Targeted deletion of the ATP binding domain of left-right dynein confirms its role in specifying development of left-right asymmetries.
Vertebrates develop distinct asymmetries along the left-right axis, which are consistently aligned with the anteroposterior and dorsoventral axes. The mechanisms that direct this handed development of left-right asymmetries have been elusive, but recent studies of mutations that affect left-right development have shed light on the molecules involved. One molecule implicated in left-right specification is left-right dynein (LRD), a microtubule-based motor protein. In the LRD protein of the inversus viscerum (iv) mouse, there is a single amino acid difference at a conserved position, and the lrd gene is one of many genes deleted in the legless (lgl) mutation. Both iv and lgl mice display randomized left-right development. Here we extend the analysis of the lrd gene at the levels of sequence, expression and function. The complete coding sequence of the lrd gene confirms its classification as an axonemal, or ciliary, dynein. Expression of lrd in the node at embryonic day 7.5 is shown to be symmetric. At embryonic day 8.0, however, a striking asymmetric expression pattern is observed in all three germ layers of the developing headfold, suggesting roles in both the establishment and maintenance of left-right asymmetries. At later times, expression of lrd is also observed in the developing floorplate, gut and limbs. These results suggest function for LRD protein in both ciliated and non-ciliated cells, despite its sequence classification as axonemal. In addition, a targeted mutation of lrd was generated that deletes the part of the protein required for ATP binding, and hence motor function. The resulting left-right phenotype, randomization of laterality, is identical to that of iv and lgl mutants. Gross defects in ciliary structure were not observed in lrd/lrd mutants. Strikingly, however, the monocilia on mutant embryonic node cells were immotile. These results prove the identity of the iv and lrd genes. Further, they argue that LRD motor function, and resulting nodal monocilia movement, are required for normal left-right development.


The differences between gonadal and extra-gonadal malignant teratomas in both genders and the effects of chemotherapy.
A tumor comprising of different types of tissues (such as hair, muscle, bone, etc.) is known as a teratoma. It is a type of germ cell (cells that make sperm or eggs) tumor. When these germ cells have rapid cancerous growth, then such a teratoma is called a malignant teratoma. We have studied the differences between gonadal and extra-gonadal malignant teratomas and the effects of chemotherapy in both genders. The samples of 3799 male and 1832 female patients with malignant teratoma samples, between the ages of 1 and 85+ years, were selected from the years 1973 to 2014. Trends in incidence, estimated prevalence, incidence rates, and frequency were calculated in gonadal and extra-gonadal tumors with age adjustment. The five-year observed, expected, and relative survival rates were analyzed to study the prognosis. The gonadal took over a majority percentage of malignant teratomas compared with the extra-gonadal (90% vs. 10% in male; 83% vs. 17% in female). For the male, the total of the gonadal and the extra-gonadal were all significantly decreased from 1973 to 2014 (p < 0.05). For the female, there were no significant trends. As for prevalence, incidence, and frequency, there were two separate peaks of malignant teratomas. One peak was at under 1 year old, which was composed of the extra-gonadal tumor; the other peak was at 20-24 for male and 10-34 for female, which was composed of the gonadal tumor. This separation of the gonadal and extra-gonadal showed a significant difference (p < 0.05). As for the prognosis, the extra-gonadal tumor showed significantly lower survival rates than the gonadal (p < 0.05). In the short term, the survival rate of the chemotherapy group was higher than the supportive care group. However, in the long term, the survival rate of the chemotherapy group was lower than the supportive care group. The gonadal and extra-gonadal malignant teratomas show lots of differences. Chemotherapy might not help improve survival rates.


Effects of the Communities That Care model in Pennsylvania on change in adolescent risk and problem behaviors.
Despite the public health burden of adolescent substance use, delinquency, and other problem behavior, few comprehensive models of disseminating evidence-based prevention programs to communities have demonstrated positive youth outcomes at a population level, capacity to maintain program fidelity, and sustainability. We examined whether the Communities That Care (CTC; Hawkins and Catalano 1992) model had a positive impact on risk/protective factors and academic and behavioral outcomes among adolescents in a quasi-experimental effectiveness study. We conducted a longitudinal study of CTC in Pennsylvania utilizing biannual surveillance data collected through anonymous in-school student surveys. We utilized multilevel models to examine CTC impact on change in risk/protective factors, grades, delinquency, and substance use over time. Youth in CTC communities demonstrated less growth in delinquency, but not substance use, than youth in non-CTC communities. Levels of risk factors increased more slowly, and protective factors and academic performance decreased more slowly, among CTC community grade-cohorts that were exposed to evidence-based, universal prevention programs than comparison grade cohorts. Community coalitions can affect adolescent risk and protective behaviors at a population level when evidence-based programs are utilized. CTC represents an effective model for disseminating such programs.


Fatal foodborne Clostridium perfringens illness at a state psychiatric hospital--Louisiana, 2010.
Clostridium perfringens, the third most common cause of foodborne illness in the United States (1), most often causes a self-limited, diarrheal disease lasting 12-24 hours. Fatalities are very rare, occurring in <0.03% of cases (1). Death usually is caused by dehydration and occurs among the very young, the very old, and persons debilitated by illness (2). On May 7, 2010, 42 residents and 12 staff members at a Louisiana state psychiatric hospital experienced vomiting, abdominal cramps, and diarrhea. Within 24 hours, three patients had died. The three fatalities occurred among patients aged 41-61 years who were receiving medications that had anti-intestinal motility side effects. For two of three decedents, the cause of death found on postmortem examination was necrotizing colitis. Investigation by the Louisiana Office of Public Health (OPH) and CDC found that eating chicken served at dinner on May 6 was associated with illness. The chicken was cooked approximately 24 hours before serving and not cooled in accordance with hospital guidelines. C. perfringens enterotoxin (CPE) was detected in 20 of 23 stool specimens from ill residents and staff members. Genetic testing of C. perfringens toxins isolated from chicken and stool specimens was carried out to determine which of the two strains responsible for C. perfringens foodborne illness was present. The specimens tested negative for the beta-toxin gene, excluding C. perfringens type C as the etiologic agent and implicating C. perfringens type A. This outbreak underscores the need for strict food preparation guidelines at psychiatric inpatient facilities and the potential risk for adverse outcomes among any patients with impaired intestinal motility caused by medications, disease, and extremes of age when exposed to C. perfringens enterotoxin.


Changes in plasma lipids predict pravastatin efficacy in secondary prevention.
BACKGROUNDStatins have pleiotropic effects on lipid metabolism. The relationship between these effects and future cardiovascular events is unknown. We characterized the changes in lipids upon pravastatin treatment and defined the relationship with risk reduction for future cardiovascular events.METHODSPlasma lipids (n = 342) were measured in baseline and 1-year follow-up samples from a Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study subcohort (n = 4991). The associations of changes in lipids with treatment and cardiovascular outcomes were investigated using linear and Cox regression. The effect of treatment on future cardiovascular outcomes was examined by the relative risk reduction (RRR).RESULTSPravastatin treatment was associated with changes in 206 lipids. Species containing arachidonic acid were positively associated while phosphatidylinositol species were negatively associated with pravastatin treatment. The RRR from pravastatin treatment for cardiovascular events decreased from 23.5% to 16.6% after adjustment for clinical risk factors and change in LDL-cholesterol (LDL-C) and to 3.0% after further adjustment for the change in the lipid ratio PI(36:2)/PC(38:4). Change in PI(36:2)/PC(38:4) mediated 58% of the treatment effect. Stratification of patients into quartiles of change in PI(36:2)/PC(38:4) indicated no benefit of pravastatin in the fourth quartile.CONCLUSIONThe change in PI(36:2)/PC(38:4) predicted benefit from pravastatin, independent of change in LDL-C, demonstrating its potential as a biomarker for monitoring the clinical benefit of statin treatment in secondary prevention.TRIAL REGISTRATIONAustralian New Zealand Clinical Trials Registry identifier ACTRN12616000535471.FUNDINGBristol-Myers Squibb; NHMRC grants 211086, 358395, and 1029754; NHMRC program grant 1149987; NHMRC fellowship 108026; and the Operational Infrastructure Support Program of the Victorian government of Australia.


Multiple pass effects in high efficiency laser pumping cavities.
Some effects connected with multiple passes of pump radiation in laser pump cavities are discussed. These effects include changes in mercury arc lamp operating characteristics, when the lamps are used inside the cavities as pump sources, and unexpectedly low pulse (but not cw) thresholds in double elliptical cavities. It is shown analytically that these effects can, at least in part, be attributed to the shapes of the pump light energy distribution curves after multiple passes through the pump cavities, and to the relative opacities of flash and continuous lamps.


Diagnostic significance of CD20 and FMC7 expression in B-cell disorders.
We analyzed by flow cytometry the expression of CD20 and FMC7 in cell suspensions from 932 patients, including 630 cases of chronic lymphocytic leukemia (CLL), 23 cases of other B-cell leukemias, and 279 cases of B-cell non-Hodgkin lymphoma (B-cell NHL). CD20 was positive in 94.5% of cases; FMC7 was positive in 35.7%. There was a correlation between CD20 and FMC7 expression in patients with B-cell NHL (P < .001) but not CLL (P = .1). We also tested a scoring system in which FMC7 was replaced by CD20 and compared it with our current scoring system for CLL. With this modification, the accuracy of the scoring system for differentiating CLL from other non-CLL disorders fell from 94.4% to 81.5%. In CD20+ CLL, the intensity of CD20 expression correlated with FMC7 and low scores (P < .001 for both comparisons). We suggest that the particular conformation of CD20 recognized by FMC7 is manifested only in cells with strong CD20 expression, which is not the case for CLL. FMC7 is of greater diagnostic value than CD20 for distinguishing CLL from other B-cell disorders; we recommend its continued use for this purpose.


