Effect of Baseline BMI and IL-6 Subgroup Membership on Gait Speed Response to Caloric Restriction in Older Adults with Obesity.

BACKGROUND: Prior work shows caloric restriction (CR) can improve physical function among older adults living with obesity. However, the contribution of starting weight and inflammatory burden to CR-associated functional improvements is unclear. The primary purpose of this study was to determine if CR-associated gait speed change varied by body mass index (BMI) and plasma interleukin 6 (IL-6) at baseline and secondarily to determine the contribution of BMI change and IL-6 change to gait speed change. DESIGN, SETTING, PARTICIPANTS: Data from eight randomized control trials were pooled, with 1184 participants randomized to CR (n=661) and No CR (n=523) conditions. All studies assessed outcomes before and five or six months after assignment to CR or No CR. MEASUREMENTS: BMI and IL-6 were assessed at baseline using standard procedures. Gait speed was assessed with the six-minute walk test or 400m walk test. Baseline BMI/IL-6 subgroups were constructed using BMI≥35 kg/m2 and IL-6>2.5 pg/mL thresholds. Participants with BMI≥35 kg/m2 were grouped into class 2+ obesity and BMI<35 kg/m2 into class 1- obesity; IL-6>2.5 pg/mL were grouped into high IL-6, and <2.5 pg/mL as low IL-6 (class 2+ obesity/high IL-6: n=288, class 2+ obesity/low IL-6: n=143, class 1- obesity/high IL-6: n=354, or class 1- obesity/low IL-6: n=399). All analyses used adjusted general linear models. RESULTS: Gait speed significantly improved with CR versus non-CR [mean difference: +0.02 m/s (95% CI: 0.01, 0.04)]. CR assignment significantly interacted with BMI/IL-6 subgroup membership (p=0.03). Greatest gait speed improvement was observed in the class 2+ obesity/high IL-6 subgroup [+0.07 m/s (0.03, 0.10)]. No other subgroups observed significant gait speed change. For each unit decrease in BMI, gait speed change increased by +0.02 m/s (p<0.001; R2=0.26), while log IL-6 change did not significantly affect gait speed change [+0.01 m/s (p=0.20)]. CONCLUSIONS: Only the class 2+ obesity/high IL-6 subgroup significantly improved gait speed in response to CR. Improvement in gait speed in this subgroup was driven by a larger decrease in BMI, but not IL-6, in response to CR. Individuals with class 2+ obesity and high IL-6 are most likely to show improved gait speed in response to CR, with improvement predominantly driven by reductions in BMI.

The Effects of a Pain Management-Focused Mobile Health Behavior Intervention on Older Adults' Self-efficacy, Satisfaction with Functioning, and Quality of Life: a Randomized Pilot Trial.

BACKGROUND: This report investigates the impact of a remote physical activity intervention on self-efficacy, satisfaction with functioning, and health-related quality of life (HRQOL) as assessed by the SF-36 in obese older adults with chronic pain. The intervention was group-mediated in nature and based in social cognitive theory and mindfulness-based relapse prevention. METHODS: Participants (N = 28; 70.21 ± 5.22 years) were randomly assigned to receive either the active intervention, which focused on reducing caloric intake and increasing steps across the day or to a waitlist control condition. RESULTS: Over 12 weeks, intervention participants reported a moderate, positive improvement in self-efficacy for walking relative to control. They also reported large magnitude improvements in satisfaction for physical functioning as well as improvements on pain and the physical functioning subscales of the SF-36. CONCLUSIONS: These findings expand on previous research showing similar effects in response to structured exercise, this time via a protocol that is likely to be scalable and sustainable for many older adults. Additional work on larger and more diverse samples is warranted.

A multi-modal virtual reality treadmill intervention for enhancing mobility and cognitive function in people with multiple sclerosis: Protocol for a randomized controlled trial.

