In vivo tumor vasculature targeted PET/NIRF imaging with TRC105(Fab)-conjugated, dual-labeled mesoporous silica nanoparticles.
Multifunctional mesoporous silica nanoparticles (MSN) with well-integrated multimodality imaging properties have generated increasing research interest in the past decade. However, limited progress has been made in developing MSN-based multimodality imaging agents to image tumors. We describe the successful conjugation of, copper-64 ((64)Cu, t1/2 = 12.7 h), 800CW (a near-infrared fluorescence [NIRF] dye), and TRC105 (a human/murine chimeric IgG1 monoclonal antibody) to the surface of MSN via well-developed surface engineering procedures, resulting in a dual-labeled MSN for in vivo targeted positron emission tomography (PET) imaging/NIRF imaging of the tumor vasculature. Pharmacokinetics and tumor targeting efficacy/specificity in 4T1 murine breast tumor-bearing mice were thoroughly investigated through various in vitro, in vivo, and ex vivo experiments. Dual-labeled MSN is an attractive candidate for future cancer theranostics.


Lower incidence of unexpected in-hospital death after interprofessional implementation of a bedside track-and-trigger system.
In-hospital patients may suffer unexpected death because of suboptimal monitoring. Early recognition of deviating physiological parameters may enable staff to prevent unexpected in-hospital death. The aim of this study was to evaluate short- and long-term effects of systematic interprofessional use of early warning scoring, structured observation charts, and clinical algorithms for bedside action. A prospective non-randomized controlled study of unexpected in-hospital death before and after implementation of a clinical intervention in a medical and surgical ward setting at an urban Danish university hospital. Information was obtained over three four-month study periods - a pre-interventional one in 2009 (1st March-30th June), and two postinterventional ones in 2010 (1st September-31st December) and 2011 (1st March-30th June). The incidence of unexpected patient death, the primary study outcome, was calculated as the rate of unexpected patient mortality based on in-hospital risk time. The adjusted unexpected patient mortality rate was significantly lower during the second postinterventional study period than before the intervention, 17 versus 61 per 100 adjusted patient years (P=0.013), corresponding to a rate ratio of 0.271 (95% confidence interval (CI) 0.097-0.762). A tendency to reduced unexpected mortality was found during the first postinterventional study period (25 versus 61 per 100 adjusted patient years, P=0.053; rate ratio 0.404, CI 0.161-1.012). Clinical intervention comprising systematic monitoring practice, early warning scoring, an observation chart, and an algorithm for bedside management, implemented by interprofessional teaching, training, and optimization of communication and collaboration, may significantly reduce unexpected in-hospital mortality.


Isolation of a monoclonal antibody that targets the alpha-2 helix of gp120 and represents the initial autologous neutralizing-antibody response in an HIV-1 subtype C-infected individual.
The C3-V4 region is a major target of autologous neutralizing antibodies in HIV-1 subtype C infection. We previously identified a Center for AIDS Program of Research in South Africa (CAPRISA) participant, CAP88, who developed a potent neutralizing-antibody response within 3 months of infection that targeted an epitope in the C3 region of the HIV-1 envelope (P. L. Moore et al., PLoS Pathog. 5:e1000598, 2009). Here we showed that these type-specific antibodies could be adsorbed using recombinant gp120 from the transmitted/founder virus from CAP88 but not by gp120 made from other isolates. Furthermore, this activity could be depleted using a chimeric gp120 protein that contained only the C3 region from the CAP88 viral envelope engrafted onto the unrelated CAP63 viral envelope (called 63-88C3). On the basis of this, a differential sorting of memory B cells was performed using gp120s made from 63-88C3 and CAP63 labeled with different fluorochromes as positive and negative probes, respectively. This strategy resulted in the isolation of a highly specific monoclonal antibody (MAb), called CAP88-CH06, that neutralized the CAP88 transmitted/founder virus and viruses from acute infection but was unable to neutralize CAP88 viruses isolated at 6 and 12 months postinfection. The latter viruses contained 2 amino acid changes in the alpha-2 helix of C3 that mediated escape from this MAb. One of these changes involved the introduction of an N-linked glycan at position 339 that occluded the epitope, while the other mutation (either E343K or E350K) was a charge change. Our data validate the use of differential sorting to isolate a MAb targeting a specific epitope in the envelope glycoprotein and provided insights into the mechanisms of autologous neutralization escape.


Quantitative T2 combined with texture analysis of nuclear magnetic resonance images identify different degrees of muscle involvement in three mouse models of muscle dystrophy: mdx, Largemyd and mdx/Largemyd.
Quantitative nuclear magnetic resonance imaging (MRI) has been considered a promising non-invasive tool for monitoring therapeutic essays in small size mouse models of muscular dystrophies. Here, we combined MRI (anatomical images and transverse relaxation time constant-T2-measurements) to texture analyses in the study of four mouse strains covering a wide range of dystrophic phenotypes. Two still unexplored mouse models of muscular dystrophies were analyzed: The severely affected Largemyd mouse and the recently generated and worst double mutant mdx/Largemyd mouse, as compared to the mildly affected mdx and normal mice. The results were compared to histopathological findings. MRI showed increased intermuscular fat and higher muscle T2 in the three dystrophic mouse models when compared to the wild-type mice (T2: mdx/Largemyd: 37.6±2.8 ms; mdx: 35.2±4.5 ms; Largemyd: 36.6±4.0 ms; wild-type: 29.1±1.8 ms, p<0.05), in addition to higher muscle T2 in the mdx/Largemyd mice when compared to mdx (p<0.05). The areas with increased muscle T2 in the MRI correlated spatially with the identified histopathological alterations such as necrosis, inflammation, degeneration and regeneration foci. Nevertheless, muscle T2 values were not correlated with the severity of the phenotype in the 3 dystrophic mouse strains, since the severely affected Largemyd showed similar values than both the mild mdx and worst mdx/Largemyd lineages. On the other hand, all studied mouse strains could be unambiguously identified with texture analysis, which reflected the observed differences in the distribution of signals in muscle MRI. Thus, combined T2 intensity maps and texture analysis is a powerful approach for the characterization and differentiation of dystrophic muscles with diverse genotypes and phenotypes. These new findings provide important noninvasive tools in the evaluation of the efficacy of new therapies, and most importantly, can be directly applied in human translational research.


EMOTIONAL MODULATION OF ATTENTION ORIENTING BY GAZE VARIES WITH DYNAMIC CUE SEQUENCE.
Recent gaze cueing studies using dynamic cue sequences have reported increased attention orienting by gaze with faces expressing fear, surprise or anger. Here, we investigated whether the type of dynamic cue sequence used impacted the magnitude of this effect. When the emotion was expressed before or concurrently with gaze shift, no modulation of gaze-oriented attention by emotion was seen. In contrast, when the face cue averted gaze before expressing an emotion (as if reacting to the object after first localizing it), the gaze orienting effect was clearly increased for fearful, surprised and angry faces compared to neutral faces. Thus, the type of dynamic sequence used, and in particular the order in which the gaze shift and the facial expression are presented, modulate gaze-oriented attention, with maximal modulation seen when the expression of emotion follows gaze shift.


A Multiple-Hit Hypothesis Involving Reactive Oxygen Species and Myeloperoxidase Explains Clinical Deterioration and Fatality in COVID-19.
Multi-system involvement and rapid clinical deterioration are hallmarks of coronavirus disease 2019 (COVID-19) related mortality. The unique clinical phenomena in severe COVID-19 can be perplexing, and they include disproportionately severe hypoxemia relative to lung alveolar-parenchymal pathology and rapid clinical deterioration, with poor response to O2 supplementation, despite preserved lung mechanics. Factors such as microvascular injury, thromboembolism, pulmonary hypertension, and alteration in hemoglobin structure and function could play important roles. Overwhelming immune response associated with "cytokine storms" could activate reactive oxygen species (ROS), which may result in consumption of nitric oxide (NO), a critical vasodilation regulator. In other inflammatory infections, activated neutrophils are known to release myeloperoxidase (MPO) in a natural immune response, which contributes to production of hypochlorous acid (HOCl). However, during overwhelming inflammation, HOCl competes with O2 at heme binding sites, decreasing O2 saturation. Moreover, HOCl contributes to several oxidative reactions, including hemoglobin-heme iron oxidation, heme destruction, and subsequent release of free iron, which mediates toxic tissue injury through additional generation of ROS and NO consumption. Connecting these reactions in a multi-hit model can explain generalized tissue damage, vasoconstriction, severe hypoxia, and precipitous clinical deterioration in critically ill COVID-19 patients. Understanding these mechanisms is critical to develop therapeutic strategies to combat COVID-19.


Effect of loop composition on the stability and folding kinetics of RNA hairpins with large loops.
RNA hairpins are ubiquitous structural elements in biological RNAs, where they have the potential to regulate RNA folding and interactions with other molecules. There are established methods for predicting the thermodynamic stability of an RNA hairpin, but there are still relatively few detailed examinations of the kinetics of folding. Nonetheless, several recent studies indicate that hairpin folding does not proceed via a simple two-state model. Here, we monitor fluorescence from hairpins constructed as molecular beacons in ensemble, fluorescence correlation spectroscopy, and stopped-flow experiments to describe the folding of RNA hairpins with long (15 nucleotide) loops. Our results show that folding of these hairpins occurs through more than two states and that the mechanism of folding includes a fast intermediate phase observed on the tens of microseconds time scale and a slow phase, attributed to formation of the native folded hairpin loop and stem, observed on the milliseconds time scale. The composition of the RNA loop determines the time scale of intermediate and native folded states. Hairpins with a polyuracil loop sequence exhibit slower relaxation of the intermediate state and faster relaxation of the native folded state when compared to that of hairpins with cytosine or adenine in the loop. We hypothesize this composition dependence could be attributed to nucleobase stacking in cytosine and adenine containing regions of the loop, which would be absent in hairpins containing polyuracil loops. Such base stacking could destabilize the intermediate folds, thereby speeding the relaxation of the intermediate relative to similar sized hairpins with no base stacking in the loop. Likewise, the lower intermediate stability could prolong the relaxation of the native folded state.


