Are Changes in Personality Traits and Alcohol Use Associated? A Cohort Study Among Young Swiss Men.

Objective: It is well known that certain personality traits are associated with alcohol use. Because less is known about it, we wished to investigate whether changes in alcohol use were longitudinally associated with changes in personality and in which direction the influence or causation might flow. Methods: Data came from the self-reported questionnaire answers of 5,125 young men at two time points during the Cohort study on Substance Use Risk Factors (C-SURF). Their average ages were 20.0 and 25.4 years old at the first and second wave assessments, respectively. Four personality traits were measured: (a) aggression-hostility; (b) sociability; (c) neuroticism-anxiety; and (d) sensation seeking. Alcohol use was measured by volume (drinks per week) and binge drinking (about 60+ grams per occasion). Cross-lagged panel models and two-wave latent change score models were used. Results: Aggression-hostility, sensation seeking, and sociability were significantly and positively cross-sectionally associated with both alcohol use variables. Drinking volume and these three personality traits bidirectionally predicted each other. Binge drinking was bidirectionally associated with sensation-seeking only, whereas aggression-hostility and sociability only predicted binge drinking, but not vice versa. Changes in alcohol use were significantly positively associated with changes in aggression-hostility, sensation seeking, and sociability. Associations reached small Cohen's effect sizes for sociability and sensation seeking, but not for aggression-hostility. Associations with neuroticism-anxiety were mostly not significant. Conclusion: The direction of effects confirmed findings from other studies, and the association between changes in personality and alcohol use support the idea that prevention programs should simultaneously target both

Online Gambling's Associations With Gambling Disorder and Related Problems in a Representative Sample of Young Swiss Men.

Background and Aims: Internet gambling has recently grown in popularity, but relatively little is known about how online and the combination of online and offline (mixed) gambling are associated with gambling disorder (GD) and related problems. The present research examined in a cohort study sample of young Swiss men how their gambling activities and gambling-related problems differed across the spectrum from offline to online gambling. Sample: A general-population based sample from the Cohort Study on Substance Use Risk Factors (C-SURF), consisting of 5,352 young Swiss men (mean age 28.26 years old). Measures: The spectrum from exclusively offline to almost exclusively online (>90% of gambling money spent online) gambling was measured using one question about the proportion of gambling money spent online. Total money gambled and time spent on gambling were also assessed. GD severity (range 0-9) was measured using items reflecting the nine DSM-5 GD criteria. The number of gambling-related problems (e.g., financial difficulties, range 0-10), other addictive disorders and mental health problems were also inquired about. Methods: We estimated a generalised linear model using a count model (negative binomial link function) for GD severity and gambling-related problems associated with the amounts and proportions of money gambled online and offline. Results: The number of GD criteria were associated with money gambled online (IRR [95%CI] = 2.81 [2.43, 3.24]) and offline (IRR = 2.68 [2.40, 3.00]). This was also found for the number of gambling-related problems (IRR = 2.43 [2.13, 2.79] and IRR = 2.89 [2.59, 3.23]). Compared with exclusively-offline gamblers, mixed gamblers (26-90% of money gambled online) showed the highest levels of GD symptoms and gambling-related problems, followed by the almost-exclusively-online gamblers (≥91% money gambled online) and, overall, these associations were still significant after adjustment for overall involvement in gambling (time spent and money gambled). Levels of other addictive disorders and mental health problems were higher among mixed gamblers than among offline-only gamblers, but levels among almost-exclusively-online gamblers were not. Conclusions: Symptoms of gambling disorder and gambling related problems are highest among gamblers engaging in both offline and online gambling. Prevention efforts need to target the combination of offline and online gambling

Unique versus shared associations between self-reported behavioral addictions and substance use disorders and mental health problems: A commonality analysis in a large sample of young Swiss men.

Behavioral addictions (BAs) and substance use disorders (SUDs) tend to co-occur; both are associated with mental health problems (MHPs). This study aimed to estimate the proportion of variance in the severity of MHPs explained by BAs and SUDs, individually and shared between addictions. A sample of 5,516 young Swiss men (mean = 25.47 years old; SD = 1.26) completed a self-reporting questionnaire assessing alcohol, cannabis, and tobacco use disorders, illicit drug use other than cannabis, six BAs (Internet, gaming, smartphone, Internet sex, gambling, and work) and four MHPs (major depression, attention-deficit hyperactivity disorder, social anxiety disorder, and borderline personality disorder). Commonality analysis was used to decompose the variance in the severity of MHPs explained (R <sup>2</sup> ) by BAs and SUDs into independent commonality coefficients. These were calculated for unique BA and SUD contributions and for all types of shared contributions. BAs and SUDs explained between a fifth and a quarter of the variance in severity of MHPs, but individual addictions explained only about half of this explained variance uniquely; the other half was shared between addictions. A greater proportion of variance was explained uniquely or shared within BAs compared to SUDs, especially for social anxiety disorder. The interactions of a broad range of addictions should be considered when investigating their associations with MHPs. BAs explain a larger part of the variance in MHPs than do SUDs and therefore play an important role in their interaction with MHPs

The psychological impact of the COVID-19 crisis on young Swiss men participating in a cohort study.

