Planctomycetes in lakes: poor or strong competitors for phosphorus?

Experiments were conducted with water samples from two perialpine lakes with differing eutrophication status in order to examine the effects of inorganic-nutrient amendments (nitrogen as NO3(-) or NH4(+) and phosphorus as PO4(3-)) on the dynamics, structure, and composition of Planctomycetes and to test the hypothesis that the community structure of Planctomycetes members and that of the other bacteria (without Planctomycetes, here referred to as bacteria-wP, the most represented groups within the community) would be similarly impacted by nutrient additions. Initial samples were characterized by high total nitrogen-to-total phosphorus ratios (range, 39 to 55), suggesting P rather than N was the limiting nutrient for microbial communities. Consistent with this, P additions stimulated phytoplankton growth and affected the community structure of bacteria-wP but, surprisingly, not that of Planctomycetes. N additions did not significantly affect the community structures of bacteria-wP and Planctomycetes or the Planctomycetes phylotype composition. The estimated generation time of Planctomycetes was 123 h. These findings could suggest that the generally well-accepted statement that bacteria (as a whole) are superior to phytoplankton in the ability to obtain phosphorus under P limitation might actually not hold for Planctomycetes. Planctomycetes might be poor competitors for P that do not respond quickly to the nutrient supply, which may help explain why their abundance is low in aquatic systems. The alternative view that Planctomycetes could be strong competitors for P (storing it) is also discussed. Our findings highlight the need for further studies examining Planctomycetes-phosphorus relationships in aquatic ecosystems.

Postpartum variations of plasma IGF and IGFBPs, oocyte production and quality in dairy cows: relationships with parity and subsequent fertility.

The aim of this study was to determine whether postpartum variations of plasma IGF-1 and IGFBP concentrations, oocyte production and quality were related to parity and subsequent conception rate in Holstein dairy cows. Holstein dairy cows [10 primiparous (PP) and 22 multiparous (MP)] were allotted in six batches and sampled once weekly between calving and oestrous synchronization treatment started at 71.2 ± 2.0 days postpartum. During the 3 weeks before treatment, ovum pick-up (OPU) was performed twice weekly. Oocytes were scored on a 4-point scale, and oocytes from OPU1, 3 and 5 were fertilized in vitro. Seventeen cows became pregnant after first and second AI and were considered as fertile (F), while the others were considered to be subfertile (SF). Logistic regression was carried out to investigate the relationships between repeated measurements and fertility including parity and batch effects in the models. Likelihood of fertility significantly increased when plasma urea and IGFBP-3 concentrations decreased and was higher in PP compared with MP cows. There was a trend for fertility to increase when plasma IGF-1 concentrations increased (p = 0.07). In vitro cleavage and development rates were similar between SF and F cows (46.4% and 28.3% in SF vs 55.0% and 22.1% in F). Parity had an effect on plasma IGF-1 concentrations (PP: 61.65 ± 2.67 vs MP: 41.63 ± 5.81 ng/ml, p < 0.001), mean number of follicles aspirated per session (PP: 5.7 ± 1.3 vs MP: 9.5 ± 0.8, p < 0.05) and fertility (PP: 8/10 = 80% vs MP: 9/22 = 41%, p < 0.05) but not on the number of oocytes recovered per session nor their quality. In conclusion, postpartum plasma urea and IGFBP-3 concentrations, but not oocyte production and quality before breeding, were related to subsequent conception rate in our experimental design. Parity had a significant effect on energy status, follicular growth and fertility and needs to be considered when investigating relationships between nutrition and reproduction.

Mercury bioaccumulation patterns in fish from the Iténez river basin, Bolivian Amazon.

