Influence of the asexual parasite biomass on in vitro susceptibility of Plasmodium falciparum to antimalarial drugs in Abidjan

The in vitro activities of artemisinin, dihydroartemisinin (the biologically active metabolite of artemisinin derivatives), chloroquine and pyronaridine were assessed in 32 isolates of Plasmodium falciparum from Abobo in the northern of Abidjan district (Cote dfIvoire) using a test based on the standard microtechnique recommended by the World Health Organization (WHO). The parasites densities were ranged between 8,000 and 540,000 rings/ƒÊl of blood. The geometric means 50% inhibitory concentration (GMIC50) values for chloroquine, pyronaridine and artemisinin were 145.5 nM (95% confidence interval (CI) =65-226 nM), 17.69 nM (95% CI=9.1-26.3 nM) and 5.72 nM (95% CI=2.3-9.1 nM), respectively. Dihydroartemisinin was the most potent drug against chloroquine-sensitive and chloroquine-resistant isolates with a geometric mean of 2.72 nM. There was no correlation between the parasite densities and the responses to chloroquine (r2=0.01, p<0.5), pyronaridine (r2=0.13, p<0.05), artemisinin (r2=0.13, p<0.05) and dihydroartemisinin (r2=0.07, p<0.1)

Early Clinical and Subclinical Visual Evoked Potential and Humphrey's Visual Field Defects in Cryptococcal Meningitis.

Cryptococcal induced visual loss is a devastating complication in survivors of cryptococcal meningitis (CM). Early detection is paramount in prevention and treatment. Subclinical optic nerve dysfunction in CM has not hitherto been investigated by electrophysiological means. We undertook a prospective study on 90 HIV sero-positive patients with culture confirmed CM. Seventy-four patients underwent visual evoked potential (VEP) testing and 47 patients underwent Humphrey's visual field (HVF) testing. Decreased best corrected visual acuity (BCVA) was detected in 46.5% of patients. VEP was abnormal in 51/74 (68.9%) right eyes and 50/74 (67.6%) left eyes. VEP P100 latency was the main abnormality with mean latency values of 118.9 (±16.5) ms and 119.8 (±15.7) ms for the right and left eyes respectively, mildly prolonged when compared to our laboratory references of 104 (±10) ms (p<0.001). Subclinical VEP abnormality was detected in 56.5% of normal eyes and constituted mostly latency abnormality. VEP amplitude was also significantly reduced in this cohort but minimally so in the visually unimpaired. HVF was abnormal in 36/47 (76.6%) right eyes and 32/45 (71.1%) left eyes. The predominant field defect was peripheral constriction with an enlarged blind spot suggesting the greater impact by raised intracranial pressure over that of optic neuritis. Whether this was due to papilloedema or a compartment syndrome is open to further investigation. Subclinical HVF abnormalities were minimal and therefore a poor screening test for early optic nerve dysfunction. However, early optic nerve dysfunction can be detected by testing of VEP P100 latency, which may precede the onset of visual loss in CM

Meditation Awareness Training (MAT) for Work-related Wellbeing and Job Performance: A Randomised Controlled Trial

Due to its potential to concurrently improve work-related wellbeing (WRW) and job performance, occupational stakeholders are becoming increasingly interested in the applications of meditation. The present study conducted the first randomized controlled trial to assess the effects of meditation on outcomes relating to both WRW and job performance. Office-based middle-hierarchy managers (n = 152) received an eight-week meditation intervention (Meditation Awareness Training; MAT) or an active control intervention. MAT participants demonstrated significant and sustainable improvements (with strong effect sizes) over control-group participants in levels of work-related stress, job satisfaction, psychological distress, and employer-rated job performance. There are a number of novel implications: (i) meditation can effectuate a perceptual shift in how employees experience their work and psychological environment and may thus constitute a cost-effective WRW intervention, (ii) meditation-based (i.e., present-moment-focussed) working styles may be more effective than goal-based (i.e., future-orientated) working styles, and (iii) meditation may reduce the separation made by employees between their own interests and those of the organizations they work for

The influence of legislators’ endorsements in party leadership elections

In the 2010 election for the post of leader of the British Labour party, almost all members of parliament endorsed one of five leadership candidates. I investigate the effect of these endorsements on the votes cast for candidates in each Westminster constituency. I find that an MP’s endorsement caused an average increase of 7.5 percentage points in the vote share of the endorsed candidate in that MP’s constituency

Revising the WHO verbal autopsy instrument to facilitate routine cause-of-death monitoring.

