Gamma delta+ T cells involvement in viral immune control of chronic human herpesvirus 8 infection

Little is known about what effector populations are associated with the control of human herpesvirus 8 (HHV-8) infection in vivo. We compared T lymphocyte subsets among HIV-HHV-8+ and HIV-HHV-8- infected human individuals. alphabeta+ T cells from HHV-8-infected individuals displayed a significantly higher percentage of differentiated effector cells among both CD4+ and CD8+ T cell subsets. HHV-8 infection was associated with significant expansion of gammadelta+ Vdelta1 T cells expressing a differentiated effector cell phenotype in peripheral blood. In vitro stimulation of PBMC from HHV-8-infected individuals with either infectious viral particles or different HHV-8 viral proteins resulted in gammadelta Vdelta1 T cell activation. In addition, gammadelta Vdelta1 T cells displayed a strong reactivity against HHV-8-infected cell lines and prevented the release of infectious viral particles following the induction of lyric replication. These data indicate that gammadelta T cells play a role in both innate and adaptive T cell responses against HHV-8 in immunocompetent individuals.     

Crystallization and Gelation Behavior of Low- and High Melting Waxes in Rice Bran Oil: a Case-Study on Berry Wax and Sunflower Wax

Low-melting berry wax (BEW) has proven to be a good oil gelator with a positive contribution to the consistency and flexibility of the structured oil. Nevertheless, the properties of BEW and the corresponding oleogel have not yet been investigated in-depth. In this research, the difference in crystallization and gelling behavior between sunflower wax (SW), a high melting wax, and BEW, a low-melting wax, in rice bran oil (RBO) was investigated. The difference in melting and crystallization temperatures can be explained by the different chemical composition (long-chain wax esters in SW and short-chain fatty acids in BEW). The heterogeneity in crystal habits (unidirectional platelets versus microcrystalline particles) and polymorphism (orthorhombic versus hexagonal) are responsible for the varying gel strength and hardness of the respective SW- and BEW-oleogels. The microcrystalline BEW particles aligned and reorganized during 1-month storage at 5 °C, which leaded to an increase in the gel strength and hardness of BEW-oleogel. The gelling property of SW-oleogel however did not significantly differ after 4 weeks at 5 °C, despite of the appearance of spherulitic crystalline clusters. The changes in the physical properties of wax-based oleogels during storage time were further explored using differential scanning calorimetry, polarized light microscope, powder X-ray diffraction and rheology.     

Calcitonin gene-related peptide (CGRP) receptor antagonists: investigations of a pyridinone template

In our effort to find potent, orally bioavailable CGRP receptor antagonists for the treatment of migraine, a novel series based on a pyridinone template was investigated. After optimizing the privileged structure and the placement of the attached phenyl ring, systematic SAR was carried out on both the N-alkyl and C-5 aryl substituents. Several analogs with good potency and pharmacokinetic profiles were identified.     

Postexercise fat intake repletes intramyocellular lipids but no faster in trained than in sedentary subjects

The hypotheses that postexercise replenishment of intramyocellular lipids (IMCL) is enhanced by endurance training and that it depends on fat intake were tested. Trained and untrained subjects exercised on a treadmill for 2 h at 50% peak oxygen consumption, reducing IMCL by 26-22%. During recovery, they were fed 55% (high fat) or 15% (low fat) lipid energy diets. Muscle substrate stores were estimated by (1)H (IMCL)- and (13)C (glycogen)-magnetic resonance spectroscopy in tibialis anterior muscle before and after exercise. Resting IMCL content was 71% higher in trained than untrained subjects and correlated significantly with glycogen content. Both correlated positively with indexes of insulin sensitivity. After 30 h on the high-fat diet, IMCL concentration was 30-45% higher than preexercise, whereas it remained 5-17% lower on the low-fat diet. Training status had no significant influence on IMCL replenishment. Glycogen was restored within a day with both diets. We conclude that fat intake postexercise strongly promotes IMCL repletion independently of training status. Furthermore, replenishment of IMCL can be completed within a day when fat intake is sufficient.     

