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Background: The second victim phenomenon refers to the emotional trauma healthcare professionals experience following adverse events (AEs) in patient care, which can compromise their ability to provide safe care. This issue has significant implications for patient safety, with AEs leading to substantial human and economic costs., Analysis: Current evidence indicates that AEs often result from systemic failures, profoundly affecting healthcare workers. While patient safety initiatives are in place, the psychological impact on healthcare professionals remains inadequately addressed. The European Researchers' Network Working on Second Victims (ERNST) emphasizes the need to support these professionals through peer support programs, systemic changes, and a shift toward a just culture in healthcare settings., Policy Options: Key options include implementing peer support programs, revising the legal framework to decriminalize honest errors, and promoting just culture principles. These initiatives aim to mitigate the second victim phenomenon, enhance patient safety, and reduce healthcare costs., Conclusion: Addressing the second victim phenomenon is essential for ensuring patient safety. By implementing supportive policies and fostering a just culture, healthcare systems can better manage the repercussions of AEs and support the wellbeing of healthcare professionals., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Mira, Carillo, Tella, Vanhaecht, Panella, Seys, Ungureanu, Sousa, Buttigieg, Vella-Bonanno, Popovici, Srulovici, Guerra-Paiva, Knezevic, Lorenzo, Lachman, Ushiro, Scott, Wu and Strametz.)

Background: Health care workers (HCWs) are often impacted by distressing situations during patient care and can experience the second victim phenomenon (SVP). Addressing an adequate response, training, and increasing awareness of the SVP can increase HCWs' well-being and ultimately improve the quality of care and patient safety., Objective: This study aims to describe and evaluate a multimodal training organized by the European Researchers' Network Working on Second Victims to increase knowledge and overall awareness of SVP and second victim programs., Methods: We implemented a multimodal training program, following an iterative approach based on a continuous quality improvement process, to enhance the methodology and materials of the training program over the duration of 2 years. We conducted web-based surveys and group interviews to evaluate the scope and design of the training, self-directed learning materials, and face-to-face activities., Results: Out of 42 accepted candidates, 38 (90%) participants attended the 2 editions of the Training School program. In the second edition, the level of participants' satisfaction increased, particularly when adjusting the allocated time for the case studies' discussion (P<.001). After the multimodal training, participants stated that they had a better awareness and understanding of the SVP, support interventions, and its impact on health care. The main strengths of this Training School were the interdisciplinary approach as well as the contact with multiple cultures, the diversity of learning materials, and the commitment of the trainers and organizing team., Conclusions: This multimodal training is suitable for different stakeholders of the health care community, including HCWs, clinical managers, patient safety and quality-of-care teams, academicians, researchers, and postgraduate students, regardless of their prior experience with SVP. Furthermore, this study represents a pioneering effort in elucidating the materials and methodology essential for extending this training approach to similar contexts., (©Sofia Guerra-Paiva, José Joaquín Mira, Reinhard Strametz, Joana Fernandes, Victoria Klemm, Andrea Madarasova Geckova, Bojana Knezevic, Eva Potura, Sandra Buttigieg, Irene Carrillo, Paulo Sousa. Originally published in JMIR Formative Research (https://formative.jmir.org), 30.08.2024.)

Competing Interests: Declaration of interests B.K. and D.Y. have a >5% ownership stake in Kaleidoscope Technologies, Inc. The remaining author has no interests to declare.

