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Anders Johan W Andersen,1 Tommy Svensson21Department of Psychosocial Health, University of Agder, Grimstad, Norway; 2Department of Behavioural Sciences and Learning, Linköping University, Linköping, SwedenAbstract: The Internet has enlarged the scope of human communication, opening new avenues for connecting with people who are struggling with their lives. This article presents a discourse analysis of 101 responses to 98 questions that were posted on 14 different Internet-based mental health services in Norway and Sweden. We aimed to examine and describe the dominant understandings and favored recommendations in the services’ answers, and we reflected upon the social consequences of those answers. The services generally understood life struggles as an abnormal state of mind, life rhythms, or self-reinforcing loops. Internet-based mental health services primarily counsel service users to seek help, talk to health care professionals face-to-face, and discuss their life struggles openly and honestly. They also urge service users to take better care of themselves and socialize with other people. However, such answers might enhance the individualization of life problems, masking social origin and construction. Consequently, the services are challenged to include social explanations in their answers and strengthen their responsibility to amplify peoples’ messages at a societal level. Potentially, such answers could strengthen democratic structures and put pressure on social equity.Keywords: depression, e-mental health, health psychology, Internet, public health

Anders Johan W Andersen,1,2 Tommy Svensson31Department of Psychosocial Health, University of Agder, Norway; 2Nordic School of Public Health, Gothenburg, Sweden; 3Department of Behavioral Sciences and Learning, Linköping University, Linköping, SwedenBackground: The Internet has enlarged the possibilities of human communication and opened new ways of exploring perceptions of mental health. This study is part of a research project aiming to explore, describe, and analyze different discourses of mental health in Norway and Sweden, using material from Internet-based services.Aim: To examine messages posed by users of publicly available question-and-answer services and to describe their content.Methods: A Web search was used to identify Norwegian and Swedish Websites offering mental health services by email or posted messages. A total of 601 messages from 20 services, 10 Norwegian and 10 Swedish, were analyzed by means of qualitative content analysis and further interpreted in light of the social theory of recognition by Honneth.Results: Eight categories emerged from the analysis: family life, couples, others, violence, the ungovernable, self-image, negotiating normality, and life struggles. These categories were then grouped into three themes: (1) relationship to significant others, (2) relationship to self, and (3) relationship to the social community. The themes promoted an understanding of mental health as closely connected to political and social factors.Conclusions: The results showed a variety of concerns from various parts of life and empowered the view that mental health should be understood broadly, at a conceptual level. Mental health emerged as a deeply relational concept that emphasized the equal distribution of chances in life. It strengthened the moral grammar of social inclusion and the acceptance of plurality in social life.Keywords: Internet-based services, mental health, public health, social theory

PTEN hamartoma tumor syndrome (PHTS) has a broad clinical spectrum including various benign and malignant tumors at varying age of diagnosis. Many patients remain unrecognized, unaware of their increased cancer risk. We aimed to describe the cancer spectrum, age of onset and histopathological cancer characteristics to assess whether specific cancer characteristics could improve PHTS recognition. Genetic testing results and pathology reports were collected for patients tested for germline PTEN variants between 1997 and 2020 from the diagnostic laboratory and the Dutch nationwide pathology databank (Palga). The cancer spectrum and age of onset were assessed in patients with (PTENpos) and without (PTENneg) a germline PTEN variant. Histopathological cancer characteristics were assessed in a nested cohort. 341 PTENpos patients (56% females) and 2882 PTENneg patients (66% females) were included. PTENpos patients presented mostly with female breast (BC, 30%), endometrial (EC, 6%), thyroid (TC, 4%) or colorectal cancer (4%). PTENpos were significantly younger at cancer onset (43 vs. 47 years) and had more often (46% vs. 18%) a second BC than PTENneg. PTEN detection rates were highest for BC <40 years (9%), TC <20 years (15%) and EC <50 years (28%), and dropped to 6%, 4%, and 15% by age 60. Histopathological characteristics were similar between groups. No histopathological cancer characteristics were distinctive for PHTS. However, PTENpos were significantly younger at cancer onset. Therefore early-onset BC, EC, or TC warrants consideration of PHTS diagnostics either through a pre-screen for other PHTS features or direct germline testing., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

According to GNSS/INSAR measurements, the Konya Basin in Central Anatolia is undergoing rapid subsidence within an uplifting orogenic plateau. Further, geophysical studies reveal thickened crust under the basin and a fast seismic wave speed anomaly in the underlying mantle, in addition to a localised depression in calculated residual topography (down to 280 m) over the Konya Basin, based on gravity-topography considerations. Using scaled laboratory (analogue) experiments we show that the active formation of the Konya Basin may be accounted for by the descent of a mantle lithospheric drip causing local circular-shaped surface subsidence. We interpret that the Konya Basin is developing through a secondary drip pulse that is contemporaneous with broad plateau uplift caused by a larger-scale lithospheric drip since the Miocene. The research reveals that basin evolution and plateau uplift may be linked in a multistage process of lithospheric removal during episodic development of orogenic systems., (© 2024. The Author(s).)

