Effects of technology-mediated mindfulness practice on stress: psychophysiological and self-report measures.
Repeated exposure to stressors, even if mild, may alter the efficiency of optimal stress responses and hinder emotion regulation skills. Mindfulness meditation, by strengthening self-regulation and awareness, may optimize the efficiency of physiological, cognitive, and behavioral reactions to stressful events but typically requires notable commitment to practice, which often leads to disengagement. Recent research suggested that such practices may be made more accessible and that the potential for self-enhancement and stress management of meditation might be improved by supporting mental training with wearable neurofeedback devices able to inform the practicer on ongoing modulation of bodily and brain activity. This study aimed at testing the effect of such novel training approach based on the integration of mental training with brain-sensing wearable devices on physiological (heart rate and variability) and subjective markers of stress (perceived stress, anxiety, and mood states). Participants (N = 55) have been randomly divided into an active control (CONTg) and an experimental group (EXPg). Both groups completed a four-week training constituted by brief daily activities based on mindfulness practices. Experimental participants practiced with the support of dedicated brain-sensing devices. By analyzing pre- and post-training assessments, we observed relevantly decreased stress and anxiety measures in EXPg, as well as relevantly decreased mental fatigue and increased vigor. EXPg also showed improved physiological markers of vagal tone both at rest and during exposure to a cognitive stressor. Reported findings add to the limited available literature on potential effects of technology-supported mental training protocols for promoting subjective well-being and enhancing self-regulation skills.


Serological survey of brucellosis in Benghazi cow project (Libya).
Sera were collected from 3753 cows in Benhazi cow project (Libya). The rose bengal, complement fixation and serum agglutination serological tests were employed to test these sera for evidence of brucellosis. The overall reactivity was detected in all (0.3%) cows. The prevalence of the highest reactors (1.0%) was in Abo Atney Dairy Station. In other dairy stations investigated the incidence of brucellosis ranged from zero to 0.3%.


Short-term prediction of major lower-limb amputation based on clinical indicators on admission: a single institutional experience in a developing country.
The aim of this study was to analyze the possibility of predicting short-term major lower-limb amputation (SMLA) in patients with vascular diagnoses, based only on clinical variables measured on admission. A longitudinal, retrospective cohort study of patients with peripheral vascular diagnoses admitted at our Institute was carried out. A stratified sample of 463 patients admitted during 1997, 2000 and 2003, was studied. Logistic regression was used to identify significant predictors of amputation; twelve clinical variables measured on admission were considered as potential predictors. Of the 463 patients, 93 (20%) were amputated. Significant predictors of amputation identified by the logistic regression analysis were ''type of lesion'' (none; neuro-infectious; ischemic; mixture), ''initial diagnosis'' (phlebolymphopathies, acute arterial insufficiency, chronic arterial insufficiency, diabetic foot, others), ''plantar region lesion'' (no; yes), ''diabetes'' (no; yes), ''number of toes affected'' (none; 1-2; 3 or more), and ''area of leg affected'' (none; lower third; + lower third). More than 80% of patients were correctly classified with the final model: sensitivity was 42% and specificity 96%. It seems that SMLA in patients with vascular diagnoses can be predicted reasonably well using as predictors only clinical variables measured on admission. This is a potentially useful result for Angiology Services located in developing/poor communities. The amputation probability for each patient obtained from the logistic regression model can be used in several ways: 1) the medical care of patients can be customized so that the amputation rate of the whole Service can be reduced, and 2) the amputation probability of the statistical model can be used as an estimation of the severity of the disease in each patient, which in turn can be used to standardize the amputation rates computed on different years; this would allow a better assessment of the Institutional performance over time.


Candidemia before and during the fluconazole era: prevalence, type of species and approach to treatment in a tertiary care community hospital.
The characteristics of candidemia before and after the introduction of fluconazole were compared at our institution. In the pre-fluconazole era (1986-89), the incidence of candidemia rose from 0.02% to 13% over the course of 4 y. Candida albicans accounted for 44/66 isolates (67%) and C. glabrata and C. parapsilosis were the predominant non-albicans species (9% each). In one-third of cases antifungal therapy was not given and the overall mortality rate was 55%. During the fluconazole era (1994-97), the incidence of candidemia remained constant between 1994 and 1996 at 0.09-0.11% and dropped to 0.06% in 1997. Bloodstream infection associated with neutropenia increased significantly but only accounted for 13% of cases; antifungal prophylaxis was not employed. The isolation of C. albicans decreased (n = 49; 50%) whereas isolation of both C. parapsilosis (n = 23; 24%) and C. tropicalis (n = 16; 16%) increased. The vast majority of patients received antifungal therapy and the overall mortality rate was 39%. These findings show that the incidence of candidemia rose steadily prior to the fluconazole era and then stabilized in spite of a shift towards non-albicans species. When candidemia was encountered in the fluconazole era, it was rare not to give antifungal treatment.


Multi-order dispersion engineering for optimal four-wave mixing.
Four-wave mixing in high refractive index materials, such as chalcogenide glass or semiconductors, is promising because of their large cubic nonlinearity. However, these materials tend to have normal dispersion at telecom wavelengths, preventing phase matched operation. Recent work has shown that the waveguide dispersion in strongly confining guided-wave structures can lead to anomalous dispersion, but the resulting four-wave mixing has limited bandwidth because of negative quartic dispersion. Here we first show that the negative quartic dispersion is an inevitable consequence of this dispersion engineering procedure. However, we also demonstrate that a slight change in the procedure leads to positive quartic dispersion, resulting in a superior bandwidth. We give an example in which the four-wave mixing bandwidth is doubled in this way.


Biosynthesis of germacrene A carboxylic acid in chicory roots. Demonstration of a cytochrome P450 (+)-germacrene a hydroxylase and NADP+-dependent sesquiterpenoid dehydrogenase(s) involved in sesquiterpene lactone biosynthesis.
Sprouts of chicory (Cichorium intybus), a vegetable grown in the dark, have a slightly bitter taste associated with the presence of guaianolides, eudesmanolides, and germacranolides. The committed step in the biosynthesis of these compounds is catalyzed by a (+)-germacrene A synthase. Formation of the lactone ring is the postulated next step in biosynthesis of the germacrene-derived sesquiterpene lactones. The present study confirms this hypothesis by isolation of enzyme activities from chicory roots that introduce a carboxylic acid function in the germacrene A isopropenyl side chain, which is necessary for lactone ring formation. (+)-germacrene A is hydroxylated to germacra-1(10),4,11(13)-trien-12-ol by a cytochrome P450 enzyme, and is subsequently oxidized to germacra-1(10),4,11(13)-trien-12-oic acid by NADP+-dependent dehydrogenase(s). Both oxidized germacrenes were detected as their Cope-rearrangement products elema-1,3,11(13)-trien-12-ol and elema-1,3,11(13)-trien-12-oic acid, respectively. The cyclization products of germacra-1(10),4,11(13)-trien-12-ol, i.e. costol, were also observed. The (+)-germacrene A hydroxylase is inhibited by carbon monoxide (blue-light reversible), has an optimum pH at 8.0, and hydroxylates beta-elemene with a modest degree of enantioselectivity.


The Impact of Positive Youth Development Attributes and Life Satisfaction on Academic Well-Being: A Longitudinal Mediation Study.
While research studies revealed that positive youth development (PYD) attributes have beneficial impact on adolescent developmental outcomes, whether and how PYD qualities are related to academic well-being (such as academic stress and academic satisfaction) are unclear. Based on a longitudinal study (N = 2,312 secondary school students; Mage = 12.54 ± 0.68; 51% female) in Hong Kong, the present study tested a longitudinal mediation model in which it was hypothesized that PYD qualities predicted life satisfaction, academic stress, and academic satisfaction, with satisfaction with life mediating the influence of PYD qualities on academic well-being. Results showed that PYD qualities positively predicted academic satisfaction but negatively predicted academic stress over time. While life satisfaction partially mediated the influence of PYD attributes on academic satisfaction, it fully mediated the influence of PYD attributes on academic stress. The present study supports the proposed conceptual model and underscores the role of PYD qualities in academic well-being through the mediation of life satisfaction.


The impact of aging-induced gut microbiome dysbiosis on dendritic cells and lung diseases.
Aging is an inevitable natural process that impacts every individual, and understanding its effect on the gut microbiome and dendritic cell (DC) functionality in elderly subjects is crucial. DCs are vital antigen-presenting cells (APCs) that orchestrate the immune response, maintaining immune tolerance to self-antigens and bridging innate and adaptive immunity. With aging, there is a shift toward nonspecific innate immunity, resulting in a decline in adaptive immune responses. This alteration raises significant concerns about managing the health of an elderly population. However, the precise impact of aging and microbiome changes on DC function and their implications in lung-associated diseases remain relatively understudied. To illuminate this subject, we will discuss recent advancements in understanding the connections between aging, gut dysbiosis, DCs, and lung diseases. Emphasizing the key concepts linking age-related gut microbiome changes and DC functions, we will focus on their relevance to overall health and immune response in elderly individuals. This article aims to improve our understanding of the intricate relationship between aging, gut microbiome, and DCs, potentially benefiting the management of age-associated diseases and promoting healthy aging.


Severe obstructive sleep apnoea secondary to pressure garments used in the treatment of hypertrophic burn scars.
Obstructive sleep apnoea (OSA) secondary to pressure garments used to treat hypertrophic scarring of burns has never been reported. The present study describes two children who presented with OSA following introduction of such garments for management of hypertrophic scars following severe facial and upper body burns. Complex sleep polysomnography confirmed severe OSA with desaturations sufficient to result in physiological dysfunction that significantly improved on removal of the garments. As there is little evidence to suggest that the use of such garments alters the end result, the potentially serious side effect of obstructive sleep apnoea should be considered before their use is advised.


