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Background Electrocardiograph-generated measurements of PR, QRS, and QT intervals are generally thought to be more precise than manual measurements on paper records. However, the performance of different programs has not been well compared. Methods Routinely obtained digital electrocardiograms (ECGs), including over 500 pediatric ECGs, were used to create over 2000 10 s analog ECGs that were replayed through seven commercially available electrocardiographs. The measurements for PR interval, QRS duration, and QT interval made by each program were extracted and compared against each other (using the median of the programs after correction for program bias) and the population mean values. Results Small but significant systematic biases were seen between programs. The smallest and largest variation from the population mean differed by 4.7 ms for PR intervals, 5.8 ms for QRS duration, and 12.4 ms for QT intervals. In pairwise comparison programs showed similar accuracy for most ECGs, with the average absolute errors at the 75th percentile for PR intervals being 4–6 ms from the median, QRS duration 4–8 ms, and QT interval 6–10 ms. However, substantial differences were present in the numbers and extent of large, clinically significant errors (e.g at the 98th percentile), for which programs differed by a factor of two for absolute errors, as well as differences in the mix of overestimations and underestimations. Conclusions When reading digital ECGs, users should be aware that small systematic differences exist between programs and that there may be large clinically important errors in difficult cases.

Ever since the first characterization of peroxisomes, a central theme has been their involvement in cellular hydrogen peroxide (H2O2) metabolism. While the reputation of H2O2 drastically changed from an exclusively toxic molecule to a signaling messenger, the regulatory role of peroxisomes in these signaling events is still largely underappreciated. This is mainly because the number of known protein targets of peroxisome-derived H2O2 is rather limited and testing of specific targets is predominantly based on knowledge previously gathered in related fields of research. To gain a broader and more systematic insight into the role of peroxisomes in redox signaling, an unbiased approach is urgently needed. To accomplish this goal, we have combined a previously developed cell system in which peroxisomal H2O2 production can be modulated with a yeast AP-1-like-based sulfenome mining strategy to inventory protein thiol targets of peroxisome-derived H2O2 in different subcellular compartments. Using this unbiased approach, we were able to identify specific and common targets of peroxisome-derived and exogenous H2O2 in peroxisomes, the cytosol, and mitochondria. We also observed that the sulfenylation kinetics profiles of key targets belonging to different protein families can vary considerably. In addition, we obtained compelling but indirect evidence that peroxisome-derived H2O2 may oxidize at least some of its targets through a redox relay mechanism. In conclusion, given that sulfenic acids function as key intermediates in H2O2 signaling, the findings presented in this study provide initial but critical insight into how peroxisomes may be integrated in the cellular H2O2 signaling network.HighlightsYAP1C-trapping is a robust tool to assess the peroxisomal H2O2-dependent sulfenomeExogenous and peroxisome-derived H2O2 have both common and distinct targetsANXA2, PRDX1, and SKP1 are major targets of peroxisome-derived H2O2The sulfenylation kinetics profiles of key redox-active proteins vary considerablyProduction of H2O2 inside peroxisomes directly impacts the mitochondrial sulfenome

Systemic immune cell dynamics during coronavirus disease 2019 (COVID-19) are extensively documented, but these are less well studied in the (upper) respiratory tract, where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates

Trials to improve oocyte developmental competence under metabolic stress by using antioxidants may start before or after oocyte maturation. In the present conceptual study, we aimed to identify the most efficient timing of antioxidant application in relation to a metabolic insult using a bovine invitro embryo production model. Pathophysiological concentrations of palmitic acid (PA) were used to induce metabolic stress during oocyte maturation or embryo development. Trolox (TR; antioxidant) treatment prior to, during or after the PA insult was tested to evaluate the protective, neutralising and rescuing capacity of TR respectively. Changes in embryo developmental competence, mitochondrial activity, reactive oxygen species (ROS) concentrations, blastocyst cell allocation and apoptosis and cell stress-related gene expression were monitored. The improvement in developmental capacity was most obvious when oocytes were preloaded with TR before the PA insult. This protective effect could be explained by the observed combination of increased mitochondrial activity with reduced ROS production. This resulted in blastocysts with normal cell counts and apoptosis, as well as increased nuclear factor erythroid 2-related factor 2 (NRF2) expression (a marker for redox regulatory processes) and normalised the expression of the mitochondrial transcription factor A (TFAM), a marker of mitochondrial biogenesis. These results indicate that ‘pretreatment’ of oocytes with antioxidants produces embryos that seem to be more resilient to a metabolic stress insult.

Background No direct comparison of current electrocardiogram (ECG) interpretation programs exists. Objective Assess the accuracy of ECG interpretation programs in detecting abnormal rhythms and flagging for priority review records with alterations secondary to acute coronary syndrome (ACS). Methods More than 2,000 digital ECGs from hospitals and databases in Europe, USA, and Australia, were obtained from consecutive adult and pediatric patients and converted to 10 s analog samples that were replayed on seven electrocardiographs and classified by the manufacturers' interpretation programs. We assessed ability to distinguish sinus rhythm from non-sinus rhythm, identify atrial fibrillation/flutter and other abnormal rhythms, and accuracy in flagging results for priority review. If all seven programs' interpretation statements did not agree, cases were reviewed by experienced cardiologists. Results All programs could distinguish well between sinus and non-sinus rhythms and could identify atrial fibrillation/flutter or other abnormal rhythms. However, false-positive rates varied from 2.1% to 5.5% for non-sinus rhythm, from 0.7% to 4.4% for atrial fibrillation/flutter, and from 1.5% to 3.0% for other abnormal rhythms. False-negative rates varied from 12.0% to 7.5%, 9.9% to 2.7%, and 55.9% to 30.5%, respectively. Flagging of ACS varied by a factor of 2.5 between programs. Physicians flagged more ECGs for prompt review, but also showed variance of around a factor of 2. False-negative values differed between programs by a factor of 2 but was high for all (>50%). Agreement between programs and majority reviewer decisions was 46–62%. Conclusions Automatic interpretations of rhythms and ACS differ between programs. Healthcare institutions should not rely on ECG software “critical result” flags alone to decide the ACS workflow.

