Dental implant treatment in patients with cancer on high-dose antiresorptive medication: A prospective feasibility study with 2 years follow-up.

OBJECTIVES: Dental implant treatment is considered contraindicated in patients with cancer on high-dose antiresorptive medication (HDAR). The aim of this prospective, feasibility study was to evaluate implant treatment in patients with cancer on HDAR, in terms of implant survival, implant success, and oral health-related quality of life (OHLQoL) after 2 years of loading. MATERIALS AND METHODS: Implants were inserted in three groups of HDAR patients: (1) Previous tooth extraction, no medication-related osteonecrosis of the jaw (MRONJ), (2) Previous MRONJ, now healed, (3) Existing MRONJ, planned surgical resection. Implants were placed without adjunctive bone or soft tissue argumentation. Abutment operation was performed after ≥12 weeks. Prosthetic treatment was initiated ≥14 weeks. Survival and success rate were determined, and OHLQoL was analyzed with OHIP-49 and QLQ-H&N35 questionnaires. Patients were seen for 6 months, 1- and 2 years follow-up. RESULTS: Twenty-two patients, 39 implants, completed the implant-based prosthetic treatment. Implant-supported crowns and overdentures were fabricated. Thirteen patients (59%) with 23 implants (59%) completed 2 years follow-up. Overall implant survival and success rate after 2 years of loading were 100% and 97.4%, respectively. OHLQoL for the patients increased in all groups after the treatment, a substantial increase was seen in group 3. Two patients developed MRONJ, but not related to the implant treatment. CONCLUSION: Dental implant treatment, with high survival and success rate and increased post-treatment OHLQoL, is feasible in HDAR patients after 2 years of loading. Caution with general recommendations should be exercised.

Factors Influencing the Formation of Nitrous Acid from Photolysis of Particulate Nitrate.

Enhanced photolysis of particulate nitrate (pNO3) to form photolabile species, such as gas-phase nitrous acid (HONO), has been proposed as a potential mechanism to recycle nitrogen oxides (NOx) in the remote boundary layer ("renoxification"). This article presents a series of laboratory experiments aimed at investigating the parameters that control the photolysis of pNO3 and the efficiency of HONO production. Filters on which artificial or ambient particles had been sampled were exposed to the light of a solar simulator, and the formation of HONO was monitored under controlled laboratory conditions. The results indicate that the photolysis of pNO3 is enhanced, compared to the photolysis of gas-phase HNO3, at low pNO3 levels, with the enhancement factor reducing at higher pNO3 levels. The presence of cations (Na+) and halides (Cl-) and photosensitive organic compounds (imidazole) also enhance pNO3 photolysis, but other organic compounds such as oxalate and succinic acid have the opposite effect. The precise role of humidity in pNO3 photolysis remains unclear. While the efficiency of photolysis is enhanced in deliquescent particles compared to dry particles, some of the experimental results suggest that this may not be the case for supersaturated particles. These experiments suggest that both the composition and the humidity of particles control the enhancement of particulate nitrate photolysis, potentially explaining the variability in results among previous laboratory and field studies. HONO observations in the remote marine boundary layer can be explained by a simple box-model that includes the photolysis of pNO3, in line with the results presented here, although more experimental work is needed in order to derive a comprehensive parametrization of this process.

