ARTIS Pheno®: a potential tool for cochlear implant surgery.

PURPOSE: Cochlear implantation is a standard approach to hearing rehabilitation and encompasses three main stages: appropriate patient selection, a challenging surgical procedure, which should be as atraumatic as possible and preserve cochlear structures, and lifelong postoperative follow-up. Computed tomography (CT) is performed to assess postoperative implant position. The Siemens Advanced Radar Target Identification System (ARTIS) Pheno provides fluoroscopic imaging during surgery and has so far been mainly used by cardiologists, neurosurgeons and trauma surgeons. METHODS: Six patients with difficult anatomy or a challenging medical history were selected for a surgical procedure, during which we planned to use the ARTIS Pheno to accurately position and assess implant position under fluoroscopy during and immediately after surgery. In all six cases, the ARTIS Pheno was used directly in the surgical setting. The procedures were performed in cooperation with the neuroradiology department in an interdisciplinary manner. RESULTS: In all six patients, fluoroscopy was used to visualise the procedure at different stages of surgery. In five patients, the procedure was successfully completed. This approach allowed us to finally assess implant position and confirm the correct and complete insertion of the electrode while the patient was still under anaesthesia. CONCLUSION: These cases showed positive surgical outcomes. Although the procedure is more complex than a standard approach, patients can be managed in a safe, effective and appropriate manner. The assessment of implant position in real time during surgery leads to greater patient and surgeon satisfaction. The approach presented here ensures a high quality of cochlear implant surgery even in difficult surgical situations and meets the requirements of modern surgery.

Ontogeny of Hepatic Transporters and Drug-Metabolizing Enzymes in Humans and in Nonclinical Species.

The liver represents a major eliminating and detoxifying organ, determining exposure to endogenous compounds, drugs, and other xenobiotics. Drug transporters (DTs) and drug-metabolizing enzymes (DMEs) are key determinants of disposition, efficacy, and toxicity of drugs. Changes in their mRNA and protein expression levels and associated functional activity between the perinatal period until adulthood impact drug disposition. However, high-resolution ontogeny profiles for hepatic DTs and DMEs in nonclinical species and humans are lacking. Meanwhile, increasing use of physiologically based pharmacokinetic (PBPK) models necessitates availability of underlying ontogeny profiles to reliably predict drug exposure in children. In addition, understanding of species similarities and differences in DT/DME ontogeny is crucial for selecting the most appropriate animal species when studying the impact of development on pharmacokinetics. Cross-species ontogeny mapping is also required for adequate translation of drug disposition data in developing nonclinical species to humans. This review presents a quantitative cross-species compilation of the ontogeny of DTs and DMEs relevant to hepatic drug disposition. A comprehensive literature search was conducted on PubMed Central: Tables and graphs (often after digitization) in original manuscripts were used to extract ontogeny data. Data from independent studies were standardized and normalized before being compiled in graphs and tables for further interpretation. New insights gained from these high-resolution ontogeny profiles will be indispensable to understand cross-species differences in maturation of hepatic DTs and DMEs. Integration of these ontogeny data into PBPK models will support improved predictions of pediatric hepatic drug disposition processes. SIGNIFICANCE STATEMENT: Hepatic drug transporters (DTs) and drug-metabolizing enzymes (DMEs) play pivotal roles in hepatic drug disposition. Developmental changes in expression levels and activities of these proteins drive age-dependent pharmacokinetics. This review compiles the currently available ontogeny profiles of DTs and DMEs expressed in livers of humans and nonclinical species, enabling robust interpretation of age-related changes in drug disposition and ultimately optimization of pediatric drug therapy.

Continuum beliefs of mental illness: a systematic review of measures.

