Pediatric reference intervals for endocrine markers in healthy children and adolescents on the Liaison XL (DiaSorin) immunoassay system.

OBJECTIVES: Prominent physiological changes occurring throughout childhood and adolescence necessitate the consideration of age and sex in biomarker interpretation. Critical gaps exist in pediatric reference intervals (RIs) for specialized endocrine markers, despite expected influence of growth and development. The current study aimed to establish and/or verify RIs for six specialized endocrine markers on a specialized immunoassay system. METHODS: Samples were collected from healthy children and adolescents (5 to <19 years) and apparently healthy outpatients (0 to <5 years) as part of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER). Serum samples were analysed for aldosterone, renin (plasma), thyroglobulin, anti-thyroglobulin, growth hormone, and insulin-like growth factor-1 (IGF-1) on the Liaison XL (DiaSorin) immunoassay platform. RIs (2.5th and 97.5th percentiles) were established for aldosterone, renin, thyroglobulin, anti-thyroglobulin, and growth hormone. Manufacturer-recommended pediatric RIs for IGF-1 were verified. RESULTS: Age-specific RIs were established for aldosterone, renin, and thyroglobulin, while no age-specific differences were observed for anti-thyroglobulin or growth hormone. IGF-1 was the only endocrine marker studied that demonstrated significant sex-specific differences. Manufacturer-recommended IGF-1 RIs were verified for children aged 6 to <19 years, while those for children aged 0 to <6 years did not verify. CONCLUSIONS: This study marks the first time that pediatric RIs for aldosterone and renin were established in the CALIPER cohort and highlights the dynamic changes that occur in water and sodium homeostasis during the first years of life. Overall, these data will assist pediatric clinical laboratories in test result interpretation and improve clinical decision-making for patients tested using Liaison immunoassays.

Density estimates reveal that fragmented landscapes provide important habitat for conserving an endangered mesopredator, the spotted-tailed quoll.

Native predators are increasingly exposed to habitat loss and fragmentation globally. When developing conservation and management strategies, it is important to determine whether fragmented landscapes can still support similar predator densities to intact areas, and thereby constitute important habitat for these species. The spotted-tailed quoll (Dasyurus maculatus) is an endangered Australian mesopredator that is often considered to be forest-dependent. While quolls are known to occur in some fragmented forest landscapes, it is unclear whether these areas represent sub-optimal habitat where quolls merely persist, or whether quolls can still occur at densities similar to those observed in intact forest landscapes. We used camera traps to detect quolls in both a fragmented and intact forested site, over three years. We used each quoll's unique pelage pattern to identify individual quolls and estimate population density at each site. We were able to assign more than 94% of quoll image sequences across both sites to identify 173 individuals during the study. Density estimates of 0.13-0.66 quolls per km2 at the fragmented site were comparable to estimates of 0.28-0.48 quolls per km2 at the intact site. Our results highlight the importance of retaining and protecting forest fragments for the conservation of endangered quoll populations.

Physiological tremor is suppressed and force steadiness is enhanced with increased availability of serotonin regardless of muscle fatigue.

Although there is evidence that 5-HT acts as an excitatory neuromodulator to enhance maximal force generation, it is largely unknown how 5-HT activity influences the ability to sustain a constant force during steady-state contractions. A total of 22 healthy individuals participated in the study, where elbow flexion force was assessed during brief isometric contractions at 10% maximal voluntary contraction (MVC), 60% MVC, MVC, and during a sustained MVC. The selective serotonin reuptake inhibitor, paroxetine, suppressed physiological tremor and increased force steadiness when performing the isometric contractions. In particular, a main effect of drug was detected for peak power of force within the 8-12 Hz range (P = 0.004) and the coefficient of variation (CV) of force (P < 0.001). A second experiment was performed where intermittent isometric elbow flexions (20% MVC sustained for 2 min) were repeatedly performed so that serotonergic effects on physiological tremor and force steadiness could be assessed during the development of fatigue. Main effects of drug were once again detected for peak power of force in the 8-12 Hz range (P = 0.002) and CV of force (P = 0.003), where paroxetine suppressed physiological tremor and increased force steadiness when the elbow flexors were fatigued. The findings of this study suggest that enhanced availability of 5-HT in humans has a profound influence of maintaining constant force during steady-state contractions. The action of 5-HT appears to suppress fluctuations in force regardless of the fatigue state of the muscle.NEW & NOTEWORTHY Converging lines of research indicate that enhanced serotonin availability increases maximal force generation. However, it is largely unknown how serotonin influences the ability to sustain a constant force. We performed two experiments to assess physiological tremor and force steadiness in unfatigued and fatigued muscle when serotonin availability was enhanced in the central nervous system. Enhanced availability of serotonin reduced physiological tremor amplitude and improved steadiness regardless of muscle fatigue.

