Intracystic papillary carcinomas of the breast: a reevaluation using a panel of myoepithelial cell markers.
Intracystic papillary carcinomas (IPC) of the breast have traditionally been considered to be variants of ductal carcinoma in situ (DCIS). However, it is not clear if all lesions categorized histologically as IPC are truly in situ carcinomas, or if some such lesions might represent circumscribed or encapsulated nodules of invasive papillary carcinoma. Given that the demonstration of a myoepithelial cell (MEC) layer around nests of carcinoma cells is a useful means to distinguish in situ from invasive carcinomas of the breast in problematic cases, assessment of the presence or absence of a MEC layer at the periphery of the nodules that comprise these lesions could help resolve this issue. We studied the presence and distribution of MEC at the periphery of the nodules of 22 IPC and, for comparison, 15 benign intraductal papillomas using immunostaining for 5 highly sensitive markers that recognize various MEC components: smooth muscle myosin heavy chain, calponin, p63, CD10, and cytokeratin 5/6. All 22 lesions categorized as IPC showed complete absence of MEC at the periphery of the nodules with all 5 markers. In contrast, a MEC layer was detected around foci of conventional DCIS present adjacent to the nodules of IPC. Furthermore, all benign intraductal papillomas, including those of sizes comparable to those of IPC, showed a MEC layer around virtually the entire periphery of the lesion with all 5 MEC markers. In conclusion we could not detect a MEC layer at the periphery of the nodules of any of 22 lesions categorized histologically as IPC. One possible explanation for this observation is that these are in situ lesions in which the delimiting MEC layer has become markedly attenuated or altered with regard to expression of these antigens, perhaps due to their compression by the expansile growth of these lesions within a cystically dilated duct. Alternatively, it may be that at least some lesions that have been categorized as IPC using conventional histologic criteria actually represent circumscribed, encapsulated nodules of invasive papillary carcinoma. Regardless of whether these lesions are in situ or invasive carcinomas, available outcome data indicate that they seem to have an excellent prognosis with adequate local therapy alone. Therefore, we believe it is most prudent to continue to manage patients with these lesions as they are currently managed (ie, similar to patients with DCIS) and to avoid categorization of such lesions as frankly invasive papillary carcinomas. Given our observations, we favor the term "encapsulated papillary carcinoma" over "intracystic papillary carcinoma" for circumscribed nodules of papillary carcinoma surrounded by a fibrous capsule in which a peripheral layer of MEC is not identifiable.


Callous-Unemotional Traits Among Adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD): Associations with Parenting.
This study examined the extent to which positive and negative parenting relates to conduct problems (CP) and callous-unemotional (CU) traits among 172 adolescents (72 % males; Mage = 16.91 years, SD = .67) with attention-deficit/hyperactivity disorder and whether CU traits moderate the link between parenting and CP. Mothers reported on their adolescents' CP, CU traits, and their own parenting practices. Maternal behaviors were observed during a problem-solving communication task. Parents who engaged in more positive parenting (self-reported and observed) reported their adolescents as having lower levels of CU traits. No effect was found for negative parenting. Moderation analyses indicated that lower levels of positive maternal behavior was only associated with higher CP in the presence of higher levels of CU traits. Negative parenting was positively related to CP regardless of CU traits. Positive parenting, irrespective of measurement approach, uniquely relates to adolescents' CU traits while both positive and negative parenting relate to CP.


Investigating the electronic structure of a supported metal nanoparticle: Pd in SiCN.
We investigate the electronic structure of a Palladium nanoparticle that is partially embedded in a matrix of silicon carbonitride. From classical molecular dynamics simulations we first obtain a representative atomic structure. This geometry then serves as input to density-functional theory calculations that allow us to access the electronic structure of the combined system of particle and matrix. In order to make the computations feasible, we devise a subsystem strategy for calculating the relevant electronic properties. We analyze the Kohn-Sham density of states and pay particular attention to d-states which are prone to be affected by electronic self-interaction. We find that the density of states close to the Fermi level is dominated by states that originate from the Palladium nanoparticle. The matrix has little direct effect on the electronic structure of the metal. Our results contribute to explaining why silicon carbonitride does not have detrimental effects on the catalytic properties of palladium particles and can serve positively as a stabilizing mechanical support.


Human Papillomavirus Prevalence in Oral and Oropharyngeal Rinse and Gargle Specimens of Dental Patients and of an HIV-Positive Cohort from Pretoria, South Africa.
Studies on HPV prevalence in the head and neck region of South Africans are sparse. Of the available reports in the literature, there were no studies on the association between HPV-DNA presence in the mouth and oropharynx in relation to high-risk behaviours such as oral sex practice or tobacco and alcohol use. Following ethical clearance and informed consent, patients attending a regional HIV-management clinic and patients attending a dental hospital were recruited to this study. The participants completed an interview-based questionnaire obtaining demographic information, data on HIV serostatus, and behavioural data including sexual practices and tobacco and alcohol use, and a rinse-and-gargle specimen was taken. Specimens were analysed for HPV DNA on 3 separate PCR/qPCR platforms. Statistical analyses were performed for associations between the study group and categorical variables, HPV status, and data from the questionnaires. Of 221 participants, 149 were from a general population and 72 from the HIV-management clinic. Smokers comprised 29.4% of the sample, and 45.2% of participants reported to have ever used alcohol. Open mouth kissing during teenage years was confirmed by 64.7% of participants, 40.3% have given oral sex with their mouth, and 44.8% confirmed to have received oral sex from their partner's mouth. Seven participants (3.2%) had detectable α-HPV DNA, and 1 (0.4%) had detectable β-HPV DNA in their rinse-and-gargle specimens. Two participants were from the HIV-management clinic and 6 from the general dental population (overall 3.6%). Five high-risk HPV, 2 low-risk HPV, and one β-HPV types were detected. The low prevalence of 3.6% compares well to similar studies in different cohorts studied in South Africa and falls within the global oral/oropharyngeal prevalence spectrum. Only 4 participants, all from the HIV-management clinic, had palatine tonsils. No significant relationships were found between HPV presence and demographic data or sexual, oral sexual, tobacco use, or alcohol use, and no associations were seen with numbers of sexual and oral-sex partners.


Effects of exogenous melatonin on sleep: a meta-analysis.
Exogenous melatonin reportedly induces drowsiness and sleep, and may ameliorate sleep disturbances, including the nocturnal awakenings associated with old age. However, existing studies on the soporific efficacy of melatonin have been highly heterogeneous in regard to inclusion and exclusion criteria, measures to evaluate insomnia, doses of the medication, and routes of administration. We reviewed and analyzed (by meta-analysis) available information on effects of exogenous melatonin on sleep. A MEDLINE search (1980 to December 2003) provided English-language articles, supplemented by personal files maintained by the authors. The analysis used information derived from 17 different studies (involving 284 subjects) that satisfied inclusion criteria. Sleep onset latency, total sleep duration, and sleep efficiency were selected as the outcome measures. The study effect size was taken to be the difference between the response on placebo and the mean response on melatonin for each outcome measured. Melatonin treatment significantly reduced sleep onset latency by 4.0 min (95% CI 2.5, 5.4); increased sleep efficiency by 2.2% (95% CI 0.2, 4.2), and increased total sleep duration by 12.8 min (95% CI 2.9, 22.8). Since 15 of the 17 studies enrolled healthy subjects or people with no relevant medical condition other than insomnia, the analysis was also done including only these 15 studies. The sleep onset results were changed to 3.9 min (95% CI (2.5, 5.4)); sleep efficiency increased to 3.1% (95% CI (0.7, 5.5)); sleep duration increased to 13.7 min (95% CI (3.1, 24.3)).


Proportional enlargement of movement by using an optically driven multi-link system with an elastic joint.
Diverse movements using optical manipulation have been introduced. These are generally performed in the focal region of the laser beam. To achieve a wider range of movements based on precise motion transformation, an effective method for optical manipulation that overcomes the important obstacles such as small optical trapping forces, friction, and the viscosity of fluids is required. A multi-link system with an elastic joint is introduced that provides precise motion transformation and amplification. By considering the physical properties of the structure and the optical trapping force, an elastic micron-scale joint with the simple shape of a thin plate was designed. As a further example of a multi-link system with an elastic joint, a double 4-link system for motion enlargement was designed and fabricated. By performing experimental evaluations of the fabricated structures, it was confirmed that multi-link systems with an elastic joint were effective tools for precise motion transformation through optical manipulation.


Wide expression of type I Na+-phosphate cotransporter 3 (NPT3/SLC17A2), a membrane potential-driven organic anion transporter.
Membrane potential (Δψ)-driven and Cl(-)-dependent organic anion transport is a primary function of the solute carrier family 17 (SLC17) transporter family. Although the transport substrates and physiological relevance of the major members are well understood, SLC17A2 protein known to be Na(+)-phosphate cotransporter 3 (NPT3) is far less well characterized. In the present study, we investigated the transport properties and expression patterns of mouse SLC17A2 protein (mNPT3). Proteoliposomes containing the purified mNPT3 protein took up radiolabeled p-aminohippuric acid (PAH) in a Δψ- and Cl(-)-dependent manner. The mNPT3-mediated PAH uptake was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDs) and Evans blue, common inhibitors of SLC17 family members. The PAH uptake was also inhibited by various anionic compounds, such as hydrophilic nonsteroidal anti-inflammatory drugs (NSAIDs) and urate. Consistent with these observations, the proteoliposome took up radiolabeled urate in a Δψ- and Cl(-)-dependent manner. Immunohistochemistry with specific antibodies against mNPT3 combined with RT-PCR revealed that mNPT3 is present in various tissues, including the hepatic bile duct, luminal membranes of the renal urinary tubules, maternal side of syncytiotrophoblast in the placenta, apical membrane of follicle cells in the thyroid, bronchiole epithelial cells in the lungs, and astrocytes around blood vessels in the cerebrum. These results suggested that mNPT3 is a polyspecific organic anion transporter that is involved in circulation of urate throughout the body.


