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Uncontrollable bleeding is recognized as the leading cause of preventable death among trauma patients. Early transfusion of blood products, especially plasma replacing crystalloid and colloid solutions, has been shown to increase survival of severely injured patients. However, the requirements for cold storage and thawing processes prior to transfusion present significant logistical challenges in prehospital and remote areas, resulting in a considerable delay in receiving thawed or liquid plasma, even in hospitals. In contrast, freeze- or spray-dried plasma, which can be massively produced, stockpiled, and stored at room temperature, is easily carried and can be reconstituted for transfusion in minutes, provides a promising alternative. Drawn from history, this paper provides a review of different forms of dried plasma with a focus on in vitro characterization of hemostatic properties, to assess the effects of the drying process, storage conditions in dry form and after reconstitution, their distinct safety and/or efficacy profiles currently in different phases of development, and to discuss the current expectations of these products in the context of recent preclinical and clinical trials. Future research directions are presented as well. [ABSTRACT FROM AUTHOR]

Summary: During World War II, Charles H. Best utilized Charles R. Drew's plasma isolation and drying technique to lead Canada's initiative to provide dried serum as a means of primary resuscitation for British casualties on the frontlines. Serum was likely utilized over plasma for its volume expansion properties without the risk of clotting during prolonged storage. We reconstituted dried serum from 1943 and discovered intact albumin, as well as anti‐thrombin, plasminogen, protein C and protein S activity. Proteomic analysis identified 71 proteins, most prominent being albumin, and positive for hepatitis B by serological testing. Transmission of blood‐borne diseases ended the programme, until modern advances in testing and pathogen reduction revived this technology. We tested the latest iteration of Canadian freeze‐dried plasma (FDP), which was stored for 4 years, and demonstrated that its clotting capacity remained equivalent to fresh frozen plasma. We recommend that FDP is a strong alternative to contemporary prehospital resuscitation fluids (e.g. normal saline/lactated Ringer's) in managing prehospital haemorrhage where whole blood is unavailable. [ABSTRACT FROM AUTHOR]

Despite the importance of the hemostatic properties of reconstituted freeze-dried plasma (FDP) for trauma resuscitation, few studies have been conducted to determine its post-reconstitution hemostatic stability. This study aimed to assess the short- (≤24 h) and long-term (≥168 h) hemostatic stabilities of Canadian and German freeze-dried plasma (CFDP and LyoPlas) after reconstitution and storage under different conditions. Post-reconstitution hemostatic profiles were determined using rotational thromboelastometry (ROTEM) and a Stago analyzer, as both are widely used as standard methods for assessing the quality of plasma. When compared to the initial reconstituted CFDP, there were no changes in ROTEM measurements for INTEM maximum clot firmness (MCF), EXTEM clotting time (CT) and MCF, and Stago measurements for prothrombin time (PT), partial thromboplastin time (PTT), D-dimer concentration, plasminogen, and protein C activities after storage at 4 °C for 24 h and room temperature (RT) (22–25 °C) for 4 h. However, an increase in INTEM CT and decreases in fibrinogen concentration, factors V and VIII, and protein S activities were observed after storage at 4 °C for 24 h, while an increase in factor V and decreases in antithrombin and protein S activities were seen after storage at RT for 4 h. Evaluation of the long-term stability of reconstituted LyoPlas showed decreased stability in both global and specific hemostatic profiles with increasing storage temperatures, particularly at 35 °C, where progressive changes in CT and MCF, PT, PTT, fibrinogen concentration, factor V, antithrombin, protein C, and protein S activities were seen even after storage for 4 h. We confirmed the short-term stability of CFDP in global hemostatic properties after reconstitution and storage at RT, consistent with the shelf life of reconstituted LyoPlas. The long-term stability analyses suggest that the post-reconstitution hemostatic stability of FDP products would decrease over time with increasing storage temperature, with a significant loss of hemostatic functions at 35 °C compared to 22 °C or below. Therefore, the shelf life of reconstituted FDP should be recommended according to the storage temperature. [ABSTRACT FROM AUTHOR]

Background: Freeze‐dried plasma (FDP) is a promising blood component for prehospital resuscitation given its logistic advantages over fresh frozen plasma (FFP). COVID‐19 convalescent (CC) plasma has been used to treat coronavirus disease 2019 (COVID‐19) patients, and its corresponding FDP has potential use during future pandemics. Therefore, we conducted the study to determine if the hemostatic and immunological properties of plasma can be retained after lyophilization. Study design and methods: Hemostatic tests were conducted with Rotational Thromboelastometry (ROTEM) and a Stago analyzer. Anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) IgG (Immunoglobulin G) and neutralizing activity were analyzed using Meso Scale Diagnostics immunoassay kits. Results: There were no differences in ROTEM parameters and Stago measurements for prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen and D‐dimer concentrations, and antithrombin, factor V, VIII, and protein S activities between FFP and FDP for either pre‐COVID‐19 or CC samples. Differences were observed in INTEM clotting time and PT and PTT when comparing reconstituted FDP stored at 4°C for 24 h or room temperature for 4 h to healthy control. Both CC‐FFP and CC‐FDP showed two orders of magnitude higher concentrations of IgG antibodies against SARS‐CoV‐2 antigens than pre‐COVID‐19‐FFP and pre‐COVID‐19‐FDP and healthy control. Similarly, the CC samples showed approximately 4‐fold higher %‐inhibition of receptor binding than the pre‐COVID‐19 samples. There were no differences in either the antibody levels or neutralization activity between CC‐FFP and CC‐FDP. Discussion: We demonstrated that FDP and CC‐FDP retained the same hemostatic and antibody functional activities relative to their initial plasma sources, supporting clinical evaluation of their benefits in severe trauma and COVID‐19 patients. [ABSTRACT FROM AUTHOR]

Let R k = diag (r k , 1 , r k , 2 , ... , r k , n) be the n × n expanding integer diagonal matrix, and let D k ⊂ Z n . We show that the sequence of Hadamard triples { (R k , D k , S k) } admits a spectrum of the associated Moran measure under specific situations. The results are new in all dimensions n greater than two. [ABSTRACT FROM AUTHOR]

A high power diode laser (HPDL) was successfully used as a surface modifying approach on a hot dip process simulator (HDPS) Zn-55Al-3Mg-1.5Si coating. The overlay microstructure was drastically refined owing to the rapid cooling rate of the laser radiation process, in which the size of a-Al dendrite was shrunk to less than 1/10 of the original. The laser also varied the solidifying path and yielded different phases in the interdendritic areas leading to modifications including, rare Si, disappearance of MgZn2 and nucleation of the Q phase. The modified Zn-55Al-3Mg-1.5Si coating induced by HPDL surface treatment is assumed to make a contribution to the improvement of the corrosion resistance. [ABSTRACT FROM AUTHOR]

