An intelligent subtitle detection model for locating television commercials.
A strategy for locating television (TV) commercials in TV programs is proposed. Based on the observation that most TV commercials do not have subtitles, the first stage exploits six subtitle constraints and an adaptive neurofuzzy inference system model to determine whether a frame contains a subtitle or not. The second stage involves locating the mark-in/mark-out points using a genetic algorithm. An interactive user interface allows users to efficiently identify and fine-tune the exact boundaries separating the commercials from the program content. Furthermore, erroneous boundaries are manually corrected. Experimental results show that the precision rate and recall rates exceed 90%.


Case managers for older persons with multi-morbidity and their everyday work - a focused ethnography.
Modern-day health systems are complex, making it difficult to assure continuity of care for older persons with multi-morbidity. One way of intervening in a health system that is leading to fragmented care is by utilising Case Management (CM). CM aims to improve co-ordination of healthcare and social services. To better understand and advance the development of CM, there is a need for additional research that provides rich descriptions of CM in practice. This knowledge is important as there could be unknown mechanisms, contextual or interpersonal, that contribute to the success or failure of a CM intervention. Furthermore, the CM intervention in this study is conducted in the context of the Swedish health system, which prior to this intervention was unfamiliar with this kind of coordinative service. The aim of this study was to explore the everyday work undertaken by case managers within a CM intervention, with a focus on their experiences. The study design was qualitative and inductive, utilising a focused ethnographic approach. Data collection consisted of participant observations with field notes as well as a group interview and individual interviews with nine case managers, conducted in 2012/2013. The interviews were recorded, transcribed verbatim and subjected to thematic analysis. An overarching theme emerged from the data: Challenging current professional identity, with three sub-themes. The sub-themes were 1) Adjusting to familiar work in an unfamiliar role; 2) Striving to improve the health system through a new role; 3) Trust is vital to advocacy. Findings from this study shed some light on the complexity of CM for older persons with multi-morbidity, as seen from the perspective of case managers. The findings illustrate how their everyday work as case managers represents a challenge to their current professional identity. These findings could help to understand and promote the development of CM models aimed at a population of older persons with complex health needs.


Antimicrobial activity of immobilized lactoferrin and lactoferricin.
Lactoferrin and lactoferricin were immobilized on glass surfaces via two linkers, 4-azidobenzoic acid (ABA) or 4-fluoro-3-nitrophenyl azide (FNA). The resulting surfaces were characterized by X-ray photoelectron spectroscopy (XPS) and contact angle measurements. The antimicrobial activity of the surfaces was determined using Pseudomonas aeruginosa and Staphylococcus aureus strains by fluorescence microscopy. Lactoferrin and lactoferricin immobilization was confirmed by XPS showing significant increases (p < 0.05) in nitrogen on the glass surface. The immobilization of both proteins slightly increased the overall hydrophobicity of the glass. Both lactoferrin and lactoferricin immobilized on glass significantly (p < 0.05) reduced the numbers of viable bacterial cells adherent to the glass. For P. aeruginosa, the immobilized proteins consistently increased the percentage of dead cells compared to the total cells adherent to the glass surfaces (p < 0.03). Lactoferrin and lactoferricin were successfully immobilized on glass surfaces and showed promising antimicrobial activity against pathogenic bacteria. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2612-2617, 2017.


Comparative evaluation of current peptide production platforms used in absolute quantification in proteomics.
Absolute quantification of peptides by mass spectrometry requires a reference, frequently using heavy isotope-coded peptides as internal standards. These peptides have traditionally been generated by chemical stepwise synthesis. Recently a new way to supply such peptides was described in which nucleotide sequences coding for the respective peptides are concatenated into a synthetic gene (QconCAT). These QconCATs are then expressed to produce a polypeptide consisting of concatenated peptides, purified, quantified by various methods, and then digested to yield the final internal standard peptides. Although both of these methods for peptide production are routinely used for absolute quantifications, there is currently no information regarding the accuracy of the quantifications made in each case. In this study, we used sets of synthetic and biological peptides in parallel to evaluate the accuracy of either method. We also addressed some technical issues regarding the preparation and proper utilization of such standard peptides. Twenty-five peptides derived from the Caenorhabditis elegans proteome were selected for this study. Twenty-four were successfully chemically synthesized. Five QconCAT genes were designed, each a concatenation of the same 25 peptides but each in separate, different randomized order, and expressed via in vitro translation reactions that contained heavy isotope-labeled lysine and arginine. Three of the five QconCATs were successfully produced. Different digestion conditions, including various detergents and incubation conditions, were tested to find those optimal for the generation of a reproducible and accurate reference sample mixture. All three QconCAT polypeptides were then digested using the optimized conditions and then mixed in a 1:1 ratio with their synthetic counterparts. Multireaction monitoring mass spectrometry was then used for quantification. Results showed that the digestion protocol had a significant impact on equimolarity of final peptides, confirming the need for optimization. Under optimal conditions, however, most QconCAT peptides were produced at an equimolar ratio. A few QconCAT-derived peptides were largely overestimated due to problems with solubilization or stability of the synthetic peptides. Although the order in which the peptide sequences appeared in the QconCAT sequence proved to affect the success rate of in vitro translation, it did not significantly affect the final peptide yields. Overall neither the chemical synthesis nor the recombinant genetic approach proved to be superior as a method for the production of reference peptides for absolute quantification.


DMD-based implementation of patterned optical filter arrays for compressive spectral imaging.
Compressive spectral imaging (CSI) captures multispectral imagery using fewer measurements than those required by traditional Shannon-Nyquist theory-based sensing procedures. CSI systems acquire coded and dispersed random projections of the scene rather than direct measurements of the voxels. To date, the coding procedure in CSI has been realized through the use of block-unblock coded apertures (CAs), commonly implemented as chrome-on-quartz photomasks. These apertures block or permit us to pass the entire spectrum from the scene at given spatial locations, thus modulating the spatial characteristics of the scene. This paper extends the framework of CSI by replacing the traditional block-unblock photomasks by patterned optical filter arrays, referred to as colored coded apertures (CCAs). These, in turn, allow the source to be modulated not only spatially but spectrally as well, entailing more powerful coding strategies. The proposed CCAs are synthesized through linear combinations of low-pass, high-pass, and bandpass filters, paired with binary pattern ensembles realized by a digital micromirror device. The optical forward model of the proposed CSI architecture is presented along with a proof-of-concept implementation, which achieves noticeable improvements in the quality of the reconstruction.


Infection risk in patients with rheumatoid arthritis treated with etanercept or adalimumab.
To compare the risk of infection for rheumatoid arthritis (RA) patients who took etanercept or adalimumab medication in a nationwide population. RA patients who took etanercept or adalimumab were identified in the Taiwan's National Health Insurance Research Database. The composite outcome of serious infections, including hospitalization for infection, reception of an antimicrobial injection, and tuberculosis were followed for 365 days. A Kaplan-Meier survival curve with a log-rank test and Cox proportional hazards regression were used to compare risks of infection between the two cohorts of tumor necrosis factor (TNF)-α antagonists users. Hazard ratios (HRs) were obtained and adjusted with propensity scores and clinical factors. Sensitivity analyses and subgroup analyses were also performed. In total, 1660 incident etanercept users and 484 incident adalimumab users were eligible for the analysis. The unadjusted HR for infection of the etanercept users was significantly higher than that of the adalimumab users (HR: 1.93; 95% confidence interval (CI): 1.09-3.42; p=0.024). The HRs were 2.04 (95% CI: 1.14-3.65; p=0.016) and 2.02 (95% CI: 1.13-3.61; p=0.018) after adjusting for propensity scores and for propensity scores in addition to clinical factors, respectively. The subgroup analyses revealed that HRs for composite infection was significantly higher in patient subgroups of older age, female, as well as patients who did not have DM, COPD, and hospitalization history at the baseline. In this head-to-head cohort study involving a nationwide population of patients with RA, etanercept users demonstrated a higher risk of infection than adalimumab users. Results of this study suggest the possible existence of an intra-class difference in infection risk among TNF-α antagonists.


Increased risk for fetal loss in carriers of the factor V Leiden mutation.
An increased risk for fetal loss caused by placental thrombosis is probable in carriers of the factor V Leiden mutation but has not been demonstrated consistently in previous studies. To determine the overall risk for fetal loss and the separate risks for miscarriage and stillbirth in carriers of the factor V Leiden mutation. Retrospective cohort study. Three university hospitals. 228 carriers of the factor V Leiden mutation (77 propositi, 151 relatives) and 121 noncarrier relatives (controls). All participants had been pregnant at least once. Risks for fetal loss, miscarriage (defined as fetal loss within 20 weeks of gestation), and stillbirth (defined as fetal loss after >20 weeks of gestation) in women and in pregnancies were estimated and compared in carriers and noncarriers. Adjusted odds ratios were calculated by using multiple regression analysis. A random-effects model was used for comparisons of pregnancies. Fetal loss occurred in 31.6% of carriers and 22.3% of noncarriers, miscarriage occurred in 29.4% of carriers and 17.4% of noncarriers, and stillbirth occurred in 5.7% of carriers and 5.0% of noncarriers. Fetal loss recurred in 10.1% of carriers and 4.1% of noncarriers (odds ratio, 2.60 [95% CI, 0.96 to 7.03]). Adjusted odds ratios were 2.12 (CI, 1.35 to 3.33) for fetal loss, 2.08 (CI, 1.33 to 3.25) for miscarriage, and 1.60 (CI, 0.58 to 4.43) for still-birth when pregnancies in carriers and noncarriers were compared. Homozygous carriers had a greater risk for fetal loss (odds ratio, 2.01 [CI, 0.94 to 4.32]) and stillbirth (odds ratio, 4.85 [CI, 0.82 to 25.58]) than heterozygous carriers. Carriers of the factor V Leiden mutation have a greater risk for fetal loss (particularly miscarriage) than noncarriers. These data further suggest a greater risk for recurrence of fetal loss in carriers than in noncarriers and a greater risk for fetal loss and stillbirth in homozygous carriers than in heterozygous carriers.


