Excitability of Rat Superficial Dorsal Horn Neurons Following a Neonatal Immune Challenge.

Previous studies have shown that neonatal exposure to a mild inflammatory challenge, such as lipopolysaccharide (LPS, ) results in altered pain behaviors later in life. To further characterize the impact of a neonatal immune challenge on pain processing, we examined the excitability of superficial dorsal horn (SDH) neurons following neonatal LPS exposure and subsequent responses to noxious stimulation at three time-points during early postnatal development. Wistar rats were injected with LPS (0.

Maternal immune activation in mid-late gestation alters amphetamine sensitivity and object recognition, but not other schizophrenia-related behaviours in adult rats.

Maternal immune activation induced by Poly(I:C) administration is one of the most commonly used animal models of schizophrenia at present. Previous work from our team has demonstrated that some, but not all of the features often reported for maternal immune activation exposure in rodents can be observed in rats exposed to maternal immune activation at mid or late gestation. To determine whether previous findings in our laboratory were due to these time points simply being less sensitive neurodevelopmental periods for rats with regard to maternal immune activation effects, we aimed to investigate whether maternal immune activation at an often-reported sensitive period (mid-late gestation, day 14) resulted in more behavioural features reflective of face validity for schizophrenia.

Modelling multi-scale cell-tissue interaction of tissue-engineered muscle constructs.

Expectation on engineered tissue substitute continues to grow, and for an effective development of a functional tissue and to control its quality, cellular mechanoresponse plays a key role. Although the mechanoresponse - in terms of cell-tissue interaction across scales - has been understood better in recent years, there are still technical limitations to quantitatively monitor the processes involved in the development of both native and engineered tissues. Computational (in silico) studies have been utilised to complement the experimental limitations and successfully applied to the prediction of tissue growth.

The identification of carbon dioxide mediated protein post-translational modifications.

Carbon dioxide is vital to the chemistry of life processes including metabolism, cellular homoeostasis, and pathogenesis. CO is generally unreactive but can combine with neutral amines to form carbamates on proteins under physiological conditions. The most widely known examples of this are CO regulation of ribulose 1,5-bisphosphate carboxylase/oxygenase and haemoglobin.

Measuring the Impact of an Adolescent and Young Adult Program on Addressing Patient Care Needs.

Purpose: We aimed to evaluate the effectiveness of an adult-based adolescent and young adult (AYA) cancer program by assessing patient satisfaction and whether programming offers added incremental benefit beyond primary oncology providers (POP) to address their needs.

Methods: A modified validated survey was used to ask two questions: (1) rate on a 10-point Likert scale their level of satisfaction with the information provided to them by their POP and (2) did the AYA consult provide added value on top of their POP. Young people at PM were recruited over two separate time points spaced 1 year apart.

The Children's Oncology Group Radiation Oncology Discipline: 15 Years of Contributions to the Treatment of Childhood Cancer.

Purpose: Our aim was to review the advances in radiation therapy for the management of pediatric cancers made by the Children's Oncology Group (COG) radiation oncology discipline since its inception in 2000.

Methods And Materials: The various radiation oncology disease site leaders reviewed the contributions and advances in pediatric oncology made through the work of the COG. They have presented outcomes of relevant studies and summarized current treatment policies developed by consensus from experts in the field.

Inbreeding intensifies sex- and age-dependent disease in a wild mammal.

The mutation accumulation theory of senescence predicts that age-related deterioration of fitness can be exaggerated when inbreeding causes homozygosity for deleterious alleles. A vital component of fitness, in natural populations, is the incidence and progression of disease. Evidence is growing for natural links between inbreeding and ageing; between inbreeding and disease; between sex and ageing; and between sex and disease.

Implementing new care models: learning from the Greater Manchester demonstrator pilot experience.

Background: Current health policy focuses on improving accessibility, increasing integration and shifting resources from hospitals to community and primary care. Initiatives aimed at achieving these policy aims have supported the implementation of various 'new models of care', including general practice offering 'additional availability' appointments during evenings and at weekends. In Greater Manchester, six 'demonstrator sites' were funded: four sites delivered additional availability appointments, other services included case management and rapid response.

Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial.

Background: Patients with metastatic castration-resistant prostate cancer and homologous recombination repair (HRR) mutations have a better response to treatment with the poly(ADP-ribose) polymerase inhibitor olaparib than patients without HRR mutations. Preclinical data suggest synergy between olaparib and androgen pathway inhibitors. We aimed to assess the efficacy of olaparib plus the androgen pathway inhibitor abiraterone in patients with metastatic castration-resistant prostate cancer regardless of HRR mutation status.

Risk, Risk Factors, and Surveillance of Subsequent Malignant Neoplasms in Survivors of Childhood Cancer: A Review.

Subsequent malignant neoplasms (SMNs) in childhood cancer survivors cause substantial morbidity and mortality. This review summarizes recent literature on SMN epidemiology, risk factors, surveillance, and interventions. Survivors of childhood cancer experience long-term increased SMN risk compared with the general population, with a greater than twofold increased solid tumor risk extending beyond age 40 years.

Prior Precision, Prior Accuracy, and the Estimation of Disease Prevalence Using Imperfect Diagnostic Tests.

Estimates of disease prevalence in any host population are complicated by uncertainty in the outcome of diagnostic tests on individuals. In the absence of gold standard diagnostics (tests that give neither false positives nor false negatives), Bayesian latent class inference can be applied to batteries of diagnostic tests, providing posterior estimates of the sensitivity and specificity of each test, alongside posterior estimates of disease prevalence. Here we explore the influence of precision and accuracy of prior information on the precision and accuracy of posterior estimates of these key parameters.

