Content and Bioaccessibility of Minerals and Proteins in Fish-Bone Containing Side-Streams from Seafood Industries.

With the aim to upcycle fish side-streams, enzymatic hydrolysis is often applied to produce protein hydrolysates with bioactive properties or just as a protein source for food and feed. However, the production of hydrolysates generates a side-stream. For underutilized fish and fish backbone this side-stream will contain fish bones and make it rich in minerals. The aim of this study was to assess the relative bioaccessibility (using the standardized in vitro model INFOGEST 2.0) of minerals in a dietary supplement compared to bone powder generated after enzymatic hydrolysis of three different fish side-streams: undersized whole hake, cod and salmon backbones consisting of insoluble protein and bones. Differences in the bioaccessibility of protein between the powders were also investigated. The enzyme hydrolysis was carried out using different enzymes and hydrolysis conditions for the different fish side-streams. The content and bioaccessibility of protein and the minerals phosphorus (P), calcium (Ca), potassium (K) and magnesium (Mg) were measured to evaluate the potential of the powder as an ingredient in, e.g., dietary supplements. The bone powders contained bioaccessible proteins and minerals. Thus, new side-streams generated from enzymatic hydrolysis can have possible applications in the food sector due to bioaccessible proteins and minerals.

Effects of 3 months of 10-h per-day time-restricted eating and 3 months of follow-up on bodyweight and cardiometabolic health in Danish individuals at high risk of type 2 diabetes: the RESET single-centre, parallel, superiority, open-label, randomised controlled trial.

BACKGROUND: Time-restricted eating (TRE) has been suggested to be a simple, feasible, and effective dietary strategy for individuals with overweight or obesity. We aimed to investigate the effects of 3 months of 10-h per-day TRE and 3 months of follow-up on bodyweight and cardiometabolic risk factors in individuals at high risk of type 2 diabetes. METHODS: This was a single-centre, parallel, superiority, open-label randomised controlled clinical trial conducted at Steno Diabetes Center Copenhagen (Denmark). The inclusion criteria were age 30-70 years with either overweight (ie, BMI ≥25 kg/m2) and concomitant prediabetes (ie, glycated haemoglobin [HbA1c] 39-47 mmol/mol) or obesity (ie, BMI ≥30 kg/m2) with or without prediabetes and a habitual self-reported eating window (eating and drinking [except for water]) of 12 h per day or more every day and of 14 h per day or more at least 1 day per week. Individuals were randomly assigned 1:1 to 3 months of habitual living (hereafter referred to as the control group) or TRE, which was a self-selected 10-h per-day eating window placed between 0600 h and 2000 h. Randomisation was done in blocks varying in size and was open for participants and research staff, but outcome assessors were masked during statistical analyses. The randomisation list was generated by an external statistician. The primary outcome was change in bodyweight, assessed after 3 months (12 weeks) of the intervention and after 3 months (13 weeks) of follow-up. Adverse events were reported and registered at study visits or if participants contacted study staff to report events between visits. This trial is registered on ClinicalTrials.gov (NCT03854656). FINDINGS: Between March 12, 2019, and March 2, 2022, 100 participants (66 [66%] were female and 34 [34%] were male; median age 59 years [IQR 52-65]) were enrolled and randomly assigned (50 to each group). Of those 100, 46 (92%) in the TRE group and 46 (92%) in the control group completed the intervention period. After 3 months of the intervention, there was no difference in bodyweight between the TRE group and the control group (-0·8 kg, 95% CI -1·7 to 0·2; p=0·099). Being in the TRE group was not associated with a lower bodyweight compared with the control group after subsequent 3-month follow-up (-0·2 kg, -1·6 to 1·2). In the per-protocol analysis, participants who completed the intervention in the TRE group lost 1·0 kg (-1·9 to -0·0; p=0·040) bodyweight compared with the control group after 3 months of intervention, which was not maintained after the 3-month follow-up period (-0·4 kg, -1·8 to 1·0). During the trial and follow-up period, one participant in the TRE group reported a severe adverse event: development of a subcutaneous nodule and pain when the arm was in use. This side-effect was evaluated to be related to the trial procedures. INTERPRETATION: 3 months of 10-h per-day TRE did not lead to clinically relevant effects on bodyweight in middle-aged to older individuals at high risk of type 2 diabetes. FUNDING: Novo Nordisk Foundation, Aalborg University, Helsefonden, and Innovation Fund Denmark.