Experimental selection of hypoxia-tolerant Drosophila melanogaster.
Through long-term laboratory selection (over 200 generations), we have generated Drosophila melanogaster populations that tolerate severe, normally lethal, levels of hypoxia. Because of initial experiments suspecting genetic mechanisms underlying this adaptation, we compared the genomes of the hypoxia-selected flies with those of controls using deep resequencing. By applying unique computing and analytical methods we identified a number of DNA regions under selection, mostly on the X chromosome. Several of the hypoxia-selected regions contained genes encoding or regulating the Notch pathway. In addition, previous expression profiling revealed an activation of the Notch pathway in the hypoxia-selected flies. We confirmed the contribution of Notch activation to hypoxia tolerance using a specific γ-secretase inhibitor, N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), which significantly reduced adult survival and life span in the hypoxia-selected flies. We also demonstrated that flies with loss-of-function Notch mutations or RNAi-mediated Notch knockdown had a significant reduction in hypoxia tolerance, but those with a gain-of-function had a dramatic opposite effect. Using the UAS-Gal4 system, we also showed that specific overexpression of the Notch intracellular domain in glial cells was critical for conferring hypoxia tolerance. Unique analytical tools and genetic and bioinformatic strategies allowed us to discover that Notch activation plays a major role in this hypoxia tolerance in Drosophila melanogaster.


How Far Have We Come in the Field of Nerve Regeneration After Trigeminal Nerve Injury?
Patients suffering from nerve injury with sensory disturbances or orofacial pain have greatly reduced quality of life, and it is a big cost for the society. Abnormal sensations caused by trigeminal nerve injury often become chronic, severely debilitating, and extremely difficult to treat. In general, non-invasive treatment such as drug treatment has been insufficient, and there are currently few available effective treatments. Surgical interventions such as end-to-end connection or nerve grafting have disadvantages such as donor site morbidity or formation of neuroma. There is need for optimizing the technique for nerve repair, especially for the trigeminal nerve system, which has so far not yet been well explored. Recently, tissue engineering using biodegradable synthetic material and cell-based therapies represents a promising approach to nerve repair and it has been reported that mesenchymal stem cell (MSC) has an anti-inflammatory effect and seems to play an important role in nerve healing and regeneration.


Pathogen-induced programmed cell death in tobacco.
Sacrificing an infected cell or cells in order to prevent systemic spread of a pathogen appears to be a conserved strategy in both plants and animals. We studied some of the morphological and biochemical events that accompany programmed cell death during the hypersensitive response of tobacco plants infected with tobacco mosaic virus. Certain aspects of this cell death process appeared to be similar to those that take place during apoptosis in animal cells. These included condensation and vacuolization of the cytoplasm and cleavage of nuclear DNA to 50 kb fragments. In contrast, internucleosomal fragmentation, condensation of chromatin at the nuclear periphery and apoptotic bodies were not observed in tobacco plants during tobacco mosaic virus-induced hypersensitive response. A unique aspect of programmed cell death during the hypersensitive response of tobacco to tobacco mosaic virus involved an increase in the amount of monomeric chloroplast DNA. Morphological changes to the chloroplast and cytosol of tobacco cells and increase in monomeric chloroplast DNA occurred prior to gross changes in nuclear morphology and significant chromatin cleavage. Our findings suggest that certain aspects of programmed cell death may have been conserved during the evolution of plants and animals.


Heteroleptic iron(iii) Schiff base spin crossover complexes: halogen substitution, solvent loss and crystallite size effects.
The influence of the halogen substituent on the qsal moiety of iron(iii) heteroleptic compounds with the formulae [Fe(qsal-X)(thsa)]·nMeCN, where qsal-X- = X-substituted quinolylsalicylaldimine; thsa2- = thiosemicarbazone-salicylaldiminate; X = F; n = 2.5, 1·2.5MeCN and X = Cl 2, Br 3 and I 4, n = 1 (labelled 2·MeCN, 3·MeCN and 4·MeCN, respectively) has been systematically investigated. Magnetic studies on solid samples show incomplete spin crossover in 1-3 which can be related to MeCN solvent loss. Complex 4·MeCN remains fully LS up to 360 K. Single crystals have been examined at variable temperatures for samples possessing different degrees of solvation. Intermolecular C-XH interactions are present for X = F, Cl and Br while a C-Iπ interaction is uniquely observed in 4·MeCN. These preferential interactions result in different supramolecular packings of the various halogen substituted compounds. However, as the LS stability increases from F to I, the ligand field strength is then also suggested to increase from F to I. Consequently, in this family, the electronic structure resulting from halogen variation is believed to influence the magnetic properties more than crystal packing effects. Mössbauer spectra, at variable temperatures, confirm the presence of Fe(iii) and the magnetic properties in these compounds. The effect of different drying methods as well as the crystal/powder effect on the magnetic properties are discussed in the case of 2·MeCN.


Utilization of HIV prevention services across racial/ethnic groups among men who have sex with men in San Francisco, California, 2008.
Human Immunodeficiency Virus (HIV) infection in the US is disproportionally higher among Black and Latino men who have sex with men (MSM), compared to other racial/ethnic groups. The 2008 US National HIV Behavioral Surveillance (NHBS) survey of MSM was analyzed to compare utilization of HIV testing, receiving condoms, and individual and group HIV prevention programs among racial/ethnic groups in San Francisco, CA. Using a weighted analysis of the time-location sampling method, racial/ethnic subpopulation estimates were obtained for utilization of these services in the prior 12 months. There was no significant difference in utilization of HIV prevention services among Black (N=37), Latino (N=128), and White (N=275) MSM in San Francisco, CA. Overall 60-70 % of MSM reported their last HIV test within the past 12 months and more than 75 % reported receiving condoms in the last 12 months. However, less than 15 % of MSM reported utilizing individual or group HIV prevention counseling sessions. The NHBS survey demonstrate that the majority of MSM in San Francisco, CA have utilized one or more HIV prevention service in the past 12 months and that there were no racial/ethnic disparities in utilization of these services. However, the utilization of individual or group HIV prevention programs is low and HIV testing is below current recommendations for MSM.


Bladder ganglioneuroma in a 5-year-old girl presenting with a urinary tract infection and hematuria: case report and review of the literature.
Ganglioneuromas are rare benign tumors arising from neural crest cells of the autonomic nervous system. These tumors may rarely localize to the bladder, and few cases have been reported in the adult literature. To date, however, bladder ganglioneuromas have not been reported in the pediatric literature. We report the case of a 5-year-old girl who presented with hematuria and a urinary tract infection and on workup was found to have a large bladder mass. Transurethral resection and pathologic examination revealed the mass to be a ganglioneuroma. The case is presented followed by a brief review of the literature.


Trade in kidneys is ethically intolerable.
In India, as in most countries where trade in human organs is legally prohibited, policies governing transplantation from living donors are designed to identify and exclude prospective donors who have a commercial interest in donation. The effective implementation of such policies requires resources, training and motivation on the part of health professionals responsible for organ procurement and transplantation. If professionals are unconvinced by or unfamiliar with the ethical justification of the relevant laws and policies, they may fail to perform a robust evaluation of prospective donors and transplant candidates, and to act on suspicions or evidence of illicit activities. I comment here on a recent paper by Aggarwal and Adhikary (2016), in which the authors imply that tolerance of illicit commercialism in living kidney donation programmes is not unreasonable, given the insufficiency of kidneys available for transplantation. I argue that such tolerance is unethical not only because of the harmful consequences of kidney trafficking, but because professional tolerance of commercialism undermines public trust in organ procurement programmes and impairs the development of sustainable donation and transplant systems.


[Patients with psychotic disorders in forensic psychiatric hospitals: are there consequences for general psychiatry?].
We assessed data concerning demographic, criminological and psychiatric characteristics of all patients with disorders of the schizophrenic spectrum, who were detained in the forensic psychiatric departments of Mecklenburg-West Pomerania, a federal state of Germany, in 2007. Of the 202 patients of both clinics, 45 suffer from a disorder of the schizophrenic spectrum assessed in ICD-10: F20-F29, which corresponds to 22%. This level is markedly lower than in other regions of Germany. But similarly to results assessed in other federal states of Germany and in Austria there is a high rate of pre-treatment in general psychiatric institutions. It remains a relevant task for general psychiatry to establish adequate interventions for hostile and violent psychotic patients, especially for those with a double diagnosis, history of delinquency and social decline.


COVID-19 Pandemic and the Global Perspective of Turkish Thoracic Society.
It has been more than 3 months now since the first case of COVID-19 was reported in Turkey. Globally, the number of confirmed cases and deaths reached 9,653,048 and 491,128 respectively, as reported by 216 countries by June 27, 2020. Turkey had 1,396 new cases, 194,511 total cases, and 5,065 deaths by the same date. From the first case until today, the Turkish Thoracic Society (TTS) has been very proactive in educating doctors, increasing public awareness, undertaking academic studies, and assisting with public health policies. In the present report, social, academic, and management perspectives of the pandemic are presented under appropriate subtitles. During this critical public health crisis, TTS has once again demonstrated its readiness and constructive stance by supporting public health, healthcare workers, and the environment. This review summarizes the perspective of TTS on each aspect of the COVID-19 pandemic and casts light on its contributions.


Pathologically proved nonspecific interstitial pneumonia: CT pattern analysis as compared with usual interstitial pneumonia CT pattern.
To assess the variability of computed tomography (CT) patterns in patients with pathologic nonspecific interstitial pneumonia (NSIP) and to evaluate correlation of CT patterns with new idiopathic pulmonary fibrosis (IPF) classification guidelines, including pathologic diagnosis and predicted mortality. The ethical review boards of the five institutions that contributed cases waived the need for informed consent for retrospective review of patient records and images. The study included 114 patients with (a) a pathologic diagnosis of idiopathic NSIP (n = 39) or (b) a pathologic diagnosis of usual interstitial pneumonia (UIP) and a clinical diagnosis of IPF (n = 75). Two groups of independent observers evaluated the extent and distribution of various CT findings and identified the following five patterns: UIP, possible UIP, indeterminate (either UIP or NSIP), NSIP, and suggestive of an alternative diagnosis. CT findings were compared with pathologic diagnoses and outcome from clinical findings by using the log-rank test and Kaplan-Meier curves. Radiologists classified 17 cases as UIP, 24 as possible UIP, 13 as indeterminate (either UIP or NSIP), and 56 as NSIP. In 35 of 39 patients with pathologic NSIP, a diagnosis of NSIP was made with CT. On the basis of CT interpretations, the mean overall survival time of patients with UIP, possible UIP, indeterminate findings, or NSIP was 33.5, 73.0, 101.0, and 140.2 months, respectively. Outcome of patients with a CT diagnosis of UIP was significantly worse than that of patients with a pattern of possible UIP, indeterminate findings, or NSIP (log-rank test: P = .013, P = .018, and P < .001, respectively). CT pattern in patients with pathologic NSIP is more uniform than that in patients with pathologic UIP, and CT NSIP pattern is associated with better patient outcome than is CT UIP pattern.


