Band 3 mutations, distal renal tubular acidosis, and Southeast Asian ovalocytosis

Band 3 mutations, distal renal tubular acidosis, and Southeast Asian ovalocytosis. Familial distal renal tubular acidosis (dRTA) and Southeast Asian ovalocytosis (SAO) may coexist in the same patient. Both can originate in mutations of the anion-exchanger 1 gene (AE1), which codes for band 3, the bicarbonate/chloride exchanger in both the red cell membrane and the basolateral membrane of the collecting tubule alpha-intercalated cell. Dominant dRTA is usually due to a mutation of the AE1 gene, which does not alter red cell morphology. SAO is caused by an AE1 mutation that leads to a nine amino acid deletion of red cell band 3, but by itself does not cause dRTA. Recent gene studies have shown that AE1 mutations are responsible for autosomal recessive dRTA in several countries in Southeast Asia; these patients may be homozygous for the mutation or be compound heterozygotes of two different AE1 mutations, one of which is usually the SAO mutation

Randomized double-blind trial of pregabalin versus placebo in conjunction with palliative radiotherapy for cancer-induced bone pain

Purpose Cancer-induced bone pain (CIBP) affects one third of patients with cancer. Radiotherapy remains the gold-standard treatment; however, laboratory and clinical work suggest that pregabalin may be useful in treating CIBP. The aim of this study was to examine pregabalin in patients with CIBP receiving radiotherapy. Patients and Methods A multicenter, double-blind randomized trial of pregabalin versus placebo was conducted. Eligible patients were age ≥ 18 years, had radiologically proven bone metastases, were scheduled to receive radiotherapy, and had pain scores ≥ 4 of 10 (on 0-to-10 numeric rating scale). Before radiotherapy, baseline assessments were completed, followed by random assignment. Doses of pregabalin and placebo were increased over 4 weeks. The primary end point was treatment response, defined as a reduction of ≥ 2 points in worst pain by week 4, accompanied by a stable or reduced opioid dose, compared with baseline. Secondary end points assessed average pain, interference of pain with activity, breakthrough pain, mood, quality of life, and adverse events. Results A total of 233 patients were randomly assigned: 117 to placebo and 116 to pregabalin. The most common cancers were prostate (n = 88; 38%), breast (n = 77; 33%), and lung (n = 42; 18%). In the pregabalin arm, 45 patients (38.8%) achieved the primary end point, compared with 47 (40.2%) in the placebo arm (adjusted odds ratio, 1.07; 95% CI, 0.63 to 1.81; P = .816). There were no statistically significant differences in average pain, pain interference, or quality of life between arms. There were differences in mood (P = .031) and breakthrough pain duration (P = .037) between arms. Outcomes were compared at 4 weeks. Conclusion Our findings do not support the role of pregabalin in patients with CIBP receiving radiotherapy. The role of pregabalin in CIBP with a clinical neuropathic pain component is unknown

The use of a single complement fixation test technique in bovine brucellosis, Johne's disease, dourine, equine piroplasmosis and Q fever serology

The same techniques may be used in the complement fixation test (CFT) for the serological diagnosis of bovine brucellosis, Johne's disease (paratuberculosis), dourine, equine piroplasmosis and Q fever (caused by Coxiella burnetii). The reproducibility of results is excellent, falling for the most part within the twofold range and never exceeding the fourfold range. Agreement with other laboratories is excellent (i.e. within twofold) in the case of brucellosis and equine piroplasmosis antibody titres. A good correlation between the occurrence of the disease and serological reactions is found on circumstantial evidence in the cases of dourine, Johne's disease and Q fever. A standard unitage system is used to report the antibody titres found in all the tests. To simplify laboratory protocols, laboratories required to employ the CFT for the diagnosis of these diseases are advised to use a single proven technique in all the tests. Problems experienced with transient false-positive Johne's disease antibody titres in cattle following on tuberculin (bovine and avian) testing make it advisable to take specimens for the Johne's disease test prior to performing the tuberculin tests.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format

Risk Factors for Mobility Decline in Community-Dwelling Older Adults: A Systematic Literature Review

Mobility is essential to maintaining independence for older adults. This systematic review aimed to summarize evidence about self-reported risk factors for self-reported mobility decline; and to provide an overview of published prognostic models for self-reported mobility decline among community-dwelling older adults. Databases were searched from inception to June 2, 2020. Studies were screened by two independent reviewers who extracted data and assessed study quality. Sixty-one studies (45,187 participants) were included, providing information on 107 risk factors. High-quality evidence and moderate/large effect sizes for the association with mobility decline were found for older age beyond 75 years, the presence of widespread pain, and mobility modifications. Moderate-high quality evidence and small effect sizes were found for a further 21 factors. Three model development studies demonstrated acceptable model performance, limited by high risk of bias. These findings should be considered in intervention development, and in developing a prediction instrument for practical application

