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Background: Equations to estimate glomerular filtration rate based on serum creatinine are commonly used in cancer patients to assess renal function. However, there is uncertainty regarding which equation is most appropriate for this population and the impact of different creatinine assays., Methods: Measured isotopic glomerular filtration rate results from 120 oncology patients were used to evaluate and compare all four versions of the Wright equation, Cockcroft and Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration and the Janowitz and Williams formula; using eight different creatinine assays (five Jaffe, three enzymatic)., Results: The enzymatic version of the Wright equation without creatine kinase performed better than the other versions for all eight creatinine assays. However, MDRD and Janowitz and Williams gave the best overall performance in this patient population. Performance was highly dependent on the creatinine assay used, for example, the percentage of results within 30% of the isotopic glomerular filtration rate (P30) ranged from 90.8% to 60.8% for MDRD., Conclusion: The performance of any equation to estimate glomerular filtration rate is highly dependent on the creatinine assay used. Oncology units should assess the performance of glomerular filtration rate equations using their laboratory creatinine assay to determine whether they can be used safely and effectively in cancer patients.

Guidelines state that patients undergoing isotope glomerular filtration rate (GFR) tests should maintain adequate hydration, but pragmatically these tests can coincide with procedures requiring the patient not to eat or drink ('nil-by-mouth') for up to 12 hours beforehand. This study investigated the impact of a 12-hour nil-by-mouth regime on GFR measurement. Twelve healthy volunteers were recruited from our institution. Exclusion criteria included diabetes mellitus, being under 18 years of age and pregnancy. Isotope GFR measurements were carried out on these volunteers twice. One of the tests adhered strictly to the British Nuclear Medicine Society (BNMS) guidelines for GFR measurement and the other test was carried out after the volunteers had refrained from eating or drinking anything for 12 hours. The order of these tests was randomly assigned. The results show that after a nil-by-mouth regime, participants' average absolute GFR fell from 108 ml/min to 97 ml/min (p < .01), while normalised GFR fell from 97 ml/min/1.73 m 2 to 88 ml/min/1.73m 2 (p < .01). Serum creatinine rose from 68 mmol/L to 73 mmol/L (p < .05). There were no changes in blood pressure, serum hydration markers or bio-impedance measured fluid status. Urine analysis showed statistically significant increases in urea, creatinine and osmolality levels after the nil-by-mouth regime. The results highlight the importance of following current guidelines recommending fluid intake during the procedure. Practitioners should consider what other outpatient appointments are being scheduled concurrently with a GFR test.

BACKGROUND: Timely detection of acute kidney injury (AKI) in hospital patients has been hampered by the multiple definitions of AKI and difficulties applying their criteria. A laboratory delta check may provide an effective means of detecting patients developing AKI. This study compared three of the proposed AKI definitions and a delta check to detect AKI using serum creatinine results of hospital inpatients. METHODS: Serum creatinine results for 2822 inpatients were gathered retrospectively from the clinical biochemistry database. All serum creatinine results within 30 d of admission were included for each patient and assessed for AKI according to four criteria: Risk, Injury, Failure (RIFLE), Acute Kidney Injury Network (AKIN), Waikar & Bonventre or a delta check (increase of >26 [mu]mol/L between two successive values). RESULTS: A total of 149 (11.3%) patients were defined as having AKI by at least one of the four criteria. Different populations of patients were identified by each criterion. The number of patients identified and the incidence of AKI were as follows: RIFLE 94 (7.1%), AKIN 125 (9.5%), Waikar & Bonventre 100 (7.6%) and delta check 146 (11.1%). The delta check detected 132 (98%) of all 135 cases detected by the other three criteria. A further 14 patients were detected solely by the delta check. CONCLUSIONS: The different definitions proposed for AKI detect different populations of patients. A laboratory delta check detected 98% of all the patients identified by AKIN, RIFLE and Waikar & Bonventre combined and could therefore provide a practical way of detecting AKI patients. [ABSTRACT FROM AUTHOR]

Background: Hyperosmolar infant feeds can cause osmotic diarrhoea and may be a risk factor for necrotising enterocolitis; the osmolality of infant formula is therefore usually <400 mOsm kg(-1) . However, in fluid-restricted infants and those needing nutritional support, formulas may be over-concentrated or supplemented. The present study aimed to determine the effect of these practices on osmolality., Methods: A clinical laboratory osmometer was used to measure the osmolality of infant formulas. The effect of over-concentration and supplementation on osmolality was then determined using three and seven different infant formulas, respectively. Osmolalities were measured in triplicate., Results: The effect of over-concentration was shown to be linear using Pepti Junior (Cow & Gate, Trowbridge, UK) at concentrations of 12.8% (standard), 17% and 19%. This linear relationship was also demonstrated with Enfamil A.R. (Mead Johnson Nutritionals, Uxbridge, UK) (15%) and Neocate (SHS International Ltd, Liverpool, UK) (21%). The effect of individual additives on osmolality was found to be similar for the seven infant formulas. All preparations of SMA High Energy (SMA Nutrition, Maidenhead, UK) and five of the 12 preparations of Nutriprem 1 (Cow & Gate) exceeded an osmolality of 400 mOsm kg(-1) ., Conclusions: The effect of over-concentrating infant formulas was shown to be linear, meaning that the osmolality at different concentrations can be predicted accurately. The over-concentrated infant formulas that were measured in the present study did not exceed 400 mOsm kg(-1) , with the exception of 21% Neocate, which would not be used in practice. When supplemented, some infant formulas exceeded an osmolality of 400 mOsm kg(-1) ; this may be relevant in cases of feed intolerance or in those at risk of necrotising enterocolitis., (© 2012 The Authors Journal of Human Nutrition and Dietetics © 2012 The British Dietetic Association Ltd.)

