Multi-omics in stress and health research: study designs that will drive the field forward.

Despite decades of stress research, there still exist substantial gaps in our understanding of how social, environmental, and biological factors interact and combine with developmental stressor exposures, cognitive appraisals of stressors, and psychosocial coping processes to shape individuals' stress reactivity, health, and disease risk. Relatively new biological profiling approaches, called multi-omics, are helping address these issues by enabling researchers to quantify thousands of molecules from a single blood or tissue sample, thus providing a panoramic snapshot of the molecular processes occurring in an organism from a systems perspective. In this review, we summarize two types of research designs for which multi-omics approaches are best suited, and describe how these approaches can help advance our understanding of stress processes and the development, prevention, and treatment of stress-related pathologies. We first discuss incorporating multi-omics approaches into theory-rich, intensive longitudinal study designs to characterize, in high-resolution, the transition to stress-related multisystem dysfunction and disease throughout development. Next, we discuss how multi-omics approaches should be incorporated into intervention research to better understand the transition from stress-related dysfunction back to health, which can help inform novel precision medicine approaches to managing stress and fostering biopsychosocial resilience. Throughout, we provide concrete recommendations for types of studies that will help advance stress research, and translate multi-omics data into better health and health care.

The association between risk perceptions, anxiety, and self-reported changes in tobacco and nicotine product use due to COVID-19 in May-June 2020 in Israel.

BACKGROUND: Early in the COVID-19 pandemic, reports about a possible protective effect of nicotine on COVID-19 conflicted with messaging by public health organizations about increased risks of COVID-19 due to smoking. The ambiguous information the public received, combined with COVID-19-induced anxiety, may have led to changes in tobacco or other nicotine product use. This study examined changes in use of combustible cigarettes (CCs), nargila (hookah/waterpipe), e-cigarettes, and IQOS and home-smoking behaviors. We also assessed COVID-19 related anxiety and perceptions regarding changes in risk of COVID-19 severity due to smoking. METHODS: We used cross-sectional data from a population telephone survey that was conducted in Israel in the early phase of the COVID-19 pandemic (May-June 2020) and included 420 adult (age 18+) individuals who reported having ever used CCs (n = 391), nargila (n = 193), and/or electronic cigarettes (e-cigarettes)/heated tobacco products (e.g., IQOS) (n = 52). Respondents were asked about the effect that COVID-19 had on their nicotine product use (quit/reduced use, no change, increased use). We assessed changes in product use, risk perceptions, and anxiety using adjusted multinomial logistic regression analyses. RESULTS: Most respondents did not change their frequency of product use (CCs: 81.0%, nargila: 88.2%, e-cigarettes/IQOS: 96.8%). A small percentage either decreased use (CCs: 7.2%, nargila: 3.2%, e-cigarettes/IQOS:2.4%) or increased use (CCs:11.8%, nargila:8.6%, e-cigarettes/IQOS:+ 0.9%). 55.6% of respondents used a product in the home prior to COVID-19; but during the first lockdown COVID-19 period, a greater percentage increased (12.6%) than decreased (4.0%) their home use. Higher levels of anxiety due to COVID-19 were associated with increased home smoking (aOR = 1.59, 95% CI:1.04-2.42, p = 0.02). Many respondents believed that increased severity of COVID-19 illness was associated with CCs (62.0%) and e-cigarettes/vaping (45.3%), with uncertainty about the association being lower for CCs (20.5%) than for vaping (41.3%). CONCLUSIONS: While many respondents believed that nicotine product use (particularly CCs and e-cigarettes) was associated with increased risk of COVID-19 disease severity, the majority of users did not change their tobacco/nicotine use. The confusion about the relationship between tobacco use and COVID-19 calls for clear evidence-based messaging from governments. The association between home smoking and increased COVID-19-related stress suggests the need for campaigns and resources to prevent smoking in the home, particularly during times of stress.

Adequacy of Web-Based Activities as a Substitute for In-Person Activities for Older Persons During the COVID-19 Pandemic: Survey Study.

