Evaluation of the effects of pine-sourced biochar on cattle performance and methane and carbon dioxide production from growing and finishing steers.
A feedlot growing (77-d) and finishing (111-d) experiment was conducted to evaluate the effects of feeding biochar on steer performance, methane and carbon dioxide emissions, and carcass characteristics. Two treatments were evaluated, a control diet without biochar and the same diet with biochar included at 0.8% of dietary DM (growing) or 1.0% of dietary DM (finishing). The growing diet consisted of 40% corn silage, 40% wheat straw, 15% modified distillers grains plus solubles, and 5% supplement, with 0.8% biochar replacing fine ground corn in supplement. The finishing diet consisted of 55% high-moisture corn (HMC), 35% Sweet Bran, 5% wheat straw, and 5% supplement, with biochar replacing 1.0% HMC and added as an ingredient. Biochar was sourced from ponderosa pine wood waste (High Plains Biochar, Laramie, WY) and was 83% C with 426 m2/g surface area for both experiments. Crossbred steers were utilized in the growing (n = 160; initial BW = 363 kg; SD = 16 kg) and finishing (n = 128; initial; BW = 480 kg; SD = 17 kg) experiments, blocked by BW, and assigned randomly to 16 pens. Pens were assigned randomly to one of two treatments (biochar vs. control) with eight replications per treatment. Four pen replications per treatment were paired within BW block and rotated randomly through an emissions barn with two chambers (each treatment was evaluated simultaneously and for two rotations) to capture average weekly emissions of CH4 and CO2. Pen was the experimental unit and chamber was included as a fixed effect for emissions data. There were no statistical differences (P ≥ 0.23) in performance outcomes between treatments for the growing experiment. Dry matter intake (DMI; P < 0.01) and average daily gain (ADG; P = 0.02) were 2.2% and 5.9% lower for biochar-fed steers in the finishing experiment, respectively, resulting in a lighter hot carcass weight (P = 0.10) and lower calculated USDA yield grade (P = 0.02). Emissions of CH4 and CO2 were not affected by biochar inclusion in the growing (P ≥ 0.22) or finishing experiment (P ≥ 0.60). Results from these experiments show no indication that feeding biochar, supplemented at 0.8% (growing), and 1.0% (finishing) of the diet DM, reduces methane emissions in growing or finishing cattle.


The polyomavirus BK large T-antigen-derived peptide elicits an HLA-DR promiscuous and polyfunctional CD4+ T-cell response.
BK virus (BKV) nephropathy and hemorrhagic cystitis are increasingly recognized causes of disease in renal and hematopoietic stem cell transplant recipients, respectively. Functional characterization of the immune response to BKV is important for clinical diagnosis, prognosis, and vaccine design. A peptide mix (PepMix) and overlapping (OPP) or random (RPP) peptide pools derived from BKV large T antigen (LTA) were used to restimulate 14-day-expanded peripheral blood mononuclear cells (PBMC) from 27 healthy control subjects in gamma interferon (IFN-γ)-specific enzyme-linked immunospot (ELISPOT) assays. A T-cell response to LTA PepMix was detected in 15/27 subjects. A response was frequently observed with peptides derived from the helicase domain (9/15 subjects), while the DNA binding and host range domains were immunologically inert (0/15 subjects). For all nine subjects who responded to LTA peptide pools, the immune response could be explained largely by a 15-mer peptide designated P313. P313-specific CD4(+) T-cell clones demonstrated (i) stringent LTA peptide specificity; (ii) promiscuous recognition in the context of HLA-DR alleles; (iii) cross recognition of homologous peptides from the polyomavirus simian virus 40 (SV40); (iv) an effector memory phenotype, CD107a expression, and intracellular production of IFN-γ and tumor necrosis factor alpha (TNF-α); (v) cytotoxic activity in a chromium release assay; and (vi) the ability to directly present cognate antigen to autologous T cells. In conclusion, T-cell-mediated immunity to BKV in healthy subjects is associated with a polyfunctional population of CD4(+) T cells with dual T-helper and T-cytotoxic properties. HLA class II promiscuity in antigen presentation makes the targeted LTA peptide sequence a suitable candidate for inclusion in immunotherapy protocols.


Risk of Pathological Upgrading and Up Staging among Men with Low Risk Prostate Cancer Varies by Race: Results from the National Cancer Database.
The impact of African-American race on oncologic outcomes for low risk prostate cancer is unclear due to conflicting data. We investigated the effect of African-American race on pathological upgrading and/or up staging at prostatectomy in men with clinically low risk prostate cancer. We queried the National Cancer Database for men with low risk prostate cancer (clinical stage T2a or less, Gleason score 6 or less, prostate specific antigen less than 10 ng/ml) treated with radical prostatectomy between 2010 and 2013. The outcomes were pathological upgrading to Gleason score greater than 6 (primary) or Gleason score greater than 3+4=7 (secondary) and/or up staging (pathological T3-4 or N1 disease). The association between race and the end points was assessed using multivariable logistic regression. To further adjust for potential confounders, stratification by urban residence and comorbidity score, and subgroup analyses were performed. With adjustment for age, comorbidity, income, urban residence, T stage, prostate specific antigen and percentage of positive biopsy cores, African-American race conferred 1.2-fold higher odds of pathological upgrading to Gleason score greater than 6 and/or up staging (OR 1.2, 95% CI 1.1-1.3, p <0.01). African-American race also was an independent predictor of pathological upgrading to Gleason score greater than 3+4=7 and/or up staging (p=0.03). African-American men with low risk prostate cancer are more likely to harbor higher risk disease, which may lead to adverse outcomes. This finding alone does not preclude active surveillance. However, race should be considered as men weigh the risks and benefits of active surveillance vs treatment.


Alternative case definitions of ventilator-associated pneumonia identify different patients in a surgical intensive care unit.
Diagnostic criteria that define ventilator-associated pneumonia (VAP) remain controversial. The purpose of this study was to evaluate common definitions of VAP and determine their relationship to each other and clinical treatment. This study prospectively evaluated several diagnostic criteria that define VAP in a cohort of 255 consecutive SICU patients ventilated for < 48 h. Definitions evaluated include the CDC definitions, the Johanson definitions which do not rely on culture data, the Physician's Probable diagnosis which relies on positive quantitative cultures, and the antibiotic treatment group. Forty-four patients (17%) received antibiotic treatment for VAP. Depending on the definition evaluated, criteria were met for a diagnosis of VAP from as low as 4% of patients by the Johanson definition to as high as 48% of patients by the CDC definition. There was poor agreement among the definitions in their ability to select the same patient as having VAP. Besides duration of mechanical ventilation and tube feeding, which were risk factors that predicted meeting the criteria for all groups, risk factors predicting VAP varied among the definitions. This study demonstrates that in a surgical ICU, the candidate definitions of pneumonia evaluated show little agreement. The particular case definition chosen to diagnose VAP will determine the incidence rate of pneumonia, the time to onset of pneumonia, and the risk factors of the type of patient treated.


Early and delayed CT findings in patients with mild-to-moderate head trauma.
The aim of this study is to evaluate the changes between the initial and late cranial CT scans in patients with mild-to-moderate head trauma. MATERIAL and Of the two thousand six hundred and forty-four patients hospitalized for head trauma within a two-year period, 112 (4.24%) patients scored 8 or above in the Glasgow coma scale and there were changes between initial and late head CT. Of these, 103 had worsening CT findings. Neurological status deteriorated in 30% of these cases. Forty-six patients required surgery based on findings seen on the delayed scans. Neurological status was stable in 50% of the cases. All the eight patients who expired had abnormal CT scans initially and had progression in their late scans. In patients with mild-to-moderate head trauma, serial CT scanning may independently modify treatment decisions in a subgroup of patients. Judgment for delayed scans should be made on an individual basis by taking the risk factors into account.


Overcoming Career Advancement Barriers to Executive Leadership Roles of Nurses From Racial and Ethnic Minority Backgrounds.
There is underrepresentation of nurses with racial and ethnic minority backgrounds in executive nursing leadership positions as compared with the general population. The management problem is that even when academically prepared, nurses with racial and ethnic minority backgrounds perceive that they face both singular and systemic barriers to promotional opportunities to executive nurse positions. A literature gap exists as to why this phenomenon persists. The purpose of this qualitative narrative inquiry study was to explore the personal stories and lived experiences of executive nurses with racial and ethnic minority backgrounds concerning the barriers they faced and overcame on their pathway to an executive leadership position. The conceptual framework combined the intersectionality of race and internal and external capabilities. Data collected through semistructured interviews underwent a 3-dimensional-space narrative structure and thematic analysis process. Eleven themes in 3 major categories emerged: (a) facing the challenges; (b) overcoming barriers; and (c) where my help came from. The social change implications include new knowledge for multiple stakeholders in supporting and developing nurses from racial and ethnic minority backgrounds to assist them in achieving executive nursing leadership positions, thereby increasing the number of these nurses in executive roles.


Virulence-related protein synthesis in Naegleria fowleri.
Protein synthesis patterns of the low-virulence Naegleria fowleri LEE strain from axenic culture, the same strain after mouse brain passage to increase virulence, and the same strain after growth on bacteria were studied. Comparisons of accumulated proteins, in vivo-synthesized proteins, and in vitro-synthesized proteins translated from poly(A)+ mRNA were made. Differences between amoebae from the different treatments were noted. After 6 months in axenic culture, pathogenic protein synthesis patterns were lost and there was a decrease in virulence. Therefore, the increase in virulence is correlated with numerous specific changes in protein synthesis.


Microvascular bypass procedures for ischemic cerebrovascular disease.
Extracranial to intracranial (EC/IC) microvascular bypass grafts are being performed with increasing frequency for the treatment of cerebral ischemia due to "inaccessible" cerebrovascular disease including carotid artery occlusion and middle cerebral artery occlusion and stenosis. Patency rates, complications, and indications for superficial temporal to middle cerebral artery (STA-MCA) bypass are discussed. EC/IC bypasses can reduce or completely arrest TIAs in selected patients. The long term effect on stroke protection of a functioning STA-MCA bypass is now the subject of multinational controlled investigation.


