Non-adherence to antiretroviral treatment among migrating fishermen in western Kenya's islands: a rapid qualitative study.

Fishing communities in many Sub-Saharan African countries are a high-risk population group disproportionately affected by the HIV epidemic. The association of migration with HIV and AIDS in sub-Saharan Africa is well documented. Frequent mobility, high consumption of alcohol, multiple sexual partners, transactional and commercial sex, poor health infrastructure and limited access to health services are reported among the main factors shaping the HIV epidemic in fishing communities. Moreover, studies have been conducted in sub-Saharan Africa on adherence to antiretroviral treatment (ART) among fishers; however, non-adherence to ART remains poorly understood among migrating fishermen in the western Kenya islands. This qualitative study investigated factors contributing to non-adherence among fishermen in the western Kenya islands. This study utilised 51 in-depth interviews and six focus group discussions to highlight factors contributing to non-adherence to ART by mobile fishermen. Data were analysed using a contextualised thematic analysis. Results show that migration, alcohol consumption and ART sharing contributed to non-adherence. Adherence to ART is a powerful predictor of survival for individuals living with HIV and AIDS. The Kenyan government can use lessons from this study to target fishermen to achieve the UNAIDS 2025 recommendations on people-centred and context-specific service responses to AIDS as this would move Kenya closer to the 90% reduction in annual infections by 2030. This article contributes to a deeper understanding of how and why fishermen from the islands in western Kenya struggle to adhere to treatment even though they can access ARTs through the public health care system. Longitudinal studies should be conducted to explore how the factors associated with non-adherence correlate with other key health outcomes such as drug resistance.

Effects of Tang Luo Ning on diabetic peripheral neuropathy in rats revealed by LC-MS metabolomics approach.

Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes with limited therapies. Tang Luo Ning (TLN), a traditional Chinese medicine compound, has been proved to be effective in the treatment of DPN in clinical and experimental studies. However, the potential metabolic mechanism of TLN for the treatment of DPN is still unclear. Here the therapeutic effect of TLN on DPN was studied, and HPLC-IT-TOF/MS was used to explore the metabolic changes related to DPN and to explore the mechanism of TLN on DPN induced by high glucose. Furthermore, metabolic pathway analysis was used to explore the metabolic changes induced by DPN and TLN. As a result, TLN could improve the peripheral nerve function of DPN rats, and TLN could reduce the demyelination of the sciatic nerve in DPN rats. Metabolomics analysis showed that 14 potential biomarkers (citrate, creatine, fumarate, glyceric acid, glycine, succinate, etc.) of both DPN and TLN treatment were identified. Pathway analysis showed that the changes in these metabolites were mainly related to the citrate cycle (TCA cycle); glycine, serine, and threonine metabolism; and glyoxylate and dicarboxylate metabolism.

Integration of voluntary male medical circumcision for HIV prevention into norms of masculinity: findings from Kisumu, Kenya.

While it is clear that in many communities ideas about masculinity and circumcision are connected, it is still unclear how young Kenyan men in the former Nyanza province from the traditionally non-circumcising Luo people perceive voluntary medical male circumcision as connected to masculinity and the role of voluntary medical male circumcision in the transition from boyhood to manhood. The objective of this study was to explore norms of masculinity and the decision-making process among Luo young men to provide a better understanding of how circumcision and masculinity relate to cultural norms within this community. The methodology consisted of eight FGDs with male peer groups and 24 in-depth interviews to elicit young men's perceptions of masculinity and voluntary medical male circumcision. Findings from thematic analysis reveal that young men described several key characteristics of masculinity including responsibility, bravery and sexual attractiveness. For some young men, voluntary medical male circumcision has embedded itself into cultural norms of masculinity by being a step in the transition from boyhood to manhood and by being a marker of some of these masculine characteristics. In the case of voluntary medical male circumcision, there may be opportunities to integrate other programming that helps men transition into healthy adulthood.

Gene flow and phylogenetic analyses of paternal lineages in the Yi-Luo valley using Y-STR genetic markers.

