Sex-dependent effects of social status on the regulation of arginine-vasopressin (AVP) V1a, oxytocin (OT), and serotonin (5-HT) 1A receptor binding and aggression in Syrian hamsters (Mesocricetus auratus).

Dominance status in hamsters is driven by interactions between arginine-vasopressin V1a, oxytocin (OT), and serotonin 1A (5-HT1A) receptors. Activation of V1a and OT receptors in the anterior hypothalamus (AH) increases aggression in males, while decreasing aggression in females. In contrast, activation of 5-HT1A receptors in the AH decreases aggression in males and increases aggression in females. The mechanism underlying these differences is not known. The purpose of this study was to determine if dominance status and sex interact to regulate V1a, OT, and 5-HT1A receptor binding. Same-sex hamsters (N = 47) were paired 12 times across six days in five min sessions. Brains from paired and unpaired (non-social control) hamsters were collected immediately after the last interaction and processed for receptor binding using autoradiography. Differences in V1a, OT, and 5-HT1A receptor binding densities were observed in several brain regions as a function of social status and sex. For example, in the AH, there was an interaction between sex and social status, such that V1a binding in subordinate males was lower than in subordinate females and V1a receptor density in dominant males was higher than in dominant females. There was also an interaction in 5-HT1A receptor binding, such that social pairing increased 5-HT1A binding in the AH of males but decreased 5-HT1A binding in females compared with unpaired controls. These results indicate that dominance status and sex play important roles in shaping the binding profiles of key receptor subtypes across the neural circuitry that regulates social behavior.

Spontaneous food allergy in Was-/- mice occurs independent of FcεRI-mediated mast cell activation.

BACKGROUND: Food allergies are a growing health problem, and the development of therapies that prevent disease onset is limited by the lack of adjuvant-free experimental animal models. We compared allergic sensitization in patients with food allergy or Wiskott-Aldrich syndrome (WAS) and defined whether spontaneous disease in Was-/- mice recapitulates the pathology of a conventional disease model and/or human food allergy. METHODS: Comparative ImmunoCAP ISAC microarray was performed in patients with food allergy or WAS. Spontaneous food allergy in Was-/- mice was compared to an adjuvant-based model in wild-type mice (WT-OVA/alum). Intestinal and systemic anaphylaxis was assessed, and the role of the high-affinity IgE Fc receptor (FcεRI) in allergic sensitization was evaluated using Was-/- Fcer1a-/- mice. RESULTS: Polysensitization to food was detected in both WAS and food-allergic patients which was recapitulated in the Was-/- model. Oral administration of ovalbumin (OVA) in Was-/- mice induced low titers of OVA-specific IgE compared to the WT-OVA/alum model. Irrespectively, 79% of Was-/- mice developed allergic diarrhea following oral OVA challenge. Systemic anaphylaxis occurred in Was-/- mice (95%) with a mortality rate >50%. Spontaneous sensitization and intestinal allergy occurred independent of FcεRI expression on mast cells (MCs) and basophils. CONCLUSIONS: Was-/- mice provide a model of food allergy with the advantage of mimicking polysensitization and low food-antigen IgE titers as observed in humans with clinical food allergy. This model will facilitate studies on aberrant immune responses during spontaneous disease development. Our results imply that therapeutic targeting of the IgE/FcεRI activation cascade will not affect sensitization to food.

Improvement of ELISA procedures through simultaneous addition of antigen and detection antibody and elimination of washing steps.

The enzyme-linked immunosorbent assay (ELISA) is extensively used for measurement of proteins utilized for various research and diagnostic purposes in the biological disciplines. However, it is a labor-intensive and lengthy procedure due to a number of incubation and washing steps required for performing the assay. The ELISA procedure in the current study has been simplified through the simultaneous addition of antigen and detection antibody and elimination of washing steps. This resulted in a decreased time required to perform the procedure and without affecting assay capability. This approach offers the possibility of increasing ELISA productivity in low throughput laboratories without the need for alternative analytical platforms which would require significant assay redevelopment and capital expense.

Approach to evaluation of fever in ambulatory cancer patients receiving chemotherapy: A systematic review.