Using a Smartphone App and Coaching Group Sessions to Promote Residents' Reflection in the Workplace.
Reflecting on workplace-based experiences is necessary for professional development. However, residents need support to raise their awareness of valuable moments for learning and to thoughtfully analyze those learning moments afterwards. From October to December 2012, the authors held a multidisciplinary six-week postgraduate training module focused on general competencies. Residents were randomly assigned to one of four conditions with varying degrees of reflection support; they were offered (1) a smartphone app, (2) coaching group sessions, (3) a combination of both, or (4) neither type of support. The app allowed participants to capture in real time learning moments as a text note, audio recording, picture, or video. Coaching sessions held every two weeks aimed to deepen participants' reflection on captured learning moments. Questionnaire responses and reflection data were compared between conditions to assess the effects of the app and coaching sessions on intensity and frequency of reflection. Sixty-four residents participated. App users reflected more often, captured more learning moments, and reported greater learning progress than nonapp users. Participants who attended coaching sessions were more alert to learning moments and pursued more follow-up learning activities to improve on the general competencies. Those who received both types of support were most alert to these learning moments. A simple mobile app for capturing learning moments shows promise as a tool to support workplace-based learning, especially when combined with coaching sessions. Future research should evaluate these tools on a broader scale and in conjunction with residents' and students' personal digital portfolios.


Assessment of brainstem auditory evoked potentials (BAEPs) in patients with acromegaly.
Acromegaly is associated by various systemic complications, involving also the nervous system. Other studies revealed peripheral but not central nervous system impairment with somatosensory evoked potentials examinations in acromegaly. Aim of the present study was to assess whether brainstem transmission in acromegaly is disturbed. The study was carried out in 37 patients. The control group consisted of 47 healthy persons. In all of the subjects, peripheral transmission, reflected by peak I latency, and brainstem transmission, tested by interpeak latency I-V (IPL I-V), were examined. Peak I latency was delayed in 6 out of 37 patients (1 - bilaterally, 2 - right side, 3 - left side). The group-mean latency of peak I was 1.53 msec and 1.56 msec, for the right and left side, respectively. There were found no statistically significant differences between the right and left side, likewise in comparison with control group. In turn, as compared with the controls, IPL I-V was disturbed in 25 out of 37 patients: in most of the cases IPL I-V prolongation was observed (8 - bilateral prolongation, 11 - right side, 6 - left side). Moreover, the statistically significant difference between the brainstem sides (4.27 vs. 4.11 msec; p<0.05) was observed. In the examined patients with acromegaly, there was no peripheral disturbance in transmission, as examined by BAEPs registrations. Conversely, in nearly half of the patients with acromegaly, brainstem transmission was found to be delayed, and significant difference between responses from the both sides of the brainstem were noted.


[Accidents and violence among women attended in Sentinel Emergency Services--Brazil, 2009].
Accidents from external causes affect the human population in different ways. This article seeks to analyze emergency care for women who are victims of accidents and violence. Data from the Surveillance System for Violence and Accidents were analyzed. This study was carried out in 74 emergency units of 23 state capitals and the Federal District in 2009 and included 6,965 women aged from 20-59 years. The age groups of 20-39 and 40-59 years were compared for the occurrence of accidents and violence. Accidents were more frequent among young black women (20-39 years) with more than nine years of schooling. The occurrence of violence was also prevalent in young black women but with less schooling. Falls were the most frequent accidents (38.6%), followed by traffic accidents. The occurrence of violence was more frequent in the home (p <0.000) and the mention of alcohol abuse among victims of violence was predominant. The most frequent type of violence was aggression (84.6%), in which the aggressor was male (79.1%) and identified as an intimate partner (44.1%). It is increasingly important that services are able to provide comprehensive and humanized care to the victims of this important public health problem.


Mitochondrial-dependent, reactive oxygen species-independent apoptosis by myricetin: roles of protein kinase C, cytochrome c, and caspase cascade.
Abrogation of mitochondrial permeability and induction of reactive oxygen species (ROS) production have been observed in chemical-induced apoptosis; however, the relationship between the mitochondria and intracellular ROS levels in apoptosis is still unclear. In the present study, myricetin (ME) but not its respective glycoside, myricitrin (MI; myricetin-3-O-rhamnose) reduced the viability of human leukemia HL-60 cells via apoptosis, characterized by the occurrence of DNA ladders and hypodiploid cells. Results of Western blotting and caspase activity assays showed that activation of caspases 3 and 9 but not caspases 1, 6 or 8 with cleavage of PARP and D4-GDI proteins is involved in ME-induced apoptosis. A reduction in mitochondrial functions characterized by a decrease in the Bcl-2/Bax protein ratio and translocation of cytochrome c (cyt c) from the mitochondria to the cytosol in accordance with a decrease in mitochondrial membrane potential were observed in ME-treated HL-60 cells. No significant induction of intracellular ROS levels by ME was observed by the DCHF-DA assay, DPPH assay or plasmid digestion assay, and antioxidants including N-acetyl-cysteine (NAC), catalase (CAT), superoxide dismutase (SOD), and tiron (TIR) showed no protective effects on ME-induced apoptosis. A PKC activator, 12-O-tetradecaoylphorbol-13-acetate (TPA) significantly attenuated ME-induced apoptosis via preventing cytochrome c release to the cytosol and maintaining the mitochondrial membrane potential by inhibiting the decrease in the Bcl-2/Bax protein ratio; these effects were blocked by protein kinase C (PKC) inhibitors including GF-109203X, H7, and staurosporin. Removing mitochondria by ethidium bromide (EtBr) treatment reduced the apoptotic effect of ME. Results of SAR studies showed that the presence of OH at C3', C4', and C5' is important for the apoptosis-inducing activities of ME, and that ME induces apoptosis in another leukemia cell line, Jurkat cells, but not in primary human polymorphonuclear (PMN) cells or in murine peritoneal macrophages (PMs). The results of the present study suggest that apoptosis induced by ME occurs through a novel mitochondrion-dependent, ROS-independent pathway; TPA protects cells from ME-induced apoptosis via PKC activation which prevents the occurrence of mitochondrial destruction during apoptosis.


HIV-related stigma, isolation, discrimination, and serostatus disclosure: a global survey of 2035 HIV-infected adults.
Little is known globally about the perspectives of people living with HIV/AIDS (PLWHA) on perceived HIV-related stigma and its consequences. Cross-sectional study (January-March 2010) of perceived HIV-related stigma among PLWHA (N = 2035) using a standardized questionnaire. Thirty-seven percent of respondents reported loneliness as a result of their HIV status. Depression was reported by 27%. While 96% reported disclosing their HIV status to at least 1 person, 17% of patients who reported being in a long-term sexual relationship had not disclosed their status to their partner. Variables associated with perceived stigma were living in Asia-Pacific versus other regions (odds ratio [OR]: 2.77; 95% confidence interval [CI] 1.96-3.92); having experienced body/face changes; reported depression (OR: 1.25; 95% CI 1.11-1.38); and nondisclosure of HIV status (OR: 1.75; 95% CI 1.28-2.41). Thirty years into the HIV pandemic, perceived HIV stigma, isolation, and discrimination persist and are associated with loneliness and depression among PLWHA.


Broadband parallel-fiber optical link for short-distance interconnection with multimode fibers.
In a multimode step-index fiber the propagation angle of a beam is conserved over short distances even if the fiber is bent slightly. This behavior can be exploited for a multiplexed signal transmission by the assignment of different channels to different propagation angles [angle-division multiplexing (ADM)]. Thus parallel transmission can be achieved. Because each channel occupies only a subrange of the fiber's numerical aperture, modal dispersion is reduced compared with single-channel transmission through the same fiber. The transmission properties of an ADM-based transmission line are analyzed for short propagation distances. Passive all-optical setups for multiplexing and demultiplexing operations are proposed. Cross-talk measurements are shown for a transmission with a length of 8 m and 13 multiplexed channels.


A bioinformatics analysis of protein tyrosine phosphatases in humans.
Protein tyrosine phosphatases (PTPs) cooperate with protein tyrosine kinases to regulate signal transduction pathways. Genome-wide surveys cataloging protein tyrosine phosphatases in humans have recently been carried out. Here, we present a bioinformatics analysis of protein tyrosine phosphatases in the human genome to examine their domain architecture, alternative splicing and pseudogenes. We present evidence that alternative transcripts exist for 25 out of 35 PTPs analyzed. These alternative transcripts include novel exons; skipped exons as well as cryptic donor/acceptor splice sites. We discovered a novel isoform of PTPN18 based on analysis of expressed sequence tags (ESTs). The deletion of 4 exons in the catalytic domain of the novel isoform may alter the enzymatic activity toward its substrates. We were able to experimentally validate 2 of our novel isoform predictions through RT-PCR. Finally, a user-friendly web-based resource that consolidates the gene and protein annotations for all human protein tyrosine phosphatases has been developed and is freely available at http://ptpr.ibioinformatics.org.