The bioaccumulation mechanism expresses an increment of mercury concentration along the lifetime of each individual. It is generally investigated along the age or size range of organisms from a same population. Water chemistry and trophic position are important factors that may influence the emergence of bioaccumulation patterns. In order to detect the influence of these parameters on fish mercury bioaccumulation patterns, we explored the relations between mercury concentration, size and isotopic trophic position of fish populations of six species (three non piscivorous and three piscivorous) in three rivers of the Iténez basin (Bolivia) with different sediment load in water and anthropogenic impact. Fishes of the Iténez basin showed fairly lower mercury contamination in relation to the regional context. They presented lower total mercury concentrations in unperturbed clear water river (average of 0.051 µg g(-1) for non piscivores; 0.088 µg g(-1) for piscivores), intermediate values (average of 0.05 and 0.104 µg g(-1)) in unperturbed white water river, whereas the highest values (average of 0.062 and 0.194 µg g(-1)) were found in the perturbed clear water river. Piscivore and invertivore species showed significant positive bioaccumulation patterns in the perturbed river and in the unperturbed white water river. No positive pattern was detected in the unperturbed clear water river. Positive patterns could not be attributed to differences in trophic condition and mean fish mercury concentration between populations. Bioaccumulation seems not to be the main factor to explain increased mercury concentrations in fish from the perturbed river.

Role of methylmercury exposure (from fish consumption) on growth and neurodevelopment of children under 5 years of age living in a transitioning (tin-mining) area of the western Amazon, Brazil.

Human occupation of the Amazon region has recently increased, bringing deforestation for agriculture and open-cast mining, activities that cause environmental degradation and pollution. Families of new settlers in mining areas might have a diet less dependent on abundant fish and their children might also be impacted by exposures to mining environments. Therefore, there is compounded interest in assessing young children's nutritional status and neurobehavioral development with regard to family fish consumption. Anthropometric (z-scores, WHO standards) and neurologic [Gesell developmental scores (GDS)] development in 688 preschool children (1-59 months of age) was studied. Overall, the prevalence of malnutrition [i.e., moderate stunting (≤2 H/A-Z), underweight (≤2 W/A-Z), and wasting (≤2 W/H-Z) were respectively 0.3% (n = 2), 1.6% (n = 11), and 2.5% (n = 17). Children's mean hair Hg (HHg) concentration was 2.56 µg/g (SD = 1.67); only 14% of children had HHg concentrations lower than 1 µg/g and 1.7% had ≥5 µg/g. The biomarker of fish consumption was weakly but positively correlated with GDS (Spearman r = 0.080; p = 0.035). In the bivariate model, attained W/H-Z scores were not significantly correlated with GDS. A moderate level of GDS deficits (70-84%) was seen in 20% of children. There was significant correlation between family fish consumption and children's hair Hg (HHg) (Spearman r = 0.1756; p < 0.0001) but no significant correlation between children's HHg and W/H-Z scores. However, the multivariate model showed that breastfeeding, a fish consumption biomarker (HHg), maternal education, and child's age were statistically significant associated with specific domains (language and personal-social) of the Gesell scale. In this mining environment, family fish-eating did not affect children's linear growth, but it showed a positive influence (along with maternal variables) on neurodevelopment. Health hazards attendant on a high prevalence of moderate neurodevelopment delays coexisting with exposure to multiple neurotoxic substances merits further investigation in poor environmental settings of tin-mining areas.

Handling of New Drug Safety Information in the Dutch Hospital Setting: A Mixed Methods Approach.

INTRODUCTION: The implementation of new drug safety information and Direct Healthcare Professional Communications (DHPCs) in hospitals is important for patient safety. OBJECTIVES: The aim of this study was to gain insight into which procedures and practices are in place to handle new drug safety information and particularly DHPCs in the Dutch hospital setting. METHODS: We first conducted focus groups including medical specialists and hospital pharmacists, focusing on handling of drug safety information at the individual and organisational level. A survey was then developed and distributed among hospital pharmacists in all Dutch hospitals to quantify the existence of specific procedures and committees to handle drug safety information and DHPCs. RESULTS: Eleven specialists and 14 pharmacists from six hospitals participated in focus groups. Drug safety information was usually considered before drugs were included in formularies or treatment protocols. Furthermore, drug safety information was consulted in response to patients experiencing adverse events. DHPCs were mostly dealt with by individual professionals. DHPCs could lead to actions but this was very uncommon. Completed surveys were received from 40 (53%) of the hospitals. In 32 (80%), the hospital pharmacy had procedures to deal with new drug safety information, whereas in 11 (28%) a hospital-wide procedure was in place. Drug safety was considered in committees concerning drug formulary decisions (69%) and antibiotic policies (63%). DHPCs were assessed by a hospital pharmacist in 50% of the hospitals. CONCLUSIONS: Drug safety information was used for evaluation of new treatments and in response to adverse events. Assessment of whether a DHPC requires action was primarily an individual task.

