The effect of a periodontal intervention on cardiovascular risk markers in Indigenous Australians with periodontal disease: the PerioCardio study.
Indigenous Australians experience an overwhelming burden of chronic disease, including cardiovascular diseases. Periodontal disease (inflammation of the tissues surrounding teeth) is also widespread, and may contribute to the risk of cardiovascular diseases via pathogenic inflammatory pathways. This study will assess measures of vascular health and inflammation in Indigenous Australian adults with periodontal disease, and determine if intensive periodontal therapy improves these measures over a 12 month follow-up. The aims of the study are: (i) to determine whether there is a dose response relationship between extent and severity of periodontal disease and measures of vascular health and inflammation among Indigenous Australian adults with moderate to severe periodontal disease; and (ii) to determine the effects of periodontal treatment on changes in measures of vascular health and inflammation in a cohort of Indigenous Australians. This study will be a randomised, controlled trial, with predominantly blinded assessment of outcome measures and blinded statistical analysis. All participants will receive the periodontal intervention benefits (with the intervention delayed 12 months in participants who are randomised to the control arm). Participants will be Indigenous adults aged ≥25 years from urban centres within the Top End of the Northern Territory, Australia. Participants assessed to have moderate or severe periodontal disease will be randomised to the study's intervention or control arm. The intervention involves intensive removal of subgingival and supragingival calculus and plaque biofilm by scaling and root-planing. Study visits at baseline, 3 and 12 months, will incorporate questionnaires, non-fasting blood and urine samples, body measurements, blood pressure, periodontal assessment and non-invasive measures of vascular health (pulse wave velocity and carotid intima-media thickness). Primary outcome measures are pulse wave velocity and carotid intima-media thickness. The study will assess the periodontal-cardiovascular disease relationship among Indigenous Australian adults with periodontal disease, and the effectiveness of an intervention aimed at improving periodontal and cardiovascular health. Efforts to understand and improve Indigenous oral health and cardiovascular risk may serve as an important means of reducing the gap between Indigenous and non-Indigenous health in Australia. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000817044.


Efficiency of peracetic acid in inactivating bacteria, viruses, and spores in water determined with ATP bioluminescence, quantitative PCR, and culture-based methods.
The disinfection efficiency of peracetic acid (PAA) was investigated on three microbial types using three different methods (filtration-based ATP (adenosine-triphosphate) bioluminescence, quantitative polymerase chain reaction (qPCR), culture-based method). Fecal indicator bacteria (Enterococcus faecium), virus indicator (male-specific (F(+)) coliphages (coliphages)), and protozoa disinfection surrogate (Bacillus subtilis spores (spores)) were tested. The mode of action for spore disinfection was visualized using scanning electron microscopy. The results indicated that PAA concentrations of 5 ppm (contact time: 5 min), 50 ppm (10 min), and 3,000 ppm (5 min) were needed to achieve 3-log reduction of E. faecium, coliphages, and spores, respectively. Scanning electron microscopy observation showed that PAA targets the external layers of spores. The lower reduction rates of tested microbes measured with qPCR suggest that qPCR may overestimate the surviving microbes. Collectively, PAA showed broad disinfection efficiency (susceptibility: E. faecium > coliphages > spores). For E. faecium and spores, ATP bioluminescence was substantially faster (∼5 min) than culture-based method (>24 h) and qPCR (2-3 h). This study suggests PAA as an effective alternative to inactivate broad types of microbial contaminants in water. Together with the use of rapid detection methods, this approach can be useful for urgent situations when timely response is needed for ensuring water quality.


Effect of Quaternary Ammonium Carboxymethylchitosan on Release Rate In-vitro of Aspirin Sustained-release Matrix Tablets.
The aim of this study was to develop a derivative of chitosan as pharmaceutical excipient used in sustained-release matrix tablets of poorly soluble drugs. A water-soluble quaternary ammonium carboxymethylchitosan was synthesized by a two-step reaction with carboxymethylchitosan (CMCTS), decylalkyl dimethyl ammonium and epichlorohydrin. The elemental analysis showed that the target product with 10.27% of the maximum grafting degree was obtained. To assess the preliminary safety of this biopolymer, cell toxicity assay was employed. In order to further investigate quaternary ammonium carboxymethylchitosan application as pharmaceutical excipient, aspirin was chosen as model drug. The effect of quaternary ammonium CMCTS on aspirin release rate from sustained-release matrix tablets was examined by in-vitro dissolution experiments. The results showed that this biopolymer had a great potential in increasing the dissolution of poorly soluble drug. With the addition of CMCTS-CEDA, the final cumulative release rate of drug rose up to 90%. After 12 h, at the grade of 10, 20 and 50 cps, the drug release rate increased from 58.1 to 90.7%, from 64.1 to 93.9%, from 69.3 to 96.1%, respectively. At the same time, aspirin release rate from sustainedrelease model was found to be related to the amount of quaternary ammonium CMCTS employed. With the increase of CMCTS-CEDA content, the accumulated release rate increased from 69.1% to 86.7%. The mechanism of aspirin release from sustained-release matrix tablets was also preliminary studied to be Fick diffusion. These data demonstrated that the chitosan derivative has positive effect on drug release from sustained-release matrix tablets.


Probucol modulates iron nitrilotriacetate (Fe-NTA)-dependent renal carcinogenesis and hyperproliferative response: diminution of oxidative stress.
Probucol is a clinically used cholesterol-lowering drug, with pronounced antioxidant properties. We have reported previously, that dietary supplementation of probucol enhances NAD(P)H:quinone reductase (Iqbal M, Okada S (2003) Pharmacol Toxicol 93:259-263) and inhibits Fe-NTA induced lipid peroxidation and DNA damage in vitro (Iqbal M, Sharma SD, Oakada (2004) Redox Rep 9:167-172). Further to this, in the present study, we evaluated the modulatory effect of probucol on iron nitrilotriacetae (Fe-NTA) dependent renal carcinogenesis, hyperproliferative response and oxidative stress. In Fe-NTA alone treated group, a 20% renal cell tumor incidence was recorded whereas, in N-diethylnitrosamine (DEN)-initiated and Fe-NTA promoted animals, the percentage tumor incidence was increased to 70% as compared with untreated controls. No tumor incidence was recorded in DEN-initiated, nonpromoted group. Diet supplemented with 1.0% probucol fed prior to, during and after Fe-NTA treatment in DEN-initiated animals afforded >65% protection in renal cell tumor incidence. Probucol fed diet pretreatment also resulted a significant and dose dependent inhibition of Fe-NTA induced renal ornithine decarboxylase (ODC) activity. In oxidative stress studies, Fe-NTA alone treatment enhanced lipid peroxidation, accompanied by a decrease in the level of GSH, activities of antioxidants and phase II metabolizing enzymes in kidney concomitant with histolopathological changes. These changes were significantly and dose-dependently alleviated by probucol fed diet. From this data, it can be concluded that probucol can modulates toxic and tumor promoting effects of Fe-NTA and can serve as a potent chemopreventive agent to suppress oxidant induced tissue injury and carcinogenesis, in addition to being a cholesterol lowering and anti-atherogenic drug.


Human immunodeficiency virus (HIV) envelope binds to CXCR4 independently of CD4, and binding can be enhanced by interaction with soluble CD4 or by HIV envelope deglycosylation.
Chemokine receptor CXCR4 (also known as LESTR and fusin) has been shown to function as a coreceptor for T-cell-tropic strains of human immunodeficiency virus type 1 (HIV-1). We have developed a binding assay to show that HIV envelope (Env) can interact with CXCR4 independently of CD4 but that this binding is markedly enhanced by the previous interaction of Env with soluble CD4. We also show that nonglycosylated HIV-1(SF-2) gp120 or sodium metaperiodate-treated oligomeric gp160 from HIV-1(451) bound much more readily to CXCR4 than their counterparts with intact carbohydrate residues did.


Knowledge of indications and utilization of EUS: a survey of oncologists in the United States.
Since its advent, endoscopic ultrasonography (EUS) has emerged as an invaluable tool in the diagnosis and management of gastrointestinal and adjacent cancers. Yet, it remains unclear how non-gastroenterologists who manage these malignancies use EUS in their practices. A link to a self-administered questionnaire, hosted on our university website, was emailed to 650 practicing medical, radiation, and surgical oncologists in the United States. Data were analyzed from 100 responses. When available, the overall utilization of EUS for staging nonsmall cell lung cancer (NSCLC) was significantly low (19.0%), although available. When EUS was unavailable, majority of the patients with pancreatobiliary cancer (79%; P<0.01) were not referred for staging, unlike those with esophageal (57.9%) and rectal cancer (73.7%) were. EUS availability did not impact its use in staging gastric cancer. Majority of the respondents thought EUS made an impact in managing patients with rectal (89.5%), esophageal (84.5%), and pancreatobiliary cancers (58.5%) but not gastric (54.7%) or NSCLC (61.5%). In staging NSCLC, endoscopic ultrasound-guided fine-needle aspirate (35.7%) and mediastinoscopy (34.7%) were noted as the most accurate for tissue sampling of lymph nodes in levels 5, 7, and 8. EUS was deemed better than computerized tomography or magnetic resonance imaging by 42% in detecting small pancreatic tumors. Majority have not referred patients for EUS-guided celiac plexus neurolysis for palliation of pain in unresectable pancreatic cancer. These data highlight the utilization of EUS that did not necessarily follow established guidelines. Further research is essential to evaluate obstacles to utilization of endoscopic ultrasound-guided fine-needle aspirate.


Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer.
The National Institute on Aging Interventions Testing Program (ITP) evaluates agents hypothesized to increase healthy lifespan in genetically heterogeneous mice. Each compound is tested in parallel at three sites, and all results are published. We report the effects of lifelong treatment of mice with four agents not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) and metformin - the latter with and without rapamycin, and two drugs previously examined: 17-α-estradiol and nordihydroguaiaretic acid (NDGA), at doses greater and less than used previously. 17-α-estradiol at a threefold higher dose robustly extended both median and maximal lifespan, but still only in males. The male-specific extension of median lifespan by NDGA was replicated at the original dose, and using doses threefold lower and higher. The effects of NDGA were dose dependent and male specific but without an effect on maximal lifespan. Protandim, a mixture of botanical extracts that activate Nrf2, extended median lifespan in males only. Metformin alone, at a dose of 0.1% in the diet, did not significantly extend lifespan. Metformin (0.1%) combined with rapamycin (14 ppm) robustly extended lifespan, suggestive of an added benefit, based on historical comparison with earlier studies of rapamycin given alone. The α-glucosidase inhibitor, acarbose, at a concentration previously tested (1000 ppm), significantly increased median longevity in males and 90th percentile lifespan in both sexes, even when treatment was started at 16 months. Neither fish oil nor UDCA extended lifespan. These results underscore the reproducibility of ITP longevity studies and illustrate the importance of identifying optimal doses in lifespan studies.