Although different detergents can give rise to detergent-resistant membranes of different composition, it is unclear whether this represents domain heterogeneity in the original membrane. We compared the mechanism of action of five detergents on supported lipid bilayers composed of equimolar sphingomyelin, cholesterol, and dioleoylphosphatidylcholine imaged by atomic force microscopy, and on raft and nonraft marker proteins in live cells imaged by confocal microscopy. There was a marked correlation between the detergent solubilization of the cell membrane and that of the supported lipid bilayers. In both systems Triton X-100 and CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) distinguished between the nonraft liquid-disordered (l(d)) and raft liquid ordered (l(o)) lipid phases by selectively solubilizing the l(d) phase. A higher concentration of Lubrol was required, and not all the l(d) phase was solubilized. The solubilization by Brij 96 occurred by a two-stage mechanism that initially resulted in the solubilization of some l(d) phase and then progressed to the solubilization of both l(d) and l(o) phases simultaneously. Octyl glucoside simultaneously solubilized both l(o) and l(d) phases. These data show that the mechanism of membrane solubilization is unique to an individual detergent. Our observations have significant implications for using different detergents to isolate membrane rafts from biological systems.

In overhydrated hereditary stomatocytosis (OHSt), the membrane raft-associated stomatin is deficient from the erythrocyte membrane. We have investigated two aspects of raft structure and function in OHSt erythrocytes. First, we have studied the distribution of other membrane and cytoskeletal proteins in rafts by analysis of detergent-resistant membranes (DRMs). In normal erythrocytes, 29% of the actin was DRM-associated, whereas in two unrelated OHSt patients the DRM-associated actin was reduced to <10%. In addition, there was a reduction in the amount of the actin-associated protein tropomodulin in DRMs from these OHSt cells. When stomatin was expressed in Madin-Darby canine kidney cells, actin association with the membrane was increased. Second, we have studied Ca2+-dependent exovesiculation from the erythrocyte membrane. Using atomic force microscopy and proteomics analysis, exovesicles derived from OHSt cells were found to be increased in number and abnormal in size, and contained greatly increased amounts of the raft proteins flotillin-1 and -2 and the calcium binding proteins annexin VII, sorcin and copine 1, while the concentrations of stomatin and annexin V were diminished. Together these observations imply that the stomatin-actin association is important in maintaining the structure and in modulating the function of stomatin-containing membrane rafts in red cells.

Glycosyl-phosphatidylinositol (GPI)-anchored proteins are enriched in cholesterol- and sphingolipid-rich lipid rafts within the membrane. Rafts are known to have roles in cellular organization and function, but little is understood about the factors controlling the distribution of proteins in rafts. We have used atomic force microscopy to directly visualize proteins in supported lipid bilayers composed of equimolar sphingomyelin, dioleoyl-sn-glycero-3-phosphocholine and cholesterol. The transmembrane anchored angiotensin converting enzyme (TM-ACE) was excluded from the liquid ordered raft domains. Replacement of the transmembrane and cytoplasmic domains of TM-ACE with a GPI anchor (GPI-ACE) promoted the association of the protein with rafts in the bilayers formed with brain sphingomyelin (mainly C18:0). Association with the rafts did not occur if the shorter chain egg sphingomyelin (mainly C16:0) was used. The distribution of GPI-anchored proteins in supported lipid bilayers was investigated further using membrane dipeptidase (MDP) whose GPI anchor contains distearoyl phosphatidylinositol. MDP was also excluded from rafts when egg sphingomyelin was used but associated with raft domains formed using brain sphingomyelin. The effect of sphingomyelin chain length on the distribution of GPI-anchored proteins in rafts was verified using synthetic palmitoyl or stearoyl sphingomyelin. Both GPI-ACE and MDP only associated with the longer chain stearoyl sphingomyelin rafts. These data obtained using supported lipid bilayers provide the first direct evidence that the nature of the membrane-anchoring domain influences the association of a protein with lipid rafts and that acyl chain length hydrophobic mismatch influences the distribution of GPI-anchored proteins in rafts.

A focused SAR study around the previously reported selective 5-HT(7) receptor antagonist, SB-269970-A has resulted in the identification of a structurally related analogue having an improved pharmacokinetic profile. Replacement of the phenolic group in SB-269970-A with an indole moiety, and replacement of the piperidinyl 4-methyl group with a heterocyclic ring system proved to be the key changes leading to the identification of SB-656104-A.

The article summarizes the "Clinical Practice Guidelines for the Management of Kidney Injury During Anticancer Drug Therapy 2022" published by several Japanese medical societies. The guidelines provide recommendations for medical professionals on managing kidney injuries that occur during cancer pharmacotherapy. Topics covered include renal function assessment, drug-induced nephrotoxicity management, anticancer drug regimen planning, and chronic kidney disease treatment in cancer survivors. The guidelines were developed based on a literature search and consensus development process. The article also discusses specific clinical questions and recommendations related to renal function assessment, interventions for malignant ureteral obstruction, the use of immune checkpoint inhibitors in different patient populations, hydration methods during cisplatin treatments, and kidney replacement therapy for childhood cancer survivors. The evidence for these recommendations varies in strength, and further research is needed to evaluate outcomes and determine the best approaches for these treatments. [Extracted from the article]

Measurement of graft dysfunction following kidney transplant through creatinine is well known to be impacted by many different factors. We report here a clinical scenario demonstrating the importance of dual measurement of glomerular filtration rate (GFR) based on creatinine and cystatin C while also examining within-subject variability of both tests. [ABSTRACT FROM AUTHOR]