PURPOSE: To define the optimal model of care for patients receiving outpatient chemotherapy who experience a fever. Fever is a common symptom in patients receiving chemotherapy, but the approach to evaluation of fever is not standardized. METHODS: We conducted a search for existing guidelines and a systematic review of the primary literature from database inception to November 2015. Full-text reports and conference abstracts were considered for inclusion. The search focused on the following topics: the relationship between temperature and poor outcome; predictors for the development of febrile neutropenia (FN); the timing, location, and personnel involved in fever assessment; and the provision of information to patients receiving chemotherapy. RESULTS: Eight guidelines and 38 studies were included. None of the guidelines were directly relevant to the target population because they dealt primarily with the management of FN after diagnosis. The primary studies tended to include fever as one of many symptoms assessed in the setting of chemotherapy. Temperature level was a weak predictor of poor outcomes. We did not find validated prediction models for identifying patients at risk of FN among patients receiving chemotherapy. Several studies presented approaches to symptom management that included fever among the symptoms, but results were not mature enough to merit widespread adoption. CONCLUSION: Despite the frequency and risks of fever in the setting of chemotherapy, there is limited evidence to define who needs urgent assessment, where the assessment should be performed, and how quickly. Future research in this area is greatly needed to inform new models of care.

Approach to fever assessment in ambulatory cancer patients receiving chemotherapy: a clinical practice guideline.

BACKGROUND: This guideline was prepared by the Fever Assessment Guideline Development Group, a group organized by the Program in Evidence-Based Care at the request of the Cancer Care Ontario Systemic Treatment Program. The mandate was to develop a standardized approach (in terms of definitions, information, and education) for the assessment of fever in cancer patients receiving chemotherapy. METHODS: The guideline development methods included a search for existing guidelines, literature searches in medline and embase for systematic reviews and primary studies, internal review by content and methodology experts, and external review by targeted experts and intended users. RESULTS: The search identified eight guidelines that had partial relevance to the topic of the present guideline and thirty-eight primary studies. The studies were mostly noncomparative prospective or retrospective studies. Few studies directly addressed the topic of fever except as one among many symptoms or adverse effects associated with chemotherapy. The recommendations concerning fever definition are supported mainly by other existing guidelines. No evidence was found that directly pertained to the assessment of fever before a diagnosis of febrile neutropenia was made. However, some studies evaluated approaches to symptom management that included fever among the symptoms. Few studies directly addressed information needs and resources for managing fever in cancer patients. CONCLUSIONS: Fever in patients with cancer who are receiving systemic therapy is a common and potentially serious symptom that requires prompt assessment, but currently, evidence to inform best practices concerning when, where, and by whom that assessment is done is very limited.

Associations of cytological endometritis with energy metabolism and inflammation during the periparturient period and early lactation in dairy cows.

Multiparous Holstein cows (n=108) were used to determine the associations of cytological endometritis (CE) with plasma nonesterified fatty acids (NEFA) and ß-hydroxybutyrate (BHBA) as markers of energy metabolism, calculated energy balance (EB), and plasma haptoglobin (Hp) as a marker of inflammation during the periparturient period and early lactation. Evaluation of endometrial cytology by low-volume uterine lavage was conducted on 1d between 40 and 60 d postcalving. The incidence of CE among cows sampled was 40%. The area under the curve (AUC) was calculated for both NEFA and BHBA using data collected from 3 wk before to 3 wk after parturition. Data for NEFA and BHBA AUC were stratified into prepartum (wk -3 to parturition) and postpartum (parturition to wk +3) for statistical analysis. Prepartum AUC for neither NEFA nor BHBA was associated with subsequent CE; however, cows that subsequently developed CE tended to have higher postpartum AUC for NEFA and had higher postpartum AUC for BHBA. Consistent with the results for plasma NEFA and BHBA, calculated EB during the prepartum period was not different in cows that did or did not develop CE; however, cows with CE had lower EB during the 6-wk postpartum period compared with cows without CE. Analysis of EB by week (wk -3 to -1 before calving and wk +1 to +6 postcalving) indicated that EB in cows with CE was lower at wk +1, +2, and +3 and tended to be lower at wk +6 than cows without CE. Plasma Hp concentrations were analyzed from wk +1 to +8 of lactation; concentrations of Hp were not different during either wk +1 or the entire postpartum period between cows that did or did not develop CE. These results suggest that lower energy status during the first 3 wk postpartum, but not necessarily systemic inflammation, is associated with subsequent development of CE.