We have previously demonstrated that the kynurenine pathway (KP), the major biochemical pathway for tryptophan metabolism, is dysregulated in many inflammatory disorders that are often associated with sexual dimorphisms. We aimed to identify a potential functional interaction between the KP and gonadal hormones. We have treated primary human macrophages with progesterone in the presence and absence of inflammatory cytokine interferongamma (interferon-γ) that is known to be a potent inducer of regulating the KP enzyme. We found that progesterone attenuates interferon-γ-induced KP activity, decreases the levels of the excitotoxin quinolinic acid, and increases the neuroprotective kynurenic acid levels. We also showed that progesterone was able to reduce the inflammatory marker neopterin. These results may shed light on the gender disparity in response to inflammation.

Purpose Whole-body computed tomography (WBCT) is the standard diagnostic method for evaluating polytrauma patients. When patients are unable to elevate their arms, the arms are placed along the body, which affects the image quality negatively. Aim of this systematic review is to evaluate the influence of below the shoulder arm positions on image quality of WBCT. Methods Literature in PubMed and Scopus databases was systematically searched. Results of the papers were stratified into 4 categories: arms elevated, 1 arm up 1 arm down, arms ventrally supported, arms along the body. A qualitative analysis was performed on subjective image quality and a quantitative analysis on objective quality (image noise). Results Eight studies were included with 1421 participants. Various studies reported significantly higher quality scores with arms elevated, compared to arms along the body. Significant differences in objective image quality were found between the arms elevated and the arms ventrally on support group. The arms ventrally supported group had a significantly higher image quality than the arms along the body group. A statistically significant difference was found in objective image quality between the 1 arm up 1 arm down and arms along the body group. No preferential below the shoulders position could be identified. Conclusion Positioning the arms alongside the body results in a poor image quality. Placing the arms on a pillow ventrally to the chest improves image quality. Interestingly, asymmetrical arm positioning has potential to improve the image quality for patients that are unable to elevate the arms.

Introduction 12-lead ECG is a standard evaluation for any patient admitted to a clinic but also for population screenings program and athlete periodical evaluation. Definition of a normal vs. abnormal ECG is a hard task and carefully trained physicians are needed to avoid inappropriate second level evaluations driven from a claim for ECG abnormality. Almost all current 1ECG recorders provide automatic diagnosis through built-in automatic-diagnostic computer programs (ACP). However, we have limited data comparing different ACP's in discriminating between normal and abnormal ECGs. Aim To assess the agreement of the main world-wide available automatic diagnostic programs implemented in current ECG recorders in discriminating between “normal” vs. “abnormal” ECGs in a large dataset of real-world ECGs. Methods We assessed seven ECG interpretation programs from seven different manufacturers (GE 12SL, Glasgow, MEANS, Midmark, Mortara VERITAS, Philips DXL and Schiller). We created a large set of representative ECGs converted from previously recorded digital ECGs acquired with equipment that complied with the requirements of International Electrotechnical Commission standard IEC 60601–2-51:2003 and were representative of those in hospital settings. We decided to exclude ECGs from pacemaker carriers. We used a specific device for playing back ECGs to 12-lead ECG recorders in appropriately setting to avoid interferences. Each statement from automatic diagnosis provided by each device was recorded and combined appropriately for the purpose of this analysis, identifying three group of ECGs: abnormal/substantially abnormal (ABN), normal/substantially normal (NRM) and borderline. Results 2155 ECGs of 10s duration were analyzed by the 7 different ACPs: 513 from a pediatric population and 1642 from patients >16 years old consecutively collected mainly in hospital settings. Figure 1 evidences the prevalence of normal to abnormal grading according to each ACP in both groups of ECGs. Focusing in adult group we found that a NRM diagnosis was reported in a range of 129 (7.9%) to 478 (29.1%) among 1642 adult ECGs. On the contrary, ABN statement was reported in a range of 774 (47.1%) to 1271 (77.4%). Notably, agreement between the 7 ACPs was present in 36 ECGs (2.2%) for NRM diagnosis, while the agreement for ABN diagnosis was present in 661 (40.3%) of the ECGs. We performed a sensitivity analysis by repeating the same calculation after taking out one of the device at turn reaching a maximum of 6.5% for NRM and 41.2%% for ABN diagnosis with 6/6 agreement. Figure 1 Conclusions In our large cohort of almost unselected hospital ECGs the agreement on “normal” and “abnormal” among programs of different manufacturers is rather low. This should be carefully considered when using automatic ACP diagnosis as a screening or priority tool for ECG interpretation. Tailor-made review by physicians is still necessary for both clinical and research purposes.

Introduction Atrial fibrillation and flutter (AF/AFl) are the more common sustained arrhythmias in the elderly. ESC guidelines underline the need for large-scale screening strategies, especially to improve primary prevention of thromboembolic complications. However, the current gold-standard for identification of AF/AFl is a 12-lead ECG reviewed by an appropriately trained physician. The availability of automatic discrimination between AF/AFl and sinus rhythm (SR) by automatic- diagnostic computer programs (ACP) implemented in current 12-lead ECG recorders is a possible solution to improve this process. Aim To assess the reliability and agreement of the main world-wide available ACPs implemented in current 12-lead ECG recorders in discriminating between AF/AFl vs. SR in a large dataset of real-world ECGs. Methods We assessed seven ECG interpretation programs from seven different manufacturers (GE 12SL, Glasgow, MEANS, Midmark, Mortara VERITAS, Philips DXL and Schiller). We created a large set of representative ECGs converted from previously recorded digital ECGs acquired with equipment that complied with the requirements of International Electrotechnical Commission standard IEC 60601–2-51:2003 and were representative of those in hospital settings. We excluded ECGs from pacemaker carriers. We used a specific device for playing back ECGs to 12-lead ECG recorders implementing the seven programs. Each statement from automatic diagnosis provided by each device was recorded and combined appropriately for the purpose of this analysis: identification of AF/AFl vs. SR. Gold standard was built by independent re-assessment by three different reviewers. Results We collected 2064 10s 12-lead ECGs with SR (1882) or AF/AFl (182) that were analyzed by seven different ACP. ECG's with other arrhythmias were excluded for this analysis (to increase transferability of the results). All seven programs agreed on SR in 1645 (87.4%) and AF/AFl in 139 cases (76.4%) (Figure 1, panel A). In 280 cases (13.6%), at least one program did not agree with the others. After revision by cardiologists 237 were found to be SR and 43 AF/AFl. Sensitivity for AF/AFl ranged between 90%-97% and false positive diagnosis ranged between 3.4% and 0.4%. Notably, the chance of obtaining at least a wrong diagnosis from one device was 280/2064 (13.6%), with a number of possible false AF/AFl greater than real prevalence of AF/AFl (Figure 1, panel B). Figure 1 Conclusions Despite a general good reliability of each single ACP for AF/AFl recognition the chance of between-device discordance is not negligible and the risk of false positive automatic diagnosis of AF/AFl should be considered when managing real-world patients especially when deciding to start oral anticoagulation.

