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1.
medrxiv; 2024.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2024.01.21.24301574

ABSTRACT

Trauma and stressor-related symptoms have been frequently reported during the COVID-19 pandemic. Few studies compare post-traumatic stress symptoms (PTSS) between patients and non-infected controls. Using data from an ongoing natural history study of COVID-19, this study compared PTSS between patients infected with SARS-CoV-2 during the first year of the pandemic and controls. Within the COVID-19 patient cohort, we also compared PTSS between patients with and without post-COVID conditions, also known as post-acute sequelae of SARS-CoV-2 infection (PASC). This study also examined the association of PTSS with trait resilience and prior trauma exposure. PTSS were assessed using the Impact of Event Scaled-Revised (IES-R), which has a validated probable PTSD cutoff (score [≥]33). The results showed that patients (n=131) reported significantly higher IES-R scores than controls (n=82) and had significantly higher odds of having scores indicative of PTSD [AOR: 4.17 p: 0.029]. IES-R scores among PASC patients (n=68) were significantly elevated compared to patients without PASC (n=63) and PASC patients did not have higher odds for probable PTSD [AOR: 2.60; p: 0.14]. Trait resilience was associated with lower PTSS. These findings help characterize the mental health impact of the COVID-19 illness experience and highlight elevated PTSS in patients with persistent post-COVID conditions.


Subject(s)
COVID-19 , Stress Disorders, Traumatic , Stress Disorders, Post-Traumatic , Wounds and Injuries
2.
Int J Methods Psychiatr Res ; : e1953, 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-20236007

ABSTRACT

OBJECTIVES: The DSM-5 Level 1 Cross-Cutting Symptom Measure (DSM-XC) was developed by the American Psychiatric Association as a transdiagnostic mental health symptom survey. Despite its promise as a screening tool, few studies have assessed its latent dimensionality or provided guidance on interpreting responses. We examined the factor structure of the DSM-XC in a convenience sample of participants with varying degrees of psychopathology. METHODS: Participants (n = 3533) were enrolled in an online study on the mental health impact of COVID-19 (NCT04339790). We used a factor analytic framework with exploratory and confirmatory analyses to evaluate candidate factor solutions. Convergent validity analysis with concurrent study measures was also performed. RESULTS: Six-factor and bifactor candidate solutions both had good fit and full measurement invariance across age, sex, and enrollment date. The six-factor solution resulted in constructs labeled as: mood, worry, activation, somatic, thought, and substance use. A general psychopathology factor and two residual factors (mood and anxiety constructs) explained the variance of the bifactor solution. CONCLUSIONS: Our analysis supports that the DSM-XC is a multidimensional instrument spanning many mental health symptoms. We provide scoring solutions for two factor structures that capture broader constructs of psychopathology. Use of a convenience sample may limit generalizability of findings.

3.
European Journal of Molecular and Clinical Medicine ; 7(11):9229-9234, 2020.
Article in English | EMBASE | ID: covidwho-2303881

ABSTRACT

Introduction and Background: The Corona virus Disease-19 (COVID-19) outbreak has rapidly transitioned into a pandemic affecting every field of life. There is a drastic transition also in field of teaching many challenges are faced by students and faculty, also regarding assessments. The present study was done to evaluate the gender wise perception of various modes of online assignments. Methodology: This study was conducted online on 100 first year medical students at the Army College of Medical Sciences, Delhi Cantt, New Delhi, India. A cross-sectional online survey was done using a pretested, self administered questionnaire. Result(s): Out of the sample group of 100 participants 98(53F,45M) responded. The most preferred mode of assessment was multiple choice questions. A significantly higher percentage of male students disliked seminar discussions and hand written assignments. Conclusion(s): A statistically significant dislike for seminars and handwritten assignments by male students could be attributed to their being from rural area and lesser accessibility. The present study conducted over a larger sample group would help medical educators in a better learning and teaching practice in the present scenario and for the future.Copyright © 2020 Ubiquity Press. All rights reserved.

