Immune Function and Muscle Adaptations to Resistance exercise in Older Adults: Study Protocol for a Randomized Controlled Trial of a Nutritional Supplement

BACKGROUND: Immune function may influence the ability of older adults to maintain or improve muscle mass, strength, and function during aging. Thus, nutritional supplementation that supports the immune system could complement resistance exercise as an intervention for age-associated muscle loss. The current study will determine the relationship between immune function and exercise training outcomes for older adults who consume a nutritional supplement or placebo during resistance training and post-training follow-up. The supplement was chosen due to evidence suggesting its ingredients [arginine (Arg), glutamine (Gln), and β-hydroxy β-methylbutyrate (HMB)] can improve immune function, promote muscle growth, and counteract muscle loss. METHODS/DESIGN: Veterans (age 60 to 80 yrs, N = 50) of the United States military will participate in a randomized double-blind placebo-controlled trial of consumption of a nutritional supplement or placebo during completion of three study objectives: 1) determine if 2 weeks of supplementation improve immune function measured as the response to vaccination and systemic and cellular responses to acute resistance exercise; 2) determine if supplementation during 36 sessions of resistance training boosts gains in muscle size, strength, and function; and 3) determine if continued supplementation for 26 weeks post-training promotes retention of training-induced gains in muscle size, strength, and function. Analyses of the results for these objectives will determine the relationship between immune function and the training outcomes. Participants will undergo nine blood draws and five muscle (vastus lateralis) biopsies so that the effects of the supplement on immune function and the systemic and cellular responses to exercise can be measured. DISCUSSION: Exercise has known effects on immune function. However, the study will attempt to modulate immune function using a nutritional supplement and determine the effects on training outcomes. The study will also examine post-training benefit retention, an important issue for older adults, usually omitted from exercise studies. The study will potentially advance our understanding of the mechanisms of muscle gain and loss in older adults, but more importantly, a nutritional intervention will be evaluated as a complement to exercise for supporting muscle health during aging. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02261961, registration date 10 June 2014, recruitment active

Wii-Fit for Improving Gait and Balance in an Assisted Living Facility: A Pilot Study

Objectives. To determine the effects on balance and gait of a Wii-Fit program compared to a walking program in subjects with mild Alzheimer's dementia (AD). Methods. A prospective randomized (1 : 1) pilot study with two intervention arms was conducted in an assisted living facility with twenty-two mild AD subjects. In both groups the intervention occurred under supervision for 30 minutes daily, five times a week for eight weeks. Repeated measures ANOVA and paired t-tests were used to analyze changes. Results. Both groups showed improvement in Berg Balance Scale (BBS), Tinetti Test (TT) and Timed Up and Go (TUG) over 8 weeks. However, there was no statistically significant difference between the groups over time. Intragroup analysis in the Wii-Fit group showed significant improvement on BBS (P = 0.003), and TT (P = 0.013). The walking group showed a trend towards improvement on BBS (P = 0.06) and TUG (P = 0.07) and significant improvement in TT (P = 0.06). Conclusion. This pilot study demonstrates the safety and efficacy of Wii-Fit in an assisted living facility in subjects with mild AD. Use of Wii-Fit resulted in significant improvements in balance and gait comparable to those in the robust monitored walking program. These results need to be confirmed in a larger, methodologically sound study

Deep Learning Frameworks for Cardiovascular Arrhythmia Classification

Arrhythmia classification is a prominent research problem due to the computational complexities of learning the morphology of various ECG patterns and its wide prevalence in the medical field, particularly during the COVID-19 pandemic. In this article, we used Empirical Mode Decomposition and Discrete Wavelet Transform for preprocessing and then the modified signal is classified using various classifiers such as Decision Tree, Logistic Regression, Gaussian Naïve Bayes, Random Forest, Linear  SVM, Polynomial SVM, RBF SVM, Sigmoid SVM and Convolutional Neural Networks. The proposed method classify the data into five classes N (Normal), S (Supraventricular premature) beat, (V) Premature ventricular contraction, F (Fusion of ventricular and normal), and Q, (Unclassifiable Beat) using softmax regressor at the end of the network. The proposed approach performs well in terms of classification accuracy when tested using ECG signals acquired from the MIT-BIH database. In comparison to existing classifiers, the Accuracy, Precision, Recall, and F1 score values of the proposed technique are 98.5%, 96.9%, 94.3%, and 91.32%, respectively.  &nbsp