The impact of pre-ictal statin use on vasospasm and outcome in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Pleiotropic effects of statins may be beneficial in alleviating cerebral vasospasm (VS) and improving outcome after aneurysmal subarachnoid hemorrhage (aSAH). Initiation of statin treatment at aSAH is not recommended; however, the effect of pre-ictal and continued statin use is not fully investigated. METHODS: Retrospective study comparing aSAH patients admitted in 2012 to 2021 with pre-ictal statin use versus those not using statins. Patient entry variables, radiological/sonological VS, symptomatic VS, and radiologically documented delayed cerebral ischemia (DCI) were registered. Outcome was scored in terms of mortality, modified Rankin score, Glasgow outcome score extended, and levels of fatigue. Patients were compared on group level and in a case-control design. RESULTS: We included 961 patients, with 204 (21.2%) statin users. Statin users were older and had more often hypertension. Severe radiological/sonological VS, symptomatic VS, and DCI were less frequent in statin users, and their length of stay was shorter. Mortality, functional outcome, and levels of fatigue were similar in both groups. When analyzing 89 pairs of statin users and non-statin users matched for age, aSAH severity, gender, and hypertension, we confirmed decreased radiological/sonological and symptomatic VS as well as shorter length of stay in statin users. They also had more often a favorable functional outcome and lower levels of fatigue. CONCLUSIONS: Patients with pre-ictal and continued use of statins have a reduced occurrence of radiological/sonological and symptomatic VS, shorter length of stay, and more often favorable functional outcome, whereas mortality is similar to non-statin users. Even though larger multicenter studies with common, strict protocols for prevention, diagnosis, and treatment of vasospasm are needed to finally establish the value of statins in aSAH, continuation of pre-ictal statin use seems worthwhile.

The interplay between the impact of household's and children's education on the risk of type 2 diabetes and death among older adults: a Danish register-based cohort study.

OBJECTIVES: This study aims to assess the association of household's and children's education on the risk of type 2 diabetes (T2D) and subsequent death. STUDY DESIGN: Danish register-based cohort study. METHODS: In total, 1,021,557 adults were included at their 65th birthday between 2000 and 2018. A multistate survival model was performed to estimate the association of household's and children's education on the transition between the three states: 1) 65th birthday; 2) diagnosis of T2D; and 3) all-cause death. RESULTS: The incidence rates per 1000 person-years were 9.1 for T2D, 18.4 for death without T2D, and 45.0 for death with T2D. Compared to long household's education and children's education, long household's education combined with either short-medium children's education or no children were associated with a 1.49- (95% confidence interval [CI]: 1.44; 1.54] and 1.69-times (95% CI: 1.61;1.78) higher hazard of T2D, respectively. Short-medium household's education combined with either long children's education or no children were associated with 0.64- (95% CI: 0.62; 0.66) and 0.77-times (95% CI: 0.74; 0.79) lower hazard of T2D, respectively. Compared to long household's education and children's education, any other combination of household's and children's education was associated with higher hazards of death both without and with T2D. CONCLUSION: Older adults living in households with long education with no children or children with short-medium education had higher hazards of T2D. Households with short-medium education and no children or children with long education were associated with lower hazards of T2D. Both household's and children's education were associated with higher hazard of death without and with T2D.

Machine learning-based immune phenotypes correlate with STK11/KEAP1 co-mutations and prognosis in resectable NSCLC: a sub-study of the TNM-I trial.

BACKGROUND: We aim to implement an immune cell score model in routine clinical practice for resected non-small-cell lung cancer (NSCLC) patients (NCT03299478). Molecular and genomic features associated with immune phenotypes in NSCLC have not been explored in detail. PATIENTS AND METHODS: We developed a machine learning (ML)-based model to classify tumors into one of three categories: inflamed, altered, and desert, based on the spatial distribution of CD8+ T cells in two prospective (n = 453; TNM-I trial) and retrospective (n = 481) stage I-IIIA NSCLC surgical cohorts. NanoString assays and targeted gene panel sequencing were used to evaluate the association of gene expression and mutations with immune phenotypes. RESULTS: Among the total of 934 patients, 24.4% of tumors were classified as inflamed, 51.3% as altered, and 24.3% as desert. There were significant associations between ML-derived immune phenotypes and adaptive immunity gene expression signatures. We identified a strong association of the nuclear factor-κB pathway and CD8+ T-cell exclusion through a positive enrichment in the desert phenotype. KEAP1 [odds ratio (OR) 0.27, Q = 0.02] and STK11 (OR 0.39, Q = 0.04) were significantly co-mutated in non-inflamed lung adenocarcinoma (LUAD) compared to the inflamed phenotype. In the retrospective cohort, the inflamed phenotype was an independent prognostic factor for prolonged disease-specific survival and time to recurrence (hazard ratio 0.61, P = 0.01 and 0.65, P = 0.02, respectively). CONCLUSIONS: ML-based immune phenotyping by spatial distribution of T cells in resected NSCLC is able to identify patients at greater risk of disease recurrence after surgical resection. LUADs with concurrent KEAP1 and STK11 mutations are enriched for altered and desert immune phenotypes.