Root Herbivores Drive Changes to Plant Primary Chemistry, but Root Loss Is Mitigated under Elevated Atmospheric CO2.
Above- and belowground herbivory represents a major challenge to crop productivity and sustainable agriculture worldwide. How this threat from multiple herbivore pests will change under anthropogenic climate change, via altered trophic interactions and plant response traits, is key to understanding future crop resistance to herbivory. In this study, we hypothesized that atmospheric carbon enrichment would increase the amount (biomass) and quality (C:N ratio) of crop plant resources for above- and belowground herbivore species. In a controlled environment facility, we conducted a microcosm experiment using the large raspberry aphid (Amphorophora idaei), the root feeding larvae of the vine weevil (Otiorhynchus sulcatus), and the raspberry (Rubus idaeus) host-plant. There were four herbivore treatments (control, aphid only, weevil only and a combination of both herbivores) and an ambient (aCO2) or elevated (eCO2) CO2 treatment (390 versus 650 ± 50 μmol/mol) assigned to two raspberry cultivars (cv Glen Ample or Glen Clova) varying in resistance to aphid herbivory. Contrary to our predictions, eCO2 did not increase crop biomass or the C:N ratio of the plant tissues, nor affect herbivore abundance either directly or via the host-plant. Root herbivory reduced belowground crop biomass under aCO2 but not eCO2, suggesting that crops could tolerate attack in a CO2 enriched environment. Root herbivory also increased the C:N ratio in leaf tissue at eCO2, potentially due to decreased N uptake indicated by lower N concentrations found in the roots. Root herbivory greatly increased root C concentrations under both CO2 treatments. Our findings confirm that responses of crop biomass and biochemistry to climate change need examining within the context of herbivory, as biotic interactions appear as important as direct effects of eCO2 on crop productivity.


Cross-species interactions between malaria parasites in humans.
The dynamics of multiple Plasmodium infections in asymptomatic children living under intense malaria transmission pressure provide evidence for a density-dependent regulation that transcends species as well as genotype. This regulation, in combination with species- and genotype-specific immune responses, results in nonindependent, sequential episodes of infection with each species.


Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells.
The breast cancer stem cell (BCSC) hypotheses suggest that breast cancer is derived from a single tumor-initiating cell with stem-like properties, but the source of these cells is unclear. We previously observed that induction of an immune response against an epithelial breast cancer led in vivo to the T-cell-dependent outgrowth of a tumor, the cells of which had undergone epithelial to mesenchymal transition (EMT). The resulting mesenchymal tumor cells had a CD24(-/lo)CD44(+) phenotype, consistent with BCSCs. In the present study, we found that EMT was induced by CD8 T cells and the resulting tumors had characteristics of BCSCs, including potent tumorigenicity, ability to reestablish an epithelial tumor, and enhanced resistance to drugs and radiation. In contrast to the hierarchal cancer stem cell hypothesis, which suggests that breast cancer arises from the transformation of a resident tissue stem cell, our results show that EMT can produce the BCSC phenotype. These findings have several important implications related to disease progression and relapse.


Isolation and characterization of Borna disease agent cDNA clones.
Borna disease (BD) is a neurologic syndrome characterized by behavioral disturbances and the accumulation of specific proteins in limbic system neurons. A viral etiology has been proposed because BD can be induced in birds, rodents, and primates by inoculation with filtered brain homogenates from animals with BD. We report here the isolation and preliminary characterization of cDNA clones from a rat with BD. These clones hybridized to specific transcripts in BD rat brain and arrested in vitro translation of BD proteins. In situ hybridization experiments using RNA probes prepared from these clones showed an abundance of these transcripts in limbic system neurons. Northern (RNA) hybridizations using these RNA probes indicated that the BD agent is probably a virus with major transcripts of 8.5, 2.1, and 0.8 kilobases.


CBA: Cluster-Guided Batch Alignment for Single Cell RNA-seq.
The power of single-cell RNA sequencing (scRNA-seq) in detecting cell heterogeneity or developmental process is becoming more and more evident every day. The granularity of this knowledge is further propelled when combining two batches of scRNA-seq into a single large dataset. This strategy is however hampered by technical differences between these batches. Typically, these batch effects are resolved by matching similar cells across the different batches. Current approaches, however, do not take into account that we can constrain this matching further as cells can also be matched on their cell type identity. We use an auto-encoder to embed two batches in the same space such that cells are matched. To accomplish this, we use a loss function that preserves: (1) cell-cell distances within each of the two batches, as well as (2) cell-cell distances between two batches when the cells are of the same cell-type. The cell-type guidance is unsupervised, i.e., a cell-type is defined as a cluster in the original batch. We evaluated the performance of our cluster-guided batch alignment (CBA) using pancreas and mouse cell atlas datasets, against six state-of-the-art single cell alignment methods: Seurat v3, BBKNN, Scanorama, Harmony, LIGER, and BERMUDA. Compared to other approaches, CBA preserves the cluster separation in the original datasets while still being able to align the two datasets. We confirm that this separation is biologically meaningful by identifying relevant differential expression of genes for these preserved clusters.


Low-energy linear oxygen plasma source.
A new version of a constricted plasma source is described, characterized by all metal-ceramic construction, a linear slit exit of 180 mm length, and cw operation (typically 50 kHz) at an average power of 1.5 kW. The plasma source is here operated with oxygen gas, producing streaming plasma that contains mainly positive molecular and atomic ions, and to a much lesser degree, negative ions. The maximum total ion current obtained was about 0.5 A. The fraction of atomic ions reached more than 10% of all ions when the flow rate was less then 10 SCCM O(2), corresponding to a chamber pressure of about 0.5 Pa for the selected pumping speed. The energy distribution functions of the different ion species were measured with a combined mass spectrometer and energy analyzer. The time-averaged distribution functions were broad and ranged from about 30 to 90 eV at 200 kHz and higher frequencies, while they were only several eV broad at 50 kHz and lower frequencies, with the maximum located at about 40 eV for the grounded anode case. This maximum was shifted down to about 7 eV when the anode was floating, indicating the important role of the plasma potential for the ion energy for a given substrate potential. The source could be scaled to greater length and may be useful for functionalization of surfaces and plasma-assisted deposition of compound films.


Standardization of house dust mite extracts in Korea.
House dust mites are the most important cause of respiratory allergy in Korea. Standardization of allergen extracts is essential for improving diagnostics and immunotherapeutics. This study was undertaken to evaluate the allergenicity of standardized house dust mite allergen extracts from Korean house dust mite isolates. Allergen extracts were prepared from cultured Korean house dust mites (Dermatophagoides farinae and D. pteronyssinus). Allergenic activities of Korean house dust mite extracts were compared to standardized extracts from a company in the United States whose allergen concentrations were expressed as Allergy Units (AUs). Specifically, we compared group 1 and 2 major allergens using two-site enzyme-linked immunosorbent assay (ELISA) kits and an in vivo intradermal test. Major allergen concentrations were 17.0 µg/mg (5.0 µg/mg of Der f 1 and 12.0 µg/mg of Der f 2) for a D. farinae extract and 24.0 µg/mg (11.6 µg/mg of Der p 1 and 12.4 µg/mg of Der p 2) for a D. pteronyssinus extract. Using chloramphenicol (CAP) inhibition assays, AUs were 12.5 AU/µg for a D. farinae extract and 12.8 AU/µg for a D. pteronyssinus extract. Allergenic activities were 3- to 4-fold stronger when assessed by intradermal skin tests for in vivo standardization. Allergen extracts were prepared from Korean house dust mites and the allergenicities of the extracts were estimated using AU measurements. House dust mite extracts prepared in this study could be utilized as a reference material, which will be useful for the development of diagnostic and immunotherapeutic reagents in Korea.


Data-driven Markov models and their application in the evaluation of adverse events in radiotherapy.
Decision-making processes in medicine rely increasingly on modelling and simulation techniques; they are especially useful when combining evidence from multiple sources. Markov models are frequently used to synthesize the available evidence for such simulation studies, by describing disease and treatment progress, as well as associated factors such as the treatment's effects on a patient's life and the costs to society. When the same decision problem is investigated by multiple stakeholders, differing modelling assumptions are often applied, making synthesis and interpretation of the results difficult. This paper proposes a standardized approach towards the creation of Markov models. It introduces the notion of 'general Markov models', providing a common definition of the Markov models that underlie many similar decision problems, and develops a language for their specification. We demonstrate the application of this language by developing a general Markov model for adverse event analysis in radiotherapy and argue that the proposed method can automate the creation of Markov models from existing data. The approach has the potential to support the radiotherapy community in conducting systematic analyses involving predictive modelling of existing and upcoming radiotherapy data. We expect it to facilitate the application of modelling techniques in medical decision problems beyond the field of radiotherapy, and to improve the comparability of their results.


Mutational screening of CHX10, GDF6, OTX2, RAX and SOX2 genes in 50 unrelated microphthalmia-anophthalmia-coloboma (MAC) spectrum cases.
Microphthalmia-anophthalmia-coloboma (MAC) are congenital eye malformations causing a significant percentage of visually impairments in children. Although these anomalies can arise from prenatal exposure to teratogens, mutations in well-defined genes originate potentially heritable forms of MAC. Mutations in genes such as CHX10, GDF6, RAX, SOX2 and OTX2, among others, have been recognised in dominant or recessive MAC. SOX2 and OTX2 are the two most commonly mutated genes in monogenic MAC. However, as more numerous samples of MAC subjects would be analysed, a better estimation of the actual involvement of specific MAC-genes could be made. Here, a comprehensive mutational analysis of the CHX10, GDF6, RAX, SOX2 and OTX2 genes was performed in 50 MAC subjects. PCR amplification and direct automated DNA sequencing of all five genes in 50 unrelated subjects. Eight mutations (16% prevalence) were recognised, including four GDF6 mutations (one novel), two novel RAX mutations, one novel OTX2 mutation and one SOX2 mutation. Anophthalmia and nanophthalmia, not previously associated with GDF6 mutations, were observed in two subjects carrying defects in this gene, expanding the spectrum of GDF6-linked ocular anomalies. Our study underscores the importance of genotyping large groups of patients from distinct ethnic origins for improving the estimation of the global involvement of particular MAC-causing genes.


