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The functional differentiation of the mammary gland (MG) is fundamental for the prevention of mammary pathologies. This process occurs throughout pregnancy and lactation, making these stages key events for the study of pathologies associated with development and differentiation. Many studies have investigated the link between mammary pathologies and thyroid diseases, but most have ignored the role of thyroid hormone (TH) in the functional differentiation of the MG. In this work, we show the long-term impact of hypothyroidism in an animal model whose lactogenic differentiation occurred at low TH levels. We evaluated the ability of the MG to respond to hormonal control and regulate cell cycle progression. We found that a deficit in TH throughout pregnancy and lactation induces a long-term decrease in Rb phosphorylation, increases p53, p21, Cyclin D1 and Ki67 expression, reduces progesterone receptor expression, and induces nonmalignant lesions in mammary tissue. This paper shows the importance of TH level control during mammary differentiation and its long-term impact on mammary function.
The finite dual
of an affine commutative-by-finite Hopf algebra H is studied. Such a Hopf algebra H is an extension of an affine commutative Hopf algebra A by a finite dimensional Hopf algebra
. The main theorem gives natural conditions under which
decomposes as a crossed or smash product of
by the finite dual
of A. This decomposition is then further analysed using the Cartier–Gabriel–Kostant theorem to obtain component Hopf subalgebras of
mapping onto the classical components of
. The detailed consequences for a number of families of examples are then studied.
Accumulating evidence suggests beneficial effects of media stories featuring individuals mastering their suicidal crises, but effects have not been assessed for psychiatric patients.
We randomized n = 172 adult psychiatric patients (n = 172, 97.1% inpatients) to read an educative article featuring a person mastering a suicidal crisis (n = 92) or an unrelated article (n = 80) in a single-blind randomized controlled trial. Questionnaire data were collected before (T1) and after exposure (T2) as well as 1 week later (study end-point, T3). The primary outcome was suicidal ideation as assessed with the Reasons for Living Inventory; secondary outcomes were help-seeking intentions, mood, hopelessness, and stigmatization. Differences between patients with affective versus other diagnoses were explored based on interaction tests.
We found that patients with affective disorders (n = 99) experienced a small-sized reduction of suicidal ideation at 1-week follow up (mean difference to control group [MD] at T3 = −0.17 [95% CI −0.33, −0.03], d = −0.15), whereas patients with nonaffective diagnoses (n = 73) experienced a small-sized increase (T2: MD = 0.24 [95% CI 0.06, 0.42], d = 0.19). Intervention group participants further experienced a nonsustained increase of help-seeking intentions (T2: MD = 0.53 [95% CI 0.11, 0.95], d = 0.19) and a nonsustained deterioration of mood (T2: MD = −0.14 [95% CI −0.27, −0.02], d = −0.17).
This study suggests that patients with affective disorders appear to benefit from media materials featuring mastery of suicidal crises. More research is needed to better understand which patient groups are at possible risk of unintended effects.
There seems to exist a general consensus on how to conceptualize cooperation in the field of international relations (IR). We argue that this impression is deceptive. In practice, scholars working on the causes of international cooperation have come to implicitly employ various understandings of what cooperation is. Yet, an explicit debate about the discipline's conceptual foundations never materialized, and whatever discussion occurred did so only latently and without much dialog across theoretical traditions. In this paper, we develop an updated conceptual framework by exploring the nature of these differing understandings and situating them within broader theoretical conversations about the role of cooperation in IR. Drawing on an array of studies in IR and philosophy, our framework distinguishes between three distinct types of cooperative state interactions – cooperation through tacit policy coordination (‘minimal’ cooperation), cooperation through explicit policy coordination (‘thin’ cooperation), and cooperation based on joint action (‘thick’ cooperation). The framework contributes to better theorization about cooperation in two main ways: it allows scholars across theoretical traditions to identify important sources of disagreement and previously unnoticed theoretical common ground; and the conceptual disaggregation it provides grants scholars crucial theoretical leverage by enabling type-specific causal theorization.
This study aims at providing estimates on the transmission risk of SARS-CoV-2 in schools and day-care centres. We calculated secondary attack rates (SARs) using individual-level data from state-wide mandatory notification of index cases in educational institutions, followed by contact tracing and PCR-testing of high-risk contacts. From August to December 2020, every sixth of overall 784 independent index cases was associated with secondary cases in educational institutions. Monitoring of 14 594 institutional high-risk contacts (89% PCR-tested) of 441 index cases during quarantine revealed 196 secondary cases (SAR 1.34%, 0.99–1.78). SARS-CoV-2 infection among high-risk contacts was more likely around teacher-indexes compared to student-/child-indexes (incidence rate ratio (IRR) 3.17, 1.79–5.59), and in day-care centres compared to secondary schools (IRR 3.23, 1.76–5.91), mainly due to clusters around teacher-indexes in day-care containing a higher mean number of secondary cases per index case (142/113 = 1.26) than clusters around student-indexes in schools (82/474 = 0.17). In 2020, SARS-CoV-2 transmission risk in educational settings was low overall, but varied strongly between setting and role of the index case, indicating the chance for targeted intervention. Surveillance of SARS-CoV-2 transmission in educational institutions can powerfully inform public health policy and improve educational justice during the pandemic.
