A national education program for rapid genomics in pediatric acute care: Building workforce confidence, competence, and capability.

Purpose: To develop and evaluate a scalable national program to build confidence, competence and capability in the use of rapid genomic testing (rGT) in the acute pediatric setting.

Methods: We used theory-informed approaches to design a modular, adaptive program of blended learning aimed at diverse professional groups involved in acute pediatric care. The program comprised 4 online learning modules and an online workshop and was centered on case-based learning.

A systematic review of simulation studies which compare existing statistical methods to account for non-compliance in randomised controlled trials.

Introduction: Non-compliance is a common challenge for researchers and may reduce the power of an intention-to-treat analysis. Whilst a per protocol approach attempts to deal with this issue, it can result in biased estimates. Several methods to resolve this issue have been identified in previous reviews, but there is limited evidence supporting their use.

Incorporation of patient and public involvement in statistical methodology research: a survey assessing current practices and attitudes of researchers.

Background: Patient and public involvement (PPI) ensures that research is designed and conducted in a manner that is most beneficial to the individuals whom it will impact. It has an undisputed place in applied research and is required by many funding bodies. However, PPI in statistical methodology research is more challenging and work is needed to identify where and how patients and the public can meaningfully input in this area.

Using the kidney failure risk equation to predict end-stage kidney disease in CKD patients of South Asian ethnicity: an external validation study.

Background: The kidney failure risk equation (KFRE) predicts the 2- and 5-year risk of needing kidney replacement therapy (KRT) using four risk factors - age, sex, urine albumin-to-creatinine ratio (ACR) and creatinine-based estimated glomerular filtration rate (eGFR). Although the KFRE has been recalibrated in a UK cohort, this did not consider minority ethnic groups. Further validation of the KFRE in different ethnicities is a research priority.

Challenges and perspectives of palliative medicine: A webinar by the Paediatric Virology Study Group.

Palliative medicine focuses on the quality of life of patients with incurable conditions, who require the adequate relief of physical symptoms, adequate information to make decisions and spiritual wellbeing. Generalist palliative care is provided by family members, general practitioners, care home workers, community nurses and social care providers, as well as non-specialist hospital doctors and nurses. Patients with more complex, physical or psycho-social problems require the shared work of specialized doctors in palliative medicine, nurses, social workers and allied professionals.

Normative isometric plantarflexion strength values for professional level, male rugby union athletes.

Objectives: The primary aim was to establish normative values of isometric plantarflexor muscle strength in professional male rugby union players and compare forwards with backs. The secondary aims were to examine how individual playing position or age influences isometric plantarflexor strength.

Design: Cross-sectional.

Women in radiation (WiR)-a perspective for the strengthening of radiation protection.

Gender balance refers to the equitable treatment and access to opportunities for all genders. In order to achieve true gender balance, a variety of proactive approaches developed collaboratively, with insight from multiple perspectives, need to be implemented. With that purpose, the participation of women in professions related to radiation and radiation protection was prioritised and given high visibility by allocating a 'Women in Radiation' (WiR) Special Session at the 15th International Congress of the International Radiation Protection Association (IRPA), hosted by South Korea on 20 January 2021.

Cross-resistance of cisplatin selected cells to anti-microtubule agents: Role of general survival mechanisms.

Although the first line of therapy for epithelial ovarian cancer typically consists of taxane-platinum combination therapy, many patients develop a platinum-resistant tumor within a year. Several previous studies have looked at this cross-resistance between cisplatin and anti-microtubule drugs, but their findings have been somewhat conflicting. Here, we developed cisplatin-resistant cell lines that are resistant to low and high levels of cisplatin and explored the effects of three anti-microtubule drugs (paclitaxel, vincristine, and colchicine) on the parental and cisplatin-resistant cells.

Human papilloma virus (HPV) vaccination in childhood: challenges and perspectives.

Vaccination against human papilloma virus (HPV) in childhood is a significant step forward in the reduction of HPV associated morbidity and mortality and a considerable scientific achievement. However, many challenges remain to be overcome if an effective HPV vaccine programme is to be successfully introduced worldwide. The aim of this review is to identify and summarize the new issues concerning HPV vaccination that have emerged since its introduction into clinical practice in school-aged girls.

The truncated phage lysin CHAP(k) eliminates Staphylococcus aureus in the nares of mice.