COVID-19 has affected all aspects of human life so far. From the outset of the pandemic, preventing the spread of COVID-19 through the observance of health protocols, especially the use of sanitizers and disinfectants was given more attention. Despite the effectiveness of disinfection chemicals in controlling and preventing COVID-19, there are critical concerns about their adverse effects on human health. This study aims to assess the health effects of sanitizers and disinfectants on a global scale. A total of 91,056 participants from 154 countries participated in this cross-sectional study. Information on the use of sanitizers and disinfectants and health was collected using an electronic questionnaire, which was translated into 26 languages via web-based platforms. The findings of this study suggest that detergents, alcohol-based substances, and chlorinated compounds emerged as the most prevalent chemical agents compared to other sanitizers and disinfectants examined. Most frequently reported health issues include skin effects and respiratory effects. The Chi-square test showed a significant association between chlorinated compounds (sodium hypochlorite and per-chlorine) with all possible health effects under investigation (p-value <0.001). Examination of risk factors based on multivariate logistic regression analysis showed that alcohols and alcohols-based materials were associated with skin effects (OR, 1.98; 95%CI, 1.87-2.09), per-chlorine was associated with eye effects (OR, 1.83; 95%CI, 1.74-1.93), and highly likely with itching and throat irritation (OR, 2.00; 95%CI, 1.90-2.11). Furthermore, formaldehyde was associated with a higher prevalence of neurological effects (OR, 2.17; 95%CI, 1.92-2.44). Furthermore, formaldehyde was associated with a higher prevalence of neurological effects (OR, 2.17; 95%CI, 1.92-2.44). The use of sodium hypochlorite and per-chlorine also had a high chance of having respiratory effects. The findings of the current study suggest that health authorities need to implement more awareness programs about the side effects of using sanitizers and disinfectants during viral epidemics especially when they are used or overused., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The COVID-19 pandemic led to the implementation of interventions to provide emotional and psychological support to healthcare workers in many countries. This ecological study aims to describe the strategies implemented in different countries to support healthcare professionals during the outbreak. Data were collected through an online survey about the measures to address the impact of the pandemic on the mental health of healthcare workers. Healthcare professionals, researchers, and academics were invited to respond to the survey. Fifty-six professionals from 35 countries contributed data to this study. Ten countries (28.6%) reported that they did not launch any national interventions. Both developed and developing countries launched similar initiatives. There was no relationship between the existence of any type of initiative in a country with the incidence, lethality, and mortality rates of the country due to COVID-19, and per capita income in 2020. The 24 h hotline for psychological support was the most frequent intervention. Tools for self-rescue by using apps or websites were extensively used, too. Other common interventions were the development of action protocols, availability of regular and updated information, implantation of distance learning systems, early detection of infection programs for professionals, economic reinforcements, hiring of staff reinforcement, and modification of leave and vacation dates.

Objective: The purpose of this study was to identify disease relevant genes and explore underlying immunological mechanisms that contribute to early and late onset forms of myasthenia gravis., Methods: We used a novel genomic methodology to integrate genomewide association study (GWAS) findings in myasthenia gravis with cell-type specific information, such as gene expression patterns and promotor-enhancer interactions, in order to identify disease-relevant genes. Subsequently, we conducted additional genomic investigations, including an expression quantitative analysis of 313 healthy people to provide mechanistic insights., Results: We identified several genes that were specifically linked to early onset myasthenia gravis including TNIP1, ORMDL3, GSDMB, and TRAF3. We showed that regulators of toll-like receptor 4 signaling were enriched among these early onset disease genes (fold enrichment = 3.85, p = 6.4 × 10 -3 ). In contrast, T-cell regulators CD28 and CTLA4 were exclusively linked to late onset disease. We identified 2 causal genetic variants (rs231770 and rs231735; posterior probability = 0.98 and 0.91) near the CTLA4 gene. Subsequently, we demonstrated that these causal variants result in low expression of CTLA4 (rho = -0.66, p = 1.28 × 10 -38 and rho = -0.52, p = 7.01 × 10 -22 , for rs231735 and rs231770, respectively)., Interpretation: The disease-relevant genes identified in this study are a unique resource for many disciplines, including clinicians, scientists, and the pharmaceutical industry. The distinct immunological pathways linked to early and late onset myasthenia gravis carry important implications for drug repurposing opportunities and for future studies of drug development. ANN NEUROL 2021;90:455-463., (© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Fibrotic diseases remain a major cause of morbidity and mortality, yet there are few effective therapies. The underlying pathology of all fibrotic conditions is the activity of myofibroblasts. Using cells from freshly excised disease tissue from patients with Dupuytren's disease (DD), a localized fibrotic disorder of the palm, we sought to identify new therapeutic targets for fibrotic disease. We hypothesized that the persistent activity of myofibroblasts in fibrotic diseases might involve epigenetic modifications. Using a validated genetics-led target prioritization algorithm (Pi) of genome wide association studies (GWAS) data and a broad screen of epigenetic inhibitors, we found that the acetyltransferase CREBBP/EP300 is a major regulator of contractility and extracellular matrix production via control of H3K27 acetylation at the profibrotic genes, ACTA2 and COL1A1 Genomic analysis revealed that EP300 is highly enriched at enhancers associated with genes involved in multiple profibrotic pathways, and broad transcriptomic and proteomic profiling of CREBBP/EP300 inhibition by the chemical probe SGC-CBP30 identified collagen VI (Col VI) as a prominent downstream regulator of myofibroblast activity. Targeted Col VI knockdown results in significant decrease in profibrotic functions, including myofibroblast contractile force, extracellular matrix (ECM) production, chemotaxis, and wound healing. Further evidence for Col VI as a major determinant of fibrosis is its abundant expression within Dupuytren's nodules and also in the fibrotic foci of idiopathic pulmonary fibrosis (IPF). Thus, Col VI may represent a tractable therapeutic target across a range of fibrotic disorders., Competing Interests: Competing interest statement: J.N. and M.F. have received consulting fees and hold equity in 180 Therapeutics, which is an exclusively licensed intellectual property from the University of Oxford to treat Dupuytren’s disease with anti-TNF., (Copyright © 2020 the Author(s). Published by PNAS.)