Accurate assessment of GFR is crucial to guiding drug eligibility, dosing of systemic therapy, and minimizing the risks of both undertreatment and toxicity in patients with cancer. Up to 32% of patients with cancer have baseline CKD, and both malignancy and treatment may cause kidney injury and subsequent CKD. To date, there has been lack of guidance to standardize approaches to GFR estimation in the cancer population. In this two-part statement from the American Society of Onco-Nephrology, we present key messages for estimation of GFR in patients with cancer, including the choice of GFR estimating equation, use of race and body surface area adjustment, and anticancer drug dose-adjustment in the setting of CKD. These key messages are based on a systematic review of studies assessing GFR estimating equations using serum creatinine and cystatin C in patients with cancer, against a measured GFR comparator. The preponderance of current data involving validated GFR estimating equations involves the CKD Epidemiology Collaboration (CKD-EPI) equations, with 2508 patients in whom CKD-EPI using serum creatinine and cystatin C was assessed (eight studies) and 15,349 in whom CKD-EPI with serum creatinine was assessed (22 studies). The former may have improved performance metrics and be less susceptible to shortfalls of eGFR using serum creatinine alone. Since included studies were moderate quality or lower, the American Society of Onco-Nephrology Position Committee rated the certainty of evidence as low. Additional studies are needed to assess the accuracy of other validated eGFR equations in patients with cancer. Given the importance of accurate and timely eGFR assessment, we advocate for the use of validated GFR estimating equations incorporating both serum creatinine and cystatin C in patients with cancer. Measurement of GFR via exogenous filtration markers should be considered in patients with cancer for whom eGFR results in borderline eligibility for therapies or clinical trials., (Copyright © 2024 by the American Society of Nephrology.)

Chronic kidney disease (CKD) encompasses diverse conditions such as congenital anomalies, glomerulonephritis, and hereditary nephropathies, necessitating individualized nutritional interventions. Early detection is pivotal due to the heightened risk of adverse outcomes, including compromised growth and increased healthcare costs. The nutritional assessment in pediatric CKD employs a comprehensive, multidisciplinary approach, considering disease-specific factors, growth metrics, and dietary habits. The prevalence of malnutrition, as identified through diverse tools and guidelines, underscores the necessity for regular and vigilant monitoring. Nutritional management strategies seek equilibrium in calorie intake, protein requirements, and electrolyte considerations. Maintaining a well-balanced nutritional intake is crucial for preventing systemic complications and preserving the remaining kidney function. The nuanced landscape of enteral nutrition, inclusive of gastrostomy placement, warrants consideration in scenarios requiring prolonged support, with an emphasis on minimizing risks for optimized outcomes. In conclusion, the ongoing challenge of managing nutrition in pediatric CKD necessitates continuous assessment and adaptation. This review underscores the significance of tailored dietary approaches, not only to foster growth and prevent complications but also to enhance the overall quality of life for children grappling with CKD., (© 2024. The Author(s).)

Twenty-six patients with severe chronic obstructive lung disease exercised on a treadmill while breathing either room air, supplementary compressed air, or O2. Endurance was significantly increased by O2, but there was no improvement in maximal work rate. No relation was found between increased endurance and the degree of hypoxia, hypercarbia, or acidosis during exercise or the changes in these while breathing O2.

Background: Sepsis is often accompanied with acute kidney injury (AKI). The incidence of AKI in patients visiting the emergency department (ED) with sepsis according to the new SOFA criteria is not exactly known, because the definition of sepsis has changed and many definitions of AKI exist. Given the important consequences of early recognition of AKI in sepsis, our aim was to assess the epidemiology of sepsis-associated AKI using different AKI definitions (RIFLE, AKIN, AKIB, delta check, and KDIGO) for the different sepsis classifications (SIRS, qSOFA, and SOFA). Methods: We retrospectively enrolled patients with sepsis in the ED in three hospitals and applied different AKI definitions to determine the incidence of sepsis-associated AKI. In addition, the association between the different AKI definitions and persistent kidney injury, hospital length of stay, and 30-day mortality were evaluated. Results: In total, 2065 patients were included. The incidence of AKI was 17.7–51.1%, depending on sepsis and AKI definition. The highest incidence of AKI was found in qSOFA patients when the AKIN and KDIGO definitions were applied (51.1%). Applying the AKIN and KDIGO definitions in patients with sepsis according to the SOFA criteria, AKI was present in 37.3% of patients, and using the SIRS criteria, AKI was present in 25.4% of patients. Crude 30-day mortality, prolonged length of stay, and persistent kidney injury were comparable for patients diagnosed with AKI, regardless of the definition used. Conclusion: The incidence of AKI in patients with sepsis is highly dependent on how patients with sepsis are categorised and how AKI is defined. When AKI (any definition) was already present at the ED, 30-day mortality was high (22.2%). The diagnosis of AKI in sepsis can be considered as a sign of severe disease and helps to identify patients at high risk of adverse outcome at an early stage. [ABSTRACT FROM AUTHOR]

Background: We aimed to assess safety, tolerability, and improvement in weight gain with an energy‐ and protein‐enriched formula (EPEF) in infants with poor growth. Methods: Infants aged 1–8 months with poor growth received EPEF for 16 weeks. Our primary objective was improvement in weight as measured by change in weight‐for‐age z‐score (WAZ) and weight gain velocity (grams per day) ≥ median for age. Secondary objectives included improvement in other anthropometric z‐scores, formula tolerance, and safety. Results: Twenty‐six patients with poor growth due to congenital heart disease (n = 15), other organic causes (n = 9), and nonorganic causes (n = 2) completed the study per protocol. Mean daily energy intake was 123 ± 32 kilocalories per kilogram of body weight, with >90% of energy coming from EPEF. Weight gain velocity exceeded the median for 83% (20 of 24) and 67% (16 of 24) of infants at ≥1 time point and for the overall study period, respectively. Mean ± SD WAZ improved from −2.92 ± 1.04 at baseline to −2.01 ± 1.12 at 16 weeks (P = 0.0001). Z‐scores for weight‐for‐length and head circumference (P = 0.0001) and for length‐for‐age (P = 0.003) improved significantly at 16 weeks. Compared with baseline, stool consistency was different at 2, 4, and 16 weeks (P < 0.05). There were no significant differences in vomiting, fussiness, or daily number of stools while there was a decrease or no change in spit‐up, flatulence, crying, or gassiness. Conclusion: EPEF is safe, well tolerated, and improves weight gain in infants with poor growth. [ABSTRACT FROM AUTHOR]