The endolysin LysK derived from staphylococcal phage K has previously been shown to have two enzymatic domains, one of which is an N-acetylmuramoyl-L-alanine amidase and the other a cysteine/histidine-dependant amidohydrolase/peptidase designated CHAP(k). The latter, when cloned as a single-domain truncated enzyme, is conveniently overexpressed in a highly-soluble form. This enzyme was shown to be highly active in vitro against live cell suspensions of S.

Cloning and expression of a mureinolytic enzyme from the mycobacteriophage TM4.

In this study, we describe the characterization, cloning, expression and purification of the lysin A gene of the mycobacteriophage TM4. The gene TM4_gp29 (gp29) is a 1644-bp gene that codes for a 58.6-kDa protein and contains peptidoglycan recognition protein, Zn-binding and amidase catalytic domains.

A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation.

Microglial cell activity increases in the rat hippocampus during normal brain aging. The neural cell adhesion molecule (NCAM)-derived mimetic peptide, FG loop (FGL), acts as an anti-inflammatory agent in the hippocampus of the aged rat, promoting CD200 ligand expression while attenuating glial cell activation and subsequent pro-inflammatory cytokine production. The aim of the current study was to determine if FGL corrects the age-related imbalance in hippocampal levels of insulin-like growth factor-1 (IGF-1) and pro-inflammatory interferon-gamma (IFNgamma), and subsequently attenuates the glial reactivity associated with aging.

Rare case of "red man" syndrome in a female patient treated with oral vancomycin for Clostridium difficile diarrhoea.

A 58-year-old Caucasian woman was admitted for knee replacement but during the postoperative period she developed sepsis due to pneumonia, which was treated with coamoxiclav and then piperacillin (for 2 weeks). She had renal failure, which needed haemofiltration. During her recovery she had diarrhoea due to Clostridium difficile, which was not controlled with metronidazole.

Interaction between interferon gamma and insulin-like growth factor-1 in hippocampus impacts on the ability of rats to sustain long-term potentiation.

There is compelling evidence to suggest that inflammation significantly contributes to neurodegenerative changes. Consistent with this is the observation that several neurodegenerative disorders are accompanied by an increase in the concentration of interleukin (IL)-1beta. IL-1beta has a negative impact on synaptic plasticity and therefore an increased concentration of IL-1beta, such as that in the hippocampus of the aged rat, is associated with a deficit in long-term potentiation (LTP).

Downregulation of IL-4-induced signalling in hippocampus contributes to deficits in LTP in the aged rat.

Ageing is characterized by deficits in learning and memory and by a deficit in long-term potentiation (LTP) in hippocampus. Several age-related changes, including dysfunction of calcium homeostatic mechanisms and upregulation of inflammatory processes are likely to contribute to these deficits. Here we exploited the fact that aged rats fall into a subgroup which fail to sustain LTP in perforant path granule cell synapses as a result of tetanic stimulation, and a subgroup which sustains LTP in a manner indistinguishable from young rats, in an effort to identify differential changes in the two subgroups.

Role of interleukin-4 in regulation of age-related inflammatory changes in the hippocampus.

It is well documented that long term potentiation (LTP) is impaired in the hippocampus of the aged animal. Among the changes that contribute to this impairment is an increase in hippocampal concentration of the pro-inflammatory cytokine interleukin-1beta (IL-1beta), and increased IL-1beta-induced signaling. In this study we investigated the possibility that these changes were a consequence of decreased concentration of the anti-inflammatory cytokine, IL-4, and decreased IL-4-stimulated signaling.

BDNF-induced LTP in dentate gyrus is impaired with age: analysis of changes in cell signaling events.

Brain-derived neurotrophic factor (BDNF) has emerged as a major regulator of synaptic plasticity in the adult brain and acute BDNF infusion has been shown to trigger long-term potentiation (BDNF-LTP) in adult rats. Here we compared the effects of acute BDNF infusion in young adult and aged anesthetized rats. In young rats, BDNF-LTP was accompanied by increased activation of the BDNF receptor TrkB, and extracellular signal-regulated kinase (ERK), as well as enhanced evoked release of glutamate in synaptosomes prepared from DG.

Increased IL-1beta in cortex of aged rats is accompanied by downregulation of ERK and PI-3 kinase.

Ageing is accompanied by a myriad of changes, which lead to deficits in synaptic function and recent studies have identified an increase in concentration of the proinflammatory cytokine, interleukin-1beta (IL-1beta), as a factor which significantly contributes to deterioration of cell function. Here, we consider that increased IL-1beta concentration and upregulation of IL-1beta-induced cell signalling cascades may be accompanied by downregulation of survival signals, perhaps as a consequence of decreased neurotrophins-associated signalling. The data indicate that increased IL-1beta concentration was coupled with downregulation of ERK and phosphoinositide-3 kinase (PI-3 kinase) in cortical tissue prepared from aged rats.