Aims: Patients with PTEN hamartoma tumour syndrome (PHTS) have an increased risk of developing cancer due to a pathogenic germline variant in the PTEN tumour suppressor gene. Early recognition of PHTS facilitates initiation of cancer surveillance which is highly effective in preventing the development of advanced malignancies. PHTS is rare and due to its varied phenotype, even within families, oral abnormalities may be a valuable tool in the identification of these patients at an early stage before cancer development., Materials and Methods: Between 1997 and 2020, phenotypic characteristics were evaluated in 81 paediatric (median age: 9 years) and 86 adult (median age: 40 years) PHTS patients by one of 2 medical experts during yearly surveillance visits at a Dutch PHTS expertise centre. Oral features evaluated included gingival hypertrophy, oral papillomas, and high palate (in adults)., Results: Within adults, gingival hypertrophy was present in 94%, oral papillomas in 88%, and a high palate in 89%. All adult patients had at least one of these oral features, and 99% showed at least 2 oral features. Oral features were less common in paediatric patients, especially under 11 years of age. Gingival hypertrophy was observed in 44% and oral papillomas in 54% of paediatric patients., Conclusions: The presence of 2 or 3 oral features may indicate PHTS in adults or adolescents, especially if macrocephaly is present. Dental professionals are well-positioned to recognise these oral manifestations could be related to PHTS. They can initiate an overall clinical assessment of the patient by alerting the patient's medical practitioner of the findings and the possible need for genetic testing. This could significantly improve outcomes, including life expectancy, for patients and possibly for their relatives., Clinical Relevance: Dental professionals are ideally placed to recognise oral features and initiate early assessment of PHTS which could significantly improve patient outcomes., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Medical cannabis, legalized in many countries, remains illegal in France. Despite an experiment in the medical use of cannabis that began in March 2021 in France, little is known about the factors associated with the use of cannabis for self-medication among adults., Methods: Data came from the French TEMPO cohort and were collected between December 2020 and May 2021. Overall, 345 participants aged 27-47 were included. Cannabis for self-medication was defined using the following questions: 'Why do you use cannabis?' and 'In what form do you use cannabis?'. The penalized regression method "Elastic net" was used to determine factors associated with the use of cannabis for self-medication, with the hypothesis that it is mainly used for pain in individuals who have already used cannabis., Results: More than half of the participants reported having ever used cannabis (58%). Only 10% used it for self-declared medical reasons (n = 36). All self-medication cannabis users, except one, were also using cannabis for recreational purposes. The main factors associated with cannabis use for self-medication vs. other reasons included cannabis use trajectories, the presence of musculoskeletal disorders, tobacco smoking, and parental divorce., Conclusions: Engaging in cannabis use during adolescence or early adulthood may increase the likelihood of resorting to self-medication in adulthood. Due to the propensity of individuals with cannabis use during adolescence to resort to uncontrolled products for self-medication, this population should be more systematically targeted and screened for symptoms and comorbidities that may be associated with cannabis use., (© 2024. The Author(s).)

Introduction: Results of the impact of lockdowns and stay-at-home orders during the COVID-19 pandemic on changes in cigarette smoking are mixed. Previous studies examining smoking changes during the early stages of the pandemic in 2020 have mainly focused on smoker's perception of changes in cigarette consumption. Such measure has not been widely used in other contexts, and therefore we aim to compare the discrepancy between smokers' perceived changes in cigarette smoking and the actual change in the number of cigarettes smoked, using repeated measurements., Methods: We included 134 smokers from the French TEMPO cohort with repeated measurements of their perceived changes in smoking habits during the first phase of the COVID-19 pandemic and the number of cigarettes smoked repeatedly from March to May 2020. We used generalized estimation equations (GEE) to examine the association between changes in the number of cigarettes smoked and the odds of mismatched answers., Results: The results suggest that at each study wave, 27-45% of participants provided mismatching answers between their perceived change in smoking habits and the actual change in the number of cigarettes smoked daily, measured repeatedly. Results from GEE analysis demonstrated that a mismatching assessment of smoking behavior was elevated among those who had an increase (OR = 2.52 [1.37;4.65]) or a decrease (OR = 5.73 [3.27;10.03]) in number of cigarettes smoked., Discussion: Our findings highlight the possibility of obtaining different results depending on how changes in tobacco smoking are measured. This highlights the risk of underestimating the actual changes in cigarette smoking during the COVID-19 pandemic, but also more generally when validating public health interventions or smoking cessation programs. Therefore, objective measures such as the actual consumption of psychoactive substances should be utilized, preferably on a longitudinal basis, to mitigate recall bias., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Andersen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: High levels of post-traumatic stress are well documented among refugees. Yet, refugee adolescents display high heterogeneity in their type of trauma and symptom levels. Objective: Following the recurrent plea for validated trauma screening tools, this study investigated the psychometric properties of the Children's Revised Impact of Event Scale (CRIES-8) among refugee adolescents from Afghanistan ( n  = 148), Syria ( n  = 234), and Somalia ( n  = 175) living in Europe. Method: The model fit for the confirmatory factor structures was tested, as well as measurement invariance between the three groups. The robustness of results was evaluated by testing measurement invariance between recently arrived and settled adolescents, and between different response labelling options. Reliability ( α , ω , and ordinal α ), criterion validity, and prevalence estimates were calculated. Results: The intrusion subscale showed a better stable model fit than the avoidance subscale, but the two-factor structure was mainly supported. Configural measurement invariance was achieved between Afghan and Somali adolescents, and strong measurement invariance between Syrian and Somali adolescents. The results were robust considering the time living in the host country and response labelling styles. Reliability was low among Afghan and Syrian adolescents (.717-.856), whereas it was higher among Somali adolescents (.831-.887). The total score had medium-sized correlations with emotional problems (.303-.418) and low correlations with hyperactivity (.077-.155). There were statistically significant differences in symptom prevalence: Afghan adolescents had higher prevalence (55.5%) than Syrian (42.8%) and Somali (37%) adolescents, and unaccompanied refugee minors had higher symptom prevalence (63.5%) than accompanied adolescents (40.7%). Conclusions: This study mostly supports the use of the CRIES-8 among adolescents from Afghanistan, Syria, and Somalia, and even comparative analyses of group means. Variation in reliability estimates, however, makes diagnostic predictions difficult, as the risk of misclassification is high.

