Social Media and Morality.

Nearly five billion people around the world now use social media, and this number continues to grow. One of the primary goals of social media platforms is to capture and monetize human attention. One means by which individuals and groups can capture attention and drive engagement on these platforms is by sharing morally and emotionally evocative content. We review a growing body of research on the interrelationship of social media and morality as well its consequences for individuals and society. Moral content often goes viral on social media, and social media makes moral behavior (such as punishment) less costly. Thus, social media often acts as an accelerant for existing moral dynamics, amplifying outrage, status seeking, and intergroup conflict while also potentially amplifying more constructive facets of morality, such as social support, prosociality, and collective action. We discuss trends, heated debates, and future directions in this emerging literature.

Individual-level solutions may support system-level change â if they are internalized as part of one's social identity.

System-level change is crucial for solving society's most pressing problems. However, individual-level interventions may be useful for creating behavioral change before system-level change is in place and for increasing necessary public support for system-level solutions. Participating in individual-level solutions may increase support for system-level solutions - especially if the individual-level solutions are internalized as part of one's social identity.

Ergonomic and individual risk factors for musculoskeletal pain in the ageing workforce.

BACKGROUND: The present study aimed to investigate the possible association between specific ergonomic and individual risk factors and musculoskeletal pain (MSP) in the back, shoulder, hip and knee region in workers aged 50-65y. METHODS: The study was a population based cross-sectional survey. The study population comprised citizens born between 1952-1966, living in Esbjerg municipality, Denmark, ultimo 2016 (n = 23,463). A questionnaire was sent electronically or by mail. The analysis included the working population only. A multivariate logistic regression was used for each of the following dependent variables; musculoskeletal pain for the past 3 months in the back, shoulder, hip and knee, where independent variables included ergonomic exposure, age, sex, body mass index (BMI) and leisure time physical activity (LTPA). RESULTS: The overall response rate was 58% and the data of individuals at work (n = 9,263) demonstrated several ergonomic exposures with increased odds for pain in specific regions. Exposure to back twisted or bend, squatting or lying on knees and to carrying or lifting were associated with musculoskeletal pain in the back, whereas exposure to back twisted or bend, arms above shoulder and repeated arm movement were associated with pain in the shoulder. Exposure to back twisted or bend, repeated arm movement, squatting or lying on knees and to carrying or lifting were associated with musculoskeletal pain in the hip. Important individual risk factors were also identified. Increasing age was significantly associated with increased pain in the hip but associated with less risk for pain in the back and shoulder. Males had higher odds for pain in the back and knee compared to females but lower odds for pain in the hip. BMI was particularly important for knee pain. The level of LTPA did not have an important association with MSP in any region. CONCLUSION: There is a significant positive association between ergonomic exposures and musculoskeletal pain, which were specific for the back, shoulder, hip and knee. In addition, the data demonstrated a differential association with age, sex and BMI. This needs to be considered for the treatment and classification of musculoskeletal pain and for future preventive initiatives.

Patient-reported outcome measures in mental health clinical research: a descriptive review in comparison with clinician-rated outcome measures.

PURPOSE: To review how patient-reported outcome (PRO) measures in mental health clinical research complement traditional clinician-rated outcome (CRO) measures. DATA SOURCES: Medline, Embase, PsycInfo and Scopus. STUDY SELECTION: Latest update of the literature search was conducted in August 2019, using a specified set of search terms to identify controlled and uncontrolled studies (published since 1996) of pharmacological or non-pharmacological interventions in adults (≥18 years) in hospital-based mental health care. DATA EXTRACTION: Two authors extracted data independently using a pre-designed extraction form. RESULTS OF DATA SYNTHESIS: Among the 2962 publications identified, 257 were assessed by full text reading. A total of 24 studies reported in 26 publications were included in this descriptive review. We identified subjective and objective outcome measures, classified these according to the pharmacopsychometric triangle and compared them qualitatively in terms of incremental information added to the clinical study question. The data reviewed here from primarily depression and schizophrenia intervention studies show that results from PRO measures and CRO measures generally point in the same direction. There was a relative lack of PRO measures on functioning and medication side effects compared with PRO measures on symptom burden and health-related quality of life. CONCLUSION: PROs and CROs supplement each other and at most times support identical study conclusions. Future studies would benefit from a more systematic approach toward use of PROs and a clearer rationale of how to weigh and report the results in comparison with CROs.

