Patient interest in and clinician reservations on polygenic embryo screening: a qualitative study of stakeholder perspectives.

PURPOSE: We explored and compared perspectives of reproductive endocrinology and infertility specialists (REIs) and in vitro fertilization (IVF) patients regarding polygenic embryo screening (PES), a new type of preimplantation screening that estimates the genetic chances of developing polygenic conditions and traits in the future. METHODS: Qualitative thematic analysis of semi-structured interviews with US-based REIs and IVF patients. RESULTS: Clinicians and patients often held favorable views of screening embryos for physical or psychiatric conditions, though clinicians tended to temper their positive attitudes with specific caveats. Clinicians also expressed negative views about screening embryos for traits more frequently than patients, who generally held more positive views. Most clinicians were either unwilling to discuss or offer PES to patients or were willing to do so only under certain circumstances, while many patients expressed interest in PES. Both stakeholder groups envisioned multiple potential benefits or uses of PES and raised multiple potential, interrelated concerns about PES. CONCLUSION: A gap exists between clinician and patient attitudes toward PES; clinicians generally maintained reservations about such screening and patients indicated interest in it. Clinicians and patients sometimes imagined using PES to prepare for the birth of a predisposed or "affected" individual-a rationale that is often associated with prenatal testing. Many clinicians and patients held different attitudes depending on what is specifically screened, despite the sometimes blurry distinction between conditions and traits. Considerations raised by clinicians and patients may help guide professional societies in developing guidelines to navigate the uncertain terrain of PES.

Genotype distributions in top-level soccer players: a role for ACE?

We determined the genotype and allelic frequency of several genetic polymorphisms (ACE I/D, GDF-8K153R [and also E164K, P198A and I225T] and AMPD1 C34T) that are candidates to influence sports performance in a group of 54 male professional soccer players. Their results were compared with those of elite endurance male athletes (52 runners) and 123 sedentary, healthy men (controls). We found statistical significance for the ACE ID (chi (2)((2))=8.176, P=0.017) and II genotypes (chi(2)((2))=16.137, P<0.001) with a higher and lower frequency of ID ( P=0.005) and II (P<0.001), respectively, in soccer players than in endurance runners. Statistical significance was also reached for AMPD1 (with a higher frequency of the CT genotype in soccer players than in runners [chi(2)((2))=7.538, P=0.006]) but not for GDF-8 K153R. Since the ACE II genotype is associated with improved potential for endurance performance but with decreased training gains in muscle mass and strength, these findings together with previous results support the notion that elite soccer players tend to have a power/strength oriented genotype.

Comparison between generalized linear modelling and additive Bayesian network; identification of factors associated with the incidence of antibodies against Leptospira interrogans sv Pomona in meat workers in New Zealand.

BACKGROUND: Additive Bayesian Network (ABN) is a graphical model which extends Generalized Linear Modelling (GLM) to multiple dependent variables. The present study compares results from GLM with those from ABN analysis used to identify factors associated with Leptospira interrogans sv Pomona (Pomona) infection by exploring the advantages and disadvantages of these two methodologies, to corroborate inferences informing health and safety measures at abattoirs in New Zealand (NZ). METHODOLOGY AND FINDINGS: In a cohort study in four sheep slaughtering abattoirs in NZ, sera were collected twice a year from 384 meat workers and tested by Microscopic Agglutination with a 91% sensitivity and 94% specificity for Pomona. The study primarily addressed the effect of work position, personal protective equipment (PPE) and non-work related exposures such as hunting on a new infection with Pomona. Significantly associated with Pomona were "Work position" and two "Abattoirs" (GLM), and "Work position" (ABN). The odds of Pomona infection (OR, [95% CI]) was highest at stunning and hide removal (ABN 41.0, [6.9-1044.2]; GLM 57.0, [6.9-473.3]), followed by removal of intestines, bladder, and kidneys (ABN 30.7, [4.9-788.4]; GLM 33.8, [4.2-271.1]). Wearing a facemask, glasses or gloves (PPE) did not result as a protective factor in GLM or ABN. CONCLUSIONS/SIGNIFICANCE: The odds of Pomona infection was highest at stunning and hide removal. PPE did not show any indication of being protective in GLM or ABN. In ABN all relationships between variables are modelled; hence it has an advantage over GLM due to its capacity to capture the natural complexity of data more effectively.