Diversity loss with persistent human disturbance increases vulnerability to ecosystem collapse.

Long-term and persistent human disturbances have simultaneously altered the stability and diversity of ecological systems, with disturbances directly reducing functional attributes such as invasion resistance, while eliminating the buffering effects of high species diversity. Theory predicts that this combination of environmental change and diversity loss increases the risk of abrupt and potentially irreversible ecosystem collapse, but long-term empirical evidence from natural systems is lacking. Here we demonstrate this relationship in a degraded but species-rich pyrogenic grassland in which the combined effects of fire suppression, invasion and trophic collapse have created a species-poor grassland that is highly productive, resilient to yearly climatic fluctuations, and resistant to invasion, but vulnerable to rapid collapse after the re-introduction of fire. We initially show how human disturbance has created a negative relationship between diversity and function, contrary to theoretical predictions. Fire prevention since the mid-nineteenth century is associated with the loss of plant species but it has stabilized high-yield annual production and invasion resistance, comparable to a managed high-yield low-diversity agricultural system. In managing for fire suppression, however, a hidden vulnerability to sudden environmental change emerges that is explained by the elimination of the buffering effects of high species diversity. With the re-introduction of fire, grasslands only persist in areas with remnant concentrations of native species, in which a range of rare and mostly functionally redundant plants proliferate after burning and prevent extensive invasion including a rapid conversion towards woodland. This research shows how biodiversity can be crucial for ecosystem stability despite appearing functionally insignificant beforehand, a relationship probably applicable to many ecosystems given the globally prevalent combination of intensive long-term land management and species loss.

Cross-ecosystem differences in stability and the principle of energy flux.

Here, we review consumer-resource (C-R) theory to show that the paradox of enrichment is a special case of a more general theoretical result. That is, we show that increased energy flux, relative to the consumer loss rate, makes C-R interactions top heavy (i.e., greater C:R biomass ratio) and less stable. We then review the literature on the attributes of aquatic and terrestrial ecosystems to argue that empirical estimates of parameters governing energy flux find that aquatic ecosystems have higher rates of relative energy flux than terrestrial ecosystems. Consistent with theory, we then review empirical work that shows aquatic ecosystems have greater herbivore:plant biomass ratios while we produce novel data to show that aquatic ecosystems have greater variability in population dynamics than their terrestrial counterparts. We end by arguing that theory, allometric relationships and a significant, negative correlation between body size and population variability suggest that these results may be driven by the smaller average body sizes of aquatic organisms relative to terrestrial organisms.

A dynamical approach to evaluate risk in resource management.

With the depletion of many natural resources, we are growing aware of the need to understand the risks that stem from different management decisions. Here, we outline an approach to test the ability of different dynamical signatures to characterize time-series data: how likely is it that a natural population is declining, sustainable, or increasing, and at what rates are these temporal changes likely occurring? These dynamical signatures can serve as a robust foundation on which to formulate alternative scenarios in a decision analysis. They take account of much of the uncertainty in model parameters and have precise mathematical underpinnings with associated risks. We present methods to evaluate the likelihood of these scenarios, and ways that the analysis can be graphically represented. We discuss different ecological factors such as climate variability, life history, ecosystem interactions, and a changing population age structure, all of which impact the dynamics of natural populations. Considering the types of dynamical signatures that emerge from these factors can change our understanding of risk and the decisions that we make.

The dynamics of spatially coupled food webs.

The dynamics of ecological systems include a bewildering number of biotic interactions that unfold over a vast range of spatial scales. Here, employing simple and general empirical arguments concerning the nature of movement, trophic position and behaviour we outline a general theory concerning the role of space and food web structure on food web stability. We argue that consumers link food webs in space and that this spatial structure combined with relatively rapid behavioural responses by consumers can strongly influence the dynamics of food webs. Employing simple spatially implicit food web models, we show that large mobile consumers are inordinately important in determining the stability, or lack of it, in ecosystems. More specifically, this theory suggests that mobile higher order organisms are potent stabilizers when embedded in a variable, and expansive spatial structure. However, when space is compressed and higher order consumers strongly couple local habitats then mobile consumers can have an inordinate destabilizing effect. Preliminary empirical arguments show consistency with this general theory.

The effect of bovine lactoferrin and lactoferricin B on the ability of feline calicivirus (a norovirus surrogate) and poliovirus to infect cell cultures.