The mycobacterium genus contains a broad range of species, including the human pathogens M. tuberculosis and M. leprae. These bacteria are best known for their residence inside host cells. Neutrophils are frequently observed at sites of mycobacterial infection, but their role in clearance is not well understood. In this review, we discuss how neutrophils attempt to control mycobacterial infections, either through the ingestion of bacteria into intracellular phagosomes, or the release of neutrophil extracellular traps (NETs). Despite their powerful antimicrobial activity, including the production of reactive oxidants such as hypochlorous acid, neutrophils appear ineffective in killing pathogenic mycobacteria. We explore mycobacterial resistance mechanisms, and how thwarting neutrophil action exacerbates disease pathology. A better understanding of how mycobacteria protect themselves from neutrophils will aid the development of novel strategies that facilitate bacterial clearance and limit host tissue damage. [ABSTRACT FROM AUTHOR]

A rapid amplification of algal population has a negative impact on the environment and the global economy. Thus, control of algal proliferation is an important issue and effective procedures which reduce algal blooms and control algal fouling are highly desired. Gemini surfactants are considered to have a low environmental impact, therefore they seem to be a promising group of detergents which could reduce algal blooms in water systems. Furthermore, due to their emulsifying properties they could replace algaecides added to antifouling paints and decrease algae adhesion to various surfaces. In this study the toxic effect of the 12-5-12 gemini surfactant was investigated on Chlorella cells and close attention was paid to a potential mechanism of its action. At the high cell density (10.05 × 107 cells/mL) a dose-dependent cell death was found and the IC50 value was reached at the concentration of 19.6 µmol/L after 72-h exposure to the surfactant. The decrease in chlorophyll autofluorescence shows that the photosynthetic apparatus seems to be the target of the tested compound. The presented studies indicate that gemini surfactants could effectively reduce algal blooms in water systems, and if added to paints, they could decrease algal growth on external building walls or other water immersed surfaces. [ABSTRACT FROM AUTHOR]

Long-chain sphingomyelins (SMs) may play an important role in the stability of myelin sheath underlying physical function. The objective of this study was to examine the cross-sectional and longitudinal associations of long-chain SMs [SM (41:1), SM (41:2), SM (43:1)] and ceramides [Cer (41:1) and Cer (43:1)] with physical function in the Atherosclerosis Risk in Communities (ARIC) study. Plasma concentrations of SM (41:1), SM (41:2), SM (43:1), Cer (41:1) and Cer (43:1) were measured in 389 ARIC participants in 2011–13. Physical function was assessed by grip strength, Short Physical Performance Battery (SPPB), 4-m walking speed at both 2011–13 and 2016–17, and the modified Rosow-Breslau questionnaire in 2016–2017. Multivariable linear and logistic regression analyses were performed, controlling for demographic and clinical confounders. In cross-sectional analyses, plasma concentrations of SM 41:1 were positively associated with SPPB score (β-coefficients [95% confidence internal]: 0.33 [0.02, 0.63] per 1 standard deviation [SD] increase in log-transformed concentration, p value 0.04), 4-m walking speed (0.042 m/s [0.01, 0.07], p value 0.003), and negatively with self-reported disability (odds ratio = 0.73 [0.65, 0.82], p value < 0.0001). Plasma concentrations of the five metabolites examined were not significantly associated with longitudinal changes in physical function or incidence of poor mobility. In older adults, plasma concentrations of long-chain SM 41:1 were cross-sectionally positively associated with physical function. [ABSTRACT FROM AUTHOR]

The use of X-ray flow visualization has brought a powerful new tool to the study of multiphase flows. Penetrating radiation can probe the spatial concentration of the different phases without the refraction, diffraction, or multiple scattering that usually produce image artifacts or reduce the signal-to-noise ratio below reliable values in optical visualization of multiphase flows; hence, X-ray visualization enables research into the three-dimensional (3D) structure of multiphase flows characterized by complex interfaces. With the commoditization of X-ray laboratory sources and wider access to synchrotron beam time for fluid mechanics, this novel imaging technique has shed light onto many multiphase flows of industrial and environmental interest under realistic 3D configurations and at realistic operating conditions (high Reynolds numbers and high volume fractions) that had defied study for decades. We present a broad survey of the most commonly studied multiphase flows (e.g., sprays, fluidized beds, bubble columns) in order to highlight the progress X-ray imaging has made in understanding the internal structure and multiphase coupling of these flows, and we discuss the potential of advanced tomography and time-resolved and particle tracking radiography for further study of multiphase flows. [ABSTRACT FROM AUTHOR]

Background: This study aimed to understand the status quo of delta checks in Chinese clinical laboratories through a nationwide online survey. Methods: The survey was divided into two parts. The first part was a general situation survey in which clinical laboratories had to provide information about the laboratories, including delta checks used. In the second part, clinical laboratories were asked to record the delta check alerts generated in their laboratories from June 1st, 2019 to June 30th, 2019. Results: The most frequently used analytes in delta checks were potassium (K), glucose (Glu), creatinine (Cre) for clinical chemistry and hemoglobin (Hgb), platelet (PLT) count and white blood cell (WBC) count for clinical hematology. The median maximum time interval between specimens for all analytes was 5 days. The most commonly used delta check calculation modes in Chinese clinical laboratories were percentage change and absolute change. K and Hgb were the analytes most involved in clinical chemistry and clinical hematology delta check alerts. The most common causes of delta check alerts were that the patients had received treatment, which was followed by the change in the patient's physiological state and interference from hemolysis, lipemia and icterus. The two most common outcomes of delta check alerts were 'no problems found, standard report issued' and 'no problems found, report issued with comment'. Conclusions: This study was the first nationwide survey of delta checks in China, the results of which help us to understand the current situation of delta checks in Chinese clinical laboratories. [ABSTRACT FROM AUTHOR]