BACKGROUND: The Yi-Luo valley witnessed the most significant socio-political transformation of China and was deeply implicated in several enormous migrations of the Han population. However, little has been done to clarify its paternal genetic variation or phylogenetic relationship, particularly concerning the genetic evidence of their migrations. AIM: This study aims to uncover the population genetic characteristics in the Yi-Luo valley and provide genetic evidence for its people's migrations. SUBJECTS AND METHODS: Seventeen Y-STR loci included in the AmpFlSTR®Yfiler™ were typed in 2,314 individuals from seven different regions along the Yi-Luo valley. A multidimensional scaling plot and neighbor-joining tree were constructed for nationwide genetic comparisons. Y-haplogroup frequencies and migration rates were estimated among the studied populations. Gene flows were detected by different migration models and directions. RESULTS: The predicted Y-haplogroups demonstrated the predominance of O2a2. Genetic affinities were observed among Han, Hakka, Danmin, and Bai. Anhui was shown to be the most crucial transfer spot for the Hakkas when they moved out of the Central Plains to South China. CONCLUSIONS: This study reveals the genetic landscape of paternal lineages living in the Yi-Luo valley and enriches our understanding of the great migration in Chinese history.

Contasure-needleless single incision slings versus transobturator slings (TOT/TVT-O) for female patients with stress urinary incontinence: a systematic review and meta-analysis.

BACKGROUND: To assess the current evidence on the effectiveness and safety of Contasure-Needleless (C-NDL) versus transobturator slings (TOT/TVT-O) in the management of female stress urinary incontinence (SUI). METHODS: A comprehensive literature review of articles that investigated the efficacy and safety of C-NDL and TOT/TVT-O was performed based on studies published before June 2019 and retrieved from PubMed, Embase, CNKI and the Cochrane Library. Two reviewers searched the literature, independently extracted the data and evaluated the quality of the data according to the inclusion and exclusion criteria. A meta-analysis was performed by using Review Manager 5.3 software. RESULTS: Seven studies with 1188 SUI female patients without intrinsic sphincter deficiency (ISD) or mixed urinary incontinence were included. Our meta-analysis showed that the clinical efficacy of C-NDL is statistically non-inferior to that of TOT / TVT-O in terms of subjective cure rate [OR = 0.77, 95% confidence interval (CI) (0.53 to 1.10), p = 0.15] and objective cure rate [OR = 0.78, 95% CI (0.53 to 1.13), p = 0.19]. In addition, operating times were statistically shorter with C-NDL compared to TOT / TVT-O [mean difference (MD) = - 7.38, 95% CI (- 10.73 to - 4.04), p < 0.0001]. In terms of the postoperative visual analogue scale (VAS) and the incidence of postoperative pain, C-NDL has a greater advantage [MD = - 1.71, 95% CI (- 2.91 to - 0.50), p = 0.005]; [OR = 0.21, 95% CI (0.05 to 0.96), p = 0.04]. Complication rates were statistically similar between the groups, except for groin pain which was higher in TOT / TVT-O. CONCLUSION: Our data suggest that C-NDL slings have similar short-term efficacy as TOT/TVT-O in curing SUI patients. Compared with TOT/TVT-O, C-NDL is associated with a shorter operative time, and the incidence of postoperative pain is decreased. Nevertheless, these findings should be further confirmed through large-volume, well-designed prospective randomized controlled trials (RCTs) with long-term follow-up.

OMICs approaches-assisted identification of macrophages-derived MIP-1γ as the therapeutic target of botanical products TNTL in diabetic retinopathy.