Unravelling the tangled web of hypertension and cancer.
Cardiovascular disease remains the primary cause of mortality globally, being responsible for an estimated 17 million deaths every year. Cancer is the second leading cause of death on a global level with roughly 9 million deaths per year being attributed to neoplasms. The two share multiple common risk factors such as obesity, poor physical exercise, older age, smoking and there exists rare monogenic hypertension syndromes. Hypertension is the most important risk factor for cardiovascular disease and affects more than a billion people worldwide and may also be a risk factor for the development of certain types of cancer (e.g. renal cell carcinoma (RCC)). The interaction space of the two conditions becomes more complicated when the well-described hypertensive effect of certain antineoplastic drugs is considered along with the extensive amount of literature on the association of different classes of antihypertensive drugs with cancer risk/prevention. The cardiovascular risks associated with antineoplastic treatment calls for efficient management of relative adverse events and the development of practical strategies for efficient decision-making in the clinic. Pharmacogenetic interactions between cancer treatment and hypertension-related genes is not to be ruled out, but the evidence is not still ample to be incorporated in clinical practice. Precision Medicine has the potential to bridge the gap of knowledge regarding the full spectrum of interactions between cancer and hypertension (and cardiovascular disease) and provide novel solutions through the emerging field of cardio-oncology. In this review, we aimed to examine the bidirectional associations between cancer and hypertension including pharmacotherapy.


Integrating and differentiating aspects of self-regulation: effortful control, executive functioning, and links to negative affectivity.
Subdisciplines within psychology frequently examine self-regulation from different frameworks despite conceptually similar definitions of constructs. In the current study, similarities and differences between effortful control, based on the psychobiological model of temperament (Rothbart, Derryberry, & Posner, 1994), and executive functioning are examined and empirically tested in three studies (n = 509). Structural equation modeling indicated that effortful control and executive functioning are strongly associated and overlapping constructs (Study 1). Additionally, results indicated that effortful control is related to the executive function of updating/monitoring information in working memory, but not inhibition (Studies 2 and 3). Study 3 also demonstrates that better updating/monitoring information in working memory and better effortful control were uniquely linked to lower dispositional negative affect, whereas the executive function of low/poor inhibition was uniquely associated with an increased tendency to express negative affect. Furthermore, dispositional negative affect mediated the links between effortful control and, separately, the executive function of updating/monitoring information in working memory and the tendency to express negative affect. The theoretical implications of these findings are discussed, and a potential framework for guiding future work directed at integrating and differentiating aspects of self-regulation is suggested.


The coordinate regulation of pharyngeal development in C. elegans by lin-35/Rb, pha-1, and ubc-18.
Organ development is a complex process involving the coordination of cell proliferation, differentiation, and morphogenetic events. Using a screen to identify genes that function coordinately with lin-35/Rb during animal development, we have isolated a weak loss-of-function (LOF) mutation in pha-1. lin-35; pha-1 double mutants are defective at an early step in pharyngeal morphogenesis leading to an abnormal pharyngeal architecture. pha-1 is also synthetically lethal with other class B synthetic multivulval (SynMuv) genes including the C. elegans E2F homolog, efl-1. Reporter analyses indicate that pha-1 is broadly expressed during embryonic development and that its functions reside in the cytoplasm. We also provide genetic and phenotypic evidence to support the model that PHA-1, a novel protein, and UBC-18, a ubiquitin-conjugating enzyme that we have previously shown to function with lin-35 during pharyngeal development, act in parallel pathways to regulate the activity of a common cellular target.


Anti-inflammatory activity of iridoid and catechol derivatives from Eucommia ulmoides Oliver.
Neuroinflammation and pro-inflammatory mediators play key roles in the pathogenesis of neurodegenerative diseases including stroke, which account for a significant burden of morbidity and mortality worldwide. Recently, the unsatisfactory pharmacotherapy and side effects of the drugs led to the development of alternative medicine for treating these diseases. Du Zhong (DZ), Eucommia ulmoides Oliver leaves, is a commonly used herb in the therapy of stroke in China. We hypothesize that the components from DZ inhibit neuroinflammation. In this study, DZ was extracted and the bioactive fractions with inhibitory effect on lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in BV-2 microglial cells were further separated using chromatography. Two purified bioactive compounds, genipin (compound C) and 4-(1,2-dimethoxyethyl)benzene-1,2-diol (compound F), were isolated and identified after spectroscopic analysis. The results showed that they inhibited LPS-stimulated NO and tumor necrosis factor-alpha (TNF-α) production. Genipin exerted its anti-inflammatory effects through PI3K/Akt signaling pathway, whereas compound F inhibited phosphorylation of p38 mitogen-activated protein kinase (MAPK). In conclusion, genipin and compound F have potential for developing into new drugs for treating neurodegenerative diseases.


Inequities in under-five mortality in Nigeria: differentials by religious affiliation of the mother.
Observations in Nigeria have indicated polio vaccination refusal related to religion that ultimately affected child morbidity and mortality. This study assessed the role of religion in under-five (0-59 months) mortality using a cross-sectional, nationally representative sample of 7,620 women aged 15-49 years from the 2003 Nigeria Demographic and Health Survey and included 6,029 children. Results show that mother's affiliation to Traditional indigenous religion is significantly associated with increased under-five mortality. Multivariable modelling demonstrated that this association is explained by differential use of maternal and child health services, specifically attendance to prenatal care. To reduce child health inequity, these results need to be incorporated in the formulation of child health policies geared towards achieving a high degree of attendance to prenatal care, irrespective of religious affiliation.


Low back pain risk factors in a large rural Australian Aboriginal community. An opportunity for managing co-morbidities?
Low back pain (LBP) is the most prevalent musculo-skeletal condition in rural and remote Australian Aboriginal communities. Smoking, physical inactivity and obesity are also prevalent amongst Indigenous people contributing to lifestyle diseases and concurrently to the high burden of low back pain. This paper aims to examine the association between LBP and modifiable risk factors in a large rural Indigenous community as a basis for informing a musculo-skeletal and related health promotion program. A community Advisory Group (CAG) comprising Elders, Aboriginal Health Workers, academics, nurses, a general practitioner and chiropractors assisted in the development of measures to assess self-reported musculo-skeletal conditions including LBP risk factors. The Kempsey survey included a community-based survey administered by Aboriginal Health Workers followed by a clinical assessment conducted by chiropractors. Age and gender characteristics of this Indigenous sample (n = 189) were comparable to those reported in previous Australian Bureau of Statistics (ABS) studies of the broader Indigenous population. A history of traumatic events was highly prevalent in the community, as were occupational risk factors. Thirty-four percent of participants reported a previous history of LBP. Sporting injuries were associated with multiple musculo-skeletal conditions, including LBP. Those reporting high levels of pain were often overweight or obese and obesity was associated with self-reported low back strain. Common barriers to medical management of LBP included an attitude of being able to cope with pain, poor health, and the lack of affordable and appropriate health care services. Though many of the modifiable risk factors known to be associated with LBP were highly prevalent in this study, none of these were statistically associated with LBP. Addressing particular modifiable risk factors associated with LBP such as smoking, physical inactivity and obesity may also present a wider opportunity to prevent and manage the high burden of illness imposed by co-morbidities such as heart disease and type-2 diabetes.


The F-box protein Cdc4/Fbxw7 is a novel regulator of neural crest development in Xenopus laevis.
The neural crest is a unique population of cells that arise in the vertebrate ectoderm at the neural plate border after which they migrate extensively throughout the embryo, giving rise to a wide range of derivatives. A number of proteins involved in neural crest development have dynamic expression patterns, and it is becoming clear that ubiquitin-mediated protein degradation is partly responsible for this. Here we demonstrate a novel role for the F-box protein Cdc4/Fbxw7 in neural crest development. Two isoforms of Xenopus laevis Cdc4 were identified, and designated xCdc4alpha and xCdc4beta. These are highly conserved with vertebrate Cdc4 orthologs, and the Xenopus proteins are functionally equivalent in terms of their ability to degrade Cyclin E, an established vertebrate Cdc4 target. Blocking xCdc4 function specifically inhibited neural crest development at an early stage, prior to expression of c-Myc, Snail2 and Snail. We demonstrate that Cdc4, an ubiquitin E3 ligase subunit previously identified as targeting primarily cell cycle regulators for proteolysis, has additional roles in control of formation of the neural crest. Hence, we identify Cdc4 as a protein with separable but complementary functions in control of cell proliferation and differentiation.


Is that me or my twin? Lack of self-face recognition advantage in identical twins.
Despite the increasing interest in twin studies and the stunning amount of research on face recognition, the ability of adult identical twins to discriminate their own faces from those of their co-twins has been scarcely investigated. One's own face is the most distinctive feature of the bodily self, and people typically show a clear advantage in recognizing their own face even more than other very familiar identities. Given the very high level of resemblance of their faces, monozygotic twins represent a unique model for exploring self-face processing. Herein we examined the ability of monozygotic twins to distinguish their own face from the face of their co-twin and of a highly familiar individual. Results show that twins equally recognize their own face and their twin's face. This lack of self-face advantage was negatively predicted by how much they felt physically similar to their co-twin and by their anxious or avoidant attachment style. We speculate that in monozygotic twins, the visual representation of the self-face overlaps with that of the co-twin. Thus, to distinguish the self from the co-twin, monozygotic twins have to rely much more than control participants on the multisensory integration processes upon which the sense of bodily self is based. Moreover, in keeping with the notion that attachment style influences perception of self and significant others, we propose that the observed self/co-twin confusion may depend upon insecure attachment.