BACKGROUND: Gait and cognitive impairments are common in individuals with Multiple Sclerosis (MS) and can interfere with everyday function. Those with MS have difficulties executing cognitive tasks and walking simultaneously, a reflection of dual-task interference. Therefore, dual-task training may improve functional ambulation. Additionally, using technology such as virtual reality can provide personalized rehabilitation while mimicking real-world environments. The purpose of this randomized controlled trial is to establish the benefits of a combined cognitive-motor virtual reality training on MS symptoms compared to conventional treadmill training. METHODS: This study will be a single-blinded, two arm RCT with a six-week intervention period. 144 people with MS will be randomized into a treadmill training alone group or treadmill training with virtual reality group. Both groups will receive 18 sessions of training while walking on a treadmill, with the virtual reality group receiving feedback from the virtual system. Primary outcome measures include dual-task gait speed and information processing speed, which will be measured prior to training, one-week post-training, and three months following training. DISCUSSION: This study will provide insight into the ability of a multi-modal cognitive-motor intervention to reduce dual-task cost and to enhance information processing speed in those with MS. This is one of the first studies that is powered to understand whether targeted dual-task training can improve MS symptoms and increase functional ambulation. We anticipate that those in the virtual reality group will have a significantly greater increase in dual-task gait speed and information processing speed than those achieved via treadmill training alone.

"I'm obviously not dying so it's not something I need to sort out today": Considering hepatitis C treatment in the era of direct acting antivirals.

BACKGROUND: People who inject drugs are the group at greatest risk of hepatitis C virus (HCV) infection. The advent of new direct-acting antiviral (DAA) treatment provides opportunities for increased uptake of therapy. METHODS: We conducted in-depth interviews with thirty HCV positive participants from the SuperMIX cohort study. Interviews were transcribed, coded, and analysed for emerging themes and similarities between participants. General descriptions and critical interpretation of themes were generated and selective quotes extracted verbatim to best illustrate the critical themes. RESULTS: Participants described their experiences of living with HCV, their knowledge of HCV treatment accessibility, and information on the types of support ain themes: Understanding the need for treatment; Knowledge and framing of treatment access; and Support during treatment. CONCLUSION: The new, highly effective DAAs for the treatment of HCV are heralded as the potential beginning of HCV elimination, especially in settings where scale up is high. Our data from active PWID show that the availability of DAA medications in and of themselves is likely not to be enough to ensure that PWID will come forward for HCV treatment in sufficient numbers to drive elimination.

Plasma gelsolin promotes re-epithelialization.

Woundhealing disorders characterized by impaired or delayed re-epithelialization are a serious medical problem that is painful and difficult to treat. Gelsolin (GSN), a known actin modulator, supports epithelial cell regeneration and apoptosis. The aim of this study was to estimate the potential of recombinant gelsolin (rhu-pGSN) for ocular surface regeneration to establish a novel therapy for delayed or complicated wound healing. We analyzed the influence of gelsolin on cell proliferation and wound healing in vitro, in vivo/ex vivo and by gene knockdown. Gelsolin is expressed in all tested tissues of the ocular system as shown by molecular analysis. The concentration of GSN is significantly increased in tear fluid samples of patients with dry eye disease. rhu-pGSN induces cell proliferation and faster wound healing in vitro as well as in vivo/ex vivo. TGF-ß dependent transcription of SMA is significantly decreased after GSN gene knockdown. Gelsolin is an inherent protein of the ocular system and is secreted into the tear fluid. Our results show a positive effect on corneal cell proliferation and wound healing. Furthermore, GSN regulates the synthesis of SMA in myofibroblasts, which establishes GSN as a key protein of TGF-ß dependent cell differentiation.

Rapid Microbiology Screening in Pharmaceutical Workflows.

Recently advances in miniaturization and automation have been utilized to rapidly decrease the time to result for microbiology testing in the clinic. These advances have been made due to the limitations of conventional culture-based microbiology methods, including agar plate and microbroth dilution, which have long turnaround times and require physicians to treat patients empirically with antibiotics before test results are available. Currently, there exist similar limitations in pharmaceutical sterility and bioburden testing, where the long turnaround times associated with standard microbiology testing drive costly inefficiencies in workflows. These include the time lag associated with sterility screening within drug production lines and the warehousing cost and time delays within supply chains during product testing. Herein, we demonstrate a proof-of-concept combination of a rapid microfluidic assay and an efficient cell filtration process that enables a path toward integrating rapid tests directly into pharmaceutical microbiological screening workflows. We demonstrate separation and detection of Escherichia coli directly captured and analyzed from a mammalian (i.e., CHO) cell culture with a 3.0 h incubation. The demonstration is performed using a membrane filtration module that is compatible with sampling from bioreactors, enabling in-line sampling and process monitoring.

