Tracking pan-continental trends in environmental contamination using sentinel raptors—what types of samples should we use?

Biomonitoring using birds of prey as sentinel species has been mooted as a way to evaluate the success of European Union directives that are designed to protect people and the environment across Europe from industrial contaminants and pesticides. No such pan-European evaluation currently exists. Coordination of such large scale monitoring would require harmonisation across multiple countries of the types of samples collected and analysed-matrices vary in the ease with which they can be collected and the information they provide. We report the first ever pan-European assessment of which raptor samples are collected across Europe and review their suitability for biomonitoring. Currently, some 182 monitoring programmes across 33 European countries collect a variety of raptor samples, and we discuss the relative merits of each for monitoring current priority and emerging compounds. Of the matrices collected, blood and liver are used most extensively for quantifying trends in recent and longer-term contaminant exposure, respectively. These matrices are potentially the most effective for pan-European biomonitoring but are not so widely and frequently collected as others. We found that failed eggs and feathers are the most widely collected samples. Because of this ubiquity, they may provide the best opportunities for widescale biomonitoring, although neither is suitable for all compounds. We advocate piloting pan-European monitoring of selected priority compounds using these matrices and developing read-across approaches to accommodate any effects that trophic pathway and species differences in accumulation may have on our ability to track environmental trends in contaminants.     

Comparison of behavioral problems between two samples of 2- to 3-year-old children in Finland and Iceland

The study objective was to compare the behavior problems of 2- to 3-year-old children in Finland and Iceland. A standardized rating scale of preschool psychopathology (CBCL 2-3), developed in the USA, was used to obtain parental information on 493 preschoolers in Finland and Iceland. Behavior scores in the two samples were rather similar. Boys had higher rates of externalizing behavior, aggressivity, and destructivity in both samples. In addition, there were relatively high rates of attention-seeking and poor concentration overall.     

Intergenerational support among migrant families in Europe

Intergenerational support is important throughout the individual life course and a major mechanism of cultural continuity. In this study, we analyse support between older parents and their adult children among international migrant and non-migrant populations in North, Centre and Southern Europe. Data from the Survey of Health, Ageing and Retirement in Europe are used to compare upward and downward practical support, grandparenting, and frequency of contact among 62,213 parent–child dyads. Findings indicate limited differences in support between migrants and non-migrants as well as between migrants of various origins. However, persistent differences in intergenerational support across Europe along a north–south gradient are found irrespective of migrant status.     

Psychosocial functioning and psychiatric comorbidity among substance-abusing Icelandic adolescents

Abstract

Background: Physical inactivity is an independent risk factor for cardiovascular diseases and Type 2 diabetes, both being highly prevalent in patients with severe mental illness. Though physical activity has become an important issue in psychiatric treatment and rehabilitation in the past decade, systematic evaluations of physical activity level in psychiatric populations could be more disseminated. Aim: The primary aim of the study was to investigate the physical activity level of psychiatric patients in comparison with healthy controls. Methods: Patients with severe mental illness (n =47) and a group of healthy controls (n =28) matched on sex and age reported their physical activity level using the Physical Activity Scale (PAS). PAS was administered as an interview in relation to patients and as a questionnaire in relation to healthy controls. Results: Patients had statistically significant lower levels of physical activity compared with healthy controls (P <0.0001) and the level of physical activity among patients was hazardously low. Conclusion: The study confirmed previous studies and clinical experience that patients with severe mental illness are physically inactive and emphasize the importance of physical activity in psychiatric treatment and rehabilitation. The PAS is an applicable and relevant method for evaluating physical activity levels in psychiatric patients.     