4.
Elementary School Journal ; 123(4):000-000, 2023.
Article in English | Academic Search Complete | ID: covidwho-2261215
5.
English Language Teacher Education in Changing Times: Perspectives, Strategies, and New Ways of Teaching and Learning ; : 137-154, 2023.
Article in English | Scopus | ID: covidwho-2257872

ABSTRACT

Elementary teachers have little to no professional development in teaching computer science (CS), and there is currently no multiple subject authorization dedicated to the discipline. Very often, elementary teachers who implement CS lessons are learning the subject while teaching their established curriculum. This chapter describes the Elementary Computing for All initiative, a federally funded collaboration between researchers and practitioners designed to develop, implement, test, and refine professional development (PD) that promotes CS for multilingual students in elementary grades. To train participating teachers, we developed an intensive, in-person, weeklong Summer Institute designed to train teachers in the use of CS education for multilingual students. However, with the COVID-19 pandemic, the PD was shifted to a virtual format. This chapter discusses the design and implementation of a virtual PD that utilized emerging technology tools including a learning management system, synchronous and asynchronous sessions, existing online CS training, collaborative activities, staggered scheduling, and networking opportunities. The chapter also describes findings that demonstrate that providing flexible teacher PD with built-in support helps teachers provide quality CS instruction to multilingual students. Furthermore, these practices can be applied to face-to-face and hybrid PD settings, providing individualized support for new CS teachers. © 2023 Taylor and Francis.

6.
Brain Stimulation ; 16(1):357, 2023.
Article in English | EMBASE | ID: covidwho-2255497

ABSTRACT

Background: Transcranial magnetic stimulation (TMS) treatment holds promise for pediatric neurological and psychiatric illnesses, but little is known about the acceptability, feasibility, and uptake of experimental TMS intervention in pediatric populations. The current study aimed to identify successful recruitment strategies and participation barriers in the CBIT+TMS Trial, an ongoing clinical trial testing TMS augmentation of behavior therapy for Tourette Syndrome in 12-21 year olds. Method(s): Participation involves 10 daily treatment sessions over two weeks plus pre/post neuroimaging and clinical assessments through 3-month follow-up. Recruitment data from November 2020 - August 2022 were examined for recruitment status, recruitment source, and reason for ineligibility or non-participation. Result(s): N = 171 individuals expressed interest in participation. Of these, 53% declined or passively declined participation, 45% completed phone screening, 19% were deemed ineligible, and 18% enrolled. The most successful recruitment strategies were community flyering, sharing information through a patient support organization, and provider referrals. The most commonly stated reasons for declining participation were related to time commitment and the need to travel to in-person appointments. Notably, participation was greatest during summer months. All enrolled participants have been retained through follow-up visits. Conclusion(s): TMS treatment is of interest to youth and parents in the TS community. As a comparison, a prior TS therapy trial screened =6 youth/month across three sites (Piacentini et al., 2010), whereas our single site is screening =4 youth/month. Stated reasons for declining participation related to schedule and travel feasibility rather than concerns about TMS. This recruitment period overlapped with the COVID-19 pandemic, which likely heightened these particular barriers. Future pediatric TMS research should include efforts to maximize efficacy within protocol schedules that are feasible for youth. Continued examination of factors contributing to pediatric TMS interest and uptake can help inform developmentally sensitive intervention and clinical trial protocols. Research Category and Technology and Methods Clinical Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: Tourette, Clinical Trial, Pediatric, FeasibilityCopyright © 2023

7.
Journal of Heart & Lung Transplantation ; 42(4):S525-S526, 2023.
Article in English | Academic Search Complete | ID: covidwho-2251015

