Structural properties of ultrathin SrO film deposited on SrTiO3.
The role of epitaxial strain and chemical termination in selected interfaces of perovskite oxide heterostructures is under intensive investigation because of emerging novel electronic properties. SrTiO 3 (STO) is one of the most used substrates for these compounds, and along its < 001 > direction allows for two nonpolar chemical terminations: TiO2 and SrO. In this paper, we investigate the surface morphology and crystal structure of SrO epitaxial ultrathin films: from 1 to about 25 layers grown onto TiO 2 -terminated STO substrates. X-ray diffraction and transmission electron microscopy analysis reveal that SrO grows along its [ 111 ] direction with a 4% out-of-plane elongation. This large strain may underlay the mechanism of the formation of self-organized pattern of stripes that we observed in the initial growth. We found that the distance between the TiO 2 plane and the first deposited SrO layer is 0.27 ( 3 ) nm, a value which is about 40% bigger than in the STO bulk. We demonstrate that a single SrO-deposited layer has a different morphology compared to an ideal atomically flat chemical termination.


Low-dose physical activity attenuates cardiovascular disease mortality in men and women with clustered metabolic risk factors.
Physical activity may ameliorate the health hazards of metabolic disorders but evidence is inconclusive, and estimates of the minimal threshold for protection remain unknown. The sample comprised 23 747 men and women (aged 54.1 ± 12.7 years [mean±SD], 45.2% men) without a known history of cardiovascular disease at baseline who were drawn from the Health Survey for England and the Scottish Health Survey. Based on blood pressure, high-density lipoprotein cholesterol, diabetes, waist circumference, and low-grade inflammation (C-reactive protein ≥ 3 mg/L), participants were classified as metabolically healthy (zero or one metabolic abnormality) or unhealthy (≥ 2 metabolic abnormalities). Self-reported physical activity was assessed at baseline. Cox proportional hazards models were used to examine the association of clustered metabolic risk and physical activity with mortality, controlling for age, sex, smoking, socioeconomic group, cardiovascular disease medication, and self-rated health. Over 7.0 ± 3.0 years follow-up, there were 2264 all-cause and 717 cardiovascular disease deaths, respectively. A physical activity threshold of at least one to 2 sessions per week was found to provide protection against mortality. Compared with active/metabolically healthy, the active with clustered metabolic abnormalities were not at elevated risk of cardiovascular disease (hazard ratio, 0.82; 95% CI, 0.54 -1.26) or all-cause mortality (hazard ratio, 1.11; 95% CI, 0.89 -1.39), although their inactive counterparts were at elevated risk of cardiovascular disease (hazard ratio, 1.41; 95% CI, 1.05 -1.91) and all-cause mortality (hazard ratio, 1.50; 95% CI, 1.27-1.78). The risk of cardiovascular disease associated with poor metabolic health is substantially lower among those who are physically active. At minimum, a weekly bout of moderate to vigorous physical activity is protective in men and women with clustered metabolic abnormalities.


Two-site reproducibility of cerebellar and brainstem neurochemical profiles with short-echo, single-voxel MRS at 3T.
To determine whether neurochemical concentrations obtained at two MRI sites using clinical 3T scanners can be pooled when a highly optimized, nonvendor short-echo, single-voxel proton MRS pulse sequence is used in conjunction with identical calibration and quantification procedures. A modified semi-LASER sequence (TE = 28 ms) was used to acquire spectra from two brain regions (cerebellar vermis and pons) on two Siemens 3T scanners using the same B0 and B1 calibration protocols from two different cohorts of healthy volunteers (N = 24-33 per site) matched for age and body mass index. Spectra were quantified with LCModel using water scaling. The spectral quality was very consistent between the two sites and allowed reliable quantification of at least 13 metabolites in the vermis and pons compared with 3-5 metabolites in prior multisite magnetic resonance spectroscopy trials using vendor-provided sequences. The neurochemical profiles were nearly identical at the two sites and showed the feasibility to detect interindividual differences in the healthy brain. Highly reproducible neurochemical profiles can be obtained on different clinical 3T scanners at different sites, provided that the same, optimized acquisition and analysis techniques are used. This will allow pooling of multisite data in clinical studies, which is particularly critical for rare neurological diseases.


A systematic review of pathways to and processes associated with radicalization and extremism amongst Muslims in Western societies.
Following the terrorist attacks of 9/11 in the USA and 7/7 in the UK, academic interest in factors involved in radicalization and terrorism has increased dramatically. Many related social and psychological theories have been put forward, however terrorism literature still lacks empirical research. In particular, little is known about the early processes and pathways to radicalization. Our aim is to investigate original research on pathways and processes associated with radicalization and extremism amongst people of Muslim heritage living in Western societies, that is, the group prioritized by counter-terrorism policy. Studies included in the review were original qualitative or quantitative primary research published in peer-reviewed journals, identified by searching research databases. All disciplines of journals were included. No single cause or pathway was implicated in radicalization and violent extremism. Individuals may demonstrate vulnerabilities that increase exposure to radicalization; however, the only common characteristic determined that terrorists are generally well-integrated, 'normal' individuals. Engagement in such activity is dependent on a wide range of interacting variables influenced by personal, localized and externalized factors. Further research should examine broader determinants of radicalization in susceptible populations. Future policy should follow this public health approach rather than constructing from perpetrators already committed to engaging in terrorism.


Effects of extracellular pH on the dynorphin A inhibition of N-methyl-D-aspartate receptors expressed in Xenopus oocytes.
Dynorphin A (Dyn A) (1-17), the postulated endogenous ligand for the kappa-opioid receptor, inhibits N-methyl-D-aspartate (NMDA) receptor-mediated currents in neuronal preparations and in Xenopus oocytes expressing recombinant NMDA receptors. Although direct interactions of Dyn A with the NMDA receptor have been reported, the mechanisms mediating the inhibitory actions of Dyn A are unknown. Extracellular pH is a crucial factor regulating NMDA receptor function. To date, however, the influence of pH on the inhibitory actions of Dyn A has not been examined. In the present study we used voltage-clamp recording techniques in Xenopus oocytes expressing recombinant NR1A/2A receptors to address this issue. We report that decreasing the pH of the external solution from 7.5 to 6.7 significantly enhances Dyn A inhibition of NMDA receptor-mediated currents. On the contrary, increasing the pH of the external solution to 9.2 prevents the inhibitory action of Dyn A. The influence of external pH was independent of membrane potential and the potentiation of inhibition with decreasing pH was not associated with alterations in the charge of the Dyn A molecule. These findings demonstrate that Dyn A inhibition of the NMDA receptor current is pH-dependent. They further suggest that the efficacy of neuronally released Dyn A in inhibiting NMDA receptor function may be increased in response to nerve injury and other conditions associated with decreased extracellular pH.


Profibrotic cytokines in aqueous humour correlate with aqueous flare in patients with rhegmatogenous retinal detachment.
Aqueous flare as determined by laser flare photometry in the anterior chamber is a strong preoperative predictor for proliferative vitreoretinopathy (PVR) in patients with primary retinal detachment (RD). We analysed various cytokines in aqueous humour samples in relation to aqueous flare and postoperative PVR incidence in patients with RD. Preoperatively, the aqueous flare of patients with RD was measured quantitatively with a laser flare metre and aqueous humour samples were collected and analysed for interferon γ, tumour necrosis factor α, monocyte chemoattractant protein (MCP)-1, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, vascular endothelial growth factor (VEGF)-A, platelet derived growth factor (PDGF)-aa, transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, fibroblast growth factor (FGF)-aa and FGF-bb by multiplex fluorescent bead-based immunoassays. Three months after RD surgery patients were examined for PVR development. Of 67 consecutive patients, 10 developed at least PVR grade C. Patients with flare values >15 pc/ms (n=20) and the 10 patients with postoperative PVR all had significantly elevated levels of IL-6, IL-8, MCP-1 and TGF-β1 in aqueous humour (p≤0.05). Levels of VEGF-A, PDGF-aa and TGF-β2 were not significantly changed. Other cytokines were below the detection threshold. Eight of the 10 patients (80%) with PVR had elevated flare values of >15 pc/ms and 8 of the 20 patients (40%) with flare >15 pc/ms developed PVR. The OR for PVR with flare values >15 pc/ms was 30.7 (p=0.0001). Laser flare photometry allows simple risk estimation for later PVR development. Elevated laser flare values correspond to an altered profibrotic intraocular cytokine milieu. These factors therefore constitute promising targets for a prophylactic intervention.


Lessons for continuing medical education from simulation research in undergraduate and graduate medical education: effectiveness of continuing medical education: American College of Chest Physicians Evidence-Based Educational Guidelines.
Simulation technology is widely used in undergraduate and graduate medical education as well as for personnel training and evaluation in other healthcare professions. Simulation provides safe and effective opportunities for learners at all levels to practice and acquire clinical skills needed for patient care. A growing body of research evidence documents the utility of simulation technology for educating healthcare professionals. However, simulation has not been widely endorsed or used for continuing medical education (CME). This article reviews and evaluates evidence from studies on simulation technology in undergraduate and graduate medical education and addresses its implications for CME. The Agency for Healthcare Research and Quality Evidence Report suggests that simulation training is effective, especially for psychomotor and communication skills, but that the strength of the evidence is low. In another review, the Best Evidence Medical Education collaboration supported the use of simulation technology, focusing on high-fidelity medical simulations under specific conditions. Other studies enumerate best practices that include mastery learning, deliberate practice, and recognition and attention to cultural barriers within the medical profession that present obstacles to wider use of this technology. Simulation technology is a powerful tool for the education of physicians and other healthcare professionals at all levels. Its educational effectiveness depends on informed use for trainees, including providing feedback, engaging learners in deliberate practice, integrating simulation into an overall curriculum, as well as on the instruction and competence of faculty in its use. Medical simulation complements, but does not replace, educational activities based on real patient-care experiences.