Molecular basis of odor coding in the malaria vector mosquito Anopheles gambiae.
A systematic functional analysis across much of the conventional Anopheles gambiae odorant receptor (AgOR) repertoire was carried out in Xenopus oocytes using two-electrode, voltage-clamp electrophysiology. The resulting data indicate that each AgOR manifests a distinct odor-response profile and tuning breadth. The large diversity of tuning responses ranges from AgORs that are responsive to a single or small number of odorants (specialists) to more broadly tuned receptors (generalists). Several AgORs were identified that respond robustly to a range of human volatiles that may play a critical role in anopheline host selection. AgOR responses were analyzed further by constructing a multidimensional odor space representing the relationships between odorants and AgOR responses. Within this space, the distance between odorants is related to both chemical class and concentration and may correlate with olfactory discrimination. This study provides a comprehensive overview of olfactory coding mechanisms of An. gambiae that ultimately may aid in fostering the design and development of olfactory-based strategies for reducing the transmission of malaria and other mosquito-borne diseases.


Determination of size, sex and maturity stage of free swimming catsharks using laser photogrammetry.
The lack of detailed life history (LH) information (e.g. age, growth, size at maturity, sex composition etc.) for many species of conservation importance limits the implementation of appropriate conservation measures. Typically, LH information is acquired using lethal sampling techniques, which undermines the goal of conservation. This is particularly problematic for many shark species that have low fecundity and slow growth rates. Here we tested the use of non-invasive laser photogrammetry to measure body morphometry in vivo. We used random forest classification models to identify allometric relationships (ratios between body measurements) that discriminated between the sex and stage of sexual maturity of Scyliorhinus canicula. We coupled the use of allometric ratios (determined from cadavers) with parallel laser photogrammetry, in order to collect total length (TL) and finer scale morphometrics from 37 free-swimming individuals. TL measurements proved to be accurate (SE = 5.2%) and precise (CV = 1.8%), and did not differ significantly from the known TL of the respective animal (t36 = 0.7, P = 0.5). Conditional Inference tree model predictions of free-swimming sharks correctly predicted 100% of mature males and 79% of immature males. Our results suggest that when used together, allometric ratios and parallel laser photogrammetry have the potential to be a promising alternative to collect essential life history information from free swimming animals and avoids the need for destructive sampling.


Evaluation of the safety and effectiveness of direct oral anticoagulants and low molecular weight heparin in gastrointestinal cancer-associated venous thromboembolism.
Gastrointestinal cancer (GICA) is associated with a higher incidence of venous thromboembolism (VTE) compared to other solid tumors, moreover, recurrent VTE and major bleeding (MB) complications during anticoagulation treatment have an associated increase rate. GICA-VTE remains a challenging clinical scenario with MB concerns for utilization of direct oral anticoagulants (DOAC), especially with active cancer therapies. To evaluate patient risk factors, effectiveness (VTE) and safety (MB) of DOACs and low molecular weight heparin (LMWH) in patients with active GICA-VTE. A retrospective chart review of patients receiving DOACs and LMWH with GICA and symptomatic or incidental VTE treated at comprehensive cancer center from November 2013 to February 2017 was performed. Inclusion criteria included active GI cancer diagnosed at any stage or treatment +/- 6 mo of VTE diagnosis, whom were prescribed 6 mo or more of DOACs or LMWH. The Chi-squared test was used for overall and the Fisher exact test for pairwise comparisons of the proportions of patients experiencing recurrent VTE and MB events. Odds ratios were used to compare the relative odds of the occurrence of the outcome given exposure to the risk factor. A total of 144 patients were prescribed anticoagulation, in which 106 fulfilled inclusion criteria apixaban (27.3%), rivaroxaban (34.9%) and enoxaparin (37.7%), and 38 were excluded. Patients median age was 66.5 years at GICA diagnosis and 67 years at CAVTE event, with 62% males, 80% Caucasian, 70% stage IV, pancreatic cancer (40.5%), 30% Khorana Score (≥ 3 points), and 43.5% on active chemotherapy. Sixty-four percent of patients completed anticoagulation therapy (range 1 to 43 mo). Recurrent VTE at 6 mo was noted in 7.5% (n = 3), 6.8% (n = 2) and 2.7% (n = 1) of patients on enoxaparin, apixaban and rivaroxaban, respectively (all P = NS). MB at 6 mo were 5% (n = 2) for enoxaparin, 6.8% (n = 2) for apixaban and 21.6% (n = 8) for rivaroxaban (overall P = 0.048; vs LMWH P = 0.0423; all other P = NS). Significant predictors of a primary or secondary outcome for all anticoagulation therapies included: Active systemic treatment (OR = 5.1, 95%CI: 1.3-19.3), high Khorana Score [≥ 3 points] (OR = 5.5, 95%CI: 1.7-17.1), active smoker (OR = 6.7, 95%CI: 2.1-21.0), pancreatic cancer (OR = 6.8, 95%CI: 1.9-23.2), and stage IV disease (OR = 9.9, 95%CI: 1.2-79.1). Rivaroxaban compared to apixaban and enoxaparin had a significantly higher risk of MB on GICA-VTE patients with equivocal efficacy.


Hormone receptor status of a first primary breast cancer predicts contralateral breast cancer risk in the WECARE study population.
Previous population-based studies have described first primary breast cancer tumor characteristics and their association with contralateral breast cancer (CBC) risk. However, information on influential covariates such as treatment, family history of breast cancer, and BRCA1/2 mutation carrier status was not available. In a large, population-based, case-control study, we evaluated whether tumor characteristics of the first primary breast cancer are associated with risk of developing second primary asynchronous CBC, overall and in subgroups of interest, including among BRCA1/2 mutation non-carriers, women who are not treated with tamoxifen, and women without a breast cancer family history. The Women's Environmental Cancer and Radiation Epidemiology Study is a population-based case-control study of 1521 CBC cases and 2212 individually-matched controls with unilateral breast cancer. Detailed information about breast cancer risk factors, treatment for and characteristics of first tumors, including estrogen receptor (ER) and progesterone receptor (PR) status, was obtained by telephone interview and medical record abstraction. Multivariable risk ratios (RRs) and 95% confidence intervals (CIs) were estimated in conditional logistic regression models, adjusting for demographics, treatment, and personal medical and family history. A subset of women was screened for BRCA1/2 mutations. Lobular histology of the first tumor was associated with a 30% increase in CBC risk (95% CI 1.0-1.6). Compared to women with ER+/PR+ first tumors, those with ER-/PR- tumors had increased risk of CBC (RR = 1.4, 95% CI 1.1-1.7). Notably, women with ER-/PR- first tumors were more likely to develop CBC with the ER-/PR- phenotype (RR = 5.4, 95% CI 3.0-9.5), and risk remained elevated in multiple subgroups: BRCA1/2 mutation non-carriers, women younger than 45 years of age, women without a breast cancer family history, and women who were not treated with tamoxifen. Having a hormone receptor negative first primary breast cancer is associated with increased risk of CBC. Women with ER-/PR- primary tumors were more likely to develop ER-/PR- CBC, even after excluding BRCA1/2 mutation carriers. Hormone receptor status, which is routinely evaluated in breast tumors, may be used clinically to determine treatment protocols and identify patients who may benefit from increased surveillance for CBC.


[Role of heredity in myopia].
Analysis of genealogic data of 100 patients addressed on occasion of myopia in 1987-1988 has shown that in 85% of the subjects myopia was of a clearly hereditary character (in 35%--a dominant and in 50%--a recessive hereditary). The author compares his own results with literature data and draws attention to Steiger's views about formation of myopic refraction and the role of hereditary factor in this process. In the light of the mentioned data, the author considers it expedient to work out a programme of special researches for development of a method of prognosticating initial myopia and a correction of several ways for approbation of existing methods of prevention of progressive myopia.


Monotonic convergence of fixed-point algorithms for ICA.
We re-examine a fixed-point algorithm proposed by Hyvarinen for independent component analysis, wherein local convergence is proved subject to an ideal signal model using a square invertible mixing matrix. Here, we derive step-size bounds which ensure monotonic convergence to a local extremum for any initial condition. Our analysis does not assume an ideal signal model but appeals rather to properties of the contrast function itself, and so applies even with noisy data and/or more sources than sensors. The results help alleviate the guesswork that often surrounds step-size selection when the observed signal does not fit an idealized model.


The quality in psychiatric care-forensic in-patient instrument: psychometric properties and patient views of the quality of forensic psychiatric services in Sweden.
The aim of this study was to evaluate the psychometric properties and dimensionality of the instrument Quality in Psychiatric Care-Forensic In-Patient and to describe the quality of psychiatric care among forensic in-patients. The study group consisted of patients all receiving care during 2 weeks in September 2009 and meeting the inclusion criteria. A sample of 134 in-patients from 34 forensic wards in Sweden participated. Confirmatory factor analysis revealed a seven-factor structure, and 69% of the patients reported the quality of care as high. The highest rating was for the secluded environment dimension, and the lowest was for the participation dimension. The Quality in Psychiatric Care-Forensic In-Patient is a reliable and valid measurement instrument recommended for use in evaluating quality in forensic in-patient care.


Using dual eye tracking to uncover personal gaze patterns during social interaction.
We report the personal eye gaze patterns of people engaged in face-to-face getting acquainted conversation. Considerable differences between individuals are underscored by a stability of eye gaze patterns within individuals. Results suggest the existence of an eye-mouth gaze continuum. This continuum includes some people showing a strong preference for eye gaze, some with a strong preference for mouth gaze, and others distributing their gaze between the eyes and mouth to varying extents. Additionally, we found evidence of within-participant consistency not just for location preference but also for the duration of fixations upon the eye and mouth regions. We also estimate that during a 4-minute getting acquainted conversation mutual face gaze constitutes about 60% of conversation that occurs via typically brief instances of 2.2 seconds. Mutual eye contact ranged from 0-45% of conversation, via very brief instances. This was despite participants subjectively perceiving eye contact occurring for about 70% of conversation. We argue that the subjective perception of eye contact is a product of mutual face gaze instead of actual mutual eye contact. We also outline the fast activity of gaze movements upon various locations both on and off face during a typical face-to-face conversation.