BACKGROUND: Inflammatory reaction in the dysfunction of retinal endotheliocytes has been considered to play a vital role in diabetic retinopathy (DR). Anti-inflammatory therapy so far gains poor outcome as DR treatment. This study aims to identify a novel therapeutic target of DR from the OMICs studies of a traditional anti-DR botanical products TNTL. METHODS: Hyperglycemic mice were treated with TNTL. The anti-hyperglycemic effect of TNTL was validated to confirm the biological consistency of the herbal products from batches. Improvement of DR by TNTL was examined by various assays on the retina. Next-generation transcriptome sequencing and cytokine array was used to identify the therapeutic targets. In vitro study was performed to validate the target. RESULTS: We observed that TNTL at its high doses possessed anti-hyperglycemic effect in murine type I diabetic model, while at its doses without reducing blood glucose, it suppressed DR incidence. TNTL restored the blood-retina barrier integrity, suppressed retinal neovascularization, and attenuated the retinal ganglion cell degeneration. Transcriptomic analysis on the retina tissue of hyperglycemic mice with or without TNTL revealed that the inflammatory retina microenvironment was significantly repressed. TNTL treatment suppressed pro-inflammatory macrophages in the retina, which resulted in the inactivation of endothelial cell migration, restoration of endothelial cell monolayer integrity, and prevention of leakage. Cytokine array analysis suggested that TNTL could significantly inhibit the secretion of MIP1γ from pro-inflammatory macrophages. Prevention of endothelial dysfunction by TNTL may be mediated by the inhibition of MIP1γ/CCR1 axis. More specifically, TNTL suppressed MIP1γ release from pro-inflammatory macrophages, which in turn inhibited the activation of CCR1-associated signaling pathways in endothelial cells. CONCLUSION: Our findings demonstrated that TNTL might be an alternative treatment to DR, and the primary source of potential drug candidates against DR targeting MIP1γ/CCR1 axis in the retinal microenvironment.

Identification of the Chemical Constituents of an Anti-Arthritic Chinese Medicine Wen Luo Yin by Liquid Chromatography Coupled with Mass Spectrometry.

Wen Luo Yin (WLY), a well-known traditional Chinese medicine formulation, has been used as a complementary therapy for the treatment of rheumatoid arthritis in clinical settings. However, the chemical constituents of WLY remain unclear. In this study, a high-performance liquid chromatography coupled with tandem mass spectrometry method was established to separate and comprehensively identify the chemical constituents of WLY. The analytes were eluted with a mobile phase of acetonitrile and 0.1% aqueous acetic acid. Mass detection was performed in both positive and negative ion mode. The MS/MS fragmentation pathways were proposed for the identification of the components. A total of 42 compounds including sesquiterpenes, alkaloids, biflavonoids, polyacetylenes, phenylpropanoids and acetylenic phenols were identified unambiguously or tentatively according to their retention times and mass behavior with those of authentic standards or literature data. The identification and structural elucidation of chemical constituents may provide important information for quality control and pharmacological research of WLY.

Identification of the absorbed components and metabolites of modified Huo Luo Xiao Ling Dan in rat plasma by UHPLC-Q-TOF/MS/MS.

To reveal the material basis of Huo Luo Xiao Ling Dan (HLXLD), a sensitive and selective ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) method was developed to identify the absorbed components and metabolites in rat plasma after oral administration of HLXLD. The plasma samples were pretreated by liquid-liquid extraction and separated on a Shim-pack XR-ODS C18 column (75 × 3.0 mm, 2.2 µm) using a gradient elution program. With the optimized conditions and single sample injection of each positive or negative ion mode, a total of 109 compounds, including 78 prototype compounds and 31 metabolites, were identified or tentatively characterized. The fragmentation patterns of representative compounds were illustrated as well. The results indicated that aromatization and hydration were the main metabolic pathways of lactones and tanshinone-related metabolites; demethylation and oxidation were the major metabolic pathways of alkaloid-related compounds; methylation and sulfation were the main metabolic pathways of phenolic acid-related metabolites. It is concluded the developed UHPLC-Q-TOF/MS method with high sensitivity and resolution is suitable for identifying and characterizing the absorbed components and metabolites of HLXLD, and the results will provide essential data for further studying the relationship between the chemical components and pharmacological activity of HLXLD.

Hydration and Ion Pair Formation in Aqueous Lu3+- Solution.