Adult Mansonella perstans in the abdominal cavity in nine Africans.
Adult Mansonella perstans infected the abdominal cavity of nine patients seen at Karawa Hospital in the Ubangi territory of Zaire. In four patients the worms were removed at laparotomy, and in the other five they were removed at autopsy. Twelve adult worms were identified in the nine patients. None of the worms caused symptoms or contributed to the patient's death. Worms were in the hernial sac in three patients, and one each was in connective tissue beside a reactive mesenteric lymph node, in peripancreatic connective tissue, in perirenal connective tissue, in hepatic portal connective tissue, on the serosal surface of the small intestine, and in connective tissue adjacent to rectum. The diameter of male worms was 45 microns to 60 microns and of female worms, 80 microns to 125 microns. One female worm was removed intact. It was 6 cm long and had a bifurcated tail characteristic of M. perstans.


Effectiveness of a universal parental support programme to promote healthy dietary habits and physical activity and to prevent overweight and obesity in 6-year-old children: the Healthy School Start Study, a cluster-randomised controlled trial.
To develop and evaluate the effectiveness of a parental support programme to promote healthy dietary and physical activity habits and to prevent overweight and obesity in Swedish children. A cluster-randomised controlled trial was carried out in areas with low to medium socio-economic status. Participants were six-year-old children (n = 243) and their parents. Fourteen pre-school classes were randomly assigned to intervention (n = 7) and control groups (n = 7). The intervention lasted for 6 months and included: 1) Health information for parents, 2) Motivational Interviewing with parents and 3) Teacher-led classroom activities with children. Physical activity was measured by accelerometry, dietary and physical activity habits and parental self-efficacy through a questionnaire. Body weight and height were measured and BMI standard deviation score was calculated. Measurements were conducted at baseline, post-intervention and at 6-months follow-up. Group differences were examined using analysis of covariance and Poisson regression, adjusted for gender and baseline values. There was no significant intervention effect in the primary outcome physical activity. Sub-group analyses showed a significant gender-group interaction in total physical activity (TPA), with girls in the intervention group demonstrating higher TPA during weekends (p = 0.04), as well as in sedentary time, with boys showing more sedentary time in the intervention group (p = 0.03). There was a significantly higher vegetable intake (0.26 servings) in the intervention group compared to the control group (p = 0.003). At follow-up, sub-group analyses showed a sustained effect for boys. The intervention did not affect the prevalence of overweight or obesity. It is possible to influence vegetable intake in children and girls' physical activity through a parental support programme. The programme needs to be intensified in order to increase effectiveness and sustain the effects long-term. These findings are an important contribution to the further development of evidence-based parental support programmes to prevent overweight and obesity in children. Controlled-trials.com ISRCTN32750699.


Spontaneous resolution of asymptomatic Chlamydia trachomatis in pregnancy.
We sought to estimate the rate of spontaneous resolution of asymptomatic Chlamydia trachomatis in pregnancy and to evaluate factors associated with its resolution. A cohort of women enrolled in a large multicenter randomized bacterial vaginosis antibiotic trial (metronidazole versus placebo) that, when randomly allocated, had asymptomatic C trachomatis diagnosed by urine ligase chain reaction (from frozen archival specimens) between 16(0/7) and 23(6/7) weeks were included. The urine ligase chain reaction is a highly accurate predictor of genital tract chlamydial infection. A follow-up ligase chain reaction was performed between 24(0/7) and 29(6/7) weeks. A total of 1,953 women were enrolled in the original antibiotic trial; 1,547 (79%) had ligase chain reaction performed both at randomization and follow-up. Women receiving antibiotics effective against Chlamydia between randomization and follow-up or having symptomatic Chlamydia infection were excluded (26 women). Of the 140 women (9%) who were diagnosed as positive via the initial ligase chain reaction assay, 61 (44%) had spontaneous resolution of Chlamydia by the follow-up ligase chain reaction assay. Factors associated with spontaneous resolution included older age (P = .02), more than 5 weeks from randomization to follow-up (P = .02), and a greater number of lifetime sexual partners (P = .02). Using a logistic regression model, maternal age and a greater-than-5-week follow-up interval remained significant; for every 5-year increase in maternal age, the odds of a positive result on the ligase chain reaction test at follow-up decreased by 40% (odds ratio 0.6; 95% confidence interval 0.4-0.9). Race, substance abuse, parity, and treatment with metronidazole were not associated with spontaneous resolution. Gram stain score and vaginal pH at randomization and follow-up also were not associated. The prevalence of asymptomatic C trachomatis in pregnancy was 9%; infection resolved spontaneously in almost half of these women. The association of older age and increasing time interval to spontaneous resolution of Chlamydia is consistent with a host immune-response mechanism.


The p63 C-terminus is essential for murine oocyte integrity.
The transcription factor p63 mediates distinct cellular responses, primarily regulating epithelial and oocyte biology. In addition to the two amino terminal isoforms, TAp63 and ΔNp63, the 3'-end of p63 mRNA undergoes tissue-specific alternative splicing that leads to several isoforms, including p63α, p63β and p63γ. To investigate in vivo how the different isoforms fulfil distinct functions at the cellular and developmental levels, we developed a mouse model replacing the p63α with p63β by deletion of exon 13 in the Trp63 gene. Here, we report that whereas in two organs physiologically expressing p63α, such as thymus and skin, no abnormalities are detected, total infertility is evident in heterozygous female mice. A sharp reduction in the number of primary oocytes during the first week after birth occurs as a consequence of the enhanced expression of the pro-apoptotic transcriptional targets Puma and Noxa by the tetrameric, constitutively active, TAp63β isoform. Hence, these mice show a condition of ovary dysfunction, resembling human primary ovary insufficiency. Our results show that the p63 C-terminus is essential in TAp63α-expressing primary oocytes to control cell death in vivo, expanding the current understanding of human primary ovarian insufficiency.


The human liver-specific proteome defined by transcriptomics and antibody-based profiling.
Human liver physiology and the genetic etiology of the liver diseases can potentially be elucidated through the identification of proteins with enriched expression in the liver. Here, we combined data from RNA sequencing (RNA-Seq) and antibody-based immunohistochemistry across all major human tissues to explore the human liver proteome with enriched expression, as well as the cell type-enriched expression in hepatocyte and bile duct cells. We identified in total 477 protein-coding genes with elevated expression in the liver: 179 genes have higher expression as compared to all the other analyzed tissues; 164 genes have elevated transcript levels in the liver shared with at least one other tissue type; and an additional 134 genes have a mild level of increased expression in the liver. We identified the precise localization of these proteins through antibody-based protein profiling and the subcellular localization of these proteins through immunofluorescent-based profiling. We also identified the biological processes and metabolic functions associated with these proteins, investigated their contribution in the occurrence of liver diseases, and identified potential targets for their treatment. Our study demonstrates the use of RNA-Seq and antibody-based immunohistochemistry for characterizing the human liver proteome, as well as the use of tissue-specific proteins in identification of novel drug targets and discovery of biomarkers.-Kampf, C., Mardinoglu, A., Fagerberg, L., Hallström, B. M., Edlund, K., Lundberg, E., Pontén, F., Nielsen, J., Uhlen, M. The human liver-specific proteome defined by transcriptomics and antibody-based profiling.


Molecularly imprinted polymer solid-phase extraction coupled to square wave voltammetry at carbon fibre microelectrodes for the determination of fenbendazole in beef liver.
A molecularly imprinted polymer was developed and used for solid-phase extraction (MISPE) of the antihelmintic fenbendazole in beef liver samples. Detection of the analyte was accomplished using square wave voltammetry (SWV) at a cylindrical carbon fibre microelectrode (CFME). A mixture of MeOH/HAc (9:1) was employed both as eluent in the MISPE system and as working medium for electrochemical detection of fenbendazole. The limit of detection was 1.9x10(-7) mol L-1 (57 microg L-1), which was appropriate for the determination of fenbendazole at the maximum residue level permitted by the European Commission (500 microg kg-1 in liver). Given that the SW voltammetric analysis could not be directly performed in the sample extract as a consequence of interference from some sample components, a sample clean-up with a MIP for selectively retaining fenbendazole was performed. The MIP was synthesized using a 1:8:22 template/methacrylic acid/ethylene glycol dimethacrylate ratio. A Britton-Robinson Buffer of pH 9.0 was selected for retaining fenbendazole in the MIP cartridges, and an eluent volume of 5.0 mL at a flow rate of 2.0 mL min-1 was chosen in the elution step. Cross-reactivity with the MIP was observed for other benzimidazoles. The synthesized MIP exhibited a good selectivity for benzimidazoles with respect to other veterinary drugs. The applicability of the MISPE-SWV method was tested with beef liver samples, spiked with fenbendazole at 5,000 and 500 microg kg-1. Results obtained for ten different liver samples yielded mean recoveries of (95+/-12)% and (96+/-11)% for the upper and lower concentration level, respectively.


Mathematical analysis of the honeybee waggle dance.
A honeybee informs her nestmates of the location of a flower by doing a waggle dance. The waggle dance encodes both the direction of and distance to the flower from the hive. To reveal how the waggle dance benefits the colony, we created a Markov model of bee foraging behavior and performed simulation experiments by incorporating the biological parameters that we obtained from our own observations of real bees as well as from the literature. When two feeders were each placed 400 m away from the hive in different directions, a virtual colony in which honeybees danced and correctly transferred information (a normal, real bee colony) made significantly greater numbers of successful visits to the feeders compared to a colony with inaccurate information transfer. Howerer, when five feeders were each located 400 m from the hive, the inaccurate information transfer colony performed better than the normal colony. These results suggest that dancing's ability to communicate accurate information depends on the number of feeders. Furthermore, because non-dancing colonies always made significantly fewer visits than those two colonies, we concluded that dancing behavior is beneficial for hives' ability to visit food sources.


Enhanced quantum interface with collective ion-cavity coupling.
We prepare a maximally entangled state of two ions and couple both ions to the mode of an optical cavity. The phase of the entangled state determines the collective interaction of the ions with the cavity mode, that is, whether the emission of a single photon into the cavity is suppressed or enhanced. By adjusting this phase, we tune the ion-cavity system from sub- to superradiance. We then encode a single qubit in the two-ion superradiant state and show that this encoding enhances the transfer of quantum information onto a photon.