Factors influencing dialysis modality for end-stage renal disease in developing countries: a survey of Filipino nephrologists.
In the Philippines, 86% of incident dialysis patients are started on hemodialysis (HD) and 14% are treated with peritoneal dialysis (PD), representing a decline over a 2-year period. One important factor which affects patients' choice of dialysis modality is the input of their physicians. Our objective was to identify the factors affecting attitudes and recommendations of Filipino nephrologists regarding HD and PD. Attendees of the annual national nephrology meeting completed an anonymous self-administered questionnaire. Respondents were heavily involved in clinical dialysis work, and 86.7% had most/all of their patients on HD. Recommendations about dialysis modality were based most strongly on overall cost to patient (4.4 on a scale of 1 [not important] to 5 [most important], residual renal function (RRF) preservation (4.4), patient preference (4.3) availability of dialysis support staff (4.3), and comparative quality of life data (4.3). Least important was physician reimbursement (2.8). Patient-related factors favoring HD were: poor personal hygiene, impaired vision and manual dexterity; while favoring PD were: age <10 years, living far from HD unit, and the availability of trainable family members. When asked which modality they would recommend to an equally eligible patient, 49.2% responded they would not recommend either modality and would allow the patient to choose, while 40.7% would recommend HD and 10.2% would recommend PD. Respondents consider overall cost and RRF preservation as the most important factors in dialysis modality selection, yet only 10.2% would recommend PD as first choice. It is likely that factors other than those addressed in the survey are stronger determinants of the patient's final choice of modality.


FLAIR lesion volume in multiple sclerosis: relation to processing speed and verbal memory.
Information processing speed and episodic memory are two commonly affected cognitive abilities in MS. Insights into the mechanisms of and relationships between these abilities have recently come from structural neuroimaging techniques, but few studies have used fluid-attenuated inversion recovery (FLAIR), a neuroimaging sequence known to be sensitive to cortical and juxtacortical lesions in MS. We hypothesized that a volumetric index of FLAIR total lesion volume (TLV) would be associated with slowed processing speed and verbal memory dysfunction in MS. Twenty MS patients underwent FLAIR imaging and were administered measures of verbal memory and processing speed. Correlational and regression analyses indicated that TLV was directly and independently related to measures of processing speed and verbal memory, and TLV accounted for 56% of the variance in cognitive performance. These findings, considered in the context of prior work, suggest that FLAIR TLV is a useful predictor of commonly impaired cognitive functions in MS, and shows promise as a functionally relevant biomarker for disease status.


[About the professional identity in nursing: punctual reconsiderations in philosophical vision].
This paper is a contribution to the 80th years of the Brazilian Nursing Journal, official journal of the Brazilian Nurses Association, first nominated Nursing Annals and created in May 1932. At that time, the issues were focused as proposals to assure exchange communication between the Professional Class -the National Brazilian Graduate Nurses Association - and the associates, including all the people. In this way, the associate leaders were impelled through professional advances allied to the knowledge production regarding to the Professional Know/Knowledge, the practice assistance and education. The approach is through discussion and analytical appreciation about professional identity with punctual reconsiderations in philosophical vision. Instead of researching parameters the author prefers a pragmatic style around examples of three situations-problem as succeeded in the practical assistance, so that they could be critically appreciated alike fundamental basis to the nurses' art and enough to assure the definition of the professional profile in the historical-evolutive trajectory - with beginning in the nightingalean modernity and the proper assumed parsonian concepts - as such they are observed in the Brazilian Nursing literature. Without through off the subject, only the specific questions are submitted. Key words: Nursing; Professional Identity; Nurse Art.


Clonal relatedness of methicillin-resistant coagulase-negative staphylococci in the haemodialysis unit of a single university centre in Greece.
Coagulase-negative staphylococci (CoNS) are frequently encountered pathogens in hospital environment. Dialysis patients, often carrying central venous catheters, are prone to CoNS infections. Methicillin-resistant (MR) staphylococci in hospitals are resistant to multiple antibiotics and may cause an overall increase in the incidence of staphylococcal infections rather than simply replacing the more susceptible strains. The aim of this study was to evaluate the antimicrobial resistance and the clonal relatedness of all clinically significant CoNS isolates recovered from haemodialysis patient infections treated in a tertiary care centre, the University Hospital of Larissa, in central Greece. In addition, the CoNS isolates from carriers among health-care workers of the local haemodialysis unit were tested. All staphylococci recovered from chronic haemodialysis patients who developed CoNS infections according to Herwaldt criteria in the University Hospital of Larissa, from October 2002 to October 2005, were included. In addition, isolates from the palms and the nasal mucosa of the nursing and medical personnel in the haemodialysis unit were also collected. Isolates were identified and tested for antimicrobial resistance by conventional microbiological methods. The clonal relationship of both patients' and carriers' isolates was tested by pulsed-field gel electrophoresis (PFGE) analysis. Forty-two CoNS isolates were recovered from clinical culture specimens of patients hospitalized for various reasons. In 37 out of 42 CoNS isolates, methicillin resistance was determined. The majority of the MR Staphylococcus epidermidis isolates from patients belonged to one main clone (27 out of 32), arbitrarily named clone z. Clone z was also found to colonize 40% of the haemodialysis unit personnel. The high prevalence of clone z emphasizes the great capacity of CoNS to colonize patients with central venous catheters such as haemodialysis patients and personnel. This emphasizes the need for the establishment of control and prevention measures.


Memories of a friend and mentor - Charlotte Auerbach.
Charlotte Auerbach, the acknowledged discoverer of chemical mutagenesis, faced many challenges growing up and beginning her career in Germany. In the 1930s she moved to Scotland, completed her doctorate and spent the rest of her career at the University of Edinburgh. She had many scientific successes there, and was eventually provided with her own research group called the Mutagenesis Research Unit, where she continued to be very productive and a leader in her field. This article provides a somewhat abbreviated summary of her early life, struggles, and scientific career and achievements. It concludes with the author's personal memories and anecdotes from a productive and enjoyable year as a visitor on sabbatical in her laboratory.


Sequential assessment of cell cycle S phase in flow cytometry: a non-isotopic method to measure lymphocyte activation in vitro.
Lymphocyte multiplication can be induced in vitro by mitogens or specific antigens, and is usually measured using isotopic methods involving tritiated thymidine. Cellular proliferation can also be analyzed by flow cytometry techniques based on cell cycle analysis through the measurement of DNA content. We applied this method to lymphocytes from 113 individuals, to evaluate lymphocyte proliferation after stimulation in vitro by a mitogen (phytohaemagglutinin, PHA) or a recall antigen (tetanus toxoid), using a kinetic approach with four points sequential measurements of the S and G2 phases over six days of culture. The proportion of cells in S phase after PHA stimulation was significantly higher than in controls overall and as early as on day three of the culture. Activation with a recall antigen significantly induced increasing S phase cell proportions up to day six. These data suggest that flow cytometric assessment of the S phase could be a useful alternative to isotopic methods measuring lymphocyte reactivity in vitro.


Effect of intravenous angiotensin II infusion on responses to hypothalamic PVN injection of bicuculline.
The hypothalamic paraventricular nucleus (PVN) plays an important role in the sympathoexcitatory response to elevated plasma angiotensin II (Ang II). However, the mechanism by which Ang II influences sympathetic activity is not fully understood. In this study, we tested the hypothesis that GABA(gamma-aminobutyric acid)-ergic function in the PVN is reduced by peripheral infusion of Ang II. To accomplish this, rats received either intravenous Ang II (12 ng/kg per minute) or vehicle (D5W) for 7 days, and renal sympathetic nerve activity (SNA), mean arterial pressure (MAP), and heart rate (HR) responses were recorded after unilateral PVN microinjection of the GABA-A receptor antagonist bicuculline methiodide (BMI, 0.1 nmol). Results indicate that in contrast to a significant increase in renal SNA, MAP, and HR observed in vehicle-infused rats (P<0.05), BMI injection into the PVN of Ang II-infused animals was without effect on all recorded variables. In a separate groups of animals, ganglionic blockade produced a significantly greater fall in MAP (P<0.01) in Ang II-infused rats than in vehicle-infused control rats, indicating that the contribution of SNA to the maintenance of blood pressure was elevated in the Ang II-infused group. Overall, these data indicate that cardiovascular and sympathoexcitatory responses to acute GABA-A receptor antagonism in the PVN are significantly blunted in rats after 7 days of intravenous infusion of Ang II. We conclude that an Ang II-induced reduction in GABAergic inhibition within the PVN may contribute to elevated SNA observed in this study.


Effects of age on passive range of motion of selected peripheral joints in healthy adult females.
The purposes of this study were to investigate whether age influences passive range of motion (PROM) in women and to compare obtained values with other available data. Ninety healthy Caucasian women from 18 to 59 years of age had the PROM of their ankle, knee, hip, shoulder, elbow, and wrist measured by using a standard goniometer. Data were analyzed by using descriptive statistics (mean/SD) and linear regression (to analyze the effect of age on ROM). Age did not significantly influence PROM for the majority of movements tested. For 11 of the tested movements (knee flexion, hip flexion, hip external rotation, glenohumeral and shoulder complex flexion, glenohumeral and shoulder complex external rotation, shoulder complex abduction, shoulder complex extension, and elbow extension), increasing age was associated with a statistically significant decrease in PROM, whereas for ankle dorsiflexion, ankle plantarflexion, ankle inversion, and hip abduction, increasing age was associated with an increase in PROM. The change in PROM associated with age was typically small and ranged from -0.420 to 0.207 degrees per year. The difference in mean PROM between this study and published normative values ranged from -16.6 to +25.9 degrees. For women aged 18 to 59, PROM of the extremities is relatively constant, suggesting that a single table of reference values for adult females is an appropriate approximation for clinical practice except for glenohumeral and shoulder complex external rotation, which were found to clinically significantly decrease with age.