Pooled analysis of NAT2 genotypes as risk factors for asbestos-related malignant mesothelioma.
Malignant mesothelioma (MM) is a rare and aggressive tumor of the pleura. The most important causal factor for the development of MM is occupational exposure to asbestos. Different lines of evidence suggest a role of genetic background in MM development, as for other cancers. Two published studies observed an association between MM and N-acetyl-transferase 2 (NAT2) polymorphisms. First, a Finnish study observed that the NAT2 slow acetylator phenotype was associated with an increased risk of MM. Conversely, MM risk was higher in Italian subjects carrying the NAT2 fast acetylator genotypes. The conflicting results obtained in Finland and Italy could be ascribed to random chance, considering the small panel of patients and controls in the two studies, but also ethnic or other differences may have been important. To ascertain the role of NAT2 genotype, we performed a study on 252 MM patients and 262 controls recruited in two Northern Italy areas that were characterized by high asbestos exposure, due to intense industrial activities (an asbestos cement factory in Casale Monferrato, mainly shipyards and refineries in Liguria). Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). NAT2 fast acetylator genotypes showed an increased OR, although not statistically significant, both in asbestos-exposed subjects (OR=1.47; 95% CI=0.96-2.26) and in the entire population (OR=1.38; 95% CI=0.93-2.04). These results suggest that NAT2 polymorphisms do not exert a strong effect on individual susceptibility to MM.


Pre-treatment evaluation of basal cell carcinoma for photodynamic therapy: comparative measurement of tumour thickness in punch biopsy and excision specimens.
Tumour thickness affects the outcome of photodynamic therapy in basal cell carcinoma (BCC). The aim of this study was to evaluate whether punch biopsy provides reliable information on BCC tumour thickness, by comparing corresponding measurements in biopsy and excision specimens for 48 lesions in 43 patients. BCC tumours were between 0.2 and 6.1 mm thick. The mean depth of the excisions were 0.14 mm greater than that of the biopsies. Bland-Altman 95% limits of agreement were (-1.3, 1.6) mm, but the difference between measurements increased with tumour thickness. A punch biopsy tumour thickness of 1.0 mm yielded an upper 95% predicted limit for excision depth within 2.0 mm. In conclusion, there was reasonable overall agreement between corresponding measurements. A biopsy thickness of 1.0 mm suggests that the tumour will most likely be within the current accepted limits for photodynamic therapy. With increasing tumour thickness, however, individual tumour measurements may differ considerably.


An invitation to die: initiators of sociality in a social amoeba become selfish spores.
Greater size and strength are common attributes of contest winners. Even in social insects with high cooperation, the right to reproduce falls to the well-fed queens rather than to poorly fed workers. In Dictyostelium discoideum, formerly solitary amoebae aggregate when faced with starvation, and some cells die to form a stalk which others ride up to reach a better location to sporulate. The first cells to starve have lower energy reserves than those that starve later, and previous studies have shown that the better-fed cells in a mix tend to form disproportionately more reproductive spores. Therefore, one might expect that the first cells to starve and initiate the social stage should act altruistically and form disproportionately more of the sterile stalk, thereby enticing other better-fed cells into joining the aggregate. This would resemble caste determination in social insects, where altruistic workers are typically fed less than reproductive queens. However, we show that the opposite result holds: the first cells to starve become reproductive spores, presumably by gearing up for competition and outcompeting late starvers to become prespore first. These findings pose the interesting question of why others would join selfish organizers.


Exploring the sustainability of estonian forestry: the socioeconomic drivers.
Forestry as an important industry has both direct as well as indirect effects on the Estonian economy. It is therefore essential that it is sustainably managed so that it can continue to contribute to the economy in the future. The first aim of this article is to establish the situation regarding felling and regeneration in Estonia. As the available forestry statistics display discrepancies and lack consistency, it was as a necessary first step to gather information about and analyze the validity and reliability of the prime data to make the data sets useful for comparison over time and establish the current trends in Estonian forestry. However, with the help of interviews we are able to show that economic instability in Estonia brings with it increased logging rates and hinders investments into regeneration and maintenance. The problems are particularly pronounced in private forestry. Second, the article seeks to explain the socioeconomic reasons behind this situation. Economic problems among private owners, a liberal forestry policy, together with rapid land reform and weak enforcement of forestry legislation are some of the reasons that can explain the forestry trends in Estonia.


The impact of pathological narcissism on psychotherapy utilization, initial symptom severity, and early-treatment symptom change: a naturalistic investigation.
The impact of pathological narcissism on psychotherapy has seldom been investigated empirically, despite extensive clinical theory proposing that highly narcissistic individuals should be reluctant to engage in treatment and derive smaller benefits from therapy. In this study, we investigate the relationship between scores on the Pathological Narcissism Inventory (PNI; Pincus et al., 2009), which assesses both narcissistic grandiosity and narcissistic vulnerability, and clinical variables in a sample of outpatients (N=60) at a community mental health center. Results indicated that grandiosity, but not vulnerability, was negatively related to the use of adjunctive services and positively predicted client-initiated termination of psychotherapy. In addition, grandiosity and vulnerability were related to initial levels of different symptoms in multilevel models using a subsample (n=41) but not generally related to the linear rate of symptom change in early psychotherapy. The results highlight the clinical utility of assessing pathological narcissism in a real-world psychotherapeutic context.


The role of gene sculptor microRNAs in human precancerous lesions.
MicroRNAs (miRNAs) are small noncoding RNAs. These noncoding RNAs regulate the expression of target genes and inhibit the translation of target proteins at the post-transcriptional level. miRNAs also play an important role in human health, from the development and differentiation of cells to the occurrence and progression of disorders such as cancer, cardiovascular diseases, and neurodegenerative diseases. Precancerous lesions are lesions prior to invasive carcinomas, and carcinogenesis is a very complicated process, which is multistage and the result of multigene synergy. miRNAs exert effects as both oncogenes and tumor suppressor genes by regulating target genes involved in signaling pathways. Hence, precancerous lesions are accompanied by relevant miRNA changes. Based on the morphology of miRNAs in vivo and the specificity of miRNA, various novel miRNA analysis methods have been developed, including reverse transcription quantitative PCR, enzyme analysis, molecular beacons, and deep sequencing. For example, in the laryngeal epithelial precancerous lesions, the data demonstrate that the expression of miR-10a-5p is downregulated and miR-484 is the most abundant miRNA in hepatic precancerous lesions. In this review, we discuss the functional roles of miRNAs in human precancerous lesions.


PCR protocol for detection of Vibrio ordalii by amplification of the vohB (hemolysin) gene.
Vibrio ordalii is the causative agent of atypical vibriosis and has the potential to cause severe losses in salmonid aquaculture. To prevent and control outbreaks, a rapid, reproducible, sensitive, and effective diagnostic method is needed. We evaluated a new conventional polymerase chain reaction (PCR) and real-time PCR (qPCR) protocol using a primer set (VohB_Fw-VohB_Rv) designed to amplify a 112 bp fragment flanking the vohB gene (coding for hemolysin production), against 24 V. ordalii strains isolated from different fish species, the V. ordalii type strain, and 42 representative related and unrelated bacterial species. The primer set was species-specific, recognizing all V. ordalii strains evaluated, with no cross-reaction with the other bacterial species. A sensitivity of 103 copies of the vohB gene was obtained with a standard curve. When the VohB_Fw-VohB_Rv qPCR protocol was applied to Atlantic salmon seeded tissues (kidney, liver, spleen, and muscle), the detection limit ranged from 5.27 × 102 to 4.13 × 103 V. ordalii CFU ml-1, i.e. 62 to 145 copies of the vohB gene, using the previously calculated standard curve. The conventional PCR also detected V. ordalii, but the total reaction time was 1 h longer. When the qPCR protocol was applied to naturally infected cage-cultured Atlantic salmon samples, 5 of 8 fish tested positive for V. ordalii, but only one of them was diagnosed as positive by direct cultivation on agar. We conclude that the PCR protocol evaluated is fast, specific, and sensitive enough to detect V. ordalii in infected tissues and is an important tool for secure diagnosis of atypical vibriosis, and is therefore helpful for the control of the disease through the prompt detection within fish populations.


Infrared thermometry for lesion monitoring in cattle lameness.
Infrared thermometry is a non-invasive tool shown to be useful in detecting claw abnormalities in cattle at an individual and herd level. This study used the technology to monitor foot temperature and investigate the association with lesion presence over time. A 990 cow dairy herd was enrolled and followed for six months, with data collection fortnightly, lesions were identified by examination of any cow with a mobility score >2, using the 0-3 scale. Two level, multilevel analysis of the association between ambient temperature and foot temperature found that the former was a significant predictor of the latter (coefficient estimate (se)=0.277 (0.02)). Actual foot temperatures were calculated by adjusting for this covariate to allow monitoring over time. Presence of a lesion was also found to be a significant predictor of foot temperature (coefficient estimate (se)=0.623 (0.19)), when added to the model, furthermore some lesion types, claw horn and multiple lesions, were found to be associated with differential foot temperatures. When monitoring lesions over time, the mean adjusted foot temperature was highest at the point of lesion identification. A marked drop in temperature then followed after the lesion was trimmed, with the lowest mean temperature recorded six weeks after treatment, significantly different from the point of lesion identification (P=0.003). This temperature was also lower than the six weeks prior to diagnosis of the lesion, suggesting inflammation was present for at least six weeks prior to the behavioural sign of lameness was seen.


Deep and highly sensitive proteome coverage by LC-MS/MS without prefractionation.
In-depth MS-based proteomics has necessitated fractionation of either proteins or peptides or both, often requiring considerable analysis time. Here we employ long liquid chromatography runs with high resolution coupled to an instrument with fast sequencing speed to investigate how much of the proteome is directly accessible to liquid chromatography-tandem MS characterization without any prefractionation steps. Triplicate single-run analyses identified 2990 yeast proteins, 68% of the total measured in a comprehensive yeast proteome. Among them, we covered the enzymes of the glycolysis and gluconeogenesis pathway targeted in a recent multiple reaction monitoring study. In a mammalian cell line, we identified 5376 proteins in a triplicate run, including representatives of 173 out of 200 KEGG metabolic and signaling pathways. Remarkably, the majority of proteins could be detected in the samples at sub-femtomole amounts and many in the low attomole range, in agreement with absolute abundance estimation done in previous works (Picotti et al. Cell, 138, 795-806, 2009). Our results imply an unexpectedly large dynamic range of the MS signal and sensitivity for liquid chromatography-tandem MS alone. With further development, single-run analysis has the potential to radically simplify many proteomic studies while maintaining a systems-wide view of the proteome.