Reported gum disease as a cardiovascular risk factor in adults with intellectual disabilities.

BACKGROUND: Several risk factors for cardiovascular disease (CVD) have been identified among adults with intellectual disabilities (ID). Periodontitis has been reported to increase the risk of developing a CVD in the general population. Given that individuals with ID have been reported to have a higher prevalence of poor oral health than the general population, the purpose of this study was to determine whether adults with ID with informant reported gum disease present greater reported CVD than those who do not have reported gum disease and whether gum disease can be considered a risk factor for CVD. METHODS: Using baseline data from the Longitudinal Health and Intellectual Disability Study from which informant survey data were collected, 128 participants with reported gum disease and 1252 subjects without reported gum disease were identified. A series of univariate logistic regressions was conducted to identify potential confounding factors for a multiple logistic regression. RESULTS: The series of univariate logistic regressions identified age, Down syndrome, hypercholesterolemia, hypertension, reported gum disease, daily consumption of fruits and vegetables and the addition of table salt as significant risk factors for reported CVD. When the significant factors from the univariate logistic regression were included in the multiple logistic analysis, reported gum disease remained as an independent risk factor for reported CVD after adjusting for the remaining risk factors. Compared with the adults with ID without reported gum disease, adults in the gum disease group demonstrated a significantly higher prevalence of reported CVD (19.5% vs. 9.7%; P = .001). CONCLUSION: After controlling for other risk factors, reported gum disease among adults with ID may be associated with a higher risk of CVD. However, further research that also includes clinical indices of periodontal disease and CVD for this population is needed to determine if there is a causal relationship between gum disease and CVD.

Pulmonary Sarcomatoid Carcinomas Commonly Harbor Either Potentially Targetable Genomic Alterations or High Tumor Mutational Burden as Observed by Comprehensive Genomic Profiling.

INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a high-grade NSCLC characterized by poor prognosis and resistance to chemotherapy. Development of targeted therapeutic strategies for PSC has been hampered because of limited and inconsistent molecular characterization. METHODS: Hybrid capture-based comprehensive genomic profiling was performed on DNA from formalin-fixed paraffin-embedded sections of 15,867 NSCLCs, including 125 PSCs (0.8%). Tumor mutational burden (TMB) was calculated from 1.11 megabases (Mb) of sequenced DNA. RESULTS: The median age of the patients with PSC was 67 years (range 32-87), 58% were male, and 78% had stage IV disease. Tumor protein p53 gene (TP53) genomic alterations (GAs) were identified in 74% of cases, which had genomics distinct from TP53 wild-type cases, and 62% featured a GA in KRAS (34%) or one of seven genes currently recommended for testing in the National Comprehensive Cancer Network NSCLC guidelines, including the following: hepatocyte growth factor receptor gene (MET) (13.6%), EGFR (8.8%), BRAF (7.2%), erb-b2 receptor tyrosine kinase 2 gene (HER2) (1.6%), and ret proto-oncogene (RET) (0.8%). MET exon 14 alterations were enriched in PSC (12%) compared with non-PSC NSCLCs (∼3%) (p < 0.0001) and were more prevalent in PSC cases with an adenocarcinoma component. The fraction of PSC with a high TMB (>20 mutations per Mb) was notably higher than in non-PSC NSCLC (20% versus 14%, p = 0.056). Of nine patients with PSC treated with targeted or immunotherapies, three had partial responses and three had stable disease. CONCLUSION: Potentially targetable GAs in National Comprehensive Cancer Network NSCLC genes (30%) or intermediate or high TMB (43%, >10 mutations per Mb) were identified in most of the PSC cases. Thus, the use of comprehensive genomic profiling in clinical care may provide important treatment options for a historically poorly characterized and difficult to treat disease.

Total body composition estimated by standing-posture 8-electrode bioelectrical impedance analysis in male wrestlers.

