Impact of Physical Activity and Exercise on the Epigenome in Skeletal Muscle and Effects on Systemic Metabolism

Exercise and physical activity induces physiological responses in organisms, and adaptations in skeletal muscle, which is beneficial for maintaining health and preventing and/or treating most chronic diseases. These adaptations are mainly instigated by transcriptional responses that ensue in reaction to each individual exercise, either resistance or endurance. Consequently, changes in key metabolic, regulatory, and myogenic genes in skeletal muscle occur as both an early and late response to exercise, and these epigenetic modifications, which are influenced by environmental and genetic factors, trigger those alterations in the transcriptional responses. DNA methylation and histone modifications are the most significant epigenetic changes described in gene transcription, linked to the skeletal muscle transcriptional response to exercise, and mediating the exercise adaptations. Nevertheless, other alterations in the epigenetics markers, such as epitranscriptomics, modifications mediated by miRNAs, and lactylation as a novel epigenetic modification, are emerging as key events for gene transcription. Here, we provide an overview and update of the impact of exercise on epigenetic modifications, including the well-described DNA methylations and histone modifications, and the emerging modifications in the skeletal muscle. In addition, we describe the effects of exercise on epigenetic markers in other metabolic tissues; also, we provide information about how systemic metabolism or its metabolites influence epigenetic modifications in the skeletal muscle.

An Accident Detection and Classification System Using Internet of Things and Machine Learning towards Smart City

Daily traffic accidents increase annually, causing a significant number of death and disability cases. Most of fatalities occur because of the late response to these emergency cases. The time after the traumatic injury is called the golden hour, where providing essential medical and surgical aid at that time increases the probability of saving human lives by one-third an average. Thus, the focus of this paper was to develop a system based on IoT for accident detection and classification. The system detects and classifies vehicle accidents based on severity level and reports the essential information about the accident to emergency services providers. The system consists of a microcontroller, GPS, and a group of sensors to determine different physical parameters related to vehicle motion. In addition, different types of machine learning classifiers were examined with the developed system to determine the most accurate classifier for the system. The classifiers are the Gaussian Mixture Model (GMM), Naive-Bayes Tree (NB), Decision Tree (DT), and Classification and Regression Trees (CART). The implementation of the system showed that GMM and CART models were better in terms of precision and recall. It was also shown that the severity of accidents depends mainly on the g-force value and fire occurrence.

Network Analysis to Determine the Optimal Route for Firefighters in Makassar City

Makassar city experiences many residential fire disasters during the last years. One of the causes of fires is difficult to overcome due to the firefighters’ late response. The number of fires occurred due to the ineffectiveness of the fire fighting road, obstructed by traffic conditions, in its operation. Developing a geospatial route analysis can help firefighters quickly find the best route to a fire point to overcome this problem. Geospatial route analysis is currently a key role in emergency responses for urban fire disasters. A routing system can provide network analysis that allows users to navigate between source and destination points. In this case, the system can help firefighters to arrive as quickly as possible. On complicated road networks, some impedance factors would slow down drivers on a particular road. This study aims to provide firefighters from the base stations to residential fire disaster locations. The method used in the studies is Dijkstra’s algorithms to calculate weights of the impedance factors to optimal routing based on length of the road, speed drive, and traffic conditions. Implementation of routing analysis using open source geospatial software, PostgreSQL as database management system with PostGIS, and pgrouting as extensions. The modeling results show that the optimal route selection with speed parameters based on road classification has a low weight value. Therefore, it can be used as a reference for selecting a firefighter’s routing.

Predictive role of lymphoscintigraphy undergoing lymphovenous anastomosis in patients with lower extremity lymphedema: a preliminary study

Background We investigated whether preoperative lymphoscintigraphy could predict the treatment response of unilateral lymphovenous anastomosis (LVA) in patients with lower extremity lymphedema. Materials and methods A total of 17 patients undergoing lymphoscintigraphy subsequent to LVA was included. As qualitative lymphoscintigraphic indicators, ilioinguinal lymph node uptake, main lymphatic vessel, collateral vessel, and four types of dermal backflow patterns (absent; distal only; proximal only; whole lower limb) were evaluated. Lymph node uptake ratio, extremity uptake ratio, and injection site clearance ratio were obtained as quantitative lymphoscintigraphic indicators at 1 and 2-h after injection. To evaluate therapy response, the volume difference ratio of the whole lower limb at 3 months (early response) and 1 year (late response) was measured. Volume difference ratios (continuous variable and binary variable with a cut-off value of zero) were compared according to the lymphoscintigraphic variables. Results The group with whole lower limb dermal backflow had a greater volume change than the other groups (p = 0.047). The group with dermal backflow in the whole lower limb OR only in the distal part had a higher rate of volume reduction than the group with dermal backflow only in the proximal part OR absent (p = 0.050). The 2-h extremity uptake ratio was the only indicator that positively correlated with early and late volume difference ratio (p = 0.016, p = 0.001). The rate of volume decrease at 1 year was high in patients with high 2-h extremity uptake ratio (p = 0.027). As the amount of dermal backflow increases, the postoperative therapeutic effect increases (p = 0.040). Conclusions Preoperative lymphoscintigraphy is useful to predict both early and late therapy response in patients with lower extremity lymphedema undergoing LVA. Both dermal backflow pattern and extremity uptake ratio may be predictive lymphoscintigraphic indicators.

