132 research outputs found

    Serum CA 125 concentrations in women with endometriosis or uterine fibroids treated with gonadotrophin-releasing hormone agonist analogues

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    We assessed the possible role of CA 125 in the monitoring of gonadotrophin-releasing hormone (GnRH) agonist analogue therapy in women with endometriosis and uterine fibroids. Serum concentrations of this cell surface antigen did not correlate with uterine volume and appeared to have no value in the assessment of shrinkage of uterine fibroids during GnRH agonist treatment. While CA 125 levels were not always elevated in subjects with endometriosis, they fell during treatment in all patients. The change accurately reflected therapeutic progress in these women and was of particular value in those patients who had commenced therapy with elevated levels. It is suggested that CA 125 may be useful in the monitoring of therapeutic progress in selected patients with endometriosis treated with GnRH agonists; the need for surgical follow-up may be obviated

    A Panel of Ancestry Informative Markers for the Complex Five-Way Admixed South African Coloured Population

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    Admixture is a well known confounder in genetic association studies. If genome-wide data is not available, as would be the case for candidate gene studies, ancestry informative markers (AIMs) are required in order to adjust for admixture. The predominant population group in the Western Cape, South Africa, is the admixed group known as the South African Coloured (SAC). A small set of AIMs that is optimized to distinguish between the five source populations of this population (African San, African non-San, European, South Asian, and East Asian) will enable researchers to cost-effectively reduce false-positive findings resulting from ignoring admixture in genetic association studies of the population. Using genome-wide data to find SNPs with large allele frequency differences between the source populations of the SAC, as quantified by Rosenberg et. al's -statistic, we developed a panel of AIMs by experimenting with various selection strategies. Subsets of different sizes were evaluated by measuring the correlation between ancestry proportions estimated by each AIM subset with ancestry proportions estimated using genome-wide data. We show that a panel of 96 AIMs can be used to assess ancestry proportions and to adjust for the confounding effect of the complex five-way admixture that occurred in the South African Coloured population.Department of HE and Training approved lis

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

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    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

    Pediatric Index of Mortality 3 - an evaluation of function among ICUs in South Africa

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    OBJECTIVES : To evaluate the performance of the Pediatric Index of Mortality 3 as mortality risk assessment model. DESIGN : This prospective study included all admissions 30 days to 18 years old for 12 months during 2016 and 2017. Data gathered included the following: age and gender, diagnosis and reason for PICU admission, data specific for the Pediatric Index of Mortality 3 calculation, PICU outcomes (death or survival), and length of PICU stay. SETTING : Nine units that care for children within tertiary or quaternary academic hospitals in South Africa. PATIENTS : All admissions 30 days to 18 years old, excluding premature infants, children who died within 2 hours of admission, or children transferred to other PICUs, and those older than 18 years old. INTERVENTIONS : None. MEASUREMENTS AND MAIN RESULTS : There were 3,681 admissions of which 2,253 (61.3%) were male. The median age was 18 months (interquartile range, 6–59.5 mo). There were 354 deaths (9.6%). The Pediatric Index of Mortality 3 predicted 277.47 deaths (7.5%). The overall standardized mortality ratio was 1.28. The area under the receiver operating characteristic curve was 0.81 (95% CI 0.79–0.83). The Hosmer-Lemeshow goodness-of-fit test statistic was 174.4 (p < 0.001). Standardized mortality ratio for all age groups was greater than 1. Standardized mortality ratio for diagnostic subgroups was mostly greater than 1 except for those whose reason for PICU admission was classified as accident, toxin and envenomation, and metabolic which had an standardized mortality ratio less than 1. There were similar proportions of respiratory patients, but significantly greater proportions of neurologic and cardiac (including postoperative) patients in the Pediatric Index of Mortality 3 derivation cohort than the South African cohort. In contrast, the South African cohort contained a significantly greater proportion of miscellaneous (including injury/accident victims) and postoperative noncardiac patients. CONCLUSIONS : The Pediatric Index of Mortality 3 discrimination between death and survival among South African units was good. Case-mix differences between these units and the Pediatric Index of Mortality 3 derivation cohort may partly explain the poor calibration. We need to recalibrate Pediatric Index of Mortality 3 to the local setting.Ann Lake Publications, Getinge, Drager, Biomerieux, Astellas, Fresenius Kabi, the University of Cape Town, Imperial College Press (royalties), Critical Care Society of Southern Africa, N Kelly attorneys.https://journals.lww.com/pccmjournal/pages/default.aspxhj2022Paediatrics and Child Healt

    Acute hyperglycemia abolishes cardioprotection by remote ischemic perconditioning