ABSTRACT

Ex vivo lung perfusion (EVLP) could impact waitlist morbidity and mortality by increasing the number of transplantable allografts. Remote EVLP with a centralized lung evaluation system (CLES) at a dedicated facility has been shown to be feasible. There are no reports comparing the outcomes of remote vs local EVLP. Our institution has access to both modes of EVLP. Hereby, we describe the outcomes for remote EVLP (r-EVLP) and local EVLP (l-EVLP) at Mayo Clinic Florida. We did a retrospective analysis of the demographics, clinical characteristics, and outcomes of recipients of lungs that underwent EVLP as part of a r-EVLP clinical trial (NCT02234128) or at Lung Bioengineering Jacksonville (l-EVLP) with data obtained from the patient's electronic medical record. The r-EVLP cohort (n=10) tended to be younger than the l-RVLP cohort (n=12) (57.3 vs 61.6 years), and had a lower percentage of female recipients (20% vs 41.67% respectively). 80% of recipients were white in both cohorts. Most recipients were in the diagnosis group D (restrictive lung disease) in both cohorts. Three recipients in the l-EVLP group received a lung transplant due to complications from COVID-19. There were 5 single lung transplants (SLTx) in the r-EVLP (50%) and one in l-EVLP (8.33%). Lungs from donors after circulatory death (DCD) accounted for 40% of the allografts in the r-EVLP cohort and for 16.67% in the l-EVLP group. The median cold ischemia time (CIT) 1 was 5h:27min for the r-EVLP and 4h:35min for l-EVLP. The median CIT-2 time was 4h:16min for the r-EVLP and 3h:12min for the l-EVLP. EVLP time was similar for both groups. The median total preservation time was 13h:44min for the r-EVLP and 11h:38min for the l-EVLP cohorts. One (10%) in the r-EVLP and five (42%) in the l-EVLP groups were on ECMO at 72 hours post-transplant. Most of the remaining patients in both groups had a PGD-1 at 72 hours. All patients were alive at 30 days, and there was one death on each group at 1-year. At our center, survival at 1-year appeared similar in recipients of lungs assessed on r-EVLP or l-EVLP. Postoperative ECMO was used more frequently in the l-EVLP group. Median CIT-1 and CIT-2 were longer in the r-EVLP compared to the l-EVLP group by 52 and 64 minutes, respectively. Limitations of this study include single center retrospective experience, small sample size and lack of long-term outcomes. Future research comparing r-EVLP vs l-EVLP is warranted. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

8.
JMIR Ment Health ; 10: e40899, 2023 Mar 01.
Article in English | MEDLINE | ID: covidwho-2286454

ABSTRACT

BACKGROUND: The COVID-19 pandemic and its associated restrictions have been a major stressor that has exacerbated mental health worldwide. Qualitative data play a unique role in documenting mental states through both language features and content. Text analysis methods can provide insights into the associations between language use and mental health and reveal relevant themes that emerge organically in open-ended responses. OBJECTIVE: The aim of this web-based longitudinal study on mental health during the early COVID-19 pandemic was to use text analysis methods to analyze free responses to the question, "Is there anything else you would like to tell us that might be important that we did not ask about?" Our goals were to determine whether individuals who responded to the item differed from nonresponders, to determine whether there were associations between language use and psychological status, and to characterize the content of responses and how responses changed over time. METHODS: A total of 3655 individuals enrolled in the study were asked to complete self-reported measures of mental health and COVID-19 pandemic-related questions every 2 weeks for 6 months. Of these 3655 participants, 2497 (68.32%) provided at least 1 free response (9741 total responses). We used various text analysis methods to measure the links between language use and mental health and to characterize response themes over the first year of the pandemic. RESULTS: Response likelihood was influenced by demographic factors and health status: those who were male, Asian, Black, or Hispanic were less likely to respond, and the odds of responding increased with age and education as well as with a history of physical health conditions. Although mental health treatment history did not influence the overall likelihood of responding, it was associated with more negative sentiment, negative word use, and higher use of first-person singular pronouns. Responses were dynamically influenced by psychological status such that distress and loneliness were positively associated with an individual's likelihood to respond at a given time point and were associated with more negativity. Finally, the responses were negative in valence overall and exhibited fluctuations linked with external events. The responses covered a variety of topics, with the most common being mental health and emotion, social or physical distancing, and policy and government. CONCLUSIONS: Our results identify trends in language use during the first year of the pandemic and suggest that both the content of responses and overall sentiments are linked to mental health.