Spatiotemporal changes in the structure and composition of a less-abundant bacterial phylum (Planctomycetes) in two perialpine lakes.

We used fingerprinting and cloning-sequencing to study the spatiotemporal dynamics and diversity of Planctomycetes in two perialpine lakes with contrasting environmental conditions. Planctomycetes, which are less-abundant bacteria in freshwater ecosystems, appeared to be structured in the same way as the entire bacterial community in these ecosystems. They were more diversified and displayed fewer temporal variations in the hypolimnia than in the epilimnia. Like the more-abundant bacterial groups in aquatic systems, Planctomycetes communities seem to be composed of a very small number of abundant and widespread operational taxonomic units (OTUs) and a large number of OTUs that are present at low abundance. This indicates that the concept of "abundant or core" and "rare" bacterial phylotypes could also be applied to less-abundant freshwater bacterial phyla. The richness and diversity of Planctomycetes were mainly driven by pH and were similar in both of the lakes studied, whereas the composition of the Planctomycetes community seemed to be determined by a combination of factors including temperature, pH, and nutrients. The relative abundances of the dominant OTUs varied over time and were differently associated with abiotic factors. Our findings demonstrate that less-abundant bacterial phyla, such as Planctomycetes, can display strong spatial and seasonal variations linked to environmental conditions and suggest that their functional role in the lakes studied might be attributable mainly to a small number of phylotypes and vary over space and time in the water column.

Hydroelectric reservoir inundation (Rio Madeira Basin, Amazon) and changes in traditional lifestyle: impact on growth and neurodevelopment of pre-school children.

OBJECTIVE: To assess the dependence on fish consumption of families and its impact on nutritional status and neurodevelopment of pre-school children. DESIGN: Cross-sectional study that measured children's hair mercury (HHg) as an indicator of family fish consumption, growth (anthropometric Z-scores, WHO standards) and neurological (Gesell developmental scores (GDS)) development. SETTING: Traditional living conditions among families residing in the area adjacent to the Samuel Dam (Western Amazon) hydroelectric reservoir. SUBJECTS: Two hundred and forty-nine pre-school children (1-59 months of age) from families transitioning from the traditional Amazonian lifestyle. RESULTS: Family fish consumption was significantly correlated with children's HHg concentration (Spearman's r=0.246, P<0.0001); however, HHg had no significant association with growth (Z-scores). Overall, the prevalence of severe malnutrition, i.e. stunting (height-for-age Z-score (HAZ)≤-3), underweight (weight-for-age Z-score (WAZ)≤-3) and wasting (weight-for-height Z-score (WHZ)≤-3) was 5.2% (n 13), 0% and 0.8% (n 2), respectively. The prevalence of moderate stunting (HAZ≥-3 to ≤-2), underweight (WAZ≥-3 to ≤-2) and wasting (WHZ≥-3 to ≤-2) was 8.8% (n 22), 2.4% (n 6) and 4.8% (n 12), respectively. Although 76% of the children showed adequate GDS (>85), multiple regression analysis showed that fish consumption (as HHg) had no impact on GDS, but that some variables did interact significantly with specific domains (motor and language development). CONCLUSIONS: The study showed that the families' shift in fish consumption had no negative impact on the growth of young children and that ensuing methylmercury exposure has not been a noticeable neurodevelopmental hindrance.

Risk of simultaneous phenotypic expression of hip and elbow dysplasia in dogs: a study of 1,411 radiographic examinations sent for official scoring.

In order to look for phenotypic correlation between hip (HD) and elbow (ED) dysplasia, we used radiographic scoring obtained from 1,411 dogs of different breeds, which were evaluated for authoritative grading of both conditions. In this population, we found that the risk ratio for an animal to be simultaneously affected by HD and ED is 1.67. For a dog with ED, the risk ratio to be affected by HD increases as the ED grade increases. Similarly, for a dog affected by HD, the risk ratio to be affected by ED increases as the HD grade increases. In a dog affected by HD or ED, the clinician should look for the second condition in the same animal. Due to the low, yet positive correlation, selection against one trait will not affect the other trait sufficiently. Therefore selection has to be conducted at reduction of HD as well as reduction of ED.

Description of the type of chemical restraint used by French veterinarians to perform hip dysplasia screening radiographs. A retrospective study based on 3302 radiographs.