ES proteins analysis of Angiostrongylus cantonensis: products of the potential parasitism genes?
The expressed sequence tags (ESTs) of Angiostrongylus cantonensis were analyzed in an attempt to gain further insight into its genomic expression patterns. A total of 1,277 ESTs of A. cantonensis were randomly downloaded from NCBI databank. ESTs were analyzed and annotated using Blastx. The result showed that there were 60 ESTs had no match to any of the proteins and gene sequences in the published databases, and 695 ESTs score more than 80. According to the function, the identified 695 ESTs could be grouped into 13 categories related to metabolism, cellular development, immune evasion, host-parasite interactions, and so on. Among them, 65 (9.4%) were proteases and protease inhibitors, represented 19 potential proteases and protease inhibitors genes; 42 (6.0%) were allergens or antigens, represented 15 potential antigens/allergens genes. Signal P analysis was applied to the 19 putative proteases and protease inhibitors and the 15 antigens/allergens protein sequences to identify the potential signal peptides and anchors. The result demonstrated that there were ten putative proteins had N-terminal signal peptides and three had signal anchors, these putative excretory/secretory proteins might be the products of potential parasitism genes which played an important role in the adaptation of A. cantonensis to a parasitism life. These parasitism genes and proteins identified are expected to become potential targets for future research on anti-A. cantonensis drugs; moreover, the resulting genetic information is useful in elucidating the mechanisms of parasitism of A. cantonensis.


Unconventional Transport Routes of Soluble and Membrane Proteins and Their Role in Developmental Biology.
Many proteins and cargoes in eukaryotic cells are secreted through the conventional secretory pathway that brings proteins and membranes from the endoplasmic reticulum to the plasma membrane, passing through various cell compartments, and then the extracellular space. The recent identification of an increasing number of leaderless secreted proteins bypassing the Golgi apparatus unveiled the existence of alternative protein secretion pathways. Moreover, other unconventional routes for secretion of soluble or transmembrane proteins with initial endoplasmic reticulum localization were identified. Furthermore, other proteins normally functioning in conventional membrane traffic or in the biogenesis of unique plant/fungi organelles or in plasmodesmata transport seem to be involved in unconventional secretory pathways. These alternative pathways are functionally related to biotic stress and development, and are becoming more and more important in cell biology studies in yeast, mammalian cells and in plants. The city of Lecce hosted specialists working on mammals, plants and microorganisms for the inaugural meeting on "Unconventional Protein and Membrane Traffic" (UPMT) during 4-7 October 2016. The main aim of the meeting was to include the highest number of topics, summarized in this report, related to the unconventional transport routes of protein and membranes.


Maternal postpartum morbidity in Marrakech: what women feel what doctors diagnose?
Information about postpartum maternal morbidity in developing countries is limited and often based on information obtained from hospitals. As a result, the reports do not usually reflect the true magnitude of obstetric complications and poor management at delivery. In Morocco, little is known about obstetric maternal morbidity. Our aim was to measure and identify the causes of postpartum morbidity 6 weeks after delivery and to compare women's perception of their health during this period to their medical diagnoses. We did a cross-sectional study of all women, independent of place of delivery, in Al Massira district, Marrakech, from December 2010 to March 2012. All women were clinically examined 6 to 8 weeks postpartum for delivery-related morbidities. We coupled a clinical examination with a questionnaire and laboratory tests (hemoglobin). During postpartum consultation, 44% of women expressed at least one complaint. Complaints related to mental health were most often reported (10%), followed by genital infections (8%). Only 9% of women sought treatment for their symptoms before the postpartum visit. Women who were aged ≥30 years, employed, belonged to highest socioeconomic class, and had obstetric complications during birth or delivered in a private facility or at home were more likely to report a complaint. Overall, 60% of women received a medical diagnosis related to their complaint, most of which were related to gynecological problems (22%), followed by laboratory-confirmed anemia (19%). Problems related to mental health represented only 5% of the diagnoses. The comparative analysis between perceived and diagnosed morbidity highlighted discrepancies between complaints that women expressed during their postpartum consultation and those they received from a physician. A better understanding of postpartum complaints is one of the de facto essential elements to ensuring quality of care for women. Sensitizing and training clinicians in mental health services is important to respond to women's needs and improve the quality of maternal care.


CD4(+) T cell clones producing both interferon-gamma and interleukin-10 predominate in bronchoalveolar lavages of active pulmonary tuberculosis patients.
The pattern of cytokine production in T cell clones derived from bronchoalveolar lavages (BAL) of active pulmonary tuberculosis (TB) patients was analyzed in clones obtained by limiting dilution procedures which expand with high efficiency either total T lymphocytes, independently of their antigen-recognition specificity, or Mycobacterium tuberculosis-specific T cells. BAL-derived clones, representative of CD4(+) cells from five patients with active TB, produced significantly higher amounts of IFN-gamma than BAL-derived CD4(+) clones from three inactive TB donors or four controls (with unrelated, noninfectious pathology). Average IL-4 and IL-10 production did not differ significantly in the three groups. Although these data suggest a predominant Th1 response to M. tuberculosis infection in the lungs, the majority of BAL-derived CD4(+) clones produced both IFN-gamma and IL-10 and the percentage of clones with this pattern of cytokine production was significantly higher in clones derived from BAL of active TB patients than from controls. Only rare clones derived from peripheral blood (PB)-derived CD45RO(+) CD4(+) T cells of both patients (nine cases) and controls (four cases) produced both IFN-gamma and IL-10; instead, the IL-10-producing clones derived from PB T cells most often also produced IL-4, displaying a typical Th2 phenotype. Higher average amounts of IFN-gamma and IL-10 were produced by BAL-derived CD8(+) clones of four active TB patients than of four controls, although the frequency of CD8(+) clones producing both IFN-gamma and IL-10 was lower than that of CD4(+) clones. The M. tuberculosis-specific BAL-derived T cell clones from three active TB patients were almost exclusively CD4(+) and produced consistently high levels of IFN-gamma often in association with IL-10, but very rarely with IL-4. Unlike the BAL-derived clones, the M. tuberculosis-specific clones derived from PB CD45RO(+) CD4(+) T cells of three different active TB patients and two healthy donors showed large individual variability in cytokine production as well as in the proportion of CD4(+), CD8(+), or TCR gamma/delta(+) clones. These results indicate the predominance of CD4(+) T cells producing both the proinflammatory cytokine IFN-gamma and the anti-inflammatory cytokine IL-10 in BAL of patients with active TB.


Impact of pneumonia on hospitalizations due to acute exacerbations of COPD.
Pneumonia is often diagnosed among patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aims of this study were to find the proportion of patients with pneumonia among admissions due to AECOPD and whether pneumonia has impact on the length of stay (LOS), usage of non-invasive ventilation (NIV) or the in-hospital mortality. Retrospectively, all hospitalizations in 2005 due to AECOPD in the Departments of Internal and Respiratory Medicine in one Swedish and two Norwegian hospitals were analyzed. A total of 1144 admittances (731 patients) were identified from patient administrative systems. Pneumonic AECOPD (pAECOPD) was defined as pneumonic infiltrates on chest X-ray and C-reactive protein (CRP) value of ≥40 mg/L, and non-pneumonic AECOPD (npAECOPD) was defined as no pneumonic infiltrate on X-ray and CRP value of <40 at admittance. In admissions with pAECOPD (n = 237), LOS was increased (median 9 days vs 5 days, P < 0.001) and usage of NIV was more frequent (18.1% vs 12.5%, P = 0.04), but no significant increase in the in-hospital mortality (3.8% vs 3.6%) was found compared to admissions with npAECOPD. A higher proportion of those with COPD GOLD stage I-II had pAECOPD compared to those with COPD GOLD stage III-IV (28.2% vs 18.7%, P = 0.001). In-hospital morbidity, but not mortality, was increased among admissions with pAECOPD compared to npAECOPD. This may, in part, be explained by the extensive treatment with antibiotics and NIV in patients with pAECOPD.


Myometrial invasion by endometrial carcinoma: assessment by MR imaging.
In patients with early-stage endometrial cancer, preoperative knowledge of myometrial tumor extension has important prognostic and therapeutic implications. The purpose of this prospective study was to determine the sensitivity and specificity of MR imaging for assessing the depth of myometrial invasion in patients with endometrial cancer that clinically was thought to be confined to the uterine corpus. Sixty-five consecutive patients were included in the study. All patients had MR imaging before radical surgery. MR imaging findings were compared with microscopic pathologic findings in all cases. On MR images and at histologic analysis, myometrial invasion was classified as absent (tumor confined to the endometrium), superficial (less than 50% of myometrial thickness), or deep (50% or more of myometrial thickness). At histologic examination, tumor limited to the endometrium was proved in 14 cases, superficial myometrial invasion by tumor was present in 34 cases, and deep tumor invasion was demonstrated in 17 cases. In determining the presence of tumor confined to the endometrium, MR imaging had a sensitivity of 57% and a specificity of 96%. In the assessment of tumor with superficial myometrial invasion, MR imaging had a sensitivity and a specificity of 74%, whereas in assessing deep myometrial penetration, the sensitivity and specificity of MR were 88% and 85%, respectively. Errors in MR interpretation when determining myometrial tumor spread were more frequently overestimations rather than underestimations. Our results indicate that MR imaging is useful for the preoperative assessment of myometrial invasion in patients with proved endometrial cancer.


Cancerous miRNAs and their regulation.
Although they account for only a very minor fraction of the expressed genome, microRNAs (miRNAs) are pivotal regulators of development and cellular homeostasis through their control of diverse cellular processes including proliferation, differentiation, apoptosis, survival, motility and morphogenesis. Accordingly, several miRNAs have been functionally classified as proto-oncogenes or tumor suppressors and are aberrantly expressed in different cancer types. Deregulation (e.g., overexpression or loss of expression) of these so-called "cancerous" miRNAs can figure prominently in tumor initiation and progression by elaborating an inappropriate cellular program promoting uncontrolled proliferation, favoring survival, inhibiting differentiation and/or promoting invasive behavior. These features would certainly promote tumor dissemination and persistence by favoring metastasis and therapy resistance. Cancerous miRNAs therefore represent attractive molecules for exploitation as biomarkers and therapeutic targets. In this review, we highlight recently characterized cancerous miRNAs and the mechanisms through which they contribute to the pathogenesis of human cancers. We also discuss the signal transduction pathways that regulate the expression of these miRNAs with particular attention to several essential transcription factors such as Myc, p53 and the androgen receptor.