Background: Hemorrhage is a leading cause of preventable death in civilian and military trauma. Freeze-dried plasma is promising for hemostatic resuscitation in remote prehospital settings, given its potential benefits in reducing blood loss and mortality, long storage at ambient temperatures, high portability, and rapid reconstitution for transfusion in austere environments. Here we assess the ex vivo characteristics of a novel Terumo's freeze-dried plasma product (TFDP).Study Design and Methods: Rotational thromboelastometry (ROTEM) tests (INTEM, EXTEM, and FIBTEM) were conducted on plasma samples at 37°C with a ROTEM delta-machine using standard reagents and procedures. The following samples were analyzed: pooled plasma to produce TFDP, TFDP reconstituted, and stored immediately at -80°C, reconstituted TFDP stored at 4°C for 24 h and room temperature (RT) for 4 h before freezing at -80°C. Analysis of plasma concentrations of selected cytokines, chemokines, and vascular molecules was performed using a multiplex immunoassay system. One-way ANOVA with post hoc tests assessed differences in hemostatic and inflammatory properties.Results: No significant differences in ROTEM variables (coagulation time [CT], clot formation time, α-angle, maximum clot firmness, and lysis index 30) between the TFDP-producing plasma and reconstituted TFDP samples were observed. Compared to control plasma, reconstituted TFDP stored at 4°C for 24 h or RT for 4 h showed a longer INTEM CT. Levels of immuno-inflammatory mediators were similar between frozen plasma and TFDP.Conclusions: TFDP is equivalent to frozen plasma with respect to global hemostatic and immuno-inflammatory mediator profiles. Further investigations of TFDP in trauma-induced coagulopathy models and bleeding patients are warranted. [ABSTRACT FROM AUTHOR]

Background: Coagulopathic bleeding is frequently present after major trauma. However, trauma-induced coagulopathy (TIC) remains incompletely understood. This laboratory analysis of blood samples derived from our completed trial on fibrinogen in the initial resuscitation of severe trauma (FiiRST) was conducted to evaluate TIC and associated responses to fibrinogen replacement.Study Design and Methods: We conducted a retrospective evaluation of TIC in 45 FiiRST trial patients based on rotational thromboelastometry (ROTEM), international normalized ratio (INR), and biomarkers for hemostasis and endotheliopathy. Whole blood was analyzed by ROTEM. Plasma was analyzed for INR and biomarkers.Results: Overall, 19.0% and 30.0% of the FiiRST trial patients were coagulopathic on admission defined by EXTEM maximum clot firmness out of the range of 40-71 mm and INR >1.2, respectively. The FiiRST patients showed lower fibrinogen, factor II and V levels, protein C and antiplasmin activities, higher activated protein C, tissue plasminogen activator, d-dimer, and thrombomodulin concentrations at admission than healthy controls. Most of the biomarkers changed their activities during 48-h hospitalization, but were at abnormal levels even 48-h after admission. The fibrinogen treatment reduced hypofibrinogenemia and increased factor XIII level, but had no significant effects on other biomarkers levels. Limited development of endotheliopathy was indicated by syndean-1, thrombomodulin, and sE-selectin.Conclusions: About 19%-30% of the trauma patients in the FiiRST trial were coagulopathic on hospital admission depending on the definition of TIC. Analyses of the TIC biomarkers demonstrated that hemostasis would not return to normal after 48-h hospitalization, and fibrinogen replacement improved hypofibrinogenemia. [ABSTRACT FROM AUTHOR]

Introduction: Canadian Armed Forces adopted fibrinogen concentrate (RiaSTAP) for hemostatic resuscitation in the far-forward combat setting, given its potential benefits of reducing blood loss, blood transfusion and mortality, and its long storage stability and high portability. The current guidance recommends that RiaSTAP should be administered within 8 hours after reconstitution when stored at room temperature. However, little information about its stability is available. There is also a need to investigate the stability and efficacy of RiaSTAP after reconstitution and exposure to extreme temperatures in which our forces may operate.Materials and Methods: RiaSTAP was reconstituted as per manufacturer's instruction and stored at specific temperatures (-20°C, 4°C, 22°C, 35°C, 42°C, or 50°C) for up to 6 months. Reconstituted RiaSTAP was also oscillated on a rocker at 18 rpm under 22°C and 50°C. Its hemostatic function was measured using rotational thromboelastometry performed with RiaSTAP-spiked whole blood. Fibrinogen concentrations were measured by a commercial enzyme-linked immunosorbent assay (ELISA) kit. Gel electrophoresis was also conducted for initial and stored samples.Results: We found no change to the hemostatic function of reconstituted RiaSTAP after storage at -20°C for 6 months. At 4°C, no obvious changes to the hemostatic effect of reconstituted RiaSTAP relative to 0 hours were seen until 1,680 hours. At 22°C, a remarkable decrease began after storage for 168 hours. Storage at 35°C significantly decreased the hemostatic effect after 144 hours, while the storage at 42°C resulted in decreased hemostatic function after 72 hours. Finally, storage at 50°C for 8 hours resulted in complete loss of hemostatic function. Compared to the hemostatic activity, the fibrinogen concentration for reconstituted RiaSTAP showed less change over time. No apparent decline in fibrinogen concentration was seen after storage at -20°C for 6 months and at 4°C for 1,680 hours. At 22°C, there were no clear alterations until 792 hours. There was a decline in fibrinogen concentration at 35°C and 42°C after 672 and 600 hours of storage, respectively. At 50°C, little amount of fibrinogen was detected by ELISA at 8 hours. Similar changes in the hemostatic effect and fibrinogen concentration over time were observed under the rocking condition in comparison with the static condition at the same temperature. The gel electrophoresis confirmed fibrinogen degradation which increased with storage temperature and time.Conclusions: The stability of reconstituted RiaSTAP decreases with increasing storage temperature. The hemostatic function deteriorated before fibrinogen concentration and integrity were significantly altered at all temperatures for the study period except at 50°C where there was a rapid decline in both hemostatic function and fibrinogen concentration. Sample oscillation did not significantly affect its stability. The shelf life of reconstituted RiaSTAP may, therefore, be recommended accordingly when stored at different temperatures and extended to 6 days at room temperature provided that sterility is maintained. [ABSTRACT FROM AUTHOR]