Pharmacological activation of PDC flux reverses lipid-induced inhibition of insulin action in muscle during recovery from exercise.

Insulin resistance is a risk factor for type 2 diabetes and exercise can improve insulin sensitivity. However, following exercise high circulating fatty acid (FA) levels might counteract this. We hypothesized that such inhibition would be reduced by forcibly increasing carbohydrate oxidation through pharmacological activation of the pyruvate dehydrogenase complex (PDC). Insulin-stimulated glucose uptake was examined with a cross-over design in healthy young men (n = 8) in a previously exercised and a rested leg during a hyperinsulinemiceuglycemic clamp five hours after one-legged exercise with: 1) infusion of saline, 2) infusion of intralipid imitating circulating FA levels during recovery from whole-body exercise, and 3) infusion of intralipid + oral PDC-activator, dichloroacetate (DCA). Intralipid infusion reduced insulin-stimulated glucose uptake by 19% in the previously exercised leg, which was not observed in the contralateral rested leg. Interestingly, this effect of intralipid in the exercised leg was abolished by DCA, which increased muscle PDC activity (130%) and flux (acetylcarnitine 130%) and decreased inhibitory phosphorylation of PDC on Ser293 (∼40%) and Ser300 (∼80%). Novel insight is provided into the regulatory interaction between glucose and lipid metabolism during exercise recovery. Coupling exercise and PDC flux activation upregulated the capacity for both glucose transport (exercise) and oxidation (DCA), which seems necessary to fully stimulate insulin-stimulated glucose uptake during recovery.

First effectiveness data of lenvatinib and pembrolizumab as first-line therapy in advanced anaplastic thyroid cancer: a retrospective cohort study.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare and aggressive neoplasm. We still lack effective treatment options, so survival rates remain very low. Here, we aimed to evaluate the activity of the combination of lenvatinib and pembrolizumab as systemic first-line therapy in ATC. METHODS: In a retrospective analysis, we investigated the activity and tolerability of combined lenvatinib (starting dose 14 to 24 mg daily) and pembrolizumab (200 mg every three weeks) as first-line therapy in an institutional cohort of ATC patients. RESULTS: Five patients with metastatic ATC received lenvatinib and pembrolizumab as systemic first-line therapy. The median progression-free survival was 4.7 (range 0.8-5.9) months, and the median overall survival was 6.3 (range 0.8-not reached) months. At the first follow-up, one patient had partial response, three patients had stable disease, and one patient was formally not evaluable due to interference of assessment by concomitant acute infectious thyroiditis. This patient was then stable for more than one year and was still on therapy at the data cutoff without disease progression. Further analyses revealed deficient DNA mismatch repair, high CD8+ lymphocyte infiltration, and low macrophage infiltration in this patient. Of the other patients, two had progressive disease after adverse drug reactions and therapy de-escalation, and two died after the first staging. For all patients, the PD-L1 combined positive score ranged from 12 to 100%. CONCLUSIONS: The combination of lenvatinib and pembrolizumab was effective and moderately tolerated in treatment-naïve ATC patients with occasional long-lasting response. However, we could not confirm the exceptional responses for this combination therapy reported before in pretreated patients.

The exometabolome of microbial communities inhabiting bare ice surfaces on the southern Greenland Ice Sheet.

Microbial blooms colonize the Greenland Ice Sheet bare ice surface during the ablation season and significantly reduce its albedo. On the ice surface, microbes are exposed to high levels of irradiance, freeze-thaw cycles, and low nutrient concentrations. It is well known that microorganisms secrete metabolites to maintain homeostasis, communicate with other microorganisms, and defend themselves. Yet, the exometabolome of supraglacial microbial blooms, dominated by the pigmented glacier ice algae Ancylonema alaskanum and Ancylonema nordenskiöldii, remains thus far unstudied. Here, we use a high-resolution mass spectrometry-based untargeted metabolomics workflow to identify metabolites in the exometabolome of microbial blooms on the surface of the southern tip of the Greenland Ice Sheet. Samples were collected every 6 h across two diurnal cycles at 5 replicate sampling sites with high similarity in community composition, in terms of orders and phyla present. Time of sampling explained 46% (permutational multivariate analysis of variance [PERMANOVA], pseudo-F = 3.7771, p = 0.001) and 27% (PERMANOVA, pseudo-F = 1.8705, p = 0.001) of variance in the exometabolome across the two diurnal cycles. Annotated metabolites included riboflavin, lumichrome, tryptophan, and azelaic acid, all of which have demonstrated roles in microbe-microbe interactions in other ecosystems and should be tested for potential roles in the development of microbial blooms on bare ice surfaces.

