Are vitamins A and E associated with persistent organic pollutants and fatty acids in the blubber of highly contaminated killer whales (Orcinus orca) from Greenland?

We quantified blubber concentrations of vitamins A (retinol) and E (α-tocopherol) and evaluated associations with persistent organic pollutants (ΣPOPs) in 14 highly-contaminated killer whales (Orcinus orca) sampled in Greenland from 2012 to 2014. We considered the influence of blubber depth, sex/age class and diet (based on biomass % of major fatty acids) in these relationships. Blubber concentrations of vitamin A averaged 34.1 ±â€¯4.7 µg g-1 wet weight (ww) and vitamin E averaged 35.6 ±â€¯4.4 µg g-1 ww. Although overall vitamin A concentrations did not vary between inner (closer to the muscle) and outer (closer to the skin) blubber layer or between sub-adults and adult females, concentrations in the outer layer of sub-adults were lower compared to the outer layer of adult females (p = 0.03). Outer layer may therefore reflect age accumulation of vitamin A, while in the more active inner layer, age effects might be masked by metabolic needs such as lactation. Neither diet nor ΣPOPs affected vitamin A variation, suggesting this vitamin is highly regulated in the body. Given the high exposures in these killer whales, vitamin A might not be a sensitive biomarker for POPs adverse effects. Vitamin E concentrations were significantly higher in inner compared to outer layer (p < 0.001), likely associated with blubber composition, suggesting that biopsies may not fully represent vitamin E concentrations in blubber. Age-accumulation of vitamin E also occurred with higher concentrations in adult females compared to sub-adults, independent of blubber depth (p < 0.01). Diet, ΣPOPs, and an interaction between these two variables significantly affected vitamin E variation in inner blubber, explaining 91% of this variation. The negative relationship between ΣPOPs (especially Σdichlorodiphenyltrichloroethane (DDT) and Σchlordanes in outer layers) and vitamin E was observed only in killer whales with a diet poorer in polyunsaturated fatty acids, suggested that killer whales feeding more consistently on marine mammals in Arctic environments over a fish-based diet, may be at higher risk of POP-induced disruption in vitamin E homeostasis. Considering diet is therefore important to understand the potential effects of elevated contaminant exposures on levels of certain essential nutrients, i.e., vitamin E, in killer whales.

Mercury and cortisol in Western Hudson Bay polar bear hair.

Non-invasive methods of assessing animal health and life history are becoming increasingly popular in wildlife research; hair samples from polar bears (Ursus maritimus), are being used to study an ever broader range of anthropogenic and endocrine compounds. A number of contaminants are known to disrupt endocrine function in polar bears. However, the relationship between mercury and cortisol remains unknown, although mercury is an endocrine disruptor in other species. Here, we examine the relationship between concentrations of cortisol and total mercury (THg) analyzed in guard hair from 378 polar bears (184 females, 194 males) sampled in Western Hudson Bay, 2004-2012. The difference in mean cortisol concentration between female (0.8 ± 0.6 pg/mg) and male (0.7 ± 0.5 pg/mg) polar bears bordered on significance (p = 0.054). However, mean mercury concentration was significantly greater (p = 0.009) in females (4.7 ± 1.4 µg/g) than males (4.3 ± 1.2 µg/g). Hair cortisol in males was significantly influenced by mercury, age, and fatness, as well as interactions between mercury and year, mercury and fatness, and year and fatness (all: p < 0.03) (multiple regression analysis, whole model: r(2) = 0.14, F(7,185) = 4.43, p = 0.0001). Fatness was the only significant variable in the multiple regression analysis for females (r(2) = 0.06, F(1,182) = 13.0, p = 0.0004). In conclusion, a significant, but complex, relationship was found between mercury and cortisol concentrations in hair from male, but not female, polar bears.

[Updated incidence of dry eye syndrome in Germany]. / Aktuelle Inzidenz des Trockenen Auges in Deutschland.

