Percentage Of Blood Cells Research Articles

Standardized Assessment of Resistance Training-Induced Subjective Symptoms and Objective Signs of Immunological Stress Responses in Young Athletes.

From a health and performance-related perspective, it is crucial to evaluate subjective symptoms and objective signs of acute training-induced immunological responses in young athletes. The limited number of available studies focused on immunological adaptations following aerobic training. Hardly any studies have been conducted on resistance-training induced stress responses. Therefore, the aim of this observational study was to investigate subjective symptoms and objective signs of immunological stress responses following resistance training in young athletes. Fourteen (7 females and 7 males) track and field athletes with a mean age of 16.4 years and without any symptoms of upper or lower respiratory tract infections participated in this study. Over a period of 7 days, subjective symptoms using the Acute Recovery and Stress Scale (ARSS) and objective signs of immunological responses using capillary blood markers were taken each morning and after the last training session. Differences between morning and evening sessions and associations between subjective and objective parameters were analyzed using generalized estimating equations (GEE). In post hoc analyses, daily change-scores of the ARSS dimensions were compared between participants and revealed specific changes in objective capillary blood samples. In the GEE models, recovery (ARSS) was characterized by a significant decrease while stress (ARSS) showed a significant increase between morning and evening-training sessions. A concomitant increase in white blood cell count (WBC), granulocytes (GRAN) and percentage shares of granulocytes (GRAN%) was found between morning and evening sessions. Of note, percentage shares of lymphocytes (LYM%) showed a significant decrease. Furthermore, using multivariate regression analyses, we identified that recovery was significantly associated with LYM%, while stress was significantly associated with WBC and GRAN%. Post hoc analyses revealed significantly larger increases in participants’ stress dimensions who showed increases in GRAN%. For recovery, significantly larger decreases were found in participants with decreases in LYM% during recovery. More specifically, daily change-scores of the recovery and stress dimensions of the ARSS were associated with specific changes in objective immunological markers (GRAN%, LYM%) between morning and evening-training sessions. Our results indicate that changes of subjective symptoms of recovery and stress dimensions using the ARSS were associated with specific changes in objectively measured immunological markers.

Effect of the arginine on some blood and biochemical parameters of Awassi Ewes

This study was carried out in The Ruminant Research Station (Abu Ghraib)/ Department of Animal Resources Research/ Office of Agricultural Research/ Ministry of Agriculture during the period from July 6, 2017 to Feb 3, 2018. Twenty one non pregnant Awassi Turkish ewes were used in the experiment. The age of the animals ranged between 2-5 years old with a weight ranged between 45-70kg. Befor insert CIDR, The animals were examined with ultrasonography to be sure that they were not pregnant. These ewes were divided into three equal groups of 7 ewes/ treatment. They were fed naturally on basal diet. The first group were not treated (T1) which serve Control group, and injected with 5-10 ml of normal saline in intramuscular. Ewes of Second group were Treated (T2) by injected with a 155 µmol/kg arginine I.V. The Third group were Treated (T3) by injected with 155µmol/kg arginine intramuscular. All Treated ewes were inseminated by rams for 7 days. The inseminate rams were revolved among folds to get rid of their effects on ewes, Each inseminated ram was given a number. Blood samples were taken from jugular vein on the 1st and 2nd days of arginine injection and then insert CIDR and on the 3rd, 5th, 7th, 10th,13th ,and 16th days of this treatment to measure the change in the levels of a blood and chemical properties during arginine treatment. The results of a lab. analysis during the treatment of amino acid arginine showed no significant differences between the treated group with arginine as compared to the control group in the percentages of white blood cells, but there were a differences in the number of Neutrophils in the group of intravenous injection, the group of intramuscular injection, (75.14, 75.00), respectively as compared with control group (71.0). Lymphocytes showed no significant differences between parameters under study as well as for Eosinophil. The differences were observed between the coefficients and the study periods. The period (4) was significantly superior (P<0.05) in the arginine treated as Compared with the control group, (20.42 ± 2.61) and the percentage of intravenous injection (17.28±1.98), respectively compared with a control group (19.00 ± 2.51), as for Basophil, there was a gradual decrease in all study groups. The results showed that the value of cholesterol a significant superiority (P<0.05) in the treated group with arginine in ewes serum as compared with the control group. It was noticed that the group of intravenous injection of arginine significantly increase the group of intramuscular injection of arginine (P<0.05) (6, 8) in blood cholesterol level. The periods (1, 2, 3, 4, 5, and 7) of injection of amino acid arginine showed no significant differences between them. The glucose concentration level, showed no significant differences between the arginine amino acid treatment group and the control group and at the different. It was concluded from this study that treatment with amino acid arginine did not affect characteristics of the blood, and its chemical properties.

A comparison between laryngeal mask airway and endotracheal intubation for anaesthesia in adult patients undergoing NUSS procedure.

