An adaptation of recombinant vaccinia-based ELISPOT and intracellular cytokine staining for a comparative measurement of cellular immune responses in HIV-1 and HIV-2 infections in West Africa

An efficient and quantitative tool for rapid assessment of human immunodeficiency virus (HIV)-induced cellular immune responses is important for resource-limited settings, such as in sub-Saharan Africa. Modifications are required to previously reported methods for evaluating ex-vivo antigen-specific cellular responses based on direct recombinant vaccinia virus (rVV) stimulation of peripheral blood mononuclear cells (PBMCs) by enzyme linked immunosorbent assay (ELISPOT) and by flow cytometry intracellular cytokine assay (ICA). We made such modifications in order to detect specific responses and compared quantitative cellular immune responses in HIV-1 and HIV-2 infected Gambians. The sensitivity of the rVV-based ELISPOT assay was on average 1.25 interferon (IFN)-gamma spot forming cells (SFC) per 50 000 PBMCs specific for either infection, and 5 IFN-gamma-secreting CD8+ T cells/50 000 in the ICA. The level of IFN-gamma SFC detected by ELISPOT and by ICA were correlated (P < 0.02). ICA detected pol-specific responses in 88% and 67% of HIV-1 and HIV-2 subjects, respectively, and gag-specific responses in more than 80% of both infections. Lower proportions of responders were obtained with ELISPOT, for which pol responses were present in 60% of HIV-1 and 46% of HIV-2 infected patients, and gag responses in 55% and 69%, respectively. The assays did not show any significant difference in cellular immune responses between HIV-1 and HIV-2 infected subjects with CD4% >or= 20%. These outcomes are comparable with results obtained using standard techniques and thus this method is a suitable, rapid and less expensive assessment of cellular immunity.     

Hemodynamical assessment of cavernous hemangioma in cavernous sinus using MR-DSA and conventional DSA

We report a hemodynamical assessment of the blood turnover pattern as well as the imaging of cavernous hemangioma in a cavernous sinus using time-resolved contrast enhanced 2D projection MRA, also known as MR-DSA, and conventional digital subtraction angiography (DSA), before and after radiotherapy. MR-DSA showed very fast dynamical images of a contrast turnover pattern and was well matched with the findings obtained from DSA. MR-DSA is a non-invasive study, and can replace DSA in examining a vascular tumor for the initial work-up and follow-up examination.     

Identification of tumor necrosis factor signaling-related proteins during Epstein-Barr virus-induced B cell transformation

Epstein-Barr virus (EBV) infection in vitro transforms primary B cells into continuously proliferating lymphoblastoid cell lines (LCLs) that have been widely used as a genomic resource for variety of immunological and genetic studies. However, the biochemical and biological characteristics that distinguish LCLs from the B cells have not been thoroughly investigated. Our proteomic approach showed that EBV infection induced changes in the profiles of tumor necrosis factor (TNF) signaling-related proteins in LCLs including heat shock protein family members TNF receptor-associated protein 1 (TRAP-1), heat shock 70-kDa protein 9 (HSPA9)) and superoxide dismutase 2 (SOD2). In addition, our literature co-occurrence study placed TNF at the center of a gene cluster network of differentially expressed proteins in LCLs. This study suggested that deregulation of TNF signaling pathway could contribute to the cellular transformation and immortalization of the EBV-infected B cells.     

Cross-Cultural Validation of the Korean Version of the Chalder Fatigue Scale

Purpose

University students are vulnerable to fatigue. If not adequately dealt with, fatigue might develop into various health problems and negatively affect quality of life (QOL). The present study examined psychometric properties of the Korean version of the Chalder Fatigue Scale (K-CFQ) in university students.

Method

Data were obtained from two samples of undergraduate students in Korea. The first dataset (N?=?557) was collected in a cross-sectional survey in 2015 and the second dataset (N?=?338) from a longitudinal survey with three time points over a semester period in 2016. Participants completed measures of fatigue, QOL, depression, anxiety, and sleep quality.

Results

Three-factor model (physical fatigue, low energy, and mental fatigue) rather than the original two-factor model (physical and mental fatigue) provided a better goodness of fit indices to the data. Internal consistency of the K-CFQ was satisfactory, with Cronbach’s α value of 0.88 for the total scale and those of subscales ranging from 0.73 to 0.87. Its convergent validity was supported by its significant association with anxiety, depression, sleep quality, and QOL. Significant association between T1 K-CFQ with physical QOL at T2 and T3 supported its predictive validity. Its known-group validity was proven with higher K-CFQ scores observed in the participants with depression and those with poor sleep quality.

