Microbiopsies of human skeletal muscle are increasingly adopted by physiologists for a variety of experimental assays given the reduced invasiveness of this procedure compared to the classic Bergstrom percutaneous biopsy technique. However, a recent report demonstrated lower mitochondrial respiration in saponin-permeabilized muscle fiber bundles (PmFB) prepared from microbiopsies vs. Bergstrom biopsies. We hypothesized that ADP-induced contraction (rigor) of smaller length microbiopsy PmFB causes a greater reduction in maximal respiration vs. Bergstrom, such that respiration could be increased by a myosin II ATPase-inhibitor (Blebbistatin; BLEB). Eleven males and females each received a 2 mm diameter percutaneous microbiopsy and a 5 mm diameter Bergstrom percutaneous biopsy in opposite legs. Glutamate/malate (5/0.5 mM)—supported respiration in microbiopsy PmFB was lower than Bergstrom at submaximal concentrations of ADP. 5 μM BLEB reduced this impairment such that there were no differences relative to Bergstrom ± BLEB. Surprisingly, pyruvate (5 mM)-supported respiration was not different between either biopsy technique ±BLEB, whereas BLEB increased succinate-supported respiration in Bergstrom only. H2O2 emission was lower in microbiopsy PmFB compared to Bergstrom PmFB in the presence of BLEB. Microbiopsies contained fewer type I fibers (37 vs. 47%) and more type IIX fibers (20 vs. 8%) compared to Bergstrom possibly due to sampling site depth and/or longitudinal location. These findings suggest that smaller diameter percutaneous biopsies yield lower glutamate-supported mitochondrial respiratory kinetics which is increased by preventing ADP-induced rigor with myosin inhibition. Microbiopsies of human skeletal muscle can be utilized for assessing mitochondrial respiratory kinetics in PmFB when assay conditions are supplemented with BLEB, but fiber type differences with this method should be considered.
Reference intervals (RIs) for biochemical and hematological markers determined using healthy adult and/or pediatric populations are vital for clinical interpretation of laboratory test results. Most clinical laboratories commonly use age- and sex-specific RIs, but the effect of ethnicity as a covariate is often overlooked. Ethnic differences in serum biomarker concentrations can occur as a result of genetic and environmental factors, while the degree to which each factor influences serum levels depends on the specific biomarker. Numerous studies have investigated ethnic differences in routine chemistry, fertility, endocrine, cancer, and hematological markers, as well as in vitamins and carotenoids, in children, adolescents and adults. In the present review, we summarize and discuss ethnic-specific differences observed for these laboratory markers and their potential impact on the clinical interpretation of laboratory test results. We categorized the available data into seven major ethnic groups (i.e. Black, Caucasian, East Asian, Hispanic, South Asian, South East Asian, and West Asian) for ease of comparison. While certain biomarkers could not be compared between ethnic groups because of insufficient information or contradictory results between studies, significant differences between ethnic groups were reported by one or more studies for most of the biomarkers included in this review. The clinical significance of these differences and the potential need for ethnic-specific RIs for certain biochemical markers are also discussed.
Introduction: Hematology laboratory parameters are among the most routinely ordered tests in support of adult and pediatric care. However, appropriate interpretation of test results has been a challenge in pediatrics since accurate and up-to-date reference intervals that reflect the dynamic physiological changes associated with growth and development have not been available. Critical gaps continue to exist in pediatric hematology reference intervals for modern laboratory platforms. To address this gap, this study establishes age-and sex-specific reference intervals for 25 hematology parameters in the CALIPER cohort of healthy children and adolescents using a common platform, the Sysmex XN-3000 analytical system. Methods: Fresh whole blood samples collected from a total of 641 healthy children and adolescents (birth to <21 years) with informed consent were analyzed for 25 hematological parameters on the Sysmex XN-3000 Hematology Analyzer. Age-and sex-specific reference standards were calculated based on Clinical and Laboratory Standards Institute guidelines. Results: Of the 25 analytes assessed, 19 required age-partitioning and seven required sex-partitioning (ie, red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, red blood cell distribution width-SD, red blood cell distribution width-CV, and monocyte percentage). Age-and sex-specific differences mostly coincided with the onset of puberty. Conclusion: This study establishes a comprehensive database of pediatric reference intervals for hematology parameters in the CALIPER cohort using the widely used Sysmex XN-3000 analytical platform. These data highlight the dynamic hematological profile observed in healthy children and adolescents and the need for reference interval stratification by age and sex.