WII-FIT FOR BALANCE AND GAIT IN SKILLED NURSING FACILITY: A RETROSPECTIVE STUDY

Background: Falls in elderly are a major public health problem. Poor balance and gait abnormalities are risk factors for falls. Exercise improves gait and balance in elderly. However, it is difficult to engage patients in exercise programs. Wii-Fit might bridge this gap by providing high level of engagement at an affordable price. Wii-Fit is a Nintendo game used for balance, yoga, aerobics, and strength training. It is a TV based self-directed activity. Virtual trainers talk the user through the activity and track progress while visual and auditory feedback improve engagement. Anecdotal reports suggest improvement in balance and social benefits with Wii-Fit, but no systematic studies are available. Objective: To compare the effect of Wii-Fit augmentation to physical therapy alone in subjects undergoing rehabilitation in skilled nursing facility (SNF) using a retrospective chart review. Methods: 100 charts were reviewed of which seventeen patients were noted to have used Wii-Fit during their rehabilitation. These subjects were matched with seventeen controls who did physical therapy alone. Results: There were no baseline differences between the groups. The mean age was 77.7 years, with 11 females in each group. All the subjects were Caucasians. The average length of stay was 30 days in each group. Mean duration of the Wii-Fit use was 4-weeks. Wii-Fit augmentation group improved significantly in Activities of Daily Living (p=0.008), balance (p=0.0001), and assistance with gait (p=0.05) when compared to the control group. Conclusion: Wii-Fit can be used safely in a SNF, and it may improve balance, gait, and functional status

An N-Terminal Extension to UBA5 Adenylation Domain Boosts UFM1 Activation: Isoform-Specific Differences in Ubiquitin-like Protein Activation

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Modification of proteins by the ubiquitin-like protein, UFM1, requires activation of UFM1 by the E1-activating enzyme, UBA5. In humans, UBA5 possesses two isoforms, each comprising an adenylation domain, but only one containing an N-terminal extension. Currently, the role of the N-terminal extension in UFM1 activation is not clear. Here we provide structural and biochemical data on UBA5 N-terminal extension to understand its contribution to UFM1 activation. The crystal structures of the UBA5 long isoform bound to ATP with and without UFM1 show that the N-terminus not only is directly involved in ATP binding but also affects how the adenylation domain interacts with ATP. Surprisingly, in the presence of the N-terminus, UBA5 no longer retains the 1:2 ratio of ATP to UBA5, but rather this becomes a 1:1 ratio. Accordingly, the N-terminus significantly increases the affinity of ATP to UBA5. Finally, the N-terminus, although not directly involved in the E2 binding, stimulates transfer of UFM1 from UBA5 to the E2, UFC1.Marie Curie Career Integration GrantIsrael Science FoundationIsraeli Cancer Associatio

Neural Adaptive Admission Control Framework: SLA-driven action termination for real-time application service management

Although most modern cloud-based enterprise systems, or operating systems, do not commonly allow configurable/automatic termination of processes, tasks or actions, it is common practice for systems administrators to manually terminate, or stop, tasks or actions at any level of the system. The paper investigates the potential of automatic adaptive control with action termination as a method for adapting the system to more appropriate conditions in environments with established goals for both system’s performance and economics. A machine-learning driven control mechanism, employing neural networks, is derived and applied within data-intensive systems. Control policies that have been designed following this approach are evaluated under different load patterns and service level requirements. The experimental results demonstrate performance characteristics and benefits as well as implications of termination control when applied to different action types with distinct run-time characteristics. An automatic termination approach may be eminently suitable for systems with harsh execution time Service Level Agreements, or systems running under conditions of hard pressure on power supply or other constraints. The proposed control mechanisms can be combined with other available toolkits to support deployment of autonomous controllers in high-dimensional enterprise information systems