Standing-posture 8-electrode bioelectrical impedance analysis is a fast and practical method for evaluating body composition in clinical settings, which can be used to estimate percentage body fat (BF%) and skeletal muscle mass in a subject's total body and body segments. In this study, dual-energy X-ray absorptiometry (DXA) was used as a reference method for validating the standing 8-electrode bioelectrical impedance analysis device BC-418 (BIA8, Tanita Corp., Tokyo, Japan). Forty-eight Taiwanese male wrestlers aged from 17.9 to 22.3 years volunteered to participate in this study. The lean soft tissue (LST) and BF% in the total body and body segments were measured in each subject by the BIA8 and DXA. The correlation coefficients between total body, arm, leg segments impedance index (BI, ht2/Z) and lean soft tissue mass measured from DXA were r = 0.902, 0.453, 0.885, respectively (p < 0.01). In addition, the total body and segmental LST estimated by the BIA8 were highly correlated with the DXA data (r = 0.936, 0.466, 0.886, p < 0.01). The estimation of total body and segmental BF% measured by BIA8 and DXA also showed a significant correlation (r > 0.820, p < 0.01). The estimated LST and BF% from BIA8 in the total body and body segments were highly correlated with the DXA results, which indicated that the standing-posture 8-electrode bioelectrical impedance analysis may be used to derive reference measures of LST and BF% in Taiwanese male wrestlers.

Informed Consent: Does Anyone Really Understand What Is Contained In The Medical Record?

BACKGROUND: Despite efforts to provide standard definitions of terms such as "medical record", "computer-based patient record", "electronic medical record" and "electronic health record", the terms are still used interchangeably. Initiatives like data and information governance, research biorepositories, and learning health systems require availability and reuse of data, as well as common understandings of the scope for specific purposes. Lacking widely shared definitions, utilization of the afore-mentioned terms in research informed consent documents calls to question whether all participants in the research process - patients, information technology and regulatory staff, and the investigative team - fully understand what data and information they are asking to obtain and agreeing to share. OBJECTIVES: This descriptive study explored the terminology used in research informed consent documents when describing patient data and information, asking the question "Does the use of the term "medical record" in the context of a research informed consent document accurately represent the scope of the data involved?" METHODS: Informed consent document templates found on 17 Institutional Review Board (IRB) websites with Clinical and Translational Science Awards (CTSA) were searched for terms that appeared to be describing the data resources to be accessed. The National Library of Medicine's (NLM) Terminology Services was searched for definitions provided by key standards groups that deposit terminologies with the NLM. DISCUSSION: The results suggest research consent documents are using outdated terms to describe patient information, health care terminology systems need to consider the context of research for use cases, and that there is significant work to be done to assure the HIPAA Omnibus Rule is applied to contemporary activities such as biorepositories and learning health systems. CONCLUSIONS: "Medical record", a term used extensively in research informed consent documents, is ambiguous and does not serve us well in the context of contemporary information management and governance.

Whole-Brain Susceptibility-Weighted Thrombus Imaging in Stroke: Fragmented Thrombi Predict Worse Outcome.

BACKGROUND AND PURPOSE: The prevalence and clinical importance of primarily fragmented thrombi in patients with acute ischemic stroke remains elusive. Whole-brain SWI was used to detect multiple thrombus fragments, and their clinical significance was analyzed. MATERIALS AND METHODS: Pretreatment SWI was analyzed for the presence of a single intracranial thrombus or multiple intracranial thrombi. Associations with baseline clinical characteristics, complications, and clinical outcome were studied. RESULTS: Single intracranial thrombi were detected in 300 (92.6%), and multiple thrombi, in 24 of 324 patients (7.4%). In 23 patients with multiple thrombi, all thrombus fragments were located in the vascular territory distal to the primary occluding thrombus; in 1 patient, thrombi were found both in the anterior and posterior circulation. Only a minority of thrombus fragments were detected on TOF-MRA, first-pass gadolinium-enhanced MRA, or DSA. Patients with multiple intracranial thrombi presented with more severe symptoms (median NIHSS scores, 15 versus 11; P = .014) and larger ischemic areas (median DWI ASPECTS, 5 versus 7; P = .006); good collaterals, rated on DSA, were fewer than those in patients with a single thrombus (21.1% versus 44.2%, P = .051). The presence of multiple thrombi was a predictor of unfavorable outcome at 3 months (P = .040; OR, 0.251; 95% CI, 0.067-0.939). CONCLUSIONS: Patients with multiple intracranial thrombus fragments constitute a small subgroup of patients with stroke with a worse outcome than patients with single thrombi.

