Embryonic Lethality, Liver Degeneration, and Impaired NF-κB Activation in IKK-β-Deficient Mice

AbstractIκB kinase-α and -β (IKK-α and IKK-β), the catalytic subunits of the IKK complex, phosphorylate IκB proteins on specific serine residues, thus targeting IκB for degradation and activating the transcription factor NF-κB. To elucidate the in vivo function of IKK-β, we generated IKK-β-deficient mice. The homozygous mouse embryo dies at ∼14.5 days of gestation due to liver degeneration and apoptosis. IKK-β-deficient embryonic fibroblasts have both reduced basal NF-κB activity and impaired cytokine-induced NF-κB activation. Similarly, basal and cytokine-inducible kinase activities of the IKK complex are greatly reduced in IKK-β-deficient cells. These results indicate that IKK-β is crucial for liver development and regulation of NF-κB activity and that IKK-α can only partially compensate for the loss of IKK-β

Structures of paediatric pain management: A PERUKI service evaluation study

Background Pain is very common in childhood emergency department (ED) attendances, but is under-recognised and undertreated. Sequential national paediatric analgesia audits demonstrate suboptimal outcomes in several domains. The Donabedian framework examines the structures, processes and outcomes to evaluate quality of care. To date there has been no network-level exploration of structures supporting analgesic practices or attempts to address failure to attain national standards. Objective To benchmark current variation in assessment and management of childhood pain at network level. Methods Online survey distributed between December 2016 and January 2017 exploring health system structures including pain score tools, pain assessment/protocols, training, practice guidelines and analgesic agent usage. We explored structures, processes and outcomes to identify interventions, and their potential effectiveness and feasibility. Results In total 95% (38/40 sites) responded, including 25 tertiary (66%) and 13 secondary hospitals (34%), with a total annual paediatric ED census of 1 225 000 (range 11 500-65 000). Availability of analgesics varied included topical wound anaesthesia in 29/38 sites (76%), oral diclofenac sodium in 22/38 sites (58%) and tramadol in 16/38 sites (42%). Pain assessment was mandatory in initial assessment in 34/38 sites (89%), and 18/38 sites had a policy on frequency of pain assessment (47%). Local guidance aligned with national guidance in 21/38 sites (55%). There was no staff training at induction/orientation in 14/38 sites (37%) and no mandatory competencies in pain management in 23/38 sites (61%). Play specialist services were available in 21/38 sites (55%). Conclusion Despite national guidance and recommendations from multiple audits, there are substantial variations in structures relating to pain assessment and management across sites. The lack of uniformity is a likely root cause for the persistent suboptimal practices identified by serial national audits. A whole system and person-centred approach to improving pain outcomes by utilising effective interventions seeks to improve paediatric pain outcomes

A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans

BACKGROUND: High fructose consumption is suspected to be causally linked to the epidemics of obesity and metabolic disorders. In rodents, fructose leads to insulin resistance and ectopic lipid deposition. In humans, the effects of fructose on insulin sensitivity remain debated, whereas its effect on ectopic lipids has never been investigated. OBJECTIVE: We assessed the effect of moderate fructose supplementation on insulin sensitivity (IS) and ectopic lipids in healthy male volunteers (n = 7). DESIGN: IS, intrahepatocellular lipids (IHCL), and intramyocellular lipids (IMCL) were measured before and after 1 and 4 wk of a high-fructose diet containing 1.5 g fructose . kg body wt(-1) . d(-1). Adipose tissue IS was evaluated from nonesterified fatty acid suppression, hepatic IS from suppression of hepatic glucose output (6,6-2H2-glucose), and muscle IS from the whole-body glucose disposal rate during a 2-step hyperinsulinemic euglycemic clamp. IHCL and IMCL were measured by 1H magnetic resonance spectroscopy. RESULTS: Fructose caused significant (P < 0.05) increases in fasting plasma concentrations of triacylglycerol (36%), VLDL-triacylglycerol (72%), lactate (49%), glucose (5.5%), and leptin (48%) without any significant changes in body weight, IHCL, IMCL, or IS. IHCL were negatively correlated with triacylglycerol after 4 wk of the high-fructose diet (r = -0.78, P < 0.05). CONCLUSION: Moderate fructose supplementation over 4 wk increases plasma triacylglycerol and glucose concentrations without causing ectopic lipid deposition or insulin resistance in healthy humans