The objective of this study was to investigate the type of chemical restraint used by French practitioners to perform official hip screening radiographs, to determine the proportion of dogs under general anesthesia versus dogs under sedation, and to search for a difference in hip dysplasia (HD) prevalence between the two groups. From September 2005 to August 2008, 3302 conventional ventrodorsal hip extended radiographs sent for official scoring to the same panellist were selected because information related to the type of chemical restraint had been provided. There were 2825 dogs under general anesthesia and 477 were sedated. Chemical restraint used by French veterinarians to perform HD screening radiographs is mainly based on general intra-venous anesthesia with an alpha2 agonist associated with ketamine. A single injection of alpha2 agonist is also mostly used for dogs which are radiographed while under sedation. A very low (1.7%) difference in HD prevalence was noted between the anesthetized and the sedated group. Except for acepromazine, which has been demonstrated to provide insufficient muscle relaxation to show evidence of hip laxity, the protocols seem acceptable as regards the Federation Cynologique Internationale requirements for HD screening.

Prevalence of hip dysplasia according to official radiographic screening, among 31 breeds of dogs in France.

In order to determine the prevalence of hip dysplasia (HD) from radiographs that were submitted for authorative grading, and its changes over the time in 31 breeds of dogs in France, a 14 year-retrospective study was conducted. Significant differences were observed between breeds, with HD prevalence ranging from 59.7% (Cane Corso) to 3.9% (Siberian Husky). When comparing the 1993-1999 with the 2000-2006 period in 15 breeds, a significant decrease in HD prevalence was detected in Berger Picard, Bernese Mountain dog, Briard, Gordon Setter, White Swiss Sheepdog and Rottweiler. Modifications observed in the other breeds were not statistically significant.

Trimester specific reference ranges for serum TSH and Free T4 among United Arab Emirates pregnant women.

BACKGROUND: The American Thyroid Association (ATA) recommended the establishment of population specific reference ranges for thyroid hormones during pregnancy. Initial studies conducted in the United Arab Emirates (UAE) in 2003 and 2004 on pregnant women published a considerably higher upper limit for thyroid stimulating hormone (TSH) than that proposed by ATA. The UAE was classified as a country with mild iodine deficiency at the time of this initial study. After the implementation of aggressive strategies to address iodine deficiency over the last decade, the UAE was recently declared as iodine sufficient. The current study re-evaluates the reference intervals for thyroid hormones for pregnant women in the UAE after the declaration of iodine sufficiency status. METHODS: TSH and free thyroxin (FT4) from 414 UAE national pregnant females were analyzed to determine trimester specific reference ranges. RESULTS: The upper limits of the TSH reference ranges were found to be significantly lower than previously reported, but still higher than those recommended by ATA in 2011.FT4 reference ranges were found to be slightly lower than previously reported. CONCLUSION: TSH trimester specific reference ranges in UAE national pregnant women are higher than those recommended by ATA in 2011 but in keeping with the latest guidelines published in 2017. This should be considered while interpreting thyroid function tests in this population. Further studies including urinary iodine measurement, body mass index and larger numbers per partition in this population are recommended.

Strong coupling between natural Planctomycetes and changes in the quality of dissolved organic matter in freshwater samples.

Dilution-regrowth experiments coupled to fluorescence in situ hybridization were conducted with samples from two humic reservoirs in order to examine how inorganic nutrients (N, P) affect free-living bacterioplankton phylogenetic groups and subsequently the quality of dissolved organic matter (DOM). The experiments were complemented by analyses of the empirical relationships between the targeted bacteria, nutrients, DOM and grazers. The ratio of absorbance of waters (A) at 250 and 365 nm (A(250 nm):A(365 nm)), which has been found to increase with the proportion of small molecules in the DOM pool in other humic waters, was used as an index of DOM quality. When nutrient stimulated bacteria, both the responses of bacterial groups (in the absence of grazers) and the ratio A(250 nm):A(365 nm) were generally different between treatments (+N, +P, +NP), suggesting that in nutrient-poor systems, differences in the type of inorganic nutrient supply will ultimately cause differences in DOM quality. The ratio A(250 nm),:A(365 nm) peaked in the +N treatments where members of the Planctomycetes (PLA) were the most stimulated group, and across treatments, PLA best explained (positive relationship) variations in this ratio. Consistent with this, the in situ data showed that the removal of the negative effects of flagellates on PLA yielded the highest R(2) in attempts to use bacterial groups to explain variations in A(250 nm):A(365 nm). These findings provide lines of evidence, not previously demonstrated in natural waters, that Planctomycetes may be an important factor changing the DOM quality, particularly in nutrient-poor systems when supplied with inorganic N.