[Biological activity of regulatory peptides in model experiments in vitro].
Biological effects of short regulatory peptides, pinealon, vesugen, vilon and epitalon were studied in model experiments in vitro. These peptides were found not to demonstrate direct antioxidant activity but be able to restrict lipid peroxidation of human lipoproteins by modification of their structure. The short peptides increase stability of red blood cell membranes toward osmotic hemolysis. They also elevate the stationary level of intracellular reactive oxygen species and at the same time decrease (all excepting epitalon) percent of dead cells in neuronal population. The suggestion was made that under in vivo conditions, short peptides may participate in apoptosis/necrosis regulation.


Natural Foxp3(+) regulatory T cells inhibit Th2 polarization but are biased toward suppression of Th17-driven lung inflammation.
nTregs prevent autoimmunity and modulate immune and inflammatory responses to foreign antigens. CD4(+)Foxp3(+) nTregs from DO11.10 mice were expanded ex vivo, and their effectiveness in suppressing the development of lung inflammatory responses, elicited by differentiated CD4(+) T cells following antigen inhalation, was examined. Effector DO11.10 CD4(+) Th2 cells, when adoptively transferred into BALB/c mice that subsequently inhaled OVA, elicited a pronounced pulmonary, eosinophilic inflammation. Surprisingly, the cotransfer of expanded nTregs failed to suppress the Th2-mediated airway inflammation. Nevertheless, expanded OVA-specific CD4(+)Foxp3(+) nTregs were highly effective at inhibiting the polarization of naïve CD4(+) T cells into a Th2 phenotype. This suppression was reversed by an antibody to GITR but was not affected by the presence of the soluble OX40L. Further analysis revealed that although nTregs also failed to inhibit the lung neutrophilic inflammation induced by effector CD4(+) Th1 cells, they markedly suppressed pulmonary inflammation elicited by CD4(+) Th17 cells but not AHR. The suppression of the Th17-mediated response was evident from a striking reduction in the proportion of OVA-specific T cells expressing IL-17 and the numbers of neutrophils present in the airways of Th17 recipient mice. Collectively, these results demonstrate that expanded nTregs clearly limit the Th2 polarization process and that Th17-mediated inflammatory responses are particularly prone to the immunoregulatory properties of nTregs. These findings thus indicate that expanded nTregs are restrictive in their ability to suppress airway inflammatory processes and AHR.


Assessment of Clinically Suspected Tubercular Lymphadenopathy by Real-Time PCR Compared to Non-Molecular Methods on Lymph Node Aspirates.
The diagnosis of tubercular lymphadenitis (TBLN) is challenging. This study assesses the role of diagnostic intervention with real-time PCR in clinically suspected tubercular lymphadenopathy in relation to cytology and microbiological methods. The cross-sectional study involved 214 patients, and PCR, cytology, and Ziehl-Neelsen (ZN) staining was performed on aspirates. The findings were compared with culture on Lowenstein-Jensen medium. The overall concordance of cytology and PCR, both individually and combined, was calculated. χ2 and Phi values were assessed between cytology, PCR, and culture. A cytological diagnosis of tuberculosis (TB), reactive lymphoid hyperplasia, and suppurative lymphadenitis was made in 71, 112, and 6 patients, respectively. PCR and culture were positive in 40% of the cases. Among the TBLN patients, PCR showed higher positivity in necrosis and culture showed higher positivity in necrotizing granuloma. Positive ZN staining was observed in 29.6% of the TBLN cases, with an overall positivity of 11%. PCR could additionally detect 82 cases missed by ZN staining. The overall concordance rate for either diagnostic modality, i.e., PCR or cytology, was highest (75%), and for PCR alone was 74%. Phi values were observed to be 0.47 between PCR and culture. Real-time PCR for Mycobacterium tuberculosis complex on aspirates offers a definitive and comparable diagnosis of TBLN. Including this approach as the primary investigation in the work-up of TBLN could reduce the burden of TB.


Drainage basin checklists and dichotomous keys for inland fishes of Texas.
Species checklists and dichotomous keys are valuable tools that provide many services for ecological studies and management through tracking native and non-native species through time. We developed nine drainage basin checklists and dichotomous keys for 196 inland fishes of Texas, consisting of 171 native fishes and 25 non-native fishes. Our checklists were updated from previous checklists and revised using reports of new established native and non-native fishes in Texas, reports of new fish occurrences among drainages, and changes in species taxonomic nomenclature. We provided the first dichotomous keys for major drainage basins in Texas. Among the 171 native inland fishes, 6 species are considered extinct or extirpated, 13 species are listed as threatened or endangered by U.S. Fish and Wildlife Service, and 59 species are listed as Species of Greatest Conservation Need (SGCN) by the state of Texas. Red River drainage basin was the most speciose with 120 fishes. Rio Grande & Pecos drainage basin had the greatest number of threatened or endangered fishes (N = 7) and the greatest number of SGCN fishes (N = 28). We revised drainage basin occurrences for 77 species. Drainage basin checklists and dichotomous keys provide finer resolution of species distributions within the geopolitical boundaries of Texas and can reduce probability of errors in fish identification errors by removing species not occurring within a natural boundary.


Hospitalized patients quantify verbal pain intensity descriptors: methodological issues and values for 26 descriptors.
Patients often tell others about their pain using their own verbal descriptors of pain intensity, but the meaning of this pain language is not universally evident, which could contribute to misinterpretation about pain severity. The study purpose was to discover the intensity values of verbal pain intensity descriptors. The 248 randomly selected inpatients used a visual analogue scale to assign a value to each of 26 pain intensity descriptors. Each participant completed 36 randomly ordered visual analogue scales, 10 of which were replications. Except for descriptors with medians close to 0 or 100 mm, there was large, across-person variability for the descriptors. For example, medians ± SD for some exemplar descriptors were no pain 0.7 ± 2.4; mild 16.2 ± 12.2; discomforting 31.3 ± 22.2; distressing 55.3 ± 24; horrible 87.8 ± 13.6; and excruciating 94.6 ± 9.3. Test-retest reliability indicated small within-person variability on scores assigned to each descriptor. Thirteen descriptors showed some statistically significant but rather small effects of presentation order. Findings contribute estimates for the magnitude of pain represented by each of the 26 descriptors. Clinicians, text data miners, and researchers should consider these values as they interpret the meaning of the descriptors that they hear in daily practice or research settings or that they find in electronic health records, email messages, or social media posts. Despite the wide variability in the magnitude of each descriptor, findings provide insights about the intensity of pain when individuals use verbal pain intensity descriptors in conversations, social media, or clinical encounters.


Treatment of the psychotic patient who is violent.
Aggression among patients with serious mental illness occurs relatively infrequently, but it is a significant concern for patients, relatives, mental health professionals, and the public. Recognition of this risk and providing access and continuity of appropriate psychiatric care should be major clinical and administrative objectives in the management of violence in psychotic patients. To date, pharmacologic approaches have been unclear and inconsistent. At present, typical antipsychotics continue to have a primary role in acute management and in long-term management, in which noncompliance necessitates the use of long-acting depot neuroleptic preparations. Atypical antipsychotics in acute and long-acting intramuscular forms doubtless will influence and expand the choice for acute management of hostile psychotic patients and the long-term management of poorly compliant patients who are at risk to become violent on relapse. Persistent aggression should be managed by atypical antipsychotics with a preferential indication for clozapine, for which the most data on efficacy are available. The role of adjunctive medications is presently unclear. A major focus of care should be to refine legal processes and to conduct intervention studies aimed at enhancing treatment compliance. Violence risk reduction is not only crucial from a societal perspective, but also it is a humanitarian necessity to alleviate the burden and stigma for patients with serious mental illness.


Induction of bona fide regulatory T cells after liver transplantation - the potential influence of polyclonal antithymocyte globulin.
T-cell-depleting strategies are an integral part of immunosuppressive regimens used in the hematological and solid organ transplant setting. Besides prevention of alloreactivity, treatment with rabbit antithymocyte globulin (rATG) has been related to the induction of immunoregulatory T cells (Treg) in vitro and in vivo. To investigate Treg induced by rATG, we prospectively studied the effect of rATG induction therapy in liver-transplanted recipients in vivo (n = 28). Treg induction was further evaluated by means of Treg-specific demethylation region (TSDR) analysis within the FOXP3 locus. Whereas no induction of CD4(+) CD25(high) CD127(-) Treg could be observed by phenotypic analysis, we could demonstrate an induction of TSDR(+) T cells within CD4(+) T cells exclusively for rATG-treated patients in the long-term (day 540) compared with controls (P = NS). Moreover, although in vitro experiments confirm that rATG primarily led to a conversion of CD4(+) CD25(-) into CD4(+) CD25(+) T cells displaying immunosuppressive capacities, these cells cannot be classified as bona fide Treg based on their FOXP3 demethylation pattern. Consequently, the generation of Treg after rATG co-incubation in vitro does not reflect the mechanisms of Treg induction in vivo and therefore the potential clinical relevance of these cells for transplant outcome remains to be determined.


Kinetic analysis of clearance of epidermal growth factor in isolated perfused rat kidney.
Our previous in vivo studies identified the saturable uptake of epidermal growth factor (EGF) by rat kidney (D.C. Kim, Y. Sugiyama, H. Sato, T. Fuwa, T. Iga, and M. Hanano, J. Pharm. Sci. 77: 200-207, 1988). In the present study, renal handling of EGF in filtering and nonfiltering isolated perfused rat kidneys was investigated. At designated times after the recirculatory perfusion of 125I-EGF in the nonfiltering kidney, the surface-bound and internalized EGF were separately determined by an acid-washing technique. Time profiles of cell-surface-bound and internalized EGF obtained at the perfusion of a tracer 125I-EGF were fitted to the pharmacokinetic model, and kinetic parameters obtained were as follows: konRs = 0.49 ml.min-1.g-1, koff = 0.87 min-1, kint = 0.20 min-1 where konRs is the binding clearance of EGF with its receptor and koff and kint represent the dissociation and internalization rate constants of the EGF-receptor complex, respectively. The Scatchard analysis of the concentration-dependent EGF binding in the nonfiltering kidney suggests the presence of two binding components, one with high affinity [the apparent dissociation constant (Kd1 = 0.1 nM) and the other with low affinity (Kd2 = 30 nM]. By comparing the internalization clearance (CLi) with filtering and nonfiltering kidneys, we concluded that the renal uptake of EGF occurs mainly from the antiluminal side via receptor-mediated endocytosis in a saturable manner and that the nonsaturable reabsorption of EGF from the luminal membrane after glomerular filtration is relatively small. The contribution of reabsorption, however, becomes larger with the increase in EGF concentration.


