products, including veterinary biologicals. In many cases, however, nations have been reluctant to allow the movement of veterinary biologicals, due to the perceived threat of importing an exotic disease. This paper discusses the history of risk analysis as a decision support tool and provides examples of how this tool may be used in a science-based regulatory system for veterinary biologicals. A wide variety of tools are described, including qualitative, semi-quantitative and quantitative methods, most with a long history of use in engineering and the health and environmental sciences.


Protein dynamics in individual human cells: experiment and theory.
A current challenge in biology is to understand the dynamics of protein circuits in living human cells. Can one define and test equations for the dynamics and variability of a protein over time? Here, we address this experimentally and theoretically, by means of accurate time-resolved measurements of endogenously tagged proteins in individual human cells. As a model system, we choose three stable proteins displaying cell-cycle-dependant dynamics. We find that protein accumulation with time per cell is quadratic for proteins with long mRNA life times and approximately linear for a protein with short mRNA lifetime. Both behaviors correspond to a classical model of transcription and translation. A stochastic model, in which genes slowly switch between ON and OFF states, captures measured cell-cell variability. The data suggests, in accordance with the model, that switching to the gene ON state is exponentially distributed and that the cell-cell distribution of protein levels can be approximated by a Gamma distribution throughout the cell cycle. These results suggest that relatively simple models may describe protein dynamics in individual human cells.


CcpA represses the expression of the divergent cit operons of Enterococcus faecalis through multiple cre sites.
In Enterococcus faecalis the genes encoding the enzymes involved in citrate metabolism are organized in two divergent operons, citHO and oadHDB-citCDEFX-oadA-citMG (citCL locus). Expression of both operons is specifically activated by adding citrate to the medium. This activation is mediated by binding of the GntR-like transcriptional regulator (CitO) to the cis-acting sequences located in the cit intergenic region. Early studies indicated that citrate and glucose could not be co-metabolized suggesting some form of catabolite repression, however the molecular mechanism remained unknown. In this study, we observed that the citHO promoter is repressed in the presence of sugars transported by the Phosphoenolpyruvate:carbohydrate Phosphotranserase System (PTS sugars). This result strongly suggested that Carbon Catabolic Repression (CCR) impedes the expression of the activator CitO and the subsequent induction of the cit pathway. In fact, we demonstrate that CCR is acting on both promoters. It is partially relieved in a ccpA-deficient E. faecalis strain indicating that a CcpA-independent mechanism is also involved in regulation of the two operons. Furthermore, sequence analysis of the citH/oadH intergenic region revealed the presence of three putative catabolite responsive elements (cre). We found that they are all active and able to bind the CcpA/P-Ser-HPr complex, which downregulates the expression of the cit operons. Systematic mutation of the CcpA/P-Ser-HPr binding sites revealed that cre1 and cre2 contribute to citHO repression, while cre3 is involved in CCR of citCL. In conclusion, our study establishes that expression of the cit operons in E. faecalis is controlled by CCR via CcpA-dependent and -independent mechanisms.


Concise synthesis of capuramycin.
A concise total synthesis of capuramycin (1), a promising preclinical TB drug lead, is achieved by high-yield formations of the cyanohydrin 5a and 4'',5''-glycal derivative 12. Capuramycin can be synthesized in eight steps from the uridine building block 5a with >30% overall yield. The synthetic intermediates reported here are useful for generation of analogs to improve pharmacokinetic properties of capuramycin.


Physical characterization of the chromosomal rearrangements that accompany the transgene insertion in the chakragati mouse mutant.
The circling phenotype of the chakragati mouse is a result of a transgenic insertional mutation. The absence of the phenotype in mice heterozygous for the transgene insertion suggests that this is due to a loss of function of an endogenous gene. Efforts to identify this gene have led to a previous report that sequences flanking the transgene, D16Ros1 and D16Ros2, map 10 cM apart in wildtype mice. We present here physical mapping data indicating that the proximity of D16Ros1 and D16Ros2 in the ckr mouse is explained by a duplication of D16Ros2 and its insertion along with the transgene at D16Ros1. We further demonstrate that D16Ros1 sequences are also duplicated and that this duplication is also part of the insertion at the endogenous D16Ros1 locus.


Substance abuse with mental disorders: specialized public systems and integrated care.
Separate public financing and regulation of substance (SA) abuse treatment distinct from mental health (MH) treatment preserves a focus on the special needs of those with substance abuse but creates challenges to providing appropriate care for the large number of people with co-occurring conditions. This paper reviews recent efforts to overcome these challenges through clinical and systems approaches that better integrate care. Although much progress has been made for some subgroups of people with co-occurring disorders, further efforts to develop and sustain clinically integrated service delivery approaches within separate systems, particularly in SA treatment settings, are needed.


Manipulatives-based laboratory for majors biology - a hands-on approach to understanding respiration and photosynthesis.
The first course in our year-long introductory series for Biology majors encompasses four learning units: biological molecules and cells, metabolism, genetics, and evolution. Of these, the metabolism unit, which includes respiration and photosynthesis, has shown the lowest student exam scores, least interest, and lowest laboratory ratings. Consequently, we hypothesized that modeling metabolic processes in the laboratory would improve student content learning during this course unit. Specifically, we developed manipulatives-based laboratory exercises that combined paper cutouts, movable blocks, and large diagrams of the cell. In particular, our novel use of connecting LEGO blocks allowed students to move model electrons and phosphates between molecules and within defined spaces of the cell. We assessed student learning using both formal (content indicators and attitude surveys) and informal (the identification of misconceptions or discussions with students) approaches. On the metabolism unit content exam, student performance improved by 46% over pretest scores and by the end of the course, the majority of students rated metabolism as their most-improved (43%) and favorite (33%) subject as compared with other unit topics. The majority of students rated manipulatives-based labs as very helpful, as compared to non-manipulatives-based labs. In this report, we will demonstrate that students made learning gains across all content areas, but most notably in the unit that covered respiration and photosynthesis.


Faster LASL Lens Design Program.
The following improvements have made the LASL lens design system much faster, though less versatile, and have maintained the calculation accuracy: an increment-vector damping technique optimized by a search procedure, analytic differentiation, simultaneous design on all variables, reliable convergence criteria, vignette control by biased violation errors, bounds for the variables, and an enlarged weighting procedure. The designing system optimizes the sizes and positions of many-ray image spots without consideringthe classical aberrations. As a sample problem the symposium lens has been redesigned.


Neurological Complications of Endocarditis: A Multidisciplinary Review with Focus on Surgical Decision Making.
Infective endocarditis (IE) is a systemic disease with many potential neurologic manifestations including ischemic and hemorrhagic strokes, cerebral microbleeding, infectious intracranial aneurysms, meningitis, brain abscesses, and encephalopathy. The majority of left-sided (heart) IE patients have brain lesions that may alter management decisions, warranting the systematic use of magnetic resonance imaging. Many patients require surgical treatment of valvular disease, and central nervous system lesions weigh into decision making. Data regarding the timing of surgery are conflicting, but earlier surgery appears to be safe in most ischemic strokes, while ideally surgery should be delayed for 3 to 4 weeks in patients with hemorrhagic strokes. IE requires a multidisciplinary team to collaboratively care for the patient. In this article, we review the current understanding and management of the neurological complications of IE and their impact on the performance and timing of cardiac surgery.


Is data missing? An assessment of publication bias in orthodontic systematic reviews from 2010 to 2021.
To assess the extent of publication bias assessment in systematic reviews (SRs) across the orthodontic literature over the last 12 years and to identify the appropriateness of assessment and association with publication characteristics, including year of publication, journal, searching practices within unpublished literature or attempts to contact primary study authors and others. We searched six journals and the Cochrane Database of Systematic Reviews for relevant articles, since January 2010, until November 2021. We recorded practices interrelated with publication bias assessment, at the SR and meta-analysis level. These pertained to reporting strategies for searching within unpublished literature, attempts to communicate with authors of primary studies and formal assessment of publication bias either graphically or statistically. Potential associations between publication bias assessment practices with variables such as journal, year, methodologist involvement, and others were sought at the meta-analysis level. A sum of 289 SRs were ultimately included, with 139 of those incorporating at least one available mathematical synthesis. Efforts to search within unpublished literature were reported in 191 out of 289 Reviews (66.1%), while efforts to communicate with primary study authors were recorded for 150 of 289 of those (51.9%). An appropriate strategy plan to address issues of publication bias, conditional on the number of studies available and the methodology plan reported, was followed in 78 of the 139 meta-analyses (56.1%). Formal publication bias assessment was actually reported in 35 of 139 meta-analyses (25.2%), while only half of those (19/35; 54.3%) followed an appropriately established methodology. Ten of the latter 19 studies detected the presence of publication bias (52.6%). Predictor variables of appropriate publication bias assessment did not reveal any significant effects. Appropriate methodology and rigorous practices for appraisal of publication bias are underreported in SRs within the orthodontic literature since 2010 and up-to-date, while other established methodologies including search strategies for unpublished data or communication with authors appear currently suboptimal.