Do school-based smoking preventive interventions have unintended effects? Post hoc analysis of the Focus cluster randomised controlled trial.

OBJECTIVES: Public health interventions are designed to improve specific health-related outcomes; however, they may also produce negative side effects, such as substitution use, psychological or social harms. Knowledge about the unintended effects of school-based smoking preventive interventions is sparse. Hence, this study examined these potential unintended effects of the smoking-reducing intervention, Focus, among students in the vocational education and training setting. DESIGN: Cluster randomised controlled trial stratified by school type with 5 months follow-up. SETTING AND PARTICIPANTS: Across Denmark, eight schools were randomised to the intervention group (n=844 students, response proportion 76%) and six schools to the control group (n=815 students, response proportion 75%). This study focused solely on students who smoked at baseline (N=491). INTERVENTIONS: The intervention was developed systematically based on theory and a thoroughly mixed-methods needs assessment. Intervention components included a comprehensive school tobacco policy (smoke-free school hours) supported by a 3-day course for school staff and launched by an edutainment session for students; class-based lessons and a quit-and-win competition; and individual telephone smoking cessation support. OUTCOMES: Alternative tobacco and nicotine products (regular use of smokeless tobacco, hookah and e-cigarettes), regular cannabis use, boredom and loneliness at school, stress and perceived stigmatisation among smokers. RESULTS: We found no statistically significant unintended effects of the intervention. Nonetheless, insignificant findings indicated that students in the intervention group were less likely to be bored during school hours (OR 0.59, 95% CI 0.32 to 1.10) and experience stress (OR 0.62, 95% CI 0.35 to 1.10), but more likely to report feeling stigmatised compared with the control group (OR 1.55, 95% CI 0.71 to 3.40). CONCLUSIONS: Overall, findings suggested no unintended effects of the Focus trial with respect to substitution use, psychological, nor group or social harms. Future research is encouraged to report potential harmful outcomes of smoking preventive interventions, and interventions should be aware of the possible stigmatisation of smokers. TRIAL REGISTRATION NUMBER: ISRCTN16455577.

Associations Between Physical Activity and Gastrointestinal Transit Times in People with Normal Weight, Overweight, and Obesity.

BACKGROUND: Rapid gastric emptying is associated with obesity and overeating, whereas delayed gastric emptying is associated with anorexia. Acute effects of exercise on gastric emptying have been investigated extensively, but the influence of habitual physical activity on gastric emptying and transit time in other regions of the gastrointestinal tract is poorly understood. OBJECTIVE: The objective was to investigate associations between objectively measured habitual physical activity and gastrointestinal transit times in adults with varying degrees of adiposity. METHODS: 50 adults (58% women) were included in this cross-sectional study. Physical activity was measured by an accelerometer placed on the lower back for 7 d. Gastric emptying time, small bowel transit time, colonic transit time, and whole gut transit time were simultaneously evaluated by a wireless motility capsule, which was ingested together with a standardized mixed meal. Linear regression models were applied to assess the associations of total activity counts and time spent at different intensities-sedentary activity (0-100 counts/min), low light activity (101-759 counts/min), high light activity (760-1951 counts/min); moderate and vigorous activity (≥1952 counts/min)) with gastrointestinal transit times. RESULTS: Median [Q1; Q3] age was 56.5 [46.6-65.5] y, and body mass index (BMI) was 32.1 [28.5-35.1] kg/m2. For every additional hour spent performing high light intensity physical activity, colonic transit time was 25.5 % [95% CI: 3.10, 42.7] more rapid (P = 0.028), and whole gut transit time was 16.2 % [95% CI: 1.84, 28.4] more rapid (P = 0.028) when adjusted for sex, age, and body fat. No other associations were observed. CONCLUSIONS: More time spent on physical activity at high light intensity was associated with more rapid colonic and whole gut transit time, independent of age, sex, and body fat, whereas other intensities of physical activity and gastrointestinal transit times were not associated. TRIAL REGISTRATION: Clinicaltrials.gov IDs (NCT03894670, NCT03854656).