Purpose: This study explored employer's perspectives on (1) their experience of good practice related to workers diagnosed with cancer and their return to work (RTW), and (2) their perceived needs necessary to achieve good practice as reported by employers from nine separate countries., Methods: Twenty-five semi-structured interviews were held in eight European countries and Israel with two to three employers typically including HR managers or line managers from both profit and non-profit organisations of different sizes and sectors. Interviews were recorded and transcribed verbatim. A grounded theory/thematic analysis approach was completed., Results: Employers' experience with RTW assistance for workers with cancer appears to be a dynamic process. Results indicate that good practice includes six phases: (1) reacting to disclosure, (2) collecting information, (3) decision-making related to initial actions, (4) remaining in touch, (5) decision-making on RTW, and (6) follow-up. The exact details of the process are shaped by country, employer type, and worker characteristics; however, there was consistency related to the need for (1) structured procedures, (2) collaboration, (3) communication skills training, (4) information on cancer, and (5) financial resources for realizing RTW support measures., Conclusions: Notwithstanding variations at country, employer, and worker levels, the employers from all nine countries reported that good practice regarding RTW assistance in workers with a history of cancer consists of the six phases above. Employers indicate that they would benefit from shared collaboration and resources that support good practice for this human resource matter., Implications for Cancer Survivors: Further research and development based on the six phases of employer support as a framework for a tool or strategy to support workers with a history of cancer across countries and organisations is warranted.

Most candidate drugs currently fail later-stage clinical trials, largely due to poor prediction of efficacy on early target selection 1 . Drug targets with genetic support are more likely to be therapeutically valid 2,3 , but the translational use of genome-scale data such as from genome-wide association studies for drug target discovery in complex diseases remains challenging 4-6 . Here, we show that integration of functional genomic and immune-related annotations, together with knowledge of network connectivity, maximizes the informativeness of genetics for target validation, defining the target prioritization landscape for 30 immune traits at the gene and pathway level. We demonstrate how our genetics-led drug target prioritization approach (the priority index) successfully identifies current therapeutics, predicts activity in high-throughput cellular screens (including L1000, CRISPR, mutagenesis and patient-derived cell assays), enables prioritization of under-explored targets and allows for determination of target-level trait relationships. The priority index is an open-access, scalable system accelerating early-stage drug target selection for immune-mediated disease.