Subcortical structure alterations impact language processing in individuals with schizophrenia and those at high genetic risk.
Cortical structural and functional anomalies have been found to associate with language impairments in both schizophrenia patients and genetic high risk individuals for developing schizophrenia. However, subcortical structures that contribute to language processing haven't been well studied in this population, and thus became the main objective of this study. We examined structural MRI data from 20 patients with schizophrenia, 21 individuals at genetic high risk, and 48 controls. Surface shape and volume differences of 6 subcortical structures that are involved in language processing, including nuclei pallidum, putamen, caudate, amygdala, thalamus, and hippocampus from both hemispheres, were compared between groups. Performance scores of language-associated cognitive tests were obtained to identify relationships of subcortical structures to language-related behaviors. Significantly reduced volumes of both the left and right side caudate nuclei, thalami and right side amygdala were shown in patients when compared with controls. Very interestingly, the high risk group demonstrated significantly increased correlations between volumes of left side pallidum nucleus and bilateral thalami and language-related cognitive test scores when compared to controls. This study furthers our understanding of subcortical structural alterations in schizophrenia and high risk individuals, and suggests the contribution of subcortical structures to the language impairments that may serve as an early sign for impending development of schizophrenia.


Mitochondrial ATP production is necessary for activation of the extracellular-signal-regulated kinases during ischaemia/reperfusion in rat myocyte-derived H9c2 cells.
To search for the stimuli involved in activating the mitogen-activated protein kinases (MAPKs) during ischaemia and reperfusion, we simulated the event in a system in vitro conducive to continuous and non-invasive measurements of several major perturbations that occur at the time: O(2) tension, mitochondrial respiration and energy status. Using H9c2 cells (a clonal line derived from rat heart), we found that activation of the extracellular signal-regulated MAPKs (ERKs) on reoxygenation was abolished if the mitochondria were inhibited prior to and during reoxygenation. Re-introduction of O(2) per se is therefore not sufficient to activate the ERKs. Recovery and maintenance of cellular ATP levels by mitochondrial respiration is necessary, although ATP recovery alone is not sufficient. ERK activation by H(2)O(2), but not phorbol esters, was also sensitive to mitochondrial inhibition. Thus, reoxygenation and H(2)O(2)-mediated oxidative stress share a mechanism of ERK activation that is ATP- or mitochondrion-dependent, and this common feature suggests that the reoxygenation response is mediated by reactive oxygen species. A correlation between ERK activity and ATP levels was also found during the anoxic phase of ischaemia, an effect that was not due to substrate limitation for the kinases. Our results reveal the importance of cellular metabolism in ERK activation, and introduce ATP as a novel participant in the mechanisms underlying the ERK cascade.


On the occurrence of cytochrome P450 in viruses.
Genes encoding cytochrome P450 (CYP; P450) enzymes occur widely in the Archaea, Bacteria, and Eukarya, where they play important roles in metabolism of endogenous regulatory molecules and exogenous chemicals. We now report that genes for multiple and unique P450s occur commonly in giant viruses in the Mimiviridae, Pandoraviridae, and other families in the proposed order Megavirales. P450 genes were also identified in a herpesvirus (Ranid herpesvirus 3) and a phage (Mycobacterium phage Adler). The Adler phage P450 was classified as CYP102L1, and the crystal structure of the open form was solved at 2.5 Å. Genes encoding known redox partners for P450s (cytochrome P450 reductase, ferredoxin and ferredoxin reductase, and flavodoxin and flavodoxin reductase) were not found in any viral genome so far described, implying that host redox partners may drive viral P450 activities. Giant virus P450 proteins share no more than 25% identity with the P450 gene products we identified in Acanthamoeba castellanii, an amoeba host for many giant viruses. Thus, the origin of the unique P450 genes in giant viruses remains unknown. If giant virus P450 genes were acquired from a host, we suggest it could have been from an as yet unknown and possibly ancient host. These studies expand the horizon in the evolution and diversity of the enormously important P450 superfamily. Determining the origin and function of P450s in giant viruses may help to discern the origin of the giant viruses themselves.


Factors Associated with Acute and Chronic Hydrocephalus in Nonaneurysmal Subarachnoid Hemorrhage.
Hydrocephalus requiring external ventricular drain (EVD) or shunt placement commonly complicates aneurysmal subarachnoid hemorrhage (SAH), but its frequency is not as well known for nonaneurysmal SAH (NA-SAH). Those with diffuse bleeding may have greater risk of hydrocephalus compared to those with a perimesencephalic pattern. We evaluated the frequency of hydrocephalus in NA-SAH and whether imaging factors could predict the need for EVD and shunting. We collected admission clinical and imaging variables for 105 NA-SAH patients, including bicaudate index (BI), Hijdra sum score (HSS), intraventricular hemorrhage (IVH) score, modified Fisher scale (mFS), and bleeding pattern. Hydrocephalus was categorized as acute (need for EVD) or chronic (shunt). We applied logistic regression to determine whether hydrocephalus risk was independently related to bleeding pattern or mediated through blood volume or ventriculomegaly. Acute hydrocephalus was seen in 26 (25%) patients but was more common with diffuse (15/28, 54%) versus perimesencephalic (10/59, 17%, p < 0.001) bleeding. Patients developing acute hydrocephalus had worse clinical grade and higher BI, HSS, and IVH scores. Adjusting the relationship between hydrocephalus and diffuse bleeding for HSS (but not BI) nullified this association. Nine (35%) patients requiring EVD eventually required shunting for chronic hydrocephalus, which was associated with greater blood burden but not poor clinical grade. Acute hydrocephalus occurs in one-quarter of NA-SAH patients. The greater risk in diffuse bleeding appears to be mediated by greater cisternal blood volume but not by greater ventriculomegaly. Imaging characteristics may aid in anticipatory management of hydrocephalus in NA-SAH.


Altered chromosomal topology drives oncogenic programs in SDH-deficient GISTs.
Epigenetic aberrations are widespread in cancer, yet the underlying mechanisms and causality remain poorly understood1-3. A subset of gastrointestinal stromal tumours (GISTs) lack canonical kinase mutations but instead have succinate dehydrogenase (SDH) deficiency and global DNA hyper-methylation4,5. Here, we associate this hyper-methylation with changes in genome topology that activate oncogenic programs. To investigate epigenetic alterations systematically, we mapped DNA methylation, CTCF insulators, enhancers, and chromosome topology in KIT-mutant, PDGFRA-mutant and SDH-deficient GISTs. Although these respective subtypes shared similar enhancer landscapes, we identified hundreds of putative insulators where DNA methylation replaced CTCF binding in SDH-deficient GISTs. We focused on a disrupted insulator that normally partitions a core GIST super-enhancer from the FGF4 oncogene. Recurrent loss of this insulator alters locus topology in SDH-deficient GISTs, allowing aberrant physical interaction between enhancer and oncogene. CRISPR-mediated excision of the corresponding CTCF motifs in an SDH-intact GIST model disrupted the boundary between enhancer and oncogene, and strongly upregulated FGF4 expression. We also identified a second recurrent insulator loss event near the KIT oncogene, which is also highly expressed across SDH-deficient GISTs. Finally, we established a patient-derived xenograft (PDX) from an SDH-deficient GIST that faithfully maintains the epigenetics of the parental tumour, including hypermethylation and insulator defects. This PDX model is highly sensitive to FGF receptor (FGFR) inhibition, and more so to combined FGFR and KIT inhibition, validating the functional significance of the underlying epigenetic lesions. Our study reveals how epigenetic alterations can drive oncogenic programs in the absence of canonical kinase mutations, with implications for mechanistic targeting of aberrant pathways in cancers.


Vegetarian Diets and Weight Reduction: a Meta-Analysis of Randomized Controlled Trials.
Vegetarian diets may promote weight loss, but evidence remains inconclusive. PubMed, EMBASE and UpToDate databases were searched through September 22, 2014, and investigators extracted data regarding study characteristics and assessed study quality among selected randomized clinical trials. Population size, demographic (i.e., gender and age) and anthropometric (i.e., body mass index) characteristics, types of interventions, follow-up periods, and trial quality (Jadad score) were recorded. The net changes in body weight of subjects were analyzed and pooled after assessing heterogeneity with a random effects model. Subgroup analysis was performed based on type of vegetarian diet, type of energy restriction, study population, and follow-up period. Twelve randomized controlled trials were included, involving a total of 1151 subjects who received the intervention over a median duration of 18 weeks. Overall, individuals assigned to the vegetarian diet groups lost significantly more weight than those assigned to the non-vegetarian diet groups (weighted mean difference, -2.02 kg; 95 % confidence interval [CI]: -2.80 to -1.23). Subgroup analysis detected significant weight reduction in subjects consuming a vegan diet (-2.52 kg; 95 % CI: -3.02 to -1.98) and, to a lesser extent, in those given lacto-ovo-vegetarian diets (-1.48 kg; 95 % CI: -3.43 to 0.47). Studies on subjects consuming vegetarian diets with energy restriction (ER) revealed a significantly greater weight reduction (-2.21 kg; 95 % CI: -3.31 to -1.12) than those without ER (-1.66 kg; 95 % CI: -2.85 to -0.48). The weight loss for subjects with follow-up of <1 year was greater (-2.05 kg; 95 % CI: -2.85 to -1.25) than those with follow-up of ≥1 year (-1.13 kg; 95 % CI: -2.04 to -0.21). Vegetarian diets appeared to have significant benefits on weight reduction compared to non-vegetarian diets. Further long-term trials are needed to investigate the effects of vegetarian diets on body weight control.


RIG-I-like helicases induce immunogenic cell death of pancreatic cancer cells and sensitize tumors toward killing by CD8(+) T cells.
Pancreatic cancer is characterized by a microenvironment suppressing immune responses. RIG-I-like helicases (RLH) are immunoreceptors for viral RNA that induce an antiviral response program via the production of type I interferons (IFN) and apoptosis in susceptible cells. We recently identified RLH as therapeutic targets of pancreatic cancer for counteracting immunosuppressive mechanisms and apoptosis induction. Here, we investigated immunogenic consequences of RLH-induced tumor cell death. Treatment of murine pancreatic cancer cell lines with RLH ligands induced production of type I IFN and proinflammatory cytokines. In addition, tumor cells died via intrinsic apoptosis and displayed features of immunogenic cell death, such as release of HMGB1 and translocation of calreticulin to the outer cell membrane. RLH-activated tumor cells led to activation of dendritic cells (DCs), which was mediated by tumor-derived type I IFN, whereas TLR, RAGE or inflammasome signaling was dispensable. Importantly, CD8α(+) DCs effectively engulfed apoptotic tumor material and cross-presented tumor-associated antigen to naive CD8(+) T cells. In comparison, tumor cell death mediated by oxaliplatin, staurosporine or mechanical disruption failed to induce DC activation and antigen presentation. Tumor cells treated with sublethal doses of RLH ligands upregulated Fas and MHC-I expression and were effectively sensitized towards Fas-mediated apoptosis and cytotoxic T lymphocyte (CTL)-mediated lysis. Vaccination of mice with RLH-activated tumor cells induced protective antitumor immunity in vivo. In addition, MDA5-based immunotherapy led to effective tumor control of established pancreatic tumors. In summary, RLH ligands induce a highly immunogenic form of tumor cell death linking innate and adaptive immunity.