Variability in right hemisphere language function after callosal section: evidence for a continuum of generative capacity.
Two recent patients in our behavioral series investigating the psychological effects of callosal section exhibit right hemisphere language. Using lateralized visual and auditory stimulation, semantic, phonetic, and expressive linguistic functions were examined. While the right hemisphere language systems in both patients were shown to be capable of semantic information processing, they differed in their abilities to process phonetic information, follow verbal commands, and produce linguistic responses. It is argued that the differences between left and right hemisphere language systems are quantitative and are best characterized along a continuum of generative capacity. It is the variability in such capacity that appears to be responsible for the variability in right hemisphere language function within the split-brain population.


Cactus graphs for genome comparisons.
We introduce a data structure, analysis, and visualization scheme called a cactus graph for comparing sets of related genomes. In common with multi-break point graphs and A-Bruijn graphs, cactus graphs can represent duplications and general genomic rearrangements, but additionally, they naturally decompose the common substructures in a set of related genomes into a hierarchy of chains that can be visualized as two-dimensional multiple alignments and nets that can be visualized in circular genome plots. Supplementary Material is available at www.liebertonline.com/cmb .


COST-RISK-BENEFIT ANALYSIS IN DIAGNOSTIC RADIOLOGY: A THEORETICAL AND ECONOMIC BASIS FOR RADIATION PROTECTION OF THE PATIENT.
In 1973, International Commission on Radiological Protection Publication 22 recommended that the acceptability of radiation exposure levels for a given activity should be determined by a process of cost-benefit analysis. It was felt that this approach could be used to underpin both the principle of ALARA as well for justification purposes. The net benefit, B, of an operation involving irradiation was regarded as equal to the difference between its gross benefit, V, and the sum of three components; the basic production cost associated with the operation, P; the cost of achieving the selected level of protection, X; and the cost Y of the detriment involved in the operation: [Formula: see text] This article presents a theoretical cost-risk-benefit analysis that is applicable to the diagnostic accuracy (Levels 1 and 2) of the hierarchical efficacy model presented by National Council on Radiation Protection and Measurements in 1992. This enables the costs of an examination to be related to the sensitivity and specificity of an X-ray examination within a defined clinical problem setting and introduces both false-positive/false-negative diagnostic outcomes into the patient radiation protection framework.


[Antimicrobial properties of bee preparations in ointment form].
High antimicrobial activity apiphytopreparation in the form of the ointments containing pine turpentine, different concentration of propolis (from 4 to 20 %), honey and carotene oil from carrots (ointment N 4) has been. While testing by the method of diffusion in agar all the studied apiphytopreparation suppressed growth of Staphylococcus aureus, Bacillus subtilis, Saccharomyces cerevisiae, Micrococcus luteus, M. roseus. This effect increased with propolis content increase in the content of ointments. Bee honey and carotene oil intensified their antimicrobial activity. The latter was caused by the action of phenolic compounds, ether oils and other biologically active substances--the apiculture and vegetative raw material.


The influence of Grindr, a geosocial networking application, on body image in gay, bisexual and other men who have sex with men: An exploratory study.
Recent evidence indicates use of geosocial networking apps is associated with body image-related issues among gay, bisexual, and other men who have sex with men. The current study aims to elaborate upon these findings by investigating how Grindr, the most widely-used dating app among this population, impacts users' body image and body satisfaction. Using an exploratory, qualitative study design, semi-structured interviews were conducted with 13 current and previous Grindr users and analyzed thematically. Our findings suggest Grindr affects users' body image through three primary mechanisms: weight stigma, sexual objectification, and social comparison. In each case, normative user attitudes and behaviours interact with the app's constitutional elements to affect bodily perceptions in a way that differs in form or intensity from social influence via offline exchanges. These interactions are often enabled by features shared with traditional social networking sites, like asynchronous, text-based communication and technology-assisted appearance augmentation, but certain features unique to Grindr may also play an important role. Moreover, participants identified several protective factors and coping strategies which suggest the relationship between Grindr and body image is dependent on a number of complex interactions between technology, user, and environment. Limitations and suggestions for future research are also discussed.


Feasibility survey for a study on selective antibiotic management of acute otitis media.
To assess the views of community physicians on management of acute otitis media (AOM) without antibiotics and their willingness to support research on this issue. Community physicians who admit to a children's hospital were surveyed using a questionnaire containing questions on current issues in AOM management and their willingness to support research on management of AOM without antibiotics. Fifty-two percent of the surveys were returned. All respondents report concern about antibiotic resistant bacteria. Sixty-three percent treat otitis media with effusion with antibiotics and 68% give prophylactic antibiotics for recurrent otitis media. Thirty-five percent consider management of AOM without antibiotics as a possible alternative management practice. Forty-five percent of the respondents are willing to support research in this practice and 46% need more information. Surveyed physicians indicate concern about antibiotic resistance and a willingness to support further research on the initial management of acute otitis media without antibiotics.


Community Based Support for People at Risk for Suicide and Those Who Care for them - Areas for Improvement.
To systematically review the quality of evidence regarding the effectiveness of supports for people affected by suicide. EMBASE, MEDLINE, and PsychINFO were searched for evaluations of community-based supports for people affected by suicide. Outcomes included suicide-related behavior, depression, grief, quality of life, caring ability, and qualitative experiences. Fifteen studies evaluated 15 supports of various modalities. Study quality was generally poor; most studies examined bereaved individuals with mixed findings. Few reduced suicide-related behavior, half improved depression, and grief, while studies of caring ability, quality of life, or qualitative experiences reported positive effects. Supports associated with better outcomes connected peers with similar experiences, were provided over a period of months, and involved veteran rather than novice facilitators. Supports for people affected by suicide may be effective for improving suicide-related behavior, psychological adjustment, quality of life and caregiving, but require further evaluation.


Potential links between health literacy and cervical cancer screening behaviors: a systematic review.
The objective of this study is to critically appraise empirical evidence investigating pathways between health literacy (HL) and cervical cancer screening. A comprehensive search was undertaken to identify English-language studies published before May 2014 that measured HL and cervical cancer screening. After screening for eligibility, we identified 12 articles that met inclusion criteria. Nine studies yielded a positive association between HL and cervical cancer screening. Five studies investigated the relationships between HL, psychosocial variables, and cervical cancer screening and found that HL was associated with cervical cancer knowledge (n = 4) and cancer worry (n = 2). Separately, cancer knowledge (n = 2) and perceived barriers (n = 1) were correlated with cervical cancer screening. One study investigated an indirect pathway of HL to cervical cancer screening through health knowledge, although the indirect pathway was non-significant. Overall, the investigations tended to focus on print-related HL domain only and included only English-speaking or Spanish-speaking women. In addition, the studies were limited by lack of theoretical basis (n = 10) or temporality (n = 10) and use of self-reported screening status (n = 7). Evidence supports a positive link between HL and cervical cancer screening. There is only limited evidence to delineate indirect pathways linking HL and cervical cancer screening. Studies using a multidimensional validated measure of HL are needed in diverse groups of women, particularly those with a heightened burden of cervical cancer. With continuing cervical cancer disparities among culturally and linguistically diverse women, delineating how HL influences cervical cancer screening may help develop effective intervention strategies to reduce the disparities experienced by these women.


Unsupervised learning of stationary and switching dynamical system models from Poisson observations.
Objective. Investigating neural population dynamics underlying behavior requires learning accurate models of the recorded spiking activity, which can be modeled with a Poisson observation distribution. Switching dynamical system models can offer both explanatory power and interpretability by piecing together successive regimes of simpler dynamics to capture more complex ones. However, in many cases, reliable regime labels are not available, thus demanding accurate unsupervised learning methods for Poisson observations. Existing learning methods, however, rely on inference of latent states in neural activity using the Laplace approximation, which may not capture the broader properties of densities and may lead to inaccurate learning. Thus, there is a need for new inference methods that can enable accurate model learning.Approach. To achieve accurate model learning, we derive a novel inference method based on deterministic sampling for Poisson observations called the Poisson Cubature Filter (PCF) and embed it in an unsupervised learning framework. This method takes a minimum mean squared error approach to estimation. Terms that are difficult to find analytically for Poisson observations are approximated in a novel way with deterministic sampling based on numerical integration and cubature rules.Main results. PCF enabled accurate unsupervised learning in both stationary and switching dynamical systems and largely outperformed prior Laplace approximation-based learning methods in both simulations and motor cortical spiking data recorded during a reaching task. These improvements were larger for smaller data sizes, showing that PCF-based learning was more data efficient and enabled more reliable regime identification. In experimental data and unsupervised with respect to behavior, PCF-based learning uncovered interpretable behavior-relevant regimes unlike prior learning methods.Significance. The developed unsupervised learning methods for switching dynamical systems can accurately uncover latent regimes and states in population spiking activity, with important applications in both basic neuroscience and neurotechnology.


From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review).
The side effects of systemic chemotherapy used to treat cancer are often severe. For decades, oncologists have focused on treating the tumor, which may result in damage to the tumor‑bearing host and its immune system. Recently, much attention has been paid to the immune system of patients and its activation via biological therapies. Biological therapies, including immunotherapy and oncolytic virus (OV) therapy, are often more physiological and well tolerated. The present review elucidated how these therapies work and why these therapies may be better tolerated: i) In contrast to chemotherapy, immunotherapies induce a memory function of the adaptive immunity system; ii) immunotherapies aim to specifically activate the immune system against cancer; side effects are low due to immune tolerance mechanisms, which maintain the integrity of the body in the presence of B and T lymphocytes with their antigen‑receptor specificities and; iii) the type I interferon response, which is evoked by OVs, is an ancient innate immune defense system. Biological and physiological therapies, which support the immune system, may therefore benefit cancer treatment. The present review focused on immunotherapy, with the aim of reducing side effects and increasing long‑lasting efficacy in cancer therapy.


gamma,delta-Dioxovalerate as a substrate for the glyoxalase enzyme system.
1. Crude gammadelta-dioxovalerate was synthesized from laevulinate by two different methods and was purified by Sephadex chromatography. Some analytical reactions of the compound are described. 2. gammadelta-Dioxovalerate is a substrate for glyoxalase I and the GSH derivative formed by this enzyme is hydrolysed by glyoxalase II to form d-alpha-hydroxyglutarate. The K(m) of glyoxalase I for gammadelta-dioxovalerate is 1.0x10(-3)m at pH5.8.3. The u.v.-absorption spectrum of thiol ester, synthesized enzymically from gammadelta-dioxovalerate and GSH by glyoxalase I, is almost identical with that for S-lactoylglutathione. Some optical properties of this thiol ester were measured. 4. Attempts to show reversibility of the glyoxalase system reactions with d-alpha-hydroxyglutarate as substrate were unsuccessful. 5. The possible metabolic role of the gammadelta-dioxovalerate reaction is discussed. It is suggested that one of the metabolic functions of the glyoxalase system may be to provide a mechanism for the entry of this compound into the tricarboxylic acid cycle.