Maternal protein deficiency affects mesenchymal stem cell activity in the developing offspring.
Epidemiological studies suggest that environmental influences such as maternal nutrition, programme skeletal growth during intrauterine and early postnatal life. However, the mechanism whereby the skeletal growth trajectory is modified remains unclear. We have addressed this using a rat model of maternal protein insufficiency to investigate the cellular mechanisms involved in the programming of bone development. The aims of this study were to determine whether colony formation (colony forming unit-fibroblastic, CFU-F), proliferation, and differentiation of bone marrow stromal cells from offspring of female rats maintained on normal (18% casein) or low (9% casein) protein was altered and, whether their responses to growth hormone (GH), 1,25(OH)(2)D3, and IGF-1 differed. Dams were fed an 18% casein (control) diet or 9% casein (low protein) diet from conception until the end of pregnancy. Offspring were then fed a normal protein diet until harvest at 8, 12, and 16 weeks after birth. At 8 weeks, total CFU-F and alkaline phosphatase-positive CFU-F were significantly (P < 0.01) reduced in the low protein group compared to controls. At 12 weeks, no significant differences were observed in colony formation. Modulation of osteoblast proliferation and differentiation by IGF-1 and GH was observed (P < 0.01) in the control group at 8 weeks and the low protein group at 12 weeks. Alkaline phosphatase specific activity was significantly decreased at 8 weeks (P < 0.001) in the low protein group. At 12 and 16 weeks this was reversed, with significantly increased specific activity in the low protein group. These results suggest that normal proliferation and differentiation of mesenchymal stem cells were delayed by maternal protein restriction during early life. Furthermore, these results suggest that, with skeletal maturity, "catch-up" or a physiological shift in bone cell activity was present in the low protein group. These alterations in mesenchymal stem cell function by the early environment may represent an important candidate mechanism for the programming of osteoporosis and associated consequences in later life.


Diabetes, Diabetes Treatment, and Risk of Thyroid Cancer.
The objective of this study was to assess the relationships among diabetes, diabetes treatment and thyroid cancer risk using a large prospective cohort, the Women's Health Initiative. A total of 147 934 women who were free of known cancer at baseline were followed prospectively. Diabetes status and diabetes treatment at baseline and during follow-up were ascertained. Incident cases of thyroid cancers were confirmed by physician review of central medical records and pathology reports. Time-dependent Cox proportional hazards regressions were used to estimate hazard ratios and 95% confidence intervals for thyroid cancer risk associated with diabetes status, diabetes treatment, and duration of diabetes. With a median follow-up time of 15.9 years, 391 incident thyroid cancers were identified. We found no significant associations between thyroid cancer and diabetes (hazard ratio = 1.09; 95% confidence interval, 0.79-1.52), diabetes treatment, or duration of diabetes. Our findings do not support the hypothesis that diabetes, or treatment of diabetes is associated with risk of thyroid cancer among postmenopausal women. Studies to investigate the specific effects of hyperinsulinemia and insulin resistance on thyroid cancer risk may provide additional information.


Abdominal Burkitt-type lymphomas in Algeria.
In a previous retrospective analysis from the principal paediatric centres of Algeria, Burkitt-type lymphomas (BL) were shown to account for around 46.5% of the total childhood non-Hodgkin's malignant lymphomas in that country. In the present study, a series of 49 abdominal BL from the Paediatric Clinic of Surgery, Mustapha Hospital, Algiers, has been studied. The age distribution shows a peak between 4 and 5 years of age, and the sex ratio is (M:F) 2.26:1. The disease is characterized by a rapid evolution in the absence of therapy. The major problem is an explosive form of the disease, which at present seems difficult to control in this country. Fifteen of the 49 patients (30.6%) died before completion of the first course of chemotherapy; however, complete remission (CR) was obtained for 30 patients (61%). Overall survival was 42.85% (21/49), whereas survival of patients who reached CR is 70% (21/30). When CR was obtained, deaths were related to cerebrospinal fluid involvement, local recurrence, secondary bone marrow involvement or therapeutic accidents. All patients alive with no evidence of disease (NED) 8-months after CR can be considered definitively cured. Epstein-Barr virus (EBV) serology performed on 31 BL patients and on a control group of 25 children with other malignant tumours showed that most Algerian BL have elevated EBV titres. A search for viral markers within malignant cells in 17 patients indicated that 88% (15/17) of the BL cases were EBV-associated. Analysis of the immunological and cytogenetic data showed that, as in the rest of the world, these BL cases involve proliferation of B-cell-type lymphocytes, with characteristic cytogenetic translocations involving chromosome 8. This report represents the most detailed description so far of BL from an area in non-equatorial Africa and the first report of a large series from North Africa.


Acoustic source localization with microphone arrays for remote noise monitoring in an Intensive Care Unit.
An approach is described to apply spatial filtering with microphone arrays to localize acoustic sources in an Intensive Care Unit (ICU). This is done to obtain more detailed information about disturbing noise sources in the ICU with the ultimate goal of facilitating the reduction of the overall background noise level, which could potentially improve the patients' experience and reduce the time needed for recovery. This paper gives a practical description of the system, including the audio hardware setup as well as the design choices for the microphone arrays. Additionally, the necessary signal processing steps required to produce meaningful data are explained, focusing on a novel clustering approach that enables an automatic evaluation of the spatial filtering results. This approach allows the data to be presented to the nursing staff in a way that enables them to act on the results produced by the system.


A new device for evaluating distance and directional performance of golf putters.
The purpose of this study was to construct and evaluate the reliability of an apparatus for testing golf putters with respect to distance and direction deviation at different impact points on the clubface. An apparatus was constructed based on the pendulum principle that allowed putter golf clubs to swing at different speeds. The mean speed of the club head before ball impact, and of the ball after impact, was calculated from time measurements with photocells. A pin profile rig was used to determine the directional deviation of the golf ball. Three different putters were used in the study, two that are commercially available (toe-heel weighted and mallet types) and one specially made (wing-type) putter. The points of impact were the sweet spot (as indicated by the manufacturer's aim line), and 1, 2 and 3 cm to the left and right of the sweet spot. Calculation of club head speed before impact, and of ball speed after impact (proportional to distance), showed errors < or = 0.5% of interval duration. The variability in ball impacts was tested by measuring time and direction deviations during 50 impacts on the same ball. The mean duration (+/- s) after ball impact in the test interval (1.16 m long) was 206 (0.8) ms and the standard deviation in the perpendicular spreading of the balls in relation to the direction of the test interval was 0.005 m. A test-retest of one putter on two consecutive days after remounting of the putter on the test apparatus showed less than 1% difference in distance deviation. We conclude that the test apparatus enables a precise recording of distance and direction deviation in golf putters as well as comparisons between different putters. The apparatus and set-up can be used in the laboratory as well as outdoors on the putting green.


Food crop production, nutrient availability, and nutrient intakes in Bangladesh: exploring the agriculture-nutrition nexus with the 2010 Household Income and Expenditure Survey.
Systematic collection of national agricultural data has been neglected in many low- and middle-income countries for the past 20 years. Commonly conducted nationally representative household surveys collect substantial quantities of highly underutilized food crop production data. To demonstrate the potential usefulness of commonly available household survey databases for analyzing the agriculture-nutrition nexus. Using household data from the 2010 Bangladesh Household Income and Expenditure Survey, the role and significance of crop selection, area planted, yield, nutrient production, and the disposition of 34 food crops in affecting the adequacy of farming households' nutrient availability and nutrient intake status are explored. The adequacy of each farming household's available energy, vitamin A, calcium, iron, and zinc and households' apparent intakes and intake adequacies are estimated. Each household's total apparent nutrient intake adequacies are estimated, taking into account the amount of each crop that households consume from their own production, together with food purchased or obtained from other sources. Even though rice contains relatively small amounts of micronutrients, has relatively low nutrient density, and is a relatively poor source of nutrients compared with what other crops can produce on a given tract of land, because so much rice is produced in Bangladesh, it is the source of 90% of the total available energy, 85% of the zinc, 67% of the calcium, and 55% of the iron produced by the agricultural sector. The domination of agriculture and diet by rice is a major constraint to improving nutrition in Bangladesh. Simple examples of how minor changes in the five most common cropping patterns could improve farming households' nutritional status are provided. Household surveys' agricultural modules can provide a useful tool for better understanding national nutrient production realities and possibilities.


Unusual presentation of alveolar echinococcosis as prostatic and paraprostatic cysts in a dog.
Alveolar echinococcosis (AE) is caused by the larval stage (metacestode) of Echinococcus multilocularis. The domestic dog can act as a definitive host and harbor adult cestodes in its small intestine or become an aberrant intermediate host carrying larval stages that may cause severe lesions in the liver, lungs and other organs with clinical signs similar to AE in humans. A case of canine AE, affecting the liver and prostate with development of multilocular hydatid paraprostatic cysts and possible lung involvement is described in an 8-year-old neutered male Labrador retriever dog.The dog presented with progressive weight loss, acute constipation, stranguria and a suspected soft tissue mass in the sublumbar region. Further evaluation included computed tomography of the thorax and abdomen, which revealed cystic changes in the prostate, a paraprostatic cyst, as well as lesions in the liver and lungs. Cytological examination of fine-needle aspirates of the liver, prostate and paraprostatic cyst revealed parasitic hyaline membranes typical of an Echinococcus infection and the presence of E. multilocularis-DNA was confirmed by PCR. The dog was treated with albendazole and debulking surgery was considered in case there was a good response to antiparasitic treatment. Constipation and stranguria resolved completely. Six months after the definitive diagnosis, the dog was euthanized due to treatment-resistant ascites and acute anorexia and lethargy. To the authors' knowledge, this is the first publication of an E. multilocularis infection in a dog causing prostatic and paraprostatic cysts. Although rare, E. multilocularis infection should be considered as an extended differential diagnosis in dogs presenting with prostatic and paraprostatic disease, especially in areas where E. multilocularis is endemic.