Conclusions

Current results suggest that K-CFQ is a valid and reliable measure of fatigue, and a better model fit of the three-factor structure of the K-CFQ implies potential cross-cultural differences in the dimensionality of fatigue.

     

Computational analysis of the effect of the type of LVAD flow on coronary perfusion and ventricular afterload

We developed a computational model to investigate the hemodynamic effects of a pulsatile left ventricular assist device (LVAD) on the cardiovascular system. The model consisted of 16 compartments for the cardiovascular system, including coronary circulation and LVAD, and autonomic nervous system control. A failed heart was modeled by decreasing the end-systolic elastance of the ventricle and blocking the mechanism controlling heart contractility. We assessed the physiological effect of the LVAD on the cardiovascular system for three types of LVAD flow: co-pulsation, counter-pulsation, and continuous flow modes. The results indicated that the pulsatile LVAD with counter-pulsation mode gave the most physiological coronary blood perfusion. In addition, the counter-pulsation mode resulted in a lower peak pressure of the left ventricle than the other modes, aiding cardiac recovery by reducing the ventricular afterload. In conclusion, these results indicate that, from the perspective of cardiovascular physiology, a pulsatile LVAD with counter-pulsation operation is a plausible alternative to the existing LVAD with continuous flow mode. An erratum to this article can be found at     

Induction of long-term immunity against respiratory syncytial virus glycoprotein by an osmotic polymeric nanocarrier

Respiratory syncytial virus (RSV) is one of the most common causes of viral deaths in infants worldwide, yet no effective vaccines are available. Here, we report an osmotically active polysaccharide-based polysorbitol transporter (PST) prepared from sorbitol diacrylate and low-molecular-weight polyethylenimine (PEI) showing a potent, yet safe, adjuvant activity and acting as an effective delivery tool for RSV glycoprotein (RGp) antigen. PST showed no toxicity in vitro or in vivo, unlike PEI and the well-known experimental mucosal adjuvant cholera toxin (CT). PST formed nano-sized complexes with RGp by simple mixing, without affecting antigenic stability. The complexes exhibited negative surface charges that made them highly efficient in the selective activation of phagocytic cells and enhancement of phagocytic uptake. This resulted in an improved cytokine production and in the significant augmentation of RGp-specific antibody production, which persisted for over 200 days. Interestingly, PST/RGp enhanced phagocytic uptake owing to the osmotic property of PST and its negative zeta potential, suggesting that PST could selectively stimulate phagocytic cells, thereby facilitating a long-lived antigen-specific immune response, which was presumably further enhanced by the polysaccharide properties of PST.     

Reference Values and Determinants of Fractional Concentration of Exhaled Nitric Oxide in Healthy Children

Purpose

Measurement of the fractional concentration of exhaled nitric oxide (FeNO) is a quantitative, noninvasive, simple, safe method of assessing airway inflammation. While FeNO measurement has been standardized, reference values for elementary school children are scarce. The aim of this study was to establish reference values for FeNO in children.

Methods

FeNO was measured in elementary school children at 6-12 years of age in Seoul, Korea, following American Thoracic Society guidelines and using a chemiluminescence analyzer (NIOX Exhaled Nitric Oxide Monitoring System, Aerocrine, Sweden). A total of 1,252 children completed a modified International Study of Asthma and Allergy in Children (ISAAC) questionnaire; FeNO was measured in 1,063 children according to the protocol and in 808 children defined as healthy controls.

Results

Mean FeNO were 10.32 ppb, 16.58 ppb, and 12.36 ppb in non-atopic, atopic, and all 808 healthy controls, respectively. FeNO was not associated with age and gender. The FeNO reference equations were determined by multiple linear regression analysis, taking into account the variables of age, height, weight, total IgE, eosinophil percent, and bronchial hyper-responsiveness (methacholine PC20). FeNO=0.776+0.003×total IgE+0.340×eosinophil percent; coefficient of determination (R2)=0.084 in the 501 healthy non-atopic controls. FeNO=-18.365+1.536×eosinophil percent, R2=0.183 in the 307 healthy atopic controls; and FeNO=-7.888+0.130×Height+0.004×total IgE+1.233×eosinophil percent, R2=0.209 in the 808 all healthy controls. Eosinophil percent was correlated with FeNO in all healthy controls. FeNO was not associated with BMI.

Conclusion

This study provides reference values for FeNO that can be used to evaluate airway inflammation in elementary school children. Determinants that could most accurately predict FeNO in healthy school-age children were assessed.     