An evaluation of PlayStreets in the South Side neighborhood of Columbus, Ohio.

AIMS: Outdoor play, physical activity, and social cohesion are crucial indicators of community health. PlayStreets, a street play initiative to engage local children and families in outdoor play, physical activity, and social interactions, were implemented in a low-income neighborhood in Columbus, Ohio throughout the summer of 2019. This article aims to describe the implementation of a hospital-sponsored PlayStreets model executed through support from a community health initiative and to assess neighborhood impact through parent and child surveys. METHODS: Approximately 350 children attended the events and 69 surveys were collected. Descriptive statistics were used to analyze survey data. RESULTS: The mean age of children was 7 years, and the majority of children who attended were male. If not for PlayStreets, 55% of caregivers reported that their children would be inside. Event satisfaction levels were high, and 54% of caregivers said that they had more contact with their neighbors because of the events. CONCLUSIONS: Hospital buy-in and community support were crucial to the success of the event. We found that this model can successfully engage the local community while increasing opportunity for childhood outdoor play, physical activity, and neighborhood social interaction.

'They only smoke in the house when I'm not in': understanding the limited effectiveness of a smoke-free homes intervention.

BACKGROUND: Children's second-hand smoke (SHS) exposure in the home is highest in socio-economically disadvantaged areas. Personalized household air-quality measurements can promote changes in smoking that reduce SHS exposure. The 'First Steps 2 Smoke-free' (FS2SF) intervention is the first to trial this approach delivered as part of health professionals' routine work. This paper reports the findings of qualitative interviews with participants that explored their experiences of the intervention and why outcomes varied. METHODS: 120 women were recruited from the NHS First Steps Programme, which supports disadvantaged mothers. They received either personalized feedback on their home air quality and advice on reducing SHS or standard SHS advice. Qualitative interviews with 15 mothers were analyzed thematically using the Capability, Opportunity, Motivation, Behaviour (COM-B) model. RESULTS: The intervention increased women's capability to change home-smoking behaviour, through increasing awareness and salience of SHS risks to their children, and motivation to act. However, taking effective action was constrained by their limited social and environmental opportunities, including others' smoking in the home. CONCLUSIONS: The FS2SF intervention was ineffective as it was unable to fully address the precarious, complex life circumstances that make creating a smoke-free home particularly difficult for women experiencing intersecting dimensions of disadvantage.

Subcutaneous immunoglobulin in primary immunodeficiency - impact of training and infusion characteristics on patient-reported outcomes.

BACKGROUND: Subcutaneous immunoglobulin (SCIG) is increasingly utilized in primary immunodeficiency (PI). Understanding factors associated with treatment experience and satisfaction can optimize patient outcomes. We analyzed Immune Deficiency Foundation (IDF) survey data to evaluate patient-reported outcomes (PROs) in relation to SCIG training and infusion characteristics. Respondents' PRO scores were rank ordered into 'best', 'intermediate', and 'worst' tertiles. Predicted probabilities of being in the best tertile with any combination of characteristics were generated for each PRO. RESULTS: In 366 SCIG respondents, higher odds of being in the best PRO tertile were driven by favorable training characteristics (particularly, higher confidence post-training and no training barriers) and efficient infusions (infusion preparation ≤20 min and actual infusion < 2 h). Age (≤17 years old) and treatment experience (> 2 years) increased the odds of being in the best tertiles. Compared with the least favorable training/infusion characteristics, those with the most favorable training/infusion characteristics had higher predicted probabilities of being in the best tertiles: TSQM side effects, 59% vs 4%; convenience, 52% vs 4%; effectiveness, 27% vs 13%; global, 26% vs 3%; PROMIS Fatigue, 44% vs 18%. CONCLUSIONS: Increased experience with SCIG consistently improved PROs, but our findings predicted that enhanced training and infusion characteristics improve patient treatment satisfaction beyond that achieved by experience alone.