Big Five traits predict stress and loneliness during the COVID-19 pandemic: Evidence for the role of neuroticism.

The rapid outbreak of the coronavirus disease (COVID-19) has affected citizens' daily lives in an unprecedented way. To curb the spread of the pandemic, governments have taken numerous measures such as social distancing and quarantine, which may be associated with psychological consequences, namely stress and loneliness globally. To understand differential associations of personality traits with psychological consequences of COVID-19, we utilize data from a sample of 99,217 individuals from 41 countries collected as part of the COVIDiSTRESS Global Survey. Data were analyzed using multigroup confirmatory factor analysis and multilevel regression models. Findings showed that while some of the associations were rather weak, Big Five personality traits were significantly associated with perceived stress and loneliness during the pandemic. Our study illustrates that neuroticism especially can be a vulnerability factor for stress and loneliness in times of crisis and can contribute to detection of at-risk individuals and optimization of psychological treatments during or after the COVID-19 pandemic.

Cannabidiol versus risperidone for treatment of recent-onset psychosis with comorbid cannabis use: study protocol for a randomized controlled clinical trial.

BACKGROUND: Cannabis use is an important risk factor for development of psychosis and further transition to schizophrenia. The prevalence of patients with psychosis and comorbid cannabis use (dual diagnosis) is rising with no approved specialized pharmacological treatment option. Cannabidiol, a constituent of the Cannabis sativa plant, has potential both as an antipsychotic and as a cannabis substituting agent. The aim of this study is to evaluate the efficacy of cannabidiol versus a first-choice second-generation antipsychotic (risperidone) in patients with early psychosis and comorbid cannabis use. METHODS: The study is a phase II randomized, double-blinded, parallel-group, active-comparator clinical trial. We plan to include 130 patients aged between 18 and 64 years with a recent diagnosis of psychosis, comorbid cannabis use, and currently not treated with antipsychotics. The participants will be randomized to seven weeks of treatment with either cannabidiol 600 mg (300 mg BID) or risperidone 4 mg (2 mg BID). Participants will undergo clinical assessment after 1, 3, 5 and 7 weeks, telephone assessment the weeks in between, and a safety visit two weeks after end of treatment. The primary outcomes are cessation of cannabis use (self-reported) and psychotic symptom severity. The secondary outcomes include frequency and quantity of cannabis use, global illness severity, psychosocial functioning, subjective well-being, cognition, sleep, circadian rhythmicity, and metabolomics. DISCUSSION: The results of this trial can potentially contribute with a new treatment paradigm for patients suffering from dual diagnosis. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04105231 , registered April 23rd, 2021.

Prevention of AcuTe admIssioN algorithm (PATINA): study protocol of a stepped wedge randomized controlled trial.

BACKGROUND: The challenges imposed by ageing populations will confront health care systems in the years to come. Hospital owners are concerned about the increasing number of acute admissions of older citizens and preventive measures such as integrated care models have been introduced in primary care. Yet, acute admission can be appropriate and lifesaving, but may also in itself lead to adverse health outcome, such as patient anxiety, functional loss and hospital-acquired infections. Timely identification of older citizens at increased risk of acute admission is therefore needed. We present the protocol for the PATINA study, which aims at assessing the effect of the 'PATINA algorithm and decision support tool', designed to alert community nurses of older citizens showing subtle signs of declining health and at increased risk of acute admission. This paper describes the methods, design and intervention of the study. METHODS: We use a stepped-wedge cluster randomized controlled trial (SW-RCT). The PATINA algorithm and decision support tool will be implemented in 20 individual area home care teams across three Danish municipalities (Kerteminde, Odense and Svendborg). The study population includes all home care receiving community-dwelling citizens aged 65 years and above (around 6500 citizens). An algorithm based on home care use triggers an alert based on relative increase in home care use. Community nurses will use the decision support tool to systematically assess health related changes for citizens with increased risk of acute hospital admission. The primary outcome is acute admission. Secondary outcomes are readmissions, preventable admissions, death, and costs of health care utilization. Barriers and facilitators for community nurse's acceptance and use of the algorithm will be explored too. DISCUSSION: This 'PATINA algorithm and decision support tool' is expected to positively influence the care for older community-dwelling citizens, by improving nurses' awareness of citizens at increased risk, and by supporting their clinical decision-making. This may increase preventive measures in primary care and reduce use of secondary health care. Further, the study will increase our knowledge of barriers and facilitators to implementing algorithms and decision support in a community care setup. TRIAL REGISTRATION: ClinicalTrials.gov , identifier: NCT04398797 . Registered 13 May 2020.