BACKGROUND: Dry eye is one of the most common eye surface disorders. Patients suffer in particular from annoying subjective symptoms that compromise quality of life. The aim of the study was to find out when patients consult ophthalmologists in Germany and what symptoms they present. PATIENTS/MATERIAL AND METHODS: 170 patients treated at ophthalmological practices in Bavaria, Saxony and Saxony-Anhalt with dry eye were surveyed regarding their symptoms. RESULTS: The majority of those questioned were 40 years of age or older (88 %) (average: 60), female (59 %) and described a variety of subjective symptoms (65 %). More than five different concurrent symptoms were named. There is a recognisable increase in cases - by more than 3.5 times - at the age of forty (in women) and fifty (in men). CONCLUSIONS: We hope to contribute with the data obtained to a more complete understanding of this highly complex pathological process. A further aim is to facilitate recognition of this mostly chronic condition in its early stages when the symptoms are still poorly defined. The data on the German population obtained here should become part of a comparative analysis within the international context. Despite considerable scientific effort, dry eye remains a difficult challenge for both patients and attending physicians.

Land-use change, not climate, controls organic carbon burial in lakes.

Lakes are a central component of the carbon cycle, both mineralizing terrestrially derived organic matter and storing substantial amounts of organic carbon (OC) in their sediments. However, the rates and controls on OC burial by lakes remain uncertain, as do the possible effects of future global change processes. To address these issues, we derived OC burial rates in (210)Pb-dated sediment cores from 116 small Minnesota lakes that cover major climate and land-use gradients. Rates for individual lakes presently range from 7 to 127 g C m(-2) yr(-1) and have increased by up to a factor of 8 since Euro-American settlement (mean increase: 2.8×). Mean pre-disturbance OC burial rates were similar (14-22 g C m(-2) yr(-1)) across all land-cover categories (prairie, mixed deciduous and boreal forest), indicating minimal effect of the regional temperature gradient (approx. 4 °C) on background carbon burial. The relationship between modern OC burial rates and temperature was also not significant after removal of the effect of total phosphorus. Contemporary burial rates were strongly correlated with lake-water nutrients and the extent of agricultural land cover in the catchment. Increased OC burial, documented even in relatively undisturbed boreal lake ecosystems, indicates a possible role for atmospheric nitrogen deposition. Our results suggest that globally, future land-cover change, intensification of agriculture and associated nutrient loading together with atmospheric N-deposition will enhance OC sequestration by lakes.

Associations between complex OHC mixtures and thyroid and cortisol hormone levels in East Greenland polar bears.

The multivariate relationship between hair cortisol, whole blood thyroid hormones, and the complex mixtures of organohalogen contaminant (OHC) levels measured in subcutaneous adipose of 23 East Greenland polar bears (eight males and 15 females, all sampled between the years 1999 and 2001) was analyzed using projection to latent structure (PLS) regression modeling. In the resulting PLS model, most important variables with a negative influence on cortisol levels were particularly BDE-99, but also CB-180, -201, BDE-153, and CB-170/190. The most important variables with a positive influence on cortisol were CB-66/95, α-HCH, TT3, as well as heptachlor epoxide, dieldrin, BDE-47, p,p'-DDD. Although statistical modeling does not necessarily fully explain biological cause-effect relationships, relationships indicate that (1) the hypothalamic-pituitary-adrenal (HPA) axis in East Greenland polar bears is likely to be affected by OHC-contaminants and (2) the association between OHCs and cortisol may be linked with the hypothalamus-pituitary-thyroid (HPT) axis.

Temporal trends and future predictions of mercury concentrations in Northwest Greenland polar bear (Ursus maritimus) hair.