From a teacher and school leader perspective: What happened with smoking rules and practices during a three-year smoking preventive intervention? - Findings from the X:IT II study.

BACKGROUND: School-based smoking preventive interventions are most effective if they consist of multiple components; one of them being strict anti-smoking rules, i.e., no smoking by anyone at any location during school hours. However, there is a lack of in-depth knowledge about how smoking practices and rules about smoking actually change over time. Therefore, the purpose of this study was to examine how smoking practices changed during a three-year period in which a smoking preventive intervention with strict anti-smoking rules was implemented at schools. METHODS: We used data from 46 Danish schools that were enrolled in the evaluation of the X:IT II study - a smoking preventive intervention with three main components: one of them being strict anti-smoking rules. We collected questionnaire data among school employees at four timepoints from the autumn of 2017 until April 2020. The questionnaire covered topics regarding students' and employees' tobacco patterns at the school, control with smoking, and aspects of the intervention delivery. RESULTS: Over time, student smoking rules got stricter; from three out of four at baseline to almost all schools having rules about no student smoking during school hours three years later. Employee smoking rules also changed, although not as much as student rules. Overall, smoking at school grounds seemed to decline - however, student smoking at other locations increased, hence, violating the rule about no smoking during school hours. Enforcement of smoking rules also increased over time. CONCLUSION: Although implementing and enforcing new rules in a school setting may be difficult, it seemed that most schools in the X:IT II study changed their rules and smoking practices for both students and employees over the three-year intervention period. It seemed, however, that students relocated their smoking to other places than the school or just outside school grounds. Implications of these findings are important to consider in future interventions, i.e., students leaving school during school hours to smoke and the physical separation between those who smoke and those who do not.

Prevalence of survey-based criteria for fibromyalgia and impact on hospital burden: a 7 year follow-up study from an outpatient clinic.

OBJECTIVES: To evaluate the prevalence of survey-based criteria for fibromyalgia (FM) among newly referred patients in a rheumatic outpatient clinic, and to compare the use of secondary healthcare services between survey-based FM and non-FM cases. METHOD: Newly referred patients to an outpatient clinic were screened for the fulfilment of the 2011 FM survey criteria during a 6 month period in 2013 in this observational cohort study. Demographic data were obtained at baseline. Patients' medical files were evaluated and comparisons between groups were made regarding the use of hospital healthcare facilities during the 7 year observation period. RESULTS: Out of 300 invited patients, 248 (83%) completed the questionnaire; 90 patients (36%) fulfilled survey-based criteria for FM at enrolment. FM cases were primarily women (80% vs 54% of non-FM cases), and received more medications (median 4 vs 3 drugs) and public economic support (62% vs 20%). At the 7 year follow-up, crude analyses showed that FM cases had a higher number of hospital courses (median 10 vs 8) and had undergone more invasive procedures (78% vs 60%). Neurologists (42% vs 28%), gastroenterologists (30% vs 13%), endocrinologists (40% vs 21%), pain specialists (13% vs 3%), psychiatrists (20% vs 7%), and abdominal surgeons (43% vs 30%) were consulted more often by FM than by non-FM cases. CONCLUSION: Fulfilment of FM survey criteria among newly referred patients to a rheumatic outpatient clinic is frequent. Our study findings show that FM continues to present a challenge for healthcare professionals as well as for patients. RESEARCH HIGHLIGHTS: ● Fulfilment of FM survey criteria among newly referred patients to a rheumatic outpatient clinic is frequent.● The burden on the secondary healthcare system for these patients is significant.● This study suggests the need for increased awareness about the diagnosis of FM among certain medical and surgical specialties.

A robust experimental and computational analysis framework at multiple resolutions, modalities and coverages.