The effect of arm training on thermoregulatory responses and calf volume during upper body exercise

The final publication is available at Springer via https://doi.org/10.1007/s00421-014-2842-9.PURPOSE: The smaller muscle mass of the upper body compared to the lower body may elicit a smaller thermoregulatory stimulus during exercise and thus produce novel training-induced thermoregulatory adaptations. Therefore, the principal aim of the study was to examine the effect of arm training on thermoregulatory responses during submaximal exercise. METHODS: Thirteen healthy male participants (Mean ± SD age 27.8 ± 5.0 years, body mass 74.8 ± 9.5 kg) took part in 8 weeks of arm crank ergometry training. Thermoregulatory and calf blood flow responses were measured during 30 min of arm cranking at 60% peak power (W peak) pre-, and post-training and post-training at the same absolute intensity as pre-training. Core temperature and skin temperatures were measured, along with heat flow at the calf, thigh, upper arm and chest. Calf blood flow using venous occlusion plethysmography was performed pre- and post-exercise and calf volume was determined during exercise. RESULTS: The upper body training reduced aural temperature (0.1 ± 0.3 °C) and heat storage (0.3 ± 0.2 J g(-1)) at a given power output as a result of increased whole body sweating and heat flow. Arm crank training produced a smaller change in calf volume post-training at the same absolute exercise intensity (-1.2 ± 0.8% compared to -2.2 ± 0.9% pre-training; P < 0.05) suggesting reduced leg vasoconstriction. CONCLUSION: Training improved the main markers of aerobic fitness. However, the results of this study suggest arm crank training additionally elicits physiological responses specific to the lower body which may aid thermoregulation.Peer reviewedFinal Accepted Versio

Presentations of children to emergency departments across Europe and the COVID-19 pandemic: A multinational observational study

During the initial phase of the Coronavirus Disease 2019 (COVID-19) pandemic, reduced numbers of acutely ill or injured children presented to emergency departments (EDs). Concerns were raised about the potential for delayed and more severe presentations and an increase in diagnoses such as diabetic ketoacidosis and mental health issues. This multinational observational study aimed to study the number of children presenting to EDs across Europe during the early COVID-19 pandemic and factors influencing this and to investigate changes in severity of illness and diagnoses. Routine health data were extracted retrospectively from electronic patient records of children aged 18 years and under, presenting to 38 EDs in 16 European countries for the period January 2018 to May 2020, using predefined and standardized data domains. Observed and predicted numbers of ED attendances were calculated for the period February 2020 to May 2020. Poisson models and incidence rate ratios (IRRs), using predicted counts for each site as offset to adjust for case-mix differences, were used to compare age groups, diagnoses, and outcomes. Reductions in pediatric ED attendances, hospital admissions, and high triage urgencies were seen in all participating sites. ED attendances were relatively higher in countries with lower SARS-CoV-2 prevalence (IRR 2·26, 95% CI 1·90 to 2·70, p < 0.001) and in children aged <12 months (12 to <24 months IRR 0·86, 95% CI 0·84 to 0·89; 2 to <5 years IRR 0·80, 95% CI 0·78 to 0·82; 5 to <12 years IRR 0·68, 95% CI 0·67 to 0·70; 12 to 18 years IRR 0·72, 95% CI 0·70 to 0·74; versus age <12 months as reference group, p < 0.001). The lowering of pediatric intensive care admissions was not as great as that of general admissions (IRR 1·30, 95% CI 1·16 to 1·45, p < 0.001). Lower triage urgencies were reduced more than higher triage urgencies (urgent triage IRR 1·10, 95% CI 1·08 to 1·12; emergent and very urgent triage IRR 1·53, 95% CI 1·49 to 1·57; versus nonurgent triage category, p < 0.001). Reductions were highest and sustained throughout the study period for children with communicable infectious diseases. The main limitation was the retrospective nature of the study, using routine clinical data from a wide range of European hospitals and health systems. Reductions in ED attendances were seen across Europe during the first COVID-19 lockdown period. More severely ill children continued to attend hospital more frequently compared to those with minor injuries and illnesses, although absolute numbers fell. ISRCTN91495258 https://www.isrctn.com/ISRCTN91495258

Pain management in children and young adults with minor injury in emergency departments in the UK and Ireland: A PERUKI service evaluation