Effectiveness of different cryotherapies on pain and disease activity in active rheumatoid arthritis. A randomised single blinded controlled trial.
Local cryotherapy is used to relieve pain and inflammation in injuries and inflammatory conditions. Whole-body cryotherapy is an extreme method administered at -110 degrees C for 2 to 3 minutes. The aim of the study was to compare the effect of cryotherapies on pain and inflammation in patients with rheumatoid arthritis (RA). Sixty patients with active seropositive RA were recruited in a randomised controlled single-blinded study to receive whole-body cryotherapy at -110 degrees C, whole-body cryotherapy at -60 degrees C, application of local cold air at -30 degrees C and the use of cold packs locally. In the final analysis, the last 2 groups were pooled. The patients had 2-3 cryotherapy sessions daily for one week plus conventional physiotherapy. Clinical and laboratory variables and patient's and physician's global assessments were used to assess the outcome. Disease activity was calculated by DAS. Pain decreased in all treatment groups, most markedly in the whole-body cryotherapy (-110 degrees C) group. DAS decreased slightly with no statistically significant differences between the groups. No serious or permanent adverse effects were detected. Six of 40 patients (15%) discontinued the whole-body cryotherapy. Pain seemed to decrease more in patients in the whole-body cryotherapy at -110 degrees C than during other cryotherapies, but there were no significant differences in the disease activity between the groups. However, cryotherapy at -110 degrees C is expensive and available only in special centres and may have minor adverse effects. Based on our results, whole-body cryotherapy at -110 degrees C is not superior to local cryotherapy commonly used in RA patients for pain relief and as an adjunct to physiotherapy.


Protective Effects of Sesamin against UVB-Induced Skin Inflammation and Photodamage In Vitro and In Vivo.
Ultraviolet (UV) exposure has been demonstrated as the most critical factor causing extrinsic skin aging and inflammation. This study explored the protective effects and mechanisms of sesamin against skin photodamage. Sesamin reduced intracellular reactive oxygen species production after UVB irradiation in human dermal fibroblasts. The sesamin treatment attenuated mitogen-activated protein (MAP) kinase phosphorylation and matrix metalloproteinase (MMPs) overexpression induced by UVB exposure, and it significantly enhanced the tissue inhibitor of metalloproteinase-1 protein expression. Sesamin also elevated the total collagen content in human fibroblasts by inhibiting UVB-induced mothers against decapentaplegic homolog 7 (Smad7) protein expression. Sesamin reduced UVB-induced inducible nitric oxide synthase (i-NOS) and cyclooxygenase-2 (COX-2) overexpression and inhibited nuclear factor-kappa B (NF-κB) translocation. Moreover, sesamin may regulate the c-Jun N-terminal kinases (JNK) and p38 MAP kinase pathways, which inhibit COX-2 expression. Sesamin could reduce UVB-induced inflammation, epidermal hyperplasia, collagen degradation, and wrinkle formation in hairless mice. It also reduced MMP-1, interleukin (IL-1), i-NOS, and NF-κB in the mouse skin. These results demonstrate that sesamin had antiphotodamage and anti-inflammatory activities. Sesamin has potential for use as a skin protection agent in antiphotodamage and skin care products.


Rapid plasma reagin titer variation in the 2 weeks after syphilis therapy.
Serologic tests for syphilis results at the time of diagnosis are the basis for evaluating response to syphilis therapy. After treatment, however, serologic tests for syphilis titers may continue to increase for several weeks. We evaluated rapid plasma reagin (RPR) titer variation during the 14 days after therapy using data from a recent large, prospective randomized controlled trial. Prospectively enrolled participants in North America and Madagascar with primary, secondary, or early latent syphilis were randomly assigned to penicillin, doxycycline (in the case of penicillin allergy), or azithromycin treatment. Blood for RPR analysis was drawn at days 0, 7, and 14 posttreatment. All RPR titers were determined simultaneously at a central laboratory. Four hundred and seventy patients had data available for at least 2 of 3 RPR measurements. Overall, 20% of patients showed a titer increase of at least 1 dilution in the 14 days after therapy. The greatest proportion of titer increases following therapy was observed in patients with primary syphilis. Comparing outcome of therapy using the initial (day 0) RPR titer versus the maximal RPR titer (during 14 days) resulted in outcome reclassification in 2.98% of participants. Despite the fact that about 20% of early syphilis patients had increases in RPR titers immediately after treatment, these changes rarely influenced assessment of therapeutic outcome. Only 3% of patients treated would have been reclassified.


Educating for Indigenous Health Equity: An International Consensus Statement.
The determinants of health inequities between Indigenous and non-Indigenous populations include factors amenable to medical education's influence-for example, the competence of the medical workforce to provide effective and equitable care to Indigenous populations. Medical education institutions have an important role to play in eliminating these inequities. However, there is evidence that medical education is not adequately fulfilling this role and, in fact, may be complicit in perpetuating inequities.This article seeks to examine the factors underpinning medical education's role in Indigenous health inequity, to inform interventions to address these factors. The authors developed a consensus statement that synthesizes evidence from research, evaluation, and the collective experience of an international research collaboration including experts in Indigenous medical education. The statement describes foundational processes that limit Indigenous health development in medical education and articulates key principles that can be applied at multiple levels to advance Indigenous health equity.The authors recognize colonization, racism, and privilege as fundamental determinants of Indigenous health that are also deeply embedded in Western medical education. To contribute effectively to Indigenous health development, medical education institutions must engage in decolonization processes and address racism and privilege at curricular and institutional levels. Indigenous health curricula must be formalized and comprehensive, and must be consistently reinforced in all educational environments. Institutions' responsibilities extend to advocacy for health system and broader societal reform to reduce and eliminate health inequities. These activities must be adequately resourced and underpinned by investment in infrastructure and Indigenous leadership.


Comparative study of endoscopic band ligation versus injection sclerotherapy with 50% dextrose in water, in symptomatic internal haemorrhoids.
Haemorrhoids are common anorectal conditions seen in surgical practice, with various treatment modalities. This study compared the short-term outcome of injection sclerotherapy with 50% dextrose in water and rubber band ligation in the management of second-and third-degree haemorrhoids, in terms of symptoms improvement, complications, recurrence rate, retreatment rate and acceptability. This was a prospective comparative study that was carried out in the endoscopic unit of the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, in southwestern Nigeria. Sixty consecutive patients with second- and third-degree haemorrhoids, who consented, were recruited into the study and were randomised into two groups. Group A had endoscopic injection sclerotherapy and Group B had endoscopic rubber band ligation. With regard to anal protrusion, more patients consistently reported either complete (16 [64.4%]) or partial (9 [40.9%]) resolution of symptoms in Group B, compared to Group A which had 7 (28.0%) and 5 (22.7%) cases, respectively (P = 0.03). Resolution of anal bleeding was initially more in Group B than A (22 [95.7%] vs. 17 [77.3%] patients, respectively), in the first 24-h post-treatment; however, within the 1st week, this ratio was reversed (P = 0.07). The retreatment rate for Group A and B was 23.3% and 13.3%, respectively,P = 0.34. More patients in Group B experienced severe pain post-treatment compared to Group A (P = 0.01). Three-month post-treatment, two (11.8%) patients in Group A and one (4.5%) in Group B had recurrence of anal bleeding (P = 0.42). There was no recurrence in anal protrusion in both treatment groups. Endoscopic rubber band ligation had a significantly higher success rate than endoscopic injection sclerotherapy, in terms of resolution of anal protrusion, but with higher pain score.


Inferring network structure from cascades.
Many physical, biological, and social phenomena can be described by cascades taking place on a network. Often, the activity can be empirically observed, but not the underlying network of interactions. In this paper we offer three topological methods to infer the structure of any directed network given a set of cascade arrival times. Our formulas hold for a very general class of models where the activation probability of a node is a generic function of its degree and the number of its active neighbors. We report high success rates for synthetic and real networks, for several different cascade models.


Chitosan in Molecularly-Imprinted Polymers: Current and Future Prospects.
Chitosan is widely used in molecular imprinting technology (MIT) as a functional monomer or supporting matrix because of its low cost and high contents of amino and hydroxyl functional groups. The various excellent properties of chitosan, which include nontoxicity, biodegradability, biocompatibility, and attractive physical and mechanical performances, make chitosan a promising alternative to conventional functional monomers. Recently, chitosan molecularly-imprinted polymers have gained considerable attention and showed significant potential in many fields, such as curbing environmental pollution, medicine, protein separation and identification, and chiral-compound separation. These extensive applications are due to the polymers' desired selectivity, physical robustness, and thermal stability, as well as their low cost and easy preparation. Cross-linkers, which fix the functional groups of chitosan around imprinted molecules, play an important role in chitosan molecularly-imprinted polymers. This review summarizes the important cross-linkers of chitosan molecularly-imprinted polymers and illustrates the cross-linking mechanism of chitosan and cross-linkers based on the two glucosamine units. Finally, some significant attempts to further develop the application of chitosan in MIT are proposed.


Chronic kidney disease, cardiovascular events, and the effects of perindopril-based blood pressure lowering: data from the PROGRESS study.
Chronic kidney disease (CKD) is associated with a high risk of cardiovascular disease, but evidence regarding the effectiveness of interventions to reduce that risk is lacking. The Perindopril Protection against Recurrent Stroke Study (PROGRESS) study enrolled 6105 participants with cerebrovascular disease and randomly allocated them to perindopril-based blood pressure-lowering therapy or placebo. Individuals with CKD were at approximately 1.5-fold greater risk of major vascular events, stroke, and coronary heart disease, and were more than twice as likely to die (all P< or =0.002). Perindopril-based treatment reduced the risk of major vascular events by 30% and stroke by 35% among subjects with CKD, and the absolute effects of treatment were 1.7-fold greater for those with CKD than for those without. Considering patients with CKD and a history of cerebrovascular disease, perindopril prevented one stroke or other cardiovascular event among every 11 patients treated over five years. In conclusion, kidney function should be considered when determining the need for blood pressure lowering therapy in patients with cerebrovascular disease.