The ability to study cancer-immune cell communication across the whole tumor section without tissue dissociation is needed, especially for cancer immunotherapy development, which requires understanding of molecular mechanisms and discovery of more druggable targets. In this work, we assembled and evaluated an integrated experimental framework and analytical process to enable genome-wide scale discovery of ligand-receptors potentially used for cellular crosstalks, followed by targeted validation. We assessed the complementarity of four different technologies: single-cell RNA sequencing and Spatial transcriptomic (measuring over >20,000 genes), RNA In Situ Hybridization (RNAscope, measuring 4-12 genes) and Opal Polaris multiplex protein staining (4-9 proteins). To utilize the multimodal data, we implemented existing methods and also developed STRISH (Spatial TRanscriptomic In Situ Hybridization), a computational method that can automatically scan across the whole tissue section for local expression of gene (e.g. RNAscope data) and/or protein markers (e.g. Polaris data) to recapitulate an interaction landscape across the whole tissue. We evaluated the approach to discover and validate cell-cell interaction in situ through in-depth analysis of two types of cancer, basal cell carcinoma and squamous cell carcinoma, which account for over 70% of cancer cases. We showed that inference of cell-cell interactions using scRNA-seq data can misdetect or detect false positive interactions. Spatial transcriptomics still suffers from misdetecting lowly expressed ligand-receptor interactions, but reduces false discovery. RNAscope and Polaris are sensitive methods for defining the location of potential ligand receptor interactions, and the STRISH program can determine the probability that local gene co-expression reflects true cell-cell interaction. We expect that the approach described here will be widely applied to discover and validate ligand receptor interaction in different types of solid cancer tumors.

Comparing 5-Year Survival Rates Before and After Re-stratification of Stage I-III Right-Sided Colon Cancer Patients by Establishing the Presence/Absence of Occult Tumor Cells and Lymph Node Metastases in the Different Levels of Surgical Dissection.

BACKGROUND: To establish the impact of re-stratification on the outcomes of patients (stage I-III right-sided colon cancer) based on the presence/absence of occult tumor cells (OTC) and/or metastatic lymph nodes in the different levels of surgical dissection. METHODS: Consecutive patients were drawn from a multicenter prospective trial. After surgery, the surgical specimen was divided into the D1/D2 and D3 volumes before being further analyzed separately. All lymph nodes were examined with cytokeratin CAM 5.2 immunohistochemically. Lymph nodes containing metastases and OTC (micrometastases; isolated tumor cells) were identified. Re-stratification was as follows: RS1, stages I/II, no OTC in D1/D2 and D3 volumes; RS2, stages I/II, OTC in D1/D2 and/or D3; RS3, stage III, lymph node metastases in D1/D2, with/without OTC in D3; RS4, stage III, lymph node metastases in D3, with/without OTC in D3. RESULTS: Eighty-seven patients (39 men, 68.4 + 9.9 years) were included. The standard stratified (SS) group contained the following: stages I/II (SS1) 57 patients; stage III (SS2) 30 patients. Re-stratified (RS) contained RS1 (38), RS2 (19), RS3 (24), and RS4 (6) patients. Lymph node ratio (OTC) RS2: 0.157 D1/D2; 0.035 D3 and 0.092 complete specimens. Lymph node ratio RS3: 0.113 D1/D2; complete specimen 0.056. Overall survival and disease-free survival were p = 0.875 and p = 0.049 for SS and p = 0.144 and p = 0.001 for RS groups, respectively. CONCLUSION: This re-stratification identifies a patient group with poor prognosis (RS4). Removing this group from SS2 eliminates all the differences in survival between RS2 and RS3 groups. The level of dissection of the affected nodes may have an impact on survival. CLINICAL TRIAL: "Safe Radical D3 Right Hemicolectomy for Cancer through Preoperative Biphasic Multi-Detector Computed Tomography (MDCT) Angiography" registered at http://clinicaltrials.gov/ct2/show/NCT01351714.

Long-term methimazole therapy in Graves' hyperthyroidism and adverse reactions: a Danish multicenter study.

