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What is this Professor Freud like? : a diary of an analysis with historical comments
\"In 1921, a young female doctor started analysis with Sigmund Freud. In a diary, she recorded what moved her. The present volume not only contains a full translation of these records, but also collects four essays by two psychoanalysts and two analytical historians who take their cue from the young doctor's notes to think about Freud and his methods. The discovery of the diary marks a small sensation for the history of social science. Three factors make the document unique: first, it records not a training analysis, but the analysis of an actual patient, second, the analysis took place before Freud fell ill with cancer, and third, the analysand obviously noted down what was said in the practice word by word. As Ernst Falzeder notes,'no other account published to date meets all three of these conditions'\"--Provided by publisher.
Book
Oxidative Stress in Non-alcoholic Fatty Liver Disease. An Updated Mini Review
Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it remains still orphan of an adequate therapeutic strategy. Herein we focus on the interplay between oxidative stress (OS) and the other causal pathogenetic factors. Different reactive oxygen species (ROS) generators contribute to NAFLD inflammatory and fibrotic progression, which is quite strictly linked to the lipotoxic liver injury from fatty acids and/or a wide variety of their biologically active metabolites in the context of either a two-hit or a (more recent) multiple parallel hits theory. An antioxidant defense system is usually able to protect hepatic cells from damaging effects caused by ROS, including those produced into the gastrointestinal tract, i.e., by-products generated by usual cellular metabolic processes, normal or dysbiotic microbiota, and/or diet through an enhanced gut–liver axis. Oxidative stress originating from the imbalance between ROS generation and antioxidant defenses is under the influence of individual genetic and epigenetic factors as well. Healthy diet and physical activity have been shown to be effective on NAFLD also with antioxidant mechanisms, but compliance to these lifestyles is very low. Among several considered antioxidants, vitamin E has been particularly studied; however, data are still contradictory. Some studies with natural polyphenols proposed for NAFLD prevention and treatment are encouraging. Probiotics, prebiotics, diet, or fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors will likely assist in further selecting the treatment that could work best for a specific patient.
Journal Article
General interests of host states in international investment law
\"Signatory States have the right to take action in order to maintain their financial stability, stimulate economic development or further their non-economic interests (such as health, the environment and food security). However, such measures can potentially conflict with the rights of foreign investors. Regulators and policy makers must take States' international commitments toward foreign investors into account when making decisions. They must also avoid resorting to protectionism in drafting new treaties. With this tension in mind, this book offers a balanced reappraisal of bilateral treaties and regional agreements on foreign investments. The sensitive issues are examined in the light of the case law of arbitral investment tribunals and other international courts, and the analysis highlights how cross-fertilisation between trade and investment can assist in resolving conflicts\"-- Provided by publisher.
Book
Adrenal Incidentalomas are Tied to Increased Risk of Diabetes: Findings from a Prospective Study
Abstract
Context
The frequency of adrenal incidentalomas and their association with comorbid conditions have been assessed mostly in retrospective studies that may be prone to ascertainment bias.
Objective
The objective of this work is to evaluate the frequency of adrenal incidentalomas and their associated comorbid conditions.
Design
A prospective cohort study was conducted.
Setting
This study took place at a radiology department at a public hospital.
Participants
Unselected outpatients who underwent an abdominal computed tomography (CT) from January 2017 to June 2018. Patients with known or suspected adrenal disease or malignancy were excluded.
Exposure
All abdominal CT scans were evaluated by an experienced radiologist. Hormonal workup including a 1-mg dexamethasone suppression test was performed in patients bearing adrenal incidentalomas.
Main Outcome and Measure
Frequency of adrenal incidentalomas in abdominal CT of unselected patients; frequency of comorbid conditions, and hormonal workup in patients bearing adrenal incidentalomas.
Results
We recruited 601 patients, and in 7.3% of them an adrenal tumor was found serendipitously. The patients bearing an adrenal incidentaloma had higher body mass index (P = .009) and waist circumference (P = .004) and were more frequently diabetic (P = .0038). At multivariable regression analysis, diabetes was significantly associated with the presence of adrenal incidentalomas (P = .003). Autonomous cortisol secretion was observed in 50% of patients who did not suppress cortisol less than 50 nmol/L after 1 mg dexamethasone.
Conclusions
The frequency of adrenal incidentalomas is higher than previously reported. Moreover, adrenal incidentalomas are tied to increased risk of type 2 diabetes. This finding is free from ascertainment bias because patients with adrenal incidentalomas were drawn from a prospective cohort with the same risk of diabetes as the background population.