Aqueous solutions of Lu3+- perchlorate, triflate and chloride were measured by Raman spectroscopy. A weak, isotropic mode at 396 cm-1 (full width at half height (fwhh) at 50 cm-1) was observed in perchlorate and triflate solutions. This mode was assigned to the totally symmetric stretching mode of [Lu(OH2)8]3+, ν1LuO8. In Lu(ClO4)3 solutions in heavy water, the ν1LuO8 symmetric stretch of [Lu(OD2)8]3+ appears at 376.5 cm-1. The shift confirms the theoretical isotopic effect of this mode. In the anisotropic scattering of aqueous Lu(ClO4)3, five bands of very low intensity were observed at 113 cm-1, 161.6 cm-1, 231 cm-1, 261.3 cm-1 and 344 cm-1. In LuCl3 (aq) solutions measured over a concentration range from 0.105⁻3.199 mol·L-1 a 1:1 chloro-complex was detected. Its equilibrium concentration, however, disappeared rapidly with dilution and vanished at a concentration < 0.5 mol·L-1. Quantitative Raman spectroscopy allowed the detection of the fractions of [Lu(OH2)8]3+, the fully hydrated species and the mono-chloro complex, [Lu(OH2)7Cl]2+. In a ternary LuCl3/HCl solution, a mixtrure of chloro-complex species of the type [Lu(OH2)8-nCln]+3-n (n = 1 and 2) were detected. DFT geometry optimization and frequency calculations are reported for Lu3+- water cluster in vacuo and with a polarizable dielectric continuum (PC) model including the bulk solvent implicitly. The bond distance and angle for [Lu(OH2)8]3+ within the PC are in good agreement with data from structural experiments. The DFT frequencies for the Lu-O modes of [Lu(OH2)8]3+ and its deuterated analog [Lu(OD2)8]3+ in a PC are in fair agreement with the experimental ones. The calculated hydration enthalpy of Lu3+ (aq) is slightly lower than the experimental value.

Genera of phytopathogenic fungi: GOPHY 1.

Genera of Phytopathogenic Fungi (GOPHY) is introduced as a new series of publications in order to provide a stable platform for the taxonomy of phytopathogenic fungi. This first paper focuses on 21 genera of phytopathogenic fungi: Bipolaris, Boeremia, Calonectria, Ceratocystis, Cladosporium, Colletotrichum, Coniella, Curvularia, Monilinia, Neofabraea, Neofusicoccum, Pilidium, Pleiochaeta, Plenodomus, Protostegia, Pseudopyricularia, Puccinia, Saccharata, Thyrostroma, Venturia and Wilsonomyces. For each genus, a morphological description and information about its pathology, distribution, hosts and disease symptoms are provided. In addition, this information is linked to primary and secondary DNA barcodes of the presently accepted species, and relevant literature. Moreover, several novelties are introduced, i.e. new genera, species and combinations, and neo-, lecto- and epitypes designated to provide a stable taxonomy. This first paper includes one new genus, 26 new species, ten new combinations, and four typifications of older names.

Ultra-high performance liquid chromatography with tandem mass spectrometry method for the simultaneous quantitation of five phthalides in rat plasma: Application to a comparative pharmacokinetic study of Huo Luo Xiao Ling Dan and herb-pair extract.

A fast, sensitive, and reliable ultra-high performance liquid chromatography with tandem mass spectrometry method has been developed and validated for the simultaneous quantitation and pharmacokinetic study of five phthalides (senkyunolide A, ligustilide, butylidenephthalide, 3-butylphthalide, and levistilide A) in rat plasma after oral administration of Huo Luo Xiao Ling Dan (HLXLD) or Angelica sinensis--Ligusticum chuanxiong herb pair (DG-CX) between normal and arthritis rats. After extraction from blood, the analytes and internal standard were subjected to ultra-high performance liquid chromatography with a Shim-pack XR-ODS column (75 × 3.0 mm(2) , 2.2 µm particles) and mobile phase was composed of methanol and water (containing 0.05% formic acid) under gradient elution conditions, with an electrospray ionization source in the positive ionization and multiple reaction monitoring mode. The lower limits of quantification were 0.192-0.800 ng/mL for all the analytes. Satisfactory linearity, precision, accuracy, mean extraction recovery, and acceptable matrix effect have been achieved. The validated method was successfully applied to a comparative pharmacokinetic study of five bioactive components in rat plasma after oral administration of HLXLD or DG-CX alone, respectively, between normal and arthritic rats. The results showed that there were unlike characters of pharmacokinetics among different groups.