Background: Evidence for the relationship between antidepressant use during pregnancy and the risk of attention-deficit/hyperactivity disorder (ADHD) in the children is conflicting.Objective: To assess the association between fetal exposure to antidepressant drugs and the subsequent development of ADHD.Search Strategy: A systematic literature search was conducted in PubMed, EMBASE, PsycINFO, and CINAHL databases to identify relevant cohort studies published from inception until October 2017.Selection Criteria: Cohort studies, identifying children with ADHD diagnosis and linking antidepressant use during pregnancy in their mothers.Data Collection: Two reviewers independently abstracted data and assessed study quality.Main Results: The literature search identified six relevant cohort studies with association between antidepressant exposure during pregnancy and the risk of ADHD in children [hazard ratio (HR) 1.34; 95% confidence interval (CI) 1.14-1.57]. However, the association was not statistically significant when the reference group was mothers with psychiatric disorders not treated during pregnancy (HR 0.96; 95% CI 0.76-1.2; n = 2 studies). Moreover, preconception exposure to antidepressants was significantly associated with increased risk of ADHD (HR 1.82; 95% CI 1.54-2.15; n = 3 studies).Conclusions: The significant association between antidepressant exposure during pregnancy and ADHD in the children can be partially explained by confounding by indication. Given the low number of included studies, further studies with prospective designs that use validated measurements and controls for important confounders are needed to verify our findings.Tweetable Abstract: Antidepressant use during pregnancy may be not associated with ADHD in the offspring. [ABSTRACT FROM AUTHOR]

Both thrombelastography (TEG) and rotational thromboelastometry (ROTEM) have been investigated for diagnosis of coagulopathy and guidance of resuscitation in trauma and surgery. Given similarities between the two systems, it is important to determine whether one is superior to the other and how comparable they are to conventional coagulation tests (CCTs). Therefore, we conducted a comparative study of functional fibrinogen and coagulation assays using TEG and ROTEM and CCTs to determine their capability to monitor coagulation profiles, diagnose coagulopathy and predict blood transfusion requirements in trauma patients. Blood samples were collected from 45 patients at admission and during 48-h hospitalization as part of a randomized control trial on early fibrinogen replacement in trauma. Functional fibrinogen (FF) TEG, ROTEM FIBTEM and EXTEM, and CCTs were performed and compared. We found significant differences between the placebo and fibrinogen groups over hospitalization time in FF TEG MA, ROTEM CT, MCF and LI30. FF TEG MA and ROTEM FIBTEM MCF mirrored plasma fibrinogen profiles, reached a maximum difference between the two groups 1–3 h after fibrinogen administration. In comparison, CCTs detected minimal hemostatic changes by fibrinogen treatment. TEG and ROTEM showed various degrees of correlations with CCTs. TEG MA and ROTEM MCF provided better predictions for plasma and RBC transfusions than CCTs, but poor accuracy for cryoprecipitate transfusion. Both TEG and ROTEM well predicted hypofibrinogenemia (fibrinogen concentration < 1 g/L), but poorly detected coagulopathy (INR ≥ 1.2). TEG and ROTEM detected increases in clot strength following early use of fibrinogen. ROTEM also detected changes in coagulation time and clot lysis. Both were better than CCTs for monitoring coagulation profiles and predicting transfusion requirements. • TEG and ROTEM play an important role in monitoring and guiding transfusion decisions in trauma. • TEG and ROTEM fibrinogen assays were compared with conventional coagulation tests (CCTs) in trauma patients. • TEG and ROTEM were superior to INR and PTT to detect the effects of fibrinogen replacement on hemostasis. • ROTEM FIBTEM detected more changes in parameters than functional fibrinogen TEG. • TEG and ROTEM fibrinogen assays provided better predictions for RBC and plasma transfusions than CCTs. [ABSTRACT FROM AUTHOR]

Fibrinogen is crucial for the formation of blood clot and clinical outcomes in major bleeding. Both Thromboelastography (TEG) and Rotational Thromboelastometry (ROTEM) have been increasingly used to diagnose fibrinogen deficiency and guide fibrinogen transfusion in trauma and surgical bleeding patients. We conducted a comprehensive and comparative review on the technologies and clinical applications of two typical functional fibrinogen assays using TEG (FF TEG) and ROTEM (FIBTEM) for assessment of fibrinogen level and deficiency, and prediction of transfusion requirement. Clot strength and firmness of FF TEG and ROTEM FIBTEM were the most used parameters, and their associations with fibrinogen levels as measured by Clauss method ranged from 0 to 0.9 for FF TEG and 0.27 to 0.94 for FIBTEM. A comparison of the interchangeability and clinical performance of the functional fibrinogen assays using the two systems showed that the results were correlated, but are not interchangeable between the two systems. It appears that ROTEM FIBTEM showed better associations with the Clauss method and more clinical use for monitoring fibrinogen deficiency and predicting transfusion requirements including fibrinogen replacement than FF TEG. TEG and ROTEM functional fibrinogen tests play important roles in the diagnosis of fibrinogen-related coagulopathy and guidance of transfusion requirements. Despite the fact that high-quality evidence is still needed, the two systems are likely to remain popular for the hemostatic management of bleeding patients. [ABSTRACT FROM AUTHOR]

Introduction: Tactical Combat Casualty Care (TCCC) training imposes psychophysiological stress on medics. It is unclear whether these stress levels vary with the training modalities selected. It is also unclear how stress levels could have an impact on medical performance and skill uptake.Materials and Methods: We conducted a pilot study to compare the effects of live tissue (LT) with a high-fidelity patient simulator (SIM) on the level of stress elicited, performance, and skill uptake during battlefield trauma training course in an operating room (OR) and in a simulated battlefield scenario (field). In the report, we studied the effects of training modalities and their changes on stress levels by measuring different biomarkers (salivary amylase, plasma catecholamines, and neuropeptide Y) at various time points during the trauma training course.Results: We found that the training resulted in significant psychophysiological stress as indicated by elevated levels of various biomarkers relative to baseline immediately after both OR and field assessment (p < 0.05). Compared with pre-OR levels, the LT training in the OR resulted in significant increases in the plasma levels of epinephrine, norepinephrine, and neuropeptide (p = 0.013, 0.023, 0.004, respectively), whereas the SIM training in the OR resulted in significant increases in the plasma levels of norepinephrine and neuropeptide (p = 0.003 and 0.008). Compared with pre-field levels, we found significant increases in plasma epinephrine concentration in the SIM group (p = 0.016), plasma norepinephrine concentration in the LT group (p = 0.015), and plasma neuropeptide Y concentration in both LT (p = 0.006) and SIM groups (p = 0.029). No differences in the changes of biomarker levels were found between LT and SIM groups in the OR and field. Compared with pre-field levels, the testing on the same modality as that in the OR in the simulated battlefield resulted in significant increases in norepinephrine and neuropeptide levels (p = 0.013 and 0.015), whereas the testing on different modalities resulted in significant increases in amylase, epinephrine, and neuropeptide levels (p = 0.016, 0.05, 0.018, respectively). There was a significantly larger increase in plasma norepinephrine concentration (p = 0.031) and a trend toward a greater increase in the salivary amylase level (p = 0.052) when the field testing involved a different modality than the OR compared with when OR and field testing involved the same modality. Although most of the biomarkers returned to baseline levels after 24 h, plasma norepinephrine levels remained significantly higher regardless of whether field testing occurred on the same or different modality compared with OR (p = 0.040 and 0.002).Conclusion: TCCC training led to significant increase in psychophysiological stress, as indicated by elevated levels of various biomarkers. The training modalities did not result in any differences in stress levels, whereas the switch in training modalities appeared to elicit greater stress as evidenced by changes in specific biomarkers (amylase and norepinephrine). A comparative study with a larger sample size is warranted. [ABSTRACT FROM AUTHOR]