STUDENTS’ INVOLVEMENT IN EFL ONLINE CLASSROOM DURING THE COVID-19 PANDEMIC ERA

One of the government's policies to stop the spread of the covid-19 pandemic is to shift face-to-face learning at school to distance learning at home. Online learning is not easy to do, it is different from conventional learning. In online classes, students were reluctant to participate in the in-class activities. This kind of reluctance made students lose motivation to learn languages. This study aims to see how the online learning model is to find out the students’ involvement in EFL online classes during the Covid-19 Pandemic at Senior High School in Bengkalis. This present study employs a descriptive case study as the research design. To collect the data, researchers used observation, video documentation, and interviews. Meanwhile, the data analysis technique used in this study were used qualitative data analysis techniques which include three activities, namely: data reduction, data presentation, concluding. The results of this study revealed that. Students could not see the screen display, teacher and student communicating to solve problems, there is a network disruption, students late response to teacher, the class leader is the student who always actively responds to the teacher, students do not respond to teacher directions, students sign in and sign out the zoom meeting

A Label-Free Proteomic and Complementary Metabolomic Analysis of Leaves of the Resurrection Plant Xerophyta schlechteri during Dehydration

Vegetative desiccation tolerance, or the ability to survive the loss of ~95% relative water content (RWC), is rare in angiosperms, with these being commonly called resurrection plants. It is a complex multigenic and multi-factorial trait, with its understanding requiring a comprehensive systems biology approach. The aim of the current study was to conduct a label-free proteomic analysis of leaves of the resurrection plant Xerophyta schlechteri in response to desiccation. A targeted metabolomics approach was validated and correlated to the proteomics, contributing the missing link in studies on this species. Three physiological stages were identified: an early response to drying, during which the leaf tissues declined from full turgor to a RWC of ~70–80%, a mid-response in which the RWC declined to 40% and a late response where the tissues declined to 10% RWC. We identified 517 distinct proteins that were differentially expressed, of which 253 proteins were upregulated and 264 were downregulated in response to the three drying stages. Metabolomics analyses, which included monitoring the levels of a selection of phytohormones, amino acids, sugars, sugar alcohols, fatty acids and organic acids in response to dehydration, correlated with some of the proteomic differences, giving insight into the biological processes apparently involved in desiccation tolerance in this species.

Induction of remission in chronic urticaria by immunotherapy using immunoglobulin/histamine complex (Histobulin™): a case report

Background Symptom control is a major concern in chronic urticaria. Histobulin™ is a histamine/immunoglobulin complex that has been approved for allergic rhinitis, bronchial asthma and chronic urticaria in some countries. Not only has the immunoglobulin/histamine complex been reported to be effective in allergic diseases, including chronic urticaria, but recently, the possibility of remission induction in chronic urticaria by the immunoglobulin/histamine complex has been reported. Case presentation Histobulin™ was administered until remission was induced instead of fixing the number of administrations in four cases of chronic urticaria. Two patients showed an early response and finished treatment with 12 injections of Histobulin™, and the other two patients showed a late response and were injected 43 and 46 times. Remission was induced successfully in all four cases. Conclusions Histobulin™ is not only effective but also induces remission in CSU. The Histobulin™ therapy protocol in CSU may be better if the treatment is continued until remission is achieved. Based on the responses of the patients, early responders and late responders were present. The progression of the disease during treatment consisted of a slow improvement phase and a rapid improvement phase. Uniquely, the appropriate allergy laboratory results, including blood eosinophil fraction, total IgE and eosinophil cationic protein level, were normal in all 4 cases. Further studies concerning the mechanisms of Histobulin™ may be needed.

A sensory memory to preserve visual representations across eye movements

Saccadic eye movements (saccades) disrupt the continuous flow of visual information, yet our perception of the visual world remains uninterrupted. Here we assess the representation of the visual scene across saccades from single-trial spike trains of extrastriate visual areas, using a combined electrophysiology and statistical modeling approach. Using a model-based decoder we generate a high temporal resolution readout of visual information, and identify the specific changes in neurons’ spatiotemporal sensitivity that underly an integrated perisaccadic representation of visual space. Our results show that by maintaining a memory of the visual scene, extrastriate neurons produce an uninterrupted representation of the visual world. Extrastriate neurons exhibit a late response enhancement close to the time of saccade onset, which preserves the latest pre-saccadic information until the post-saccadic flow of retinal information resumes. These results show how our brain exploits available information to maintain a representation of the scene while visual inputs are disrupted.