BACKGROUND: Senior centers and other types of clubs provide activities for older adults to address boredom, social isolation, and loneliness. Due to the COVID-19 pandemic, most of these activities have been cancelled. A limited range of web-based activities have been offered as alternatives. However, the effectiveness of these web-based group activities for older adults has scarcely been researched. OBJECTIVE: We aimed to understand the extent to which web-based activities for older adults provide an adequate substitute for in-person activities. METHODS: In this telephone survey, we interviewed 105 older adults in Israel who had been offered the opportunity to participate in web-based activities after routine activities closed due to the COVID-19 pandemic. Of the total sample, 49/105 (46.7%) participated in the activities and 56/105 (53.3%) did not. We inquired about the respondents' background characteristics, satisfaction with the activities, and reasons for participation or nonparticipation. RESULTS: The respondents who participated in the web-based activities tended to be highly satisfied with at least some of them. They rated the enjoyment derived from the content of the activity as the most important motivator, followed by maintaining a routine and by enjoying the group and the presence of others. Over 50% of the participants (28/49, 57%) wished to continue with the exercise programming after the end of the COVID-19 pandemic, and 41% (20/49) wished to continue with the web-based lectures. Participants were more likely to report partaking in alternative activities than nonparticipants (P=.04). The most common reasons cited by nonparticipants were being unaware of the web-based program (24/56, 43%) despite a notification having been sent to the entire sample, lack of interest in the content (18/56, 32%), and technical issues (13/56, 23%), such as not owning or being able to fully use a computer. Both participants and nonparticipants were interested in a wide range of topics, with many being very particular about the topics they wished to access. Approximately half expressed willingness to pay for access; those who were willing to pay tended to have more years of education (P=.03). CONCLUSIONS: Our findings suggest a need for web-based activities for countering boredom and feelings of isolation. The main factors that influence the use, efficacy, and sustainability of online activities are access, motivational and need-fulfilling factors, and whether the activities are sufficiently tailored to individuals' preferences and abilities. Challenges in substituting in-person services are promoting social relationships that are currently not sufficiently incorporated into most web-based programs, accommodating a wider range of topics, and increasing the accessibility of current programs to older adults, especially those who are homebound, both during and after the COVID-19 pandemic.

Correction: Adequacy of Web-Based Activities as a Substitute for In-Person Activities for Older Persons During the COVID-19 Pandemic: Survey Study.

[This corrects the article DOI: 10.2196/25848.].

[The effects of "The Work" meditation technique on psychological scales among a non-clinical sample].

BACKGROUND: "The Work" is a meditative technique developed by Byron Katie in 1986 and is practiced by hundreds of thousands of people in more than 30 countries. The technique trains individuals to identify the thoughts that cause stress and suffering in a systematic and comprehensive way and to meditatively "investigate" these thoughts, thus enabling them to experience a different interpretation of reality. GOALS: The current study aimed to assess the effect of "The Work" meditation on psychological scales among a non-clinical sample. METHODS: This was a prospective research study conducted without a control group. The intervention consisted of a 9-day workshop of "The Work" meditation technique. Fifty-eight participants completed the following questionnaires before and after the intervention: satisfaction with life (SWLS), sense of coherence (SOC), general well-being (MHI), self-esteem (SES) and demographics. RESULTS: A significant improvement was obtained in all measures after "The Work" intervention: SWLS (21.6 to 25.07, p<0.001); SOC-comprehensibility subscale (4.05 to 4.55, p<0.001), SOC-manageability subscale (4.39 to 4.9, p<0.001) and meaningfulness subscale (4.58 to 5.07, p<0.001); SES (17.61 to 21.56, p<0.001); General wellbeing-well-being subscale (4.34 to 4.87, p<0.001) and distress subscale (3.42 to 2.79, p<0.001). DISCUSSION: A sense of coherence is an important resource for coping with challenging life events and promoting well-being and health. This resource can be influenced by mind-body interventions. Satisfaction with life is a subjective judgment of satisfaction with one's life in relation to one's own unique criteria. It is a central resource in mental and physical health promotion. "The Work" meditation technique includes cognitive conceptualization and processes, which may have contributed to the increase demonstrated in this scale. Psychological well-being scales also improved--a finding which has health, social and economic implications in the general population. The findings of the current study should be evaluated in light of its limitations, mainly the lack of a control group. CONCLUSIONS: The current pilot study shows the potentially beneficial effects of "The Work" technique as a method of intervention for improving results on psychological scales and promoting mental health among the general population. Future randomized controlled studies should examine the effectiveness of "The Work" intervention in this population.