Metastases to the pituitary gland: insights from the German pituitary tumor registry.

Metastatic involvement of the pituitary gland is a rare but clinically significant phenomenon, that often poses diagnostic and therapeutic challenges. The aim of this study was to provide a comprehensive analysis of the origin of pituitary metastases using data from the German Pituitary Tumor Registry, one of the globally largest collections of pituitary pathology specimens. Here, we report data from a retrospective analysis of patients with metastases to the pituitary registered between 1990 and 2022. Out of 17,896 pituitary cases in the registry during this period, a total of 96 metastases to the pituitary gland were identified, accounting for 0.5% of all pituitary tumors in the registry. The mean age of the patients was 64 years. Breast cancer was identified as the primary tumor in 25% of total cases (n = 24/96) and in 50% of female patients. The second most prevalent primary tumor was lung cancer (18.75%, n = 18/96), followed by renal cell carcinoma (14.58%, n = 14/96). In comparison to current meta-analyses, this cohort shows a higher prevalence of metastases originating from the kidney. Furthermore, in contrast to the existing literature, no case of primary thyroid tumor was identified. Our study highlights the importance of pituitary metastases as a differential diagnosis in patients presenting with pituitary tumors.

Primary settling changes the microbial community of influent wastewater to wastewater treatment plants.

The continuous immigration of bacteria in influent wastewater strongly impacts the microbial community of activated sludge (AS) in wastewater treatment plants (WWTP), both in terms of species composition and their abundance. Therefore, it is of interest to elucidate the route of immigrating bacteria into the biological tanks, including the effect of primary settlers. These are commonly used pretreatment units that can possibly selectively increase or reduce the relative abundance of certain bacteria. Species-level identification of the microbial composition of influent wastewater before and after primary settling was carried out in four full-scale municipal WWTPs biweekly over one year by 16S rRNA gene amplicon sequencing. Overall, 37-49% of incoming COD was removed in the primary settlers. Most genera and species were present in the wastewater to all four plants and the trend of these were investigated across the primary settlers. Approximately 50% of the genera had the same trend across at least three WWTPs. Few genera significantly increased in relative read abundance (3.7%) after settling, while 22.3% showed a significant reduction in relative abundance. We investigated process-critical species in AS, such as known nitrifiers, polyphosphate-accumulating organisms, and filamentous bacteria. Most taxa were affected similarly in all WWTPs including multiple genera involved in bulking in AS. However, some genera, e.g., important polyphosphate-accumulating bacteria, had inconsistent trends across WWTPs, suggesting that the characteristics of the wastewater are important for the trend of some bacteria through primary settling. In all cases, primary settling changed the microbial community of the influent wastewater, posing an obvious candidate for upstream control to optimize the assembly of the microbial communities in activated sludge.

Outcome of immunotherapy in adrenocortical carcinoma: a retrospective cohort study.

OBJECTIVE: Clinical trials with immune checkpoint inhibitors (ICI) in adrenocortical carcinoma (ACC) have yielded contradictory results. We aimed to evaluate treatment response and safety of ICI in ACC in a real-life setting. DESIGN: Retrospective cohort study of 54 patients with advanced ACC receiving ICI as compassionate use at 6 German reference centres between 2016 and 2022. METHODS: Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAE) were assessed. RESULTS: In 52 patients surviving at least 4 weeks after initiation of ICI, ORR was 13.5% (6-26) and DCR was 24% (16-41). PFS was 3.0 months (95% CI, 2.3-3.7). In all patients, median OS was 10.4 months (3.8-17). 17 TRAE occurred in 15 patients, which was associated with a longer PFS of 5.5 (1.9-9.2) vs 2.5 (2.0-3.0) months (HR 0.29, 95% CI, 0.13-0.66, P = 0.001) and OS of 28.2 (9.5-46.8) vs 7.0 (4.1-10.2) months (HR 0.34, 95% CI, 0.12-0.93). Positive tissue staining for programmed cell death ligand 1 (PD-L1) was associated with a longer PFS of 3.2 (2.6-3.8) vs 2.3 (1.6-3.0, P < 0.05) months. Adjusted for concomitant mitotane use, treatment with nivolumab was associated with lower risk of progression (HR 0.36, 0.15-0.90) and death (HR 0.20, 0.06-0.72) compared to pembrolizumab. CONCLUSIONS: In the real-life setting, we observe a response comparable to other second-line therapies and an acceptable safety profile in ACC patients receiving different ICI. The relevance of PD-L1 as a marker of response and the potentially more favourable outcome in nivolumab-treated patients require confirmation.