The full-length calcium-sensing receptor dampens the calcemic response to 1alpha,25(OH)2 vitamin D3 in vivo independently of parathyroid hormone.
1Alpha,25(OH)(2) vitamin D(3) [1,25(OH)(2)D(3)] increases serum Ca(2+) concentration in vivo, an action counteracted by activation of the Ca(2+)-sensing receptor (CaSR), which decreases parathyroid hormone (PTH) secretion and increases renal Ca(2+) excretion. Relatively little is known of the role the CaSR plays in this response through its potentially direct actions in kidney, gut, and bone independently of PTH. We report PTH-independent roles of the CaSR in modulating the response to exogenous 1,25(OH)(2)D(3) in mice with targeted disruption of both the CaSR and PTH genes (C(-)P(-)) compared with that in mice with disruption of the PTH gene alone (C(+)P(-)) or wild-type mice (C(+)P(+)). After intraperitoneal injection of 0.5 ng/g body wt 1,25(OH)(2)D(3), peak calcemic responses were observed at 24 h in all three genotypes in association with 1) a greater increase in serum Ca(2+) in C(-)P(-) mice than in the other genotypes on a Ca(2+)-replete diet that was attenuated by a Ca(2+)-deficient diet and pamidronate, 2) increased urinary Ca(2+)-to-creatinine ratios (UCa/Cr) in the C(+)P(-) and C(+)P(+) mice but a lowered ratio in the C(-)P(-) mice on a Ca(2+)-replete diet, and 3) no increase in calcitonin (CT) secretion in the C(+)P(+) and C(+)P(-) mice and a small increase in the C(-)P(-) mice. PTH deficiency had the anticipated effects on the expression of key genes involved in Ca(2+) transport at baseline in the duodenum and kidney, and injection of 1,25(OH)(2)D(3) increased gene expression 8 h later. However, the changes in the genes evaluated did not fully explain the differences in serum Ca(2+) seen among the genotypes. In conclusion, mice lacking the full-length CaSR have increased sensitivity to the calcemic action of 1,25(OH)(2)D(3) in the setting of PTH deficiency. This is principally from enhanced 1,25(OH)(2)D(3)-mediated gut Ca(2+) absorption and decreased renal Ca(2+) excretion, without any differences in bone-related release of Ca(2+) or CT secretion among the three genotypes that could explain the differences in their calcemic responses.


N-[4-(9-Chloro-quino[3,2-b]benzo[1,4]thia-zin-6-yl)but-yl]acetamide.
In the title mol-ecule, C21H20ClN3OS, the tetra-cyclic system is close to planar [r.m.s. deviation = 0.110 (4) Å]. The dihedral angle between the quinoline ring system and the benzene ring is 178.3 (1)° and the angle between two (S-C=C-N) halves of the thia-zine ring is 173.4 (1)°. In the crystal, mol-ecules are arranged via π-π inter-actions [centroid-centroid distances = 3.603 (2)-3.739 (2) Å] into slipped stacks extending along [010]. Inter-molecular N-H⋯O hydrogen bonds link the amide groups of neighbouring mol-ecules along the stack, generating a C(4) motif. The title compound shows promising anti-proliferative and anti-cancer activity.


Increased frequencies of hysterectomy and early menopause in fibromyalgia patients: a comparative study.
The objective was to determine the relationship between symptoms of fibromyalgia (FM) and early menopause and hysterectomy. We included 115 postmenopausal patients with FM (mean age 54.6 +/- 7.6) and 67 rheumatoid arthritis (RA) patients (mean age 55.5 +/- 9) into our study. All patients were questioned about the severity of their symptoms of FM, anxiety, and depression by using a visual analog scale and FM impact questionnaire. Patients' history of menopause and hysterectomy were recorded. Menopause (<or=45 years) was accepted to be early. The frequencies of early menopause (38.3% vs. 13.4%, p = 0.001) and hysterectomy (16.5% vs. 6%, p = 0.039) in FM patients were significantly higher than in RA patients. While chronic widespread pain and other FM-related symptoms started after menopause in 58.3% of FM patients, the disease started after menopause in 64.2% of RA patients (p > 0.05). FM-related symptoms started in 30 patients (26.1%) with FM with menopause or within the first postmenopausal year. When the clinical features of FM patients whose symptoms started within the first menopausal year were compared to other FM patients; it was observed that the frequency of early menopause was higher in the former group (p = 0.048). Duke anxiety and depression score was higher in patients with hysterectomy whose FM symptoms started within the first year of post-hysterectomy than other FM patients (9.1 +/- 2.7 vs. 6.7 +/- 2.7, p = 0.022). Early menopause and hysterectomy may be one of the factors contributing to the development of FM.


Beta-glucans from oats and/or barley in a ready-to-eat cereal manufactured via pressure cooking and reduction of blood-glucose rise after consumption: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006.
Following an application from Nestlé S.A. submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to beta-glucans from oats and/or barley in a ready-to-eat cereal manufactured via pressure cooking and reduction of blood glucose rise after consumption. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed is 'beta-glucans from oats and/or barley incorporated into ready-to-eat breakfast cereals manufactured via pressure cooking'. The applicant proposed that at least 1.3 g of beta-glucans/25 g of available carbohydrates in ready-to-eat breakfast cereals manufactured via pressure cooking should be consumed. Beta-glucans from oats, barley or any combination thereof incorporated into ready-to-eat cereals manufactured by pressure cooking, are sufficiently characterised. The claimed effect proposed is 'reduction of the blood glucose rise after the meal'. The reduction of post-prandial glycaemic responses (as long as post-prandial insulinaemic responses are not disproportionally increased) may be a beneficial physiological effect. One human intervention study showed an effect of beta-glucans from oats and/or barley, incorporated into breakfast cereals manufactured via pressure cooking at a level of at least 1.2 g/25 g available carbohydrates, on decreasing post-prandial glycaemic responses without disproportionally increasing insulinaemic responses. Dose-response relationships were not tested, and no evidence has been provided that beta-glucans incorporated into cereals processed using pressure cooking would exert a higher effect on post-prandial glucose responses than beta-glucans added to other carbohydrate containing foods. Whereas the effect of beta-glucans in reducing post-prandial blood glucose responses is well established, the evidence provided is insufficient to establish such an effect at doses of 1.3 g beta-glucans per 25 g of available carbohydrate incorporated into ready-to-eat breakfast cereals manufactured via pressure cooking (i.e. either batch cooking or extrusion).


Predicting success on conditional release for insanity acquittees: regionalized versus nonregionalized hospital patients.
This research compared the outcomes of two cohorts of insanity acquittees: one group was treated solely in the maximum security state forensic hospital before their release to the community (nonregionalized) and the other group was treated at the state forensic hospital and transferred for further treatment at less secure state regional hospitals (regionalized). This research describes the outcome of a group of insanity acquittees (regionalized patients) never previously studied. The applicability of a prediction model based on earlier research of insanity acquittees was tested on the patients. Findings on four outcome indicators are reported: rearrests within five years after release, overall functioning in the community five years after release, rehospitalizations for mental illness, and successful completion of the terms of the five-year conditional release (nonrevocation). Discriminant analysis was performed on the four outcome variables. The model was found to accurately predict the four types of outcome from 69 percent to 94 percent accurately for the nonregionalized insanity acquittees and from 87.5 percent to 95.8 percent for the regionalized patients. This model is currently being adapted to classify patients into potential high- and low-risk groups at the time of conditional release for the purpose of determining the intensity of outpatient supervision.


Genetic polymorphisms and the impact of a higher clopidogrel dose regimen on active metabolite exposure and antiplatelet response in healthy subjects.
A double-blind crossover study was conducted in four CYP2C19 genotype-defined metabolizer groups to assess whether increase in clopidogrel dosing can overcome reduced pharmacodynamic response in CYP2C19 poor metabolizers (PMs). Ten healthy subjects in each of four metabolizer groups were randomized to a clopidogrel regimen of a 300-mg loading dose (LD) and a 75-mg/day maintenance dose (MD) for 4 days followed by 600-mg LD and 150 mg/day MD, or vice versa. The exposure levels of clopidogrel's active metabolite H4 (clopi-H4) in PMs were 71% lower on the 75-mg/day regimen and 64% lower on the 150-mg/day regimen than the corresponding exposure levels in extensive metabolizers (EMs). In PMs, the maximal platelet aggregation (MPA) induced by adenosine diphosphate (ADP) 5 µmol/l was 10.5% lower on the 75-mg/day regimen and 7.9% lower on the 150-mg/day regimen than the corresponding values in EMs. PMs who were on the clopidogrel regimen of 600-mg LD/150 mg/day MD showed clopi-H4 exposure and MPA levels similar to those in EMs who were on the regimen of 300-mg LD/75 mg/day MD. In a pooled analysis evaluating CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A5, CYP2D6, ABCB1, and P2RY12 polymorphisms (N = 396 healthy subjects), only CYP2C19 had a significant impact on antiplatelet response. In healthy CYP2C19 PMs, a clopidogrel regimen of 600-mg LD/150 mg/day MD largely overcomes diminished clopi-H4 exposure and antiplatelet response, as assessed by MPA levels.


Primary stability of inferior tilt fixation of the glenoid component in reverse total shoulder arthroplasty: A finite element study.
Glenoid component fixation with inferior tilt has been suggested as one of the surgical methods to decrease scapular notching and improve stability, but its clinically beneficial effect remains a concern. We evaluated the influence of inferior tilt fixation of the glenoid component on primary stability in reverse total shoulder arthroplasty by finite element analysis. Finite element models were constructed from cadaveric scapulae of females over the age of 60 years and glenoid components from reverse total shoulder arthroplasty. The relative micromotion at the bone-glenoid component interface, distribution of bone stress under the glenoid component and around the screws, contact area between the bone and screws, and cut surface area of the cancellous bone exposed after glenoid reaming were analyzed and compared between a neutral and 10° inferior tilt fixation of the glenoid component. The 10° inferior tilt fixation demonstrated greater relative micromotion and higher bone stress than the neutral tilt fixation. Eccentric reaming, which is done to produce the inferior tilt fixation of the glenoid component, increased glenoid cancellous bone exposure and decreased bone-screws contact area. Inferior tilt fixation of the glenoid component may adversely affect primary stability and longevity after reverse total shoulder arthroplasty. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1061-1068, 2016.


