Gel chromatographic characterization of immunoreactive adrenocorticotropin in patients with ACTH hypersecretion

We investigated the molecular size of circulating immunoreactive ACTH by gel chromatography in patients with ACTH hypersecretion due to various disorders of the hypothalamic-pituitary-adrenal axis. 4 patients with Addison's disease, 2 with Nelson's syndrome, 4 with Cushing's disease, 6 with the ectopic ACTH syndrome (2 bronchial carcinoma, 1 medullary carcinoma, 1 metastatic islett cell carcinoma, 1 benign bronchial carcinoid and 1 patient with occult ectopic Cushing's syndrome) and 1 patient with hypersecretion of ACTH from a clinically nonfunctioning pituitary adenoma were studied. Analysis of the molecular size of immunoreactive ACTH was performed by gel chromatography on a Sephadex G-75 column (superfine, 100×1.5 cm) equilibrated with 1% formic acid. 2 ml fractions were collected and evaporated to dryness. The ACTH content of the recovered samples was determined by RIA. In Addison's disease, Nelson's syndrome and Cushing's disease the plasma showed a single peak of ACTH immunoreactivity at the expected position of 1–39 ACTH. In the ectopic ACTH syndrome the plasma of 4 patients revealed at chromatography at least one other peak eluting between the void volume and 1–39 ACTH suggestive of a high molecular weight form of ACTH whereas plasma of 2 patients showed only a single ACTH peak at the position of labeled 1–39 ACTH. The patient with a clinically non-functioning pituitary adenoma revealed a gel filtration pattern similar to the patients with ectopic ACTH syndrom and secretion of high molecular weight ACTH. We conclude that secretion of high molecular weight forms of ACTH is not a unique feature of the ectopic ACTH syndrome. It may therefore not serve as a marker of the ectopic Cushing's syndrome in the differential diagnosis of the ACTH dependent Cushing's syndrome. Vice versa, lack of high molecular weight ACTH does not exclude an ectopic source of ACTH secretion as cause of Cushing's syndrome

Genetic Predisposition to Mosaic Chromosomal Loss Is Associated With Functional Outcome After Ischemic Stroke.

Background and Objectives: To test the hypothesis that a predisposition to acquired genetic alterations is associated with ischemic stroke outcome by investigating the association between a polygenic risk score (PRS) for mosaic loss of chromosome Y (mLOY) and outcome in a large international data set. Methods: We used data from the genome-wide association study performed within the Genetics of Ischemic Stroke Functional Outcome network, which included 6,165 patients (3,497 men and 2,668 women) with acute ischemic stroke of mainly European ancestry. We assessed a weighted PRS for mLOY and examined possible associations with the modified Rankin Scale (mRS) score 3 months poststroke in logistic regression models. We investigated the whole study sample as well as men and women separately. Results: Increasing PRS for mLOY was associated with poor functional outcome (mRS score >2) with an odds ratio (OR) of 1.11 (95% confidence interval [CI] 1.03-1.19) per 1 SD increase in the PRS after adjustment for age, sex, ancestry, stroke severity (NIH Stroke Scale), smoking, and diabetes mellitus. In sex-stratified analyses, we found a statistically significant association in women (adjusted OR 1.20, 95% CI 1.08-1.33). In men, the association was in the same direction (adjusted OR 1.04, 95% CI 0.95-1.14), and we observed no significant genotype-sex interaction. Discussion: In this exploratory study, we found associations between genetic variants predisposing to mLOY and stroke outcome. The significant association in women suggests underlying mechanisms related to genomic instability that operate in both sexes. These findings need replication and mechanistic exploration

A radiographic measurement of left atrial size in dogs

The dimensions of the left atrium in cases with mitral regurgitation are an indirect measurement of its severity. The objective of this study was to evaluate the value of a new radiographic measurement, the radiographic left atrial dimension (RLAD), for detecting left atrial enlargement (LAE) in dogs. Thirty one dogs without LAE and 46 dogs with LAE were recruited in a prospective fashion. Reference left atrium dimension was measured by standard left atrium to aorta ratio (LA/Ao) by 2D echocardiography. LAE was considered if LA/Ao > 1.6. Left atrium dimension was then quantified on lateral radiographs by measuring RLAD. Vertebral heart size (VHS) was measured and RLAD was obtained by drawing a line bisecting the 90 degrees angle defined by the long and short cardiac axes lines of the VHS, up to the dorsal edge of the left atrium and comparing its length to T4’s vertebral body length. The correlation of VHS and RLAD methods with LA/Ao was estimated, as well as their sensitivity and specificity for detecting LAE. Receiver Operating Characteristic (ROC) curves were used to estimate the optimal decision criteria for each method

Cancer associated auto-antibodies to MUC1 and MUC4 - A blinded case control study of colorectal cancer in UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