Factors influencing cessation of pregnancy care in Oregon.
Anecdotal evidence suggests that many providers who previously delivered babies are no longer doing so, both in Oregon and nationally. This study determined the proportion of pregnancy care providers who have stopped or are planning to stop providing this care in Oregon and identified the important factors influencing such practice changes. We mailed a survey in October and November 2002 to all obstetrician-gynecologists, family physicians, general practitioners, and certified nurse midwives practicing in Oregon. The survey inquired about whether they currently perform deliveries. If they did not do so, or if they did so but planned to stop, further questions were asked about reasons for not providing this care. A total of 2,158 surveys were mailed; 1,232 were returned (58% adjusted response rate), and 1,069 had sufficient information to be included in our analysis. Of respondents, 511 (47.8%) currently perform deliveries. Of these, 157 (30.7%) indicated that they planned to stop doing so in 1 to 5 years, with cost of professional liability insurance (59%) and fear of lawsuits (43%) most frequently cited as major reasons. A total of 367 (34%) respondents had previously stopped performing deliveries. Providers who stopped providing this care since 1999 were significantly more likely to cite cost of medical liability insurance and low reimbursement as major reasons, compared to providers who stopped earlier. Our study suggests that as many as half of clinicians who previously performed or currently perform deliveries in Oregon are planning to stop or have already stopped providing this service, raising concern about access to pregnancy care services for women in the state.


Red and NIR light dosimetry in the human deep brain.
Photobiomodulation (PBM) appears promising to treat the hallmarks of Parkinson's Disease (PD) in cellular or animal models. We measured light propagation in different areas of PD-relevant deep brain tissue during transcranial, transsphenoidal illumination (at 671 and 808 nm) of a cadaver head and modeled optical parameters of human brain tissue using Monte-Carlo simulations. Gray matter, white matter, cerebrospinal fluid, ventricles, thalamus, pons, cerebellum and skull bone were processed into a mesh of the skull (158 × 201 × 211 voxels; voxel side length: 1 mm). Optical parameters were optimized from simulated and measured fluence rate distributions. The estimated μeff for the different tissues was in all cases larger at 671 than at 808 nm, making latter a better choice for light delivery in the deep brain. Absolute values were comparable to those found in the literature or slightly smaller. The effective attenuation in the ventricles was considerably larger than literature values. Optimization yields a new set of optical parameters better reproducing the experimental data. A combination of PBM via the sphenoid sinus and oral cavity could be beneficial. A 20-fold higher efficiency of light delivery to the deep brain was achieved with ventricular instead of transcranial illumination. Our study demonstrates that it is possible to illuminate deep brain tissues transcranially, transsphenoidally and via different application routes. This opens therapeutic options for sufferers of PD or other cerebral diseases necessitating light therapy.


Committee Opinion No.675: Management of Vulvar Intraepithelial Neoplasia.
Vulvar intraepithelial neoplasia (VIN) is an increasingly common problem, particularly among women in their 40s. Although spontaneous regression has been reported, VIN should be considered a premalignant condition. Immunization with the quadrivalent or 9-valent human papillomavirus vaccine, which is effective against human papillomavirus genotypes 6, 11, 16, and 18, and 6, 11, 16, 18, 31, 33, 45, 52, and 58, respectively, has been shown to decrease the risk of vulvar high-grade squamous intraepithelial lesion (HSIL) (VIN usual type) and should be recommended for girls aged 11-12 years with catch-up through age 26 years if not vaccinated in the target age. There are no screening strategies for the prevention of vulvar cancer through early detection of vulvar HSIL (VIN usual type). Detection is limited to visual assessment with confirmation by histopathology when needed. Treatment is recommended for all women with vulvar HSIL (VIN usual type). Because of the potential for occult invasion, wide local excision should be performed if cancer is suspected, even if biopsies show vulvar HSIL. When occult invasion is not a concern, vulvar HSIL (VIN usual type) can be treated with excision, laser ablation, or topical imiquimod (off-label use). Given the relatively slow rate of progression, women with a complete response to therapy and no new lesions at follow-up visits scheduled 6 months and 12 months after initial treatment should be monitored by visual inspection of the vulva annually thereafter.


Dynamical movement primitives: learning attractor models for motor behaviors.
Nonlinear dynamical systems have been used in many disciplines to model complex behaviors, including biological motor control, robotics, perception, economics, traffic prediction, and neuroscience. While often the unexpected emergent behavior of nonlinear systems is the focus of investigations, it is of equal importance to create goal-directed behavior (e.g., stable locomotion from a system of coupled oscillators under perceptual guidance). Modeling goal-directed behavior with nonlinear systems is, however, rather difficult due to the parameter sensitivity of these systems, their complex phase transitions in response to subtle parameter changes, and the difficulty of analyzing and predicting their long-term behavior; intuition and time-consuming parameter tuning play a major role. This letter presents and reviews dynamical movement primitives, a line of research for modeling attractor behaviors of autonomous nonlinear dynamical systems with the help of statistical learning techniques. The essence of our approach is to start with a simple dynamical system, such as a set of linear differential equations, and transform those into a weakly nonlinear system with prescribed attractor dynamics by means of a learnable autonomous forcing term. Both point attractors and limit cycle attractors of almost arbitrary complexity can be generated. We explain the design principle of our approach and evaluate its properties in several example applications in motor control and robotics.


Sulfopin is a covalent inhibitor of Pin1 that blocks Myc-driven tumors in vivo.
The peptidyl-prolyl isomerase, Pin1, is exploited in cancer to activate oncogenes and inactivate tumor suppressors. However, despite considerable efforts, Pin1 has remained an elusive drug target. Here, we screened an electrophilic fragment library to identify covalent inhibitors targeting Pin1's active site Cys113, leading to the development of Sulfopin, a nanomolar Pin1 inhibitor. Sulfopin is highly selective, as validated by two independent chemoproteomics methods, achieves potent cellular and in vivo target engagement and phenocopies Pin1 genetic knockout. Pin1 inhibition had only a modest effect on cancer cell line viability. Nevertheless, Sulfopin induced downregulation of c-Myc target genes, reduced tumor progression and conferred survival benefit in murine and zebrafish models of MYCN-driven neuroblastoma, and in a murine model of pancreatic cancer. Our results demonstrate that Sulfopin is a chemical probe suitable for assessment of Pin1-dependent pharmacology in cells and in vivo, and that Pin1 warrants further investigation as a potential cancer drug target.


Binding and cross-linking of recombinant mouse interferon-gamma to receptors in mouse leukemic L1210 cells; interferon-gamma internalization and receptor down-regulation.
Recombinant E. coli-derived murine IFN-gamma (Mu-rIFN-gamma; 5 X 10(7) U/mg) was radiolabeled with 125I by the chloramine-T method without loss of its antiviral activity. The 125I-Mu-rIFN-gamma showed specific binding to L1210 cells. Scatchard analysis indicates about 4000 binding sites per cell and an apparent Kd of 5 X 10(-10)M. Binding of 125I-Mu-rIFN-gamma to cells was inhibited by both natural (glycosylated) and rIFN-gamma, but not by IFN-alpha/beta. Receptor-bound 125I-Mu-rIFN-gamma was rapidly internalized when incubation temperature was raised from 4 degrees C to 37 degrees C. On internalization, almost no IFN-gamma degradation was observed during 16 hr incubation. 125I-Mu-rIFN-gamma binding capacity decreased in cells preincubated with low doses of unlabeled Mu-rIFN-gamma, but not with IFN-alpha/beta. This receptor down-regulation was dose-dependent: 90% reduction of 125I-Mu-rIFN-gamma binding was observed after preincubation with 100 U/ml. After removal of IFN-gamma from the culture medium, the binding capacity increased with time. However, reappearance of receptor was completely blocked by cycloheximide or tunicamycin, suggesting that re-expression of receptors is not due to recycling but to the synthesis of new receptors, and that the receptor is probably a glycoprotein. Cross-linking of 125I-Mu-rIFN-gamma to surface L1210 cell proteins by using bifunctional agents yielded a predominant complex of m.w. 110,000 +/- 5000. Thus, assuming a bimolecular complex, the m.w. of the receptor or receptor subunit would be close to 95,000 +/- 5000. The formation of such a complex appeared highly specific on the basis of the following criteria: it could be inhibited by the addition of Mu-rIFN-gamma but not by Mu-rIFN-alpha/beta, it was not obtained in cells pretreated with IFN-gamma to induce down-regulation of IFN-gamma receptors, and it was also identified in the IFN-alpha/beta-resistant L1210R cell line, known to be sensitive to IFN-gamma and which we have recently shown to express IFN-gamma receptors.


Applications of blood-based protein biomarker strategies in the study of psychiatric disorders.
Major psychiatric disorders such as schizophrenia, major depressive and bipolar disorders are severe, chronic and debilitating, and are associated with high disease burden and healthcare costs. Currently, diagnoses of these disorders rely on interview-based assessments of subjective self-reported symptoms. Early diagnosis is difficult, misdiagnosis is a frequent occurrence and there are no objective tests that aid in the prediction of individual responses to treatment. Consequently, validated biomarkers are urgently needed to help address these unmet clinical needs. Historically, psychiatric disorders are viewed as brain disorders and consequently only a few researchers have as yet evaluated systemic changes in psychiatric patients. However, promising research has begun to challenge this concept and there is an increasing awareness that disease-related changes can be traced in the peripheral system which may even be involved in the precipitation of disease onset and course. Converging evidence from molecular profiling analysis of blood serum/plasma have revealed robust molecular changes in psychiatric patients, suggesting that these disorders may be detectable in other systems of the body such as the circulating blood. In this review, we discuss the current clinical needs in psychiatry, highlight the importance of biomarkers in the field, and review a representative selection of biomarker studies to highlight opportunities for the implementation of personalized medicine approaches in the field of psychiatry. It is anticipated that the implementation of validated biomarker tests will not only improve the diagnosis and more effective treatment of psychiatric patients, but also improve prognosis and disease outcome.