[Interaction of replication protein A and flap endonuclease 1 with DNA duplexes containing a nick or flap].
Nicks and flaps are intermediates in various processes of DNA metabolism, including replication and repair. Photoaffinity modification was employed in studying the interaction of the replication protein A (RPA) and flap endonuclease 1 (FEN-1) with DNA duplexes similar to structures arising during long-patch base excision repair. The proteins were also tested for effect on DNA polymerase beta (Pol beta) interaction with DNA. Using Pol beta, a photoreactive dTTP analog was added to the 3' end of an oligonucleotide flanking a nick or a flap in DNA intermediates. The character and intensity of protein labeling depended on the type of intermediates and on the presence of the phosphate or tetrahydrofuran at the 5' end of a nick or a flap. Photoaffinity labeling of Pol beta substantially (up to three times) increased in the presence of RPA or FEN-1. Various DNA substrates were used to study the effects of RPA and FEN-1 on Pol beta-mediated DNA synthesis with displacement of a downstream primer. In contrast to FEN-1, RPA had no effect on DNA repair synthesis by Pol beta during long-patch base excision repair.


[Ultrasound evaluation of uterine scar after segmental transverse cesarean surgery].
To evaluate the thickness of the lower uterine segment by transvaginal ultrasound in a group of non-pregnant women and to describe the morphologic findings in the scar of those submitted to cesarean section. A retrospective study of 155 transvaginal ultrasound images obtained from premenopausal and non-pregnant women, conducted between January 2008 and November 2011. the subjects were divided into three groups: women who were never pregnant (Control Group I), women with previous vaginal deliveries (Control Group II) and women with previous cesarean section (Observation Group). We excluded women with a retroverted uterus, intrauterine device users, pregnant women and those with less than one year of tsince the last obstetrical event. The data were analyzed statistically with Statistica, version 8.0 software. ANOVA and LSD were used to compare the groups regarding quantitative variables and the Student's t-test was used to compare the thickness of the anterior and posterior isthmus. The Spearman correlation coefficient was calculated to estimate the association between quantitative variables. P values <0.05 were considered statistically significant. There was significant difference between the thickness of the anterior and posterior isthmus only in the group of women with previous cesarean section. Comparing the groups two by two, no significant differences between the thickness of the anterior and posterior isthmus were observed in the Control Groups, but this difference was significant when we compared the Observation Group with each Control Group. In the Observation Group, no correlation was found between the thickness of the isthmus and the number of previous cesarean deliveries or the time elapsed since the last birth. A niche was found in the cesarean scar in 30.6% of the women in the Observation Group, 93% of whom complained of post-menstrual bleeding. The relationship between the thickness of the anterior and posterior wall of the lower uterine segment by transvaginal ultrasound is a suitable method for the evaluation of the uterine lower segment in women with previous cesarean sections.


Patterns and correlates of drug-related ED visits: results from a national survey.
Drug treatment can be effective in community-based settings, but drug users tend to underuse these treatment options and instead seek services in emergency departments (EDs) and other acute care settings. The goals of this study were to describe prevalence and correlates of drug-related ED visits. This study used data from the National Epidemiologic Survey on Alcohol and Related Conditions, which is a nationally representative survey of 43,093 US residents. The overall prevalence of drug-related ED visits among lifetime drug users was 1.8%; for those with a lifetime drug use disorder, 3.7%. Persons with heroin dependence and inhalant dependence had the highest rates of ED visits, and marijuana dependence was associated with the lowest rates. Multivariate analyses revealed that being socially connected (ie, marital status) was a protective factor against ED visits, whereas psychopathology (ie, personality or mood disorders) was a risk factor. Significant variability exists for risk of ED use for different types of drugs. These findings can help inform where links between EDs with local treatment programs can be formed to provide preventive care and injury-prevention interventions to reduce the risk of subsequent ED visits.


Complementary medicines (herbal and nutritional products) in the treatment of Attention Deficit Hyperactivity Disorder (ADHD): a systematic review of the evidence.
Complementary and Alternative Medicines (CAMs) are frequently given to children and adolescents for reputed benefits in the treatment of hyperkinetic and concentration disorders such as Attention Deficit Hyperactivity Disorder (ADHD). In such vulnerable populations high quality evidence is required to support such claims. The aim of the paper is to assess the current evidence of herbal and nutritional interventions for ADHD using a systematic search of clinical trials meeting an acceptable standard of evidence. PubMed, PsycINFO, Cochrane Library and CINAHL were searched up to May 26th, 2011 for randomised, controlled clinical trials using CAM products as interventions to treat ADHD. A quality analysis using a purpose-designed scale, and an estimation of effect sizes (Cohen's d) where data were available, were also calculated. The review revealed that 16 studies met inclusion criteria, with predominant evidentiary support found for zinc, iron, Pinus marinus (French maritime pine bark), and a Chinese herbal formula (Ningdong); and mixed (mainly inconclusive) evidence for omega-3, and l-acetyl carnitine. Current data suggest that Ginkgo biloba (ginkgo), and Hypercium perforatum (St. John's wort) are ineffective in treating ADHD. The research suggests only some CAMs may be beneficial in ADHD, thus clinicians need to be aware of the current evidence. Promising candidates for future research include Bacopa monniera (brahmi) and Piper methysticum (kava), providing potential efficacy in improving attentional and hyperkinetic disorders via a combination of cognitive enhancing and sedative effects.


A Randomized Controlled Trial Comparing Learners' Decision-making, Anxiety, and Task Load During a Simulated Airway Crisis Using Two Difficult Airway Aids.
The American Society of Anesthesiologists (ASA) difficult airway algorithm and the Vortex approach are difficult airway aids. Our objective was to demonstrate that a simpler cognitive model would facilitate improved decision-making during a process such as difficult airway management. We hypothesized the simpler Vortex approach would be associated with less anxiety and task load. Medical students were randomized to the ASA algorithm (n = 33) or Vortex approach (n = 34). All learned basic airway techniques on day 1 of their rotation. Next, they watched a video of their respective aid then managed a simulated airway crisis. We assessed decision-making using a seven-point airway management score and a completeness score. Completeness was at least one attempt at each of four techniques (mask ventilation, supraglottic airway, intubation, and cricothyrotomy). Two validated tools, the State-Trait Anxiety Inventory Form Y and the National Aeronautics and Space Administration Task Load Index, were used to assess anxiety and task load. Students in the Vortex group had higher airway management scores [4.0 (interquartile range = 4.0 to 5.0) vs. 4.0 (3.0 to 4.0), P = 0.0003] and completeness (94.1% vs. 63.6%, P = 0.003). In the ASA group, the means (SD) of National Aeronautics and Space Administration Task Load Index scores of 55 or higher were observed in mental [61.4 (14.4)], temporal [62.3 (22.9)], and effort [57.1 (15.6)] domains. In the Vortex group, only the temporal load domain was 55 or higher [mean (SD) = 57.8 (25.4)]. There was no difference in anxiety. Medical students perform better in a simulated airway crisis after training in the simpler Vortex approach to guide decision-making. Students in the ASA group had task load scores indicative of high cognitive load.


Coevolution of yeast mannan digestion: Convergence of the civilized human diet, distal gut microbiome, and host immunity.
The complex carbohydrates accessible to the distal gut microbiota (DGM) are key drivers in determining the structure of this ecosystem. Typically, plant cell wall polysaccharides and recalcitrant starch (i.e. dietary fiber), in addition to host glycans are considered the primary nutrients for the DGM; however, we recently demonstrated that α-mannans, highly branched polysaccharides that decorate the surface of yeast, are also nutrients for several members of Bacteroides spp. This relationship suggests that the advent of yeast in contemporary food technologies and the colonization of the intestine by endogenous fungi have roles in microbiome structure and function. Here we discuss the process of yeast mannan metabolism, and the intersection between various sources of intestinal fungi and their roles in recognition by the host innate immune system.


Haematological implications of folate food fortification.
Reports from some Western countries indicate that mandatory folate food fortification (FFF) has substantially reduced the prevalence of folate deficiency, leading to calls for folate testing following FFF to be limited to specific indications such as macrocytic anaemia. This is premature for low-income countries, where folate deficiency is predominantly the result of poor intake coupled with the increasing demand in pregnancy. There is also evidence that HIV infection is prejudicial to folate nutrition, and low-income HIV-infected women and their offspring could be among the most susceptible to folate deficiency. In assessing folate nutrition, the value of serum folate has been compromised by FFF, and both serum and red cell folate are necessary for optimal assessment of folate status. Although the limited data available suggest that large-scale masking of vitamin B12 deficiency by FFF has not occurred, it has been suggested that B12 be incorporated into folate-fortified foods. However, significant B12 deficiency is usually due to malabsorption, and physiological doses added to food would be of questionable value because they would not be absorbed. Extensive work, especially randomised clinical trials, must be done before dietary intervention with B12 on a national scale can be justified.


IgG1 antibodies to acetylcholine receptors in 'seronegative' myasthenia gravis.
Only around 80% of patients with generalized myasthenia gravis (MG) have serum antibodies to acetylcholine receptor [AChR; acetylcholine receptor antibody positive myasthenia gravis (AChR-MG)] by the radioimmunoprecipitation assay used worldwide. Antibodies to muscle specific kinase [MuSK; MuSK antibody positive myasthenia gravis (MuSK-MG)] make up a variable proportion of the remaining 20%. The patients with neither AChR nor MuSK antibodies are often called seronegative (seronegative MG, SNMG). There is accumulating evidence that SNMG patients are similar to AChR-MG in clinical features and thymic pathology. We hypothesized that SNMG patients have low-affinity antibodies to AChR that cannot be detected in solution phase assays, but would be detected by binding to the AChRs on the cell membrane, particularly if they were clustered at the high density that is found at the neuromuscular junction. We expressed recombinant AChR subunits with the clustering protein, rapsyn, in human embryonic kidney cells and tested for binding of antibodies by immunofluorescence. To identify AChRs, we tagged either AChR or rapsyn with enhanced green fluorescence protein, and visualized human antibodies with Alexa Fluor-labelled secondary or tertiary antibodies, or by fluorescence-activated cell sorter (FACS). We correlated the results with the thymic pathology where available. We detected AChR antibodies to rapsyn-clustered AChR in 66% (25/38) of sera previously negative for binding to AChR in solution and confirmed the results with FACS. The antibodies were mainly IgG1 subclass and showed ability to activate complement. In addition, there was a correlation between serum binding to clustered AChR and complement deposition on myoid cells in patients' thymus tissue. A similar approach was used to demonstrate that MuSK antibodies, although mainly IgG4, were partially IgG1 subclass and capable of activating complement when bound to MuSK on the cell surface. These observations throw new light on different forms of MG paving the way for improved diagnosis and management, and the approaches used have applicability to other antibody-mediated conditions.