Data on Leptospira interrogans sv Pomona infection in Meat Workers in New Zealand.

The data presented in this article are related to the research article entitled "Comparison between Generalized Linear Modelling and Additive Bayesian Network; Identification of Factors associated with the Incidence of Antibodies against Leptospira interrogans sv Pomona in Meat Workers in New Zealand" (Pittavino et al., 2017) [5]. A prospective cohort study was conducted in four sheep slaughtering abattoirs in New Zealand (NZ) (Dreyfus et al., 2015) [1]. Sera were collected twice a year from 384 meat workers and tested by Microscopic Agglutination for Leptospira interrogans sv Pomona (Pomona) infection, one of the most common Leptospira serovars in humans in NZ. This article provides an extended analysis of the data, illustrating the different steps of a multivariable (i.e. generalized linear model) and especially a multivariate tool based on additive Bayesian networks (ABN) modelling.

Volatile N-nitrosamines in the urine of normal donors and of bladder cancer patients.

Volatile N-nitrosamines were detected in the urine of male volunteers with gas-liquid and high-pressure liquid chromatography interfaced to the thermal energy analyzer. Of 50 samples from normal males, 10 contained nitrosodimethylamine (0.02 to 0.10 micrograms/liter), 6 contained nitrosodiethylamine (0.02 to 3.10), 9 contained nitrosomorpholine (0.006 to 0.67), and none contained nitrosodibutylamine. Of 4 samples from bladder cancer patients, 2 contained nitrosodibutylamine (0.35 and 0.66). Cigarette smoking did not appear to be related to the pattern or amount of urinary volatile N-nitrosamines. The possibility that the N-nitrosamines arise from the diet or from endogenous production is considered.

The effect of fecapentaenes on nuclear aberrations in murine colonic epithelial cells.

Fecapentaenes, human fecal mutagens of bacterial origin, were intrarectally administered to mice in suppository form. Despite the strong, positive mutagenic response of fecanpentaenes using Ames tester strains TA 98 and TA 100, no increase in nuclear aberrations, taken as a measure of genotoxicity in colonic epithelial cells, was observed over control levels. In fecapentaene treated animals, however, the incidence of mitotic figures was increased above control levels to values comparable to those observed in mice treated with the known colon carcinogen, N-ethyl-N-nitrosourea. Thus, it would appear that fecapentaenes are not cytotoxic to murine colonic epithelia as judged by the nuclear aberration assay.

Characterization of cytotoxic steroids in human faeces and their putative role in the etiology of human colonic cancer.

It has been shown previously that chemically induced nuclear abeerrations in the murine colon are correlated with the carcinogenicity of the respective chemicals. Consequently, the nuclear aberration assay was utilized for the identification of putatife carcinogens in human faeces. Human fecal samples were fractionated by several chromatographic methods, and the assay led to the isolation of two substances. A combination of spectroscopic (mass, nuclear magnetic resonance, ultraviolet, and infrared) and chromatographic (HPLC and GLC) methods showed that they are 5-alpha- cholestan-3-one (I) and cholest-4-en-3-one (II). A number of C-27-C-30 steroids isolated from closely related fractions of feces were inactive in this assay. Thus I and II could play a role in etiology of large bowel cancer in humans.

Proliferative activity of rectal mucosa and soluble fecal bile acids in patients with normal colons and in patients with colonic polyps or cancer.

Rectal biopsies and fecal collections were obtained from a consecutive series of 34 outpatients prior to colonoscopy at a gastroenterology clinic. Subsequently, 14 were found to have no colonic pathology, 13 had adenomatous polyps, (3 of those had a previous history of colon cancer) and 7 were diagnosed with colon cancer. In confirmation of earlier studies the tritiated thymidine labelling index was higher in patients with tumors than in those without pathology (7.9% vs. 5.8% with P = 0.06). The patients with colonic tumors also had significantly higher levels of deoxycholic acid (P = 0.01) and lithocholic acid (P = 0.005) in the aqueous extract of their feces. This study shows that these biochemical measures may indicate colon cancer risk.

