Thigmotaxis Mediates Trail Odour Disruption.

Disruption of foraging using oversupply of ant trail pheromones is a novel pest management application under investigation. It presents an opportunity to investigate the interaction of sensory modalities by removal of one of the modes. Superficially similar to sex pheromone-based mating disruption in moths, ant trail pheromone disruption lacks an equivalent mechanistic understanding of how the ants respond to an oversupply of their trail pheromone.

Case Report: Immune-mediated Complete Response in a Patient With Recurrent Advanced Ewing Sarcoma (EWS) After Vigil Immunotherapy.

Ewing sarcoma is a highly resistant disease with a <10% chance of survival at 5 years after failure of frontline chemotherapy. This is a case report of an Ewing sarcoma patient with metastatic disease recurrence <2 years after standard chemotherapy/radiation who achieved a durable and sustained complete response after 2 series of treatments with Vigil (GMCSF/bi-shRNA furin DNA autologous tumor immunotherapy) serially manufactured from first and second recurrences with ELISPOT assay correlation. Results support justification of further testing of Vigil with ELISPOT assay as a biomarker to assess level of immune response and correlation with disease control.

Continuing or Temporarily Stopping Prestroke Antihypertensive Medication in Acute Stroke: An Individual Patient Data Meta-Analysis.

Over 50% of patients are already taking blood pressure-lowering therapy on hospital admission for acute stroke. An individual patient data meta-analysis from randomized controlled trials was undertaken to determine the effect of continuation versus temporarily stopping preexisting antihypertensive medication in acute stroke. Key databases were searched for trials against the following inclusion criteria: randomized design; stroke onset ≤48 hours; investigating the effect of continuation versus stopping prestroke antihypertensive medication; and follow-up of ≥2 weeks.

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial.

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes.

Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m, or at least 27 kg/m with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity.

Wearable Cameras Are Useful Tools to Investigate and Remediate Autobiographical Memory Impairment: A Systematic PRISMA Review.

Autobiographical memory, central in human cognition and every day functioning, enables past experienced events to be remembered. A variety of disorders affecting autobiographical memory are characterized by the difficulty of retrieving specific detailed memories of past personal events. Owing to the impact of autobiographical memory impairment on patients' daily life, it is necessary to better understand these deficits and develop relevant methods to improve autobiographical memory.

Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia.

Behaviour of Arctic charr Salvelinus alpinus during an induced mating season in captivity: how male relative size influences male behavioural investment and female preference over time.

The behaviour of sexually mature Arctic charr Salvelinus alpinus specimens (fifth farm generation) was observed in captivity for four consecutive days. Only agonistic interactions between males of different size were facilitated on the first 2 days, while both agonistic and courtship interactions were possible from the third day up to the end of the experiment. The reliability of behavioural analysis was assessed in order to reduce the possibility of observer errors within the generated datasets.

Gel filtration of dilute human embryonic hemoglobins reveals basis for their increased oxygen binding.

This report establishes a correlation between two known properties of the human embryonic hemoglobins-- their weak subunit assemblies as demonstrated here by gel filtration at very dilute protein concentrations and their high oxygen affinities and reduced cooperativities reported previously by others but without a mechanistic basis. We demonstrate here that their high oxygen affinities are a consequence of their weak assemblies. Weak vs strong hemoglobin tetramers represent a regulatory mechanism to modulate oxygen binding capacity by altering the equilibrium between the various steps in the assembly process that can be described as an inverse allosteric effect.

Immunofluorescent antibody staining of intact Drosophila larvae.

Antibody staining is a vital technique for studying the development of many model organisms, including Drosophila. Reliable protocols have long been available for antibody staining of Drosophila whole-mount embryos and dissected larvae. By contrast, methods for staining whole larvae have rarely been reported, are unreliable, and fail to work on large third-instar larvae.

Discoidin Domain Receptor 2 as a Potential Therapeutic Target for Development of Disease-Modifying Osteoarthritis Drugs.

Osteoarthritis (OA) is the most common form of arthritis disorders, but the identification of therapeutic targets to effectively prevent OA has been increasingly difficult. The goal of this investigation is to provide experimental evidence that discoidin domain receptor 2 (DDR2) may be an ideal target for the development of disease-modifying OA drugs. Ddr2 was conditionally deleted from articular cartilage of adult mouse knee joints.

Balancing satisfaction and stress: carer burden among White and British Asian Indian carers of stroke survivors.

Objectives: This paper presents the findings of a qualitative study exploring White and British Indian informal stroke carers' experiences of caring, factors contributing to their stress, and strategies used to overcome stress.

Design: A qualitative approach involving in-depth interviews was used to explore informal carers' experiences of caring for stroke survivors and the stress of caring at one and three to six months from the onset of stroke. Interviewers bilingual in English and Gujarati or Punjabi conducted interviews with carers.

Benefits from an autobiographical memory facilitation programme in relapsing-remitting multiple sclerosis patients: a clinical and neuroimaging study.

While the efficacy of mental visual imagery (MVI) to alleviate autobiographical memory (AM) impairment in multiple sclerosis (MS) patients has been documented, nothing is known about the brain changes sustaining that improvement. To explore this issue, 20 relapsing-remitting MS patients showing AM impairment were randomly assigned to two groups, experimental (n = 10), who underwent the MVI programme, and control (n = 10), who followed a sham verbal programme. Besides the stringent AM assessment, the patients underwent structural and functional MRI sessions, consisting in retrieving personal memories, within a pre-/post-facilitation study design.

Phase II study of Vigil® DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer.