[Study on rapid determination of active ingredient of agrochemicals by near-infrared spectroscopy].
The main problem of disqualification of the agrochemicals is the insufficiency and abuse of its active ingredient, but lacking of the rapid and on the site analysis method. In the present thesis, the content of haloxyfop-r-methyl in the emulsifiable concentration was analyzed quantitatively by the FT-NIR spectroscopy combined with partial least square (PLS) method. The calibration models of haloxyfop-r-methyl were developed, the determination coefficients (R2) of the calibration models were no less than 0.999 9, the SEC were less than 0.019, and the SEP were less than 0.030. Meanwhile, the factors affecting the calibration model were studied and the validation was done by the actual sample. The result indicated that the method of near-infrared spectroscopy can predict the content of the active ingredient in emulsifiable concentration accurately; while the resolution of the instrument and the content of addition agent will not affect the prediction precision of the calibration model remarkably. Therefore, it is a feasible, convenient and quick method to analyze the active ingredient in the commodity agrochemicals by near-infrared spectroscopy, which has an important significance in the on-line determination, analysis on site in the enterprise and the rapid quantitative analysis of agrichemicals in the department of quality monitoring.


Effects of mineral and rapeseed phosphorus supplementation on phytate degradation in dairy cows.
The objective of this study was to evaluate the effects of diet composition on phytate (InsP6) degradation in dairy cows. In Experiment 1, four diets that differed in the amount and source of phosphorus (P) were fed to 24 lactating cows in a 4 × 4 Latin Square design. The control diet (Diet C) contained 4.18 g P/kg dry matter (DM). Diet MP contained additional mineral P (5.11 g P/kg DM), Diet RS contained rapeseed and rapeseed meal as organic P sources (5.26 g P/kg DM) and Diet RSM contained rapeseed meal and rapeseed oil (5.04 g P/kg DM). Total P (tP) and InsP6 excretion in faeces were measured. In Experiment 2, we used a rumen simulation technique (Rusitec) to estimate ruminal disappearance of tP and InsP6 from Diets C, MP and RSM. In Experiment 1, tP concentration in faeces increased with tP intake and was highest for Diets RS and RSM. The source of supplemented P had no influence on tP digestibility, but tP digestibility was reduced for Diets MP, RS and RSM in comparison to that for Diet C. InsP6 disappearance decreased in Diet MP (85.0%) and increased in Diets RS (92.7%) and RSM (94.0%) compared to that in Diet C (90.0%). In Experiment 2, P source influenced ruminal tP disappearance (Diet MP, 78.6%; Diet RSM, 75.3%). InsP6 disappearance for Diet C (98.1%) was higher than that for Diets MP (95.6%) and RSM (94.9%). The results confirmed the high potential of ruminants to degrade InsP6, but differences in diet composition influenced InsP6 disappearance. Further studies of the site of InsP6 degradation are required to understand the relevance of InsP6 degradation for the absorption of P.


Syntheses and structures of cationic and neutral, homo- and heteroleptic tert-butoxides of the group 4 metals.
The utility of tri-tert-butoxystannate as a chelating tridentate ligand for group 4 metals was investigated. The highly Lewis acidic metals degraded the stannate ion in a series of tert-butoxide abstraction steps to produce a variety of group 4 tert-butoxides. A total of 1 equiv of NaSn(O(t)Bu)(3) reacted with cis-MCl(4)(THF)(2) [M = Zr (1), Hf (2)] in THF solutions to furnish the salts fac-{[M(O(t)Bu)(3)(THF)(3)](SnCl(3))}, which are separated ion pairs featuring weakly coordinating trichlorostannate ions. Neutral complexes, namely, [M(O(t)Bu)(2)Cl(2)(THF)(2)] [M = Zr (3), Hf (4)], were isolated when 2/3 equiv of sodium stannate was used in these reactions. Titanium tetrachloride formed analogues neither of 1 and 2 nor of 3 and 4, but Ti(O(t)Bu)(3)Cl reacted with silver triflate to give [Ti(O(t)Bu)(2)(OTf)(2)(THF)(2)] (5). Anion exchange of triflate for trichlorostannate transformed 1 to the contact ion pair fac-[Zr(O(t)Bu)(3)OTf(THF)(2)] (6). A total of 2 equiv of NaSn(O(t)Bu)(3) reacted with cis-MCl(4)(THF)(2) to give the complexes fac-[Sn(mu-O(t)Bu)(3)M(O(t)Bu)(3)] [M = Zr (7), Hf (8)]. Tri-tert-butoxystannate may be used as a selective alkoxylating agent for group 4 metals, and it can be transferred to these metals intact if their Lewis acidity is appropriately attenuated as in fac-{[M(O(t)Bu)(3)(THF)(3)](SnCl(3))}. Single-crystal X-ray studies revealed distorted octahedral coordination geometries for all compounds (1-8), with 1, 2, 7, and 8 being crystallographically C(3) symmetric.


Passive and active deflections of ampullary kinocilia correlated with changes in transepithelial voltage.
Deflections of individual ampullary kinocilia were optically recorded in the undissected vestibular system of young eels. At mechanical stimulation, transepithelial receptor potentials and nerve activity were recorded. Saturating responses occurred at ciliary deflections of +6 degrees and -3 degrees. Kinocilia occasionally oscillate spontaneously in a snaking or pointer-like mode as the preparation deteriorates. In nearly all kinocilia of fresh preparations exogenous transepithelial voltage change induces active pointer-like deflection in a graded and tonic manner. A voltage change of a given sign induces a deflection that counteracts mechanical stimuli producing a voltage change of the same sign.


Effect of Moderate Exercise on Serum Interferon-Gamma and Interleukin-17 Levels in the Morphine Withdrawal Period.
Drug addiction triggers the infliction of a variety of diseases. Various subjects have indicated that during the withdrawal syndrome period, the immune system is weakened. This study aimed to investigate the changes in serum levels of interferon-gamma (IFN-γ) and interleukin-17 (IL-17) during the morphine withdrawal syndrome induced by 8 weeks of moderate exercise and their effects on the immune system function. Twenty-four male Wistar rats (220 ± 10 g) were divided into four groups (n = 6): healthy control (HC), addicted control (AC), healthy trained (HT), and addicted trained (AT) groups. AC and AT groups were made addicted to morphine sulfate (0.4 mg/mL) in 21 days. To ensure their dependence on morphine, naloxone (3 mg/kg, i.p.) was injected into the body of a number of the rats. HT and AT groups were made to run on a treadmill 5 days per week for 8 weeks while time and speed gradually increased. Both prior to the exercises and 24 hours after the last training session, blood samples were collected from all the animals, and serum IFN-γ and IL-17 serum levels were measured using the ELISA method. This research was performed at the Bu-Ali Sina University, Hamadan, Iran. After 8 weeks of exercise, a significant increase was observed in the serum IFN-γ level in the HT group (251.17 ± 13.045) in comparison with the HC group (234 ± 12.884) (P = 0.045). Furthermore, the serum IFN-γ level in the AT group (218.33 ± 5.164) in comparison to the AC group (190.67 ± 8.477) showed a significant increase (P = 0.000). In addition, the serum level of IFN-γ in the HT group showed a significant increase compared to the AT group (P = 0.000). After 8 weeks of exercise, there was a significant decrease in the serum IL-17 level in the HT group (22.67 ± 4.46) compared with the HC group (38.17 ± 7.68) (P = 0.005). In addition, a significant decrease was observed in serum IL-17 in the AT group (42.17 ± 7.41) in comparison with the AC group (57.17 ± 7.83) (P = 0.007). In addition, the serum IL-17 level in the HT group significantly decreased in comparison with the AT group (P = 0.001). Moderate exercise for 8 weeks increased the IFN-γ and decreased the IL-17 serum levels in the morphine-dependent rats. For this reason, this type of exercise can improve the function of the immune system during morphine withdrawal syndrome.


Using the Lorenz Curve to Characterize Risk Predictiveness and Etiologic Heterogeneity.
The Lorenz curve is a graphical tool that is used widely in econometrics. It represents the spread of a probability distribution, and its traditional use has been to characterize population distributions of wealth or income, or more specifically, inequalities in wealth or income. However, its utility in public health research has not been broadly established. The purpose of this article is to explain its special usefulness for characterizing the population distribution of disease risks, and in particular for identifying the precise disease burden that can be predicted to occur in segments of the population that are known to have especially high (or low) risks, a feature that is important for evaluating the yield of screening or other disease prevention initiatives. We demonstrate that, although the Lorenz curve represents the distribution of predicted risks in a population at risk for the disease, in fact it can be estimated from a case-control study conducted in the population without the need for information on absolute risks. We explore two different estimation strategies and compare their statistical properties using simulations. The Lorenz curve is a statistical tool that deserves wider use in public health research.