Blood potassium concentration ([K+]blood) influences the ECG T-wave morphology. T-wave slope-to-amplitude ratio (TS/A) has been shown to be correlated with [K+]blood, suggesting that it is a metric for the repolarizing IKr current, which flows through the hERG ion channels in cardiac cells. In this study we tested whether TS/A can also be used as an alternate ECG-based metric of the amount of hERG block in drug safety trials. We used data from two FDA-sponsored placebo-controlled cross-over studies, in which healthy subjects received a single or multiple doses of hERG-blocking drugs, either alone or in combination with compounds that block late sodium or calcium ion channels. TS/A was compared with other ECG markers for the ability to measure the amount of hERG block independent from other confounding ion channel block of the same drug or a combination of drugs. TS/A appeared to be exclusively sensitive to hERG block and independent of the drug type. It is a more accurate and stable ECG metric for hERG block than Tpeak-Tend, LRD30% and QTc (which is also sensitive to late sodium block). We conclude that TS/A should be added to the set of ECG markers measured in phase I drug safety trials.

Schizophrenia has a clear sexual dimorphism in age of onset and progression. The underlying mechanisms of this dimorphism are not known, but may be found in the interactions of sex hormones with the tryptophan catabolising kynurenine pathway. Schizophrenia is associated with general inflammation and disruption of glutamatergic and dopaminergic signalling. Metabolites of the kynurenine pathway have been shown to be immunomodulatory and have effects on glutamatergic and dopaminergic signalling. This review discusses the currently available literature on sex hormones and their effect on the kynurenine pathway in the context of the glutamatergic, dopaminergic and immunological features of schizophrenia.

Maternal metabolic disorders are associated with elevated concentrations of palmitic acid (PA), which is known to jeopardize bovine oocyte and embryo development and quality. Analyses of PA-exposed bovine oocytes and embryos point toward oxidative stress (OS)-related pathways. Previous research has shown that the detrimental effects of PA exposure during oocyte IVM cannot be alleviated by antioxidant supplementation, e.g. Trolox (TR, water-soluble vitamin E), during IVM or invitro culture (IVC). In contrast, supplementing TR during IVM could protect developing zygotes from PA-induced lipotoxicity by increasing their development into 4-cell embryos and Day 8 blastocysts. In the present study, we examined the effects of TR during IVM or IVC on PA-exposed oocytes and embryos by evaluating OS and mitochondrial membrane potential (MMP) of the produced ≥2-cell Day 2 embryos (Table 1). Bovine cumulus-oocyte complexes (COCs) were matured, fertilised, and cultured in 2 experiments. In Experiment 1, COCs were exposed to pathophysiological follicular PA concentrations (150 µM), and subsequent embryos were cultured under solvent control (ethanol) conditions (PA-SC). The TR treatment was applied during IVM or IVC (100 µM; PATR-SC, PA-TR). In Experiment 2, COCs were matured under SC conditions, and subsequent embryos were exposed to pathophysiological oviductal PA concentrations (230 µM; SC-PA). The TR treatment was applied during IVM or IVC (100 µM; TR-PA, SC-PATR). In each experiment, a SC was included (SC-SC). A total of 126 and 137 Day 2 embryos were stained with JC-1 and CellRox Deep Red in Experiment 1 and Experiment 2 (3 repeats), respectively. The MMP was evaluated as active/total mitochondria and OS as OS/total mitochondria and analysed by one-way ANOVA. Exposure of oocytes and embryos to PA significantly increased OS and MMP in Day 2 embryos compared with controls. Regardless of the moment of PA exposure, TR treatment during IVM increased MMP even more. The increased MMP levels in PA-exposed oocytes and embryos were not influenced by TR treatment during IVC. Regardless of the antioxidant effect of TR, increased embryonic OS levels observed in PA-exposed oocytes and embryos could not be reversed to control levels by TR treatment during IVM or IVC. However, when OS levels were expressed on active mitochondria, we found that TR treatment before the PA insult (TR-PA) generated Day 2 embryos that displayed significantly lower OS/active mitochondria rates compared with SC-PA-treated embryos. Taken together, we conclude that the combination of relatively low OS levels with highly active mitochondria may be a mechanism implicated in the protective effect of TR before the PA insult on embryo developmental competence. Table 1.Effects of TR during IVM or IVC on PA-exposed oocytes and embryos in Experiments 1 and 2 Controls PA exposure TR during IVM TR during IVC SC-SC PA-SC PATR-SC PA-TR Exp. 1 MMP 0.39±0.02a 0.53±0.02b 0.65±0.02c 0.50±0.02b OS 0.55±0.04a 0.68±0.04b 0.78±0.03b 0.59±0.03ab SC-SC SC-PA TR-PA SC-PATR Exp. 2 MMP 0.39±0.02a 0.50±0.02b 0.65±0.02c 0.58±0.02b OS 0.55±0.04a 0.69±0.04b 0.70±0.03b 0.71±0.02b abcDifferent letters in the same row indicate significant differences (P

Background Despite high expectations and numerous initiatives in the area of eHealth, implementation and use of eHealth applications on a national level is no common practice yet. There is no full understanding of patients’ attitude on eHealth yet. Aim of this study is to gain insight into the level of knowledge and experiences with eHealth of people with chronic lung diseases. Method A telephone survey among 400 people with a medical diagnosis of asthma or COPD was conducted. All patients participated in the larger research program National Panel of people with Chronic diseases or Disabilities (NPCD) conducted by NIVEL. Results Eight percent of the asthma and COPD patients knew of the term eHealth. Knowledge of specific eHealth applications (e.g. electronic medical record, electronic consultations, monitoring from a distance) was higher and ranged from 21 to 88%. Most available applications were used by less than 20% of the patients, although figures differ by age and educational level. People who have used applications were in general rather positive about their use. Non-users did not see clear advantages of using eHealth applications. A majority thought that eHealth decreases human contact in health care and will not contribute to a higher quality of care. On the contrary, almost half of the patients considered eHealth as a possibility to take more responsibility in their own care. Asthma and COPD patients were unanimous that the use of eHealth should always be a free choice. Conclusion Although most asthma and COPD patient know of one or more eHealth applications, actual use remains low. Patients who do have experience with the use of eHealth are on the whole positive. However, patients without experience have no clear ideas about the advantages. They should be convinced first, and stressing the possibilities for more personal control might be an important argument to persuade them.