US Velocimetry in Participants with Aortoiliac Occlusive Disease.
Background The accurate quantification of blood flow in aortoiliac arteries is challenging but clinically relevant because local flow patterns can influence atherosclerotic disease. Purpose To investigate the feasibility and clinical application of two-dimensional blood flow quantification using high-frame-rate contrast-enhanced US (HFR-CEUS) and particle image velocimetry (PIV), or US velocimetry, in participants with aortoiliac stenosis. Materials and Methods In this prospective study, participants with a recently diagnosed aortoiliac stenosis underwent HFR-CEUS measurements of the pre- and poststenotic vessel segments (August 2018 to July 2019). Two-dimensional quantification of blood flow was achieved by performing PIV analysis, which was based on pairwise cross-correlation of the HFR-CEUS images. Visual inspection of the entire data set was performed by five observers to evaluate the ability of the technique to enable adequate visualization of blood flow. The contrast-to-background ratio and average vector correlation were calculated. In two participants who showed flow disturbances, the flow complexity and vorticity were calculated. Results Thirty-five participants (median age, 67 years; age range, 56-84 years; 22 men) were included. Visual scoring showed that flow quantification was achieved in 41 of 42 locations. In 25 locations, one or multiple issues occurred that limited optimal flow quantification, including loss of correlation during systole (n = 12), shadow regions (n = 8), a short vessel segment in the image plane (n = 7), and loss of contrast during diastole (n = 5). In the remaining 16 locations, optimal quantification was achieved. The contrast-to-background ratio was higher during systole than during diastole (11.0 ± 2.9 vs 6.9 ± 3.4, respectively; P < .001), whereas the vector correlation was lower (0.58 ± 0.21 vs 0.47 ± 0.13; P < .001). The flow complexity and vorticity were high in regions with disturbed flow. Conclusion Blood flow quantification with US velocimetry is feasible in patients with an aortoiliac stenosis, but several challenges must be overcome before implementation into clinical practice. Clinical trial registration no. NTR6980 © RSNA, 2021 Online supplemental material is available for this article.


Monoclonal antibodies specific to yellow-head virus (YHV) of Penaeus monodon.
Monoclonal antibodies specific to 22, 67 and 135 kDa proteins of yellow-head virus (YHV) were produced from a mouse immunized with partially purified YHV isolated from the haemolymph of experimentally YHV-infected Penaeus monodon. Four groups of monoclonal antibodies were identified. One group of antibodies bound only to native protein of YHV while the others were specific to 135, 67 and 22 kDa proteins in both native and denatured forms. All antibodies could be used to detect YHV infection by means of dot blot and immunohistochemistry. However, antibodies specific to the 22 kDa protein gave the best immunohistochemistry results in terms of intensity and sharpness of staining.


Study the Expression of ompf Gene in Esherichia coli Mutants.
The outer membrane porin proteins are the major factors in controlling the permeability of cell membrane. OmpF is an example of porin proteins in Esherichia coli. In normal growth condition a large amount of this protein is synthesised, but under stress condition, such as the presence of antibiotics in environment its expression is decreased inhibiting the entrance of antibiotics into cell. The expression of ompF is inhibited by antisense RNA transcribed from micF. In normal condition the expression of micF is low, but in the presence of antibiotics its expression is increased and causes multiple resistances to irrelevant antibiotics. The aims of this research were to study first, the intactness of micF and then quantify the expression of ompF in ciprofloxacin and tetracycline resistant mutants of E. coli. For this purpose the 5' end of micF was amplified and then sequenced. None of these mutants except one and its clone has a mutation in this gene. Then the relative expression of ompF in these mutants was quantified by real time PCR. There was no significant difference between ompF transcription of mutants and wild type strain. Based on this study and previous study it is concluded that low to intermediate levels of resistance to ciprofloxacin and tetracycline does not decrease ompF transcription.


Fluctuating selection driven by global and local climatic conditions leads to stasis in breeding time in a migratory bird.
The origin of natural selection is linked to environmental heterogeneity, which influences variation in relative fitness among phenotypes. However, individuals in wild populations are exposed to a plethora of biotic and abiotic environmental factors. Surprisingly, the relative influence of multiple environmental conditions on the relative fitness of phenotypes has rarely been tested in wild populations. Identifying the main selection agent(s) is crucial when the target phenotype is tightly linked to reproduction and when temporal variation in selection is expected to affect evolutionary responses. By using individual-based data from a 29-year study of a short-lived migratory songbird, the pied flycatcher (Ficedula hypoleuca), we studied the relative influence of 28 temperature- and precipitation-based factors at local and global scales on selection on breeding time (egg laying) at the phenotypic level. Selection, estimated using the number of recruits as a proxy for fitness, penalized late breeders. Minimum temperatures in April and May were the environmental drivers that best explained selection on laying date. In particular, there was negative directional selection on laying date mediated by minimum temperature in April, being strongest in cold years. In addition, nonlinear selection on laying date was influenced by minimum temperatures in May, with selection on laying date changing from null to negative as the breeding season progressed. The intensity of selection on late breeders increased when minimum temperatures in May were highest. Our results illustrate the complex influence of environmental factors on selection on laying date in wild bird populations. Despite minimum temperature in April being the only variable that changed over time, its increase did not induce a shift in laying date in the population. In this songbird population, stabilizing selection has led to a three-decade stasis in breeding time. We suggest that variation in the effects of multiple climatic variables on selection may constrain phenotypic change.


The Evolutionary History of Ephs and Ephrins: Toward Multicellular Organisms.
Eph receptor (Eph) and ephrin signaling regulate fundamental developmental processes through both forward and reverse signaling triggered upon cell-cell contact. In vertebrates, they are both classified into classes A and B, and some representatives have been identified in many metazoan groups, where their expression and functions have been well studied. We have extended previous phylogenetic analyses and examined the presence of Eph and ephrins in the tree of life to determine their origin and evolution. We have found that 1) premetazoan choanoflagellates may already have rudimental Eph/ephrin signaling as they have an Eph-/ephrin-like pair and homologs of downstream-signaling genes; 2) both forward- and reverse-downstream signaling might already occur in Porifera since sponges have most genes involved in these types of signaling; 3) the nonvertebrate metazoan Eph is a type-B receptor that can bind ephrins regardless of their membrane-anchoring structure, glycosylphosphatidylinositol, or transmembrane; 4) Eph/ephrin cross-class binding is specific to Gnathostomata; and 5) kinase-dead Eph receptors can be traced back to Gnathostomata. We conclude that Eph/ephrin signaling is of older origin than previously believed. We also examined the presence of protein domains associated with functional characteristics and the appearance and conservation of downstream-signaling pathways to understand the original and derived functions of Ephs and ephrins. We find that the evolutionary history of these gene families points to an ancestral function in cell-cell interactions that could contribute to the emergence of multicellularity and, in particular, to the required segregation of cell populations.


Optimal timing for solids introduction - why are the guidelines always changing?
There have been dramatic changes in timing of first exposure to solid foods for children over the last 40 years, ranging from exposure prior to 4 months of age for most infants in the 1960s, to guidelines recommending delaying solids until after 6 months of age introduced in the 1990s. Infant diet, specifically age of weaning and age at introduction of allergenic foods, has long been thought to play a role food allergy. However, controversy surrounding the relationship between timing of introduction of foods and development of food allergy has lead to a plethora of inconsistent infant feeding guidelines both between and within countries. The aims of this article were to discuss the history of changing guidelines for optimal timing of introduction of solids in general and allergenic solids in particular and the evidence (or lack thereof) underpinning recommendations at each of these time-points. We present the current clinical equipoise with regards to recently revised guidelines published almost simultaneously in the UK, US and Australia and argue that guideline modification about timing of introduction (both for high risk infants but also for the general population) will require careful review of emerging literature to provide a true evidence base to inform public health practice such as infant feeding guidelines.


EMG and kinematics analysis of the trunk and lower extremity during the sit-to-stand task while wearing shoes with different heel heights in healthy young women.
This study investigated the EMG characteristics and the kinematics of the trunk and lower extremity during the sit-to-stand (STS) task while wearing 1-, 4-, and 8-cm high-heeled shoes. We examined differences in the EMG data of the internal oblique, erector spinae, medial hamstring, and rectus femoris muscles during the STS task. The motion of the hip joint during an STS task was measured with a NorAngle Electrogoniometer System. Twelve young healthy women were recruited to this study. EMG characteristics and the hip joint angle were recorded during the performance of an STS task by subjects wearing high-heeled shoes of three different heel heights. The muscle onset time and EMG activity during this task were analyzed. In 8-cm high-heeled shoes, the onset time for the erector spinae muscle was significantly delayed, and the onset latency for the medial hamstring and the rectus femoris was significantly decreased. There was increased activity in the erector spinae and rectus femoris muscle during this task when wearing 8-cm high-heeled shoes. The initial hip flexion angle at the start point of the STS task did not differ among the 1-, 4-, and 8-cm heel-height conditions, but the trunk flexion angle, corresponding to the displacement between the peak hip flexion and initial hip flexion, was significantly larger in the 8-cm heel-height condition than in the 1- and 4-cm heel-height conditions. The findings suggest that excessive heel height has the potential to induce muscle imbalance during the STS task.