The COVID-19 pandemic caused many disturbances to daily life worldwide and may also have significantly affected people's psychological well-being. The present study aimed to describe the psychological impact of the crisis on our sample of young Swiss men and to examine differences due to their linguistic region, experiencing COVID-19 symptoms and living arrangements. Based on an ongoing cohort study, we assessed a general-population sample of young Swiss men (n = 2345; average 29 years old) shortly before (from April 2019) and early on during the COVID-19 crisis (between 13 May and 8 June 2020). This was a unique opportunity to estimate the crisis' psychological impact in the form of depression, perceived stress and sleep quality (assessed before and during COVID-19), and any crisis-induced fears, isolation or psychological trauma. Associations of psychological impact with living arrangements, experiencing COVID-19 symptoms and linguistic region (German-speaking vs French-speaking) were investigated using linear regression models. By the time participants responded to our questionnaire, less than 1% had been tested positive for COVID-19, 2.6% had been tested negative and 14.7% had had some COVID-19 symptoms but had not been tested. About 8.2% of the sample reported at least some symptoms of psychological trauma (≥24 points on the Impact of Event Scale). On average, participants reported higher levels of fear for others (43.6% at least moderate) and economic fear (12.7% at least moderate) than fear for themselves (5.8% at least moderate). Those living alone and those who reported having COVID-19 symptoms themselves, or knowing someone with symptoms, reported higher overall psychological impact in the form of depression, perceived stress, sleep quality, psychological trauma, fear and isolation. Associations with linguistic region varied by outcome, with higher levels of depression and fear in French-speaking regions and higher levels of perceived stress and isolation in German-speaking regions. The crisis had a considerable impact on the psychological well-being of our sample of young Swiss men, and some groups were more affected than others: those living alone and those who had shown COVID-19 symptoms themselves or had known someone with symptoms may have felt a greater psychological impact from the crisis. Supporting those at a higher risk of psychological consequences in such crises, whether through structural measures or via individual support, should be an important aspect of crisis management and could help reduce the overall impact of the current pandemic on Switzerland's population

Vena cava inferior thrombosis detected by venous hum: a case report

We describe a patient in which a venous hum, heard during abdominal auscultation, lead to the diagnosis of a vena cava inferior thrombosis

Structure-based prediction of BRAF mutation classes using machine-learning approaches.

The BRAF kinase is attracting a lot of attention in oncology as alterations of its amino acid sequence can constitutively activate the MAP kinase signaling pathway, potentially contributing to the malignant transformation of the cell but at the same time rendering it sensitive to targeted therapy. Several pathologic BRAF variants were grouped in three different classes (I, II and III) based on their effects on the protein activity and pathway. Discerning the class of a BRAF mutation permits to adapt the treatment proposed to the patient. However, this information is lacking new and experimentally uncharacterized BRAF mutations detected in a patient biopsy. To overcome this issue, we developed a new in silico tool based on machine learning approaches to predict the potential class of a BRAF missense variant. As class I only involves missense mutations of Val600, we focused on the mutations of classes II and III, which are more diverse and challenging to predict. Using a logistic regression model and features including structural information, we were able to predict the classes of known mutations with an accuracy of 90%. This new and fast predictive tool will help oncologists to tackle potential pathogenic BRAF mutations and to propose the most appropriate treatment for their patients

Developing research priorities for palliative care of people with intellectual disabilities in Europe: a consultation process using nominal group technique

BACKGROUND: Empirical knowledge around palliative care provision and needs of people with intellectual disabilities is extremely limited, as is the availability of research resources, including expertise and funding. This paper describes a consultation process that sought to develop an agenda for research priorities for palliative care of people with intellectual disabilities in Europe. METHODS: A two-day workshop was convened, attended by 16 academics and clinicians in the field of palliative care and intellectual disability from six European countries. The first day consisted of round-table presentations and discussions about the current state of the art, research challenges and knowledge gaps. The second day was focused on developing consensus research priorities with 12 of the workshop participants using nominal group technique, a structured method which involved generating a list of research priorities and ranking them in order of importance. RESULTS: A total of 40 research priorities were proposed and collapsed into eleven research themes. The four most important research themes were: investigating issues around end of life decision making; mapping the scale and scope of the issue; investigating the quality of palliative care for people with intellectual disabilities, including the challenges in achieving best practice; and developing outcome measures and instruments for palliative care of people with intellectual disabilities. CONCLUSIONS: The proposal of four major priority areas and a range of minor themes for future research in intellectual disability, death, dying and palliative care will help researchers to focus limited resources and research expertise on areas where it is most needed and support the building of collaborations. The next steps are to cross-validate these research priorities with people with intellectual disabilities, carers, clinicians, researchers and other stakeholders across Europe; to validate them with local and national policy makers to determine how they could best be incorporated in policy and programmes; and to translate them into actual research studies by setting up European collaborations for specific studies that require such collaboration, develop research proposals and attract research funding