Structural basis for UFM1 transfer from UBA5 to UFC1

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: Atomic coordinates and structure factors were deposited in the RCSB PDB (https://www.rcsb.org/) with the accession codes 7NW1, 7NVK, and 7NVJ for UFC1-UBA5 (389–404), UBA5(347-404)-UFC1, and UFC1(Y110A and F121A), respectively. NMR assignments for UFC1 were taken from the BMRB entry 6546. Previously published crystal structures used in this study are available from the RCSB PDB under the accession codes: 3TGD; 1J7D; 1U9A; 1×23; 1Y6L; 4Q5E; 4YII; 1Y8X; 1WZW; 6CYO; 1FZY; 1YLA; 2YBF; 2C4P; 5LBN; 3FN1; 2CYX; 2Z5D; 2F4W; 5BNB; 1YH2; 1YRV; 2Z6P; 2Z6O; 1JBB; 4Q5H; 1WZV; 3RZ3; 2DYT; 6H77. The coordinates of the structural models generated by in silico docking are provided as Supplementary Data 1–3. Source data are provided with this paper.Ufmylation is a post-translational modification essential for regulating key cellular processes. A three-enzyme cascade involving E1, E2 and E3 is required for UFM1 attachment to target proteins. How UBA5 (E1) and UFC1 (E2) cooperatively activate and transfer UFM1 is still unclear. Here, we present the crystal structure of UFC1 bound to the C-terminus of UBA5, revealing how UBA5 interacts with UFC1 via a short linear sequence, not observed in other E1-E2 complexes. We find that UBA5 has a region outside the adenylation domain that is dispensable for UFC1 binding but critical for UFM1 transfer. This region moves next to UFC1’s active site Cys and compensates for a missing loop in UFC1, which exists in other E2s and is needed for the transfer. Overall, our findings advance the understanding of UFM1’s conjugation machinery and may serve as a basis for the development of ufmylation inhibitors.Israel Science FoundationIsrael Cancer Research FundUS-Israel Binational Science Foundatio

Cloud-scale VM Deflation for Running Interactive Applications On Transient Servers

Transient computing has become popular in public cloud environments for running delay-insensitive batch and data processing applications at low cost. Since transient cloud servers can be revoked at any time by the cloud provider, they are considered unsuitable for running interactive application such as web services. In this paper, we present VM deflation as an alternative mechanism to server preemption for reclaiming resources from transient cloud servers under resource pressure. Using real traces from top-tier cloud providers, we show the feasibility of using VM deflation as a resource reclamation mechanism for interactive applications in public clouds. We show how current hypervisor mechanisms can be used to implement VM deflation and present cluster deflation policies for resource management of transient and on-demand cloud VMs. Experimental evaluation of our deflation system on a Linux cluster shows that microservice-based applications can be deflated by up to 50\% with negligible performance overhead. Our cluster-level deflation policies allow overcommitment levels as high as 50\%, with less than a 1\% decrease in application throughput, and can enable cloud platforms to increase revenue by 30\%.Comment: To appear at ACM HPDC 202

A comparison of low-dose risperidone to paroxetine in the treatment of panic attacks: a randomized, single-blind study

<p>Abstract</p> <p>Background</p> <p>Because a large proportion of patients with panic attacks receiving approved pharmacotherapy do not respond or respond poorly to medication, it is important to identify additional therapeutic strategies for the management of panic symptoms. This article describes a randomized, rater-blind study comparing low-dose risperidone to standard-of-care paroxetine for the treatment of panic attacks.</p> <p>Methods</p> <p>Fifty six subjects with a history of panic attacks were randomized to receive either risperidone or paroxetine. The subjects were then followed for eight weeks. Outcome measures included the Panic Disorder Severity Scale (PDSS), the Hamilton Anxiety Scale (Ham-A), the Hamilton Depression Rating Scale (Ham-D), the Sheehan Panic Anxiety Scale-Patient (SPAS-P), and the Clinical Global Impression scale (CGI).</p> <p>Results</p> <p>All subjects demonstrated a reduction in both the frequency and severity of panic attacks regardless of treatment received. Statistically significant improvements in rating scale scores for both groups were identified for the PDSS, the Ham-A, the Ham-D, and the CGI. There was no difference between treatment groups in the improvement in scores on the measures PDSS, Ham-A, Ham-D, and CGI. Post hoc tests suggest that subjects receiving risperidone may have a quicker clinical response than subjects receiving paroxetine.</p> <p>Conclusion</p> <p>We can identify no difference in the efficacy of paroxetine and low-dose risperidone in the treatment of panic attacks. Low-dose risperidone appears to be tolerated equally well as paroxetine. Low-dose risperidone may be an effective treatment for anxiety disorders in which panic attacks are a significant component.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: NCT100457106</p