Lumbar spine marker placement errors and soft tissue artifact during dynamic flexion/extension and lateral bending in individuals with chronic low back pain.

Quantitative in vivo biomechanical assessments are typically performed with optoelectronic motion capture (MoCap) using retroreflective markers attached to skin. This technique inherently contains measurement errors from both marker placement on palpated bony landmarks and skin motion relative to the underlying bone (i.e., soft tissue artifact (STA)). Research on lumbar spine STA is scarce and limited to young, healthy participants in static positions. This study aimed to evaluate static placement errors, lumbar spine STA from MoCap marker clusters (MMC), and linear relationships between STA and patient characteristics. Thirty-nine participants with cLBP performed three trials each of flexion/extension and lateral bending while imaged simultaneously by MoCap (120 Hz) and dynamic biplane radiography DBR (20 Hz). MMCs were placed 29.5 ± 18.0 mm and 27.1 ± 13.4 mm superior to the most prominent aspect of the L1 and L5 spinous process, respectively. L1 relative to L5 STA was larger during flexion/extension (8.6 ± 5.7°) than lateral bending (4.5 ± 2.1°) (p < 0.001). After correcting for marker placement errors, components of the L1 and L5 STA averaged as much as 16.3 mm and 11.4° during flexion/extension, but only 4.0 mm and 4.8° or less during lateral bending. On average, STA for individual L1 and L5 vertebrae increased as participants moved away from the upright neutral position. STA was participant-dependent, however, age and BMI did not model STA well. Given the inaccuracy in marker placement and wide range of patterns of STA, caution is urged when making clinical decisions or when using computational models to estimate spine tissue loading based upon lumbar spine kinematics obtained from skin-mounted markers.

Predicting how varying moisture conditions impact the microbiome of dust collected from the International Space Station.

BACKGROUND: The commercialization of space travel will soon lead to many more people living and working in unique built environments similar to the International Space Station, which is a specialized closed environment that contains its own indoor microbiome. Unintended microbial growth can occur in these environments as in buildings on Earth from elevated moisture, such as from a temporary ventilation system failure. This growth can drive negative health outcomes and degrade building materials. We need a predictive approach for modeling microbial growth in these critical indoor spaces. RESULTS: Here, we demonstrate that even short exposures to varying elevated relative humidity can facilitate rapid microbial growth and microbial community composition changes in dust from spacecraft. We modeled fungal growth in dust from the International Space Station using the time-of-wetness framework with activation and deactivation limited growth occurring at 85% and 100% relative humidity, respectively. Fungal concentrations ranged from an average of 4.4 × 106 spore equivalents per milligram of dust in original dust with no exposure to relative humidity to up to 2.1 × 1010 when exposed to 100% relative humidity for 2 weeks. As relative humidity and time-elevated increased, fungal diversity was significantly reduced for both alpha (Q < 0.05) and beta (R2 = 0.307, P = 0.001) diversity metrics. Bacteria were unable to be modeled using the time-of-wetness framework. However, bacterial communities did change based on constant relative humidity incubations for both beta (R2 = 0.22, P = 0.001) and alpha diversity decreasing with increasing moisture starting at 85% relative humidity (Q < 0.05). CONCLUSION: Our results demonstrate that moisture conditions can be used to develop and predict changes in fungal growth and composition onboard human-occupied spacecraft. This predictive model can be expanded upon to include other spacecraft environmental factors such as microgravity, elevated carbon dioxide conditions, and radiation exposure. Understanding microbial growth in spacecraft can help better protect astronaut health, fortify spacecraft integrity, and promote planetary protection as human activity increases in low-Earth orbit, the moon, Mars, and beyond. Video Abstract.

Algorithm Validation for Quantifying ActiGraph™ Physical Activity Metrics in Individuals with Chronic Low Back Pain and Healthy Controls.