Central serotonin and melanocortin pathways regulating energy homeostasis.
It is now established that the hypothalamus is essential in coordinating endocrine, autonomic, and behavioral responses to changes in energy availability. However, the interaction of key peptides, neuropeptides, and neurotransmitters systems within the hypothalamus has yet to be delineated. Recently, we investigated the mechanisms through which central serotonergic (5-hydroxytryptamine, 5-HT) systems recruit leptin-responsive hypothalamic pathways, such as the melanocortin systems, to affect energy balance. Through a combination of functional neuroanatomy, feeding, and electrophysiology studies in rodents, we found that 5-HT drugs require functional melanocortin pathways to exert their effects on food intake. Specifically, we observed that anorectic 5-HT drugs activate pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (Arc). We provide evidence that the serotonin 2C receptor (5-HT(2C)R) is expressed on POMC neurons and contributes to this effect. Finally, we found that 5-HT drug-induced hypophagia is attenuated by pharmacological or genetic blockade of downstream melanocortin 3 and 4 receptors. We review candidate brain regions expressing melanocortin 3 and 4 receptors that play a role in energy balance. A model is presented in which activation of the melanocortin system is downstream of 5-HT and is necessary to produce the complete anorectic effect of 5-HT drugs. The data reviewed in this paper incorporate the central 5-HT system to the growing list of metabolic signals that converge on melanocortin neurons in the hypothalamus.


The inconstancy of the transient climate response parameter under increasing CO2.
In the Coupled Model Intercomparison Project Phase 5 (CMIP5), the model-mean increase in global mean surface air temperature T under the 1pctCO2 scenario (atmospheric CO(2) increasing at 1% yr(-1)) during the second doubling of CO(2) is 40% larger than the transient climate response (TCR), i.e. the increase in T during the first doubling. We identify four possible contributory effects. First, the surface climate system loses heat less readily into the ocean beneath as the latter warms. The model spread in the thermal coupling between the upper and deep ocean largely explains the model spread in ocean heat uptake efficiency. Second, CO(2) radiative forcing may rise more rapidly than logarithmically with CO(2) concentration. Third, the climate feedback parameter may decline as the CO(2) concentration rises. With CMIP5 data, we cannot distinguish the second and third possibilities. Fourth, the climate feedback parameter declines as time passes or T rises; in 1pctCO2, this effect is less important than the others. We find that T projected for the end of the twenty-first century correlates more highly with T at the time of quadrupled CO(2) in 1pctCO2 than with the TCR, and we suggest that the TCR may be underestimated from observed climate change.


Male-like sexual behavior of female mouse lacking fucose mutarotase.
Mutarotases are recently characterized family of enzymes that are involved in the anomeric conversions of monosaccharides. The mammalian fucose mutarotase (FucM) was reported in cultured cells to facilitate fucose utilization and incorporation into protein by glycosylation. However, the role of this enzyme in animal has not been elucidated. We generated a mutant mouse specifically lacking the fucose mutarotase (FucM) gene. The FucM knockout mice displayed an abnormal sexual receptivity with a drastic reduction in lordosis score, although the animals were fertile due to a rare and forced intromission by a typical male. We examined the anteroventral periventricular nucleus (AVPv) of the preoptic region in brain and found that the mutant females showed a reduction in tyrosine hydoxylase positive neurons compared to that of a normal female. Furthermore, the mutant females exhibited a masculine behavior, such as mounting to a normal female partner as well as showing a preference to female urine. We found a reduction of fucosylated serum alpha-fetoprotein (AFP) in a mutant embryo relative to that of a wild-type embryo. The observation that FucM-/- female mouse exhibits a phenotypic similarity to a wild-type male in terms of its sexual behavior appears to be due to the neurodevelopmental changes in preoptic area of mutant brain resembling a wild-type male. Since the previous studies indicate that AFP plays a role in titrating estradiol that are required to consolidate sexual preference of female mice, we speculate that the reduced level of AFP in FucM-/- mouse, presumably resulting from the reduced fucosylation, is responsible for the male-like sexual behavior observed in the FucM knock-out mouse.


Low-Frequency Mutational Heterogeneity of Invasive Ductal Carcinoma Subtypes: Information to Direct Precision Oncology.
Information regarding the role of low-frequency hotspot cancer-driver mutations (CDMs) in breast carcinogenesis and therapeutic response is limited. Using the sensitive and quantitative Allele-specific Competitor Blocker PCR (ACB-PCR) approach, mutant fractions (MFs) of six CDMs (PIK3CA H1047R and E545K, KRAS G12D and G12V, HRAS G12D, and BRAF V600E) were quantified in invasive ductal carcinomas (IDCs; including ~20 samples per subtype). Measurable levels (i.e., ≥ 1 × 10-5, the lowest ACB-PCR standard employed) of the PIK3CA H1047R, PIK3CA E545K, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E mutations were observed in 34/81 (42%), 29/81 (36%), 51/81 (63%), 9/81 (11%), 70/81 (86%), and 48/81 (59%) of IDCs, respectively. Correlation analysis using available clinicopathological information revealed that PIK3CA H1047R and BRAF V600E MFs correlate positively with maximum tumor dimension. Analysis of IDC subtypes revealed minor mutant subpopulations of critical genes in the MAP kinase pathway (KRAS, HRAS, and BRAF) were prevalent across IDC subtypes. Few triple-negative breast cancers (TNBCs) had appreciable levels of PIK3CA mutation, suggesting that individuals with TNBC may be less responsive to inhibitors of the PI3K/AKT/mTOR pathway. These results suggest that low-frequency hotspot CDMs contribute significantly to the intertumoral and intratumoral genetic heterogeneity of IDCs, which has the potential to impact precision oncology approaches.


Accidental injection of succinylcholine into epidural space as a test dose.
Inadvertent injection of nonepidural drugs into the epidural space is a rare situation, which is under-reported, and can lead to serious complications, such as cardiovascular and respiratory complications, paraplegia, or quadriplegia, and can worsen the patients' outcome from surgery. Succinylcholine administered epidurally leads to the appearance of fasciculation and shortness of breath and can prolong neuromuscular blockade. We report a case of accidental administration of 100 mg of succinylcholine via an epidural catheter as a test dose instead of 2 ml 0.5% bupivacaine in a patient planned for major abdominal surgery. After 2 min, the patient complained of shortness of breath; dysarthria; and fasciculation in the trunk, upper limbs, and face. This was managed with induction to general anesthesia (GA). In the postoperative period, no neurological or cardiovascular complications were observed. There is no adequate drug as an antidote of accidentally given nonepidural drugs via an epidural catheter. Succinylcholine given via epidural catheter has been shown to prolong neuromuscular blockade. Proper labeling and storage of syringes are of utmost importance for avoiding these unpleasant situations.


Clinicodemographic Profile of Children with Seizures in a Tertiary Care Hospital: A Cross-Sectional Observational Study.
Seizures are one of the common causes for hospital admissions in children with significant mortality and morbidity. This study was conducted to study the prevalence and clinicodemographic profile of children with seizures in a tertiary care hospital of western Nepal. This prospective cross-sectional study conducted over a period of 2 years included all admitted children (2 months-16 years) with seizures. Among 4962 admitted children, seizures were present in 3.4% (n = 168) of children, with male preponderance. 138 (82.1%) children had generalized tonic-clonic seizures (GTCS) and 30 (17.9%) children had partial seizures. GTCS were more common than partial seizures in both sexes (male = 82.7%; female = 81.2%) and age groups. There was no statistical significance in the distribution of seizures (GTCS and partial seizures) with sexes (P = 0.813) and age groups (P = 0.955). Mean ages of children having GTCS and partial seizures were 8.2 ± 4.6 years and 8.2 ± 4.2 years, respectively. Loss of consciousness (55.4%), fever (39.9%), vomiting (35.1%), and headache (16.1%) were common complaints in seizure patients. Significant number of GTCS cases had fever (P = 0.041) and neurocysticercosis (n = 72; 43%) was the most common etiology in seizure patients. Idiopathic epilepsy (38 (22.6%)), meningoencephalitis (26 (15.5%)), and febrile convulsions (14 (8.33%)) were other leading disorders in children with seizures.


Exploring psychosocial predictors of STI testing in University students.
To explore university students' Sexually Transmitted Infection (STI) testing knowledge, psychosocial and demographic predictors of past STI testing behaviour, intentions to have an STI test, and high risk sexual behaviour, to inform interventions promoting STI testing in this population. A cross-sectional, quantitative online survey was conducted in March 2016, recruiting university students from North East Scotland via an all-student email. The anonymous questionnaire assessed student demographics (e.g. sex, ethnicity, age), STI testing behaviours, sexual risk behaviours, knowledge and five psychological constructs thought to be predictive of STI testing from theory and past research: attitudes, perceived susceptibility to STIs, social norms, social fear and self-efficacy. The sample contained 1294 sexually active students (response rate 10%) aged 18-63, mean age = 23.61 (SD 6.39), 888 (69%) were female. Amongst participants, knowledge of STIs and testing was relatively high, and students held generally favourable attitudes. 52% reported ever having an STI test, 13% intended to have one in the next month; 16% reported unprotected sex with more than one 'casual' partner in the last six months. Being female, older, a postgraduate, longer UK residence, STI knowledge, perceived susceptibility, subjective norms, attitudes and self-efficacy all positively predicted past STI testing behaviour (p < 0.01). Perceived susceptibility to STIs and social norms positively predicted intentions to have an STI test in the next month (p < 0.05); perceived susceptibility also predicted past high-risk sexual behaviour (p < 0.01). Several psychosocial predictors of past STI testing, of high-risk sexual behaviour and future STI intentions were identified. Health promotion STI testing interventions could focus on male students and target knowledge, attitude change, and increasing perceived susceptibility to STIs, social norms and self-efficacy towards STI-testing.


Membrane glycomics reveal heterogeneity and quantitative distribution of cell surface sialylation.
Given that unnatural sugar expression is metabolically achieved, the kinetics and disposition of incorporation can lend insight into the temporal and localization preferences of sialylation across the cell surface. However, common detection schemes lack the ability to detail the molecular diversity and distribution of target moieties. Here we employed a mass spectrometric approach to trace the placement of azido sialic acids on membrane glycoconjugates, which revealed substantial variations in incorporation efficiencies between N-/O-glycans, glycosites, and glycosphingolipids. To further explore the propensity for sialylation, we subsequently mapped the native glycome of model epithelial cell surfaces and illustrate that while glycosylation sites span broadly across the extracellular region, a higher number of heterogeneous glycoforms occur on sialylated sites closest to the transmembrane domain. Beyond imaging techniques, this integrative approach provides unprecedented details about the frequency and structure-specific distribution of cell surface sialylation, a critical feature that regulates cellular interactions and homeostatic pathways.