Hair samples from 117 Northwest Greenland polar bears (Ursus maritimus) were taken during 1892-2008 and analyzed for total mercury (hereafter Hg). The sample represented 28 independent years and the aim of the study was to analyze for temporal Hg trends. Mercury concentrations showed yearly significant increases of 1.6-1.7% (p < 0.0001) from 1892 to 2008 and the two most recent median concentrations from 2006 and 2008 were 23- to 27-fold higher respectively than baseline level from 1300 A.D. in the same region (Nuullit). This indicates that the present (2006-2008) Northwest Greenland polar bear Hg exposure is 95.6-96.2% anthropogenic in its origin. Assuming a continued anthropogenic increase, this model estimated concentrations in 2050 and 2100 will be 40- and 92-fold the baseline concentration, respectively, which is equivalent to a 97.5 and 98.9% man-made contribution. None of the 2001-2008 concentrations of Hg in Northwest Greenland polar bear hair exceeded the general guideline values of 20-30 µg/g dry weight for terrestrial wildlife, whereas the neurochemical effect level of 5.4 µg Hg/g dry weight proposed for East Greenland polar bears was exceeded in 93.5% of the cases. These results call for detailed effect studies in main target organs such as brain, liver, kidney, and sexual organs in the Northwest Greenland polar bears.

The Baltic Sea: An ecosystem with multiple stressors.

This introductory chapter to our Environment International VSI does not need an abstract and therefore we just include our recommendations below in order to proceed with the resubmission. Future work should examine waterbirds as food web sentinels of multiple stressors as well as Baltic Sea food web dynamics of hazardous substances and how climate change may modify it. Also, future work should aim at further extending the new frameworks developed within BALTHEALTH for energy and contaminant transfer at the population level (Desforges et al., 2018, Cervin et al., 2020/this issue Silva et al., 2020/this issue) and their long term effects on Baltic Sea top predators, such as harbour porpoises, grey seals ringed seals, and white-tailed eagles. Likewise, the risk evaluation conducted for PCB in connection with mercury on Arctic wildlife (Dietz et al., 2019, not a BONUS BALTHEALTH product) could be planned for Baltic Sea molluscs, fish, bird and marine mammals in the future. Finally, future efforts could include stressors not covered by the BONUS BALTHEALTH project, such as food web fluxes, overexploitation, bycatches, eutrophication and underwater noise.

Mercury and neurochemical biomarkers in multiple brain regions of five Arctic marine mammals.

Mercury is a neurotoxic chemical that represents one of the greatest pollution threats to Arctic ecosystem health. Evaluating the direct neurotoxic effects of mercury in free ranging wildlife is challenging, necessitating the use of neurochemical biomarkers to assess potential sub-clinical neurological changes. The objective of this study was to characterize the distribution and speciation of mercury, as well as exposure-associated changes in neurochemistry, across multiple brain regions (n = 10) and marine mammal species (n = 5) that each occupy a trophic niche in the Arctic ecosystem. We found consistent species differences in mean brain and brain region-specific concentrations of total mercury (THg) and methyl mercury (MeHg), with higher concentrations in toothed whales (narwhal, pilot whales and harbour porpoise) compared to fur-bearing mammals (polar bear and ringed seal). Mean THg (µg/g dw) in decreasing rank order was: pilot whale (11.9) > narwhal (7.7) > harbour porpoise (3.6) > polar bear (0.6) > ringed seal (0.2). The higher THg concentrations in toothed whales was associated with a marked reduction in the percentage of MeHg (<40 %) compared to polar bears (>70 %) that had lower brain THg concentrations. This pattern in mercury concentration and speciation corresponded broadly to an overall higher number of mercury-associated neurochemical biomarker correlations in toothed whales. Of the 226 correlations between mercury and neurochemical biomarkers across brain regions, we found 60 (27 %) meaningful relationships (r>0.60 or p < 0.10). We add to the growing weight of evidence that wildlife accumulate mercury in their brains and demonstrate that there is variance in accumulation across species as well as across distinct brain regions, and that some of these exposures may be associated with sub-clinical changes in neurochemistry.

Next generation 1.5 microm terahertz antennas: mesa-structuring of InGaAs/InAlAs photoconductive layers.

Mesa-structuring of InGaAs/InAlAs photoconductive layers is performed employing a chemical assisted ion beam etching (CAIBE) process. Terahertz photoconductive antennas for 1.5 microm operation are fabricated and evaluated in a time domain spectrometer. Order-of-magnitude improvements versus planar antennas are demonstrated in terms of emitter power, dark current and receiver sensitivity.

