The heart and hypothyroidism

The association of hypothyroidism with heart disease is reviewed. The. relative rarity of cardiac failure due to hypothyroidism is stressed, and structural abnormalities of the heart due to hypothyroidism are discussed. The clinical management of hypothyroid patients with heart disease is described

Coronary heart disease risk factors in a rural and urban Orange Free State black population

Objective. To determine and compare the prevalence of ischaemic heart disease (IHD) risk factors in a rural and an urban black population.Design. A survey to determine the prevalence of hypertension, diabetes mellitus, smoking, obesity, central obesity and dyslipidaemia in black subjects 25 years and older.Setting. The indigenous black populations of QwaQwa and Mangaung.Participants. A random sample of 950 households was selected from each area. From each household an unrelated male and/or female subject was selected in a standardised way. From QwaQwa 853 subjects (279 men and 574 women) and from Mangaung 758 subjects (290 men and 468 women) participated in the study. The response rate was 68% and 62% respectively for QwaQwa and Mangaung.Main outcome measures. Few urban-rural differences in the prevalence of IHD risk factors were found in this study. A low prevalence of clustering of major IHD risk factors was noted.Results. The age- and sex-adjusted prevalences of hypertension were 29% in QwaQwa and 30,3% in Mangaung. Oiabetes was present in 4,8% of the QwaQwa sample and 6% of the Mangaung sample. The prevalence of heavy smoking in the Mangaung sample was almost double that of the QwaQwa sample and mostly confined to men. High-risk hypercholesterolaemia was present in 12,5% of QwaQwa and 6% of Mangaung men in the  25 - 34-year age group. The corresponding figures for moderate-risk hypercholesterolaemia were 34% and 44,8% and both levels of risk declined with increasing age. The mean body mass index of women in both samples exceeded 25 kg/m2.Conclusion. All the elements for a potential epidemic of atherosclerotic cardiovascular disease are present in the study populations. The similarity of findings in the two samples may be indicative of the advanced stage of urbanisation and westernisation of the rural group. It is alarming that subjects in the younger age groups tendeo to have the highest prevalences of moderate and even high-risk hypercholesterolaemia

Ophthalmoscopy versus non-mydriatic fundus photography in the detection of diabetic retinopathy in black patients

The contribution of non-mydriatic fundus photography in the detection of diabetic retinopathy before and after dilatation of the pupils in black diabetics was investigated and compared with direct ophthalmoscopy. Eighty-six patients were examined and good-quality photographs were obtained for 54,7% of eyes before and 86,6% of eyes after dilatation. Photographically documented retinopathy was detected by ophthalmoscopy in only 64,7% of eyes. The two methods were concordant for the presence of retinopathy in 62,2% of eyes before and 56,9% of eyes after dilatation. Photography through dilated pupils also i.mproved the rate of detection of diabetic retinopathy from 24% to 30%. The 45° non-mydriatic fundus camera was found to be a valuable adjunct in the detection of diabetic retinopathy in a busy diabetic clinic

Functional characterisation of the amyotrophic lateral sclerosis risk locus GPX3/TNIP1

Background Amyotrophic lateral sclerosis (ALS) is a complex, late-onset, neurodegenerative disease with a genetic contribution to disease liability. Genome-wide association studies (GWAS) have identified ten risk loci to date, including the TNIP1/GPX3 locus on chromosome five. Given association analysis data alone cannot determine the most plausible risk gene for this locus, we undertook a comprehensive suite of in silico, in vivo and in vitro studies to address this. Methods The Functional Mapping and Annotation (FUMA) pipeline and five tools (conditional and joint analysis (GCTA-COJO), Stratified Linkage Disequilibrium Score Regression (S-LDSC), Polygenic Priority Scoring (PoPS), Summary-based Mendelian Randomisation (SMR-HEIDI) and transcriptome-wide association study (TWAS) analyses) were used to perform bioinformatic integration of GWAS data (Ncases = 20,806, Ncontrols = 59,804) with ‘omics reference datasets including the blood (eQTLgen consortium N = 31,684) and brain (N = 2581). This was followed up by specific expression studies in ALS case-control cohorts (microarray Ntotal = 942, protein Ntotal = 300) and gene knockdown (KD) studies of human neuronal iPSC cells and zebrafish-morpholinos (MO). Results SMR analyses implicated both TNIP1 and GPX3 (p < 1.15 × 10−6), but there was no simple SNP/expression relationship. Integrating multiple datasets using PoPS supported GPX3 but not TNIP1. In vivo expression analyses from blood in ALS cases identified that lower GPX3 expression correlated with a more progressed disease (ALS functional rating score, p = 5.5 × 10−3, adjusted R2 = 0.042, Beffect = 27.4 ± 13.3 ng/ml/ALSFRS unit) with microarray and protein data suggesting lower expression with risk allele (recessive model p = 0.06, p = 0.02 respectively). Validation in vivo indicated gpx3 KD caused significant motor deficits in zebrafish-MO (mean difference vs. control ± 95% CI, vs. control, swim distance = 112 ± 28 mm, time = 1.29 ± 0.59 s, speed = 32.0 ± 2.53 mm/s, respectively, p for all < 0.0001), which were rescued with gpx3 expression, with no phenotype identified with tnip1 KD or gpx3 overexpression. Conclusions These results support GPX3 as a lead ALS risk gene in this locus, with more data needed to confirm/reject a role for TNIP1. This has implications for understanding disease mechanisms (GPX3 acts in the same pathway as SOD1, a well-established ALS-associated gene) and identifying new therapeutic approaches. Few previous examples of in-depth investigations of risk loci in ALS exist and a similar approach could be applied to investigate future expected GWAS findings

Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis

We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI95% = [0.62–0.68], p = 8.3 × 10−22). The maximum AUC achieved was 0.69 (CI95% = [0.66–0.71], p = 4.3 × 10−34) when cell-type proportion was included in the predictor

Long-range Angular Correlations On The Near And Away Side In P-pb Collisions At √snn=5.02 Tev

7191/Mar294

The SARAO MeerKAT 1.3 GHz Galactic Plane Survey

We present the SARAO MeerKAT Galactic Plane Survey (SMGPS), a 1.3 GHz continuum survey of almost half of the Galactic Plane (251○ ≤l ≤ 358○ and 2○ ≤l ≤ 61○ at |b| ≤ 1 5). SMGPS is the largest, most sensitive and highest angular resolution 1 GHz survey of the Plane yet carried out, with an angular resolution of 8″ and a broadband RMS sensitivity of ∼10–20 μJy beam−1. Here we describe the first publicly available data release from SMGPS which comprises data cubes of frequency-resolved images over 908–1656 MHz, power law fits to the images, and broadband zeroth moment integrated intensity images. A thorough assessment of the data quality and guidance for future usage of the data products are given. Finally, we discuss the tremendous potential of SMGPS by showcasing highlights of the Galactic and extragalactic science that it permits. These highlights include the discovery of a new population of non-thermal radio filaments; identification of new candidate supernova remnants, pulsar wind nebulae and planetary nebulae; improved radio/mid-IR classification of rare Luminous Blue Variables and discovery of associated extended radio nebulae; new radio stars identified by Bayesian cross-matching techniques; the realisation that many of the largest radio-quiet WISE H II region candidates are not true H II regions; and a large sample of previously undiscovered background H I galaxies in the Zone of Avoidance

Intoxicação por monofluoroacetato em animais

O monofluoroacetato (MF) ou ácido monofluoroacético é utilizado na Austrália e Nova Zelândia no controle populacional de mamíferos nativos ou exóticos. O uso desse composto é proibido no Brasil, devido ao risco de intoxicação de seres humanos e de animais, uma vez que a substância permanece estável por décadas. No Brasil casos recentes de intoxicação criminosa ou acidental têm sido registrados. MF foi identificado em diversas plantas tóxicas, cuja ingestão determina "morte súbita"; de bovinos na África do Sul, Austrália e no Brasil. O modo de ação dessa substância baseia-se na formação do fluorocitrato, seu metabólito ativo, que bloqueia competitivamente a aconitase e o ciclo de Krebs, o que reduz produção de ATP. As espécies animais têm sido classificadas nas quatro Categorias em função do efeito provocado por MF: (I) no coração, (II) no sistema nervoso central (III) sobre o coração e sistema nervoso central ou (IV) com sintomatologia atípica. Neste trabalho, apresenta-se uma revisão crítica atualizada sobre essa substância. O diagnóstico da intoxicação por MF é realizado pelo histórico de ingestão do tóxico, pelos achados clínicos e confirmado por exame toxicológico. Uma forma peculiar de degeneração hidrópico-vacuolar das células epiteliais dos túbulos uriníferos contorcidos distais tem sido considerada como característica dessa intoxicação em algumas espécies. O tratamento da intoxicação por MF é um desafio, pois ainda não se conhece um agente capaz de reverte-la de maneira eficaz; o desfecho geralmente é fata