A negative energy balance in metabolically compromised high producing dairy cows has been shown to influence oocyte and embryo quality. However, the possible involved pathways needed more attention to better understand specific deleterious effects. Oocyte maturation is the first process to be scrutinized. Because many possible metabolic factors might directly impact oocyte quality, systematic in vitro approaches were used to investigate the effects of oocyte maturation under elevated NEFA concentrations. Blastocysts originating from NEFA-exposed oocytes showed a lower cell number, an increased apoptotic cell index, signs of glucose intolerance, sensitive to oxidative stress and mitochondrial dysfunction. Defining these embryos' transcriptome and epigenome signatures revealed changes in DNA methylation patterns. Long-term exposure of developing murine follicles to elevated NEFA concentrations showed to impair oocyte developmental competence even more. While little is known on how the oviductal micro-environment can change as a consequence of a negative energy balance, a validated in vitro bovine oviduct model offered some valuable insights on how NEFAs disturb oviductal cell physiology. NEFA exposure reduces cell proliferation, cell migration, sperm binding capacity and monolayer integrity. In addition, oviductal cells seem to play an active role in regulating luminal NEFA-concentrations through increased permeability, intracellular lipid accumulation and fatty acid metabolism. This might favour early embryo development. The establishment of a successful pregnancy largely depends on the ability of the embryo to interact with a properly prepared endometrium. Because suboptimal physiological conditions influence oocyte maturation and embryo development to the extent that epigenetic consequences are unavoidable, the question arises if these changes hamper embryo implantation and subsequent development. Gene expression studies on epithelial endometrial cells brought in contact with in vitro embryos cultured for 4 days under suboptimal conditions reveal that the embryo-endometrial signaling is affected. Transfer of bovine embryos derived from compromised oocytes showed disturbed embryo development following recovery at day 14 with a negative impact on IFNt secretion and therefore suggesting carry-over effects from suboptimal culture conditions. The current paper will document the most important recent findings and comment on extrapolation possibilities from in vitro studies to field conditions in daily dairy practice. In addition, the possibility of remediating approaches will be discussed to see how this knowledge might generate insights on possible alleviating strategies.

Background Worldwide obesity has nearly doubled since 1980 and is a leading risk for global deaths, profoundly affecting morbidity, mortality, health-care costs, and professional and personal quality of life. Treatment of obesity and its consequences include lifestyle intervention, pharmacotherapy, and bariatric surgery. Polyglucosamines have been proposed as an alternative strategy for treating obesity, by reducing the amount of absorbed fat through interaction with dietary fat through various mechanisms. The objective of this study is to investigate the influence of polyglucosamine on the bioavailability of the model compound [9-14C]-oleic acid in female Göttingen minipigs. Method The study consisted of two treatment groups, each consisting of six adult female Göttingen minipigs with a catheterized vena jugularis to enable frequent blood sampling. One group served as the untreated group (control) and the other group was pre-treated with 2 tablets of 500 mg formoline L112. After 30 min, all animals were dosed orally with [9-14C]-oleic acid. Excreta and blood samples were collected for analysis of radioactivity from 48 h pre-dose up to 144 h post-dosing. At sacrifice, the liver and contents of the gastrointestinal tract were collected for radioanalysis. Results Upon treatment with polyglucosamine (formoline L112), the Tmax of [14C]-oleic acid in plasma was shifted from 4 to 16 h, and the Cmax decreased significantly from 14.1 μg/g to 3.3 μg/g. In addition, upon treatment with polyglucosamine the internal exposure to [14C]-oleic acid as reflected by the area under the curve during the 0–12 h post-dose time interval (AUC0-12h), is significantly decreased to 32.9 % of the plasma value of [14C]-oleic acid in untreated animals. Even up to 24 h post-dose, the AUC0-24h is significantly decreased to 50.7 % of the plasma value in untreated animals and this significant effect is prolonged up to 60 h post-dose. Conclusions This study shows that treatment with polyglucosamine (formoline L112) reduces (as judged by Cmax & AUC) and delays (as judged by Tmax) fat absorption from the gastrointestinal tract into the systemic circulation and limits peak exposure to free fatty acids which may contribute to a more beneficial condition in overweight humans.

Abstract Maternal metabolic pressure due to a cows negative energy balance (NEB) has a negative effect on oocyte quality as a result of increased oxidative stress. In this study, we hypothesized that a NEB status may negatively affect the availability of β-carotene (bC, an antioxidant) in the micro-environment of the oocyte or follicular fluid (FF) and that daily bC supplementation can increase bC availability. We aimed to (1) determine the effect of a nutritionally induced NEB on bC concentrations in serum and FF as well as on the presence of bC metabolites, oxidative stress levels, and follicular growth in a nonlactating dairy cow model, and (2) investigate how this effect could be altered by dietary bC supplementation. Six multiparous nonlactating Holstein Friesian cows were subjected to 4 consecutive dietary treatments, 28 d each: (1) 1.2 × maintenance (M) or positive energy balance (PEB) without bC supplement (PEB-bC), (2) 1.2 × M with daily supplement of 2,000 mg of bC comparable to the level of bC intake at grazing (PEB+bC), (3) 0.6 × M with 2,000 mg of bC (NEB+bC), and (4) 0.6 × M (NEB-bC). At the end of each treatment, estrous cycles were synchronized and blood and FF of the largest follicle were sampled and analyzed for bC, retinol, α-tocopherol, free fatty acids, estradiol, and progesterone. Serum cholesterol, triglycerides, urea, insulin growth factor 1, growth hormone, total antioxidant status (TAS), and red blood cell glutathione (GSH) concentrations were determined as well. All cows lost body weight during both energy restriction periods and showed increased serum free fatty acid concentrations, illustrating a NEB. A dietary induced NEB reduced FF bC, but not plasma bC or plasma and FF retinol concentrations. However, bC and retinol concentrations drastically increased in both fluid compartments after bC supplementation. Follicular diameter was increased in supplemented PEB cows. Energy restriction reduced the TAS and red blood cell GSH, whereas daily bC supplementation could restore GSH concentrations, but not the TAS, to levels present in healthy PEB cows. In conclusion, daily bC supplementation can substantially improve bC and retinol availability in the oocytes micro-environment, irrespective of the energy balance, which may affect follicular development and oocyte quality in the presence of maternal metabolic stress. This knowledge can be of importance to optimize nutritional strategies in the dairy industry to feed for optimal oocyte quality and fertility.