Purpose: In this prospective multicenter study with patients newly diagnosed with Graves' hyperthyroidism (GH), we studied the timing and characteristics of adverse drug reactions in patients treated with anti-thyroid drugs (ATD) for up to 48 months. Methods: Patients with GH were treated with ATD until remission and hereafter with a low-dose regime to keep the patients in remission. The patients were followed with blood samples and recording of adverse events approximately every second month for the first 2 years and every third month for the following 2 years. Results: We included 208 patients and the patients were treated for a median of 22 (range: 0.5-49) months. Ten percent of the patients experienced adverse drug reactions and 75% of the cases occurred during the first 6 months. After 24 months, the methimazole dose was lowered to 5 mg/day, and after this time point, no further adverse drug reactions were recorded. Skin reactions were the most prominent reaction, comprising 68% of the registered reactions, and no hepatic and bonemarrow affection was recorded. Conclusion: With this study, we report the frequency, timing of occurrence, and characteristics of adverse drug reactions when treating GH with the ATD drug methimazole for up to 48 months. Long-term low-dose methimazole treatment can be a cost-effective and straightforward treatment option if adverse drug reactions such as severe hepatic and bone marrow affection are kept in mind.

The prevalence of atrial fibrillation in Greenland: a register-based cross-sectional study based on disease classifications and prescriptions of oral anticoagulants.

Previous studies of the prevalence of atrial fibrillation (AF) in Greenland are based on either single-point electrocardiograms (ECGs) or patients admitted with stroke. This study estimates the prevalence of AF based on disease classifications in the electronic medical record system (EMR) and prescriptions of oral anticoagulants (OACs). Patients given a diagnose classification code for AF or atrial flutter or prescribed the vitamin K antagonist Warfarin or the direct-acting oral anticoagulant Rivaroxaban were identified in the EMR. Descriptive data and selected laboratory values were extracted, and a minimum CHA2DS2-VASc score was calculated for the 790 patients identified in the EMR (66% men). A total prevalence of AF of 1.4% was found in the general population (1.8% among men and 1.0% among women), with a significantly lower prevalence among women younger than 70 years. There was a significant increase in AF-prevalence with advancing age (p<0.001) for both men and women. A minimum CHA2DS2-VASc was estimated and app. 10% of the patients may be undertreated with OACs. The prevalence of AF found in this study is higher than that found in previous studies in Greenland and comparable to the prevalence found in other Western countries, indicating that AF is common in Greenland.

Automated summative feedback improves performance and retention in simulation training of mastoidectomy: a randomised controlled trial.

OBJECTIVE: This study aimed to investigate the effects of automated metrics-based summative feedback on performance, retention and cognitive load in distributed virtual reality simulation training of mastoidectomy. METHOD: Twenty-four medical students were randomised in two groups and performed 15 mastoidectomies on a distributed virtual reality simulator as practice. The intervention group received additional summative metrics-based feedback; the control group followed standard instructions. Two to three months after training, participants performed a retention test without learning supports. RESULTS: The intervention group had a better final-product score (mean difference = 1.0 points; p = 0.001) and metrics-based score (mean difference = 12.7; p < 0.001). At retention, the metrics-based score for the intervention group remained superior (mean difference = 6.9 per cent; p = 0.02). Also at the retention, cognitive load was higher in the intervention group (mean difference = 10.0 per cent; p < 0.001). CONCLUSION: Summative metrics-based feedback improved performance and lead to a safer and faster performance compared with standard instructions and seems a valuable educational tool in the early acquisition of temporal bone skills.

Effectiveness of patient education for patients with osteoporosis: a systematic review.