Adolescent alcohol exposure produces sex differences in negative affect-like behavior and group I mGluR BNST plasticity.

Adolescent alcohol exposure increases the risk of developing alcohol use disorders (AUDs), yet the mechanisms responsible for this vulnerability remain largely unknown. One potential target for alcohol-induced changes is the circuitry that modulates negative affect and stress, two sexually dependent drivers of alcohol relapse. The bed nucleus of the stria terminalis (BNST) is a sexually dimorphic region that critically regulates negative affective- and stress-induced relapse. Group I metabotropic glutamate receptors (mGluR) are a target of interest due to their regulation of stress, anxiety behaviors, and BNST plasticity. The current studies investigate sex-dependent sensitivity to the effects of adolescent intermittent ethanol vapor exposure (AIE) on negative affect during acute and protracted alcohol withdrawal and following stress in adulthood. This work also assessed whether BNST group I mGluR-mediated long-term depression (LTD) was disrupted at these timepoints. During acute withdrawal, AIE altered LTD induced by the group I mGluR antagonist DHPG in females, but not males. During adulthood, stress unmasked persistent changes in DHPG-induced LTD and behavior that were not present under basal conditions. Females with an AIE history demonstrated enhanced negative affective-like behavior in the novelty-induced hypophagia test following restraint stress-a phenotype that could be blocked with systemic mGluR5 allosteric antagonism via MTEP. Conversely, males with an AIE history demonstrated elevated freezing in a contextual fear conditioning paradigm. These studies demonstrate long-lasting, sex-dependent phenotypes produced by AIE and suggest pharmaceutical interventions for alcohol use and comorbid disorders may be more effective if designed with sex differences in mind.

Factors associated with increasing campylobacteriosis incidence in Michigan, 2004-2013.

This study was conducted to examine the incidence trend of campylobacteriosis in Michigan over a 10-year period and to investigate risk factors and clinical outcomes associated with infection. Campylobacter case data from 2004 to 2013 was obtained from the Michigan Disease Surveillance System. We conducted statistical and spatial analyses to examine trends and identify factors linked to campylobacteriosis as well as ecological associations using animal density data from the National Agricultural Statistics Service. An increasing trend of Campylobacter incidence and hospitalization was observed, which was linked to specific age groups and rural residence. Cases reporting ruminant contact and well water as the primary drinking source had a higher risk of campylobacteriosis, while higher cattle density was associated with an increased risk at the county level. Additional studies are needed to identify age-specific risk factors and examine prevalence and transmission dynamics in ruminants and the environment to aid in the development of more effective preventive strategies.

Increasing incidence of non-O157 Shiga toxin-producing Escherichia coli (STEC) in Michigan and association with clinical illness.

Infection with Shiga toxin-producing Escherichia coli (STEC) by serotypes other than O157 (non-O157) have been increasingly reported in the United States. This increase in reporting is primarily due to the improvements in diagnostic tests. We analysed 1497 STEC cases reported in Michigan from 2001 to 2012. A significant increase in the number of non-O157 STEC cases was observed over time, and similar incidence rates were observed for O157 and non-O157 STEC cases in certain time periods. The odds of hospitalization was two times higher in O157 STEC cases relative to non-O157 STEC cases when adjusted for age and gender, suggesting that O157 STEC causes more severe clinical outcomes in all age groups. The use of population-based surveillance to better define trends and associations with disease severity are critical to enhance our understanding of STEC infections and improve upon current prevention and control efforts.

Human albumin eye drops as a therapeutic option for the management of keratoconjunctivitis sicca secondary to chronic graft-versus-host disease after stem-cell allografting.