The coevolution of cooperation and dispersal in social groups and its implications for the emergence of multicellularity.
Recent work on the complexity of life highlights the roles played by evolutionary forces at different levels of individuality. One of the central puzzles in explaining transitions in individuality for entities ranging from complex cells, to multicellular organisms and societies, is how different autonomous units relinquish control over their functions to others in the group. In addition to the necessity of reducing conflict over effecting specialized tasks, differentiating groups must control the exploitation of the commons, or else be out-competed by more fit groups. We propose that two forms of conflict - access to resources within groups and representation in germ line - may be resolved in tandem through individual and group-level selective effects. Specifically, we employ an optimization model to show the conditions under which different within-group social behaviors (cooperators producing a public good or cheaters exploiting the public good) may be selected to disperse, thereby not affecting the commons and functioning as germ line. We find that partial or complete dispersal specialization of cheaters is a general outcome. The propensity for cheaters to disperse is highest with intermediate benefit:cost ratios of cooperative acts and with high relatedness. An examination of a range of real biological systems tends to support our theory, although additional study is required to provide robust tests. We suggest that trait linkage between dispersal and cheating should be operative regardless of whether groups ever achieve higher levels of individuality, because individual selection will always tend to increase exploitation, and stronger group structure will tend to increase overall cooperation through kin selected benefits. Cheater specialization as dispersers offers simultaneous solutions to the evolution of cooperation in social groups and the origin of specialization of germ and soma in multicellular organisms.


Soluble Urokinase Plasminogen Activator Receptor and Decline in Kidney Function in Autosomal Dominant Polycystic Kidney Disease.
Levels of soluble urokinase plasminogen activator receptor (suPAR), an inflammation marker, are strongly predictive of incident kidney disease. Patients with autosomal dominant polycystic kidney disease (ADPKD) experience progressive decline in renal function, but rates of decline and outcomes vary greatly. Whether suPAR levels are predictive of declining kidney function in patients with ADPKD is unknown. We assessed suPAR levels in 649 patients with ADPKD who underwent scheduled follow-up for at least 3 years, with repeated measurements of height-adjusted total kidney volume and creatinine-derived eGFR. We used linear mixed models for repeated measures and Cox proportional hazards to characterize associations between baseline suPAR levels and follow-up eGFR or incident ESRD. The median suPAR level was 2.47 ng/ml and median height-adjusted total kidney volume was 778, whereas mean eGFR was 84 ml/min per 1.73 m2. suPAR levels were associated with height-adjusted total kidney volume (β=0.02; 95% confidence interval, 0.01 to 0.03), independent of age, sex, race, hypertension, and eGFR. Patients in the lowest suPAR tertile (<2.18 ng/ml) had a 6.8% decline in eGFR at 3 years and 22% developed CKD stage 3, whereas those in the highest tertile (suPAR>2.83 ng/ml) had a 19.4% decline in eGFR at 3 years and 68% developed CKD stage 3. suPAR levels >2.82 ng/ml had a 3.38-fold increase in the risk of incident ESRD. suPAR levels were associated with progressive decline in renal function and incident ESRD in patients with ADPKD, and may aid early identification of patients at high risk of disease progression.


First Report of Xanthomonas hortorum pv. hederae Causing Bacterial Leaf Spot of Hedera hibernica in Slovenia.
In October 2008, water-soaked spots, each 5 to 10 mm in diameter and surrounded by a pale green halo, were observed on leaves of a single Atlantic ivy plant (Hedera hibernica Kirchn.) out of 89 plants imported from the European Union into a commercial greenhouse in Slovenia. Leaves were surface disinfected, and spots were cut and suspended in 10 mM phosphate buffered saline. From this extract, yellow-pigmented, Xanthomonas-like bacterial colonies were isolated onto nutrient agar, and two colonies (NIB Z 1310 and NIB Z 1312) were each identified as a Xanthomonas sp. based on biochemical tests (oxidase negative; positive for hydrolysis of H2S, starch, and tributyrin; and positive for acid production from sucrose). Both isolates caused a hypersensitive reaction (1) on leaves of tomato cv. Moneymaker. A repetitive extragenic palindromic sequence (REP)-PCR assay using the BOXA1R primer (3) resulted in highly similar DNA fragment banding patterns (Pearson's correlation: 95% identity) between the two isolates (NIB Z 1310 and NIB Z 1312) and the type strain of Xanthomonas hortorum pv. hederae CFBP 4925 (ICMP 453). Partial sequences of the gyrB gene (DNA gyrase, subunit B) (2) from isolates NIB Z 1310 (Accession No. JF794785; 599 bp) and NIB Z 1312 (Accession No. JF794784; 544 bp), showed identical sequences (100% identity with 100% coverage) to type strain ICMP 453 (Accession No. EU498975.1). The pathogenicity of the two isolates from H. hibernica was confirmed on three plants of H. helix 'Evita' (each 6 months old) for each isolate. Plants were sprayed on the abaxial and adaxial side of leaves with 10 ml of a 48-h suspension of the appropriate isolate with approximately 106 CFU/ml (1), covered individually with plastic bags for 24 h, and incubated under high relative humidity (>80%) with 16 h of daylight at 25°C by day and 20°C by night. Three positive and three negative control plants were inoculated with the type strain of X. hortorum pv. hederae CFBP 4925 and 0.01 M magnesium sulfate buffer, respectively. After 21 days, water-soaked spots with a pale green halo were observed on all plants inoculated with the bacterial strains, including the positive control plants. Colonies isolated from these lesions were identical in morphology and BOX-PCR DNA fragment banding patterns to the original isolates. Negative control plants did not develop symptoms, and colonies similar to X. hortorum pv. hederae were not isolated from these plants. To our knowledge, this is the first report of X. hortorum pv. hederae on H. hibernica in greenhouse production in Slovenia. If the disease spreads, it could reduce quality and marketability of this popular ground cover plant. References: (1) Z. Klement et al. Inoculation of Plant Tissues. In: Methods in Phytobacteriology. Akadémiai Kiadó, Budapest, 1990. (2) N. Parkinson et al. Int. J. Syst. Evol. Microbiol. 59:264, 2009. (3) J. Versalovic et al. Methods Mol. Cell Biol. 5:25, 1994.


White matter pathway asymmetry underlies functional lateralization.
Structural and functional asymmetry of the human brain has been well documented using techniques such as magnetic resonance imaging (MRI). However, asymmetry of underlying white matter connections is less well understood. We applied an MRI technique known as diffusion tensor tractography to reveal the morphology of the white matter in vivo by mapping directions of maximum water diffusion in brain tissue. White matter pathway asymmetry was investigated in a normalized image data set of 30 right-handed young healthy individuals. We identified, for the first time, a rightwardly asymmetric pathway connecting the posterior temporal lobe to the superior parietal lobule. This pathway may be related to auditory spatial attention and working memory for which there is evidence for a rightward laterality from functional imaging studies. Additional leftward asymmetries connecting the parietal and frontal lobes to the temporal lobe may be more closely related to laterality of language.


Management of early stage non-small cell lung cancer in high-risk patients.
The preferred treatment of stage I non-small cell lung cancer (NSCLC) is anatomic resection with systematic mediastinal lymph node evaluation. However, 20% of patients with operable lung cancer are not candidates for this type of resection. Recent advancements in radiology-guided technologies have expanded the treatment options for high-risk patients with early-stage NSCLC. There has simultaneously been resurgence in interest and refinement of indications and techniques for sublobar resection in this population. While these treatments appear to have decreased peri-procedural morbidity and mortality, their oncologic efficacy compared to that of lobectomy remains to be determined.


Efficient example-based painting and synthesis of 2D directional texture.
We present a new method for converting a photo or image to a synthesized painting following the painting style of an example painting. Treating painting styles of brush strokes as sample textures, we reduce the problem of learning an example painting to a texture synthesis problem. The proposed method uses a hierarchical patch-based approach to the synthesis of directional textures. The key features of our method are: 1) Painting styles are represented as one or more blocks of sample textures selected by the user from the example painting; 2) image segmentation and brush stroke directions defined by the medial axis are used to better represent and communicate shapes and objects present in the synthesized painting; 3) image masks and a hierarchy of texture patches are used to efficiently synthesize high-quality directional textures. The synthesis process is further accelerated through texture direction quantization and the use of Gaussian pyramids. Our method has the following advantages: First, the synthesized stroke textures can follow a direction field determined by the shapes of regions to be painted. Second, the method is very efficient; the generation time of a synthesized painting ranges from a few seconds to about one minute, rather than hours, as required by other existing methods, on a commodity PC. Furthermore, the technique presented here provides a new and efficient solution to the problem of synthesizing a 2D directional texture. We use a number of test examples to demonstrate the efficiency of the proposed method and the high quality of results produced by the method.


Arfs at a glance.
The Arf small G proteins regulate protein and lipid trafficking in eukaryotic cells through a regulated cycle of GTP binding and hydrolysis. In their GTP-bound form, Arf proteins recruit a specific set of protein effectors to the membrane surface. These effectors function in vesicle formation and tethering, non-vesicular lipid transport and cytoskeletal regulation. Beyond fundamental membrane trafficking roles, Arf proteins also regulate mitosis, plasma membrane signaling, cilary trafficking and lipid droplet function. Tight spatial and temporal regulation of the relatively small number of Arf proteins is achieved by their guanine nucleotide-exchange factors (GEFs) and GTPase-activating proteins (GAPs), which catalyze GTP binding and hydrolysis, respectively. A unifying function of Arf proteins, performed in conjunction with their regulators and effectors, is sensing, modulating and transporting the lipids that make up cellular membranes. In this Cell Science at a Glance article and the accompanying poster, we discuss the unique features of Arf small G proteins, their functions in vesicular and lipid trafficking in cells, and how these functions are modulated by their regulators, the GEFs and GAPs. We also discuss how these Arf functions are subverted by human pathogens and disease states.


