Mechanism of interferon induction by cannabidiol (CBD) and analogues in lung cancer cells

CBD, an FDA approved drug for epilepsy, may have therapeutic potential for other diseases and is currently being tested for efficacy in cancer-related clinical trials. As the literature about CBD, especially in vitro reports, is often contradictory, increasing our understanding of its specific action on a molecular level will allow to determine whether CBD can become a useful therapy or exacerbates specific cancers in a context-dependent manner. Due to its relative lipophilicity, CBD is challenging to dispense at therapeutic concentrations;therefore, one goal is to identify cannabinoid congeners with greater efficacy and reduced drug delivery challenges. We recently showed that CBD activates interferons as a mechanism of inhibiting SARS-CoV-2 replication in lung carcinoma cells. As factors produced by the innate immune system, interferons have been implicated in both pro-survival and growth arrest and apoptosis signaling in cancer. Here we show that CBD induces interferon production and interferon stimulated genes (ISGs) through a mechanism involving NRF2 and MAVS in lung carcinoma cells. We also show that CBDV, which differs from CBD by 2 fewer aliphatic tail carbons, has limited potency, suggesting that CBD specifically interacts with one or more cellular proteins rather than having a non-specific effect. We also identified other CBD-related cannabinoids that are more effective at inducing ISGs. Taken together, these results characterize a novel mechanism by which CBD activates the innate immune system in lung cancer cells and identify related cannabinoids that have possible therapeutic potential in cancer treatment.

Harvesting Renewable Energy from Foot Pedal Using Rotational Electromagnetic Induction Flywheel

Philippines is one of the highest electricity prices in the ASEAN where harnessing renewable energy using wasted human effort is necessary. The global pandemic COVID-19 is spreading and because of this, establishments have required sanitation. The study's main objective is to Develop a Rotational Electromagnetic Induction Flywheel using Foot Pedal as Actuation to Harvest Renewable Energy. T-test was used to validate the results using the battery percentage of a power bank as the parameter, where there is a significant difference between single and multiple actuations with an attached mechanical dispenser and without. The system was able to harness an average of 0.30992 Watt-hour and 6.11476 Watt-hour in 5 daily trials for single and multiple controlled set-ups without mechanical dispenser respectively. An average of 0.2441 Watt-hour and 5.0027 Watt-hour for single and multiple controlled set-ups with mechanical dispenser correspondingly. Lastly, an average of 3.2924 Watt-hour in 5 daily trials for uncontrolled set-up. © 2023 IEEE.

SARS-CoV-2 NSP13 interacts with host IRF3, blocking antiviral immune responses.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an unprecedented threat to human health since late 2019. Notably, the progression of the disease is associated with impaired antiviral interferon (IFN) responses. Although multiple viral proteins were identified as potential IFN antagonists, the underlying molecular mechanisms remain to be fully elucidated. In this study, we firstly demonstrate that SARS-CoV-2 NSP13 protein robustly antagonizes IFN response induced by the constitutively active form of transcription factor IRF3 (IRF3/5D). This induction of IFN response by IRF3/5D is independent of the upstream kinase, TBK1, a previously reported NSP13 target, thus indicating that NSP13 can act at the level of IRF3 to antagonize IFN production. Consistently, NSP13 exhibits a specific, TBK1-independent interaction with IRF3, which, moreover, is much stronger than that of NSP13 with TBK1. Furthermore, the NSP13-IRF3 interaction was shown to occur between the NSP13 1B domain and IRF3 IRF association domain (IAD). In agreement with the strong targeting of IRF3 by NSP13, we then found that NSP13 blocks IRF3-directed signal transduction and antiviral gene expression, counteracting IRF3-driven anti-SARS-CoV-2 activity. These data suggest that IRF3 is likely to be a major target of NSP13 in antagonizing antiviral IFN responses and provide new insights into the SARS-CoV-2-host interactions that lead to viral immune evasion.

The multifactorial complexities of autoimmune development in Pemphigus vulgaris: Critical evaluation of the role of environmental and lifestyle "exposome" factors.