School-based psychosocial interventions are increasingly put forward as a way to support young refugees' and migrants' well-being and mental health in resettlement. However, the evidence on these interventions' effectiveness remains scarce and scholars denounce particular gaps in the evidence to date, pointing to a lack of large-scale, controlled studies and studies including social outcome measures. This cluster randomized study aims to strengthen the evidence base on school-based psychosocial interventions for refugee and migrant youth by assessing the effect of two interventions, Classroom Drama and Welcome to School, on youth's mental health, resilience, and social relations in Belgium, Denmark, Norway, and the United Kingdom. Multilevel analyses were conducted separately for the two interventions (Classroom Drama, n = 307, ages 11-19; Welcome to School, n = 251, ages 11-23), using separate no-treatment control groups. Our analyses indicated a significant main, positive effect of Classroom Drama on perceived family support, and an effect on perceived support from friends that was moderated by country: in the United Kingdom, the intervention group reported an increase in perceived friend support, whereas the control group reported a decrease. Furthermore, baseline resilience moderated the effect of the Classroom Drama intervention on behavioral difficulties and well-being. No effects of Welcome to School on any of the outcome variables were found. Overall, this study provides novel, nuanced evidence on school-based psychosocial interventions for refugee and migrant adolescents., Competing Interests: Conflict of Interest: The authors of this article declare no conflict of interest., (Copyright © 2023, Colegio Oficial de la Psicología de Madrid.)

Background: The COVID-19 pandemic as a public health crisis has led to a significant increase in mental health difficulties. Smoking is strongly associated with mental health conditions, which is why the pandemic might have influenced the otherwise decline in smoking rates. Persons belonging to socioeconomically disadvantaged groups may be particularly affected, both because the pandemic has exacerbated existing social inequalities and because this group was more likely to smoke before the pandemic. We examined smoking prevalence in a French cohort study, focusing on differences between educational attainment. In addition, we examined the association between interpersonal changes in tobacco consumption and educational level from 2018 to 2021., Methods: Using four assessments of smoking status available from 2009 to 2021, we estimated smoking prevalence over time, stratified by highest educational level in the TEMPO cohort and the difference was tested using chi 2 test. We studied the association between interpersonal change in smoking status between 2018 and 2021 and educational attainment among 148 smokers, using multinomial logistic regression., Results: Smoking prevalence was higher among those with low education. The difference between the two groups increased from 2020 to 2021 (4.8-9.4%, p < 0.001). Smokers with high educational level were more likely to decrease their tobacco consumption from 2018 to 2021 compared to low educated smokers (aOR = 2.72 [1.26;5.89])., Conclusion: Current findings showed a widening of the social inequality gap in relation to smoking rates, underscoring the increased vulnerability of persons with low educational level to smoking and the likely inadequate focus on social inequalities in relation to tobacco control policies during the pandemic., (© 2023. The Author(s).)

•Symptoms of anxiety/depression were found in 28.8% of the participants at least once.•Unemployment and financial difficulties were associated with anxiety/depression.•Targeted mental health support could lessen mental health impact., Competing Interests: None., (© 2022 The Authors.)

While scholarly literature indicates that both refugee and non-refugee migrant young people display increased levels of psychosocial vulnerability, studies comparing the mental health of the two groups remain scarce. This study aims to further the existing evidence by examining refugee and non-refugee migrants' mental health, in relation to their migration history and resettlement conditions. The mental health of 883 refugee and 483 non-refugee migrants (mean age 15.41, range 11-24, 45.9% girls, average length of stay in the host country 3.75 years) in five European countries was studied in their relation to family separation, daily material stress and perceived discrimination in resettlement. All participants reported high levels of post-traumatic stress symptoms. Family separation predicted post-trauma and internalizing behavioral difficulties only in refugees. Daily material stress related to lower levels of overall well-being in all participants, and higher levels of internalizing and externalizing behavioral difficulties in refugees. Perceived discrimination was associated with increased levels of mental health problems for refugees and non-refugee migrants. The relationship between perceived discrimination and post-traumatic stress symptoms in non-refugee migrants, together with the high levels of post-traumatic stress symptoms in this subsample, raises important questions on the nature of trauma exposure in non-refugee migrants, as well as the ways in which experiences of discrimination may interact with other traumatic stressors in predicting mental health., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Several studies show an increased risk of coronary heart disease (CHD) among people with obesity, but it is largely unknown whether this association also depends on a familial predisposition to obesity. This study examined if associations between Body Mass Index (BMI) or waist circumference (WC) and incident CHD differed among Danish female nurses with and without familial overweight and obesity. Analyses were based on data from the Danish Nurse Cohort (n = 20,701). Self-reported height, weight and self-measured WC were assessed in 1999, as was information on familial overweight/obesity, defined as having one or both parents with overweight/obesity. Information on the development of or death from CHD was collected from nationwide Danish registries in 2015. Analyses were based on Cox proportional hazard regression models adjusted for potential confounding factors. Both BMI and WC were directly associated with CHD risk, but we found no evidence of effect modification from familial predisposition to obesity. Hence a familial predisposition to obesity does not seem to influence the risk of CHD associated with general or central obesity., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Genodermatoses are inherited syndromes with cutaneous manifestations. Some genodermatoses are associated with malignancy of internal organs and tissues. Early detection of the typical signs of these syndromes is important, because those lesions are a sign of underlying predisposition to extracutaneous neoplasms. The dermatologist has an important role in the early detection of these signs and syndromes, as early detection may affect the clinical course of the disease. We report here the characteristic cutaneous findings that dermatologists should be aware of in order to identify a genodermatosis with a possible associated malignancy. An updated overview of the pathogenesis and clinical findings of these syndromes is provided. Furthermore, surveillance protocols and treatment recommendations are explored.

Background: To cope with the COVID-19 pandemic, social distancing restrictions where implemented in France, which could have led to social isolation. This is expected to have affected the mental health situation, including increasing risk of symptoms of anxiety and depression in the general population. Persons with prior mental health difficulties could be an especially vulnerable group, however, few studies have tested this empirically considering preexisting mental health difficulties. We examine the association between preexisting symptoms of anxiety/depression and anxiety/depression during lockdown due to the COVID-19 pandemic in a longitudinal community sample., Methods: A longitudinal follow-up during lockdown (data collection March-June 2020) was implemented among participants of the TEMPO cohort. Prior knowledge of anxiety/depression was included from prior waves of data collection. Generalized estimation equations models were used to estimate the association between preexisting symptoms of anxiety/depression and symptoms of anxiety/depression during lockdown among 662 mid-aged individuals., Results: Individuals with symptoms of anxiety/depression measured prior to lockdown had 6.73 higher odds [95% CI = 4.45-10.17] of symptoms of anxiety/depression during lockdown. Additionally, the likelihood of symptoms of anxiety/depression during lockdown was elevated among women (OR = 2.07 [95% CI = 1.32-3.25]), subjects with low household income (OR = 2.28 [1.29-4.01]) and persons who reported being lonely (OR = 3.94 [95% CI = 2.47-6.28])., Conclusions: Our study underlines the role of preexisting symptoms of anxiety/depression as a vulnerability factor of anxiety/depression during lockdown. Interventions focusing on individuals with mental health difficulties as well as people feeling lonely should be considered, to reduce the psychological impact of the COVID-19 pandemic., (© 2021. The Author(s).)

