Combined associations of obesity and physical activity with pain, fatigue, stiffness and anxiety in adults with spondyloarthropathies: UK Biobank study.

Objective: Inflammatory spondyloarthropathies are associated with pain, fatigue, stiffness and anxiety. The National Institute for Health and Care Excellence and the EULAR provide limited lifestyle guidance for managing symptoms with inflammatory spondyloarthropathies. We investigated the combined associations of obesity and physical activity with symptom severity in inflammatory spondyloarthropathies. Methods: The relationship between BMI, physical activity and symptom severity (spinal and general pain, fatigue, anxiety, mobility) was examined in people with ISpAs (n = 1577). BMI categories were normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2) and obese (≥30 kg/m2). Physical activity was assessed via the International Physical Activity Questionnaire (low < 600 metabolic equivalent of task (MET)-min/week, moderate ≥ 600 METs, high ≥ 3000 METs). Statistical models adjusted for confounders, including medication, estimated the likelihood (odds ratios, OR) of higher symptom severity across BMI and physical activity categories. Results: Overweight and obesity, compared with normal weight, were linked to higher severity of all symptoms, with stronger associations for obesity (OR ≥ 2.34, P < 0.001) than overweight (OR ≥ 1.37, P ≤ 0.032). Moderate activity, compared with low, was associated with lower severity of all symptoms (OR ≤ 0.77, P ≤ 0.032). High activity, compared with low, was associated with lower severity of fatigue, anxiety and mobility issues (OR ≤ 0.74, P ≤ 0.029), but associations with spinal and general pain were not significant (OR ≤ 0.80, P ≥ 0.056). No BMI-by-physical activity combinations were detected, indicating physical activity benefits all BMI groups to a similar extent. Conclusion: National Institute for Health and Care Excellence and EULAR guidance for inflammatory spondyloarthropathies should emphasize maintaining a normal weight. Moderate physical activity is optimal for reducing symptom severity and should be promoted in lifestyle guidance.

Rituximab and lenalidomide for the treatment of relapsed or refractory indolent non-Hodgkin lymphoma: real-life experience.

The combination of rituximab and lenalidomide (R-len) stands as an established treatment for relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). However, the reproducibility of clinical trial results in routine clinical practice is unknown. To address this gap in knowledge, we reviewed our experience with patients diagnosed with R/R follicular lymphoma (FL) or marginal zone lymphoma (MZL) treated with this combination. Eighty-four patients underwent treatment with R-len, 69 (82%) affected by FL and 15 (18%) by MZL. The median age at the time of treatment initiation was 65 years (range, 39-94), 38 patients (45%) had a pre-treatment FLIPI score of 3-5, 19 (23%) had a bulky disease, 29 (37%) had a lymphoma refractory to the last treatment line, while in 20 (24%) cases the disease was refractory to rituximab. The best overall response rate (ORR) was 82%, and 52% achieved a complete response (CR). The best CR rates for FL and MZL patients were 55% and 40%, respectively. With a median follow-up of 22 months, the median progression-free survival (mPFS) was 22 months (95% CI 19-36) and the 2-year overall survival (OS) was 83% (95% CI 74-93). The median duration of CR (DoCR) was 46 months (95% CI 22-NR). Factors associated with shorter PFS in multivariate analysis were bulky disease and rituximab refractoriness. The most common adverse events (AE) included hematologic toxicity, fatigue and gastrointestinal disorders, such as diarrhea and constipation. Neutropenia and thrombocytopenia were the most common severe toxicities (grade ≥3 in 25% and 4%, respectively). No new safety signals were reported. Real-life results of R-len in patients with R/R iNHL appear consistent with those reported in prospective studies, and further support its use as comparator arm in controlled clinical trials.

A semiautomated microfluidic ELISA for the detection of hemophagocytic lymphohistiocytosis biomarkers.