In this systematic review, the effects of osteoporosis patient education were examined. All studies found an effect on physical function, but for the other themes, the results were inconclusive. The findings indicate a need for further research in this topic. INTRODUCTION: Osteoporosis is a chronic disease with serious consequences for the individual and major societal costs. With the aim of fracture prevention, many countries offer osteoporosis patient education. The objectives were to examine the effects and mediators of osteoporosis patient education and describe the characteristics of studies with and without an effect. Though, none of the included studies reported mediators, and therefore, we could not examine that. METHODS: Six databases were searched in October 2020. Two researchers independently conducted title and abstract screening as well as full-text review. Records were included if participants had osteoporosis, and the patient education was group-based, face-to-face, and addressed two or more aspects, e.g., diet, medication, and exercise. The Cochrane Collaboration tools were used for risk of bias assessment. Finally, data were extracted into a standardized form and presented narratively. RESULTS: In total, 2934 records were identified, and 13 studies met the inclusion criteria. All six studies examining the effects of patient education on physical function demonstrated improvements. In addition, one out of two RCT studies and one non-randomized study reported improved psychological wellbeing. Just one out of five RCT studies showed improvements regarding physical discomfort and disability. Effects on health-related quality of life, adherence and persistence, and knowledge of osteoporosis were inconclusive. CONCLUSION: There is limited evidence for the effectiveness of osteoporosis patient education. There is a need for high-quality randomized controlled trials, which should describe the characteristics of the interventions and examine the mechanisms of osteoporosis patient education. PROSPERO REGISTRATION NUMBER: CRD42020211930.

Who lives in care homes in Greenland? A nationwide survey of demographics, functional level, medication use and comorbidities.

BACKGROUND: Greenland is facing an ageing population, and little is known about the characteristics of the elderly population in Greenland. This study offers both a comparison and a description of the demographics, causes of admission, comorbidities and medication of the residents in care homes in the capital, major and minor towns in four of the five administrative regions of Greenland. METHODS: The study was conducted from 2010 to 2016 as a descriptive questionnaire-based cross-sectional study. Data from eligible residents from eight care homes were collected from the regular care staff. Data were categorised into three groups based on town size for analysis. RESULTS: 244 (100 %) of eligible residents participated in the study. Nearly 100 % were of Greenlandic ethnicity based on parents' place of birth, and 62 % were women. The median age at admission/study was 69/71 years for men and 77/79 years for women (both p = 0.001). The median Body Mass Index was 25.6 kg/m2, more than half of the population were previous- or never-smokers and less than ten per cent consumed more than ten drinks of alcohol per week. The most common causes of admission were dementia (25.4 %), stroke (19.3 %) and social causes (11.1 %), while stroke (30.7 %), dementia (29.5 %) and musculoskeletal diseases (25.8 %) were the most common diagnoses at the time of the study. The Barthel Index was used to estimate the residents' level of independence, and residents in smaller towns were found to have a higher level of independence than residents in the capital. The median number of prescribed medications was five, and more residents in the capital were prescribed more than ten medications than elsewhere in Greenland. CONCLUSIONS: This study is the first to describe care home residents in Greenland. We found a population younger than residents in comparable Danish care homes and that women were older than men at admission. In addition, care home residents in the capital had a lower level of independence and a higher number of prescribed medications, which could relate to differences in morbidity, access to health care services and differences in social circumstances influencing the threshold for care home admission.

Interactions of occult tumor spread and surgical technique on overall and disease-free survival in patients operated for stage I and II right-sided colon cancer.

