Outbreak of West Nile virus causing severe neurological involvement in children, Nuba Mountains, Sudan, 2002.

An atypical outbreak of West Nile virus (WNV) occurred in Ngorban County, South Kordophan, Sudan, from May to August 2002. We investigated the epidemic and conducted a case-control study in the village of Limon. Blood samples were obtained for cases and controls. Patients with obvious sequelae underwent cerebrospinal fluid (CSF) sampling as well. We used enzyme-linked immunosorbent assay (ELISA) and neutralization tests for laboratory diagnosis and identified 31 cases with encephalitis, four of whom died. Median age was 36 months. Bivariate analysis did not reveal any significant association with the risk factors investigated. Laboratory analysis confirmed presence of IgM antibodies caused by WNV in eight of 13 cases, indicative of recent viral infection. The unique aspects of the WNW outbreak in Sudan, i.e. disease occurrence solely among children and the clinical domination of encephalitis, involving severe neurological sequelae, demonstrate the continuing evolution of WNV virulence. The spread of such a virus to other countries or continents cannot be excluded

Circuit Design to Stabilize the Reflectometer Local Oscillator Signals

Reflectometry, which uses the microwave radar technique to probe the magnetically confined fusion plasmas, is a very powerful tool to observe the density fluctuations in the fusion plasmas. Typically, two or more microwave beams of different frequencies are used to study the plasma density fluctuations. The frequency separation between these two beams of the PPPL designed reflectometer system upgrade on the DIII-D tokamak can be varied over 18 GHz. Due to the performance of the associated electronics, the local oscillator (LO) power level at the LO port of the I/Q demodulator suffers more than 12 dB of power fluctuations when the frequency separation is varied. Thus, the I/Q demodulator performance is impaired. In order to correct this problem, a power leveling circuit is introduced in the PPPL upgrade. According to the test results, the LO power fluctuation was regulated to be within 1 dB for greater than 16 dB of input power variation over the full dynamic bandwidth of the receiver

Vigorous star formation hidden by dust in a galaxy at z=1.4z=1.4

Near-infrared surveys have revealed a substantial population of enigmatic faint galaxies with extremely red optical-to-near-infrared colours and with a sky surface density comparable to that of faint quasars. There are two scenarios for these extreme colours: (i) these distant galaxies have formed virtually all their stars at very high redshifts and, due to the absence of recently formed stars, the colours are extremely red and (ii) these distant galaxies contain large amounts of dust, severely reddening the rest-frame UV--optical spectrum. HR10 ($z = 1.44$) is considered the archetype of the extremely red galaxies. Here we report the detection of the continuum emission from HR10 at 850$\mu$m and at 1250$\mu$m, demonstrating that HR10 is a very dusty galaxy undergoing a major episode of star formation. Our result provides a clear example of a high-redshift galaxy where the star formation rate inferred from the ultraviolet luminosity would be underestimated by a factor up to 1000, and shows that great caution should be used to infer the global star formation history of the Universe from optical observations only.Comment: 12 pages, 1 figure, Nature, in press (30 April 1998

Left atrial structure and function in cardiac amyloidosis

Aims: Although cardiac amyloidosis (CA) is characterized by significant left atrial (LA) dilatation, the characteristics of LA function remain to be fully investigated. // Methods and results: We assessed LA function by speckle-tracking echocardiography in 124 patients with CA and sinus rhythm: 68 with light chain (AL), 29 with mutant (ATTRm), 27 with wild-type (ATTRwt) transthyretin amyloidosis. Conventional and strain-derived parameters, including LA peak longitudinal strain (LS) and strain rate (peak LSR: reservoir function; early LSR: conduit function; late LSR: active function), were assessed compared between CA patients and 20 healthy controls of similar age and gender. All LA function phases, including LA longitudinal strain, peak LSR, early and late LSR were significantly impaired in CA compared to healthy controls after adjusting for LA size, LV ejection fraction and LV filling pressures (E/E’) (all P < 0.05). Peak LA LS was moderately correlated with LV global LS (R = −0.60, P < 0.001); late LSR was correlated with A wave at the level of LV inflow (R = −0.69, P < 0.001). Among the different CA subtypes, peak LS and LA active emptying fraction were worse in ATTRwt than AL and ATTRm [P < 0.05 after adjustment for age, sex, body mass index, systolic blood pressure, heart rate, LA volume index, severity of mitral regurgitation, left ejection fraction, and left ventricular end-diastolic pressure (E/E’)]. // Conclusion: In CA, LA function was severely impaired and highly correlated with LV deformation. Differences in LA function between amyloid subtypes suggest that amyloid aetiology plays a role in the pathophysiology of cardiac dysfunction in CA

Left atrial structure and function in cardiac amyloidosis

Aims: Although cardiac amyloidosis (CA) is characterized by significant left atrial (LA) dilatation, the characteristics of LA function remain to be fully investigated. // Methods and results: We assessed LA function by speckle-tracking echocardiography in 124 patients with CA and sinus rhythm: 68 with light chain (AL), 29 with mutant (ATTRm), 27 with wild-type (ATTRwt) transthyretin amyloidosis. Conventional and strain-derived parameters, including LA peak longitudinal strain (LS) and strain rate (peak LSR: reservoir function; early LSR: conduit function; late LSR: active function), were assessed compared between CA patients and 20 healthy controls of similar age and gender. All LA function phases, including LA longitudinal strain, peak LSR, early and late LSR were significantly impaired in CA compared to healthy controls after adjusting for LA size, LV ejection fraction and LV filling pressures (E/E’) (all P < 0.05). Peak LA LS was moderately correlated with LV global LS (R = −0.60, P < 0.001); late LSR was correlated with A wave at the level of LV inflow (R = −0.69, P < 0.001). Among the different CA subtypes, peak LS and LA active emptying fraction were worse in ATTRwt than AL and ATTRm [P < 0.05 after adjustment for age, sex, body mass index, systolic blood pressure, heart rate, LA volume index, severity of mitral regurgitation, left ejection fraction, and left ventricular end-diastolic pressure (E/E’)]. // Conclusion: In CA, LA function was severely impaired and highly correlated with LV deformation. Differences in LA function between amyloid subtypes suggest that amyloid aetiology plays a role in the pathophysiology of cardiac dysfunction in CA