Response Kinetics of Daratumumab-Based Regimens in Patients with Newly Diagnosed or Refractory/Relapsed Multiple Myeloma

Background: It is controversial in multiple myeloma (MM) whether early and late responders to therapies have similar clinical outcomes. Daratumumab (DARA) is a human anti-CD38 antibody that has been increasingly used in newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM). The association between response kinetics to DARA and clinical outcomes remains unexplored. Methods: Individual-participant data were obtained from phase 3 trials: POLLUX (Dimopoulos, NEJM, 2016), CASTOR (Palumbo, NEJM, 2016), and MAIA (Facon, NEJM, 2019). Patients were divided into early and late response groups based on the median time to the response of interest. Modified PFS (mPFS) and OS (mOS) were calculated from the time of first response of interest. Minimal residual disease (MRD) negativity was defined as less than 10 5 tumor cells by NGS assays. Results: After a median follow up of 16.1 months, 670 patients achieved a response of very good partial response (VGPR) or better, and 213 achieved MRD negativity. The median time to achieving VGPR or better was similar between NDMM and RRMM (86 vs. 84 days, respectively), while the median time to MRD negativity was longer among NDMM than RRMM (407 vs. 197 days, respectively). Among patients achieving VGPR or better, there was no significant difference of mPFS (HR 1.00, 95%CI 0.69 to 1.44) (fig. a), duration of response (DOR) (HR 1.02, 95%CI 0.68 to 1.53) (fig. b), or mOS (HR 0.98, 95%CI 0.54 to 1.75) (fig. c) between early and late responders. In the subgroup analysis, no significant difference of DOR was observed across all prespecified groups, including sex, age, cytogenetic risk groups, lines of previous therapy, types of measurable disease, NDMM vs. RRMM, prior treatment with autologous hematopoietic cell transplant, immunomodulatory drugs, or proteasome inhibitors. Among patients with NDMM achieving MRD negativity, there was no significant difference of mPFS (p=0.66) (fig. d), DOR (p=0.21) (fig. e) or mOS (p=0.87) (fig. f) between early and late responders. However, among patients with RRMM achieving MRD negativity, late responders had significantly longer mPFS (p=0.038) (fig. g) and DOR (p=0.043) (fig. h) than early responders; mOS was not significantly different (fig. i). In the multivariable Cox analysis among patients achieving MRD negativity, only lower baseline LDH level, NDMM, and IgG type MM were independently associated with later response. Conclusions: For patients with NDMM or RRMM achieving VGPR or better, early and late responders had similar survival; for patients with RRMM achieving MRD negativity, late responders had significantly longer mPFS and DOR. Our data support that in patients who failed to achieve an early or deep response to daratumumab based regimens, therapies should be continued with the goal of achieving ongoing and stepwise improvement of response. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Predictive role of lymphoscintigraphy undergoing lymphovenous anastomosis in patients with lower extremity lymphedema

Background We investigated whether preoperative lymphoscintigraphy could predict the treatment response of unilateral lymphovenous anastomosis (LVA) in patients with lower extremity lymphedema. Materials and methods A total of 17 patients undergoing lymphoscintigraphy subsequent to LVA was included. As qualitative lymphoscintigraphic indicators, ilioinguinal lymph node uptake, main lymphatic vessel, collateral vessel, and dermal backflow pattern were evaluated. Lymph node uptake ratio, extremity uptake ratio, and injection site clearance ratio were obtained as quantitative lymphoscintigraphic indicators at 1 and 2-h after injection. To evaluate therapy response, the volume difference ratio of the whole leg at 3 months (early response) and 1 year (late response) was measured. Results The group with whole leg dermal backflow had a greater volume change than the other groups (p=0.047). The group with dermal backflow in the whole leg OR only in the distal part had a higher rate of volume reduction than the group with dermal backflow only in the proximal part OR absent (p=0.050). The 2-h extremity uptake ratio was the only indicator that positively correlated with early and late volume difference ratio (p=0.016, p=0.001). The rate of volume decrease at 1 year was high in patients with high 2-h extremity uptake ratio (p=0.027). As the amount of dermal backflow increases, the postoperative therapeutic effect increases (p=0.040). Conclusions Preoperative lymphoscintigraphy is useful to predict both early and late therapy response in patients with lower extremity lymphedema undergoing LVA. Both dermal backflow pattern and extremity uptake ratio may be predictive lymphoscintigraphic indicators.