The effect of cannabidiol on canine neoplastic cell proliferation and mitogen-activated protein kinase activation during autophagy and apoptosis.
Low tetrahydrocannabinol Cannabis sativa products, also known as hemp products, have become widely available and their use in veterinary patients has become increasingly popular. Despite prevalence of use, the veterinary literature is lacking and evidence-based resource for cannabinoid efficacy. The most prevailing cannabinoid found in hemp is cannabidiolic acid (CBDA) and becomes cannabidiol (CBD) during heat extraction; CBD has been studied for its direct anti-neoplastic properties alone and in combination with standard cancer therapies, yielding encouraging results. The objectives of our study were to explore the anti-proliferative and cell death response associated with in vitro treatment of canine cancer cell lines with CBD alone and combination with common chemotherapeutics, as well as investigation into major proliferative pathways (eg, p38, JNK, AKT and mTOR) potentially involved in the response to treatment with CBD. CBD significantly reduced canine cancer cell proliferation far better than CBDA across five canine neoplastic cell lines when treated with concentrations ranging from 2.5 to 10 μg/mL. Combinatory treatment with CBD and vincristine reduced cell proliferation in a synergistic or additive manner at anti-proliferative concentrations with less clear results using doxorubicin in combination with CBD. The cellular signalling effects of CBD treatment, showed that autophagy supervened induction of apoptosis and may be related to prompt induction of ERK and JNK phosphorylation prior to autophagy. In conclusion, CBD is effective at hindering cell proliferation and induction of autophagy and apoptosis rapidly across neoplastic cell lines and further clinical trials are needed to understand its efficacy and interactions with traditional chemotherapy.


Rapid "turn-on" photoluminescence detection of bisulfite in wines and living cells with a formyl bearing bis-cyclometalated Ir(iii) complex.
A new photoluminescence (PL) probe based on a formyl bearing bis-cyclometalated Ir(iii) complex, [Ir(ppy)2phen-CHO]+PF6- (1), is synthesized and applied to the selective detection of a bisulfite anion (HSO3-). Probe 1 is prepared using 2-phenylpyridine (ppy) as the C^N main ligand and 1,10-phenanthroline-5-carboxaldehyde (phen-CHO) as the N^N ancillary ligand. Probe 1 displayed excellent selective PL enhancement in response to HSO3- in acetic acid-sodium acetate buffer solution (pH = 5.0). The increase of PL signal is directly proportional to the concentration of HSO3- in the range of 2 μM to 45 μM with a detection limit of 0.9 μM using 50 μM probe 1 and in the range of 0.5 μM to 6 μM with a detection limit of 0.3 μM using 10 μM probe 1. More importantly, probe 1 can respond to HSO3- rapidly within 40 s. Furthermore, probe 1 was successfully applied to detect HSO3- in real white wines and the bioimaging of HSO3- in living cells. The superior properties of probe 1 make it of great potential use for studying the effects of HSO3- in other biosystems.


The development of a creative work rehabilitation organisation.
Work as therapy has a place in mental healthcare, but there is disagreement about how and why it might be helpful, and how best to conceptualise or represent those benefits. Over the last 50 years, occupational and industrial therapy sheltered workshops have been key elements in the provision of work activities in psychiatric settings, and community-based horticultural activities and creative craft work have offered additional approaches. Using archival material, interviews, witness seminars and personal reflections, this article charts the birth and initial growth of Restore, a charity providing creative work-based services in Oxfordshire between 1977 and 1988. Although Restore might be understood as a response to national trends in mental healthcare policy and research, its trajectory reflects local contingencies.


Rat-brain Na,K-ATPase beta-chain gene: primary structure, tissue-specific expression, and amplification in ouabain-resistant HeLa C+ cells.
We deduced the complete amino acid sequence of the rat brain Na,K-ATPase beta-subunit from cDNA. The rat brain beta-subunit exhibits a high degree of primary sequence and secondary structural homology with the human and Torpedo beta-subunit polypeptides. Analysis of rat tissue RNA reveals that the beta-subunit gene encodes four separate mRNA species which are expressed in a tissue-specific fashion. In ouabain-resistant HeLa C+ cells, beta-subunit DNA sequences are amplified (approximately 20-fold) and beta-subunit mRNAs are overproduced relative to levels in parental HeLa cells. These results suggest that the beta-subunit plays an important role in Na,K-ATPase structure-function and in the mechanism underlying cellular resistance to the cardiac glycosides.


The oldest records of photosynthesis.
There is diverse, yet controversial fossil evidence for the existence of photosynthesis 3500 million years ago. Among the most persuasive evidence is the stromatolites described from low grade metasedimentary rocks in Western Australia and South Africa. Based on the understanding of the paleobiology of stromatolites and using pertinent fossil and Recent analogs, these Early Archean stromatolites suggest that phototrophs evolved by 3500 million years ago. The evidence allows further interpretation that cyanobacteria were involved. Besides stromatolites, microbial and chemical fossils are also known from the same rock units. Some microfossils morphologically resemble cyanobacteria and thus complement the adduced cyanobacterial involvement in stromatolite construction. If cyanobacteria had evolved by 3500 million years ago, this would indicate that nearly all prokaryotic phyla had already evolved and that prokaryotes diversified rapidly on the early Earth.


Discovery of a New Song Mode in Drosophila Reveals Hidden Structure in the Sensory and Neural Drivers of Behavior.
Deciphering how brains generate behavior depends critically on an accurate description of behavior. If distinct behaviors are lumped together, separate modes of brain activity can be wrongly attributed to the same behavior. Alternatively, if a single behavior is split into two, the same neural activity can appear to produce different behaviors. Here, we address this issue in the context of acoustic communication in Drosophila. During courtship, males vibrate their wings to generate time-varying songs, and females evaluate songs to inform mating decisions. For 50 years, Drosophila melanogaster song was thought to consist of only two modes, sine and pulse, but using unsupervised classification methods on large datasets of song recordings, we now establish the existence of at least three song modes: two distinct pulse types, along with a single sine mode. We show how this seemingly subtle distinction affects our interpretation of the mechanisms underlying song production and perception. Specifically, we show that visual feedback influences the probability of producing each song mode and that male song mode choice affects female responses and contributes to modulating his song amplitude with distance. At the neural level, we demonstrate how the activity of four separate neuron types within the fly's song pathway differentially affects the probability of producing each song mode. Our results highlight the importance of carefully segmenting behavior to map the underlying sensory, neural, and genetic mechanisms.


Non-coding RNAs as regulators in epigenetics (Review).
Epigenetics is a discipline that studies heritable changes in gene expression that do not involve altering the DNA sequence. Over the past decade, researchers have shown that epigenetic regulation plays a momentous role in cell growth, differentiation, autoimmune diseases, and cancer. The main epigenetic mechanisms include the well-understood phenomenon of DNA methylation, histone modifications, and regulation by non-coding RNAs, a mode of regulation that has only been identified relatively recently and is an area of intensive ongoing investigation. It is generally known that the majority of human transcripts are not translated but a large number of them nonetheless serve vital functions. Non-coding RNAs are a cluster of RNAs that do not encode functional proteins and were originally considered to merely regulate gene expression at the post-transcriptional level. However, taken together, a wide variety of recent studies have suggested that miRNAs, piRNAs, endogenous siRNAs, and long non-coding RNAs are the most common regulatory RNAs, and, significantly, there is a growing body of evidence that regulatory non-coding RNAs play an important role in epigenetic control. Therefore, these non-coding RNAs (ncRNAs) highlight the prominent role of RNA in the regulation of gene expression. Herein, we summarize recent research developments with the purpose of coming to a better understanding of non-coding RNAs and their mechanisms of action in cells, thus gaining a preliminary understanding that non-coding RNAs feed back into an epigenetic regulatory network.


Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling.
Planar cell polarity signaling in Drosophila requires the receptor Frizzled and the cytoplasmic proteins Dishevelled and Prickle. From initial, symmetric subcellular distributions in pupal wing cells, Frizzled and Dishevelled become highly enriched at the distal portion of the cell cortex. We describe a Prickle-dependent intercellular feedback loop that generates asymmetric Frizzled and Dishevelled localization. In the absence of Prickle, Frizzled and Dishevelled remain symmetrically distributed. Prickle localizes to the proximal side of pupal wing cells and binds the Dishevelled DEP domain, inhibiting Dishevelled membrane localization and antagonizing Frizzled accumulation. This activity is linked to Frizzled activity on the adjacent cell surface. Prickle therefore functions in a feedback loop that amplifies differences between Frizzled levels on adjacent cell surfaces.


Endovascular Treatment of Infrarenal Aneurysms: Comparison of the Results of Second- and Third-Generation Stent Grafts.
The stent grafts used for endovascular abdominal aortic repair (EVAR) profited from many technological changes since their appearance. The objective of this study was to compare the medium-term results of the second- and third-generation stent grafts. Three hundred thirty-four patients treated by EVAR between 2005 and 2013 were included in this retrospective study. Demographic, anatomical, perioperative, and follow-up data were collected in a prospective way in an electronic database and compared between 2 groups. The preoperative angio-computed tomographies were all analyzed in depth on a suitable three-dimensional work station. Group 1 (n = 219) represented the patients treated by second-generation stent grafts (Medtronic Talent(®), Cook Medical Zenith Flex(®), Vascutek-Terumo Anaconda(®), Gore Excluder low-porosity(®)) and group 2 (n = 115) represented the patients treated with third-generation stent grafts (Medtronic Enduring I and II(®), Cook Medical Zenith LP(®), Gore Excluder C3(®)). The mean follow-up was 42.4 ± 26.8 months with a longer duration in group 1 (52.4 ± 27.2 vs. 23.2 ± 10.9 months, P < 0.0001). The patients of group 2 had significantly more risk factors and cardiovascular comorbidities (coronary disease, tobacco addiction, dyslipidemia, peripheral arterial disease, chronic renal insufficiency). Anatomical characteristics were similar in the 2 groups, in particular regarding the iliac arteries which were significantly more calcified and had a smaller diameter in group 2. The rate of perioperative complications was similar in the 2 groups, in particular for complications related to the iliac axes (3.7% vs. 2.6%, P = 0.96). During the follow-up, there was no significant difference between the 2 groups in the rates of survival, reinterventions, or endoleaks and the progression of the aneurysmal sac. This study shows that third-generation stent grafts allow results comparable with those of the second-generation stent grafts in spite of more complex iliac anatomies. These results make it possible to expand the indications of EVAR to patients presenting more cardiovascular comorbidities without increasing the risk of complications in the short and medium term.


