Novel coronavirus disease 2019 (COVID-19) severity is highly variable, with pediatric patients typically experiencing less severe infection than adults and especially the elderly. The basis for this difference is unclear. We find that mRNA and protein expression of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, increases with advancing age in distal lung epithelial cells. However, in humans, ACE2 expression exhibits high levels of intra- and interindividual heterogeneity. Further, cells infected with SARS-CoV-2 experience endoplasmic reticulum stress, triggering an unfolded protein response and caspase-mediated apoptosis, a natural host defense system that halts virion production. Apoptosis of infected cells can be selectively induced by treatment with apoptosis-modulating BH3 mimetic drugs. Notably, epithelial cells within young lungs and airways are more primed to undergo apoptosis than those in adults, which may naturally hinder virion production and support milder COVID-19 severity.

Posttraumatic stress disorder (PTSD) after the pandemic has emerged as a major neuropsychiatric component of post-acute COVID-19 syndrome, yet the current pharmacotherapy for PTSD is limited. The use of adrenergic drugs to treat PTSD has been suggested; however, it is hindered by conflicting clinical results and a lack of mechanistic understanding of drug actions. Our studies, using both genetically modified mice and human induced pluripotent stem cell-derived neurons, reveal a novel α2A adrenergic receptor (α2AAR)-spinophilin-cofilin axis in the hippocampus that is critical for regulation of contextual fear memory reconsolidation. In addition, we have found that two α2 ligands, clonidine and guanfacine, exhibit differential abilities in activating this signaling axis to disrupt fear memory reconsolidation. Stimulation of α2AAR with clonidine, but not guanfacine, promotes the interaction of the actin binding protein cofilin with the receptor and with the dendritic spine scaffolding protein spinophilin to induce cofilin activation at the synapse. Spinophilin-dependent regulation of cofilin is required for clonidine-induced disruption of contextual fear memory reconsolidation. Our results inform the interpretation of differential clinical observations of these two drugs on PTSD and suggest that clonidine could provide immediate treatment for PTSD symptoms related to the current pandemic. Furthermore, our study indicates that modulation of dendritic spine morphology may represent an effective strategy for the development of new pharmacotherapies for PTSD.

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening clinical syndrome whose potential to become one of the most grievous challenges of the healthcare system evidenced by the COVID-19 pandemic. Considering the lack of target-specific treatment for ARDS, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve quality of life and outcomes for ARDS patients. ARDS is a systemic inflammatory disease starting with the pulmonary system and involves all other organs in a morbid bidirectional fashion. Mounting evidence including our findings supporting the notion that cannabinoids have potential to be targeted as regulatory therapeutic modalities in the treatment of inflammatory diseases. Therefore, it is plausible to test their capabilities as alternative therapies in the treatment of ARDS. In this study, we investigated the potential protective effects of cannabichromene (CBC) in an experimental model of ARDS. Methods: We used, for the first time, an inhalant CBC treatment as a potential therapeutic target in a murine model of ARDS-like symptoms. ARDS was induced by intranasal administration of Poly(I:C), a synthetic mismatched double-stranded RNA, into the C57BL/6 mice (6–10 male mice/group, including sham, placebo, and CBC treated), three once-daily doses followed by a daily dose of inhalant CBC or placebo for the period of 8 days starting the first dose 2 h after the second Poly(I:C) treatment. We employed histologic, immunohistochemistry, and flow cytometry methods to assess the findings. Statistical analysis was performed by using one way analysis of variance (ANOVA) followed by Newman–Keuls post hoc test to determine the differences among the means of all experimental groups and to establish significance (p < 0.05) among all groups. Results: Our data showed that CBC was able to reverse the hypoxia (increasing blood O2 saturation by 8%), ameliorate the symptoms of ARDS (reducing the pro-inflammatory cytokines by 50% in lung and blood), and protect the lung tissues from further destruction. Further analysis showed that CBC may wield its protective effects through transient receptor potential (TRP) cation channels, TRPA1 and TRPV1, increasing their expression by 5-folds in lung tissues compared to sham and untreated mice, re-establishing the homeostasis and immune balance. Conclusion: Our findings suggest that inhalant CBC may be an effective alternative therapeutic target in the treatment of ARDS. In addition, Increased expression of TRPs cation channels after CBC treatment proposes a novel role for TRPs (TRPA1 and TRPV2) as new potential mechanism to interpret the beneficial effects of CBC as well as other cannabinoids in the treatment of ARDS as well as other inflammatory diseases. Importantly, delivering CBC through an inhaler device is a translational model supporting the feasibility of trial with human subjects, authorizing further research.