Stability and Dissociation of the Large Subunit RuBisCO Binding Protein Complex in Vitro and in Organello.
We are studying the stability of the binding protein which associates with newly synthesized large subunits of ribulose bisphosphate carboxylase. In chloroplast extracts, it has been shown that a dodecameric complex of the large subunit binding protein dissociates extensively into binding protein monomers and 7S (117 kilodaltons) large subunit-containing complexes in the presence of ATP. The concentrations of ATP which bring this about are quite low, prompting some investigators to suggest that the dodecameric complex might not exist in vivo. We have found, however, that in concentrated chloroplast extracts, at protein concentrations which are closer to those which occur in organello, the dissociation of the binding protein complex by ATP is much less extensive. For this reason, we have tested the stability of the binding protein in organello, by illuminating chloroplasts followed by lysis and polyacrylamide gel electrophoresis of the extracts. Radioactive large subunits associated with the dodecameric binding protein dissociated extensively in the light. The results are consistent with the idea that the high molecular weight form of the binding protein can function as a reservoir of large subunits which can be tapped in vivo, in a reaction dependent on light and ATP.


Differences in Eysenck's Personality Dimensions between a Group of Breast Cancer Survivors and the General Population.
Cancer may influence personality in patients and survivors. However, the possible relations between the treatments that the patients have undergone and the personality in survivors are not clear. This study aimed to establish the differences in personality between a group of breast cancer survivors and a control group, and to test the predictive utility of the treatments on the personality traits in survivors. Thirty breast cancer survivors and thirty participants from the general population completed the Eysenck personality questionnaire-revised (EPQ-R) and a socio-demographic questionnaire. Survivors had lower scores on extraversion and higher scores on neuroticism than the control group, but these differences were not significant. However, differences in psychoticism were significant, with higher scores in the survivor group. Breast-conserving therapy predicted extraversion while breast reconstruction predicted psychoticism. These results suggest that the physical consequences of surgery may lead to social and psychological impairments in this group of patients.


Long-Term Impact of Disasters on the Public Health System: A Multi-Case Analysis.
As past events have shown, disasters can have a tremendous impact on the affected population's health. However, research regarding the long-term impact on a systems level perspective is still scarce. In this multi-case study, we analyzed and compared the long-term impacts on the public health system of five disasters which took place in Europe: avalanche (Austria), terror attack (Spain), airplane crash (Luxembourg), cable-car tunnel fire (Austria), and a flood in Central Europe. We used a mixed-methods approach consisting of a document analysis and interviews with key stakeholders, to examine the various long-term impacts each of the disasters had on health-system performance, as well as on security and health protection. The results show manifold changes undertaken in the fields of psychosocial support, infrastructure, and contingency and preparedness planning. The holistic approach of this study shows the importance of analyzing long-term impacts from the perspective of the type (e.g., disasters associated with natural hazards) and characteristic (e.g., duration and extent) of a disaster, as well as the regional context where a disaster took place. However, the identified recurring themes demonstrate the opportunity of learning from case studies in order to customize the lessons and apply them to the own-disaster-management setting.


Prolonged inhibition of growth hormone secretion by peripheral injection of bombesin is mediated by somatostatin in the rat.
Peripherally injected bombesin inhibits GH secretion in conscious, freely moving rats and in sodium pentobarbital-anesthetized rats. This inhibition of GH secretion is unusually prolonged, lasting up to 90 min after a single ip injection. The duration of inhibition of GH secretion by bombesin is greater than that observed for somatostatin (SRIF) in the same bioassay. The inhibition of GH release occurs concomitantly with stimulation of gastrin release and is independent of stimulatory effects of bombesin on plasma glucose. The structurally related mammalian gastrin-releasing peptide also inhibits GH secretion in the pentobarbital-anesthetized rat after peripheral injection. Peripherally administered bombesin blocks GH-releasing factor stimulation of GH secretion. Prior treatment of pentobarbital-anesthetized rats with SRIF-specific anti-serum blocks the inhibitory effect of bombesin on GH secretion. No effect of bombesin on GH secretion was observed in primary cultures of rat anterior pituitary cells. These data suggest that peripherally administered bombesin stimulates SRIF secretion, most probably of hypothalamic origin, which, in turn, inhibits pituitary secretion of GH. This sensitivity of the hypothalamus to a peripherally rather than centrally administered peptide has important mechanistic and therapeutic implications.


Melatonin Improves the Photosynthetic Carbon Assimilation and Antioxidant Capacity in Wheat Exposed to Nano-ZnO Stress.
The release of nanoparticles into the environment is inevitable, which has raised global environmental concern. Melatonin is involved in various stress responses in plants. The present study investigated the effects of melatonin on photosynthetic carbon (C) assimilation and plant growth in nano-ZnO stressed plants. It was found that melatonin improved the photosynthetic C assimilation in nano-ZnO stressed wheat plants, mainly due to the enhanced photosynthetic energy transport efficiency, higher chlorophyll concentration and higher activities of Rubisco and ATPases. In addition, melatonin enhanced the activities of antioxidant enzymes to protect the photosynthetic electron transport system in wheat leaves against the oxidative burst caused by nano-ZnO stress. These results suggest that melatonin could improve the tolerance of wheat plants to nano-ZnO stress.


Translational research into species differences of endocrine toxicity via steroidogenesis inhibition by SMP-028--for human safety in clinical study.
SMP-028 is a drug candidate developed for the treatment of asthma. In a 13-week repeated dose toxicity study of SMP-028 in rats and monkeys, differences of endocrine toxicological events between rats and monkeys were observed. In rats, these toxicological events mainly consisted of pathological changes in the adrenal, testis, ovary, and the other endocrine-related organs. On the other hand, in monkeys, no toxicological events were observed. The goal of this study is to try to understand the reason why only rats, but not monkeys, showed toxicological events following treatment with SMP-028 and to eventually predict the possible toxicological effect of this compound on human endocrine organs. Our results show that SMP-028 inhibits neutral cholesterol esterase more strongly than other steroidogenic enzymes in rats. Although SMP-028 also inhibits monkeys and human neutral cholesterol esterase, this inhibition is much weaker than that of rat neutral cholesterol esterase. These results indicate (1) that the difference in endocrine toxicological events between rats and monkeys is mainly due to inhibition of steroidogenesis by SMP-028 in rats, not in monkeys, and (2) that SMP-028 may not affect steroidogenesis in humans and therefore might cause no endocrine toxicological events in clinical studies.


Evolution strategy optimization for adiabatic pulses in MRI.
We propose a new type of adiabatic pulses for uniform inversion of the magnetization in magnetic resonance imaging. We produced these pulses with an evolution strategy optimization, by which the search of the "best solution" has been made more efficient than by deterministic algorithms. The pulse parametrization takes into account an "offset-independent adiabaticity condition," which guarantees insensitivity to RF inhomogeneities. The RF pulse power (both peak and mean) contributes to the cost to be minimized, as well as the error function does: in this way we obtain solutions that require lower energy than the well-known hyperbolic-secant pulse, with no loss of quality in the response profile.


Potential value of in situ cellular immune response in HPV subtype 16 and 18 positive cervical cancer.
There is no doubt that the association between infection of the cervical epithelium by carcinogenic Human Papilloma Virus (HPV), particularly types 16 and 18, and cervical cancer (CC) is responsible for the activation of the immune response (IR). Research on tumor infiltrating lymphocytes at the primary tumor site could give us important information on how the immune cells are fighting against cancer. The aims of our study were to assess HPV status and to evaluate the significance of in situ cellular IR in CC. We performed a two-step retrospective analysis of IR in 18 CC: evaluation of HPV 16 and 18 infections by in situ hybridization and immune biomarkers (CD20, CD3, CD45) by immunohistochemistry. Immune cell profile, densities (assigned scores "0" if no inflammatory infiltrate, "1+" low, "2+" intense), tissue distribution and classical negative prognosis factors in relationship with survival and relapse were further assessed. We successfully demonstrated HPV 16 and/or 18 in all cases. We reported statistical significant correlations (p<0.005) between CD3, CD20, CD45 and survival (r=0.800), relapse (r=-0.892), clinical stage (r=-0.914), tumor size (r=-1) as well as the association between survival and CC subtype (r=0.548), FIGO stage (r=-0.914), tumor size (r=-0.800) and grading (r=0.61). The density of different immune cells is significantly involved in guiding prognosis of the CC in high-risk 16 and 18 HPV positive women; low cellular densities for CD3, CD20 and CD45 meaning limited immune response reflect negative disease outcomes promoting local relapse and decreased survival in such settings.


miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs.
Gemin3 is a DEAD-box RNA helicase that binds to the Survival of Motor Neurons (SMN) protein and is a component of the SMN complex, which also comprises SMN, Gemin2, Gemin4, Gemin5, and Gemin6. Reduction in SMN protein results in Spinal muscular atrophy (SMA), a common neurodegenerative disease. The SMN complex has critical functions in the assembly/restructuring of diverse ribonucleoprotein (RNP) complexes. Here we report that Gemin3 and Gemin4 are also in a separate complex that contains eIF2C2, a member of the Argonaute protein family. This novel complex is a large approximately 15S RNP that contains numerous microRNAs (miRNAs). We describe 40 miRNAs, a few of which are identical to recently described human miRNAs, a class of small endogenous RNAs. The genomic sequences predict that miRNAs are likely to be derived from larger precursors that have the capacity to form stem-loop structures.