A procedure to prepare cultured cells in suspension for electron probe X-ray microanalysis: application to scanning and transmission electron microscopy.
We describe a simple procedure to prepare cultured cells in suspension to analyse elemental content at the cellular level by electron probe X-ray microanalysis. Cells cultured in suspension were deposited onto polycarbonate tissue, culture plate well inserts, centrifuged at low g, washed to remove the extracellular medium, cryofixed and freeze-dried, and analysed in the scanning mode of a scanning electron microscope. We tested the effect of different washing solutions (150 mM ammonium acetate, 300 mM sucrose, and distilled water) on the elemental content of cultured cells in suspension. The results demonstrated that distilled water was the best washing solution to prepare cultured cells. In addition, the low Na content, high K content and high K/Na ratio of the cells indicated that this procedure, based on the centrifugation at low g followed by cryopreparation, constitutes a satisfactory method to prepare cultured cells in suspension. We also investigated the effects of different accelerating voltages on X-ray signal collection. The results showed that moderate accelerating voltages, i.e. 10-11 kV, should be used to analyse whole cells in the scanning mode of the scanning electron microscope. We show that this method of preparation makes it possible to prepare cryosections of the cultured cells, thus permitting analysis of the elemental content at the subcellular level, i.e. nucleus, cytoplasm and mitochondria, using a scanning transmission electron microscope.


Serum high mobility group box-1 levels associated with cardiovascular events after lower extremity revascularization: a prospective study of a diabetic population.
Peripheral arterial disease (PAD) is one of the most disabling cardiovascular complications of type 2 diabetes mellitus and is indeed associated with a high risk of cardiovascular and limb adverse events. High mobility group box-1 (HMGB-1) is a nuclear protein involved in the inflammatory response that acts as a pro-inflammatory cytokine when released into the extracellular space. HMBG-1 is associated with PAD in diabetic patients. The aim of this study was to evaluate the association between serum HMGB-1 levels and major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after lower-extremity endovascular revascularization (LER) in a group of diabetic patients with chronic limb-threatening ischemia (CLTI). We conducted a prospective observational study of 201 diabetic patients with PAD and CLTI requiring LER. Baseline serum HMGB-1 levels were determined before endovascular procedure. Data on cardiovascular and limb outcomes were collected in a 12-month follow-up. During the follow-up period, 81 cases of MACE and 93 cases of MALE occurred. Patients who subsequently developed MACE and MALE had higher serum HMGB-1 levels. Specifically, 7.5 ng/mL vs 4.9 ng/mL (p < 0.01) for MACE and 7.2 ng/mL vs 4.8 ng/mL (p < 0.01) for MALE. After adjusting for traditional cardiovascular risk factors, the association between serum HMGB-1 levels and cardiovascular outcomes remained significant in multivariable analysis. In our receiver operating characteristic (ROC) curve analysis, serum HMGB-1 levels were a good predictor of MACE incidence (area under the curve [AUC] = 0.78) and MALE incidence (AUC = 0.75). This study demonstrates that serum HMGB-1 levels are associated with the incidence of MACE and MALE after LER in diabetic populations with PAD and CLTI.


Ependymal cyst of the ovary. A case report.
An unusual morphological variant of a mature cystic teratoma was found at caesarean section in a 23-year-old patient; it appeared as a thin-walled cyst containing clear fluid. Microscopy showed the cyst to be lined by ependyma and the wall to be composed of glial tissue with a small protuberance containing squamous epithelium, adipose tissue and bone.


A glial origin for periventricular nodular heterotopia caused by impaired expression of Filamin-A.
Periventricular nodular heterotopia (PH) is a human brain malformation caused by defective neuronal migration that results in ectopic neuronal nodules lining the lateral ventricles beneath a normal appearing cortex. Most affected patients have seizures and their cognitive level varies from normal to severely impaired. Mutations in the Filamin-A (or FLNA) gene are the main cause of PH, but the underlying pathological mechanism remains unknown. Although two FlnA knockout mouse strains have been generated, none of them showed the presence of ectopic nodules. To recapitulate the loss of FlnA function in the developing rat brain, we used an in utero RNA interference-mediated knockdown approach and successfully reproduced a PH phenotype in rats comparable with that observed in human patients. In FlnA-knockdown rats, we report that PH results from a disruption of the polarized radial glial scaffold in the ventricular zone altering progression of neural progenitors through the cell cycle and impairing migration of neurons into the cortical plate. Similar alterations of radial glia are observed in human PH brains of a 35-week fetus and a 3-month-old child, harboring distinct FLNA mutations not previously reported. Finally, juvenile FlnA-knockdown rats are highly susceptible to seizures, confirming the reliability of this novel animal model of PH. Our findings suggest that the disorganization of radial glia is the leading cause of PH pathogenesis associated with FLNA mutations. Rattus norvegicus FlnA mRNA (GenBank accession number FJ416060).


Eye and gonad: role in the dual-oscillator circadian system of female Japanese quail.
Experiments were conducted to determine the anatomic and physiological basis of the dual-oscillator circadian system of female Japanese quail. After blocking of ocular light perception by eye-patching, the circadian body temperature rhythm dissociates into two circadian components in continuous lighting (LL). One component free runs with a period significantly shorter than 24 h [mean period (tau) = 22.7 h] and is driven by an ocular pacemaker, whereas the other component free runs with a period significantly longer than 24 h (tau = 26.3 h). The long free-running rhythm is driven by the same circadian clock that drives the circadian rhythm of ovulation. The expression of the long free-running rhythm in LL depends on the presence of the ovary: body temperature rhythmicity is abolished by ovariectomy. The two free-running oscillators in eye-patched birds showed evidence of mutual interaction. Significantly, the phase relationships that occur as the two oscillators interact can determine whether or not ovulation occurs. The results are discussed in terms of an "internal coincidence" mechanism for photoperiodic time measurement.


Improving universal prenatal screening for human immunodeficiency virus.
To evaluate the effect of implementation of a human immunodeficiency virus (HIV) educational intervention on universal screening for HIV in a prenatal clinic setting. In this retrospective cohort study, frequencies of offering and acceptance of HIV testing were compared before and after an educational intervention performed by an HIV-focused nurse. The records of 293 women seeking prenatal care before the intervention and 206 women seeking prenatal care after the intervention were reviewed for offering and acceptance of HIV testing. Fisher's exact test and logistic regression were used to evaluate the relationship between the educational intervention and the offering and acceptance of HIV testing. The frequency of HIV test offering at first visit and test acceptance before the educational intervention were 96.5% and 74.8%, respectively, and after the intervention were 99.5% and 84.3%, respectively. This improvement in offering (3% change) and acceptance (9.5% change) was statistically significant (offering at first visit: OR = 7.27, 95% CI = 1.02 to 316.9; test acceptance: OR = 1.82, 95% CI = 1.14 to 2.88). Test acceptance was statistically significantly improved in the post-intervention group after controlling for confounding variables (OR = 2.02, 95% CI = 1.2 to 3.39). The addition of an HIV-focused nurse to a clinic setting improved the frequency of test offering at first visit and of acceptance of HIV testing by pregnant women.


Self-Stigma and Consumer Participation in Shared Decision Making in Mental Health Services.
People with mental illness struggle with symptoms and with public stigma. Some accept common prejudices and lose self-esteem, resulting in shame and self-stigma, which may affect their interactions with mental health professionals. This study explored whether self-stigma and shame are associated with consumers' preferences for participation in medical decision making and their behavior in psychiatric consultations. In a cross-sectional study conducted in Germany, 329 individuals with a diagnosis of a schizophrenia spectrum disorder or an affective disorder and their psychiatrists provided sociodemographic and illness-related information. Self-stigma, shame, locus of control, and views about clinical decision making were assessed by self-report. Psychiatrists rated their impression of the decision-making behavior of consumers. Regression analyses and structural equation modeling were used to determine the association of self-stigma and shame with clinical decision making. Self-stigma was not related to consumers' participation preferences, but it was associated with some aspects of communicative behavior. Active and critical behavior (for example, expressing views, daring to challenge the doctor's opinion, and openly speaking out about disagreements with the doctor) was associated with less shame, less self-stigma, more self-responsibility, less attribution of external control to powerful others, and more years of education. Self-stigma and shame were associated with less participative and critical behavior, which probably leads to clinical encounters that involve less shared decision making and more paternalistic decision making. Paternalistic decision making may reinforce self-stigma and lead to poorer health outcomes. Therefore, interventions that reduce self-stigma and increase consumers' critical and participative communication may improve health outcomes.


Fitness to drive in seizure and epilepsy: A protocol for Iranian clinicians.
Driving restriction is a well-known undesirable consequence of epilepsy and causes significant problems regarding independence and employment for epileptic patients. Many countries all over the world have provided comprehensive protocols in this regard with the aim of providing the possibility of less restricted, but safe driving for epileptic patients and also providing the opportunity for uniform decision-making for clinicians. However, the available fitness to drive protocol in Iran still lacks sufficient details and clinicians might encounter serious problems in terms of the driving issue in epileptic patients. In order to provide a uniform protocol containing adequate practical data, a systematic review of literature addressing guidelines about driving and epilepsy and driving laws of different countries for epileptic patients was performed and, after consideration of cultural issues, a practical protocol for Iranian neurologists was suggested.


Skeletal-related events among breast and prostate cancer patients: towards new treatment initiation in Malaysia's hospital setting.
The human skeleton is the most common organ to be affected by metastatic cancer and bone metastases are a major cause of cancer morbidity. The five most frequent cancers in Malaysia among males includes prostate whereas breast cancer is among those in females, both being associated with skeletal lesions. Bone metastases weaken bone structure, causing a range of symptoms and complications thus developing skeletal-related events (SRE). Patients with SRE may require palliative radiotherapy or surgery to bone for pain, having hypercalcaemia, pathologic fractures, and spinal cord compression. These complications contribute to a decline in patient health- related quality of life. The multidimensional assessment of health-related quality of life for those patients is important other than considering a beneficial treatment impact on patient survival, since the side effects of treatment and disease symptoms can significantly impact health-related quality of life. Cancer treatment could contribute to significant financial implications for the healthcare system. Therefore, it is essential to assess the health-related quality of life and treatment cost, among prostate and breast cancer patients in countries like Malaysia to rationalized cost-effective way for budget allocation or utilization of health care resources, hence helping in providing more personalized treatment for cancer patients.


Auditory discrimination abilities of emotionally disturbed children in day psychiatric treatment: a replication study.
The abilities of 17 emotionally disturbed children enrolled in a day psychiatric treatment center were studied using the Goldman-Fristoe-Woodcock Test of Auditory Discrimination, replicating an earlier study (Blager, J. Audit. Res., 1978, 18, 221-227) and extending it to other factors possibly influencing auditory discrimination abilities. It was confirmed that, as a group, such children perform less well than the GFW normative sample both in quiet and in noise conditions. Despite normal HTLs, their performance more closely resembles that of the GFW "poor discriminator" normative group. Age, sex, socioeconomic status, severity of disturbance, and intelligence were shown not to be significantly associated with test performance. Although there were 7 children whose rank orders in the group of 17 were better when the GFW was administered in noise than in quiet, and might have been thought to form a subgroup of those less impaired by noise than usual, this hypothesis was not borne out (p = .07) as in the previous study it had been. Several questions regarding the GFW were raised and suggestions for future research discussed.