Geographic variation and plasticity in climate stress resistance among southern African populations of Ceratitis capitata (Wiedemann) (Diptera: Tephritidae).
Traits of thermal sensitivity or performance are typically the focus of species distribution modelling. Among-population trait variation, trait plasticity, population connectedness and the possible climatic covariation thereof are seldom accounted for. Here, we examine multiple climate stress resistance traits, and the plasticity thereof, for a globally invasive agricultural pest insect, the Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae). We also accounted for body size and population genetic connectivity among distinct populations from diverse bioclimatic regions across southern Africa. Desiccation resistance, starvation resistance, and critical thermal minimum (CTmin) and maximum (CTmax) of C. capitata varied between populations. For thermal tolerance traits, patterns of flexibility in response to thermal acclimation were suggestive of beneficial acclimation, but this was not the case for desiccation or starvation resistance. Population differences in measured traits were larger than those associated with acclimation, even though gene flow was high. Desiccation resistance was weakly but positively affected by growing degree-days. There was also a weak positive relationship between CTmin and temperature seasonality, but CTmax was weakly but negatively affected by the same bioclimatic variable. Our results suggest that the invasive potential of C. capitata may be supported by adaptation of tolerance traits to local bioclimatic conditions.


Effects of the crinivirus coat protein-interacting plant protein SAHH on post-transcriptional RNA silencing and its suppression.
In plants, post-transcriptional gene silencing (PTGS) is a sequence-specific mechanism of RNA degradation induced by double-stranded RNA (dsRNA), which is processed into small interfering RNAs (siRNAs). siRNAs are methylated and, thereby, stabilized by the activity of the S-adenosylmethionine-dependent RNA methyltransferase HEN1. PTGS is amplified by host-encoded RNA-dependent RNA polymerases (RDR), which generate dsRNA that is processed into secondary siRNAs. To counteract this RNA silencing-mediated response of the host, plant viruses express proteins with silencing suppression activity. Here, we report that the coat protein (CP) of crinivirus (family Closteroviridae, genus Crinivirus) Tomato chlorosis virus, a known suppressor of silencing, interacts with S-adenosylhomocysteine hydrolase (SAHH), a plant protein essential for sustaining the methyl cycle and S-adenosylmethionine-dependent methyltransferase activity. Our results show that, by contributing to an increased accumulation of secondary siRNAs generated by the action of RDR6, SAHH enhances local RNA silencing. Although downregulation of SAHH prevents local silencing, it enhances the spread of systemic silencing. Our results also show that SAHH is important in the suppression of local RNA silencing not only by the crinivirus Tomato chlorosis virus CP but also by the multifunctional helper component-proteinase of the potyvirus Potato virus Y.


Phase transformations, anisotropic pyroelectric energy harvesting and electrocaloric properties of (Pb,La)(Zr,Sn,Ti)O3 single crystals.
(Pb,La)(Zr,Sn,Ti)O3 (PLZST) single crystals with their chemical composition located at the tetragonal antiferroelectric region are grown via the flux method in a PbO-PbF2-B2O3 mixture. Segregation of the Ti4+ component in the as-grown crystals is observed due to the strong affinity between the oxygen anion and Ti4+ ions. The critical electric field of the antiferroelectric to ferroelectric phase transition is determined to be about 0.5 kV mm-1. The electric field induced ferroelectric phase transforms back into the antiferroelectric phase at a depolarization temperature of 125 °C. Anisotropy of the harvested energy density and electrocaloric behaviors are achieved for the [100], [110] and [111]-oriented PLZST crystals. Based on the thermodynamic theory approach, all the abovementioned behaviors originate from the anisotropic total entropy change. Enhanced electrocaloric strength (0.3 K mm kV-1) and the harvested energy density of 0.62 J cm-3 are obtained in the [111]-oriented PLZST crystals. Our results demonstrate the competence of PLZST single crystals for cooling devices and pyroelectric energy harvesting and provide new opportunities to improve energy harvesting density and electrocaloric properties via the anisotropic structural layout, which make the PLZST crystals attractive for solid state cooling devices and energy conversion technologies.


Comprehensive Immunologic Evaluation of Bronchoalveolar Lavage Samples from Human Patients with Moderate and Severe Seasonal Influenza and Severe COVID-19.
Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or seasonal influenza may lead to respiratory failure requiring intubation and mechanical ventilation. The pathophysiology of this respiratory failure is attributed to local immune dysregulation, but how the immune response to viral infection in the lower airways of the human lung differs between individuals with respiratory failure and those without is not well understood. We used quantitative multiparameter flow cytometry and multiplex cytokine assays to evaluate matched blood and bronchoalveolar lavage (BAL) samples from control human subjects, subjects with symptomatic seasonal influenza who did not have respiratory failure, and subjects with severe seasonal influenza or SARS-CoV-2 infection with respiratory failure. We find that severe cases are associated with an influx of nonclassical monocytes, activated T cells, and plasmablast B cells into the lower airways. Cytokine concentrations were not elevated in the lower airways of moderate influenza patients compared with controls; however, 28 of 35 measured cytokines were significantly elevated in severe influenza, severe SARS-CoV-2 infection, or both. We noted the largest elevations in IL-6, IP-10, MCP-1, and IL-8. IL-1 family cytokines and RANTES were higher in severe influenza infection than severe SARS-CoV-2 infection. Interestingly, only the concentration of IP-10-correlated between blood and BAL during severe infection. Our results demonstrate inflammatory immune dysregulation in the lower airways during severe viral pneumonia that is distinct from lower airway responses seen in human patients with symptomatic, but not severe, illness and suggest that measurement of blood IP-10 concentration may predict this unique dysregulation.


GRIN2B predicts attention problems among disadvantaged children.
It is well established that adversities and GRIN2B (coding an N-methyl-D-aspartate receptor subunit) are independently associated with behavioral and cognitive impairments in childhood. However, a high proportion of children exposed to adversities have good, long-term outcomes. We hypothesized that among children exposed to adversities, GRIN2B variants would predict the worst cognitive and behavioral outcomes. 6 single nucleotide polymorphisms of GRIN2B were genotyped in 625 children aged 6-11 years from an Italian community-based sample. The interacting effect of GRIN2B variants with 4 measures of adversities [low socioeconomic status (SES), preterm delivery, maternal smoking during pregnancy, and absence of breastfeeding] was investigated upon blindly assessed cognitive abilities (vocabulary, block design, digit spans of Wechsler's Intelligence Scale, and Rey complex figure) and parents-rated behavioral problems (Child Behavior Checklist/6-18). Rs2268119 × SES interaction (Hotelling's Trace = 0.07; F(12,1154) = 3.53; p = 0.00004) influenced behavior, with more attention problems among children in the 'either A/T or T/T genotype and low SES' group, compared to all other groups. This interaction effect was not significant in an independent, replication sample of 475 subjects from an Italian community-based sample. GRIN2B variants predict children with the worst outcome in attention functioning among children exposed to low SES. Our findings, if replicated, could help in the identification of children with the highest risk and may prompt cost-effective preventive/treatment strategies.


Hirschsprung disease, associated syndromes and genetics: a review.
Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development.


Juvenile idiopathic arthritis presenting with prolonged fever.
Systemic-onset juvenile idiopathic arthritis (s-JIA) is a systemic disease often accompanied by a fever. We examined 16 patients with s-JIA and reported the clinical manifestations, laboratory data, treatments and outcomes. From 1984 to 2007, 16 children (aged 1-16 years), who were diagnosed as having s-JIA, were admitted to the Mackay Memorial Hospital in Taiwan. We retrospectively reviewed their medical charts. There were nine boys and seven girls, with mean age of onset of 7.4±5.5 years. Fever (100%), typical rash (63%), and arthritis (75%) were the three most common symptoms. Lymphadenopathy (50%), hepatosplenomegaly (63%), pleural pulmonary manifestations (13%) and myalgia (25%) were also noted. One patient had Epstein-Barr virus-associated hemophagocytic syndrome complications. Neutrophilic leukocytosis was a common feature. Other laboratory data showed elevated C-reactive protein levels (25.1±50.3 mg/dL), and erythrocyte sedimentation rates (69±28 mm/hr) and abnormal liver enzymes. Marked hyperferritinemia (> 2,000 ng/mL) was noted in 57% (4/7) of the patients. The mean time from onset of symptoms to diagnosis was 9.2 weeks. Non-steroidal anti-inflammatory drugs, steroids, disease-modifying anti-rheumatic drugs and anti-tumor necrosis factor agents were used for treatment. Due to prolonged fever, 2.0±1.6 (maximum=5) different kinds of antibiotics were used before a diagnosis was made. Most cases had satisfactory therapeutic outcomes except one boy, who had permanent joint contracture. The clinical manifestations of s-JIA in Taiwan were often accompanied by a prolonged fever. This results in clinicians often suspecting bacterial infections and prescribing several kinds of antibiotics. In the case of prolonged fever, s-JIA should always be placed on the list of differential diagnoses.


Alternative to the inferior alveolar nerve block anesthesia when placing mandibular dental implants posterior to the mental foramen.
Local anesthesia block of the inferior alveolar nerve is routinely taught throughout dental education. This commonly used technique eliminates all somatosensory perception of the mandible, mandibular teeth, floor of the mouth, ipsilateral tongue, and all but the lateral (buccal) gingivae. Generally, the dentist or surgeon desires these structures to be anesthetized. However, in the placement of mandibular implants, it may be useful for the patient to be able to sense when the inferior alveolar nerve is in danger of being damaged, possibly producing permanent paresthesia. In this article, the technique of mandibular infiltration prior to mandibular implant placement in the mandible is discussed.


Chemical vapor deposition of mesoporous graphene nanoballs for supercapacitor.
A mass-producible mesoporous graphene nanoball (MGB) was fabricated via a precursor-assisted chemical vapor deposition (CVD) technique for supercapacitor application. Polystyrene balls and reduced iron created under high temperature and a hydrogen gas environment provide a solid carbon source and a catalyst for graphene growth during the precursor-assisted CVD process, respectively. Carboxylic acid and sulfonic acid functionalization of the polystyrene ball facilitates homogeneous dispersion of the hydrophobic polymer template in the metal precursor solution, thus, resulting in a MGB with a uniform number of graphene layers. The MGB is shown to have a specific surface area of 508 m(2)/g and is mesoporous with a mean mesopore diameter of 4.27 nm. Mesopores are generated by the removal of agglomerated iron domains, permeating down through the soft polystyrene spheres and providing the surface for subsequent graphene growth during the heating process in a hydrogen environment. This technique requires only drop-casting of the precursor/polystyrene solution, allowing for mass-production of multilayer MGBs. The supercapacitor fabricated by the use of the MGB as an electrode demonstrates a specific capacitance of 206 F/g and more than 96% retention of capacitance after 10,000 cycles. The outstanding characteristics of the MGB as an electrode for supercapacitors verify the strong potential for use in energy-related areas.