The Case for Fellowship Training in Emergency Psychiatry.
This article was migrated. The article was marked as recommended. Emergency departments (EDs) are a critical setting for behavioral health treatment particularly for minority and underserved communities, yet quality emergency psychiatric care remains inconsistently available. Subspecialty fellowship training in emergency psychiatry represents the most transformative potential approach to improving psychiatric care in EDs and crisis centers. We describe a new network of emergency psychiatry fellowship programs that are training a new generation of expert clinicians and leaders. Proposed educational milestones are described. These efforts will improve access to and the quality of mental health care for all patients regardless of treatment setting.


Detection of the oxygen consumption rate of migrating zebrafish by electrochemical equalization systems.
A novel measurement system to determine oxygen consumption rates via respiration in migrating Zebrafish (Danio rerio) has been developed. A signal equalization system was adapted to detect oxygen in a chamber with one fish, because typical electrochemical techniques cannot measure respiration activities for migrating organisms. A closed chamber was fabricated using a pipet tip attached to a Pt electrode, and a columnar Vycor glass tip was used as the salt bridge. Pt electrode, which was attached to the chamber with one zebrafish, and Ag electrode were immersed in 10 mM potassium iodide (KI), and both the electrodes were connected externally to form a galvanic cell. Pt and Ag electrodes act as the cathode and anode to reduce oxygen and oxidize silver, respectively, allowing the deposition of insoluble silver iodide (AgI). The AgI acts as the signal source accumulated on the Ag electrode by conversion of oxygen. The amount of AgI deposited on the Ag electrode was determined by cathodic stripping voltammetry. The presence of zebrafish or its embryo led to a decrease in the stripping currents generated by a 10 min conversion of oxygen to AgI. The conversion of oxygen to AgI is disturbed by the migration of the zebrafish and allows the detection of different equalized signals corresponding to respiration activity. The oxygen consumption rates of the zebrafish and its embryo were estimated and determined to be ∼4.1 and 2.4 pmol·s(-1), respectively. The deposited AgI almost completely disappeared with a single stripping process. The signal equalization system provides a method to determine the respiration activities for migrating zebrafish and could be used to estimate environmental risk and for effective drug screening.


Computed tomography of Wilson disease.
Computed tomography (CT) was performed on 25 patients with Wilson disease (hepatolenticular degeneration). The diagnosis was confirmed biochemically. CT was normal in seven patients, five of whom presented clinically with the hepatic form of the disease. In 10 patients, CT abnormalities were graded as mild: there were atrophic changes around the basal ganglia and in the cortex and cerebellum. In eight patients, besides areas of atrophy there were low absorption areas subcortically in the frontal lobi and in the cerebellar hemispheres, as well as brainstem atrophy. Hypodense lesions in the lentiform nucleus and the area of the dentate nucleus were also noted, although mathematical analysis in terms of decrease of Hounsfield units failed to demonstrate significant differences from normal values.


Pharmacokinetics of anticancer agents in patients with impaired liver function.
This report reviews published information on the clinical pharmacokinetics of antitumour agents in patients with liver dysfunction, associated with primary liver disease or liver metastases. Information was available for anthracyclines and their related compounds, antimetabolites, cyclophosphamide, vinca alkaloids, taxanes and epipodophyllotoxins. Changes in the pharmacokinetic profile or metabolism in patients with mild or severe hepatobiliary dysfunction are described and the relationships between serum levels, parameters employed for measuring hepatic function and toxic or therapeutic effects are examined. Current knowledge of the pharmacokinetics of antineoplastic agents in liver disease is far from complete, mostly obtained in small numbers of non-homogeneous patients often presenting only moderate liver dysfunction, and empirical guidelines for dose assessment are still largely applied in clinical practice. Because of the complex pathophysiological mechanisms of liver insufficiency in cancer patients, there is still doubt whether endogenous markers are useful. Although caution in treating cancer patients with liver insufficiency is compulsory, for most compounds there seems no need to recommend dose reductions for moderate impairment. However, for the tubulin acting agents, vincristine, vinblastine and possibly for paclitaxel and docetaxel, there is strong evidence that dose adjustment is mandatory in order to avoid excessive neutropenia and neurotoxicity.


Influence of preoperative allograft function (effective renal plasma flow) on the short-term outcome following living donor kidney transplantation.
Predonation kidney function is supposed to be an important factor affecting graft outcome. Controversial evidence suggests that higher predonation glomerular filtration rate (GFR) positively correlated with posttransplant graft outcome. The purpose of this study was to examine the relationship between living donor graft kidney function as measured by effective renal plasma flow (ERPF) and short-term graft function. We performed a retrospective analysis of 45 patients who underwent living donor renal transplantation at our institution from 2001 to 2007. The comprehensive nuclear medicine evaluation of donors' ERPF was performed before laparoscopic nephrectomy. The preoperative absolute ERPF-recipient body surface area (F/BSA) ratio and absolute ERPF-recipient body weight (F/Wt) ratio were determined for each donor-recipient pair. Posttransplant graft function was estimated by the four-variable Modification of Diet in Renal Disease (Chinese MDRD) equation. Estimated GFR correlated with F/BSA ratio at 3 months and 6 months (Pearson r = .495, P = .001 and r = .441, P = .012). Estimated GFR correlated with F/Wt ratio at 3 months and 6 months (r = .567, P < .001 and r = .453, P = .009). The correlations between the estimated GFR at 3 months and other variables were investigated. However, in the final multivariate model, F/BSA ratio and F/Wt ratio were the independent predictors of graft function. Preoperative ERPF can be used to calculate F/BSA and F/Wt ratios before living donor kidney transplantation. Our study provided evidence that F/BSA and F/Wt ratios may be considered predictive indices for short-term outcomes. An extreme discrepancy should be avoided between preoperative allograft function (absolute ERPF) and recipient body surface area or body weight.


Malnutrition and hypernatremic dehydration in breast-fed infants.
Despite the well-recognized advantages of breast-feeding to both mother and child, malnutrition of breast-fed infants can occur. We report two cases of breast-fed infants with cachexia, hypernatremia, and, in the one case in which it was measured, an elevated level of breast-milk sodium. These cases, along with several reported previously, emphasize the need for proper education and close and early follow-up of the nursing mother and infant, especially since a lack of parental awareness can be part of this syndrome.


Hereditary breast cancer. Identifying and managing BRCA1 and BRCA2 carriers.
To present a strategy for identifying candidates for consideration of BRCA1 and BRCA2 mutation testing. To discuss the implications of identifying patients as BRCA1 or BRCA2 mutation carriers, and to provide recommendations for managing them. A MEDLINE search from January 1990 to May 1998 was performed using the terms genetic breast screening, BRCA1, and BRCA2. The bibliographies of articles found were searched for further relevant titles. There are no published, randomized controlled clinical trials of management strategies for known BRCA carriers. Many recommendations for management are based on expert opinion only. About 5% of women with breast cancer are carriers of genetic mutations. An accurate and detailed family history is the most important tool for identifying potential BRCA1 and BRCA2 mutation carriers. Women identified as carriers have a substantially increased risk of breast and ovarian cancer. Male carriers have a moderately increased risk of prostate cancer. Management strategies for carriers are not well studied but include increased surveillance, preventive surgery, chemoprevention, and lifestyle modification. Family physicians must be able to identify people at risk, to discuss management strategies, and when appropriate, to offer referral for consideration of genetic testing. There is an urgent need for research to determine the effectiveness of surveillance strategies, preventive surgery, chemoprevention, and lifestyle modification for BRCA1 and BRCA2 mutation carriers.


Cross-linking of Fas by antibodies to a peculiar domain of gp120 V3 loop can enhance T cell apoptosis in HIV-1-infected patients.
Previous studies have demonstrated that T cell-reactive antibodies in HIV-1 infection contribute to lymphocyte depletion by cytotoxicity that involves differential membrane targets, such as the 43.5-kD receptor on CEM cells. Here, we show that these antibodies bind Fas as result of a molecular mimicry of the gp120. Both flow cytometry and immunoblotting using the human Fas-transfected mouse WC8 lymphoma revealed positive binding of immunoglobulin G from several patients to a 43.8-kD membrane receptor that also reacts with the CH11 anti-Fas monoclonal antibody. Specificity to Fas was further confirmed to chimeric recombinant human Fas-Fc by ELISA, whereas overlapping peptide mapping of a Fas domain (VEINCTR-N) shared by gp120 V3 loop demonstrated a predominant affinity to the full-length 10-mer peptide. Four anti-Fas affinity preparations greatly increased the subdiploid DNA peak of CEM cells similar to agonist ligands of Fas. In addition, anti-Fas immunoglobulin G strongly inhibited the [3H]thymidine uptake of CEM cells in proliferative assays, inducing a suppression as high as provoked by both CH11 mAb and recombinant human Fas ligand. Since anti-Fas were reactive to gp120, it is conceivable that antibodies binding that domain within the V3 region are effective cross-linkers of Fas and increase apoptosis in peripheral T cells. These results suggest that autologous stimulation of the Fas pathway, rather than of lymphocytotoxic antibodies, may aggravate lymphopenia in a number of HIV-1+ subjects.


[Protein C system and thrombosis diseases].
The mechanism of protein C system functioning and role of its components in the regulation of the coagulation and the fibrinolysis was considered in the review. There are also new data about the anticoagulation, profibrinolysis and antiinflammatory functions of protein C system. Activated protein C is inhibited by the protein C inhibitor, alpha 1-antitripsin, and inhibitor of tissue activator plasminogen-1. Hereditary or acquired deficiency of protein C, protein S and thrombomodulin lead to thrombotic diseases. Injection of exogenous recombinant protein C or activated protein C into the blood increases the anticoagulant activity of the blood and produced the antithrombotic effect.