Canine hip dysplasia radiographic screening. Prevalence of rotation of the pelvis along its length axis in 7,012 conventional hip extended radiographs.

The prevalence of rotation of the pelvis along its length axis was noted, as was the number of rotations towards the right or left hand side of the dog, on 7,012 conventional hip extended radiographs, which were sent for official screening. 29.8% of the radiographs showed a rotation the pelvis. The rotation was statistically more frequent towards the left hand side of the dog. The number of rejected radiographs for too important pelvis rotation was only 5.2%. The consequences of the pelvis rotation on the Norberg-Olsson angle, on the dorsal femoral head coverage, and in the aspect of cranial acetabular edge have to be taken into account when scoring the dog for hip dysplasia.

Discovery of high-affinity ligands of sigma1 receptor, ERG2, and emopamil binding protein by pharmacophore modeling and virtual screening.

ERG2, emopamil binding protein (EBP), and sigma-1 receptor (sigma(1)) are enzymes of sterol metabolism and an enzyme-related protein, respectively, that share high affinity for various structurally diverse compounds. To discover novel high-affinity ligands, pharmacophore models were built with Catalyst based upon a series of 23 structurally diverse chemicals exhibiting K(i) values from 10 pM to 100 microM for all three proteins. In virtual screening experiments, we retrieved drugs that were previously reported to bind to one or several of these proteins and also tested 11 new hits experimentally, of which three, among them raloxifene, had affinities for sigma(1) or EBP of <60 nM. When used to search a database of 3525 biochemicals of intermediary metabolism, a slightly modified ERG2 pharmacophore model successfully retrieved 10 substrate candidates among the top 28 hits. Our results indicate that inhibitor-based pharmacophore models for sigma(1), ERG2, and EBP can be used to screen drug and metabolite databases for chemically diverse compounds and putative endogenous ligands.

Checking dwelling performance for Aging-in-Place.

About 90% of persons aged 55 and older would prefer to stay in their current residences as long as possible because older adults value their independence. However, aging-in-place is not always a choice. Recently, the Dutch government tightened the criteria for older adults to be admitted in a nursing home. Throughout the past 5 years TNO was requested by the trade association for building service contractors in the Netherlands to develop a number of tools for building service professionals. The 'dwelling check' was developed as a 'basic' check on the possibility for aging-in-place. A pilot study was conducted to assess the added value of the dwelling check for older adults. During this pilot study the occupants of over 200 dwellings were interviewed by 11 building services contractors using the dwelling check. Based on these interviews a personal advice was written. After which the interviewees were asked to evaluate this service, comprising the interview and written advice. The dwelling check contributed most to the awareness of and interest in possible alterations for aging-in-place. In a few cases the decision (17%) or even action (5%) was taken to make alterations. Overall the dwelling check was rated 8 out of 10 by the interviewees and may therefore be considered of added value.

Antiarrhythmic agents. 2-, 3-, And 4-substituted benzylamines.

The synthesis of a series of 2-, 3-, and 4-substituted benzylamine derivatives is described. These compounds were studied for their effect on experimental cardiac arrhythmias. Many of the derivatives, but in particular 2-(p-methoxyphenylethynyl)benzylamine (3d), alpha,alpha-dimethyl-4y(phenylethynyl)benzylamine (7a), and alpha,alpha-dimethyl-4-phenethylbenzylamine (12g), showed good antiarrhythmic activity.

Synthesis and orexigenic activity of some 1-methyl-4-piperidylidene-Substituted pyrrolo[2,1-g][3] benzazepine and dibenzocycloheptene derivatives.