This study evaluates and compares the feasibility and safety of application of laryngeal mask airway (LMA) and endotracheal intubation (ETT) for anaesthesia in adult patients undergoing thoracoscopic surgery. Sixty adult patients with pectus excavatum (PE) undergoing video-assisted thoracoscopic surgery for the NUSS procedure (VATS-NUSS) between September 2016 and March 2017 were selected and randomly separated into two groups with different methods of airway management. In one group, LMA was applied for general anaesthesia, and in the other group, ETT was used. The clinical parameters before, during and after the surgery in patients from both groups were collected from multiple data resources in a hospital. SPSS software was used for the analysis. Of all the selected patients, the physiological parameters showed similarity between the LMA and ETT groups, indicating consistency in the clinical characteristics of the study sample. Additionally, no significant differences were discovered between the two groups in terms of the anaesthesia and surgical time, peak PetCO2 during operation, anaesthetic satisfaction score, and amount of blood loss as well as inpatient time for recovery. However, with a similar level of anaesthesia effects and suitable parameters for mechanical ventilation, patients in the LMA group showed much more stability in the physiological indicators for inflammation and haemodynamics, including white blood cell count (ΔWBC) and percentage of neutrophil granulocytes (ΔNEU%) in the blood as well as heart rate (ΔHR) and mean arterial pressure (ΔMAP). Moreover, the LMA patients had a significantly shorter time for recovery of consciousness and food/water intake. Finally, compared to the ETT group, patients in the LMA group also had a significantly lower incidence of side effects induced by the anaesthesia procedure after surgery, such as gastrointestinal reactions, throat discomfort and hoarseness. Compared with ETT, the application of LMA for general anaesthesia may demonstrate promising advantages in airway management for the VATS-NUSS procedure.

Anti-arthritic properties of crude extract from Chenopodium ambrosioides L. leaves.

To evaluate the effect of hydroalcoholic crude extract (HCE) from Chenopodium ambrosioides leaves on the development of type II collagen-induced arthritis (CIA) and on pro-inflammatory cytokine balance. Collagen-induced arthritis was induced in DBA1/J mice. On the 21st day, the mice were treated orally with HCE or methotrexate, daily. Six weeks after beginning the treatment, the following measures were determined: lymphoid organs cell numbers, percentage of blood cells, IL-6, IFN-γ, TNF-α and IL-17 serum concentrations, activity of hepatic and kidney glutathione S-transferase, hepatic 7-ethoxyresorufin-O-deethylase activity, bone density and histopathology. Treatment of CIA mice with HCE 5mg/kg (HCE5) reduced the percentage of neutrophils and macrophages and the number of bone marrow cells and increased the lymphocyte numbers and the inguinal lymph node cellularity. This treatment inhibited the serum concentration of IL-6 and TNF-α, which may be related to the preservation of bone density and to the slight thickening of periarticular tissues, with minimal fibrosis and fibroblast proliferation in the joints. The CIA group presented advanced articular erosion and synovial hyperplasia. Phytochemical analysis showed mainly flavonols. HCE5 presented anti-arthritic potential and reduced IL-6 and TNF-α, which participate directly in the development and maintenance of the inflammatory process in rheumatoid arthritis.

Effects of Dried Blood Spot Storage on Lipidomic Analysis.

During the lipidomic analysis of red blood cell membranes, the distribution and percentage ratios of the fatty acids are measured. Since fatty acids are the key constituents of cell membranes, by evaluating their quantities it possible to understand the general health of the cells and to obtain health indicators of the whole organism. However, because the analysis is precise, it is necessary to ensure that the blood does not undergo significant variations between the point of collection and analysis. The composition of the blood may vary dramatically weeks after collection, hence, here an attempt is made to stabilize these complex matrixes using antioxidants deposited on the paper cards on which the blood itself is deposited.

Essential Role of c-MYC for Natural Killer Cell Development, Proliferation and Anti-Tumor Activity