Background: Self-reported antibiotic allergies are common among hospitalized adults and children. However, there is a paucity of studies investigating the impact of an antibiotic allergy label in childhood., Objective: To investigate the impact of antibiotic allergy labeling on clinical outcomes in children., Methods: A retrospective study was conducted in a major pediatric tertiary hospital to capture inpatient admissions (N = 1672) in April 2014 and April 2015. Data, collected by chart review, included documented antibiotic allergy labels, antibiotic prescriptions, admitting specialty, hospital length of stay, and hospital readmissions., Results: Of the 1672 pediatric patients surveyed, 58.1% were male and 44.8% were prescribed antibiotics. Antibiotic allergy labels were recorded in 5.3% of patients; most were β-lactam allergy labels (85%), mostly to unspecified penicillins. There was an increasing incidence of antibiotic allergy label with age, which was statistically significant (P < .001); no sex effect was seen. Patients with antibiotic allergy labels received more macrolide (P = .045), quinolones (P = .01), lincosamide (P < .001), and metronidazole (P = .009) antibiotics than did patients without an antibiotic allergy label. After adjusting for patient age, sex, principal diagnosis, and admitting specialty, children with any antibiotic or β-lactam allergy label had longer hospital stays (odds ratio, 1.62; 95% CI, 1.05-2.50; P = .03) with a mean length of hospital stay of 3.8 days for those without a label and 5.2 days for those with a β-lactam allergy label., Conclusions: This is the first study demonstrating the negative impact of antibiotic allergy labels on clinical outcomes in children, as evidenced by significant alternate antibiotic use and longer hospital stays., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Introduction: In its annual report for 2008, the World Health Organization (WHO) states fragmentation is one of the five most common shortcomings experienced by health systems in health care provision, while an integrated healthcare model can significantly improve efficacy/efficiency, reduce visits to doctors, improve patient satisfaction, and ensure safe and quality healthcare., Aim: The aim of our study is to point out importance of the cooperation between healthcare professionals from different sectors, institutions and levels of care involved in patient treatment and care and to propose measures for integration including criteria for clinical review and audit., Methods: In this paper, feedback and results from three workshops held in Tuzla on October 16 th , 2007, Bihac on December 9 th , 2013, and Sarajevo on November 24 th , 2018, were analyzed. All three workshops used the same methodology: first they have had a lecture on the topic of "Interface theory and protection blocks in the health system" and the second part took the form of six working groups in accordance with participants' affinities and places of employment., Results: The measures proposed to improve the interface are included: Development and adoption existing of clinical practice guidelines and pathways; Maintain joint working group meetings; Eliminate conflicts between PHC and hospital care and seek consensus through formal cooperation. Criteria for clinical audit of the PHC-hospital interface are: annual analysis of unnecessary or inadequate referrals as well as of any duplication of tests and prescriptions (failure to control costs); joint planning of preventive treatments (including the ministry and public health authorities); and clear responsibilities related to screening programs and patient path analysis., Discussion: Standardized communication protocols should be used to improve communication between health professionals at different levels and to moderate integration processes and protect data., Conclusion: Regular communication between healthcare professionals across the various institutions and levels of health care is a prerequisite for organizational, functional, service and clinical integration., Competing Interests: There are no conflicts of interest.

Background: Biological interpretation of genomic summary data such as those resulting from genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) studies is one of the major bottlenecks in medical genomics research, calling for efficient and integrative tools to resolve this problem., Results: We introduce eXploring Genomic Relations (XGR), an open source tool designed for enhanced interpretation of genomic summary data enabling downstream knowledge discovery. Targeting users of varying computational skills, XGR utilises prior biological knowledge and relationships in a highly integrated but easily accessible way to make user-input genomic summary datasets more interpretable. We show how by incorporating ontology, annotation, and systems biology network-driven approaches, XGR generates more informative results than conventional analyses. We apply XGR to GWAS and eQTL summary data to explore the genomic landscape of the activated innate immune response and common immunological diseases. We provide genomic evidence for a disease taxonomy supporting the concept of a disease spectrum from autoimmune to autoinflammatory disorders. We also show how XGR can define SNP-modulated gene networks and pathways that are shared and distinct between diseases, how it achieves functional, phenotypic and epigenomic annotations of genes and variants, and how it enables exploring annotation-based relationships between genetic variants., Conclusions: XGR provides a single integrated solution to enhance interpretation of genomic summary data for downstream biological discovery. XGR is released as both an R package and a web-app, freely available at http://galahad.well.ox.ac.uk/XGR .