Objectives: The global COVID-19 pandemic has affected various populations differently. We investigated the relationship between socioeconomic determinants of health obtained from the Robert Wood Johnson Foundation County Health Rankings and COVID-19 incidence and mortality at the county level in Georgia. Methods: We analyzed data on COVID-19 incidence and case-fatality rates (CFRs) from the Georgia Department of Public Health from March 1 through August 31, 2020. We used repeated measures generalized linear mixed models to determine differences over time in Georgia counties among quartile health rankings of health outcomes, health behaviors, clinical care, social and economic factors, and physical environment. Results: COVID-19 incidence per 100 000 population increased across all quartile county groups for all health rankings (range, 23.1-51.6 in May to 688.4-1062.0 in August). COVID-19 CFRs per 100 000 population peaked in April and May (range, 3312-6835) for all health rankings, declined in June and July (range, 827-5202), and increased again in August (range, 1877-3310). Peak CFRs occurred later in counties with low health rankings for health behavior and clinical care and in counties with high health rankings for social and economic factors and physical environment. All interactions between the health ranking quartile variables and month were significant (P <.001). County-level Gini indices were associated with significantly higher rates of COVID-19 incidence (P <.001) but not CFRs. Conclusions: From March through August 2020, COVID-19 incidence rose in Georgia’s counties independent of health rankings categorization. Differences in time to peak CFRs differed at the county level based upon key health rankings. Public health interventions should incorporate unique strategies to improve COVID-19–related patient outcomes in these environments.

Tyrosine kinase inhibitors (TKIs) have vastly improved long-term outcomes for patients with chronic myeloid leukemia (CML). After imatinib (a first-generation TKI), second- and third-generation TKIs were developed. With five TKIs (imatinib, dasatinib, bosutinib, nilotinib, and ponatinib) targeting BCR::ABL approved in most countries, and with the recent approval of asciminib in the USA, treatment decisions are complex and require assessment of patient-specific factors. Optimal treatment strategies for CML continue to evolve, with an increased focus on achieving deep molecular responses. Using clinically relevant case studies developed by the authors of this review, we discuss three major scenarios from the perspective of international experts. Firstly, this review explores patient-specific characteristics that affect decision-making between first- and second-generation TKIs upon initial diagnosis of CML, including patient comorbidities. Secondly, a thorough assessment of therapeutic options in the event of first-line treatment failure (as defined by National Comprehensive Cancer Network and European LeukemiaNet guidelines) is discussed along with real-world considerations for monitoring optimal responses to TKI therapy. Thirdly, this review illustrates the considerations and importance of achieving treatment-free remission as a treatment goal. Due to the timing of the writing, this review addresses global challenges commonly faced by hematologists treating patients with CML during the COVID-19 pandemic. Lastly, as new treatment approaches continue to be explored in CML, this review also discusses the advent of newer therapies such as asciminib. This article may be a useful reference for physicians treating patients with CML with second-generation TKIs and, as it is focused on the physicians’ international and personal experiences, may give insight into alternative approaches not previously considered.

Objective: The COVID-19 pandemic has been associated with decreased incidence of acute coronary syndrome with worsened outcomes. Few studies have addressed the effects beyond the initial phases of the pandemic. This study elucidated the incidence, clinical characteristics, management, and outcomes of NSTEMI at a tertiary referral center from sample time periods of 2019–2022. Methods: This study included consecutive NSTEMI patients from March 14–May 9, 2019–2022. Variables included baseline characteristics, clinical features on arrival, management strategy, time parameters, and adverse outcomes. The primary outcome was defined as death, heart failure requiring diuretics, and/or sustained ventricular arrhythmia. Results: This study comprised 250 patients of whom 181 who were admitted during the COVID-19 outbreak. Baseline characteristics were similar among groups. There was a reduction in door-to-angiography time from 29 h in 2019 to 19 h in 2020 [p = 0.01] and 20 h in 2021 [p = 0.02]. PCI intervention increased from 31.8% in 2019% to 50.0% in 2020 [p = 0.05] and 54.7% in 2021 [p < 0.01]. Median length-of-stay (LOS) was reduced from 3 days in 2019 to 2 days in 2020 [p = 0.03]. There was no significant change in outcomes in COVID-19 cohorts compared to control year. Conclusions: NSTEMI patients during the first 2 years of the COVID-19 pandemic were associated with reduced door-to-angiography times and increased percutaneous coronary intervention (PCI), and patients in year one were associated with reduced LOS. This study suggests that NSTEMI may be managed more efficiently thus reducing hospital bed utilization and potential costs.