Assessing physical activity is important in the treatment of chronic conditions, including chronic low back pain (cLBP). ActiGraph™, a widely used physical activity monitor, collects raw acceleration data, and processes these data through proprietary algorithms to produce physical activity measures. The purpose of this study was to replicate ActiGraph™ algorithms in MATLAB and test the validity of this method with both healthy controls and participants with cLBP. MATLAB code was developed to replicate ActiGraph™'s activity counts and step counts algorithms, to sum the activity counts into counts per minute (CPM), and categorize each minute into activity intensity cut points. A free-living validation was performed where 24 individuals, 12 cLBP and 12 healthy, wore an ActiGraph™ GT9X on their non-dominant hip for up to seven days. The raw acceleration data were processed in both ActiLife™ (v6), ActiGraph™'s data analysis software platform, and through MATLAB (2022a). Percent errors between methods for all 24 participants, as well as separated by cLBP and healthy, were all less than 2%. ActiGraph™ algorithms were replicated and validated for both populations, based on minimal error differences between ActiLife™ and MATLAB, allowing researchers to analyze data from any accelerometer in a manner comparable to ActiLife™.

Fungal diversity differences in the indoor dust microbiome from built environments on earth and in space.

Human occupied built environments are no longer confined to Earth. In fact, there have been humans living and working in low-Earth orbit on the International Space Station (ISS) since November 2000. With NASA's Artemis missions and the age of commercial space stations set to begin, more human-occupied spacecraft than ever will be in Earth's orbit and beyond. On Earth and in the ISS, microbes, especially fungi, can be found in dust and grow when unexpected, elevated moisture conditions occur. However, we do not yet know how indoor microbiomes in Earth-based homes and in the ISS differ due to their unique set of environmental conditions. Here we show that bacterial and fungal communities are different in dust collected from vacuum bags on Earth and the ISS, with Earth-based homes being more diverse (465 fungal OTUs and 237 bacterial ASVs) compared to the ISS (102 fungal OTUs and 102 bacterial ASVs). When dust from these locations were exposed to varying equilibrium relative humidity conditions (ERH), there were also significant fungal community composition changes as ERH and time elevated increased (Bray Curtis: R2 = 0.35, P = 0.001). These findings can inform future spacecraft design to promote healthy indoor microbiomes that support crew health, spacecraft integrity, and planetary protection.

Trends in Incidence of Hospitalization for Hypoglycemia and Diabetic Ketoacidosis in Individuals With Type 1 or Type 2 Diabetes With and Without Severe Mental Illness in Denmark From 1996 to 2020: A Nationwide Study.

OBJECTIVE: To examine trends in incidence of acute diabetes complications in individuals with type 1 or type 2 diabetes with and without severe mental illness (SMI) in Denmark by age and calendar year. RESEARCH DESIGN AND METHODS: We conducted a cohort study using nationwide registers from 1996 to 2020 to identify individuals with diabetes, ascertain SMI status (namely, schizophrenia, bipolar disorder, or major depression) and identify the outcomes: hospitalization for hypoglycemia and diabetic ketoacidosis (DKA). We used Poisson regression to estimate incidence rates (IRs) and incidence rate ratios (IRRs) of recurrent hypoglycemia and DKA events by SMI, age, and calendar year, accounting for sex, diabetes duration, education, and country of origin. RESULTS: Among 433,609 individuals with diabetes, 8% had SMI. Risk of (first and subsequent) hypoglycemia events was higher for individuals with SMI than for those without SMI (for first hypoglycemia event, IRR: type 1 diabetes, 1.77 [95% CI 1.56-2.00]; type 2 diabetes, 1.64 [95% CI 1.55-1.74]). Individuals with schizophrenia were particularly at risk for recurrent hypoglycemia events. The risk of first DKA event was higher in individuals with SMI (for first DKA event, IRR: type 1 diabetes, 1.78 [95% CI 1.50-2.11]; type 2 diabetes, 1.85 [95% CI 1.64-2.09]). Except for DKA in the type 2 diabetes group, IR differences between individuals with and without SMI were highest in younger individuals (<50 years old) but stable across the calendar year. CONCLUSIONS: SMI is an important risk factor for acute diabetes complication and effective prevention is needed in this population, especially among the younger population and those with schizophrenia.

Heterogeneity in glycaemic control in children and adolescents with type 1 diabetes: A latent class trajectory analysis of Danish nationwide data.