Synthesis and processing of the three major envelope glycoproteins of Epstein-Barr virus.
In pulse-chase experiments, the three major Epstein-Barr virus envelope glycoproteins, gp350/300, gp250/200, and gp85, were shown to be synthesized from separate precursors of 190,000, 160,000, and 83,000 daltons, respectively. These three pulse-labeled species were chased into the mature forms of the glycoproteins between 1 and 3 h after transfer to nonradioactive medium. Digestion of precursor forms with endo-beta-N-acetylglucosaminidase H (endo H) yielded polypeptides of 160,000, 120,000, and 75,000 daltons. Comparison of these results with those from experiments with tunicamycin, which specifically blocks N-linked glycosylation, indicated that some other post-translational modification(s), probably O-linked glycosylation, contributes about 100,000 and 60,000 daltons of apparent molecular mass to gp350/300 and gp250/200, respectively. Experiments with endo H showed that mature gp350/300 and gp250/200 contain complex-type (endo H-resistant) N-linked glycosyl chains, whereas gp85 contains both high-mannose (endo H-sensitive)- and complex-type oligosaccharides. In contrast to the results obtained with the three envelope glycoproteins, no precursor forms of the two unglycosylated protein, p160 (the major Epstein-Barr virus capsid antigen) and p140 (an envelope protein), were detected. The partial proteolytic maps of gp350/300 and gp250/200 were quite similar, suggesting that polypeptide sequence homology could account for at least part of the observed serological cross-reactivity of the two proteins. Taken together, these results demonstrate that the polypeptide portions of gp350/300 and gp250/200 are closely related but not derived from a common precursor. Furthermore, the polypeptide portions comprise half or less of the apparent molecular weight of the mature glycoproteins on sodium dodecyl sulfate-polyacrylamide gel electrophoresis.


Patterns of distant metastases in patients with clear cell renal cell carcinoma--A population-based analysis.
We developed this study to describe the patterns of distant metastasis (DM) and explore the predictive and prognostic factors of DM in clear cell renal cell carcinoma (ccRCC) patients. We collected the eligible patients from the Surveillance, Epidemiology, and End Result (SEER) database from 2010 to 2015. Then, comparisons of baseline characteristics between patients in different metastatic patterns were made. In addition, proportional mortality ratios (PMRs) and proportion trends of different patterns were calculated. Afterward, survival outcomes were explored by Kaplan-Meier (KM) analyses. Finally, predictive and prognostic factors of DM were investigated. A total of 33,449 ccRCC patients were eventually identified, including 2931 patients with DM and 30,518 patients without DM. 8.76% of patients suffered DM at their initial diagnosis, 35.01% of them had multiple metastases. Generally, lung (6.19%) was the most common metastatic site in patients with DM, and brain (1.20%) was the least frequent metastatic organ. The proportion trends of different metastatic patterns tended to be stable between 2010 and 2015. Moreover, higher tumor grade, T stage, and N stage were identified as risk factors of DM. Finally, age at diagnosis, grade, T stage, N stage, the administration of surgery, the number of metastatic sties, marital status, and household income were found to be significantly associated with prognosis. Lung was the most common metastatic site in ccRCC patients. Different survival outcomes and prognostic factors were identified for different metastatic patterns. Hence, our study would have great value for clinical practice in the future.


Quantitative descriptions of rice plant architecture and their application.
Plant architecture is an important agronomic trait, and improving plant architecture has attracted the attention of scientists for decades, particularly studies to create desirable plant architecture for high grain yields through breeding and culture practices. However, many important structural phenotypic traits still lack quantitative description and modeling on structural-functional relativity. This study defined new architecture indices (AIs) derived from the digitalized plant architecture using the virtual blade method. The influences of varieties and crop management on these indices and the influences of these indices on biomass accumulation were analyzed using field experiment data at two crop growth stages: early and late panicle initiation. The results indicated that the vertical architecture indices (LAI, PH, 90%-DRI, MDI, 90%-LI) were significantly influenced by variety, water, nitrogen management and the interaction of water and nitrogen, and compact architecture indices (H-CI, Q-CI, 90%-LI, 50%-LI) were significantly influenced by nitrogen management and the interaction of variety and water. Furthermore, there were certain trends in the influence of variety, water, and nitrogen management on AIs. Biomass accumulation has a positive linear correlation with vertical architecture indices and has a quadratic correlation with compact architecture indices, respectively. Furthermore, the combination of vertical and compact architecture indices is the indicator for evaluating the effects of plant architecture on biomass accumulation.


Climate predicts which sex acts as helpers among cooperatively breeding bird species.
Among avian cooperative breeders, help in raising offspring is usually provided by males or by both sexes. Sex bias in helping should evolve in response to sex-specific ecological constraints on independent reproduction, with mate shortage for males and breeding vacancy shortage for each sex. Given that male-biased adult sex ratios are prevalent among birds, we predict that male-only helping mainly occurs in temperate species where fast population turnovers deriving from low adult annual survival allow all adult females to hold breeding vacancies, whereas some males overflow as helpers, and both-sex helping in tropical species where saturated habitats prevent not only males, but also females from breeding themselves. As expected, we found that across species, adult survival increased towards tropical zones and warmer climates, and higher adult survival tended to be associated with both-sex helping. Furthermore, sex bias in helping was predicted by latitude and ambient temperature. Our findings of demographic response of species to climate as a potential determinant of bias in helper sex uncover how ecological constraints operate to limit independent reproduction in sex-specific ways.


Species differences in expression pattern of arginase isoenzymes and differential effects of arginase inhibition on collagen synthesis in human and rat pulmonary fibroblasts.
Arginase was shown to be up-regulated in different animal models of inflammatory and fibrotic airway diseases. Since arginase provides L-ornithine, one precursor for L-proline, an essential substrate for collagen synthesis, it has been suggested that arginase might be a key enzyme in airway remodelling. The present study aimed to characterize expression of arginase isoenzymes in rat and human pulmonary fibroblasts, and to test whether arginase inhibition affects collagen synthesis. In primary rat tracheal and lung fibroblasts, mRNA for arginase I and II could be detected, with arginase I as predominant isoenzyme. In contrast, in human lung fibroblasts (primary cells and different cells lines) mRNA levels for arginase I were at or below detection limit whereas arginase II mRNA was markedly higher than in rat pulmonary fibroblasts. Arginase activity in rat tracheal and lung fibroblasts was between 20 and 30 mU/mg protein, but was below detection limit (2.5 mU/mg) in human lung fibroblasts. In rat tracheal and lung fibroblasts cultured in proline-free medium, arginase inhibition by N(omega)-hydroxy-nor-L-arginine caused a reduction by about one-third of basal collagen I accumulation (determined by western blot analysis) and largely attenuated transforming growth factor beta 1 (TGF-beta(1))-induced increase in collagen accumulation, whereas basal and TGF-beta(1)-induced collagen accumulation by human lung fibroblasts was not affected by arginase inhibition. In conclusion, arginase isoenzymes reveal a species specific expression pattern. Arginase contributes significantly to L-proline supply for collagen synthesis in rat fibroblasts, in which arginase I is the predominant isoenzyme, but not in human fibroblasts, in which arginase II is the only isoenzyme expressed.


Resistin is elevated in cystic fibrosis sputum and correlates negatively with lung function.
Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease. Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function. Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50-100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype). Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF.


Pdx-1 links histone H3-Lys-4 methylation to RNA polymerase II elongation during activation of insulin transcription.
Expression of the insulin gene is nearly exclusive to the beta cells of the pancreatic islets. Although the sequence-specific transcription factors that regulate insulin expression have been well studied, the interrelationship between these factors, chromatin structure, and transcriptional elongation by RNA polymerase II (pol II) has remained undefined. In this regard, recent studies have begun to establish a role for the methylation of histone H3 in the initiation or elongation of transcription by pol II. To determine a role for the transcriptional activator Pdx-1 in the maintenance of chromatin structure and pol II recruitment at the insulin gene, we performed small interfering RNA-mediated knockdown of Pdx-1 in betaTC3 cells and subsequently studied histone modifications and pol II recruitment by chromatin immunoprecipitation. We demonstrated here that the 50% fall in insulin transcription following knockdown of Pdx-1 is accompanied by a 60% fall in dimethylated histone H3-Lys-4 at the insulin promoter. H3-Lys-4 methylation at the insulin promoter may be mediated, at least partially, by the methyltransferase Set9. Immunohistochemical analysis revealed that Set9 is expressed in an islet-enriched pattern in the pancreas, similar to the pattern of Pdx-1 expression. The recruitment of Set9 to the insulin gene appears to be a consequence of its direct interaction with Pdx-1, and small interfering RNA-mediated knockdown of Set9 attenuates insulin transcription. Pdx-1 knockdown was also associated with an overall shift in the recruitment of pol II isoforms to the insulin gene, from an elongation isoform (Ser(P)-2) to an initiation isoform (Ser(P)-5). Our findings therefore suggest a model whereby Pdx-1 plays a novel role in linking H3-Lys-4 dimethylation and pol II elongation to insulin transcription.


Update on Brugada Syndrome 2019.
Brugada syndrome (BrS) was first described in 1992 as an aberrant pattern of ST segment elevation in right precordial leads with a high incidence of sudden cardiac death (SCD) in patients with structurally normal heart. It represents 4% ∼ 12% of all SCD and 20% of SCD in patients with structurally normal heart. The extremely wide genetic heterogeneity of BrS and other inherited cardiac disorders makes this new area of genetic arrhytmology a fascinating one. This review shows the state of art in diagnosis, management, and treatment of BrS focusing all the aspects regarding genetics and Preimplant Genetic Diagnosis (PGD) of embryos, overlapping syndromes, risk stratification, familial screening, and future perspectives. Moreover the review analyzes key points like electrocardiogram (ECG) criteria, the role of electrophysiological study (the role of ventricular programmed stimulation and the need of universal accepted protocol) and the importance of a correct risk stratification to clarify when implantable cardioverter defibrillator or a close follow-up is needed. In recent years, cardiovascular studies have been focused on personalized risk assessment and to determine the most optimal therapy for an individual. The BrS syndrome has also benefited of these advances although there remain several key points to be elucidated. We will review the present knowledge, progress made, and future research directions on BrS.