Benign afebrile cluster convulsions with gastroenteritis: an observational study

BACKROUND: The occurrence of afebrile seizures in association with viral gastroenteritis, without dehydration or electrolyte imbalance, is virtually unknown outside Asia. They are reported to have a benign prognosis and not to require specific investigations or therapy. METHODS: We report the occurrence of such afebrile convulsions in association with viral gastroenteritis without dehydration or electrolyte imbalance, over a 3-year period, in a cohort of 14 British children. RESULTS: The children (5 males and 9 females, 10 Caucasians and 4 Asians) were aged 9 to 60 months (median 14.5 months). All 14 had a normal neurological examination and normal serum biochemistry. Twelve children had generalised seizures and 2 had, in addition, absence seizures. The number of seizures per child ranged from 1 to 8. Most convulsions were short with 85.7% of children having the longest seizure not longer than 4 minutes. The longest duration for a seizure was 10 minutes and occurred in 2 children. Convulsions did not recur after the first day in 10 children, 3 children had recurrences the second day and one child on the fourth day. No convulsions recurred after 4 days. Cerebrospinal fluid studies, computed tomography and electroencephalogram (EEG) were performed on two children who had prolonged seizures and the results were normal. No pathogenic bacteria were grown in any of the stools. Enzyme immunoassay detection of Rotavirus in the stools was positive in 7 of the 10 children where it was tested. All 14 children recovered spontaneously within a few days. On long-term follow of up to 31 months (median 16 months), none had further convulsions and all had normal development milestones. CONCLUSIONS: Afebrile seizures in association with viral gastroenteritis do also occur outside Asia. Recognition of this entity should lead to reassurance of the parents. As in previously published series, investigations such as lumbar puncture, neuroimaging and EEG are usually normal and may not be necessary in most cases. Likewise, published data indicate that long-term anticonvulsant therapy is not usually warranted and the prognosis seems to be reassuring

Active Trachoma and Ocular Chlamydia trachomatis Infection in Two Gambian Regions: On Course for Elimination by 2020?

Trachoma is the leading infectious cause of blindness worldwide, and is mainly found in tropical and poor countries. It is caused by infection of the eyes with the bacterium Chlamydia trachomatis. However, sometimes the clinical signs of disease can be present without infection being detected. Control efforts involve surgery, antibiotic treatment, face washing, and environmental improvement for better hygiene. Surveys of trachoma help countries to know whether and where they should implement control interventions. The Gambia is found in West Africa and has suffered from trachoma for decades. We conducted a survey of two Gambian regions to look at how much trachoma disease and C. trachomatis infection there is in the eyes. We found that although there was enough disease (≥10%) to warrant antibiotic treatment for everyone in the regions, there was nearly no infection (0.3%). This means that using clinical signs alone to make treatment decisions in low prevalence settings like The Gambia can lead to the waste of scarce resources. Our results also suggest that since less than 1% of children are infected with C. trachomatis, The Gambia is on course to achieve the World Health Organization's aim of eliminating blinding trachoma by the year 2020

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

Background risk of breast cancer and the association between physical activity and mammographic density

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The Amyloidogenic V122I Transthyretin Variant in Elderly Black Americans

BACKGROUND: Approximately 4% of black Americans carry a valine-to-isoleucine substitution (V122I) in the transthyretin protein, which has been associated with late-onset restrictive amyloid cardiomyopathy and increased risks of death and heart failure. METHODS: We determined genotype status for the transthyretin gene (TTR) in 3856 black participants in the Atherosclerosis Risk in Communities study and assessed clinical profiles, mortality, and the risk of incident heart failure in V122I TTR variant carriers (124 participants [3%]) versus noncarriers (3732 participants). Cardiac structure and function and features suggestive of cardiac amyloidosis were assessed in participants who underwent echocardiography during visit 5 (2011 to 2013), when they were older than 65 years of age. RESULTS: After 21.5 years of follow-up, we did not detect a significant difference in mortality between carriers (41 deaths, 33%) and noncarriers (1382 deaths, 37%; age- and sex-stratified hazard ratio among carriers, 0.99; 95% confidence interval [CI], 0.73 to 1.36; P=0.97). The TTR variant was associated with an increased risk of incident heart failure (age- and sex-stratified hazard ratio, 1.47; 95% CI, 1.03 to 2.10; P=0.04). On echocardiography at visit 5, carriers (46 participants) had worse systolic and diastolic function, as well as a higher level of N-terminal pro–brain natriuretic peptide, than noncarriers (1194 participants), although carriers had a low prevalence (7%) of overt manifestations of amyloid cardiomyopathy. CONCLUSIONS: We did not detect a significant difference in mortality between V122I TTR allele carriers and noncarriers, a finding that contrasts with prior observations; however, the risk of heart failure was increased among carriers. The prevalence of overt cardiac abnormalities among V122I TTR carriers was low. (Funded by the National Heart, Lung, and Blood Institute and others.