Peripheral Heating with Negative Pressure Increases Arterial Blood Flow

Over half (53%) of adults in the United States have some form of diabetes. Traditional treatments have been inadequate in stopping this epidemic suggesting the need for novel therapies. Peripheral heating with negative pressure has previously been shown to reduce blood glucose. The mechanisms behind this effect are unknown but may be related to changes in blood flow to the treated extremity. PURPOSE: To examine changes in flow rate (time averaged mean velocity (TAMV)), vessel cross-sectional area (CSA), and blood flow in the popliteal artery before and during peripheral heating with negative pressure applied to the feet. METHODS: Measures of TAMV, CSA, and blood flow were obtained from the left and right popliteal artery of participants using an ultrasound doppler (Philips CX50, General Electric, USA) before and during peripheral heating with negative pressure. Heat (42°C) was applied to the sole of the feet and negative pressure (-75 mmHg) applied from the feet to the top of the calves while participants remained seated. Vessels were matched for pre and post measures using anatomical landmarks and vessel diameter. Blood flow was calculated as TAMV * CSA. Data are presented as mean (SD) and were analyzed with paired two-sided t-tests. RESULTS: Participants’ (N=8, 4 men and 4 women) demographics are as follows: age: 26.5 (6.1) years; height: 177.7 (9.0) cm; BMI: 25.5 (3.9) kg/m2; body fat: 18.9 (5.7) %. From baseline to during the intervention, TAMV increased 22.3% from 13.0 (13.4) to 16.0 (16.5) cm/sec, p=.059 and 24.7% from 10.5 (10.7) to 13.0 (13.3) cm/sec, p=.067; CSA increased 9.7% from 0.42 (0.34) to 0.46 (0.39) cm2, p=.247, and 10.4% from 0.65 (0.62) to 0.72 (0.70) cm2, p=.122; and blood flow increased 32.3% from 5.2 (3.1) to 7.0 (4.0) mL/sec, p=.115 and 29.5% from 7.2 (7.3) to 9.3 (7.4) mL/sec, p=.032, in the left and right popliteal arteries respectively. CONCLUSION: In this pilot study, applying heat and negative pressure to the feet increased arterial blood flow largely by increasing flow rate with lesser changes to vessel CSA. Without reader blinding and assurance that the same vessel and portion of said vessel were used for pre and post measures, these results should be considered exploratory and interpreted with caution

The East Midlands Knee Pain Multiple Randomised Controlled Trial Cohort Study: Cohort Establishment and Feasibility study protocol

Introduction: Knee pain and osteoarthritis (OA) are a common cause of disability. The UK National Institute of Health and Care Excellence (NICE) OA guidelines recommend education, exercise and weight-loss advice (if overweight) as core interventions before pharmacological adjuncts. However, implementation of these in primary care is often suboptimal. This study aims to develop a complex intervention with non-pharmacological and pharmacological components that can be delivered by nurses. The feasibility and acceptability of the intervention, and feasibility of undertaking a future cohort-randomised controlled trial (RCT) will be explored. Methods and analysis: In phase 1, we will develop a training programme for nurses and evaluate the fidelity and acceptability of the non-pharmacological element of the intervention. Fidelity checklists completed by the nurse will be compared to video-analysis of the treatment sessions. Patients and nurses will be interviewed to determine the acceptability of the intervention and explore challenges to intervention delivery. The non-pharmacological component will be modified based upon the findings. In phase 2, we will assess the feasibility of conducting a cohort RCT comprising of both the pharmacological and modified non-pharmacological components. We will compare three groups: group A will receive the non-pharmacological components delivered before pharmacological components; group B will receive pharmacological components followed by the non-pharmacological components; and group C (control arm) will continue to receive usual care. Study outcomes will be collected at 3 time points: baseline and weeks 13 and 26 after randomisation. Qualitative interviews will be conducted with a sample of participants from each of the two active intervention arms. Ethics and dissemination: This protocol was approved by the East Midlands-Derby Research Ethics Committee (18/EM/0288) and registered at clinicaltrials.gov (NCT03670706). The study will be reported in accordance with the CONSORT guidance and standards. The results will be submitted for publication in peer-reviewed academic journals