During the COVID-19 pandemic, most cancer centers shifted from in-person to virtual cancer care to curb community spread and ensure care continuity. This qualitative descriptive study aimed to understand cancer patient-perceived risks related to COVID-19 and cancer treatment, as well as the patient-perceived and experienced value of virtual care. From June to August 2020, focus groups were conducted with patients under active management or observation for a diagnosed malignancy in Toronto, Canada. A thematic analysis of six focus groups found that most participants worried more about treatment delays than they did about COVID-19 infection. Despite some concern about COVID-19 exposure in the hospital, care delays contributed to increased anxiety among participants who already subscribed to strict safety measures in their everyday lives. Most participants accepted virtual care for some appointment types; however, preference for in-person care was found to sustain the humanistic and therapeutic aspects of cancer care that many participants valued. Nuances in the appropriateness and adequacy of virtual cancer care still need exploration. Preserving the humanistic aspects of care is of paramount importance.
Objectives The objective of this study was to establish comprehensive age- and sex-specific reference intervals for hematologic parameters in the CALIPER cohort of healthy children and adolescents. Methods A total of 536 healthy children and adolescents (birth to 21 years) were recruited with informed consent, and whole blood samples were analyzed for 27 hematologic parameters on the Beckman Coulter DxH 520 system. Age- and sex-specific pediatric reference standards were established. Reference values obtained on the DxH 520 were also compared with data obtained on a larger laboratory-based instrument (DxH 900). Results Most hematologic parameters showed significant age- and/or sex-specific changes during growth and development. Of the 27 hematologic parameters, all except four (mean corpuscular hemoglobin concentration, basophil percentage, low hemoglobin density, immature cell percentage) required age partitioning, and eight required sex partitioning. Conclusions This study establishes a robust pediatric hematology reference database that will assist in more accurate test result interpretation. Our data clearly demonstrate significant variation in hematologic parameter concentrations in children and adolescents, necessitating the use of pediatric-specific reference standards.
Objectives Accurate hematologic test interpretation based on normative reference standards is critical to ensure appropriate clinical decision making. However, healthy pediatric reference data for most hematology parameters are lacking. To address this gap, this study establishes age- and sex-specific hematologic reference standards in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents. Methods Fresh whole blood samples collected from a total of 566 healthy children and adolescents (birth to <21 years) with informed consent were analyzed for 47 hematologic parameters on the Beckman Coulter DxH 900. Age- and sex-specific reference standards were calculated based on the Clinical and Laboratory Standards Institute guidelines. Results Reference value distributions for most hematology parameters demonstrated dynamic changes across the pediatric age range with significant age-specific differences observed for 39 of the 47 parameters examined. Sex-specific differences were also observed for eight hematologic parameters, primarily during and after puberty. Conclusions This study establishes a robust database of pediatric reference standards for 47 hematologic parameters in the CALIPER cohort for the first time. These comprehensive reference value data sets report potentially important and physiologically relevant trends in hematologic markers, clearly demonstrating the need for pediatric reference standards for hematologic test interpretation.
Background The prevalence of pediatric obesity is increasing worldwide and strongly associates with metabolic abnormalities, including inflammation, insulin resistance, and dyslipidemia. This study assessed the influence of 3 measures of adiposity on levels of routinely assessed biochemical markers in apparently healthy children and adolescents. Methods The influence of adiposity on 35 biochemical markers was examined in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents by comparing serum biomarker levels between subjects with a normal weight, overweight, and obese body mass index (BMI). The cohort comprised 1332 subjects 5.1 to 19.0 years of age with a BMI ranging from 13.4 to 65.0 kg/m2. The association between each biochemical marker and BMI, waist circumference, and waist-to-height ratio z-scores was assessed, while adjusting for age and sex. Reference intervals were established for all biochemical markers before and after removing overweight/obese subjects. Results In children and adolescents, levels of 13 routinely assessed biochemical markers, including alanine aminotransferase, apolipoprotein B, complement components 3 and 4, cholinesterase, high sensitivity C-reactive protein, gamma-glutamyl transferase, haptoglobin, high-density lipoprotein cholesterol, iron, transferrin, triglycerides, and uric acid, were significantly different between BMI categories. BMI, waist circumference, and/or waist-to-height ratio were significantly associated with the serum concentration of 24 of the 35 markers examined, after adjusting for age and sex. Conclusions Excess adiposity significantly influences circulating levels of routinely assessed laboratory markers, most notably liver enzymes, lipids/lipoproteins, inflammatory markers, and uric acid in children and adolescents. Although it is unknown whether altered biochemical marker levels in subjects with overweight/obesity reflect health or indolent disease, clinicians should be aware of the effect of weight status on several laboratory tests.
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