Renal function-based carboplatin dosing is a well-accepted practice in pediatric oncology. However, the accuracy of this approach is only as precise as the method of kidney function measurement, most commonly involving determination of glomerular filtration rate (GFR). Recent work by the Children's Oncology Group has raised concerns over nuclear medicine-based methodologies used to calculate GFR across US clinical centers. Current practices of GFR measurement, methods used to calculate carboplatin dosage and the utility of therapeutic drug monitoring were investigated in 21 UK primary pediatric oncology treatment centers through a questionnaire-based study. Information obtained was compared to results previously published in 2008 following a similar survey. In relation to GFR measurement, the main changes observed were a shift toward a greater number of samples being taken following tracer administration and an increase in number of centers using the Brochner-Mortensen correction factor. In relation to the use of renal function assessment data to inform dosing, EDTA elimination half-life in conjunction with body weight was used to calculate carboplatin dose in 18/21 (86%) centers, with uncorrected GFR and body weight utilized in 9/21 (43%) centers. A total of 14/21 (67%) centers utilize therapeutic drug monitoring approaches to carboplatin treatment in defined patient groups including neonates and infants. Results suggest that while GFR measurement across UK centers is relatively consistent, some uncertainties remain. In addition, for patient sub-populations where there are concerns over the potential for marked inter-patient variability in carboplatin exposures, adaptive dosing approaches are now well established. [ABSTRACT FROM AUTHOR]

Background: Hematology analysis is a common test among patients in hospital. However, manual verification of hematology analysis is time consuming and tedious, with variation between inter-individual laboratory workers. This study was to establish and validate a set of autoverification rules for hematology analysis in the department of laboratory medicine, Zhongshan Hospital of Sun Yat-sen University. Methods: Hematology analysis was measured by a Sysmex XN-9000 hematology system in the Department of Laboratory Medicine, Zhongshan Hospital of Sun Yat-sen University. SYSMEX Laboman EasyAccess 6.0 and the laboratory information system were used to construct the algorithm and design the autoverification rules of hematology analysis according to Clinical and Laboratory Standards Institute document Auto 10A and 41 rules of Hematology Review Criteria. The laboratory turnaround time (TAT), autoverification pass rates, false positive, false negative, and the average error rate were verified after implementing autoverification rules. Results: Approximate 1,300 specimens were collected daily and transferred to our laboratory for hematology analysis; that is necessary to build a database and to design autoverification rules. The average autoverification passing rate was 81%; the false positive rate was 13.6%; the false negative rate and the average error rate was nearly zero, indicating that incorrect reports were almost eliminated. Moreover, since implementing autoverification, the TAT was reduced by 27.0% in in-patient reports, by 21.9% in out-patient reports, and by 39.0% in emergency reports, which enhanced the productivity in our laboratory. Conclusions: Our laboratory accelerated verification and decreased TAT and the odds of human review errors in the released results since implementing the autoverification. Thus, we can save more time and concentrate on verifying the abnormal results and processing emergency tests. [ABSTRACT FROM AUTHOR]

Liquid-ordered lipid domains represent a lateral inhomogeneity in cellular membranes. These domains have elastic and physicochemical properties different from those of the surrounding membrane. In particular, their thickness exceeds that of the disordered membrane. Thus, elastic deformations arise at the domain boundary in order to compensate for the thickness mismatch. In equilibrium, the deformations lead to an incomplete register of monolayer ordered domains: the elastic energy is minimal if domains in opposing monolayers lie on the top of each other, and their boundaries are laterally shifted by about 3 nm. This configuration introduces a region, composed of one ordered and one disordered monolayers, with an intermediate bilayer thickness. Besides, a jump in a local monolayer curvature takes place in this intermediate region, concentrating here most of the elastic stress. This region can participate in a lateral sorting of membrane inclusions by offering them an optimal bilayer thickness and local curvature conditions. In the present study, we consider the sorting of deformable lipid inclusions, undeformable peripheral and deeply incorporated peptide inclusions, and undeformable transmembrane inclusions of different molecular geometry. With rare exceptions, all types of inclusions have an affinity to the ordered domain boundary as compared to the bulk phases. The optimal lateral distribution of inclusions allows relaxing the elastic stress at the boundary of domains. [ABSTRACT FROM AUTHOR]

International standards and practice guidelines recommend the use of delta check alerts for laboratory test result interpretation and quality control. The value of contemporary applications of simple univariate delta checks determined as an absolute change, percentage change, or rate of change to recognize specimen misidentification or other laboratory errors has not received much study. This review addresses these three modes of calculation, but in line with the majority of published work, most attention is focused on the identification of specimen misidentification errors. Investigation of delta check alerts are time-consuming and the yield of identified errors is usually small compared to the number of delta check alerts; however, measured analytes with low indices of individuality frequently perform better. While multivariate approaches to delta checks suggest improved usefulness over simple univariate delta check strategies, some of these are complex and not easily applied in contemporary laboratory information systems and middleware. Nevertheless, a simple application of delta checks may hold value in identifying clinically significant changes in several clinical situations: for acute kidney injury using changes in serum creatinine, for risk of osmotic demyelination syndrome using rapid acute changes in serum sodium levels, or for early triage of chest pain patients using high sensitivity troponin assays. A careful and highly selective approach to identifying delta check analytes, calculation modes, and thresholds before putting them into practice is warranted; then follow-up with careful monitoring of performance and balancing true positives, false negatives, and false positives among delta check alerts is needed. [ABSTRACT FROM AUTHOR]