BACKGROUND: Keratoconjunctivitis sicca from chronic graft-versus-host disease (cgvhd) after allogeneic stem cell transplantation is common, leading to severe corneal damage and blindness if not treated. We retrospectively examined the efficacy and safety of pooled human albumin eye drops (haeds) for symptom relief in 40 stem-cell transplantation patients after other alternatives had failed. METHODS: The Common Terminology Criteria for Adverse Events (version 4.0) and the cgvhd grading scale were used to compare response in the patients during January 2000 and July 2013. In addition, on days 1 and 30, the haeds were subjected to quality assurance testing for sterility, oncotic pressure, albumin measurement, viscosity, pH, and purity by protein electrophoresis. RESULTS: Use of haeds resulted in symptom relief for 37 patients (92.5%); 3 patients (7.5%) failed to improve with use of haeds (p ≤ 0.0001). Of the 37 patients having symptom relief, 7 (19%) improved from grade 3 to no dry eye symptoms. Proportionately, post-treatment symptom improvement by two grade levels, from 3 to 1 (70%), was significantly higher than improvement by one grade level, from 3 to 2 (11%) or from 2 to 1 (19%, p ≤ 0.0001). Time to symptom relief ranged from 2 weeks to 28 weeks. Of the 40 patients, 38 (95%) had no adverse reactions. Days 1 and 30 quality assurance testing results were equivalent. CONCLUSIONS: Complications of keratoconjunctivitis sicca were well managed and well tolerated with haeds when other remedies failed. Quality assurance testing confirmed that haeds were safe and stable in extreme conditions.

Challenges in interpreting the evidence for genetic predictors of ototoxicity.

There has been recent controversy regarding predictors of cisplatin-induced ototoxicity in children, as highlighted in a previous issue of this journal. We have reviewed the two articles that purport to show an association between TPMT and COMT variants and ototoxicity, as well as the related patent applications dating back to 2006. We summarize statistical issues not fully addressed by the authors that appear to have confounded the results of their studies.

Novel approaches to preventing ischemia-reperfusion injury during liver transplantation.

Ischemia-reperfusion injury (IRI) results in profound allograft damage during liver transplantation. The process of IRI results in adenosine triphosphatase (ATP) depletion, the production of reactive oxygen species, and progressive tissue destruction. This injury process is accelerated on reperfusion in the recipient. Over the last decade an increasing body of literature has identified a complex interplay of molecular and cellular pathways responsible for causing IRI. This article summarizes recent developments, drawing on preclinical and clinical studies, focusing on how the detrimental effects of IRI can be prevented in liver transplantation. We present a balanced overview on how machine preservation technologies, the coagulation system, antioxidants, cytoprotective agents, cytokines, preservation solutions, and the innate and adaptive immune system can be targeted to prevent IRI in liver transplantation.

Nasal cytokine responses to natural colds in asthmatic children.

BACKGROUND: The mechanisms by which viruses induce asthma exacerbations are not well understood. OBJECTIVE: We characterized fluctuations in nasal aspirate cytokines during naturally occurring respiratory viral infections in children with asthma. METHODS: Sixteen children underwent home collections of nasal aspirates when they were without cold symptoms and again during self-reported respiratory illnesses. The presence of viral infection was ascertained by multiplex PCR. Cytokines were measured using multiplex immune assay. mRNA expression for selected markers of viral infection was measured using RT-PCR. A cumulative respiratory symptom score was calculated for each day of measurement. Generalized estimated equations were used to evaluate associations between viral infection and marker elevation, and between marker elevation and symptom score. RESULTS: The 16 patients completed a total of 37 weeks of assessment (15 'well' weeks; 22 self-assessed 'sick' weeks). Viral infections were detected in 3 of the 'well' weeks and 17 of the 'sick' weeks (10 rhinovirus, three coronavirus, two influenza A, two influenza B, two respiratory syncytial virus, one parainfluenza). Compared to virus-negative well weeks, nasal aspirate IFN-γ, CXCL8/IL-8, CXCL10/IP-10, CCL5/RANTES, CCL11/eotaxin-1, CCL2/MCP-1, CCL4/MIP-1ß, CCL7/MCP-3, and CCL20/MIP3α protein levels increased during virus-positive sick weeks. Only a subset of cytokines (IFN-γ, CXCL8, CCL2, CCL4, CCL5, and CCL20) correlated with self-reported respiratory tract symptoms. While many aspirates were dilute and showed no mRNA signal, viral infection significantly increased the number of samples that were positive for IFN-λ1, IFN-λ2/3, TLR3, RIG-I, and IRF7 mRNA. CONCLUSIONS AND CLINICAL RELEVANCE: We conclude that in children with asthma, naturally occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs, and IFN-responsive genes.