AIMS: To characterize the effect of bovine lactoferrin and lactoferricin B against feline calicivirus (FCV), a norovirus surrogate and poliovirus (PV), as models for enteric viruses. METHODS AND RESULTS: Crandell-Reese feline kidney (CRFK) cells were used for the propagation of FCV and monkey embryo kidney (MEK) cells for PV. The assays included visual assessment of cell lines for cytopathic effects and determination of the percentage cell death using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium] dye reduction assay. Incubation of bovine lactoferrin with CRFK cells either prior to or together with FCV inoculation substantially reduced FCV infection. In contrast, the interference of lactoferrin with the infection of cells with PV was demonstrated only when lactoferrin was present with cell lines and virus for the entire assay period. Using indirect immunofluorescence, lactoferrin was detected on the surface of both CRFK and MEK cells, suggesting that the interference of viral infection may be attributed to lactoferrin binding to the surfaces of susceptible cells, thereby preventing the attachment of the virus particles. Lactoferricin B, a cationic antimicrobial peptide derived from the N-terminal domain of bovine lactoferrin, reduced FCV but not PV infection. CONCLUSION: Lactoferrin was shown to interfere with the infection of cells for both FCV and PV. However, lactoferricin B showed no interference of infection with PV and interference with infection for FCV required the presence of lactoferricin B together with the cell line and virus. SIGNIFICANCE AND IMPACT OF THE STUDY: An in vitro basis is provided for the effects of bovine lactoferrin and lactoferricin B in moderating food-borne infections of enteric viruses.

Assessing adult ADHD using a self-report symptom checklist.

The self-ratings of DSM-IV ADHD symptoms by adults reporting a previous ADHD diagnosis were contrasted with ratings by controls matched for age and sex. Adults previously diagnosed with ADHD endorsed significantly more symptoms of inattention and of hyperactivity-impulsivity. Specifically, 13 of the 18 DSM-IV ADHD symptoms were endorsed more frequently by the group previously diagnosed with ADHD than by the control group. Predictive power analysis showed that persons endorsing ADHD symptoms were highly likely to have reported a prior ADHD diagnosis. Finally, the data suggested that the DSM-IV diagnostic criteria of 6 symptoms of inattention or 6 symptoms of hyperactivity-impulsivity could be appropriately applied during adult ADHD assessment.

Non-local concepts and models in biology.

In this paper, we consider local and non-local spatially explicit mathematical models for biological phenomena. We show that, when rate differences between fast and slow local dynamics are great enough, non-local models are adequate simplifications of local models. Non-local models thus avoid describing fast processes in mechanistic detail, instead describing the effects of fast processes on slower ones. As a consequence, non-local models are helpful to biologists because they describe biological systems on scales that are convenient to observation, data collection, and insight. We illustrate these arguments by comparing local and non-local models for the aggregation of hypothetical organisms, and we support theoretical ideas with concrete examples from cell biology and animal behavior.

Fatigue in persons with renal failure who require maintenance haemodialysis.

Fatigue is a highly prevalent symptom experienced by persons who live with chronic illness, including those with renal failure who require maintenance haemodialysis. Fatigue, however, is a non-specific and invisible symptom and is a phenomenon that is poorly understood by health care professionals. This study examined the symptom of fatigue as experienced by a group of 39 adult haemodialysis patients. The theory of unpleasant symptoms formed the conceptual framework for the study. A descriptive correlational design was utilized to examine fatigue from an inductive approach, considering relevant physiological, psychological and situational variables based on a review of the literature. Data were collected using a structured self-report questionnaire and biochemical data from retrospective monthly blood tests. The results of the study indicated that high levels of fatigue are experienced, with correspondingly low levels of vitality, in all the areas measured - general fatigue, physical fatigue, reduced motivation, reduced activity and mental fatigue, by adult haemodialysis patients. Individual variation was noted in the dimensions of fatigue predominantly expressed. Fatigue was significantly associated with the presence of symptoms such as sleep problems, poor physical health status and depression. No associations between fatigue and the biochemical and situational variables measured were noted. Further examination of the data revealed complex relationships between the physiological and psychological factors examined. Depression was significantly associated with physical health status, sleep problems, symptoms and anxiety. Correlations were also noted between symptoms and poor physical functioning, sleep problems and depression. Based on the results, a revised version of the theory of unpleasant symptoms relating to fatigue is presented.