An overview of Indian research in personality disorders.
Personality disorders have significant, but often unrealized, public health importance. The present review summarizes the published work on personality disorders in the Indian population or by Indian researchers residing in the country. Researchers who have worked on assessment methodology in India have demonstrated that clinical diagnosis has a low reliability when compared with semi-structured interviews; and have attempted to increase the feasibility of the standardized use of International Personality Disorder Examination, a semi-structured interview developed by the World Health Organization (WHO). Studies on epidemiology demonstrate that none of the general population studies have employed standardized interviews, and hence, they grossly underestimate the prevalence of personality disorders in the community. The clinical epidemiology studies have employed questionnaires and interviews developed in the West, mostly without local adaptations, with discrepant results. However, these studies show that personality disorders are common in the clinical population and that rates vary across sub populations. While, there are a few reports attesting the theoretical importance of the role of culture in the formation and expression of personality disorders, empirical literature from India in this area is scanty. Similarly, there are few reports on the treatment of personality disorders, while, important areas such as service delivery, etiology, and validity of personality disorders, are unaddressed. The study of personality disorder in India is maturing, with researchers showing increased familiarity with the methodological nuances of this complex area of research.


Development of a Bio-PCR Protocol for the Detection of Xanthomonas arboricola pv. pruni.
A real-time SYBR Green I assay was developed and evaluated as a biological and enzymatic polymerase chain reaction (Bio-PCR) protocol for the detection of Xanthomonas arboricola pv. pruni. Suppression subtractive hybridization was used to generate a X. arboricola pv. pruni-specific subtracted DNA library, using X. arboricola pv. corylina as the driver strain. Primer pair 29F/R, designed from cloned sequence, showed no homology to GenBank sequences and amplified a 344-bp product in all X. arboricola pv. pruni isolates. Compared with other published X. arboricola pv. pruni primers, this primer pair was shown to be the only one capable of differentiating X. arboricola pv. pruni from all other X. arboricola pathovars. A real-time assay was developed and shown to be capable of detecting less than 10 CFU and 0.1 pg of DNA. Epiphytic bacteria isolated from plum tissue was used to further evaluate the specificity of the assay. A Bio-PCR protocol, developed for field evaluation, confirmed X. arboricola pv. pruni isolation from asymptomatic and symptomatic plum tissue over a 9-week period between host flowering and the first appearance of leaf and fruit symptoms in an orchard. Dilution plating enabled X. arboricola pv. pruni numbers to be quantified, providing supportive evidence for the usefulness of the Bio-PCR protocol in plant pathology and quarantine surveillance.


Progressive amnestic dementia, hippocampal sclerosis, and mutation in C9ORF72.
The most common cause of familial frontotemporal lobar degeneration with TAR DNA-binding protein-43 pathology (FTLD-TDP) has been found to be an expansion of a hexanucleotide repeat (GGGGCC) in a noncoding region of the gene C9ORF72. Hippocampal sclerosis (HpScl) is a common finding in FTLD-TDP. Our objective was to screen for the presence of C9ORF72 hexanucleotide repeat expansions in a pathologically confirmed cohort of "pure" hippocampal sclerosis cases (n = 33), outside the setting of FTLD-TDP and Alzheimer's disease (AD). Using a recently described repeat-associated non-ATG (RAN) translation (C9RANT) antibody that was found to be highly specific for c9FTD/ALS, we identified a single "pure" HpScl autopsy case with a repeat expansion in C9ORF72 (c9HpScl). Mutation screening was also performed with repeat-primed polymerase chain reaction and further confirmed with Southern blotting. The c9HpScl patient had a 14-year history of a slowly progressive amnestic syndrome and a clinical diagnosis of probable AD. Neuropsychological testing revealed memory impairment, but no deficits in other cognitive domains. Autopsy showed hippocampal sclerosis with TDP-43 immunoreactive neuronal inclusions relatively limited to limbic lobe structures. Neuritic pathology immunoreactive for p62 was more frequent than TDP-43 in amygdala and hippocampus. Frequent p62-positive neuronal inclusions were present in cerebellar granule neurons as is typical of C9ORF72 mutation carriers. There was no significant FTLD or motor neuron disease. C9RANT was found to be sensitive and specific in this autopsy-confirmed series of HpScl cases. The findings in this patient suggest that the clinical and pathologic spectrum of C9ORF72 repeat expansion is wider than frontotemporal dementia and motor neuron disease, including cases of progressive amnestic dementia with restricted TDP-43 pathology associated with HpScl.


Comparing Five Comorbidity Indices to Predict Mortality in Chronic Kidney Disease: A Retrospective Cohort Study.
Several different indices summarize patient comorbidity using health care data. An accurate index can be used to describe the risk profile of patients, and as an adjustment factor in analyses. How well these indices perform in persons with chronic kidney disease (CKD) is not well known. Assess the performance of 5 comorbidity indices at predicting mortality in 3 different patient groups with CKD: incident kidney transplant recipients, maintenance dialysis patients, and individuals with low estimated glomerular filtration rate (eGFR). Population-based retrospective cohort study. Ontario, Canada, between 2004 and 2014. Individuals at the time they first received a kidney transplant, received maintenance dialysis, or were confirmed to have an eGFR less than 45 mL/min per 1.73m2. Five comorbidity indices: Charlson comorbidity index, end-stage renal disease-modified Charlson comorbidity index, Johns Hopkins' Aggregated Diagnosis Groups score, Elixhauser score, and Wright-Khan index. Our primary outcome was 1-year all-cause mortality. Comorbidity indices were estimated using information in the prior 2 years. Each group was randomly divided 100 times into derivation and validation samples. Model discrimination was assessed using median c-statistics from logistic regression models, and calibration was evaluated graphically. We identified 4111 kidney transplant recipients, 23 897 individuals receiving maintenance dialysis, and 181 425 individuals with a low eGFR. Within 1 year, 108 (2.6%), 4179 (17.5%), and 17 898 (9.9%) in each group had died, respectively. In the validation sample, model discrimination was inadequate with median c-statistics less than 0.7 for all 5 comorbidity indices for all 3 groups. Calibration was also poor for all models. The study used administrative health care data so there is the potential for misclassification. Indices were modeled as continuous scores as opposed to indicators for individual conditions to limit overfitting. Existing comorbidity indices do not accurately predict 1-year mortality in patients with CKD. Current indices could be modified with additional risk factors to improve their performance in CKD, or a new index could be developed for this population.


Streptococcus oriloxodontae sp. nov., isolated from the oral cavities of elephants.
Two strains were isolated from oral cavity samples of healthy elephants. The isolates were Gram-positive, catalase-negative, coccus-shaped organisms that were tentatively identified as a streptococcal species based on the results of biochemical tests. Comparative 16S rRNA gene sequence analysis suggested classification of these organisms in the genus Streptococcus with Streptococcus criceti ATCC 19642(T) and Streptococcus orisuis NUM 1001(T) as their closest phylogenetic neighbours with 98.2 and 96.9% gene sequence similarity, respectively. When multi-locus sequence analysis using four housekeeping genes, groEL, rpoB, gyrB and sodA, was carried out, similarity of concatenated sequences of the four housekeeping genes from the new isolates and Streptococcus mutans was 89.7%. DNA-DNA hybridization experiments suggested that the new isolates were distinct from S. criceti and other species of the genus Streptococcus. On the basis of genotypic and phenotypic differences, it is proposed that the novel isolates are classified in the genus Streptococcus as representatives of Streptococcus oriloxodontae sp. nov. The type strain of S. oriloxodontae is NUM 2101(T) ( =JCM 19285(T) =DSM 27377(T)).


Neonatal maternal separation elevates thalamic corticotrophin releasing factor type 1 receptor expression response to colonic distension in rat.
Early life psychological stress is an essential factor contributing to the development of irritable bowel syndrome (IBS), with corticotrophin releasing factor (CRF) having been implicated in this common gastrointestinal disorder. The aim of our study is to examine the effect of neonatal maternal separation (NMS), an early life stress model, on the brain CRF expression following visceral pain induced by colorectal distension (CRD) stimuli in male rats. Male neonatal Sprague-Dawley rats were subjected to 3-hr daily maternal separation on postnatal day 2-21, with unseparated normal (N) rats serving as controls. Electromyogram signals (EMG) in response to phasic CRD were measured. The results demonstrated an increased pain response and EMG magnitudes in NMS rats as compared to N rats in response to CRD stimulation. The mRNA and protein expressions of CRF in hippocampus, cortex and thalamus of NMS and N group following the CRD stress were determined by real-time quantitative PCR and western-blotting studies respectively. There was an increased mRNA and protein level of CRF in thalamus of NMS rats but no apparent change in CRF expression in hippocampus and cortex of both groups. Furthermore, an increased expression of CRF type 1 receptor (CRF-R1) was observed in the thalamus of NMS rats. These results suggested an up-regulation of thalamus CRF-R1 is associated with visceral hyperalgesia in the rat model of NMS.


New insight into the helium-induced damage in MAX phase Ti3AlC2 by first-principles studies.
In the present work, the behavior of He in the MAX phase Ti3AlC2 material is investigated using first-principle methods. It is found that, according to the predicted formation energies, a single He atom favors residing near the Al plane in Ti3AlC2. The results also show that Al vacancies are better able to trap He atoms than either Ti or C vacancies. The formation energies for the secondary vacancy defects near an Al vacancy or a C vacancy are strongly influenced by He impurity content. According to the present results, the existence of trapped He atoms in primary Al vacancy can promote secondary vacancy formation and the He bubble trapped by Al vacancies has a higher tendency to grow in the Al plane of Ti3AlC2. The diffusion of He in Ti3AlC2 is also investigated. The energy barriers are approximately 2.980 eV and 0.294 eV along the c-axis and in the ab plane, respectively, which means that He atoms exhibit faster migration parallel to the Al plane. Hence, the formation of platelet-like bubbles nucleated from the Al vacancies is favored both energetically and kinetically. Our calculations also show that the conventional spherical bubbles may be originated from He atoms trapped by C vacancies. Taken together, these results are able to explain the observed formation of bubbles in various shapes in recent experiments. This study is expected to provide new insight into the behaviors of MAX phases under irradiation from electronic structure level in order to improve the design of MAX phase based materials.