Pemphigus vulgaris (PV) is a potentially life-threatening blistering disorder characterized by autoantibodies directed against cell-cell adhesion molecules that serves as an excellent model to study human autoimmune development. Numerous studies have identified specific Human Leukocyte Antigen (HLA) genes, in particular DRB1*0402 and DQB1*0503, that confer disease risk. Although HLA is required, it is not sufficient for the initiation of disease. As with all autoimmune diseases, the etio-pathogenesis of PV is complex, meaning it is multifactorial. Susceptibility is polygenic, and the search for non-HLA disease-linked genes continues. Moreover, twin studies across autoimmune conditions indicate that non-genetic environmental and lifestyle factors, which can be collectively grouped under the term "exposome", are also major contributors to disease development. The literature presents evidence for the potential role of multiple triggers such as medications, infections, stress, diet, immunizations, and sleep to influence the etiology, pathophysiology, and prognosis of PV. However, a clear understanding of the degree to which specific factors impact PV is lacking. In this investigation, we comprehensively review the environmental elements listed above and consider the strength of evidence for these factors. The overall goals of this work are to provide greater insights into the factors that influence disease susceptibility, disease development and disease course and ultimately help to better guide clinicians and inform patients in the management of PV.

Low Barrier Tele-Buprenorphine in the Time of COVID-19: A Case Report

Background: To reduce the spread of coronavirus disease 2019 (COVID-19), many substance use disorder treatment programs have transitioned to telemedicine. Emergency regulatory changes allow buprenorphine initiation without an in-person visit. We describe the use of videoconferencing for buprenorphine initiation combined with street outreach to engage 2 patients experiencing homelessness with severe opioid use disorder (OUD). Case Presentation: Patient 1 was a 30-year-old man with severe OUD who had relapsed to injection heroin/fentanyl after incarceration. A community drop-in center outreach harm reduction specialist facilitated a videoconference with an addiction specialist at an OUD bridge clinic. The patient completed a community buprenorphine/naloxone initiation and self-titrated to his prior dose, 8/2 mg twice daily. One week later, he reconnected with the outreach team for a follow-up videoconference visit. Patient 2, a 36-year-old man with severe OUD, connected to the addiction specialist via a syringe service program harm reduction specialist. He had been trying to connect to a community buprenorphine/naloxone provider, but access was limited due to COVID-19, so he was using diverted buprenorphine/naloxone to reduce opioid use. He was restarted on his previous dose of 12/3 mg daily which was continued via phone follow-up 16 days later. Conclusion(s): COVID-19-related regulatory changes allow buprenorphine initiation via telemedicine. We describe 2 cases where telemedicine was combined with street outreach to connect patients experiencing homelessness with OUD to treatment. These cases highlight an important opportunity to provide access to life-saving OUD treatment for vulnerable patients in the setting of a pandemic that mandates reduced face-to-face clinical interactions.Copyright © 2020 Lippincott Williams and Wilkins. All rights reserved.

Does IFITM3 link inflammation to tumorigenesis?

Uncontrolled chronic inflammation, in most cases due to excessive cytokine signaling through their receptors, is known to contribute to the development of tumorigenesis. Recently, it has been reported that the antiviral membrane protein interferon-induced transmembrane protein 3 (IFITM3), induced by interferon signaling as part of the inflammatory response after viral infection, contributes to the development of B-cell malignancy. The unexpected oncogenic signaling of IFITM3 upon malignant B cell activation elucidated the mechanism by which the uncontrolled expression of inflammatory proteins contributes to leukemogenesis. In this review, the potential effects of inflammatory cytokines on upregulation of IFITM3 and its contribution to tumorigenesis are discussed.

A covalent opsonization approach to enhance synthetic immunity against viral escape variants.