Novel mutations in neuroendocrine carcinoma of the breast: possible therapeutic targets.
Primary neuroendocrine carcinoma of the breast is a rare variant, accounting for only 2% to 5% of diagnosed breast cancers, and may have relatively aggressive behavior. Mutational profiling of invasive ductal breast cancers has yielded potential targets for directed cancer therapy, yet most studies have not included neuroendocrine carcinomas. In a tissue microarray screen, we found a 2.4% prevalence (9/372) of neuroendocrine breast carcinoma, including several with lobular morphology. We then screened primary or metastatic neuroendocrine breast carcinomas (excluding papillary and mucinous) for mutations in common cancer genes using polymerase chain reaction-mass spectroscopy (643 hotspot mutations across 53 genes), or semiconductor-based next-generation sequencing analysis (37 genes). Mutations were identified in 5 of 15 tumors, including 3 with PIK3CA exon 9 E542K mutations, 2 of which also harbored point mutations in FGFR family members (FGFR1 P126S, FGFR4 V550M). Single mutations were found in each of KDR (A1065T) and HRAS (G12A). PIK3CA mutations are common in other types of breast carcinoma. However, FGFR and RAS family mutations are exceedingly rare in the breast cancer literature. Likewise, activating mutations in the receptor tyrosine kinase KDR (VEGFR2) have been reported in angiosarcomas and non-small cell lung cancers; the KDR A1065T mutation is reported to be sensitive to VEGFR kinase inhibitors, and fibroblast growth factor receptor inhibitors are in trials. Our findings demonstrate the utility of broad-based genotyping in the study of rare tumors such as neuroendocrine breast cancer.


Geminivirus AL2 and L2 proteins interact with and inactivate SNF1 kinase.
Geminivirus AL2 and L2 proteins cause enhanced susceptibility, characterized primarily by an increase in viral infectivity, when expressed in transgenic plants. Here, we present genetic and biochemical evidence that enhanced susceptibility is attributable to the interaction of AL2 and L2 with SNF1 kinase, a global regulator of metabolism. Specifically, we show that AL2 and L2 inactivate SNF1 in vitro and in vivo. We further demonstrate that expression of an antisense SNF1 transgene in Nicotiana benthamiana plants causes enhanced susceptibility similar to that conditioned by the AL2 and L2 transgenes, whereas SNF1 overexpression leads to enhanced resistance. Transgenic plants expressing an AL2 protein that lacks a significant portion of the SNF1 interaction domain do not display enhanced susceptibility. Together, these observations suggest that the metabolic alterations mediated by SNF1 are a component of innate antiviral defenses and that SNF1 inactivation by AL2 and L2 is a counterdefensive measure. They also indicate that geminiviruses are able to modify host metabolism to their own advantage, and they provide a molecular link between metabolic status and inherent susceptibility to viral pathogens.


Estimating the allele frequency of autosomal recessive disorders through mutational records and consanguinity: the Homozygosity Index (HI).
In principle mutational records make it possible to estimate frequencies of disease alleles (q) for autosomal recessive disorders using a novel approach based on the calculation of the Homozygosity Index (HI), i.e., the proportion of homozygous patients, which is complementary to the proportion of compound heterozygous patients P(CH). In other words, the rarer the disorder, the higher will be the HI and the lower will be the P(CH). To test this hypothesis we used mutational records of individuals affected with Familial Mediterranean Fever (FMF) and Phenylketonuria (PKU), born to either consanguineous or apparently unrelated parents from six population samples of the Mediterranean region. Despite the unavailability of precise values of the inbreeding coefficient for the general population, which are needed in the case of apparently unrelated parents, our estimates of q are very similar to those of previous descriptive epidemiological studies. Finally, we inferred from simulation studies that the minimum sample size needed to use this approach is 25 patients either with unrelated or first cousin parents. These results show that the HI can be used to produce a ranking order of allele frequencies of autosomal recessive disorders, especially in populations with high rates of consanguineous marriages.


DEPRESSION AND ITS ASSOCIATED FACTORS AMONG SECONDARY SCHOOL STUDENTS IN MALAYSIA.
Research in the field of factors associated with depression among adolescents is lacking in Malaysia. The aims of the present study were to assess the current prevalence of depression and its related factors among secondary school students in Pasir Gudang, South Malaysia. In this cross sectional study, 2,927 secondary school students (13-17 years old) from urban areas were screened for symptoms of mental disorder as well as demographic and risk behaviors using a validated Depression, Anxiety and Stress Scale (DASS) 12 questionnaire. The majority of the respondents (53.8%) were Malay, of which 53.1% were female. Symptoms of mild depression were found in 33.2% of the respondents, while the prevalence of the symptoms of moderate, severe, and extremely severe depression was 21.5%, 18.1%, and 3.0%, respectively. Logistic regression suggested that participants who were Chinese or had a lower average grade were three times more likely to have depression, while those who came from a single-parent family were twice as likely to have this condition. This study indicated that academic performance and risk behaviors along with the demographic characteristics are important contributors to adolescent depression.


Photoembossing of surface relief structures in polymer films for biomedical applications.
Photoembossing is a technique used to create relief structures using a patterned contact photo-mask exposure and a thermal development step. Typically, the photopolymer consists of a polymer binder and a monomer in a 1/1 ratio together with a photo-initiator, which results in a solid and non-tacky material at room temperature. Here, new mixtures for photoembossing are presented which are potentially biocompatible. Poly(methyl methacrylate) is used as a polymer binder and two different acrylate monomers trimethylolpropane ethoxylate triacrylate (TPETA) and dipentaerythritol penta-/hexa-acrylate (DPPHA) are tested. PMMA-TPETA had a higher surface relief features. Biocompatibility is evaluated by culturing human umbilical vein endothelial cells (HUVECs) on films of these photopolymer blends. PMMA with TPETA and PMMA-DPPHA films showed enhanced cell adhesion compared to PMMA. The cells also showed alignment on surface textured films with the highest degree of alignment on films with 20 μm pitch and 2 μm height. This study shows that photoembossing is a feasible method to produce surface textures on films that can be adopted in the field of tissue engineering to promote cell adhesion and alignment.


Chondroitin 6-O-sulfotransferases are required for morphogenesis of the notochord in the ascidian embryo.
Chondroitin sulfate (CS) is a sulfated polysaccharide chain that binds to various core proteins to form proteoglycans. The amount and position of sulfate groups in CS are variable among different tissues, and are determined by specific sulfotransferases. Although the ascidians are the closest relatives of vertebrates, the functions of their sulfotransferases have not been studied. The genome of the ascidian Ciona intestinalis contains eight genes encoding proteins similar to chondroitin 6-O-sulfotransferases (C6STs), which appear to have independently diverged in the ascidian lineage during evolution. Among them, Ci-C6ST-like1 and Ci-C6ST-like7 were predominantly expressed in the developing notochord. In addition, they were weakly expressed in the neural tube. The disruption of either one of them affected the convergent extension movement of notochordal cells. Presumptive notochord cells coming from both sides of the embryo did not intercalate. The results suggest that both of them are necessary. In some cases, the anterior neural tube failed to close. Forced expression of Ci-C6ST-like1 or Ci-C6ST-like7 in the notochord restored the normal intercalation of notochordal cells, indicating that the effects of morpholino oligos are specific. Ci-C6ST-like1 and Ci-C6ST-like7 are required for the morphogenesis of the notochord in the ascidian embryo.


Histopathologic effects of transarterial bucrylate occlusion of intracerebral arteries in mongrel dogs.
Bucrylate was injected directly into the cerebral cortical arteries of mongrel dogs. Preparations for light and electron microscopy were obtained from 5 min to 5 months after the introduction of the polymer. A mixed pattern of damage to arterial endothelium was seen, including electron microscopic documentation of stripping away of the endothelium. Acute effects include a subocclusive thrombogenic matrix, which causes partial or complete thrombosis. The long-term reactions are those of a chronic inflammatory response to a foreign body.


Multimode fiber modal decomposition based on hybrid genetic global optimization algorithm.
Numerical modal decomposition (MD) is an effective approach to reveal modal characteristics in high power fiber lasers. The main challenge is to find a suitable multi-dimensional optimization algorithm to reveal exact superposition of eigenmodes, especially for multimode fiber. A novel hybrid genetic global optimization algorithm, named GA-SPGD, which combines the advantages of genetic algorithm (GA) and stochastic parallel gradient descent (SPGD) algorithm, is firstly proposed to reduce local minima possibilities caused by sensitivity to initial values. Firstly, GA is applied to search the rough global optimization position based on near- and far-field intensity distribution with high accuracy. Upon those initial values, SPGD algorithm is afterwards used to find the exact optimization values based on near-field intensity distribution with fast convergence speed. Numerical simulations validate the feasibility and reliability.


Variation in the kinetics of caspase-3 activation, Bcl-2 phosphorylation and apoptotic morphology in unselected human ovarian cancer cell lines as a response to docetaxel.
Paclitaxel is able to cause cell death through the induction of apoptosis. Cell death characteristics for docetaxel have not yet been described in detail. We investigated four unselected human ovarian cancer cell lines for the sensitivity to a 1hr exposure to docetaxel and calculated the concentrations inhibiting 50% (IC(50)) and 90% (IC(90)) of cell growth. Of the cell lines A2780, H134, IGROV-1 (all wild-type p53) and OVCAR-3 (mutant, mt p53) A2780 was most sensitive and OVCAR-3 least sensitive. Equitoxic drug concentrations representing IC(90) values (25-510nM) were applied for 1hr to measure cell cycle distribution, DNA degradation, and to count apoptotic cell bodies and cells with multifragmented nuclei at various time-points after drug exposure. H134, IGROV-1 and OVCAR-3 showed a continued mitotic block up to at least 72hr and prolonged presence of cells with multifragmented nuclei. High percentages of apoptosis were calculated at 48hr and at later time-points. In contrast, A2780 cells accumulated in the S-phase of the cell cycle and apoptosis was hardly present. The changes in the expression levels of p53, p21/WAF1, Bax and Bcl-2, were not predictive for docetaxel-induced apoptosis. Caspase-3 activation occurred only in cells with accumulation in the G2/M phase starting as early as 8hr in OVCAR-3. Prolonged Bcl-2 phosphorylation was evident in OVCAR-3, visible at 24hr in H134 and IGROV-1, while this phenomenon did not occur in A2780. The mitogen-activated protein kinase pathway (JNKs/SAPKs or c-Jun N-terminal kinases/stress-activated protein kinases, JNK1/2; extracellular response kinase, ERK1/2; p38) did not seem to be directly involved in Bcl-2 phosphorylation or apoptosis. We conclude that docetaxel is able to activate caspase-3, induce Bcl-2 phosphorylation and apoptosis in cells that show a prolonged G2/M arrest, but cells may also die by a caspase-3-independent cell death mechanism.