PURPOSE: To determine if "medial to lateral" (ML) dissection with devascularization first is superior to "lateral to medial" (LM) dissection regarding numbers of lymph node micro metastases (MM) and isolated tumor cells (ITC) as well as 5-year disease-free (5YDFS) and 5-year overall survival (5YOS) in stage I/II right-sided colon cancer. METHODS: Two datasets are used. ML group consists of consecutive stage I/II patients from a prospective trial. LM group is the original dataset from a previous publication. All harvested lymph nodes are examined with monoclonal antibody CAM 5.2 (immunohistochemically). Lymph node harvest and 5YOS/5YDFS were compared between ML/LM groups, stage I/II tumors and MM/ITC presence/absence. RESULTS: 117 patients included ML:51, LM:66. MM/ITC positive in ML 37.3% (19/51), LM 31.8% (21/66) p = 0.54. The 5YDFS for patients in ML 70.6% and LM 69.7%, p = 0.99, 5YOS: 74.5% ML and 71.2% LM (p = 0.73). No difference in 5YDFS/5YOS between groups for Stage I/II tumors; however, LM group had an excess of early tumors (16) when compared to ML group, while lymph node harvest was significantly higher in ML group (p < 0.01) 15.1 vs 26.7. 5YDFS and 5YOS stratified by MM/ITC presence/absence was 67.5%/71.4%, p = 0.63, and 75.0%/71.4%, p = 0.72, respectively. Death due to recurrence in MM/ITC positive was significantly higher than MM/ITC negative (p = 0.012). CONCLUSION: Surgical technique does not influence numbers of MM/ITC or 5YDFS/5YOS. Presence of MM/ITC does not affect 5YOS/5YDFS but can be a potential prognostic factor for death due to recurrence. CLINICAL TRIAL: Safe Radical D3 Right Hemicolectomy for Cancer through Preoperative Biphasic Multi-Detector Computed Tomography (MDCT) Angiography" registered at http://clinicaltrials.gov/ct2/show/NCT01351714 .

High expression of miR-17-5p in tumor epithelium is a predictor for poor prognosis for prostate cancer patients.

MicroRNAs (miRs) are small non-coding RNA molecules, which are involved in the development of various malignancies, including prostate cancer (PCa). miR-17-5p is considered the most prominent member of the miR-17-92 cluster, with an essential regulatory function of fundamental cellular processes. In many malignancies, up-regulation of miR-17-5p is associated with worse outcome. In PCa, miR-17-5p has been reported to increase cell proliferation and the risk of metastasis. In this study, prostatectomy specimens from 535 patients were collected. Tissue microarrays were constructed and in situ hybridization was performed, followed by scoring of miR-17-5p expression on different tumor compartments. High expression of miR-17-5p in tumor epithelium was associated with biochemical failure (BF, p < 0.001) and clinical failure (CF, p = 0.019). In multivariate analyses, high miR-17-5p expression in tumor epithelial cells was an independent negative prognostic factor for BF (HR 1.87, 95% CI 1.32-2.67, p < 0.001). In vitro analyses confirmed association between overexpression of miR-17-5p and proliferation, migration and invasion in prostate cancer cell lines (PC3 and DU145). In conclusion, our study suggests that a high cancer cell expression of miR-17-5p was an independent negative prognostic factor in PCa.

Intake of seaweed as part of a single sushi meal, iodine excretion and thyroid function in euthyroid subjects: a randomized dinner study.

OBJECTIVE: Globalisation has extended to the kitchen and the Asian cuisine has gained international popularity with sushi and seaweed now being widespread. We explored the possible acute adverse effects of an iodine load from a single sushi-and-seaweed meal as seaweed iodine may induce thyroid dysfunction. METHODS: Nine euthyroid participants were randomized into three groups: Halibut maki roll with either (A) newly harvested Greenlandic seaweed salad, (B) no seaweed salad on the side, or (C) Japanese seaweed salad purchased at a local store. We collected spot urine and blood samples daily for a week for measurement of iodine and creatinine in urine, thyroid stimulating hormone (TSH), and estimated-free T4 (fT4) in serum. RESULTS: All participants ingested the full meal and the drop-out was nil. No adverse effects were reported. Pre-meal urinary iodine excretion (UIE) was 75 µg/g. UIE rose (p < 0.001) by 385%, 59% and 43% for groups A, B, and C, peaked in the 6-h spot urine sample at 393, 120, and 109 µg/g, and was down to pre-meal values by day 2. Serum TSH rose (p = 0.012) 150% on day 2 and was down to pre-meal values by day 3. Serum fT4 remained at the same level. No adverse reactions were reported. CONCLUSION: A sushi meal increased urinary iodine excretion by 40 µg/g, or 400 µg/g if a newly harvested seaweed salad was added. An ensuing rise in serum TSH was brief, and a single sushi meal with seaweed salad did not cause any adverse events.

Lifespan data on postural balance in multiple standing positions.