OBJECTIVES: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition characterized by a massive overactivation of the immune system. Because the clinical findings are nonspecific, the development of assays to facilitate rapid diagnosis is critical for patient care. The objectives of this study were to evaluate the performance of a microfluidic enzyme-linked immunosorbent assay (ELISA) for HLH biomarkers and investigate the impact of insourcing this testing on workflow, cost, and turnaround time in a tertiary-care cancer hospital. METHODS: Trends in order volume were evaluated for C-X-C motif chemokine ligand 9 (CXCL9) and soluble interleukin 2 receptor ɑ (sIL2R), and a microfluidic ELISA was used to measure these analytes in serum samples. Analyte values, turnaround time, and costs were compared for this assay relative to reference laboratory testing. RESULTS: Test ordering has increased from 187 to 1030 requests annually over the past 5 years. Insourcing these analytes on a semiautomated ELISA can decrease time to result by approximately 2 days and generate a cost savings of roughly $140,000 annually within our laboratory. CONCLUSIONS: Using a semiautomated ELISA for sIL2R and CXCL9 may help physicians arrive at a diagnosis and monitor therapy for patients with HLH while decreasing turnaround time and costs within the clinical laboratory.

Reversible bilateral central scotoma under scotopic conditions associated with oral semaglutide.

Introduction: Semaglutide is a glucagon-like peptide-1 receptor agonist that treats type 2 diabetes mellitus and can be used as an adjunct for weight loss when combined with exercise and diet. Here we report a case of a bilateral, incongruent central visual scotoma under scotopic conditions in a board-certified ophthalmologist associated with semaglutide use that resolved quickly following medication discontinuation. Case report: A 72-year-old male ophthalmologist (JAD) started 3.0 mg daily oral semaglutide (Rybelsus) to help with weight loss and seventeen days after treatment initiation developed a small, round central scotoma in his right eye that enlarged over several days. After two days a similar but smaller scotoma developed in his left eye. These symptoms were present only under scotopic conditions and were not visible in daylight or artificially lit conditions. When symptoms developed in the left eye, the medication was discontinued, and all symptoms completely resolved two days later. A subsequent clinical evaluation revealed no abnormalities on macular optical coherence tomography, fundus photography, fundus autofluorescence or Humphrey visual field. Conclusions: This case of a bilateral central scotoma under scotopic conditions that resolved after medication discontinuation expands the knowledge of potential side effects from this increasingly popular diabetic and weight loss medication.

Combining Enhanced Resolving Power with Duty Cycle Improvements on a Multi-Reflecting Time-of-Flight Mass Spectrometer.

The combination of enhanced resolving power and improved duty cycle on a multireflecting time-of-flight mass spectrometer is described. Resolving power increases are achieved by extending the effective ion path length from 47 m to greater than 200 m. Path length increases are achieved through containment of ions within the analyzer for up to N = 5 passes using a pulsed deflection electrode. Resolving power was shown to increase from 220,000 to 402,000 (fwhm) at m/z 785 for N = 1 and N = 4 analyzer passes, respectively. Due to the timing of the pulsed deflection electrode, the approach is particularly suited to high resolution analysis over a targeted m/z range. Duty cycle enhancements are achieved for ions of the targeted m/z range via accumulation prior to orthogonal acceleration, providing signal improvements of 2 orders of magnitude. Achieving such high resolving powers at fast scan rates (30 Hz) can yield additional information such as fine isotope structure; when combined with ppb mass measurement accuracy, high confidence in analyte identification can be achieved. The technique is applied for N = 2 analyzer passes, demonstrating fine isotope structure for a typical UHPLC metabolite identification experiment at a 10 Hz acquisition rate. Additionally, mass spectrometry imaging data is acquired using DESI, demonstrating the improved image clarity achieved at >300,000 (fwhm).

Co-inoculations of bacteria and mycorrhizal fungi often drive additive plant growth responses.

Controlled greenhouse studies have shown the numerous ways that soil microbes can impact plant growth and development. However, natural soil communities are highly complex, and plants interact with many bacterial and fungal taxa simultaneously. Due to logistical challenges associated with manipulating more complex microbiome communities, how microbial communities impact emergent patterns of plant growth therefore remains poorly understood. For instance, do the interactions between bacteria and fungi generally yield additive (i.e. sum of their parts) or nonadditive, higher order plant growth responses? Without this information, our ability to accurately predict plant responses to microbial inoculants is weakened. To address these issues, we conducted a meta-analysis to determine the type (additive or higher-order, nonadditive interactions), frequency, direction (positive or negative), and strength that bacteria and mycorrhizal fungi (arbuscular and ectomycorrhizal) have on six phenotypic plant growth responses. Our results demonstrate that co-inoculations of bacteria and mycorrhizal fungi tend to have positive additive effects on many commonly reported plant responses. However, ectomycorrhizal plant shoot height responds positively and nonadditively to co-inoculations of bacteria and ectomycorrhizal fungi, and the strength of additive effects also differs between mycorrhizae type. These findings suggest that inferences from greenhouse studies likely scale to more complex field settings and that inoculating plants with diverse, beneficial microbes is a sound strategy to support plant growth.