9.
EMBO Rep ; 24(4): e56660, 2023 04 05.
Article in English | MEDLINE | ID: covidwho-2265979

ABSTRACT

Interferon-induced transmembrane protein 3 (IFITM3) is an antiviral protein that alters cell membranes to block fusion of viruses. Conflicting reports identified opposing effects of IFITM3 on SARS-CoV-2 infection of cells, and its impact on viral pathogenesis in vivo remains unclear. Here, we show that IFITM3 knockout (KO) mice infected with SARS-CoV-2 experience extreme weight loss and lethality compared to mild infection in wild-type (WT) mice. KO mice have higher lung viral titers and increases in inflammatory cytokine levels, immune cell infiltration, and histopathology. Mechanistically, we observe disseminated viral antigen staining throughout the lung and pulmonary vasculature in KO mice, as well as increased heart infection, indicating that IFITM3 constrains dissemination of SARS-CoV-2. Global transcriptomic analysis of infected lungs shows upregulation of gene signatures associated with interferons, inflammation, and angiogenesis in KO versus WT animals, highlighting changes in lung gene expression programs that precede severe lung pathology and fatality. Our results establish IFITM3 KO mice as a new animal model for studying severe SARS-CoV-2 infection and overall demonstrate that IFITM3 is protective in SARS-CoV-2 infections in vivo.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Mice , COVID-19/genetics , Interferons/genetics , Lung , Mice, Knockout
10.
J Immunol ; 210(9): 1257-1271, 2023 05 01.
Article in English | MEDLINE | ID: covidwho-2280819

ABSTRACT

Vaccines against SARS-CoV-2 that induce mucosal immunity capable of preventing infection and disease remain urgently needed. In this study, we demonstrate the efficacy of Bordetella colonization factor A (BcfA), a novel bacteria-derived protein adjuvant, in SARS-CoV-2 spike-based prime-pull immunizations. We show that i.m. priming of mice with an aluminum hydroxide- and BcfA-adjuvanted spike subunit vaccine, followed by a BcfA-adjuvanted mucosal booster, generated Th17-polarized CD4+ tissue-resident memory T cells and neutralizing Abs. Immunization with this heterologous vaccine prevented weight loss following challenge with mouse-adapted SARS-CoV-2 (MA10) and reduced viral replication in the respiratory tract. Histopathology showed a strong leukocyte and polymorphonuclear cell infiltrate without epithelial damage in mice immunized with BcfA-containing vaccines. Importantly, neutralizing Abs and tissue-resident memory T cells were maintained until 3 mo postbooster. Viral load in the nose of mice challenged with the MA10 virus at this time point was significantly reduced compared with naive challenged mice and mice immunized with an aluminum hydroxide-adjuvanted vaccine. We show that vaccines adjuvanted with alum and BcfA, delivered through a heterologous prime-pull regimen, provide sustained protection against SARS-CoV-2 infection.


Subject(s)
Aluminum Hydroxide , COVID-19 , Humans , Animals , Mice , Immunity, Mucosal , COVID-19 Vaccines , COVID-19/prevention & control , SARS-CoV-2 , Immunization , Adjuvants, Immunologic , Antibodies, Viral , Antibodies, Neutralizing
11.
J Clin Invest ; 2022 Oct 20.
Article in English | MEDLINE | ID: covidwho-2281117

ABSTRACT

SARS-CoV-2 infection in immunocompromised individuals is associated with prolonged virus shedding and evolution of viral variants. Rapamycin and its analogs (rapalogs, including everolimus, temsirolimus, and ridaforolimus) are FDA-approved as mTOR inhibitors for the treatment of human diseases, including cancer and autoimmunity. Rapalog use is commonly associated with increased susceptibility to infection, which has been traditionally explained by impaired adaptive immunity. Here, we show that exposure to rapalogs increases susceptibility to SARS-CoV-2 infection in tissue culture and in immunologically naive rodents by antagonizing the cell-intrinsic immune response. By identifying one rapalog (ridaforolimus) that is less potent in this regard, we demonstrate that rapalogs promote Spike-mediated entry into cells by triggering the degradation of antiviral proteins IFITM2 and IFITM3 via an endolysosomal remodeling program called microautophagy. Rapalogs that increase virus entry inhibit the mTOR-mediated phosphorylation of the transcription factor TFEB, which facilitates its nuclear translocation and triggers microautophagy. In rodent models of infection, injection of rapamycin prior to and after virus exposure resulted in elevated SARS-CoV-2 replication and exacerbated viral disease, while ridaforolimus had milder effects. Overall, our findings indicate that preexisting use of certain rapalogs may elevate host susceptibility to SARS-CoV-2 infection and disease by activating lysosome-mediated suppression of intrinsic immunity.