Over recent years, our understanding of the tricarboxylic acid cycle (TCAC) in living organisms has expanded beyond its canonical role in cellular energy production. In plants, TCAC metabolites and related enzymes have important roles in physiology, including vacuolar function, chelation of metals and nutrients, photorespiration, and redox regulation. Research in other organisms, including animals, has demonstrated unexpected functions of the TCAC metabolites in a number of biological processes, including signaling, epigenetic regulation, and cell differentiation. Here, we review the recent progress in discovery of non-canonical roles of the TCAC. We then discuss research on these metabolites in the context of plant development, with a focus on research related to tissue-specific functions of the TCAC. Additionally, we review research describing connections between TCAC metabolites and phytohormone signaling pathways. Overall, we discuss the opportunities and challenges in discovering new functions of TCAC metabolites in plants. [ABSTRACT FROM AUTHOR]

The corrosion behavior of Sn-50Zn-xCu ( x = 0, 1, 2 wt%) touch-up solder alloys was investigated by electrochemical techniques (potentiodynamic polarization, electrochemical impedance spectroscopy, and open circuit potential) and surface characterization (scanning electron microscopy, energy dispersive X-ray spectrometry, and X-ray diffraction), aiming to explore the effects of the Cu addition on the corrosion resistance. The results reveal that the dendritic-like Zn-rich phase of Sn-50Zn was disadvantageous to form a protective corrosion product layer and offered convenient paths for the Cl− penetration into the substrate. However, the Cu addition to Sn-50Zn based alloys led to the refinement of microstructure and the transformation of Zn-rich phase's morphology which could result in the formation of more compact corrosion product layer. Thus, the corrosion resistance of Sn-Zn-Cu alloys was improved. The corrosion mechanism is also discussed. [ABSTRACT FROM AUTHOR]

Prader-Willi syndrome (PWS) is the most prevalent syndromic form of obesity, which starts during early childhood in the setting of hyperphagia. Due to the development of obesity, there is a high prevalence of obstructive sleep apnea (OSA) among these patients. This case report presents a patient with PWS with morbid obesity, severe OSA, and obesity hypoventilation syndrome admitted to the hospital for hypoxemic and hypercapnic respiratory failure. Noninvasive ventilation (NIV) with average volume-assured pressure support, a newer NIV modality, was used successfully to treat this patient, achieving major clinical and gas exchange improvement both during the hospitalization and long term after discharge. [ABSTRACT FROM AUTHOR]

Highlights: [•] A new quaternary phase was discovered in laser treated Zn–55Al–2Mg–1Si coating. [•] The crystal structure of the new phase was determined by TEM. [•] The new phase was not a metastable phase induced by the rapid cooling of the laser treatment. [•] Laser treatment led to not only a much finer microstructure but also changes of phases in the interdendritic areas of the coating. [Copyright &y& Elsevier]

Physiologically based pharmacokinetic (PBPK) models were developed using MATLAB Simulink® to predict diurnal variations of endogenous melatonin with light as well as pharmacokinetics of exogenous melatonin via different routes of administration. The model was structured using whole body, including pineal and saliva compartments, and parameterized based on the literature values for endogenous melatonin. It was then optimized by including various intensities of light and various dosage and formulation of melatonin. The model predictions generally have a good fit with available experimental data as evaluated by mean squared errors and ratios between model-predicted and observed values considering large variations in melatonin secretion and pharmacokinetics as reported in the literature. It also demonstrates the capability and usefulness in simulating plasma and salivary concentrations of melatonin under different light conditions and the interaction of endogenous melatonin with the pharmacokinetics of exogenous melatonin. Given the mechanistic approach and programming flexibility of MATLAB Simulink®, the PBPK model could provide predictions of endogenous melatonin rhythms and pharmacokinetic changes in response to environmental (light) and experimental (dosage and route of administration) conditions. Furthermore, the model may be used to optimize the combined treatment using light exposure and exogenous melatonin for maximal phase advances or delays. [ABSTRACT FROM AUTHOR]

Physiologically based pharmacokinetic models were developed using MATLAB Simulink® and PK-Sim®. We compared the capability and usefulness of these two models by simulating pharmacokinetic changes of midazolam under exercise and heat stress to verify the usefulness of MATLAB Simulink® as a generic PBPK modeling software. Although both models show good agreement with experimental data obtained under resting condition, their predictions of pharmacokinetics changes are less accurate in the stressful conditions. However, MATLAB Simulink® may be more flexible to include physiologically based processes such as oral absorption and simulate various stress parameters such as stress intensity, duration and timing of drug administration to improve model performance. Further work will be conducted to modify algorithms in our generic model developed using MATLAB Simulink® and to investigate pharmacokinetics under other physiological stress such as trauma. [ABSTRACT FROM AUTHOR]

Most perianal abscesses originate from infected anal glands at the base of the anal crypts. Most abscesses below are usually drained through perianal incision and can be treated successfully. However, when perianal abscesses extend to the high intrapelvic cavity, it may be inadequate treatment through a single route incision through a perianal approach. The aim of this technical note is to show that combined anterior ilioinguinal and perianal incisions may provide optimal surgical field and multiple drainages. Here, we report a 56-year-old male patient with perianal-originating parapsoas abscesses. Residual abscess still remained after initial perianal incision and drainage after 1-month treatment. We presented combined anterior ilioinguinal and perianal incision technique methods for proper drainage in this complicated case. No recurrent or residual abscess remained after 2 weeks of operation. So, combined anterior ilioinguinal incision is feasible for high-located perianal abscess. [ABSTRACT FROM AUTHOR]