Neurocardiac response to esophageal electric stimulation in humans: effects of varying stimulation frequencies.
The purpose of this study was to determine if the cardioautonomic responses to esophageal electric stimulation were mediated entirely through modulation of respiratory frequency or a direct vagal effect. We performed electric stimulation of the esophagus in 13 healthy male controls (24 +/- 6 yr) using a manometric catheter to which a stainless steel electrode was attached. Stimulation frequencies ranged from 0.1 to 1 Hz and were applied in random fashion. We computed the power spectra of the heart rate variability and respiratory frequency as measures of autonomic function. Electric stimulation of the esophagus produced significant increases in the high-frequency power of the heart rate autospectrum at all stimulation frequencies (maximal at 0.2 Hz). However, regardless of the frequency of esophageal stimulation, the respiratory rate was not changed from baseline. These studies indicate that enhancement of cardiac vagal modulation observed in response to esophageal electric stimulation is not primarily due to changes in respiratory frequency, but rather occurs through a direct, vagally mediated action through sensory neural pathways involving vagal esophageal afferents.


Anti-Inflammatory Effect of Emblica officinalis in Rodent Models of Acute and Chronic Inflammation: Involvement of Possible Mechanisms.
Emblica officinalis, commonly known as amla in Ayurveda, is unarguably the most important medicinal plant for prevention and treatment of various ailments. The present study investigated the anti-inflammatory activity of hydroalcoholic extract of Emblica officinalis (HAEEO). Acute inflammation in rats was induced by the subplantar injection of carrageenan, histamine, serotonin, and prostaglandin E2 and chronic inflammation was induced by the cotton pellet granuloma. Intraperitoneal (i.p.) administration of HAEEO at all the tested doses (300, 500, and 700 mg/kg) significantly (P < 0.001) inhibited rat paw edema against all phlogistic agents and also reduced granuloma formation. However, at the dose of 700 mg/kg, HAEEO exhibited maximum anti-inflammatory activity in all experimental models, and the effects were comparable to that of the standard anti-inflammatory drugs. Additionally, in paw tissue the antioxidant activity of HAEEO was also measured and it was found that HAEEO significantly (P < 0.001) increased glutathione, superoxide dismutase, and catalase activity and subsequently reduced lipid peroxidation evidenced by reduced malondialdehyde. Taken all together, the results indicated that HAEEO possessed potent anti-inflammatory activity and it may hold therapeutic promise in the management of acute and chronic inflammatory conditions.


Experimental observation of stimulated low-frequency Raman scattering in water suspensions of silver and gold nanoparticles.
In this Letter we report on experimental observation of stimulated low-frequency Raman scattering (SLFRS) in gold and silver nanoparticle suspensions excited by 20 ns ruby laser pulses, SLFRS propagated in forward and backward directions with a maximum conversion efficiency up to 20%. Frequency shift for silver nanoparticle suspension was found to be 0.33 THz and for gold nanoparticle suspension 0.435 THz. This type of stimulated scattering of light can be used as an effective source of biharmonic pumping for solving a large number of practical tasks.


Patient-specific radiation dose and cancer risk for pediatric chest CT.
To estimate patient-specific radiation dose and cancer risk for pediatric chest computed tomography (CT) and to evaluate factors affecting dose and risk, including patient size, patient age, and scanning parameters. The institutional review board approved this study and waived informed consent. This study was HIPAA compliant. The study included 30 patients (0-16 years old), for whom full-body computer models were recently created from clinical CT data. A validated Monte Carlo program was used to estimate organ dose from eight chest protocols, representing clinically relevant combinations of bow tie filter, collimation, pitch, and tube potential. Organ dose was used to calculate effective dose and risk index (an index of total cancer incidence risk). The dose and risk estimates before and after normalization by volume-weighted CT dose index (CTDI(vol)) or dose-length product (DLP) were correlated with patient size and age. The effect of each scanning parameter was studied. Organ dose normalized by tube current-time product or CTDI(vol) decreased exponentially with increasing average chest diameter. Effective dose normalized by tube current-time product or DLP decreased exponentially with increasing chest diameter. Chest diameter was a stronger predictor of dose than weight and total scan length. Risk index normalized by tube current-time product or DLP decreased exponentially with both chest diameter and age. When normalized by DLP, effective dose and risk index were independent of collimation, pitch, and tube potential (<10% variation). The correlations of dose and risk with patient size and age can be used to estimate patient-specific dose and risk. They can further guide the design and optimization of pediatric chest CT protocols. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101900/-/DC1.


Post-Disaster Food and Nutrition from Urban Agriculture: A Self-Sufficiency Analysis of Nerima Ward, Tokyo.
Background: Post-earthquake studies from around the world have reported that survivors relying on emergency food for prolonged periods of time experienced several dietary related health problems. The present study aimed to quantify the potential nutrient production of urban agricultural vegetables and the resulting nutritional self-sufficiency throughout the year for mitigating post-disaster situations. Methods: We estimated the vegetable production of urban agriculture throughout the year. Two methods were developed to capture the production from professional and hobby farms: Method I utilized secondary governmental data on agricultural production from professional farms, and Method II was based on a supplementary spatial analysis to estimate the production from hobby farms. Next, the weight of produced vegetables [t] was converted into nutrients [kg]. Furthermore, the self-sufficiency by nutrient and time of year was estimated by incorporating the reference consumption of vegetables [kg], recommended dietary allowance of nutrients per capita [mg], and population statistics. The research was conducted in Nerima, the second most populous ward of Tokyo's 23 special wards. Self-sufficiency rates were calculated with the registered residents. Results: The estimated total vegetable production of 5660 tons was equivalent to a weight-based self-sufficiency rate of 6.18%. The average nutritional self-sufficiencies of Methods I and II were 2.48% and 0.38%, respectively, resulting in an aggregated average of 2.86%. Fluctuations throughout the year were observed according to the harvest seasons of the available crops. Vitamin K (6.15%) had the highest self-sufficiency of selected nutrients, while calcium had the lowest (0.96%). Conclusions: This study suggests that depending on the time of year, urban agriculture has the potential to contribute nutrients to diets during post-disaster situations as disaster preparedness food. Emergency responses should be targeted according to the time of year the disaster takes place to meet nutrient requirements in periods of low self-sufficiency and prevent gastrointestinal symptoms and cardiovascular diseases among survivors.


Choosing implementation strategies to address contextual barriers: diversity in recommendations and future directions.
A fundamental challenge of implementation is identifying contextual determinants (i.e., barriers and facilitators) and determining which implementation strategies will address them. Numerous conceptual frameworks (e.g., the Consolidated Framework for Implementation Research; CFIR) have been developed to guide the identification of contextual determinants, and compilations of implementation strategies (e.g., the Expert Recommendations for Implementing Change compilation; ERIC) have been developed which can support selection and reporting of implementation strategies. The aim of this study was to identify which ERIC implementation strategies would best address specific CFIR-based contextual barriers. Implementation researchers and practitioners were recruited to participate in an online series of tasks involving matching specific ERIC implementation strategies to specific implementation barriers. Participants were presented with brief descriptions of barriers based on CFIR construct definitions. They were asked to rank up to seven implementation strategies that would best address each barrier. Barriers were presented in a random order, and participants had the option to respond to the barrier or skip to another barrier. Participants were also asked about considerations that most influenced their choices. Four hundred thirty-five invitations were emailed and 169 (39%) individuals participated. Respondents had considerable heterogeneity in opinions regarding which ERIC strategies best addressed each CFIR barrier. Across the 39 CFIR barriers, an average of 47 different ERIC strategies (SD = 4.8, range 35 to 55) was endorsed at least once for each, as being one of seven strategies that would best address the barrier. A tool was developed that allows users to specify high-priority CFIR-based barriers and receive a prioritized list of strategies based on endorsements provided by participants. The wide heterogeneity of endorsements obtained in this study's task suggests that there are relatively few consistent relationships between CFIR-based barriers and ERIC implementation strategies. Despite this heterogeneity, a tool aggregating endorsements across multiple barriers can support taking a structured approach to consider a broad range of strategies given those barriers. This study's results point to the need for a more detailed evaluation of the underlying determinants of barriers and how these determinants are addressed by strategies as part of the implementation planning process.


Covalent Protein Labeling by SpyTag-SpyCatcher in Fixed Cells for Super-Resolution Microscopy.
Labeling proteins with high specificity and efficiency is a fundamental prerequisite for microscopic visualization of subcellular protein structures and interactions. Although the comparatively small size of epitope tags makes them less perturbative to fusion proteins, they require the use of large antibodies that often limit probe accessibility and effective resolution. Here we use the covalent SpyTag-SpyCatcher system as an epitope-like tag for fluorescent labeling of intracellular proteins in fixed cells for both conventional and super-resolution microscopy. We also applied this method to endogenous proteins by gene editing, demonstrating its high labeling efficiency and capability for isoform-specific labeling.


Electrostatic self-assembly of binary nanoparticle crystals with a diamond-like lattice.
Self-assembly of charged, equally sized metal nanoparticles of two types (gold and silver) leads to the formation of large, sphalerite (diamond-like) crystals, in which each nanoparticle has four oppositely charged neighbors. Formation of these non-close-packed structures is a consequence of electrostatic effects specific to the nanoscale, where the thickness of the screening layer is commensurate with the dimensions of the assembling objects. Because of electrostatic stabilization of larger crystallizing particles by smaller ones, better-quality crystals can be obtained from more polydisperse nanoparticle solutions.


Parental training and involvement in sexuality education for students who are deaf.
The study examined whether schools for the deaf were providing services to assist parents in communicating with their children about sexuality (including sexual signs) and whether parents were involved in the sexuality education curriculum within their child's school. The Sexuality Curriculum Questionnaire for Educators of Students Who Are Deaf (Getch & Gabriel, 1998) was completed by 71 educators teaching sexuality curricula in schools for the deaf across the United States. Results indicated that parents were more likely to be involved in approval and development of their children's sexuality education than to receive assistance with sexuality education from the schools. Although the level of parental participation in curriculum development and approval is encouraging, the number of parents actually participating in curriculum development and approval remains low.