Therapeutic efficacy of microtube-embedded chondroitinase ABC in a canine clinical model of spinal cord injury

Many hundreds of thousands of people around the world are living with the long-term consequences of spinal cord injury and they need effective new therapies. Laboratory research in experimental animals has identified a large number of potentially translatable interventions but transition to the clinic is not straightforward. Further evidence of efficacy in more clinically-relevant lesions is required to gain sufficient confidence to commence human clinical trials. Of the many therapeutic candidates currently available, intraspinally applied chondroitinase ABC has particularly well documented efficacy in experimental animals. In this study we measured the effects of this intervention in a double-blinded randomized controlled trial in a cohort of dogs with naturally-occurring severe chronic spinal cord injuries that model the condition in humans. First, we collected baseline data on a series of outcomes: forelimb-hindlimb coordination (the prespecified primary outcome measure), skin sensitivity along the back, somatosensory evoked and transcranial magnetic motor evoked potentials and cystometry in 60 dogs with thoracolumbar lesions. Dogs were then randomized 1:1 to receive intraspinal injections of heat-stabilized, lipid microtube-embedded chondroitinase ABC or sham injections consisting of needle puncture of the skin. Outcome data were measured at 1, 3 and 6 months after intervention; skin sensitivity was also measured 24 h after injection (or sham). Forelimb-hindlimb coordination was affected by neither time nor chondroitinase treatment alone but there was a significant interaction between these variables such that coordination between forelimb and hindlimb stepping improved during the 6-month follow-up period in the chondroitinase-treated animals by a mean of 23%, but did not change in controls. Three dogs (10%) in the chondroitinase group also recovered the ability to ambulate without assistance. Sensitivity of the dorsal skin increased at 24 h after intervention in both groups but subsequently decreased to normal levels. Cystometry identified a non-significant improvement of bladder compliance at 1 month in the chondroitinase-injected dogs but this did not persist. There were no overall differences between groups in detection of sensory evoked potentials. Our results strongly support a beneficial effect of intraspinal injection of chondroitinase ABC on spinal cord function in this highly clinically-relevant model of chronic severe spinal cord injury. There was no evidence of long-term adverse effects associated with this intervention. We therefore conclude that this study provides strong evidence in support of initiation of clinical trials of chondroitinase ABC in humans with chronic spinal cord injury

A Cell Motility Screen Reveals Role for MARCKS-Related Protein in Adherens Junction Formation and Tumorigenesis

Invasion through the extracellular matrix (ECM) is important for wound healing, immunological responses and metastasis. We established an invasion-based cell motility screen using Boyden chambers overlaid with Matrigel to select for pro-invasive genes. By this method we identified antisense to MARCKS related protein (MRP), whose family member MARCKS is a target of miR-21, a microRNA involved in tumor growth, invasion and metastasis in multiple human cancers. We confirmed that targeted knockdown of MRP, in both EpRas mammary epithelial cells and PC3 prostate cancer cells, promoted in vitro cell migration that was blocked by trifluoperazine. Additionally, we observed increased immunofluoresence of E-cadherin, β-catenin and APC at sites of cell-cell contact in EpRas cells with MRP knockdown suggesting formation of adherens junctions. By wound healing assay we observed that reduced MRP supported collective cell migration, a type of cell movement where adherens junctions are maintained. However, destabilized adherens junctions, like those seen in EpRas cells, are frequently important for oncogenic signaling. Consequently, knockdown of MRP in EpRas caused loss of tumorigenesis in vivo, and reduced Wnt3a induced TCF reporter signaling in vitro. Together our data suggest that reducing MRP expression promotes formation of adherens junctions in EpRas cells, allowing collective cell migration, but interferes with oncogenic β-catenin signaling and tumorigenesis

MyCTC chip: microfluidic-based drug screen with patient-derived tumour cells from liquid biopsies

Cancer patients with advanced disease are characterized by intrinsic challenges in predicting drug response patterns, often leading to ineffective treatment. Current clinical practice for treatment decision-making is commonly based on primary or secondary tumour biopsies, yet when disease progression accelerates, tissue biopsies are not performed on a regular basis. It is in this context that liquid biopsies may offer a unique window to uncover key vulnerabilities, providing valuable information about previously underappreciated treatment opportunities. Here, we present MyCTC chip, a novel microfluidic device enabling the isolation, culture and drug susceptibility testing of cancer cells derived from liquid biopsies. Cancer cell capture is achieved through a label-free, antigen-agnostic enrichment method, and it is followed by cultivation in dedicated conditions, allowing on-chip expansion of captured cells. Upon growth, cancer cells are then transferred to drug screen chambers located within the same device, where multiple compounds can be tested simultaneously. We demonstrate MyCTC chip performance by means of spike-in experiments with patient-derived breast circulating tumour cells, enabling >95% capture rates, as well as prospective processing of blood from breast cancer patients and ascites fluid from patients with ovarian, tubal and endometrial cancer, where sensitivity to specific chemotherapeutic agents was identified. Together, we provide evidence that MyCTC chip may be used to identify personalized drug response patterns in patients with advanced metastatic disease and with limited treatment opportunities