Time-course study of the protection induced by an interferon-inducible DNA vaccine against viral haemorrhagic septicaemia in rainbow trout.

The highly effective DNA vaccines against diseases caused by fish rhabdoviruses in farmed fish consist of a DNA plasmid vector encoding the viral glycoprotein under the control of a constitutive cytomegalovirus promoter (CMV). Among others, attempts to improve efficacy and safety of these DNA vaccines have focused on regulatory elements of plasmid vectors, which play a major role in controlling expression levels of vaccine antigens. Depending on the context, use of a fish-derived promoter with minimal activity in mammalian cells could be preferable. Another aspect related to the CMV promoter is that constitutive expression of the vaccine antigen may lead to rapid elimination of antigen expressing cells in the fish and thereby potentially reduce the long-term effects of the vaccine. In this study, we compared DNA vaccines with the interferon-inducible Mx promoter from rainbow trout and the CMV promoter, respectively. Plasmid constructs encoding the enhanced green fluorescent protein (EGFP) were used for the in vitro analysis, whereas DNA vaccines encoding the glycoprotein (G) of the viral haemorrhagic septicaemia virus (VHSV) were applied for the in vivo examination. The in vitro analysis showed that while the DNA vaccine with the CMV promoter constitutively drove the expression of EGFP in both fish and human cell lines, the DNA vaccine with the Mx promoter inducibly enhanced the expression of EGFP in the fish cell line. To address the impact on protection, a time-course model was followed as suggested by Kurath et al. (2006), where vaccinated fish were challenged with VHSV at 2, 8 and 78 weeks post-vaccination (wpv). The DNA vaccine with the CMV promoter protected at all times, while vaccination with the DNA vaccine containing the Mx promoter only protected the fish at 8 wpv. However, following induction with Poly (I:C) one week before the challenge, high protection was also evident at 2 wpv. In conclusion, the results revealed a more fish host dependent activity of the trout Mx promoter compared to the traditionally used cross species-active CMV promoter, but improvements will be needed for its application in DNA vaccines to ensure long term protection.

Pharmacological interventions for benzodiazepine discontinuation in chronic benzodiazepine users.