Task-oriented training in rehabilitation after stroke: systematic review.
This paper is a report of a review conducted to provide an overview of the evidence in the literature on task-oriented training of stroke survivors and its relevance in daily nursing practice. Stroke is the second leading cause of death and one of the leading causes of adult disability in the Western world. The use of neurodevelopmental treatment in the daily nursing care of stroke survivors does not improve clinical outcomes. Nurses are therefore exploring other forms of rehabilitation intervention, including task-oriented rehabilitation. Despite the growing number of studies showing evidence on task-oriented interventions, recommendations for daily nursing practice are lacking. A range of databases was searched to identify papers addressing task-oriented training in stroke rehabilitation, including Medline, CINAHL, Embase and the Cochrane Library of systematic reviews. Papers published in English between January 1996 and September 2007 were included. There were 42 papers in the final dataset, including nine systematic reviews. The selected randomized controlled trials and systematic reviews were assessed for quality. Important characteristics and outcomes were extracted and summarized. Studies of task-related training showed benefits for functional outcome compared with traditional therapies. Active use of task-oriented training with stroke survivors will lead to improvements in functional outcomes and overall health-related quality of life. Generally, task-oriented rehabilitation proved to be more effective. Many interventions are feasible for nurses and can be performed in a ward or at home. Nurses can and should play an important role in creating opportunities to practise meaningful functional tasks outside of regular therapy sessions.


Effects of Acute and Chronic Exercise on Immunological Parameters in the Elderly Aged: Can Physical Activity Counteract the Effects of Aging?
Immunosenescence is characterized by deterioration of the immune system caused by aging which induces changes to innate and adaptive immunity. Immunosenescence affects function and phenotype of immune cells, such as expression and function of receptors for immune cells which contributes to loss of immune function (chemotaxis, intracellular killing). Moreover, these alterations decrease the response to pathogens, which leads to several age-related diseases including cardiovascular disease, Alzheimer's disease, and diabetes in older individuals. Furthermore, increased risk of autoimmune disease and chronic infection is increased with an aging immune system, which is characterized by a pro-inflammatory environment, ultimately leading to accelerated biological aging. During the last century, sedentarism rose dramatically, with a concomitant increase in certain type of cancers (such as breast cancer, colon, or prostate cancer), and autoimmune disease. Numerous studies on physical activity and immunity, with focus on special populations (i.e., people with diabetes, HIV patients) demonstrate that chronic exercise enhances immunity. However, the majority of previous work has focused on either a pathological population or healthy young adults whilst research in elderly populations is scarce. Research conducted to date has primarily focused on aerobic and resistance exercise training and its effect on immunity. This review focuses on the potential for exercise training to affect the aging immune system. The concept is that some lifestyle strategies such as high-intensity exercise training may prevent disease through the attenuation of immunosenescence. In this context, we take a top-down approach and review the effect of exercise and training on immunological parameters in elderly at rest and during exercise in humans, and how they respond to different modes of training. We highlight the impact of these different exercise modes on immunological parameters, such as cytokine and lymphocyte concentration in elderly individuals.


Longitudinal changes in body weight and body composition among women previously treated for breast cancer consuming a high-vegetable, fruit and fiber, low-fat diet.
Excess adiposity has been shown to be associated with increased risk for breast cancer recurrence, and a plant-based eating pattern has been hypothesized to be protective. Whether a plant-based diet without specific energy goals will result in weight loss or changes in body composition in women who have been diagnosed with breast cancer has not been fully explored. This study was conducted to identify changes in body weight, anthropometric measures, and body composition over a four year period in a sub-sample of breast cancer survivors participating in a dietary intervention targeting increased intake of vegetables, fruit and fiber and decreased dietary fat intake. This randomized, controlled dietary intervention study compared longitudinal changes in intakes, body weight, waist:hip ratio (WHR), body mass index (BMI) and body composition by treatment group among fifty-two women previously treated for Stage I, II, or IIIA breast cancer from the Arizona site of the Women's Healthy Eating and Living Study. The dietary intervention aimed for eight servings of fruit and vegetables, 30 g fiber, < or = 20% total energy from fat per day, as well as daily intake of vegetable juice. The comparison group was advised to follow general dietary guidelines for cancer prevention. The dietary intervention resulted in a significant and sustained increase in fiber, fruit, vegetable, and vegetable juice consumption (p < 0.05) among intervention group subjects as compared to comparison group subjects. The first 6 months resulted in a reduction in body weight and body fat among the intervention group subjects while the comparison group subjects remained stable. Subsequent measurements, at 12, 24 or 36, and 48 months, showed no significant differences in mean body weight, BMI, WHR, or body composition by study group. Also, no significant changes in these measures were demonstrated for either study group between baseline and 48 months. The dietary intervention efforts resulted in significant changes in diet toward an increase in plant foods and a decrease in dietary fat. Changes in weight, WHR, BMI, and body composition were not different over time or by study group assignment. Interventions that promote a plant-based diet without specific energy restriction do not appear to promote changes in body weight or body composition in women who have been diagnosed with breast cancer. To adequately examine the role of energy restriction in reducing obesity-associated breast cancer recurrence, future interventions should include prescribed energy imbalance either through reduced intake and/or increased expenditure.


Four SNPs in the CHRNA3/5 alpha-neuronal nicotinic acetylcholine receptor subunit locus are associated with COPD risk based on meta-analyses.
Several single nucleotide polymorphisms (SNPs) in an α-neuronal nicotinic acetylcholine receptor subunit (CHRNA3/5) were identified to be associated with chronic obstructive pulmonary disease (COPD) in a study based on a Norwegian population. However, results from subsequent studies have been controversial, particularly in studies recruiting Asians. In the present study, we conducted a comprehensive search and meta-analyses to identify susceptibility SNPs for COPD in the CHRNA3/5 locus. A comprehensive literature search was conducted to find studies that have reported an association between SNPs in the CHRNA3/5 locus and COPD risk. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for each SNP were calculated with the major allele or genotype as the reference group. The influence of individual studies on pooled measures was assessed, in addition to publication bias. A total of 12 articles with 14 eligible studies were included in this analysis. Association between 4 SNPs in the CHRNA3/5 locus and COPD was evaluated and included rs1051730, rs8034191, rs6495309, and rs16969968. Significant associations between the 4 SNPs and COPD were identified under allele (rs1051730: OR = 1.14, 95%CI = 1.10-1.18; rs8034191: OR = 1.29, 95%CI = 1.18-1.41; rs6495309: OR = 1.26, 95%CI = 1.09-1.45; rs16969968: OR = 1.27, 95%CI = 1.17-1.39) and genotype models. Subgroup analysis conducted for rs1051730 showed a significant association between this SNP and COPD risk in non-Asians (OR = 1.14, 95%CI = 1.10-1.18), but not Asians (OR = 1.23, 95%CI = 0.91-1.67). Rs1051730 and rs6495309 were also significantly associated with COPD after adjusting for multiple variables, including age and smoking status. Our results indicate that 4 SNPs in the CHRNA3/5 locus are associated with COPD risk. Rs1051730 was particularly associated with COPD in non-Asians, but its role in Asians still needs to be verified. Additional studies will be necessary to assess the effect of rs6495309 on COPD. Although rs1051730 and rs6495309 were shown to be independent risk factors for COPD, validation studies should be performed.


Accounting for the role of habit in behavioural strategies for injury prevention.
The limited success of behavioural strategies in injury prevention has been attributed to failure to properly apply behaviour change models to intervention design and the explanation of safety behaviours. However, this paper contends that many health behaviour change interventions do not succeed because they fail to take into account the habitual quality of most health and safety-related behaviour; a more complete model of behaviour change needs to be based on a better understanding of the role of habit. The overall aim is to contribute to better understanding of behavioural strategies for injury prevention. When habits are weak, attitudes and intentions predict behaviours, but as behaviours turn into habits, they become better predictors of future behaviour than attitudes or intentions. Furthermore, where habits are strong, individuals are less likely to act on new information, evaluating counter-habitual information negatively. Integrating the concepts of strong and weak habits with upstream and downstream strategies, a framework is presented for tailoring strategies to the habit strength of the target behaviour.


How molecular is the chemisorptive bond?
Trends in adsorption energies as a function of transition metal differ for adsorbates that are attached atop a surface atom or are adsorbed onto a high coordination site. When adsorption onto early and late transition metals is compared variation in relative bond energies of adsorbates attached to different sites is large. A theoretical understanding is provided based on the analysis of the electronic structure of the respective chemical bonds. The electronic structure analysis is based on partial density of states (PDOS) and bond order overlap population densities from crystal orbital Hamiltonian population (COHP) calculations available from DFT electronic structure computations. This is complemented by calculations of Bader charge densities and electron density topology properties. Variation of the respective bond energies depends on the symmetry of the molecular orbitals that form the chemical bond. The key electronic structure parameters are the position of the Fermi level in the bonding or antibonding molecular orbital partial density of states region of the chemical bond and chemical bond polarity. These are very different for adsorbates adsorbed onto the same transition metal surface, but which have different coordination with surface metal atoms. The adsorption energies and the respective electronic structures of adatoms H, C and O and molecular fragments CHx (x = 1-3) are compared with those of the analogous molecules that contain a single transition metal atom. When adsorbed atop, trends in bond energies are remarkably similar to those of the corresponding molecules. The difference in bond energies of adsorbates and transition metal molecules, i.e. the embedding energy, is shown to consist of three contributions: quenching of the sometimes high molecular spin states, weakening of the adsorbate-surface interaction energy and weakening of the metal-metal atom bond energies next to the adsorbate. Conventional scaling rules of the interaction energies of adsorbed CHx (0 < x ≤ 3) fragments are satisfied only for adsorbates in high coordination sites. For the early transition metals a breaking of this rule is found for C and CH or N and NH when adsorbed atop a transition metal surface or when they are part of a transition metal molecule. The M-C bond energy is found to be only stronger than that of the M-CH bond as long as the Fermi level or the HOMO is located in the antibonding molecular orbital partial density of states of the chemical bond.