Pharmacokinetic comparison of five tanshinones in normal and arthritic rats after oral administration of Huo Luo Xiao Ling Dan or its single herb extract by UPLC-MS/MS.

A fast, sensitive and reliable ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated for simultaneous quantitation and pharmacokinetic study of five tanshinones (tanshinone I, tanshinone IIA, tanshinone IIB, dihydrotanshinone I, cryptotanshinone), the bio-active ingredients of Huo Luo Xiao Ling Dan (HLXLD) in rat plasma. After liquid-liquid extraction, chromatographic separation was accomplished on a Shim-pack XR-ODS column (75 × 3.0 mm, 2.2 µm particles) and eluted with a mobile phase consisting of acetonitrile-0.05% formic acid aqueous solution (80:20, v/v) at a flow rate of 0.4 mL/min, and the total run time was 7.0 min. The detection was performed on a triple quadrupole tandem mass spectrometry equipped with an electrospray ionization source in positive ionization and multiple reaction monitoring mode. The lower limits of quantification were 0.050-0.400 ng/mL for all the analytes. Linearity, precision and accuracy, the mean extraction recoveries and matrix effects all satisfied criteria for acceptance. This validated method was successfully applied to a comparative pharmacokinetic study of five bio-active components in rat plasma after oral administration of HLXLD or Salvia miltiorrhiza extract in normal and arthritic rats. The results showed that there were different pharmacokinetic characteristics among different groups. Copyright © 2016 John Wiley & Sons, Ltd.

Simultaneous determination of four secoiridoid and iridoid glycosides in rat plasma by ultra performance liquid chromatography-tandem mass spectrometry and its application to a comparative pharmacokinetic study.

A simple, reliable and rapid ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of four secoiridoid (gentiopicroside, swertiamarin, sweroside) and iridoid glycosides (loganic acid), the bio-active ingredients in rat plasma. After liquid-liquid extraction, chromatographic separation was accomplished on a Shim-pack XR-ODS column with a mobile phase consisting of methanol and 0.1% formic acid in water. A triple quadrupole tandem mass spectrometry equipped with an electrospray ionization source was used as detector operating both in positive and negative ionization mode and operated by multiple-reaction monitoring scanning. The lower limits of quantitation were 0.25-30 ng/mL for all the analytes. Both intra-day and inter-day precision and accuracy of analytes were well within acceptance criteria (±15%). The mean extraction recoveries of analytes and internal standard (amygdalin) from rat plasma were all >71.4%. The validated method was successfully applied to a comparative pharmacokinetic study of four analytes in rat plasma between normal and arthritic rats after oral administration of Huo Luo Xiao Ling Dan and Gentiana macrophylla extract, respectively. Results showed significant differences in pharmacokinetic properties of the analytes among the different groups.

Metabolites identification of Huo Luo Xiao Ling Dan in rat urine by UPLC coupled with electrospray ionization time-of-flight mass spectrometry.

Huo Luo Xiao Ling Dan (HLXLD), a Chinese herbal formula, is used in folk medicine for the treatment of arthritis and other chronic inflammatory diseases. However, the in vivo integrated metabolism of its multiple components remains unknown. In this paper, an ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) method was developed for detection and identification of HLXLD metabolites in rat urine at high and normal clinical dosages. The prototype constituents and their metabolites in urine were analyzed. The mass measurements were accurate within 8 ppm, and subsequent fragment ions offered higher quality structural information for interpretation of the fragmentation pathways of various compounds. A total of 85 compounds were detected in high dosages urine samples by a highly sensitive extracted ion chromatograms method, including 31 parent compounds and 54 metabolites. Our results indicated that phase 2 reactions (e.g. glucuronidation, glutathionidation and sulfation) were the main metabolic pathways of lactones, alkaloids and flavones, while phase I reactions (e.g. hydrogenation and hydroxylation) were the major metabolic reaction for coumarins, paeoniflorin and iridoids. This investigation provided important structural information on the metabolism of HLXLD and provided scientific evidence to obtain a more comprehensive metabolic profile.

Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine, for patients with osteoarthritis of the knee: a multi-site, randomized, double-blind, placebo-controlled phase II clinical trial.

OBJECTIVE: To examine the efficacy and safety of Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine (TCM), in patients with knee osteoarthritis (OA). DESIGN: A multi-site, randomized, double-blind, placebo-controlled phase II dose-escalation clinical trial was conducted. Eligible patients who fulfilled American College of Rheumatology criteria were randomized to receive either HLXL or placebo. Clinical assessments included measurement of knee pain and function with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), patient global assessment (PGA), and knee pain scores every 2 weeks. A Data and Safety Monitoring Board (DSMB) was established to review the data for ensuring the quality of the trial. RESULTS: In the first stage, 28 participants were randomized to receive either low-dose HLXL-Dan (2400 mg/day) or placebo for 6 weeks. The results showed no statistical difference between the two groups. The study was then re-designed following the recommendation of DSMB. Ninety-two patients were enrolled in the second stage and were randomized to receive either high-dose HLXL-Dan (4000 mg/day for week 1-2, and 5600 mg/day for week 3-8) or placebo for 8 weeks. All outcome assessments showed significant improvements for both groups after 8 weeks but no significant between-group differences. The change (mean ± SD) of WOMAC pain and WOMAC function scores of HLXL and placebo group after 8 weeks were -1.2 ± 1.7 vs -1.4 ± 1.5, and -1.1 ± 1.6 vs -1.3 ± 1.5 respectively. No serious adverse events were reported. CONCLUSION: Although safe to use, an 8-week treatment of HLXL-Dan was not superior to placebo for reduction in pain or functional improvement in patients with knee OA. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov (NCT00755326).

The Mechanism of Reflection Type Reentry: A Simulation Study.

INTRODUCTION: Reflection is a special type of reentry in which an electrical wave front travels in a forward direction through tissue that is then re-excited by a wave front that propagates backward. This type of reentry has been studied computationally in 1-dimensional fibers and verified experimentally. Different hypotheses explaining reflected reentry have been proposed based on the structure and heterogeneity of the tissue properties, but the mechanism remains uncertain. METHODS AND RESULTS: We used the bidomain model to represent cardiac tissue and the Luo-Rudy model to describe the active membrane properties. We consider an ischemic region in a volume of ventricular myocardium. Our results show that a slow depolarization in the ischemic border zone caused by electrotonic coupling to depolarized tissue in the normal region creates a delay between proximal and distal regions that produces enough electrotonic current in the distal region to re-excite the proximal region. CONCLUSION: Our simulation shows that an early afterdepolarization (EAD) is not the source of the reflection. It depends on the pacing interval and stimulus strength necessary to maintain enough time delay between proximal and distal regions.

Systematic chemical profiling of a multicomponent Chinese herbal formula Huo Luo Xiao Ling Dan by ultra high performance liquid chromatography coupled with electrospray ionization quadrupoletime-of-flight mass spectrometry.

Huo Luo Xiao Ling Dan, a Chinese herbal formula consisting of 11 different herbs, has been used in folk medicine for the treatment of arthritis and other chronic inflammatory diseases. However, the chemical compositions of Huo Luo Xiao Ling Dan are not completely characterized. In the present study, an ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry method in positive and negative ion modes was employed to identify biochemical constitutes in Huo Luo Xiao Ling Dan. As a result, a total of 76 compounds including alkaloids, monoterpene glycosides, iridoids, phenolic acids, and tanshinones, coumarins, lactones, flavones, and their glycosides, triterpenes, and triterpene saponins were characterized by comparing the retention time and mass spectrometry data with reference standards within 5 ppm error or by reference to the reference literature. These results would provide the basis for a further in vivo study of Huo Luo Xiao Ling Dan and information for potential new drug candidates for treating arthritis and other chronic inflammatory diseases.

Effects of four traditional Chinese medicines on the pharmacokinetics of simvastatin.