BACKGROUND: Prolonged treatment with benzodiazepines is common practice despite clinical recommendations of short-term use. Benzodiazepines are used by approximately 4% of the general population, with increased prevalence in psychiatric populations and the elderly. After long-term use it is often difficult to discontinue benzodiazepines due to psychological and physiological dependence. This review investigated if pharmacological interventions can facilitate benzodiazepine tapering. OBJECTIVES: To assess the benefits and harms of pharmacological interventions to facilitate discontinuation of chronic benzodiazepine use. SEARCH METHODS: We searched the following electronic databases up to October 2017: Cochrane Drugs and Alcohol Group's Specialised Register of Trials, CENTRAL, PubMed, Embase, CINAHL, and ISI Web of Science. We also searched ClinicalTrials.gov, the WHO ICTRP, and ISRCTN registry, and checked the reference lists of included studies for further references to relevant randomised controlled trials. SELECTION CRITERIA: We included randomised controlled trials comparing pharmacological treatment versus placebo or no intervention or versus another pharmacological intervention in adults who had been treated with benzodiazepines for at least two months and/or fulfilled criteria for benzodiazepine dependence (any criteria). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 38 trials (involving 2543 participants), but we could only extract data from 35 trials with 2295 participants. Many different interventions were studied, and no single intervention was assessed in more than four trials. We extracted data on 18 different comparisons. The risk of bias was high in all trials but one. Trial Sequential Analysis showed imprecision for all comparisons.For benzodiazepine discontinuation, we found a potential benefit of valproate at end of intervention (1 study, 27 participants; risk ratio (RR) 2.55, 95% confidence interval (CI) 1.08 to 6.03; very low-quality evidence) and of tricyclic antidepressants at longest follow-up (1 study, 47 participants; RR 2.20, 95% CI 1.27 to 3.82; low-quality evidence).We found potentially positive effects on benzodiazepine withdrawal symptoms of pregabalin (1 study, 106 participants; mean difference (MD) -3.10 points, 95% CI -3.51 to -2.69; very low-quality evidence), captodiame (1 study, 81 participants; MD -1.00 points, 95% CI -1.13 to -0.87; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -3.57 points, 95% CI -5.34 to -1.80; very low-quality evidence), tricyclic antidepressants (1 study, 38 participants; MD -19.78 points, 95% CI -20.25 to -19.31; very low-quality evidence), and flumazenil (3 studies, 58 participants; standardised mean difference -0.95, 95% CI -1.71 to -0.19; very low-quality evidence) at end of intervention. However, the positive effect of paroxetine on benzodiazepine withdrawal symptoms did not persist until longest follow-up (1 study, 54 participants; MD -0.13 points, 95% CI -4.03 to 3.77; very low-quality evidence).The following pharmacological interventions reduced symptoms of anxiety at end of intervention: carbamazepine (1 study, 36 participants; MD -6.00 points, 95% CI -9.58 to -2.42; very low-quality evidence), pregabalin (1 study, 106 participants; MD -4.80 points, 95% CI -5.28 to -4.32; very low-quality evidence), captodiame (1 study, 81 participants; MD -5.70 points, 95% CI -6.05 to -5.35; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -6.75 points, 95% CI -9.64 to -3.86; very low-quality evidence), and flumazenil (1 study, 18 participants; MD -1.30 points, 95% CI -2.28 to -0.32; very low-quality evidence).Two pharmacological treatments seemed to reduce the proportion of participants that relapsed to benzodiazepine use: valproate (1 study, 27 participants; RR 0.31, 95% CI 0.11 to 0.90; very low-quality evidence) and cyamemazine (1 study, 124 participants; RR 0.33, 95% CI 0.14 to 0.78; very low-quality evidence). Alpidem decreased the proportion of participants with benzodiazepine discontinuation (1 study, 25 participants; RR 0.41, 95% CI 0.17 to 0.99; number needed to treat for an additional harmful outcome (NNTH) 2.3 participants; low-quality evidence) and increased the occurrence of withdrawal syndrome (1 study, 145 participants; RR 4.86, 95% CI 1.12 to 21.14; NNTH 5.9 participants; low-quality evidence). Likewise, magnesium aspartate decreased the proportion of participants discontinuing benzodiazepines (1 study, 144 participants; RR 0.80, 95% CI 0.66 to 0.96; NNTH 5.8; very low-quality evidence).Generally, adverse events were insufficiently reported. Specifically, one of the flumazenil trials was discontinued due to severe panic reactions. AUTHORS' CONCLUSIONS: Given the low or very low quality of the evidence for the reported outcomes, and the small number of trials identified with a limited number of participants for each comparison, it is not possible to draw firm conclusions regarding pharmacological interventions to facilitate benzodiazepine discontinuation in chronic benzodiazepine users. Due to poor reporting, adverse events could not be reliably assessed across trials. More randomised controlled trials are required with less risk of systematic errors ('bias') and of random errors ('play of chance') and better and full reporting of patient-centred and long-term clinical outcomes. Such trials ought to be conducted independently of industry involvement.

Treatment of adult patients with schizophrenia and complex mental health needs - A national clinical guideline.