The influence of adjuvants on local recurrence rate in giant cell tumour of the bone.

INTRODUCTION: Intralesional surgery of giant cell tumour of the bone (GCT) may result in a high rate of local recurrence. The introduction of local adjuvants, such as cementation, cryosurgery or phenolization, has proved to be successful in the reduction of recurrence rates. This study presents the results of a single institution in surgery of GCT with an evolution in treatment strategies. MATERIAL & METHODS: Forty primary and 25 recurrent surgical procedures in 46 patients with GCT of the bone with a median follow-up of 72 months were reviewed retrospectively. The mean age was 32.6 years (range 13.6-57.9 years). Forty-seven curettages and 18 resections were performed. For the curettages, a large bone window was cut followed by high speed burring and bone grafting or cementation. In 34 of 47 curettages and 7 of 18 resections, phenol was additionally applied. RESULTS: Two patients showed pulmonary metastasis, one died due to metastatic disease. In total, a third of the patients developed local recurrence (32.3%). This was evenly spread among primary and recurrent diesease (32.5% vs. 32%). Seven of 13 curettages without adjuvant recurred (53.9%), compared to 11 of 34 curettages with adjuvant phenol (32.4%). Three of 18 resections developed a recurrence (16.7%). No complications in respect to the use of phenol were seen. DISCUSSION: Phenolization is a safe local adjuvant therapy for GCT. Although the recurrence rate was lower with the use of phenol, this drop was not significant. The comparable high recurrence rate in our study, even if phenol was used, might be due to the fact that curettage was our favoured treatment, even in cases with an extensive juxta-articular tumour. We recommend adjuvant phenolization in the treatment of GCT of the bone after thorough curettage in applicable cases, including where cementation is used for defect filling.

Stranded cetaceans warn of high perfluoroalkyl substance pollution in the western Mediterranean Sea.

Perfluoroalkyl substances (PFASs) are a class of organohalogenated compounds of environmental concern due to similar characteristics as the well-studied legacy persistent organic pollutants (POPs) that typically show environmental persistence, biomagnification and toxicity. Nevertheless, PFAS are still poorly regulated internationally and in many aspects poorly understood. Here, we studied liver and muscle concentrations in five cetacean species stranded at the southeastern coast of Spain during 2009-2018. Twelve of the fifteen targeted compounds were detected in >50% of the liver samples. Hepatic concentrations were significantly higher than those in muscle reflecting the particular toxicokinetics of these compounds. Bottlenose dolphins Tursiops truncatus showed the highest hepatic ΣPFAS (n = 5; 796.8 ± 709.0 ng g-1 ww) concentrations, followed by striped dolphin Stenella coeruleoalba (n = 29; 259.5 ± 136.2 ng g-1 ww), sperm whale Physeter macrocephalus (n = 1; 252.8 ng g-1 ww), short-beaked common dolphin Delphinus delphis (n = 2; 240.3 ± 218.6 ng g-1 ww) and Risso's dolphin Grampus griseus (n = 1; 78.7 ng g-1 ww). These interspecies differences could be partially explained by habitat preferences, although they could generally not be related to trophic position or food chain proxied by stable N (δ15N) and C (δ13C) isotope values, respectively. PFAS profiles in all species showed a similar pattern of concentration prevalence in the order PFOS>PFOSA>PFNA≈PFFUnA>PFDA. The higher number of samples available for striped dolphin allowed for evaluating their PFAS burden and profile in relation to the stranding year, stable isotope values, and biological variables including sex and length. However, we could only find links between δ15N and PFAS burdens in muscle tissue, and between stranding year and PFAS profile composition. Despite reductions in the manufacturing industry, these compounds still appear in high concentrations compared to more than two decades ago in the Mediterranean Sea and PFOS remains the dominating compound.

The impact of rising sea temperatures on an Arctic top predator, the narwhal.