Laser divided-aperture differential confocal sensing technology with improved axial resolution.
In this study, we found that the axial response curve of divided-aperture confocal microscopy has a shift while the point detector has a transverse offset from the optical axis. Based on this, a novel laser divided-aperture differential confocal sensing technology (LDDCST) with absolute zero and high axial resolution, as well as an LDDCST-based sensor, is proposed. LDDCST sets two micro-regions as virtual pinholes that are symmetrical to the optical axis along the x(d) direction on the focal plane of the divided-aperture confocal system to achieve the spot-division detection and to simplify the detection system, uses differential subtraction of two intensity responses simultaneously detected from the two micro-regions to achieve high axial resolution absolute measurement and low noise, and considers both resolution and measurement range by adjusting virtual pinholes in software. Theoretical analyses and packaged LDDCST sensor experiments indicate that LDDCST has high axial resolution as well as strong anti-interference and sectioning detection capability.


High consumption of pulses is associated with lower risk of abnormal glucose metabolism in women in Mauritius.
To investigate if consumption of pulses was associated with a reduced risk of developing abnormal glucose metabolism, increases in body weight and increases in waist circumference in a multi-ethnic cohort in Mauritius. Population-based surveys were performed in Mauritius in 1992 and in 1998. Pulse consumption was estimated from a food frequency questionnaire in 1992 and outcomes were measured in 1998. At both time points, anthropometry was undertaken and an oral glucose tolerance test was performed. Mauritian women with the highest consumption of pulses (highest tertile) had a reduced risk of developing abnormal glucose metabolism [odds ratio 0.52; 95% CI 0.27, 0.99) compared with those with the lowest consumption, and also after multivariable adjustments. In women, a high consumption of pulses was associated with a smaller increase in BMI. High consumption of pulses was associated with a reduced risk of abnormal glucose metabolism and a smaller increase in BMI in Mauritian women. Promotion of pulse consumption could be an important dietary intervention for the prevention of Type 2 diabetes and obesity in Mauritius and should be examined in other populations and in clinical trials.


Anti-CD22 90Y-epratuzumab tetraxetan combined with anti-CD20 veltuzumab: a phase I study in patients with relapsed/refractory, aggressive non-Hodgkin lymphoma.
A lingering criticism of radioimmunotherapy in non-Hodgkin lymphoma is the use of cold anti-CD20 antibody along with the radiolabeled anti-CD20 antibody. We instead combined radioimmunotherapy with immunotherapy targeting different B-cell antigens. We evaluated the anti-CD22 (90)Y-epratuzumab tetraxetan with the anti-CD20 veltuzumab in patients with aggressive lymphoma in whom at least one prior standard treatment had failed, but who had not undergone stem cell transplantation. Eighteen patients (median age 73 years, median of 3 prior treatments) received 200 mg/m(2) veltuzumab once-weekly for 4 weeks, with (90)Y-epratuzumab tetraxetan at planned doses in weeks 3 and 4, and (111)In-epratuzumab tetraxetan in week 2 for imaging and dosimetry. Veltuzumab effectively lowered levels of B cells in the blood prior to the radioimmunotherapy doses. No significant immunogenicity or change in pharmacokinetics of either agent occurred in combination. (111)In imaging showed tumor targeting with acceptable radiation dosimetry to normal organs. For (90)Y-epratuzumab tetraxetan, transient myelosuppression was dose-limiting with 6 mCi/m(2) (222 MBq/m(2)) × 2 being the maximal tolerated dose. Of 17 assessable patients, nine (53%) had objective responses according to the 2007 revised treatment response criteria, including three (18%) complete responses (2 relapsing after 11 and 13 months, 1 continuing to be clinically disease-free at 19 months), and six (35%) partial responses (1 relapsing after 14 months, 5 at 3 - 7 months). Responses occurred in patients with different lymphoma histologies, treated at different (90)Y dose levels, and with a predicted risk of poor outcome, most importantly including five of the six patients treated with the maximal tolerated dose (2 of whom achieved durable complete responses). In conclusion, the combination of (90)Y-epratuzumab tetraxetan and veltuzumab was well-tolerated with encouraging therapeutic activity in this difficult-to-treat population.


Resource use and cost of initial coronary revascularization. Coronary angioplasty versus coronary bypass surgery.
Although there is intense interest in the cost-saving potential of therapeutic alternatives, most studies have analyzed hospital charges rather than actual economic costs. To analyze cost differences rigorously, we studied 115 patients undergoing initial elective angioplasty (percutaneous transluminal coronary angioplasty, PTCA) and 274 patients undergoing initial elective surgery (coronary artery bypass graft surgery, CABG). Detailed resource consumption profiles were constructed and used to estimate the cost savings from switching a patient from CABG to PTCA. Four cost-accounting methods were used in the analysis; each method made different assumptions about the costs that would vary and the costs that would be fixed according to the number of procedures performed. The variable costs in the four methods were the 1) cost of supplies, 2) cost of personnel and supplies, 3) average direct costs, and 4) average direct costs plus allocated hospital overhead. The mean hospital charges for CABG patients were $19,644 versus $9,556 for PTCA patients (p less than 0.0001). The estimated cost difference between CABG and PTCA was substantially less than the $10,088 difference in charges, however, with net savings of 19%, 46%, 53%, and 78% of charges using cost-accounting methods 1-4, respectively. Thus, although the initial hospital charges for PTCA are significantly less than for CABG, the actual economic cost savings may be significantly overestimated by the use of hospital charge data.


Comparison of implicit and explicit learning processes in a probabilistic task.
This experiment compared the performance with explicit (rule-application and rule-discovery) and implicit (nonrule-instructed) learning approaches on the performance of a probabilistic video game task requiring fine motor control. The task required visual tracking of a small ball of light and "catching" it by means of joystick manipulation. A general pattern of improvement with practice occurred for all conditions. All conditions showed use of predictive relations among stimulus events. However, task performance of the rule-application and rule-discovery conditions were inferior to the nonrule-instructed implicit condition, particularly during the early phases of rule acquisition and application. This pattern strongly suggests substantial performance costs associated with attempting to discover or apply probabilistic rules. Decrements are likely due to increased cognitive demands associated with attempting to remember and strategically apply provided probability rules or attempting to discover and apply potentially important and useful probability information from a complex visual display.


Nursing structure, processes, and patient outcomes in army medical centers.
The purpose of this study was to describe patient outcomes in Army Medical Centers, identify differences in outcomes between mixed medical-surgical bed and specialty intensive care units (ICUs), and explore predictive models for outcomes attributable to nursing structure and processes. Data were collected from 138 patients and 103 nurses in four medical-surgical and four ICUs in two Army Medical Centers. Significant differences for unit type were found for length of stay and patient satisfaction with nursing care. Outcome predictive models were modest (adjusted R2 = .16 to .24) and significant for length of stay, satisfaction with nursing care, satisfaction with pain management, and health status following discharge. Exploring differences and commonalities between military and civilian hospitals will ultimately provide insight into ways of improving patient outcomes and bettering the work environment of nurses.


Grid enabled high throughput virtual screening against four different targets implicated in malaria.
After having deployed a first data challenge on malaria and a second one on avian flu, respectively in summer 2005 and spring 2006, we are demonstrating here again how efficiently the computational grids can be used to produce massive docking data at a high-throughput. During more than 2 months and a half, we have achieved at least 140 million dockings, representing an average throughput of almost 80,000 dockings per hour. This was made possible by the availability of thousands of CPUs through different infrastructures worldwide. Through the acquired experience, the WISDOM production environment is evolving to enable an easy and fault-tolerant deployment of biological tools; in this case it is the FlexX commercial docking software which is used to dock the whole ZINC database against 4 different targets.


Two decades of the gonococcal antimicrobial surveillance program in South America and the Caribbean: challenges and opportunities.
The WHO has called for a global action plan to control the spread and impact of antibiotic resistant Neisseria gonorrhoeae. We report on key antimicrobial susceptibility (AMS) trends in countries in Latin America and the Caribbean from 1990 to 2011. Data collected between 1990 and 2011 by up to 23 countries in the Latin American and Caribbean region were aggregated and analysed for overall trends in N gonorrhoeae AMS to six antibiotics. Methods for gonococcal identification, susceptibility testing and interpretation were standardised. More than 21 500 N gonorrhoeae isolates were tested for AMS between 1990 and 2011. The number of countries reporting yearly declined from 17 in the 1990 s to 7 in 2011. The first isolates (0.4%, 20/5171) with reduced susceptibility (minimum inhibitory concentration ≥ 0.125 mg/L) to ceftriaxone were reported between 2007 and 2011. Ciprofloxacin resistance, first noted in the mid-1990 s, ranged from 1.6% of isolates tested in 1997 rising to 42.1% in 2010. Overall, azithromycin resistance reached a high of 25.8% of isolates tested in 2008 falling to 1.0% in 2010. Resistance to penicillin ranged between 24.2% in 2003 to a high of 48.5% in 1993. Tetracycline resistance ranged between a high of 61.1% of isolates tested in 2001 to 21.8% in 2010. Plasmid mediated penicillin and tetracycline resistance declined over the period. Gonococcal AMS surveillance initiatives are urgently needed in every country in the region to ensure that effective treatments for gonococcal infections are in place and to better understand emerging trends in gonococcal antimicrobial resistance.


Hymenobacter ruber sp. nov., isolated from grass soil.
A taxonomic study using a polyphasic approach was performed on a Gram-stain-negative, aerobic, non-motile, non-spore-forming, rod-shaped bacterium, designated strain PB156(T), isolated from grass soil. Comparative 16S rRNA gene sequence studies showed that the isolate was clearly affiliated with the phylum Bacteroidetes, and most closely related to Hymenobacter soli PB17(T), Hymenobacter antarcticus VUG-A42aa(T) and Hymenobacter glaciei VUG-A130(T), showing 96.4, 96.2 and 95.9 % 16S rRNA gene sequence similarity, respectively, while all other species of the genus shared only 89.3-95.2 % similarity. The main polyamine present was sym-homospermidine. The predominant menaquinone was MK-7. The major fatty acids were C15 : 0 iso, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c/t), C16 : 1ω5c and C15 : 0 anteiso. The G+C content of the genomic DNA of strain PB156(T) was 61.7 mol%. The combined genotypic and phenotypic data supported the conclusion that strain PB156(T) represents a novel species of the genus Hymenobacter, for which the name Hymenobacter ruber sp. nov. is proposed. The type strain is PB156(T) ( = KCTC 32477(T) = JCM 19433(T)).