Background: The outbreak of the COVID-19 epidemic lead to high levels of morbidity and mortality around the globe. Consequences of this outbreak and possible associated infection are an increase in mental health disorders and an increased likelihood of internalizing problems, particularly depression. However, to date few studies have tested this hypothesis while taking into account individuals' preexisting mental health difficulties., Methods: We used longitudinal data collected among 729 persons in the context of the French TEMPO cohort between March and June 2020 (7 waves of data collection). COVID-19-like symptoms as well as anxiety/depression (assessed by the Adult Self Report), were reported at each wave of data collection. To study the relationship between COVID-19-like symptoms and anxiety/depression, we used generalized estimation equation (GEE) models controlled for socio-demographic and health-related characteristics, including anxiety/depression prior to 2020., Results: Overall, 27.2% of study participants reported anxiety/depression during lockdown. 17.1% of participants reported COVID-19-like symptoms during the course of follow-up, 7.3% after the beginning of lockdown, with an average number of 2.7 symptoms, and 3.6% reported respiratory distress. In multivariate analyses, nearly all the considered indicators of COVID-19-like symptoms were associated with higher odds of symptoms of anxiety/depression (symptoms Yes/No: OR = 1.66, 95% CI = 1.08-2.55; symptoms after the beginning of lockdown: OR = 1.91, 95% CI = 1.03-3.52; number of symptoms: OR for each additional symptom = 1.19, 95% CI = 1.02-1.39. This relationship exists after taking into account prior symptoms of anxiety/depression, which are associated with a 5-fold increased likelihood of psychological distress. And this impact is stronger among men than women., Conclusions: Our study shows higher risk of anxiety/depression among persons who experienced COVID-19-like symptoms, even after accounting for prior mental health difficulties. COVID-19 infection could have both a direct and indirect impact on the occurrence of psychological difficulties, and this association should be studied in greater detail., Competing Interests: The authors have declared that no competing interests exist.

Despite considerable progress within wilderness and adventure therapy research over the last decade, researchers are still unable to precisely answer why, how, and for whom this treatment modality works. There is also a need for more knowledge regarding the circumstances under which the treatment does not appear to be effective. In this realist synthesis, we attempt to unpack this "black box" of wilderness therapy more specifically, defined as a specialized approach to mental health treatment for adolescents. Through a focused review of the primary qualitative wilderness therapy studies, empirical findings are used to test and refine a key program theory. The synthesis results in a proposed wilderness therapy clinical model and offers informed implications for future theory development, research, and practice., (© The Author(s) 2016.)

Dynamic cluster analysis (DCA) is an automated, unbiased technique which can identify Cl, Br, S, and other A + 2 element containing metabolites in liquid chromatographic high-resolution mass spectrometric data. DCA is based on three features, primarily the previously unutilized A + 1 to A + 2 isotope cluster spacing which is a strong classifier in itself but improved with the addition of the monoisotopic mass, and the well-known A:A+2 intensity ratio. Utilizing only the A + 1 to A + 2 isotope cluster spacing and the monoisotopic mass it was possible to filter a chromatogram for metabolites which contain Cl, Br, and S. Screening simulated isotope patterns of the Antibase Natural Products Database it was determined that the A + 1 to A + 2 isotope cluster spacing can be used to correctly classify 97.4% of molecular formulas containing these elements, only misclassifying a few metabolites which were either over 2800 u or metabolites which contained other A + 2 elements, such as Cu, Ni, Mg, and Zn. It was determined that with an interisotopic mass accuracy of 1 ppm, in a fully automated process, using all three parameters, it is possible to specifically filter a chromatogram for S containing metabolites with monoisotopic masses less than 825 u. Furthermore, it was possible to specifically filter a chromatogram for Cl and Br containing metabolites with monoisotopic masses less than 1613 u. Here DCA is applied on (i) simulated isotope patterns of the Antibase natural products databases, (ii) LC-QTOF data of reference standards, and (iii) LC-QTOF data of crude extracts of 10 strains of laboratory grown cultures of the microalga Prymnesium parvum where it identified known metabolites of the prymnesin series as well as over 20 previously undescribed prymnesin-like molecular features.

Aim: To evaluate current insulin pump settings in an optimally regulated paediatric population using bolus wizard., Methods: We used a retrospective study design to analyse data from 124 children on insulin pump therapy who had optimum HbA1c levels [< 59 mmol/mol (< 7.5%)] and no history of severe hypoglycaemic events. Bolus wizard settings were used to calculate the insulin to carbohydrate factors and insulin sensitivity factors. Multiple regression analysis was used to analyse the variables associated with the calculation factors., Results: Insulin to carbohydrate factor varied from 276 in the youngest group to 424 in the oldest group, and increased according to age. Insulin sensitivity factor was highest in the group aged 6 to < 12 years, with a value of 125. Age, amount of carbohydrates, number of boluses per day and insulin per kg were all significantly associated with both calculation factors. Furthermore, duration of insulin pump treatment was significantly associated with insulin sensitivity factor and percentage bolus/basal was significantly associated with insulin to carbohydrate factor. Gender, diabetes duration and BMI were not associated with any of the calculation factors., Conclusion: Optimum insulin pump settings at pump initiation depend on both insulin requirements and use of the pump. Settings need to be individualized because the standardized calculation factors are not constant for children. There is a need to develop specific age- and insulin dose-dependent calculation factors., (© 2016 Diabetes UK.)