Recently developed quantitative models of psychopathology (i.e., Hierarchical Taxonomy of Psychopathology) identify an Antagonistic Externalizing spectrum that captures the psychological disposition toward criminal and antisocial behavior. The purpose of the present study was to examine relations between Antagonistic psychopathology (and associated Five-Factor model Antagonism/Agreeableness) and neural functioning related to social-cognitive Theory of Mind using a large sample (N = 973) collected as part of the Human Connectome Project (Van Essen et al., 2013a). No meaningful relations between Antagonism/Antagonistic Externalizing and Theory of Mind-related neural activity or synchrony were observed (p < .005). We conclude by outlining methodological considerations (e.g., validity of social cognition task and low test–retest reliability of functional biomarkers) that may account for these null results, and present recommendations for future research.
Negotiated agreements in criminal proceedings have often been regarded as the embodiment of a negative wider trend towards the informalization of the criminal procedure, and have—especially in Germany—long been the subject of vivid controversies. A criminal proceeding in the traditional sense aims to establish the truth ex officio, which is achieved by means of a comprehensive inquiry into the facts conducted by the court during the trial, followed by a sentence that appropriately reflects the individual guilt of the defendant, which can then, in turn, achieve the procedural objective of “justice.” A streamlining of the extensive inquiry into the facts that the court would normally have to conduct via the consensual process of negotiation does not, a priori, fit the mold of a criminal procedure in the aforementioned sense. At the same time, the consensual termination of criminal proceedings—which also includes other forms of termination of the proceeding besides the concept of Verständigung, which occur by means of a preferment of public charges—is, in fact, more prevalent in practice these days than judgments rendered in adversarial trials are. Our Article focuses on the reasons why this stark contrast between legal doctrine and reality came to pass and which aspects of the implementation of the concept of consensus into the German law of criminal procedure still seem problematic.
Air-breathing propulsion has the potential to decrease the cost per kilogram for access-to-space, while increasing the flexibility of available low earth orbits. However, to meet the performance requirements, fuel-air mixing inside of scramjet engines and thermal management still need to be improved.
An option to address these issues is to use intrinsically generated vortices from scramjet inlets to enhance fuel-air mixing further downstream, leading to shorter, less internal drag generating, and thus more efficient engines. Previous works have studied this vortex-injection interaction numerically, but validation was impractical due to lack of published experimental data. This paper extends upon these previous works by providing experimental data for a canonical geometry, obtained in the T4 Stalker Tube at Mach 8 flight conditions, and assesses the accuracy of numerical methodologies such as RANS CFD to predict the vortex-injection interaction.
Focus is placed on understanding the ability of the numerical methodology to replicate the most important aspects of the vortex-injection interaction. Results show overall good agreement between the numerical and experimental results, as all major features are captured. However, limitations are encountered, especially due to a localised region of over predicted heat flux.
Genetic and environmental influences are both known to be causal factors in the development and maintenance of obesity. Stress related chronic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis and resulting increased glucocorticoid exposure is known to be an important pathophysiological mechanism in the development of obesity. We show that the natriuretic peptide system, that mediates endocrine and behavioural responses to stress, plays a role in the control of long-term body weight in chronically ethanol drinking mice. In mice lacking functional NPR-A receptors, physical, and in particular psychological stress leads to enhanced and continuous increase in body weight in homozygote NPR-A mice. The effect of repeated stress on body weight appeared rapidly and persisted throughout life. Over a longer period of time without stress, body weights do not differ between the different genotypes. Moreover, we could demonstrate that NPR-A homozygote mice show significant higher corticosterone levels following stress. Heterozygote animals show an intermediate phenotype concerning body weights and corticosterone levels following stress. Alterations in the NPR-A receptor gene may constitute a genetic risk factor for stress-induced eating and obesity.
Neurophysiological hyperactivation of cortical and subcortical brain areas has been reported in obsessive-compulsive disorder (OCD) using functional imaging techniques and electroencephalography (EEG). Also sleep disturbances and delayed sleep phases have been associated with OCD symptomatology. However, vigilance regulation in OCD during the transition phase from wakefulness to sleep onset remains unclear. Therefore the aim of this study was to analyze EEG-source estimates and EEG vigilance regulation in OCD patients in comparison to healthy controls.