PURPOSE: The continuum of mental health/illness has been subject to scientific debate for decades. While current research indicates that continuum belief interventions can reduce mental health stigma and improve treatment seeking in affected populations, no study has yet systematically examined measures of continuum beliefs. METHODS: This preregistered systematic review summarizes measures of continuum beliefs. Following the PRISMA statement, three scientific databases (PubMed, PsycInfo and PsycArticles via EBSCOhost, Web of Science) are searched, instruments are described and discussed regarding their scope, and methodological quality. RESULTS: Overall, 7351 records were identified, with 35 studies reporting relevant findings on 11 measures. Most studies examined general population samples and used vignette-based measures. Schizophrenia and depression were most commonly examined, few studies focused on dementia, ADHD, OCD, eating disorders, and problematic alcohol use, or compared continuum beliefs across disorders. Validity was very good for most measures, but reliability was rarely tested. Measures mostly assessed beliefs in the normality of mental health symptoms or the normality of persons with such symptoms but rarely nosological aspects (i.e., categorical v continuous conceptualization of mental disorders). CONCLUSIONS: Current research provides psychometrically sound instruments to examine continuum beliefs for a variety of mental disorders. While studies suggest utility for general population samples and mental health professionals, more research is necessary to corroborate findings, for instance, regarding age (e.g., in adolescents), gender, or type of mental disorder. Future research should also compare self-report ratings, and vignette-based measures, include measures of nosological concepts to fully grasp the continuum concept of mental illness. PREREGISTRATION: PROSPERO: CRD42019123606.

External and Internal Microbiomes of Antarctic Nematodes are Distinct, but More Similar to each other than the Surrounding Environment.

Host-associated microbiomes have primarily been examined in the context of their internal microbial communities, but many animal species also contain microorganisms on external host surfaces that are important to host physiology. For nematodes, single strains of bacteria are known to adhere to the cuticle (e.g., Pasteuria penetrans), but the structure of a full external microbial community is uncertain. In prior research, we showed that internal gut microbiomes of nematodes (Plectus murrayi, Eudorylaimus antarcticus) and tardigrades from Antarctica's McMurdo Dry Valleys were distinct from the surrounding environment and primarily driven by host identity. Building on this work, we extracted an additional set of individuals containing intact external microbiomes and amplified them for 16S and 18S rRNA metabarcoding. Our results showed that external bacterial microbiomes were more diverse than internal microbiomes, but less diverse than the surrounding environment. Host-specific bacterial compositional patterns were observed, and external microbiomes were most similar to their respective internal microbiomes. However, external microbiomes were more influenced by the environment than the internal microbiomes were. Non-host eukaryotic communities were similar in diversity to internal eukaryotic communities, but exhibited more stochastic patterns of assembly compared to bacterial communities, suggesting the lack of a structured external eukaryotic microbiome. Altogether, we provide evidence that nematode and tardigrade cuticles are inhabited by robust bacterial communities that are substantially influenced by the host, albeit less so than internal microbiomes are.

Forensic age assessment by 3.0 T MRI of the wrist: adaption of the Vieth classification.

OBJECTIVES: In order to find a reliable method to correctly assess majority in both sexes by MRI, a study was conducted to evaluate the applicability of the recently presented Vieth classification in wrist MRI, after it had originally been proposed for knee MRI. METHODS: After receiving a positive vote by the ethics committee, the left-hand wrists of 347 male and 348 female volunteers of German nationality in the age bracket 12-24 years were scanned. Before conducting the prospective, cross-sectional examinations, an informed consent was obtained from each volunteer. A 3.0 T MRI scanner was used, acquiring a T1 turbo spin-echo sequence (TSE) and a T2 TSE sequence with fat suppression by spectral presaturation with inversion recovery (SPIR). The images were assessed by applying the Vieth classification. Minimum, maximum, mean ± standard deviation, and median with lower and upper quartiles were defined. Intra- and interobserver agreements were determined by calculating the kappa coefficients. Differences between the sexes were analyzed using the Mann-Whitney U test. RESULTS: By applying the unmodified Vieth classification with corresponding schematics, it was possible to assess majority in both sexes via the epiphyseal-diaphyseal fusion of the distal radius and in males also via the epiphyseal-diaphyseal fusion of the distal ulna. The Mann-Whitney U test implied significant sex-related differences for all stages. For both epiphyses, the intra- and interobserver agreement levels were very good (κ > 0.8). CONCLUSION: If confirmed by further studies, it would be possible to determine the completion of the 18th year of life in both sexes by 3.0 T MRI of the wrist and using the Vieth classification. KEY POINTS: • The Vieth classification allows determining majority in males and females alike based on the distal radius' epiphysis by 3.0 T MRI of the wrist. • The Vieth classification also allows determining majority in males based on the distal ulna's epiphysis by 3.0 T MRI of the wrist, but not in females. • The presented data can be deemed referential within certain discussed boundaries.