Natural killer (NK) cells are the major component of innate immunity with both cytotoxicity and cytokine producing effector functions. NK cells also regulate the interplay between innate immunity and adaptive immunity by secreting certain cytokines. Extrinsic regulators of NK cell development and function, including diverse ligands of NK cell receptors and cytokines from the microenvironment, have been extensively studied. However, intrinsic regulators for NK cell biology are still less understood. In our previous study on aggressive NK cell leukemia (ANKL), genomics and transcriptomics analyses indicated that c-MYC was universally upregulated and responsible for the proliferation and survival in ANKL cells (Manuscript in revision). Furthermore, STAT5, as a transcriptional regulator of c-MYC, was found to be essential in the survival and development of NK cells (Eckelhart et al., Blood 2011). In this regard, we want to understand the physiological and oncological roles of c-MYC in NK cells.To achieve our goal, we made two mouse models including c-Myc loss-of-function (LOF) and c-Myc gain-of-function (GOF) in NK cells. Ncr1Cre knock-in mice, in which Cre recombinase was inserted into the Nkp46 locus, was used. We crossed the c-Mycf/f mice with Ncr1Cre mice to generate the NK cell specific c-Myc LOF model c-MycΔ/Δ/Ncr1Cre. To generate the c-Myc GOF model, we crossed the Tg(tetO-MYC) mice with Ncr1Cre and Rosa26-Loxp-Stop-Loxp(LSL)-rtTA-GFP mice to get the Tg(tetO-MYC)/ Ncr1Cre/LSL-rtTA-GFP (iMYC) mice, in which c-Myc expression can be induced in a doxycycline dependent manner in NK cells. c-MycΔ/Δ/Ncr1Cre mice were analyzed between 6 to 14-weeks old. iMYC mice were induced by doxycycline from 6-weeks old for over 2 months and then analyzed. Wild type littermates were used as controls. In both models, mice were born normally and showed no obvious difference in growth compared to their littermates.In c-MycΔ/Δ/Ncr1Cre mice, a significant reduction of NK1.1+/DX5+ NK cell percentages in peripheral blood (3.6 ± 0.4% vs. 0.5 ± 0.1%, P < 0.0001, N=7) and spleen (2.4 ± 0.5% vs. 0.7 ± 0.1%, P < 0.01, N=6) was detected. In addition, the percentage of CD11b+ mature NK cells in the NK1.1+/DX5+ population was also reduced. In bone marrow (BM), although the total percentage of NK1.1+/DX5+ NK cells did not change, an obvious block of NK cell development was seen, as the majority of NK1.1+/DX5+ cells in BM were CD27+/CD11b- cells, which represent an immature pattern. To assess whether the NK cell proliferation is altered in this model, we performed BrdU labeling assays and found that BrdU incorporation rates decreased dramatically both in peripheral NK cells and BM NK progenitors. Functionally, we measured the IFN-γ secretion of splenic NK cells after PMA/Ionomycin stimulation. We found that the percentage of IFN-γ positive NK cells decreased significantly in c-MycΔ/Δ/Ncr1Cre mice (77.1 ± 7.0% vs. 53.8 ± 1.0%, N=3). Consistent with these data, the tumor surveillance was also severely impaired in this LOF model, as the number of lung metastatic sites significantly increased compared to the control mice in a B16F10 transplantation assay.In contrast to the LOF model, in our GOF model, the NK1.1+/DX5+ NK cell number in peripheral blood increased (3.1 ± 0.2% vs. 4.4 ± 0.5%, P < 0.05, N=7). Additionally, a small increase in the percentage of CD27-/CD11b+ population in NK1.1+/DX5+ cells was seen. Interestingly, however, the ability of IFN-γ secretion of splenic NK cells after PMA/Ionomycin stimulation was decreased in iMYC mice (72.8 ± 0.3% vs. 58.7 ± 1.1%, N=3), which showed the same alteration observed in c-MycΔ/Δ/Ncr1Cre mice. This result is probably not due to the impaired maturation, but rather it is the result of the higher percentage of CD27-/CD11b+ cells, which were considered terminally differentiated NK cells with lower cytotoxic functions.In summary, we found that c-Myc is essential for NK cell development, proliferation, and tumor surveillance. NK cell maturation and proliferation were impaired in the c-Myc LOF models and were boosted in the c-Myc GOF models. Our results also provide a mechanism basis for the potential application of targeting c-Myc in NK cells ex vivo or in vivo expansion, and NK-mediated immunotherapy. Future studies are needed to delineate the underlying mechanisms and explore the applications. DisclosuresNo relevant conflicts of interest to declare.

Hematological Risk Factors for High-Altitude Headache in Chinese Men Following Acute Exposure at 3,700 m.

Background: High-altitude headache (HAH) is a notably common disorder affecting the daily life of travelers ascending to high altitude. Hematological parameters are important clinical examinations for various diseases. Today, hematological characteristics of HAH remain unrevealed. Above all, we aimed to ascertain hematological characteristics and independent risk factors/predictors associated with HAH before and after exposure at 3,700 m.Methods: Forty five healthy men were enrolled in present study. Demographic and clinical data, physiological and hematological parameters were collected 3 days before the ascent and after acute exposure at 3,700 m.Results: HAH patients featured significantly lower white blood cell count (WBC), neutrophil count (NEU#) and percentage (NEU%), and higher percentage of lymphocyte (LYM%) at 3,700 m and significantly lower NEU#, reticulocyte count (RET#) and percentage (RET%) at sea level (all P < 0.05). HAH severity was significantly and negatively associated with WBC, NEU#, and NEU% at 3,700 m and RET# at sea level, whereas was positively associated with LYM% at 3,700 m (all P < 0.05). Moreover, we have found that RET# at sea level and NEU% at 3,700 m was an independent predictor and risk factor for HAH, respectively.Conclusion: The present study is the first to examine the hematological characteristics of HAH. Furthermore, lower RET# at sea level and lower NEU% at 3,700 m is a novel independent predictor and risk factor for HAH, respectively.