1. Concomitant traditional Chinese medicines (TCMs) could be the reason for relative poor efficacy of statins in dyslipidemia patients in China. 2. An open-label, randomized, 5-period crossover study in healthy Chinese was designed to evaluate the pharmacokinetic interaction and tolerability of multiple doses of certain TCMs on a single dose of simvastatin. In each period, subjects received one of five treatments. In Treatment A, subjects received a single dose of 20 mg simvastatin. In Treatment B, C, D or E, subjects received Tong Xin Luo, Nao Xin Tong, Guan Mai Ning or Yin Xing Ye for 7 days and a single dose of 20 mg simvastatin on Day 7. The washout period was 7 days. 3. The 97.5% confidence interval of the AUC0-48 h geometric mean ratio of simvastatin acid and simvastatin for simvastatin given after multiple oral doses of one of the TCMs versus simvastatin given alone were fully contained within the prespecified bounds of (0.50, 2.00). 4. Exposures to simvastatin acid and simvastatin following a single dose of simvastatin alone were similar to those following coadministration of a single dose of simvastatin with multiple doses of each of the TCM preparations tested. Simvastatin and these TCMs were well tolerated.

Generic concepts in Nectriaceae.

The ascomycete family Nectriaceae (Hypocreales) includes numerous important plant and human pathogens, as well as several species used extensively in industrial and commercial applications as biodegraders and biocontrol agents. Members of the family are unified by phenotypic characters such as uniloculate ascomata that are yellow, orange-red to purple, and with phialidic asexual morphs. The generic concepts in Nectriaceae are poorly defined, since DNA sequence data have not been available for many of these genera. To address this issue we performed a multi-gene phylogenetic analysis using partial sequences for the 28S large subunit (LSU) nrDNA, the internal transcribed spacer region and intervening 5.8S nrRNA gene (ITS), the large subunit of the ATP citrate lyase (acl1), the RNA polymerase II largest subunit (rpb1), RNA polymerase II second largest subunit (rpb2), α-actin (act), ß-tubulin (tub2), calmodulin (cmdA), histone H3 (his3), and translation elongation factor 1-alpha (tef1) gene regions for available type and authentic strains representing known genera in Nectriaceae, including several genera for which no sequence data were previously available. Supported by morphological observations, the data resolved 47 genera in the Nectriaceae. We re-evaluated the status of several genera, which resulted in the introduction of six new genera to accommodate species that were initially classified based solely on morphological characters. Several generic names are proposed for synonymy based on the abolishment of dual nomenclature. Additionally, a new family is introduced for two genera that were previously accommodated in the Nectriaceae.

Sickle cell trait is not associated with endemic Burkitt lymphoma: an ethnicity and malaria endemicity-matched case-control study suggests factors controlling EBV may serve as a predictive biomarker for this pediatric cancer.

Endemic Burkitt lymphoma (eBL) is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum coinfections. Malaria appears to dysregulate immunity that would otherwise control EBV, thereby contributing to eBL etiology. Juxtaposed to human genetic variants associated with protection from malaria, it has been hypothesized that such variants could decrease eBL susceptibility, historically referred to as "the protective hypothesis." Past studies attempting to link sickle cell trait (HbAS), which is known to be protective against malaria, with protection from eBL were contradictory and underpowered. Therefore, using a case-control study design, we examined HbAS frequency in 306 Kenyan children diagnosed with eBL compared to 537 geographically defined and ethnically matched controls. We found 23.8% HbAS for eBL patients, which was not significantly different compared to 27.0% HbAS for controls [odds ratio (OR) = 0.85; 95% confidence interval (CI) 0.61-1.17; p-value = 0.33]. Even though cellular EBV titers, indicative of the number of latently infected B cells, were significantly higher (p-value < 0.0003) in children residing in malaria holoendemic compared to hypoendemic areas, levels were not associated with HbAS genotype. Combined, this suggests that although HbAS protects against severe malaria and hyperparasitemia, it is not associated with viral control or eBL protection. However, based on receiver operating characteristic curves factors that enable the establishment of EBV persistence, in contrast to those involved in EBV lytic reactivation, may have utility as an eBL precursor biomarker. This has implications for future human genetic association studies to consider variants influencing control over EBV in addition to malaria as risk factors for eBL.