Steric bulk at cycloartenol synthase position 481 influences cyclization and deprotonation.

Cycloartenol synthase converts oxidosqualene to the pentacyclic sterol precursor cycloartenol. An Arabidopsis thaliana cycloartenol synthase Ile481Val mutant was previously shown to produce lanosterol and parkeol in addition to its native product cycloartenol. Experiments are described here to construct Phe, Leu, Ala, and Gly mutants at position 481 and to determine their cyclization product profiles. The Phe mutant was inactive, and the Leu mutant produced cycloartenol and parkeol. The Ala and Gly mutants formed lanosterol, cycloartenol, parkeol, achilleol A, and camelliol C. Monocycles comprise most of the Gly mutant product, showing that an alternate cyclization route can be made the major pathway by a single nonpolar mutation.

Population outbreaks in a discrete world.

We present and analyze a simple three-patch host-parasitoid model where population growth is discrete. The model gives solutions that are qualitatively similar to the stable large-amplitude patterns in space found in reaction-diffusion theory. In the context of host-parasitoid interactions, the large-amplitude portions of the solution can be thought of as spatially localized host population outbreaks. Here, we show that the biological requirements for localized population outbreaks in a discrete world are identical to those found in reaction- diffusion theory. Furthermore, the model conveniently allows investigation into the robustness of these population outbreaks under the influence of density-dependent dispersal behavior. We find that localized population outbreaks in space can still occur with modest amounts of pursuit and aggregative behavior by parasitoids. We end by showing that evidence from a real host-parasitoid system is consistent with the predictions of the model.

The diversity-stability debate.

There exists little doubt that the Earth's biodiversity is declining. The Nature Conservancy, for example, has documented that one-third of the plant and animal species in the United States are now at risk of extinction. The problem is a monumental one, and forces us to consider in depth how we expect ecosystems, which ultimately are our life-support systems, to respond to reductions in diversity. This issue--commonly referred to as the diversity-stability debate--is the subject of this review, which synthesizes historical ideas with recent advances. Both theory and empirical evidence agree that we should expect declines in diversity to accelerate the simplification of ecological communities.

Suicide within 12 months of contact with mental health services: national clinical survey.

OBJECTIVE: To describe the clinical circumstances in which psychiatric patients commit suicide. DESIGN: National clinical survey. SETTING: England and Wales. SUBJECTS: A two year sample of people who had committed suicide, in particular those who had been in contact with mental health services in the 12 months before death. MAIN OUTCOME MEASURES: Proportion of suicides in people who had had recent contact with mental health services; proportion of suicides in inpatients; proportion of people committing suicide and timing of suicide within three months of hospital discharge; proportion receiving high priority under the care programme approach; proportion who were recently non-compliant and not attending. RESULTS: 10 040 suicides were notified to the study between April 1996 and March 1998, of whom 2370 (24%; 95% confidence interval 23% to 24%) had had contact with mental health services in the year before death. Data were obtained on 2177, a response rate of 92%. In general these subjects had broad social and clinical needs. Alcohol and drug misuse were common. 358 (16%; 15% to 18%) were psychiatric inpatients at the time of death, 21% (17% to 25%) of whom were under special observation. Difficulties in observing patients because of ward design and nursing shortages were both reported in around a quarter of inpatient suicides. 519 (24%; 22% to 26%) suicides occurred within three months of hospital discharge, the highest number occurring in the first week after discharge. 914 (43%; 40% to 44%) were in the highest priority category for community care. 488 (26% excluding people whose compliance was unknown; 24% to 28%) were non-compliant with drug treatment while 486 (28%; 26% to 30%) community patients had lost contact with services. Most people who committed suicide were thought to have been at no or low immediate risk at the final service contact. Mental health teams believed suicide could have been prevented in 423 (22%; 20% to 24%) cases. CONCLUSIONS: Several suicide prevention measures in mental health services are implied by these findings, including measures to improve compliance and prevent loss of contact with services. Inpatient facilities should remove structural difficulties in observing patients and fixtures that can be used in hanging. Prevention of suicide after discharge may require earlier follow up in the community. Better suicide prevention in psychiatric patients is likely to need measures to improve the safety of mental health services as a whole, rather than specific measures for people known to be at high risk.