Background: Patients frequently report antibiotic allergies; however, only 10% of labelled patients have a true allergy., Aim: We investigated the documentation of antibiotic 'allergy' labels (AAL) and the effect of labelling on clinical outcomes, in a West Australian adult tertiary hospital., Methods: Retrospective cross-sectional analysis of patients captured in the 2013 and 2014 National Antimicrobial Prescribing Surveys was carried out. Data were collected on documented antibiotic adverse drug reactions, antibiotic cost, prescribing appropriateness, prevalence of multi-drug resistant organisms, length of stay, intensive care admission and readmissions., Results: Of the 687 patients surveyed, 278 (40%) were aged 70 or above, 365 (53%) were male and 279 (41%) were prescribed antibiotics. AAL were recorded in 122 (18%) patients and the majority were penicillin labels (n = 87; 71%). Details of AAL were documented for 80 of 141 (57%) individual allergy labels, with 61 describing allergic symptoms. Patients with beta-lactam allergy labels received fewer penicillins (P = 0.0002) and more aminoglycosides (P = 0.043) and metronidazole (P = 0.021) than patients without beta-lactam labels. Five patients received an antibiotic that was contraindicated according to their allergy status. Patients with AAL had significantly more hospital readmissions within 4 weeks (P = 0.001) and 6 months (P = 0.025) of discharge, compared with unlabelled patients. The majority (81%) of readmitted labelled patients had major infections., Conclusions: AAL are common, but poorly documented in hospital records. Patients with AAL are significantly more likely to require alternative antibiotics and hospital readmissions. There may be a role for antibiotic allergy delabelling to mitigate the clinical and economic burdens for patients with invalid allergy labels., (© 2016 Royal Australasian College of Physicians.)

The ability to remember is influenced by environmental and lifestyle factors, such as stress and diet. A flavanol contained in chocolate, epicatechin (Epi), has been shown to enhance long-term memory (LTM) formation in Lymnaea. Combining two stressors (low-calcium pond water and crowding) blocks learning and all forms of memory; that is, this combination of environmentally relevant stressors creates a memory-unfriendly state. We tested the hypothesis that Epi will immediately reverse the memory-unfriendly state, i.e. that snails in the memory-deficit state when trained in Epi will immediately become competent to learn and form memory. We found that Epi not only reverses the memory-deficit state but also further enhances LTM formation. Thus, a naturally occurring bioactive plant compound can overcome a memory-unfriendly state. This supports the idea that bioactive substances may mitigate memory-making deficits that, for example, occur with ageing., (© 2016. Published by The Company of Biologists Ltd.)

Learning and subsequent memory formation are influenced by both environmental and lifestyle factors, such as stress and diet. Epicatechin, a plant flavonol found in cocoa, red wine and green tea enhances long-term memory (LTM) formation in Lymnaea. By contrast, an ecologically relevant stressor, low-calcium pond water, suppresses LTM formation. We tested the hypothesis that epicatechin overcomes the suppressive effects of the stressor on LTM formation in the continued presence of the stressor. Snails trained in low-calcium pond water exhibit learning but not LTM. Epicatechin (15 mg l(-1)) in control pond water enhances LTM formation. When epicatechin was added to the low-calcium pond water an enhanced LTM similar to that seen in control pond water was observed. Thus, a naturally occurring bioactive plant compound was able to overcome the suppressive effects of an ecologically relevant stressor on LTM formation., (© 2014. Published by The Company of Biologists Ltd.)