Active Engagement: The Impact of Group-Based Physical Activities on the Resilience of Israeli Adolescents with ADHD.

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a pressing concern in pediatric public health, with its prevalence rising among children and teenagers. This study explored the relationship between group-based physical activity and the well-being, resilience, and distress levels of Israeli youth, with a specific focus on those with ADHD symptoms. Methods: This cross-sectional study surveyed 699 Israeli teenagers, assessing their participation in three types of physical activities: unorganized, structured, and the "Five Fingers" program. Data were collected through an online platform and analyzed using ANOVA, t-tests, and multivariable regression models to identify predictors of resilience. Results: Structured, group-based sport activities are associated with higher resilience (p < 0.01) and lower distress (p < 0.01) in adolescents. Adolescents with ADHD symptoms exhibited lower resilience (p < 0.001) and well-being (p < 0.001), and higher distress (p < 0.001). However, those with ADHD symptoms who participated in group-based activities fared better in terms of distress (p < 0.01) and well-being (p = 0.018) than those who did not. Participation in any sport activity, older age, male gender, and a higher socio-economic status predicted greater resilience in youth, generally. Conclusions: This study presents the potential of structured physical activities that involve psychosocial and group integration training to improve the mental health of adolescents, especially in the context of ADHD symptoms.

Perceived functional resilience in schools according to key stakeholders.

Amid the COVID-19 outbreak, Israel and numerous other governments closed schools as a precaution, leading to a sudden shift to online learning. The aim of the current study is to provide foundational insight into the perceived readiness of the school system to withstand future adversities, based on the challenges, complexities, as well as successes in adaptation faced by stakeholders during COVID-19. In this cross-sectional study, we assess the perceived levels of functional resilience of the school system among the key stakeholders of the Israeli education system-high school students, parents, teachers, and principals, as well as a composite functional resilience scale. The composite functional resilience consists of 10 main indexes: communication during distance learning (DL) and frontal learning (FL); Perceived stress scale-4 (PSS); psychosocial aspects during distance learning (DL) and frontal learning (FL); digital literacy; pedagogic support; resources; infrastructure; and distance versus frontal learning. The study findings demonstrate differences according to the stakeholders with regard to the perceived functional resilience and the composite functional resilience scores (e.g., students with respect to both of these scores exhibit the lowest results, while teachers display the highest scores). Furthermore, no one variable was significant across the board for all stakeholders in predicting the perceived functional resilience, with the most common predictors among the stakeholders being digital literacy, pedagogic support, PSS, as well as communication during distance and frontal learning. The findings of this study reveal areas for recommended priority actions to be conducted among school system stakeholders.

Occult Serologically Confirmed Cases of SARS-CoV-2 Coronavirus among the General Population in the Era of the Fourth Vaccination.

Background: Asymptomatic SARS-CoV-2 infection can significantly increase the spread of the COVID-19 pandemic. We aimed to investigate the epidemiological and clinical predictors of occult serologically confirmed SARS-CoV-2 cases among the general population during the fourth vaccination era in Israel. Methods: We conducted a cross-sectional study among individuals aged ≥18 years who had not been tested for COVID-19 in the preceding 5 months. Occult serologically confirmed cases were based on the presence of anti-N IgG antibodies. Potential risk factors were examined. Multivariable regression analysis identified independent predictors of subclinical SARS-CoV-2 infection. Results: This study included 504 participants. The prevalence of occult serologically confirmed SARS-CoV-2 was 12.5%. Chronic disease was found to be an independent predictor for the absence of occult disease (aOR) 0.4 [95% (CI): 0.18-0.87], p-value = 0.02). No significant differences were observed in age, sex, marital status, number of children, vaccination status, or exposure to COVID-19 infection between participants with and without SARS-CoV-2 sub-infection. Conclusions: We found a lower prevalence of occult serologically confirmed SARS-CoV-2 cases, compared to previous reports, and a negative correlation between chronic disease and occult SARS-CoV-2. Continued research, surveillance, and intervention strategies are needed to optimize long-term health outcomes and provide valuable insights for public health policymakers and clinicians.