Arctic top predators are expected to be impacted by increasing temperatures associated with climate change, but the relationship between increasing sea temperatures and population dynamics of Arctic cetaceans remains largely unexplored. Narwhals (Monodon monoceros) are considered to be among the most sensitive of Arctic endemic marine mammals to climate change due to their limited prey selection, strict migratory patterns and high site fidelity. In the context of climate change, we assume that the population dynamics of narwhals are partly influenced by changes in environmental conditions, with warm areas of increasing sea temperatures having lower abundance of narwhals. Using a unique large dataset of 144 satellite tracked narwhals, sea surface temperature (SST) data spanning 25 years (1993-2018) and narwhal abundance estimates from 17 localities, we (1) assessed the thermal exposure of this species, (2) investigated the SST trends at the summer foraging grounds, and (3) assessed the relationship between SST and abundance of narwhals. We showed a sharp SST increase in Northwest, Mideast and Southeast Greenland, whereas no change could be detected in the Canadian Arctic Archipelago (CAA) and in the Greenland Sea. The rising sea temperatures were correlated with the smallest narwhal abundance observed in the Mideast and Southeast Greenland (< 2000 individuals), where the mean summer sea temperatures were the highest (6.3 °C) compared to the cold waters of the CAA (0.7 °C) that were associated with the largest narwhal populations (> 40,000 individuals). These results support the hypothesis that warming ocean waters will restrict the habitat range of the narwhal, further suggesting that narwhals from Mideast and Southeast Greenland may be under pressure to abandon their traditional habitats due to ocean warming, and consequently either migrate further North or locally go extinct.

Improvement of fractional flow reserve and collateral flow by treatment with external counterpulsation (Art.Net.-2 Trial).

BACKGROUND: Arteriogenesis (collateral artery growth) is nature's most efficient rescue mechanism to overcome the fatal consequences of arterial occlusion or stenosis. The goal of this trial was to investigate the effect of external counterpulsation (ECP) on coronary collateral artery growth. MATERIALS AND METHODS: A total of 23 patients (age 61 +/- 2.5 years) with stable coronary artery disease and at least one haemodynamic significant stenosis eligible for percutaneous coronary intervention were prospectively recruited into the two study groups in a 2 : 1 manner (ECP : control). One group (ECP group, n = 16) underwent 35 1-h sessions of ECP in 7 weeks. In the control group (n = 7), the natural course of collateral circulation over 7 weeks was evaluated. All patients underwent a cardiac catheterization at baseline and after 7 weeks, with invasive measurements of the pressure-derived collateral flow index (CFIp, primary endpoint) and fractional flow reserve (FFR). RESULTS: In the ECP group, the CFIp (from 0.08 +/- 0.01 to 0.15 +/- 0.02; P < 0.001) and FFR (from 0.68 +/- 0.03 to 0.79 +/- 0.03; P = 0.001) improved significantly, while in the control group no change was observed. Only the ECP group showed a reduction of the Canadian Cardiovascular Society (CCS, P = 0.008) and New York Heart Association (NYHA, P < 0.001) classification. CONCLUSION: In this study, we provide direct functional evidence for the stimulation of coronary arteriogenesis via ECP in patients with stable coronary artery disease. These data might open a novel noninvasive and preventive treatment avenue for patients with non-acute vascular stenotic disease.

Aster-free spindle poles in insect spermatocytes: evidence for chromosome-induced spindle formation?

Tipulid spermatocytes form normally functioning bipolar spindles after one of the centrosomes is experimentally dislocated from the nucleus in late diakinesis (Dietz, R., 1959, Z. Naturforsch., 14b:749-752; Dietz, R., 1963, Zool. Anz. Suppl., 23:131-138; Dietz, R., 1966, Heredity, 19:161-166). The possibility that dissociated pericentriolar material (PCM) is nevertheless responsible for the formation of the spindle in these cells cannot be ruled out based on live observation. In studying serial sections of complete cells and of lysed cells, it was found that centrosome-free spindle poles in the crane fly show neither pericentriolar-like material nor aster microtubules, whereas the displaced centrosomes appear complete, i.e., consist of a centriole pair, aster microtubules, and PCM. Exposure to a lysis buffer containing tubulin resulted in an increase of centrosomal asters due to aster microtubule polymerization. Aster-free spindle poles did not show any reaction, also indicating the absence of PCM at these poles. The results favor the hypothesis of chromosome-induced spindle pole formation at the onset of prometaphase and the dispensability of PCM in Pales.