A 15 minute resting EEG was recorded in 30 unmedicated OCD patients and 30 healthy, age and gender matched controls. EEG power source estimates of the whole time series were computed by exact Low Resolution Brain Electromagnetic Tomography (eLORETA). Each consecutive one second EEG-segment was classified into one out of seven EEG-vigilance stages (0, A1, A2, A3, B1, B2/3, C) using Vigilance Algorithm Leipzig (VIGALL). The eLORETA analysis (log of F-ratios, p < 0.05, corrected for multiple comparison) revealed significantly increased delta power in the right superior frontal gyrus for OCD patients in comparison to healthy controls. Vigilance analysis yielded significantly increased amounts of high vigilance stage A2 (Mann-Whitney test, p < 0.001, corrected for multiple comparison) for OCD patients.
This study repeated findings of altered EEG-power in frontal areas in OCD patients. Alterations of EEG-vigilance regulation were found with increased amounts of high vigilance stage A2. This is in line with a hypothesis of cortical hyperactivation in OCD. The value of EEG-vigilance as a possible biological marker for e.g. treatment response should be focus of further studies.
Schizophrenia is frequently complicated by depressive or negative symptoms that respond only moderately to treatment with antipsychotic drugs. Reboxetine is a novel antidepressant, which inhibits the reuptake of norepinephrine. We sought to study the efficacy and tolerability of the adjunctive use of reboxetine in a cohort of schizophrenic patients with prominent depressive or negative symptoms.
Sixteen schizophrenic inpatients were recruited for this study. All subjects received 4–8 mg of reboxetine/day while the antipsychotic medication (typical antipsychotics = 4; atypical antipsychotics = 12) was continued. All subjects underwent a standardized assessment including PANSS, CGI, HAMD, and CDSS before and after treatment with reboxetine (mean 26 ± 17 d).
All subjects tolerated treatment with reboxetine. Adverse effects were mild and did not require discontinuation of reboxetine. All clinical scores (PANSS 93.1 vs. 63.1; CGI 5.4 vs. 4.1; HAMD 20.4 vs. 8.1; CDSS 12.5 vs. 4.6) improved significantly under adjunctive treatment with reboxetine (all P < 0.01).
The adjunctive use of reboxetine in schizophrenic patients was safe and well-tolerated. Our results suggest that the adjunctive use of reboxetine may be an effective treatment for depressive and negative symptoms in schizophrenia.
Dysregulation in the neuroendocrine stress system has been attributed repeatedly to the stressful and anxiogenic state observed during alcohol withdrawal. Activity of the atrial natriuretic peptide (ANP) has been shown to inhibit the release of corticotrophin releasing hormone (CRH) and corticotrophin (ACTH) and opioid neurotransmission also plays a role in counteracting effects of sustained stress by facilitating the termination of the hypothalamo-pituitary-adrenocortical (HPA) axis stress response. Thus ANP and ß-endorphin may be involved in modulating the HPA axis activity in alcohol withdrawal. Aim of the study was to evaluate the anxiolytic activity of ANP and ß-endorphin during alcohol withdrawal in mice habitated to chronic alcohol intake.
24 male mice (C57/Bl6J) were studied following 21 days of free-choice and forced alcohol intake. Anxiety related behavior (elevated plus maze, open field) was tested during acute ethanol withdrawal (12 hours after last ethanol consumption). 30 minutes before testing, randomized groups of mice were given i.p. injections of ANP (60 μg/kg), ß-endorphin (2 μg/kg) or saline.
Acute alcohol withdrawal in alcohol habituated mice was associated with increased anxiety related behavior. Application of both, ß-endorphin and ANP, was significantly associated with reduced anxiety related behavior.
Taking into consideration data from studies in humans, where decreased levels of ß-endorphin and ANP were associated with anxiety during acute and protracted alcohol withdrawal, our results suggest a causal relationship between ANP, ß-endorphin and withdrawal-induced anxiety in alcohol related disorders.
Recent results suggest that the endocrine system can affect as well as modulate ethanol drinking behavior. In mice and humans a correlation has been found between ANP plasma concentration and craving, anxiety as well as the severity of the withdrawal symptoms. To further elucidate the involvement of the natriuretic peptide system in neurobehavioral effects of alcohol, we examined ethanol drinking behavior in mice lacking a functional natriuretic peptide-A (NPR-A) receptor.
NPR-A heterozygote, -knockout and wild-type mice were given a free choice between water and increasing concentrations of ethanol. Once a stable baseline of 16% ethanol consumption was established, access to ethanol was withdrawn for 2 weeks and then reinstated to measure the alcohol deprivation effect (ADE). A forced swim stress was performed thereafter on 3 consecutive days.