Improvement of the intersection method for the quantification of filamentous organisms: basis and practice for bulking and foaming bioindication purposes.
Bulking and foaming phenomena in activated sludge wastewater treatment plants are in most cases related to the abundance of filamentous microorganisms. Quantifying these microorganisms should be a preliminary stage in their control. In this paper, the simplicity of quantifying them based on the intersection method is demonstrated, by redescribing the theory and applying a new improved protocol; new data of interest are also provided. The improved method allows us to use it with stained smears, including epifluorescence techniques. The error that could be made, when considering the distribution of filamentous bacteria in fresh microscope preparations in two dimensions rather than three is negligible. The effect of the different types of filamentous microorganisms on the settleability was also studied. The effect of the total extended filament length on the sludge settleability was shown to depend on the type of filamentous organism and how it aggregates. When these groups of filamentous organisms are found in small aggregations and there is an increase in the number of filamentous organisms, the sludge volume index (SVI) increases proportionally to the filament length. However, when aggregation increases, the impact on the SVI is significantly lower.


Suffering assessment: a review of available instruments for use in palliative care.
The prevention and relief of suffering in palliative care are critical to the well-being and quality of life of patients and families facing life-threatening diseases. Many tools to assess different issues in health care are available, but few are specifically designed to evaluate suffering, which is essential for its prevention, early management, and treatment. The purpose of this review was to identify and describe existing instruments developed to assess suffering in palliative care, as well as to comment on their psychometric properties. A review of articles indexed in MEDLINE, PsycINFO, and SciELO up to June 2011 was conducted. All articles reporting the development, description, or psychometric properties of instruments that assess suffering were included. An assessment of their psychometric quality was performed following a structured checklist. Ten instruments that assess suffering were identified. Their main features and psychometric properties are described in order to facilitate the selection of the appropriate one given each patient's context. By taking into consideration all features of the assessment instruments under review, the evaluation of suffering can be made easier. A wide and ever expanding range of approaches is now available, which facilitates the selection of the suffering-assessment instrument that is best suited to the needs of the specific patient. One of the challenges ahead will be to further analyze the psychometric properties of some existing instruments.


Expression comparison of azithromycin and clarithromycin in triple-therapy regimens for eradication of Helicobacter pylori in hemodialysis patients.
To compare a triple-therapy regimen based on change of antibiotic (azithromycin and clarithromycin) for the eradication of Helicobacter pylori in hemodialysis (HD) patients, we studied in a prospective, randomized, double-blinded clinical trial 39 patients who had dyspepsia and showed two positive results from the diagnostic tests of H. pylori infection including anti-H. pylori serology and stool antigen (HpSAg) and urease breath test (UBT). The patients were divided into two groups: Group-A received omeprazol 20 mg, amoxycilin 500 mg and clarithromycin 500 mg twice a day and Group-B received omeprazol 20 mg, amoxicillin 500 mg and azithromycin 250 mg twice a day. The adverse events and compliance with triple therapy were reviewed at one visit per week. Both groups were prescribed their medications for 14 days. Of the 39 patients, only 37 patients completed the treatment schedule (20 men and 19 women, with the mean being 59 years). Two patients died due to myocardial infarction before the start of treatment and were out of the study. The eradication rate of H. pylori, evaluated by negative results of UBT, was 82.4% in Group-A and 80% in Group-B (P-value = 1.0). The results of our study showed no significant difference of azitromycin versus claritromycin in the eradication of H. pylori infection in HD patients.


Boron-doped few-walled carbon nanotubes: novel synthesis and properties.
Few-walled carbon nanotubes offer a unique marriage of graphitic quality and robustness to ink-processing; however, doping procedures that may alter the band structure of these few-walled nanotubes are still lacking. This report introduces a novel solution-injected chemical vapor deposition growth process to fabricate the first boron-doped few-walled carbon nanotubes (B-FWNTs) reported in literature, which may have extensive applications in battery devices. A comprehensive characterization of the as-grown B-FWNTs confirms successful boron substitution in the graphitic lattice, and reveals varying growth parameters impact the structural properties of B-FWNT yield. An investigation into the optimal growth purification parameters and ink-making procedures was also conducted. This study introduces the first process technique to successfully grow intrinsically p-doped FWNTs, and provides the first investigation into the impact factors of the growth parameters, purification steps, and ink-making processes on the structural properties of the B-FWNTs and the electrical properties of the resulting spray-coated thin-film electrodes.


Pediatric residency education: is sports medicine getting its fair share?
Sports are the leading injury-related cause for pediatric primary care visits. Pediatric residency education guidelines suggest incorporating sports medicine (SM) education into curricula; however, research is lacking regarding effective teaching methods. To assess reported US pediatric residency SM curricula, teaching methods, and resident evaluation of SM education. Chief residents (CRs) and third-year residents (PL3s) from 100 randomly selected US Accreditation Council for Graduate Medical Education-accredited residency programs, stratified by size and geographic location, received surveys regarding programs' SM curriculum and teaching methods and individuals' methods for learning SM. Response rates were 63% and 39% for CRs and PL3s, respectively. According to CRs, 34% of programs had no one in charge of their SM curriculum. Lecture (77%) was the primary method used for teaching SM. Hands-on teaching (37%) was used less frequently. CRs stated that 29% of programs did not include musculoskeletal examination teaching in their curriculums; 24% did not include formal teaching of concussion management, and 29% did not include reasons for medical disqualification. PL3s rated teaching of joint examinations and the preparticipation physical as the most poorly taught components of the physical examination. PL3s rated hands-on teaching and patient experience as the best methods for improving SM education. CRs reported that only 36% of programs have discussed incorporating more SM into their curriculum. SM education is deficient in US pediatric residency programs. Standardized curricula should be developed with a focus on hands-on training as a means for teaching SM to pediatric residents.


Cognitive neuroscience: resolving conflict in and over the medial frontal cortex.
The medial surface of the brain's frontal lobe has been implicated both in the voluntary initiation of action and in monitoring actions in situations where several conflicting responses are possible. Recent work casts light on how these functions are parcelled out in the medial frontal cortex.


[Aggravating factors of rosacea].
Rosacea is a chronic, inflammatory skin disease which is mainly localized in the central region of the face. Papules and pustules appear on the erythematic ground. Rosacea is common in population. Four subtypes of rosacea (erythematoteleangiectatic rosacea, ETR; papulo - pustular rosacea, PPR; ocular rosacea and phymatous rosacea) are classified (according to current classification) and one variant rosacea (granulomatous rosacea, GR). It is considered that an attempt to determine of triggering factors of rosacea should be the first step to treatment. Then it should be tried to eliminate contact with them. The aim of this study was an analysis of triggering factors of rosacea. 43 women and 26 men treated in the Dermatology Outpatient's Clinic of Jagiellonian University School of Medicine in Cracow were enrolled in the study. All patients were asked which factors trigger skin changes according to them. Patients mentioned most often: stress (58 percent), sun exposure (56.5 per. cent), alcohol (33.3 percent), exercise (29 percent), drinking coffee (21.7 percent) and hot meals (20.3 percent). They regarded the sun as the most strongly aggravating factor of rosacea (29.2 percent). It seems, that elimination and reduction of contact with aggravating factors is still an undervalued aspect of rosacea's treatment. Patients' motivation for use of prevention seems to be also very important. Knowledge about aggravating factors of rosacea, coming directly from patients' observations, may help in more effective treatment.


Antimicrobial functions of spices: why some like it hot.
Although spices have been important for centuries in food preparation throughout the world, patterns of spice use differ considerably among cultures and countries. What factors underlie these differences? Why are spices used at all? To investigate these questions, we quantified the frequency of use of 43 spices in the meat-based cuisines of the 36 countries for which we could locate traditional cookbooks. A total of 4578 recipes from 93 cookbooks was analysed. We also complied information on the temperature and precipitation in each country, the ranges of spice plants, and the antibacterial properties of each spice. These data were used to investigate the hypothesis that spices inhibit or kill food-spoilage microorganisms. In support of this is the fact that spice plant secondary compounds are powerful antimicrobial (i.e., antibacterial and antifungal) agents. As mean annual temperatures (an indicator of relative spoilage rates of unrefrigerated foods) increased, the proportion of recipes containing spices, number of spices per recipe, total number of spices used, and use of the most potent antibacterial spices all increased, both within and among countries. Likewise, the estimated fraction of bacterial species inhibited per recipe in each country was positively correlated with annual temperature. Several alternative hypotheses were considered--that spices provide macronutrients, disguise the taste and smell of spoiled foods, or increase perspiration and thus evaporative cooling; it also is conceivable that spice use provides no benefits. However, none of these four alternatives was well supported by our data. The proximate reason spices are used obviously is to enhance food palatability. But the ultimate reason is most likely that spices help cleanse foods of pathogens and thereby contribute to the health, longevity and reproductive success of people who find their flavors enjoyable.


[Nasal congestion and earache--upper respiratory tract infections in 4-year-old children].
Few population-based studies in Norway have addressed upper respiratory infections in children. A questionnaire concerning health, diseases and living condition was administered to parents of all four-year-old children in Vestfold county (n = 1912). Participation rate was 79%. Close to one out of three of the children suffered from recurrent common cold (four episodes or more) during the last year. One third experienced otitis at least once, and one out of twenty experienced four episodes of otitis or more. Day-care centre attendance was the only significant risk factor for recurrent common cold (odds ratio 1.50; 95% CI 1.18-1.92) or otitis (odds ratio 1.42; 95% CI 1.12-1.77). The odds ratios were essentially unchanged after logistic regression analysis, when mother's education, housing, other children in the family, passive smoking, and history of breastfeeding were included in the analysis. Children with otitis or recurrent common cold consulted a doctor almost ten times as often as other children. Day-care centre attendance has significant influence on the occurrence of upper respiratory infections in four-year-olds, but less influence than reported for younger children. Other environmental differences seem to be of little importance and do not represent any potential for prophylaxis.