Aims To develop a national system of quality indicators for community pharmacy care, reported by community pharmacies. Methods After preliminary validation, an online consensus study was conducted. Pharmacy practice experts (round 1) and practising pharmacists (round 2) were approached. Face-validity scores for risk of harm and quality of care were obtained, as well as data on feasibility and clarity. To field test the data collection a random sample of 30 community pharmacies reported on the indicators, and were visited by a healthcare inspector to discuss practical and interpretation issues. Results After preliminary validation of 159 topics, 53 indicators were rated in round 1 by 14 of the 16 experts who were approached. The resulting 48 indicators were rated by 76 pharmacists of the 150 pharmacists who were approached (response 50%). Of the 48 indicators in the second round, 33 (69%) were rated face valid (median relevance score ≥7) for risk of harm to patients, while 43 (90%) were rated face valid for quality of care. In the field test the participating pharmacies reported on the resulting set of 44 indicators. This resulted in an adjusted set of 42 indicators. The set contains indicators on patient counselling (6), clinical risk management (10), compounding (7), dispensing (3), monitoring of medication use (11) and quality management (5). Conclusions A set of 42 quality indicators was developed for community pharmacy care. It is expected that this will have a positive impact on quality and safety of community pharmacy care in the Netherlands.

This study aimed to investigate whether reversal of rocuronium-induced neuromuscular blockade with sugammadex reduced the incidence of residual blockade and facilitated operating room discharge readiness.Adult patients undergoing abdominal surgery received rocuronium, followed by randomized allocation to sugammadex (2 or 4 mg kg(-1)) or usual care (neostigmine/glycopyrrolate, dosing per usual care practice) for reversal of neuromuscular blockade. Timing of reversal agent administration was based on the providers' clinical judgement. Primary endpoint was the presence of residual neuromuscular blockade at PACU admission, defined as a train-of-four (TOF) ratio0.9, using TOF-Watch® SX. Key secondary endpoint was time between reversal agent administration and operating room discharge-readiness; analysed with analysis of covariance.Of 154 patients randomized, 150 had a TOF value measured at PACU entry. Zero out of 74 sugammadex patients and 33 out of 76 (43.4%) usual care patients had TOF-Watch SX-assessed residual neuromuscular blockade at PACU admission (odds ratio 0.0, 95% CI [0-0.06], P0.0001). Of these 33 usual care patients, 2 also had clinical evidence of partial paralysis. Time between reversal agent administration and operating room discharge-readiness was shorter for sugammadex vs usual care (14.7 vs. 18.6 min respectively; P=0.02).After abdominal surgery, sugammadex reversal eliminated residual neuromuscular blockade in the PACU, and shortened the time from start of study medication administration to the time the patient was ready for discharge from the operating room.Clinicaltrials.gov:NCT01479764.

Systemic exposure was measured in humans after hair dyeing with oxidative hair dyes containing 2.0% (A) or 1.0% (B) [(14)C]-p-phenylenediamine (PPD). Hair was dyed, rinsed, dried, clipped and shaved; blood and urine samples were collected for 48 hours after application. [(14)C] was measured in all materials, rinsing water, hair, plasma, urine and skin strips. Plasma and urine were also analysed by HLPC/MS/MS for PPD and its metabolites (B). Total mean recovery of radioactivity was 94.30% (A) or 96.21% (B). Mean plasma Cmax values were 132.6 or 97.4 ng [(14)C]-PPDeq/mL, mean AUC(0-∞) values 1415 or 966 ng [(14)C]-PPDeq/mL*hr in studies A or B, respectively. Urinary excretion of [(14)C] mainly occurred within 24 hrs after hair colouring with a total excretion of 0.72 or 0.88% of applied radioactivity in studies A or B, respectively. Only N,N'-diacetylated-PPD was detected in plasma and the urine. A TK-based human safety assessment estimated margins of safety of 23.3- or 65-fold relative to respective plasma AUC or Cmax values in rats at the NOAEL of a toxicity study. Overall, hair dyes containing PPD are unlikely to pose a health risk since they are used intermittently and systemic exposure is limited to the detoxified metabolite N,N'-diacetyl-PPD.

Occurrence of problems with, refusals of orders and contemplated refusals of orders for risky procedures by nurses in Dutch hospitals and views on the safety of performance was studied using postal questionnaires (600 physicians and 3200 nurses, response 60-71 %). Of the respondents, 11-30% experienced problems with and (contemplated) refusals of orders for risky procedures in the previous 12 months. Gynaecologists and internists most frequently mentioned problems concerning the practical performance of the procedure (44% and 30%, respectively). The reason for a problem or a contemplated refusal most frequently given by nurses was that they disagreed with the medication policy (34% and 35%, respectively). The reason for a refusal most frequently given by the gynaecologists, internists and nurses was that the nurses themselves were of the opinion that they did not have the necessary authorisation (95%, 67%, and 62%, respectively). With regard to certain procedures, the views of professionals are more strict than the current legal regulations. (c) 2005 Elsevier Ltd. All rights reserved

(Abstracted from Br J Anaesth, 115:743–751, 2015)This study sought to ascertain if reversal of rocuronium-induced neuromuscular blockade with sugammadex reduced the incidence of residual blockade, thereby facilitating operating room discharge readiness.

Summary Background IL-16 has been described as a natural soluble CD4-ligand with immunosuppressive effects in vitro. However, little is known about the effect of IL-16 on immune responses in vivo. Objective In the present study, we examined the effect of IL-16 administration in a murine model of allergic asthma. Next, we determined whether these effects were mediated by modulation of CD4+ T lymphocytes. Methods and results Intraperitoneal administration of IL-16 completely inhibits antigen-induced airway hyper-responsiveness and largely decreases the number of eosinophils in bronchoalveolar lavage fluid (> 90%) and airway tissue of ovalbumin-sensitized and challenged mice. Firstly, it appears that thoracic lymph node cells isolated from in vivo IL-16-treated ovalbumin-challenged animals produce less IL-4 (77%) and IL-5 (85%) upon antigenic re-stimulation, when compared to vehicle-treated mice. Secondly, pre-incubation of lymphocytes with IL-16 in vitro reduces antigen-induced proliferation (55%) and Th2-type cytokine production (IL-4; 56%, IL-5; 77%). Thirdly, the presence of IL-16 during priming cultures of TCR transgenic T cells (DO11.10), reduces IL-4 (33%) and IL-5 (35%), but not IL-10 and IFNγ levels upon re-stimulation. Conclusion It can be concluded that IL-16 has potent immunosuppressive effects on a Th2-dominated allergic airway response.