12.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2653722.v1

ABSTRACT

Background Neurological manifestations have been widely reported in adults with COVID-19, yet the extent of involvement among the pediatric population is currently poorly characterized. The objective of our systematic review is to evaluate the association of SARS-CoV-2 infection with neurological symptoms and neuroimaging manifestations in the pediatric population.Methods A literature search of Cochrane Library; EBSCO CINAHL; Global Index Medicus; OVID AMED, Embase, Medline, PsychINFO; and Scopus was conducted in accordance with the Peer Review of Electronic Search Strategies form (October 1, 2019 to March 15, 2022). Studies were included if they reported (1) COVID-19-associated neurological symptoms and neuroimaging manifestations in individuals aged < 18 years with a confirmed, first SARS-CoV-2 infection and were (2) peer-reviewed. Full-text reviews of 222 retrieved articles were performed, along with subsequent reference searches.Results A total of 843 nonduplicate records were retrieved. Of the 19 identified studies, there were ten retrospective observational studies, seven case series, one case report, and one prospective cohort study. A total of 6,985 individuals were included, where 12.8% of hospitalized patients experienced neurocognitive impairments: MIS-C (24.2%), neuroinflammation (10.1%), and encephalopathy (8.1%) were the most common disorders; headaches (16.8%) and seizures (3.8%) were the most common symptoms. Based on pediatric-specific cohorts, children experienced more drowsiness (7.3% vs. 1.3%) and muscle weakness (7.3% vs. 6.3%) as opposed to adolescents. Agitation or irritability was observed more in children (7.3%) than infants (1.3%).Conclusion Our findings revealed a high prevalence of immune-mediated patterns of disease among COVID-19 positive pediatric patients with neurocognitive abnormalities.


Subject(s)
Headache , Muscle Weakness , Cognitive Dysfunction , Nervous System Diseases , Central Nervous System Diseases , COVID-19 , Seizures , Brain Diseases , Psychomotor Agitation
13.
J Acad Consult Liaison Psychiatry ; 64(2): 118-127, 2023.
Article in English | MEDLINE | ID: covidwho-2244546

ABSTRACT

BACKGROUND: Several studies report the incidence of psychiatric symptoms and disorders among patients who recovered from coronavirus disease 2019 (COVID-19); however, little is known about the emotional impact of acute COVID-19 illness and recovery on these survivors. Qualitative methods are ideal for understanding the psychological impact of a novel illness. OBJECTIVE: To describe the emotional experience of the acute COVID-19 illness and recovery in patients who contracted the virus during the early months of the pandemic. METHODS: Semi-structured interviews conducted by consultation-liaison (C-L) psychiatrists were used to elicit participant responses about the emotional impact of the acute and recovery phases of the COVID-19 illness. Participants recruited from the Maryland, District of Columbia, and Virginia area were interviewed which was audio recorded between June 2020 and December 2020. The research team extracted qualitative themes from the recordings using the principles of thematic analysis. RESULTS: One hundred and one COVID-19 survivors (54 women; mean [SD] age, 50 [14.7] years) were interviewed at a mean of 5.16 months after their acute illness, and their responses were audio-recorded. Most participants were White (77%), non-Hispanic/Latino (86.1%), and not hospitalized for COVID-19 (87.1%). Coders identified 26 themes from participant responses. The most frequently coded themes included anxiety/worry (49), uncertainty (37), supportfrom others (35), alone/isolation (32), and positive reframe/positive emotions (32). CONCLUSIONS: Survivors who contracted severe acute respiratory syndrome coronavirus 2 during the early months of the pandemic described both negative and positive valence emotions. They experienced emotional distress and psychosocial stressors associated with the acute illness and recovery but also drew upon personal resiliency to cope. This report highlights the utility of qualitative research methods in identifying emotional responses to a novel illness that may otherwise go unnoted. Consultation-liaison psychiatrists may be uniquely positioned to work in collaboration with medical colleagues in developing a multidimensional approach to evaluating an emerging illness.