Hypoglossal Neuropathology and Respiratory Activity in Pompe Mice

Pompe disease is a lysosomal storage disorder associated with systemic deficiency of acid α-glucosidase (GAA). Respiratory-related problems in Pompe disease include hypoventilation and upper airway dysfunction. Although these problems have generally been attributed to muscular pathology, recent work has highlighted the potential role of central nervous system (CNS) neuropathology in Pompe motor deficiencies. We used a murine model of Pompe disease to test the hypothesis that systemic GAA deficiency is associated with hypoglossal (XII) motoneuron pathology and altered XII motor output during breathing. Brainstem tissue was harvested from adult Gaa−/− mice and the periodic acid Schiff method was used to examine neuronal glycogen accumulation. Semi-thin (2 μm) plastic sections showed widespread medullary neuropathology with extensive cytoplasmic glycogen accumulation in XII motoneuron soma. We next recorded efferent XII bursting in anesthetized and ventilated Gaa−/− and B6/129 mice both before and after bilateral vagotomy. The coefficient of variation of respiratory cycle duration was greater in Gaa−/− compared to B6/129 mice (p < 0.01). Vagotomy caused a robust increase in XII inspiratory burst amplitude in B6/129 mice (239 ± 44% baseline; p < 0.01) but had little impact on burst amplitude in Gaa−/− mice (130 ± 23% baseline; p > 0.05). We conclude that CNS GAA deficiency results in substantial glycogen accumulation in XII motoneuron cell bodies and altered XII motor output. Therapeutic strategies targeting the CNS may be required to fully correct respiratory-related deficits in Pompe disease

Multicenter Evaluation of Candida QuickFISH BC for Identification of Candida Species Directly from Blood Culture Bottles

Candida species are common causes of bloodstream infections (BSI), with high mortality. Four species cause >90% of Candida BSI: C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis. Differentiation of Candida spp. is important because of differences in virulence and antimicrobial susceptibility. Candida QuickFISH BC, a multicolor, qualitative nucleic acid hybridization assay for the identification of C. albicans (green fluorescence), C. glabrata (red fluorescence), and C. parapsilosis (yellow fluorescence), was tested on Bactec and BacT/Alert blood culture bottles which signaled positive on automated blood culture devices and were positive for yeast by Gram stain at seven study sites. The results were compared to conventional identification. A total of 419 yeast-positive blood culture bottles were studied, consisting of 258 clinical samples (89 C. glabrata, 79 C. albicans, 23 C. parapsilosis, 18 C. tropicalis, and 49 other species) and 161 contrived samples inoculated with clinical isolates (40 C. glabrata, 46 C. albicans, 36 C. parapsilosis, 19 C. tropicalis, and 20 other species). A total of 415 samples contained a single fungal species, with C. glabrata (n = 129; 30.8%) being the most common isolate, followed by C. albicans (n = 125; 29.8%), C. parapsilosis (n = 59; 14.1%), C. tropicalis (n = 37; 8.8%), and C. krusei (n = 17; 4.1%). The overall agreement (with range for the three major Candida species) between the two methods was 99.3% (98.3 to 100%), with a sensitivity of 99.7% (98.3 to 100%) and a specificity of 98.0% (99.4 to 100%). This study showed that Candida QuickFISH BC is a rapid and accurate method for identifying C. albicans, C. glabrata, and C. parapsilosis, the three most common Candida species causing BSI, directly from blood culture bottles

Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients

<p>Abstract</p> <p>Background</p> <p>Amyotrophic Lateral Sclerosis (ALS) is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis is mainly based on clinical symptoms, and there is currently no therapy to stop the disease or slow its progression. Since access to spinal cord tissue is not possible at disease onset, we investigated changes in gene expression profiles in whole blood of ALS patients.</p> <p>Results</p> <p>Our transcriptional study showed dramatic changes in blood of ALS patients; 2,300 probes (9.4%) showed significant differential expression in a discovery dataset consisting of 30 ALS patients and 30 healthy controls. Weighted gene co-expression network analysis (WGCNA) was used to find disease-related networks (modules) and disease related hub genes. Two large co-expression modules were found to be associated with ALS. Our findings were replicated in a second (30 patients and 30 controls) and third dataset (63 patients and 63 controls), thereby demonstrating a highly significant and consistent association of two large co-expression modules with ALS disease status. Ingenuity Pathway Analysis of the ALS related module genes implicates enrichment of functional categories related to genetic disorders, neurodegeneration of the nervous system and inflammatory disease. The ALS related modules contain a number of candidate genes possibly involved in pathogenesis of ALS.</p> <p>Conclusion</p> <p>This first large-scale blood gene expression study in ALS observed distinct patterns between cases and controls which may provide opportunities for biomarker development as well as new insights into the molecular mechanisms of the disease.</p