Diverse fibrillar peptides directly bind the Alzheimer's amyloid precursor protein and amyloid precursor-like protein 2 resulting in cellular accumulation.

The Alzheimer's disease Abeta peptide can increase the levels of cell-associated amyloid precursor protein (APP) in vitro. To determine the specificity of this response for Abeta and whether it is related to cytotoxicity, we tested a diverse range of fibrillar peptides including amyloid-beta (Abeta), the fibrillar prion peptides PrP106-126 and PrP178-193 and human islet-cell amylin. All these peptides increased the levels of APP and amyloid precursor-like protein 2 (APLP2) in primary cultures of astrocytes and neurons.

Involvement of the 5-lipoxygenase pathway in the neurotoxicity of the prion peptide PrP106-126.

Transmissible spongiform encephalopathies are characterised by the transformation of the normal cellular prion protein (PrP(C)) into an abnormal isoform (PrP(TSE)). Previous studies have shown that N-methyl-D-aspartate (NMDA) receptor antagonists can inhibit glutathione depletion and neurotoxicity induced by PrP(TSE) and a toxic prion protein peptide, PrP106-126, in vitro. NMDA receptor activation is known to increase intracellular accumulation of Ca(2+), resulting in up-regulation of arachidonic acid (AA) metabolism.

Presenilin 2 expression in neuronal cells: induction during differentiation of embryonic carcinoma cells.

Mutations in the presenilin 1 and 2 (PS1 and PS2) genes cause most cases of early onset Alzheimer's disease. The genes encode two homologous multipass membrane proteins. Since the endogenous expression of PS2 has been poorly analyzed to date, we studied PS2 expression and localization in cultured human neuroblastoma cells and mouse neuronal cells.

Cerebral glucose utilization and glucose transporter expression: response to water deprivation and restoration.

The relationship between local rates of cerebral glucose utilization (ICMRglc) and glucose transporter expression was examined during physiologic activation of the hypothalamoneurohypophysial system. Three days of water deprivation, which is known to activate the hypothalamoneurohypophysial system, resulted in increased ICMRglc and increased concentrations of GLUT1 and GLUT3 in the neurohypophysis; mRNA levels of GLUT1 and GLUT3 were decreased and increased, respectively. Water deprivation also increased ICMRglc in the hypothalamic supraoptic and paraventricular nuclei; mRNA levels of GLUT1 and GLUT3 appeared to increase in these nuclei, but the changes did not achieve statistical significance.

Prion protein-deficient neurons reveal lower glutathione reductase activity and increased susceptibility to hydrogen peroxide toxicity.

The prion protein (PrP) has a central role in the pathogenesis of transmissible spongiform encephalopathies (TSE). Accumulating evidence suggests that normal cellular PrP (PrP(c)) may be involved in copper homeostasis and modulation of copper/zinc superoxide dismutase (Cu/ZnSOD) activity in neurons. Hydrogen peroxide (H(2)O(2)) is a toxic reactive oxygen species generated through normal cellular respiration, and neurons contain two important peroxide detoxifying systems (glutathione pathway and catalase).

The Alzheimer's disease amyloid precursor protein modulates copper-induced toxicity and oxidative stress in primary neuronal cultures.

The amyloid precursor protein (APP) of Alzheimer's disease can reduce copper (II) to copper (I) in a cell-free system potentially leading to increased oxidative stress in neurons. We used neuronal cultures derived from APP knock-out (APP(-/-)) and wild-type (WT) mice to examine the role of APP in copper neurotoxicity. WT cortical, cerebellar, and hippocampal neurons were significantly more susceptible than their respective APP(-/-) neurons to toxicity induced by physiological concentrations of copper but not by zinc or iron.

Non-Abeta component of Alzheimer's disease amyloid (NAC) revisited. NAC and alpha-synuclein are not associated with Abeta amyloid.

alpha-Synuclein (alphaSN), also termed the precursor of the non-Abeta component of Alzheimer's disease (AD) amyloid (NACP), is a major component of Lewy bodies and Lewy neurites pathognomonic of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). A fragment of alphaSN termed the non-Abeta component of AD amyloid (NAC) had previously been identified as a constituent of AD amyloid plaques. To clarify the relationship of NAC and alphaSN with Abeta plaques, antibodies were raised to three domains of alphaSN.