Evolutionary implications of a high selfing rate in the freshwater snail Lymnaea truncatula.
Self-compatible hermaphroditic organisms that mix self-fertilization and outcrossing are of great interest for investigating the evolution of mating systems. We investigate the evolution of selfing in Lymnaea truncatula, a self-compatible hermaphroditic freshwater snail. We first analyze the consequences of selfing in terms of genetic variability within and among populations and then investigate how these consequences along with the species ecology (harshness of the habitat and parasitism) might govern the evolution of selfing. Snails from 13 localities (classified as temporary or permanent depending on their water availability) were sampled in western Switzerland and genotyped for seven microsatellite loci. F(IS) (estimated on adults) and progeny array analyses (on hatchlings) provided similar selfing rate estimates of 80%. Populations presented a low polymorphism and were highly differentiated (F(ST) = 0.58). Although the reproductive assurance hypothesis would predict higher selfing rate in temporary populations, no difference in selfing level was observed between temporary and permanent populations. However, allelic richness and gene diversity declined in temporary habitats, presumably reflecting drift. Infection levels varied but were not simply related to either estimated population selfing rate or to differences in heterozygosity. These findings and the similar selfing rates estimated for hatchlings and adults suggest that within-population inbreeding depression is low in L. truncatula.


Do nurses and other health professionals' in elderly care have education in family nursing?
Family caregivers are an important resource for providing care to elderly living at home. How nurses and other health professionals interact with family caregivers can have both a positive and a negative impact on the family caregivers' situation. We lack knowledge of Norwegian nurses' and other health professionals' participation in educational programmes about family caregivers' needs and situations. The purpose of this study was to investigate whether nurses and other health professionals working in home-care nursing had participated in educational programmes about family caregivers. Additionally, the study aimed to determine whether participation in educational programmes was associated with awareness of family caregivers' contributions to elder care. This is a quantitative study, and it was conducted as a cross-sectional study. The participants were required to be educated as nurses, nursing assistants or other health professionals with relevant health education and to be working with the elderly in home-care nursing settings. Descriptive statistics and trivariate table analysis using the Pearson Chi-square t-test were conducted using Statistical Package for the Social Sciences (SPSS). A total of 152 nurses and health professionals in home-care nursing in 23 municipalities have participated (in one county in Norway). The results showed that only half of the respondents had participated in educational programmes about family caregivers' needs and situations. The study did not provide a clear answer regarding the association between participation in educational programmes and awareness of family caregivers' contributions. The results indicate that nurses and other health professionals, to a small extent, have participated in educational programmes about family caregivers. Our findings indicate that participation in educational programmes may be particularly important for health professionals in leadership positions and for health professionals with vocational training.


Biopsies of pediatric brainstem lesions display low morbidity but strong impact on further treatment decisions.
The course of malignant brain stem gliomas in childhood is rarely positive. Because of limited therapeutic options and potentially hazardous biopsies oncologist often relay on MRI diagnoses only for further therapy decisions. In this study we show that brain stem biopsies display a low morbidity rate and neuropathological assessment has a considerable impact on further treatment decision. Within 18-months five children with brainstem symptoms and the radiological diagnosis of a malignant brainstem glioma, were identified. From this time point it was possible to analyze all samples with the 450K methylome analysis. Other neuropathological techniques included classical histology with immunohistochemistry. Surgery was performed as biopsy, either microsurgical, frame-guided (Leksell), robot-assisted (ROSA) or navigated (BrainLab, two children). Mean age of the children was 7.5years (range: newborn to 12years). There was no biopsy-related morbidity or mortality. The mean number of taken samples was 12 (range: 1-25). Histologic diagnosis could be established in all children, however, 450K methylome diagnosis was positive in only two out of five patients. Despite the technically difficult biopsies, all specimens were sufficient for immunohistochemical diagnosis, however, 450K methylome analysis could only be better established where multiple small samples were taken, instead of few larger ones. Based on the preoperative radiological diagnosis suggesting malignant brainstem glioma, all children would have been treated with combined radiation and temozolomid chemotherapy. Nevertheless, due to the availability of histology and molecular diagnostics, individualized therapy could be performed, preventing in two out of five children from unnecessary radiation and chemotherapy.


Automatic quantity processing in 5-year olds and adults.
In this study adults performed numerical and physical size judgments on a symbolic (Arabic numerals) and non-symbolic (groups of dots) size congruity task. The outcomes would reveal whether a size congruity effect (SCE) can be obtained irrespective of notation. Subsequently, 5-year-old children performed a physical size judgment on both tasks. The outcomes will give a better insight in the ability of 5-year-olds to automatically process symbolic and non-symbolic numerosities. Adult performance on the symbolic and non-symbolic size congruity tasks revealed a SCE for numerical and physical size judgments, indicating that the non-symbolic size congruity task is a valid indicator for automatic processing of non-symbolic numerosities. Physical size judgments on both tasks by children revealed a SCE only for non-symbolic notation, indicating that the lack of a symbolic SCE is not related to the mathematical or cognitive abilities required for the task but instead to an immature association between the number symbol and its meaning.


The developmental trajectory of pointing perception in the first year of life.
The present study investigated the development of the neural basis of pointing perception in 6-month- and 13-month-old infants. In a spatial-cueing paradigm, infants were presented with a peripheral target followed by a hand pointing toward (congruent condition) or away (incongruent condition) from the previously cued location. EEG responses to the presentation of the hand were measured. Thirteen-month-olds demonstrated larger amplitudes of ERP component P400 to incongruent compared to congruent pointing gestures over posterior temporal areas; 6-month-olds did not show any differential activation. This result suggests that the neural correlates of pointing perception undergo substantial development between 6 and 13 months of age.


Autonomous and extrinsic regulation of thymopoiesis in human immune system (HIS) mice.
Human Immune System (HIS) mice represent a novel biotechnology platform to dissect human haematopoiesis and immune responses. However, the limited human T-cell development that is observed in HIS mice restricts its utility for these applications. Here, we address whether reduced thymopoiesis in HIS mice reflects an autonomous defect in T-cell precursors and/or a defect in the murine thymic niche. Human thymocyte precursors seed the mouse thymus and their reciprocal interactions with murine thymic epithelial cells (TECs) led to both T-cell and TEC maturation. The human thymocyte subsets observed in HIS mice demonstrated survival, proliferative and phenotypic characteristics of their normal human counterparts, suggesting that the intrinsic developmental program of human thymocytes unfolds normally in this xenograft setting. We observed that exogenous administration of human IL-15/IL-15Rα agonistic complexes induced the survival, proliferation and absolute numbers of immature human thymocyte subsets, without any obvious effect on cell-surface phenotype or TCR Vβ usage amongst the newly selected mature single-positive (SP) thymocytes. Finally, when IL-15 was administered early after stem cell transplantation, we noted accelerated thymopoiesis resulting in the more rapid appearance of peripheral naïve T cells. Our results highlight the functional capacity of murine thymic stroma cells in promoting human thymopoiesis in HIS mice but suggest that the "cross-talk" between murine thymic stroma and human haematopoietic precursors may be suboptimal. As IL-15 immunotherapy promotes early thymopoiesis, this novel approach could be used to reduce the period of T-cell immunodeficiency in the post-transplant clinical setting.


Climate change, household vulnerability and smart agriculture: The case of two South African provinces.
The impact of climate-change disasters poses significant challenges for South Africa, especially for vulnerable rural households. In South Africa, the impact of climate change at the local level, especially in rural areas, is not well known. Rural households are generally poor and lack resources to adapt to and mitigate the impact of climate change, but the extent of their vulnerability is largely not understood. This study looked at the micro-level impact of climate change, evaluated household vulnerability and assessed alternative adaptation strategies in rural areas. The results indicate that climate change will hit crop yields hard and that households with less capital are most vulnerable. These households consist of the elderly and households headed by females. Households that receive remittances or extension services or participate in formal savings schemes in villages are less vulnerable. The results suggest that households need to move towards climate-smart agriculture, which combines adaptation, mitigation and productivity growth.


Antiviral cytotoxic T cell response induced by in vivo priming with a free synthetic peptide.
Induction in vivo of antiviral cytotoxic T cell response was achieved in a MHC class I-dependent fashion by immunizing mice three times with a free unmodified 15-mer peptide derived from the nucleoprotein of lymphocytic choriomeningitis virus in IFA. The effector T cells are CD8+, restricted to the class I Ld allele of the analyzed mouse strain, and are specific both at the level of secondary restimulation in vitro and at the effector T cell level. These results suggest that cocktails of viral peptides may be used as antiviral T cell vaccines.


Differentiation of the mammary gland and susceptibility to carcinogenesis.
It has been demonstrated that in humans certain factors such as early menarche, late pregnancy, and nulliparity are associated with a higher risk of developing breast cancer, while early pregnancy acts as a protective factor. Induction of mammary cancer in rats by administration of the chemical carcinogen 7,12-dimethylbenz(a)anthracene reveals that the same factors influencing human breast cancer risk also affect the susceptibility of the rat mammary gland to the chemical carcinogen. Nulliparous rats and rats undergoing pregnancy interruption are more susceptible to developing carcinomas. This fact has been attributed to the incomplete differentiation of the gland at the time of carcinogen administration. Parous rats are resistant to the carcinogenic effect of DMBA, which is explained by the complete development of the gland attained during pregnancy and lactation. This development is manifested by the differentiation of terminal end buds into secretory units, which have a smaller proliferative compartment; the epithelial cells of these secretory units have a longer cell cycle, less avidity for binding DMBA, and possess a more efficient DNA excision repair capacity.


Mobilization of the inferior alveolar nerve with simultaneous implant insertion: a new technique. Case report.
For reconstruction of an atrophied posterior mandible, different therapeutic options have been proposed, such as autologous bone grafting, guided bone regeneration for vertical ridge augmentation, and inferior alveolar nerve (IAN) mobilization with simultaneous implant placement. The possible dehiscence of soft tissues covering the surgical zone makes the first and second techniques unpredictable. Moreover, two surgical sites are necessary and a long treatment time is required (about 12 months). With IAN mobilization, only one surgical intervention is required and the total treatment time is shorter (about 6 months). However, this technique risks irreversible damage to the IAN, with consequent functional alterations. Current studies have shown extreme variability in the examination of functionality of the neurovascular bundle after its mobilization. This variability can be attributed both to the methodology used for the tests, which evoke subjective answers from the patient, and to the surgical procedure, which is highly dependent on operator technique. Nerve damage can be the result of an overstretched mucoperiosteal flap in the premolar area to achieve optimal visibility of the surgical zone. This article reports a case in which a new surgical approach to IAN mobilization is performed using a specifically engineered device for simplified bone surgery (Mectron Piezosurgery). This device enables the surgeon to cut hard tissue without injuring the soft tissues. Therefore, there is a lower risk of damaging the IAN, and it is possible to reduce overstretching of the mental nerve by creating a smaller bone window and using an apicocoronal inclination of instruments to capture the neurovascular bundle.