Subject(s)
COVID-19 , Humans , Female , Middle Aged , Pandemics , Acute Disease , Emotions , Qualitative Research
14.
Clin Microbiol Infect ; 29(3): 302-309, 2023 Mar.
Article in English | MEDLINE | ID: covidwho-2242477

ABSTRACT

BACKGROUND: COVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises. OBJECTIVE: We aimed to describe the impact of the COVID-19 pandemic on AMR across health care settings. DATA SOURCE: A search was conducted in December 2021 in WHO COVID-19 Research Database with forward citation searching up to June 2022. STUDY ELIGIBILITY: Studies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted. Reporting of enhanced infection prevention and control and/or antimicrobial stewardship programs was noted. METHODS: Pooling was done separately for Gram-negative and Gram-positive organisms. Random-effects meta-analysis was performed. RESULTS: Of 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n = 25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (incidence rate ratio 0.99, 95% CI: 0.67-1.47) or proportion (risk ratio 0.91, 95% CI: 0.55-1.49) of methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci cases. A non-statistically significant increase was noted for resistant Gram-negative organisms (i.e. extended-spectrum beta-lactamase, carbapenem-resistant Enterobacterales, carbapenem or multi-drug resistant or carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii, incidence rate ratio 1.64, 95% CI: 0.92-2.92; risk ratio 1.08, 95% CI: 0.91-1.29). The absence of reported enhanced infection prevention and control and/or antimicrobial stewardship programs initiatives was associated with an increase in gram-negative AMR (risk ratio 1.11, 95% CI: 1.03-1.20). However, a test for subgroup differences showed no statistically significant difference between the presence and absence of these initiatives (p 0.40). CONCLUSION: The COVID-19 pandemic may have hastened the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. But there is considerable heterogeneity in both the AMR metrics used and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic.


Subject(s)
COVID-19 , Methicillin-Resistant Staphylococcus aureus , Humans , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial , Carbapenems
15.
Am J Respir Cell Mol Biol ; 68(5): 566-576, 2023 05.
Article in English | MEDLINE | ID: covidwho-2228029

ABSTRACT

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a significant public health burden with limited treatment options. Many ß-coronaviruses, including SARS-CoV-2, gain entry to host cells through the interaction of SARS-CoV-2 spike protein with membrane-bound ACE2 (angiotensin-converting enzyme 2). Given its necessity for SARS-CoV-2 infection, ACE2 represents a potential therapeutic target in COVID-19. However, early attempts focusing on ACE2 in COVID-19 have not validated it as a druggable target nor identified other ACE2-related novel proteins for therapeutic intervention. Here, we identify a mechanism for ACE2 protein modulation by the deubiquitinase (DUB) enzyme UCHL1 (ubiquitin carboxyl-terminal hydrolase isozyme L1). ACE2 is constitutively ubiquitinated and degraded by the proteasome in lung epithelia. SARS-CoV-2 spike protein cellular internalization increased ACE2 protein abundance by decreasing its degradation. Using an siRNA library targeting 96 human DUBs, we identified UCHL1 as a putative regulator of ACE2 function as a viral receptor. Overexpressed UCHL1 preserved ACE2 protein abundance, whereas silencing of the DUB in cells destabilized ACE2 through increased polyubiquitination. A commercially available small molecule inhibitor of UCHL1 DUB activity decreased ACE2 protein concentrations coupled with inhibition of SARS-CoV-2 infection in epithelial cells. These findings describe a unique pathway of ACE2 regulation uncovering UCHL1 as a potential therapeutic target to modulate COVID-19 viral entry as a platform for future small molecule design and testing.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Ubiquitin Thiolesterase/metabolism , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Protein Binding
16.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.01.25.524586

ABSTRACT

Cardiovascular sequelae of severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) disease 2019 (COVID-19) contribute to the complications of the disease. One potential complication is lung vascular remodeling, but the exact cause is still unknown. We hypothesized that endothelial TLR3 insufficiency contributes to lung vascular remodeling induced by SARS-CoV-2. In the lungs of COVID-19 patients and SARS-CoV-2 infected Syrian hamsters, we discovered thickening of the pulmonary artery media and microvascular rarefaction, which were associated with decreased TLR3 expression in lung tissue and pulmonary artery endothelial cells (ECs). In vitro, SARS-CoV-2 infection reduced endothelial TLR3 expression. Following infection with mouse-adapted (MA) SARS-CoV-2, TLR3 knockout mice displayed heightened pulmonary artery remodeling and endothelial apoptosis. Treatment with the TLR3 agonist polyinosinic:polycytidylic acid reduced lung tissue damage, lung vascular remodeling, and endothelial apoptosis associated with MA SARS-CoV-2 infection. In conclusion, repression of endothelial TLR3 is a potential mechanism of SARS-CoV-2 infection associated lung vascular remodeling and enhancing TLR3 signaling is a potential strategy for treatment.