BACKGROUND: Maintaining balance is important throughout life. The Nintendo Wii Balance Board (WBB) can give reliable quantitative measures of postural balance, but reference data are lacking. Furthermore, one-leg standing balance across the adult lifespan is not fully described. The aim of the study was (1) to provide reference data on postural balance in multiple standing positions using a WBB, (2) to determine an age cut-off for the ability to stand on one-leg in men and women. METHODS: This was a cross-sectional study and data was collected in two cities in Denmark (Aalborg and Odense) and Norway (Oslo and Ålesund) during spring and summer of 2016. Postural balance was assessed in individuals across the adult lifespan in three different bases of support positions (hip-wide and narrow two-legged stance, and one-legged stance) using a WBB. Reference data were analyzed and presented in 10-year intervals. RESULTS: A total of 354 individuals aged 20-99 years were recruited. Reference data were presented in percentiles stratified by gender for the following age categories: 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80+. Data showed that the difference between men and women's balance was larger at older age with men performing worst. The cut-off ability to stand on one-leg was 72.5 years without statistical evidence of gender difference. CONCLUSION: This study reports reference data for postural balance across the entire adult lifespan using a WBB. More than half of the individuals over 72.5 years of age were unable to stand balanced on one-leg.

Low Expression of miR-424-3p is Highly Correlated with Clinical Failure in Prostate Cancer.

Prostate cancer (PC) is a highly heterogenous disease and one of the leading causes of mortality in developed countries. Recently, studies have shown that expression of immune checkpoint proteins are directly or indirectly repressed by microRNAs (miRs) in many types of cancers. The great advantages of using miRs based therapy is the capacity of these short transcripts to target multiple molecules for the same- or different pathways with synergistic immune inhibition effects. miR-424 has previously been described as a biomarker of poor prognosis in different types of cancers. miR-424 is also found to target both the CTLA-4/CD80- and PD-1/PD-L1 axis. In the present study, the clinical significance of miR-424-3p expression in PC tissue was evaluated. Naïve radical prostatectomy specimens from 535 patients was used for tissue microarray construction. In situ hybridization was used to evaluate the expression of miR-424-3p and immunohistochemistry was used for CTLA-4 protein detection. In univariate- and multivariate analyses, low expression of miR-424-3p was significant associated with clinical failure-free survival, (p = 0.004) and p = 0.018 (HR:0.44, CI95% 0.22-0.87). Low expression of miR-424-3p also associated strongly with aggressive phenotype of PC. This highlight the importance of miR-424-3p as potential target for therapeutic treatment in prostate cancer.

Conditional approval of cancer drugs in Canada: accountability and impact on public funding.

Background: We examined how conditional market approval of cancer pharmaceuticals by Health Canada (hc) affects public funding recommendations by the pan-Canadian Oncology Review (pcodr). We were also interested to see how often hc conditions are enforced. Methods: Health Canada and pcodr databases for 2010-2017 were analyzed for patterns in hc conditional authorization and post-authorization reviews of cancer drugs and for correlation with pcodr reimbursement recommendations. Results: Between 2010 and 2017, pcodr reviewed 105 unique drug-indication pairings; 21% (n = 22) had conditional hc authorization. In all cases, conditional authorization was given on the basis of preliminary data in a surrogate endpoint and was contingent on further data showing benefit in more robust outcome measures (for example, overall survival). Of those 22 drugs, 36% did not have updated data, 36% had updated data that met hc conditions, and 27% had data that met some, but not all, conditions. During the period considered, hc never revoked conditional authorization for failure to meet conditions. None of the 22 drugs was given an unconditional positive recommendation for public reimbursement by pcodr. A conditional recommendation was given to 11 of the drugs (50%), and reimbursement was not recommended for 6 drugs (27%) because of insufficient evidence. Conclusions: One fifth of the cancer drugs reviewed for public reimbursement in Canada were conditionally authorized by hc based on preliminary data. Conditional authorization was associated with a recommendation against public funding by pcodr. No drugs had their conditional market authorization revoked for failure to meet conditions, suggesting that a more robust hc reappraisal framework is needed.