The diagnostic value of complete blood count parameters in patients with subarachnoid hemorrhage

ObjectivesDiagnosis of subarachnoid hemorrhage (SAH) in patients presenting with headache is challenging and there has been any biomarker studied for excluding of SAH in those patients. We aim to determine the sensitivity of leukocytosis or left shift to exclude the diagnosis of SAH in ED patients presenting with headache. MethodAdult patients with headache who received a computed tomography (CT) with the diagnosis of SAH and had a complete blood count (CBC) represent the case group, headache patients with normal CT and had a CBC represent the control group. The white blood cell (WBC) count and percentage of polymorphonuclear cells (PMNs%) taken during admission and within the first 6 and 12 h of admission were recorded. ResultsA hundred ninety seven patients with SAH and 197 patients without SAH were enrolled in to study. Sensitivity, specificity, NPV and PPV of leukocytosis or increase in PMNs% (left shift) in the diagnosis of SAH was 89.8% (84.5–93.5, 95% CI), 46.7% (39.6–53.9, 95% CI), 82.1% (73.5–88.4, 95% CI) and 62.8% (56.8–68.4, 95% CI) respectively on initial emergency department (ED) admission. ConclusionCBC should be considered as a noninvasive test for the exclusion of SAH in ED patients with 6 h observation.

Combined effects of Chinese medicine feed and ginger extract bath on co-infection of Ichthyophthirius multifiliis and Dactylogyrus ctenopharyngodonid in grass carp.

Dactylogyrus ctenopharyngodonid and Ichthyophthirius multifiliis are two important ectoparasites of freshwater fish. Co-infection by the two parasites leads to high fish mortality and results in heavy economic losses. This study aimed to evaluate the efficacy of medicated feed and a ginger extract bath against D. ctenopharyngodonid and I. multifiliis on grass carp and investigate the hematological response of grass carp co-infected by the two parasites. These results demonstrated that red blood cell (RBC) and thrombocyte percentage among leucocytes significantly decreased after grass carp were co-infected by D. ctenopharyngodonid and I. multifiliis. The monocyte and neutrophil percentages significantly increased with the increment of parasite mean intensities, while the lymphocyte percentage decreased. The activities of serum acid phosphatase (ACP), alkaline phosphatase (AKP), lysozyme (LZM), and superoxide dismutase (SOD) significantly increased after co-infection. When grass carp treated with medicated feed containing 4% of Astragalus membranaceus, Allium sativum, Morus alba, and Glycyrrhiza uralensis, the activities of ACP, AKP, LZM, and SOD were significantly enhanced, and the mean intensities of D. ctenopharyngodonid and I. multifiliis were significantly decreased. When grass carp was treated with medicated feed and a 4-mg/L ginger extract bath, all parasites were eliminated during 28days. The bath of ginger extract at a concentration of 4mg/L kept a low mean intensity of I. multifiliis and D. ctenopharyngodonid, then the two parasites were eliminated by oral administration of the medicated feed with an immunostimulant (Chinese medicine compound).

Construction and evaluation of models for early diagnosis and prognosis assessment of trauma sepsis risks

Objective To investigate the value of multiple inflammatory cells and clinical score in early diagnosis and prognosis assessment of trauma sepsis risks. Methods This retrospective control study enrolled 209 severe trauma patients admitted from January 2010 and May 2016. White blood cell count, lymphocyte count and percentage, monocyte count and percentage, neutrophil count and percentage, ratio of neutrophil to lymphocyte count (N/L), acute physiology and chronic health evaluation (APACHE) Ⅱ score, sequential organ failure assessment (SOFA), improved early warning score (MEWS), Glasgow coma score (GCS), multiple organ dysfunction syndrome (MODS) score and lactic acid (LAC) were collected on the day of admission and 3, 5, 7 days after trauma. These data were applied to construct weighted and biological score models for early diagnosis and prognosis of traumatic sepsis. Receiver operating characteristic curve (ROC) was performed and area under the curve (AUC) was calculated to measure the value of the two models in early diagnosis and prognosis of sepsis. Results AUC of the weighted model combined by APACHE Ⅱ score, SOFA score and MEWS was 0.729 on the day of admission. AUC of the weighted model combined by inflammatory cells was 0.680 and AUC of the biological score model was 0.800 3 days after trauma (P 0.05). AUC of the biological score model had significant difference 3 days and 5 days after trauma (P<0.05). Of the weighted model combined by APACHE Ⅱ score, MODS score, GCS and LAC to evaluate the prognosis of sepsis, the AUC showed significant difference on the day of admission (0.838), 3 days after trauma (0.878), 5 days after trauma (0.947) and 7 days after trauma (0.936) (P<0.05). Conclusions Biological score possesses better effect on early diagnosis of sepsis 3 days after trauma. Weighted model combined by APACHE Ⅱ score, MODS score, GCS and LAC can effectively predict the prognosis of sepsis 5 days after trauma. Key words: Sepsis; Diagnosis, differential; Prognosis

Testosterone and Tendency to Engage in Self-Employment

Does testosterone increase the tendency to engage in self-employment? The results presented to date have been mixed. Using three different studies, we provide additional evidence on the relationship between testosterone and self-employment. Drawing on a cross section of 2,146 individuals (1,178 males and 968 females) from the National Health and Nutrition Examination Surveys’ 2011–2012 sample, and controlling for endogeneity (with red blood cell count, percentage hematocrit, and zinc supplement intake in the past 30 days as instruments), we find that serum testosterone levels are positively associated with self-employment for males (marginally significant, two-tailed test). As testosterone levels could be affected by social, economic, and biological factors during one’s life course, we draw more robust inferences by assessing whether the 2D:4D digit ratio, a marker of prenatal testosterone exposure, influences the likelihood of self-employment. From Understanding Society’s Innovation Panel Wave 6, we tested separate models for 449 males and 525 females, and our results indicate that males (respectively, females) with a lower 2D:4D ratio in their left hand, or higher prenatal testosterone exposure, have a significantly greater (respectively, marginally significant) likelihood of self-employment (two-tailed test). Finally, we examine the twin testosterone transfer effect in a sample of opposite-sex and same-sex twins from the National Survey of Midlife Development in the United States and provide additional support for the marginally significant (two-tailed test) positive association between testosterone and self-employment. Data are available at https://doi.org/10.1287/mnsc.2016.2664 . This paper was accepted by Toby Stuart, entrepreneurship and innovation.

