Evaluating the relationship between external markers and internal vertebral kinematics in the cervical spine

Published ArticleThe objective of this study was to examine the relationship between external markers typically used in external motion capturing devices and the true vertebral kinematics in the cervical spine. Twenty one healthy subjects were subjected to low dosage X-rays in five different positions, while radio opaque markers were attached to the skin at each vertebral level. Distance and angle parameters were constructed for vertebral prediction from skin surface markers. The causes of variation in these parameters were identified by investigating the correlations of these parameters with anthropometrical variables. Strong correlations of the parameters were observed in flexion, but in extension, especially full extension, the correlations were poor to insignificant. In neutral, half flexion, and full flexion it is possible to predict the vertebral position from surface markers by using the parameters and anthropometrical variables. In half extension this prediction is less accurate and in full extension alternative methods should be investigated for external motion capturing

Genetic variations in androgen metabolism genes and associations with prostate cancer in South African men

Background. In South Africa white men have the highest incidence of prostate cancer (PCa), coloured (mixed ancestry) men have an intermediate incidence, and low incidences are reported for black and Asian men. It has been suggested that ethnic differences in incidence and mortality of PCa are related to genetic variations in genes that regulate androgen metabolism. We investigated the role of genetic variants in the androgen metabolism genes and the probability of developing PCa in South African coloured and white men. Methods. Genotype and allele counts and frequencies of single nucleotide polymorphisms (SNPs) in CYP3A5, CYP3A4 and CYP3A43 were assessed in coloured men (160 case individuals, 146 control individuals) and white men (121 case individuals, 141 control individuals). Results. A genetic association indicating an increased probability of developing PCa was observed with the G allele of the SNP rs2740574 in CYP3A4 in coloured men, the A allele of rs776746 (CYP3A5) and the G allele of rs2740574 (CYP3A4) in white men, and the G allele of rs2740574 and the C allele of rs501275 (CYP3A43) in the combined ethnic groups analysis. In addition, we identified allele combinations (termed haplotypes) with significantly higher frequencies in the PCa case individuals than in the control individuals. Conclusions. The findings support the role of variants in genes that regulate androgen metabolism and the probability of developing PCa. The study paves the way to identify other genetic associations in South African men, and to establish genetic profiles that could be used to determine disease progression and prognosis

Medical students as research participants: Student experiences, questionnaire response rates and preferred modes

Background. Research projects frequently include students, a potentially vulnerable population, as participants. Objectives. To determine University of the Free State (UFS) medical students’ experiences as research participants. Response rates to and preferences for hard copy and electronic questionnaires were also investigated. Methods. All 804 UFS undergraduate medical students in 2020 were approached to participate in this cross-sectional survey. Fourth- and fifth-year students and one-half of the third-year class were approached in person to complete anonymous hard copy questionnaires in a class setting. First- and second-year students and the other half of the third-year class were contacted electronically to complete anonymous electronic questionnaires. Results. Response rates to hard copy questionnaires were at least ~45% of the entire year group (and >70% of those to whom the questionnaire was distributed in class) compared with approximately a third of those contacted electronically. Students who responded to electronic questionnaires preferred electronic completion, whereas those who responded to hard copy questionnaires preferred the hard copy format, except fifth-year students. The majority of students (except those in their first year) had previously been approached to participate in research projects. Between a fifth and a third of all year groups indicated that they had refused participation at least once. More than a third of fifth-year students experienced insufficient time to decide on participation. Up to a quarter of third- to fifth-year groups had felt pressurised to participate. Conclusion. Hard copy questionnaires in class, the preferred data collection method for many students, produced better response rates but placed potential pressure on students to participate

Genetic variations in androgen metabolism genes and associations with prostate cancer in South African men

Background. In South Africa white men have the highest incidence of prostate cancer (PCa), coloured (mixed ancestry) men have an intermediate incidence, and low incidences are reported for black and Asian men. It has been suggested that ethnic differences in incidence and mortality of PCa are related to genetic variations in genes that regulate androgen metabolism. We investigated the role of genetic variants in the androgen metabolism genes and the probability of developing PCa in South African coloured and white men. Methods. Genotype and allele counts and frequencies of single nucleotide polymorphisms (SNPs) in CYP3A5, CYP3A4 and CYP3A43 were assessed in coloured men (160 case individuals, 146 control individuals) and white men (121 case individuals, 141 control individuals). Results. A genetic association indicating an increased probability of developing PCa was observed with the G allele of the SNP rs2740574 in CYP3A4 in coloured men, the A allele of rs776746 (CYP3A5) and the G allele of rs2740574 (CYP3A4) in white men, and the G allele of rs2740574 and the C allele of rs501275 (CYP3A43) in the combined ethnic groups analysis. In addition, we identified allele combinations (termed haplotypes) with significantly higher frequencies in the PCa case individuals than in the control individuals. Conclusions. The findings support the role of variants in genes that regulate androgen metabolism and the probability of developing PCa. The study paves the way to identify other genetic associations in South African men, and to establish genetic profiles that could be used to determine disease progression and prognosis

Validation of a quantitative liquid chromatography tandem mass spectrometry assay for linezolid in cerebrospinal fluid and its application to patients with HIV-associated TB-meningitis.