Subject(s)
COVID-19 , Vascular Remodeling , Severe Acute Respiratory Syndrome , Addison Disease
17.
iScience ; : 105701, 2022 Dec 02.
Article in English | MEDLINE | ID: covidwho-2131224

ABSTRACT

Influenza A virus (IAV) and SARS-CoV-2 virus are both acute respiratory viruses currently circulating in the human population. This study aims to determine the impact of IAV infection on SARS-CoV-2 pathogenesis and cardiomyocyte function. Infection of human bronchial epithelial cells (HBEC), A549 cells, lung fibroblasts (HLF), monocyte derived macrophages (MDMs), cardiac fibroblasts (HCF) and hiPSC-derived cardiomyocytes with IAV enhanced the expression of ACE2, the SARS-CoV-2 receptor. Similarly, IAV infection increased levels of ACE2 in the lungs of mice and humans. Interestingly, we detected heavily glycosylated form of ACE2 in hiPSC-CMs and poorly glycosylated ACE2 in other cell types. Also, prior IAV infection enhances SARS-CoV-2 spike protein binding and viral entry in all cell types. However, efficient SARS-CoV-2 replication was uniquely inhibited in cardiomyocytes. Glycosylation of ACE2 correlated with enzymatic conversion of its substrate Ang II, induction of eNOS and nitric oxide production, may provide a potential mechanism for the restricted SARS-CoV-2 replication in cardiomyocytes.

18.
J Neurosurg ; : 1-9, 2022 Nov 04.
Article in English | MEDLINE | ID: covidwho-2109667

ABSTRACT

A cancer diagnosis is life altering and frequently associated with both acute and long-lasting psychosocial and behavioral distress for patients. The impact of a diffuse glioma diagnosis on mental health is an important aspect of the patient experience with their disease. This needs to be understood by neurosurgeons so these concerns can be appropriately addressed in a timely fashion and integrated into the multidisciplinary care of neuro-oncology patients. The relatively grave prognosis associated with diffuse gliomas, the morbidity associated with treatment, and the constant threat of developing a new neurological deficit all can negatively affect a patient's mental ability to cope and ultimately manifest in mental health disorders such as anxiety and depression. The objective of this systematic review was to describe the variety of behavioral health disorders patients may experience following a glioma diagnosis and discuss possible treatment options. The PubMed, Web of Science, Embase, and PsycINFO databases were searched through July 1, 2022, using broad search terms, which resulted in 5028 studies that were uploaded to Covidence systematic review software. Duplicates, non-English-language studies, and studies with irrelevant outcomes or incorrect design were removed (n = 3167). A total of 92 articles reporting behavioral health outcomes in brain tumor patients were categorized and extracted for associations with overall mental health, anxiety, depression, distress, stress, pharmacology, interventions, and mental health in caregivers. The authors identified numerous studies reporting the prevalence of mental health disorders and their negative influence in this population. However, there is a paucity of literature on therapeutic options for patients. Given the strong correlation between patient quality of life and mental well-being, there is a considerable need for early recognition and treatment of these behavioral health disorders to optimize everyday functioning for patients.