Under extreme conditions of heat exposure and exercise stress, the human body undergoes major physiological changes. Perturbations in organ blood flows, gastrointestinal properties, and vascular physiology may impact the body's ability to absorb, distribute, and eliminate drugs. Clinical studies on the effect of these stressors on drug pharmacokinetics demonstrate that the likelihood of pharmacokinetic alteration is dependent on drug properties and the intensity of the stressor. The objectives of this study were to use literature data to quantify the correlation between exercise and heat exposure intensity to changing physiological parameters and further, to use this information for the parameterization of a whole-body, physiologically based pharmacokinetic model for the purposes of determining those drug properties most likely to demonstrate altered drug pharmacokinetics under stress. Cardiac output and most organ blood flows were correlated with heart rate using regression analysis. Other altered parameters included hematocrit and intravascular albumin concentration. Pharmacokinetic simulations of intravenous and oral administration of hypothetical drugs with either a low or high value of lipophilicity, unbound fraction in plasma, and unbound intrinsic hepatic clearance demonstrated that the area under the curve of those drugs with a high unbound intrinsic clearance was most affected (up to a 130% increase) following intravenous administration, whereas following oral administration, pharmacokinetic changes were smaller (<40% increase in area under the curve) for all hypothetical compounds. A midazolam physiologically based pharmacokinetic model was also used to demonstrate that simulated changes in pharmacokinetic parameters under exercise and heat stress were generally consistent with those reported in the literature. [ABSTRACT FROM AUTHOR]

To promote and understand the structure-property relationship for hemostasis, we modified melittin (MLT) using a four-arm poly(ethylene glycol) (PEG) with N-hydroxysuccinimide ester. The PEGylation was characterized by FTIR, MALDI-MS, NMR, a bicinchoninic acid assay, circular dichroism, hemolysis assay, and thromboelastography. Changes in the reaction conditions affected the extent of the modification, the numbers of MLT conjugated to PEG arms, and possible PEGylation sites. The reaction at pH 9.2 with a high MLT/PEG ratio, resulted in the highest modification. Reactions in dimethylsulfoxide (DMSO) resulted in more multi-arm coupled MLT, reaching a maximum of four MLT per PEG. The helicity of the modified peptide, relative to the native peptide, was essentially maintained in DMSO, but substantially lost at pH 9.2. PEGylation reduced the hemolytic effects of MLT and subsequently changed its coagulation profiles. The overall hemostatic effects of MLT modified in DMSO indicate that this may be a convenient approach to the PEGylation of biomolecules for biomedical applications. [ABSTRACT FROM AUTHOR]

Distribution feeder faults cause power outages, therefore it is crucial to diagnose and thus locate the fault quickly to reduce the duration of the outage. In practice, feeder patrols usually identify the fault locations by referencing the regional distribution of the calls reporting trouble, the abnormal observations of the feeders that have been reported in the calls, and the observed conditions in the surrounding environments. Feeder patrols in Taiwan have recorded each fault on a table that includes time, date, month, year, address, equipment at fault, causes or accidents, and etc. The database has accumulated a large base of information for many years. This study aims to use rough set theory as a data-mining tool to derive useful patterns and rules for distribution feeder faulty equipment diagnosis and fault location. In particular, the historical data of distribution feeder faults of Taiwan Power Company was used for validation and the results show the practical viability of the proposed approach. [ABSTRACT FROM AUTHOR]

The Xikuangshan antimony mine located at Central Hunan, China, is the largest antimony deposit in the world. Hydrothermal calcites from the Xikuangshan Mine display relatively large variations in REE abundance and Sm/Nd ratios and are characterized by MREE- and HREE-enriched and LREE-depleted patterns. Sm–Nd isotopic compositions of syn-sulfide calcites fall on well-defined lines in the isochron plot. Calcites from early- and late-stage mineralization form two distinct isochrons corresponding to 155.5±1.1 and 124.1±3.7 Ma, respectively. The isochron ages suggest that Sb mineralization took place during the Late Jurassic–Early Cretaceous Period in the Xikuangshan district, consistent with previous geological observations and with independent isotope data. Samarium–neodymium dating of calcites shows potential for determining ages of hydrothermal mineralization. [Copyright &y& Elsevier]

Background Kimura's disease (KD) is a rare chronic inflammatory condition characterized by nodules and lymphadenopathy in the head and neck region, exhibiting type II inflammation. Dupilumab is commonly used against type II inflammation. Aim To evaluate the efficacy and safety of dupilumab in KD patients. Design The real-world study was conducted in a hospital in China. Methods Six male patients with a mean age of 24.50 ± 15.47 years were treated with dupilumab following the same protocol as that for atopic dermatitis (AD). Clinical and laboratory indicators, such as maximum nodule diameter, blood eosinophil count, eosinophil percentage, and total serum IgE levels were assessed at baseline, Week 12 and Week 24. Adverse events were documented. Paired t -tests and one-way ANOVA were used for statistical analysis. Results The results showed significant reductions in the longest nodule diameter at Week 12 (P  =   0.006) and Week 24 (P  =   0.017) compared to baseline. Blood eosinophil count decreased by 57.95% (P  =   0.024) at Week 12 and 90.59% (P  =   0.030) at Week 24. Eosinophil percentage decreased by 58.44% (P  =   0.026) at Week 12 and 89.37% (P  =   0.013) at Week 24. Total serum IgE levels decreased by 78.02% (P  =   0.040) at Week 12 and 89.55% (P  =   0.031) at Week 24. The presence of AD did not affect the results. One patient experienced temporary facial erythema after 32 weeks of treatment, which resolved with topical treatment. No other adverse events were reported. Conclusion Dupilumab demonstrated effectiveness in treating KD without severe adverse events. [ABSTRACT FROM AUTHOR]

ABSTRACT. Objective. To assess the effects of early postnatal dexamethasone therapy on hematologic values in preterm infants. Materials and Methods. We reviewed the hematologic data of 179 preterm infants who participated in a double-blind clinical trial of early postnatal dexamethasone therapy (<12 hours after birth) for the prevention of chronic lung disease. One group (86 infants) received saline and the other group (93 infants) received dexamethasone. Dexamethasone was given intravenously every 12 hours in tapering doses: 0.25 mg/kg on days 1 to 7, 0.12 mg/kg on days 8 to 14, 0.05 mg/kg on days 15 to 21, and 0.02 mg/kg on days 21 to 28. Blood samples were obtained on days 0, 3, 7, 10, 14, 21, and 28. None of the infants received prenatal steroid therapy. Results. Multiple regression analysis revealed significant differences in the values versus time curves of the white blood cell, neutrophil, lymphocyte, basophil, and eosinophil counts between the two groups. The white blood cell count was significantly higher in the dexamethasone group on days 7 through 14, and this was associated with significantly higher numbers of segmented neutrophils and band forms and significantly lower numbers of lymphocytes and eosinophils. The hematocrit and platelet counts were similar in the two groups throughout most of the trial. Except for platelet count, steroid therapy did not alter the hematologic values for infants with bacteremia. Conclusion. Dexamethasone affects white blood cell, segmented neutrophil, lymphocyte, basophil, and eosinophil counts in neonates. This should be taken into consideration when evaluating preterm infants who are receiving dexamethasone. Pediatrics 1999; 104:476-481; early dexamethasone therapy; neonatal blood count; preterm infant; respiratory distress syndrome. [ABSTRACT FROM AUTHOR]