For my thesis I will be examining the influence full-leg compression garments have on oxygen consumption and heart rate. It is speculated that compression garments assist with blood flow velocity as well as increasing oxygen delivery to the muscles. It is well known that compression garments aid in recovery and are widely used in the diabetic community to reduce pooling in the lower limbs. What has not been well explored are the benefits to performance during running. Studies show that compression garments reduce muscle oscillation, as well as soft tissue movement (Bringard et al. 2006; Doan et al. 2003). It has been theorized this reduction creates lower stress at the joints and a reduction in injury risk. It is reasonable to question that if compression garments reduce muscle oscillation, then muscle activation time will also be reduced because the muscles will not have to work as hard to counteract the additional oscillating stress at impact. If muscles are not active for as long, then the muscles will not need to produce as much energy or use as much oxygen. With an increase in blood flow and reduction in muscle activation, the heart will not have to work as hard to circulate oxygen and similar effects may occur for heart rate. However, very few studies have examined full-leg compression garments while performing a submaximal endurance run. Therefore, we are testing subjects in full-leg compression garments while performing a 40-minute submaximal effort run to determine the effect on oxygen consumption and heart rate. From a runner's perspective I am intrigued with this topic because I am always looking for new ways to enhance my performance during competition and compression garments could be that next step. By gathering results from this research, it could potentially give us more information on enhancing running performance. In the future we could expand on this research by looking at more variables such as maximal oxygen uptake or examining the effects for longer endurance runs like marathons.

Although in recent decades deaths from prostate cancer have declined among all men, Black men in the US are twice as likely as non-Hispanic White men to die of prostate cancer and continue to have the highest prostate cancer mortality among all US population groups (American Cancer Society, 2021). Within the United States this phenomenon becomes more apparent in areas with a high density of Black Americans, for example the state of Georgia. There, disparity can be seen in prostate cancer with a rate of 50.3 deaths per 100,000 versus 18.4 deaths per 100,000 for non-Hispanic White men (Georgia Cancer Data Reports, 2016). Consensus agrees that these health inequalities exist due to a multitude of social, economic, and cultural factors. These include cultural attitudes towards cancer, and accessibility to healthcare. The cost of health inequality is human lives, thus, reducing the disparities seen in the Black American community is imperative. One initiative that has set out to tackle this is the Cancer Health Awareness through screeNinG and Education (CHANGE) program. CHANGE aims to reduce Black American racial disparities in prostate, colorectal, and breast cancer through education, navigation to screening, and provider cultural competency improvement. Researchers used an evidence-based template, with an emphasis on modifiable risk factor prevention (such as smoking or obesity), to develop informative classes on cancer screening eligibility, access to screening at the Georgia Cancer Center, and encouragement of early detection behaviors to promote health knowledge and self-efficacy. The CHANGE initiative presented four community-tailored sessions with a focus on cancer, screening, and modifiable risk factors guided by a trained facilitator. To gather evidence of acquired health knowledge an assessment survey was sent out before and after the sessions took place

There are insufficient data regarding the safety of otologic procedures in the setting of the coronavirus disease 2019 (COVID-19) pandemic. Given the proclivity for respiratory pathogens to involve the middle ear and the significant aerosolization associated with many otologic procedures, safety precautions should follow current recommendations for procedures involving the upper airway. Until preoperative diagnostic testing becomes standardized and readily available, elective cases should be deferred and emergent/urgent cases should be treated as high risk for COVID-19 exposure. Necessary otologic procedures on positive, suspected, or unknown COVID-19 status patients should be performed using enhanced personal protective equipment, including an N95 respirator and eye protection or powered air-purifying respirator (PAPR, preferred), disposable cap, disposable gown, and gloves. Powered instrumentation should be avoided unless absolutely necessary, and if performed, PAPR or sealed eye protection is recommended.

The COVID-19 pandemic caused by the novel SARS-CoV-2 coronavirus is an ongoing pandemic causing severe health crisis worldwide. Recovered COVID-19 patients go through several long-term side effects such as fatigue, headaches, dizziness, weight loss, and muscle loss among others. Our study sought to determine the molecular mechanisms behind muscle loss in COVID-19 patients. We hypothesized that multiple factors such as cytokine storm and therapeutic drugs (glucocorticoid and antiviral drugs) might be involved in muscle loss. Using the Gene Expression Omnibus database, we identified several studies that performed RNA sequencing on skeletal muscles with the treatment of cytokine, glucocorticoid, and antiviral drugs. Our study identified cytokines, such as IL-1b, and IL-6, associated with altered regulation of several genes involved in the myogenic processes, including Ttn, Cxxc5, Malat1, and Foxo1. We also observed that glucocorticoid altered the expression of Foxo1, Lcn2, Slc39a14, and Cdkn1a. Finally, we found out that the antiviral (RNA-dependent RNA polymerase inhibitor) drug regulates the expression of some of the muscle-related genes (Txnip, Ccnd1, Hdac9, and Fbxo32). Based on our findings, we hypothesize that the cytokine storm, glucocorticoids, and antiviral drugs might be synergistically involved in COVID-19-dependent muscle loss.