A generic framework for tracking using particle filter with dynamic shape prior.
Tracking deforming objects involves estimating the global motion of the object and its local deformations as functions of time. Tracking algorithms using Kalman filters or particle filters (PFs) have been proposed for tracking such objects, but these have limitations due to the lack of dynamic shape information. In this paper, we propose a novel method based on employing a locally linear embedding in order to incorporate dynamic shape information into the particle filtering framework for tracking highly deformable objects in the presence of noise and clutter. The PF also models image statistics such as mean and variance of the given data which can be useful in obtaining proper separation of object and background.


Incidence of Hepatocellular Carcinoma in All 50 United States, From 2000 Through 2012.
The incidence and mortality of hepatocellular carcinoma (HCC) have been reported to be plateauing in the United States. The United States has large racial, ethnic, and regional variation; we collected data from all 50 states to better analyze changes in HCC incidence in the entire United States. We collected data from the US Cancer Statistics registry, which covers 97% of the population, and calculated adjusted incidence rates. We assessed annual trends among sociodemographic and geographic subgroups using joinpoint analysis. HCC incidence increased from 4.4/100,000 in 2000 to 6.7/100,000 in 2012, increasing by 4.5% (95% confidence interval [CI], 4.3%-4.7%) annually between 2000 and 2009, but only by 0.7% annually (95% CI, -0.2% to 1.6%) from 2010 through 2012. The average annual percentage change (AAPC) between 2000 and 2012 was higher in men (increase, 3.7%) than in women (increase, 2.7%), and highest in 55- to 59-year-old individuals (AAPC, 8.9%; 95% CI, 7.1%-10.7%) and 60- to 64-year-old individuals (AAPC, 6.4%; 95% CI, 4.7%-8.2%). By 2012, rates in Hispanics surpassed those in Asians, and rates in Texas surpassed those in Hawaii (9.71/100,000 vs 9.68/100,000). Geographic variation within individual race and ethnic groups was observed, but rates were highest in all major race and ethnic groups in Texas. In an analysis of the incidence of HCC in all 50 US states, we found the rate of increase in HCC to have slowed from 2010 through 2012. However, incidence is increasing in subgroups such as men ages 55 to 64 years old-especially those born in the peak era of hepatitis C virus infection and among whites/Caucasians. Rates in Hispanics have surpassed those in Asian Americans. We observed geographic differences, with Texas having the highest age-adjusted HCC rates nationwide.


Longevity and the costs of reproduction in a historical human population.
It has been argued that the priority that natural selection places on reproduction negatively affects other processes such as longevity and the problem posed by this trade-off underlies the disposable soma theory for the evolution of human ageing. Here we examine the relationship between reproduction and longevity in a historical human population (the Krummhörn, north-west Germany 1720-1870). In our initial analyses, we found no support for the hypothesized negative effects of reproduction on longevity: married women who remained childless lived no longer than women who reproduced and women who had few children lived no longer than women who had many children. However, more detailed analyses in relation to socio-economic class revealed that the extent to which reproduction has an effect on longevity is a function of the level of economic deprivation. We found that, when possible sources of confound were controlled for (e.g. duration of marriage and amount of time spent in fecund marriage), there is an increasingly strong relationship between longevity and reproduction with increasing poverty.


Demonstrating public health at work: a demonstration project of congenital syphilis prevention efforts in Bolivia.
We introduced syphilis immunochromatic strip (ICS) tests into antenatal care (ANC) settings in Bolivia and evaluated feasibility, patient and provider acceptability, and introduction costs. We conducted complementary studies on related topics, strengthened quality of care, and aided the response to sensitive aspects of maternal/congenital syphilis control (e.g., partner notification). The goal of this study was to discuss our experience working with Bolivian stakeholders to document potential public health benefits of syphilis ICS test introduction in ANC settings. We trained public health personnel and offered the Abbott Determine Rapid Syphilis TP test in 4 urban maternity hospitals and 37 rural clinics. Using the ICS test, 11,618 women were tested for syphilis; 5% had positive results and 93.2% received treatment. Women and health personnel found the test acceptable and introduction costs were not prohibitive. Based on these findings, by mid-2006, the Bolivian Ministry of Health will offer the ICS tests in rural ANC settings.


Morning surge in blood pressure and blood pressure variability in Asia: Evidence and statement from the HOPE Asia Network.
Hypertension is a major risk factor for cardiovascular and cerebrovascular diseases. To effectively prevent end-organ damage, maintain vascular integrity and reduce morbidity and mortality, it is essential to decrease and adequately control blood pressure (BP) throughout each 24-hour period. Exaggerated early morning BP surge (EMBS) is one component of BP variability (BPV), and has been associated with an increased risk of stroke and cardiovascular events, independently of 24-hour average BP. BPV includes circadian, short-term and long-term components, and can best be documented using out-of-office techniques such as ambulatory and/or home BP monitoring. There is a large body of evidence linking both BPV and EMBS with increased rates of adverse cardio- and cerebrovascular events, and end-organ damage. Differences in hypertension and related cardiovascular disease rates have been reported between Western and Asian populations, including a higher rate of stroke, higher prevalence of metabolic syndrome, greater salt sensitivity and more common high morning and nocturnal BP readings in Asians. This highlights a need for BP management strategies that take into account ethnic differences. In general, long-acting antihypertensives that control BP throughout the 24-hour period are preferred; amlodipine and telmisartan have been shown to control EMBS more effectively than valsartan. Home and ambulatory BP monitoring should form an essential part of hypertension management, with individualized pharmacotherapy to achieve optimal 24-hour BP control particularly the EMBS and provide the best cardio- and cerebrovascular protection. Future research should facilitate better understanding of BPV, allowing optimization of strategies for the detection and treatment of hypertension to reduce adverse outcomes.


Power to the will: how exerting physical effort boosts the sense of agency.
The sense of agency refers to the experience of being in control of one's actions and their consequences. The 19th century French philosopher Maine de Biran proposed that the sensation of effort might provide an internal cue for distinguishing self-caused from other changes in the environment. The present study is the first to empirically test the philosophical idea that effort promotes self-agency. We used intentional binding, which refers to the subjective temporal attraction between an action and its sensory consequences, as an implicit measure of the sense of agency. Effort was manipulated independent of the primary task by requiring participants to pull stretch bands of varying resistance levels. We found that intentional binding was enhanced under conditions of increased effort. This suggests not only that the experience of effort directly contributes to the sense of agency, but also that the integration of effort as an agency cue is non-specific to the effort requirement of the action itself.


Indicators of Horse Welfare: State-of-the-Art.
Animal welfare is defined as a chronic state reflecting an individual's subjective perception of its situation. Because it is possible to be in a good welfare state and nevertheless experience acute fear or pain, and conversely, short-term positive emotions can be experienced during impaired welfare states, welfare as a chronic state has to be clearly distinguished from temporary states related to emotions, pain or stress. The evaluation of non-verbal individuals' welfare state, particularly in interspecific situations, is a real challenge that necessarily implies animal-based measures and requires multidisciplinary scientifically validated measures. In the last decade, studies investigating horses' welfare flourished together with new measures that were not always scientifically tested before being used. At a time were legal decisions are made on animal welfare, it is crucial to rely on reliable welfare indicators in order to prevent false evaluation. The aim of this review is to identify the scientifically tested and reliable indicators of horses' welfare (e.g., body lesions, apathy, aggressiveness, stereotypic behaviours) from signals of temporary states related to acute pain emotions or stress and from popular beliefs, in order to give the scientific community and the horse industry accurate evaluation tools.


The IKKbeta subunit of IkappaB kinase (IKK) is essential for nuclear factor kappaB activation and prevention of apoptosis.
The IkappaB kinase (IKK) complex is composed of three subunits, IKKalpha, IKKbeta, and IKKgamma (NEMO). While IKKalpha and IKKbeta are highly similar catalytic subunits, both capable of IkappaB phosphorylation in vitro, IKKgamma is a regulatory subunit. Previous biochemical and genetic analyses have indicated that despite their similar structures and in vitro kinase activities, IKKalpha and IKKbeta have distinct functions. Surprisingly, disruption of the Ikkalpha locus did not abolish activation of IKK by proinflammatory stimuli and resulted in only a small decrease in nuclear factor (NF)-kappaB activation. Now we describe the pathophysiological consequence of disruption of the Ikkbeta locus. IKKbeta-deficient mice die at mid-gestation from uncontrolled liver apoptosis, a phenotype that is remarkably similar to that of mice deficient in both the RelA (p65) and NF-kappaB1 (p50/p105) subunits of NF-kappaB. Accordingly, IKKbeta-deficient cells are defective in activation of IKK and NF-kappaB in response to either tumor necrosis factor alpha or interleukin 1. Thus IKKbeta, but not IKKalpha, plays the major role in IKK activation and induction of NF-kappaB activity. In the absence of IKKbeta, IKKalpha is unresponsive to IKK activators.


Maintenance and integrity of the mitochondrial genome: a plethora of nuclear genes in the budding yeast.
Instability of the mitochondrial genome (mtDNA) is a general problem from yeasts to humans. However, its genetic control is not well documented except in the yeast Saccharomyces cerevisiae. From the discovery, 50 years ago, of the petite mutants by Ephrussi and his coworkers, it has been shown that more than 100 nuclear genes directly or indirectly influence the fate of the rho(+) mtDNA. It is not surprising that mutations in genes involved in mtDNA metabolism (replication, repair, and recombination) can cause a complete loss of mtDNA (rho(0) petites) and/or lead to truncated forms (rho(-)) of this genome. However, most loss-of-function mutations which increase yeast mtDNA instability act indirectly: they lie in genes controlling functions as diverse as mitochondrial translation, ATP synthase, iron homeostasis, fatty acid metabolism, mitochondrial morphology, and so on. In a few cases it has been shown that gene overexpression increases the levels of petite mutants. Mutations in other genes are lethal in the absence of a functional mtDNA and thus convert this petite-positive yeast into a petite-negative form: petite cells cannot be recovered in these genetic contexts. Most of the data are explained if one assumes that the maintenance of the rho(+) genome depends on a centromere-like structure dispensable for the maintenance of rho(-) mtDNA and/or the function of mitochondrially encoded ATP synthase subunits, especially ATP6. In fact, the real challenge for the next 50 years will be to assemble the pieces of this puzzle by using yeast and to use complementary models, especially in strict aerobes.