Knowledge and perception of dental practitioners regarding the use of devitalizing agents.
Pulpal pain is amongst the most severe pains experienced by humans. Various chemical agents are used routinely to devitalize the severely inflamed pulpal tissue. Most of these agents are harmful and have detrimental effects. This questionnaire-based study evaluated the awareness and perception of dental practitioners regarding the use of devitalizing agents during endodontic procedures, and various alternatives to minimize the use of these agents. An open questionnaire was distributed to a total of 250 dental practitioners. It carried detailed information about the most common devitalizing agent used, the purpose of use, method, and duration of application, recommendations, complications encountered, awareness of complications, and various alternatives. The collected data were subjected to statistical analysis using SPSS (Statistical Package for Social Sciences) version 17.0 (IBM Statistics, Chicago, Illinois, USA). Descriptive statistics were drawn with respective percentages to have a comparative overview. 209 responses to 250 questionnaires circulated gave a response rate of 83.6%. Amongst them, 63.15% of dentists were using devitalizing agents. The most widely and frequently used devitalizing agent was Devitec (PD Swiss, Vevey, Switzerland) (36.3%), followed by Caustinerf forte (Septodont, Saint-Maur-des-Fosses, France) (29.5%). A total of 32.9% dentists were aware of the recommendations, and 66.02% were aware of the complications of devitalizing agents; 16.26% of dental practitioners encountered complications due to the use of devitalizing agents. The dentists listed the alternate methods regarding the use of pulp devitalizing agents. Although most of the dentists were aware of the harmful effects and few encountered complications with the use of devitalizers, they continued to use these agents because of the lack of an effective alternative.


Controversies in clinical trials in proton radiotherapy: the present and the future.
Proponents of proton radiotherapy have cited the dose distribution characteristics of proton beams as evidence of its superiority over photon radiotherapy. Outcomes after photon radiotherapy remain suboptimal owing to poor local control and normal-tissue toxicity in many clinical indications. Critics of proton radiotherapy have noted the relative lack of prospective data from clinical trials showing a benefit for proton radiotherapy despite its theoretical advantages. Questions remain with regard to physical uncertainties in proton dose delivery and variations in their radiobiological effect in different tissues and tumors. Although prospective data have been scant in the past, clinical trials using proton radiotherapy are now being conducted with increasing frequency. However, very few of these are randomized controlled trials comparing protons directly with photons. Randomized controlled trials should remain the ideal tool for research in proton radiotherapy: they should be focused on areas where clinical equipoise is present, ideally in tumor sites where there is a low risk of systemic failure, a high risk of local progression, and/or a high risk of toxicity with conventional therapy. Proton radiotherapy centers should develop prospective registries with the goal of long-term data collection on an international basis to support the evidence provided by observational studies and comparative effectiveness research trials.


The bifunctional enzyme, GenB4, catalyzes the last step of gentamicin 3',4'-di-deoxygenation via reduction and transamination activities.
New semi-synthetic aminoglycoside antibiotics generally use chemical modifications to avoid inactivity from pathogens. One of the most used modifications is 3',4'-di-deoxygenation, which imitates the structure of gentamicin. However, the mechanism of di-deoxygenation has not been clearly elucidated. Here, we report that the bifunctional enzyme, GenB4, catalyzes the last step of gentamicin 3',4'-di-deoxygenation via reduction and transamination activities. Following disruption of genB4 in wild-type M. echinospora, its products accumulated in 6'-deamino-6'-oxoverdamicin (1), verdamicin C2a (2), and its epimer, verdamicin C2 (3). Following disruption of genB4 in M. echinospora ΔgenK, its products accumulated in sisomicin (4) and 6'-N-methylsisomicin (5, G-52). Following in vitro catalytic reactions, GenB4 transformed sisomicin (4) to gentamicin C1a (9) and transformed verdamicin C2a (2) and its epimer, verdamicin C2 (3), to gentamicin C2a (11) and gentamicin C2 (12), respectively. This finding indicated that in addition to its transamination activity, GenB4 exhibits specific 4',5' double-bond reducing activity and is responsible for the last step of gentamicin 3',4'-di-deoxygenation. Taken together, we propose three new intermediates that may refine and supplement the specific biosynthetic pathway of gentamicin C components and lay the foundation for the complete elucidation of di-deoxygenation mechanisms.


Extracorporeal shock-wave treatment for tennis elbow. A randomised double-blind study.
The efficacy of extracorporeal shock-wave therapy for tennis elbow was investigated using a single fractionated dosage in a randomised, double-blind study. Outcomes were assessed using the Disabilities of Arm, Shoulder and Hand questionnaire, measurements of grip strength, levels of pain, analgesic usage and the rate of progression to surgery. Informed consent was obtained before patients were randomised to either the treatment or placebo group. In the final assessment, 74 patients (31 men and 43 women) with a mean age of 43.4 years (35 to 71), were included. None of the outcome measures showed a statistically significant difference between the treatment and control groups (p > 0.05). All patients improved significantly over time, regardless of treatment. Our study showed no evidence that extracorporeal shock-wave therapy for tennis elbow is better than placebo.


Dietitians in South Africa require more competencies in public health nutrition and management to address the nutritional needs of South Africans.
The aim of this study was to determine whether dietitians in South Africa are competent to meet the requirements of working in a health care setting during a compulsory one-year community service (CS) program immediately after receiving their degree. A national survey was conducted using questionnaires to illicit information from dietitians on their training and competencies. In 2009, data were collected from both community service dietitians (CSDs) participating in community service programs in primary, secondary and tertiary health care centers in all provinces of South Africa, as well as from their provincial managers (nutrition coordinators). Sixteen (100% response) nutrition coordinators and 134 (80% response) dietitians participated in the quantitative survey. The majority of the CSDs reported that, overall, their academic training had prepared them for most aspects of nutrition service delivery. However, some recommended that academic programs include more training on community-based nutrition programs and in delivering optimal services to under-resourced communities as they believed that their competencies in these two areas were weakest. Furthermore, many CSDs were required to establish dietetics departments where none had previously existed; consequently, their capacity in management and administration needed improvement. In conclusion, academic training institutions should align their programs to the transformation of the health sector in South Africa by ensuring that dietitians are empowered to provide optimal public health nutrition services in under-resourced communities.


Differential role of all-trans retinoic acid in promoting the development of CD4+ and CD8+ regulatory T cells.
It is known that ATRA promotes the development of TGF-β-induced CD4(+)Foxp3(+) iTregs, which play a vital role in the prevention of autoimmune diseases; however, the role of ATRA in facilitating the differentiation and function of CD8(+)Foxp3(+) iTregs remains elusive. Using a head-to-head comparison, we found that ATRA promoted expression of Foxp3 and development of CD4(+) iTregs, but it did not promote Foxp3 expression on CD8(+) cells. Using a standard in vitro assay, we demonstrated that CD8(+) iTregs induced by TGF-β and ATRA were not superior to CD8(+) iTregs induced by TGF-β alone. In cGVHD, in a typical lupus syndrome model where DBA2 spleen cells were transferred to DBA2xC57BL/6 F1 mice, we observed that both CD8(+) iTregs induced by TGF-β and ATRA and those induced by TGF-β alone had similar therapeutic effects. ATRA did not boost but, conversely, impaired the differentiation and function of human CD8(+) iTregs. CD8(+) cells expressed the ATRA receptor RAR and responded to ATRA, similar to CD4(+) cells. We have identified the differential role of ATRA in promoting Foxp3(+) Tregs in CD4(+) and CD8(+) cell populations. These results will help to determine a protocol for developing different Treg cell populations and may provide novel insights into clinical cell therapy for patients with autoimmune diseases and those needing organ transplantation.


Association of fecal indicator bacteria with human viruses and microbial source tracking markers at coastal beaches impacted by nonpoint source pollution.
Water quality was assessed at two marine beaches in California by measuring the concentrations of culturable fecal indicator bacteria (FIB) and by library-independent microbial source tracking (MST) methods targeting markers of human-associated microbes (human polyomavirus [HPyV] PCR and quantitative PCR, Methanobrevibacter smithii PCR, and Bacteroides sp. strain HF183 PCR) and a human pathogen (adenovirus by nested PCR). FIB levels periodically exceeded regulatory thresholds at Doheny and Avalon Beaches for enterococci (28.5% and 31.7% of samples, respectively) and fecal coliforms (20% and 5.8%, respectively). Adenoviruses were detected at four of five sites at Doheny Beach and were correlated with detection of HPyVs and human Bacteroides HF183; however, adenoviruses were not detected at Avalon Beach. The most frequently detected human source marker at both beaches was Bacteroides HF183, which was detected in 27% of samples. Correlations between FIBs and human markers were much more frequent at Doheny Beach than at Avalon Beach; e.g., adenovirus was correlated with HPyVs and HF183. Human sewage markers and adenoviruses were routinely detected in samples meeting FIB regulatory standards. The toolbox approach of FIB measurement coupled with analysis of several MST markers targeting human pathogens used here demonstrated that human sewage is at least partly responsible for the degradation of water quality, particularly at Doheny Beach, and resulted in a more definitive assessment of recreational water quality and human health risk than reliance on FIB concentrations alone could have provided.


Engineering of nanoscale defect patterns in CeO2 nanorods via ex situ and in situ annealing.
Single-crystalline ceria nanorods were fabricated using a hydrothermal process and annealed at 325 °C-800 °C. As-synthesized CeO2 nanorods contain a high concentration of defects, such as oxygen vacancies and high lattice strains. Annealing resulted in an improved lattice crystalline quality along with the evolution of novel cavity-shaped defects in the nanorods with polyhedral morphologies and bound by e.g. {111} and {100} (internal) surfaces, confirmed for both air (ex situ) and vacuum (in situ) heating. We postulate that the cavities evolve via agglomeration of vacancies within the as-synthesized nanorods.