Abstract beta-Thalassemia, a hematologic disorder characterized by the deficiency or the absence of beta-globin production, is the most widespread inherited disorder in the world; it is also common in Taiwan. We studied 38 patients in central Taiwan with beta-thalassemia major, using amplified created restriction site analysis for detection. On analysis, six different point mutations were found among 76 chromosomes, of which 32 chromosomes (42.1%) had a C to T substitution at nucleotide 654, 30 (40%) had frameshift codons 41/42 with four nucleotides (TCTT) deletion, 7 (9.2%) had an A to T substitution at codon 17, 3 (3.9%) had frameshift codons 71/72 (insertion of A), 2 (2.6%) had an A to G substitution at position -28, and 2 (2.6%) had frameshift codons 27/28 (insertion of C). The first two mutations accounted for 62 of the 76 beta-thalassemia mutations in this study. As to mutations in each individual with beta-thalassemia major, the incidence of compound heterozygotes of two different mutations was higher than that of homozygotes of a single mutation (60% vs 40%). Compound heterozygotes of C to T substitution at nucleotide 654 of IVS-2 and frameshift codons 41/42 with four-nucleotide deletion was the most common pattern of beta-thalassemia mutations in each individual (23.7%). Our results were unique compared with those from similar studies performed in southern China. Frequencies of beta-thalassemia mutations found in the current study were assessed and compared with frequencies found in previous studies conducted in northern and southern Taiwan. [ABSTRACT FROM AUTHOR]

Hemoglobin (Hb) gene disorders are one of the most common inherited diseases in Taiwan, which include α-thalassemia, β-thalassemia, and Hb variants. In this study, we collected and analyzed mutations found in 930 patients with Hb gene disorders except Hb Bart’s Hydrops and β-thalassemia major. The patients included 650 cases of α-thalassemia, 225 cases of β-thalassemia, 9 cases of α-thalassemia combined with β-thalassemia, and 46 cases of Hb variants or Hb variants combined with α-thalassemia or β-thalassemia. The most common type of α0-thalassemia and α++-thalassemia mutations in our study were the SEA type deletion and the α3.7 deletion, respectively; the most common β-thalassemia mutation was the IVS-2 nt 654 C→T mutation; and the most common Hb variant was the HbE. We compared the relationships between genotype and hematological phenotypes of various Hb gene disorders and found that different genotypes of α0-thalassemia have similar hematological features. In conclusion, the results of our study provide data of the complex interaction of thalassemias and Hb variants which might be useful for other researchers in this field. [ABSTRACT FROM AUTHOR]

Kawasaki disease is an acute febrile illness typically elicited by vascitlitis and occurring in young children. We investigated the polymorphism of the angiotensin-l converting enzyme (ACE) gene in children with Kawasaki disease and also in agematched controls. A total of 107 children, with a mean age at diagnosis of 1.71 &plusmnn; 1.48 years, who suffered from Kawasaki disease and who were treated with aspirin as well as intravenous immunoglobulin were enrolled in this study. Control subjects consisted of 107 children, with a mean age of 1,84 &plusmnn; 1.20 years. The polymorphisms of the ACE gene, including I D , A-240T. and G2350A. were examined using a polymorase chain reaction method for Kawasaki disease patients and also for control subjects. We noted a significant difference in the distribution of the ACE gene I D genotype between Kawasaki disease and control groups. The ACE gene G2350A polymorphism and associated allelic frequencies demonstrated an association with Kawasaki disease. Our results revealed no evidence of any association between the ACE gene polymorphism and the frequency of coronary artery aneurysm associated with Kawasaki disease, although our results do support a role for the I/D and G235OA polymorphism of the ACE gene in determining the risk of Kawasaki disease in the population of Taiwan. [ABSTRACT FROM AUTHOR]

Patients with β-thalassemia major still suffer growth retardation. After excluding patients with cortisol deficiency, hypothyroidism, hypogonadism, delayed puberty, malnutrition, severe congestive heart failure, and severely impaired liver function, 29 patients were enrolled in this study. Fifteen (52%) patients exhibited growth retardation and underwent two growth hormone (GH) provocation tests. Eight (53%) of the 15 patients had GH deficiency and were subsequently treated with subcutaneous recombinant human GH (Genotropin, Pharmacia Corporation, Sweden). Growth velocity increased from the pretreatment rate of 3.1±0.4 cm/year to 7.1±1.6 cm/yr (p<0.001) after 1 year and to 6.8±1.3 cm/year (p<0.001) after 2 years. Patients with growth retardation had lower insulin like growth factor-1 (p=0.001) and insulin like growth factor binding protein-3 (p=0.003) levels than those without growth retardation. In patients with β-thalassemia major, growth retardation is a common complication and GH deficiency plays an important role. Thalassemic patients with GH deficiency can safely increase their growth velocity with recombinant human GH for2 years; however, the effect on final height still needs to be determined. [ABSTRACT FROM AUTHOR]

Summary Current body mass index (BMI) norms for children and adolescents are developed from a reference population that includes obese and slim subjects. The validity of these norms is influenced by the observed secular increase in body weight and BMI. We hypothesized that the performance of children in health-related physical fitness tests would be negatively related to increased BMIs, and therefore fitness tests might be used as criteria for developing a more appropriate set of BMI norms. We evaluated the existing data from a nation-wide fitness survey for students in Taiwan (444 652 boys and 433 555 girls) to examine the relationship between BMI and fitness tests. The fitness tests used included: an 800/1600-m run/walk; a standing long jump; bent-leg curl-ups; and a sit-and-reach test. The BMI percentiles developed from the subgroup whose test scores were better than the ‘poor’ quartile in all four tests were compared with those of the whole population and linked to the adult criteria for overweight and obesity. The BMIs were significantly related to the results of fitness testing. A total of 43% of students had scores better than the poorest quartile in all of their tests. The upper BMI percentile curves of this fitter subgroup were lower than those of the total population. The 85th and 95th BMI percentile values of the fitter 18-year-old-students (23.7 and 25.5 kg m-2 for boys; 22.6 and 24.6 kg m-2 for girls) linked well with the adult cut-off points of 23 and 25 kg m-2 , which have been recommended as the Asian criteria for adult overweight and obesity. Hence, the BMI norms for children and adolescents could be created from selected subgroups that have better physical fitness. We expect that the new norms based on this approach will be used not only to assess the current status of obesity or overweight, but also to encourage activity and exercise. [ABSTRACT FROM AUTHOR]