Mindfulness-Based Cognitive Therapy as Migraine Intervention: a Randomized Waitlist Controlled Trial.

BACKGROUND: Based on promising effects seen in a pilot study evaluating a generic mindfulness-based program for migraine, we developed a migraine-specific adaptation of the Mindfulness-Based Cognitive Therapy (MBCT) program. The aim of this study was to evaluate this program for feasibility and effectiveness in a randomized controlled trial. METHOD: Fifty-four patients suffering from migraine were randomly allocated to either waitlist or the adapted MBCT. Outcomes were migraine-related parameters as well as variables of psychological functioning and coping. Assessment took place at baseline and post-intervention, for the intervention group also at follow-up (7 months). The effects of the intervention were analyzed by the use of ANCOVAs and linear mixed models. RESULTS: With respect to migraine parameters we did not find a significant group difference in the primary outcome (headache-related impairment), but the intervention resulted in a significant reduction of headache frequency (p = .04). In the analysis of secondary outcomes, MBCT showed superiority in four out of eight psychological parameters (perceived stress, anxiety, rumination, catastrophizing) with small to medium effect sizes. The intervention proved to be feasible and participants reported high degrees of contentment and achievement of personal goals. CONCLUSIONS: The migraine-specific MBCT program did not result in improvements with regard to headache-related impairment but showed a reduction in headache frequency as well as improved psychological functioning in secondary outcomes. TRIAL REGISTRATION: This trial was registered in the German Trial Registry "Deutsches Register Klinischer Studien" (ID: DRKS00007477), which is a WHO-listed primary trial register.

Functional properties of cream from dairy cows with experimentally altered milk fat composition.

Modification of milk fat composition might be a desirable method to alter manufacturing characteristics or produce dairy products low in saturated fat that more closely meet consumer dietary preferences. The aim of this research was to evaluate functional properties of cream obtained from milks with fat composition modified by altering the profile of long-chain fatty acids (FA) absorbed from the intestine. A control and 5 mixtures of long-chain free FA were infused into the abomasum of lactating dairy cows in a 6 × 6 Latin square design with 21-d periods. Treatments were as follows: (1) control (no FA infused), (2) mostly saturated FA (C16:C18 = 0.74), (3) low linoleic palm FA (C16:C18 = 0.73), (4) palm FA (C16:C18 = 0.73), (5) soy FA (C16:C18 = 0.10), and (6) high palmitic soy FA (C16:C18 = 0.73). All treatments included meat solubles and Tween 80 as emulsifiers. Viscosity, overrun, whipping time, foam firmness, and foam stability were evaluated in creams (33% fat). Cream from cows infused with soy FA (treatment 5) had the longest whipping time and lowest overrun, foam stability, viscosity, melting point, firmness, and solid fat content at 5 and 20°C because the fat had the highest unsaturated FA content. Increasing palmitic acid content of soy FA (treatment 6) improved functional variables in cream relative to soy FA alone. Differences among treatments 1 to 4 were less pronounced because of the effect of C18:1 trans in treatments 3 and 4 on milk fat yield and composition. Milk fat from cows infused with palm FA (treatment 4) exhibited comparable or better functionality than control cream. Increased polyunsaturated FA in milk fat resulted in increased amounts of triglyceride (TG) fractions with 28, 30, 38, and 40 carbon numbers, increased oleic acid resulted in increased 50-carbon TG, and higher palmitic and myristic acids resulted in greater 44, 46, and 48 carbon number TG. These TG groups consistently correlated with functional properties of creams from different treatments. Our results indicated that optimal functionality of cream is dependent more on its content of palmitic acid than on unsaturated FA. However, an optimal composition of milk fat for cream functional characteristics might be obtained through nutritional manipulation of diets for dairy cows to deliver an optimal profile of FA.