Objectives: The majority of women with Stage III/IV ovarian cancer who achieve clinical complete response with frontline standard of care will relapse within 2years. Vigil immunotherapy, a GMCSF/bi-shRNA furin DNA engineered autologous tumor cell (EATC) product, demonstrated safety and induction of circulating activated T-cells against autologous tumor in Phase I trial Senzer et al. (2012, 2013) .

Giving meaning to illness: An investigation of self-defining memories in patients with relapsing-remitting multiple sclerosis patients.

Multiple sclerosis (MS) patients are often unable to adequately fulfill their established roles due to physical disabilities and cognitive changes, making this chronic illness particularly threatening to personal identity. Twenty-five MS patients and 25 healthy controls were asked to recall five self-defining memories (SDM). Overall characteristics of SDM did not differ between patients and controls; MS patients displayed preserved capacity to draw meaning upon past events.

Reference Ranges for Thyroid-Stimulating Hormone and Free Thyroxine in Older Men: Results From the Health In Men Study.

Background: In older adults, thyroid-stimulating hormone (TSH) concentrations are raised and higher free thyroxine (FT4) is associated with poorer health outcomes. As use of nonage-appropriate reference ranges could lead to suboptimal management, we aimed to define reference intervals for TSH and FT4 in older men.

Methods: We conducted the study on community-dwelling men aged 70-89 years.

The DEG/ENaC cation channel protein UNC-8 drives activity-dependent synapse removal in remodeling GABAergic neurons.

Genetic programming and neural activity drive synaptic remodeling in developing neural circuits, but the molecular components that link these pathways are poorly understood. Here we show that the C. elegans Degenerin/Epithelial Sodium Channel (DEG/ENaC) protein, UNC-8, is transcriptionally controlled to function as a trigger in an activity-dependent mechanism that removes synapses in remodeling GABAergic neurons.

Noninvasive hemoglobin measurement in pediatric trauma patients.

Introduction: Hemorrhage is a major cause of preventable death secondary to traumatic injury. Diagnosis often requires multiple blood draws, which are psychologically stressful in pediatric patients. The Pronto device is a pulse co-oximeter that measures the total hemoglobin level using multiple wavelengths of light.

Tigecycline use in the outpatient parenteral antibiotic therapy setting.

In the context of globally increasing antimicrobial resistance, tigecycline appears to be a useful therapeutic option. The need for prolonged courses for complex infections has prompted consideration of its use via outpatient parenteral antibiotic therapy (OPAT) programmes, although clinical outcomes when used in this setting remain unknown. We retrospectively reviewed the patient characteristics and outcomes of 11 patients who received tigecycline, most commonly delivered as 100 mg once daily, via OPAT at three tertiary Australian hospitals.

Validation and Application of a Dried Blood Spot Assay for Biofilm-Active Antibiotics Commonly Used for Treatment of Prosthetic Implant Infections.

Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK)/pharmacodynamic (PD) studies in situations where venous blood sampling is logistically difficult. We sought to develop, validate, and apply a DBS assay for rifampin (RIF), fusidic acid (FUS), and ciprofloxacin (CIP). These antibiotics are considered active against organisms in biofilms and are therefore commonly used for the treatment of infections associated with prosthetic implants.

An alternative allergen risk management approach.

Protein components in food can trigger immune-mediated response in susceptible individuals. International law requires risk assessment to be undertaken by competent individuals to minimize food safety risk to consumers. Historically, allergen control legislation has been food-focused and on the requirement for on pack labeling, and the need for formal food recalls in the event of misleading or inappropriate labeling.

Naphthoquine: An Emerging Candidate for Artemisinin Combination Therapy.

Naphthoquine is a 4-aminoquinoline antimalarial drug first synthesised in China in 1986 but which was not developed for clinical use until the late 1990s. Early in vitro parasite sensitivity and in vivo efficacy data, together with a long terminal elimination half-life (up to 23 days), suggested that it could be used as monotherapy for uncomplicated falciparum and vivax malaria, but is now marketed as a single-dose, fixed co-formulation with artemisinin in a milligram per kilogram ratio of 1:2.5.

Functional and structural cerebral changes in key brain regions after a facilitation programme for episodic future thought in relapsing-remitting multiple sclerosis patients.

Increasingly studied, episodic future thought (EFT) impairment negatively affects patients' daily life. Along these lines, working with relapsing-remitting multiple sclerosis (RR-MS) patients, we documented the clinical effectiveness of a mental visual imagery (MVI)-based facilitation programme on EFT impairment related to executive function difficulties. We aimed at improving the characterisation of the cognitive and neural underpinnings of RR-MS patients' EFT amelioration, by exploring the structural and functional brain changes following the MVI programme.

Food Safety, Food Fraud, and Food Defense: A Fast Evolving Literature.

Intentional food crime is plural in nature in terms of the types of crime and the differing levels of financial gain. Successful models of food crime are dependent on how well the crime has been executed and at what point, or even if, detection actually occurs. The aim of this paper is to undertake a literature review and critique the often contradictory definitions that can be found in the literature in order to compare and contrast existing food crime risk assessment tools and their application.

Use of quantitative pharmacology tools to improve malaria treatments.

The use of pharmacokinetic (PK) and pharmacodynamic (PD) data to inform antimalarial treatment regimens has accelerated in the past few decades, due in no small part to the stimulus provided by progressive development of parasite resistance to most of the currently available drugs. An understanding of the disposition, interactions, efficacy and toxicity of the mainstay of contemporary antimalarial treatment, artemisinin combination therapy (ACT), has been facilitated by PK/PD studies which have been used to refine treatment regimens across the spectrum of disease, especially in special groups including young children and pregnant women. The present review highlights recent clinically-important examples of the ways in which these quantitative pharmacology tools have been applied to improve ACT, as well as 8-aminoquinoline use and the characterisation of novel antimalarial therapies such as the spiroindolones.