BACKGROUND AND AIM: The Danish Health and Medicines Authority assembled a group of experts to develop a national clinical guideline for patients with schizophrenia and complex mental health needs. Within this context, ten explicit review questions were formulated, covering several identified key issues. METHODS: Systematic literature searches were performed stepwise for each review question to identify relevant guidelines, systematic reviews/meta-analyses, and randomized controlled trials. The quality of the body of evidence for each review question was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Clinical recommendations were developed on the basis of the evidence, assessment of the risk-benefit ratio, and perceived patient preferences. RESULTS: Based on the identified evidence, a guideline development group (GDG) recommended that the following interventions should be offered routinely: antipsychotic maintenance therapy, family intervention and assertive community treatment. The following interventions should be considered: long-acting injectable antipsychotics, neurocognitive training, social cognitive training, cognitive behavioural therapy for persistent positive and/or negative symptoms, and the combination of cognitive behavioural therapy and motivational interviewing for cannabis and/or central stimulant abuse. SSRI or SNRI add-on treatment for persistent negative symptoms should be used only cautiously. Where no evidence was available, the GDG agreed on a good practice recommendation. CONCLUSIONS: The implementation of this guideline in daily clinical practice can facilitate good treatment outcomes within the population of patients with schizophrenia and complex mental health needs. The guideline does not cover all available interventions and should be used in conjunction with other relevant guidelines.

Hearing loss and its association with the proteome of perilymph, cerebrospinal fluid, and tumor tissue in patients with vestibular schwannoma.

This study examined the association between hearing loss in sporadic vestibular schwannoma patients and the proteome of perilymph (PL), cerebrospinal fluid (CSF), and vestibular schwannoma. Intraoperative sampling of PL and of CSF, and biopsy of vestibular schwannoma tissue, was performed in 32, 32, and 20 patients with vestibular schwannoma, respectively. Perilymph and CSF in three patients with meningioma and normal hearing were also sampled. The proteomes were identified by liquid chromatography coupled to high-resolution tandem mass spectrometry. Preoperative hearing function of the patients was evaluated with pure tone audiometry, with mean values at frequencies of 500, 1000, 2000, and 4000 Hz (PTA4) in the tumor-affected ear used to delineate three hearing groups. Analysis of the PL samples revealed significant upregulation of complement factor H-related protein 2 (CFHR2) in patients with severe to profound hearing loss after false discovery rate correction. Pathway analysis of biofunctions revealed higher activation scores in the severe/profound hearing loss group of leukocyte migration, viral infection, and migration of cells in PL. Upregulation of CFHR2 and activation of these pathways indicate chronic inflammation in the cochlea of vestibular schwannoma patients with severe to profound hearing loss compared with patients with normal hearing or mild hearing loss.

Low quality of life in binge eating disorder compared to healthy controls.

INTRODUCTION: Patients with binge eating disorder (BED) tend to report a lower quality of life (QoL) than patients with other eating disorders. However, most research on QoL in eating disorders include generic rather than disease-specific measures. Depression and obesity are frequent comorbid conditions in patients with BED affecting QoL. In the present study, we aimed to assess disease-specific QoL in BED and to investigate the impact of obesity and depression. METHODS: Adult patients who met the DSM-5 criteria for BED (N = 98) were recruited from a newly established specialised online treatment programme for BED and completed the following questionnaires: the Eating Disorder Quality of Life Questionnaire (EDQLS), the Major Depression Inventory (MDI) and the newly introduced Binge Eating Disorder Questionnaire for measuring BED severity. Healthy, normal-weight individuals were recruited through online invitations on social media, n = 190. RESULTS: QoL in BED individuals was significantly lower than in healthy individuals. No relationship was found between BMI and EDQLS, whereas significant, negative correlations were found between depression and all subscales of the EDQLS. CONCLUSION: Disease-specific QoL in BED was associated with depression but not with BMI. FUNDING: none. CLINICALTRIALS: gov NCT05010798.

Structured decision support to prevent hospitalisations of community-dwelling older adults in Denmark (PATINA): an open-label, stepped-wedge, cluster-randomised controlled trial.