Multi-omic characterization of antibody-producing CHO cell lines elucidates metabolic reprogramming and nutrient uptake bottlenecks.

Characterizing the phenotypic diversity and metabolic capabilities of industrially relevant manufacturing cell lines is critical to bioprocess optimization and cell line development. Metabolic capabilities of production hosts limit nutrient and resource channeling into desired cellular processes and can have a profound impact on productivity. These limitations cannot be directly inferred from measured data such as spent media concentrations or transcriptomics. Here, we present an integrated multi-omic analysis pipeline combining exo-metabolomics, transcriptomics, and genome-scale metabolic network analysis and apply it to three antibody-producing Chinese Hamster Ovary cell lines to identify reprogramming features associated with high-producing clones and metabolic bottlenecks limiting product formation in an industrial bioprocess. Analysis of individual datatypes revealed a decreased nitrogenous byproduct secretion in high-producing clones and the topological changes in peripheral metabolic pathway expression associated with phase shifts. An integrated omics analysis in the context of the genome-scale metabolic model elucidated the differences in central metabolism and identified amino acid utilization bottlenecks limiting cell growth and antibody production that were not evident from exo-metabolomics or transcriptomics alone. Thus, we demonstrate the utility of a multi-omics characterization in providing an in-depth understanding of cellular metabolism, which is critical to efforts in cell engineering and bioprocess optimization.

Autonomic and Enteric Profiling May Help Predict Response to Diverse Obesity Therapies.

PURPOSE: Changes in autonomic (ANS) and enteric nervous systems (ENS) may be involved in pathogenesis of obesity. We hypothesized that baseline autonomic and enteric parameters may predict outcomes of diverse obesity therapies. MATERIAL AND METHODS: We studied ANS and ENS physiology in 37 patients (8 male, 29 female, age 45 years, weight 129.7 kg) at 4 centers in patients undergoing medical (9: low-calorie diet) versus invasive (22: 16 sleeve, 6 bypass) and semi-invasive (6: 2 band, 2 high energy stimulation, 2 aspiration) weight loss therapies. Weight loss was reported as percent weight loss from baseline to latest values at 1 year and in some up to 5 years; classified as < or > /= 20% for each group. ANS testing included sympathetic adrenergic function by measuring reflex vasoconstriction and postural adjustment ratio. ENS was measured non-invasively using cutaneous low-resolution electrogastrogram. RESULTS: Percent weight loss was greater with the invasive (28.5%) than semi-invasive (9.1%) or non-invasive low-calorie diet (4.4%) (p < .001). Percent weight loss at 1 year (and up to 5 years) corresponded to the adrenergic measure of postural adjustment ratio (r = .42, p = .012), total pulse amplitude at rest (r = .56, p < .001), and electrogastrogram standing-to-rest difference (r = .33, p = .056). CONCLUSION: Baseline autonomic and enteric function measures correspond to percentage with loss in this pilot study using diverse weight loss methods. Autonomic and enteric profiling has potential clinical use for evaluation and treatment of obesity but needed larger controlled trials.

Management of a Twisted Flow Diverting Stent With a Balloon Mounted Cardiac Stent in a Pediatric Aneurysm: A Technical Report.

BACKGROUND AND IMPORTANCE: Giant aneurysms can present technical challenges during treatment with flow diversion including inability to access the aneurysm outflow directly. Encircling the aneurysm with a microwire/microcatheter has been well described; however, it can result in a twisted stent because of catheter twisting during the reduction maneuver, which, in turn, could lead to thromboembolic complications. CASE PRESENTATION: Here, we describe a novel technique to manage the twist of the flow diverter in a giant internal carotid artery aneurysm using a combination of angioplasty and off-label placement of a balloon-mounted cardiac stent within the flow diverter. CONCLUSION: At 1 year, the aneurysm is completely occluded on digital subtraction angiography and MRI, and the patient is neurologically intact.