Mendelian randomization analysis supports the causal role of dysglycaemia and diabetes in the risk of coronary artery disease.
Type 2 diabetes is a strong risk factor for coronary artery disease (CAD). However, the absence of a clear reduction in CAD by intensive glucose lowering in randomized controlled trials has fuelled uncertainty regarding the causal role of dysglycaemia and CAD. To assess whether Mendelian randomization supports a causal role of dysglycaemia and diabetes for risk of CAD. Effect size estimates of common genetic variants associated with fasting glucose (FG), glycated haemoglobin (HbA1c), and diabetes were obtained from the Meta-Analyses of Glucose and Insulin-Related Traits Consortium and Diabetes Genetics Replication and Meta-Analysis consortia. The corresponding effect estimates of these single nucleotide polymorphisms (SNPs) on the risk of CAD were then evaluated in CARDIOGRAMplusC4D. SNPs associated with HbA1c and diabetes were associated with an increased risk of CAD. Using information from 59 genetic variants associated with diabetes, the causal effect of diabetes on the risk of CAD was estimated at an odds ratio (OR) of 1.63 (95% Confidence Interval (CI): 1.23-2.07; P = 0.002). On the other hand, nine genetic variants associated with HbA1c were associated with an OR of 1.53 per 1% HbA1c increase (95% CI: 1.14-2.05; P = 0.023) in the risk of CAD while this effect was non-significant among 30 genetic variants associated with FG per mmol/L (OR: 1.18, 95% CI: 0.97-1.42; P = 0.102). No significant differences were observed when categorizing genetic loci according to their effect on either β-cell dysfunction or insulin resistance. These Mendelian randomization analyses support a causal role for diabetes and its associated high glucose levels on CAD, and suggest that long-term glucose lowering may reduce CAD events.


The effects of subcutaneous insulin-like growth factor-I infusion in insulin-dependent diabetes mellitus.
Insulin-dependent diabetes can be associated with low insulin-like growth factor-I (IGF-I) levels despite normal or even high GH secretion. The basis of the diabetic abnormalities in GH-IGF dynamics that contribute to insulin resistance and impaired fuel metabolism are not well understood. To further investigate these matters, this study evaluated baseline IGF system parameters and responses to recombinant human IGF-I in four diabetic adolescents and six pubertal stage-matched controls. Spontaneous overnight and arginine-stimulated GH secretion, insulin, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 levels were measured before, during, and after daily 10-h sc infusions of saline or IGF-I (20 micrograms/kg.h). Baseline overnight GH secretion and IGFBP-1 and -3 levels were not significantly different in the two groups, but IGF-I levels were significantly lower and IGF-II levels were higher in diabetic subjects. IGF-I infusion produced a 3-fold increase in serum IGF-I levels and a reciprocal profound reduction in IGF-II levels in both groups. IGFBP-1 levels increased dramatically in diabetics and modestly in normal subjects in response to IGF-I infusion, but IGFBP-3 levels were not significantly altered. Spontaneous overnight and arginine-stimulated GH secretion were suppressed by about 50% in both groups after IGF-I infusion. Insulin requirements were substantially reduced in diabetics receiving IGF-I, and insulin secretion was suppressed in normal subjects, with no evidence of a change in insulin half-life. Blood glucose remained stable in both groups throughout saline and IGF-I infusions, and no hypoglycemia or other adverse effect occurred during IGF-I infusions. Further studies are necessary to determine whether the addition of IGF-I to insulin replacement therapy may stably reduce the insulin requirement, maintain normal GH levels, and perhaps achieve better metabolic and anabolic balance in the treatment of insulin-dependent diabetes.


Radiation exposure in interventional procedures.
The aim of this study was to estimate radiation doses patients and staff are exposed to during interventional procedures (IPs), compare them with the international diagnostic reference levels and to develop initial National Diagnostic Reference Levels. The IP survey was undertaken as the initial task of which, retrospective data were collected from the only four Kenyan hospitals carrying out interventional radiology and cardiology procedures at the time of the study. Real-time measurement of radiation dose to patients and staff during these procedures was done. To the patients, kerma-area product (KAP) and fluoroscopy time measurements were done using an in-built KAP meter, while peak skin dose (PSD) was measured using slow Extended Dose Range (EDR2(®)) radiographic films. The staff occupational doses were measured using individual thermoluminescence dosemeters. The maximum and minimum KAP values were found to be 137.1 and 4.2 Gy cm(2), while the measured PSD values were 740 and 52 mGy, respectively. The fluoroscopic time range was between 3.3 and 70 min. The staff doses per procedure ranged between 0.05 and 1.41 mSv for medical doctors, 0.03 and 1.16 mSv for nurses, 0.04 and 0.78 mSv for radiographers and 0.04 and 0.88 mSv for clinical staff. The measured patient PSDs were within the threshold limit for skin injuries. However, with the current few IP specialists, an annual increase in workload as determined in the study will result in the International Commission on Radiation Protection annual eye lens dose limit being exceeded by 10 %. A concerted effort is required to contain these dose levels through use of protective gear, optimisation of practice and justification.


Generation of carrier fringes in holography and shearography.
Double-exposure holography and double-exposure shearography are often used together with the carrier fringe technique, which requires additional shifting of the light source in a prescribed manner between exposures. In the holographic carrier fringe technique, difficulty in prescribing a suitable movement of the light source may be alleviated through visualization of the moiré fringes that are reconstructed by slight displacement of two overlaid families of ellipsoids in a holodiagram. Because shearography is the first differential of holography, it is often impractical to perform two successive optical differentiations on the ellipsoids to visualize the shearographic carrier fringes. A simple method of discerning holographic and shearographic carrier fringes is described. The method is based on the hyperboloids in a holodiagram that represent Young's (interference) fringes produced by the interference of two point sources. The hyperboloids are analogous to holographic carrier fringes, whereas the moiré patterns reconstructed from two overlaid hyperboloids are analogous to shearographic carrier fringes. Use of this method for explaining the formation of deformation fringes in plate bending, as well as the effect of light-source movement on the deformation fringes, is also illustrated.


Cyclin-dependent kinase 5 associated with p39 promotes Munc18-1 phosphorylation and Ca(2+)-dependent exocytosis.
Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine protein kinase that requires association with a regulatory protein, p35 or p39, to form an active enzyme. Munc18-1 plays an essential role in membrane fusion, and its function is regulated by phosphorylation. We report here that both p35 and p39 were expressed in insulin-secreting beta-cells, where they exhibited individual subcellular distributions and associated with membranous organelles of different densities. Overexpression of Cdk5, p35, or p39 showed that Cdk5 and p39 augmented Ca(2+)-induced insulin exocytosis. Suppression of p39 and Cdk5, but not of p35, by antisense oligonucleotides selectively inhibited insulin exocytosis. Transient transfection of primary beta-cells with Munc18-1 templates mutated in potential Cdk5 or PKC phosphorylation sites, in combination with Cdk5 and the different Cdk5 activators, suggested that Cdk5/p39-promoted Ca(2+)-dependent insulin secretion from primary beta-cells by phosphorylating Munc18-1 at a biochemical step immediately prior to vesicle fusion.


Antimalarial exposure delays Plasmodium falciparum intra-erythrocytic cycle and drives drug transporter genes expression.
Multi-drug resistant Plasmodium falciparum is a major obstacle to malaria control and is emerging as a complex phenomenon. Mechanisms of drug evasion based on the intracellular extrusion of the drug and/or modification of target proteins have been described. However, cellular mechanisms related with metabolic activity have also been seen in eukaryotic systems, e.g. cancer cells. Recent observations suggest that such mechanism may occur in P. falciparum. We therefore investigated the effect of mefloquine exposure on the cell cycle of three P. falciparum clones (3D7, FCB, W2) with different drug susceptibilities, while investigating in parallel the expression of four genes coding for confirmed and putative drug transporters (pfcrt, pfmdr1, pfmrp1 and pfmrp2). Mefloquine induced a previously not described dose and clone dependent delay in the intra-erythrocytic cycle of the parasite. Drug impact on cell cycle progression and gene expression was then merged using a non-linear regression model to determine specific drug driven expression. This revealed a mild, but significant, mefloquine driven gene induction up to 1.5 fold. Both cell cycle delay and induced gene expression represent potentially important mechanisms for parasites to escape the effect of the antimalarial drug.


Lower-limb alignment and posterior tibial slope in Pakistanis: a radiographic study.
To assess the lower-limb alignment and posterior tibial slope in Pakistanis. 40 male and 19 female healthy Pakistanis aged 20 to 45 years were recruited. A full weight-bearing anteroposterior radiograph of the entire lower limb of each subject was obtained. The axial alignment was measured based on the centres of the femoral head, knee, and ankle. The tibiofemoral (TF) angle, knee joint line obliquity angle (angle J), and posterior tibial slope were determined. The mean TF angle was more varus in men than women (178.4 degrees vs. 180.0 degrees, p<0.001). The mean angle J was more medially inclined in men than women (93.4 degrees vs. 91.4 degrees, p=0.007). The mean medial tibial slope was greater in women than men (16.0 degrees vs. 12.5 degrees, p<0.001). The posterior tibial slope was greater in women than men (14.1 degrees vs. 12.5 degrees, p=0.02), and was greater than the 5 degrees to 10 degrees commonly reported. Knee alignment and geometry vary in different population subsets. With regard to total knee arthroplasty, the more medially inclined angle J in Pakistani men suggests that an anteroposterior cut of the distal femur should be in increased external rotation, compared with Pakistani women. Whereas the greater posterior tibial slope in Pakistanis suggests that a proximal tibial cut with a greater posterior tibial slope may reduce the chance of tibial loosening and increase postoperative knee range of motion, especially when using posterior cruciate ligament-retaining designs.