Abstract TP35: Estimation of Red Blood Cells in the Thrombus Using MRI. A Phantom Study with Predetermined Thrombus Components

Background and Purpose: Better understanding about thrombus composition seems necessary, as treatment of acute ischemic stroke (AIS) is focus on clot chemical dissolution and mechanical extraction. We propose to evaluate whether magnetic resonance imaging (MRI) can differentiate white from red clots and estimate red blood cells percentage (RBC%) using clots with predetermined components and an index based on MRI signal intensity (SI). Material and Methods: 5 clots (A=100% fibrin, B=80% RBC, C=50% RBC, D=20% RBC, E=unknown) were fixed in gelatin-manganese solution and studied by: high-resolution 3D T1-weighted (T1MPR), T2-weighted turbo spin echo (T2TSE), T2-weighted gradient echo (T2GE), susceptibility weighted (SWI), fluid-attenuated inversion recovery (FLAIR) and diffusion weighted imaging (DWI) with apparent diffusion coefficient (ADC). SI index was calculated with clot SI and gelatin SI. Statistical analysis compared RBC-clots to fibrin-clot SI index and the correlation of RBC% and SI index in each MRI sequence. Results: Each red clot was different from clot A except clot D in FLAIR. Correlation between clots SI index and RBC concentration were found in T1MPR (r=-0.84), SWI (r=-0.79), T2GE (r=-0.72) and FLAIR (r=0.80). Linear regression resolution provided an indirect RBC estimation for clot E: 47.3 % in T1MPR, SWI 41.5%, T2GE 45.1% and FLAIR 50.9%. Histological analysis confirmed clot E composition. Conclusion: This in vitro study suggests that MRI can differentiate white from red clots except clots with low RBC% in FLAIR and also provide approximate RBC%.

Analysis of clinical characteristics of 26 patients with melioiclosis spleen abscesses in Hainan province

Objective To analyze the clinical features of melioidosis spleen abscess. Methods A retrospective analysis of 26 cases with melioidosis spleen abscess at Hainan People′s Hospital between October 2002 and March 2015 was performed. Data with general conditions, clinical characteristics, imaging features, treatment and outcome were all extracted and analyzed. Results High fever (100.0%) and splenomegaly (73.1%) were the main clinical symptoms and signs. Laboratory examinations showed that white blood cell and neutrophil percentage increased, with a mean value of 12.6×109/L and 0.86, respectively. 88.5% cases had diabetes mellitus which was the main underlying disease. Apart from spleen abscess, pulmonary infection (73.1%) and liver abscess (38.5%) were the majority. Imaging showed multiple small abscess (92.3%). All patients had at least one positive blood culture of Burkholderia pseudomallei and were treated with imipenem, ceftazidime and sulfamethoxazole alone or in combination. Hospitalization days ranged between 8 to 65 days with the mean of 29.5 days. Twenty-three cases (88.5%) were cured, the remaining 3 cases (11.5%) abandoned treatment and were all lost for follow-up. Conclusions Melioidosis should be suspected in patients from epidemic areas, who have diabetes and imaging shows spleen abscess and other organ infections including pulmonary infection and liver abscess. Microbiological culture is needed immediately. Key words: Melioidosis; Spleen abscess; Hainan

Effect of Aqua Aerobics on Selected Somatic, Physiological and Aerobic Capacity Parameters in Postmenopausal Women

The world’s population is aging. Aquatic exercises can improve the physical function in humans and raise the quality of their lives in middle and older age. The study aimed to determine the effect of aqua aerobics on the selected somatic, physiological and aerobic capacity parameters in postmenopausal women. 11 purposively selected women that were confirmed overweight or obese by 20% and had Body Mass Index of 30±5 (the first stage of obesity) took part in aqua aerobics classes three times a week for 14 weeks. Their mean age was 56.18±3.19 years and mean height was 166.5±7.41 cm. The value of LBM and muscle mass (p=0.04 in both cases) were statistically significantly higher at study end compared with their baseline values, likewise haemoglobin concentration (p=0.001), haematocrit (p=0.03) and blood cell count (p=0.01), whereas BMI (p=0.02) and percentage body fat (p=0.04) were significantly lower. The lactate analysis revealed significant changes in LAmax (p=0.04), LAres9' (p=0.02), DeltaLAmax-LAsp (p=0.02) and DeltaLAres9’-LAres3’ (p=0,0004). After 14 weeks of aqua aerobic workout, significant changes were noted in the selected somatic, morphological and aerobic capacity parameters in postmenopausal women, but the differences between the lipid profiles were insignificant.