The sensitivity of therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral "escape" mutations has inspired efforts to develop treatment strategies that are still effective in the face of rapidly mutating viral surface proteins. Here, we demonstrate a chemical strategy that enforces viral opsonization by natural serum antibodies. This strategy uses chimeric molecules that we call covalent viral opsonizers, which covalently label viral surface proteins, with synthetic antibody-binding ligands. As a proof of concept, we develop covalent viral opsonizers that covalently label the spike protein on SARS-CoV-2 using a "mutation-proof" small-molecule-binding ligand for anti-dinitrophenyl serum antibodies. In model assays, we observe that covalent viral opsonizers can rapidly and selectively covalently label the receptor-binding domain of both native and mutant spike proteins, leading to antibody opsonization. Opsonization mediated by this strategy is able to efficiently block the key binding domain interactions, in contrast to non-covalent analogs. We also show that covalent viral opsonizers enact targeted anti-viral phagocytotic immune function. This strategy has potential general utility for the rapid deployment of anti-viral synthetic immunotherapeutics at the onset of a new pandemic to reinforce vaccination and antibody engineering efforts.

Various charging Methods in Electric Vehicle Application: A Review

During the covid pandemic, air quality has improved due to prolonged lockdown conditions. Hence according to the international energy agency, about 22% of environmental pollution is contributed by the transportation sector. Electric vehicles help in reducing the contribution towards carbon emission and help in mitigating the fossil fuel crisis and also promotes sustainable transportation. To enhance the growth of electric vehicle, charging infrastructure and range anxiety issues in the long drive has to be resolved. This paper reviews the various charging methods available for an electric vehicle. Some charging methods are wired and wireless charging, solar-powered, battery-swapping, vehicle-to-grid and vehicle-to-vehicle charging. A comparative study of these methods is tabulated. Based on the limitation of each method the optimum charging method for a vehicle is adapted for a particular application. © 2023 IEEE.

Polytrauma patient with lateral thoracic spondyloptosis: case report and literature review

Background: Spondyloptosis is caused by high force trauma. The vast majority of cases occur in the sagittal plane and at transition points where ridged sections meet more flexible regions. Lateral thoracic spondyloptosis is extremely rare and there is no current consensus on the optimal treatment plan. Case Description: Here we present a case of a previously physically healthy 24-year-old polytrauma patient after he was struck as a pedestrian by a motor vehicle. Of note the patient was found to have lateral spondyloptosis between T9-10 with complete spinal cord transection. The patient also sustained multi-ligamentous left knee injury, pelvic fractures, open comminuted left tibia and fibular fracture, lacerated liver, bilateral renal lacerations, ischemic bowel, and an aortic arch pseudoaneurysm. Conclusion(s): Lateral thoracic spondyloptosis is a devastating injury with an extreme rate of persistent neurologic deficits. There is no unanimously accepted treatment because of the rarity if the injury and the poor outcomes that patients face. Additionally, patients who experience high level trauma often develop severe psychiatric illness, and the importance of identifying risk factors and implementing care early may improve patient outcomes.Copyright © AME Medical Journal.

Development of Personalized Sleep Induction System based on Mental States

Sleep is an essential behavior to prevent the decrement of cognitive, motor, and emotional performance and various diseases. However, it is not easy to fall asleep when people want to sleep. There are various sleep-disturbing factors such as the COVID-19 situation, noise from outside, and light during the night. We aim to develop a personalized sleep induction system based on mental states using electroencephalogram and auditory stimulation. Our system analyzes users' mental states using an electroencephalogram and results of the Pittsburgh sleep quality index and Brunel mood scale. According to mental states, the system plays sleep induction sound among five auditory stimulation: white noise, repetitive beep sounds, rainy sound, binaural beat, and sham sound. Finally, the sleep-inducing system classified the sleep stage of participants with 94.7% and stop auditory stimulation if participants showed non-rapid eye movement sleep. Our system makes 18 participants fall asleep among 20 participants. © 2023 IEEE.