AIMS: Suboptimal glycaemic control in children and adolescents with type 1 diabetes is prevalent and associated with increased risk of diabetes-related complications and mortality later in life. First, we aimed to identify distinct glycated haemoglobin (HbA1c) trajectories in children and adolescents (2-19 years) with type 1 diabetes. Second, we examined their associations with clinical and socio-demographic factors. METHODS: Data were obtained from the Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids) comprising all Danish children and adolescents diagnosed with type 1 diabetes from 1996 to 2019. Subgroups of distinct mean trajectories of HbA1c were identified using data-driven latent class trajectory modelling. RESULTS: A total of 5889 children (47% female) had HbA1c measured a median of 6 times (interquartile range 3-8) and contributing to 36,504 measurements. We identified four mean HbA1c trajectories, referred to as 'Stable but elevated HbA1c' (83%), 'Increasing HbA1c' (5%), 'Late HbA1c peak' (7%), and 'Early HbA1c peak' (5%). Compared to the 'Stable but elevated HbA1c' group, the three other groups presented rapidly deteriorating glycaemic control during late childhood or adolescence, had higher HbA1c at study entry, and included fewer pump users, higher frequency of inadequate blood glucose monitoring, more severe hypoglycaemic events, lower proportions with Danish origin, and worse educational status of parents. The groups also represented significant differences by healthcare region. CONCLUSIONS: Children and adolescents with type 1 diabetes experience heterogenous trajectories with different timings and magnitudes of the deterioration of HbA1c levels, although the majority follow on average a stable, yet elevated HbA1c trajectory. The causes and long-term health implications of these heterogenous trajectories need to be addressed.

Patient referrals from Greenland to Rigshospitalet in Denmark.

INTRODUCTION: Patients from Greenland are transferred overseas for highly specialised treatment, mainly to the National University Hospital, Rigshospitalet, Denmark. We aimed to investigate the pattern of transfers from Greenland to Denmark, focusing on cardiology. METHODS: This descriptive quality assurance study included all Greenlandic citizens receiving healthcare services at Rigshospitalet from 2017-2021. Unique patients and disease courses were accounted for and patients were stratified across specialties. RESULTS: A total of 3,201 unique patients (56% males, mean age 51.0 years, 325 were 18 years or younger) from Greenland received healthcare services at Rigshospitalet. As some patients were seen two or more times, this corresponds to almost 900 patients (approximately 1,500 disease courses) or 1.2% of the entire Greenlandic population being referred annually. The referrals increased by 52% during the period. The Centre of Head and Orthopaedics received most referrals, followed by the Heart Centre. A modest increase in referrals due to heart diseases was observed with ischaemic heart disease being the more prevalent diagnosis. Coronary artery revascularisation rates in Greenlandic citizens aged 55-74 years were at least as high as in the same age-group for all Danes. CONCLUSION: During the past five years, a 52% increase has been observed in the referral rate from Greenland to Rigshospitalet for diagnostics and treatment. In cardiology, ischaemic heart disease represented the largest share with a high revascularisation rate being observed in older Greenlandic citizens. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Time Trends in the Incidence of Diabetic Ketoacidosis Leading to Hospital Admission Among Adults With Type 1 Diabetes: A Nationwide Danish Register Study.

OBJECTIVE: Diabetic ketoacidosis (DKA) is a life-threatening but preventable complication in people with type 1 diabetes. We aimed to quantify the incidence of DKA according to age and describe the time trend of DKA among adults with type 1 diabetes in Denmark. RESEARCH DESIGN AND METHODS: Individuals aged ≥18 years with type 1 diabetes were identified from a nationwide Danish diabetes register. Hospital admissions due to DKA were ascertained from the National Patient Register. The follow-up period was from 1996 to 2020. RESULTS: The cohort consisted of 24,718 adults with type 1 diabetes. The incidence rate of DKA per 100 person-years (PY) decreased with increasing age for both men and women. From 20 to 80 years of age, the DKA incidence rate decreased from 3.27 to 0.38 per 100 PY. From 1996 to 2008, the incidence rate of DKA increased for all age-groups, with a subsequent minor decrease in incidence rate until 2020. From 1996 to 2008, the incidence rates increased from 1.91 to 3.77 per 100 PY for a 20-year-old individual and from 0.22 to 0.44 per 100 PY for an 80-year-old individual living with type 1 diabetes. From 2008 to 2020 the incidence rates decreased from 3.77 to 3.27 and from 0.44 to 0.38 per 100 PY, respectively. CONCLUSIONS: The incidence rates of DKA are declining for all ages, with an overall decline from 2008 for both men and women. This likely reflects improved diabetes management for individuals with type 1 diabetes in Denmark.