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Purpose Following the analytical phase, the current practice of many hospital laboratories involves the manual verification of all test results followed by the production of the report. However, manual verification is a time-consuming and tedious process. In this paper, we provide a detailed description of how to design autoverification rules for thyroid function test profiles and sex hormones. Materials and methods We used DM2 (Data manager 2) to construct the algorithm and build the database for autoverification of thyroid function test profiles and sex hormones, with reference to Boolean logic, Auto 10-A and CLSI'88. The rules consist of checking quality control, instrument error flags, critical values, the analytical measurement range (AMR), the limit range, consistency check and delta check. Firstly, we established the rules in the DM2, collected clinical specimens for validation, then tested the rules in a 'live' environment. Results Agreement was achieved between manual verification by two senior laboratory personnel and verification using the autoverification rules in 99.78% of the cases. The total autoverification rate for all tests was 77.06%. Following implementation of the rules, the laboratory turnaround time (TAT) was reduced by 54.55% and staffing numbers fell from three to two whole time equivalents (WTE). Statistical analysis resulted in a kappa statistic of 0.99 ( P < 0.001). Moreover, after implementing the autoverification rules, the error rate fell to 0.04%, indicating that errors were almost completely eliminated. Conclusion Implementing autoverification rules can reduce TAT, minimize the number of samples that require manual verification and allow for a reduction in staffing numbers. It also allows laboratory staff to devote more time and effort to the handling of problematic test results and contributing to improved patient care. [ABSTRACT FROM AUTHOR]

The significance of minimal increases in serum creatinine below the levels indicative of the acute kidney injury (AKI) stage is not well established. We aimed to investigate the influence of pre-stage AKI (pre-AKI) on clinical outcomes. We enrolled a total of 21,261 patients who were admitted to the Seoul National University Bundang Hospital from January 1, 2013 to December 31, 2013. Pre-AKI was defined as a 25–50% increase in peak serum creatinine levels from baseline levels during the hospital stay. In total, 5.4% of the patients had pre-AKI during admission. The patients with pre-AKI were predominantly female (55.0%) and had a lower body weight and lower baseline levels of serum creatinine (0.63 ± 0.18 mg/dl) than the patients with AKI and the patients without AKI (P < 0.001). The patients with pre-AKI had a higher prevalence of diabetes mellitus (25.1%) and malignancy (32.6%). The adjusted hazard ratio of in-hospital mortality for pre-AKI was 2.112 [95% confidence interval (CI), 1.143 to 3.903]. In addition, patients with pre-AKI had an increased length of stay (7.7 ± 9.7 days in patients without AKI, 11.4 ± 11.4 days in patients with pre-AKI, P < 0.001) and increased medical costs (4,061 ± 4,318 USD in patients without AKI, 4,966 ± 5,099 USD in patients with pre-AKI, P < 0.001) during admission. The adjusted hazard ratio of all-cause mortality for pre-AKI during the follow-up period of 2.0 ± 0.6 years was 1.473 (95% CI, 1.228 to 1.684). Although the adjusted hazard ratio of pre-AKI for overall mortality was not significant among the patients admitted to the surgery department or who underwent surgery, pre-AKI was significantly associated with mortality among the non-surgical patients (adjusted HR 1.542 [95% CI, 1.330 to 1.787]) and the patients admitted to the medical department (adjusted HR 1.384 [95% CI, 1.153 to 1.662]). Pre-AKI is associated with increased mortality, longer hospital stay, and increased medical costs during admission. More attention should be paid to the clinical significance of pre-AKI. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a significant independent risk factor for morbidity and mortality. In the last ten years a large number of publications have highlighted the limitations of traditional approaches and the inadequacies of conventional biomarkers to diagnose and monitor renal insufficiency in the acute setting. A great effort was directed not only to the discovery and validation of new biomarkers aimed to detect AKI more accurately but also to standardise the definition of AKI. Despite the advances in both areas, biomarkers have not yet entered into routine clinical practice and the definition of this syndrome has many areas of uncertainty. This review will discuss the controversies in diagnosis and the potential of novel biomarkers to improve the definition of the syndrome. [ABSTRACT FROM AUTHOR]

Lipid rafts play a pivotal role in physiological functions of platelets. Their isolation using nonionic mild detergents is considered as the gold standard method, but there is no consensual detergent for lipid raft studies. We aimed to investigate which detergent is the most suitable for lipid raft isolation from platelet membrane, based on lipidomics and proteomics analysis. Platelets were obtained from healthy donors. Twelve sucrose fractions were extracted by three different detergents, namely Brij 35, Lubrol WX, and Triton X100, at 0.05% and 1%. After lipidomics analysis and determination of fractions enriched in cholesterol (Ch) and sphingomyelin (SM), proteomics analysis was performed. Lipid rafts were mainly observed in 1–4 fractions, and non-rafts were distributed on 5–12 fractions. Considering the concentration of Ch and SM, Lubrol WX 1% and Triton X100 1% were more suitable detergents as they were able to isolate lipid raft fractions that were more enriched than non-raft fractions. By proteomics analysis, overall, 822 proteins were identified in platelet membrane. Lipid raft fractions isolated with Lubrol WX 0.05% and Triton X100 1% contained mainly plasma membrane proteins. However, only Lubrol WX 0.05 and 1% and Triton X100 1% were able to extract non-denaturing proteins with more than 10 transmembrane domains. Our results suggest that Triton X100 1% is the most suitable detergent for global lipid and protein studies on platelet plasma membrane. However, the detergent should be adapted if investigation of an association between specific proteins and lipid rafts is planned. [ABSTRACT FROM PUBLISHER]

Cancer-related and primary lymphedema (LE) are associated with the production of adipose tissue (AT). Nothing is known, however, about the lipid-based molecules that comprise LE AT. We therefore analyzed lipid molecules in lipoaspirates and serum obtained from LE patients, and compared them to lipoaspirates from cosmetic surgery patients and healthy control cohort serum. LE patient serum analysis demonstrated that triglycerides, HDL- and LDL-cholesterol and lipid transport molecules remained within the normal range, with no alterations in individual fatty acids. The lipidomic analysis also identified 275 lipid-based molecules, including triacylglycerides, diacylglycerides, fatty acids and phospholipids in AT oil and fat. Although the majority of lipid molecules were present in a similar abundance in LE and non-LE samples, there were several small changes: increased C20:5-containing triacylglycerides, reduced C10:0 caprinic and C24:1 nervonic acids. LE AT oil also contained a signature of increased cyclopropane-type fatty acids and inflammatory mediators arachidonic acid and ceramides. Interestingly C20:5 and C22:6 omega-3-type lipids are increased in LE AT, correlating with LE years. Hence, LE AT has a normal lipid profile containing a signature of inflammation and omega-3-lipids. It remains unclear, however, whether these differences reflect a small-scale global metabolic disturbance or effects within localised inflammatory foci. [ABSTRACT FROM AUTHOR]