BACKGROUND: Ageing populations and health-care staff shortages encourage efforts in primary care to recognise and prevent health deterioration and acute hospitalisation in community-dwelling older adults. The PATINA algorithm and decision-support tool alerts home-based-care nurses to older adults at risk of hospitalisation. The study aim was to test whether use of the PATINA tool was associated with changes in health-care use. METHODS: An open-label, stepped-wedge, cluster-randomised controlled trial was done in three Danish municipalities, covering 20 area teams providing home-based care to around 7000 recipients. During a period of 12 months, area teams were randomly assigned to an intervention crossover for older adults (aged 65 years or older) who received care at home. The primary outcome was hospitalisation within 30 days of identification by the algorithm as being at risk of hospitalisation. Secondary outcomes were hospital readmission and other hospital contacts, outpatient contacts, contact with primary care physicians (PCPs), temporary care, and death, within 30 days of identification. This study was registered at ClinicalTrials.gov (NTC04398797). FINDINGS: In total, 2464 older adults participated in the study: 1216 (49·4%) in the control phase and 1248 (50·6%) in the intervention phase. In the control phase, 102 individuals were hospitalised within 30 days during 33 943 days of risk (incidence 0·09 per 30 days), compared with 118 individuals within 34 843 days of risk (0·10 per 30 days) during the intervention phase. The intervention was not associated with a reduction in the number of first hospitalisations within 30 days (incidence rate ratio [IRR] 1·10 [90% CI 0·90-1·40]; p=0·28). Furthermore it was not associated with reduced rates of other hospital contacts (IRR 1·10 [95% CI 0·90-1·40]; p=0·28), outpatient contacts (1·10 [0·88-1·40]; p=0·42), or mortality (0·82 [0·58-1·20]; p=0·25). The intervention was associated with a 59% reduction in readmissions within 30 days of hospital discharge (IRR 0·41 [95% CI 0·24-0·68]; p=0·0007), a 140% increase in contacts with PCPs (2·40 [1·18-3·20]; p<0·0001), and a 150% increase in use of temporary care (2·50 [1·40-4·70]; p=0·0027). INTERPRETATION: Despite having no effect on the primary outcome, the PATINA tool showed other benefits for older adults receiving home-based care. Such algorithms have the potential to shift health-care use from secondary to primary care but need to be tested in other home-based care settings. Implementation of algorithms in clinical practice should be informed by analysis of cost-effectiveness and potential harms as well as the benefits. FUNDING: Innovation Fund Denmark and Region of Southern Denmark. TRANSLATIONS: For the Danish, French and German translations of the abstract see Supplementary Materials section.

Chronic rhinosinusitis and occupational risk factors among 20- to 75-year-old Danes-A GA(2) LEN-based study.

BACKGROUND: Very little is known about occupational risk factors for chronic rhinosinusitis (CRS). The aim of this study was to evaluate occupational and other potential risk factors for CRS in a Danish population. METHODS: A cross sectional survey study among 4,554 Danes aged 20-75 years evaluated self-reported symptoms of CRS, asthma, and nasal allergy, along with information on smoking habits and occupation. RESULTS: A total of 3,099 returned completed questionnaires (response rate 68.1%). The overall CRS prevalence was 7.8% with no significant differences related to age or gender. Risk ratio estimates revealed an increased risk of CRS among female blue collar workers compared to female white collar workers. Among men the effect of occupation depended on smoking status. Occupational exposure to gasses, fumes, dust, or smoke increased the overall risk of CRS. CRS was reported approximately four times as often in subjects with asthma and in subjects with nasal allergy. Current smoking doubled the CRS prevalence. CONCLUSIONS: CRS prevalence was affected by occupation (blue vs. white collar), but the observed effect depended on gender and smoking status. Exposure to airway irritants (occupational or smoking) increased the CRS prevalence. Studies on larger cohorts are needed to fully assess these tendencies, for example, by more extensive use of Job Exposure Matrix models.

Predictive Factors of Successful Return to Work Following Discectomy.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE: To identify modifiable factors associated with successful return to work 12 weeks following discectomy. Lumbar disc herniation is a common cause of sciatica and sick leave. This presents an economic burden to the individual and the society. METHODS: Data from DaneSpine on a consecutive cohort of patients operated due to lumbar disc herniation during a 3-year period was identified and merged with data from the Ministry of Employment's register on public welfare payments. Data on welfare payments 2 years prior to the date of operation and 1 year postoperative was included. Patients were considered to be on sick leave if they received welfare payments for the week. Patients are considered to have returned to work if they did not receive public welfare payments for a 4-week period. RESULTS: Of 1134 patients meeting inclusion criteria, 98.5% had complete preoperative surgical data available. Postoperatively, 79.1% of the patients returned to the work within 12 weeks. Physically demanding jobs, low preoperative EQ5D score, and long duration of sick leave prior to surgery were associated negatively with return to work at 12 weeks. CONCLUSION: The results of this study indicate that patients who have a longer duration of sick leave have a physically demanding job and are in a poor health are more likely not to return to work by 12 weeks after surgery for lumbar disc herniation. Future studies are needed to determine if earlier referral to a surgeon leads to an earlier return to work.