Background To establish long-term safety, follow-up data on pregnancy, birth and neonatal outcome were collected during clinical development trials with ganirelix (Orgalutran) in women undergoing controlled ovarian stimulation for conventional IVF or ICSI. Methods Results of an analysis of the pooled data of all follow-up data of the phase 2 and 3 programme for the development of ganirelix are presented. Obstetrical data on 340 ongoing pregnancies ( vertical line16 gestational weeks) after ganirelix treatment and 134 pregnancies after GnRH agonist treatment in a long protocol are shown. Furthermore, the neonatal outcome of 432 children [258 (75.9%) singletons, 72 (21.2%) twins and 10 (2.9%) triplets] born in the ganirelix group is presented and compared with 184 children [91 (67.9%) singletons, 36 (26.9%) twins and seven (5.2%) triplets] in the agonist group. Results There were no differences between the two groups in pregnancy loss after 16 weeks gestation. Incidence and nature of complications during pregnancy and delivery did not differ between the two groups. The overall mean gestational age was approximately 38.0 weeks, ranging from an average of 39 weeks for singletons to 34 weeks for triplets. No major differences were observed in neonatal characteristics of infants in the ganirelix and agonist groups, who had an overall mean birth weight of on average 3200 g for singletons, 2300 g for twins and 1800-1900 g for triplets. Congenital malformations were observed in 32 of 424 (7.5%) fetuses vertical line26 gestational weeks in the ganirelix group and in 10 of 181 (5.5%) in the agonist group. When applying a broad definition of major malformation (a major congenital malformation is a condition that causes functional impairment or requires surgical intervention) the rates were 4.5 versus 3.3 (odds ratio 1.37, 95% confidence interval 0.54-3.48) for the ganirelix and agonist group respectively. Conclusions Reviewing the presented data and the literature on obstetric and neonatal outcome after conventional IVF or ICSI, we conclude that a controlled ovarian stimulation protocol including the novel GnRH antagonist ganirelix has been shown to be safe for pregnant women and their newborn babies.

Lipolytic metabolic conditions are traditionally associated with elevated non-esterified fatty acid (NEFA) concentrations, but may also be accompanied by hyperglycaemia in obesity or by hypoglycaemia during a negative energy balance status. Elevated NEFA concentrations disrupt oocyte and embryo development and quality, but little is known about whether the effects of lipolytic conditions on oocyte developmental competence are modulated by glucose availability. To answer this, bovine cumulus–oocyte complexes (COCs) were matured under different conditions: physiological NEFA (72 µM) and normal glucose (5.5 mM), pathophysiologically high NEFA (420 µM) and normal glucose, high NEFA and high glucose (9.9 mM), high NEFA and low glucose (2.8 mM). Developmental potential, cumulus expansion and metabolism of COCs exposed to high NEFA and low glucose were affected to a greater extent compared with COCs matured under high NEFA and high glucose conditions. High NEFA and high glucose conditions caused a moderate increase in oocyte reactive oxygen species compared with their high NEFA and low glucose or control counterparts. Blastocyst metabolism and the transcriptome of metabolic and oxidative stress-related genes were not affected. However, both lipolytic conditions associated with hyper- or hypoglycaemia led to surviving embryos of reduced quality with regards to apoptosis and blastomere allocation.

European tradition on vegetation classification provides an extraordinary legacy for understanding biodiversity. However, this classification lacks explicit data on vegetation attributes, especially if we extend national or regional concepts to a continental perspective. An additional effort for evaluating and characterizing European vegetation types is therefore needed, and the data contained in vegetation databases are probably the main tool for these purposes. The Braun-Blanquet project is an initiative of the European Vegetation Survey for characterizing vegetation alliances across Europe. By analyzing more than 500, 000 vegetation plots from 22 European countries, we developed a framework consisting of: (1) evaluating the consistency and robustness of alliances using the information provided by vegetation plot databases, (2) calibrating assignment rules for classifying, at least partially, the plots not assigned to alliances and (3) characterizing vegetation types by providing lists of diagnostic species and major distributional patterns. The Braun-Blanquet project represents the first attempt for extrapolating European vegetation information into a comprehensive definition of vegetation types. Furthermore, the outputs of the project are expected to improve biodiversity assessment and the conservation management of natural habitats. As a study case, we illustrate how our framework can be used to characterize different forest types across Europe.

Integrated Pest Management in the Netherlands was developed in the 1980s and 1990s of the last century as a part of the wider concept of Integrated Farming. The potential proved to be very high in comparative farming systems studies proving that agrochemical inputs could be strongly reduced, notably pesticides. The Dutch government subsequently strongly advocated and supported the further development and implementation of “Integrated Farming” and “Integrated Pest Management” in practice. In the 1990s and 2000s, pilot farm networks were the cornerstone in the government strategy. The adoption of methods and techniques in practice however, progressed only slowly and unevenly. The support of the stakeholders in the agricultural community appeared to be essential to create sufficient momentum and ambition among farmers and contractors. The government’s covenant on sustainable crop protection united in 2003 the stakeholders in a roundtable approach. At the same time, the national network project, Farming with Future,adopted a stakeholder management approach to mobilize the support and contribution of stakeholders in the development and subsequent introduction of Integrated Pest Management in practice. The results are promising.