Screening two biodegradable polymers in enhanced efficiency fertiliser formulations reveals the need to prioritise performance goals.

Enhanced efficiency fertilisers (EEF) may reduce nitrogen (N) losses and improve uptake efficiency through synchronising N release with in-season plant requirements. We hypothesised that EEF formed via matrix encapsulation in biodegradable polymers will improve N use efficiency when compared to conventional urea fertiliser. This hypothesis was investigated for two biodegradable polymer matrices: polyhydroxyalkanoate (PHA), containing 11.6% urea (by mass), and polybutylene-adipate-co-terephthalate (PBAT), containing either 19.4 or 32.7% urea; and two contrasting soil types: sand and clay. Nitrogen availability and form was investigated under leaching conditions (water) with a growth accelerator pot experiment involving a horticultural crop and novel non-destructive three-dimensional scanning to measure in-season biomass development. The PBAT 32.7% formulation enabled greater above ground biomass production at both 50 and 100 kg N ha-1 equivalent application rates compared to conventional urea. For the sandy soil, plant scanning indicated that improved uptake performance with PBAT 32.7% was probably the result of greater N availability after 25 days than for conventional urea. Two of the encapsulated formulations (PHA and PBAT 19.4%) tended to decrease nitrogen leaching losses relative to urea (P < 0.05 for the red clay soil). However, decreased N leaching loss was accompanied by poorer N uptake performance, indicative of N being less available in these biopolymer formulations. A snapshot of nitrous oxide emissions collected during peak nitrate concentration (prior to planting and leaching) suggested that the biopolymers promoted N loss via gaseous emission relative to urea in the sandy soil (P < 0.05), and carbon dioxide emissions data suggested that biopolymer-carbon increased microbial activity (P < 0.1). Controlled testing of N release in water was a poor predictor of biomass production and leaching losses. The diverse behaviours of the tested formulations present the potential to optimise biopolymers and their N loadings by taking into account soil and environmental factors that influence the efficient delivery of N to target crops. The greater N uptake efficiency demonstrated for the PBAT 32.7% formulation confirms our hypothesis that matrix encapsulation can enable better synchronisation of N release with crop requirements and decrease leaching losses.

The Dysregulated Galectin Network Activates NF-κB to Induce Disease Markers and Matrix Degeneration in 3D Pellet Cultures of Osteoarthritic Chondrocytes.

This work aimed to study the dysregulated network of galectins in OA chondrocyte pellets, and to assess whether their recently discovered activity as molecular switches of functional biomarkers results in degradation of extracellular matrix in vitro. Scaffold-free 3D pellet cultures were established of human OA chondrocytes. Expression and secretion of galectin(Gal)-1, -3, and -8 were monitored relative to 2D cultures or clinical tissue sections by RT-qPCR, immunohistochemistry and ELISAs. Exposure of 2D and 3D cultures to an in vivo-like galectin mixture (Gal-1 and Gal-8: 5 µg/ml, Gal-3: 1 µg/ml) was followed by the assessment of pellet size, immunohistochemical matrix staining, and/or quantification of MMP-1, -3, and -13. Application of inhibitors of NF-κB activation probed into the potential of intervening with galectin-induced matrix degradation. Galectin profiling revealed maintained dysregulation of Gal-1, -3, and -8 in pellet cultures, resembling the OA situation in situ. The presence of the galectin mixture promoted marked reduction of pellet size and loss of collagen type II-rich extracellular matrix, accompanied by the upregulation of MMP-1, -3, and -13. Inhibition of p65-phosphorylation by caffeic acid phenethyl ester effectively alleviated the detrimental effects of galectins, resulting in downregulated MMP secretion, reduced matrix breakdown and augmented pellet size. This study suggests that the dysregulated galectin network in OA cartilage leads to extracellular matrix breakdown, and provides encouraging evidence of the feasible inhibition of galectin-triggered activities. OA chondrocyte pellets have the potential to serve as in vitro disease model for further studies on galectins in OA onset and progression.