Entorhinal denervation induces homeostatic synaptic scaling of excitatory postsynapses of dentate granule cells in mouse organotypic slice cultures.
Denervation-induced changes in excitatory synaptic strength were studied following entorhinal deafferentation of hippocampal granule cells in mature (≥ 3 weeks old) mouse organotypic entorhino-hippocampal slice cultures. Whole-cell patch-clamp recordings revealed an increase in excitatory synaptic strength in response to denervation during the first week after denervation. By the end of the second week synaptic strength had returned to baseline. Because these adaptations occurred in response to the loss of excitatory afferents, they appeared to be in line with a homeostatic adjustment of excitatory synaptic strength. To test whether denervation-induced changes in synaptic strength exploit similar mechanisms as homeostatic synaptic scaling following pharmacological activity blockade, we treated denervated cultures at 2 days post lesion for 2 days with tetrodotoxin. In these cultures, the effects of denervation and activity blockade were not additive, suggesting that similar mechanisms are involved. Finally, we investigated whether entorhinal denervation, which removes afferents from the distal dendrites of granule cells while leaving the associational afferents to the proximal dendrites of granule cells intact, results in a global or a local up-scaling of granule cell synapses. By using computational modeling and local electrical stimulations in Strontium (Sr(2+))-containing bath solution, we found evidence for a lamina-specific increase in excitatory synaptic strength in the denervated outer molecular layer at 3-4 days post lesion. Taken together, our data show that entorhinal denervation results in homeostatic functional changes of excitatory postsynapses of denervated dentate granule cells in vitro.


Widespread and dynamic translational control of red blood cell development.
Cell development requires tight yet dynamic control of protein production. Here, we use parallel RNA and ribosome profiling to study translational regulatory dynamics during murine terminal erythropoiesis. Our results uncover pervasive translational control of protein synthesis, with widespread alternative translation initiation and termination, robust discrimination of long noncoding from micropeptide-encoding RNAs, and dynamic use of upstream open reading frames. Further, we identify hundreds of messenger RNAs (mRNAs) whose translation efficiency is dynamically controlled during erythropoiesis and that enrich for target sites of RNA-binding proteins that are specific to hematopoietic cells, thus unraveling potential regulators of erythroid translational programs. A major such program involves enhanced decoding of specific mRNAs that are depleted in terminally differentiating/enucleating cells with decreasing transcriptional capacity. We find that RBM38, an erythroid-specific RNA-binding protein previously implicated in splicing, interacts with the general translation initiation factor eIF4G and promotes translation of a subset of these irreplaceable mRNAs. Inhibition of RBM38 compromises translation in erythroblasts and impairs their maturation, highlighting a key function for this protein during erythropoiesis. These findings thus reveal critical roles for dynamic translational control in supporting specialized mammalian cell formation.


Noncoding RNAs in acute kidney injury.
Acute kidney injury (AKI) is an important health issue concerning ∼50% of patients treated in intensive care units. AKI mainly occurs after sepsis, acute ischemia, nephrotoxicity, or hypoxia and leads to severe damage of the kidney and to an increased risk of mortality. The diagnosis of AKI is currently based on creatinine urea levels and diuresis. Yet, novel markers may improve the accuracy of this diagnosis at an early stage of the disease, thereby allowing early prevention and therapy, ultimately leading to a reduction in the need for renal replacement therapy and decreased mortality. Non-protein-coding RNAs or noncoding RNAs are central players in development and disease. They are important regulatory molecules that allow a fine-tuning of gene expression and protein synthesis. This regulation is necessary to maintain homeostasis, and its dysregulation is often associated with disease development. Noncoding RNAs are present in the kidney and in body fluids and their expression is modulated during AKI. This review article assembles the current knowledge of the role of noncoding RNAs, including microRNAs, long noncoding RNAs and circular RNAs, in the pathogenesis of AKI. Their potential as biomarkers and therapeutic targets as well as the challenges to translate research findings to clinical application are discussed. Although microRNAs have entered clinical testing, preclinical and clinical trials are needed before long noncoding RNAs and circular RNAs may be considered as useful biomarkers or therapeutic targets of AKI.


Sexual dimorphism of Broca's region: More gray matter in female brains in Brodmann areas 44 and 45.
Although a sexual dimorphism in brain structure is generally well established, evidence for sex differences in Brodmann areas (BA) 44 and 45 is inconclusive. This may be due to the difficulty of accurately defining BA 44 and BA 45 in magnetic resonance images, given that these regions are variable in their location and extent and that they do not match well with macroanatomic landmarks. Here we set out to test for possible sex differences in the local gray matter of BA 44/45 by integrating imaging-based signal intensities with cytoarchitectonically defined tissue probabilities in a sample of 50 male and 50 female subjects. In addition to testing for sex differences with respect to left- and right-hemispheric measures of BA 44/45, we also assessed possible sex differences in BA 44/45 asymmetry. Our analyses revealed significantly larger gray matter volumes in females compared with males for BA 44 and BA 45 bilaterally. However, there was a lack of significant sex differences in BA 44/45 asymmetry. These results corroborate reports of a language-related female superiority, particularly with respect to verbal fluency and verbal memory tasks. © 2016 Wiley Periodicals, Inc.


Uniformly cationized protein efficiently reaches the cytosol of mammalian cells.
Protein cationization techniques are powerful protein transduction methods for mammalian cells. As we demonstrated previously, cationized proteins with limited conjugation to polyethylenimine have excellent ability to enter into cells by adsorption-mediated endocytosis [Futami, J., et al. (2005) J. Biosci. Bioeng. 99, 95-103]. In this study, we show that proteins with extensive and uniform cationization covering the protein surface reach the cytoplasm and nucleus more effectively than proteins with limited cationic polymers or proteins that are fused to cationic peptides. Although extensive modification of carboxylates results in loss of protein function, chicken avidin retains biotin-binding ability even after extensive amidation of carboxylates. Using this cationized avidin carrier system, the protein transduction ability of variously cationized avidins was investigated using biotinylated protein as a probe. The results revealed that cationized avidins bind rapidly to the cell surface followed by endocytotic uptake. Small amounts of uniformly cationized avidin showed direct penetration into the cytoplasm within a 15 min incubation. This penetration route seemed to be energy dependent and functioned under cellular physiological conditions. A biotinylated exogenous transcription factor protein that penetrated cells was demonstrated to induce target gene expression in living cells.


The effects of the Trendelenburg position and intrathoracic pressure on the subclavian cross-sectional area and distance from the subclavian vein to pleura in anesthetized patients.
The effects of maneuvers to increase intrathoracic pressure and of Trendelenburg position on the cross-sectional area (CSA) of the subclavian vein (SCV) and the relationship between the SCV and adjacent structures have not been investigated. In ultrasonography-guided SCV catheterization (N = 30), the CSA of the SCV and the distance between the SCV and pleura (DSCV-pleura) were determined during 10-second airway opening, and 10-second positive inspiratory hold with 20 cm H2O in the supine position (S-0, and S-20) and the 10° Trendelenburg position (T-0, and T-20). In addition to a statistical significance of P < 0.05, CSA and DSCV-pleura differences of ≥15% were defined as clinically relevant changes. CSA (mean [95% confidence interval]) in S-20, T-0, and T-20 (1.02 [0.95-1.14] cm(2), 1.04 [0.95-1.15] cm(2), and 1.14 [1.04-1.24] cm(2), respectively) was significantly larger than a CSA in S-0 (0.93 [0.86-1.00] cm(2), all P < 0.001). However, only the increase of CSA in T-20 vs S-0 (0.21 cm(2), 23.2%) was clinically meaningful (≥15%). The number of patients who showed CSA increase ≥15% was more in S-0 to T-20 (57%) compared with those in S-0 to S-20 (23%) and S-0 to T-0 (27%). DSCV-pleura measurements (mean) in S-20 and T-20 (0.61 and 0.60 cm) were significantly shorter than those in S-0 (0.70 cm, all P < 0.001), but the reductions of DSCV-pleura were not clinically meaningful (≥15%). The combined application of inspiratory hold and Trendelenburg position provided a greater and more relevant degree of CSA increase without compromising DSCV-pleura, which may facilitate SCV catheterization. Further investigations are needed to determine whether these results affect the success rate of catheterization and the risk of procedural injury.


Gene therapy of viral hepatitis and hepatocellular carcinoma.
Gene therapy represents an attractive approach to treat a great variety of diseases, both inherited and acquired, and it is moving slowly from a proof-of-principle phase to a wide application in most medical fields. Liver cancer and viral hepatitis are natural targets for this new therapeutic alternative due to the lack of success of conventional antitumoral and antiviral treatments and the ominous prognosis related with liver tumours. Gene therapy for viral hepatitis is aimed to boost the patient immune response against viral antigens or to make cells resistant to infection by blocking the viral life cycle. Gene transfer techniques applied to the treatment of hepatocellular carcinoma include drug sensitization by suicide genes, genetic immunotherapy, normal tissue protection by transfer of the multidrug resistance gene, replacement of tumour suppressor genes, inhibition of oncogenes and modifications of the biology of the tumour (antiangiogenesis). However, major advances in our understanding of the regulation of gene expression, design of the expression cassettes and development of more efficient gene transfer vectors are mandatory before gene therapy can become a widely used therapeutic modality.


The evidence supporting educational videos for patients and caregivers receiving hospice and palliative care: A systematic review.
The purpose of this study is to explore the evidence surrounding educational videos for patients and family caregivers in hospice and palliative care. We ask three research questions: 1. What is the evidence for video interventions? 2. What is the quality of the evidence behind video interventions? 3. What are the outcomes of video interventions? The study is a systematic review, following Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. Researchers systematically searched five databases for experimental and observational studies on the evidence supporting video education for hospice and palliative care patients and caregivers, published in 1969-2019. The review identified 31 relevant articles with moderate-high quality of evidence. Most studies were experimental (74 %), came from the United States (84 %) and had a mean sample size of 139 participants. Studies showed that video interventions positively affect preferences of care and advance care planning, provide emotional support, and serve as decision and information aids. A strong body of evidence has emerged for video education interventions in hospice and palliative care. Additional research assessing video interventions' impact on clinical outcomes is needed. Videos are a promising tool for patient and family education in hospice and palliative care.