Microalgae, particularly those from the lineage Dinoflagellata, are very well-known for their ability to produce phycotoxins that may accumulate in the marine food chain and eventually cause poisoning in humans. This includes toxins accumulating in shellfish, such as saxitoxin, okadaic acid, yessotoxins, azaspiracids, brevetoxins, and pinnatoxins. Other toxins, such as ciguatoxins and maitotoxins, accumulate in fish, where, as is the case for the latter compounds, they can be metabolized to even more toxic metabolites. On the other hand, much less is known about the chemical nature of compounds that are toxic to fish, the so-called ichthyotoxins. Despite numerous reports of algal blooms causing massive fish kills worldwide, only a few types of compounds, such as the karlotoxins, have been proven to be true ichthyotoxins. This review will highlight marine microalgae as the source of some of the most complex natural compounds known to mankind, with chemical structures that show no resemblance to what has been characterized from plants, fungi, or bacteria. In addition, it will summarize algal species known to be related to fish-killing blooms, but from which ichthyotoxins are yet to be characterized.

The accumulation of extracellular amyloid-beta (Aβ) peptide and intracellular neurofibrillary tangles in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). It is thought that an equilibrium exists between Aβ in the brain and in the peripheral blood and thus, it was hypothesized that shifting this equilibrium towards the blood by enhancing peripheral clearance might reduce Aβ levels in the brain: the 'sink effect'. We tested this hypothesis by intraperitoneally injecting APP/PS1 transgenic mice with small unilamellar vesicles containing either phosphatidic acid or cardiolipin over 3weeks. This treatment reduced significantly the amount of Aβ in the plasma and the brain levels of Aβ were lighter affected. Nevertheless, this dosing regimen did modulate tau phosphorylation and glycogen synthase kinase 3 activities in the brain, suggesting that the targeting of circulating Aβ may be therapeutically relevant in AD., From the Clinical Editor: Intraperitoneal injection of small unilamellar vesicles containing phosphatidic acid or cardiolipin significantly reduced the amount of amyloid-beta (Aß) peptide in the plasma in a rodent model. Brain levels of Aß were also affected - although to a lesser extent - suggesting that targeting of circulating Aß may be therapeutically relevant of Alzheimer's disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In Norway and many other countries, political guidelines prescribe the development of mental health strategies with both a service user's perspective and a treatment system established by the local authority. The development of new strategies frequently involves challenges regarding procedures and treatment as well as a view of knowledge and humanity. Dialogical practices might provide a solution for these challenges not only because of its procedures but also due to its attitudes toward service users. The aim is to explore the implementation of three dialogical practice programs in Southern Norway from 1998 to 2008 and to critically analyze and discuss the authors' experiences during the implementation process. Three different programs of dialogical practices were initiated, established, and evaluated within the framework of participatory action research. Sustainable changes succeed individually and organizationally when all participants engage as partners during the implementation of new mental health practices. Generating dialogic practice requires shared understanding of the Open Dialogue Approach (ODA) and collaboration between professional networks and among the leaders. Developing a collaboration area that includes service users in all stages of the projects was one of the essential implementation factors. Other factors involved a common vision of ODA by the leaders and the actors, similar experiences, and a culture of collaboration. However, ODA challenged traditional medical therapy and encountered obstacles to collaboration. Perhaps the best way of surmounting those obstacles is to practice ODA itself during the implementation process.

Carboxylated (4%) multi-walled carbon nanotubes were covalently functionalized with poly(ethylene glycol)₁₀₀₀ (PEG₁₀₀₀), PEG₁₅₀₀ and PEG₄₀₀₀ with a PEG loading of approximately 11% in all cases. PEG loading generated non-uniform and heterogeneous higher surface structures and increased nanotube width considerably, but all PEGylated nanotube species activated the complement system in human serum equally. Increased PEG loading, through adsorption of methoxyPEG₂₀₀₀(or ₅₀₀₀)-phospholipid conjugates, generated fewer complement activation products; however, complement activation was never completely eliminated. Our observations address the difficulty in making carbon nanotubes more compatible with innate immunity through covalent PEG functionalization as well as double PEGylation strategies., From the Clinical Editor: Complement-mediated toxicity is a major limiting factor in certain nanomedicine applications. This study clarifies that PEGylation of carbon nanotubes is unlikely to address this complication., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Internet-based mental health services increase rapidly. However, national surveys are incomplete and the consequences for such services are poorly discussed. This study describes characteristics of 60 Internet-based mental health services in Norway and Sweden and discusses their social consequences. More than half of the services were offered by voluntary organisations and targeted towards young people. Professionals answered service users' questions in 60% of the services. Eight major themes were identified. These characteristics may indicate a shift in the delivery of mental health services in both countries, and imply changes in the understanding of mental health.

Carbon nanotubes (CNTs) are receiving considerable attention in site-specific drug and nucleic acid delivery, photodynamic therapy, and photoacoustic molecular imaging. Despite these advances, nanotubes may activate the complement system (an integral part of innate immunity), which can induce clinically significant anaphylaxis. We demonstrate that single-walled CNTs coated with human serum albumin activate the complement system through C1q-mediated classical and the alternative pathways. Surface coating with methoxypoly(ethylene glycol)-based amphiphiles, which confers solubility and prolongs circulation profiles of CNTs, activates the complement system differently, depending on the amphiphile structure. CNTs with linear poly(ethylene glycol) amphiphiles trigger the lectin pathway of the complement through both L-ficolin and mannan-binding lectin recognition. The lectin pathway activation, however, did not trigger the amplification loop of the alternative pathway. An amphiphile with branched poly(ethylene glycol) architecture also activated the lectin pathway but only through L-ficolin recognition. Importantly, this mode of activation neither generated anaphylatoxins nor induced triggering of the effector arm of the complement system. These observations provide a major step toward nanomaterial surface modification with polymers that have the properties to significantly improve innate immunocompatibility by limiting the formation of complement C3 and C5 convertases.