The effect of traditional diet on glucose homoeostasis in carriers and non-carriers of a common TBC1D4 variant in Greenlandic Inuit: a randomised crossover study.

Consumption of traditional foods is decreasing amid a lifestyle transition in Greenland as incidence of type 2 diabetes (T2D) increases. In homozygous carriers of a TBC1D4 variant, conferring postprandial insulin resistance, the risk of T2D is markedly higher. We investigated the effects of traditional marine diets on glucose homoeostasis and cardio-metabolic health in Greenlandic Inuit carriers and non-carriers of the variant in a randomised crossover study consisting of two 4-week dietary interventions: Traditional (marine-based, low-carbohydrate) and Western (high in imported meats and carbohydrates). Oral glucose tolerance test (OGTT, 2-h), 14-d continuous glucose and cardio-metabolic markers were assessed to investigate the effect of diet and genotype. Compared with the Western diet, the Traditional diet reduced mean and maximum daily blood glucose by 0·17 mmol/l (95 % CI 0·05, 0·29; P = 0·006) and 0·26 mmol/l (95 % CI 0·06, 0·46; P = 0·010), respectively, with dose-dependency. Furthermore, it gave rise to a weight loss of 0·5 kg (95 % CI; 0·09, 0·90; P = 0·016) relative to the Western diet and 4 % (95 % CI 1, 9; P = 0·018) lower LDL:HDL-cholesterol, which after adjustment for weight loss appeared to be driven by HDL elevation (0·09 mmol/l (0·03, 0·15), P = 0·006). A diet-gene interaction was indicated on insulin sensitivity in the OGTT (p = 0·093), which reflected a non-significant increase of 1·4 (-0·6, 3·5) mmol/l in carrier 2-h glucose. A Traditional diet marginally improved daily glycaemic control and plasma lipid profile compared with a Westernised diet in Greenlandic Inuit. Possible adverse effects on glucose tolerance in carriers of the TBC1D4 variant warrant further studies.

Predicting the HbA1c level following glucose-lowering interventions in individuals with HbA1c-defined prediabetes: a post-hoc analysis from the randomized controlled PRE-D trial.

PURPOSE: To investigate whether the prediction of post-treatment HbA1c levels can be improved by adding an additional biomarker of the glucose metabolism in addition to baseline HbA1c. METHODS: We performed an exploratory analysis based on data from 112 individuals with prediabetes (HbA1c 39-47 mmol) and overweight/obesity (BMI ≥ 25 kg/m2), who completed 13 weeks of glucose-lowering interventions (exercise, dapagliflozin, or metformin) or control (habitual living) in the PRE-D trial. Seven prediction models were tested; one basic model with baseline HbA1c as the sole glucometabolic marker and six models each containing one additional glucometabolic biomarker in addition to baseline HbA1c. The additional glucometabolic biomarkers included: 1) plasma fructosamine, 2) fasting plasma glucose, 3) fasting plasma glucose × fasting serum insulin, 4) mean glucose during a 6-day free-living period measured by a continuous glucose monitor 5) mean glucose during an oral glucose tolerance test, and 6) mean plasma glucose × mean serum insulin during the oral glucose tolerance test. The primary outcome was overall goodness of fit (R2) from the internal validation step in bootstrap-based analysis using general linear models. RESULTS: The prediction models explained 46-50% of the variation (R2) in post-treatment HbA1c with standard deviations of the estimates of ~2 mmol/mol. R2 was not statistically significantly different in the models containing an additional glucometabolic biomarker when compared to the basic model. CONCLUSION: Adding an additional biomarker of the glucose metabolism did not improve the prediction of post-treatment HbA1c in individuals with HbA1c-defined prediabetes.

Does interpolation and intra-user variability affect the accuracy of arthrokinematic measurements in the knee? A dual fluoroscopic imaging and model-based tracking study.