Effect of cocoa and green tea on biomarkers of glucose regulation, oxidative stress, inflammation and hemostasis in obese adults at risk for insulin resistance.

BACKGROUND/OBJECTIVES: Flavanols may provide protection against insulin resistance, but little is known about the amounts and types of flavanols that may be efficacious. SUBJECTS/METHODS: This study was designed to determine whether cocoa flavanols, over a range of intakes, improve biomarkers of glucose regulation, inflammation and hemostasis in obese adults at risk for insulin resistance. As an adjunct, green tea and cocoa flavanols were compared for their ability to modulate these biomarkers. In a randomized crossover design, 20 adults consumed a controlled diet for 5 days along with four cocoa beverages containing 30-900 mg flavanol per day, or tea matched to a cocoa beverage for monomeric flavanol content. RESULTS: Cocoa beverages produced no significant changes in glucose, insulin, total area under the concentration-time curve (AUC) for glucose or total insulin AUC. As the dose of cocoa flavanols increased, total 8-isoprostane concentrations were lowered (linear contrast, P=0.02), as were C-reactive protein (CRP) concentrations (linear contrast, P=0.01). The relationship between cocoa flavanol levels and interleukin-6 (IL-6) concentrations was quadratic, suggesting that a maximum effective dose was achieved (quadratic contrast, P=0.01). There were no significant effects on measured indices of glucose regulation, nor on those of total 8-isoprostane, CRP and IL-6 concentrations, when cocoa and green tea were compared. However, relative to cocoa, green tea lowered fibrinogen concentrations (P=0.0003). CONCLUSIONS: Short-term intake of cocoa and green tea flavanols does not appear to improve glucose metabolism; they do affect selected markers of one or more measures of oxidative stress, inflammation or hemostasis in obese adults at risk for insulin resistance.

Improved semiconductor lattice parameters and band gaps from a middle-range screened hybrid exchange functional.

We show that the middle-range exchange-correlation hybrid of Henderson, Izmaylov, Scuseria and Savin (HISS) performs extremely well for elemental and binary semiconductors with narrow or visible spectrum band gaps, as well as some wider gap or more ionic systems used in devices. The lattice parameters are superior to those predicted by the screened hybrid functional of Heyd, Scuseria and Ernzerhof (HSE), and provide a significant improvement over the geometries predicted by typical semilocal functionals, yielding results competitive with PBEsol, which was specially tuned for solids. HISS also yields band gaps superior to those produced by functionals developed specifically for the solid state. Timings indicate that HISS is more computationally efficient than HSE, implying that the high quality lattice constants coupled with improved optical band gap predictions render HISS a useful adjunct to HSE in the modeling of geometry-sensitive semiconductors.

The prevalence and causes of visual impairment in indigenous Australians within central Australia: the Central Australian Ocular Health Study.

AIM: To determine the prevalence and causes of visual impairment and blindness among indigenous Australians living in central Australia. METHODS: 1884 individuals aged 20 years or older, living in one of 30 remote communities within the statistical local area of "Central Australia", were recruited for this study, from which 1883 were assessable. This equated to 36% of those > or =20 years old and 67% of those > or =40 years old within this district. Participants were recruited as they presented to the eye clinic at each remote community. Patients underwent Snellen visual acuity testing and subjective refraction. After this, an assessment of their anterior and posterior segments was made. Rates and causes of bilateral visual impairment (vision worse than Snellen visual acuity 6/12 in the better eye) and bilateral blindness (Snellen visual acuity worse than 6/60 in the better eye) were presented. RESULTS: 19.4% (365/1883) had bilateral visual impairment (25.1% of those > or =40 years old) and 2.8% (53/1883) had bilateral blindness (3.6% of those > or =40 years old). Refractive error followed by cataract were the main causes for bilateral visual impairment and blindness. Following these, diabetic eye disease and trachomatous corneal opacification were the main causes of bilateral visual impairment and bilateral blindness, respectively. CONCLUSION: This study indicates that bilateral visual impairment and blindness are, respectively, 25.1% and 3.6% among indigenous Australians, four to seven times higher than among the non-indigenous Australian population. Trachoma is the leading cause of bilateral blindness after refractive error and cataract.