Fit between Africa and Antarctica: A Continental Drift Reconstruction.

A computerized (smallest average misfit) best fit position is obtained for the juxtaposition of Africa and Antarctica in a continental drift reconstruction. An S-shaped portion of the Weddell and Princess Martha Coast regions of western East Antarctica is fitted into a similar profile along southeastern Africa. The total amount of overlap is 36,300 square kilometers, and the underlap is 23,600 square kilometers; the total mismatch is thus of 59,900 square kilometers. The congruency along the 1000-fathom isobath is remarkably good and suggests that this reconstruction is valid within the overall framework of the Gondwana supercontinent.

Prevalence of antibodies against Toxoplasma gondii in polar bears (Ursus maritimus) from Svalbard and East Greenland.

Serum samples from 419 polar bears (Ursus maritimus) from Svalbard and the Barents Sea (collected 1990-2000) and 108 polar bears from East Greenland (collected 1999-2004) were assayed for antibodies against Toxoplasma gondii using the modified agglutination test. Antibody prevalences were 3.6% among cubs dependent on their mothers and 21.4% among subadults and adults. Among subadults and adults there was an interaction between population and sex, with similar prevalences among females (Svalbard = 19.5%, Greenland = 18.0%), but a high frequency among Svalbard males (28.7%) as compared to Greenland males (5.8%). The pattern was also significant after correcting for differences in age distribution. The sex-population interaction term is believed to be connected to area- and sex-specific feeding ecology. The prevalences of antibodies against T. gondii in Svalbard and Greenland were high compared to previously reported findings in polar bears from Russian and Alaskan areas.

Toxaphene in minke whales (Balaenoptera acutorostrata) from the North Atlantic.

Toxaphene contamination of minke whales (Balaenoptera acutorostrata) from North Atlantic waters was examined for the first time. Total toxaphene and SigmaCHB (sum of 11 chlorobornanes) concentrations in blubber samples ranged from 170+/-110 and 41+/-39 ng/g lipid weight (l.w.) for female minke whales from southeastern Greenland to 5800+/-4100 and 1100+/-780 ng/g l.w. for males from the North Sea, respectively. Very large variations in toxaphene concentrations among sampling areas were observed suggesting a spatial segregation of minke whales. However, much of the apparent geographical discrimination was explained by the seasonal fluctuation of animal fat mass. Patterns of CHBs in males revealed that recalcitrant CHBs were in higher proportions in animals from the more easterly areas than in animals from the more westerly areas. This trend may be influenced by the predominance of the US, over the European, input of toxaphene to North Atlantic waters.

Novel splice donor site mutation in the cardiac myosin-binding protein-C gene in familial hypertrophic cardiomyopathy. Characterization Of cardiac transcript and protein.

Familial hypertrophic cardiomyopathy is a disease generally believed to be caused by mutations in sarcomeric proteins. In a family with hypertrophic cardiomyopathy linked to polymorphic markers on chromosome 11, we found a new mutation of a splice donor site of the cardiac myosin-binding protein-C gene. This mutation causes the skipping of the associated exon in mRNA from lymphocytes and myocardium. Skipping of the exon with a consecutive reading frame shift leads to premature termination of translation and is thus expected to produce a truncated cardiac myosin-binding protein-C with loss of the myosin- and titin-binding COOH terminus. However, Western blot analysis of endomyocardial biopsies from histologically affected left ventricular myocardium failed to show the expected truncated protein. These data show for the first time that a splice donor site mutation in the myosin-binding protein-C gene is transcribed to cardiac mRNA. Truncated cardiac myosin-binding protein-C does not act as a "poison polypeptide," since it seems not to be incorporated into the sarcomere in significant amounts. The absence of mutant protein and of significantly reduced amounts of wild-type protein in the presence of the mutated mRNA argues against the "poison protein" and the "null allele" hypotheses and suggests yet unknown mechanisms relevant to the genesis of chromosome-11- associated familial hypertrophic cardiomyopathy.