The Acute Effects of Furosemide on Na-K-Cl Cotransporter-1, Fetuin-A and Pigment Epithelium-Derived Factor in the Guinea Pig Cochlea.

Background: Furosemide is a loop diuretic used to treat edema; however, it also targets the Na-K-Cl cotransporter-1 (NKCC1) in the inner ear. In very high doses, furosemide abolishes the endocochlear potential (EP). The aim of the study was to gain a deeper understanding of the temporal course of the acute effects of furosemide in the inner ear, including the protein localization of Fetuin-A and PEDF in guinea pig cochleae. Material and Method: Adult guinea pigs were given an intravenous injection of furosemide in a dose of 100 mg per kg of body weight. The cochleae were studied using immunohistochemistry in controls and at four intervals: 3 min, 30 min, 60 min and 120 min. Also, cochleae of untreated guinea pigs were tested for Fetuin-A and PEDF mRNA using RNAscope® technology. Results: At 3 min, NKCC1 staining was abolished in the type II fibrocytes in the spiral ligament, followed by a recovery period of up to 120 min. In the stria vascularis, the lowest staining intensity of NKCC1 presented after 30 min. The spiral ganglion showed a stable staining intensity for the full 120 min. Fetuin-A protein and mRNA were detected in the spiral ganglion type I neurons, inner and outer hair cells, pillar cells, Deiters cells and the stria vascularis. Furosemide induced an increased staining intensity of Fetuin-A at 120 min. PEDF protein and mRNA were found in the spiral ganglia type I neurons, the stria vascularis, and in type I and type II fibrocytes of the spiral ligament. PEDF protein staining intensity was high in the pillar cells in the organ of Corti. Furosemide induced an increased staining intensity of PEDF in type I neurons and pillar cells after 120 min. Conclusion: The results indicate rapid furosemide-induced changes of NKCC1 in the type II fibrocytes. This could be part of the mechanism that causes reduction of the EP within minutes after high dose furosemide injection. Fetuin-A and PEDF are present in many cells of the cochlea and probably increase after furosemide exposure, possibly as an otoprotective response.

White matter microstructure and sleep-wake disturbances in individuals at ultra-high risk of psychosis.

Aim: White matter changes in individuals at ultra-high risk for psychosis (UHR) may be involved in the transition to psychosis. Sleep-wake disturbances commonly precede the first psychotic episode and predict development of psychosis. We examined associations between white matter microstructure and sleep-wake disturbances in UHR individuals compared to healthy controls (HC), as well as explored the confounding effect of medication, substance use, and level of psychopathology. Methods: Sixty-four UHR individuals and 35 HC underwent clinical interviews and diffusion weighted imaging. Group differences on global and callosal mean fractional anisotropy (FA) was tested using general linear modeling. Sleep-wake disturbances were evaluated using the subjective measures disturbed sleep index (DSI) and disturbed awakening index (AWI) from the Karolinska Sleep Questionnaire, supported by objective sleep measures from one-night actigraphy. The primary analyses comprised partial correlation analyses between global FA/callosal FA and sleep-wake measures. Secondary analyses investigated multivariate patterns of covariance between measures of sleep-wake disturbances and FA in 48 white matter regions of interest using partial least square correlations. Results: Ultra-high risk for psychosis individuals displayed lower global FA (F = 14.56, p < 0.001) and lower callosal FA (F = 11.34, p = 0.001) compared to HC. Subjective sleep-wake disturbances were significantly higher among the UHR individuals (DSI: F = 27.59, p < 0.001, AWI: F = 36.42, p < 0.001). Lower callosal FA was correlated with increased wake after sleep onset (r = -0.34, p = 0.011) and increased sleep fragmentation index (r = -0.31, p = 0.019) in UHR individuals. Multivariate analyses identified a pattern of covariance in regional FA which were associated with DSI and AWI in UHR individuals (p = 0.028), but not in HC. Substance use, sleep medication and antipsychotic medication did not significantly confound these associations. The association with objective sleep-wake measures was sustained when controlling for level of depressive and UHR symptoms, but symptom level confounded the covariation between FA and subjective sleep-wake measures in the multivariate analyses. Conclusion: Compromised callosal microstructure in UHR individuals was related to objectively observed disruptions in sleep-wake functioning. Lower FA in ventrally located regions was associated with subjectively measured sleep-wake disturbances and was partly explained by psychopathology. These findings call for further investigation of sleep disturbances as a potential treatment target.