A Case Report Of The Effects Of Chemotherapy On Post-heart-transplant Gene Expression Profiling

Introduction: Malignancies are a major complication of heart transplant (HT). Noninvasive surveillance after HT using gene expression (GEP) profiling and donor derived cell free DNA (dd-cfDNA) are noninferior to biopsy and are widely utilized. The interpretation of % dd-cfDNA, is not well understood in malignancies with a conceptual increase in the recipient fraction. The effect of chemotherapy on GEP in the setting of post-HT surveillance has not been described to the best of our knowledge. Hypothesis: Induction of chemotherapy will cause global transcriptional reduction in GEP. Method(s): GEP was performed with AlloMap (AM, CareDx), which evaluates expression levels of 11 mononuclear cell genes, involved in lymphocyte activation, T-cell priming, cell migration, hematopoietic proliferation, steroid sensitivity, and platelet activation. Scores range from 0-40, higher scores have a stronger correlation with rejection. At our center a total of 995 draws were analyzed from 2019-2022. In parallel dd-cfDNA, which informs about graft injury was analyzed using AlloSure (AS, CareDx). Case Events: A 71-year-old male HT recipient for nonischemic cardiomyopathy and no rejection history was diagnosed with metastatic gastric adenocarcinoma at 16 months post-HT. Following diagnosis, mycophenolic acid was stopped, prednisone 5 mg was started, and tacrolimus trough goal was gradually lowered to 4-6 given infectious complications. Palliative chemotherapy with folinic acid, fluorouracil (5-FU), oxaliplatin (FOLFOX) was initiated at 18 months post-HT with planned dose reduction of oxaliplatin and holding of 5-FU bolus to reduce risk of myelosuppression given comorbidities. Oxaliplatin was stopped at 18 months post HT. Due to COVID he last received 5-FU at 33 months post-HT. Graft function remained stable and DSA negative. At 36 months post-HT, he developed a bowel obstruction without surgical options for interventions and expired shortly thereafter. Result(s): With initiation of prednisone and following chemotherapy there was a drastic decrease in AM scores (Fig. A). Steroid therapy led to an 18% decline in AM scores, the greatest decrease occurred with chemotherapy, with 67% decline from the mean when compared to all center patients (Fig B). Dd-cfDNA levels remained stable during the course aside from one early elevation. Conclusion(s): To the best of our knowledge this is the first published case on the effect of chemotherapy on GEP profiling in the setting of post-HT surveillance. This case advises caution when interpreting GEP in the setting of chemotherapy showing great reduction in GEP scores. While dd-cfDNA levels remained relatively stable after malignancy diagnosis and treatment initiation further studies will need to inform on the use of both GEP and dd-cfDNA in these patients.Copyright © 2022

Evaluation of pre-induction dynamic arterial elastance as an adjustable predictor of post-induction hypotension: A prospective observational study.

STUDY OBJECTIVE: Dynamic arterial elastance (Eadyn) has been suggested as a functional measure of arterial load. We aimed to evaluate whether pre-induction Eadyn can predict post-induction hypotension. DESIGN: Prospective observational study. PATIENTS: Adult patients undergoing general anesthesia with invasive and non-invasive arterial pressure monitoring systems. MEASUREMENTS: We collected invasive and non-invasive Eadyns (n = 38 in each), respectively. In both invasive and non-invasive Eadyns, pre-induction Eadyns were obtained during one-minute tidal and deep breathing in each patient before anesthetic induction. Post-induction hypotension was defined as a decrease of >30% in mean blood pressure from the baseline value or any absolute mean blood pressure value of <65 mmHg for 10 min after anesthetic induction. The predictabilities of Eadyns for the development of post-induction hypotension were tested using receiver-operating characteristic curve analysis. MAIN RESULTS: Invasive Eadyn during deep breathing showed significant predictability with an area under the curve (AUC) of 0.78 (95% Confidence interval [CI], 0.61-0.90, P = 0.001). But non-invasive Eadyn during tidal breathing (AUC = 0.66, 95% CI, 0.49-0.81, P = 0.096) and deep breathing (AUC = 0.53, 95% CI, 0.36-0.70, P = 0.75), and invasive Eadyn during tidal breathing (AUC = 0.66, 95% CI, 0.41-0.74, P = 0.095) failed to predict post-induction hypotension. CONCLUSION: In our study, invasive pre-induction Eadyn during deep breathing -could predict post-induction hypotension. Despite its invasiveness, future studies will be needed to evaluate the usefulness of Eadyn as a predictor of post-induction hypotension because it is an adjustable parameter.