Supra-Inguinal Inflow for Distal Bypasses Have Acceptable Patency and Limb Salvage Rates.

BACKGROUND: There is a paucity of data evaluating outcomes of lower extremity bypass (LEB) using supra-inguinal inflow for revascularization of infra-inguinal vessels. The purpose of this study is to report outcomes after LEB originating from aortoiliac arteries to infra-femoral targets. METHODS: The Vascular Quality Initiative database (2003-2020) was queried for patients undergoing LEB from the aortoiliac arteries to the popliteal and tibial arteries. Patients were stratified into 3 cohorts based on outflow targets (above-knee [AK] popliteal, below-knee [BK] popliteal, and tibial arteries). Perioperative and 1-year outcomes including primary patency, amputation-free survival (AFS), and major adverse limb events (MALEs) were compared. A Cox proportional hazards model was used to estimate the independent prognostic factors of outcomes. RESULTS: Of 403 LEBs, 389 (96.5%) originated from the external iliac artery, while the remaining used the aorta or common iliac artery as inflow. In terms of the distal target, the AK popliteal was used in 116 (28.8%), the BK popliteal in 151 (27.5%), and tibial vessels in 136 (43.7%) cases. BK popliteal and tibial bypasses, compared to AK popliteal bypasses, were more commonly performed in patients with chronic limb-threatening ischemia (69.5% and 69.9% vs. 48.3%; P < 0.001). Vein conduit was more often used for tibial bypass than for AK and BK popliteal bypasses (46.3% vs. 21.9% and 16.3%; P < 0.001). In the perioperative period, BK popliteal and tibial bypass patients had higher reoperation rates (16.9% and 13.2% vs. 5.2%; P = 0.02) and lower primary patency (89.4% and 89% vs. 95.7%; P = 0.04) than AK bypass patients. At 1 year, compared with AK popliteal bypasses, BK and tibial bypasses demonstrated lower primary patency (81.9% vs. 56.7% vs. 52.4%, P < 0.001) and freedom from MALE (77.6% vs. 70.2% vs. 63.1%, P = 0.04), although AFS was not significantly different (89.7% vs. 90.6% vs. 83.8%, P = 0.19).On multivariable analysis, compared with AK popliteal bypasses, tibial bypasses were independently associated with increased loss of primary patency (hazard ratio 1.9, 95% confidence interval, 1.03-3.51, P = 0.04). Subanalysis of patients with chronic limb-threatening ischemia demonstrated significantly higher primary patency in the AK popliteal cohort at discharge and 1 year, but no difference in AFS or freedom from MALE between the cohorts at follow-up. CONCLUSIONS: LEB with supra-inguinal inflow appear to have acceptable rates of 1-year patency and limb salvage in patients at high risk of bypass failure. Tibial outflow target was independently associated with worse primary patency but not with MALE or AFS.

The association of smoking with different eating and dietary behaviours: A cross-sectional analysis of 80 296 United Kingdom adults.

BACKGROUND AND AIMS: Smokers typically have a lower body mass index (BMI) than non-smokers, while smoking cessation is associated with weight gain. In pre-clinical research, nicotine in tobacco smoking suppresses appetite and influences subsequent eating behaviour; however, this relationship is unclear in humans. This study measured the associations of smoking with different eating and dietary behaviours. DESIGN: A cross-sectional analysis of data from health assessments conducted between 2004 and 2022. SETTING: An independent healthcare-based charity within the United Kingdom. PARTICIPANTS: A total of 80 296 men and women (mean ± standard deviation [SD]: age, 43.0 ± 10.4 years; BMI, 25.7 ± 4.2 kg/m2; 62.5% male) stratified into two groups based on their status as a smoker (n = 6042; 7.5%) or non-smoker (n = 74 254; 92.5%). MEASUREMENTS: Smoking status (self-report) was the main exposure, while the primary outcomes were selected eating and dietary behaviours. Age, sex and socioeconomic status (index of multiple deprivation [IMD]) were included as covariates and interaction terms, while moderate-to-vigorous exercise and sleep quality were included as covariates only. FINDINGS: Smokers had lower odds of snacking between meals and eating food as a reward or out of boredom versus non-smokers (all odds ratio [OR] ≤ 0.82; P < 0.001). Furthermore, smokers had higher odds of skipping meals, going more than 3 h without food, adding salt and sugar to their food, overeating and finding it hard to leave something on their plate versus non-smokers (all OR ≥ 1.06; P ≤ 0.030). Additionally, compared with non-smokers, smoking was associated with eating fried food more times per week (rate ratio [RR] = 1.08; P < 0.001), eating fewer meals per day, eating sweet foods between meals and eating dessert on fewer days per week (all RR ≤ 0.93; P < 0.001). Several of these relationships were modified by age, sex and IMD. CONCLUSIONS: Smoking appears to be associated with eating and dietary behaviours consistent with inhibited food intake, low diet quality and altered food preference. Several of these relationships are moderated by age, sex and socioeconomic status.