Radicals in natural product synthesis.
Free radical intermediates have intrigued chemists since their discovery, and an ever-increasing appreciation for their unique reactivity has resulted in the widespread utilization of these species throughout the field of chemical synthesis. This is most evident from the recent surge in the application of intermolecular radical reactions that feature in complex molecule syntheses. This tutorial review will discuss the diverse methods utilized for radical generation and reactivity to form critical bonds in natural product total synthesis. In particular, stabilized (e.g. benzyl) and persistent (e.g. TEMPO) radicals will be the primary focus.


Synthesis of the C-terminal half of thymosin alpha 1 by the polymeric reagent method.
In this report we further show the utility and efficiency of polymer-bound 1-hydroxybenzotriazole (PHBT) as an almost ideal support for the polymeric reagent method of peptide synthesis. This was demonstrated by the synthesis of thymosin alpha 1 (15-28), in which two suitably blocked segments, Boc-Asp (OtBu)-Leu-Lys (2Cz)-Glu (OBzl)-Lys (2Cz)-Lys (2Cz)-OH (3) and Boc-Glu (OBzl)-Val-Val-Glu (OBzl)-Glu (OBzl)-Ala-Glu (OBzl)-Asn-OBzl (2), were prepared entirely by utilizing PHBT activation for each coupling step. After appropriate deblocking of 2, segments 2 and 3 were coupled by the DCC-HOBT method, followed by complete deblocking and ion-exchange chromatographic purification, affording the C-terminal half of thymosin alpha 1, H-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-OH (1).


Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension.
Hypertension is a modifiable cardiovascular risk factor. Although it is established that low-dose thiazides reduce mortality as well as cardiovascular morbidity, the dose-related effect of thiazides in decreasing blood pressure has not been subject to a rigorous systematic review. It is not known whether individual drugs within the thiazide diuretic class differ in their blood pressure-lowering effects and adverse effects. To determine the dose-related decrease in systolic and/or diastolic blood pressure due to thiazide diuretics compared with placebo control in the treatment of patients with primary hypertension. Secondary outcomes included the dose-related adverse events leading to patient withdrawal and adverse biochemical effects on serum potassium, uric acid, creatinine, glucose and lipids. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 1), Ovid MEDLINE (1946 to February 2014), Ovid EMBASE (1974 to February 2014) and ClinicalTrials.gov. We included double-blind, randomized controlled trials (RCTs) comparing fixed-dose thiazide diuretic monotherapy with placebo for a duration of 3 to 12 weeks in the treatment of adult patients with primary hypertension. Two authors independently screened articles, assessed trial eligibility, extracted data and determined risk of bias. We combined data for continuous variables using a mean difference (MD) and for dichotomous outcomes we calculated the relative risk ratio (RR) with 95% confidence interval (CI). We included 60 randomized, double-blind trials that evaluated the dose-related trough blood pressure-lowering efficacy of six different thiazide diuretics in 11,282 participants treated for a mean duration of eight weeks. The mean age of the participants was 55 years and baseline blood pressure was 158/99 mmHg. Adequate blood pressure-lowering efficacy data were available for hydrochlorothiazide, chlorthalidone and indapamide. We judged 54 (90%) included trials to have unclear or high risk of bias, which impacted on our confidence in the results for some of our outcomes.In 33 trials with a baseline blood pressure of 155/100 mmHg, hydrochlorothiazide lowered blood pressure based on dose, with doses of 6.25 mg, 12.5 mg, 25 mg and 50 mg/day lowering blood pressure compared to placebo by 4 mmHg (95% CI 2 to 6, moderate-quality evidence)/2 mmHg (95% CI 1 to 4, moderate-quality evidence), 6 mmHg (95% CI 5 to 7, high-quality evidence)/3 mmHg (95% CI 3 to 4, high-quality evidence), 8 mmHg (95% CI 7 to 9, high-quality evidence)/3 mmHg (95% CI 3 to 4, high-quality evidence) and 11 mmHg (95% CI 6 to 15, low-quality evidence)/5 mmHg (95% CI 3 to 7, low-quality evidence), respectively.Direct comparison of doses did not show evidence of dose dependence for blood pressure-lowering for any of the other thiazides for which RCT data were available: bendrofluazide, chlorthalidone, cyclopenthiazide, metolazone or indapamide.In seven trials with a baseline blood pressure of 163/88 mmHg, chlorthalidone at doses of 12.5 mg to 75 mg/day reduced average blood pressure compared to placebo by 12.0 mmHg (95% CI 10 to 14, low-quality evidence)/4 mmHg (95% CI 3 to 5, low-quality evidence).In 10 trials with a baseline blood pressure of 161/98 mmHg, indapamide at doses of 1.0 mg to 5.0 mg/day reduced blood pressure compared to placebo by 9 mmHg (95% CI 7 to 10, low-quality evidence)/4 (95% CI 3 to 5, low-quality evidence).We judged the maximal blood pressure-lowering effect of the different thiazides to be similar. Overall, thiazides reduced average blood pressure compared to placebo by 9 mmHg (95% CI 9 to 10, high-quality evidence)/4 mmHg (95% CI 3 to 4, high-quality evidence).Thiazides as a class have a greater effect on systolic than on diastolic blood pressure, therefore thiazides lower pulse pressure by 4 mmHg to 6 mmHg, an amount that is greater than the 3 mmHg seen with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and renin inhibitors, and the 2 mmHg seen with non-selective beta-blockers. This is based on an informal indirect comparison of results observed in other Cochrane reviews on ACE inhibitors, ARBs and renin inhibitors compared with placebo, which used similar inclusion/exclusion criteria to the present review.Thiazides reduced potassium, increased uric acid and increased total cholesterol and triglycerides. These effects were dose-related and were least for hydrochlorothiazide. Chlorthalidone increased serum glucose but the evidence was unclear for other thiazides. There is a high risk of bias in the metabolic data. This review does not provide a good assessment of the adverse effects of these drugs because there was a high risk of bias in the reporting of withdrawals due to adverse effects. This systematic review shows that hydrochlorothiazide has a dose-related blood pressure-lowering effect. The mean blood pressure-lowering effect over the dose range 6.25 mg, 12.5 mg, 25 mg and 50 mg/day is 4/2 mmHg, 6/3 mmHg, 8/3 mmHg and 11/5 mmHg, respectively. For other thiazide drugs, the lowest doses studied lowered blood pressure maximally and higher doses did not lower it more. Due to the greater effect on systolic than on diastolic blood pressure, thiazides lower pulse pressure by 4 mmHg to 6 mmHg. This exceeds the mean 3 mmHg pulse pressure reduction achieved by ACE inhibitors, ARBs and renin inhibitors, and the 2 mmHg pulse pressure reduction with non-selective beta-blockers as shown in other Cochrane reviews, which compared these antihypertensive drug classes with placebo and used similar inclusion/exclusion criteria.Thiazides did not increase withdrawals due to adverse effects in these short-term trials but there is a high risk of bias for that outcome. Thiazides reduced potassium, increased uric acid and increased total cholesterol and triglycerides.


Relativistic coupled cluster study of diatomic compounds of Hg, Cn, and Fl.
The structure and energetics of eight diatomic heavy-atom molecules are presented. These include the species MAu, M2, and MHg, with M standing for the Hg, Cn (element 112), and Fl (element 114) atoms. The infinite-order relativistic 2-component Hamiltonian, known to closely reproduce 4-component results at lower computational cost, is used as framework. High-accuracy treatment of correlation is achieved by using the coupled cluster scheme with single, double, and perturbative triple excitations in large converged basis sets. The calculated interatomic separation and bond energy of Hg2, the only compound with known experimental data, are in good agreement with measurements. The binding of Fl to Au is stronger than that of Cn, predicting stronger adsorption on gold surfaces. The bond in the M2 species is strongest for Fl2, being of chemical nature; weaker bonds appear in Cn2 and Hg2, which are bound by van der Waals interactions, with the former bound more strongly due to the smaller van der Waals radius. The same set of calculations was also performed using the relativistic density functional theory approach, in order to test the performance of the latter for these weakly bound systems with respect to the more accurate coupled cluster calculations. It was found that for the MAu species the B3LYP functional provides better agreement with the coupled cluster results than the B88/P86 functional. However, for the M2 and the MHg molecules, B3LYP tends to underestimate the binding energies.


Merkel cell carcinoma of the lower extremity: a case report.
Merkel cell carcinoma is a rare, often fatal, neuroendocrine cutaneous malignancy with a highly variable clinical presentation. Due to the rapid progression of the disease, early detection and treatment is vital to survival. Here, we report the case of a 45-year-old woman whose podiatrist noticed an unusual lesion on her lower left leg and referred her to a dermatologist for work-up. A diagnostic excisional biopsy confirmed the diagnosis and was followed by treatment that included wide local excision of the primary lesion with subsequent chemotherapy and radiation. At the time of diagnosis, sentinel lymph node biopsy was positive. Due to the increasing prevalence of Merkel cell carcinoma in the past decade and its propensity to present on the lower extremity, podiatric physicians need to be aware of the clinical presentation and treatment guidelines for this elusive disease.


[Old and new anticoagulants. Antidotes and measures for acute hemorrhaging and urgent interventions].
Anticoagulation medications are frequently used for primary and secondary treatment of several thrombo-embolic disorders. An important side effect of all anticoagulants is hemorrhagic diathesis which necessitates acute treatment, ideally using medicinal therapy with an antidote. Much experience has been gained in treating bleeding while on traditional anticoagulants, such as heparins and vitamin K antagonists by the use of antagonists. A multitude of factor-specific anticoagulants have recently been introduced or will soon receive approval. With this new generation of anticoagulants no valid laboratory parameters or effective antagonists are presently available. Due to a lack of adequate studies regarding acute treatment this can at present only be carried out on a symptomatic basis.