OBJECTIVE: Verbal autopsy (VA) is a systematic approach for determining causes of death (CoD) in populations without routine medical certification. It has mainly been used in research contexts and involved relatively lengthy interviews. Our objective here is to describe the process used to shorten, simplify, and standardise the VA process to make it feasible for application on a larger scale such as in routine civil registration and vital statistics (CRVS) systems. METHODS: A literature review of existing VA instruments was undertaken. The World Health Organization (WHO) then facilitated an international consultation process to review experiences with existing VA instruments, including those from WHO, the Demographic Evaluation of Populations and their Health in Developing Countries (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium (PHMRC). In an expert meeting, consideration was given to formulating a workable VA CoD list [with mapping to the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and utility of existing VA interview questions, with a view to undertaking systematic simplification. FINDINGS: A revised VA CoD list was compiled enabling mapping of all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public health significance as well as potential for ascertainment from VA. A set of 221 indicators for inclusion in the revised VA instrument was developed on the basis of accumulated experience, with appropriate skip patterns for various population sub-groups. The duration of a VA interview was reduced by about 40% with this new approach. CONCLUSIONS: The revised VA instrument resulting from this consultation process is presented here as a means of making it available for widespread use and evaluation. It is envisaged that this will be used in conjunction with automated models for assigning CoD from VA data, rather than involving physicians

Critical Appraisal of Four IL-6 Immunoassays

BACKGROUND: Interleukin-6 (IL-6) contributes to numerous inflammatory, metabolic, and physiologic pathways of disease. We evaluated four IL-6 immunoassays in order to identify a reliable assay for studies of metabolic and physical function. Serial plasma samples from intravenous glucose tolerance tests (IVGTTs), with expected rises in IL-6 concentrations, were used to test the face validity of the various assays. METHODS AND FINDINGS: IVGTTs, administered to 14 subjects, were performed with a single infusion of glucose (0.3 g/kg body mass) at time zero, a single infusion of insulin (0.025 U/kg body mass) at 20 minutes, and frequent blood collection from time zero to 180 minutes for subsequent Il-6 measurement. The performance metrics of four IL-6 detection methods were compared: Meso Scale Discovery immunoassay (MSD), an Invitrogen Luminex bead-based multiplex panel (LX), an Invitrogen Ultrasensitive Luminex bead-based singleplex assay (ULX), and R&D High Sensitivity ELISA (R&D). IL-6 concentrations measured with MSD, R&D and ULX correlated with each other (Pearson Correlation Coefficients r = 0.47-0.94, p<0.0001) but only ULX correlated (r = 0.31, p = 0.0027) with Invitrogen Luminex. MSD, R&D, and ULX, but not LX, detected increases in IL-6 in response to glucose. All plasma samples were measurable by MSD, while 35%, 1%, and 4.3% of samples were out of range when measured by LX, ULX, and R&D, respectively. Based on representative data from the MSD assay, baseline plasma IL-6 (0.90 ± 0.48 pg/mL) increased significantly as expected by 90 minutes (1.29 ± 0.59 pg/mL, p = 0.049), and continued rising through 3 hours (4.25 ± 3.67 pg/mL, p = 0.0048). CONCLUSION: This study established the face validity of IL-6 measurement by MSD, R&D, and ULX but not LX, and the superiority of MSD with respect to dynamic range. Plasma IL-6 concentrations increase in response to glucose and insulin, consistent with both an early glucose-dependent response (detectable at 1-2 hours) and a late insulin-dependent response (detectable after 2 hours)

Persistence of back pain symptoms after pregnancy and bone mineral density changes as measured by quantitative ultrasound - a two year longitudinal follow up study