Recent reports suggest that autoantibodies directed to aberrantly glycosylated mucins, in particular MUC1 and MUC4, are found in patients with colorectal cancer. There is, however, limited information on the autoantibody levels prior to clinical diagnosis, and their utility in cancer screening in the general population. In this study, we have generated O-glycosylated synthetic MUC1 and MUC4 peptides in vitro, to mimic cancer associated glycoforms, and displayed these on microarrays. The assay's performance was tested through an initial screening of serum samples taken from patients at the time of colorectal cancer diagnosis and healthy controls. Subsequently the selected biomarkers were evaluated in a blinded nested case control study, using stored serum samples from among the 50,640 women randomised to the multimodal arm of the UKCTOCS, where women gave annual blood samples for several years. Cases were 97 postmenopausal women who developed colorectal cancer following recruitment, and were age-matched to 97 women without any history of cancer. MUC1-STn and MUC1-Core3 IgG autoantibodies identified cases with 8.2% and 13.4% sensitivity, respectively, at 95% specificity. IgA to MUC4-glycoforms were unable to discriminate between cases and controls in the UKCTOCS sera. Additional analysis was undertaken by combining the data of MUC1-STn and MUC1-Core3 with previously generated data on autoantibodies to p53 peptides, which increased the sensitivity to 32.0% at 95% specificity in the UKCTOCS set. These findings suggest that a combination of antibody signatures may have a role as part of a biomarker panel for the early detection of colorectal cancer

Abnormal increase in urinary aquaporin-2 excretion in response to hypertonic saline in essential hypertension

<p>Abstract</p> <p>Background</p> <p>Dysregulation of the expression/shuttling of the aquaporin-2 water channel (AQP2) and the epithelial sodium channel (ENaC) in renal collecting duct principal cells has been found in animal models of hypertension. We tested whether a similar dysregulation exists in essential hypertension.</p> <p>Methods</p> <p>We measured urinary excretion of AQP2 and ENaC β-subunit corrected for creatinine (u-AQP2_CR, u-ENaC_β-CR), prostaglandin E2 (u-PGE₂) and cyclic AMP (u-cAMP), fractional sodium excretion (FE_Na), free water clearance (C_H2O), as well as plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), and atrial and brain natriuretic peptide (ANP, BNP) in 21 patients with essential hypertension and 20 normotensive controls during 24-h urine collection (baseline), and after hypertonic saline infusion on a 4-day high sodium (HS) diet (300 mmol sodium/day) and a 4-day low sodium (LS) diet (30 mmol sodium/day).</p> <p>Results</p> <p>At baseline, no differences in u-AQP2_CRor u-ENaC_β-CRwere measured between patients and controls. U-AQP2_CRincreased significantly more after saline in patients than controls, whereas u-ENaC_β-CRincreased similarly. The saline caused exaggerated natriuretic increases in patients during HS intake. Neither baseline levels of u-PGE₂, u-cAMP, AVP, PRC, Ang II, Aldo, ANP, and BNP nor changes after saline could explain the abnormal u-AQP2_CRresponse.</p> <p>Conclusions</p> <p>No differences were found in u-AQP2_CRand u-ENaC_β-CRbetween patients and controls at baseline. However, in response to saline, u-AQP2_CRwas abnormally increased in patients, whereas the u-ENaC_β-CRresponse was normal. The mechanism behind the abnormal AQP2 regulation is not clarified, but it does not seem to be AVP-dependent.</p> <p>Clinicaltrial.gov identifier</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=00345124">NCT00345124</a>.</p

Nitrogen uptake and internal recycling in Zostera marina exposed to oyster farming: eelgrass potential as a natural biofilter

Oyster farming in estuaries and coastal lagoons frequently overlaps with the distribution of seagrass meadows, yet there are few studies on how this aquaculture practice affects seagrass physiology. We compared in situ nitrogen uptake and the productivity of Zostera marina shoots growing near off-bottom longlines and at a site not affected by oyster farming in San Quintin Bay, a coastal lagoon in Baja California, Mexico. We used benthic chambers to measure leaf NH4 (+) uptake capacities by pulse labeling with (NH4)-N-15 (+) and plant photosynthesis and respiration. The internal N-15 resorption/recycling was measured in shoots 2 weeks after incubations. The natural isotopic composition of eelgrass tissues and vegetative descriptors were also examined. Plants growing at the oyster farming site showed a higher leaf NH4 (+) uptake rate (33.1 mmol NH4 (+) m(-2) day(-1)) relative to those not exposed to oyster cultures (25.6 mmol NH4 (+) m(-2) day(-1)). We calculated that an eelgrass meadow of 15-16 ha (which represents only about 3-4 % of the subtidal eelgrass meadow cover in the western arm of the lagoon) can potentially incorporate the total amount of NH4 (+) excreted by oysters (similar to 5.2 x 10(6) mmol NH4 (+) day(-1)). This highlights the potential of eelgrass to act as a natural biofilter for the NH4 (+) produced by oyster farming. Shoots exposed to oysters were more efficient in re-utilizing the internal N-15 into the growth of new leaf tissues or to translocate it to belowground tissues. Photosynthetic rates were greater in shoots exposed to oysters, which is consistent with higher NH4 (+) uptake and less negative delta C-13 values. Vegetative production (shoot size, leaf growth) was also higher in these shoots. Aboveground/belowground biomass ratio was lower in eelgrass beds not directly influenced by oyster farms, likely related to the higher investment in belowground biomass to incorporate sedimentary nutrients