Portable smartphone-integrated paper sensors for fluorescence detection of As(III) in groundwater.
Arsenic contamination in groundwater is a supreme environmental problem, and levels of this toxic metalloid must be strictly monitored by a portable, sensitive and selective analytical device. Herein, a new system of smartphone-integrated paper sensors with Cu nanoclusters was established for the effective detection of As(III) in groundwater. For the integration system, the fluorescence emissive peak of Cu nanoclusters at 600 nm decreased gradually with increasing As(III) addition. Meanwhile, the fluorescence colour also changed from orange to colourless, and the detection limit was determined as 2.93 nM (0.22 ppb) in a wide detection range. The interfering ions also cannot influence the detection selectivity of As(III). Furthermore, the portable paper sensors based on Cu nanoclusters were fabricated for visual detection of As(III) in groundwater. The quantitative determination of As(III) in natural groundwater has also been accomplished with the aid of a common smartphone. Our work has provided a portable and on-site detection technique toward As(III) in groundwater with high sensitivity and selectivity.


Immunoperoxidase detection of polycyclic aromatic hydrocarbon-DNA adducts in mouth floor and buccal mucosa cells of smokers and nonsmokers.
Tobacco smoking is a major risk factor for oral cancer; mouth floor and buccal mucosa are among the most and least cancer-prone subsites, respectively, in the oral cavity. We investigated the applicability of immunohistochemistry of smoking-induced DNA adducts in oral cells for assessing the exposure to carcinogens, and estimating the risk for oral cancer. Polycyclic aromatic hydrocarbon (PAH)-DNA adducts were measured in mouth floor and buccal mucosa cells of smokers (n = 26) and nonsmokers (n = 22) by means of a semiquantitative immunoperoxidase assay. Smokers had elevated levels of PAH-DNA adducts compared to nonsmokers in their mouth floor cells (0.045 +/- 0.022 versus 0.022 +/- 0.016, P = 0.0008 arbitrary units of immunohistochemistry) as well as in their buccal mucosa cells (0.058 +/- 0.028 versus 0.028 +/- 0.012, P = 0.001). Also, there was a correlation between the levels of PAH-DNA adducts in mouth floor cells and those in buccal mucosa cells (r = 0.4, P = 0.01). Furthermore, PAH-DNA adduct levels in both mouth floor and buccal mucosa cells were significantly related to current smoking indices (amount of tar and number of cigarettes consumed per day). Expectedly, the levels of PAH-DNA adducts neither in mouth floor cells nor in buccal mucosa cells, both being short-lived cells, were related to smoking history index (pack years). The levels of PAH-DNA adducts, however, in mouth floor cells as the cancer prone cells were lower than those in buccal mucosa cells (0.037 +/- 0.023 versus 0.044 +/- 0.026, P = 0.04). We conclude that immunohistochemistry of PAH-DNA adducts in oral cells can be used for exposure assessment of tobacco-related carcinogens, however, it cannot be used for oral cancer risk estimation.


SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985.
During leptin signaling, each of the phosphorylated tyrosine residues on the long form of the leptin receptor (LRb) mediates distinct signals. Phosphorylated Tyr(1138) binds STAT3 to mediate its tyrosine phosphorylation and transcriptional activation, while phosphorylated Tyr(985) binds the tyrosine phosphatase SHP-2 and reportedly mediates both activation of ERK kinases and inhibition of LRb-mediated STAT3 activation. We show here that although mutation of Tyr(985) does not alter STAT3 signaling by erythropoietin receptor-LRb (ELR) chimeras in transfected 293 cells at short times of stimulation, this mutation enhances STAT3 signaling at longer times of stimulation (>6 h). These data suggest that Tyr(985) may mediate feedback inhibition of LRb signaling by an LRb-induced LRb inhibitor, such as SOCS3. Indeed, SOCS3 binds specifically to phosphorylated Tyr(985) of LRb, and SOCS3 fails to inhibit transcription by ELR following mutation of Tyr(985), suggesting that SOCS3 inhibits LRb signaling by binding to phosphorylated Tyr(985). Additionally, overexpression of SOCS3, but not SHP-2, impairs ELR signaling, and the overexpression of SHP-2 blunts SOCS3-mediated inhibition of ELR signaling. Thus, our data suggest that in addition to mediating SHP-2 binding and ERK activation during acute stimulation, Tyr(985) of LRb mediates feedback inhibition of LRb signaling by binding to LRb-induced SOCS3.


Monitoring of transcutaneous carbon dioxide tension.
The authors studied the analytic and clinical characteristics of transcutaneous carbon dioxide monitoring in acutely ill NICU infants. Most infants were premature. The authors used both developmental and commercially available equipment. Monitoring was performed at temperature settings of 44 degrees C. With commercially available equipment, it was found that the least-squares linear regression relationship (r = 0.86, Sy.x = 12.9 torr, n = 100 patients) between transcutaneous PCO2 (y) and arterial PCO2 (x) was: y = -2.8 + (1.86)(x) (in torr). Calibration drift was unacceptably large in about 10% of the 500 monitoring sessions performed. Therefore, the authors conclude that transcutaneous PCO2 monitoring is most appropriate for following short-term trends in PCO2 over a period of one to three hours. Continuous transcutaneous PCO2 monitoring was most useful clinically after extubation when the objectives were careful observation for changes in PCO2 and prevention of reintubation.


[Clinical appearance of corneal lattice-type dystrophy (author's transl)].
Autosomal dominant hereditary lattice-type corneal dystrophy is a purely corneal hereditary metabolic disturbance, i.e. a localized amyloidosis. The author describes the findings in a family presenting with this disease. The condition progresses slowly; three stages may be distinguished, namely stage A, characterized by paracentrally arranged reticular lattice lines; stage B, characterized by paracentral lattice lines and patchy central subepithelial opacifications, and stage C, distinguished by paracentral lattice lines and diffuse white central subepithelial opacifications. Frequently, lattice-type corneal dystrophy is accompanied by symptoms of a pseudo-inflammation, e.g., photophobia, epiphora, "red eye" and pain due to recurrent corneal erosions. With regard to penetrating keratoplasty, changes of the donor cornea after a certain period of latency may be observed lattice-type corneal dystrophy as a result of which three types of opacifications may occur: 1) peripheral lattice lines and spots in the stroma; 2) diffuse whitish subepithelial opacifications, and 3) recurrent straited eruptions of the corneal epithelium.


Correlation of cell-envelope phenotypes of Neisseria gonorrhoeae with site of infection and serogroup.
The envelope phenotypes and coagglutination (CoA) W serogroups of 301 unselected clinical isolates of Neisseria gonorrhoeae were studied. Of the 287 isolates from infections acquired in the Edinburgh area, 252 (88%) were of the wild-type phenotype, 17 (6%) were of Env phenotype with increased permeability of the cell envelope, and 18 (6%) were of Mtr phenotype with reduced permeability of the cell envelope. Mtr strains were isolated significantly more often from homosexual men than from heterosexual men and women (p less than 0.001). Of the isolates from homosexual men there were considerably fewer Mtr phenotypes among rectal isolates than among urethral and throat isolates. All isolates from homosexual men, 57% from heterosexual men and 52% from women were of CoA serogroup WII (including WII/WIII). Although the Mtr phenotype was strongly associated with serogroup-WII isolates from homosexual men, there was no such correlation between the Mtr phenotype and serogroup-WII isolates from heterosexual patients. It is suggested that hydrophobic compounds in the rectal environment are not the major factor in selecting serogroup-WII strains of Mtr phenotype associated with homosexually acquired infection. The hypothesis that the Mtr phenotype and serogroup WII are selected independently as a result of a more general selective pressure such as antibiotic usage, common to all infected sites, is discussed.


Interference in immunoenzymometric assays caused by IgM anti-mouse IgG antibodies.
Serum samples from a female patient gave falsely elevated results in nine of ten immunoenzymometric assays (IEMAs) that used mouse monoclonal antibodies specific for human chorionic gonadotropin (n = 8), thyrotropin, or creatine kinase-MB isozyme. In contrast, normal results were obtained in five radioimmunoassays that used either mouse monoclonal antibodies or antisera specific for human chorionic gonadotropin (n = 3) or thyrotropin (n = 2). Incubation of her serum with IgG from different species or with F(ab)'2 from mouse IgG prior to IEMA showed that the interference was markedly inhibited by mouse IgG, indicating an antibody specific for the Fc portion of mouse IgG. The interfering activity was bound to and eluted from a column containing Protein A-Sepharose CL-4B. Fractionation of the eluted protein over another column containing Sephacryl S300 showed the activity was enriched in the first protein peak, which contained predominantly IgM. A model is proposed to explain how IgM anti-mouse IgG antibody selectively interferes in IEMAs that use mouse monoclonal antibodies.


Defending the leaf surface: intra- and inter-specific differences in silicon deposition in grasses in response to damage and silicon supply.
Understanding interactions between grasses and their herbivores is central to the conservation of species-rich grasslands and the protection of our most important crops against pests. Grasses employ a range of defenses against their natural enemies; silicon-based defenses have been shown to be one of the most effective. Silicon (Si) is laid down on the leaf surface as spines and other sharp bodies, known as phytoliths, making grasses abrasive and their foliage indigestible to herbivores. Previous studies on Si defenses found that closely related species may have similar levels of Si in the leaves but differ markedly in abrasiveness. Here we show how the number, shape and distribution of Si-rich phytoliths and spines differ within and between different grass species and demonstrate that species also differ in their ability to change the deposition and distribution of these defenses in response to damage or increases in Si supply. Specifically, we tested the response of two genotypes of Festuca arundinacea known to differ in their surface texture and three different grass species (F. ovina, F. rubra, and Deschampsia cespitosa) differing in their abrasiveness to combined manipulation of leaf damage and Si supply. F. arundinacea plants with a harsh leaf surface had higher Si content and more spines on their leaf surface than soft varieties. F. ovina and D. cespitosa plants increased their leaf Si concentration and produced an increase in the number of leaf spines and phytoliths on the leaf surface in response to Si addition. F rubra also increased leaf Si content in response to treatments, particularly in damaged leaves, but did not deposit this in the form of spines or increased densities of phytoliths. We discuss how the form in which grasses deposit Si may affect their anti-herbivore characteristics and consider the ecological and agricultural implications of the differences in allocation to Si-based defenses between grass species.