Objective: The aim of the present study was to evaluate subjective voice changes by voice handicap index (VHI) and voice related quality of life questionnaire (VRQL) and perceptual voice changes by Grade Roughness Breathiness Asthenia Strain (GRBAS) scale and to compare these findings with expanded disability status scale (EDSS) in multiple sclerosis (MS) patients., Methods: The patient group was composed of 36 MS patients, (mean age 45.2 ± 12.9, 13 male and 23 female) and compared with 32 healthy sex and age match individuals without neurological and voice symptoms., Results: The mean VHI was significantly higher in patients group (15.64 to 5.43; p=0.043). Forty-four percent of MS patients (52% of female patients) report voice problems. According to the GRBAS scale, differences between two groups were significant for Grade, Roughness, Breathiness and Strain items. The mean EDSS was 2.69 ± 1.1, for a male patients 2.54 ± 1.1 and for female 2.78 ± 1.3. There was no correlation between the EDSS and the total VHI score, between the EDSS and each of the three item of VHI, between the EDSS and VRQL, nor between the EDSS and components of GRBAS scale except for EDSS and asthenia item, (r=-0.5213, p=0.011)., Conclusions: Significant number of MS patients experienced voice problems. We did not establish any significant correlation between the intensity of the voice disorders and EDSS, except between EDSS and asthenia item of the GRBAS scale. The patients with low EDSS may have serious voice problems and vice versa., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background and Objectives: Because most studies of pathological gambling gather data from participants recruited from treatment, this study compared community and treatment-enrolled pathological gamblers (PGs) with respect to demographics, gambling severity, impulsivity, and psychopathology., Methods: One hundred six PGs were recruited as part of two larger studies in Farmington, Connecticut (n= 61) and Windsor, Ontario (n= 45) using radio advertising, word of mouth, and/or newspaper ads, as well as a gambling treatment program at each location., Results: Community (n= 49) and treatment-enrolled (n= 57) PGs did not differ on age, education, gender, race, employment, or marital status. Treatment-enrolled PGs were more likely to report past year illegal behaviors, preoccupation with gambling, and higher scores on the Barratt Impulsiveness Scale (BIS) Attention Impulsivity subscale. Assessment of psychopathology in the Ontario study indicated that treatment-enrolled PGs were more likely to present with Major Depressive and Dysthymic Disorders. Community-recruited PGs in the Connecticut study were overall more likely to present with any substance use disorder relative to their treatment-enrolled counterparts., Conclusions and Scientific Significance: Our findings inform intervention and research within the field of pathological gambling. Specifically, the distressing aspects of pathological gambling, such as legal issues, preoccupation with gambling, and depression, may be present more in treatment-enrolled PGs than in those recruited from the community. Such emotional disturbances should be further explored to increase motivation and treatment adherence in PGs. In addition, due to relative absence of overall differences between the groups, research findings utilizing treatment-enrolled PGs may be a good representation of both groups., (Copyright © American Academy of Addiction Psychiatry.)

Aims and Objectives: To examine quality of life determinants among clinical nurses in Croatia with an emphasis on their work ability., Background: An important personnel management challenge is to explore factors that stimulate or hinder the development of individual work ability and quality of life throughout a career., Design: A cross-sectional study., Methods: The study was performed during 2007-2008 in six randomly selected hospitals in Croatia. The self-administered questionnaires included the Work Ability Index (WAI) developed by the Finnish Institute of Occupational Health, the Quality of Life questionnaire (WHOQL-BREF) developed by the World Health Organization and additional socio-demographic questions. A total number of 1212 nurses completed the questionnaires, giving a response rate of 67(.) 3%. Binary logistic regression was performed to assess how socio-demographic characteristics and work ability groups predict each of the WHOQL-BREF domains., Results: Having a satisfactory WAI score (WAI ≥ 37) was significantly the most important predictor for all quality of life domains, with the odds ratios (OR) being as follows: OR = 6(.) 8 (95% CI: 4(.) 8-9(.) 6) for the physical domain, OR = 2(.) 3 (95% CI: 1(.) 7-3(.) 1) for the psychological domain, OR = 1(.) 7 (95% CI: 1(.) 3-2(.) 4) for the social relationship domain and OR = 1(.) 7 (95% CI: 1(.) 3-2(.) 3) for the environmental domain., Conclusions: Satisfactory work ability was a major quality of life determinant in all WHOQL-BREF domains with the highest odds ratio for the physical domain. Maintaining clinical nurses' work ability is an important issue, because it is foundational for the quality of life of the workforce., Relevance to Clinical Practice: Our study provides quantified estimates of the extent to which a satisfactory WAI score predicts a better score in physical, psychosocial, social relationships and environmental domain of nurses' quality of life. Therefore, maintaining or improving nurses' work ability remains the essential aim of hospital managers., (© 2011 Blackwell Publishing Ltd.)