Defining the cause of skewed X-chromosome inactivation in X-linked mental retardation by use of a mouse model.
Extreme skewing of X-chromosome inactivation (XCI) is rare in the normal female population but is observed frequently in carriers of some X-linked mutations. Recently, it has been shown that various forms of X-linked mental retardation (XLMR) have a strong association with skewed XCI in female carriers, but the mechanisms underlying this skewing are unknown. ATR-X syndrome, caused by mutations in a ubiquitously expressed, chromatin-associated protein, provides a clear example of XLMR in which phenotypically normal female carriers virtually all have highly skewed XCI biased against the X chromosome that harbors the mutant allele. Here, we have used a mouse model to understand the processes causing skewed XCI. In female mice heterozygous for a null Atrx allele, we found that XCI is balanced early in embryogenesis but becomes skewed over the course of development, because of selection favoring cells expressing the wild-type Atrx allele. Unexpectedly, selection does not appear to be the result of general cellular-viability defects in Atrx-deficient cells, since it is restricted to specific stages of development and is not ongoing throughout the life of the animal. Instead, there is evidence that selection results from independent tissue-specific effects. This illustrates an important mechanism by which skewed XCI may occur in carriers of XLMR and provides insight into the normal role of ATRX in regulating cell fate.


Molecular determinants of inactivation within the I-II linker of alpha1E (CaV2.3) calcium channels.
Voltage-dependent inactivation of CaV2.3 channels was investigated using point mutations in the beta-subunit-binding site (AID) of the I-II linker. The quintuple mutant alpha1E N381K + R384L + A385D + D388T + K389Q (NRADK-KLDTQ) inactivated like the wild-type alpha1E. In contrast, mutations of alpha1E at position R378 (position 5 of AID) into negatively charged residues Glu (E) or Asp (D) significantly slowed inactivation kinetics and shifted the voltage dependence of inactivation to more positive voltages. When co-injected with beta3, R378E inactivated with tau(inact) = 538 +/- 54 ms (n = 14) as compared with 74 +/- 4 ms (n = 21) for alpha1E (p < 0.001) with a mid-potential of inactivation E(0.5) = -44 +/- 2 mV (n = 10) for R378E as compared with E(0.5) = -64 +/- 3 mV (n = 9) for alpha1E. A series of mutations at position R378 suggest that positively charged residues could promote voltage-dependent inactivation. R378K behaved like the wild-type alpha1E whereas R378Q displayed intermediate inactivation kinetics. The reverse mutation E462R in the L-type alpha1C (CaV1.2) produced channels with inactivation properties comparable to alpha1E R378E. Hence, position 5 of the AID motif in the I-II linker could play a significant role in the inactivation of Ca(V)1.2 and CaV2.3 channels.


Social interaction in augmented reality.
There have been decades of research on the usability and educational value of augmented reality. However, less is known about how augmented reality affects social interactions. The current paper presents three studies that test the social psychological effects of augmented reality. Study 1 examined participants' task performance in the presence of embodied agents and replicated the typical pattern of social facilitation and inhibition. Participants performed a simple task better, but a hard task worse, in the presence of an agent compared to when participants complete the tasks alone. Study 2 examined nonverbal behavior. Participants met an agent sitting in one of two chairs and were asked to choose one of the chairs to sit on. Participants wearing the headset never sat directly on the agent when given the choice of two seats, and while approaching, most of the participants chose the rotation direction to avoid turning their heads away from the agent. A separate group of participants chose a seat after removing the augmented reality headset, and the majority still avoided the seat previously occupied by the agent. Study 3 examined the social costs of using an augmented reality headset with others who are not using a headset. Participants talked in dyads, and augmented reality users reported less social connection to their partner compared to those not using augmented reality. Overall, these studies provide evidence suggesting that task performance, nonverbal behavior, and social connectedness are significantly affected by the presence or absence of virtual content.


Open database of epileptic EEG with MRI and postoperational assessment of foci--a real world verification for the EEG inverse solutions.
This paper introduces a freely accessible database http://eeg.pl/epi , containing 23 datasets from patients diagnosed with and operated on for drug-resistant epilepsy. This was collected as part of the clinical routine at the Warsaw Memorial Child Hospital. Each record contains (1) pre-surgical electroencephalography (EEG) recording (10-20 system) with inter-ictal discharges marked separately by an expert, (2) a full set of magnetic resonance imaging (MRI) scans for calculations of the realistic forward models, (3) structural placement of the epileptogenic zone, recognized by electrocorticography (ECoG) and post-surgical results, plotted on pre-surgical MRI scans in transverse, sagittal and coronal projections, (4) brief clinical description of each case. The main goal of this project is evaluation of possible improvements of localization of epileptic foci from the surface EEG recordings. These datasets offer a unique possibility for evaluating different EEG inverse solutions. We present preliminary results from a subset of these cases, including comparison of different schemes for the EEG inverse solution and preprocessing. We report also a finding which relates to the selective parametrization of single waveforms by multivariate matching pursuit, which is used in the preprocessing for the inverse solutions. It seems to offer a possibility of tracing the spatial evolution of seizures in time.


Fomepizole for the treatment of pediatric ethylene and diethylene glycol, butoxyethanol, and methanol poisonings.
The use and clinical efficacy of the alcohol dehydrogenase inhibitor fomepizole is well established for the treatment of ethylene glycol and methanol poisonings in adults. A computerized search of the U.S. National Academy of medicine and EMBase databases was undertaken to identify published cases of patients treated with fomepizole. This search strategy identified 14 published cases related to the topic of this review: 10 due to ethylene glycol poisoning, 1 due to diethylene glycol poisoning, 1 due to butoxyethanol ingestion, and 2 due to methanol poisoning. The median age of these cases was 5.5 years old. FOMEPIZOLE IN GLYCOL AND GLYCOL ETHER POISONING: For the 10 ethylene glycol poisoned patients, the median recorded values of their arterial pH was 7.27 (range 7.03-7.38), serum bicarbonate concentration was 13 mEq/L (range 2-25), and ethylene glycol concentration was 2,140 mg/L (range 130-3,840). Eight of these patients were not hemodialyzed. The eight patients who were not hemodialyzed had ethylene glycol concentrations as high as 3,500 mg/L and serum bicarbonate concentrations as low as 4 mEq/L. All 10 patients had resolution of their metabolic acidosis and recovered without sequelae. The half-times of ethylene glycol elimination ranged from 9 to 15 h during fomepizole therapy, which is faster than the 19.7 h reported in adults. The two patients who ingested diethylene glycol or butoxyethanol all recovered without sequelae. The patient who ingested the butoxyethanol had a serum bicarbonate concentration of 13 mEq/L and was not hemodialyzed. FOMEPIZOLE IN METHANOL POISONING: One of the two children who ingested methanol was hemodialyzed. Both cases had a similar degree of severity. DOES FOMEPIZOLE OBVIATE THE NEED FOR HEMODIALYSIS?: Based on the experience reviewed herein it appears that, as in adults, hemodialysis may not be necessary in most cases of pediatric ethylene glycol poisoning if treated with fomepizole. FOMEPIZOLE PHARMACOKINETICS: Plasma fomepizole concentrations were measured in three cases and were found to be therapeutic with apparent Michaelis-Menton kinetics, having a zero-order elimination rate of 0.6-1 mg/L/h at higher concentrations and a first-order elimination with an apparent elimination half-time of 3.9 h at lower concentrations. FOMEPIZOLE REGIMEN: Most cases used the current U.S.-approved regimen. ADVERSE EFFECTS OF FOMEPIZOLE: The one adverse effect reported during fomepizole therapy was transient nystagmus in a 6-year-old with a serum ethylene glycol concentration of 130 mg/L and a serum bicarbonate concentration of 2 mEq/L; it is likely that ethylene glycol itself was the cause. COMPARISON OF FOMEPIZOLE WITH ETHANOL THERAPY: Two cases were originally treated with ethanol but switched to fomepizole because of adverse effects. In both cases, the adverse reactions to ethanol resolved once fomepizole treatment was initiated. The limited data available suggest that fomepizole, using the same dosage regimen as that used for adults, is efficacious and well tolerated in pediatric patients. In many cases of pediatric ethylene glycol poisoning treated with fomepizole, hemodialysis may not be necessary despite high concentrations and the presence of metabolic acidosis.


In vitro microwave effects on human neutrophil precursor cells (CFU-C).
Human marrow cells were irradiated with 2450-MHz CW microwaves in a fluid-filled waveguide irradiation system. Cell exposure was conducted by placing a marrow cell suspension in 20-microliter glass microcapillary tubes were positioned in the exposure chamber, and irradiated at power densities from 31 to 1,000 mW/cm2 (with corresponding specific absorption rates of 62 to 2,000 mW/g) for 15 minutes. The temperature of the sample was maintained at a fixed point. Sham-irradiated (SI) and microwave-irradiated (MWI) cells were cultured in a methylcellulose culture system for neutrophil colony proliferation. There was no reduction in neutrophil colony number on days 6-7 or 12-14 in cells exposed at 31 or 62 mW/cm2, but as the power density was increased to 1,000 mW/cm2, there was a reduction in colony number of MWI cells compared with SI cells. The microwave interaction with the human neutrophil colony-forming cells was apparently not related to temperature rise, or to the state of cells cycle, and was irreversible.


Focal inhibitory seizure with prolonged deficit in adult Sturge-Weber syndrome.
Sturge-Weber syndrome is a sporadic congenital neurocutaneous disorder often related to varying degrees of motor impairment. The phenomenon of prolonged ictal paresis is a rare seizure sign that can be due to lesions affecting the centro-parietal lobe. Focal inhibitory motor seizures can be difficult to differentiate from other clinical entities such as stroke, migraine or postictal paresis. We describe the case of a 40-year-old patient suffering from Sturge-Weber syndrome, admitted due to prolonged right-sided hemiparesis following a usual seizure. Repeated EEGs during the prolonged deficit showed only intermittent left fronto-parietal sharp waves. (99m)Tc HMPAO-brain SPECT performed seven days after the last seizure showed a vast area of parieto-occipital hyperperfusion in the left hemisphere. Aggressive antiepileptic therapy dramatically improved the clinical symptoms and scintigraphic images, which corroborated the diagnosis of ictal paresis. This case highlights the role of SPECT in the evaluation of Sturge-Weber syndrome, not only to investigate progressive neurological deterioration, but also exacerbation of seizures or prolonged neurological deficits. In fact, it may be possible to document ongoing epileptic activity using SPECT, despite a non-contributory EEG, which may be of help in adapting a therapeutic strategy.