A Data Mining Approach to Predict In Situ Detoxification Potential of Chlorinated Ethenes.
Despite advances in physicochemical remediation technologies, in situ bioremediation treatment based on Dehalococcoides mccartyi (Dhc) reductive dechlorination activity remains a cornerstone approach to remedy sites impacted with chlorinated ethenes. Selecting the best remedial strategy is challenging due to uncertainties and complexity associated with biological and geochemical factors influencing Dhc activity. Guidelines based on measurable biogeochemical parameters have been proposed, but contemporary efforts fall short of meaningfully integrating the available information. Extensive groundwater monitoring data sets have been collected for decades, but have not been systematically analyzed and used for developing tools to guide decision-making. In the present study, geochemical and microbial data sets collected from 35 wells at five contaminated sites were used to demonstrate that a data mining prediction model using the classification and regression tree (CART) algorithm can provide improved predictive understanding of a site's reductive dechlorination potential. The CART model successfully predicted the 3-month-ahead reductive dechlorination potential with 75.8% and 69.5% true positive rate (i.e., sensitivity) for the training set and the test set, respectively. The machine learning algorithm ranked parameters by relative importance for assessing in situ reductive dechlorination potential. The abundance of Dhc 16S rRNA genes, CH4, Fe(2+), NO3(-), NO2(-), and SO4(2-) concentrations, total organic carbon (TOC) amounts, and oxidation-reduction potential (ORP) displayed significant correlations (p < 0.01) with dechlorination potential, with NO3(-), NO2(-), and Fe(2+) concentrations exhibiting precedence over other parameters. Contrary to prior efforts, the power of data mining approaches lies in the ability to discern synergetic effects between multiple parameters that affect reductive dechlorination activity. Overall, these findings demonstrate that data mining techniques (e.g., machine learning algorithms) effectively utilize groundwater monitoring data to derive predictive understanding of contaminant degradation, and thus have great potential for improving decision-making tools. A major need for realizing the predictive capabilities of data mining approaches is a curated, open-access, up-to-date and comprehensive collection of biogeochemical groundwater monitoring data.


Expression of plasminogen activator inhibitors 1 and 2 in lung cancer and their role in tumor progression.
The plasminogen activator cascade initiated by urokinase type plasminogen activator (u-PA) is involved in extracellular matrix degradation during the tumor invasion process. The plasminogen activator inhibitors 1 (PAI-1) and 2 (PAI-2) are two specific inhibitors of u-PA. We hypothesized that the balance between u-PA and its two inhibitors could be disrupted to favor plasminogen activation during lung cancer progression. Using immunohistochemistry, we analyzed the pattern of expression of u-PA, PAI-1, and PAI-2 in non-small cell lung carcinomas (NSCLC) and neuroendocrine (NE) lung tumors. u-PA and PAI-1 were both detected in stromal fibroblasts and in tumor cells. In 84 NSCLCs, their epithelial expression was strongly correlated and linked to the presence of node metastasis (P = 0.008), whereas their coexpression in fibroblasts was associated with larger tumor size (P = 0.04) and advanced stages (P = 0.009). In 72 NE tumors, u-PA and PAI-1 were more frequently expressed in fibroblasts in high-grade NE tumors (SCLC and large cell NE tumors) than in low- and intermediate-grade tumors (typical and atypical carcinoids). Comparison of in situ hybridization and immunohistochemistry in 14 cases showed that PAI-1 was consistently expressed by stromal fibroblasts, although the protein was also localized in tumor cells. In contrast, the expression of PAI-2 was restricted to fibroblasts and correlated with the absence of nodal involvement (P = 0.005). Considering NE tumors, the frequency of PAI-2 expression decreased along the NE spectrum from typical carcinoids to SCLCs. These data suggest that PAI-lacts in synergy with u-PA to favor tumor invasion process and connotes aggressivity, in contrast with PAI-2, which may block u-PA-mediated proteolysis and is inversely correlated with tumor progression.


Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation.
The Leishmania developmental cycle comprises three main life forms in two hosts, indicating that the parasite is continually challenged due to drastic environmental changes. The disruption of this cycle is critical for discovering new therapies to eradicate leishmaniasis, a neglected disease that affects millions worldwide. Telomeres, the physical ends of chromosomes, maintain genome stability and cell proliferation and are potential antiparasitic drug targets. Therefore, understanding how telomere length is regulated during parasite development is vital. Here, we show that telomeres form clusters spread in the nucleoplasm of the three parasite life forms. We also observed that amastigotes telomeres are shorter than metacyclic and procyclic promastigotes and that in parasites with continuous in vitro passages, telomere length increases over time. These observed differences in telomere length among parasite's life stages were not due to lack/inhibition of telomerase since enzyme activity was detected in all parasite life stages, although the catalysis was temperature-dependent. These data led us to test if, similar to other eukaryotes, parasite telomere length maintenance could be regulated by Hsp83, the ortholog of Hsp90 in trypanosomatids, and Leishmania (LHsp90). Parasites were then treated with the Hsp90 inhibitor 17AAG. The results showed that 17AAG disturbed parasite growth, induced accumulation into G2/M phases, and telomere shortening in a time-dependent manner. It has also inhibited procyclic promastigote's telomerase activity. Besides, LHsp90 interacts with the telomerase TERT component as shown by immunoprecipitation, strongly suggesting a new role for LHsp90 as a parasite telomerase component involved in controlling telomere length maintenance and parasite life span.


Polio, politics, publicity, and duplicity: ethical aspects in the development of the Salk vaccine.
This paper is an historical account of the discovery, testing, and early distribution of the Salk polio vaccine. The discovery posed fundamental dilemmas of medical research, pharmaceutical production, and public health. This paper assesses the ethical problems which arose, and examines critically their resolution. The National Foundation for Infantile Paralysis (March of Dimes) financed and directed the discovery of the vaccine, subsequent field trials, and early distribution. The Foundation's role is analyzed with special attention to the conflicts between its philanthropic and scientific functions. The reat public demand which the discovery of the vaccine generated created a need for federal control which was only partly met. The federal government did not have sufficient institutional and legal mechanisms to assure the safety of the vaccine and protect the public. This discussion illustrates the failure of the government to keep pace with medical technology.


Rumination syndrome in ethiopia: a case study.
Eating disorders are commonly believed to be rare or nonexistent in Africa. However, due to exposure to Western culture, a rise in eating disorders among African women is reported in the literature. This case study describes a 17-year-old Ethiopian girl who meets the DSM-IV-TR and DSM-5 diagnostic criteria for bulimia nervosa and the Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders criteria for rumination syndrome. The article discusses the diagnostic delays, the difficulties in terms of therapy, and the context determinants that-combined with individual psychopathological features-are thought to contribute to the disorders. Health professionals should be informed about the prevalence of eating disorders in Africa and, more specifically, of rumination syndrome in young women with normal intelligence. In light of this case study, it seems necessary to raise awareness with regard to the insufficient evidence on effective therapies for rumination syndrome in individuals without intellectual impairment.


Temporal decoding of MAP kinase and CREB phosphorylation by selective immediate early gene expression.
A wide range of growth factors encode information into specific temporal patterns of MAP kinase (MAPK) and CREB phosphorylation, which are further decoded by expression of immediate early gene products (IEGs) to exert biological functions. However, the IEG decoding system remain unknown. We built a data-driven based on time courses of MAPK and CREB phosphorylation and IEG expression in response to various growth factors to identify how signal is processed. We found that IEG expression uses common decoding systems regardless of growth factors and expression of each IEG differs in upstream dependency, switch-like response, and linear temporal filters. Pulsatile ERK phosphorylation was selectively decoded by expression of EGR1 rather than c-FOS. Conjunctive NGF and PACAP stimulation was selectively decoded by synergistic JUNB expression through switch-like response to c-FOS. Thus, specific temporal patterns and combinations of MAPKs and CREB phosphorylation can be decoded by selective IEG expression via distinct temporal filters and switch-like responses. The data-driven modeling is versatile for analysis of signal processing and does not require detailed prior knowledge of pathways.


Improving the culture of safety on a high-acuity inpatient child/adolescent psychiatric unit by mindfulness-based stress reduction training of staff.
The purpose of this study was to reduce perceived levels of interprofessional staff stress and to improve patient and staff safety by implementing a brief mindfulness-based stress reduction (MBSR) training program on a highacuity psychiatric inpatient unit. A one-group repeated measure design was utilized to measure the impact of the (MBSR) training program on staff stress and safety immediately posttraining and at 2 months. Two instruments were utilized in the study: the Toronto Mindfulness Scale and the Perceived Stress Scale. The MBSR program reduced staff stress across the 2-month post-training period and increased staff mindfulness immediately following the brief training period of 8 days, and across the 2-month post-training period. A trend toward positive impact on patient and staff safety was also seen in a decreased number of staff call-ins, decreased need for 1:1 staffing episodes, and decreased restraint use 2 months following the training period. A brief MBSR training program offered to an interprofessional staff of a high-acuity inpatient adolescent psychiatric unit was effective in decreasing their stress, increasing their mindfulness, and improving staff and patient safety.


Joint angle affects volitional and magnetically-evoked neuromuscular performance differentially.
This study examined the volitional and magnetically-evoked neuromuscular performance of the quadriceps femoris at functional knee joint angles adjacent to full extension. Indices of volitional and magnetically-evoked neuromuscular performance (N=15 healthy males, 23.5 ± 2.9 years, 71.5 ± 5.4 kg, 176.5 ± 5.5 cm) were obtained at 25°, 35° and 45° of knee flexion. Results showed that volitional and magnetically-evoked peak force (PF(V) and P(T)F(E), respectively) and electromechanical delay (EMD(V) and EMD(E), respectively) were enhanced by increased knee flexion. However, greater relative improvements in volitional compared to evoked indices of neuromuscular performance were observed with increasing flexion from 25° to 45° (e.g. EMD(V), EMD(E): 36% vs. 11% improvement, respectively; F([2,14])=6.8, p<0.05). There were no significant correlations between EMD(V) and EMD(E) or PF(V) and P(T)F(E), at analogous joint positions. These findings suggest that the extent of the relative differential between volitional and evoked neuromuscular performance capabilities is joint angle-specific and not correlated with performance capabilities at adjacent angles, but tends to be smaller with increased flexion. As such, effective prediction of volitional from evoked performance capabilities at both analogous and adjacent knee joint positions would lack robustness.