Th17- and Treg-related cytokine and mRNA expression are associated with acute and resolving Kawasaki disease.

BACKGROUND: Kawasaki disease is a vasculitis most commonly afflicting children <5 years of age. Many autoimmune diseases are associated with up-regulation of T helper (Th) 17 cells, and down-regulation Treg cells. Few studies have examined the Th17/Treg expression in Kawasaki disease. METHODS: Blood samples were obtained from 186 children with Kawasaki disease at 24 h before IVIG therapy, followed by 3 days and 21 days after IVIG therapy. Thirty children with an acute febrile infectious disease and 30 healthy children were obtained as control. Plasma levels of Th17- and Treg-related cytokines including IL-6, IL-17A, IL-10, TGF-ß, and mRNA expression levels of RORγt and Foxp3 were tested. RESULTS: Patients with Kawasaki disease had higher levels of plasma IL-17A (25.35 ± 3.21 vs 7.78 ± 1.78 pg/ml, P < 0.001) and IL-6 (152.29 ± 21.94 vs 38.63 ± 12.40 pg/ml, P < 0.001) when compared to the febrile control group. IVIG resulted in a reduction in IL-6 and IL-17A at both 3 and 21 days after IVIG therapy. FoxP3 levels increased significantly 3 days after IVIG therapy (2.28 ± 0.34 vs 0.88 ± 0.14, P < 0.001). IVIG resistance was associated with higher levels of IL-10 and IL-17A. CONCLUSION: Kawasaki disease was associated with higher IL-17A and IL-6, a cytokine profile similar to other autoimmune diseases. IVIG therapy resulted in increased expression of Treg-related FoxP3. IVIG resistance was associated with higher levels of IL-10 and IL-17A. Our findings provide further evidence that Kawasaki disease is an autoimmune-like disease.

Stent-retriever thrombectomy: impact on the future of interventional stroke treatment.

Endovascular treatment for acute ischemic stroke has evolved in the past years. The current development of stent-retriever thrombectomy is a landmark in the clinical treatment and study results of acute ischemic stroke. This review summarizes the recent study results, elucidates the shortcomings of endovascular stroke treatment, and takes the opportunity for an outlook on the role of stroke interventions in the future.

Obesity and associated factors in adults with intellectual disability.

BACKGROUND: We examined the prevalence of obesity in adults with intellectual disabilities (ID) compared with the general population, and the factors associated with obesity and weight management status, comparing individuals with ID who were overweight or obese to those who were not. METHODS: We analysed baseline data (n = 1450) from the ongoing 4-year Longitudinal Health and Intellectual Disabilities Study (LHIDS) using a multivariate approach. Measures included body mass index (BMI), demographics, level of ID, diagnoses related to ID, health behaviours (i.e. physical activity, dietary habits, smoking, and alcohol consumption), various health parameters (e.g. mobility limitation, medications), and residential type and location. RESULTS: Compared with the general population, adults (≥ 18 years) with ID had a higher prevalence of obesity (38.3% vs. 28%) and morbid obesity (7.4% vs. 4.2%). Being female (AOR = 1.40, 95% CI = 1.09-1.81), having Down syndrome (AOR = 2.53, 95% CI = 1.86-3.45), taking medications that cause weight gain (AOR = 1.80, 95% CI = 1.38-2.37), engaging in less moderate physical activity (AOR = 0.89, 95% CI = 0.79-0.99), and drinking greater amounts of soda (AOR = 1.20, 95% CI = 1.02-1.42) were associated with higher rates of obesity. CONCLUSION: Adults with ID, in general, have a high risk of developing obesity, and women with ID have a high risk of developing morbid obesity. Health promotion initiatives should target individuals with the greatest risk.

c-Fos expression in neurons projecting from the preoptic and lateral hypothalamic areas to the ventrolateral periaqueductal gray in relation to sleep states.