<p>Abstract</p> <p>Background</p> <p>Previous research has shown a loss of bone mineral density (BMD) during pregnancy. This loss has been correlated to the occurrence of back pain symptoms during pregnancy. The objective of this study was to evaluate whether persistence of back pain symptoms 2 years after pregnancy could be associated with BMD changes as measured by quantitative USG of the os calcis.</p> <p>Methods</p> <p>A cohort of patients who reported significant back pain symptoms during pregnancy were surveyed for persistent back pain symptoms 24 to 28 months after the index pregnancy. Os calcis BMD was measured by quantitative ultrasound and compared with the BMD values during pregnancy.</p> <p>Results</p> <p>A cohort of 60 women who had reported significant back pain symptoms in their index pregnancy completed a 24-28 months follow-up survey and BMD reassessment. Persistence of significant back pain symptoms was seen in 24 (40%) of this cohort. These women had higher BMD loss during pregnancy compared to those without further pain (0.047 Vs 0.030 g/cm²; p = 0.03). Those that remained pain free after pregnancy appeared to have completely recovered their BMD loss in pregnancy, while those with persistent pain had lower BMD values (ΔBMD - 0.007 Vs - 0.025 g/cm²; p = 0.023) compared to their early pregnancy values.</p> <p>Conclusion</p> <p>Persistence of back pain symptoms after pregnancy could be related to an inability to recover fully from BMD loss during the index pregnancy.</p

The direction of effects between perceived parental behavioral control and psychological control and adolescents’ self-reported GAD and SAD symptoms

This study examined the direction of effects and age and sex differences between adolescents’ perceptions of parental behavioral and psychological control and adolescents’ self-reports of generalized anxiety disorder (GAD) and separation anxiety disorder (SAD) symptoms. The study focused on 1,313 Dutch adolescents (early-to-middle cohort n = 923, 70.3%; middle-to-late cohort n = 390, 29.7%) from the general population. A multi-group, structural equation model was employed to analyze the direction of the effects between behavioral control, psychological control and GAD and SAD symptoms for the adolescent cohorts. The current study demonstrated that a unidirectional child effect model of the adolescents’ GAD and SAD symptoms predicting parental control best described the data. Additionally, adolescent GAD and SAD symptoms were stronger and more systematically related to psychological control than to behavioral control. With regard to age–sex differences, anxiety symptoms almost systematically predicted parental control over time for the early adolescent boys, whereas no significant differences were found between the late adolescent boys and girls

The DISC1 Pathway Modulates Expression of Neurodevelopmental, Synaptogenic and Sensory Perception Genes

Genetic and biological evidence supports a role for DISC1 across a spectrum of major mental illnesses, including schizophrenia and bipolar disorder. There is evidence for genetic interplay between variants in DISC1 and in biologically interacting loci in psychiatric illness. DISC1 also associates with normal variance in behavioral and brain imaging phenotypes.Here, we analyze public domain datasets and demonstrate correlations between variants in the DISC1 pathway genes and levels of gene expression. Genetic variants of DISC1, NDE1, PDE4B and PDE4D regulate the expression of cytoskeletal, synaptogenic, neurodevelopmental and sensory perception proteins. Interestingly, these regulated genes include existing targets for drug development in depression and psychosis.Our systematic analysis provides further evidence for the relevance of the DISC1 pathway to major mental illness, identifies additional potential targets for therapeutic intervention and establishes a general strategy to mine public datasets for insights into disease pathways

High HIV Incidence and Sexual Behavior Change among Pregnant Women in Lilongwe, Malawi: Implications for the Risk of HIV Acquisition

HIV incidence is higher among pregnant women than their non-pregnant counterparts in some sub-Saharan African settings. Our aims were (1) to estimate HIV incidence during pregnancy and (2) to compare sexual activity between pregnant, postpartum, and non-pregnant women.We examined a retrospective cohort of 1087 women to identify seroconverters using antenatal and labor ward HIV test results. We also conducted a cross-sectional survey, including a quantitative questionnaire (n = 200) and in-depth interviews (n = 20) among women in early pregnancy, late pregnancy, postpartum, and non-pregnancy. Outcomes included measures of sexual activity, reported spouse's risky behavior, and beliefs about abstinence.11 of 1087 women seroconverted during pregnancy yielding a 1% seroconversion risk and an incidence rate of 4.0/100 person years (95% CI 2.2-7.2). The reported sexual activity of the early pregnancy and non-pregnancy groups was similar, but significantly higher than the late pregnancy and postpartum groups (p<0.001). During pregnancy, sex acts decreased as gestation increased (p = 0.001). There was no reported difference in the spouse's risky behavior. Most women believed that sex should cease between the 6(th) and 8(th) month of pregnancy and should not resume until 6 months postpartum. Some talked about conflict between their cultural obligation to abstain and fear of HIV infection if their spouses find other partners.HIV incidence is high among pregnant women in Malawi, and sexual activity decreases during pregnancy and postpartum. Pregnant women need to be informed of their increased risk for HIV and the importance of using condoms throughout pregnancy and the postpartum period