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    BACKGROUND: Remote ischemic perconditioning (RIPerC) has a promising therapeutic insight to improve the prognosis of acute myocardial infarction. Chronic comorbidities such as diabetes are known to interfere with conditioning interventions by modulating cardioprotective signaling pathways, such as e.g., mTOR pathway and autophagy. However, the effect of acute hyperglycemia on RIPerC has not been studied so far. Therefore, here we investigated the effect of acute hyperglycemia on cardioprotection by RIPerC. METHODS: Wistar rats were divided into normoglycemic (NG) and acute hyperglycemic (AHG) groups. Acute hyperglycemia was induced by glucose infusion to maintain a serum glucose concentration of 15-20 mM throughout the experimental protocol. NG rats received mannitol infusion of an equal osmolarity. Both groups were subdivided into an ischemic (Isch) and a RIPerC group. Each group underwent reversible occlusion of the left anterior descending coronary artery (LAD) for 40 min in the presence or absence of acute hyperglycemia. After the 10-min LAD occlusion, RIPerC was induced by 3 cycles of 5-min unilateral femoral artery and vein occlusion and 5-min reperfusion. After 120 min of reperfusion, infarct size was measured by triphenyltetrazolium chloride staining. To study underlying signaling mechanisms, hearts were harvested for immunoblotting after 35 min in both the NG and AHG groups. RESULTS: Infarct size was significantly reduced by RIPerC in NG, but not in the AHG group (NG + Isch: 46.27 +/- 5.31 % vs. NG + RIPerC: 24.65 +/- 7.45 %, p < 0.05; AHG + Isch: 54.19 +/- 4.07 % vs. 52.76 +/- 3.80 %). Acute hyperglycemia per se did not influence infarct size, but significantly increased the incidence and duration of arrhythmias. Acute hyperglycemia activated mechanistic target of rapamycine (mTOR) pathway, as it significantly increased the phosphorylation of mTOR and S6 proteins and the phosphorylation of AKT. In spite of a decreased LC3II/LC3I ratio, other markers of autophagy, such as ATG7, ULK1 phopsphorylation, Beclin 1 and SQSTM1/p62, were not modulated by acute hyperglycemia. Furthermore, acute hyperglycemia significantly elevated nitrative stress in the heart (0.87 +/- 0.01 vs. 0.50 +/- 0.04 microg 3-nitrotyrosine/mg protein, p < 0.05). CONCLUSIONS: This is the first demonstration that acute hypreglycemia deteriorates cardioprotection by RIPerC. The mechanism of this phenomenon may involve an acute hyperglycemia-induced increase in nitrative stress and activation of the mTOR pathway

    Associations between human leukocyte antigen class I variants and the Mycobacterium tuberculosis subtypes causing disease

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    BACKGROUND. The development of active tuberculosis disease has been shown to be multifactorial. Interactions between host and bacterial genotype may influence disease outcome, with some studies indicating the adaptation of M. tuberculosis strains to specific human populations. Here we investigate the role of the human leukocyte antigen (HLA) class I genes in this biological process. METHODS. Three hundred patients with tuberculosis from South Africa were typed for their HLA class I alleles by direct sequencing. Mycobacterium tuberculosis genotype classification was done by IS6110 restriction fragment length polymorphism genotyping and spoligotyping. RESULTS. We showed that Beijing strain occurred more frequently in individuals with multiple disease episodes (P < .001) with the HLA-B27 allele lowering the odds of having an additional episode (odds ratio, 0.21; P = .006). Associations were also identified for specific HLA types and disease caused by the Beijing, LAM, LCC, and Quebec strains. HLA types were also associated with disease caused by strains from the Euro-American or East Asian lineages, and the frequencies of these alleles in their sympatric human populations identified potential coevolutionary events between host and pathogen. CONCLUSIONS. This is the first report of the association of human HLA types and M. tuberculosis strain genotype, highlighting that both host and pathogen genetics need to be taken into consideration when studying tuberculosis disease development.Web of Scienc

    The MeerKAT telescope as a pulsar facility: System verification and early science results from MeerTime

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    We describe system verification tests and early science results from the pulsar processor (PTUSE) developed for the newly commissioned 64-dish SARAO MeerKAT radio telescope in South Africa. MeerKAT is a high-gain ( ) low-system temperature ( ) radio array that currently operates at 580–1 670 MHz and can produce tied-array beams suitable for pulsar observations. This paper presents results from the MeerTime Large Survey Project and commissioning tests with PTUSE. Highlights include observations of the double pulsar , pulse profiles from 34 millisecond pulsars (MSPs) from a single 2.5-h observation of the Globular cluster Terzan 5, the rotation measure of Ter5O, a 420-sigma giant pulse from the Large Magellanic Cloud pulsar PSR , and nulling identified in the slow pulsar PSR J0633–2015. One of the key design specifications for MeerKAT was absolute timing errors of less than 5 ns using their novel precise time system. Our timing of two bright MSPs confirm that MeerKAT delivers exceptional timing. PSR exhibits a jitter limit of whilst timing of PSR over almost 11 months yields an rms residual of 66 ns with only 4 min integrations. Our results confirm that the MeerKAT is an exceptional pulsar telescope. The array can be split into four separate sub-arrays to time over 1 000 pulsars per day and the future deployment of S-band (1 750–3 500 MHz) receivers will further enhance its capabilities
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