Treating hepatic encephalopathy in cirrhotic patients admitted to ICU with sodium phenylbutyrate: a preliminary study

Hepatic encephalopathy (HE) influences short‐term and long‐term prognoses. Recently, glycerol phenylbutyrate (PB), that lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion, has shown that it was effective in preventing the occurrence of HE in RCT. The aim was to assess the benefits of sodium PB in cirrhotic patients admitted to ICU for overt HE, in terms of ammonia levels decrease, neurological improvement, and survival. Cirrhotic patients who presented with overt HE, ammonia levels >100 μmol/L, and did not display any contra‐indication were included. Sodium PB was administered at 200 mg/kg/day. Control group included historical controls treated by standard therapy, matched for age, sex, MELD score, and severity of HE. Eighteen patients were included and treated with sodium PB (age: 59 [45–68], male gender: 15 [83%], Child–Pugh B: 8 [44%], Child–Pugh C: 10 [56%], and MELD score: 16 [13–23]). Ammonia levels significantly decreased in the PB as compared to the control group from inclusion to 12 h and from inclusion to 48 h (P = 0.0201 and P = 0.0230, respectively). The proportion of patients displaying neurological improvement was only higher in the PB‐treated group as compared to controls at ICU discharge (15 [83%] vs. 9 [50%], P = 0.0339). ICU discharge survival was significantly higher in patients treated with PB (17 [94%] vs. 9 [50%], P = 0.0017). In cirrhotic patients with overt HE, sodium PB could be effective in reducing ammonia levels and might be effective in improving neurological status and ICU discharge survival. More extensive data, especially a RCT, are mandatory.     

Pharmacokinetics-Pharmacodynamics of the Helicase-Primase Inhibitor Pritelivir following Treatment of Wild-Type or Pritelivir-Resistant Virus Infection in a Murine Herpes Simplex Virus 1 Infection Model

Herpes simplex virus (HSV) infections can cause considerable morbidity. Transmission of HSV-2 has become a major health concern, since it has been shown to promote transmission of other sexually transmitted diseases. Pritelivir (AIC316, BAY 57-1293) belongs to a new class of HSV antiviral compounds, the helicase-primase inhibitors, which have a mode of action that is distinct from that of antiviral nucleoside analogues currently in clinical use. Analysis of pharmacokinetic-pharmacodynamic parameters is a useful tool for the selection of appropriate doses in clinical trials, especially for compounds belonging to new classes for which no or only limited data on therapeutic profiles are available. For this purpose, the effective dose of pritelivir was determined in a comprehensive mouse model of HSV infection. Corresponding plasma concentrations were measured, and exposures were compared with efficacious concentrations derived from cell cultures. The administration of pritelivir at 10 mg/kg of body weight once daily for 4 days completely suppressed any signs of HSV infection in the animals. Associated plasma concentrations adjusted for protein binding stayed above the cell culture 90% effective concentration (EC₉₀) for HSV-1 for almost the entire dosing interval. Interestingly, by increasing the dose 6-fold and prolonging the treatment duration to 8 days, it was possible to treat mice infected with an approximately 30-fold pritelivir-resistant but fully pathogenic HSV-1 virus. Corresponding plasma concentrations exceeded the EC₉₀ of this mutant for <8 h, indicating that even suboptimal exposure to pritelivir is sufficient to achieve antiviral efficacy, possibly augmented by other factors such as the immune system.     

Disruption of vascular Ca2+-activated chloride currents lowers blood pressure

High blood pressure is the leading risk factor for death worldwide. One of the hallmarks is a rise of peripheral vascular resistance, which largely depends on arteriole tone. Ca²⁺-activated chloride currents (CaCCs) in vascular smooth muscle cells (VSMCs) are candidates for increasing vascular contractility. We analyzed the vascular tree and identified substantial CaCCs in VSMCs of the aorta and carotid arteries. CaCCs were small or absent in VSMCs of medium-sized vessels such as mesenteric arteries and larger retinal arterioles. In small vessels of the retina, brain, and skeletal muscle, where contractile intermediate cells or pericytes gradually replace VSMCs, CaCCs were particularly large. Targeted disruption of the calcium-activated chloride channel TMEM16A, also known as ANO1, in VSMCs, intermediate cells, and pericytes eliminated CaCCs in all vessels studied. Mice lacking vascular TMEM16A had lower systemic blood pressure and a decreased hypertensive response following vasoconstrictor treatment. There was no difference in contractility of medium-sized mesenteric arteries; however, responsiveness of the aorta and small retinal arterioles to the vasoconstriction-inducing drug U46619 was reduced. TMEM16A also was required for peripheral blood vessel contractility, as the response to U46619 was attenuated in isolated perfused hind limbs from mutant mice. Out data suggest that TMEM16A plays a general role in arteriolar and capillary blood flow and is a promising target for the treatment of hypertension.