Effectiveness of the multi-component intervention 'Focus' on reducing smoking among students in the vocational education setting: a cluster randomized controlled trial.

BACKGROUND: Social inequality in smoking remains an important public health issue. Upper secondary schools offering vocational education and training (VET) comprise more students from lower socioeconomic backgrounds and have higher smoking prevalence than general high schools. This study examined the effects of a school-based multi-component intervention on students' smoking. METHODS: A cluster randomized controlled trial. Eligible participants were schools offering VET basic courses or preparatory basic education in Denmark, and their students. Schools were stratified by subject area and eight schools were randomly allocated to intervention (1,160 invited students; 844 analyzed) and six schools to control (1,093 invited students; 815 analyzed). The intervention program comprised smoke-free school hours, class-based activities, and access to smoking cessation support. The control group was encouraged to continue with normal practice. Primary outcomes were daily cigarette consumption and daily smoking status at student level. Secondary outcomes were determinants expected to impact smoking behavior. Outcomes were assessed in students at five-month follow-up. Analyses were by intention-to-treat and per protocol (i.e., whether the intervention was delivered as intended), adjusted for covariates measured at baseline. Moreover, subgroup analyses defined by school type, gender, age, and smoking status at baseline were performed. Multilevel regression models were used to account for the cluster design. Missing data were imputed using multiple imputations. Participants and the research team were not blinded to allocation. RESULTS: Intention-to-treat analyses showed no intervention effect on daily cigarette consumption and daily smoking. Pre-planned subgroup analyses showed statistically significant reduction in daily smoking among girls compared with their counterparts in the control group (OR = 0.39, 95% CI: 0.16, 0.98). Per-protocol analysis suggested that schools with full intervention had higher benefits compared with the control group (daily smoking: OR = 0.44, 95% CI: 0.19, 1.02), while no marked differences were seen among schools with partial intervention. CONCLUSION: This study was among the first to test whether a complex, multicomponent intervention could reduce smoking in schools with high smoking risk. Results showed no overall effects. There is a great need to develop programs for this target group and it is important that they are fully implemented if an effect is to be achieved. TRIAL REGISTRATION: https://www.isrctn.com/ISRCTN16455577 , date of registration 14/06/2018.

Associations between saliva alpha-amylase, heart rate variability, saliva cortisol and cognitive performance in individuals at ultra high-risk for psychosis.

BACKGROUND: Cognitive impairments are present in individuals at ultra-high risk (UHR) of psychosis and UHR individuals exhibit a hyperactive and dysfunctional HPA-axis. Increasing stress levels could potentially lead to cognitive impairments and no previous studies have examined the association between physiological stress biomarkers and cognition in UHR individuals. This study aims to examine the association between saliva alpha amylase (SAA), heart rate variability (HRV), saliva cortisol, and cognition in UHR individuals. METHOD: We included 72 UHR individuals, aged 18-40, fulfilling criteria of the comprehensive assessment of at-risk mental state (CAARMS). Cognitive tests indexed the 7 core domains as stated by Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS). Physiological stress levels were observed for one day: saliva was collected at awakening, 30 min and 60 min after awakening and at bedtime. HRV was measured during sleep and before awakening. We used generalized linear model and controlled for multiple testing using false discovery rate (FDR). RESULTS: Higher levels of SAA were significantly associated with lower cognitive performance in the domains of verbal and visual learning and memory, sustained attention, working memory and global neurocognition looking at unadjusted data. Controlling for FDR visual memory, sustained attention and global neurocognition remained significant associated with SAA. We discovered no associations between cortisol and cognition. CONCLUSION: Visual learning and memory, sustained attention and global neurocognition remained significantly associated with SAA. This finding supports our hypothesis that an association between abnormal stress biomarkers and impaired cognition might be present in UHR individuals.

A longitudinal study on physiological stress in individuals at ultra high-risk of psychosis.