The effect of lowering faecal pH on the rate of proliferation of the normal colonic mucosa.

Epidemiological and animal studies suggest that faecal pH may be a risk factor for colorectal cancer with low faecal pH associated with a lower incidence of the disease. The aim of this study was to determine whether faecal pH (or dietary fibre) affects the short-term risk factors for colon cancer. Sixty-nine normal volunteers were randomized into three equal groups (A-C). They provided food records, faecal specimens and submitted to rectal biopsy for thymidine labelling studies before and after a 2-week intervention. Group A received a placebo of fruit juice. Group B, approximately 3.0 g d-1 sodium sulphate in juice. Group C, 30 g d-1 supplementary dietary fibre as wheat bran in bread. Age, sex, weight, height and intake of macronutrients and minerals were similar in the groups prior to intervention. Faecal pH was similar for the three groups before and was reduced in Group B after intervention (P = 0.001) with a relative reduction of 0.5 pH units. The labelling index for the three groups was similar prior to intervention; after, it was lowest in Group B with a relative reduction of 0.5% points, although this difference was not statistically significant. The results thus do not support the hypothesis that an acidification of faecal pH leads to a reduction in risk markers for colon cancer.

Concentrations and specific loads of polycyclic musks in sewage sludge originating from a monitoring network in Switzerland.

Polycyclic musks (HHCB, AHTN, ADBI, AHDI, ATII) and a metabolite of HHCB (HHCB-lactone) were analyzed in sewage sludge samples within the framework of a monitoring network in Switzerland. Mean values in stabilised sludge from 16 wastewater treatment plants were 20.3 mg/kg d.m. for HHCB, 7.3 mg/kg d.m. for AHTN and 1.8 mg/kg d.m. for HHCB-lactone, respectively. Contents of ADBI, AHDI and ATII were between 0.1 and 1.8 g/kg d.m. The results show that polycyclic musks origin mainly from private households and that loads from craft industry, industry and atmospheric deposition are negligible. The technology of wastewater treatment and sludge processing seems to be of minor importance for degradation processes of polycyclic musks. The calculated input in wastewater of polycyclic musks is lower by a factor of 5-7 than the estimates based on use volumes. This discrepancy might be explained by degradation processes, other emission pathways than wastewater or inappropriate estimation of production volumes.

Use of active barriers to reduce eutrophication problems in urban lakes.

Excessive concentration of phosphorus is one of the main causes of algal blooms and eutrophic conditions in lakes. In many urban lakes, it appears that a large proportion of the phosphorus in the water column comes from the sediments, particularly when these are anaerobic. Sub-aqueous capping is a relatively new method that has become an attractive option for isolating contaminated sediments from the environment, thus preventing or delaying the release of contaminants into surface waters. Active barrier materials (i.e. capping layers that consist of one or more reactive components) are gaining increasing attention for their greater efficiency in inactivating contaminants held in sediment layers. This paper reports laboratory bioreactor experiments to test the effectiveness of three forms of calcium carbonate (CaCO3) in reducing the release of phosphorus from anaerobic sediment from Lake Carramar, a small urban lake in Melbourne. Two of the CaCO3 active barrier materials tested proved to be quite effective, the most effective materials being the fine particle size, precipitated forms of CaCO3. Over the 20-day experimental period, a 2% layer of the German material SoCal reduced the amount of phosphorus released by almost 100 times over that occurring with no barrier. The Australian product ESCal, while not as effective as the SoCal, still reduced the phosphorus released by around 15 times that with no barrier. A finely ground Lilydale limestone was essentially ineffective in reducing phosphorus release from the sediments. A preliminary cost-benefit analysis suggests that SoCal is unlikely to be attractive for use in Australia, given the estimated application cost of around 3,800 dollars per tonne. However, although the ESCal is slightly less effective in retaining phosphorus, its potential application cost estimated at 2,000 dollars per tonne, makes it an attractive option. On the basis of these most promising preliminary results, we intend to further test the use of the ESCal. Further investigations will include: longer term laboratory studies using ESCal, optimisation of the barrier layer and methods for applying this material, mesocosms and full lake studies, and risk assessment studies to ensure there are no adverse ecological effects from its use.