Model-based tracking (MBT) is a time-consuming and semiautomatic approach, and thus subject to errors during the tracking process. The present study aimed primarily to quantify the effects that interpolation and intra-user variability associated with MBT have on the kinematic and arthrokinematic measurements in comparison to a gold standard radiostereometric analysis (RSA). Cadaveric knee specimens were imaged at 125 Hz while simulating standing, walking, jogging, and lunging motions. (Arthro)kinematic metrics were calculated via MBT without interpolation, MBT with two interpolation techniques when every fifth or tenth frame was analyzed, and RSA. Tracking the same activity multiple times affected (p-value, largest mean difference) the flexion-extension (FE) joint angle during walking (0.03, 0.6°), and the internal-external joint angle during jogging (0.048, -0.9°). Only during jogging for the FE joint angle was there an effect of interpolation (0.046, 0.3°). Neither tracking multiple times nor interpolation affected arthrokinematic metrics (contact path locations and excursions). The present study is the first to quantify the effects that intra-user variability and interpolation have on the (arthro)kinematic measurement accuracy using MBT. Results suggest interpolation may be used without sacrificing (arthro)kinematic outcome measurement accuracy and the errors associated with intra-user variability, while small, were larger than errors due to interpolation.

Long-term Quality of Life and Functional Outcome of Patients With Rectal Cancer Following a Watch-and-Wait Approach.

Importance: A watch-and-wait approach for patients with rectal cancer and a clinical complete response after neoadjuvant chemoradiotherapy or radiotherapy is associated with better quality of life and functional outcome. Nevertheless, prospective data on both parameters are scarce. Objective: To prospectively evaluate quality of life and functional outcome, including bowel, urinary, and sexual function, of patients following a watch-and-wait approach. Design, Setting, and Participants: A total of 278 patients with rectal cancer and a clinical complete response or near-complete response after neoadjuvant chemoradiotherapy or radiotherapy were included in 2 prospective cohort studies: a single-center study (March 2014 to October 2017) and an ongoing multicenter study (from September 2017). Patients were observed by a watch-and-wait approach. Additional local excision or total mesorectal excision was performed for residual disease or regrowth. Data were analyzed between April 1, 2021, and August 27, 2021, for patients with a minimum follow-up of 24 months. Main Outcomes and Measures: Quality of life was evaluated with the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-C30 (EORTC-QLQ-C30), EORTC-QLQ-CR38, or EORTC-QLQ-CR29 and 36-Item Short-Form Health Survey. The score for the questionnaires and 36-Item Short-Form Health Survey ranges from 0 to 100. For some scales, a high score indicates a high level of functioning, and for others it indicates a high level of complaints and symptomatology. Functional outcome was assessed by the Low Anterior Resection Syndrome score, Vaizey incontinence score, International Prostate Symptom Score, International Index of Erectile Function, and Female Sexual Function Index. Results: Of 278 patients included, 187 were male (67%), and the median age was 66 years (range, 34-85 years). In the first 24 months, 221 patients (80%) were observed by a watch-and-wait approach without requiring surgery, 18 patients (6%) underwent additional local excision, and 39 patients (14%) underwent total mesorectal excision. In general, patients observed by a watch-and-wait approach reported good quality of life, with limited variation over time. At 3 months, 56 of 221 patients (25.3%) reported major bowel dysfunction; at 12 months, 53 patients (24.0%) reported it; and at 24 months, 55 patients (24.9%) reported it. At 24 months, 48 of 151 male patients (31.8%) reported severe erectile dysfunction. For female patients, sexual satisfaction and overall sexual function decreased during follow-up. Patients who underwent local excision reported more major bowel dysfunction (10 of 18 patients [55.6%]) compared with those without additional surgery. Quality-of-life scores, however, were comparable. After total mesorectal excision, patients scored significantly worse on several quality-of-life subscales. Conclusions and Relevance: Results of this study suggest that patients with rectal cancer who were observed by a watch-and-wait approach had good quality of life, with some patients reporting bowel and sexual dysfunction. Quality of life and functional outcome deteriorated when patients required surgery. These data will be useful in daily care to counsel patients on what to expect from a watch-and-wait approach.

Dyslipidemia and the preventive potential in the Greenlandic population.