Ceramides are mediators of inflammatory processes. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we observed that CerS6 mRNA expression was upregulated 15‐fold in peripheral blood leukocytes before the onset of EAE symptoms. In peripheral blood leukocytes from MS patients, a 3.9‐fold upregulation was found. Total genetic deletion of CerS6 and the selective deletion of CerS6 in peripheral blood leucocytes exacerbated the progression of clinical symptoms in EAE mice. This was associated with enhanced leukocyte, predominantly neutrophil infiltration and enhanced demyelination in the lumbar spinal cord of EAE mice. Interferon‐gamma/tumor necrosis factor alpha (IFN‐γ/TNF‐α) and granulocyte colony‐stimulating factor (G‐CSF) both drive EAE development and induce expression of the integrin CD11b and the chemokine receptor C‐X‐C motif chemokine receptor 2 (CXCR2), and we found they also induce CerS6 expression. In vivo, the genetic deletion of CerS6 enhanced the activation/migration of neutrophils, as reflected by an enhanced upregulation of CD11b and CXCR2. In vitro, the genetic deletion of CerS6 enhanced the activation status of IFN‐γ/TNF‐α‐stimulated neutrophils, as shown by increased expression of nitric oxide and CD11b and an increased adhesion capacity. In G‐CSF‐stimulated neutrophils, the migration status was enhanced, as reflected by an elevated level of CXCR2 and an increased migration capacity. These data suggest that CerS6/C16‐Cer mediates feedback regulation by inhibiting the formation of CD11b and CXCR2, which are induced either by IFN‐γ/TNF‐α or by G‐CSF, respectively. We conclude that CerS6/C16‐Cer mediates anti‐inflammatory effects during the development of EAE and MS possibly by suppressing the migration and deactivation of neutrophils. [ABSTRACT FROM AUTHOR]

Oxygen is necessary for aerobic metabolism. Since the human body cannot produce or store oxygen, a continuous and adequate delivery of oxygen needs to be secured by oxygen uptake from inhaled air via the respiratory system and oxygen delivery to body tissues via the circulation. Severely reduced lung function in advanced chronic obstructive pulmonary disease (COPD) may be a limiting factor for adequate oxygen uptake and patients with this disease may require supplemental oxygen therapy. While the methodology of oxygen delivery in home settings represents a continuously evolving field, oxygen therapy itself has been an integral part of the management of severely hypoxemic patients with COPD for more than 50 years despite the lack of full understanding of its effects and the relative paucity of clinical evidence supporting its use. In this article, we review the physiological effects and discuss the clinical benefits of oxygen therapy. We also evaluate the evidence supporting and arguing against its use in the published literature, discuss its risks and benefits, define criteria for prescribing oxygen therapy, and review methods of oxygen delivery in home settings. [ABSTRACT FROM AUTHOR]

Background: Population-based reference intervals have very limited value for the interpretation of laboratory results when analytes display high biological individuality. In these cases, the longitudinal evaluation of individual results using the reference change value (RCV) is the recommended approach. However, the traditional model for RCV calculation requires a Gaussian frequency distribution of data and risks to overestimate the parameter if a correlation between within-subject serial measurements is present. Methods: We propose and validate an alternative non-parametric statistical model for interpretation of differences in serial results from an individual, overcoming data distribution and correlation issues. Results: After describing the traditional and newly proposed statistical models, we compared them with each other using a simulation on three specific analytes displaying different concentration distributions in biological setting. We demonstrated that when analyte concentrations followed a Gaussian frequency distribution, as in the case of glycated hemoglobin, both methods can be used equally. On the contrary, if analyte concentrations present a bimodal (e.g., chromogranin A) or skewed (e.g., C-reactive protein) distribution, the information obtained by two statistical methods is different. Conclusions: The proposed statistical approach may be more appropriate in assessing difference between serial measurements when individual data are not normally distributed. [ABSTRACT FROM AUTHOR]

Increases in muscle energy needs activate AMPK and induce sarcolemmal recruitment of the fatty acid (FA) translocase CD36. The resulting rises in FA uptake and FA oxidation are tightly correlated, suggesting coordinated regulation. We explored the possibility that membrane CD36 signaling might influence AMPK activation. We show, using several cell types, including myocytes, that CD36 expression suppresses AMPK, keeping it quiescent, while it mediates AMPK activation by FA. These dual effects reflect the presence of CD36 in a protein complex with the AMPK kinase LKB1 (liver kinase B1) and the src kinase Fyn. This complex promotes Fyn phosphorylation of LKB1 and its nuclear sequestration, hindering LKB1 activation of AMPK. FA interaction with CD36 dissociates Fyn from the protein complex, allowing LKB1 to remain cytosolic and activate AMPK. Consistent with this, CD362/2 mice have constitutively active muscle and heart AMPK and enhanced FA oxidation of endogenous triglyceride stores. The molecular mechanism described, whereby CD36 suppresses AMPK, with FA binding to CD36 releasing this suppression, couples AMPK activation to FA availability and would be important for the maintenance of cellular FA homeostasis. Its dysfunction might contribute to the reported association of CD36 variants with metabolic complications of obesity in humans. [ABSTRACT FROM AUTHOR]