Moringa Oleifera aqueous leaf extract down-regulates nuclear factor-kappaB and increases cytotoxic effect of chemotherapy in pancreatic cancer cells.

BACKGROUND: Fewer than 6% patients with adenocarcinoma of the pancreas live up to five years after diagnosis. Chemotherapy is currently the standard treatment, however, these tumors often develop drug resistance over time. Agents for increasing the cytotoxic effects of chemotherapy or reducing the cancer cells' chemo-resistance to the drugs are required to improve treatment outcome. Nuclear factor kappa B (NF-kB), a pro-inflammatory transcription factor, reportedly plays a significant role in the resistance of pancreatic cancer cells to apoptosis-based chemotherapy. This study investigated the effect of aqueous Moringa Oleifera leaf extract on cultured human pancreatic cancer cells - Panc-1, p34, and COLO 357, and whether it can potentiates the effect of cisplatin chemotherapy on these cells. METHODS: The effect of Moringa Oleifera leaf extract alone and in combination with cisplatin on the survival of cultured human pancreatic cancer cells was evaluated by XTT-based colorimetric assay. The distribution of Panc-1 cells in the cell cycle following treatment with Moringa leaf extract was evaluated by flow cytometry, and evaluations of protein levels were via immunoblotting. Data of cell survival following combined treatments were analyzed with Calcusyn software. RESULTS: Moringa Oleifera leaf extract inhibited the growth of all pancreatic cell lines tested. This effect was significant in all cells following exposure to ≥0.75 mg/ml of the extract. Exposure of Panc-1 cells to Moringa leaf extract induced an elevation in the sub-G1 cell population of the cell-cycle, and reduced the expression of p65, p-IkBα and IkBα proteins in crude cell extracts. Lastly, Moringa Oleifera leaf extract synergistically enhanced the cytotoxic effect of cisplatin on Panc-1 cells. CONCLUSION: Moringa Oleifera leaf extract inhibits the growth of pancreatic cancer cells, the cells NF-κB signaling pathway, and increases the efficacy of chemotherapy in human pancreatic cancer cells.

Resilience, Stress, Well-Being, and Sleep Quality in Multiple Sclerosis.

(1) Background: Multiple Sclerosis (MS) is a chronic, progressive, immune-mediated disorder that affects the Central Nervous System and is the most common cause of non-traumatic neurological disability in young adults. The study aimed to assess the levels of stress, resilience, well-being, sleep quality, and fatigue in Israeli people with MS (PwMS), and to examine the associations between these factors and the sociodemographic and clinical characteristics. These factors had never before been studied in conjunction in PwMS, nor had they been systematically addressed in Israel, the unique geopolitical situation of which may pose unique challenges. (2) Methods: This was a survey-based, cross-sectional study conducted through an Internet platform. (3) Results: Israeli PwMS who participated in the study were experiencing relatively high levels of stress and low resilience, poor sleep quality, and severe fatigue. The analysis revealed significant associations between resilience and stress, well-being, and anxiety, as well as stress and well-being, resilience, sleep quality, fatigue, and Clinically Isolated Syndrome (CIS). (4) Conclusions: the Israeli PwMS who participated in the study were experiencing higher levels of stress, lower resilience and worse sleep quality than PwMS in other countries, as compared to results previously reported in literature. The findings of this study ought to serve as a call to action for the MS care providers in Israel and warrant further research into the possible causes of the phenomenon and strategies to address it.

Distress following the COVID-19 Pandemic among Schools' Stakeholders: Psychosocial Aspects and Communication.