The Impact of Cognitive Function on Adherence to Hydroxyurea Therapy in Patients with Sickle Cell Disease

Introduction:Cognitive impairment is a serious complication of sickle cell disease (SCD) that affects both children and adults. While it is known to adversely affect school performance and overall development in children, its functional impact in adults is not known. Importantly, poor disease self-management and adherence to hydroxyurea are major problems in SCD and are likely to be impacted by cognitive impairment. In the study presented herein, we hypothesized that lower cognitive function in areas of memory and executive function would be associated with worse adherence to hydroxyurea therapy in adults with SCD.Methods:We designed a cross-sectional study of patients with SCD from the University of Pittsburgh Medical Center Adult Sickle Cell Clinic. Patients who underwent neurocognitive testing between 2011 and 2016 as part of an ongoing neurocognitive study and whose adherence to hydroxyurea therapy has been monitored by a dedicated clinical nurse were included. Performance on four neurocognitive tests of verbal learning, memory and executive function - the Hopkins Verbal Learning Test-Revised (HVLT-R) retention, HVLT-R total recall, Delis-Kaplan Executive Function System Trail Making Condition 4 vs. 5, and Color Word Condition 3 - were selected a priori as explanatory variables. We explored the association between the four test scores and the most recent adherence data at the time of the study. Adherence measures included the laboratory biomarkers red blood cell corpuscular volume (MCV) and percentage of fetal hemoglobin (HbF) - whose values are expected to rise with hydroxyurea therapy - and the patient’s self-report of adherence categorized as "good" (≥ 80% adherence) or "less-than-good" (< 80% adherence). Differences between groups were compared by 2-sided t-test or chi-square tests where indicated.Results:Study participants (n=48) had a mean age of 35.2 years (range 22-60) and were predominantly female (58.3%). Fifty-two percent had higher than high-school level education, and 72.9% had a HbSS or HbS/β0 thalassemia phenotype. There were no statistically significant differences between the "good" adherence and "less-than-good" adherence groups with regard to these baseline characteristics. As expected, the mean MCV, an objective marker of hydroxyurea adherence, was significantly higher in the "good" adherence group (102.3 ± 15.0 vs. 89.1 ± 11.5 fL, p=0.005), corroborating the patients’ self-report. We observed a statistically significant positive correlation between the HVLT-R retention score and MCV that remained significant after adjustment for demographic characteristics (Pearson r=0.309, p=0.033) and a similar correlation with HVLT-R total recall (Pearson r=0.269, p=0.065). A similar trend between HVLT-R retention and HbF percentage was observed (Pearson r=0.260, p=0.081). The mean HVLT-R retention and HVLT-R total recall scores were higher in the "good" adherence group (80.1% ± 27% vs. 64.9% ± 33%, and 41.9% ± 14% vs.34.1% ± 13%, respectively), although the difference between the two groups did not reach statistical significance. There was no significant difference in performance on the Trail Making Condition 4 vs. 5 or the Color Word Condition 3 tests.Discussion:Our study suggests that adherence to hydroxyurea therapy in adult patients with SCD might be affected by impairment in episodic memory, as measured in our study through HVLT-R retention, with qualitatively similar patterns by HVLT-R total recall. Although more extensive investigation is warranted, these results suggest that a brief, targeted neurocognitive assessment should be considered as a component of any strategy aimed at improving adherence to hydroxyurea and other therapeutic interventions in patients with SCD. DisclosuresJonassaint:Sicklesoft: Other: officer of Sicklesoft. Kato:Mast Therapeutics: Consultancy; Bayer: Research Funding.

Stochastic Modeling of Hematopoietic Stem and Progenitor Cell Barcoding Data from Rhesus Macaques Challenges the Classic Model of Hematopoiesis