Objective: To define the nature and incidence of minor anomalies in Chinese newborn infants and to evaluate the validity of the hypothesis that infants with three or more minor surface anomalies will also have a major malformation. Methods: A total of 3,345 Chinese newborn infants were examined based on a list of 67 items of minor anomalies. Results: About 44.9% of the newborn infants had at least one minor anomaly that was unrelated to gender, maternal age, or gestational age, but significantly associated with fetal presentation. Breech-presented newborn infants had double the risk of minor anomalies. Simian crease, upward slant and frontal bossing could be considered normal variants for Chinese newborn infants, because the incidence of each was higher than 4%. Conclusions: Although some studies have shown that approximately 90% of infants having three or more minor anomalies are associated with a major malformation, we found only a 10.1% predictive value based on this study. Nevertheless, we suggest that infants with three or more minor anomalies be carefully evaluated for the possibility of major malformation in order to provide early management. [ABSTRACT FROM AUTHOR]

Focuses on a study which compared the efficacy and safety to clarithromycin in multidrug regimens and in rifabutin versus clofazimine as the third drug in regimens containing ethambutol in disseminated mycobacterium avium complex disease in AIDS patients. How the study was conducted; Results; Discussion of the results.

Photovoltaic (PV) effects, power-conversion efficiencies, and structures have been systematically measured in (Bi1-xCax)FeO3-δ ceramics for x = 0.05, 0.10, and 0.15. The heterostructures of indium tin oxide (ITO) film/(Bi1-xCax)FeO3-δ ceramics/Au film exhibit significant PV effects under illumination of λ = 405 nm. The maximum power-conversion efficiency in the ITO/(Bi0.90Ca0.10)FeO2.95 (BFO10C)/Au can reach 0.0072%, which is larger than 0.0025% observed in the graphene/polycrystalline BFO/Pt films [Zang et al., Appl. Phys. Lett. 99, 132904 (2011)]. A theoretical model based on optically excited current in the depletion region between ITO film and Ca-doped BFO ceramics is used to describe the I-V characteristic, open-circuit voltage, and short-circuit current density as a function of illumination intensity. This work suggests that the Ca-substitution can reduce the rhombohedral distortion and stabilize the single-phase structure. [ABSTRACT FROM AUTHOR]

The tensile-strained Si, based on the misfit between Si and SiGe gives high speed and high drive current to the metal-oxide-silicon field effect transistors. In order to achieve the total system minimum energy, the island edge, within some characteristic length, bends upwards giving rise to a distorted lattice, as simulated by the finite element method. The finding indicates that the conventional strain partition rule of Si/SiGe/Si layers used for a large island size (>10 μm) is not adequate for a small island size (<200 nm) due to the significant local-strain effect of the edge lattice distortion. For a small island size, the bending from the edge can significantly affect the strain on the surface of the top Si layer, and a compressive strain or reduced tensile strain occurs at the center of the top Si layer, while the conventional strain partition rule predicts a uniform tensile strain on the top Si layer for any size of Si/SiGe/Si islands. [ABSTRACT FROM AUTHOR]

It has been nearly 110 years since the discovery of histamine and its profound physiological actions as well as the four distinct binding sites that constitute its receptor family. Histamine agonists and antagonists when labelled with tritium have been very valuable in advancing our understanding of histamine receptors. Over the years, scores of histamine receptor ligands have been tritiated but few if any have been methylated derivatives of histamine. For that reason, this paper describes the tritiation of several methylated histamine analogues as well as their analytical characterization by HPLC, MS and tritium NMR. [ABSTRACT FROM AUTHOR]

Litchi (Litchi chinensis) pepper spot disease results in black spotting symptoms on litchi fruits. This disease was first observed on litchi cultivar Guiwei, in Guangzhou, China, in 2009, and then found widespread in other litchi‐growing regions of China. Colletotrichum isolates were consistently recovered from typical black spot lesions of diseased fruits with frequency ranging from 83% to 100%. Three representative Colletotrichum isolates from Maoming, Guangzhou and Shenzhen were selected for identification and pathogenicity testing in the field. Based on morphology and phylogenetic analysis using the ribosomal internal transcribed spacer region (ITS), glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), calmodulin (CAL), actin (ACT), β‐tubulin (TUB2) and glutamine synthetase (GS) gene sequences, the three isolates were identified as C. siamense. In the pathogenicity experiments, typical symptoms appeared on the inoculated litchi fruits, including black spots and green patches around these black spots. These symptoms were consistent with the symptoms originally observed in the field. Colletotrichum siamense was successfully reisolated from the typical black spot lesions of the inoculated litchi fruits. To the authors' knowledge, this is the first report on characterization of C. siamense as the causal agent of litchi pepper spot disease in mainland China by successful inoculation on fruits under field conditions. [ABSTRACT FROM AUTHOR]

Presents a study which developed a method for determining the magnetic critical current density on thallium strontium[sub2]calcium[sub2]barium[sub2]copper[sub3]oxygen[suby]. Experimental details; Results and discussion; Conclusion.

The pseudogap, d-wave superconductivity and electron-boson coupling are three intertwined key ingredients in the phase diagram of the cuprates. Sr2IrO4 is a 5d-electron counterpart of the cuprates in which both the pseudogap and a d-wave instability have been observed. Here, we report spectroscopic evidence for the presence of the third key player in electron-doped Sr2IrO4: electron-boson coupling. A kink in nodal dispersion is observed with an energy scale of ~50 meV. The strength of the kink changes with doping, but the energy scale remains the same. These results provide the first noncuprate platform for exploring the relationship between the pseudogap, d-wave instability, and electron-boson coupling in doped Mott insulators. [ABSTRACT FROM AUTHOR]

A novel complex [Pb(bptm)(NO3)(H2O)2] (bptm = 1,1-bis(5-(pyrazin-2-yl)-1,2,4-triazol-3-yl) methane) is synthesized and characterized by IR spectroscopy and single crystal X-ray diffraction. Its reactivity with calf thymus DNA and HeLa cell DNA is measured using UV absorption and fluorescence spectroscopies. Gel electrophoresis assay demonstrates the ability of the complex to cleave pBR322 plasmid DNA. Eventually, the complex can suitably dock with a special DNA. [ABSTRACT FROM AUTHOR]