Prospects for plant defence activators and biocontrol in IPM - Concepts and lessons learnt so far

There is an urgent need to develop new interventions to manage pests because evolution of pesticide resistance and changes in legislation are limiting conventional control options for farmers. We investigated β-aminobutyric acid (BABA), jasmonic acid (JA) and fructose as possible plant defence activators against grey mould disease, . Botrytis cinerea, and root knot nematode, . Meloidogyne incognita. We also tested . Trichogramma achaeae parasitoid wasps and an antifeedant plant extract for biocontrol of the invasive tomato leafminer, . Tuta absoluta. BABA and JA enhanced resistance of tomato plants to . B. cinerea but neither treatment provided complete protection and the efficacy of treatment varied over time with BABA being more durable than JA. Efficacy was partly dependent on tomato cultivar, with some cultivars responding better to BABA treatment than others. Furthermore, treatment of tomato with BABA, JA and fructose led to partial suppression of . M. incognita egg mass development. Biocontrol agent, . T. achaeae, performance against . T. absoluta could be enhanced by adjusting the rearing conditions. Both attack rate and longevity were improved by rearing the parasitoids on . T. absoluta rather than on other insects. Finally, . Ajuga chamaepitys extract was shown to have significant antifeedant activity against . T. absoluta. Our findings suggest that there are potential new solutions for protection of crops but they are more complicated to deploy, more variable and require more biological knowledge than conventional pesticides. In isolation, they may not provide the same level of protection as pesticides but are likely to be more potent when deployed in combination in IPM strategies

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Fifteen Genetic Loci Associated with the Electrocardiographic P Wave

The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave terminal force from 12 cohort studies. Methods and Results - We included 44 456 individuals, of which 6778 (16%) were of African ancestry. Genotyping, imputation, and genome-wide association study were performed at each study site. Summary-level results were meta-analyzed centrally using inverse-variance weighting. In meta-analyses of P-wave duration, we identified 6 significant (P<5×10-8) novel loci and replicated a prior association with SCN10A. We identified 3 loci at SCN5A, TBX5, and CAV1/CAV2 that were jointly associated with the PR interval, PR segment, and P-wave duration. We identified 6 novel loci in meta-analysis of P-wave terminal force. Four of the identified genetic loci were significantly associated with gene expression in 329 left atrial samples. Finally, we observed that some of the loci associated with the P wave were linked to overall atrial conduction, whereas others identified distinct phases of atrial conduction. Conclusions - We have identified 6 novel genetic loci associated with P-wave duration and 6 novel loci associated with P-wave terminal force. Future studies of these loci may aid in identifying new targets for drugs that may modify atrial conduction or treat atrial arrhythmias

The GEOTRACES Intermediate Data Product 2014

The GEOTRACES Intermediate Data Product 2014 (IDP2014) is the first publicly available data product of the international GEOTRACES programme, and contains data measured and quality controlled before the end of 2013. It consists of two parts: (1) a compilation of digital data for more than 200 trace elements and isotopes (TEIs) as well as classical hydrographic parameters, and (2) the eGEOTRACES Electronic Atlas providing a strongly inter-linked on-line atlas including more than 300 section plots and 90 animated 3D scenes. The IDP2014 covers the Atlantic, Arctic, and Indian oceans, exhibiting highest data density in the Atlantic. The TEI data in the IDP2014 are quality controlled by careful assessment of intercalibration results and multi-laboratory data comparisons at cross-over stations. The digital data are provided in several formats, including ASCII spreadsheet, Excel spreadsheet, netCDF, and Ocean Data View collection. In addition to the actual data values the IDP2014 also contains data quality flags and 1-? data error values where available. Quality flags and error values are useful for data filtering. Metadata about data originators, analytical methods and original publications related to the data are linked to the data in an easily accessible way. The eGEOTRACES Electronic Atlas is the visual representation of the IDP2014 data providing section plots and a new kind of animated 3D scenes. The basin-wide 3D scenes allow for viewing of data from many cruises at the same time, thereby providing quick overviews of large-scale tracer distributions. In addition, the 3D scenes provide geographical and bathymetric context that is crucial for the interpretation and assessment of observed tracer plumes, as well as for making inferences about controlling processes