Meaningful Use of Electronic Health Records: Experiences From the Field and Future Opportunities.
With the aim of improving health care processes through health information technology (HIT), the US government has promulgated requirements for "meaningful use" (MU) of electronic health records (EHRs) as a condition for providers receiving financial incentives for the adoption and use of these systems. Considerable uncertainty remains about the impact of these requirements on the effective application of EHR systems. The Agency for Healthcare Research and Quality (AHRQ)-sponsored Centers for Education and Research in Therapeutics (CERTs) critically examined the impact of the MU policy relating to the use of medications and jointly developed recommendations to help inform future HIT policy. We gathered perspectives from a wide range of stakeholders (N=35) who had experience with MU requirements, including academicians, practitioners, and policy makers from different health care organizations including and beyond the CERTs. Specific issues and recommendations were discussed and agreed on as a group. Stakeholders' knowledge and experiences from implementing MU requirements fell into 6 domains: (1) accuracy of medication lists and medication reconciliation, (2) problem list accuracy and the shift in HIT priorities, (3) accuracy of allergy lists and allergy-related standards development, (4) support of safer and effective prescribing for children, (5) considerations for rural communities, and (6) general issues with achieving MU. Standards are needed to better facilitate the exchange of data elements between health care settings. Several organizations felt that their preoccupation with fulfilling MU requirements stifled innovation. Greater emphasis should be placed on local HIT configurations that better address population health care needs. Although MU has stimulated adoption of EHRs, its effects on quality and safety remain uncertain. Stakeholders felt that MU requirements should be more flexible and recognize that integrated models may achieve information-sharing goals in alternate ways. Future certification rules and requirements should enhance EHR functionalities critical for safer prescribing of medications in children.


Mechanical work makes important contributions to surface chemistry at steps.
The effect of mechanical strain on the binding energy of adsorbates to late transition metals is believed to be entirely controlled by electronic factors, with tensile stress inducing stronger binding. Here we show, via computation, that mechanical strain of late transition metals can modify binding at stepped surfaces opposite to well-established trends on flat surfaces. The mechanism driving the trend is mechanical, arising from the relaxation of stored mechanical energy. The mechanical energy change can be larger than, and of opposite sign than, the energy changes due to electronic effects and leads to a violation of trends predicted by the widely accepted electronic 'd-band' model. This trend has a direct impact on catalytic activity, which is demonstrated here for methanation, where biaxial tension is predicted to shift the activity of nickel significantly, reaching the peak of the volcano plot and comparable to cobalt and ruthenium.


Midwives' reflections on their educational programme: a traditional or problem-based learning approach?
to explore the longer-term effect of a problem-based learning (PBL) programme on midwives in practice. qualitative study. Graduates involved in an earlier study of the implementation of a PBL programme were interviewed between 5 and 6 years after graduating to explore the possible longer-term effect of a PBL programme on their practice as midwives. Thames Valley University with graduates who had completed an 18-month programme on one of two campuses on a variety of clinical sites. interviews were held with four graduates who had completed their programme before the implementation of PBL and five who had completed a PBL programme. Key themes were identified and compared cross-sectionally. midwives who had graduated from a PBL programme found that the approach was valuable in enabling them to access information and to develop a critical questioning approach. Some felt anxious at the beginning of their programme and said that they would have benefited from more direction and feedback from the facilitator early on in the programme. The focus on individual presentations sometimes inhibited the students learning from others in the group. The success of the PBL approach was felt to be dependent on the way in which the group worked together. The quality of the clinical placement, and the support of mentors and link teachers in the clinical setting, was a key factor in learning for students from both programmes. PBL has been incorporated into some programmes because it is thought to benefit practice disciplines, especially in a world of uncertain and changing evidence. However, no clear picture has emerged about the benefits of a PBL programme for midwifery education. our findings have implications for curriculum development to ensure the potential benefits of PBL are realised in practice. This may include providing further guidance and feedback to students, particularly at the start of their programme. Further research using innovative methodologies is needed to critically assess the longer-term effect of this approach to education.


Imaging oxygen metabolism with hyperpolarized magnetic resonance: a novel approach for the examination of cardiac and renal function.
Every tissue in the body critically depends on meeting its energetic demands with sufficient oxygen supply. Oxygen supply/demand imbalances underlie the diseases that inflict the greatest socio-economic burden globally. The purpose of this review is to examine how hyperpolarized contrast media, used in combination with MR data acquisition methods, may advance our ability to assess oxygen metabolism non-invasively and thus improve management of clinical disease. We first introduce the concept of hyperpolarization and how hyperpolarized contrast media have been practically implemented to achieve translational and clinical research. We will then analyse how incorporating hyperpolarized contrast media could enable realization of unmet technical needs in clinical practice. We will focus on imaging cardiac and renal oxygen metabolism, as both organs have unique physiological demands to satisfy their requirements for tissue oxygenation, their dysfunction plays a fundamental role in society's most prevalent diseases, and each organ presents unique imaging challenges. It is our aim that this review attracts a multi-disciplinary audience and sparks collaborations that utilize an exciting, emergent technology to advance our ability to treat patients adversely affected by an oxygen supply/demand mismatch.


Diversity in clinical management and protocols for the treatment of major bleeding trauma patients across European level I Trauma Centres.
Uncontrolled haemorrhage is still the leading cause of preventable death after trauma and the primary focus of any treatment strategy should be related to early detection and control of blood loss including haemostasis. For assessing management practices across six European level I trauma centres with academic interest and research in the field of coagulopathy an online survey was conducted addressing local management practice for bleeding trauma patients including algorithms for detection, management and monitoring coagulation disorders and immediate interventions. Each centre provided their locally applied massive transfusion protocol. All participating trauma centres have developed and implemented a local algorithm and protocol for the bleeding trauma patient. These are uniformly activated by clinical triggers and deactivated once the bleeding has stopped according to clinical assessment in combination with laboratory signs of achieved haemostasis. The severity of coagulopathy and shock is mostly assessed via standard coagulation tests and partially used extended viscoelastic tests. All centres have implemented the immediate use of tranexamic acid. Initial resuscitation is started either pre-hospital or after hospital admission by using transfusion packages with pre-fixed universal blood product combinations and ratios following the concept of "damage control resuscitation" at which applied ratios substantially vary. Two centres initially start with transfusion packages but with viscoelastic tests running in parallel to quickly allow a shift towards a viscoelastic test-guided therapy. Diversity in the management of bleeding trauma patients such as pre-hospital blood administration and routinely performed viscoelastic tests exists even among level I trauma centres. The paucity of consensus among these centres highlights the need for further primary research followed by clinical trials to improve the evidence for sophisticated guidelines and strategies.


Magnetic measurement of S-T and T-Q segment shifts in humans. Part II: Exercise-induced S-T segment depression.
The direct-current magnetocardiogram, which shows the T-Q (baseline) shift, is used to clarify the cause of S-T depression induced by stress testing in the human heart. Measurements are made of the amount of baseline shift associated with the S-T depression. Results are presented of a well-documented patient, with typical coronary artery disease, undergoing a two-step exercise test. Before exercise, there was no S-T or baseline shift. During exercise, the S-T segment became depressed and the baseline segment was simultaneously elevated, at about 70% of the S-T amplitude. After termination of exercise, the baseline elevation disappeared somewhat more rapidly than the S-T depression. These results were consistent in repeated tests of this patient. Because the baseline shift is a reflection of an injury current, these results confirm the belief that exercise-induced S-T depression is mostly due to an injury current which is interrupted during the S-T interval. The baseline shift seen here is the first non-invasive measurement of an injury current in the human heart, and its presence and time-course generally agree with measurements in the animal heart. This work also confirms that the direct-current magnetocardiogram, although not practical for clinical purposes, is useful as a research tool.


Prognosis of herpes zoster in healthy children.
Previous investigators have suggested that herpes zoster may be the presenting sign of a malignancy. However, no data have been available concerning the prognosis of herpes zoster in normal children. To assess outcome and prognosis for healthy children with a diagnosis of herpes zoster, we collected and reviewed 22 cases of herpes zoster from 90 pediatric practices in our community. In all cases, the illness was of short duration and resolved completely. Patients were followed up by their pediatricians for a mean of 4.2 years, and in no case did malignancy manifest subsequent to the zoster infection. We conclude that herpes zoster is a relatively benign infection in children and, given the period of follow-up, the onset of zoster does not appear to herald the occurrence of malignancy in this population.


DNA Binding to Gold Nanoparticles through the Prism of Molecular Selection: Sequence-Affinity Relation.
Native DNA strongly adsorbs to citrate-coated gold nanoparticles (AuNPs). The resulting composites (DNA/AuNPs) are valuable materials in many fields, especially in biomedicine. For this reason, the process of adsorption is a focus for intensive research. In this work, DNA adsorption to gold nanoparticles was studied using a molecular selection procedure followed by high-throughput DNA sequencing. The chemically synthesized DNA library containing a central N26 randomized fragment was sieved through four cycles of adsorption to AuNPs in a tree-like selection-amplification scheme (SELEX (Selective Evolution of Ligands by EXponential enrichment)). The frequencies of occurrence of specific oligomeric DNA motifs, k-mers ( k = 1-6), in the initial and selected pools were calculated. Distribution of secondary structures in the pools was analyzed. A large set of diverse A, T, and G enriched k-mers undergo a pronounced positive selection, and these sequences demonstrate faster and strong binding to the AuNPs. For facile binding, such structural motifs should be located in the loop regions of weak intramolecular complexes-hairpins with imperfect stem, or other portion of the structure, which is unpaired under selection conditions. Our data also show that, under the conditions employed in this study, cytosine is significantly depleted during the selection process, although guanine remains unchanged. These regularities were confirmed in a series of binding experiments with a set of synthetic DNA oligonucleotides. The detailed analysis of DNA binding to AuNPs shows that the sequence specificity of this interaction is low due to its nature, although the presence and the number of specific structural motifs in DNA affect both the rate of formation and the strength of the formed noncovalent associates with AuNPs.