Background: Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for development of cardiovascular diseases. Based on available clinical data, we aimed to investigate the plasma lipid profile in the Greenlandic population, the proportion on cholesterol-lowering treatment and the adherence to local indications for cholesterol-lowering therapy. Methods: This is an observational cross-sectional study of the adult (≥21 years) Greenlandic population with focus on clinically determined lipid levels from 2017 to early 2022. We investigated levels of dyslipidemia and assessed cholesterol-lowering medication usage in individuals with an indication according to current Greenlandic guidelines, which include a) LDL-C >5 mmol/l, b) diabetes, c) diagnosed atherosclerotic disease and 4) a SCORE2 >7.5%. Results: In the adult Greenlandic population of 40,565 individuals a lipid profile was available in 13,895 with a mean LDL-C of 3.0 mmol/L and 976 (7%) had a LDL-C >5 mmol/l. One or more indications for cholesterol-lowering medication was present in 3988 individuals and a total of 5464 adult Greenlanders either fulfilled local criteria for statin therapy or received a statin (some without current indication) and among these, 2232 (41%) individuals received no statin. Conclusion: These findings indicate that clinically significant dyslipidemia is common in the adult Greenlandic population and that the cardiovascular preventive potential of cholesterol-lowering therapy is currently underutilized.

Indicators of quality of diabetes care in persons with type 2 diabetes with and without severe mental illness: a Danish nationwide register-based cohort study.

Background: This study aims to examine quality of diabetes care in persons with type 2 diabetes with and without severe mental illness (SMI). Methods: In a nationwide prospective register-based study, we followed persons with type 2 diabetes in Denmark with and without SMI including schizophrenia, bipolar disorder, or major depression. Quality of care was measured as receipt of care (hemoglobin A1c, low-density lipoprotein-cholesterol and urine albumin creatinine ratio assessment and eye and foot screening) and achievement of treatment targets between 2015 and 2019. Quality of care was compared in persons with and without SMI using generalized linear mixed models adjusted for key confounders. Findings: We included 216,537 persons with type 2 diabetes. At entry 16,874 (8%) had SMI. SMI was associated with lower odds of receiving care, with the most pronounced difference in urine albumin creatinine ratio assessment and eye screening (OR: 0.55, 95% CI: 0.53-0.58 and OR: 0.37 95% CI: 0.32-0.42, respectively). Among those with an assessment, we found that SMI was associated with higher achievement of recommended hemoglobin A1c levels and lower achievement of recommended low-density lipoprotein-cholesterol levels. Achievement of recommended low-density lipoprotein-cholesterol levels was similar in persons with versus without schizophrenia. Interpretation: Compared to persons without SMI, persons with SMI were less likely to receive process of care, with the most pronounced differences in urine albumin creatinine ratio assessment and eye screening. Funding: This study was funded by Steno Diabetes Center Copenhagen through an unrestricted grant from Novo Nordisk Foundation.

A novel splice-affecting HNF1A variant with large population impact on diabetes in Greenland.

Background: The genetic disease architecture of Inuit includes a large number of common high-impact variants. Identification of such variants contributes to our understanding of the genetic aetiology of diseases and improves global equity in genomic personalised medicine. We aimed to identify and characterise novel variants in genes associated with Maturity Onset Diabetes of the Young (MODY) in the Greenlandic population. Methods: Using combined data from Greenlandic population cohorts of 4497 individuals, including 448 whole genome sequenced individuals, we screened 14 known MODY genes for previously identified and novel variants. We functionally characterised an identified novel variant and assessed its association with diabetes prevalence and cardiometabolic traits and population impact. Findings: We identified a novel variant in the known MODY gene HNF1A with an allele frequency of 1.9% in the Greenlandic Inuit and absent elsewhere. Functional assays indicate that it prevents normal splicing of the gene. The variant caused lower 30-min insulin (ß = -232 pmol/L, ßSD = -0.695, P = 4.43 × 10-4) and higher 30-min glucose (ß = 1.20 mmol/L, ßSD = 0.441, P = 0.0271) during an oral glucose tolerance test. Furthermore, the variant was associated with type 2 diabetes (OR 4.35, P = 7.24 × 10-6) and HbA1c (ß = 0.113 HbA1c%, ßSD = 0.205, P = 7.84 × 10-3). The variant explained 2.5% of diabetes variance in Greenland. Interpretation: The reported variant has the largest population impact of any previously reported variant within a MODY gene. Together with the recessive TBC1D4 variant, we show that close to 1 in 5 cases of diabetes (18%) in Greenland are associated with high-impact genetic variants compared to 1-3% in large populations. Funding: Novo Nordisk Foundation, Independent Research Fund Denmark, and Karen Elise Jensen's Foundation.

Comparing Single-Incision Midurethral Sling with Bulking Agents for Female Stress Urinary Incontinence: Rationale for a Non-Randomized Controlled Trial.