Data analysis revealed a higher ethanol preference and voluntary ethanol intake in NPR-A-transgenic mice. Throughout the experiments the ethanol intake was highest in heterozygote animals. Stress-induced drinking led to an immediate increase in ethanol consumption in the homozygote subgroup. Deprivation from alcohol resulted in a classical ADE in wild-type and heterozygote animals. The homozygote mice do not show an increase in alcohol intake during the ADE.
We demonstrated that the NPR-A receptor gene is involved in free choice ethanol consumption, preference and ethanol consumption following stress. Mice lacking a functional NPR-A receptor represent a useful animal model to adress the question of whether a dysfunctonal natriuretic peptide receptor system influences longterm alcohol self-administration and stress induced alcohol drinking.
Under naturalistic conditions the influence of monotherapy versus combined therapy on the outcome of psychoeducation was to be investigated. As amisulpride has a very positive receptor profile and causes no sedation, it was of interest to which degree amisulpride has a positive influence on knowledge gain in comparison to other atypicals.
In-patients with schizophrenia (ICD -10: F2) under therapy with atypicals. 8 psychoeducational group sessions; indication for groups independent of psychopathology, insight and compliance. Medication with atypicals non restricted.
94 patients (47% female, 35 years), 40 % (38 of 94) were treated at discharge with a monotherapy and 60 % with a combination of atypicals. PANSS monotherapy at admission: 74; at discharge: 49. Patients with combination therapy had significantly higher values: 92 at admission and 66 at discharge (p<0.001). Knowledge-gain was comparable; monotherapy group: Mean= 6,0 (SD 6,5); combination therapy: Mean=6,9 (SD 12,4) (n.s.). 23 % (22 of 94) got amisulpride (5 in monotherapy and 17 in combination). Concerning safety profile and therapeutic effectiveness the non-inferior hypothesis could be confirmed. Patients with monotherapy of amisulpride at discharge had a mean knowledge gain of 10.7; that was higher than the mean knowledge gain of 6.5 of all patients (n.s.).
Monotherapy with atypicals was only possible among 40 %. Psychoeducation is efficient for severely ill patients with combined therapy as well. Amisulpride monotherapy showed a knowledge-gain higher than the average atypicals. For patients with high expectations concerning rehabilitation, a monotherapy with amisulpride seems to be useful.
Knowing the factors that can predict the occurrence of suicidal ideation in mental health patients assessed in Emergency Rooms (ERs) will enhance patient risk assessments.
To examine the factors that can predict the likelihood that a patient presenting to the Emergency Room will have suicidal ideation
Twenty-four independent demographic and clinical factors contained on a data assessment tool for 337 patients assessed by the crisis team in the ER over 6 months were compiled. Data was analysed using SPSS Version 20 with univariate analyses and logistic regression.
Only two (reason for presenting to the ER and Global Assessment of Function (GAF) score) of the seven-predictor variables on univariate analysis made unique statistically significant contributions to a logistic regression model. The odds ratio for ‘reason for presenting to the ER’ was 7.53, which suggests that patients who presented with a complaint of ‘low mood’ were seven and a half times more likely to report suicidal ideation compared with those presenting with other complaints, controlling for other factors in the model. Also the odds ratio for ‘GAF score’ was 9.92, which suggests that those who had GAF scores of 50 or less were ten times more likely to present with suicidal ideation compared with those who had GAF scores of more than 50, controlling for other factors.
Patients presenting to the ER with ‘low mood’ and those with a GAF score of less than 50 should be properly assessed for the presence of suicidal ideation.
To improve services by examining the factors that can predict the likelihood that patients assessed by crisis nurses in a task-shifting model of care at the Emergency Room (ER) will refer them to a psychiatrist for further management.
Twenty-four independent demographic and clinical factors extracted from a data assessment tool for 337 patients assessed by the crisis team in the ER over 6 months were compiled. Data was analysed using SPSS Version 20 with univariate analyses and logistic regression.
Only four of the fourteen-predictor variables on univariate analysis made unique statistically significant contributions to a logistic regression model. The odds ratios suggest that crisis nurses were twice as likely to refer patients who were not in any relationship or those who were known to psychiatric services compared to those who were in a relationship or not known to psychiatric services respectively; nineteen and six times respectively more likely to refer patients presenting with psychotic symptoms or a drug or alcohol problem compared to someone presenting with a medical problem and twenty and seven times respectively less likely to refer patients who were given a probable primary diagnosis of ‘drug/alcohol use disorder’ or ‘personality disorders’ compared to patients who were given the probable primary diagnosis of a ‘Depressive disorder’, controlling for other factors in the model.
In a task-shifting model of care, protocols need to be developed with clear guidelines around patients who need to be referred to a psychiatrist for further management.