The ventrolateral division of the periaqueductal gray (vlPAG) and the adjacent deep mesencephalic reticular nucleus have been implicated in the control of sleep. The preoptic hypothalamus, which contains populations of sleep-active neurons, is an important source of afferents to the vlPAG. The perifornical lateral hypothalamus (LH) contains populations of wake-active neurons and also projects strongly to the vlPAG. We examined nonREM and REM sleep-dependent expression of c-Fos protein in preoptic-vlPAG and LH-vlPAG projection neurons identified by retrograde labeling with Fluorogold (FG). Separate groups of rats (n=5) were subjected to 3 h total sleep deprivation (TSD) followed by 1 h recovery sleep (RS), or to 3 h of selective REM sleep deprivation (RSD) followed by RS. A third group of rats (n=5) was subjected to TSD without opportunity for RS (awake group). In the median preoptic nucleus (MnPN), the percentage of FG+ neurons that were also Fos+ was higher in TSD-RS animals compared to both RSD-RS rats and awake rats. There were significant correlations between time spent in deep nonREM sleep during the 1 h prior to sacrifice across groups and the percentage of double-labeled cells in MnPN and ventrolateral preoptic area (VLPO). There were no significant correlations between percentage of double-labeled neurons and time spent in REM sleep for any of the preoptic nuclei examined. In the LH, percentage of double-labeled neurons was highest in awake rats, intermediate in TSD-RS rats and lowest in the RSD-RS group. These results suggest that neurons projecting from MnPN and VLPO to the vlPAG are activated during nonREM sleep and support the hypothesis that preoptic neurons provide inhibitory input to vlPAG during sleep. Suppression of excitatory input to the vlPAG from the LH during sleep may have a permissive effect on REM sleep generation.

Imaging the interaction of the heliosphere with the interstellar medium from Saturn with Cassini.

We report an all-sky image of energetic neutral atoms (ENAs) >6 kilo-electron volts produced by energetic protons occupying the region (heliosheath) between the boundary of the extended solar atmosphere and the local interstellar medium (LISM). The map obtained by the Ion and Neutral Camera (INCA) onboard Cassini reveals a broad belt of energetic protons whose nonthermal pressure is comparable to that of the local interstellar magnetic field. The belt, centered at approximately 260 degrees ecliptic longitude extending from north to south and looping back through approximately 80 degrees, appears to be ordered by the local interstellar magnetic field. The shape revealed by the ENA image does not conform to current models, wherein the heliosphere resembles a cometlike figure aligned in the direction of Sun's travel through the LISM.

Neurotoxic lesions at the ventral mesopontine junction change sleep time and muscle activity during sleep: an animal model of motor disorders in sleep.

There is no adequate animal model of restless legs syndrome (RLS) and periodic leg movements disorder (PLMD), disorders affecting 10% of the population. Similarly, there is no model of rapid eye movement (REM) sleep behavior disorder (RBD) that explains its symptoms and its link to Parkinsonism. We previously reported that the motor inhibitory system in the brainstem extends from the medulla to the ventral mesopontine junction (VMPJ). We now examine the effects of damage to the VMPJ in the cat. Based on the lesion sites and the changes in sleep pattern and behavior, we saw three distinct syndromes resulting from such lesions; the rostrolateral, rostromedial and caudal VMPJ syndromes. The change in sleep pattern was dependent on the lesion site, but was not significantly correlated with the number of dopaminergic neurons lost. An increase in wakefulness and a decrease in slow wave sleep (SWS) and REM sleep were seen in the rostrolateral VMPJ-lesioned animals. In contrast, the sleep pattern was not significantly changed in the rostromedial and caudal VMPJ-lesioned animals. All three groups of animals showed a significant increase in periodic and isolated leg movements in SWS and increased tonic muscle activity in REM sleep. Beyond these common symptoms, an increase in phasic motor activity in REM sleep, resembling that seen in human RBD, was found in the caudal VMPJ-lesioned animals. In contrast, the increase in motor activity in SWS in rostral VMPJ-lesioned animals is similar to that seen in human RLS/PLMD patients. The proximity of the VMPJ region to the substantia nigra suggests that the link between RLS/PLMD and Parkinsonism, as well as the progression from RBD to Parkinsonism may be mediated by the spread of damage from the regions identified here into the substantia nigra.