A chromosome 1q44 deletion in a 4-month-old girl; The first report in Korea.
The deletion of the distal long arm of chromosome 1 is associated with a characteristic facial appearance and a pattern of associated malformations. Characteristic manifestations include a round face with prominent 'cupid's bow' and downturned corners of the mouth, thin vermilion borders of lips, a long upper lip with a smooth philtrum, a short and broad nose, epicanthal folds, apparently low-set ears, micrognathia, microcephaly, abnormal hands and feet, variable cardiac or genital anomalies, moderate to severe mental retardation, and growth retardation. Using fluorescent in situ hybridization (FISH) analysis to map precisely the deletion, we present a case of chromosome 1q44 deletion with craniofacial characteristics, multiple congenital anomalies, and growth and psychomotor retardation. In comparison with other reported cases of 1q43-44 deletion, the subject does not show hydrocephalus, seizure, syn- or polydactyly of hands, and a urogenital anomaly. However, an arachnoid cyst, pinpoint dimple on the midline of the forehead, a right-sided supernumerary nipple and auricular pit, polydactyly of the right foot, adducted thumb, and flexion restriction of the proximal interphalangeal joint with a simian line in both hands were observed additionally.


On-chip quantum interference with heralded photons from two independent micro-ring resonator sources in silicon photonics.
High visibility on-chip quantum interference among indistinguishable single-photons from multiples sources is a key prerequisite for integrated linear optical quantum computing. Resonant enhancement in micro-ring resonators naturally enables brighter, purer and more indistinguishable single-photon production without any tight spectral filtering. The indistinguisha-bility of heralded single-photons from multiple micro-ring resonators has not been measured in any photonic platform. Here, we report on-chip indistinguishability measurements of heralded single-photons generated from independent micro-ring resonators by using an on-chip Mach-Zehnder interferometer and spectral demultiplexer. We measured the raw heralded two-photon interference fringe visibility as 72 ± 3%. This result agrees with our model, which includes device imperfections, spectral impurity and multi-pair emissions. We identify multi-pair emissions as the main factor limiting the nonclassical interference visibility, and show a route towards achieving near unity visibility in future experiments.


Anatomical study of petrous and cavernous parts of internal carotid artery.
The petrous and cavernous parts of internal carotid artery (ICA) are obscure and are not readily accessible to observation/imaging. These parts have broad biological and medical interest because of their peculiar shape. Given the their clinical importance and the scarce data available based mostly on imaging, the present study was aimed at studying these parts of ICA by dissection. The study was carried out on 56 ICAs obtained from embalmed adult cadavers and 10 ICAs from five fetuses. The foetal ICAs were studied in situ. The morphometric analysis of the adult ICA was done after its removal from cranial cavity to gain an insight into the geometry of the vessel, i.e., length, various bends, and diameters at various locations. ICAs in fetuses ran a relatively straighter course taking gentle curves at three positions (two intrapetrous, one cavernous). Adult ICAs were more tortuous and exhibited greater variability in length and angulations. The length of respective portions of the ICA correlate negatively with the measure of angles. The angles in the petrous and cavernous parts were positively correlated to each other. The carotid siphon was positively, highly significantly correlated to other angles. Longer vessels are more tortuous with acute bends. An acute carotid siphon is an indication of more tortuous ICA. The findings of the present study have created a reference data of unsuspected adult population and has potential implications for studying cause/effect relationship of vessel geometry and hemodynamic factors.


Dynamic adhesions and MARCKS in melanoma cells.
Cell motility necessitates the rapid formation and disassembly of cell adhesions. We have studied adhesions in a highly motile melanoma cell line using various biochemical approaches and microscopic techniques to image close adhesions. We report that WM-1617 melanoma cells contain at least two types of close adhesion: classic focal adhesions and more extensive, irregularly shaped adhesions that tend to occur along lamellipodial edges. In contrast to focal adhesions, these latter adhesions are highly dynamic and can be disassembled rapidly via protein kinase C (PKC) activation (e.g. by eicosanoid) and MARCKS phosphorylation. MARCKS overexpression, however, greatly increases the area of close adhesions and renders them largely refractory to PKC stimulation. This indicates that nonphosphorylated MARCKS is an adhesion stabilizer. Unlike focal adhesions, the dynamic adhesions contain alpha3 integrin and MARCKS, but they do not contain the focal adhesion marker vinculin. Overall, these results begin to define the molecular and functional properties of dynamic close adhesions involved in cell motility.


Enhancing Prediction of Forelimb Movement Trajectory through a Calibrating-Feedback Paradigm Incorporating RAT Primary Motor and Agranular Cortical Ensemble Activity in the Goal-Directed Reaching Task.
Complete reaching movements involve target sensing, motor planning, and arm movement execution, and this process requires the integration and communication of various brain regions. Previously, reaching movements have been decoded successfully from the motor cortex (M1) and applied to prosthetic control. However, most studies attempted to decode neural activities from a single brain region, resulting in reduced decoding accuracy during visually guided reaching motions. To enhance the decoding accuracy of visually guided forelimb reaching movements, we propose a parallel computing neural network using both M1 and medial agranular cortex (AGm) neural activities of rats to predict forelimb-reaching movements. The proposed network decodes M1 neural activities into the primary components of the forelimb movement and decodes AGm neural activities into internal feedforward information to calibrate the forelimb movement in a goal-reaching movement. We demonstrate that using AGm neural activity to calibrate M1 predicted forelimb movement can improve decoding performance significantly compared to neural decoders without calibration. We also show that the M1 and AGm neural activities contribute to controlling forelimb movement during goal-reaching movements, and we report an increase in the power of the local field potential (LFP) in beta and gamma bands over AGm in response to a change in the target distance, which may involve sensorimotor transformation and communication between the visual cortex and AGm when preparing for an upcoming reaching movement. The proposed parallel computing neural network with the internal feedback model improves prediction accuracy for goal-reaching movements.


Effect of GLP-1 mimetics on blood pressure and relationship to weight loss and glycemia lowering: results of a systematic meta-analysis and meta-regression.
Incretin therapies such as glucagon-like peptide 1 (GLP-1) agonists are commonly used for the treatment of type 2 diabetes mellitus. GLP-1 mimetics, besides improving glycemic control, have been shown to influence multiple pathways regulating blood pressure (BP). We investigated the GLP-1 analogs effects on BP from published randomized studies using a meta-analytic approach. Thirty-three trials (12,469 patients) that assessed the efficacy of GLP-1 analogs on glycemic control (HbA1C) over 12-56 weeks that met additional criteria, including the availability of standardized sitting BP assessment and weight parameters, were identified. Comparator therapy included oral antiglycemic drugs or placebo. The weighted mean difference (WMD) in systolic BP (SBP) change was calculated using a random-effects model after performing a test for heterogeneity. Forty-one percent of patients were treated with liraglutide (0.3-3mg once daily), whereas 59% were treated with exenatide (5-10 µg twice daily or 2mg weekly). GLP-1 treatment achieved a greater SBP reduction than comparator therapy (WMD = 2.22mm Hg; 95% confidence interval (CI) = -2.97 to -1.47). In the pooled analysis, GLP-1 had beneficial effects on weight loss (WMD = -2.56kg; 95% CI = -3.12 to -2.00), HbA1c reduction (WMD = -0.41%; 95% CI = -0.78 to -0.04) but was associated with a heart rate increase (WMD = 1.30 bpm; 95% CI = 0.26-2.33). In a separate meta-regression analysis, the degree of SBP change was not related to baseline BP, weight loss, or improvement in HbA1C. This meta-analysis provides evidence that GLP-1 analogs reduce sitting SBP. These findings may support potentially favorable long-term cardiovascular outcomes.


Pharmaceuticals in farms and surrounding surface water bodies: Hazard and ecotoxicity in a swine production area in Costa Rica.
The presence of pharmaceuticals in the environment is known to have multiple origins; livestock activities comprise one scarcely studied source, both globally and specially in Latin-America. This work aims to study the occurrence of pharmaceuticals in wastewater from swine farms and their surrounding surface waters, in a highland livestock production area of Costa Rica. The monitoring of 70 pharmaceutical active compounds resulted in the detection of 10 molecules in farm wastewater (influents and effluents of the on-farm treatment system), including compounds of animal and human use. A 57% of effluents showed high hazard (ΣHQ > 1), mainly due to the compounds risperidone, ketoprofen, ibuprofen and naproxen. Additionally, ecotoxicological tests with Daphnia magna and Microtox classified at least 21% of the effluents as very toxic (10 < TU ≤ 100); likewise, 86% of effluents exhibited germination index (GI) inhibition values over 90% for Lactuca sativa. Seven molecules were detected in surface water, six of them of human use (1,7-dimethylxanthine, caffeine, cephalexin, carbamazepine, gemfibrozil, ibuprofen) and one (acetaminophen) of dual (human and veterinary) use; nonetheless, most of the detections were found in sampling points closer to human settlements than animal farms. Considering the set of molecules and their distribution, the livestock influence on surface water seems minimal in comparison with the urban influence. Only 16% of surface water samples showed high risk, mainly due to ibuprofen, gemfibrozil and caffeine; similarly, 45% samples presented GI inhibition >20% (no toxicity was determined towards Daphnia magna or Microtox). These findings in surface water suggest an incipient environmental risk in the area.


Sexual behavior, seminal pH and accessory sex gland weights in geldings administered testosterone and(or) estradiol-17 beta.
Sixteen stallions were castrated and 30 days later assigned to one of four treatments: (1) testosterone propionate (175 microgram/kg body weight), (2) 17 beta-estradiol-3-benzoate (44 micrograms/kg body weight), (3) a combination of both steroids or, (4) vehicle only. These dosage were administered every other day for 18 days. The dosages were then doubled and continued for 20 days. Concentrations of testosterone and estradiol in serum decreased rapidly after castration and stabilized within about 6 hours. Mean concentrations of testosterone and estradiol maintained by the steroids were 1.4 and 90 pg/ml, respectively, during treatment at the lower dosage, and 2.6 and 186 pg/ml during treatment at the higher dosage. Libido and the ability to ejaculate were gradually lost after castration. Testosterone restored both aspects of sexual behavior within 2 weeks. Estradiol effectively restored libido at the higher dosage, but was less effective in restoring the ability to ejaculate. The pH of gel-free semen increased after castration and was subsequently decreased by treatment with testosterone or the combination of both steroids. Estradiol had no effect on seminal pH. Weights of the seminal vesicles, ampullae and prostate were greater in geldings treated with testosterone or with both steroids than in estradiol-treated or control geldings. Since estradiol alone was able to restore libido in geldings, it is possible that the maintenance of libido in intact stallions involves either estradiol secreted directly by the testes or estradiol arising from aromatization in peripheral tissues. Treatment with estradiol at either concentration, did not appear to affect the size or function of sex glands in geldings.