Testing a Model of Patient Portal Use in Adult Patients.
The aim of this study was to test a modified version of the Technology Acceptance Model, which describes users' technology adoption, to examine the relations between patient portal use and potential influencing factors in adult patients who have used patient portals. The modified model posits that patient portal use can be explained by attitude and self-efficacy for using patient portals, perceived usefulness and ease of use, data privacy and security concerns, eHealth literacy, education level, and age. A cross-sectional anonymous online survey was conducted for adult patients who had used their patient portals in the past 12 months. Participants were recruited from 20 settings selected in a large integrated health care system. Data from 743 patients were subject to structural equation modeling for model testing. Sixty-eight percent were White and female, with a mean age of 53.1 years (SD = 15.34). Forty-seven percent used patient portals about monthly or more frequently. Scores for perceived usefulness and ease of use of patient portals were relatively high (as measured using the modified Perceived Health Web Site Usability Questionnaire; each item mean, 6.0-6.2; range, 1-7). The final model adequately fit the data (comparative fit index = .983, standardized root mean square residual = .064, root mean square error of approximation = .059). Patient portal self-efficacy and data privacy and security concerns had a direct impact on patient portal use. Perceived usefulness and ease of use, eHealth literacy, education level, and age indirectly influenced patient portal use. This study contributes to expanding a theoretical understanding of adult patients' patient portal use in a real health care environment. Future studies need to include more diverse populations in various settings. Knowledge gained from this study can be used by technology experts to make patient portals more user friendly and by administrators to implement patient portals more effectively.


Glutamate mediates acute glucose transport inhibition in hippocampal neurons.
Although it is known that brain activity is fueled by glucose, the identity of the cell type that preferentially metabolizes the sugar remains elusive. To address this question, glucose uptake was studied simultaneously in cultured hippocampal neurons and neighboring astrocytes using a real-time assay based on confocal epifluorescence microscopy and fluorescent glucose analogs. Glutamate, although stimulating glucose transport in astrocytes, strongly inhibited glucose transport in neurons, producing in few seconds a 12-fold increase in the ratio of astrocytic-to-neuronal uptake rate. Neuronal transport inhibition was reversible on removal of the neurotransmitter and displayed an IC50 of 5 microm, suggesting its occurrence at physiological glutamate concentrations. The phenomenon was abolished by CNQX and mimicked by AMPA, demonstrating a role for the cognate subset of ionotropic glutamate receptors. Transport inhibition required extracellular sodium and calcium and was mimicked by veratridine but not by membrane depolarization with high K+ or by calcium overloading with ionomycin. Therefore, glutamate inhibits glucose transport via AMPA receptor-mediated sodium entry, whereas calcium entry plays a permissive role. This phenomenon suggests that glutamate redistributes glucose toward astrocytes and away from neurons and represents a novel molecular mechanism that may be important for functional imaging of the brain using positron emission tomography.


Self-referenced spectral domain interferometry for improved signal-to-noise measurement of terahertz radiation.
In this work, we demonstrate self-referenced spectral domain interferometry for the electro-optic sampling of terahertz (THz) electric fields. This technique allows reduction of the phase noise of the measurement, thus increasing the signal-to-noise ratio (SNR). Using the proposed technique, we achieve a more than sixfold improvement in the SNR of the detected THz electric field.


Drug resistance profiles of Mycobacterium tuberculosis complex and factors associated with drug resistance in the Northwest and Southwest Regions of Cameroon.
Anti-tuberculosis drug resistance continues to be a major obstacle to tuberculosis (TB) control programmes with HIV being a major risk factor in developing TB. We investigated anti-TB drug resistance profiles and the impact of socioeconomic as well as behavioural factors on the prevalence of TB and drug resistance in two regions of Cameroon with such data paucity. This was a hospital-based study in which 1706 participants, comprising 1133 females and 573 males consecutively enrolled from selected TB and HIV treatment centres of the Northwest and Southwest regions. Demographic, clinical and self-reported risk behaviours and socioeconomic data were obtained with the consent of participants using questionnaires. Culture and drug resistance testing were performed according to standard procedures. The prevalence of resistance to at least one anti-TB drug was 27.7% and multi-drug resistance was 5.9%. Smoking, concurrent alcohol consumption and smoking, being on antiretroviral therapy for ≤ 12 months and previous household contact with TB patient were independently associated with tuberculosis prevalence, while only previous tuberculosis infection was associated with drug resistance in a univariate analysis. The study showed a high prevalence of drug resistance TB in the study population with only previous TB infection associated with drug resistance in a univariate analysis. It also provides evidence in our context, of the role of alcohol and smoking in increasing the risk of developing TB, which is more likely in people living with HIV/AIDS. Therefore, it is important for public health authorities to integrate and intensify alcohol/smoking abstention interventions in TB and HIV control programs in Cameroon.


Parenchymatous cell division characterizes the fungal cortex of some common foliose lichens.
Lichen-forming fungi produce diverse vegetative tissues, some closely resembling those of plants. Yet it has been repeatedly affirmed that none is a true parenchyma, in which cellular compartments are subdivided from all adjacent neighbors by cross walls adjoining older cross walls. Using transmission electron microscopy (TEM), we tested this assumption by examining patterns of septum formation in the parenchyma-like cortex of three lichens of different phylogenetic affinities: Sticta canariensis, Leptogium cyanescens, and Endocarpon pusillum. In the cortex of all three lichens, new septa adjoined perpendicularly or obliquely to previous septa. Septal walls possessed an electron-transparent core (median) layer covered on both sides by layers of intermediate electron density. At septal junctures, the core layer of the newer septum was not continuous with that of the older septum. Amorphous, electron-dense material often became deposited in the core region of older septal walls, and the septum gradually delaminated along its median into what could then be recognized as the distinct walls of neighboring cells. However, cells maintained continuity at pores, where adjacent remnants of the electron-transparent core layer suggested septal partition rather than secondary establishment of a lateral wall connection via anastomosis. Although fungal tissues first arise by the coalescence of filaments early in lichen ontogeny, the mature cortical tissues of some lichens are comparable to true parenchyma in the unrestricted orientation of their septal cross walls and the resulting ontogenetic relationship among neighboring cell compartments.


A comparison of antibody responses to commercial equine influenza vaccines following primary vaccination of Thoroughbred weanlings--a randomised blind study.
Many racing authorities, sales companies and equestrian bodies have mandatory vaccination policies for equine influenza (EI). The consequences of lack of vaccine efficacy include clinical disease, disruption to training programmes, the cancellation of equestrian events and the introduction of virus to susceptible populations. The correlation between antibody against the virus haemagglutinin and protection against influenza has been well established. The objective of this study was to compare the antibody responses of 66 unvaccinated Thoroughbred weanlings on four different stud farms, following primary vaccination (V1, V2 and V3) with the five EI vaccines commercially available in Ireland (Duvaxyn IET Plus, Equilis Resequin, Equip FT, Equilis Prequenza Te, ProteqFlu Te). Antibody responses were monitored for 6 months post V3 by single radial haemolysis. The pattern of antibody response was similar for all vaccines and for all antigens tested. A rapid decline of antibody level was observed by 3 months post V2 for all vaccines. The antibody response of the horses vaccinated with the whole virus vaccine Duvaxyn IET Plus was significantly higher than that of the horses vaccinated with the other four products. Five weanlings had maternally derived antibodies (MDA) at the time of V1. The canary pox recombinant vaccine, subunit vaccine and whole virus inactivated vaccines administered to these weanlings did not induce a detectable antibody response against the background of MDA but effectively primed the animals as revaccination resulted in a strong antibody response. In this study 43% of the weanlings failed to seroconvert after V1. This high incidence of poor responders has not been reported in previous experimental studies relating to these products. The poor responders were observed in all vaccine groups except those vaccinated with Duvaxyn IET Plus. Post V2 the incidence of poor responders was reduced to 7% and all horses responded to V3. The study demonstrates that independent evaluation of influenza vaccine performance in the field is critical to add to the body of knowledge gained from experimental challenge experiments carried out for regulatory or marketing purposes.


In vitro and in vivo cytotoxic activity of human lactoferricin derived antitumor peptide R-DIM-P-LF11-334 on human malignant melanoma.
Di-peptides derived from the human host defense peptide lactoferricin were previously described to specifically interact with the negatively charged lipid phosphatidylserine exposed by cancer cells. In this study one further derivative, namely R-DIM-P-LF11-334 is shown to exhibit even increased cancer toxicity in vitro and in vivo while non-neoplastic cells are not harmed. In liposomal model systems composed of phosphatidylserine mimicking cancerous and phosphatidylcholine mimicking non-cancerous membranes the specific interaction with the cancer marker PS was confirmed by specific induction of membrane perturbation and permeabilization in presence of the peptide. In vitro studies with cell lines of human malignant melanoma, such as A375, or primary cells of human melanoma metastases to the brain, as MUG Mel1, and non-neoplastic human dermal fibroblasts NHDF revealed high cytotoxic effect of R-DIM-P-LF11-334 on melanoma cells of A375 and MUG Mel1, whereas only minor effect on the dermal fibroblasts NHDF was observed, yielding an about 20-fold killing-specificity for A375 and MUG-Mel1. The LC50 values for melanoma A375 and MUG Mel1 were about 10 μM. Analysis of secondary structure of the peptide revealed an increase in the proportion of β-sheets exclusively in presence of the cancer mimic. Stability studies further indicated a potential adequate stability in blood or under stringent conditions. Importantly the cytotoxic effect on cancer cells was also proven in vivo in mouse xenografts of human melanoma, where peptide treatment induced strong tumor regression and in average a tumor area reduction of 85% compared to tumors of control mice without peptide treatment.