OBJECTIVES: Midurethral slings are considered the gold standard for the surgical treatment of stress urinary incontinence (SUI), with an efficacy up to 80%. Another therapeutic option is the use of bulking agents, which create an artificial mass in the urethral submucosa, with an efficacy varying from 64% to 74%. Although bulking agents have a lower risk of complications than midurethral sling surgery, they are mainly used in case a midurethral sling is not an option or if midurethral sling surgery failed to cure stress urinary incontinence. In this study, we offer all patients with SUI in secondary care a choice between a single-incision midurethral sling procedure and treatment with a bulking agent. We want to examine patient preference and patient satisfaction for both procedures. We expect that offering both interventions in combination with standardized counselling will result in high patient satisfaction. DESIGN: In this non-randomized controlled trial, 266 patients will be objectively counselled for both interventions, after which all patients will choose between single-incision midurethral slings and polyacrylamide hydrogel (PAHG), followed by the standard care procedure for women with SUI. PARTICIPANTS/MATERIALS, SETTING, METHODS: From January 1, 2021, onward, all consecutive adult patients (between 18 and 80 years of age) attending the outpatient gynaecology department with objectively confirmed, moderate to severe SUI will be eligible for enrolment in this non-randomized study. The primary outcome is patient satisfaction at 1 year, measured by the Patient Global Impression of Improvement; secondary outcomes are patient satisfaction at 3 months, objective and subjective cure at 3 months and 1 year, adverse events, post-operative pain, and cost-effectiveness. Differences in outcome measures will be assessed through logistic and linear regression analyses, both unadjusted and adjusted with covariate adjustment using the propensity score. RESULTS: No results are available yet. LIMITATIONS: The major disadvantage of this study design is the potential confounding bias. We intend to eliminate this bias by applying propensity scoring. CONCLUSION: By designing a non-randomized patient preference trial, we not only expect to demonstrate high patient satisfaction with both interventions but also provide insight into the possible role of PAHG-injections in the treatment of female SUI as a first-choice non-conservative treatment.

Innovative seated vertical lumbar traction allows simultaneous computer work while inducing spinal height changes similar to supine lying.

BACKGROUND: Lumbar intervertebral disc height loss has been associated with spinal height change (SHC) and low back pain (LBP), including stenosis. Non-invasive methods to improve disc height loss require forms of lying down, which are unconducive to computer work. OBJECTIVE: Intermittent vertical traction (VT) integrated with seated computer work may provide ergonomic alternatives for increasing SHC to promote LBP relief. The primary aim was to develop and introduce a safe VT prototype and dosage to induce and measure SHC. Prototype comfort and LBP ratings were exploratory secondary aims. METHODS: Forty-one participants were stadiometry-measured for pre- and post-intervention SHC from seated VT at 35% body weight removed, supine lying (SL), and sitting at a computer (SIT) without VT. Pain ratings were recorded for those self-reporting LBP. VT prototype evaluations were compiled from a 3-question, 7-point Likert-style survey. RESULTS: SHC increased by 3.9 ± 3.4 mm in VT, 1.7 ± 3.4 mm in SIT, and 4.3 ± 3.1 mm in SL (P< 0.000). Post hoc findings were significant between VT and SIT (P< 0.000), and SL and SIT (P< 0.000). VT and SL LBP ratings both decreased, but not SIT. CONCLUSION: Intermittent seated VT is a promising alternative for postural relief during seated computer work, producing SHC similar to lying down without compromising workflow.

Biomechanical Phenotyping of Chronic Low Back Pain: Protocol for BACPAC.

OBJECTIVE: Biomechanics represents the common final output through which all biopsychosocial constructs of back pain must pass, making it a rich target for phenotyping. To exploit this feature, several sites within the NIH Back Pain Consortium (BACPAC) have developed biomechanics measurement and phenotyping tools. The overall aims of this article were to: 1) provide a narrative review of biomechanics as a phenotyping tool; 2) describe the diverse array of tools and outcome measures that exist within BACPAC; and 3) highlight how leveraging these technologies with the other data collected within BACPAC could elucidate the relationship between biomechanics and other metrics used to characterize low back pain (LBP). METHODS: The narrative review highlights how biomechanical outcomes can discriminate between those with and without LBP, as well as among levels of severity of LBP. It also addresses how biomechanical outcomes track with functional improvements in LBP. Additionally, we present the clinical use case for biomechanical outcome measures that can be met via emerging technologies. RESULTS: To answer the need for measuring biomechanical performance, our "Results" section describes the spectrum of technologies that have been developed and are being used within BACPAC. CONCLUSION AND FUTURE DIRECTIONS: The outcome measures collected by these technologies will be an integral part of longitudinal and cross-sectional studies conducted in BACPAC. Linking these measures with other biopsychosocial data collected within BACPAC increases our potential to use biomechanics as a tool for understanding the mechanisms of LBP, phenotyping unique LBP subgroups, and matching these individuals with an appropriate treatment paradigm.