Perceived psychological stress and risk of herpes zoster: a nationwide population-based cohort study.

BACKGROUND: Psychological stress may reduce cellular immunity, but its role in triggering latent infections, including herpes zoster (HZ), is controversial. OBJECTIVES: To examine the association between perceived psychological stress and risk of HZ. METHODS: In a linked registry-based cohort study, we followed 77 310 persons aged 40 years or older who participated in the 2010 Danish National Health Survey from 1 May 2010 until HZ diagnosis, death, emigration or 1 July 2014, whichever occurred first. We computed hazard ratios (HRs) of HZ associated with Cohen's Perceived Stress Scale (PSS) score (range 0-40) using Cox regression with age as the timescale, adjusted for sex, immunosuppressive and selected chronic conditions, immunosuppressive drugs, and sociodemographic, lifestyle and anthropometric factors. The PSS measures chronic stress perceived by an individual in response to various demands of daily life. We modelled the PSS score using quintiles and a restricted cubic spline function. RESULTS: The unadjusted rate of HZ varied from 5·53 to 7·20 per 1000 person-years from the lowest to the highest PSS score quintile. Compared with the lowest PSS score quintile, the adjusted HR for HZ was 1·00 [95% confidence interval (CI) 0·86-1·16], 1·08 (95% CI 0·92-1·26), 1·05 (95% CI 0·90-1·23) and 1·14 (95% CI 0·97-1·34) for the second to the fifth quintile, respectively. In cubic spline analyses, PSS scores < 20 were not associated with increased HR of HZ, but thereafter the HR increased linearly from 1·10 (95% CI 0·85-1·41) to 2·22 (95% CI 1·32-3·75). CONCLUSIONS: Our study indicated that high levels of psychological stress are associated with increased risk of HZ.

Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP).

PURPOSE: Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. METHODS: The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. RESULTS: As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once. CONCLUSION: NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00023742).

CIP2A regulates MYC translation (via its 5'UTR) in colorectal cancer.

BACKGROUND: Deregulated expression of MYC is a driver of colorectal carcinogenesis, suggesting that decreasing MYC expression may have significant therapeutic value. CIP2A is an oncogenic factor that regulates MYC expression. CIP2A is overexpressed in colorectal cancer (CRC), and its expression levels are an independent marker for long-term outcome of CRC. Previous studies suggested that CIP2A controls MYC protein expression on a post-transcriptional level. METHODS: To determine the mechanism by which CIP2A regulates MYC in CRC, we dissected MYC translation and stability dependent on CIP2A in CRC cell lines. RESULTS: Knockdown of CIP2A reduced MYC protein levels without influencing MYC stability in CRC cell lines. Interfering with proteasomal degradation of MYC by usage of FBXW7-deficient cells or treatment with the proteasome inhibitor MG132 did not rescue the effect of CIP2A depletion on MYC protein levels. Whereas CIP2A knockdown had marginal influence on global protein synthesis, we could demonstrate that, by using different reporter constructs and cells expressing MYC mRNA with or without flanking UTR, CIP2A regulates MYC translation. This interaction is mainly conducted by the MYC 5'UTR. CONCLUSIONS: Thus, instead of targeting MYC protein stability as reported for other tissue types before, CIP2A specifically regulates MYC mRNA translation in CRC but has only slight effects on global mRNA translation. In conclusion, we propose as novel mechanism that CIP2A regulates MYC on a translational level rather than affecting MYC protein stability in CRC.

Norms for emotion-false memory lists.