Atomic ensemble effects in electrocatalysis: the site-knockout strategy.
During an electrocatalytic reaction bonds are broken and formed, and this requires that the reactants, the intermediates formed at the elementary reaction steps, and the products interact with a given number of surface atoms of the catalyst. Modifying the number of groups with an adequate number of surface atoms in a suitable geometric arrangement for a determined reaction step to proceed may affect the activity and/or selectivity of the catalyst. Although separating purely geometric atomic ensemble effects from electronic effects is not straightforward, the insights extracted from a detailed investigation of atomic ensemble effects can have a profound impact in the determination of electrocatalytic reaction mechanisms and in the design of more active and more selective electrocatalysts. This Minireview illustrates, using cyanide-modified Pt(111) electrodes as an archetype, how eliminating only one kind of site from the surface (the site-knockout strategy) by means of a regular array of inert adsorbates can be used to successfully study atomic ensemble effects in electrocatalysis. The possible consequences for the design of more efficient and more selective electrocatalysts are also commented on.


Osteoinductive potential and bone-bonding ability of ProRoot MTA, MTA Plus and Biodentine in rabbit intramedullary model: Microchemical characterization and histological analysis.
To study the in vivo osteoinductive potential, bone-bonding ability (bioactivity) and bone biomineralization of current hydraulic calcium silicate cements used as graft materials and placed in contact with medullary bone. ProRoot MTA, MTA Plus and Biodentine were used to fill surgical bone defects (2-mm diameter through the entire cortical thickness to reach the medullary bone) in the tibia of mature male rabbits. Tibiae were retrieved after 30days and submitted to histological analysis and microchemical characterization using Optical Microscopy (OM) and Environmental Scanning Electron Microscopy with Energy Dispersive X-ray analysis (ESEM-EDX). Bone neoformation and histomorphometric evaluations, degree of mineralization (by Ca/P, Ca/N and P/N ratios) and the diffusion of material elements were studied. Bone neoformation was observed in response to all materials. No sign of necrosis were found on the walls of the pre-existing cortical bone. No osteoclasts and no formation of fibrous tissue were evident. Sign of angiogenesis were present. EDX (element content, line profile and element mapping) showed the increase in Ca and P and decrease in C, S and N from the mature bone towards the mineralizing interface. Ca/P, Ca/N and P/N ratios showed differences in the degree of mineralization/maturation stage of bone. MTA Plus and ProRoot MTA exhibited close contact with the pre-existing bone and good bone-bonding with neoformed bone juxtaposed on the medullary side of the materials without interposed connective tissue or resorption lacunae or gaps. The materials showed a dense appearance with 100% of residual materials and no colonization by fluids and cells. No migration of Bi or Al material elements to the newly formed bone was found. Biodentine showed newly formed trabecular bone with marrow spaces and sparse traces of residual material (≈9%). The in vivo osteoinductive properties with dynamic biomineralization processes around these calcium silicate materials extruded in medullary bone in appropriate animal model have been demonstrated by ESEM-EDX in association with OM. Good biocompatibility was evident as only slight inflammatory infiltrate and no sign of necrosis at the interface with the pre-existing bone were found. MTA Plus and ProRoot MTA exhibited bioactive potential as they can bond to bone directly without interposed connective tissue. Biodentine was replaced by newly formed bone. The results of the study demonstrate the capacity of calcium silicate cements to allow osteoid matrix deposition by activated osteoblasts and favour its biomineralization, and to achieve a direct bond between the (bioactive) materials surface and the mineralized bone matrix.


Shaped by our thoughts--a new task to assess spontaneous cognition and its associated neural correlates in the default network.
Self-generated cognition, or mind wandering, refers to the quintessentially human tendency to withdraw from the immediate external environment and engage in internally driven mentation. This thought activity is suggested to be underpinned by a distributed set of regions in the brain, referred to as the default network. To date, experimental assessment of mind wandering has typically taken place during performance of a concurrent attention-demanding task. The attentional demands of concurrent tasks can influence the emergence of mind wandering, and their application to clinical disorders with reduced cognitive resources is limited. Furthermore, few paradigms have investigated the phenomenological content of mind wandering episodes. Here, we present data from a novel thought sampling task that measures both the frequency and qualitative content of mind wandering, in the absence of a concurrent task to reduce cognitive demand. The task was validated in a non-pathological cohort of 31 older controls and resting-state functional connectivity analyses in a subset of participants (n=18) was conducted to explore the neural bases of mind wandering. Overall, instances of mind wandering were found to occur in 37% of experimental trials. Resting state functional connectivity analyses confirmed that mind wandering frequency was associated with regional patterns of both increased and decreased default network connectivity, namely in the temporal lobe, posterior cingulate cortex and dorsal medial prefrontal cortex. Our findings demonstrate that the novel task provides a context of low cognitive demand, which is conducive to mind wandering. Furthermore, performance on the task is associated with specific patterns of functional connectivity in the default network. Together, this new paradigm offers an important avenue to investigate the frequency and content of mind wandering in the context of low cognitive demands, and has significant potential to be applied in clinical conditions with reduced cognitive resources.


TLR2 controls intestinal carcinogen detoxication by CYP1A1.
Intestinal cytochrome P450 subclass 1A1 (CYP1A1) contributes to a metabolic "shield" protecting the host from ingested carcinogens such as polycyclic aromatic hydrocarbons (PAH). The expression of CYP1 (including CYP1A2 and CYP1B1) is considered to depend solely on a heterodimeric transcription factor consisting of the arylhydrocarbon receptor (AHR) and the AHR nuclear translocator (ARNT). So far, no interference has been noted between the regulation of CYP1 and the activation of Toll-like receptor 2 (TLR2), which modulates the inflammatory response to bacterial cell wall components in immune cells and enterocytes. Here we report that intestinal CYP1A1 is silenced in TLR2-deficient mice, even when under exposure to the carcinogenic PAH benzo[a]pyrene (BaP). In contrast, hepatic CYP1A1 was moderately induced in TLR2-deficient mice without restoring their ability to clear BaP from systemic circulation, as present in wild-type animals. After feeding of BaP for 21 days, only TLR2(-/-) mice, but not their wild type littermates developed polyps in the colon. Gene expressions and protein concentrations of AHR and ARNT in the intestine did not differ between the genotypes. In conclusion, the presence of ligands for TLR2 of bacterial origin seems to be crucial for detoxication of luminal carcinogens by CYP1A1 in the intestine. This unprecedented finding indicates a complex interplay between the immune system of the host and intestinal bacteria with detoxication mechanisms. This highlights the relevance of intestinal microbiota when trying to unravel pathways present in mammals and opens new perspectives for research in human health.


A comparative analysis of senescence in adult damselflies and dragonflies (Odonata).
Any population whose members are subject to extrinsic mortality should exhibit an increase in mortality with age. Nevertheless, the prevailing opinion is that populations of adult damselflies and dragonflies do not exhibit such senescence. Here, we challenge this contention by fitting a range of demographic models to the data on which these earlier conclusions were based. We show that a model with an exponential increase in age-related mortality (Gompertz) generally provides a more parsimonious fit than alternative models including age-independent mortality, indicating that many odonates do indeed senesce. Controlling for phylogeny, a comparison of the daily mortality of 35 odonate species indicates that although male and female mortalities are positively correlated, mortality tends to be higher in males of those species that exhibit territoriality. Hence, we show for the first time that territoriality may impose a survivorship cost on males, once the underlying phylogenetic relationships are accounted for.


The curious case of zeolite-clay/binder interactions and their consequences for catalyst preparation.
Zeolite-based catalyst bodies are commonly employed in a range of important industrial processes. Depending on the binder and shaping method chosen, vast differences in the reactivity, selectivity and stability are obtained. Here, three highly complementary micro-spectroscopic techniques were employed to study zeolite ZSM-5-binder interactions in SiO2-, Al2O3-, SiO2 : Al2O3- (2 : 1 mix) and kaolinite-bound catalyst pellets. We establish how their preparation influences the zeolite-clay/binder interactions. Using thiophene as an acid-catalyzed staining reaction, light absorbing oligomers produced in each sample were followed. To our surprise, kaolinite decreased the overall reactivity of the sample due to the phase change of the binder, creating a hard impenetrable outer layer. Aluminum migration to the zeolite was observed when Al2O3 was selected as a binder, creating additional Brønsted acid sites, which favored the formation of ring-opened thiophene oligomers compared to the larger oligomer species produced when SiO2 was used as a binder. In the latter case, the interaction of the Si-OH groups in the binder with thiophene was revealed to have a large impact in creating such large oligomer species. Furthermore, the combination of a SiO2 : Al2O3 mix as a binder enhanced the reactivity, possibly due to the creation of additional Brønsted acid sites between the two binder components during pellet preparation. It is evident that, independent of the shaping method, the intimate contact between the zeolite and binder heavily impacts the reactivity and product selectivity, with the type of binder playing a vital role.


[Mauriac syndrome--a rare complication of type 1 diabetes mellitus].
The treatment of children with type 1 diabetes mellitus has improved dramatically over the last few decades. The maintenance of acceptable metabolic control, nevertheless, remains challenging because the success of treatment is so dependent on patient compliance. Children with type 1 diabetes and poor metabolic control are at risk of developing Mauriac syndrome, a condition characterised by hepatomegaly, growth retardation and cushingoid features. A similar complication may occur in type-1 or type-2 adult diabetics; namely, glycogenic hepatopathy. We describe two children, a 12-year-old girl and a 16-year-old boy, who presented with classic symptoms of Mauriac syndrome. After metabolic control was achieved, reduction of hepatomegaly and the disappearance of cushingoid features were observed, proving the reversibility of the syndrome. Awareness that this syndrome still exists despite improved insulin therapy is crucial for earlier recognition and treatment.


Dynamic molecular combing: stretching the whole human genome for high-resolution studies.
DNA in amounts representative of hundreds of eukaryotic genomes was extended on silanized surfaces by dynamic molecular combing. The precise measurement of hybridized DNA probes was achieved directly without requiring normalization. This approach was validated with the high-resolution mapping of cosmid contigs on a yeast artificial chromosome (YAC) within yeast genomic DNA. It was extended to human genomic DNA for precise measurements ranging from 7 to 150 kilobases, of gaps within a contig, and of microdeletions in the tuberous sclerosis 2 gene on patients' DNA. The simplicity, reproducibility, and precision of this approach makes it a powerful tool for a variety of genomic studies.