[Vasoproliferative retinal tumors]. / Vasoproliferative retinale Tumore.

BACKGROUND: Vasoproliferative Tumors of the retina (VPTR) are benign tumors of unknown origin, occurring mostly in otherwise systemically healthy patients. These highly vascularised tumors are characterised by a pink to yellow colour on funduscopy and are usually situated in the inferior part of the retina. They are associated with intraretinal hemorrhages, intra- or subretinal exudates and hyperpigmentation of the retinal pigment epithelium. MATERIALS AND METHODS: We performed a retrospective case review of seven cases which have been diagnosed with VPTR between 2004 and 2006 in the Department of Ophthalmology, University Hospital Zurich. RESULTS: The median follow up was 8 months (range: 1-24 months). We found a presumed underlying cause for the VPTR in 6 out of 7 patients. 3 patients showed a long standing retinal detachment; in the other 3 there was an untreated chronic uveitis. In one case the tumour was surgically excised and histology was performed. CONCLUSIONS: VPTR of the ocular fundus are a distinct entity in the differential diagnosis of intraocular tumors. These benign lesions represent reactive gliovascular proliferations, with varying degrees of both gliosis and of vascular proliferation. VPTR can be idiopathic, or they develop after inflammatory, vascular, traumatic, dystrophic or degenerative ocular diseases, in particular, uveitis. The major differential diagnosis includes other vascular lesions or tumors of the ocular fundus like capillary retinal hemangiomas, Coat' Disease or malignancies. The natural course of VPTR appears to be variable. The therapy is based on tumor size, localisation and complications.

The separation, physical characterization, and differentiation kinetics of spermatogonial cells of the mouse.

By means of the velocity sedimentation technique for cell separation, single cell suspensions from the testes of the mouse could be separated into at least seven peaks each with a different sedimentation velocity. These were named and characterized as follows: alpha (12 mm/hr); beta (10 mm/hr); gamma (6.5 mm/hr); delta (4.3 mm/hr); theta (broad peak with median 2.5 mm/hr); kappa (1.1 mm/hr); lambda (0.75 mm/hr). Tritiated thymidine was injected into thirty groups of mice. The spermatogonial cells of each group were separated at one hour and then at daily intervals, and the acid insoluble activity of each fraction was measured. This method enabled us to determine the differentiation patterns of mouse spermatogenesis by following the thymidine label with time. It was found that the spermatogonia and primary spermatocytes formed the theta peak with S-phase spermatogonia and primary spermatocytes having a similar sedimentation velocity of 2.1 mm/hr. The beta cells were identified as late pachytenes and diplotene cells, the gamma cells as secondary spermatocytes, the delta cells as earliest spermatids, the kappa cells as spermatids, and the lambda cells as mature spermatozoa.

Simulation of Space-Adaptation Syndrome on Earth.

The three Spacelab D-1 Scientist Astronauts were exposed to a 1.5 h centrifuge run in the supine position, resulting in a linear 3 g acceleration. They used their space experience to evaluate their readaptation to normal gravity and compared their observations with 'Space Adaptation Syndrome'. After the centrifuge runs, the vestibular visual system appeared to be modified in a very specific and reproducible manner. Readaptation to the normal 1 g environment took at least 6 h. During this period there was a striking similarity to the astronauts' experience during adaptation to weightlessness in space. Vestibular tests were subsequently performed, which confirmed these subjective findings.

Simulation of space adaptation syndrome on earth.

The three Spacelab D-1 Scientist Astronauts were exposed to a 1 1/2 h 3 g centrifuge run in the supine position, resulting in a linear 3 g acceleration in the x-direction. They used their space experience to evaluate their readapting to normal gravity and compared their observations with 'Space Adaptation Syndrome'. After the centrifuge runs, the vestibular visual system appeared to be modified in a very specific and reproducible manner. Readapting to the normal 1 g environment took at least 6 h. During this period there was a striking similarity to the astronaut's experience during adaptation to weightlessness in space. A series of vestibular tests were then performed, confirming these subjective findings.