INTRODUCTION: Individuals at ultra high-risk (UHR) of psychosis exhibit significantly higher stress levels than healthy controls (HC). This study investigates how physiological stress measures differ between HC and UHR individuals and how physiological stress is associated with attenuated psychotic symptoms and changes over time in UHR individuals. Additionally, it examines how the use of medication affects physiological levels of stress. METHOD: The study included 72 UHR individuals and 36 HC. UHR were included according to the comprehensive assessment of at-risk mental state (CAARMS); a total-CAARMS score measured the attenuated psychotic symptoms and was calculated from the four psychosis subscales. HC and UHR were examined at baseline, and 47 UHR individuals were followed up after six months. Physiological stress measures were salivary cortisol, alpha-amylase (SAA) and heart-rate variability (HRV). Saliva was collected at four-time points during the day. RESULTS: There was no significant difference regarding cortisol (awakening response) or SAA measures between HC and UHR individuals. The use of antipsychotics and antidepressants was associated with low HRV in UHR individuals. In an exploratory analysis of 19 UHR individuals, we found an association between the change in total-CAARMS (six months total-CAARMS minus baseline total CAARMS) and the change in HRV during sleep (six months HRV minus baseline HRV). CONCLUSION: Our findings indicate that the use of antipsychotics and antidepressants could be associated with lower HRV in UHR individuals. There might be potential to investigate how HRV develops during the course of illness in UHR individuals.

Preventing Stress among High School Students in Denmark through the Multicomponent Healthy High School Intervention-The Effectiveness at First Follow-Up.

Stress is a widespread phenomenon and young people especially are experiencing high levels of stress. School-related factors are the most frequently self-reported stressors among adolescents, but few interventions have targeted the school environment. This study evaluated the effectiveness of the Healthy High School (HHS) intervention on stress at a 9-month follow-up. The study included 5201 first-year high school students (~16 years) in Denmark. Participating schools were randomized into the HHS intervention (N = 15) or control group (N = 15). Baseline measurements were conducted in August 2016 and the follow-up was conducted in May 2017. The intervention was designed to promote well-being (primary outcome) by focusing on physical activity, meals, sleep, sense of security, and stress (secondary outcomes). The intervention comprised: structural initiatives at the school level; a teaching material; peer-led innovation workshops; and a smartphone app. The 10-item Perceived Stress Scale was used to measure stress. Intervention effects on perceived stress were estimated using an intention-to-treat approach with multiple imputations of missing data and multilevel general linear regression modelling. A total of 4577 students answered the baseline questionnaire. No statistically significant difference was found in stress between students at intervention and control schools at the follow-up (mean score: 16.7 versus 16.7, adjusted b = 0.42, 95% CI: -0.16;1.00). The HHS Study is one of the first large randomized controlled trials targeting school environmental stressors. Potential implementation failures and the failures of the program theory are discussed.

Genetic potential for exopolysaccharide synthesis in activated sludge bacteria uncovered by genome-resolved metagenomics.

A good floc formation of activated sludge (AS) is crucial for solid-liquid separation and production of clean effluent during wastewater treatment. Floc formation is partly controlled by self-produced extracellular polymeric substances (EPS) such as exopolysaccharides, proteins, and nucleic acids. Little is known about the composition, structure, and function of EPS in AS and which bacteria produce them. To address this knowledge gap for the exopolysaccharides, we took advantage of 1083 high-quality metagenome-assembled genomes (MAGs) obtained from 23 Danish wastewater treatment plants. We investigated the genomic potential for exopolysaccharide biosynthesis in bacterial species typical in AS systems based on genome mining and gene synteny analyses. Putative gene clusters associated with the biosynthesis of alginate, cellulose, curdlan, diutan, hyaluronic acids, Pel, poly-ß-1,6-N-acetyl-d-glucosamine (PNAG), Psl, S88 capsular polysaccharide, salecan, succinoglycan, and xanthan were identified and linked to individual MAGs, providing a comprehensive overview of the genome-resolved potential for these exopolysaccharides in AS bacteria. The approach and results provide a starting point for a more comprehensive understanding of EPS composition in wastewater treatment systems, which may facilitate a more refined regulation of the activated sludge process for improved stability.

Sleep disturbances and the association with attenuated psychotic symptoms in individuals at ultra high-risk of psychosis.