Late gestation immune activation increases IBA1-positive immunoreactivity levels in the corpus callosum of adult rat offspring.

Animal models of maternal immune activation study the effects of infection, an environmental risk factor for schizophrenia, on brain development. Microglia activation and cytokine upregulation may have key roles in schizophrenia neuropathology. We hypothesised that maternal immune activation induces changes in microglia and cytokines in the brains of the adult offspring.

A brief introduction to mixed effects modelling and multi-model inference in ecology.

The use of linear mixed effects models (LMMs) is increasingly common in the analysis of biological data. Whilst LMMs offer a flexible approach to modelling a broad range of data types, ecological data are often complex and require complex model structures, and the fitting and interpretation of such models is not always straightforward. The ability to achieve robust biological inference requires that practitioners know how and when to apply these tools.

Translational control plays an important role in the adaptive heat-shock response of Streptomyces coelicolor.

Stress-induced adaptations require multiple levels of regulation in all organisms to repair cellular damage. In the present study we evaluated the genome-wide transcriptional and translational changes following heat stress exposure in the soil-dwelling model actinomycete bacterium, Streptomyces coelicolor. The combined analysis revealed an unprecedented level of translational control of gene expression, deduced through polysome profiling, in addition to transcriptional changes.

Alkene protection against acid using a bromide substituent: application in a total synthesis of (-)-6,7-dideoxysqualestatin H5.

The presence of a bromide substituent, instead of a hydrogen or methyl group, on a carbon-carbon double bond, protects the alkene from addition reactions when exposed to trifluoroacetic acid. This concept is used to circumvent concomitant loss of unsaturation in a late-stage acid-catalysed 6,8- to 2,8-dioxabicyclo[3.2.

The Role of Radiation Therapy in Patients With Relapsed or Refractory Hodgkin Lymphoma: Guidelines From the International Lymphoma Radiation Oncology Group.

Relapsed and refractory Hodgkin lymphoma (HL) challenges clinicians to devise treatment strategies that are effective and safe. This problem is particularly prominent in an era when de-escalation trials are designed to minimize therapeutic toxicities in both early- and advanced-stage disease. Radiation therapy is the single most effective treatment modality for HL, and its integration into salvage regimens, or its independent use in select patients, must be understood to maximize our success in treating these patients.

The effects of different durations of static stretching within a comprehensive warm-up on voluntary and evoked contractile properties.

Evidence for performance decrements following prolonged static stretching (SS) has led to a paradigm shift in stretching routines within a warm-up. Rather than SS, dynamic stretching (DS) and dynamic activity (DA) have replaced SS within warm-up routines. The objective of the present study was to compare the effect of differing lower limb SS durations (30 [SS30s], 60 [SS60s] or 120 s [SS120s] of SS per muscle group or no-stretch control) within a comprehensive warm-up protocol consisting of aerobic activity, DS and DA.

Early-stage Hodgkin lymphoma in the modern era: simulation modelling to delineate long-term patient outcomes.

We developed a novel simulation model integrating multiple data sets to project long-term outcomes with contemporary therapy for early-stage Hodgkin lymphoma (ESHL), namely combined modality therapy (CMT) versus chemotherapy alone (CA) via F-fluorodeoxyglucose positron emission tomography response-adaption. The model incorporated 3-year progression-free survival (PFS), probability of cure with/without relapse, frequency of severe late effects (LEs), and 35-year probability of LEs. Furthermore, we generated estimates for quality-adjusted life years (QALYs) and unadjusted survival (life years, LY) and used model projections to compare outcomes for CMTversusCA for two index patients.

Design, rationale and feasibility of a multidimensional experimental protocol to study early life stress.

There is a rapidly accumulating body of evidence regarding the influential role of early life stress (ELS) upon medical and psychiatric conditions. While self-report instruments, with their intrinsic limitations of recall, remain the primary means of detecting ELS in humans, biological measures are generally limited to a single biological system. This paper describes the design, rationale and feasibility of a study to simultaneously measure neuroendocrine, immune and autonomic nervous system (ANS) responses to psychological and physiological stressors in relation to ELS.

GPs' views of health policy changes: a qualitative 'netnography' study of UK general practice online magazine commentary.

Background: Shifts in health policy since 2010 have brought major structural changes to the English NHS, with government stating intentions to increase GPs' autonomy and improve access to care. Meanwhile, GPs' levels of job satisfaction are low, while stress levels are high. is a popular UK general practice online magazine that provides a key discussion forum on news relevant to general practice.

Cybersickness-related changes in brain hemodynamics: A pilot study comparing transcranial Doppler and near-infrared spectroscopy assessments during a virtual ride on a roller coaster.

Our aim was to assess cerebral blood flow changes during cybersickness. Transcranial Doppler (TCD) ultrasound and near infrared spectroscopy (NIRS) were used separately in two independent experiments. In both studies, a 15-min virtual roller coaster ride was used as a provocative visual stimulus.

On the ozonolysis of unsaturated tosylhydrazones as a direct approach to diazocarbonyl compounds.

The scope and limitations are described of reacting unsaturated tosylhydrazones with O3 followed by Et3N for the generation of 1,4- and 1,5-diazocarbonyl systems. Tosylhydrazones, from tosylhydrazide condensation with readily available δ- and ε-unsaturated α-ketoesters, led in the former case to a 2-pyrazoline whereas the latter cases led to α-diazo-ε-ketoesters, although a terminal alkene produced a tetrahydropyridazinol. Using the ozonolysis-Et3N strategy, tosylhydrazones from cyclic enones give 2,5- and 2,6-diazoketones with aldehyde or ester functionality at the 1-position; the α-diazoaldehydes prefer the s-trans conformation, with a rotation barrier of 74 kJ mol-1 at 25 °C determined by NMR.