B Part of It study: a longitudinal study to assess carriage of Neisseria meningitidis in first year university students in South Australia.
N. meningitidis carriage in Australia is poorly understood. This study aimed to estimate prevalence and risk factors for carriage of N. meningitidis in South Australian university students. We also sought to identify whether delayed freezing of oropharyngeal samples altered PCR positivity, cycle threshold, or culture positivity. Oropharyngeal swabs were taken from first year university students and repeated after 3 months, with risk factor questionnaires completed at both visits. Specimens were subjected to real-time PCR screening for the presence of specific meningococcal DNA. The study enrolled 421 individuals, 259 returned at 3 months. At baseline, 56% of participants were female and 1.9% smokers. Carriage of N. meningitidis at baseline was 6.2% (95% CI, [4.2%, 8.9%]). Visiting a bar more than once a week (OR 9.07; [2.44, 33.72]) and intimate kissing (OR 4.37; [1.45, 13.14]) were associated with increased carriage. After imputing missing data, the point estimate for carriage at 3 months was 8.6% compared to 6.2% at baseline (OR 1.42; 0.91 to 2.20). Recovery of N. meningitidis on selective agar was significantly reduced in cryovials frozen at 48 hours compared to 6 hours (24/26, 92.3% vs. 14/26, 53.9%, p = 0.002). Attending bars and engaging in intimate kissing is associated with oropharyngeal carriage in South Australian university students. Adolescent meningococcal vaccine programs should be implemented at school, prior to increased attendance at bars, intimate contact, and carriage acquisition. Delaying freezing of oropharyngeal specimens longer than 16 hours reduces yield of N. meningitidis by culture but not PCR detection.


Drosophila Courtship: Love Is Not Blind.
Animals rely on sensory cues to help them find suitable mates. Visual cues are particularly useful for locating mates during the day. A new study has revealed key visual neurons in male Drosophila used to identify and pursue potential mates.


Anal use of the female condom: does uncertainty justify provider inaction?
Despite limited safety data and the absence of efficacy data, several studies have reported that the female condom is being used for anal sex by men who have sex with men. We describe providers' awareness of female condom use during anal sex among their clients and their experiences in counseling clients. We conducted semi-structured interviews with 78 health-care providers recruited from various health-care delivery systems in New York City: a family planning agency, a sexually transmitted infection agency, a hospital-based obstetrics and gynecology clinic, and two community-based AIDS service organizations. While two-thirds of providers reported that they were uncertain as to whether the female condom could or should be used for anal intercourse, nearly one-third believed that anything is better than nothing to prevent HIV/sexually transmitted infections during anal sex. Few providers had actually talked with clients about anal use of the female condom, and clients themselves had seldom mentioned nor asked for information about such use. Our findings highlight providers' uncertainty about anal use of the female condom. Lacking guidelines regarding the safety and efficacy of female condom use during anal sex, health-care providers are left to make their own well-intentioned recommendations (or not) to potential users. The dearth of information on female condom use during anal sex could encourage individuals to use the female condom for anal sex, which may increase HIV transmission risk or represent a missed opportunity for protecting non-condom users. There is a need for a series of harm-reduction, acceptability, and efficacy studies and, in the interim, for the development of a carefully qualified safety set of guidelines regarding anal use of the female condom for health-care providers.


Interventions for replacing missing teeth: bone augmentation techniques for dental implant treatment.
Dental implants require sufficient bone to be adequately stabilised. For some patients implant treatment would not be an option without bone augmentation. A variety of materials and surgical techniques are available for bone augmentation. General objectives: To test the null hypothesis of no difference in the success, function, morbidity and patient satisfaction between different bone augmentation techniques for dental implant treatment. (A) to test whether and when augmentation procedures are necessary; (B) to test which is the most effective augmentation technique for specific clinical indications. Trials were divided into three broad categories according to different indications for the bone augmentation techniques: (1) major vertical or horizontal bone augmentation or both; (2) implants placed in extraction sockets; (3) fenestrated implants. The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE were searched. Several dental journals were handsearched. The bibliographies of review articles were checked, and personal references were searched. More than 55 implant manufacturing companies were also contacted. Last electronic search was conducted on 9th January 2008. Randomised controlled trials (RCTs) of different techniques and materials for augmenting bone for implant treatment reporting the outcome of implant therapy at least to abutment connection. Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted independently and in duplicate. Authors were contacted for any missing information. Results were expressed as random-effects models using mean differences for continuous outcomes and odd ratios for dichotomous outcomes with 95% confidence intervals. The statistical unit of the analysis was the patient. Seventeen RCTs out of 40 potentially eligible trials reporting the outcome of 455 patients were suitable for inclusion. Since different techniques were evaluated in different trials, no meta-analysis could be performed. Ten trials evaluated different techniques for vertical or horizontal bone augmentation or both. Four trials evaluated different techniques of bone grafting for implants placed in extraction sockets and three trials evaluated different techniques to treat bone dehiscence or fenestrations around implants. Major bone grafting procedures of resorbed mandibles may not be justified. Bone substitutes (Bio-Oss or Cerasorb) may replace autogenous bone for sinus lift procedures of atrophic maxillary sinuses. Various techniques can augment bone horizontally and vertically, but it is unclear which is the most efficient. It is unclear whether augmentation procedures at immediate single implants placed in fresh extraction sockets are needed, and which is the most effective augmentation procedure, however, sites treated with barrier plus Bio-Oss showed a higher position of the gingival margin when compared to sites treated with barriers alone. Non-resorbable barriers at fenestrated implants regenerated more bone than no barriers, however it remains unclear whether such bone is of benefit to the patient. It is unclear which is the most effective technique for augmenting bone around fenestrated implants. Bone morphogenetic proteins may enhance bone formation around implants grafted with Bio-Oss. Titanium may be preferable to resorbable screws to fixate onlay bone grafts. The use of particulate autogenous bone from intraoral locations, also taken with dedicated aspirators, might be associated with an increased risk of infective complications. These findings are based on few trials including few patients, sometimes having short follow up, and often being judged to be at high risk of bias.


The effect of chain membership on hospital costs.
To compare the cost structures of hospitals in multihospital systems and independently owned hospitals. The American Hospital Association's Annual Survey from 1990 for data on hospital costs and attributes. Area characteristics came from the Area Resource File, and the Medicare case-mix index came from the Health Care Financing Administration. Data on wages are from the Bureau of the Census' State and Metropolitan Area Data Book. The Guide to Hospital Performance from HCIA, Inc. provided data on quality of care. Separate cost functions were estimated for chain and independent hospitals. Hybrid translog cost functions included measures of outputs, input prices, and hospital and area characteristics. The estimation method accounted for the simultaneous determination of costs and chain membership, and for any nonrandom selection of hospitals into chains. Several economic cost measures were calculated to compare the cost structures of the two types of hospitals. Data from all sources were merged at the hospital level to form the study sample. Hospitals in multihospital systems were less costly than independently owned hospitals. Among independent hospitals, for-profits had the highest costs. There were no statistically significant differences in costs by ownership among chain members. Economies of scale were enjoyed in both types of hospitals only at high volumes of output, while economies of scope occurred at all volumes for chain hospitals, but only at low and medium volumes for independent hospitals. This study provides support for the idea that growth of the multihospital system sector can provide a market solution to the problem of constraining costs. It does not, however, support the property rights theory that proprietary hospitals are more efficient than nonprofit hospitals.


Who seeks primary care for musculoskeletal disorders (MSDs) with physicians prescribing homeopathic and other complementary medicine? Results from the EPI3-LASER survey in France.
There is a paucity of information describing patients with musculoskeletal disorders (MSDs) using complementary and alternative medicines (CAMs) and almost none distinguishing homeopathy from other CAMs. The objective of this study was to describe and compare patients with MSDs who consulted primary care physicians, either certified homeopaths (Ho) or regular prescribers of CAMs in a mixed practice (Mx), to those consulting physicians who strictly practice conventional medicine (CM), with regard to the severity of their MSD expressed as chronicity, co-morbidity and quality of life (QOL). The EPI3-LASER study was a nationwide observational survey of a representative sample of general practitioners and their patients in France. The sampling strategy ensured a sufficient number of GPs in each of the three groups to allow comparison of their patients. Patients completed a questionnaire on socio-demographics, lifestyle and QOL using the Short Form 12 (SF-12) questionnaire. Chronicity of MSDs was defined as more than twelve weeks duration of the current episode. Diagnoses and co-morbidities were recorded by the physician. A total of 825 GPs included 1,692 MSD patients (predominantly back pain and osteoarthritis) were included, 21.6% in the CM group, 32.4% Ho and 45.9% Mx. Patients in the Ho group had more often a chronic MSD (62.1%) than the CM (48.6%) or Mx (50.3%) groups, a result that was statistically significant after controlling for patients' characteristics (Odds ratio = 1.43; 95% confidence interval (CI): 1.07 - 1.89). Patients seen by homeopaths or mixed practice physicians who were not the regular treating physician, had more often a chronic MSD than those seen in conventional medicine (Odds ratios were 1.75; 95% CI: 1.22 - 2.50 and 1.48; 95% CI: 1.06 - 2.12, respectively). Otherwise patients in the three groups did not differ for co-morbidities and QOL. MSD patients consulting primary care physicians who prescribed homeopathy and CAMs differed from those seen in conventional medicine. Chronic MSD patients represented a greater proportion of the clientele in physicians offering alternatives to conventional medicine. In addition, these physicians treated chronic patients as consulting rather than regular treating physicians, with potentially important impacts upon professional health care practices and organisation.