Objectives: While acute kidney injury (AKI) can be diagnosed based on specified increases in a patient's plasma creatinine level, standard creatinine reporting methods typically only flag creatinine results as abnormal when outside the reference range and often fail to identify rising creatinine values indicative of AKI. Here, we evaluate the impact of this limitation in standard creatinine reporting and develop and implement an enhanced creatinine reporting algorithm. Methods: We evaluated 59,712 plasma creatinine results collected over approximately 3 months, using computational simulations and statistical analyses. Results: Our analyses demonstrated that 29% of creatinine results substantially increased over the patient's baseline and concerning for AKI remained within the normal reference range. These concerning results would not be flagged as abnormal using standard reporting. Likewise, we found that simple delta checks are also insensitive at AKI detection. To improve creatinine reporting, we developed and implemented an algorithm within our laboratory information system to alert clinicians to rising creatinine results, which we describe in this report. Conclusion: While both creatinine reference limits and simple delta checks are insensitive for AKI identification, a simple algorithm can be implemented within a common laboratory information system to enhance AKI identification. [ABSTRACT FROM AUTHOR]

ABSTRACT We report here the results of studies aimed to investigate the involvement of serotonin receptor 7 subtype (5-HT7-R) in the modulation of emotional response in Naples High-Excitability (NHE) rat, a validated model for hyperactivity and impaired attention. A range of dosages (0.0, 0.125, 0.250, or 0.500 mg/kg) of LP-211, a selective agonist of 5-HT7-Rs, has been evaluated in animals at different age (adolescence and adulthood). Male NHE and random bred (NRB) control rats were tested in an Elevated Zero-Maze (EZM) after LP-211 treatment in two different regimens: at the issue of adolescent, subchronic exposure (14 intraperitoneal [i.p.] injections, once/day, pnd 31-44, tested on pnd 45-Exp. 1) or as adult, acute effect (15 min after i.p. injection-Exp. 2). Adolescent, subchronic LP-211 at 0.500 mg/kg dosage increased the frequency of head-dips only in NHE rats. Drug effect on time spent and entries in open EZM quadrants were revealed with adult, acute administration of 0.125 mg/kg LP-211 (both strains), indicating a tendency toward anxiolytic effects. In conclusion, data demonstrate that subchronic stimulation of 5-HT7-Rs during prepuberal period increases novelty-seeking/risk-taking propensity in NHE adults. These sequels are revealing increased disinhibition and/or motivation to explore in the NHE rats, which are characterized by a hyperactive dopaminergic system. These data may open new perspectives in studying mechanism of risk-seeking behavior. Synapse 68:159-167, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The cell type of election for the study of cell membranes, the mammalian non-nucleated erythrocyte, has been scarcely considered in the research of membrane rafts of the plasma membrane. However, detergent-resistant-membranes (DRM) were actually first described in human erythrocytes, as a fraction resisting solubilization by the nonionic detergent Triton X-100. These DRMs were insoluble entities of high density, easily pelleted by centrifugation, as opposed to the now accepted concept of lipid raft-like membrane fractions as material floating in low-density regions of sucrose gradients. The present article reviews the available literature on membrane rafts/DRMs in human erythrocytes from an historical point of view, describing the experiments that provided the solution to the above described discrepancy and suggesting possible avenue of research in the field of membrane rafts that, moving from the most studied model of living cell membrane, the erythrocyte's, could be relevant also for other cell types. [ABSTRACT FROM AUTHOR]

Objective: Recent data suggest that 5-HT receptors (5-HTR) are involved in memory processes and, particularly, those related to novelty-induced arousal, even though this remains so far speculative and controversial. In order to assess the role of 5-HTR in episodic-like memory, mice were administered 5-carboxamidotryptamine (5-CT, a 5-HTR agonist) and/or SB-269970 (a selective 5-HTR antagonist) immediately after the acquisition session of the novel object recognition test. Materials and methods: The object recognition test was performed in order to assess the effects of modulation of 5-HTR during consolidation phase on episodic-like memory performances in mice. A protocol including 3 days of familiarisation to the apparatus has been realised in order to decrease the effect of novelty-induced arousal. Results: With a 2-h delay, SB-269970 (3 and 10 mg/kg, administered subcutaneously) impaired the discrimination of the novel object. With a 4-h delay, while control mice were not able to discriminate the novel object, mice treated with 5-CT (1 mg/kg) showed a significant discrimination. This promnesic effect with a long delay is effectively mediated by 5-HTR activation since it was blocked by SB-269970 (10 mg/kg), but not by WAY-100135 (10 mg/kg) or by GR-127935 (10 mg/kg). Conclusion: These data suggest that 5-HTR tonically modulates cognitive processes involved in consolidation performances in object recognition. Therefore, 5-HTR could be a promising target to treat memory dysfunctions (especially episodically related deficits) related to normal or pathological ageing. [ABSTRACT FROM AUTHOR]

Serotonin 7 (5-hydroxytryptamine7 or 5-HT) is the most recently identified serotonin receptor. It is involved in mood disorders and is studied as a target for antidepressants. Here, we report on the structural manipulation of the 5-HT receptor ligand 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine ( 1a) aimed at obtaining 5-HT receptor ligands endowed with good in vitro metabolic stability. A set of N-[3-methoxyphenyl)ethyl-substituted] 1-arylpiperazine, 4-arylpiperidine and 1-aryl-4-aminopiperidine was synthesized and tested in radioligand binding assays at human cloned 5-HT and 5-HT receptors. In vitro metabolic stability of the target compounds was assessed after incubation with rat hepatic S9 microsomal fraction. Among the new compounds, 1-(2-biphenyl)-4-[2-(3-methoxyphenyl)ethyl]piperazine ( 1d) and 4-(2-biphenyl)-1-[2-(3-methoxyphenyl)ethyl]piperidine ( 2d) showed a good compromise between affinity at 5-HT receptor ( K = 7.5 nM and 13 nM, respectively) and in vitro metabolic stability (26 and 65 % recovery of parent compound, respectively) but were poorly selective over 5-HT receptor. [ABSTRACT FROM AUTHOR]