Incidence and pattern of acute anterior uveitis in Central Australia.

AIM: To investigate the incidence and patterns of acute anterior uveitis (AAU) in Central Australia and specifically to study the relative frequency of AAU in Australian Aborigines compared with that in non-Aboriginal patients. METHODS: Prospective, observational study of all patients seen by the Central Australian Ophthalmology service over an 8-month period. RESULTS: The incidence rate of AAU in Central Australia was 35.9 cases/100,000 population per year. Forty-two per cent of the 1955 patients seen during the study period were Australian Aboriginal patients; however, all but one patient with AAU were Caucasian. The difference in the incidence of AAU between the Indigenous and non-Indigenous populations was statistically significant (p = 0.03, Fisher's exact test). Four of the nine Caucasian patients with AAU were HLA-B27-positive. The single case of AAU in an Australian Aborigine was a recurrent episode of HLA-B27-positive AAU. A family history of this patient revealed that both her grandfathers were Caucasian. CONCLUSION: The incidence and pattern of AAU in Central Australia is comparable with that in other geographical regions. However, AAU occurs very infrequently in Australian Aborigines compared with that in the non-Indigenous population of Central Australia, further implicating the importance of genetic factors in the pathogenesis of AAU.

Trends and geographic variations in hospital admissions for asthma in Victoria. Opportunities for targeted interventions.

OBJECTIVE: To describe variations in rates of hospital admissions for asthma in Victoria as health indicators of quality of primary care services and access. DESIGN: Routine analyses of age and sex standardised admission rates of asthma in rural and metropolitan Victoria from 1993-1994 to 1999-2000. RESULTS: There were 10,079 admissions for asthma, with an average of 2.71 bed days in 1999-2000. The admission rate for asthma decreased from 3.1/1000 (95% CI: 3.1-3.2) in 1993-1994 to 2.2/1000 (2.1-2.2) in 1999-2000, with a 37% reduction in rural regions and 26% in metropolitan regions. Sixteen primary care partnerships (small areas), 13 of them rural, had significantly higher admission rates than the Victorian average. CONCLUSION: Although asthma hospital admission rates are falling faster in rural than metropolitan areas, rural areas still have higher admission rates with significant variation between small areas.

Is type 2 diabetes a chronic inflammatory/autoimmune disease?

The classification of diabetes mellitus into 2 main types, defined as Type 1 and 2 diabetes (T1DM, T2DM) relies mostly on the requirement of insulin therapy and on the presence of detectable immunologic abnormalities. However, this distinction is far from straightforward and there is considerable overlap between these 2 types of diabetes. Islet cell autoimmunity, which is characteristic of T1DM, appears in fact to be present in up to 10-15% of subjects diagnosed clinically with T2DM. In the UK Prospective Diabetes Study (UKPDS), it was reported that in patients diagnosed with in T2DM, the presence of autoantibodies to the enzyme glutamic acid decarboxylase (GAD) and cytoplasmic islet cell antibodies (ICA) were a predictor of insulin requirement as compared with patients not carrying these autoantibodies. These results are strikingly similar to a number of prospective studies carried out in childhood diabetes. If islet cell autoimmunity is truly present in 10-15% of subjects clinically diagnosed with T2DM, up to two million Americans might have an unidentified autoimmune form of T2DM, a prevalence similar to that of recent onset childhood diabetes. In addition, we found that in a subset of T2DM patients, a pronounced activation of the acute phase response that seems to be associated with islet cell autoimmunity. These results may in part explain the defect in insulin secretion as well as insulin resistance seen in T2DM. The identification of a subgroup of individuals at risk of developing T2DM using autoantibody as well as inflammatory markers is of public health interest, not only for the correct classification of diabetes, but also because immunomodulatory therapeutic strategies could potentially be instituted sufficiently early in a large number of patients diagnosed as having T2DM and most likely delay the onset of insulin requirement and the complications related with hyperglycemia.