Induction and regulation of hepatocyte apoptosis by oxidative stress.
Reactive oxygen intermediates (ROI) have been implicated in the induction of hepatocyte apoptosis that results from a variety of forms of liver injury. Exogenous oxidants induce hepatocyte apoptosis and may mediate death during inflammatory liver injury. Lethal levels of intracellularly generated ROI resulting from hepatotoxin metabolism, or the induction of enzymes in the cytochrome P450 family, are also important inducers of apoptosis. In addition, ROI production may mediate death from a number of diverse factors, including tumor necrosis factor-alpha, bile acids, ischemia, and transforming growth factor-beta1. Oxidants alter many redox-sensitive cellular signaling pathways, including mitogen-activated protein kinases and transcription factors such as activator protein-1 and nuclear factor-kappaB. The mechanisms of oxidant-induced hepatocyte apoptosis remain unclear, but probably involve effects on cell signaling, as well as direct chemical interactions. The delineation of stimulus-specific mechanisms of oxidant-dependent hepatocyte apoptosis is important to the design of effective therapies for a number of forms of liver injury.


Developing a digital data collection platform to measure the prevalence of sepsis in Wales.
To develop a secure, efficient, and easy-to-use data collection platform to measure the prevalence of sepsis in Wales over 24 hours. Open Data Kit was used on Android devices with Google App Engine and a digital data collection form. A total of 184 students participated in the study using 59 devices across 16 hospitals, 1198 datasets were submitted, and 97% of participants found the Open Data Kit form easy to use. We successfully demonstrated that by combining a reliable Android device, a free open-source data collection framework, a scalable cloud-based server, and a team of 184 medical students, we can deliver a low-cost, highly reliable platform that requires little training or maintenance, providing results immediately on completion of data collection. Our platform allowed us to measure, for the first time, the prevalence of sepsis in Wales over 24 hours.


Manufacture and Property of Warp-Knitted Fabrics with Polylactic Acid Multifilament.
This study investigates the properties of polylactic acid (PLA) multifilament and its warp-knitted fabrics. Multifilament properties were tested and compared with PET multifilament with different diameters. The 83.3 dtex PLA multifilament was used to knit the fabric, and the fabric properties before and after dyeing were studied. Results showed that the mechanical properties of PLA multifilament were comparable to those of PET. However, PLA had a higher heat shrinkage rate. The dyed PLA warp-knitted fabric has excellent color fastness. Due to the influence of temperature and dye particles during the dyeing process, the breaking strength, air permeability and moisture permeability of the fabric were decreased. On the contrary, the elongation at break, abrasion resistance, anti-pilling properties, drape and crochet value of the fabric were increased.


Pretreatment and outcome correlates of sexual and physical trauma in an epidemiological cohort of first-episode psychosis patients.
High prevalence of trauma has been reported in psychosis. While role of trauma as a risk factor for developing psychosis is still debated, its negative impact on outcome has been described. Few studies have explored this issue in first-episode psychosis (FEP) patients. We assessed rate of stressful events, as well as premorbid and outcome correlates of past sexual and/or physical abuse (SPA) in an epidemiological FEP patients cohort. The Early Psychosis Prevention and Intervention Centre admitted 786 FEP patients between 1998 and 2000. Data were collected from patients' files using a standardized questionnaire. A total of 704 files were available, 43 excluded because of a nonpsychotic diagnosis at end point and 3 due to missing data regarding past stressful events; 658 patients were analyzed. A total of 83% patients had been exposed to at least one stressful event and 34% to SPA. SPA patients were more likely to have presented other psychiatric disorders before psychosis onset (posttraumatic stress disorder, substance use disorder), to have made suicide attempts in the past, and to have had poorer premorbid functional levels. Additionally, SPA patients had higher rate of comorbid diagnosis at program entry and were more likely to attempt suicide during treatment. SPA prevalence is high in FEP patients and must be explored by clinicians considering its durable impact on psychological balance and link with long-lasting suicidal risk. More research is warranted to better understand mechanisms involved between trauma and its potential consequences, as well as to develop psychological interventions adapted to this very sensitive and complex issue.


Identification of unstable sequences within the common fragile site at 3p14.2: implications for the mechanism of deletions within fragile histidine triad gene/common fragile site at 3p14.2 in tumors.
The FRA3B, at 3p14.2, lies within the fragile histidine triad (FHIT) gene and is the most highly expressed of the common fragile sites observed when DNA replication is perturbed by aphidicolin. Common fragile sites are highly unstable regions of the genome. Large intragenic deletions within FHIT, localized within the FRA3B sequences, have been identified in a variety of tumor cells. To characterize the FRA3B deletions in tumor cells and identify FRA3B sequences that are required for fragile site induction, we used microcell-mediated chromosome transfer to isolate hybrid cell clones that retain chromosome 3 homologues with various deletions within FRA3B. Detailed molecular mapping of the FHIT/FRA3B locus in the resultant hybrid cells revealed a complex pattern of instability within FRA3B. Each tumor cell line contained multiple chromosome 3 homologues with variable deletion patterns, often with discontinuous deletions, suggesting that the process of breakage and repair within FRA3B is an ongoing one. By comparing the approximate location of the breakpoints in the hybrid clones, we identified 11 recurring breakpoint/repair regions within the FRA3B. A comparison of the frequency of breaks/gaps within FRA3B in the hybrid clones with various deletions of FRA3B sequences revealed that the loss of FRA3B sequences does not reduce the overall rate of breakage and instability within the remaining FRA3B sequences. The majority of breaks occurred in the proximal portion of the FRA3B, in a 300-kb interval between exon 4 and the proximal 50 kb of intron 5. Our observations suggest that there is no single sequence within the FRA3B that influences breakage or recombination within this region; however, we cannot rule out the presence of multiple "hot spots" within the FHIT/FRA3B locus. Together, the results suggest that factors other than the DNA sequence per se are responsible for the formation of DNA breaks/gaps.


Genome Insights into the Novel Species Microvirga brassicacearum, a Rapeseed Endophyte with Biotechnological Potential.
Plants harbor a diversity of microorganisms constituting the plant microbiome. Many bioinoculants for agricultural crops have been isolated from plants. Nevertheless, plants are an underexplored niche for the isolation of microorganisms with other biotechnological applications. As a part of a collection of canola endophytes, we isolated strain CDVBN77T. Its genome sequence shows not only plant growth-promoting (PGP) mechanisms, but also genetic machinery to produce secondary metabolites, with potential applications in the pharmaceutical industry, and to synthesize hydrolytic enzymes, with potential applications in biomass degradation industries. Phylogenetic analysis of the 16S rRNA gene of strain CDVBN77T shows that it belongs to the genus Microvirga, its closest related species being M. aerophila DSM 21344T (97.64% similarity) and M. flavescens c27j1T (97.50% similarity). It contains ubiquinone 10 as the predominant quinone, C19:0 cycloω8c and summed feature 8 as the major fatty acids, and phosphatidylcholine and phosphatidylethanolamine as the most abundant polar lipids. Its genomic DNA G+C content is 62.3 (mol %). Based on phylogenetic, chemotaxonomic, and phenotypic analyses, we suggest the classification of strain CDVBN77T within a new species of the genus Microvirga and propose the name Microvirga brassicacearum sp. nov. (type strain CDVBN77T = CECT 9905T = LMG 31419T).


Characterization and Detection of ϵ-Berge-Zhukovskii Equilibria.
The Berge-Zhukovskii equilibrium is an alternate solution concept in non-cooperative game theory that formalizes cooperation in a noncooperative setting. In this paper, the ϵ-Berge-Zhukovskii equilibrium is introduced and characterized by using a generative relation. The generative relation also provides a solution to the problem of computing the ϵ-Berge-Zhukovskii equilibrium for large games, by using evolutionary algorithms. Numerical examples illustrate the approach and provide a possible application for this equilibrium concept.


Oxybutynin for treatment of urge urinary incontinence and overactive bladder: an updated review.
Urge urinary incontinence (UUI) and overactive bladder are common conditions often associated with profound impairment of the health and quality of life of the patient. Antimuscarinic medications have been the mainstay of treatment for these disorders. Oxybutynin hydrochloride, one of the most widely used antimuscarinic agents, has attracted considerable interest from both clinicians and pharmacologists over the last three decades. Although efficacy of this drug has been proven to be high, its use is limited by antimuscarinic adverse effects, possibly related to its active metabolite N-desethyloxybutynin (N-DEO). The extended-release form of oxybutynin uses a push-pull osmotic release system which has significantly improved its tolerability and safety profile. A transdermal transport system has also been developed, bypassing the first-pass metabolism in the liver and gut. This system is associated with significant reduction in the production of the primary metabolite and additional improvement in the tolerability profile of the drug. Intravesical instillation of oxybutynin has been reported although the efficacy and safety of this delivery system has yet to be determined. This article comprehensively reviews the contemporary literature on the pharmacology, clinical efficacy and adverse reactions of oxybutynin in its various delivery forms, and compares them to other frequently used medications for UUI and overactive bladder.