Journal Article
Linagliptin prevents left ventricular stiffening by reducing titin cleavage and hypophosphorylation
The metabolic syndrome (MetS) is an escalating problem worldwide, causing left ventricular stiffening, an early characteristic of diastolic dysfunction for which no treatment exists. As diastolic dysfunction and stiffening in MetS patients are associated with increased circulating dipeptidyl peptidase‐4 (DPP‐4) levels, we investigated whether the clinically approved DPP‐4 inhibitor linagliptin reduces left ventricular stiffness in MetS‐induced cardiac disease. Sixteen‐week‐old obese ZSF1 rats, displaying the MetS and left ventricular stiffness, received linagliptin‐supplemented or placebo diet for four weeks. Linagliptin significantly reduced obesity, hyperlipidaemia, and hyperglycaemia and improved left ventricular relaxation. This improved relaxation was related to decreased cardiac fibrosis and cardiomyocyte passive stiffness (Fpassive). The reduced Fpassive was the result of titin isoform switching from the stiff N2B to the more flexible N2BA and increased phosphorylation of total titin and specifically its N2Bus region (S4080 and S3391). Importantly, DPP‐4 directly cleaved titin in vitro, resulting in an increased Fpassive, which was prevented by simultaneous administration of linagliptin. In conclusion, linagliptin improves left ventricular stiffness in obese ZSF1 rats by preventing direct DPP4‐mediated titin cleavage, as well as by modulating both titin isoform levels and phosphorylation. Reducing left ventricular stiffness by administering linagliptin might prevent MetS‐induced early diastolic dysfunction in human.
Journal Article
AMPKα1 deletion in myofibroblasts exacerbates post-myocardial infarction fibrosis by a connexin 43 mechanism
We have previously demonstrated that systemic AMP-activated protein kinase α1 (AMPKα1) invalidation enhanced adverse LV remodelling by increasing fibroblast proliferation, while myodifferentiation and scar maturation were impaired. We thus hypothesised that fibroblastic AMPKα1 was a key signalling element in regulating fibrosis in the infarcted myocardium and an attractive target for therapeutic intervention. The present study investigates the effects of myofibroblast (MF)-specific deletion of AMPKα1 on left ventricular (LV) adaptation following myocardial infarction (MI), and the underlying molecular mechanisms. MF-restricted AMPKα1 conditional knockout (cKO) mice were subjected to permanent ligation of the left anterior descending coronary artery. cKO hearts exhibit exacerbated post-MI adverse LV remodelling and are characterised by exaggerated fibrotic response, compared to wild-type (WT) hearts. Cardiac fibroblast proliferation and MF content significantly increase in cKO infarcted hearts, coincident with a significant reduction of connexin 43 (Cx43) expression in MFs. Mechanistically, AMPKα1 influences Cx43 expression by both a transcriptional and a post-transcriptional mechanism involving miR-125b-5p. Collectively, our data demonstrate that MF-AMPKα1 functions as a master regulator of cardiac fibrosis and remodelling and might constitute a novel potential target for pharmacological anti-fibrotic applications.
Journal Article
Effectiveness of gamified digital interventions in mental health prevention and health promotion among adults: a scoping review
Background
Though still a young field of research, gamified digital interventions have demonstrated potential in exerting a favourable impact on health and overall well-being. With the increasing use of the internet and digital devices, the integration of game elements presents novel opportunities for preventing mental disorders and enhancing mental health. Hence, this review aims to assess the effectiveness of gamified interventions focusing on preventing mental disorders or promoting mental health among adults.
Methods
Based on a scoping review across four databases (MEDLINE, Embase, PsycInfo and Web of Science), 7,953 studies were initially identified. After removing duplicates and screening titles, abstracts and full texts, 16 studies were identified as suitable for inclusion in a narrative synthesis of findings. We included interventional studies encompassing an intervention and a control group aiming to investigate the effectiveness of the use of gamified digital mental health interventions and the use of gamified digital elements.
Results
Overall, positive effects of gamified interventions on mental health-related outcomes were identified. In particular, beneficial consequences for psychological well-being and depressive symptoms were observed in all studies. However, further outcomes, such as resilience, anxiety, stress or satisfaction with life, showed heterogenous findings. Most game elements used were reward, sensation and progress, whilst the quantity of elements was not consistent and, therefore, no substantiated conclusion regarding the (optimal) quantity or composition of game elements can be drawn. Further, the outcomes, measurements and analyses differed greatly between the 16 included studies making comparisons difficult.
Conclusion
In summary, this review demonstrates the potential of integrating digital game elements on mental health and well-being with still a great gap of research. A taxonomy is needed to adequately address relevant game elements in the field of mental health promotion and prevention of mental disorders. Therefore, future studies should explicitly focus on the mechanisms of effect and apply rigorous study designs.