False memory has been a flourishing research area for decades, and recently there has been considerable interest in how emotional content affects it. Literature reviews have noted a lack of normed materials that vary in emotional valence and arousal as a factor that contributes to the mixed findings on emotion-false memory effects. We report a pool of normed materials of this sort, the Cornell/Cortland Emotional Lists (CEL). This is a Deese/Roediger/McDermott (DRM) type list pool in which words' mean valence and arousal ratings are factorially manipulated across 32 lists. These lists' levels of mean backward associative strength (MBAS) are all high enough to induce significant levels of false memory. The lists were normed by administering them to 228 subjects at three different universities, all of whom responded to recall and recognition tests for the lists. The norming data revealed that false recall and false recognition were higher for negative lists than for positive lists, whereas true recall and true recognition were higher for positive lists than for negative lists. In addition, high arousal strengthened the valence effects on both true and false recall. These results indicate that the CEL lists are useful tozols for emotion-false memory research.

Developing New Drugs for Mycobacterium tuberculosis Therapy: What Information Do We Get from Preclinical Animal Models?

Preclinical animal models of infection are employed to develop new agents but also to screen among molecules to rank them. There are often major differences between human pharmacokinetic (PK) profiles and those developed by animal models of infection, and these may lead to substantial differences in efficacy relative to that seen in humans. Linezolid is a repurposed agent employed to great effect for therapy of Mycobacterium tuberculosis In this study, we used the hollow-fiber infection model (HFIM) to evaluate the impact of different pharmacokinetic profiles of mice and nonhuman primates (NHP) versus humans on bacterial cell kill as well as resistance suppression. We examined both plasma and epithelial lining fluid (ELF) profiles. We examined simulated exposures equivalent to 600 mg and 900 mg daily of linezolid in humans. For both plasma and ELF exposures, the murine PK profile provided estimates of effect that were biased low relative to human and NHP PK profiles. Mathematical modeling identified a linkage between minimum concentrations (Cmin) and bacterial kill and peak concentrations (Cpeak) and resistance suppression, with the latter being supported by a prospective validation study. Finding new agents with novel mechanisms of action against M. tuberculosis is difficult. It would be a tragedy to discard a new agent because of a biased estimate of effect in a preclinical animal system. The HFIM provides a system to benchmark evaluation of new compounds in preclinical animal model systems against human PK effects (species scale-up estimates of PK), to safeguard against unwarranted rejection of promising new agents.

Psychosocial factors associated with HbA1c in adults with insulin pump-treated type 1 diabetes: a systematic review.

AIMS: To identify currently available studies on the association between psychosocial factors and HbA1c in adults with insulin pump-treated type 1 diabetes, by performing a systematic review of the literature. METHODS: MEDLINE, Embase, CINAHL and PsycINFO were searched for original studies on the association between psychosocial factors and HbA1c in ≥ 50 adult, non-pregnant, insulin pump users with type 1 diabetes. RESULTS: The search resulted in 1777 unique records, of which eight were eligible for inclusion. All identified studies were observational, with sample sizes ranging from 51 to 214. Seven different psychosocial factors were investigated in the eight studies. Study analysis suggested that HbA1c may be associated with diabetes numeracy and quality of life. There were no indications of associations between HbA1c and fear of hypoglycaemia or self-efficacy. Results regarding associations between HbA1c and coping style, diabetes distress and locus of control were inconsistent. CONCLUSIONS: This systematic review summarizes the currently limited information on the association between psychosocial factors and HbA1c during insulin pump therapy. The evidence base of the included studies was weak, and this review highlights the need for more research in these areas, with improved methodological and theoretical frameworks, including exploration of a broader spectrum of psychosocial variables and their potential association with HbA1c and other metabolic outcomes. (PROSPERO International prospective register of systematic reviews registration no: CRD42020145705).

Partner bereavement and risk of psoriasis and atopic eczema: cohort studies in the U.K. and Denmark.