Severity of alveolar cleft affects prognosis of infant orthopedics in complete unilateral cleft lip and palate: three-dimensional evaluation from cheiloplasty to palatoplasty.
The purpose of this study was to investigate the relationships between severity of alveolar cleft and treatment outcome of infant orthopedics in patients affected by complete unilateral cleft lip and palate from cheiloplasty to palatoplasty with a three-dimensional evaluation method. Treatment outcomes of infant orthopedics were evaluated using three-dimensional linear and angular measurements of plaster models after cheiloplasty (T1) and before palatoplasty (T2). Eleven patients who had a width of alveolar cleft (WC) less than 4.0 mm at T1 (mild group) and 13 patients who had a WC 4.0 mm or greater (severe group) were compared and analyzed. From T1 to T2, the lengths of the alveolar segments were increased, and the WC was decreased without palatal collapse of alveolar segments in both groups. However, the WC in the severe group was significantly decreased by increased growth of the major segment compared with the mild group. The incisive papilla had a more evoked growth to the alveolar cleft side than in the severe group. Conclusively, infant orthopedics was quite useful in reducing WC in patients affected by unilateral cleft lip and palate after cheiloplasty, and the severity of WC significantly affected the prognosis of infant orthopedics.


Report of the fourth International Workshop on molecular blood group genotyping.
The fourth International Society of Blood Transfusion (ISBT) workshop on molecular blood group genotyping was held in 2010, with a feedback meeting at the ISBT Congress in Berlin, Germany. Fifty laboratories participated, 17 more than in 2008. Six samples were distributed. Samples 1-3 were DNA samples for all red cell blood group tests available to the participants. Of the 46 laboratories that tested these samples, 37 obtained completely correct results, although the extent of testing varied considerably. Sample 4, also a DNA sample, was an Rh problem in which RHDΨ and RHCE*ceCF were present, but the participants were only informed that the donor's red cells typed as positive with some monoclonal anti-D. Of the 42 laboratories that participated in this exercise, seven performed the sequencing necessary to obtain the correct result. Samples 5 and 6 were plasma samples from RhD-negative pregnant women, for foetal RhD testing. These were sent to 25 laboratories, and two incorrect results were reported. Overall, the level of accuracy was about equal to that of the previous workshop. The main conclusion for the last two workshops can be reiterated: with greater care and attention to detail, very high standards could be set for molecular blood group genotyping.


Contrasting impacts of climate-driven flowering phenology on changes in alien and native plant species distributions.
• Plant phenology is particularly sensitive to climate and a key indicator of environmental change. Globally, first flowering dates (FFDs) have advanced by several days per decade in response to recent climate warming, but, while earlier flowering should allow plant distributions to increase, a link between FFD and range changes has not been observed. • Here I show for 347 species that the extent to which FFD has responded to climate warming is linked to the degree to which their relative distributions have changed over 30 yr across the British Isles. • Native plant species whose phenology did not track climate change declined in distribution, whereas species that became more widespread all exhibited earlier flowering. In contrast, alien neophytes showed both a stronger phenological response to warming and a more marked increase in distribution, but no link between the two. • These trends were consistent both for relative changes in the national distribution and for local abundance. At the national scale, the more recently an alien species became established in Britain, the more likely it was to increase in distribution irrespective of FFD, suggesting that recent changes in alien species distributions are decoupled from climate and driven by other factors.


Severity of leukoaraiosis correlates with clinical outcome after ischemic stroke.
Leukoaraiosis (LA) is closely associated with aging, a major determinant of clinical outcome after ischemic stroke. In this study we sought to identify whether LA, independent of advancing age, affects outcome after acute ischemic stroke. LA volume was quantified in 240 patients with ischemic stroke and MRI within 24 hours of symptom onset. We explored the relationship between LA volume at admission and clinical outcome at 6 months, as assessed by the modified Rankin Scale (mRS). An ordinal logistic regression model was developed to analyze the independent effect of LA volume on clinical outcome. Bivariate analyses showed a significant correlation between LA volume and mRS at 6 months (r = 0.19, p = 0.003). Mean mRS was 1.7 +/- 1.8 among those in the lowest (< or =1.2 mL) and 2.5 +/- 1.9 in the highest (>9.9 mL) quartiles of LA volume (p = 0.01). The unfavorable prognostic effect of LA volume on clinical outcome was retained in the multivariable model (p = 0.002), which included age, gender, stroke risk factors (hypertension, diabetes mellitus, atrial fibrillation), previous history of brain infarction, admission plasma glucose level, admission NIH Stroke Scale score, IV rtPA treatment, and acute infarct volume on MRI as covariates. The volume of leukoaraiosis is a predictor of clinical outcome after ischemic stroke and this relationship persists after adjustment for important prognostic factors including age, initial stroke severity, and infarct volume.


Effect of membrane potential on the initiation of acetylcholine-induced Ca2+ transients in isolated guinea pig coronary myocytes.
The muscarinic stimulation of single voltage-clamped coronary arterial smooth muscle cells of the guinea pig was used to evaluate the effect of membrane potential on the inositol 1,4,5-tris-phosphate (IP3)-mediated changes of ionized [Ca2+] in the cytoplasm (Ca2+ transient) measured with indo 1. When applied at the membrane potential of -50 mV, 10 micromol/L acetylcholine (ACh) induced a [Ca2+]i increase after the mean latency of 2.6+/-0.9 s. The latency was reduced to 1.1 +/- 0.3 s when the same dose was applied at a holding potential of +50 mV. In paired experiments in the same cells, the latency of response at +50 mV was reduced by a factor of 2.2 +/- 0.3 compared with the response at -50 mV. Supramaximal [ACh] (100 micromol/L) induced Ca2+ transients with a 0.4 +/- 0.1-s latency, which was independent of membrane potential. When applied repetitively at -50 mV, ACh induced Ca2+ transients with a progressively reduced amplitude and slower rate of rise. Depolarization to +50 mV accelerated the rate of rise of the Ca2+ transient by a factor of 3.4 +/- 0.4 without affecting the amplitude. The modulation of the initiation of Ca2+ transient by a 100-mV depolarization can be explained by an approximately threefold increase in the rate of IP3 accumulation.


A group B Streptococcus indexed transposon mutant library to accelerate genetic research on an important perinatal pathogen.
Group B Streptococcus (GBS) is a significant global cause of serious infections, most of which affect pregnant women, newborns, and infants. Studying GBS genetic mutant strains is a valuable approach for learning more about how these infections are caused and is a key step toward developing more effective preventative and treatment strategies. In this resource report, we describe a newly created library of defined GBS genetic mutants, containing over 1,900 genetic variants, each with a unique disruption to its chromosome. An indexed library of this scale is unprecedented in the GBS field; it includes strains with mutations in hundreds of genes whose potential functions in human disease remain unknown. We have made this resource freely available to the broader research community through deposition in a publicly funded bacterial maintenance and distribution repository.


Treatment of failed native arteriovenous fistulae for hemodialysis by interventional radiology.
We studied the feasibility, technical problems, safety, and effectiveness of percutaneous declotting of thrombosed native arteriovenous fistulae for hemodialysis. Between 1992 and 1998, 93 declotting procedures were performed in 73 consecutive upper limb native fistulae (forearm 56 and upper arm 17), and 162 procedures were performed in 78 prosthetic grafts using manual catheter-directed thrombo-aspiration, with or without previous urokinase infusion. Detection of restenosis by clinical surveillance led to redilation or stent placement. Rethrombosis in four forearm and six upper arm fistulae were treated by 20 further declottings by aspiration. The initial success was 93% in the forearm and 76% in the upper arm (99% in grafts). The complications included one pulmonary embolism, one acute pseudoaneurysm, and one blood depletion requiring transfusion. Primary patency rates at one year were 49% in the forearm and 9% in the upper arm (14% in grafts). Secondary patency rates were 81 and 50% at one year, respectively (83% in grafts). Reinterventions were necessary every 19.6 months in the forearm and every 5.7 months in the upper arm (every 6.4 months in grafts, P < 0.05). Stents were placed in 11% of forearm fistulae and in 41% of upper arm fistulae (45% of grafts) for treatment of acute rupture (5 out of 19), stenosis recoil (6 out of 19), and early (< 6 months) recurring stenosis (8 out of 19). The percutaneous declotting of forearm fistulae by manual catheter-directed thrombo-aspiration was effective in more than 90% of cases and yielded 50% primary and 80% secondary patency rates at one year. The results were poorer in upper arm fistulae. The need for maintenance reinterventions was three times smaller in forearm fistulae than in upper arm fistulae and grafts.