In response to the COVID-19 pandemic, many governments ordered school closures as a containment measure, with Israel being among over 100 countries to do so. This resulted in the abrupt shift to online and remote education for many students. Despite attempts to minimize the effects of disrupted education and create a dynamic virtual learning environment, the literature highlights various challenges including lack of communication with implications of distress faced by key stakeholders (students and their parents, teachers, and principals). In this cross-sectional study, we assess the perceived levels of communication and psychosocial aspects during both distance and frontal learning, as well as the long-term impacts (following over two and a half years of an ongoing pandemic) on distress among the key stakeholders of the Israeli education system- high school students, parents, teachers, and principals. The study findings demonstrate severe implications of distance learning on communication and psychosocial aspects, with lingering long-term impacts on distress, among all stakeholders (particularly among students). This reveals the need for tailored capacity building and resilience intervention programs to be integrated in the long-term response to the current ongoing pandemic to improve well-being and reduce distress among the various stakeholders, with particular attention to those that are most vulnerable and were hit the hardest.

An innovative tool to assess the functional resilience of a school system: learning from the COVID-19 pandemic.

Introduction: Preparing the school system for a future crisis requires the ability to examine the effectiveness of schools' functioning during distant learning and their level of preparedness for future crises. Functional resilience (FR) is defined as the ability to maintain vital operational continuity in the face of disturbance. The study objectives included to develop a FR index of schools and to evaluate and validate it. Methods: To enable examination of the study objectives, the study design included tool development, followed by a validation process among 20 content experts. Concurrently, an eDelphi process for building an inclusive index, based on various components of resilience was conducted. The final study tool consists of four tailored questionnaires to examine perceptions of key stakeholders, i.e.- teachers, principals, parents, and highschool students regarding communication, psychosocial aspects, perceived stress, infrastructure, resources, pedagogic support, digital literacy, and perceived FR. Using an internet panel, the tool was disseminated cross-sectionally among the four groups of stakeholders. Results: The results showed high reliability of most of the scales developed. Furthermore, a high consensus level was reached on the relative importance of each component/ stakeholder to the schools FR. The findings further suggest that there were no significant differences in the composite FR score based on characteristics such as school type/ size/geographic location. However, the findings revealed interesting variations among stakeholders, with findings suggesting greater vulnerability among some. Discussion: To increase resilience and preparedness for future adversities that school systems may face, it is recommended to periodically incorporate an assessment based on a structured tool.

Mental Health for All: The Case for Investing in Digital Mental Health to Improve Global Outcomes, Access, and Innovation in Low-Resource Settings.

Mental health disorders are an increasing global public health concern that contribute to morbidity, mortality, disability, and healthcare costs across the world. Biomedical and psychological research has come a long way in identifying the importance of mental health and its impact on behavioral risk factors, physiological health, and overall quality of life. Despite this, access to psychological and psychiatric services remains widely unavailable and is a challenge for many healthcare systems, particularly those in developing countries. This review article highlights the strengths and opportunities brought forward by digital mental health in narrowing this divide. Further, it points to the economic and societal benefits of effectively managing mental illness, making a case for investing resources into mental healthcare as a larger priority for large non-governmental organizations and individual nations across the globe.

Using Ecological Momentary Assessments to Study How Daily Fluctuations in Psychological States Impact Stress, Well-Being, and Health.

Despite great interest in how dynamic fluctuations in psychological states such as mood, social safety, energy, present-focused attention, and burnout impact stress, well-being, and health, most studies examining these constructs use retrospective assessments with relatively long time-lags. Here, we discuss how ecological momentary assessments (EMAs) address methodological issues associated with retrospective reports to help reveal dynamic associations between psychological states at small timescales that are often missed in stress and health research. In addition to helping researchers characterize daily and within-day fluctuations and temporal dynamics between different health-relevant processes, EMAs can elucidate mechanisms through which interventions reduce stress and enhance well-being. EMAs can also be used to identify changes that precede critical health events, which can in turn be used to deliver ecological momentary interventions, or just-in-time interventions, to help prevent such events from occurring. To enable this work, we provide examples of scales and single-item questions used in EMA studies, recommend study designs and statistical approaches that capitalize on EMA data, and discuss limitations of EMA methods. In doing so, we aim to demonstrate how, when used carefully, EMA methods are well poised to greatly advance our understanding of how intrapersonal dynamics affect stress levels, well-being, and human health.