A randomised controlled trial among cleaners-Effects on strength, balance and kinesiophobia

<p>Abstract</p> <p>Background</p> <p>Cleaners constitute a job group with poor health and low socioeconomic resources. Therefore, there is a great need for scientifically documented health promoting initiatives for cleaners. However, both workplace initiatives and high quality intervention studies are lacking. The aim of this study was to evaluate the effects of a 3-month workplace trial with interventions to improve physical or cognitive behavioural resources among cleaners.</p> <p>Methods</p> <p>A cluster randomised controlled trial was conducted among 294 female cleaners from 9 workplaces. The participants were allocated to three groups: Physical coordination training (PCT, n = 95), Cognitive behavioural theory-based training (CBTr, n = 99) and Reference group (REF, n = 100). Interventions were conducted during work hours for an average of 1 hour/week. Muscle strength was measured by maximal voluntary contractions in trunk/extension, and shoulder abduction/elevation. Postural balance was measured on a force platform. Kinesiophobia was measured with Tampa Scale for Kinesiophobia. Test and questionnaires were completed at baseline and at 3-month follow-up and analyses followed the intention-to-treat (ITT) principle with last observation carried forward in case of missing data at follow-up. Reports and analyses are given on true observations as well.</p> <p>Results</p> <p>ITT-analyses revealed that PCT improved strength of the trunk (p < .05) and postural balance (p < .05) compared to CBTr and REF. Based on true observations the strength and balance improvements corresponded to ~20% and ~16%, respectively. ITT-analyses showed that CBTr reduced kinesiophobia compared to PCT and REF (p < .05). Based on true observations, the improvement corresponded to a ~16% improvement.</p> <p>Conclusion</p> <p>This workplace-based intervention study including PCT and CBTr among cleaners improved strength and postural balance from PCT, and kinesiophobia from CBTr. The improved strength, postural balance and kinesiophobia may improve the cleaners' tolerance for high physical work demands. Future studies should investigate the potential in the combination of PCT and CBTr in a workplace intervention.</p> <p>Trial registration</p> <p>Current controlled trials <a href="http://www.controlled-trials.com/ISRCTN96241850">ISRCTN96241850</a></p

ALBATROSS: Publicly AttestabLe BATched Randomness Based On Secret Sharing

In this paper we present ALBATROSS, a family of multiparty randomness generation protocols with guaranteed output delivery and public verification that allows to trade off corruption tolerance for a much improved amortized computational complexity. Our basic stand alone protocol is based on publicly verifiable secret sharing (PVSS) and is secure under in the random oracle model under the decisional Diffie-Hellman (DDH) hardness assumption. We also address the important issue of constructing Universally Composable randomness beacons, showing two UC versions of Albatross: one based on simple UC NIZKs and another one based on novel efficient ``designated verifier\u27\u27 homomorphic commitments. Interestingly this latter version can be instantiated from a global random oracle under the weaker Computational Diffie-Hellman (CDH) assumption. An execution of ALBATROSS with $n$ parties, out of which up to $t=(1/2-\epsilon)\cdot n$ are corrupt for a constant $\epsilon>0$, generates $\Theta(n^2)$ uniformly random values, requiring in the worst case an amortized cost per party of $\Theta(\log n)$ exponentiations per random value. We significantly improve on the SCRAPE protocol (Cascudo and David, ACNS 17), which required $\Theta(n^2)$ exponentiations per party to generate one uniformly random value. This is mainly achieved via two techniques: first, the use of packed Shamir secret sharing for the PVSS; second, the use of linear $t$-resilient functions (computed via a Fast Fourier Transform-based algorithm) to improve the randomness extraction

Appointing Women to Boards: Is There a Cultural Bias?

Companies that are serious about corporate governance and business ethics are turning their attention to gender diversity at the most senior levels of business (Institute of Business Ethics, Business Ethics Briefing 21:1, 2011). Board gender diversity has been the subject of several studies carried out by international organizations such as Catalyst (Increasing gender diversity on boards: Current index of formal approaches, 2012), the World Economic Forum (Hausmann et al., The global gender gap report, 2010), and the European Board Diversity Analysis (Is it getting easier to find women on European boards? 2010). They all lead to reports confirming the overall relatively low proportion of women on boards and the slow pace at which more women are being appointed. Furthermore, the proportion of women on corporate boards varies much across countries. Based on institutional theory, this study hypothesizes and tests whether this variation can be attributed to differences in cultural settings across countries. Our analysis of the representation of women on boards for 32 countries during 2010 reveals that two cultural characteristics are indeed associated with the observed differences. We use the cultural dimensions proposed by Hofstede (Culture’s consequences: International differences in work-related values, 1980) to measure this construct. Results show that countries which have the greatest tolerance for inequalities in the distribution of power and those that tend to value the role of men generally exhibit lower representations of women on boards