Endovascular treatment of 306 anterior communicating artery aneurysms: overall, perioperative results.
A series of 306 consecutive patients with an anterior communicating artery (ACoA) aneurysm is presented. The goal in this study was to report the results of endovascular treatment of ACoA aneurysms in these patients. The aneurysms were managed with an endovascular approach in which detachable coils were used. A brief anatomical description of the ACoA and its branches as well as a review of the surgical and endovascular literature is presented. The "ACoA Syndrome" (that is, amnesia and personality changes), which may occur after subarachnoid hemorrhage, is briefly reviewed and described. Recent technical developments that can lead to improved results are also discussed. Of the 306 aneurysms, 268 (87.5%) were small, 30 (10%) were large, and 8 (2.6%) were giant. One hundred ninety-three aneurysms (63%) had a small neck, whereas 113 (37%) had a wide neck. Sixty-five lesions (21%) were incidental, 5 (2%) presented with symptoms of mass effect, and 236 (77%) presented with a subarachnoid hemorrhage. A complete aneurysm occlusion was attained in 139 cases (45.5%), a neck remnant was detected in 145 (47.5%), and in 22 cases (7%) a residual filling of the aneurysm was observed. Regarding the clinical neurological outcome, 280 patients (91.5%) remained neurologically intact, improved, or unchanged from their initial clinical status. Two large, wide-necked, subtotally occluded aneurysms ruptured 3-7 months after the procedure, with subsequent death of the patients. The procedure-related morbidity and mortality rates were 3.5% (11 cases) and 1% (3 cases), respectively. The inherently lower risk of injuring or occluding the delicate branches and perforating vessels arising from the ACoA makes the endovascular approach attractive, interesting, and elegant.


Double-balloon enteroscopy: a descriptive study of 50 explorations.
To evaluate the utility of double-balloon enteroscopy for small-bowel disease. A prospective study of 50 consecutive enteroscopies performed from December 2004 to July 2005 to analyze diagnoses and treatments. 44 patients (33 had undergone a previous capsule endoscopy) with indications for obscure digestive hemorrhage, angiodysplasia, Peutz-Jeghers syndrome, ulcer, suspected Crohn's disease, tumors, and refractory celiac disease. We carried out enteroscopy studies in 44 patients by the oral route and, in 6 additional patients, by both the oral and anal routes. We reached the ileon with the oral route in all cases but one (jejunal stenosis), and in 4 cases out of 7 with the anal route, with an average duration of 73 minutes. We found angiodysplasia in 19 cases, as well as NSAID-related enteropathy, Crohn's disease, diverticulosis, and Waldenström's disease. We performed biopsies in 31% of cases with diagnoses of adenocarcinoma, lymphangiectasia secondary to tumor in celiac disease, and Whipple's disease. We treated 19 patients with angiodysplasia (1 to 20 synchronous lesions) with argon, and 4 patients with polyps using polipectomy (sporadic polyps or Peutz-Jeghers syndrome). A retained capsule in one patient with stenosis was removed. Double-balloon enteroscopy is a useful and effective technique in the diagnosis and treatment of small intestine diseases, thus complementing capsule endoscopy. More studies are needed to analyze its impact on the management of this condition.


Visual field constriction in children with epilepsy on vigabatrin treatment.
Vigabatrin is considered the drug of choice for infantile spasms and simple and complex partial epilepsy in childhood. Its mechanism of action relies on the irreversible inhibition of gamma-aminobutyric acid (GABA) transaminase. Since June 1997 several articles have been published reporting visual field constriction in adult patients on vigabatrin therapy. Recently, 7 pediatric patients, 1 on vigabatrin monotherapy and 6 on add-on therapy with visual field constriction have been described. We have observed 30 pediatric patients with epilepsy (14 boys and 16 girls), ages ranging from 4 to 20 years (mean: 11 years and 2 months) treated with vigabatrin for infantile spasms, simple and complex partial epilepsy, who had never complained of ophthalmologic disturbances. Twenty-one patients underwent complete routine ophthalmologic examination (fundus oculi, visual acuity, intraocular pressure, and visual field tests); 9 children (<6 years old) underwent only fundus examination, because collaboration was lacking. We report on 4 children showing constriction of visual field, prevailing in nasal hemifield. In 1 child, visual abnormalities were stable even 10 months after vigabatrin discontinuation, while in another a greater improvement was observed 5 months after discontinuation. The possible mechanisms have been discussed and the cone dysfunction, connected with GABA augmentation in the outer retina, has been outlined. We suggest a possible protocol to control visual abnormalities in epileptic children.


The determinants of nurses' therapeutic attitude to patients who use illicit drugs and implications for workforce development.
To examine the determinants of generalist nurses' therapeutic attitude to patients who use illicit drugs, and to model workforce development initiatives. Individuals who use illicit drugs rely heavily on healthcare in emergency departments and inpatient hospital wards. Little is known about the determinants of generalist nurses' therapeutic attitude to provide care, therefore limiting our understanding of the important issues for workforce development. The study was a cross-sectional survey of registrants on the Australian Capital Territory Nurses Registration Roll 2002 (N = 3241, 50% response rate). The associations between variables and nurses' therapeutic attitude were examined by multi-variable linear regression analysis. Nurses' therapeutic attitude was assessed using a modified version of the Alcohol and Alcohol Problems Perception Questionnaire. Personal characteristics, attitudes to illicit drugs and professional practice variables such as drug and alcohol education, experience with the patient group and role support were examined using a mix of standardised and new questions. Professional practice variables explained 53% of the variation of nurses' therapeutic attitude, the most important being role support. Although a negative attitude to illicit drugs had a statistically significant association with therapeutic attitude, it added less than 1% to the variation explained. Personal characteristics showed no association. Generalist nurses struggle to provide care to this patient group. Role support was found to be the strongest driver of nurses' therapeutic attitude, and workplace illicit drug education was only useful in combination with high role support. Nurses' caring role with patients who use illicit drugs is complex and demanding. Nursing workforce development must focus on increasing nurses' role support, in terms of appropriately skilled staff readily available for consultation and advice. Support for nurses, in the form of evidence-based practice standards and appropriate time allocation, is also important.


Influence of different wild-garlic (Allium ursinum) extracts on the gastrointestinal system: spasmolytic, antimicrobial and antioxidant properties.
As there are no previous studies of the European wild-garlic (Allium ursinum) effects on the gastrointestinal system, despite its traditional applications in gastrointestinal disorders' treatment and regular use in the human diet, we have quantified and compared spasmolytic, antimicrobial and antioxidant activities of its different leaf extracts. Wild-garlic extracts were tested for spasmolytic activity on isolated rat ileum, antimicrobial activity on selected Gram-positive and Gram-negative bacteria and fungi by microdilution method and antioxidant capacity by DPPH radical-scavenging assay. Wild-garlic extracts were found to decrease ileal basal tone. As the relaxation of K+ -induced contractions was similar to one caused by papaverin, the observed spasmolytic effect was most likely mediated through Ca2+ -channel inhibition. Ethanolic extract (with the highest phenolic and high alk(en)yl cysteine sulphoxides' levels) produced the strongest spasmolytic activity. In case of acetylcholine-induced contractions, only hydromethanolic extract showed no statistical difference in comparison with positive control. All samples exhibited certain antioxidant potential and strong antimicrobial activity against tested enteropathogenic strains (Salmonella enteritidis was the most sensitive, followed by Escherichia coli, Proteus mirabilis and Enterococcus faecalis). Besides other already established health-promoting effects, wild garlic could be useful in treatment of mild gastrointestinal disturbances.


[Significance of PRRS virus infections for respiratory tract infections in swine--a literature review].
The paper summarises present knowledge concerning the possible role of a virus which has in the meantime been classified as belonging to the arteriviridae and which causes PRRS (Porcine Reproductive and Respiratory Syndrome), in the pathogenesis of respiratory diseases four years after first isolation of the virus. Although the fact that PRRSV-infection produces an immunity which protects swine from repeated bouts of PRRSV is common knowledge by now, reinfection with the virus might be possible. An immunosuppression, which has been suggested by many investigators, and which was thought to be the result of destruction of alveolar macrophages during virus replication, was not found as yet. The significance of the extent and the duration of the decrease in the number of alveolar macrophages, which belong to the unspecific immunity, for the total immune system of swine infected with PRRSV remains unclear. A general impairment of specific immunity through PRRSV-infection could not be shown. The present role of PRRS for the pathogenesis of respiratory disease is seen very differently. The significance of PRRSV as primary cause of an "influenza-like" illness which is principally followed by severe bacterial infection of the respiratory tract, is questioned by the results of studies which identify PRRSV-infection as a mainly subclinical disease. In these studies, clinical cases are the exemption. Attempts at experimental reproduction of a clinically manifest, respiratory disease was not successful as yet. The paper describes factors which might be responsible for these variable results. Control of PRRS is difficult in areas with a high density of the swine population, since the spreading of the virus with the wind seems to be important besides the recruitment of new, infected animals. A vaccine has not yet been registered in Germany. First experimental experiences with vaccination are available from Denmark and the USA.


Ethnographic study of incidence and severity of intravenous drug errors.
To determine the incidence and clinical importance of errors in the preparation and administration of intravenous drugs and the stages of the process in which errors occur. Prospective ethnographic study using disguised observation. Nurses who prepared and administered intravenous drugs. 10 wards in a teaching and non-teaching hospital in the United Kingdom. Number, type, and clinical importance of errors. 249 errors were identified. At least one error occurred in 212 out of 430 intravenous drug doses (49%, 95% confidence interval 45% to 54%). Three doses (1%) had potentially severe errors, 126 (29%) potentially moderate errors, and 83 (19%) potentially minor errors. Most errors occurred when giving bolus doses or making up drugs that required multiple step preparation. The rate of intravenous drug errors was high. Although most errors would cause only short term adverse effects, a few could have been serious. A combination of reducing the amount of preparation on the ward, training, and technology to administer slow bolus doses would probably have the greatest effect on error rates.