1. Since both histamine and 5-hydroxytryptamine (5-HT) can be released by murine mast cells, we investigated the possible role of these autacoids on airway hyperresponsiveness (AHR), eosinophil infiltration and serum-IgE levels in a murine model of allergic asthma. 2. Ovalbumin-sensitized mice were exposed to either ovalbumin (2 mg ml(-1)) or saline aerosols on 8 consecutive days. Starting one day before the challenge, animals were injected i.p. twice a day with a 5-HT-type 1 (5-HT1) or type 2 (5-HT2) receptor antagonist (methiotepine, 1.25 or 2.0 mg kg(-1) and ketanserin, 12 mg kg(-1), respectively) or a histamine-type 1 (H1) or type 2 (H2) receptor antagonist (mepyramine, 12 or 20 mg kg(-1) and cimetidine, 10 or 25 mg kg(-1), respectively). Furthermore, animals were injected with a combination of cimetidine and ketanserin or with an alpha-adrenoceptor antagonist (phentolamine, 5 mg kg(-1)). 3. In vehicle-treated ovalbumin-challenged animals airway responsiveness to intravenous injections of methacholine in vivo was significantly (9 fold increase, P

Experiments were designed to investigate the role of IL-16 in a mouse model of allergic asthma. OVA-sensitized mice were repeatedly exposed to OVA or saline aerosols. Bronchoalveolar lavage fluid (BALF) was collected after the last aerosol, and the presence of IL-16 was evaluated using a migration assay with human lymphocytes. Migration of lymphocytes was significantly increased in the presence of cell-free BALF from OVA-challenged mice compared with BALF from saline-challenged controls. This response was significantly inhibited after addition of antibodies to IL-16, demonstrating the presence of IL-16 in BALF of OVA-challenged animals. Immunohistochemistry was performed and revealed IL-16 immunoreactivity particularly in airway epithelial cells but also in cellular infiltrates in OVA-challenged mice. IL-16 immunoreactivity was absent in nonsensitized animals; however, some reactivity was detected in epithelial cells of sensitized but saline-challenged mice, suggesting that sensitization induced IL-16 expression in airway epithelium. Treatment of mice with antibodies to IL-16 during the challenge period significantly suppressed up-regulation of OVA-specific IgE in OVA-challenged animals. Furthermore, antibodies to IL-16 significantly inhibited the development of airway hyper-responsiveness after repeated OVA inhalations, whereas the number of eosinophils in bronchoalveolar lavage or airway tissue was not affected. In conclusion, IL-16 immunoreactivity is present in the airways after sensitization. After repeated OVA inhalation, IL-16 immunoreactivity is markedly increased and IL-16 is detectable in BALF. Furthermore, IL-16 plays an important role in airway hyper-responsiveness and up-regulation of IgE but is not important for eosinophil accumulation in a mouse model of allergic asthma.

Contents In many countries, fat supplementation in the diet has become common in the dairy industry. There are several ideas as to how dietary fat could influence reproductive performance. Saturated fatty acids, such as palm oil, can increase milk yield but may aggravate negative energy balance and thus may impair fertility when fed during the first week post-partum. However, priming the lipid oxidation in the liver by feeding saturated fats during the dry period has recently been shown to be a potentially promising strategy to mitigate fat mobilization and liver accumulation post-partum. Furthermore, polyunsaturated fats (omega-3 fatty acids and conjugated linoleic acids) are fed to reduce the de novo' fat synthesis in the udder and thus the milk fat content, which may be of modest benefit for overall energy balance. Furthermore, omega-6 and omega-3 polyunsaturated fatty acids are reported to alter follicular growth, steroid synthesis and prostaglandin metabolism in the ovary and endometrium, respectively. Omega-6 fatty acids are believed to have pro-inflammatory and thus PGF2-stimulating properties rendering them extra value as nutraceutical' early post-partum, while omega-3 fatty acids can weaken this inflammatory potency, leading to a higher chance of survival of the embryo when supplemented during the periconceptual period. Unfortunately, research results rarely provide a consensus in this perspective. The consequences of these fat-feeding strategies on oocyte and embryo quality remain an intriguing issue for debate. Fat feeding may alter the microenvironment of the growing and maturing oocyte of the early and older embryo and thus may affect reproductive outcome. We recently reported that dietary-induced hyperlipidaemic conditions can be harmful for embryo development and metabolism. However, to date, research results remain somewhat conflicting most probably due to differences in fat sources used, in diet and duration of supplementation and in experimental set-up in general.

To investigate the mechanisms underlying airway hyperresponsiveness a murine model was developed with several important characteristics of human allergic asthma. Mice were intraperitoneally sensitized with ovalbumin and after 4 weeks challenge via an ovalbumin aerosol. After aerosol, lung function was evaluated with a non-invasive forced oscillation technique. The amount of mucosal exudation into the airway lumen and the presence of mast cell degranulation was determined. Tracheal responsiveness was measured at several time points after challenge. At these time points also bronchoalveolar lavage and histology were performed. Sensitization induced high antigen-specific IgE levels in serum. Inhalation of ovalbumin in sensitized mice induced an immediate but no late bronchoconstrictive response. During this immediate phase, respiratory resistance was increased (54%). Within the first hour after ovalbumin inhalation increased mucosal exudation and mast cell degranulation were observed. At 12 and 24 h after ovalbumin challenge, mice showed tracheal hyperresponsiveness (29% and 34%, respectively). However, no apparent inflammation was found in the lungs or bronchoalveolar lavage. From these results it can be concluded that hyperresponsiveness can develop via mechanisms independent of an inflammatory infiltrate. Since mast cell degranulation occurred after ovalbumin exposure, we hypothesize that mast cells are involved in the induction of airway hyperresponsiveness in this model.

Differences in autonomic nerve activity between athletes and controls during supine rest and standing were investigated by recording the cardiac rhythm in 18 professional cyclists and 11 controls. We computed four indexes of autonomic control: the standard deviation (SD) of the interbeat intervals, the coefficient of variance (CV) of the interbeat intervals, the percentage of successive intervals differing by more than 50 ms (pNN50), and the fraction low-frequency (0.07–0.14 Hz) spectral power (LF), and we also measured the mean interbeat interval (MI). Significant differences (Student's t-test, P < 0.005) between the athletes and the controls in the supine position were found for pNN50 [mean 52.6 (SEM 2.5) vs 37.1 (SEM 3.4)%], LF [mean 32.2 (SEM 1.6) vs 40.7 (SEM 2.1) normalized units], and MI [mean 1241 (SEM 20) vs 1021 (SEM 25) ms]. A significant difference between the athletes and the controls in the standing position was found for MI [mean 888 (SEM 13) vs 801 (SEM 23) ms]. These results would suggest that there is a parasympathetic predominance in athletes in the supine, but not in the standing position. The finding that pNN50 and LF, but not SD and CV, differed between the athletes and the controls, would seem to demonstrate that the differences in autonomic control between the athletes and the controls are reflected in the quality (balance between slow and fast heart rate fluctuations) rather than in the quantity of heart rate variability.