Identifying social norms in physical aspects of food environments: A photo study.
It is widely accepted that physical food environments can contribute to unhealthy eating, but less is known about how physical cues in these environments actually stimulate eating. Our study starts from the assumption that social norms are embedded in physical cues and aims to make an inventory of physical cues that communicate what is socially accepted as normal and/or appropriate to eat in a Dutch outside-the-home food context. In Study 1, we conducted a qualitative study in which photographs taken in self-service food environments were analyzed using strategies from photo documentation and semiology. Grounded theory was applied to identify a wide variety of specific physical cues that were ultimately grouped into 18 higher level categories of physical cues (e.g. consumption traces, product availability). Most cue categories were associated with either descriptive or injunctive social norms, but some were associated with both types. In Study 2, we aimed to quantitatively cross-validate the social norm interpretations among laypeople (N = 173) by focusing on two selected photographs. More than half of the physical cues that participants identified in these photographs as being influential had been identified in Study 1 as cues bearing a normative message. The results further indicated that other people's behavior is easier to recognize in physical food environments than signals about what ought to be done. Given the great variety of identified physical cues associated with social norms, we posit that social norms are widely embedded in food environments and might guide eating behavior. Further research should study the effects of these cues on behavior and test whether the underlying process can be attributed to social norm interpretations.


Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18.
Platelets bound to thrombogenic surfaces have been shown to support activation-dependent firm adhesion of neutrophils in flow following selectin-mediated tethering and rolling. The specific receptor(s) responsible for mediating adhesion-strengthening interactions between neutrophils and platelets has not previously been identified. Furthermore, the ability of adherent platelets to support the migration of bound neutrophils has not been tested. We studied neutrophil interactions with activated, surface-adherent platelets as a model for leukocyte binding in vascular shear flow and emigration at thrombogenic sites. Our results demonstrate that the beta 2-integrin Mac-1 (CD11b/CD18) is required for both firm attachment to and transmigration of neutrophils across surface-adherent platelets. In flow assays, neutrophils from patients with leukocyte adhesion deficiency-1 (LAD-I), which lack beta 2-integrin receptors, formed P-selectin-mediated rolling interactions, but were unable to develop firm adhesion to activated platelets, in contrast to healthy neutrophils, which developed firm adhesion within 5 to 30 seconds after initiation of rolling. Furthermore, the adhesion-strengthening interaction observed for healthy neutrophils could be specifically inhibited by monoclonal antibodies (mAbs) to Mac-1, but not to lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) or intercellular adhesion molecule-2 (ICAM-2; CD102). Further evidence for a beta 2-integrin-dependent neutrophil/platelet interaction is demonstrated by the complete inhibition of interleukin (IL)-8-induced neutrophil transmigration across platelets bound to fibronectin-coated polycarbonate filters by mAbs to Mac-1. Thus, Mac-1 is required for firm adhesion of neutrophils to activated, adherent platelets and may play an important role in promoting neutrophil accumulation on and migration across platelets deposited at sites of vascular injury.


Rapid evaluation of bioactive Ti-based surfaces using an in vitro titration method.
The prediction of implant behavior in vivo by the use of easy-to-perform in vitro methods is of great interest in biomaterials research. Simulated body fluids (SBFs) have been proposed and widely used to evaluate the bone-bonding ability of implant materials. In view of its limitations, we report here a rapid in vitro method based on calcium titration for the evaluation of in vivo bioactivity. Using four different titanium surfaces, this method identifies that alkaline treatment is the key process to confer bioactivity to titanium whereas no significant effect from heat treatment is observed. The presence of bioactive titanium surfaces in the solution during calcium titration induces an earlier nucleation of crystalline calcium phosphates and changes the crystallization pathway. The conclusions from this method are also supported by the standard SBF test (ISO 23317), in vitro cell culture tests using osteoblasts and in vivo animal experiments employing a pelvic sheep model.


Roads as conduits for alien plant introduction and dispersal: The amplifying role of road construction in Ambrosia trifida dispersal.
The initial disruption caused by road construction, combined with ongoing vehicular traffic and regular road maintenance, can repeatedly disturb the environment in ways that favor introduced alien plants. We hypothesized that several characteristics of road construction influence the introduction of alien plants and analyzed 444 Environmental Impact Assessment reports for insights into the relationship between the progression of construction and alien plant richness. Additionally, we believed that roads enhance seed dispersal post-construction, and tested this using Ambrosia trifida patches on completed roads. In 41 construction sites, a total of 137 alien plant species were identified, with 120 introduced after the onset of construction. Significant correlations were found between alien plant richness and road characteristics, with wider roads experiencing more newly introduced species, while longer roads had more total alien plants. As construction progressed, the richness of alien plants generally increased, with around 88 % of sites showing this trend. Changes in alien plant composition during construction revealed a transition from perennial to annual dominance. Post-construction, we found that vehicles played a role in Ambrosia trifida seed dispersal, with seeds predominantly dispersing in the direction of traffic. This study provides information on alien plant species that are commonly introduced and rapidly dispersed due to road construction. Overall, we showed that road construction and subsequent vehicle traffic are primary factors in the spread of alien plants, necessitating early management measures during construction to prevent their proliferation.


Carcinoma of the duodenum: management and survival in 14 cases.
The aim of this study is to evaluate the role of surgery in the treatment of adenocarcinoma of the duodenum. From 1955 to 1994, 14 patients with primary adenocarcinoma of the duodenum underwent surgical treatment in our department. Presenting signs and symptoms were mainly related to obstruction and bleeding. Upper gastrointestinal contrast study, Computed Tomography (CT) and duodenoscopy were the primary diagnostic procedure modalities. All diagnoses were confirmed histologically. The tumors were staged pathologically according to the new TNM classification (UICC, 1992). Eight patients received palliative treatment or exploratory laparotomy. The remaining 6 patients were resectable for cure. Operative mortality was 35.7%. The 5-year survival rate for patients who underwent curative resection was 33.3%. None of the patients who underwent palliative procedures or exploratory laparotomy survived for more than 11 months. In the management of resectable adenocarcinomas of the duodenum surgical radicality including lymphadenectomy should be pursued. Unresectable adenocarcinomas treated with palliative procedure had a very poor prognosis.


Quetiapine versus other atypical antipsychotics for schizophrenia.
In many countries, second-generation ('atypical') antipsychotic drugs have become the first-line drug treatment for people with schizophrenia. It is not clear how the effects of the various second-generation antipsychotic drugs differ. To evaluate the effects of quetiapine compared with other second-generation (atypical) antipsychotic drugs in the treatment of people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane Schizophrenia Group Trials Register (May 2010), inspected references of all identified studies, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. We included all randomised controlled trials (RCTs) comparing oral quetiapine with other oral forms of atypical antipsychotic medication in people with schizophrenia or schizophrenia-like psychoses. We extracted data independently. For dichotomous data, we calculated risk ratios (RRs) and their 95% confidence intervals (CIs) on an intention-to-treat basis based on a random-effects model. We calculated number needed to treat for an additional beneficial outcome (NNTB) where appropriate. For continuous data, we calculated mean differences (MDs), again based on a random-effects model. Efficacy data tended to favour the control drugs over quetiapine (Positive and Negative Syndrome Scale (PANSS) total score vs olanzapine: 11 RCTs, n = 1486, mean quetiapine endpoint score 3.67 higher, CI 1.95 to 5.39, low quality; vs risperidone: 13 RCTs, n = 2155, mean quetiapine endpoint score 1.74 higher, CI 0.19 to 3.29, moderate quality; vs paliperidone: 1 RCT, n = 319, mean quetiapine endpoint score 6.30 higher, CI 2.77 to 9.83, moderate quality), but the clinical meaning of these data is unclear. No clear mental state differences were noted when quetiapine was compared with clozapine, aripiprazole or ziprasidone. Compared with olanzapine, quetiapine produced slightly fewer movement disorders (7 RCTs, n = 1127, RR use of antiparkinson medication 0.51, CI 0.32 to 0.81, moderate quality) and less weight gain (8 RCTs, n = 1667, RR 0.68, CI 0.51 to 0.92, moderate quality) and glucose elevation, but increased QTc prolongation (3 RCTs, n = 643, MD 4.81, CI 0.34 to 9.28). Compared with risperidone, quetiapine induced slightly fewer movement disorders (8 RCTs, n = 2163, RR use of antiparkinson medication 0.5, CI 0.36 to 0.69, moderate quality), less prolactin increase (7 RCTs, n = 1733, MD -35.25, CI -43.59 to -26.91) and some related adverse effects but greater cholesterol increase (6 RCTs, n = 1473, MD 8.57, CI 4.85 to 12.29). On the basis of limited data, compared with paliperidone, quetiapine induced fewer parkinsonian side effects (1 RCT, n = 319, RR use of antiparkinson medication 0.64, CI 0.45 to 0.91, moderate quality) and less prolactin increase (1 RCT, n = 319, MD -49.30, CI -57.80 to -40.80) and weight gain (1 RCT, n = 319, RR weight gain of 7% or more of total body weight 2.52, CI 0.5 to 12.78, moderate quality). Compared with ziprasidone, quetiapine induced slightly fewer extrapyramidal adverse effects (1 RCT, n = 522, RR use of antiparkinson medication 0.43, CI 0.2 to 0.93, moderate quality) and less prolactin increase. On the other hand, quetiapine was more sedating and led to greater weight gain (2 RCTs, n = 754, RR 2.22, CI 1.35 to 3.63, moderate quality) and cholesterol increase when compared with ziprasidone. Available evidence from trials suggests that most people who start quetiapine stop taking it within a few weeks (around 60%). Comparisons with amisulpride, sertindole and zotepine do not exist. Although efficacy data favour olanzapine and risperidone compared with quetiapine, the clinical meaning of these data remains unclear. Quetiapine may produce fewer parkinsonian effects than paliperidone, aripiprazole, ziprasidone, risperidone and olanzapine. Quetiapine appears to have a similar weight gain profile to risperidone, as well as clozapine and aripiprazole (although data are very limited for the latter two comparators). Quetiapine may produce greater weight gain than ziprasidone and less weight gain than olanzapine and paliperidone. Most data that have been reported within existing comparisons are of very limited value because of assumptions and biases within them. Much scope is available for further research into the effects of this widely used drug.