Analysis of the cost-effectiveness of PACS.
Picture archiving and communications systems (PACS) have emerged as an important part of digital imaging technology. However, the future of PACS is uncertain because its economic viability is in doubt. Cost-effectiveness analysis is an accepted technique for evaluating the economics of new technologies. This paper addresses the cost-effectiveness of PACS and identifies factors that are important in determining the cost of PACS relative to film-based radiology. These include the impact of PACS on physician productivity, maintenance costs, discount rates, and the time period for amortization of capital goods. The effectiveness of PACS is also explored in terms of improvements in diagnostic accuracy and timely diagnosis. Financial and clinical impacts should be integrated to provide information about how PACS expenditures will affect radiology departments, hospitals, and national research and development objectives.


Management of chronic daily headache in children.
Children and adolescents can develop frequent, at times daily, headaches. The more severe forms of headaches that these children experience are often migrainous. This article discusses the typical characteristics of these patients and reviews treatments considered in this condition. Unfortunately, there are no high-quality studies to definitively guide treatment in children with chronic daily headache. Treatment decisions are often made using data from adult studies, childhood studies on episodic migraine or expert opinion. Current data on which to base treatment decisions are reviewed in this article.


Microbial Control of the Emerald Ash Borer (Coleoptera: Buprestidae) Using Beauveria bassiana (Hypocreales: Cordycipitaceae) by the Means of an Autodissemination Device.
The FraxiProtec, an autodissemination device loaded with the fungus Beauveria bassiana isolate CFL-A, was tested in the field to evaluate its potential to infect emerald ash borer adults and reduce their populations. During the 2-yr experimental period, the dispersion of B. bassiana-infected adults was also documented to assess the dissemination capacity of the biocontrol agent beyond the treated areas. The mean percentage of infected emerald ash borer in 2017 and 2018 in 15 treated sites was 43.3 ± 2.9% and 39.7 ± 3.9%, respectively, and no significant variation was observed over the tested years. Furthermore, a 40% significant reduction of the mean emerald ash borer population growth per tree in treated sites was recorded when compared to the control sites. Emerald ash borer infected with B. bassiana isolate CFL-A were collected from baited sticky traps in the sentinel stations in the area surrounding the FraxiProtec-treated sites. Even at a distance of 125 m, an average of 9.4 ± 2.6% infected emerald ash borer were collected. Finally, exploratory analyzes were carried out on parameters such as the area to be treated, ash tree density, and FraxiProtec density to document potential relationships, which could be used in the determination of a prescription.


Urinary incontinence in nulliparous women and their parous sisters.
To investigate the role of vaginal delivery and familial factors in the development of urinary incontinence by comparing the prevalence of this condition in nulliparous women and their parous sisters. A sample of 143 pairs of nulliparous/parous postmenopausal sisters completed a comprehensive questionnaire regarding symptoms of pelvic floor disorders. Of these, 101 pairs underwent clinical evaluation of urinary incontinence and genital prolapse. Among this sample of biological sisters, urinary incontinence was reported by 47.6% of nulliparous women and by 49.7% of parous women (P = .782). We found no difference in the severity or type of urinary incontinence between these 2 groups. There was a high concordance in continence status, however, within biological sisters. Vaginal birth does not seem to be associated with urinary incontinence in postmenopausal women. Considering the high concordance in continence status between sister pairs, and considering that the majority of parous women are continent, an underlying familial predisposition toward the development of urinary incontinence may be present.


Improving the Quality of Dissimilar Al/Steel Butt-Lap Joint via Ultrasonic-Assisted Friction Stir Welding.
A dissimilar AA7075/Q235 butt-lap joint was fabricated via ultrasonic-assisted friction stir welding (UaFSW), and the characteristics of the UaFSW joint were investigated systematically. The acoustoplastic effect of the ultrasonic vibration led to the softening of the materials and enhanced the material flow during welding, decreasing the volume of welding defects in the nugget zone of the UaFSW joint. With the help of ultrasonic vibration, a smooth and thin intermetallic compounds (IMCs) layer could generate along the Al/steel interface at the top of nugget zone, which possibly consisted of Al5Fe2 and Al13Fe4 phases. However, the positive effects of the ultrasonic vibration were weakened at low temperatures; consequently, the IMCs layer became discontinuous at the bottom of the nugget zone and the welding defects also formed. The ultrasonic vibration accelerated the dynamic recrystallization and refined the microstructures in the nugget zone due to the increased strain rate and stored energy. As a result, the UaFSW joint exhibited a better mechanical performance in comparison to the FSW joint, and the increment in the peak tensile load/elongation was more than twice. In addition, the UaFSW joint failed in the nugget zone along with the Al/steel interface, and the fracture mode was a mixture of ductile and brittle.


Central precocious puberty in multisystem Langerhans cell histiocytosis: a case report.
The authors describe a girl with multisystem Langerhans cell histiocytosis (LCH) who developed central precocious puberty (CPP). At the age of 19 months she presented with otorrhea and polypoid formations in the ear canal; polyps were removed and LCH suspected. She subsequently developed diabetes insipidus with a documented lesion of the pituitary stalk; she received chemotherapy and began therapy with l-desamino-8-D-argininevasopressin. Growth hormone deficiency was diagnosed at the age of 4.4 years and GH replacement therapy started. The patient has been off therapy for LCH since the age of 6. Signs of pubertal development appeared at 7.5 years (bone age 8 years) and gonadotropin-releasing hormone analog (GnRHa) treatment was started. During the observation period she developed central hypothyroidism. Development of CPP during LCH is extremely rare; to the authors 'knowledge, no patient has been described so far. The authors believe that CPP was secondary to LCH and did not represent a casual finding, even in the absence of hypothalamic-pituitary axis involvement. The presence of preceding lesions producing excessive cytokine levels, with damage on the neurosecretory apparatus that inhibits the GnRH pulse generator, represents the most intriguing hypothesis. The possibility of CPP development should be considered during the follow-up of these patients.


[A case of pituitary apoplexy with severe consciousness disturbance following mild head trauma].
A rare case of pituitary apoplexy following mild head trauma is reported. A 56-year-old woman was referred to our hospital for loss of consciousness following a traffic accident. Magnetic resonance (MR) imaging showed a large suprasellar tumor containing a low intensity area on the T 1-, T 2-weighted images and fluid-attenuated inversion recovery (FLAIR) image. These findings indicated fresh intratumoral hemorrhage. The tumor extended to the suprasellar region and put pressure on the hypothalamus and brain stem. The tumor, with marked intratumoral hemorrhage, was resected with an emergency right front-temporal craniotomy. And the patient was left severely disabled. The tumor histology was diffuse-type pituitary adenoma. In our case, we suggest that the cause of pituitary apoplexy following head trauma was shearing stress between the intra- and suprasellar part of the easy bleeding tumor, or direct injury by bone structure such as teberculum sellae, dorsum sellae, or anterior clinoid process.


Evaluation of selective defunctioning stoma after low anterior resection for rectal cancer.
Anastomotic leakage is a major concern after resection for low rectal cancer. Therefore, the use of a defunctioning stoma (DS) has been suggested, but limited data exist to clearly determine the necessity of a routine diversion. In our department, the indication of DS was evaluated subjectively by the operating surgeon. The aim of this study was to evaluate the selective use of fecal diversion. Retrospective chart review of patients who underwent low anterior resection for carcinoma was performed. The incidence and consequences of clinical leaks were determined in these patients who were considered in two groups: defunctioning stoma and no defunctioning stoma. From 1995 to 2005, 132 consecutive patients underwent low anterior resection; a DS was performed in 42 patients (31.8%). Median level of anastomosis was 4 cm in both groups. Overall clinical leakage rate was 9.8%: 7.1% (n = 3) with a DS and 11% (n = 10) without a stoma. Mortality rate was 1.5% (n = 2), both in the unprotected group. No patient in the diversion group required a permanent stoma, contrasting with four unprotected patients in which continuity could not be restored after break down of the anastomosis. Finding lower clinical leakage rate in a probable higher risk group and better outcome when a leak occurs in our study constituted strong evidence of the effectiveness of a DS. Selective use of a DS based on subjective assessment at the time of surgery could not allow experienced surgeons to perform single-stage procedure safely. Construction of a DS seems useful for patients with distal rectal cancer.


Daily use of whitening strips on tetracycline-stained teeth: comparative results after 2 months.
This article reviews the efficacy of a new 6.5% hydrogen peroxide tooth-whitening gel strip for bleaching teeth that have been intrinsically stained from tetracycline. Given the severity of staining in the cases presented during a recently conducted clinical trial, the resulting efficacy is dramatic. Additionally, the continuous use of these strips for 30 minutes per day, twice daily for 2 months with no meaningful adverse effects is noteworthy.