Data From a One-Stop-Shop Comprehensive Cancer Screening Center.

PURPOSE: Cancer is the second leading cause of death globally. However, by implementing evidence-based prevention strategies, 30%-50% of cancers can be detected early with improved outcomes. At the integrated cancer prevention center (ICPC), we aimed to increase early detection by screening for multiple cancers during one visit. METHODS: Self-referred asymptomatic individuals, age 20-80 years, were included prospectively. Clinical, laboratory, and epidemiological data were obtained by multiple specialists, and further testing was obtained based on symptoms, family history, individual risk factors, and abnormalities identified during the visit. Follow-up recommendations and diagnoses were given as appropriate. RESULTS: Between January 1, 2006, and December 31, 2019, 8,618 men and 8,486 women, average age 47.11 ± 11.71 years, were screened. Of 259 cancers detected through the ICPC, 49 (19.8%) were stage 0, 113 (45.6%) stage I, 30 (12.1%) stage II, 25 (10.1%) stage III, and 31(12.5%) stage IV. Seventeen cancers were missed, six of which were within the scope of the ICPC. Compared with the Israeli registry, at the ICPC, less cancers were diagnosed at a metastatic stage for breast (none v 3.7%), lung (6.7% v 11.4%), colon (20.0% v 46.2%), prostate (5.6% v 10.5%), and cervical/uterine (none v 8.5%) cancers. When compared with the average stage of detection in the United States, detection was earlier for breast, lung, prostate, and female reproductive cancers. Patient satisfaction rate was 8.35 ± 1.85 (scale 1-10). CONCLUSION: We present a proof of concept study for a one-stop-shop approach to cancer screening in a multidisciplinary outpatient clinic. We successfully detected cancers at an early stage, which has the potential to reduce morbidity and mortality as well as offer substantial cost savings.[Media: see text].

[The role of medicinal herbs with anti-inflammatory properties in prevention and treatment of cancer].

The association between chronic inflammation and carcinogenesis, as well as neoplastic progression, has been researched and is well-established. Being a central coordinator of immune responses, nuclear factor-kappa B (NFkappaB) signaling plays a critical role in cancer development and progression. The activation of the NFkappaB signaling pathway is highly monitored under normal conditions, and is mainly known as a key pathway in activation of immune responses. Constitutively active NFkappaB has been identified in most tumor cell lines, as well as in a wide variety of tumor tissues derived from cancer patients. Such activation may also affect the cancer's response to therapy, making it less susceptive to radio and chemo treatment. Hence, NFkappaB has become a target for inhibition by chemotherapeutic agents. Traditionally, medicinal herbs have been used to prevent and treat a variety of diseases, including cancer. In this article, we review several natural, herbal-derived compounds shown to have anti-inflammatory and anticancer activities mediated, at least in part, by NFkappaB signaling inhibition. Compounds of this sort may potentially serve as clinically effective anticancer treatments.

The Use of Smart Devices for Mental Health Diagnosis and Care.

In 2019, more than 970 million people worldwide suffered from a mental disorder, with anxiety and depressive disorders as the leading culprits [...].

The Association between the Sense of Coherence and the Self-Reported Adherence to Guidelines during the First Months of the COVID-19 Pandemic in Israel.