19.
J Am Coll Health ; : 1-4, 2022 Oct 24.
Article in English | MEDLINE | ID: covidwho-2082231

ABSTRACT

Objective: To examine the associations between coping methods and college adjustment among a sample of U.S. undergraduate students during the COVID-19 pandemic. Participants: We used a sample of 117 undergraduate students between the age of 18-25 years old. Approximately 76% of the sample identified as women and 58% identified as White. Methods: Participants completed online questionnaires that assessed the use of forward-focused coping, trauma-focused coping, and several domains of college adjustment (i.e., academic adjustment, social adjustment, personal-emotional adjustment, and attachment). We used multiple regression to identify the association between coping methods and college adjustment, using race and gender as control variables. Results: Forward-focused coping methods were significantly and positively related to academic adjustment, social adjustment, and attachment, while and trauma-focused coping methods were significantly and negatively related to personal-emotional adjustment. Conclusions: The use of forward-focused coping methods may be beneficial for undergraduate students during the COVID-19 pandemic.

20.
Chest ; 162(4):A87-A88, 2022.
Article in English | EMBASE | ID: covidwho-2060538

ABSTRACT

SESSION TITLE: Rare Cases in Cardiothoracic Surgery SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Membranous dehiscence after tracheal resection is an uncommon but deadly complication. It may present acutely with loss of airway, insidiously with progressive stridor, infection or subcutaneous emphysema, or asymptomatically. Treatment may be conservative if the separation is minimal but may require re-exploration if the defect is more severe. The extent of dehiscence amenable to conservative treatment is not well described in the literature. This case report describes the conservative treatment of a posterior membrane dehiscence. CASE PRESENTATION: A 50-year-old woman suffered from stridor due to tracheal stenosis after prolonged intubation from COVID-19. Endobronchial treatments were unsuccessful because of a malacic segment of airway. Via a cervical approach, approximately 2cm of malacic trachea was resected. Reconstruction was performed with a running suture of the posterior membrane and interrupted, figure-of-eight sutures of the anterior trachea. On postoperative day 5, the patient developed subcutaneous emphysema. A CT scan was obtained (Figure 1A), demonstrating disruption of the membranous portion of the anastomosis. As the patient's breathing was not affected, conservative treatment was preferred. She was encouraged to maintain her neck in a flexed position while continuously monitored with a pulse oximeter and treated with intravenous and aerosolized antibiotics. A repeat CT scan was obtained one week after (Figure 1B), showing no residual tracheal wall defect. Postoperative bronchoscopy showed that the posterior membrane had healed entirely. She remains asymptomatic on follow-up visits. DISCUSSION: Wound dehiscence after tracheal resection and reconstruction occurs in about 1-4% of the cases (1, 2), and it is associated with a significant morbidity and a 0.6% chance of mortality (1). We believe the membranous anastomosis failed because the posterior membrane was inflamed and adhered to the esophagus during the index operation. We did not want to perform a bronchoscopy in this situation, as positioning and coughing could exacerbate the dehiscence. As her breathing was unaffected at this point, we debated between a conservative or invasive approach. Conservative management is preferred for small defects and mild symptoms (3), but there is sparse further elaboration in the literature. Because the cartilaginous anastomosis appeared intact and she was breathing spontaneously, we decided to treat conservatively with expectant management. This included aggressive treatment with antibiotics to avoid infection and further anastomotic breakdown. More examples are needed to establish the likelihood of success with conservative treatment versus revisional surgery for partial dehiscence. CONCLUSIONS: Dehiscence after tracheal resection increases morbidity and mortality significantly. This is an example of a posterior membrane dehiscence that resolved spontaneously with conservative measures. Reference #1: Stock C, Gukasyan N, Muniappan A, Wright C, Mathisen D. Hyperbaric oxygen therapy for the treatment of anastomotic complications after tracheal resection and reconstruction. J Thorac Cardiovasc Surg. 2014;147(3):1030-5. Reference #2: Young A, Bigcas JLM. Tracheal Resection. [Updated 2022 Feb 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK563234/. Reference #3: Auchincloss HG, Wright CD. Complications after tracheal resection and reconstruction: prevention and treatment. J Thorac Dis. 2016;8(Suppl 2):S160-7. DISCLOSURES: No relevant relationships by Rocio Castillo-Larios No relevant relationships by Magdy El-Sayed Ahmed No relevant relationships by Sebastian Fernandez-Bussy No relevant relationships by daniel hernandez No relevant relationships by Samuel Jacob No relevant relationships by Ian Makey No relevant relationships by Sai Priyanka Pulipaka No relevant relationships b Mathew Thomas No relevant relationships by Alejandra Yu Lee-Mateus

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