Carbon nanotubes are entities of different morphology and aspect ratios with anisotropic character. Due to their unique electronic, photonic, mechanical and chemical properties, carbon nanotubes are receiving increasing attention in nanomedicine research where examples include site-specific drug and nucleic acid delivery, photodynamic therapy and photoacoustic molecular imaging. The interaction of carbon nanotubes with the immune system, which plays a key role in the recognition and elimination of foreign materials, and consequential responses, is of central importance for the proposed successful biomedical applications of nanotubes. Research in this avenue, however, is scant and the limited available data are rather contradictory. In this progress article we have collected some of the most important experimental results obtained thus far on carbon nanotube-mediated immune toxicity with an emphasis on cardiovascular exposure, including activation of the complement system, macrophage recognition and clearance, and overall effects on the functionality of different immune cells. Mapping these immune-related risks as well as understanding their molecular mechanisms is a crucial step in the development of any carbon nanotube-containing nanopharmaceuticals., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Slurry acidification using sulfuric acid reduces ammonia emissions but also affects sulfur (S) cycling. Emission of sulfur is a source of malodor and reduces the sulfur fertilizer value of the slurry. We investigated the effect of sulfate and methionine amendments, alone or in combination with acidification, on sulfur transformations in slurry and emissions of volatile sulfur compounds (VSC) during storage of fresh and aged cattle slurry. When pH was lowered to 5.5 it resulted in an almost complete inhibition of sulfate reduction. There was a huge emission of hydrogen sulfide (HS) with addition of sulfate and methionine ( < 0.01). Methanethiol (MT) was emitted in treatments with addition of methionine, especially when simultaneously acidified ( < 0.01). The large HS production in the sulfate-amended slurries resulted in little accumulation of MT and dimethyl sulfide (DMS) under neutral conditions, in contrast to acidic conditions where the degradation was inhibited and both MT and DMS accumulated. Based on odor activity values, untreated slurry had little odor development from S compounds, especially the aged slurry. Acidification did not significantly increase odor contribution from any of the compounds in fresh or aged slurry. Generally, addition of a sulfate increased the contribution from HS dramatically, whereas acidification lowered the HS contribution but increased that of MT. Thus, acidification of slurry with sulfuric acid may potentially produce more odor from S compounds than untreated slurry., (Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)

Several nanoparticle systems and supramolecular assemblies are under investigation as potential therapeutic entities for Alzheimer's disease and other neurological disorders through both brain-specific targeting and peripheral effects. However, activation of the complement system, a complex innate immune network of over 30 circulating and membrane-bound proteins, remains a serious concern related to the use of these prospective neurological nanomedicines. The role of complement in processes of neurodegeneration in the injured or aged and diseased central nervous system is well known. Nanoparticle-mediated complement activation cannot only induce adverse cardiopulmonary distress in sensitive subjects, but may further aggravate the already-compromised condition of neurological disorders and diseases. This minireview briefly examines the role of complement in neurological diseases and outlines the current status of the development of key neurological nanomedicines with respect to complement activation. Understanding of these topics is crucial for rational design and development of safe neurological nanomedicines., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Some people who by themselves or by others are understood as having mental health problems have written autobiographies about their experiences., Aims: The aim of this study is to explore how people write about their experiences of being mentally ill., Method: Twelve Scandinavian autobiographies were studied using content analysis based on phenomenology and hermeneutics., Results: Three themes were identified: feeling like a stranger in life and places, the transformation of life experiences into questions of disease and feeling ashamed., Conclusions: People's experiences of being mentally ill might be understood as the result of medical constructions unsuitable for the persons themselves. We could instead say that mental problems are not diseases, but severe and painful phenomena in people's lives.

Slurry acidification before storage is known to reduce NH(3) emissions, but recent observations have indicated that CH(4) emissions are also reduced. We investigated the evolution of CH(4) from fresh and aged cattle slurry during 3 mo of storage as influenced by pH adjustment to 5.5 with sulfuric acid. In a third storage experiment, cattle slurry acidified with commercial equipment on two farms was incubated. In the manipulation experiments, effects of acid and sulfate were distinguished by adding hydrochloric acid and potassium sulfate separately or in combination, rather than sulfuric acid. In one experiment sulfur was also added to slurry as the amino acid methionine in separate treatments. In each treatment 20-kg portions of slurry (n = 4) were stored for 95 d. All samples were subsampled nine to 10 times for determination of NH(3) and CH(4) evolution rates using a 2-L flow-through system. In all experiments, the pH of acidified cattle slurry increased gradually to between 6.5 and 7. Acidification of slurry reduced the evolution of CH(4) by 67 to 87%. The greatest reduction was observed with aged cattle slurry, which had a much higher potential for CH(4) production than fresh slurry. Sulfate and methionine amendment to cattle slurry without pH adjustment also significantly inhibited methanogenesis, probably as a result of sulfide production. The study suggests that complex microbial interactions involving sulfur transformations and pH determine the potential for CH(4) emission during storage of cattle slurry, and that slurry acidification may be a cost-effective greenhouse gas mitigation option., (Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)

The shortage of plant-available nutrients probably constrained prehistoric cereal cropping but there is very little direct evidence relating to the history of ancient manuring. It has been shown that the long-term addition of animal manure elevates the δ(15)N value of soil and of modern crops grown on the soil. We have examined the δ(15)N and δ(13)C values of soil and of the grain and straw fractions of three ancient cereal types grown in unmanured, PK amended and cattle manured plots of the Askov long-term field experiment. Manure increased biomass yields and the δ(15)N values of soil and of grain and straw fractions of the ancient cereal types; differences in δ(15)N between unmanured and PK treatments were insignificant. The offset in straw and grain δ(15)N due to manure averaged 7.9 and 8.8 ‰, respectively, while the soil offset was 1.9 ‰. The soil and biomass δ(13)C values were not affected by nutrient amendments. Grain weights differed among cereal types but increased in the order: unmanured, PK, and animal manure. The grain and straw total-N concentration was generally not affected by manure addition. Our study suggests that long-term application of manure to permanently cultivated sites would have provided a substantial positive effect on cereals grown in early agriculture and will have left a significant N isotopic imprint on soil, grains and straw. We suggest that the use of animal manure can be identified by the (15)N abundance in remains of ancient cereals (e.g. charred grains) from archaeological sites and by growing test plants on freshly exposed palaeosols., (Copyright © 2011 John Wiley & Sons, Ltd.)