Peptidomimetic Src/pretubulin inhibitor KX-01 alone and in combination with paclitaxel suppresses growth, metastasis in human ER/PR/HER2-negative tumor xenografts.
Src kinase is elevated in breast tumors that are ER/PR negative and do not overexpress HER2, but clinical trials with Src inhibitors have shown little activity. The present study evaluated preclinical efficacy of a novel peptidomimetic compound, KX-01 (KX2-391), that exhibits dual action as an Src and pretubulin inhibitor. KX-01 was evaluated as a single-agent and in combination with paclitaxel in MDA-MB-231, MDA-MB-157, and MDA-MB-468 human ER/PR/HER2-negative breast cancer cells. Treatments were evaluated by growth/apoptosis, isobologram analysis, migration/invasion assays, tumor xenograft volume, metastasis, and measurement of Src, focal adhesion kinase (FAK), microtubules, Ki67, and microvessel density. KX-01 inhibited cell growth in vitro and in combination with paclitaxel resulted in synergistic growth inhibition. KX-01 resulted in a dose-dependent inhibition of MDA-MB-231 and MDA-MB-157 tumor xenografts (1 and 5 mg/kg, twice daily). KX-01 inhibited activity of Src and downstream mediator FAK in tumors that was coincident with reduced proliferation and angiogenesis and increased apoptosis. KX01 also resulted in microtubule disruption in tumors. Combination of KX-01 with paclitaxel resulted in significant regression of MDA-MB-231 tumors and reduced metastasis to mouse lung and liver. KX-01 is a potently active Src/pretubulin inhibitor that inhibits breast tumor growth and metastasis. As ER/PR/HER2-negative patients are candidates for paclitaxel therapy, combination with KX-01 may potentiate antitumor efficacy in management of this aggressive breast cancer subtype.


Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy.
The American Academy of Ophthalmology recommendations for screening of chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy were published in 2002, but improved screening tools and new knowledge about the prevalence of toxicity have appeared in the ensuing years. No treatment exists as yet for this disorder, so it is imperative that patients and their physicians be aware of the best practices for minimizing toxic damage. New data have shown that the risk of toxicity increases sharply toward 1% after 5 to 7 years of use, or a cumulative dose of 1000 g, of HCQ. The risk increases further with continued use of the drug. The prior recommendation emphasized dosing by weight. However, most patients are routinely given 400 mg of HCQ daily (or 250 mg CQ). This dose is now considered acceptable, except for individuals of short stature, for whom the dose should be determined on the basis of ideal body weight to avoid overdosage. A baseline examination is advised for patients starting these drugs to serve as a reference point and to rule out maculopathy, which might be a contraindication to their use. Annual screening should begin after 5 years (or sooner if there are unusual risk factors). Newer objective tests, such as multifocal electroretinogram (mfERG), spectral domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF), can be more sensitive than visual fields. It is now recommended that along with 10-2 automated fields, at least one of these procedures be used for routine screening where available. When fields are performed independently, even the most subtle 10-2 field changes should be taken seriously and are an indication for evaluation by objective testing. Because mfERG testing is an objective test that evaluates function, it may be used in place of visual fields. Amsler grid testing is no longer recommended. Fundus examinations are advised for documentation, but visible bull's-eye maculopathy is a late change, and the goal of screening is to recognize toxicity at an earlier stage. Patients should be aware of the risk of toxicity and the rationale for screening (to detect early changes and minimize visual loss, not necessarily to prevent it). The drugs should be stopped if possible when toxicity is recognized or strongly suspected, but this is a decision to be made in conjunction with patients and their medical physicians.


Assessment of iris vasculature abnormalities in dogs with diabetes mellitus.
To identify and characterize abnormalities of iris vasculature in dogs with diabetes mellitus, compared to clinically normal, age-matched control dogs, by means of anterior segment angiography. 10 dogs with naturally occurring diabetes mellitus and 10 age-matched control dogs with no ocular or systemic disease. The day before iris vasculature abnormality (IVA) assessment, all dogs underwent complete physical and ophthalmic examinations and baseline clinicopathologic analyses. For diabetic dogs, serum fructosamine concentration and a 12-hour blood glucose concentration curve were generated. The next day, all dogs were sedated and anterior segment angiography (following IV injection of indocyanine green [1 mg/kg] and subsequently sodium fluorescein [20 mg/kg]) was performed with a full-spectrum camera and camera adapter system. Group findings were compared, and multiple linear regression analysis was performed to identify potential factor associations with IVAs. During anterior segment angiography, the arterial, capillary, and venous phases were identified in all dogs. Times to onset of all phases in diabetic dogs were significantly less than those in control dogs. Vascular disruptions within the peripupillary region (evident following sodium fluorescein administration) were common in diabetic dogs. Severity of dye leakage into the iris stroma and aqueous humor was significantly greater in diabetic dogs than in control dogs. Duration of disease, mean blood glucose concentration, and serum fructosamine concentration were significantly associated with IVAs. In diabetic dogs, anterior segment angiography revealed IVAs that were not evident in control dogs. The severity of those changes appeared to be associated with disease duration and blood glucose regulation.


Treatment mechanism in the MRC preschool autism communication trial: implications for study design and parent-focussed therapy for children.
The PACT randomised-controlled trial evaluated a parent-mediated communication-focused treatment for children with autism, intended to reduce symptom severity as measured by a modified Autism Diagnostic Observation Schedule-Generic (ADOS-G) algorithm score. The therapy targeted parental behaviour, with no direct interaction between therapist and child. While nonsignificant group differences were found on ADOS-G score, significant group differences were found for both parent and child intermediate outcomes. This study aimed to better understand the mechanism by which the PACT treatment influenced changes in child behaviour though the targeted parent behaviour. Mediation analysis was used to assess the direct and indirect effects of treatment via parent behaviour on child behaviour and via child behaviour on ADOS-G score. Alternative mediation was explored to study whether the treatment effect acted as hypothesised or via another plausible pathway. Mediation models typically assume no unobserved confounding between mediator and outcome and no measurement error in the mediator. We show how to better exploit the information often available within a trial to begin to address these issues, examining scope for instrumental variable and measurement error models. Estimates of mediation changed substantially when account was taken of the confounder effects of the baseline value of the mediator and of measurement error. Our best estimates that accounted for both suggested that the treatment effect on the ADOS-G score was very substantially mediated by parent synchrony and child initiations. The results highlighted the value of repeated measurement of mediators during trials. The theoretical model underlying the PACT treatment was supported. However, the substantial fall-off in treatment effect highlighted both the need for additional data and for additional target behaviours for therapy.


First-principles study of the structural stability and electrochemical properties of Na2MSiO4 (M = Mn, Fe, Co and Ni) polymorphs.
Sodium orthosilicates Na2MSiO4 (M = Mn, Fe, Co and Ni) have attracted much attention due to the possibility of exchanging two electrons per formula unit. They are also found to exhibit great structural stability due to a diamond-like arrangement of tetrahedral groups. In this work, we have systematically studied the possible polymorphism of these compounds by means of density functional theory, optimising the structure of a number of systems with different group symmetries. The ground state is found to be Pc-symmetric for all the considered M = Mn, Fe, Co, Ni, and several similar structures exhibiting different symmetries coexist within a 0.3 eV energy window from this structural minimum. The intercalation/deintercalation potential is calculated for varying transition metal atoms M. Iron sodium orthosilicates, attractive due to the natural abundance of both materials, exhibit a low voltage, which can be enhanced by doping with nickel. The diffusion pathways for Na atoms are discussed, and the relevant barriers are calculated using the nudged elastic band method on top of DFT calculations. Also in this case, nickel impurities would improve the material performances by lowering the barrier heights. Notably, the ionic conductivity is found to be systematically larger with respect to the case of lithium orthosilicates, due to a larger spacing between atomic layers and to the non-directional bonding between Na and the neighbouring atoms. Overall, the great structural stability of the material together with the low barriers for Na diffusion indicates this class of materials as good candidates for modern battery technologies.


COMT-by-sex interaction effect on psychosis proneness.
Schizotypy phenotypes in the general population share etiopathogenic mechanisms and risk factors with schizophrenia, supporting the notion of psychosis as a continuum ranging from nonclinical to clinical deviance. Catechol-O-methyltransferase (COMT) is a candidate susceptibility gene for schizophrenia that is involved in the regulation of dopamine in the prefrontal cortex. Several recent studies have reported a sex difference in the impact of COMT genotype on psychiatric and cognitive phenotypes and personality traits. The present study investigated the association of COMT Val158Met (rs4680) with psychometric positive and negative schizotypy and psychotic experiences in a sample of 808 nonclinical young adults. The main finding was that sex moderates the association of COMT genotype with the negative dimension of both schizotypy and psychotic experiences. Male subjects carrying the Val allele tended to score higher on the negative dimension of both trait and symptom-like measures. The results from the present study are consistent with recent work suggesting an association between negative schizotypy and diminished prefrontal dopamine availability. They support the idea that a biological differentiation underlies the positive and negative schizotypy dimensions. Additionally, these findings contribute to the growing literature on sex-specific effects of COMT on the predisposition to psychiatric disorders and personality traits.