Task switching and novelty processing activate a common neural network for cognitive control.
The abrupt onset of a novel event captures attention away from, and disrupts, ongoing task performance. Less obvious is that intentional task switching compares with novelty-induced behavioral distraction. Here we explore the hypothesis that intentional task switching and attentional capture by a novel distracter both activate a common neural network involved in processing contextual novelty [Barcelo, F., Periáñez, J. A., & Knight, R. T. Think differently: A brain orienting response to task novelty. NeuroReport, 13, 1887-1892, 2002.]. Event-related potentials were recorded in two task-cueing paradigms while 16 subjects sorted cards following either two (color or shape; two-task condition) or three (color, shape, or number; three-task condition) rules of action. Each card was preceded by a familiar tone cueing the subject either to switch or to repeat the previous rule. Novel sound distracters were interspersed in one of two blocks of trials in each condition. Both novel sounds and task-switch cues impaired responses to the following visual target. Novel sounds elicited novelty P3 potentials with their usual peak latency and frontal-central scalp distribution. Familiar tonal switch cues in the three- and two-task conditions elicited brain potentials with a similar latency and morphology as the novelty P3, but with relatively smaller amplitudes over frontal scalp regions. Covariance and principal component analyses revealed a sustained frontal negative potential that was distorting concurrent novelty P3 activity to the tonal switch cues. When this frontal negativity was statistically removed, P3 potentials to novel sounds and task-switch cues showed similar scalp topographies. The degree of activation in the novelty P3 network seemed to be a function of the information (entropy) conveyed by the eliciting stimulus for response selection, over and above its relative novelty, probability of occurrence, task relevance, or feedback value. We conclude that novelty P3 reflects transient activation in a neural network involved in updating task set information for goal-directed action selection and might thus constitute one key element in a central bottleneck for attentional control.


Effects of the Intake of Sesame Seeds (Sesamum indicum L.) and Derivatives on Oxidative Stress: A Systematic Review.
This study is aimed at assessing the scientific evidence on the effect of the intake of sesame seeds and derivatives on oxidative stress of individuals with systemic hypertension, dyslipidemia, and type 2 diabetes mellitus. A systematic review was conducted in seven databases (Lilacs, PubMed, ISI Web of Knowledge, Cochrane Library, Scopus, Trip Database, and Scielo) from September 2013 to January 2014. Clinical trials on the intake of sesame seeds and derivatives assessing the outcomes related to oxidative stress were retrieved. The risk of bias in the results of the studies selected was assessed according to the criteria of the Cochrane Handbook for Systematic Reviews of Interventions. This review included seven clinical trials showing that the intake of sesame resulted in the increase in enzymatic and nonenzymatic antioxidants, as well as in a reduction in oxidative stress markers. This was mainly observed with the use of sesame oil for hypertensive individuals during 2 months and black sesame meal capsules for prehypertensive individuals during four weeks. Most studies involved a small number of participants, sample size being considered a limiting factor for this review. In addition, a significant heterogeneity was observed in the type of population studied and the type of sesame and derivatives used, as well as their amount. The follow-up time was considered a limiting factor, because it varied in the different studies. The high risk of randomization and blinding biases found in the studies assessed determines lower scientific evidence of the results. Despite the limitations and biases identified in this systematic review, sesame showed relevant effects on oxidative stress, suggesting it could increase the antioxidant capacity.


Nuclear localization signal(s) required for nuclear targeting of the maize regulatory protein Opaque-2.
The maize regulatory protein Opaque-2 (O2) localizes to the nucleus in both maize and tobacco cells. Here we show that in-frame carboxy- and amino-terminal fusions of O2 to reporter protein beta-glucuronidase (GUS) were sufficient to direct GUS to the nucleus in transgenic tobacco plants and in transiently transformed onion cells. Two independent regions of O2 containing 135 and 149 amino acids were identified that were able to redirect GUS to the nucleus in both systems. A quantitative biochemical analysis of GUS in nuclei isolated from transgenic tobacco plants revealed that the second region was more efficient than the first one. The precise location of nuclear localization signals (NLSs) was determined using an onion transformation system. The first NLS was located between residues 101 and 135 and had the structure of a simian virus 40 NLS. The second NLS was located in the basic, DNA binding domain (between residues 223 and 254) and had a bipartite structure. The presence of one of the O2 NLSs in the basic domain is in complete agreement with similar findings of NLSs in the basic domain of three other basic/leucine zipper proteins, suggesting that this domain may be bifunctional. The effect of amino- versus carboxy-terminal GUS fusions is discussed.


Contraception use and pregnancy among 15-24 year old South African women: a nationally representative cross-sectional survey.
Adolescent reproductive health has not continued to receive the attention it deserves since the start of the HIV epidemic. In South Africa, high numbers of adolescent women report pregnancies that are unwanted and yet few have accessed available termination of pregnancy services. Enabling contraception use is vital for meeting the goals of HIV prevention. A nationally representative survey of South African 15-24 year olds was undertaken. Participants completed a questionnaire on sexual behaviour and provided an oral fluid sample for HIV testing. Analysis of the data was restricted to women (n = 6217), particularly those who reported being sexual active in the last 12 months (n = 3618) and was conducted using svy methods in the program STATA 8.0 to take account of sampling methods. Univariate and multivariate analyses were conducted to explore factors associated with contraceptive use. Two thirds of all women reported having ever been sexually active and among these 87% were sexually active in the past 12 months. Among women who reported currently being sexually active, 52.2% reported using contraceptives. There was evidence of association between contraceptive use and being employed or a student (vs unemployed); fewer sex partners; type of last sex partner; having talked to last partner about condom use and having ever been pregnant. Specific emphasis must be placed on encouraging young women to use contraceptive methods that offer protection against pregnancy and STIs/HIV. Our consistent finding of a relationship between discussing condom use with partners and condom use indicates the importance of involvement of male partners in women's contraceptive decisions.


Ejaculation frequency and subsequent risk of prostate cancer.
Sexual activity has been hypothesized to play a role in the development of prostate cancer, but epidemiological data are virtually limited to case-control studies, which may be prone to bias because recall among individuals with prostate cancer could be distorted as a consequence of prostate malignancy or ongoing therapy. To examine the association between ejaculation frequency, which includes sexual intercourse, nocturnal emission, and masturbation and risk of prostate cancer. Prospective study using follow-up data from the Health Professionals Follow-up Study (February 1, 1992, through January 31, 2000) of 29 342 US men aged 46 to 81 years, who provided information on history of ejaculation frequency on a self-administered questionnaire in 1992 and responded to follow-up questionnaires every 2 years to 2000. Ejaculation frequency was assessed by asking participants to report the average number of ejaculations they had per month during the ages of 20 to 29 years, 40 to 49 years, and during the past year (1991). Incidence of total prostate cancer. During 222 426 person-years of follow-up, there were 1449 new cases of total prostate cancer, 953 organ-confined cases, and 147 advanced cases of prostate cancer. Most categories of ejaculation frequency were unrelated to risk of prostate cancer. However, high ejaculation frequency was related to decreased risk of total prostate cancer. The multivariate relative risks for men reporting 21 or more ejaculations per month compared with men reporting 4 to 7 ejaculations per month at ages 20 to 29 years were 0.89 (95% confidence interval [CI], 0.73-1.10); ages 40 to 49 years, 0.68 (95% CI, 0.53-0.86); previous year, 0.49 (95% CI, 0.27-0.88); and averaged across a lifetime, 0.67 (95% CI, 0.51-0.89). Similar associations were observed for organ-confined prostate cancer. Ejaculation frequency was not statistically significantly associated with risk of advanced prostate cancer. Our results suggest that ejaculation frequency is not related to increased risk of prostate cancer.


Broadband optical switch based on liquid crystal dynamic scattering.
This work demonstrates a novel broadband optical switch, based on dynamic-scattering effect in liquid crystals (LCs). Dynamic-scattering-mode technology was developed for display applications over four decades ago, but was displaced in favor of the twisted-nematic LCs. However, with the recent development of more stable LCs, dynamic scattering provides advantages over other technologies for optical switching. We demonstrate broadband polarization-insensitive attenuation of light directly passing thought the cell by 4 to 5 orders of magnitude at 633 nm. The attenuation is accomplished by light scattering to higher angles. Switching times of 150 μs to 10% transmission have been demonstrated. No degradation of devices is found after hundreds of switching cycles. The light-rejection mechanism is due to scattering, induced by disruption of LC director orientation with dopant ion motion with an applied electric field. Angular dependence of scattering is characterized as a function of bias voltage.


Profile of women seeking medical termination of pregnancy in South India.
To investigate the demographic and obstetric profile of women seeking medical termination of pregnancy (MTP) in South India in accordance with the MTP Act of India. A registry-based retrospective study was carried out at a tertiary care teaching hospital in South India. The hospital records of all pregnant women seeking MTP over a 2-year period between January 2011 and December 2012 were reviewed. A total of 244 women underwent MTP during the study period. More than one-third (37.8%) were aged between 26 and 30 years. The majority of women underwent MTP during the first trimester (79.5%). Medical reasons were cited as the most common reason for undergoing MTP (39.3%), followed by unplanned pregnancy (34.8%). The majority of women were seeking MTP for the first time (84.8%). More than half of the women (52.9%) opted for post-MTP contraception. MTP for unplanned pregnancy can be prevented if people are well informed about methods of contraception. MTP is an opportunity for healthcare professionals to discuss fertility needs and need for contraception with women seeking MTP so that appropriate decisions can be taken for suitable family planning.


Complete Genome Sequence and Comparative Genomics of a Novel Myxobacterium Myxococcus hansupus.
Myxobacteria, a group of Gram-negative aerobes, belong to the class δ-proteobacteria and order Myxococcales. Unlike anaerobic δ-proteobacteria, they exhibit several unusual physiogenomic properties like gliding motility, desiccation-resistant myxospores and large genomes with high coding density. Here we report a 9.5 Mbp complete genome of Myxococcus hansupus that encodes 7,753 proteins. Phylogenomic and genome-genome distance based analysis suggest that Myxococcus hansupus is a novel member of the genus Myxococcus. Comparative genome analysis with other members of the genus Myxococcus was performed to explore their genome diversity. The variation in number of unique proteins observed across different species is suggestive of diversity at the genus level while the overrepresentation of several Pfam families indicates the extent and mode of genome expansion as compared to non-Myxococcales δ-proteobacteria.


The elephant in the room: quality control of endometriosis data.
With the steadily increasing volume of endometriosis articles, and titles and abstracts readily available online, there is a growing risk that references are cited without the full articles having been read by the author(s) or by referees. Too often the titles and statements in abstracts are not supported by data in the published articles. Therefore, the peer-review process should direct extra attention to titles and abstracts to ensure that they are supported by data in the manuscript. Moreover, it is suggested that authors explicitly indicate which references have been read in full. To support the secondary peer-review process, we urge open-access journals to welcome letters to the editor and publish them instead of quietly "burying" them on the Internet.