Efficacy of DNA Vaccines in Protecting Rainbow Trout against VHS and IHN under Intensive Farming Conditions.

Despite the negative impact of viral hemorrhagic septicemia (VHS) and infectious hematopoietic necrosis (IHN) on European rainbow trout farming, no vaccines are commercially available in Europe. DNA vaccines are protective under experimental conditions, but testing under intensive farming conditions remains uninvestigated. Two DNA vaccines encoding the glycoproteins (G) of recent Italian VHSV and IHNV isolates were developed and tested for potency and safety under experimental conditions. Subsequently, a field vaccination trial was initiated at a disease-free hatchery. The fish were injected intramuscularly with either the VHS DNA vaccine or with a mix of VHS and IHN DNA vaccines at a dose of 1 µg/vaccine/fish, or with PBS. At 60 days post-vaccination, fish were moved to a VHSV and IHNV infected facility. Mortality started 7 days later, initially due to VHS. After 3 months, IHN became the dominant cause of disease. Accordingly, both DNA vaccinated groups displayed lower losses compared to the PBS group during the first three months, while the VHS/IHN vaccinated group subsequently had the lowest mortality. A later outbreak of ERM caused equal disease in all groups. The trial confirmed the DNA vaccines to be safe and efficient in reducing the impact of VHS and IHN in farmed rainbow trout.

The proteome of the human endolymphatic sac endolymph.

The endolymphatic sac (ES) is the third part of the inner ear, along with the cochlea and vestibular apparatus. A refined sampling technique was developed to analyse the proteomics of ES endolymph. With a tailored solid phase micro-extraction probe, five ES endolymph samples were collected, and six sac tissue biopsies were obtained in patients undergoing trans-labyrinthine surgery for sporadic vestibular schwannoma. The samples were analysed using nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS) to identify the total number of proteins. Pathway identification regarding molecular function and protein class was presented. A total of 1656 non-redundant proteins were identified, with 1211 proteins detected in the ES endolymph. A total of 110 proteins were unique to the ES endolymph. The results from the study both validate a strategy for in vivo and in situ human sampling during surgery and may also form a platform for further investigations to better understand the function of this intriguing part of the inner ear.

Workability in the Ageing Workforce-A Population-Based Cross-Sectional Study.

BACKGROUND: The purpose of this study was to investigate the impact of age, musculoskeletal pain and ergonomic exposure on workability in the oldest group of workers. METHODS: The study was a population based cross-sectional survey. The study population comprised citizens born between 1952-1966, living in Esbjerg municipality ultimo 2016 (n = 23,463). A questionnaire was sent electronically or by mail. The analysis included the working population only. A stereotype logistic regression was used with the primary dependent variable being workability and independent variables included age, musculoskeletal pain, and ergonomic exposure. RESULTS: The response rate was 58% and the data demonstrated a significant negative association between age and workability. With excellent workability as a reference, the odds for poor workability increased by 97% being 60+ y compared to 50-55 y. Both moderate intensity and severe musculoskeletal pain in the back, shoulder and knee/hip all showed significantly higher odds for poor workability. Ergonomic exposures, such as standing/walking, working with back bent or twisted and carrying or lifting had a significant negative impact on workability. CONCLUSION: Age, musculoskeletal pain and ergonomic exposures showed a significant negative impact on workability in the oldest group of workers and should be targeted with preventive initiatives.