Sleep disturbances are common in individuals at ultra high-risk (UHR) of psychosis and have proven to play a causal role in the occurrence of psychotic symptoms in healthy individuals. Only a few studies have systematically investigated sleep disturbances in UHR individuals. The help-seeking UHR individuals were 18-40 years old, and we included 72 UHR individuals according to the Comprehensive Assessment of At-Risk Mental State criteria (CAARMS) and 36 healthy controls. Sleep was measured with a modified version of the Karolinska Sleep Questionnaire and actigraphy for one night, and melatonin was measured at awakening and bedtime. We compared subjective rated sleep and actigraphy between healthy and UHR individuals (t-test and chi-square test) and examined the association between a CAARMS-composite score (linear regression). UHR individuals subjectively experienced poor sleep, categorised as disturbed sleep- and awakening index compared with healthy controls. We found no differences in actigraphy variables or morning/evening melatonin between UHR and healthy controls (t-test and chi-square). A high CAARMS-composite score was associated with high morning melatonin (B = 0.15, CI 0.02 to 0.27, p = 0.024) and high awakening index (B = 1.86, CI 0.58 to 3.14, p = 0.004) in UHR individuals. The results suggest that UHR individuals with high CAARMS scores have a delayed sleep phase; they have difficulties waking up and feel exhausted at awakening. It might be necessary to evaluate how UHR individuals sleep, and it would be of great interest to follow these patients over time according to the development of psychosis.

The association between nonpharmacological interventions and quality of life in children with attention deficit hyperactivity disorder: A systematic review.

BACKGROUND: Attention deficit hyperactivity disorder is a common psychiatric disorder with a worldwide prevalence of about five percent among children and adolescents. This disorder affects most aspects of their lives e.g., academic performance and social relations, and their overall quality of life is reduced compared to healthy peers. The majority of children with ADHD are treated with medication that potentially has an insufficient effect and/or frequently occurring side effects. OBJECTIVES: To enable nurses and other health care professionals to guide children with ADHD and their families in their choices of treatment, based on the best available literature on the association between nonpharmacological interventions and quality of life. DATA SOURCES: A literature search was performed in the databases CENTRAL, Embase, PubMed, CINAHL, and PsycINFO. Seven randomized controlled trials were included in this systematic review. They examined the use of polyunsaturated fatty acids, physical activity, psychoeducation, cognitive therapy, cognitive training, hippotherapy, and behavioral therapy. CONCLUSIONS: The study of behavioral therapy in the form of a sleep intervention detected an improvement in quality of life which was statistically significant compared to the control group. IMPLICATIONS FOR PRACTICE: Children with ADHD and a sleep disorder may gain improvement in their quality of life from a sleep intervention.

Previous rotator cuff repair increases the risk of revision surgery for periprosthetic joint infection after reverse shoulder arthroplasty.

BACKGROUND: Previous studies have indicated an increased risk of periprosthetic joint infection (PJI) in patients treated with reverse shoulder arthroplasty (RSA) compared with patients treated with anatomic total shoulder arthroplasty. The reason for this is unclear but may be related to a high prevalence of previous rotator cuff repair in patients who are treated with RSA. The purpose of this study was to determine previous non-arthroplasty surgery as a risk factor for revision owing to PJI after RSA for cuff tear arthropathy, massive irreparable rotator cuff tears, or osteoarthritis. METHODS: Data were retrieved from the Danish Shoulder Arthroplasty Registry and medical records. We included 2217 patients who underwent RSA for cuff tear arthropathy, massive irreparable rotator cuff tears, or osteoarthritis between 2006 and 2019. PJI was defined as ≥3 of 5 tissue samples positive for the same bacteria or as definite or probable PJI evaluated based on criteria from the International Consensus Meeting. The Kaplan-Meier method was used to illustrate the unadjusted 14-year cumulative rates of revision. A Cox regression model was used to report hazard for revision owing to PJI. Results were adjusted for previous non-arthroplasty surgery, sex, diagnosis, and age. RESULTS: Revision was performed in 88 shoulders (4.0%), of which 40 (1.8%) underwent revision owing to PJI. There were 272 patients (12.3%) who underwent previous rotator cuff repair, of whom 11 (4.0%) underwent revision owing to PJI. The 14-year cumulative rate of revision owing to PJI was 14.1% for patients with previous rotator cuff repair and 2.7% for patients without previous surgery. The adjusted hazard ratio for revision owing to PJI for patients with previous rotator cuff repair was 2.2 (95% confidence interval, 1.04-4.60) compared with patients without previous surgery. CONCLUSION: There is an increased risk of revision owing to PJI after RSA for patients with previous rotator cuff repair. We recommend that patients with previous rotator cuff repair be regarded as high-risk patients when considering RSA.