Identification of a cis-acting regulatory element conferring inducibility of the atrial natriuretic factor gene in acute pressure overload.

To identify the cis-acting regulatory element(s) which control the induction of the atrial natriuretic factor (ANF) gene in acute pressure overload, DNA constructs consisting of promoter elements linked to a reporter gene were injected into the myocardium of dogs, which underwent aortic banding or were sham-operated. Expression of a reporter gene construct harboring the ANF promoter (-3400ANF) was induced 6-12-fold after 7 d of pressure overload. An internal deletion of 556 bp (nucleotide sequence -693 to -137) completely abrogated the inducibility of the ANF reporter gene construct. An activator protein-1 (AP1)-like site (-496 to -489) and a cAMP regulatory element (CRE) (-602 to -596) are located within the deleted sequence. Site-directed mutagenesis of the AP1-like site but not the CRE completely prevented the induction of this construct to acute pressure overload. Further, the AP1-like site was able to confer inducibility of a heterologous promoter (beta-myosin heavy chain) to higher values than controls. Gel mobility shift assay (GMSA) supershift analysis was performed using a radiolabeled probe of the ANF promoter (-506/-483) that included the AP1-like site (ATGAATCA) sequence, as well as a probe converted to contain an AP1 consensus sequence (ATGACTCA). GMSA analysis demonstrated that the ANF AP1-like element could bind both a constitutively expressed factor and the AP1 proteins, and conversion to a true AP1 site increased its affinity for AP1. However, 7 d after the onset of pressure overload, the AP1 proteins were present only at low levels, and the major complex formed by the ANF AP1-like probe was not supershifted by a jun antibody. Using a large animal model of pressure overload, we have demonstrated that a unique cis-acting element was primarily responsible for the overload induction of the ANF gene.

Impact of pharmacist interventions in older patients: a prospective study in a tertiary hospital in Germany.

BACKGROUND: Inappropriate pharmacotherapy among older adults remains a critical issue in our health care systems. Besides polypharmacy and multiple comorbidities, the age-related pharmacokinetic and pharmacodynamic changes may increase the risk of adverse drug reactions and medication errors. OBJECTIVE: The main target of this study was to describe the characteristics of pharmaceutical interventions in two geriatric wards (orthogeriatric ward and geriatric day unit) of a general teaching hospital and to evaluate the clinical significance of the detected medication errors. MATERIALS AND METHODS: The study was conducted between August 2014 and October 2015 and was based on a triple approach that included validation of medical orders, medication reconciliation at patients' admission, and a predischarge planning appointment with the patient. The validation of medical orders was based on analyzing the suitability of the drugs prescribed, the drug dose depending on the patient's characteristics, the presence of contraindications and interactions between drugs, and the proposal of alternative drugs included in the hospital formulary. RESULTS: A total of 2,307 interventions associated to a medication error in 15,282 medical orders for 1,859 older patients were recorded. The greater part of the interventions carried out on the orthogeriatric ward at admission and at discharge were due to omission of a drug in the medical order (20.0%) and clinically significant interactions requiring monitoring (30.4%), respectively. The main factor triggering pharmacist's recommendations on the geriatric day unit was clinically significant interactions (21.1%). With regard to the clinical severity of the detected errors, 68.1% were considered significant, 24.8% were of minor significance, and 7.2% were clinically serious. CONCLUSION: Our findings show the importance of clinical pharmacist involvement in the optimization of pharmacotherapy in older adults, ensuring that they receive effective, safe, and efficient drug therapy.