Protocol: Reducing community violence: A systematic meta-review of what works.

This is the protocol for a Campbell Collaboration systematic review. Our objective is to synthesize what is known about the effectiveness of strategies for reducing community violence, focusing on those strategies that have been subjected to a systematic review. We aim to answer the following questions in this review: what strategies to reduce community violence have been rigorously evaluated through systematic reviews; which have sufficient evidence of effectiveness, which seem promising, and which appear ineffective; and what implications for practice and policy can be drawn from this large body of research? We anticipate categorizing the results of our review similarly to the original review by Abt and Winship (2016). That is, categorizing reviews by people-based approaches, place-based approaches, and behavior-based approaches. However, given that this is an updated review and we will be incorporating additional studies, we may find that an alternative or additional categorization is warranted and update our categorization accordingly. Implications for policy and practice as they relate to these categories will be discussed.

Advancing Exoskeleton Development: Validation of a Robotic Surrogate to Measure Tibial Strain.

Bone stress injuries are prevalent among athletes and military recruits and can significantly compromise training schedules. The development of an ankle-foot orthosis to reduce tibial load and enable a faster return to activity will require new device testing methodologies capable of capturing the contribution of muscular force on tibial strain. Thus, an actuated robotic surrogate leg was developed to explore how tibial strain changes with different ankle-foot orthosis conditions. The purpose of this work was to assess the reliability, scalability, and behavior of the surrogate. A dual actuation system consisting of a Bowden cable and a vertical load applied to the femur via a material testing system, replicated the action-reaction of the Achilles-soleus complex. Maximum and minimum principal strain, maximum shear strain, and axial strain were measured by instrumented strain gauges at five locations on the tibia. Strains were highly repeatable across tests but did not consistently match in vivo data when scaled. However, the stiffness of the ankle-foot orthosis strut did not systematically affect tibial load, which is consistent with in vivo findings. Future work will involve improving the scalability of the results to match in vivo data and using the surrogate to inform exoskeletal designs for bone stress injuries.

Curriculum mapping to audit and grow longitudinal graduate medical education leadership training.

BACKGROUND: Residents need and want practical leadership training, yet leadership curricula are lacking in graduate medical education (GME). We describe our process of curriculum mapping, a method for auditing a curriculum, and its role in iterative leadership curriculum development. AIMS: To show how to create a curriculum map for auditing a curriculum using examples from our leadership curriculum and to demonstrate its value through case examples of leadership education integration into existing resident experiences. METHODS: We selected our recent systematic review on current leadership curricula to prioritise leadership content given it was the basis for our initial curriculum. We identified existing resident experiences where training can occur. We use the selected content and training environments, layered with a modified Miller's pyramid, to construct a curriculum map. RESULTS: Our curriculum map provides an example of curriculum auditing that reveals opportunities for leadership training that could be integrated into current residency experiences. We provide case examples of application. DISCUSSION: Effective leadership training should address critical topics and capitalise on experiential learning opportunities that exist within residency training programmes. The training must be seamlessly integrated into the demanding obligations of GME trainees, a process that can be achieved using curriculum mapping. Curriculum mapping can provide insight into a residency programme's leadership curriculum and create a direction for future leadership curriculum development.