The synthesis and orexigenic activity of some unsubstituted and Bz-carboxylic acid substituted 1-methyl-4-piperidylidenepyrrolo[2,1-b][3]benzazepine and dibenzocycloheptene derivatives are described. 10,11-Dihydro-3-carboxycyproheptadine (7c) has been selected for clinical evaluation as a orexigenic agent based on its low threshold dose for increasing food consumption in cats (0.031 mg/kg po) and its lack of undesirable central nervous system activity. The levorotatory enantiomer of 3-carboxycyproheptadine (1d) and the 9-carboxypyrrolobenzazepine derivative 4f also possess orexigenic activity, but with these compounds such activity diminishes sharply below 0.25 mg/kg po. The unsubstituted 1-methyl-4-(5H-pyrrolo[2,1-b][3]benzazepin-11-ylidene)piperidine (4d) and its 6,11-dihydroanalogue (4a) are comparable to cyproheptadine (1a) in promoting hyperphagia in cats.

(+)- and (-)-3-Methoxycyproheptadine. A comparative evaluation of the antiserotonin, antihistaminic, anticholinergic, and orexigenic properties with cyproheptadine.

The synthesis and resolution of (+/-)-3-methoxycyproheptadine [(+/-)-4] are described. As a peripheral serotonin antagonist, (+/-)-4 was found to be one-half as potent as cyproheptadine (1b). The peripheral anticholinergic and antihistaminic activities as well as the orexigenic property of (+/-)-4 are less than those of 1b. A further comparison of the enantiomers (+)-4 and (-)-4 shows that all of the anticholinergic activity of (+/-)-4 resides solely in the dextrorotatory enantiomer, (+)-4, while the antiserotonin activity, which is similar to that of 1b, resides in the levorotatory enantiomer, (-)-4. Antihistaminic and orexigenic activity also resides in (-)-4 but these properties are reduced compared to those of 1b.

A comparison of the antiserotonin, antihistamine, and anticholinergic activity of cyproheptadine with analogues having furan nuclei fused to the 10,11-vinylene bridge.

A series of cyproheptadine derivatives having furan nuclei fused to the 10,11-vinylene bridge has been prepared. None of the compounds retain the potent antiserotonin and antihistaminic actions of cyproheptadine. 1-methyl-4-(1-methyl-8H-dibenzo[a,e]furo[3,4-c]cyclohepten-8-ylidene)piperidine (7), 1-methyl-4-(1,3-dihydro-1-oxo-8H-[3,4:6,7]cycloheptal[1,2-c]furan-8-ylidene)piperidine (10), and its reduction product 11 retained the peripheral anticholinergic activity of cyproheptadine.

Synthesis and receptor binding studies relevant to the neuroleptic activities of some 1-methyl-4-piperidylidene-9-substituted-pyrrolo[2,1-b][3]benzazepine derivatives.

The synthesis of a series of 1-methyl-4-(9-substituted-11H-pyrrolo[2,1-b]benzazepin-11-ylidene)piperidines (4a-f) and 1-methyl-4-(9-substituted-6,11-dihydro-5H-pyrrolo[2,1-b][3]benzazepin-11-ylidene)piperidines (4g-l) is described. As with th e 3-substituted cyproheptadine compounds 1b-e, atropisomerism exists in 4b-f, but unlike the enantiomers of 1b-e, the pyrrolobenzazepine enantiomers racemize at room temperature. Thus, the bromo compound (+)-4b has a half-life of 128 +/- 1 min at 25 degrees C, while the chloro compound (-)-4c has a half-life of 114 +/- 9 min at 25 degrees C. Compounds 4a-l have been examined for receptor binding affinities in assays that have been recognized as predictive for antipsychotic activity. The displacement of specifically bound tritiated ligands, comprising the dopamine antagonist [3H]spiperone, the dopamine agonist [3H]apomorphine, the muscarinic cholinergic antagonist [3H]quinuclidinyl benzilate (QNB), the alpha-adrenergic antagonist [3H]prazosin, the alpha-adrenergic agonist [3H]clonidine, the serotonin-1 binding agent [3H]serotonin, and the mixed serotonin agonist-antagonist [3H]lysergic acid diethylamide (LSD), by 4a-l has been measured utilizing membrane preparations of mammalian brain. Certain of the features of the receptor binding of these compounds have been shown to be common to several of the receptor sites. Data from these binding studies have been compared to corresponding data previously obtained for a series of chiral 3-substituted cyproheptadine analogues, and the receptor binding data of the two classes of compounds are discussed with respect to their molecular geometries.