Comparison of Intubation Conditions Between Airtraq, McGrath Video Laryngoscopes, and Macintosh Under Conditions of Simulated Trauma Airway and Rapid Sequence Induction Intubation.

BACKGROUND: Patients arriving at the emergency department with a potential cervical spine injury and immobilized in a rigid cervical collar often require emergency airway management and rapid sequence induction intubation (RSII). There have been several advances in airway management with the advent of channeled (AirtraqⓇ; Prodol Meditec) and nonchanneled (McGrathⓇ; Meditronics) video laryngoscopes, which enable intubation without the removal of the cervical collar, but their efficacy and superiority over conventional laryngoscopy (Macintosh) in the presence of a rigid cervical collar and cricoid pressure have not been evaluated. OBJECTIVE: Our aim was to compare the channeled (Airtraq [group A]) and nonchanneled (McGrath [Group M]) video laryngoscopes with a conventional laryngoscope (Macintosh [Group C]) in a simulated trauma airway. METHODS: A prospective randomized controlled study was conducted in a tertiary care center. Participants were 300 patients requiring general anesthesia (American Society of Anesthesiologists class I or II), of both sexes, and aged 18-60 years. Airway management was simulated without removal of a rigid cervical collar and using cricoid pressure during intubation. After RSI, patients were intubated with one of the study techniques according to randomization. Intubation time and intubation difficulty scale (IDS) score were noted. RESULTS: Mean intubation time was 42.2 s in group C, 35.7 s in group M, and 21.8 s in group A (p = 0.001). Intubation was easy in group M and group A (median IDS score of 0; interquartile range [IQR] 0-1 for group M and median IDS score of 1; IQR 0-2 for group A and group C; p < 0.001). A higher proportion (95.1%) of patients had an IDS score of < 1 in group A. CONCLUSIONS: The performance of RSII with cricoid pressure in the presence of a cervical collar was easier and more rapid with channeled video laryngoscope than with other techniques.

Recent advances in regenerative biomaterials.

Nowadays, biomaterials have evolved from the inert supports or functional substitutes to the bioactive materials able to trigger or promote the regenerative potential of tissues. The interdisciplinary progress has broadened the definition of 'biomaterials', and a typical new insight is the concept of tissue induction biomaterials. The term 'regenerative biomaterials' and thus the contents of this article are relevant to yet beyond tissue induction biomaterials. This review summarizes the recent progress of medical materials including metals, ceramics, hydrogels, other polymers and bio-derived materials. As the application aspects are concerned, this article introduces regenerative biomaterials for bone and cartilage regeneration, cardiovascular repair, 3D bioprinting, wound healing and medical cosmetology. Cell-biomaterial interactions are highlighted. Since the global pandemic of coronavirus disease 2019, the review particularly mentions biomaterials for public health emergency. In the last section, perspectives are suggested: (i) creation of new materials is the source of innovation; (ii) modification of existing materials is an effective strategy for performance improvement; (iii) biomaterial degradation and tissue regeneration are required to be harmonious with each other; (iv) host responses can significantly influence the clinical outcomes; (v) the long-term outcomes should be paid more attention to; (vi) the noninvasive approaches for monitoring in vivo dynamic evolution are required to be developed; (vii) public health emergencies call for more research and development of biomaterials; and (viii) clinical translation needs to be pushed forward in a full-chain way. In the future, more new insights are expected to be shed into the brilliant field-regenerative biomaterials.