BACKGROUND: Stress is commonly cited as a risk factor for psoriasis and atopic eczema, but such evidence is limited. OBJECTIVES: To investigate the association between partner bereavement (an extreme life stressor) and psoriasis or atopic eczema. METHODS: We conducted cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). The exposed cohort was partners who experienced partner bereavement. The comparison cohort was up to 10 nonbereaved partners, matched to each bereaved partner by age, sex, county of residence (Denmark) and general practice (U.K.). Outcomes were the first recorded diagnosis of psoriasis or atopic eczema. We estimated hazard ratios (HRs) and confidence intervals (CIs) using a stratified Cox proportional hazards model in both settings, which were then pooled in a meta-analysis. RESULTS: The pooled adjusted HR for the association between bereavement and psoriasis was 1·01 (95% CI 0·98-1·04) across the entire follow-up. Similar results were found in other shorter follow-up periods. Pooled adjusted HRs for the association between bereavement and atopic eczema were 0·97 (95% CI 0·84-1·12) across the entire follow-up, 1·09 (95% CI 0·86-1·38) within 0-30 days, 1·18 (95% CI 1·04-1·35) within 0-90 days, 1·14 (95% CI 1·06-1·22) within 0-365 days and 1·07 (95% CI 1·02-1·12) within 0-1095 days. CONCLUSIONS: We found a modest increase in the risk of atopic eczema within 3 years following bereavement, which peaked in the first 3 months. Acute stress may play a role in triggering onset of new atopic eczema or relapse of atopic eczema previously in remission. We observed no evidence for increased long-term risk of psoriasis and atopic eczema following bereavement.

The association between partner bereavement and melanoma: cohort studies in the U.K. and Denmark.

BACKGROUND: Psychological stress is commonly cited as a risk factor for melanoma, but clinical evidence is limited. OBJECTIVES: This study aimed to evaluate the association between partner bereavement and (i) first-time melanoma diagnosis and (ii) mortality in patients with melanoma. METHODS: We conducted two cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). In study 1, we compared the risk of first melanoma diagnosis in bereaved vs. matched nonbereaved people using stratified Cox regression. In study 2 we estimated hazard ratios (HRs) for death from melanoma in bereaved compared with nonbereaved individuals with melanoma using Cox regression. We estimated HRs separately for the U.K. and for Denmark, and then pooled the data to perform a random-effects meta-analysis. RESULTS: In study 1, the pooled adjusted HR for the association between partner bereavement and melanoma diagnosis was 0·88 [95% confidence interval (CI) 0·84-0·92] across the entire follow-up period. In study 2, we observed increased melanoma-specific mortality in people experiencing partner bereavement across the entire follow-up period (HR 1·17, 95% CI 1·06-1·30), with the peak occurring during the first year of follow-up (HR 1·31, 95% CI 1·07-1·60). CONCLUSIONS: We found decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. These findings may be partly explained by delayed detection resulting from the loss of a partner who could notice skin changes. Stress may play a role in melanoma progression. Our findings indicate the need for a low threshold for skin examination in individuals whose partners have died. What is already known about this topic? Psychological stress has been proposed as a risk factor for the development and progression of cancer, including melanoma, but evidence is conflicting. Clinical evidence is limited by small sample sizes, potential recall bias associated with self-report, and heterogeneous stress definitions. What does this study add? We found a decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. While stress might play a role in the progression of melanoma, an alternative explanation is that bereaved people no longer have a close person to help notice skin changes, leading to delayed melanoma detection. Linked Comment: Talaganis et al. Br J Dermatol 2020; 183:607-608.

ESGAR consensus statement on the imaging of fistula-in-ano and other causes of anal sepsis.