Separation by column chromatography of cells active in delayed-onset hypersensitivities.
Lymph node cells from guinea-pigs contact sensitive to 1-thiocyamo-2,4-dinitrobenzene have been fractionated by affinity chromatography over modified polyacrylamide beads. Cells mediating lymphokine release in response to active sensitizer were depleted only by chromatography over dinitrophyenyl (DNP) containing substrates and could be specifically eluted with DNP-glycine. DNP rosette-forming cells (RFC) were equally well depleted by chromatography using either DNP or trinitrophenyl containing materials but could not be eluted from the columns by DNP-glycine. While the antigen receptors of cells mediating the release of macrophage agglutination factor in response to DNP-containing antigens and of DNP-RFC were found to be hapten-specific, their specificity was shown to differ using chromatography over trinitrophenyl containing polyacrylamide.


Sjogern's syndrome.
Sjogren's syndrome (SS) is a systemic autoimmune exocrinopathy that affects the salivary and lacrimal glands. It typically presents as the "sicca complex" of dry eyes (xerophthalmia) and dry mouth (xerostomia) along with other symptoms such as arthritis. SS is classified as either primary or secondary. In the primary form, dry eyes and dry mouth occur alone. In the secondary form, the dry eyes and dry mouth occur in the context of another rheumatic disease, most commonly rheumatoid arthritis. There is an increasing list of systemic manifestations affecting the lung, kidney, and nervous system in patients with SS. The skin is affected in half of SS patients. Despite this high frequency of cutaneous involvement, patients with SS are not commonly seen in dermatology practices. SS is underrecognized and underdiagnosed because the cutaneous manifestations are nonspecific (eg, xerosis, pruritus) and less severe than the oral, ocular, or musculoskeletal symptoms. Nonetheless, because of its high prevalence, risk of cutaneous vasculitis, and the increased risk of a lymphoproliferative disorder, it is important for dermatologists to be familiar with SS.


Positive end expiratory pressure during one-lung ventilation: selecting ideal patients and ventilator settings with the aim of improving arterial oxygenation.
The efficacy of positive end-expiratory pressure (PEEP) in treating intraoperative hypoxemia during one-lung ventilation (OLV) remains in question given conflicting results of prior studies. This study aims to (1) evaluate the efficacy of PEEP during OLV, (2) assess the utility of preoperative predictors of response to PEEP, and (3) explore optimal intraoperative settings that would maximize the effects of PEEP on oxygenation. Forty-one thoracic surgery patients from a single tertiary care university center were prospectively enrolled in this observational study. After induction of general anesthesia, a double-lumen endotracheal tube was fiberoptically positioned and OLV initiated. Intraoperatively, PEEP = 5 and 10 cm H(2)O were sequentially applied to the ventilated lung during OLV. Arterial oxygenation, cardiovascular performance parameters, and proposed perioperative variables that could predict or enhance response to PEEP were analysed. T-test and χ(2) tests were utilized for continuous and categorical variables, respectively. Multivariate analyses were carried out using a classification tree model of binary recursive partitioning. PEEP improved arterial oxygenation by ≥20% in 29% of patients (n = 12) and failed to do so in 71% (n = 29); however, no cardiovascular impact was noted. Among the proposed clinical predictors, only intraoperative tidal volume per kilogram differed significantly between responders to PEEP and non-responders (mean 6.6 vs. 5.7 ml/kg, P = 0.013); no preoperative variable predicted response to PEEP. A multivariate analysis did not yield a clinically significant model for predicting PEEP responsiveness. PEEP improved oxygenation in a subset of patients; larger, although still protective tidal volumes favored a positive response to PEEP. No preoperative variables, however, could be identified as reliable predictors for PEEP responders.


From the importance of organic carbon in reproduction tests with Eisenia fetida.
The standard Eisenia fetida chronic toxicity reproduction test is normalized and needs up to 8 weeks of experimentation. Many matrixes have shown toxic effects on the earthworms' survey, growth and reproduction. But the food factor may affect the organisms' responses to contaminated media in such tests. We try to evaluate the effect, or not, of the organic carbon content present in the environment, as spreadable organic wastes added in soil, on the reproduction test of Eisenia fetida. We confirm the influence of the organic matter content on earthworm reproduction. This "food" factor must be considered when studying environmental samples rich in organic matter, since that could mask potentially harmful effects. To minimize this potential "food" effect during reproduction tests, we recommend an inverse gradient of organic matter contribution by the "horse dung" food applied in all conditions according to the dose of agricultural amendments tested.


Detection of PrP(Sc) in formalin-fixed, paraffin-embedded tissue by Western blot differentiates classical scrapie, Nor98 scrapie, and bovine spongiform encephalopathy.
Transmissible, spongiform encephalopathies including bovine spongiform encephalopathy (BSE) and scrapie are fatal neurodegenerative disorders associated with the presence of an infectious abnormal isoform of normal mammalian proteins called prions. Identification of the prion protein associated with scrapie (PrP(Sc)) in the central nervous system is typically based upon immunoassays including immunohistochemistry (IHC) using formalin-fixed tissues or Western blot (WB) assays using fresh and/or frozen, non-formalin-fixed tissues. Each assay can discriminate between BSE, classical scrapie, and a previously reported strain of scrapie recently identified in the United States named Nor98 scrapie. Different tissue samples are required from the same animal to run these 2 different immunoassays. This may result in inconsistent test results for the same animal. Sampling problems such as collecting insufficient volumes of fresh tissue or less than optimal anatomic location of brainstem for IHC can affect the ability of the test procedures to offer definitive and discriminatory results. Recently, a WB method using formalin-fixed, paraffin-embedded (FFPE) tissue to identify PrP(Sc) was developed that successfully identified PrP(Sc) in sheep affected by classical scrapie. In the current study, the use of this technique to produce discriminatory results identifying classical BSE in bovine tissue and both classical and Nor98 scrapie in ovine tissue using paraffin-embedded brain samples is described. Protein-banding patterns from WB using FFPE tissue were similar to protein-banding patterns produced by WB assays utilizing fresh tissues from the same animals, and results correlated well with the IHC PrP(Sc)-positive staining present in the cerebellum and obex regions of brain samples from these animals.


Individual and Instructional Determinants of Student Engagement in Physical Education.
This study was conducted to identify student characteristics and instructional factors that impact student engagement in physical education (PE). Data were derived from the systematic observation of 124 sessions taught by 31 physical educators and the administration of health and PE engagement questionnaires to 2,018 students in grades 5-8. Physical activity was directly affected by student engagement and perceived competence in PE and indirectly affected by students' body image through its association with PE engagement. Multilevel analyses revealed that the proportion of class time devoted to game play was negatively associated with student engagement in PE. Although less frequently used during PE sessions, skill practice was positively associated with student engagement and inactive instruction was negatively associated with student engagement. These effects were particularly pronounced among students with poor competence beliefs. Implications for PE instructional practice and future research are presented.


Microplastic in a macro filter feeder: Humpback whale Megaptera novaeangliae.
Marine filter feeders are exposed to microplastic because of their selection of small particles as food source. Baleen whales feed by filtering small particles from large water volumes. Macroplastic was found in baleen whales before. This study is the first to show the presence of microplastic in intestines of a baleen whale (Megaptera novaeangliae). Contents of its gastrointestinal tract were sieved, dissolved in 10% potassium hydroxide and washed. From the remaining dried material, potential synthetic polymer particles were selected based on density and appearance, and analysed by Fourier transform infrared (FTIR) spectroscopy. Several polymer types (polyethylene, polypropylene, polyvinylchloride, polyethylene terephthalate, nylon) were found, in varying particle shapes: sheets, fragments and threads with a size of 1mm to 17cm. This diversity in polymer types and particle shapes, can be interpreted as a representation of the varying characteristics of marine plastic and the unselective way of ingestion by M. novaeangliae.


A patient recall program to enhance decisions about prostate cancer screening: a feasibility study.
Lack of time and competing demands limit the ability of patients and providers to engage in informed decision-making discussions about prostate cancer screening during primary care visits. We evaluated a patient recall intervention to mitigate these challenges. Using mail and telephone outreach we invited men age 50-74 years without a PSA test in the prior 12 months to make appointments with their primary care providers in order to discuss the pros and cons of PSA-based prostate cancer screening. We assessed patient responsiveness to the program, provider documentation of screening discussions, orders for PSA laboratories, and provider attitudes. Out of 80 eligible patients, 37 (46%) scheduled and 28 (35%) completed a recall appointment. A large majority (91%) of patients eligible for PSA screening received an order for this test. Providers documented PSA discussions more often for these patients than for a recent sample of their other patients who received traditional care (47.8% vs. 12.5%, p = 0.009). Twelve of 14 participating providers felt the program improved their ability to impart information about the risks and benefits of screening, but were uncertain whether it influenced their patients' preexisting preferences for screening. Some expressed doubts about the advisability of PSA-specific appointments. To a limited extent, this pilot recall intervention enhanced opportunities for discussions of prostate cancer screening between patients and their primary care providers. As currently configured, however, this program was not found to be feasible for this purpose. A future version should promote screening discussions in the context of a broader range of health maintenance concerns and include more detailed, low-literacy information to educate patients in advance of clinic visits.