A modified normalization method is presented for obtaining crack tip opening displacement (CTOD) resistance curves of single edge-notched tension specimens. For the applied load mode, the normalization method should be based on force-crack mouth opening displacement. A formula is proposed for CLL(i), the core parameter used in the normalization calculation. The modified method is validated using the unloading compliance method. The study of specimen geometry shows that side-groove depth and crack depth have significant impacts on the obtained CTOD resistance curves, and the shape of the crack front affects the determination accuracy of crack length. [ABSTRACT FROM AUTHOR]

Introduction These recommendations are intended to develop a consensus in the previously published papers as to which parameters and what values should be considered critical. A practical guide on the standardization of critical results management in haematology laboratories would be beneficial as part of good laboratory and clinical practice and for use by laboratory-accrediting agencies. Methods A working group with members from Europe, America, Australasia and Asia was formed by International Council for Standardization in Haematology. A pattern of practice survey of 21 questions was distributed in 2014, and the data were collected electronically by Survey Monkey. The mode, or most commonly occurring value, was selected as the threshold for the upper and lower alert limits for critical results reporting. Results A total of 666 laboratories submitted data to this study and, of these, 499 submitted complete responses. Full blood count critical results alert thresholds, morphology findings that trigger critical result notification, critical results alert list, notification process and maintenance of critical results management protocol are described. This international survey provided a snapshot of the current practice worldwide and has identified the existence of considerable heterogeneity of critical results management. Conclusion The recommendations in this study represent a consensus of good laboratory practice. They are intended to encourage the implementation of a standardized critical results management protocol in the laboratory. [ABSTRACT FROM AUTHOR]

Hypopituitarism in leukemia is very rare. In addition, central nervous system (cns) relapse and leukemic retinopathy in childhood acute lymphoblastic leukemia (all) have declined with the use of modern systemic chemotherapy that includes cns prophylaxis. Here, we report the case of a 4-year-old girl who received chemotherapy and intrathecal therapy without cns radiation after a diagnosis of B-precursor all without cns involvement. Three months after chemotherapy completion, she presented with lower-extremity weakness and was diagnosed with an isolated cns relapse. Concurrent hypopituitarism and leukemic retinopathy were also found. After receiving craniospinal radiotherapy and systemic chemotherapy, her retinopathy and vision improved. She is now in complete remission, and she is still on chemotherapy according to the guideline from the Pediatric Oncology Group. Although rare, hypopituitarism and leukemic retinopathy should be taken into consideration in patients with cns involvement by leukemia. [ABSTRACT FROM AUTHOR]

Background: There is growing interest in viscoelastic hemostatic assays rotational thromboelastometry (ROTEM) and thromboelastography (TEG) for trauma. Despite shared features, it is unknown whether their results are interchangeable and whether one is clinically superior in predicting mortality, blood transfusion, and diagnosing early trauma coagulopathy.Methods: We conducted a prospective observational study comparing equivalent ROTEM and TEG parameters. Severely injured patients expected to receive massive transfusion were included. Assays were performed simultaneously on admission and repeated over subsequent 12 hours. International normalized ratio ≥1.2 or fibrinogen <1 g/L defined coagulopathy. TEG used kaolin as coagulation initiator and ROTEM used tissue factor (conventional). Spearman nonparametric analysis and Bland-Altman difference mean plot revealed parameter association. Logistic regression and receiver operating characteristic curves measured predictive values.Results: 33 patients (74 ROTEM, 74 TEG) were included; 79% were male, mean Injury Severity Score was 23.5 ± 14, admission international normalized ratio was 1.33 ± 0.4, and 63.4% received blood transfusions. Overall, parameter agreement fell outside acceptable limits, with weak or no association. Clinically, ROTEM maximum clot firmness and TEG maximum amplitude showed reasonable predictive accuracy for mortality, strong accuracy for any or massive blood transfusion, reasonable for plasma transfusion and similar poor predictive accuracy for diagnosing coagulopathy.Conclusions: ROTEM and TEG results are not interchangeable, arguably due to different coagulation triggers. Assays had similar clinical performance. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a two patients who achieved hematopoietic recovery after receiving umbilical cord matrix cells (USMCs) during the peripheral blood stem cell (PBSC) transplantation.

Imatinib has improved outcomes in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Minimal residual disease (MRD) is a useful tool for predicting leukemia relapse. However, there is no consensus on how to treat children with elevation of BCR-ABL transcripts but no evidence of hematologic relapse during chemotherapy combined with imatinib. Here, we report the case of a child with Ph+ ALL who had persistent elevation of mrd, but no evidence of hematologic relapse while receiving imatinib plus intensive chemotherapy. Dasatinib was substituted for imatinib because no suitable donor for allogeneic hematopoietic stem-cell transplantation (HSCT) was available. Less-intensive chemotherapy with methotrexate and 6-mercaptopurine was administered concomitantly. No serious adverse events were encountered. With continuous dasatinib combined with chemotherapy, but no allogeneic HSCT, our patient reached complete molecular remission and has been in complete molecular remission for more than 13 months. This report is the first about the long-term use of dasatinib in patients with Ph+ ALL and MRD elevation but hematologic remission during imatinib chemotherapy. In a similar situation, chemotherapy combined with dasatinib instead of allogeneic HSCT could be considered to avoid HSCT-related mortality and morbidity. Clinical trials are needed. [ABSTRACT FROM AUTHOR]

Background and Objectives Ael is a rare blood type that is characterized by weak agglutination of RBCs when reacts with anti- A antibody in adsorption-elution test. Although IVS6 + 5 G→ A mutation is known to associate with the Ael blood type, genetic and mechanistic evaluation for the weak agglutination of Ael with IVS6 + 5 G→ A mutation has not yet been completely addressed. Materials and Methods In this study, five cases of confirmed Ael individuals were analysed. The c DNAs for the A el alleles were obtained by cloning method for sequence analyses. The erythroleukemia K562 cells were used as the cell study model and were transfected with the A el expression construct. Flow cytometry analysis was then performed to determine the levels of surface antigen expression. Results The results indicated that IVS6 + 5 G→ A attributes to all cases of Ael. RT- PCR analyses revealed the presence of at least 10 types of aberrant A el splicing transcripts. Most of the transcripts caused early termination and produced non-functional protein during translation. Nevertheless, the transcript without exons 5-6 was predicted to generate functional Ael glycosyltransferase lacking 57 amino acids at the N-terminal segment. When the exons 5-6 deletion transcript was stably expressed in the K562 cells, weak agglutination of the cells can be induced by adding anti- A antibody followed by adsorption-elution test. Conclusion This study demonstrates that aberrant splicing of A transcripts contributes to weak A expression and the weak agglutination of Ael- RBCs, adding to the complexity for the regulatory mechanisms of ABO gene expression. [ABSTRACT FROM AUTHOR]