The Concussion Recognition Tool 5th Edition (CRT5): Background and rationale

The Concussion Recognition Tool 5 (CRT5) is the most recent revision of the Pocket Sport Concussion Assessment Tool 2 that was initially introduced by the Concussion in Sport Group in 2005. The CRT5 is designed to assist non-medically trained individuals to recognise the signs and symptoms of possible sport-related concussion and provides guidance for removing an athlete from play/sport and to seek medical attention. This paper presents the development of the CRT5 and highlights the differences between the CRT5 and prior versions of the instrument

AMI-LA radio continuum observations of Spitzer c2d small clouds and cores: Perseus region

We present deep radio continuum observations of the cores identified as deeply embedded young stellar objects in the Perseus molecular cloud by the Spitzer c2d programme at a wavelength of 1.8 cm with the Arcminute Microkelvin Imager Large Array (AMI-LA). We detect 72% of Class 0 objects from this sample and 31% of Class I objects. No starless cores are detected. We use the flux densities measured from these data to improve constraints on the correlations between radio luminosity and bolometric luminosity, infrared luminosity and, where measured, outflow force. We discuss the differing behaviour of these objects as a function of protostellar class and investigate the differences in radio emission as a function of core mass. Two of four possible very low luminosity objects (VeLLOs) are detected at 1.8 cm.Comment: 18 pages, 9 figures, accepted MNRA

East Midlands knee pain multiple randomised controlled trial cohort study: cohort establishment and feasibility study protocol

© 2020 BMJ Open Introduction Knee pain due to osteoarthritis (OA) is a common cause of disability. The UK National Institute for Health and Care Excellence OA guidelines recommend education, exercise and weight loss advice (if overweight) as core interventions before pharmacological adjuncts. However, implementation of these in primary care is often suboptimal. This study aims to develop a complex intervention with non-pharmacological and pharmacological components that can be delivered by nurses. The feasibility and acceptability of the intervention, and feasibility of undertaking a future cohort randomised controlled trial (RCT) will be explored. Methods and analysis In phase 1, we will develop a training programme for nurses and evaluate the fidelity and acceptability of the non-pharmacological element of the intervention. Fidelity checklists completed by the nurse will be compared with video analysis of the treatment sessions. Patients and nurses will be interviewed to determine the acceptability of the intervention and explore challenges to intervention delivery. The non-pharmacological component will be modified based on the findings. In phase 2, we will assess the feasibility of conducting a cohort RCT comprising both the pharmacological and modified non-pharmacological components. We will compare three groups: group A will receive the non-pharmacological components delivered before pharmacological components; group B will receive pharmacological components followed by the non-pharmacological components; and group C (control arm) will continue to receive usual care. Study outcomes will be collected at three time points: baseline, 13 and 26 weeks after randomisation. Qualitative interviews will be conducted with a sample of participants from each of the two active intervention arms. Ethics and dissemination This protocol was approved by the East Midlands-Derby Research Ethics Committee (18/EM/0288) and registered at ClinicalTrials.gov (protocol v4.0, 10/02/2020). The study will be reported in accordance with the Consolidated Standards of Reporting Trials guidance and standards. The results will be submitted for publication in peer-reviewed academic journals. Trial registration number NCT0367070

AMI Large Array radio continuum observations of Spitzer c2d small clouds and cores

We perform deep 1.8 cm radio continuum imaging towards thirteen protostellar regions selected from the Spitzer c2d small clouds and cores programme at high resolution (25") in order to detect and quantify the cm-wave emission from deeply embedded young protostars. Within these regions we detect fifteen compact radio sources which we identify as radio protostars including two probable new detections. The sample is in general of low bolometric luminosity and contains several of the newly detected VeLLO sources. We determine the 1.8 cm radio luminosity to bolometric luminosity correlation, L_rad -L_bol, for the sample and discuss the nature of the radio emission in terms of the available sources of ionized gas. We also investigate the L_rad-L_IR correlation and suggest that radio flux density may be used as a proxy for the internal luminosity of low luminosity protostars.Comment: submitted MNRA