The classical model of hematopoiesis states that differentiation proceeds from hematopoietic stem cells (HSC) to mature blood cells via specified multipotent and bipotent progenitors, such as the common myeloid progenitor (CMP), common lymphoid progenitor (CLP), erythrocyte-megakaryoctye progenitor and granulocyte-monocyte progenitor. However, recent studies question this assumption and suggest that these intermediates are neither required nor prevalent. As an example, analyses of binarized data from murine barcoding experiments (Perie et al, Cell Reports, 2014) raise the possibility that hematopoiesis progresses via a random loss of potentials rather than discrete steps. Additionally, Notta et al (Science, 2015) showed that oligopotent progenitor cells form only a negligible component in the hierarchy by studying the distribution of progenitors in human marrow, leading them to infer that HSC and earliest multipotent progenitors differentiate directly into unipotent cells. Although these data challenge fundamental beliefs, the quantitative contributions of HSC and progenitors to cell lineages could not be tracked in individual mice or persons over time.We developed a statistical method to infer the rates and probabilities of cell fate decisions in a class of stochastic branching models and used this to analyze sequence data from a rhesus macaque transplanted with lentivirally barcoded CD34+ HSC and progenitor cells. The macaque's blood granulocytes (Gr), monocytes (Mo), B cells, T cells, and NK cells were tracked over 30 months. Our quantitative framework is based on computing correlations between pairs of observable mature blood cell types across all independently barcoded lineages. The method also accounts for experimental uncertainties intrinsic to blood sampling, cell purification and PCR amplification.Specifically, our approach relies on a loss function estimator that minimizes residuals between empirical pairwise correlations across barcode lineages and analytical model-based correlations derived generally for continuous-time multi-type branching processes. We integrate over sampling distributions accounting for noise in experimental protocol and CBC counts. Candidate models represent possible hematopoietic structures and allow an arbitrary number of progenitor and mature cell types descended from each HSC. We identify best-fitting fate decision rates and initial marking levels with corresponding confidence intervals via nonlinear least squares and can assess whether a given model is statistically consistent with the data. This is the first statistical method to our knowledge for fitting stochastic models of hematopoiesis to lineage barcoding time-series, and together with the rhesus macaque data, enables quantitative analysis of in vivo dynamics in a large animal model.Using this new approach, we confirmed the major finding in Wu et al. (Cell Stem Cell, 2014) of a distinct NK cell ontogeny, i.e., that CD16+ blood NK cells do not overlap in origin with T and B cell lineages. We estimate that 13.9% of HSC and 86.1% of progenitors were initially barcoded, which is consistent with the finding by Wu that the percentage of blood cells expressing GFP stabilized at 13% after 6 months. Additionally, we estimate that HSC self-renew approximately once every 12 weeks, which is consistent with the range estimated in previous primate studies based on telomere studies (Shepherd, Blood, 2007). These initial analyses help validate our method. We then showed that Gr and Mo cells derive from a common precursor in vivo (correlation ρ ≈.9 across time). We also estimated progenitor differentiation rates and showed that Gr and Mo cells are produced up to 10- to 100-fold more rapidly than T, B and NK cells, and that each progenitor committed to the Gr/Mo lineage (i.e., CFUGM) produces thousands of mature cells per day. Importantly, we tested models requiring an ordered differentiation through defined intermediaries and found that they did not suitably fit the data compared to models allowing for non-restricted pathways. Together these analyses challenge the classic model of blood cell differentiation and provide new insights into the structure of hematopoiesis. DisclosuresDunbar:GSK/Novartis: Research Funding.

White blood cell inflammatory markers are associated with depressive symptoms in a longitudinal study of urban adults

Total white blood cell count (TWBCC) and percentage (%) composition of lymphocytes (PL) or neutrophils (PN) are linked to mid- and late-life depression, though sex-specific temporal relationships between those inflammatory markers and depressive symptoms remain unclear. The association between inflammation and depressive symptoms in longitudinal data on ethnically and socioeconomically diverse urban adults was examined with two hypotheses. In hypothesis 1, we examined the relationship between TWBCC, PL and PN with change in level of depressive symptoms from baseline to follow-up, stratifying by sex. In hypothesis 2, we examined reverse causality, by testing the relationship of depressive symptoms with change in TWBCC, PL and PN. Multiple linear mixed-effects regression models were performed to examine both the hypotheses. The sample sizes of participants (n) and repeated observations (n') were: Hypothesis 1 (n=2009; n'=3501); Hypothesis 2 (n=2081; n'=3560). Among key findings (Hypothesis 1), in women, higher TWBCC was linked to a faster increase in depressive symptom total score (γ1112±s.e.: +0.81±0.28, P=0.003), with a slower increase over time in the positive affect subdomain coupled with faster increases in depressed affect and somatic complaints. Among women, baseline score on somatic complaints was positively associated with low PN (γ01a=+1.61±0.48, P<0.001) and high PL (γ01a=+1.16±0.45, P=0.011), whereas baseline score on positive affect was inversely related to higher PL (γ01a=−0.69±0.28, P=0.017). Results among men indicated that there was a positive cross-sectional relationship between low TWBCC and depressive symptoms, depressed affect and an inverse cross-sectional relationship with positive affect. However, over time, a low TWBCC in men was linked to a higher score on positive affect. There was no evidence of a bi-directional relationship between WBC parameters and depressive symptoms (Hypothesis 2). In sum, TWBCC and related markers were linked to depressive symptoms, mostly among women. Further longitudinal studies are needed to replicate this sex-specific association.

Abstract 2039: Exploring the longitudinal transcriptomic landscape of tyrosine kinase inhibitor treatment response in chronic myeloid leukemia patients