(1) Background: Social distancing became a central strategy employed to limit the spread of the SARS-CoV-2 virus. We explore self-reported adherence (SRA) and factors associated with SRA among Israeli adults at the end of the first national lockdown in Israel. (2) Methods: We conducted a cross-sectional consumer panel survey of 820 Israeli adults aged 18 to 70 in May and June 2020. We collected data on the SRA to the social distancing measures, sociodemographic variables, perceptions of pandemic-related danger and of protection provided by the social distancing measures, as well as Sense of Coherence (SoC). (3) Results: 60% of respondents reported complying with 7 measures. Higher SoC was associated with higher SRA (p = 0.04), and was related to income, marital status, age, profession, and education. The SRA was higher among Jews than Arabs (Jews: Mean = 10.5, SD = 4.5; Arabs: Mean = 9.1, SD = 4.1, p < 0.001) and among males (Males: Mean = 10.8, SD = 4.7; Females: Mean = 9, SD = 4.1; p = 0.003). SoC, perception of protection and perception of danger were associated with higher SRA (p = 0.42, p < 0.001 and p = 0.005 respectively). Single people reported higher levels of SRA than people in relationships (Partnered: Mean = 9.7, SD = 4.2, Non-partnered: Mean = 10.9, SD = 4.7, p = 0.033). (4) Conclusions: At the time of exit from the first lockdown, compliance with social distancing measures was high, with Jewish, single and male Israelis more likely to adhere to the guidelines. We identified the populations at risk for non-adherence and associated factors, reporting for the first time the correlation between SoC and SRA. Further research is needed to assess the role of these factors in Jewish and Arab populations.

A novel platform for attenuating immune hyperactivity using EXO-CD24 in COVID-19 and beyond.

A small but significant proportion of COVID-19 patients develop life-threatening cytokine storm. We have developed a new anti-inflammatory drug, EXO-CD24, a combination of an immune checkpoint (CD24) and a delivery platform (exosomes). CD24 inhibits the NF-kB pathway and the production of cytokines/chemokines. EXO-CD24 discriminates damage-from pathogen-associated molecular patterns (DAMPs and PAMPs) therefore does not interfere with viral clearance. EXO-CD24 was produced and purified from CD24-expressing 293-TREx™ cells. Exosomes displaying murine CD24 (mCD24) were also created. EXO-CD24/mCD24 were characterized and examined, for safety and efficacy, in vitro and in vivo. In a phase Ib/IIa study, 35 patients with moderate-high severity COVID-19 were recruited and given escalating doses, 108 -1010 , of EXO-CD24 by inhalation, QD, for 5 days. No adverse events related to the drug were observed up to 443-575 days. EXO-CD24 effectively reduced inflammatory markers and cytokine/chemokine, although randomized studies are required. EXO-CD24 may be a treatment strategy to suppress the hyper-inflammatory response in the lungs of COVID-19 patients and further serve as a therapeutic platform for other pulmonary and systemic diseases characterized by cytokine storm.

Age Differences in Recovery Rate Following an Aerobic-Based Exercise Protocol Inducing Muscle Damage Among Amateur, Male Athletes.

Purpose: Compare recovery rates between active young (Y) and middle-aged (MA) males up to 48H post aerobically based, exercise-induced muscle damage (EIMD) protocol. A secondary aim was to explore the relationships between changes in indices associated with EIMD and recovery throughout this timeframe. Methods: Twenty-eight Y (n = 14, 26.1 ± 2.9y, 74.5 ± 9.3 kg) and MA (n = 14, 43.6 ± 4.1y, 77.3 ± 12.9 kg) physically active males, completed a 60-min downhill running (DHR) on a treadmill at -10% incline and at 65% of maximal heart rate (HR). Biochemical, biomechanical, psychological, force production and muscle integrity (using MRI diffusion tensor imaging) markers were measured at baseline, immediately-post, and up to 48H post DHR. Results: During the DHR, HR was lower (p < 0.05) in MA compared to Y, but running pace and distance covered were comparable between groups. No statistical or meaningful differences were observed between groups for any of the outcomes. Yet, Significant (p < 0.05) time-effects within each group were observed: markers of muscle damage, cadence and perception of pain increased, while TNF-a, isometric and dynamic force production and stride-length decreased. Creatine-kinase at 24H-post and 48H-post were correlated (p < 0.05, r range = -0.57 to 0.55) with pain perception, stride-length, and cadence at 24H-post and 48H-post. Significant (p < 0.05) correlations were observed between isometric force production at all time-points and IL-6 at 48H-post DHR (r range = -0.62 to (-0.74). Conclusion: Y and MA active male amateur athletes recover in a comparable manner following an EIMD downhill protocol. These results indicate that similar recovery strategies can be used by trainees from both age groups following an aerobic-based EIMD protocol.