Childhood body mass index trajectories, adult-onset type 2 diabetes, and obesity-related cancers.

BACKGROUND: Elevated childhood body mass index (BMI), commonly examined as a "once-only" value, increases the risk of cancer and type 2 diabetes (T2D) in adulthood. Continuous exposure to adiposity during childhood may further increase cancer risk. We examined whether longitudinal childhood BMI trajectories were associated with adult obesity-related cancer and the role of adult-onset T2D in these associations. METHODS: Five sex-specific latent class BMI trajectories were generated for 301 927 children (149 325 girls) aged 6-15 years from the Copenhagen School Health Records Register. Information on obesity-related cancers and T2D was obtained from national health registers. Incidence rate ratios (IRR), cumulative incidences, and confidence intervals (CI) were estimated using Poisson regressions. RESULTS: Compared with the average childhood BMI trajectory (containing approximately 40% of individuals), the rate of obesity-related cancer (excluding breast cancer) increased with higher childhood BMI trajectories among women. The highest rates occurred in the overweight (IRR = 1.27, 95% CI = 1.17 to 1.38) and obesity (IRR = 1.79, 95% CI = 1.53 to 2.08) BMI trajectories. Similar patterns were observed among men. In contrast, women with the obesity childhood BMI trajectory had the lowest rate of pre- and postmenopausal breast cancer (IRR = 0.59, 95% CI = 0.43 to 0.80, and IRR = 0.41, 95% CI = 0.30 to 0.57, respectively). For all trajectories, the cumulative risk of obesity-related cancer increased with adult-onset T2D. CONCLUSION: Consistent childhood overweight or obesity may increase the rates of adult obesity-related cancer and decrease the rates of breast cancer. Adult-onset T2D conferred additional risk for obesity-related cancer, but the effect did not differ across childhood BMI trajectories.

The circadian transcription factor ARNTL2 is regulated by weight-loss interventions in human white adipose tissue and inhibits adipogenesis.

Misalignment of physiological circadian rhythms promotes obesity which is characterized by white adipose tissue (WAT) expansion. Differentiation of Adipose stem/progenitor cells (ASCs) contributes to WAT increase but the importance of the cellular clock in this process is incompletely understood. In the present study, we reveal the role of the circadian transcription factor Aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) in human ASCs, isolated from subcutaneous (s)WAT samples of patients undergoing routine elective plastic abdominal surgery. We show that circadian synchronization by serum-shock or stimulation with adipogenic stimuli leads to a different expression pattern of ARNTL2 relative to its well-studied paralogue ARNTL1. We demonstrate that ARNTL2 mRNA is downregulated in ASCs upon weight-loss (WL) whereas ARNTL2 protein is rapidly induced in the course of adipogenic differentiation and highly abundant in adipocytes. ARNTL2 protein is maintained in ASCs cooperatively by mechanistic Target of Rapamycin (mTOR) and Mitogen-activated Protein Kinase (MAPK) signalling pathways while ARNTL2 functions as an inhibitor on both circuits, leading to a feedback mechanism. Consistently, ectopic overexpression of ARNTL2 repressed adipogenesis by facilitating the degradation of ARNTL1, inhibition of Kruppel-Like Factor 15 (KLF15) gene expression and down-regulation of the MAPK-CCAAT/enhancer-binding protein ß (C/EBPß) axis. Western blot analysis of sWAT samples from normal-weight, obese and WL donors revealed that ARNTL2 protein was solely elevated by WL compared to ARNTL1 which underscores unique functions of both transcription factors. In conclusion, our study reveals ARNTL2 to be a WL-regulated inhibitor of adipogenesis which might provide opportunities to develop strategies to ameliorate obesity.