Forgetting may allow an animal to react more appropriately to current conditions, rather than continuing to exhibit a previously learned, possibly maladaptive behaviour based on previous experience. One theory is that forgetting is an active process, whereby the previously learnt response is replaced by new learning that interferes with the older memory. Hence, we hypothesized that an appropriately timed environmental stressor that blocks long-term memory (LTM) formation would also block forgetting. Lymnaea stagnalis (L.) is a freshwater snail, which requires environmental calcium of at least 20 mg l(-1) to meet its requirements. Low environmental Ca(2+) (i.e. 20 mg l(-1)) in their environment acts as a stressor, and prevents LTM formation. Here, we asked whether a low Ca(2+) environment would also prevent forgetting, concordant with the retrograde interference model of Jenkins and Dallenbach. Snails were operantly conditioned to reduce aerial respiration in hypoxia. When maintained in standard conditions (80 mg l(-1) Ca(2+)), snails demonstrated LTM following training lasting 24 h, but not 72 h; however, when trained in standard conditions then exposed to a low Ca(2+) environment (20 mg l(-1)) immediately following training, they retained memory for at least 96 h, indicating that forgetting had been blocked. Thus, when exposed to low environmental Ca(2+), Lymnaea will fail to form new memories, but will also continue to retain information previously learned and remembered as the low calcium blocks forgetting.

Objective: to explore the sources and levels of stress at work and work ability among Croatian midwives., Background: midwives are subjected to multiple stressors. Among health-care professionals, psychological distress for a prolonged period of time has negative effects on the worker's health, work ability and quality of patient care. 'Work ability' is a term describing a worker's resources related to physical, mental and social demands at work. As a measure of work ability in midwifery, the Work Ability Index (WAI) is considered to be a very predictive instrument; midwives with a poor WAI score usually leave their current job within five years., Setting: university hospitals in Zagreb, Croatia., Design: cross-sectional design survey., Participants: 300 health-care workers (105 qualified midwives and 195 paediatric nurses) were invited to complete the questionnaire. The total response rate was 53% (158/300). The sample included 14.7% of all hospital-based midwives in Zagreb hospitals., Methods: the Occupational Stress Assessment Questionnaire (OSAQ) for health-care workers and the WAI questionnaire., Findings: over three-quarters of the midwives (46/60, 76.7%) believed that their job was stressful, and considered that insufficient work resources caused the most stress. More than half of the midwives associated an insufficient number of coworkers, unexpected situations, inadequate income, night work, incurable patients and poor organisation at work with a high level of stress. The perceived specific stressors differed between midwives and paediatric nurses in the same hospital. Insufficient work resources and poor organisation at work were more common stressors among midwives than paediatric nurses (p<0.05). Midwives and nurses differed significantly with respect to age (p=0.002). Midwives were younger and had spent fewer years working in their current workplace compared with paediatric nurses (p<0.001). Also, midwives had a lower level of education than paediatric nurses (p=0.044). The mean WAI score for midwives was 40.0 [95% confidence interval (CI) 38.4-41.4], compared with 37.5 (95% CI 36.4-38.8) for paediatric nurses, both indicating good work ability. After adjusting for age, the difference in WAI score between the groups of workers was not significant., Conclusions: Croatian midwives experienced work-related stress due to: insufficient work resources, insufficient number of coworkers, poor organisation at work, communication with superiors and emotional work. Midwives' work ability in relation to the demands of their job was good. These results confirmed that the WAI score decreases significantly with age., Implications for Practice: hospital management needs to improve organisational factors and resources, as well as midwives' education and position in the health-care system., (Copyright © 2009 Elsevier Ltd. All rights reserved.)