Journal Article
Extracellular SPARC increases cardiomyocyte contraction during health and disease
Secreted protein acidic and rich in cysteine (SPARC) is a non-structural extracellular matrix protein that regulates interactions between the matrix and neighboring cells. In the cardiovascular system, it is expressed by cardiac fibroblasts, endothelial cells, and at lower levels by ventricular cardiomyocytes. SPARC expression levels are increased upon myocardial injury and also during hypertrophy and fibrosis. We have previously shown that SPARC improves cardiac function after myocardial infarction by regulating post-synthetic procollagen processing, however whether SPARC directly affects cardiomyocyte contraction is still unknown. In this study we demonstrate a novel inotropic function for extracellular SPARC in the healthy heart as well as in the diseased state after myocarditis-induced cardiac dysfunction. We demonstrate SPARC presence on the cardiomyocyte membrane where it is co-localized with the integrin-beta1 and the integrin-linked kinase. Moreover, extracellular SPARC directly increases cardiomyocyte cell shortening ex vivo and cardiac function in vivo, both in healthy myocardium and during coxsackie virus-induced cardiac dysfunction. In conclusion, we demonstrate a novel inotropic function for SPARC in the heart, with a potential therapeutic application when myocyte contractile function is diminished such as that caused by a myocarditis-related cardiac injury.
Journal Article
Prevalence of breast-feeding in the Norwegian Mother and Child Cohort Study and health service-related correlates of cessation of full breast-feeding
First, to describe the prevalence of both full and partial breast-feeding during the first 6 months; second, to study the associations between selected health service-related factors and cessation of full breast-feeding at three time intervals.
Retrospective questionnaires, 6 months after birth.
The Norwegian Mother and Child Cohort Study (MoBa).
In total, 29 621 women.
While 96·6 %, 94·0 %, 90·8 %, 86·9 %, 83·8 % and 80·0 % of the infants were breast-fed at 1, 2, 3, 4, 5 and 6 months, respectively, the corresponding proportions for full breast-feeding were 84·6 %, 79·1 %, 70·9 %, 44·0 %, 16·7 % and 2·1 %. An increased risk of cessation of full breast-feeding during the first month was associated with supplementation during the first week of life with water (relative risk (RR) 1·77; 95 % CI 1·52, 2·06), sugar water (RR 1·73; 95 % CI 1·49, 2·00) or formula (RR 5·99; 95 % CI 5·58, 6·42). An increased risk was also associated with Caesarean delivery (RR 1·08; 95 % CI 1·00, 1·16) and breast-feeding problems (RR 1·56; 95 % CI 1·45, 1·67). Between months 1 and 3, the risk of cessation of full breast-feeding remained elevated in the case of supplementation during the first week of life with water (RR 1·29; 95 % CI 1·14, 1·45), sugar water (RR 1·48; 95 % CI 1·34, 1·64) or formula (RR 1·18; 95 % CI 1·07, 1·29). The same applied to Caesarean delivery (RR 1·15; 95 % CI 1·06, 1·25).
Supplementation during the first week, breast-feeding problems and Caesarean delivery are associated with early cessation of full breast-feeding. The results support a cautious approach to supplementation during the first week of life.
Journal Article
Development and Validation of the MAST ISOPLEX® VTEC Kit for Simultaneous Detection of Shiga Toxin/Verotoxin 1 and 2 (stx1/vt1 and stx2/vt2) with Inhibition Control (IC) in a Rapid Loop-Mediated Isothermal Amplification (LAMP) Multiplex Assay
Loop-mediated isothermal amplification (LAMP) is a cost-effective, rapid, and highly specific method of replicating nucleic acids. Adding multiple targets into a single LAMP assay to create a multiplex format is highly desirable for clinical applications but has been challenging due to a need to develop specific detection techniques and strict primer design criteria. This study describes the evaluation of a rapid triplex LAMP assay, MAST ISOPLEX® VTEC, for the simultaneous detection of Shiga toxin/verotoxin 1 and 2 (stx1/vt1 and stx2/vt2) genes in verotoxigenic Escherichia coli (E. coli) (VTEC) isolates with inhibition control (IC) synthetic DNA using a single fluorophore–oligonucleotide probe, MAST ISOPLEX® Probes, integrated into the primer set of each target. MAST ISOPLEX® Probes used in the MAST ISOPLEX® VTEC kit produce fluorescent signals as they integrate with reaction products specific to each target, allowing tracking of multiple amplifications in real time using a real-time analyzer. Initial validation on DNA extracts from fecal cultures and synthetic DNA sequences (gBlocks) showed that the MAST ISOPLEX® VTEC kit provides a method for sensitive simultaneous triplex detection in a single assay with a limit of detection (LOD) of less than 100 target copies/assay and 96% and 100% sensitivity and specificity, respectively.
Journal Article