Intestinal immune system modulating polysaccharides in a Japanese herbal (Kampo) medicine, Juzen-Taiho-To.
A commercially available dried extract (TJ-48) of Japanese herbal (Kampo) prescription, Juzen-Taiho-To has been found to enhance functions of Peyer's patch cells (intestinal immune system modulating activity) in vitro and in vivo. When TJ-48 was fractionated, the dialyzable fraction (F-3) and the polysaccharide fraction (F-5) expressed the in vitro activity. Oral administration of F-5 (150 mg/kg/day) to mice showed the intestinal immune system modulating activity. When the galacturonan moiety of pectic polysaccharides in F-5 was degraded enzymatically by endo-polygalacturonase, the digestion products significantly increased the activity of F-5. Purification the polygalacturonase-digested F-5 indicated that the active substances were composed mainly of the enzyme-resistant or undigestable polysaccharide molecules. Gel filtrations and anion-exchange chromatographies of F-5 gave 12 kinds of polysaccharides, and among them, 7 polysaccharides had significant intestinal immune system modulating activity. Component sugar analysis suggests that some active polysaccharides are grouped into pectic polysaccharides containing arabinogalactan or heteroglycan chains. Single radial gel diffusion analysis using beta-D-glucosyl-Yariv antigen indicated that some of the active polysaccharides comprised arabino-3,6-galactan moiety, and this moiety was suggested to play an important role partly for expression of the activity by single linear regression analysis between degree of the activity and reactivity with beta-D-glyucosyl-Yariv antigen.


The global access initiative at the University of British Columbia (UBC): Availability of UBC discoveries and technologies to the developing world.
The University of British Columbia (UBC) became the first university in Canada to develop a strategy for enhancing global access to its technologies. UBC's University-Industry Liaison Office, in collaboration with the UBC chapter of Universities Allied for Essential Medicines (UAEM), established a mandate and developed principles that provide the developing world with access to UBC technologies. This commentary will discuss these principles and provide examples of where they have been applied to several UBC technologies.


How do volatiles escape their shallow magmatic hearth?
Only a small fraction (approx. 1-20%) of magmas generated in the mantle erupt at the surface. While volcanic eruptions are typically considered as the main exhaust pipes for volatile elements to escape into the atmosphere, the contribution of magma reservoirs crystallizing in the crust is likely to dominate the volatile transfer from depth to the surface. Here, we use multiscale physical modelling to identify and quantify the main mechanisms of gas escape from crystallizing magma bodies. We show that most of the outgassing occurs at intermediate to high crystal fraction, when the system has reached a mature mush state. It is particularly true for shallow volatile-rich systems that tend to exsolve volatiles through second boiling, leading to efficient construction of gas channels as soon as the crystallinity reaches approximately 40-50 vol.%. We, therefore, argue that estimates of volatile budgets based on volcanic activity may be misleading because they tend to significantly underestimate the magmatic volatile flux and can provide biased volatile compositions. Recognition of the compositional signature and volumetric dominance of intrusive outgassing is, therefore, necessary to build robust models of volatile recycling between the mantle and the surface. This article is part of the Theo Murphy meeting issue 'Magma reservoir architecture and dynamics'.


Rules of engagement: factors that regulate activity-dependent synaptic plasticity during neural network development.
Overproduction and pruning during development is a phenomenon that can be observed in the number of organisms in a population, the number of cells in many tissue types, and even the number of synapses on individual neurons. The sculpting of synaptic connections in the brain of a developing organism is guided by its personal experience, which on a neural level translates to specific patterns of activity. Activity-dependent plasticity at glutamatergic synapses is an integral part of neuronal network formation and maturation in developing vertebrate and invertebrate brains. As development of the rodent forebrain transitions away from an over-proliferative state, synaptic plasticity undergoes modification. Late developmental changes in synaptic plasticity signal the establishment of a more stable network and relate to pronounced perceptual and cognitive abilities. In large part, activation of glutamate-sensitive N-methyl-d-aspartate (NMDA) receptors regulates synaptic stabilization during development and is a necessary step in memory formation processes that occur in the forebrain. A developmental change in the subunits that compose NMDA receptors coincides with developmental modifications in synaptic plasticity and cognition, and thus much research in this area focuses on NMDA receptor composition. We propose that there are additional, equally important developmental processes that influence synaptic plasticity, including mechanisms that are upstream (factors that influence NMDA receptors) and downstream (intracellular processes regulated by NMDA receptors) from NMDA receptor activation. The goal of this review is to summarize what is known and what is not well understood about developmental changes in functional plasticity at glutamatergic synapses, and in the end, attempt to relate these changes to maturation of neural networks.


Influence of film-substrate adhesion on the mechanical properties of thin polymer films.
The mechanical properties of mechanical double layers (thin amorphous films of poly(n-butyl methacrylate) on considerably stiffer silicon substrates) were investigated by force-displacement curves acquired with an atomic force microscope. The substrate surface was modified to provide a hydrophilic and a hydrophobic moiety. Such a modification affects the adhesion between film and substrate, since the polymer film adheres strongly on the hydrophilic side and weakly on the hydrophobic one. In this way, we were able to investigate the influence of the adhesion between the polymer film and substrate on the mechanical properties of the mechanical double layer. We were able to show that force-displacement curves on the two moieties of the sample have a different shape, and we propose an interpretation of the mechanisms determining the force-deformation curves on films with small adhesion to the substrate. This experiment can also provide an approach to the question of how the mechanical properties of a bulk material change with the volume to surface ratio, since a film with vanishing adhesion to the substrate is the only experimental accessible setup approximating a free-standing thin film.


Role of self-care in COVID-19 pandemic for people living with comorbidities of diabetes and hypertension.
People living with comorbidities especially chronic non-communicable disease (NCDs) like diabetes and hypertension are at greater risk of acquiring severe form of Corona Virus Disease (COVID-19) infection known to be caused by Severe Acute Respiratory Syndrome-CoV -2 (SARS-CoV-2) due to underlying immunodeficiency. The government has taken various public health measures to reduce the risk of infection, such as physical distancing, Information Education and Communication (IEC) messages regarding hand-washing, usage of masks, and avoidance of unnecessary travel including lockdown to combat the spread of disease. However, nationwide lockdown due to COVID-19 pandemic has also confronted the existing health care system (clinician centric approach) for the management of diabetes and hypertension in India. Using secondary source of data from specific website and search engine a review was done for existing guidelines and literature focusing on the various components of self-care management (patient-centered care) and highlights the importance of self-care management education to cope up with twin pandemic of COVID-19 and NCDs. An attempt was also made to highlight the use of eHealth to manage diabetes and hypertension which may act as a bridge to fill the gap between primary care physician and patient's amid lockdown and help physician to deliver comprehensive care for people suffering from comorbidities.


Comparative histology of experimental allergic neuritis induced with minimum length neuritogenic peptides by adoptive transfer with sensitized cells or direct sensitization.
Using synthetic peptides representing specific regions of the bovine myelin protein P2, the minimum peptide length requirement for the T-cell epitope necessary for successful production of experimental allergic neuritis (EAN) has been shown to involve residues 61-70 of the P2 protein. In this study, morphometric analysis was used to compare the histologic changes in sciatic nerves of Lewis rats after disease was induced by P2 specific neuritogenic T-cell lines (P(2)3) or, alternatively, by direct inoculation of synthetic peptides representing residues 60-70 or 61-70 of the P2 protein sequence. Inoculation with cell line P(2)3 stimulated with residue 61-70 failed to elicit demyelination in sciatic nerves. However, cells stimulated with residue 60-70 produced inflammation, endoneurial edema, mild demyelination and axonal degeneration within seven days. In contrast, disease induced with either peptide by direct sensitization was more severe. Morphometric analysis revealed that inflammation was most severe in animals sensitized to the decapeptide. In the sciatic nerve, axonal degeneration was proportional in frequency to the extent of inflammation. Inflammation was especially intense in spinal roots with extensive destruction of axons including unmyelinated fibers. Spinal root changes were associated with Wallerian degeneration in the posterior white matter tracts of the spinal cord and were apparently secondary to endoneurial inflammation. Disruption of the blood-nerve-barrier (BNB), evident as physical separation of endothelial cells in association with severe perivascular inflammation, was observed.


What can we infer about the origin of sex in early eukaryotes?
Current analysis shows that the last eukaryotic common ancestor (LECA) was capable of full meiotic sex. The original eukaryotic life cycle can probably be described as clonal, interrupted by episodic sex triggered by external or internal stressors. The cycle could have started in a highly flexible form, with the interruption of either diploid or haploid clonal growth determined by stress signals only. Eukaryotic sex most likely evolved in response to a high mutation rate, arising from the uptake of the endosymbiont, as this (proto) mitochondrion generated internal reactive oxygen species. This is consistent with the likely development of full meiotic sex from a diverse set of existing archaeal (the host of the endosymbiont) repair and signalling mechanisms. Meiotic sex could thus have been one of the fruits of symbiogenesis at the basis of eukaryotic origins: a product of the merger by which eukaryotic cells arose. Symbiogenesis also explains the large-scale migration of organellar DNA to the nucleus. I also discuss aspects of uniparental mitochondrial inheritance and mitonuclear interactions in the light of the previous analysis.This article is part of the themed issue 'Weird sex: the underappreciated diversity of sexual reproduction'.