Polymer Coatings Affect Transport and Remobilization of Colloidal Activated Carbon in Saturated Sand Columns: Implications for In Situ Groundwater Remediation.

Colloidal activated carbon (CAC) is an emerging technology for the in situ remediation of groundwater impacted by per- and polyfluoroalkyl substances (PFAS). In assessing the long-term effectiveness of a CAC barrier, it is crucial to evaluate the potential of emplaced CAC particles to be remobilized and migrate away from the sorptive barrier. We examine the effect of two polymer stabilizers, carboxymethyl cellulose (CMC) and polydiallyldimethylammonium chloride (PolyDM), on CAC deposition and remobilization in saturated sand columns. CMC-modified CAC showed high mobility in a wide ionic strength (IS) range from 0.1 to 100 mM, which is favorable for CAC delivery at a sufficient scale. Interestingly, the mobility of PolyDM-modified CAC was high at low IS (0.1 mM) but greatly reduced at high IS (100 mM). Notably, significant remobilization (release) of deposited CMC-CAC particles occurred upon the introduction of solution with low IS following deposition at high IS. In contrast, PolyDM-CAC did not undergo any remobilization following deposition due to its favorable interactions with the quartz sand. We further elucidated the CAC deposition and remobilization behaviors by analyzing colloid-collector interactions through the application of Derjaguin-Landau-Verwey-Overbeek theory, and the inclusion of a discrete representation of charge heterogeneity on the quartz sand surface. The classical colloid filtration theory was also employed to estimate the travel distance of CAC in saturated columns. Our results underscore the roles of polymer coatings and solution chemistry in CAC transport, providing valuable guidelines for the design of in situ CAC remediation with maximized delivery efficiency and barrier longevity.

The natural history of celiac artery aneurysms.

OBJECTIVES: The goal of this study was to document the natural history of celiac artery aneurysms (CAAs). BACKGROUND: Celiac artery aneurysms are rare. Existing literature is skewed towards outcomes after intervention of large, symptomatic aneurysms but the behavior of untreated CAAs is poorly understood. METHODS: This is a single institution, retrospective analysis of patients with CAA diagnosed by CT imaging (2015-2019) identified through an institutional radiology database. Radiologic, demographic, and follow-up data were analyzed. The primary endpoint was the mean growth rate of CAAs. RESULTS: Of the 76 patients included, 86.8% were men with a mean age at presentation of 69.8 years. The mean CAA diameter on index imaging was 15.4 +/- 3.8 mm (range, 7-30 mm). All were classified as true aneurysms and 76.3% were saccular. All patients had clinical follow-up with mean follow-up 31.2 months +/- 21.6 months. No patient developed symptoms or rupture. The mean radiological follow-up among 45 patients was 25.2 +/- 16.8 months. Over this period, 16 CAAs (35.6%) enlarged, while 29 (64.4%) remained stable. One patient (1.3%) underwent intervention for increasing size in the setting of a chronic dissection. On multivariate analysis, age <70 was significantly associated with increased risk of aneurysm growth. CONCLUSIONS: In this institutional review of patients with CAAs, the majority of aneurysms remained stable in size, with no patients developing symptoms or rupture over clinical follow-up. Given the observed benign behavior of these aneurysms, guidelines that suggest conservative management of CAAs less than 2 cm seems appropriate.

Insights into child abuse and neglect: Findings from the Minnesota Longitudinal Study of Risk and Adaptation.

The Minnesota Longitudinal Study of Risk and Adaptation (MLSRA) is a landmark prospective, longitudinal study of human development focused on a sample of mothers experiencing poverty and their firstborn children. Although the MLSRA pioneered a number of important topics in the area of social and emotional development, it began with the more specific goal of examining the antecedents of child maltreatment. From that foundation and for more than 40 years, the study has produced a significant body of research on the origins, sequelae, and measurement of childhood abuse and neglect. The principal objectives of this report are to document the early history of the MLSRA and its contributions to the study of child maltreatment and to review and summarize results from the recently updated childhood abuse and neglect coding of the cohort, with particular emphasis on findings related to adult adjustment. While doing so, we highlight key themes and contributions from Dr Dante Cicchetti's body of research and developmental psychopathology perspective to the MLSRA, a project launched during his tenure as a graduate student at the University of Minnesota.