Background Management of acute pain should commence at the earliest opportunity, as it has many short-term and long-term consequences. A research priority of Paediatric Emergency Research in the UK and Ireland (PERUKI) was to examine paediatric pain practices.Objective To describe the outcomes for paediatric pain management of minor injuries presenting to emergency departments (EDs) across PERUKI.Methods A retrospective service evaluation was performed over a 7-day period in late 2016/early 2017 across PERUKI sites, and analysis performed using an adapted Donabedian framework. Patients under 16 years presenting with minor trauma were eligible, and data were collected on prehospital management, pain assessment, analgesia administered and injury diagnosed.Results Thirty-one sites submitted data on 3888 patients. There were 111 missed cases (missed rate 3.6%). The most common injuries were sprains, lacerations, contusions/abrasions and fractures. Documentation of receiving analgesia before arrival in ED occurred in 21% of patients (n=818). A pain assessment was documented in 57.5% of patients (n=2235) during their ED visit, and 3.5% of patients had their pain reassessed (n=138). Of the patients who presented in severe pain (pain score 7–10 or rated severe), 11% were reassessed. Site variability of initial pain assessment ranged from 1.4% to 100% (median 62%). The characteristics of the top quartile performing centres against the bottom quartile performing centres based on completion rate of initial pain scores were identified.Conclusion Pain assessment was documented in under 60% of children with minor injury, re-assessment of pain was almost completely absent, data and outcomes were missing in a substantial volume of patients, indicating that pain management and the associated outcomes have not been adequately addressed and prioritised within existing network structures and processes

Ketones in non-diabetic children with vomiting, diarrhoea or reduced intake: a prospective cohort study

Objective: To establish the relationship between serum point-of-care (POC) ketones at triage with clinical dehydration based on the validated Gorelick scales. Design, setting and patients: Prospective unblinded exploratory study fromApril 2016 to February 2017in a tertiary paediatric Emergency Department. Patients aged 1 month to 5 years, with vomiting and/or diarrhoea and/or decreased intake with signs of dehydration or clinical concern for hypoglycaemia were eligible. Main outcome measures: POC ketones were analysed at triage and 4-hours later or upon discharge if earlier.Secondary outcomes were to examine the response of ketone levels to fluid/glucose administration and patient disposition. Results:Two-hundred and one attendances were included(198 patients); median age 1.8years. The median triage ketones were 4.4 (interquartile range (IQR) 2.8–5.6) mmol/L. Aweak correlation was identified between triage ketones and 10-point Gorelick scale (Pearson r=0.215), however the 4-point Gorelick scale was non-significant. Those admitted to hospital had median triage ketones of 5.2 (IQR 5-6) mmol/L and repeat ketones of 4.6 (IQR 3.3-5.7) mmol/L compared to 4.2 (IQR 2.4–5.2) mmol/Land 2.9 (IQR 1.6–4.2) mmol/L in those discharged home. Conclusion: Elevated POC ketones were demonstrated in non-diabetic childrenwith acute illness. A weak correlation was demonstrated between triage POC ketones and the 10-point Gorelick scale, however,this was not demonstrated with the 4-point Gorelick scale. The use of POC ketones, at triage and at 4-hours,to predict the patient’s disposition had poor and fair accuracy respectively. Ketosis and the potential impact of tailored treatments in paediatric acute illness warrants further research.2020-07-08 JG: PDF has been replaced with correct versio

Evaluation of Factors Affecting Erodibility Improvement for MICP-Treated Beach Sand

Microbially induced calcite precipitation (MICP) was used to treat several sandboxes filled with naturally occurring beach sand collected from Atlantic Beach, Florida. A surface-spray/percolation technique was used to treat these sandboxes where a relatively high-concentration bacteria solution and high-concentration calcium chloride/urea solutions were applied directly to the boxes\u27 surfaces. Several different treatment combinations were tested whereby bacterial optical density, bacteria/urea/calcium chloride volume relative to pore volume, and bacteria/urea/calcium chloride ratio were manipulated. Treated sandboxes were tested for erodibility using a pocket erodometer. In addition, sandboxes were dissected after erosion testing to examine crust depth. Results showed that higher optical densities, higher bacteria quantities relative to void volume, and higher bacteria quantities relative to urea led to lower erodibility and greater crust depth. When MICP constituent quantities were maximized to give the best erosion/crust-depth results, erodibility improvements began to approach what may be considered adequate erosive resistance. Further investigation is required to better classify this behavior more quantitatively