A phase 1 clinical trial of flavopiridol consolidation in chronic lymphocytic leukemia patients following chemoimmunotherapy.
Patients with chronic lymphocytic leukemia (CLL) who receive chemoimmunotherapy and do not achieve complete remission experience significantly shortened progression-free interval (PFS). Additionally, the majority of patients treated for relapsed disease demonstrate evidence of measurable disease. Eradication of minimal residual disease (MRD) results in improved PFS and overall survival. Maintenance therapy might result in eradication of MRD and improve response duration but might be associated with an increase in incidence of infectious complications. Flavopiridol is a broad cyclin-dependent kinase (CDK) inhibitor with established safety and efficacy in patients with relapsed CLL, particularly patients with high-risk cytogenetic features. A pharmacologically derived schedule was utilized as consolidation therapy in this phase I study to assess the safety and feasibility of outpatient therapy with flavopiridol in patients with low tumor burden. Flavopiridol was administered as a 30-min loading dose of 30 mg/m(2) followed by a 4-h infusion of 30 mg/m(2) once weekly for 3 weeks every 5 weeks (1 cycle) for planned 2 cycles in ten patients. Therapy was extremely well tolerated and no patient developed acute tumor lysis syndrome. The most common toxicities were gastrointestinal. Of the patients, 22 % improved their response from a PR to CR. Eighty-eight percent experienced a reduction in tumor burden as measured by extent of bone marrow involvement including patients with del17p and complex karyotype. The study establishes the safety and efficacy of flavopiridol as consolidation therapy after chemoimmunotherapy for patients with CLL. Further evaluation is required in larger trials for the utility of CDK inhibitors as consolidation or maintenance strategies.Registration number at ClinicalTrials.gov: NCT00377104.


Immunohistochemistry of great scallop Pecten maximus larvae experimentally challenged with pathogenic bacteria.
Three challenge experiments were carried out on larvae of the great scallop Pecten maximus. Larvae were bath-challenged with Vibrio pectenicida and 5 strains resembling Vibrio splendidus and one Pseudoalteromonas sp. Unchallenged larvae were used as negative controls. The challenge protocol was based on the use of a multidish system, where the scallop larvae (10, 13 and 15 d post-hatching in the 3 experiments, respectively) were distributed to 2 ml wells with stagnant seawater and exposed to the bacterial cultures by bath challenge. Presence of the challenge bacteria in the wells was verified by polymerase chain reaction (PCR). A significantly increased mortality was found between 24 and 48 h in most groups challenged with V. pectenicida or V. splendidus-like strains. The exception was found in larval groups challenged with a Pseudoalteromonas sp. LT 13, in which the mortality rate fell in 2 of the 3 challenge experiments. Larvae from the challenge experiments were studied by immunohistochemistry protocol. Examinations of larval groups challenged with V. pectenicida revealed no bacterial cells, despite a high degree of positive immunostaining. In contrast, intact bacterial cells were found in larvae challenged with V. splendidus. In the case of larvae challenged with the Pseudoalteromonas sp., positive immuno-staining was limited to visible bacteria inside the digestive area and cells of the mucosa. The experiments confirm that V. splendidus and V. pectenicida are pathogenic to scallop larvae, and that the Pseudoalteromonas strain is probably not a primary pathogen, although it cannot be ruled out as a secondary pathogen.


Immunohistochemical study of p21 and Bcl-2 in leukoplakia, oral submucous fibrosis and oral squamous cell carcinoma.
Oral Squamous cell carcinoma (OSCC) results from genetic damage, leading to uncontrolled cell proliferation of damaged cells and the cell death. In the course of its progression, visible changes are taking place at the cellular level (atypical) and the resultant at the tissue level (epithelial dysplasia). The Aim of the present study was to evaluate and compare the expressions of intensity of p21 and Bcl-2 in Leukoplakia, oralsubmucous fibrosis (OSMF) and oral squamous cell carcinoma. Total 60 cases, 30 cases of oral squamous cell carcinoma, 15 cases of oral submucous fibrosis and 15 cases of Leukoplakia were evaluated immunohistochemically for p21 and Bcl-2 expression. p21 showed positive expression in 13 (86.67%) cases out of 15 cases of OSMF, 12 (80%) cases of leukoplakia out of 15 cases and 24 (80%) cases out of 30 cases of OSCC. The Bcl-2 expression was positive in 13 (86.67%) cases of OSMF, all cases of Leukoplakia and 25 (83.33%) cases of OSCC. No statistical significance was noted in the expression of p21 and Bcl-2 positive expression between OSMF, Leukoplakia and OSCC. Statistical analysis for comparison of intensity of p21 expression in different grades of OSCC showed no significance. Statistical significance difference was found between the expressions of Bcl-2 in moderately and poorly differentiated SCC. The intensity of p21 and Bcl-2 expressions in different grades of OSCC indicates a key role in progression of oral neoplasia.


Minimally invasive techniques in the management of pilonidal disease.
Pilonidal sinus disease (PD) is a chronic condition involved in natal cleft. Excision surgery carries equally morbid course of recovery to that of disease itself. Minimally invasive treatments therefore have been developed to minimise morbidity and improve healing rates. This review looks at the literature on effectiveness of endoscopic pilonidal sinus treatment (EPSiT) and compares that of the other minimally invasive techniques in practice. MEDLINE, EMBASE, Cochrane and CINAHL databases were searched to look at the peer-reviewed articles on minimally invasive treatments on PD. Primary endpoint was to determine complication rates. Data were pooled using random effect model. Heterogeneity among studies was estimated with χ2 tests. Statistical analysis was performed with Review Manager Version 5.1.2. Out of 371 papers, ten were retrieved for full appraisal. One randomised clinical trial (RCT) and four case series presented retrospective data on EPSiT. Five RCTs were on alternative minimally invasive treatments. Complication rate, return to work, wound healing rate and pain scores were superior in minimally invasive treatments compared to excision surgery. There was no statistically significant difference in complication rate or return to work in EPSiT compared to that of alternate minimally invasive techniques. Minimally invasive treatments of pilonidal disease were found to be safe and effective compared to conventional techniques. It is also demonstrated that EPSiT is a safe alternative with a low short-term complication rate. Further randomised controlled trials are required to more accurately define its effectiveness and closely evaluate the side effect profile.


Concealing Emotions at Work Is Associated with Allergic Rhinitis in Korea.
Concealing emotions at work can cause considerable psychological stress. While there is extensive research on the adverse health effects of concealing emotions and the association between allergic diseases and stress, research has not yet investigated whether concealing emotions at work is associated with allergic rhinitis. Allergic rhinitis is a common disease in many industrialized countries, and its prevalence is increasing. Thus, our aim was to determine the strength of this association using data from three years (2007-2009) of the 4th Korean National Health and Nutrition Examination Survey. Participants (aged 20-64) were 8,345 individuals who were economically active and who had completed the questionnaire items on concealing emotions at work. Odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated for allergic rhinitis using logistic regression models. Among all participants, 3,140 subjects (37.6%) reported concealing their emotions at work: 1,661 men and 1,479 women. The OR (95% CIs) for allergic rhinitis among those who concealed emotions at work versus those who did not was 1.318 (1.148-1.512). Stratified by sex, the OR (95% CIs) was 1.307 (1.078-1.585) among men and 1.346 (1.105-1.639) among women. Thus, individuals who concealed their emotions at work were significantly more likely to have a diagnosis of AR in comparison to those who did not. Because concealing emotions at work has adverse health effects, labor policies that aim to reduce this practice are needed.


Murine model of cutaneous infection with gram-positive cocci.
Staphylococcus aureus has remained an important cause of nosocomial wound infections, but standardized or reproducible systems for analyzing cutaneous infections caused by S. aureus do not exist. A variety of foreign materials, variable inocula, and skin traumas have been used to promote infection. To minimize these variables and ensure reproducibility, we chose a model using subcutaneous injections of a fixed quantity of dextran microbeads (Cytodex) as the foreign material added to standardized broth suspensions of S. aureus. Suspensions (0.2 ml) injected into an outbred strain of immunocompetent hairless mice generated reproducible, measurable lesions. With S. aureus Smith Diffuse, fluctuant, erythematous lesions with a peak diameter of 15 mm were observed; these lesions yielded purulent material containing gram-positive cocci and neutrophils and yielded growth of S. aureus on culture. Lesion size was proportional to the bacterial inoculum size. Histologic examination of excised lesions revealed typical abscesses. A second strain of S. aureus (SLC3) produced dermonecrosis instead of abscesses at an inoculum size of 10(7) CFU. Control injections with a sterile Cytodex suspension regularly produced nondraining, nonerythematous nodules with maximum diameters of less than or equal to 5 mm. Streptococcus pyogenes produced late-onset necrotic lesions and abscesses. Using a foreign substance, this model generates easily observed and reproducible cutaneous infection with S. aureus and streptococci that can potentially discriminate between inter- and intrastrain differences. Such a model could be used to test the pathogenicity of isogeneic strains of these bacterial species and to evaluate the efficacy of antimicrobial agents.


Multicentre prospective cohort study of body mass index and postoperative complications following gastrointestinal surgery.
There is currently conflicting evidence surrounding the effects of obesity on postoperative outcomes. Previous studies have found obesity to be associated with adverse events, but others have found no association. The aim of this study was to determine whether increasing body mass index (BMI) is an independent risk factor for development of major postoperative complications. This was a multicentre prospective cohort study across the UK and Republic of Ireland. Consecutive patients undergoing elective or emergency gastrointestinal surgery over a 4-month interval (October-December 2014) were eligible for inclusion. The primary outcome was the 30-day major complication rate (Clavien-Dindo grade III-V). BMI was grouped according to the World Health Organization classification. Multilevel logistic regression models were used to adjust for patient, operative and hospital-level effects, creating odds ratios (ORs) and 95 per cent confidence intervals (c.i.). Of 7965 patients, 2545 (32·0 per cent) were of normal weight, 2673 (33·6 per cent) were overweight and 2747 (34·5 per cent) were obese. Overall, 4925 (61·8 per cent) underwent elective and 3038 (38·1 per cent) emergency operations. The 30-day major complication rate was 11·4 per cent (908 of 7965). In adjusted models, a significant interaction was found between BMI and diagnosis, with an association seen between BMI and major complications for patients with malignancy (overweight: OR 1·59, 95 per cent c.i. 1·12 to 2·29, P = 0·008; obese: OR 1·91, 1·31 to 2·83, P = 0·002; compared with normal weight) but not benign disease (overweight: OR 0·89, 0·71 to 1·12, P = 0·329; obese: OR 0·84, 0·66 to 1·06, P = 0·147). Overweight and obese patients undergoing surgery for gastrointestinal malignancy are at increased risk of major postoperative complications compared with those of normal weight.