OBJECTIVES: To develop imaging guidelines for patients with fistula-in-ano and other causes of anal sepsis. METHODS: An expert group of 13 members of the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) used a modified Delphi process to vote on a series of consensus statements relating to the imaging of patients with potential anal sepsis. Participants first completed a questionnaire to gather practice information and to help frame the statements posed. RESULTS: In the first round of voting, the expert group scored 51 statements of which 45 (88%) achieved immediate consensus. The remaining 6 statements were redrafted following input from the expert group and consensus achieved for all during a second round of voting, including an additional statement drafted. No statement was rejected due to a lack of consensus. After redrafting to improve clarity, 53 individual statements were presented. CONCLUSION: These expert consensus statements can be used to guide appropriate indication, acquisition, interpretation and reporting of medical imaging for patients with potential fistula-in-ano and other causes of anal sepsis. KEY POINTS: • Medical imaging, notably magnetic resonance imaging, is used widely for the diagnosis and monitoring of fistula-in-ano and other causes of anal and perianal sepsis. • While the indexed medical literature is clear that diagnostic accuracy is potentially excellent, this depends on competent image acquisition and interpretation. • In order to facilitate this, the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) has produced expert consensus guidelines regarding the imaging of fistula-in-ano and related conditions.

Forensic age assessment of living adolescents and young adults at the Institute of Legal Medicine, Münster, from 2009 to 2018.

Due to high migration inflows to Europe, forensic age assessment of living persons has clearly gained importance. If there is a legal justification for X-ray examinations without a medical indication, the Study Group on Forensic Age Diagnostics (AGFAD) recommends the combination of a physical examination with anamnesis, an X-ray examination of the hand and a dental examination with evaluation of an orthopantomogram for age assessments of adolescents and young adults. If the development of the hand skeleton has been completed, an additional CT examination of the clavicles is to be performed. To demonstrate the outcome of forensic age assessments according to AGFAD recommendations with regard to migrants of doubtful minority declaration, this study analyzes the expert reports carried out at the Institute of Legal Medicine, Münster, from 2009 to 2018. A total of 597 age assessments were performed during the study period. A total of 227 age assessments were issued on behalf of youth welfare offices in the legal area of social law, 282 in family law proceedings, 76 in criminal proceedings, and 12 age assessments in immigration law proceedings. In 211 out of 597 cases, the stated age was compatible with the findings of the age assessment. In the remaining 386 cases, the average difference between the stated age and the minimum age was 1.9 years. The average difference between stated age and most probable age was 5.1 years. Of the 521 age assessments carried out outside criminal proceedings, 197 unaccompanied minors with questionable age minority (37.8%) have reached the age of majority beyond doubt. A total of 388 unaccompanied minors (74.5%) have most probably reached the age of majority. Forensic age assessments with the AGFAD methodology make an important contribution to legal certainty, the welfare of the child, and the fair distribution of resources.

Ready, Willing and Able? An Investigation of the Theory of Planned Behaviour in Help-Seeking for a Community Sample with Current Untreated Depressive Symptoms.

Applying health behaviour change models, such as the theory of planned behaviour (TPB), to help-seeking for mental health problems can address the deficit in health care utilisation. However, previous studies largely focused on help-seeking intentions and not behaviour, which might be problematic due to the intention-behaviour gap. Hence, TPB and help-seeking were examined in a German community sample with current untreated depressive symptoms: 188 adults (Mage = 50.34; SD = 16.19; 70.7% female) participated in a baseline interview and survey measuring components of the TPB (attitudes, subjective norms and perceived behavioural control) and help-seeking intentions. They reported actual help-seeking from mental health professionals via telephone surveys 3 and 6 months later. To better understand the potential gap between help-seeking intentions and behaviour and to investigate the contributions of readiness, willingness and ability to seek help, two path models were constructed in accordance with the TPB controlling for covariates. Attitudes (ß = .24), subjective norms (ß = .25) and self-efficacy (ß = .15) were significantly associated with intentions (R2 = 26%), which predicted help-seeking (Cox and Snell's pseudo-R2 = 23%); controllability did not predict help-seeking. In sum, the TPB provides a reliable framework to explore help-seeking behaviour for mental health problems. Based on these findings, prevention efforts should focus on readiness and willingness to seek help (e.g. foster positive attitudes and social support of treatment). However, the role of ability, operationalised as perceived behavioural control and (perceived) barriers to help-seeking, warrants further research, as self-efficacy but not controllability was associated with help-seeking.