Long-term prognostic effect of coronary atherosclerotic burden: validation of the computed tomography-Leaman score.
Computed tomography-adapted Leaman score (CT-LeSc) was developed to quantify coronary CT angiography information about atherosclerotic burden (lesion localization, stenosis degree, and plaque composition). The objective of the study is to evaluate CT-LeSc long-term prognostic value in patients with suspected coronary artery disease (CAD). Single-center prospective registry including 1304 consecutive patients undergoing coronary CT angiography for suspected CAD. High CT-LeSc was defined by upper tertile (score, >5) cutoff. Segment involvement score and segment stenosis score were also evaluated. Hard cardiac events (cardiac death and nonfatal acute coronary syndromes) were considered for analysis. Different Cox regression models were used to identify independent event predictors. Kaplan-Meier event-free survival was evaluated in 4 patient subgroups stratified by obstructive (≥50% stenosis) versus nonobstructive CAD and a high (>5) versus a low (≤5) CT-LeSc. Of 1196 patients included in the final analysis (mean follow-up of 52±22 months), 125 patients experienced 136 hard events (18 cardiac deaths and 118 nonfatal myocardial infarction). All atherosclerotic burden scores were independent predictors of cardiac events (hazard ratios of 3.09 for segment involvement score, 4.42 for segment stenosis score, and 5.39 for CT-LeSc). Cumulative event-free survival was 76.8% with a high CT-LeSc and 96.0% with a low CT-LeSc. Event-free survival in nonobstructive CAD with high CT-LeSc (78.6%) was similar to obstructive CAD with high CT-LeSc (76.5%) but lower than obstructive CAD with low CT-LeSc (80.7%). CT-LeSc is an independent long-term predictor of hard cardiac events. Patients with nonobstructive CAD and high CT-LeSc had hard event-free survival similar to patients with obstructive CAD.


Mice overexpressing progastrin are predisposed for developing aberrant colonic crypt foci in response to AOM.
Recent studies show that nonamidated gastrins (Gly-gastrin and progastrin) stimulate colonic proliferation. However, the role of nonamidated vs. amidated gastrins in colon carcinogenesis has not been defined. We measured intermediate markers of carcinogenesis in transgenic mice overexpressing either progastrin (hGAS) or amidated gastrin (INS-GAS) in response to azoxymethane (AOM). The hGAS mice showed significantly higher numbers of aberrant crypt foci (140-200% increase) compared with that in wild-type (WT) and INS-GAS mice (P < 0.05) after AOM treatment. The bromodeoxyuridine-labeling index of colonic crypts also was significantly elevated in hGAS mice vs. that in WT and INS-GAS mice. The results therefore provide evidence for a mitogenic and cocarcinogenic role of nonamidated gastrins (progastrin), which is apparently not shared by the amidated gastrins. Although nonamidated gastrins are now believed to mediate mitogenic effects via novel receptors, amidated gastrins mediate biological effects via different receptor subtypes, which may explain the difference in the cocarcinogenic potential of nonamidated vs. amidated gastrins. In conclusion, our results provide strong support for a cocarcinogenic role for nonamidated gastrins in colon carcinogenesis.


Evaluation of the optimal plate position for the fixation of supraglenoid tubercle fractures in warmbloods.
To determine scapular cortex thickness, distal scapular bone density and describe the exact suprascapular nerve course to evaluate the best plate position for the fixation of supraglenoid tubercle fractures in horses. Twelve equine cadaveric shoulders were examined with computed tomography. Computed tomography morphometry and density measurements (Hounsfield units [HU]) of the scapula were recorded. Statistical comparisons were made between the cranial and caudal aspects of the scapula. Dissection of each shoulder was performed and the suprascapular nerve course was described morphometrically and morphologically. The suprascapular nerve was found on the periosteum and embedded in connective tissue at the cranial aspect of the scapula. It ramified proximally and distally into the supraspinatus muscle, coursed caudolaterally at a median of 2 cm (1-2 cm) distal to the scapular spine and ramified proximally and distally into the infraspinatus muscle. The scapular cortex measurements (HU) cranially were significantly larger than caudally at most levels of the scapula. The bone density of the distal scapula cranially (651.3 ± 104.2) was significantly lower than caudally (745.7 ± 179.1). For surgical access to the supraglenoid tubercle, knowledge of the anatomy is important. It is easiest to avoid the suprascapular nerve at the most cranial aspect of the scapula, where it has not yet ramified. For a stable fixation, knowledge of the characteristics of the equine scapula, such as scapular cortex thickness, is important.


Social judgments of behavioral versus substance-related addictions: a population-based study.
Recently, the concept of addiction has expanded to include many types of problematic repetitive behaviors beyond those related to substance misuse. This trend may have implications for the way that lay people think about addictions and about people struggling with addictive disorders. The aim of this study was to provide a better understanding of how the public understands a variety of substance-related and behavioral addictions. A representative sample of 4000 individuals from Alberta, Canada completed an online survey. Participants were randomly assigned to answer questions about perceived addiction liability, etiology, and prevalence of problems with four substances (alcohol, tobacco, marijuana, and cocaine) and six behaviors (problematic gambling, eating, shopping, sexual behavior, video gaming, and work). Bivariate analyses revealed that respondents considered substances to have greater addiction liability than behaviors and that most risk factors (moral, biological, or psychosocial) were considered as more important in the etiology of behavioral versus substance addictions. A discriminant function analysis demonstrated that perceived addiction liability and character flaws were the two most important features differentiating judgments of substance-related versus behavioral addictions. Perceived addiction liability was judged to be greater for substances. Conversely, character flaws were viewed as more associated with behavioral addictions. The general public appreciates the complex bio-psycho-social etiology underlying addictions, but perceives substance-related and behavioral addictions differently. These attitudes, in turn, may shape a variety of important outcomes, including the extent to which people believed to manifest behavioral addictions feel stigmatized, seek treatment, or initiate behavior changes on their own.


Effects of linear versus sigmoid coding of visual or audio biofeedback for the control of upright stance.
Although both visual and audio biofeedback (BF) systems for postural control can reduce sway during stance, a direct comparison between the two systems has never been done. Further, comparing different coding designs of audio and visual BF may help in elucidating how BF information is integrated in the control of posture, and may improve knowledge for the design of innovative BF systems for postural control. The purpose of this paper is to compare the effects of linear versus sigmoid coding of trunk acceleration for audio and visual BF on postural sway in a group of eight, healthy subjects while standing on a foam surface. Results showed that sigmoid-coded audio BF reduced sway acceleration more than did a linear-coded audio BF, whereas a linear-coded visual BF reduced sway acceleration more than a sigmoid-coded visual BF. In addition, audio BF had larger effects on reducing center of pressure (COP) displacement whereas visual BF had larger effects on reducing trunk sway. These results suggest that audio and visual BF for postural control benefit from different types of sensory coding and each type of BF may encourage a different type of postural sway strategy.


Birth after a previous cesarean section - what is most important in making a decision?
A retrospective analysis of the course of labour in patients after one caesarean section (CS) and of factors influencing successful attempt of vaginal birth after caesarean (VBAC). A group of 296 patients after one CS was divided into: group G1 (206 patients) - elective CS, group G2 (90) - VBAC attempt, and G2 to: G2a (35) - VBAC and G2b (55) - CS after an unsuccessful VB attempt. A comparative analysis between the groups and logistic regression analysis of factors influencing a successful VBAC was made. There were no differences regarding age, BMI, weight gain during pregnancy or gestational age between groups G1 and G2, as well as G2a and G2b. G2a patients had more often already given VB previously (28.6% vs 10.9%; p=0.03). The most frequent indication for a repeat elective CS was the lack of informed consent for VBAC (29.13% of all indications). The mean neonatal birthweight was highest in G1 (3 410 g), and in G2b higher than in G2a (3 275 g vs 3 098 g; p=0.009). There were no differences in newborns' general condition between the group. There were no cases of uterine rupture and 4 cases of uterine scar dehiscence in G1 and 1 in G2. Of all the analysed factors only spontaneous delivery onset (OR 7.78) and previous vaginal birth after the caesarean (OR 1.99) or before the caesarean (OR 2.03) had significant influence on successful VBAC trial. The right classification of patients is a significant factor having effect on the success of a VB attempt after CS.


Enhancement of Meditation Analgesia by Opioid Antagonist in Experienced Meditators.
Studies have consistently shown that long-term meditation practice is associated with reduced pain, but the neural mechanisms by which long-term meditation practice reduces pain remain unclear. This study tested endogenous opioid involvement in meditation analgesia associated with long-term meditation practice. Electrical pain was induced with randomized, double-blind, cross-over administration of the opioid antagonist naloxone (0.15-mg/kg bolus dose, then 0.2-mg/kg per hour infusion dose) with 32 healthy, experienced meditation practitioners and a standardized open monitoring meditation. Under saline, pain ratings were significantly lower during meditation (pain intensity: 6.41 ± 1.32; pain unpleasantness: 3.98 ± 2.17) than at baseline (pain intensity: 6.86 ±1.04, t(31) = 2.476, p = .019, Cohen's d = 0.46; pain unpleasantness: 4.96 ±1.75, t(31) = 3.746, p = .001, Cohen's d = 0.68), confirming the presence of meditation analgesia. Comparing saline and naloxone revealed significantly lower pain intensity (t(31) = 3.12, p = .004, d = 0.56), and pain unpleasantness (t(31) = 3.47, p = .002, d = 0.62), during meditation under naloxone (pain intensity: 5.53 ± 1.54; pain unpleasantness: 2.95 ± 1.88) than under saline (pain intensity: 6.41 ± 1.32; pain unpleasantness: 3.98 ± 2.17). Naloxone not only failed to eliminate meditation analgesia but also made meditation analgesia stronger. Long-term meditation practice does not rely on endogenous opioids to reduce pain. Naloxone's blockade of opioid receptors enhanced meditation analgesia; pain ratings during meditation were significantly lower under naloxone than under saline. Possible biological mechanisms by which naloxone-induced opioid receptor blockade enhances meditation analgesia are discussed.