Ca2+ conduction by plant cyclic nucleotide gated channels and associated signaling components in pathogen defense signal transduction cascades.
Ca(2+) elevation in the cytosol is an essential early event during pathogen response signaling cascades. However, the specific ion channels involved in Ca(2+) influx into plant cells, and how Ca(2+) signals are initiated and regulate downstream events during pathogen defense responses, are at present unclear. Plant cyclic nucleotide gated ion channels (CNGCs) provide a pathway for Ca(2+) conductance across the plasma membrane (PM) and facilitate cytosolic Ca(2+) elevation in response to pathogen signals. Recent studies indicate that the recognition of pathogens results in cyclic nucleotide production and the activation of CNGCs, which leads to downstream generation of pivotal signaling molecules (such as nitric oxide (NO)). Calmodulins (CaMs) and CaM-like proteins (CMLs) are also involved in this signaling, functioning as Ca(2+) sensors and mediating the synthesis of NO during the plant pathogen response signaling cascade. In this article, these and other pivotal signaling components downstream from the Ca(2+) signal, such as Ca(2+)-dependent protein kinases (CDPKs) and CaM-binding transcription activators (CAMTAs), are discussed in terms of their involvement in the pathogen response signal transduction cascade.


Cofactor-dependent assembly of the flavoenzyme vanillyl-alcohol oxidase.
The oligomerization of the flavoprotein vanillyl-alcohol oxidase (VAO) and its site-directed mutant H61T was studied by mass spectrometry. Native VAO has a covalently bound FAD and forms primarily octameric assemblies of 507 kDa. H61T is purified as a FAD-free apoprotein and mainly exists as a dimeric species of 126 kDa. Binding of FAD to apoH61T rapidly restores enzyme activity and induces octamerization, although association of H61T dimers seems not to be crucial for enzyme activity. Reconstitution of H61T with the cofactor analog 5'-ADP also promotes octamerization. FMN on the other hand, interacts with apoH61T without stimulating dimer association. These results are in line with observations made for several other flavoenzymes, which contain a Rossmann fold. Members of the VAO flavoprotein family do not contain a Rossmann fold but do share two conserved loops that are responsible for binding the pyrophosphate moiety of FAD. Therefore, the observed FAD-induced oligomerization might be general for this family. We speculate that upon FAD binding, small conformational changes in the ADP-binding pocket of the dimeric VAO species are transmitted to the protein surface, promoting oligomerization.


Comparison of Sub-Scalp EEG and Endovascular Stent-Electrode Array for Visual Evoked Potential Brain-Computer Interface.
Brain-computer interfaces (BCI) have the potential to improve the quality of life for persons with paralysis. Sub-scalp EEG provides an alternative BCI signal acquisition method that compromises between the limitations of traditional EEG systems and the risks associated with intracranial electrodes, and has shown promise in long-term seizure monitoring. However, sub-scalp EEG has not yet been assessed for suitability in BCI applications. This study presents a preliminary comparison of visual evoked potentials (VEPs) recorded using sub-scalp and endovascular stent electrodes in a sheep. Sub-scalp electrodes recorded comparable VEP amplitude, signal-to-noise ratio and bandwidth to the stent electrodes.Clinical relevance-This is the first study to report a comparision between sub-scalp and stent electrode array signals. The use of sub-scalp EEG electrodes may aid in the long-term use of brain-computer interfaces.


[Bone loss owing to inflammatory bowel disease: prospective study, 50 cases].
To evaluate the prevalence of osteoporosis during inflammatory bowel disease (IBD) and to determine the risk factors. We conducted a prospective study that includes IBD patients. For all patients, bone mineral density was measured by dual-energy X-rays absorptiometry. Study has included 50 IBD patients; thirty had Crohn's disease and 20 had ulcerative colitis. The average age of our patients was of 36.4 + 9.9 years. A low osseous mineral density was noted in 21 patients (45%) distributed in 13% of osteoporosis and 32% of osteopenia. Only the age superior to 35 years, the duration of evolution of the disease superior to 10 years and intestinal resection constituted a risk factors of osteoporosis. After adaptation on the age and the intestinal resection the duration of evolution superior to 10 years persisted as risk factor of osteoporosis. The other risk factors: sex, type of IBD, denutrition and corticoids were not incriminated in the low osseous mineral density during IBD. These results confirm the necessity of the systematic search of the osteoporosis during IBD with the aim of proposing an early and effective treatment.


Tolerance strategies employing antigen-coupled apoptotic cells and carboxylated PLG nanoparticles for the treatment of type 1 diabetes.
The development of therapies that specifically target autoreactive immune cells for the prevention and treatment of type 1 diabetes (T1D) without inducing generalized immunosuppression that often compromises the host's ability to clear non-self antigen is highly desired. This review discusses the mechanisms and potential therapeutic applications of antigen-specific T cell tolerance techniques using syngeneic apoptotic cellular carriers and synthetic nanoparticles that are covalently cross-linked to diabetogenic peptides or proteins through ethylene carbodiimide (ECDI) to prevent and treat T1D. Experimental models have demonstrated that intravenous injection of autoantigen decorated splenocytes and biodegradable nanoparticles through ECDI fixation effectively induce and maintain antigen-specific T cell abortive activation and anergy by T cell intrinsic and extrinsic mechanisms. The putative mechanisms include, but are not limited to, the uptake and processing of antigen-coupled nanoparticles or apoptotic cellular carriers for tolerogenic presentation by host splenic antigen-presenting cells, the induction of regulatory T cells, and the secretion of immune-suppressive cytokines, such as IL-10 and TGF-β. The safety profile and efficacy of this approach in preclinical animal models of T1D, including non-obese diabetic (NOD), BDC2.5 transgenic, and humanized mice, have been extensively investigated, and will be the focus of this review. Translation of this approach to clinical trials of T1D and other T cell-mediated autoimmune diseases will also be reviewed in this chapter.


An intervention to promote patient participation and self-management in long term conditions: development and feasibility testing.
There is worldwide interest in managing the global burden of long-term conditions. Current health policy places emphasis on self-management and supporting patient participation as ways of improving patient outcomes and reducing costs. However, achieving genuine participation is difficult. This paper describes the development of an intervention designed to promote participation in the consultation and facilitate self-management in long-term conditions. In line with current guidance on the development of complex interventions, our aim was to develop and refine the initial intervention using qualitative methods, prior to more formal evaluation. We based the intervention on published evidence on effective ways of improving participation. The intervention was developed, piloted and evaluated using a range of qualitative methods. Firstly, focus groups with stakeholders (5 patients and 3 clinicians) were held to introduce the prototype and elucidate how it could be improved. Then individual 'think aloud' and qualitative interviews (n = 10) were used to explore how patients responded to and understood the form and provide further refinement. The literature highlighted that effective methods of increasing participation include the use of patient reported outcome measures and values clarification exercises. The intervention (called PRISMS) integrated these processes, using a structured form which required patients to identify problems, rate their magnitude and identify their priority. PRISMS was well received by patients and professionals. In the individual qualitative interviews the main themes that emerged from the data related to (a) the content of the PRISMS (b) the process of completing PRISMS and how it could be operationalised in practice and (c) the outcomes of completing PRISMS for the patient. A number of different functions of PRISMS were identified by patients including its use as an aide-memoire, to provide a focus to consultations, to give permission to discuss certain issues, and to provide greater tailoring for the patient. There was evidence that patients found the PRISMS form acceptable and potentially useful. The challenge encountered by patients in completing PRISMS may encourage exploration of these issues within the consultation, complementing the more 'task focussed' aspects of consultations resulting from introduction of clinical guidelines and financial incentives. Further research is required to provide a rigorous assessment of the ability of tools like PRISMS to achieve genuine change in the process and outcome of consultations.


Is low body mass index a risk factor for semen quality? A PRISMA-compliant meta-analysis.
Male infertility has become a worldwide public health problem. However, the effect of low body mass index (BMI) is still controversial. Relevant articles in Pubmed, Embase, Web of science, and Wanfang database published until September 2017 were searched without language restriction. We performed a meta-analysis about low BMI and semen parameters containing total sperm count, concentration, semen volume, and sperm motility (overall and progressive), including 709 men with low BMI and 14,622 men with normal BMI. Thirteen studies were included in this meta-analysis and a total of 15,331 individuals were accumulated. We pooled data from these articles and found standardized weighted mean differences in semen parameters (total sperm count and semen volume) showed significant difference between low BMI and normal BMI. This systematic review with meta-analysis has confirmed that there was a relationship between low BMI and semen quality, which suggesting low BMI may be a harmful factor of male infertility. Yet lacking of the raw data may influence the accuracy of the results. Further researches are needed to identify the role of underweight in male sterility.


Trends in metaplastic breast cancer incidence and mortality, and the effect of contralateral prophylactic mastectomy: A population-based study.
Metaplastic breast cancer (MBC) is considered rare and aggressive. We examined the epidemiology of and prognostic factors for MBC and investigated the effect of contralateral prophylactic mastectomy (CPM), because neither had been thoroughly examined previously. We obtained data from the Surveillance, Epidemiology, and End Results (SEER)-18(2000-2018) for epidemiological and survival analysis. The age-adjusted incidence per 100,000 persons of MBC increased significantly from 0.12 to 0.35 [annual percent change (APC):2.95%, 95% confidence interval [CI], 1.73-4.19]. The incidence-based mortality increased from 0.01 to 0.12 (APC: 5.01%, 95% CI: 2.50-7.58). The incidence of MBC patients who underwent CPM significantly increased from 0.003 to 0.039 with an APC of 10.96% (95%CI, 7.26-14.78). Older patients and those with higher T classification were less likely to receive CPM. The multivariate Cox model showed that CPM was not an independent predictor of good prognosis for both overall survival (OS) and breast cancer-specific survival (BCSS) (pre-propensity score matching (PSM): OS: P = 0.331; BCSS: P = 0.462. post-PSM: OS: P = 0.916; BCSS: P = 0.967). Subgroup analysis showed that CPM still did not provide a survival benefit to any risk groups. In this study, we demonstrated that the incidence and incidence-based mortality of MBC have increased over the past decades. Although the number of MBC patients who underwent CPM has significantly increased recently, CPM did not confer a survival benefit compared with unilateral mastectomy, indicating that the decision to undergo CPM should be considered carefully.


Injury prevention for modern dancers: a pilot study of an educational intervention.
Modern dancers suffer a high rate of musculoskeletal injuries. Preventing injury prolongs dance careers and eases financial burden on both individual dancers and dance companies alike. A medical student partnered with Garth Fagan Dance to develop a curriculum to teach principles of injury prevention specific to preprofessional and professional modern dancers. Quantitative assessments showed a significant increase in participant injury prevention knowledge after completion of the course (P < 0.0001). Participants' concern that injury may end their careers showed no significant change after the course (P = 0.35). Injury prevention and dance-related injuries were reported the most often as useful topics while weight management was reported the least often as a useful topic. Qualitative evaluations showed that participants' found a course on injury prevention valuable and desired a course of longer duration that includes a greater number of topics. These findings show that modern dancers perceive an educational course on injury prevention as valuable and retain information presented in the course in the short-term. Further study is warranted to assess changes in injury rates after the course and to continue to improve curriculum content and implementation.