Tuberculous meningitis treatment outcomes are poor and alternative regimens are under investigation. Reliable methods to measure drug concentrations in cerebrospinal fluid are required to evaluate distribution into the cerebrospinal fluid. A simple and quick method was developed and validated to analyse linezolid in human cerebrospinal fluid. Samples were prepared by protein precipitation followed by isocratic liquid chromatography and tandem mass spectrometry. The run time was 3.5 min. Accuracy and precision were assessed in three independent validation batches with a calibration range of 0.100-20.0 μg/mL. The method was used to analyse cerebrospinal fluid samples from patients with tuberculous meningitis enrolled in a clinical trial. Potentially infective patient samples could be decontaminated using Nanosep® nylon and Costar® nylon filter tubes under biosafety level 3 conditions before analysis. The filtration process did not significantly affect the quantification of linezolid. Linezolid concentration in cerebrospinal fluid obtained from tuberculous meningitis patients ranged from 0.197 μg/mL to 15.0 μg/mL. The ratio between average CSF and plasma linezolid concentrations varied with time, reaching a maximum of 0.9 at 6 h after dosing

Maternal and neonatal outcomes of COVID-19 in a high-risk pregnant cohort with and without HIV

Background. The impact of SARS-CoV-2 infection in pregnant women living with HIV (PLHIV) has not been described previously.Objectives. To describe the clinical presentation and outcomes of a cohort of women with high-risk pregnancies with confirmed COVID-19 to determine whether risk factors for disease severity and adverse outcomes of COVID-19 differed in pregnant women without HIV compared with PLHIV.Methods. We prospectively enrolled pregnant women with COVID-19 attending the high-risk obstetric service at Tygerberg Hospital, Cape Town, South Africa, from 1 May to 31 July 2020, with follow-up until 31 October 2020. Women were considered high risk if they required specialist care for maternal, neonatal and/or anaesthetic conditions. Common maternal or obstetric conditions included hypertensive disorders, morbid obesity (body mass index (BMI) ≥40 kg/m2) and diabetes. Information on demographics, clinical features, and maternal and neonatal outcomes was collected and compared for PLHIV v. pregnant women without HIV.Results. One hundred women (72 without HIV and 28 PLHIV) with high-risk pregnancies had laboratory-confirmed COVID-19. Among the 28 PLHIV, the median (interquartile range) CD4 count was 441 (317 - 603) cells/µL, and 19/26 (73%) were virologically suppressed. COVID-19 was diagnosed predominantly in the third trimester (81%). Obesity (BMI ≥30 in n=61/81; 75%) and hypertensive disorders were frequent comorbidities. Of the 100 women, 40% developed severe or critical COVID-19, 15% required intensive care unit admission and 6% needed invasive ventilation. Eight women died, 1 from advanced HIV disease complicated by bacteraemia and urosepsis. The crude maternal mortality rate was substantially higher in women with COVID-19 compared with all other deliveries at our institution during this period (8/91 (9%) v. 7/4 058 (0.2%); p<0.001). Neonatal outcomes were favourable. No significant differences in COVID-19 risk factors, disease severity, and maternal/neonatal outcome were noted for PLHIV v. those without HIV.Conclusions. In this cohort of high-risk pregnant women, the impact of COVID-19 was severe, significantly increasing maternal mortality risk compared with baseline rates. Virally suppressed HIV infection was not associated with worse COVID-19 outcomes in pregnancy

Revival of the magnetar PSR J1622-4950: observations with MeerKAT, Parkes, XMM-Newton, Swift, Chandra, and NuSTAR

New radio (MeerKAT and Parkes) and X-ray (XMM-Newton, Swift, Chandra, and NuSTAR) observations of PSR J1622-4950 indicate that the magnetar, in a quiescent state since at least early 2015, reactivated between 2017 March 19 and April 5. The radio flux density, while variable, is approximately 100x larger than during its dormant state. The X-ray flux one month after reactivation was at least 800x larger than during quiescence, and has been decaying exponentially on a 111+/-19 day timescale. This high-flux state, together with a radio-derived rotational ephemeris, enabled for the first time the detection of X-ray pulsations for this magnetar. At 5%, the 0.3-6 keV pulsed fraction is comparable to the smallest observed for magnetars. The overall pulsar geometry inferred from polarized radio emission appears to be broadly consistent with that determined 6-8 years earlier. However, rotating vector model fits suggest that we are now seeing radio emission from a different location in the magnetosphere than previously. This indicates a novel way in which radio emission from magnetars can differ from that of ordinary pulsars. The torque on the neutron star is varying rapidly and unsteadily, as is common for magnetars following outburst, having changed by a factor of 7 within six months of reactivation.Comment: Published in ApJ (2018 April 5); 13 pages, 4 figure