Everyday ethics of participation: a case study of a CBPR in Nunavik.
Multiple reports highlight the need for community-based family-oriented prevention services for Aboriginal peoples in order to address important health and social inequalities. Participatory, empowerment-based approaches are generally favoured for these means. Faced with important social issues, in a context of colonisation and complex power dynamics, we question how community members experience participation, as well as the everyday dynamics that take place when attempting to create community-level change. The initial steps of this community-based participatory research (CBPR) took place over a two-year period in a community of Nunavik, a large northern region of the province of Quebec. The objective of the CBPR was to develop a community-driven project aimed at supporting families to be able to keep children within their homes or communities, rather than having to be placed under child welfare services. We participated in, and documented, various group meetings, community workshops, informal reflexive discussions, and formal interviews with community partners to explore their everyday experiences of participation in community-based change. We describe some of the initial actions taken in this project. We describe how certain social and power dynamics infiltrated into the process of participation leading to various tensions, personal and interpersonal experiences and needs. We discuss how these experiences led to everyday ethical dilemmas regarding participation. We conclude that although participatory approaches towards community change may be effective, they are also ethically challenging and at times disempowering for those who participate. We describe some of the approaches used to work with these ethical challenges.


Plaque removal with triple-headed vs single-headed manual toothbrushes-a systematic review.
The aim of this systematic review was to establish the effectiveness of brushing with a triple-headed manual toothbrush compared to a single-headed manual toothbrush on plaque removal. The MEDLINE-PubMed and Cochrane-CENTRAL databases were searched. The inclusion criteria were clinical trials conducted with humans without fixed orthodontic appliances who were not dental care professionals. Papers that evaluated the effect of toothbrushing with a triple-headed manual toothbrush compared to a single-headed manual toothbrush on plaque removal were included. Data were extracted from the eligible studies, and a descriptive analysis was performed. The search retrieved 15 eligible publications including 18 relevant comparisons. Heterogeneity was most obvious with respect to the person who performed the brushing, either the participants themselves or a caregiver responsible for daily oral hygiene. Additionally, participant characteristics such as age and individual disabilities varied. A lack of appropriate data and a variation in the indices used allowed only a descriptive analysis. Of the 14 comparisons with self-performed brushing by the participants, the majority showed no difference between triple-headed and single-headed toothbrushes, with a few favouring the triple-headed. In the comparisons in which a caregiver performed the brushing, three of the four showed that the triple-headed toothbrush performed significantly better on the reduction in plaque scores. From this review emerges the recommendation that the use of a triple-headed manual toothbrush instead of a single-headed manual toothbrush might be favorable with respect to plaque removal in case a care-dependent individual is brushed by a caregiver.


Comparison of Two-Year Outcomes of Acute Myocardial Infarction Caused by Coronary Artery Spasm Versus that Caused by Coronary Atherosclerosis.
The study compared the 2-year outcomes of patients diagnosed with acute myocardial infarction (AMI) triggered by coronary artery atherosclerosis and AMI caused by coronary artery spasm. A total of 36,797 patients in the Korea AMI Registry were grouped into 2 categories-(1) AMI due to coronary artery spasm without stenotic lesion (CAS-AMI, n = 484); and (2) AMI induced by coronary artery atherosclerosis (CAA-AMI, n = 36,313). The major clinical outcomes of the 2 groups were compared over a 2-year clinical follow-up period. Major adverse cardiac events (MACE) were defined as the composite of total death, nonfatal myocardial infarction, and repeat revascularization. The incidence of MACE (7.1% vs 11.1%; p = 0.007) and repeat revascularization (0.4% vs 4.2%; p <0.001) in the CAS-AMI group were significantly lower than in the CAA-AMI group at 2 years. However, the incidence of total death and nonfatal myocardial infarction was similar in both the groups. Aborted cardiac arrest was strongly associated with 2-year mortality in the CAS-AMI group (hazard ratios 13.5, 95% confidence interval 5.34 to 34.15, p <0.001) The incidence of MACE in CAS-AMI patients was significantly lower than in the CAA-AMI group of patients up to 2 years due to the relatively lower rate of repeat revascularization in CAS-AMI patients. However, the incidence of total death or nonfatal myocardial infarction in CAS-AMI patients was not different from that of patients with CAA-AMI.


Facile synthesis and growth mechanism of Ni-catalyzed GaAs nanowires on non-crystalline substrates.
GaAs nanowires (NWs) have been extensively explored for next generation electronics, photonics and photovoltaics due to their direct bandgap and excellent carrier mobility. Typically, these NWs are grown epitaxially on crystalline substrates, which could limit potential applications requiring high growth yield to be printable or transferable on amorphous and flexible substrates. Here, utilizing Ni as a catalytic seed, we successfully demonstrate the synthesis of highly crystalline, stoichiometric and dense GaAs NWs on amorphous SiO(2) substrates. Notably, the NWs are found to grow via the vapor-solid-solid (VSS) mechanism with non-spherical NiGa catalytic tips and low defect densities while exhibiting a narrow distribution of diameter (21.0 ± 3.9 nm) uniformly along the entire length of the NW (>10 µm). The NWs are then configured into field-effect transistors showing impressive electrical characteristics with I(ON)/I(OFF) > 10(3), which further demonstrates the purity and crystal quality of NWs obtained with this simple synthesis technique, compared to the conventional MBE or MOCVD grown GaAs NWs.


Realistically coupled neural mass models can generate EEG rhythms.
We study the generation of EEG rhythms by means of realistically coupled neural mass models. Previous neural mass models were used to model cortical voxels and the thalamus. Interactions between voxels of the same and other cortical areas and with the thalamus were taken into account. Voxels within the same cortical area were coupled (short-range connections) with both excitatory and inhibitory connections, while coupling between areas (long-range connections) was considered to be excitatory only. Short-range connection strengths were modeled by using a connectivity function depending on the distance between voxels. Coupling strength parameters between areas were defined from empirical anatomical data employing the information obtained from probabilistic paths, which were tracked by water diffusion imaging techniques and used to quantify white matter tracts in the brain. Each cortical voxel was then described by a set of 16 random differential equations, while the thalamus was described by a set of 12 random differential equations. Thus, for analyzing the neuronal dynamics emerging from the interaction of several areas, a large system of differential equations needs to be solved. The sparseness of the estimated anatomical connectivity matrix reduces the number of connection parameters substantially, making the solution of this system faster. Simulations of human brain rhythms were carried out in order to test the model. Physiologically plausible results were obtained based on this anatomically constrained neural mass model.


Changing Landscape of Liver Cancer in California: A Glimpse Into the Future of Liver Cancer in the United States.
Asians and Hispanics currently have the highest incidence rates of hepatocellular carcinoma (HCC) in the United States. The numbers of these minority populations are rapidly increasing, reshaping the demographic in the United States and particularly California, where approximately one-third of US Asians and Hispanics reside. With the changing demographic and rising incidence of HCC that has tripled during the past three decades, it is important to forecast the future burden of HCC by age, sex, and race/ethnicity to plan prevention and control strategies for HCC. We used four Surveillance, Epidemiology, and End Results Program registries to obtain incidence data for California during 2000 to 2013, and 14 registries to represent non-California states. We applied age-period-cohort models to estimate future HCC incidence rates, and estimated HCC burden by multiplying incidence forecasts by corresponding US Census population projections. Our forecasts for California suggest that in 2030 Hispanics and blacks will have the highest HCC incidence rates and Asians the lowest. While incidence among whites, blacks, and Hispanics in California increased successively for each birth year cohort from 1915 through 1955, incidence among Asians in California decreased for each successive birth year cohort from 1915 through 1975. In contrast, consistent declines were not seen among Asians in the rest of the United States. In California, the estimated burden of HCC is 6482 new cases in 2030, where 80.0% of these patients are older than 65 years (vs 44.5% in 2014). The relative increase of burden in 2030 vs 2014 for this 65 years and older age group is especially high among Hispanics (318.3%), whereas it is the lowest among Asians (53.2%) in California. Prevention efforts in California should target persons currently ages 50 to 64 years who will make up the older age group (>65 years) in 2030, especially among Hispanics with the most rapid increase of HCC burden through 2030.


Extracting drug-drug interaction from the biomedical literature using a stacked generalization-based approach.
Drug-drug interaction (DDI) detection is particularly important for patient safety. However, the amount of biomedical literature regarding drug interactions is increasing rapidly. Therefore, there is a need to develop an effective approach for the automatic extraction of DDI information from the biomedical literature. In this paper, we present a Stacked Generalization-based approach for automatic DDI extraction. The approach combines the feature-based, graph and tree kernels and, therefore, reduces the risk of missing important features. In addition, it introduces some domain knowledge based features (the keyword, semantic type, and DrugBank features) into the feature-based kernel, which contribute to the performance improvement. More specifically, the approach applies Stacked generalization to automatically learn the weights from the training data and assign them to three individual kernels to achieve a much better performance than each individual kernel. The experimental results show that our approach can achieve a better performance of 69.24% in F-score compared with other systems in the DDI Extraction 2011 challenge task.


A randomized clinical trial of alprazolam versus progressive muscle relaxation in cancer patients with anxiety and depressive symptoms.
A randomized nonblinded study was performed in three cancer centers to test over a 10-day period the efficacy of (1) a triazolobenzodiazepine, alprazolam, 0.5 mg three times a day and (2) use of a behavioral technique in which patients were trained in progressive muscle relaxation at an initial session with a behavioral psychologist and then asked to listen at home to an audiotape of the session three times a day. Of 147 cancer patients who met entry levels of distress and completed the study, uncontrolled for site or disease stage, 70 were randomized to drug, 77 to relaxation. Four measures of anxiety and depression were used: Covi, Raskin, Affects Balance, and Symptoms Checklist-90 (SCL-90). Results showed that both treatment arms resulted in significant (P less than .001) decrease in observer and patient-reported anxious and depressed mood symptoms. Although both treatment arms were effective, patients receiving the drug showed a slightly more rapid decrease in anxiety and greater reduction of depressive symptoms. These findings confirm efficacy of both alprazolam and relaxation to reduce cancer-related anxiety and depression. As safe, inexpensive, and effective interventions, physicians should consider their use in cancer patients experiencing anxiety and depressive symptoms.