Developmental and cellular expression pattern of epithelial sodium channel alpha, beta and gamma subunits in the inner ear of the rat.
Endolymphatic ion composition in the adult inner ear is characterized by high K(+) and low Na(+) concentration. This unique ion composition is essential for proper functioning of sensory processing. Although a lot has been learned in recent years about molecules involved in K(+) transport in inner ear, the molecules involved in Na(+) transport are only beginning to emerge. The epithelial Na(+) channel (ENaC) is a highly selective Na(+) channel that is expressed in many Na(+)-reabsorbing tissues. The aim of our study was to investigate whether ENaC is expressed in inner ear of rats and could account for Na(+) reabsorption from endolymph. We detected mRNA for the three channel-forming subunits (alpha, beta and gamma ENaC) in cochlea, vestibular system and endolymphatic sac. mRNA abundance increased during the first 12 days of life in cochlea and vestibular system, coinciding with decreasing Na(+) concentration in endolymph. Expression was strongest in epithelial cells lining scala media, most notably Claudius' cells. As these cells are characterized by a very negative resting potential they would be ideally suited for reabsorption of Na(+). mRNA abundance in endolymphatic sac decreased during the first 6 days of life, suggesting that ENaC might be implicated in reabsorption of endolymph in the endolymphatic sac of neonatal animals. Together, our results suggest that the epithelial Na+ channel is a good candidate for a molecule involved in Na(+) homeostasis in inner ear.


Static and dynamic features of granular material failure due to upward pulling of a buried sphere by a slowly increasing force.
A spherical intruder embedded in a confined granular column is extracted by pulling it upward by an attached string. As the tension of the string gradually increases, a failure event occurs at a certain pulling force, leading to rapid upward acceleration of the intruder. The threshold force and the dynamics of the failure event are experimentally investigated for different filling heights and column diameters, using Ottawa sand and glass beads. For the Ottawa sand, we find that the failure force can be fit by a model describing the weight of the granular material in a cone with the vertex at the bottom of the intruder and a vertex angle of 72°. The agreement between the model and experiments is good for heights less than the column (tube) diameter, but measured values deviate from the model for larger heights. We also report on experiments with glass beads that reveal unexpected effects for relatively small ratios of tube diameters to grain size. The dynamics of the intruder during the failure event is studied using high-speed video analysis. The granular drag force monotonically decays during the pullout for sufficiently large tube diameters. In narrow columns, a monotonic decay of drag force after failure is observed for low heights, whereas a secondary peak can be seen in sufficiently deep and narrow columns, indicating the existence of different mechanisms of failure. The normalized drag force declines with intruder displacement closely for all tube diameters within small displacements.


The development of a feasible community-specific cardiovascular disease prevention program: triangulation of methods and sources.
Triangulation of methods, sources, and investigators can lead to a multidimensional understanding of a particular issue. In this study, the combination of qualitative and quantitative data collection methods, and information from community and coalition members resulted in the development of a tailored community-specific intervention. Three components were triangulated after analyzing each separately. A household survey of community members between the ages of 25 and 64 years was conducted to identify knowledge, attitudes, and behaviors related to cardiovascular disease and to assess risk factor levels. Focus group discussions were conducted with community members to describe facilitators and barriers to healthy lifestyles, as well as possible interventions. Natural group discussions with coalition members analyzed the relevance, feasibility, affordability, acceptability, and sustainability of specific intervention activities. Results from the different components were compared and contrasted. Areas of added information, validation, and contradiction were analyzed and guided the development of intervention activities.


How do aminoadamantanes block the influenza M2 channel, and how does resistance develop?
The interactions between channels and their cognate blockers are at the heart of numerous biomedical phenomena. Herein, we unravel one particularly important example bearing direct pharmaceutical relevance: the blockage mechanism of the influenza M2 channel by the anti-flu amino-adamantyls (amantadine and rimantadine) and how the channel and, consequently, the virus develop resistance against them. Using both computational analyses and experimental verification, we find that amino-adamantyls inhibit M2's H(+) channel activity by electrostatic hindrance due to their positively charged amino group. In contrast, the hydrophobic adamantyl moiety on its own does not impact conductivity. Additionally, we were able to uncover how mutations in M2 are capable of retaining drug binding on the one hand yet rendering the protein and the mutated virus resistant to amino-adamantyls on the other hand. We show that the mutated, drug-resistant protein has a larger binding pocket for the drug. Hence, despite binding the channel, the drug remains sufficiently mobile so as not to exert a H(+)-blocking positive electrostatic hindrance. Such insight into the blocking mechanism of amino-adamantyls, and resistance thereof, may aid in the design of next-generation anti-flu agents.


Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial.
Vitamin K antagonists, the current standard treatment for prophylaxis against stroke and systemic embolism in patients with atrial fibrillation, require regular monitoring and dose adjustment; an unmonitored, fixed-dose anticoagulant regimen would be preferable. The aim of this randomised, open-label non-inferiority trial was to compare the efficacy and safety of idraparinux with vitamin K antagonists. Patients with atrial fibrillation at risk for thromboembolism were randomly assigned to receive either subcutaneous idraparinux (2.5 mg weekly) or adjusted-dose vitamin K antagonists (target of an international normalised ratio of 2-3). Assessment of outcome was done blinded to treatment. The primary efficacy outcome was the cumulative incidence of all stroke and systemic embolism. The principal safety outcome was clinically relevant bleeding. Analyses were done by intention to treat; the non-inferiority hazard ratio was set at 1.5. This trial is registered with ClinicalTrials.gov, number NCT00070655. The trial was stopped after randomisation of 4576 patients (2283 to receive idraparinux, 2293 to receive vitamin K antagonists) and a mean follow-up period of 10.7 (SD 5.4) months because of excess clinically relevant bleeding with idraparinux (346 cases vs 226 cases; 19.7 vs 11.3 per 100 patient-years; p<0.0001). There were 21 instances of intracranial bleeding with idraparinux and nine with vitamin K antagonists (1.1 vs 0.4 per 100 patient-years; p=0.014); elderly patients and those with renal impairment were at greater risk of such complications. There were 18 cases of thromboembolism with idraparinux and 27 cases with vitamin K antagonists (0.9 vs 1.3 per 100 patient-years; hazard ratio 0.71, 95% CI 0.39-1.30; p=0.007), satisfying the non-inferiority criterion. There were 62 deaths with idraparinux and 61 with vitamin K anatagonists (3.2 vs 2.9 per 100 patient-years; p=0.49). In patients with atrial fibrillation at risk for thromboembolism, long-term treatment with idraparinux was no worse than vitamin K antagonists in terms of efficacy, but caused significantly more bleeding.


Studies on multiple trait and random regression models for genetic evaluation of beef cattle for growth.
A simulation study examined issues important for genetic evaluation of growth in beef cattle by random regression models with cubic Legendre polynomials (RRML) and linear splines with three knots (RRMS) compared with multiple-trait models (MTM). Parameters for RRML were obtained by conversion from covariance functions. Parameters for MTM and RRMS were extracted from RRML at 1, 205, and 365 d; parameters for RRMS were the same as MTM for all effects except the permanent environment and the residual. Four data sets were generated assuming RRML included records at 1, 205, and 365 d; at 1, 160 to 250, and 320 to 410 d; at 1, 100, 205, 300, and 365 d; and at 1, 55 to 145, 160 to 250, 275 to 325, and 320 to 410 d. Accuracies were computed as correlations between the true (simulated) and predicted breeding values. With the first data set, excellent agreement in accuracy was obtained for all models. With the second data set, the accuracy of MTM dropped by up to 1.5% compared with the first data set, but accuracy was unchanged for both RRML and RRMS. With the third (fourth) data set, accuracies of RRML were up to 2.4% (2.5%) higher than with the first (second) data set. Small differences in accuracy between RRML and RRMS were found with the third and fourth data sets, which were traced to inflated correlations especially between 1 and 205 d in RRMS; inflation could be decreased by adding one extra knot at 100 d to RRMS. Diagonalization of random coefficients was crucial for RRML but not for RRMS, resulting in approximately six (two) times faster convergence with RRML (RRMS). Reduction of dimensionality in RRML associated with small eigenvalues caused a less accurate evaluation for birth weight. Genetic evaluation of growth by RRM requires careful implementation. The RRMS is simpler to implement than the RRML.


Explicit identification and implicit recognition of facial emotions: I. Age effects in males and females across 10 decades.
A number of psychiatric and neurological disorders are characterized by impairments in facial emotion recognition. Recognition of individual emotions has implicated limbic, basal ganglionic, and frontal brain regions. Since these regions are also implicated in age-related decline and sex differences in emotion processing, an understanding of normative variation is important for assessing deficits in clinical groups. An internet-based test ("WebNeuro") was administered to 1,000 healthy participants (6 to 91 years, 53% female) to assess explicit identification of basic expressions of emotion (happiness, sadness, fear, anger, disgust, neutral). A subsequent implicit recognition condition was based on a priming protocol, in which explicit identification provided the "study" phase. Responses were most accurate for happiness and slowest for fear in the explicit condition, but least accurate for happiness and fastest for fear in the implicit condition. The effects of age, by contrast, showed a similar pattern for both explicit and implicit conditions, following a nonlinear distribution in which performance improved from childhood through adolescence and early adulthood and declined in later adulthood. Females were better than males at explicit identification of fear in particular. These findings are consistent with the priority of threat-related signals, but indicate opposing biases depending on whether emotion processing is conscious or nonconscious. The lifespan trends in emotion processing over 10 decades point to an interaction of brain-based (maturation, stability, and then atrophy of cortical and subcortical systems) and experiential contributing factors. These findings provide a robust normative platform for assessing clinical groups.


Revised Parallel Analysis With Nonnormal Ability and a Guessing Parameter.
Previous work showing that revised parallel analysis can be effective with dichotomous items has used a two-parameter model and normally distributed abilities. In this study, both two- and three-parameter models were used with normally distributed and skewed ability distributions. Relatively minor skew and kurtosis in the underlying ability distribution had almost no effect on Type I error for unidimensional data and reduced power for two-dimensional data slightly with smaller sample sizes of 400. Using a two-parameter model on three-parameter data produced dramatically increased rejection rates for the unidimensional data. Using the correct three-parameter model reduced the unidimensional rejection rates but yielded lower power than the two-parameter data in some conditions.