Abstract The interpretation and implementation of large-scale genetic profiles into clinical practice remains a challenge despite substantial growth in our understanding of genetic contributors to drug response. Most current omic studies focus on identifying genetic features that are distinct between normal and tumor samples, but fail to capture the dynamics of association between omic profiles, treatment response and disease progression over time. The focus of this research is to analyze the longitudinal transcriptomic profile of chronic myeloid leukemia patients (CML) in context of tyrosine kinase inhibitor (TKI) treatment and clinical status. The main objectives were to compare a series of post-TKI treatment transcriptome profiles to their baseline levels, and characterize the impact of TKI treatment and CML disease status on the individual's transcriptome over time. Our ultimate goal is to develop TKI response predictors using the longitudinal expression data collected over the treatment course. Peripheral blood samples, buccal swabs and detailed clinical data were collected from each study participant (screened for BCR-ABL1 translocation) for a period of 6 months, in addition to pre-therapy baseline. RNA was extracted from granulocytes isolated from peripheral blood samples, and profiled using RNA sequencing. RNAseq profiles over TKI treatment course were compared to baseline, as well as against hematologic response (complete blood count), cytogenetic response (FISH), and clinical disease progression. We investigated dynamic trends in RNAseq profiles associated TKI response, as well as with the clinical status of the patient over time. We identified genetic features that were either 1) Differentially expressed between baseline and post-TKI time points; 2) Showed non-random spikes in expression levels at specific time points; 3) Associated with hematological and clinical phenotypes, including white blood cell count, percentage granulocytes and percentage cells with BCR-ABL1 translocation; 4) Demonstrated highly correlated patterns of expression over time. Through clustering and enrichment analysis of the selected transcripts, we identified several pathways and molecular features associated with TKI-response, and altered disease state. Of note, we found mTOR signaling, and pro-apoptotic pathways to be significantly altered between baseline and TKI-responding individuals. In addition, we observed significant changes in transcription regulatory network of several transcription factors, notably AP-1, over the treatment time course. To our knowledge, this is the first study to establish the utility of comprehensive longitudinal multiple transcriptome profile analysis of TKI-response in CML. We believe this study will pave way for future large-scale longitudinal omic profiling of CML and other cancer-types. Citation Format: Aritro Nath, Fan Wang, Divya Lenkala, Bonnie LaCroix, Nancy Glavin, Kristen Kipping-Johnson, Paul Geeleher, Michael Thirman, Lucy Godley, Gordana Raca, Richard Larson, R. Stephanie Huang. Exploring the longitudinal transcriptomic landscape of tyrosine kinase inhibitor treatment response in chronic myeloid leukemia patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2039.

Impact of hepatic function on serum procalcitonin for the diagnosis of bacterial infections in patients with chronic liver disease: A retrospective analysis of 324 cases.

Although procalcitonin (PCT) is a valid marker for early diagnosis of bacterial infections, it is unclear whether its accuracy in predicting bacterial infections is affected by impaired liver function. This study aimed to assess the impact of compromised liver function on the diagnostic value of PCT.This retrospective study was conducted between January 2013 and May 2015. A total of 324 patients with chronic liver disease were enrolled. Routine laboratory measurements and PCT were performed. Patients were divided into 3 groups according to clinical diagnosis: chronic hepatitis (group 1), decompensated cirrhosis (group 2), and acute-on-chronic liver failure/chronic liver failure (group 3). The correlation between PCT and liver function was analyzed. The area under the receiver operating characteristic (AUCROC) curve of PCT was analyzed according to infection status and liver function.PCT was more accurate than white blood cell count (P < 0.001) and percentage of neutrophils (P < 0.001) in detecting bacterial infections in patients with impaired liver function. In patients without infection, PCT had a moderate positive correlation with serum total bilirubin (TBIL) (r = 0.592), and a weak correlation with model for end-stage liver disease score (r = 0.483) and international normalized ratio (r = 0.389). The AUCROC and optimum thresholds of PCT and for predicting bacterial infections at different levels of TBIL were 0.907 (95% CI 0.828-0.958) and 0.38 ng/mL, respectively, for TBIL <5 mg/dL, 0.927 (95% CI 0.844-0.974) and 0.54 ng/mL (5 mg/dL ≤TBIL<10 mg/dL), 0.914 (95% CI 0.820-0.968) and 0.61 ng/mL (10 mg/dL ≤TBIL<20 mg/dL), 0.906 (95% CI 0.826-0.958) and 0.94 ng/mL (TBIL ≥20 mg/dL), respectively.This study demonstrated that PCT was a valuable marker of bacterial infection in patients with chronic liver diseases. TBIL affected PCT threshold, so different cut-offs should be used according to different TBIL values.

Assessment of some Immunological and Hematological Factors among Radiation Workers

Although the ionizing radiations cause various disorders in different parts of the human body, the importance and extensive application of radiations in medicine are undeniable. In this study, we have tried to evaluate the effect of radiation on immunological and hematological parameters in the radiation workers compared with the control group. Two groups including radiation workers (test group) and a control group were determined. Test and control groups were selected from imaging staffs in teaching hospitals of Hamadan and healthy employees working in other parts of the hospital, respectively. They were matched according to age and sex. The serum levels of cytokines IFN-γ, IL-4, IL-10 and IL-17 were determined and the results were analyzed by using SPSS 18. The obtained results indicated that the level of the IFN-γ and IL-10 in the radiation workers were significantly lower than the control group (P <0.05). There was a statistically significant difference in the white blood cell count and percentage of peripheral blood lymphocytes between the radiation workers and the control group (P <0.05). Based on the results of this study and comparison with the results obtained from other studies, the effects of ionizing radiation (in the radiation workers) appear certain on blood and immune systems. However, type, the exact location and severity of the effect, require more extensive researches on the number of people under study.