IR spectroscopic studies of major cellular components. III. Hydration of protein,nucleic acid,and phospholipid films

The IR absorption spectra of protein, DNA, RNA, and phospholipid films as a function of the water content are reported. We find that the hydration of protein films affects the peak intensity of amide I and amide II bands and the shape of the amide III band. For nucleic acids, the symmetric (nu(S) PO(2) (-)) and antisymmetric (nu(AS) PO(2) (-)) stretching vibrations of the phosphate linkage are the most affected by hydration, because both intensity changes and frequency shifts are observed. The spectra of phospholipid films are also sensitive to hydration, and they exhibit changes in the peak intensities and frequencies of both nu(S) PO(2) (-) and nu(AS) PO(2) (-) vibrations. We interpret the spectral differences between water saturated and dried films both in terms of structural changes and the change in the local dielectric in the vicinity of the polar and solvent exposed groups. In addition, we observe that the most significant change in the absorption intensity, frequency, and shape of the water sensitive vibrations occurs at high hydration levels. The principal component analysis of hydration results and the kinetics of water removal from sample films are also discussed. In addition, protein spectra acquired using film and KBr pellet sampling techniques are compared.     

Spatially resolved IR microspectroscopy of single cells

Fourier transform IR (FTIR) microspectroscopy at a spatial resolution of 18 microm was used to study skin fibroblasts and giant sarcoma cells. Both cell lines were derived from the same patient; they were metabolically active and in the exponentially growing phase. The IR spectra were acquired for the nuclei and cytosol of untreated cells, cells washed with ethanol, and cells treated with RNase or DNase. A comparison of the spectra of the two cell lines yielded only insignificant spectral differences, indicating that IR spectroscopy monitors the overall cell activity rather than specific signs of cancer.     

Determination of peptide conformation via vibrational coupling: Application to diastereoisomeric alanyl dipeptides

Solution-phase Raman spectra of diastereomeric alanyl dipeptides, D -Ala-L -Ala and L -Ala-L -Ala, and various mono- and dideuterated isotopomers in H₂O and D₂O, are reported. Spectral differences between the diastereomeric forms are interpreted, using the Raman analog of the coupled oscillator model, in terms of geometric differences between certain vibrations in the diastereomeric forms. Application of the coupled-oscillator formalism allows the determination of a dihedral angle between the coupling vibrations. The results are compared with vibrational coupling employed by other workers in the determination of the vibrational spectra of peptides.     

Infrared spectroscopy of human cells and tissue. VIII. Strategies for analysis of infrared tissue mapping data and applications to liver tissue

Experimental and computational methods of infrared microspectroscopy (IRI-MSP) and infrared spectral mapping (ISM) are presented. These methods are subsequently applied to the analysis of cirrhotic liver tissue. The sensitivity of infrared spectral mapping toward spectral changes caused by disease will be demonstrated. In addition, the excellent agreement between ISM data and histopathological information will be discussed.     

Research Trends in Evidence-Based Medicine: A Joinpoint Regression Analysis of More than 50 Years of Publication Data

Background

Evidence-based medicine (EBM) has developed as the dominant paradigm of assessment of evidence that is used in clinical practice. Since its development, EBM has been applied to integrate the best available research into diagnosis and treatment with the purpose of improving patient care. In the EBM era, a hierarchy of evidence has been proposed, including various types of research methods, such as meta-analysis (MA), systematic review (SRV), randomized controlled trial (RCT), case report (CR), practice guideline (PGL), and so on. Although there are numerous studies examining the impact and importance of specific cases of EBM in clinical practice, there is a lack of research quantitatively measuring publication trends in the growth and development of EBM. Therefore, a bibliometric analysis was constructed to determine the scientific productivity of EBM research over decades.

Methods

NCBI PubMed database was used to search, retrieve and classify publications according to research method and year of publication. Joinpoint regression analysis was undertaken to analyze trends in research productivity and the prevalence of individual research methods.

Findings

Analysis indicates that MA and SRV, which are classified as the highest ranking of evidence in the EBM, accounted for a relatively small but auspicious number of publications. For most research methods, the annual percent change (APC) indicates a consistent increase in publication frequency. MA, SRV and RCT show the highest rate of publication growth in the past twenty years. Only controlled clinical trials (CCT) shows a non-significant reduction in publications over the past ten years.

Conclusions

Higher quality research methods, such as MA, SRV and RCT, are showing continuous publication growth, which suggests an acknowledgement of the value of these methods. This study provides the first quantitative assessment of research method publication trends in EBM.