Influence of continuous and discontinuous training protocols on subcutaneous adipose tissue and plasma substrates.

It has been shown that bouts of high-intensity exercise may reduce subcutaneous adipose tissue more than low-intensity exercise. The aim of the present study was to examine if a discontinuous training protocol is more successful in reducing adipose tissue than a continuous endurance training protocol. Fourteen untrained male volunteers were divided into two groups and trained for 10 weeks performing 3 discontinuous or 3 continuous workouts weekly (discontinuous exercise: 25 times 80 s 35% VO2max and 40 s 80% VO2max; continuous exercise: 50 min 50% VO2max). The discontinuous and the continuous training resulted in a similar subcutaneous adipose tissue loss, determined by skinfold measurement, in the leg above the patella (-2.4+/-2.4 and -2.4+/-1.4mm, respectively). The normalised plasma concentrations of free fatty acid, glycerol, beta-hydroxybutyrate, and lactate were similar throughout the final exercise test at the end of the training period. Our data suggested that the discontinuous protocol, selected so that the average intensity was similar to that of the continuous protocol, was not better than the latter in reducing subcutaneous adipose tissue.

Toxicity of orally administered fat to the colonic epithelium of mice.

C57BL/6J mice were given a gavage of from 0.1 to 0.4 ml beef tallow (BT) or corn oil (CO). The damaging effect of the orally administered fat boluses could be visualized 2-4 h later by instilling the excised animal colons with Trypan blue, a vital dye that stains non-viable cells. Microscopic examination of sections prepared at these times revealed that the tall columnar cells on the surface of the normal epithelium were replaced with cells demonstrating flattened, pleomorphic, pyknotic and fragmented nuclei. This phenomenon was quantitated by scoring 100 intercrypt epithelial zones between well-defined crypts. The maximum damage, affecting 25-45% of the epithelial zones, was seen at 2-4 h after treatment with 0.4 ml of BT or CO and the epithelium appeared normal with less than 10% damage at 12 h. The mitotic activity in the colonic crypts was unchanged up to 8 h and then showed a marked increase of 2- to 3-fold at 12-16 h. The severity of the epithelial damage and ensuing mitogenic response was related to the size of the fat bolus. These observations would suggest that the effects of any carcinogens present in the diet or formed in the feces could be enhanced if a fatty meal results in colonic damage and subsequent cell proliferation as we have observed in mice.

Non-volatile N-nitroso compounds in human feces.

A bacterial mutagen has been detected in ether extracts of freeze-dried feces of humans on Western diet. Several types of evidence suggest that nitroso compounds are present in human feces and the mutagen could be a nitroso compound. Ascorbic acid supplement in the diet reduces the levels of both the mutagens and nitroso compounds in the feces.

Effects of calcium and pH on the mucosal damage produced by deoxycholic acid in the rat colon.

A single pass perfusion system was used in anaesthetised, restrained rats to examine the effect of changing the composition of the perfusion fluid on the damage caused to the colonic epithelium by deoxycholic acid. Damage to the colonic surface was monitored with light microscopy, transmission and scanning electron microscopy and with measurements of deoxyribonucleic acid and carbohydrate in the perfusate. New scoring techniques for monitoring alterations in surface epithelium of light microscopy sections were used. The damaging effect of 5 mM deoxycholic acid to the colonic epithelium is inhibited by lowering the pH of the perfusion fluid from 7.9 to 5.5, or by increasing the calcium concentration from 0 to 4 mM. This inhibition is shown to be because of a decreased amount of bile acid in solution. Thus it is not the total concentration of deoxycholic acid in the colon that is responsible for the colonic damage, but the concentration in solution. Although extrapolation to the human situation must be made with caution, the concentration of bile acid in solution in the faecal water may be more relevant to colonic mucosal damage than total bile acid concentration.