A screening model for oral cancer using risk scores: development and validation.
A study was conducted to develop and validate a screening model using risk scores to identify individuals at high risk for developing oral cancer in an Indian population. Life-course data collected from a multicentre case-control study in India were used. Interview was conducted to collect information on predictors limited to the time before the onset of symptoms or cancer diagnosis. Predictors included statistically significant risk factors in the multivariable model. A risk score for each predictor was derived from respective odds ratios (OR). Discrimination of the final model, risk scores and various risk score cut-offs was examined using the c statistic. The optimal cut-off was determined as the one with good area under curve (AUC) and high sensitivity. Predictive ability of the regression model and cut-off risk score was determined by calculating sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Models were validated from a bootstrap sample. Smoking, chewing quid and/or tobacco, alcohol, a family history of upper aero-digestive tract cancer, diet and oral hygiene behaviour were the predictors. Risk scores ranged from 0 to 28. Area under the receiver operating characteristic (ROC) curve for risk scores was good (0.866). The sensitivity (0.928) and negative predictive value (0.927) were high, while specificity (0.603) and positive predictive value (0.607) were low for a risk score cut-off of 6. A risk score model to screen for individuals with high risk of oral cancer with satisfactory predictive ability was developed in the Indian population. Validation of the model in other populations is necessary before it can be recommended to identify subgroups of the population to be directed towards more extensive clinical evaluation.


Picture recognition of food by macaques (Macaca silenus).
Pictorial representations of three-dimensional objects are often used to investigate animal cognitive abilities; however, investigators rarely evaluate whether the animals conceptualize the two-dimensional image as the object it is intended to represent. We tested for picture recognition in lion-tailed macaques by presenting five monkeys with digitized images of familiar foods on a touch screen. Monkeys viewed images of two different foods and learned that they would receive a piece of the one they touched first. After demonstrating that they would reliably select images of their preferred foods on one set of foods, animals were transferred to images of a second set of familiar foods. We assumed that if the monkeys recognized the images, they would spontaneously select images of their preferred foods on the second set of foods. Three monkeys selected images of their preferred foods significantly more often than chance on their first transfer session. In an additional test of the monkeys' picture recognition abilities, animals were presented with pairs of food images containing a medium-preference food paired with either a high-preference food or a low-preference food. The same three monkeys selected the medium-preference foods significantly more often when they were paired with low-preference foods and significantly less often when those same foods were paired with high-preference foods. Our novel design provided convincing evidence that macaques recognized the content of two-dimensional images on a touch screen. Results also suggested that the animals understood the connection between the two-dimensional images and the three-dimensional objects they represented.


Inhibition of transglutaminase 2 mitigates transcriptional dysregulation in models of Huntington disease.
Caused by a polyglutamine expansion in the huntingtin protein, Huntington's disease leads to striatal degeneration via the transcriptional dysregulation of a number of genes, including those involved in mitochondrial biogenesis. Here we show that transglutaminase 2, which is upregulated in HD, exacerbates transcriptional dysregulation by acting as a selective corepressor of nuclear genes; transglutaminase 2 interacts directly with histone H3 in the nucleus. In a cellular model of HD, transglutaminase inhibition de-repressed two established regulators of mitochondrial function, PGC-1alpha and cytochrome c and reversed susceptibility of human HD cells to the mitochondrial toxin, 3-nitroproprionic acid; however, protection mediated by transglutaminase inhibition was not associated with improved mitochondrial bioenergetics. A gene microarray analysis indicated that transglutaminase inhibition normalized expression of not only mitochondrial genes but also 40% of genes that are dysregulated in HD striatal neurons, including chaperone and histone genes. Moreover, transglutaminase inhibition attenuated degeneration in a Drosophila model of HD and protected mouse HD striatal neurons from excitotoxicity. Altogether these findings demonstrate that selective TG inhibition broadly corrects transcriptional dysregulation in HD and defines a novel HDAC-independent epigenetic strategy for treating neurodegeneration.


Transient cerebral vasodilatory effect of neuropeptide Y mediated by nitric oxide.
The effects of intracarotidly injected neuropeptide Y (NPY; 0.1 micrograms/kg) on the local cerebral blood volume (CBV) and blood flow (CBF) in the parieto-temporal cortex were examined by the photoelectric method in 17 anesthetized cats. CBV reflects the cumulative crosssectional area of the cerebral microvascular beds. NPY immediately caused transient but significant increases in CBV and CBF, which lasted for less than 5 min. Thereafter, CBV returned to and remained at the control level, although CBF was decreased by 30-40% for 60 min during the monitoring period. The CBV increases after NPY were prevented by a 15-min preinjection of 0.35 mg/kg/min of NG-monomethyl-L-arginine (L-NMMA), which is a competitive blocker of nitric oxide synthesis. The CBV increases after NPY reappeared following a 15-min administration of 0.25 mg/kg/min of L-arginine, which is a precursor of nitric oxide. We conclude that NPY administered in vivo exerts a previously unreported effect of transient vasodilatation on the cerebral microvessels. This action appears to be mediated by nitric oxide, which is a major candidate as an endothelium-derived relaxing factor (EDRF).


Scanning laser topography and scanning laser polarimetry: comparing both imaging methods at same distances from the optic nerve head.
To compare the performance of scanning laser topography (SLT) and scanning laser polarimetry (SLP) on the rim of the optic nerve head and its surrounding area and thereby to evaluate whether these imaging technologies are influenced by other factors beyond the thickness of the retinal nerve fiber layer (RNFL). A total of 154 eyes from 5 different groups were examined: young healthy subjects (YNorm), old healthy subjects (ONorm), patients with normal tension glaucoma (NTG), patients with open-angle glaucoma and early glaucomatous damage (OAGE) and patients with open-angle glaucoma and advanced glaucomatous damage (OAGA). SLT and SLP measurements were taken. Four concentric circles were superimposed on each of the images: the first one measuring at the rim of the optic nerve head (1.0 ONHD), the next measuring at 1.25 optic nerve head diameters (ONHD), at 1.5 ONHD and at 1.75 ONHD. The aligned images were analyzed using GDx/NFA software. Both methods showed peaks of RNFL thickness in the superior and inferior segments of the ONH. The maximum thickness, registered by the SLT device was at the ONH rim where the SLP device tended to measure the lowest values. SLT measurements at the ONH were influenced by other tissues besides the RNFL like blood vessels and glial tissues. SLT and SLP were most strongly correlated at distances of 1.25 and 1.5 ONHD. While both imaging technologies are valuable tools in detecting glaucoma, measurements at the ONH rim should be interpreted critically since both methods might provide misleading results. For the assessment of the retinal nerve fiber layer we would like to recommend for both imaging technologies, SLT and SLP, measurements in 1.25 and 1.5 ONHD distance of the rim of the optic nerve head.


Phase variations of the Mycoplasma penetrans main surface lipoprotein increase antigenic diversity.
Mycoplasma penetrans is a recently identified mycoplasma, isolated from urine samples collected from human immunodeficiency virus (HIV)-infected patients. Its presence is significantly associated with HIV infection. The major antigen recognized during natural and experimental infections is an abundant P35 lipoprotein which, upon extraction, segregates in the Triton X-114 detergent phase and is the basis of M. penetrans-specific serological assays. We report here that the P35 antigen undergoes spontaneous and reversible phase variation at high frequency, leading to heterogeneous populations of mycoplasmas, even when derived from a clonal lineage. This variation was found to be determined at the transcription level, and although this property is not unique among the members of the class Mollicutes, the mechanism by which it occurs in M. penetrans differs from those previously described for other Mycoplasma species. Indeed, the P35 phase variation was due neither to a p35 gene rearrangement nor to point mutations within the gene itself or its promoter. The P35 phase variation in the different variants obtained was concomitant with modifications in the pattern of other expressed lipoproteins, probably due to regulated expression of selected members of a gene family which was found to potentially encode similar lipoproteins. M. penetrans variants could be selected on the basis of their lack of colony immunoreactivity with a polyclonal antiserum against a Triton X-114 extract, strongly suggesting that the mechanisms involved in altering surface antigen expression might allow evasion of the humoral immune response of the infected host.


Comparative evaluation of linear and exponential amplification techniques for expression profiling at the single-cell level.
Single-cell microarray expression profiling requires 108-109-fold amplification of the picogram amounts of total RNA typically found in eukaryotic cells. Several methods for RNA amplification are in general use, but little consideration has been given to the comparative analysis of those methods in terms of the overall validity of the data generated when amplifying from single-cell amounts of RNA, rather than their empirical performance in single studies. We tested the performance of three methods for amplifying single-cell amounts of RNA under ideal conditions: T7-based in vitro transcription; switching mechanism at 5' end of RNA template (SMART) PCR amplification; and global PCR amplification. All methods introduced amplification-dependent noise when mRNA was amplified 108-fold, compared with data from unamplified cDNA. PCR-amplified cDNA demonstrated the smallest number of differences between two parallel replicate samples and the best correlation between independent amplifications from the same cell type, with SMART outperforming global PCR amplification. SMART had the highest true-positive rate and the lowest false-positive rate when comparing expression between two different cell types, but had the lowest absolute discovery rate of all three methods. Direct comparison of the performance of SMART and global PCR amplification on single-cell amounts of total RNA and on single neural stem cells confirmed these findings. Under the conditions tested, PCR amplification was more reliable than linear amplification for detecting true expression differences between samples. SMART amplification had a higher true-positive rate than global amplification, but at the expense of a considerably lower absolute discovery rate and a systematic compression of observed expression ratios.


Strain tuning of closed topological nodal lines and opposite pockets in quasi-two-dimensional α-phase FeSi2.
Following topological nodal point semimetals, topological nodal line semimetals with one dimensional (1D) topological elements have recently aroused great interest worldwide in the fields of quantum chemistry and condensed matter physics. In this study, by means of first-principles, we predict that quasi-two-dimensional (2D) α-FeSi2 with a P4/mmm space group is a topological nodal line semimetal with two nodal lines close to the Fermi level, in the kz = 0 and kz = π planes. Usually, topological nodal line semimetals can be classified into type I, type II, and hybrid-type categories, each type with different physical properties. Importantly, for the first time, we find that type I, type II, and hybrid-type nodal lines can be realized in a realistic material, i.e., quasi-2D α-FeSi2, by strain switching. The realization of tunable nodal line types occurs because quasi-2D α-FeSi2 has special opposite-pocket-behaving bands around the Fermi level. The results presented herein reflect that α-FeSi2 is a valuable candidate for spintronics application by utilization of type I, type II, and hybrid-type topological nodal line semimetals in a single material tuned by mechanical strain.