Aim: This paper is a report of a study conducted to determine which occupational stressors are present in nurses' working environment; to describe and compare occupational stress between two educational groups of nurses; to estimate which stressors and to what extent predict nurses' work ability; and to determine if educational level predicts nurses' work ability., Background: Nurses' occupational stress adversely affects their health and nursing quality. Higher educational level has been shown to have positive effects on the preservation of good work ability., Method: A cross-sectional study was conducted in 2006-2007. Questionnaires were distributed to a convenience sample of 1392 (59%) nurses employed at four university hospitals in Croatia (n = 2364). The response rate was 78% (n = 1086). Data were collected using the Occupational Stress Assessment Questionnaire and Work Ability Index Questionnaire., Findings: We identified six major groups of occupational stressors: 'Organization of work and financial issues', 'public criticism', 'hazards at workplace', 'interpersonal conflicts at workplace', 'shift work' and 'professional and intellectual demands'. Nurses with secondary school qualifications perceived Hazards at workplace and Shift work as statistically significantly more stressful than nurses a with college degree. Predictors statistically significantly related with low work ability were: Organization of work and financial issues (odds ratio = 1.69, 95% confidence interval 122-236), lower educational level (odds ratio = 1.69, 95% confidence interval 122-236) and older age (odds ratio = 1.07, 95% confidence interval 1.05-1.09)., Conclusion: Hospital managers should develop strategies to address and improve the quality of working conditions for nurses in Croatian hospitals. Providing educational and career prospects can contribute to decreasing nurses' occupational stress levels, thus maintaining their work ability.

To examine the genetic factors influencing clozapine kinetics in vivo, 75 patients treated with clozapine were genotyped for CYPs and ABCB1 polymorphisms and phenotyped for CYP1A2 and CYP3A activity. CYP1A2 activity and dose-corrected trough steady-state plasma concentrations of clozapine correlated significantly (r = -0.61; P = 1 x 10), with no influence of the CYP1A2*1F genotype (P = 0.38). CYP2C19 poor metabolizers (*2/*2 genotype) had 2.3-fold higher (P = 0.036) clozapine concentrations than the extensive metabolizers (non-*2/*2). In patients comedicated with fluvoxamine, a strong CYP1A2 inhibitor, clozapine and norclozapine concentrations correlate with CYP3A activity (r = 0.44, P = 0.075; r = 0.63, P = 0.007, respectively). Carriers of the ABCB1 3435TT genotype had a 1.6-fold higher clozapine plasma concentrations than noncarriers (P = 0.046). In conclusion, this study has shown for the first time a significant in vivo role of CYP2C19 and the P-gp transporter in the pharmacokinetics of clozapine. CYP1A2 is the main CYP isoform involved in clozapine metabolism, with CYP2C19 contributing moderately, and CYP3A4 contributing only in patients with reduced CYP1A2 activity. In addition, ABCB1, but not CYP2B6, CYP2C9, CYP2D6, CYP3A5, nor CYP3A7 polymorphisms, influence clozapine pharmacokinetics.

Primary evidence-based treatment approaches for ADHD involve pharmacological and behavioral treatments. However, there continue to be investigations of cognitive-behavioral, cognitive, and neural-based intervention approaches that are not considered evidence-based practice. These particular treatments are summarized, as they all involve training in cognitive skills or cognitive strategies. We identified 26 studies (six cognitive-behavioral, six cognitive, and 14 neural-based), and calculated effect sizes where appropriate. Overall, our analysis suggests that further research is needed to determine the efficacy of these approaches on both cognitive and behavioral outcome measures, but that some of these methods show promise for treating ADHD. We discuss some important conceptual and methodological issues that need to be taken into account for future research in order to evaluate the clinical efficacy of these approaches.