Relationship between Tetrahydrobiopterin and Portal Hypertension in Patients with Chronic Liver Disease

Tetrahydrobiopterin (BH4) is an essential cofactor in NO synthesis by endothelial nitric oxide synthase (eNOS) enzymes. It has been previously suggested that reduced intrahepatic BH4 results in a decrease in intrahepatic NO and contributes to increased hepatic vascular resistance and portal pressure in animal models of cirrhosis. The main aim of the present study was to evaluate the relationship between BH4 and portal hypertension (PHT). One hundred ninety-three consecutive patients with chronic liver disease were included in the study. Liver biopsy, measurement of BH4 and hepatic venous pressure gradient (HVPG) were performed. Hepatic fibrosis was classified using the Laennec fibrosis scoring system. BH4 levels were determined in homogenized liver tissues of patients using a high performance liquid chromatography (HPLC) system. Statistical analysis was performed to evaluate the relationship between BH4 and HVPG, grade of hepatic fibrosis, clinical stage of cirrhosis, Child-Pugh class. A positive relationship between HVPG and hepatic fibrosis grade, clinical stage of cirrhosis and Child-Pugh class was observed. However, the BH4 level showed no significant correlation with HVPG or clinical features of cirrhosis. BH4 concentration in liver tissue has little relation to the severity of portal hypertension in patients with chronic liver disease.

Graphical Abstract

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Feasibility of the Short Hospital Stays after Laparoscopic Appendectomy for Uncomplicated Appendicitis

Purpose

The aim of this study was to evaluate the feasibility of short hospital stays after laparoscopic appendectomy for uncomplicated appendicitis.

Materials and Methods

The records of 142 patients who underwent laparoscopic appendectomy for uncomplicated appendicitis from January 2010 to December 2012 were analyzed retrospectively. Patients were allocated to an early (<48 hours) or a late (>48 hours) group by postoperative hospital stay. Postoperative complications and readmission rates in the two groups were evaluated and compared.

Results

Overall mean patient age was 50.1 (±16.0) years, and mean hospital stay was 3.8 (±2.8) days. Fifty-four patients (group E, 38.0%) were discharged within 48 hours of surgery, and 88 patients (group L, 62.0%) stayed more than 48 hours. Overall complication rates were similar in the two groups (14.8% vs. 21.6%, p=0.318), and wound complications (13.0% vs. 12.5%), postoperative bowel obstruction (1.9% vs. 2.3%), and abdominal pain (1.9% vs. 3.4%) were not significantly different.

Conclusion

Patients that undergo laparoscopic appendectomy due to uncomplicated appendicitis may be safely discharged within 48 hours. Further study should be conducted to determine the optimal length of hospital stay after laparoscopic appendectomy to reduce hospital costs.     

Incidence and Risk Factors of Postoperative Nausea and Vomiting in Patients with Fentanyl-Based Intravenous Patient-Controlled Analgesia and Single Antiemetic Prophylaxis

Purpose

We evaluated the incidence and risk factors of postoperative nausea and vomiting (PONV) in patients with fentanyl-based intravenous patient-controlled analgesia (IV-PCA) and single antiemetic prophylaxis of 5-hydroxytryptamine type 3 (5 HT₃)-receptor antagonist after the general anesthesia.

Materials and Methods

In this retrospective study, incidence and risk factors for PONV were evaluated with fentanyl IV-PCA during postoperative 48 hours after various surgeries.

Results

Four hundred-forty patients (23%) of 1878 had showed PONV. PCA was discontinued temporarily in 268 patients (14%), mostly due to PONV (88% of 268 patients). In multivariate analysis, female, non-smoker, history of motion sickness or PONV, long duration of anesthesia (>180 min), use of desflurane and intraoperative remifentanil infusion were independent risk factors for PONV. If one, two, three, four, five, or six of these risk factors were present, the incidences of PONV were 18%, 19%, 22%, 31%, 42%, or 50%. Laparoscopic surgery and higher dose of fentanyl were not risk factors for PONV.

Conclusion

Despite antiemetic prophylaxis with 5 HT₃-receptor antagonist, 23% of patients with fentanyl-based IV-PCA after general anesthesia showed PONV. Long duration of anesthesia and use of desflurane were identified as risk factors, in addition to risk factors of Apfel''s score (female, non-smoker, history of motion sickness or PONV). Also, intraoperative remifentanil infusion was risk factor independent of postoperative opioid use. As the incidence of PONV was up to 50% according to the number of risk factors, risk-adapted, multimodal or combination therapy should be applied.