A 51-year-old woman suffering an epileptic seizure came to the emergency unit. A ct scan showed a mass lesion in the right frontal lobe. The psychiatric examination indicated a frontal syndrome with severe cognitive impairment. A stereotactical biopsy was carried out. Histopathology produced an unusual diagnosis, namely an intracerebral amyloidoma. By reviewing the literature on intracerebral amyloidoma we were able to compare the psychiatric symptoms of published cases with those of this case.

Elevated serum NEFA concentrations, typically present in negative energy balance (NEB) cows, are known to compromise bovine in vitro oocyte and embryo quality and developmental competence. These observations seem to be associated with oxidative stress. Therefore, antioxidant supplementation such as β-carotene (bC) can be a promising solution to ameliorate embryo quality and survival. However, little is known about the possible neutralizing effect of bC on NEB-compromised embryos. Accordingly, we hypothesise that bC can overcome the potential negative effects of metabolic conditions associated with NEB on embryo development. To investigate this we aimed to evaluate the effect of serum from bC-supplemented positive energy balance (PEB) or NEB cows on embryonic developmental competence. A total of 5 nonlactating Holstein-Friesian cows were subjected to 4 consecutive dietary treatments, 28 days each: 1) 1.2 × maintenance (M) (= PEB–bC), 2) 1.2 × M with daily 2000 mg of bC (Rovimix 10% bC, DSM) (= PEB+bC), 3) 0.6 × M + bC (= NEB+bC), and 4) after a 6 week acclimatization period 0.6 × M (= NEB–bC). Serum was collected 72 h after ovulation, pooled per dietary treatment, and heat inactivated during 30 min at 56°C. In total 1404 bovine slaughterhouse grade 1 cumulus-oocyte complexes were serum-free matured (4 repeats), routinely fertilized, and cultivated for 6.7 days with the addition of 10% serum of the 4 different treatments. Cleavage (48 h post-insemination), blastocyst rates (7.7 days post-insemination), and the rates of blastocysts from cleaved zygotes were calculated. Developmental competence data were compared between the 4 treatments using a binary logistic regression model taking replicate, treatment, and the interaction of both factors into account. The NEFA and bC data were analysed using a paired-samples t-test (IBM SPSS Statistics 20). Bonferroni correction was applied. Serum NEFA concentrations were significantly elevated in NEB compared to PEB (0.36 ± 0.18 mM v. 0.21 ± 0.11 mM; P = 0.011). β-Carotene supplementation drastically increased bC concentrations in serum in NEB (0.44 ± 0.18 μg mL–1 v. 3.28 ± 0.78 μg mL–1; P

The availability on the market of advanced Personal Digital Assistants (PDA) and the widesprcad use of reliable Wireless LANs pennit the development of new solutions, which allow the improvement of medical procedures and the reduction of emergency response time. In ihis study, we developed a Windows CE based application, which can display real-time ECG traces, clinical data and alarms of monitored patients on a WiFienabled FDA device. The purpose of our study was to check whether this system could improve the standard medical procedures and decrease the emergency response time, through a usability test in ICU. The system was judged useful by nursing and medical stafi The clinical test confirmed the feasibility and usability of the system.

The evidence regarding the co-morbidity of chronic hepatitis C, psychiatric illness and intravenous drug abuse is reviewed from the literature. Also the occurrence and the treatment of psychiatric side effects during treatment with interferon in patients with a history of drug abuse are reviewed. There is insufficient evidence for a specific hepatitis C induced depression or fatigue, but a direct link between hepatitis C and cerebral dysfunction is not excluded. Immune system activation rather than drug use may explain cerebral symptoms. In HCV positive substance users anxiety and depression are more prevalent than in HCV negative substance users. During treatment with regular or pegylated (PEG) interferon depression is a frequent side effect (ca 30%) and occurs independently from pre-existing psychiatric disorders or drug abuse. A history of drug abuse per se does not increase the risk of depression as a side effect of interferon treatment. It is extremely important to monitor symptoms of depression in the early weeks of treatment and to start antidepressant treatment as early as possible. Antidepressants should be continued throughout the interferon treatment period. There are insufficient data to assess these situations in which preventive antidepressant treatment should be started before interferon treatment. Clinical judgement can, however, lead to preventive antidepressant treatment, even at subclinical levels of depression. A cut off score of10 on the Beck Depression Inventory before interferon treatment is associated with a higher risk of depression during treatment. Both selective serotonin reuptake inhibitors and other classes of antidepressants can be used.

Over het belang van psychische factoren en de rol van de psychiater in de behandeling van patienten met chronische pijn wordt al lang geschreven.1,2,3,4 Pridmore et al. poneerden recent vier vragen aan de hand waarvan ze de bijdrage van de psychiatrische discipline in de behandeling van patienten met chronische pijn verdedigen.5

Het Ziekenhuis Oost-Limburg (ZOL) is in 1996 gestart met een Pijncentrum, waarvan de staf oorspronkelijk bestond uit een anesthesioloog-pijntherapeut, een secretaresse en een verpleegkundige. Al snel is de equipe uitgebreid met een kinesitherapeute, een psychiater en een psycholoog. De afgelopen jaren is het pijncentrum, mede door een nieuwe overheidsfinanciering, gestaag blijven groeien tot de huidige omvang van vijf verpleegkundigen, twee kinesitherapeuten, twee psychologen, drie verpleegkundig pijnspecialisten, een psychiater, een revalidatiearts, drie anesthesiologen-pijntherapeuten en drie secretariaatsmedewerkers.

The Individual Health Care Professions Act came into force in The Netherlands in 1997, introducing a mixed system for the regulation of the practice of medicine. One of its components, the reserved procedures regulations, was studied in hospitals to Cain insight into the knowledge, experiences and views of physicians and nurses with regard to these regulations. Questionnaires were sent to representative samples of 250 gynaecologists, 350 internists, and 3200 nurses, response rates were 65. 60 and 71%. respectively. Almost all respondents were aware that physicians are authorised to perform reserved procedures on their own initiative (93-99%), and 48-63% knew that nurses are not authorised to do this. A substantial percentage of the nurses performed reserved procedures on their own initiative (17-53%). A majority of gynaecologists and internists presumed that the hospital had ensured the proficiency of the nurses to perform reserved procedures (58% resp. 65%), while 82% of the nurses determined their own proficiency for each procedure. Most respondents felt that the reserved procedures regulations offer adequate protection for patients (58-72%). Although recommendations are made for improvement, the functioning of the reserved procedures regulations in hospitals is considered to be moderately positive. (C) 2003 Elsevier Ireland Ltd. All rights reserved