Mechano-Responsive Luminescence via Crystal-to-Crystal Phase Transitions between Chiral and Non-Chiral Space Groups.
Herein, a novel mechano-responsive luminescent (MRL) material based on crystal-to-crystal phase transitions between crystals of a chiral and those of a centrosymmetric space group, accompanied by a change of emission properties, is described. Initially, a gold complex containing a biphenyl moiety, which exhibits an achiral structure in solution, afforded an orange-emitting amorphous phase together with a viscous isotropic oil after evaporation of the solvent. Upon pricking, the orange-emitting oil spontaneously crystallized either in a centrosymmetric or in a chiral space group while simultaneously changing the emission properties. Remarkably, grinding the chiral crystals induced a solid-state phase transition to the achiral crystals under concomitant changes of the emission properties.


Multiple contour extraction from graylevel images using an artificial neural network.
For active contour modeling (ACM), we propose a novel self-organizing map (SOM)-based approach, called the batch-SOM (BSOM), that attempts to integrate the advantages of SOM- and snake-based ACMs in order to extract the desired contours from images. We employ feature points, in the form of an edge-map (as obtained from a standard edge-detection operation), to guide the contour (as in the case of SOM-based ACMs) along with the gradient and intensity variations in a local region to ensure that the contour does not "leak" into the object boundary in case of faulty feature points (weak or broken edges). In contrast with the snake-based ACMs, however, we do not use an explicit energy functional (based on gradient or intensity) for controlling the contour movement. We extend the BSOM to handle extraction of contours of multiple objects, by splitting a single contour into as many subcontours as the objects in the image. The BSOM and its extended version are tested on synthetic binary and gray-level images with both single and multiple objects. We also demonstrate the efficacy of the BSOM on images of objects having both convex and nonconvex boundaries. The results demonstrate the superiority of the BSOM over others. Finally, we analyze the limitations of the BSOM.


Behavior of immunologically castrated barrows in comparison to gilts, physically castrated barrows, and intact male pigs.
The behavior of immunologically castrated barrows (IC; with Improvest; Zoetis, Parsippany, NJ) was compared with that of intact males (IM), physically castrated barrows (PC), and gilts (G). The study used 160 commercial crossbred pigs in a randomized complete block design (blocking factor was start date of study) and was performed over an 8-wk period from 16 wk of age (67.2 ± 2.50 kg BW) to a final BW of 126.5 ± 6.05 kg. The first Improvest dose was given to IC at the start of the study (d 0), and the second dose was given 28 d later. Pigs were housed in single-gender groups of 4 and had ad libitum access to feed and water. General, aggressive, and sexual behaviors were observed over a 12-h period from 0600 to 1800 h by the same trained investigators on d -1 (d prior to first dose), 13, 27 (day prior to second dose), 34, 41, and 55 of study (end of test). General behaviors (number of pigs lying, sitting, standing, at feeder, and at drinker) were recorded every 10 min in all pens (10 pens/gender), and aggressive (bites, head butts, and fights) and sexual (mounts) behaviors were recorded continuously over the 12-h period on a subsample of 4 pens/gender. There was no difference ( > 0.05) between the genders for lying, sitting, or drinker-related behavior. For the 4-wk period prior to second dose, a greater percentage of PC and G were at the feeder ( < 0.05) than IC or IM (8.0%, 7.4%, 10.2%, and 9.3% for IC, IM, PC, and G, respectively; SEM = 0.44). However, after the second dose, the percentage of pigs at the feeder was similar ( > 0.05) for IC, PC, and G and was greater ( < 0.05) for those genders than IM (10.1%, 7.1%, 10.0%, and 8.8%, respectively; SEM = 0.50). Prior to the second dose, the incidence of aggressive behaviors was generally greater for IC and IM compared with PC and G; however, after the second dose, the incidence of aggressive behaviors was similar for IC and PC and lower ( < 0.05) for those genders than for IM. The frequency of mounts for IC was greater ( < 0.05) than for PC before (25.5, 27.3, 2.5, and 1.5 total mounts/pen, respectively; SEM = 4.37) but not after ( > 0.05; 3.3, 33.3, 0.25, and 0.25 total mounts/pen, respectively; SEM = 1.15) the second dose. These results suggest that prior to the second Improvest dose, the behavior of IC was similar to that of IM and transitioned to become more similar to the behavior of PC after the second dose.


Adenovirus-mediated inducible gene expression in vivo by a hybrid ecdysone receptor.
Precise control of transgene expression would markedly facilitate certain applications of gene therapy. To regulate expression of a transferred gene in response to an exogenous compound in vivo, we modified the ecdysone-responsive system. We combined the advantages of the Drosophila (DmEcR) and the Bombyx ecdysone receptor (BmEcR) by creating a chimeric Drosophila/Bombyx ecdysone receptor (DB-EcR) that preserved the ability to bind to the modified ecdysone promoter without exogenous retinoid X receptor (RXR). In cultured cells, DB-EcR effectively mediates ligand-dependent transactivation of a reporter gene at lower concentrations of the chemical ecdysone agonist GS-E than VgRXR (DmEcR + RXR). Transgene delivery in vivo was achieved by intramyocardial injection of recombinant adenovirus vectors in adult rats. Upon stimulation with GS-E, DB-EcR potently (>40-fold induction) activated gene expression in vivo while VgRXR was not induced. This hybrid ecdysone receptor represents an important new tool for in vivo transgene regulation with potentially diverse applications in somatic and germline transfer.


The Alpha-Synuclein RT-QuIC Products Generated by the Olfactory Mucosa of Patients with Parkinson's Disease and Multiple System Atrophy Induce Inflammatory Responses in SH-SY5Y Cells.
Parkinson's disease (PD) and multiple system atrophy (MSA) are caused by two distinct strains of disease-associated α-synuclein (αSynD). Recently, we have shown that olfactory mucosa (OM) samples of patients with PD and MSA can seed the aggregation of recombinant α-synuclein by means of Real-Time Quaking-Induced Conversion (αSyn_RT-QuIC). Remarkably, the biochemical and morphological properties of the final α-synuclein aggregates significantly differed between PD and MSA seeded samples. Here, these aggregates were given to neuron-like differentiated SH-SY5Y cells and distinct inflammatory responses were observed. To deepen whether the morphological features of α-synuclein aggregates were responsible for this variable SH-SY5Y inflammatory response, we generated three biochemically and morphologically distinct α-synuclein aggregates starting from recombinant α-synuclein that were used to seed αSyn_RT-QuIC reaction; the final reaction products were used to stimulate SH-SY5Y cells. Our study showed that, in contrast to OM samples of PD and MSA patients, the artificial aggregates did not transfer their distinctive features to the αSyn_RT-QuIC products and the latter induced analogous inflammatory responses in cells. Thus, the natural composition of the αSynD strains but also other specific factors in OM tissue can substantially modulate the biochemical, morphological and inflammatory features of the αSyn_RT-QuIC products.


DAMAGE RESEARCH WITH P. PENETRANS IN ASPARAGUS PLANTS.
During cultivation of asparagus plants growth can be inhibited and yield can be reduced by plant-parasitic nematodes. Plant raising companies assume that the root lesion nematode (Pratylenchus penetrans) can cause severe yield loss in asparagus plants. However quantitative information about yield reduction in relation to the degree of infestation of this nematode species in the field is lacking. Research was done in The Netherlands by Applied Plant Research (part of Wageningen University and Research Centre) to determine the maximum degree of yield loss of asparagus plants at high infestation levels of P. penetrans and to establish the height of the tolerance limit for this nematode species. Also was investigated whether a field application of a granular nematicide could prevent or reduce yield loss caused by P. penetrans. Research was done in the field at sandy soils at the PPO location near Vredepeel in The Netherlands over a period of two years. In the first year the most suitable field was selected and on this field different infestation levels of P. penetrans were created. In the second year asparagus was cultivated and plant yield (number and quality of deliverable plants and financial yield) was calculated. At high infestation levels of Pratylenchus penetrans maximum yield loss was 12% (which can mean a financial loss of 7.000 C per ha). Yield started to decrease at very low infestation levels of P. penetrans and no statistical reliable tolerance limit could be calculated. Field application of 40 kg per ha of Vydate 10 G just before sowing of asparagus, could almost completely prevent yield loss caused by P. penetrans. After harvest infestation levels of P. penetrans were much lower than could be expected if asparagus was a non-host for this nematode species. In this paper therefore it is suggested that asparagus plants are (actively) controlling P. penetrans.


Successful transvaginal aspiration of interstitial pregnancy after failed methotrexate treatment.
Interstitial pregnancy is an uncommon condition that is challenging, not only in making an accurate diagnosis, but also in the choice of treatment. Systemic methotrexate (MTX) treatment has been favored to prevent scarring of the uterus. Nevertheless, surgery is generally indicated when this treatment fails. Transvaginal aspiration of the gestational tissue has been proposed as an alternative to surgery. The authors present a case of interstitial pregnancy in which the patient failed to respond to multidose MTX treatment and was successfully treated with transvaginal sonography-guided transvaginal aspiration of the gestational tissue, thereby bypassing the risk associated with undergoing major surgery. Transvaginal aspiration of conceptive tissue may be a novel treatment for patients with unruptured interstitial pregnancy.


Pulmonary thromboembolism in cats.
Pulmonary thromboembolism (PTE) is rarely diagnosed in cats, and the clinical features of the disease are not well known. PTE was diagnosed at postmortem examination in 17 cats, a prevalence of 0.06% over a 24-year period. The age of affected cats ranged from 10 months to 18 years, although young (<4 years) and old (>10 years) cats were more commonly affected than were middle-aged cats. Males and females were equally affected. The majority of cats with PTE (n = 16) had concurrent disease, which was often severe. The most common diseases identified in association with PTE were neoplasia, anemia of unidentified cause, and pancreatitis. Cats with glomerulonephritis, encephalitis, pneumonia, heart disease, and hepatic lipidosis were also represented in this study. Most cats with PTE demonstrated dyspnea and respiratory distress before death or euthanasia, but PTE was not recognized ante mortem in any cat studied. In conclusion, PTE can affect cats of any age and is associated with a variety of systemic and inflammatory disorders. It is recommended that the same clinical criteria used to increase the suspicion of PTE in dogs should also be applied to cats.