Resilient Leaders: Resilient Determinants When Entering Principalship

The study examines factors that boost principals' sense of resilience in their first year, as well as those that undermine it. 61 interviews were conducted with 21 school principals from five different districts throughout their first year in the role. Analysis revealed five categories of resilience-undermining factors. (1) Work overload that creates a sense of stress;(2) Difficulties in dealing with key players;(3) Lack of administrative knowledge;(4) Acceptance or rejection by the staff;and (5) Coping with the Covid-19 crisis. The analysis also revealed five categories of resilience-boosting factors: (1) Growth resulting from biographical events;(2) Short-term successes;(3) Supportive environment;(4) Drawing strength from the student environment;and (5) Acceptance by the staff. This study proposes ways of coping with the challenges of principalship through the prism of the resilience determinants of principals when entering their role. AD -, Ramat Gan, Israel ;, Ramat Gan, Israel

Neuroanesthesia practice during COVID-19: A single-center experience

The coronavirus disease 2019 (COVID-19) pandemic is a challenge for all health care providers (HCPs). Anesthesiologists are vulnerable to acquiring the disease during aerosol-generating procedures in operating theater and intensive care units. High index of suspicion, detailed history including travel history, strict hand hygiene, use of face masks, and appropriate personal protective equipment are some ways to minimize the risk of exposure to disease. Neurologic manifestations of COVID-19, modification of anesthesia regimen based on the procedure performed, and HCP safety are some implications relevant to a neuroanesthesiologist. National and international guidelines, recommendations, and position statements help in risk stratification, prioritization, and scheduling of neurosurgery and neurointervention procedures. Institutional protocols can be formulated based on the guidelines wherein each HCP has a definite role in this ever-changing scenario. Mental and physical well-being of HCPs is an integral part of successful management of patients. We present our experience in managing 143 patients during the lockdown period in India.Copyright © 2020 Wolters Kluwer Medknow Publications. All rights reserved.

Special considerations in the premature and ex-premature infant

Advances in neonatal medicine have progressively increased the survival of premature infants. Increased survival has however come at the cost of increased number of infants with prematurity-related complications. This is represented by high rates of respiratory distress syndrome, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), sepsis, periventricular leukomalacia (PVL), intraventricular haemorrhage (IVH), cerebral palsy, hypoxic ischaemic encephalopathy (HIE) and visual and hearing problems in survivors. In addition to prolonged hospital stay after birth, readmission to hospital in the first year of life is common if chronic lung disease exists. Around 3% of newborns have a congenital physical anomaly with 60% of congenital anomalies affecting the brain or heart and around 1% having multiple anomalies. Individual congenital conditions requiring surgical intervention in the neonatal period are rare. Neonates have a higher perioperative mortality risk largely due to the degree of prior illness, the complexity of their surgeries, and infant physiology. The maintenance of oxygenation and perfusion in the perioperative phase is critical as both affect cerebral perfusion and neurocognitive outcome but the triggers for intervention and the thresholds of physiological parameters during neonatal anaesthesia are not well described. After even minor surgical procedures, ex-premature infants are at higher risk for postoperative complications than infants born at term.Copyright © 2022

Antagonism and Evasion of Cellular Innate Immunity by SARS-CoV-2

The replication cycle of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) shares many features with other human Coronaviruses such as SARS-CoV and Middle East respiratory syndrome Coronavirus (MERS-CoV). Recent studies have elucidated the viral strategies of antagonizing the host immune response, including a multitude of mechanisms by which SARS-CoV-2 can dampen the interferon-mediated innate immunity. Furthermore, an imbalance and delay in interferon production, and exaggerated secretion of pro-inflammatory cytokines contribute to the severe immunopathology of Coronavirus disease 2019 (COVID-19). This chapter summarizes our current understanding of the intimate relationship between SARS-CoV-2 and the host innate and adaptive immune responses. The strategies that the virus utilizes to exploit cellular resources and to evade the innate immune system are described. The chapter provides a detailed discussion of interferonmediated innate immunity, interferon evasion and antagonism by SARSCoV- 2 and human Coronaviruses. © 2023 by World Scientific Publishing Co. Pte. Ltd.