Uncontrolled complement activation can induce many inflammatory and life threatening conditions. Accordingly, the role of complement in initiation of adverse reactions to polymers and nanoparticulate drug carriers is receiving increasing attention and has prompted extensive 'structure-immune performance' relationship studies in nanomedicine research at many fronts. The interaction between nanomaterials and the complement system is complex and regulated by inter-related factors that include nanoscale size, morphology and surface characteristics. Each of these parameters may affect complement activation differently and through different sensing molecules and initiation pathways. The importance of material properties in triggering complement is considered and mechanistic aspects discussed. Mechanistic understanding of complement events could provide rational approaches for improved material design and nanoengineering strategies for clinical medicine., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Since their introduction, poly(ethylene glycol)-phospholipid (PEG-PL) conjugates have found many applications in design and engineering of nanosized delivery systems for controlled delivery of pharmaceuticals especially to non-macrophage targets. However, there are reports of idiosyncratic reactions to certain PEG-PL engineered nanomedicines in both experimental animals and man. These reactions are classified as pseudoallergy and may be associated with cardiopulmonary disturbance and other related symptoms of anaphylaxis. Recent studies suggest that complement activation may be a contributing, but not a rate limiting factor, in eliciting hypersensitivity reactions to such nanomedicines in sensitive individuals. This is rather surprising since PEGylated structures are generally assumed to suppress protein adsorption and blood opsonization events including complement. Here, we examine the molecular basis of complement activation by PEG-PL engineered nanomedicines and carbon nanotubes and discuss the challenges ahead., (Copyright 2010 Elsevier B.V. All rights reserved.)

Administration of liposome- and polymer-based clinical nanomedicines, as well as many other proposed multifunctional nanoparticles, often triggers hypersensitivity reactions without the involvement of IgE. These anaphylactic reactions are believed to be secondary to activation of the complement system, giving rise to the release of anaphylatoxins C3a and C5a that initiate a wide array of responses through their effect on mast cells, polymorphonuclear cells, platelets and monocytes. Additionally, the terminal complement C5b-9 complex induces platelet activation, thereby enhancing their procoagulant activity, and has the capacity to elicit non-lytic stimulatory responses from vascular endothelial cells. Here we discuss the molecular basis of complement activation by liposomes, including poly(ethylene glycol) coated vesicles, and other related lipid-based and phospholipid-poly(ethylene glycol) conjugate stabilized entities. We have further considered the role of these complement activating entities in experimental oncology since intra-tumoural complement activation is suggested to induce tumour growth and progression.

During the manufacture of a proprietary peptide drug substance a new impurity appeared unexpectedly. Investigation of its chemical structure established the impurity as a beta-Ala insertion mutant of the mother peptide. The source of the beta-Ala was identified as contamination of the Fmoc-Ala-OH raw material with Fmoc-beta-Ala-Ala-OH. Further studies also demonstrated the presence of beta-Ala in other Fmoc-amino acids, particularly in Fmoc-Arg(Pbf)-OH. In this case, it was due to the presence of both Fmoc-beta-Ala-OH and Fmoc-beta-Ala-Arg(Pbf)-OH. It is concluded that beta-Ala contamination of Fmoc-amino acid derivatives is a general and hitherto unrecognized problem to suppliers of Fmoc-amino acid derivatives. The beta-Ala is often present as Fmoc-beta-Ala-OH and/or as a dipeptide, Fmoc-beta-Ala-amino acid-OH. In collaboration with the suppliers, new specifications were introduced, recognizing the presence of beta-Ala-related impurities in the raw materials and limiting them to acceptable levels. The implementation of these measures has essentially eliminated beta-Ala contamination as a problem in the manufacture of the drug substance.

The wasp toxin philanthotoxin-433 (PhTX-433) is a nonselective and noncompetitive antagonist of ionotropic receptors, such as ionotropic glutamate receptors and nicotinic acetylcholine receptors. Polyamine toxins are extensively used for the characterization of subtypes of ionotropic glutamate receptors, in particular Ca(2+)-permeable AMPA and kainate receptors. We have previously shown that an analogue of PhTX-433 with one of the amino groups replaced by a methylene group, philanthotoxin-83 (PhTX-83) is a selective and potent antagonist of AMPA receptors. We now describe the solid-phase synthesis of analogues of PhTX-83 and the electrophysiological characterization of these analogues on cloned AMPA and kainate receptors. The polyamine portion of PhTX-83 was modified systematically by changing the position of the secondary amino group along the polyamine chain. In another series of analogues, the acyl moiety of PhTX-83 was replaced by acids of different size and lipophilicity. Using electrophysiological techniques, PhTX-56 was shown to be a highly potent (K(i) = 3.3 +/- 0.78 nM) and voltage-dependent antagonist of homomeric GluR1 receptors and was more than 1000-fold less potent when tested on heteromeric GluR1+GluR2, as well as homomeric GluR5(Q) receptors, thus being selective for Ca(2+)-permeable AMPA receptors. Variation of the acyl group of PhTX-83 had only minor effect on antagonist potency at homomeric GluR1 receptors but led to a significant decrease in the voltage-dependence. In conclusion, PhTX-56 is a novel, very potent, and selective antagonist of Ca(2+)-permeable AMPA receptors and is a promising tool for structure/function studies of the ion channel of the AMPA receptor.

A method for isolation of mitochondria from 25-100 mg skeletal muscle is described. The instrumental developments include a refined homogenization setup, special handling techniques, and equipment for biopsy storage. The preparation medium was a standard ionic medium. All fractions were assayed for marker enzymes and the data used in optimization of the yield. It was observed that the homogenization procedure exerts strong control on the integrity of the isolated mitochondria. The method was developed with pigeon breast muscle as the model tissue and used virtually unaltered for preparation from muscles of pigs, rats, and humans. The relative yield was 40-50% and the mitochondria were well coupled and showed high rates of phosphorylating respiration.

Mitochondria were isolated from biopsies of the biceps femoris muscle of Danish landrace pigs. Three groups of animals were compared: (1) normal pigs; (2) pigs that were homozygous with respect to the gene Hal(n)/Hal(n) coding for the porcine malignant hyperthermia syndrome; and (3) heterozygote animals. A newly developed micro-method for preparation and assaying of small quantities of intact mitochondria was employed. With this technique mitochondria from biopsies weighing less than 100 mg were examined with respect to cytochrome content as well as phosphorylating and respiratory activities, including the nonphosphorylating exo-NADH oxidase activity. The mitochondria, prepared in a yield of 48%, showed high respiratory activities with tricarboxylic acid-cycle intermediates and pyruvate, and somewhat lower activity with palmitoyl-carnitine as substrate. The ATP synthase activity was about 1000 micromol ATP/min per g of protein and the maximal respiratory activity approx. 700 micromol of O2/min per g of protein. No differences among the three groups of animals were detected, except for the exo-NADH oxidase activities, which were 43, 78 and 107 micromol of O2/min per g of protein in the groups of normal, heterozygous and homozygous animals respectively. It is concluded that the exo-NADH oxidase activity may be a genetic manifestation of malignant hyperthermia and may play a significant role in the heat production characteristic of the syndrome.

Flow cytometric DNA analysis was performed on unfixed frozen tissue samples from 48 cases of invasive breast cancer (IC) with a predominance of ductal carcinoma in situ (DCIS). In 15 cases the samples contained only the DCIS component, in 17 cases only the IC component, whereas in 16 cases separate samples from the DCIS as well as the IC part within the individual lesion were available. In the latter 16 cases, complete or partial accordance in DNA ploidy between DCIS and IC was found in 12 cases, whereas no correspondence could be demonstrated in the remaining 4 cases, possibly due to intratumoral DNA heterogeneity. Comparison of the DNA index distribution in samples of DCIS and IC from the 48 cases showed concordant results except for the DNA hyperdiploid subclass, in which 6 clones were found in the DCIS portion compared to 18 clones in the IC portion. S-phase fractions were also comparable in the two groups. A comparison of the DCIS component from the present series of breast cancers to our previous series of pure DCIS also showed similar results with respect to the DNA index distribution, DNA heterogeneity, and S-phase fraction. No differences could be demonstrated between DCIS with and without invasion. The results indicate that the DNA ploidy pattern of breast cancer, as detected by flow cytometric DNA analysis, is established at the preinvasive stage of carcinogenesis.

In a prospective randomized trial the frequency of infectious complications and natural killer cell function were investigated in 197 patients undergoing elective colorectal surgery and having either no blood transfusion (n = 93), transfusion with whole blood (n = 56), or filtered blood free from leucocytes (n = 48). Postoperative infections developed in 13 patients transfused with whole blood (23%), in one patient transfused with blood free from leucocytes (2%) and in two non-transfused patients (2%) (p < 0.01). Natural killer cell function was significantly (p < 0.001) impaired up to 30 days after surgery in patients transfused with whole blood. These data provide a strong case against the use of whole blood transfusion in patients undergoing elective colorectal surgery.

The frequency of infection in 197 patients undergoing elective colorectal surgery and having either no blood transfusion, transfusion with whole blood, or filtered blood free from leucocytes and platelets was investigated in a prospective randomized trial. Natural killer cell function was measured before operation and 3, 7 and 30 days after surgery in 60 consecutive patients. Of the patients 104 required blood transfusion; 48 received filtered blood and 56 underwent whole blood transfusion. Postoperative infections developed in 13 patients transfused with whole blood (23 per cent, 95 per cent confidence interval 13-32 per cent), in one patient transfused with blood free from leucocytes and platelets (2 per cent, 95 per cent confidence interval 0.05-11 per cent) and in two non-transfused patients (2 per cent, 95 per cent confidence interval 0.3-8 per cent) (P less than 0.01). Natural killer cell function was significantly (P less than 0.001) impaired up to 30 days after surgery in patients transfused with whole blood. These data provide a strong case against the use of whole blood transfusion in patients undergoing elective colorectal surgery.

A probe for simultaneous measurement of cross-sectional area and pressure was used to elucidate biomechanical wall properties during anal distension. Measurements in distal sphincter regions demonstrated a high resistance to stretch and a large hysteresis compared to proximal sphincter regions. Resistance to stretch decreased during anal distension indicating an active relaxation mechanism at all recording levels. The zone with high resistance to stretch was located more distal than the high-pressure zone measured by anal-pressure profilometry. In conclusion, biomechanical wall properties of the anal canal cannot be described by classic viscoelastic theories but rather by a loss of sphincter tone caused by reflex mechanism during anal distension.

Seventy one patients were included in a prospective study of non-surgical treatment of vesico-ureteral reflux (VUR). We found 111 refluxing ureters, with 20 grade 1, 4 grade 2, 41 grade 3, 5 grade 4 and 1 grade 5. There was no correlation between presenting symptoms and degree of VUR or nephropathy, or between renal function in terms of glomerular filtration rate. During followup the patients were treated with long-term low-dose antibiotic prophylaxis and voiding disorders were corrected pharmacologically or by micturitional training. With a median follow up time of 6 years (3-10) 63% of the patients had cessation or down grading of VUR, irrespective of initial VUR degree. There was no correlation between cessation rate and urodynamic parameters, GFR, history of enuresis or previous urinary infections. The study supports a non-surgical attitude towards VUR patients irrespective of VUR degree, with prophylaxis of urinary infections and possibly correction of voiding disorders.