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1.
Heliyon ; : e13090, 2023.
Article in English | ScienceDirect | ID: covidwho-2179059

ABSTRACT

Objective During the coronavirus disease 2019 (COVID-19) pandemic, an increased mental burden has been widely reported among medical health workers such as physicians and nurses. However, data on laboratory technicians exposed to COVID-19 have rarely been published. The aim of this study was to assess the magnitude of psychological symptoms among laboratory technicians and analyze potential risk factors associated with these symptoms. Methods A cross-sectional online survey was performed via the Wenjuanxing platform (a professional online questionnaire platform) (https://www.wjx.cn/mobile/statnew.aspx) to investigate the mental health of laboratory technicians during the COVID-19 pandemic in Hebei, China from October 4, 2021, to November 3, 2021. The online questionnaire included demographic and occupational characteristics data of responders, and the Symptom Check List-90-Revised (SCL90-R)was used to quantify the magnitude of psychological symptoms among laboratory technicians. Participants' demographic and occupational characteristics were analyzed using descriptive statistical analyses. Chi-square tests were applied to compare the severity of each symptom between two or more groups. A binary logistic regression model was developed to identify the predictors of laboratory technicians' mental health in response to the COVID-19 pandemic, and outcomes are presented as odds ratios and 95% confidence interval. Statistical analysis was performed using SPSS version 21 (SPSS, New Orchard Road, Armonk, New York, USA). Results A total of 3081 valid questionnaires were collected. Of these 3081 participants, 338 (11.0%) reported a total SCL90-R score >160, which indicated positive psychological symptoms. Among the 338 participants who reported psychological problems, most of them were mild symptoms. Several factors associated with mental health problems in laboratory technicians during COVID-19 were found, which include a history of physical and/or psychological problems (all 10 symptoms p < 0.001), more than 10 years of work experience (depression symptoms: OR = 2.350, p = 0.024;anxiety symptoms: OR = 2.642, p = 0.038), frontline work (depression symptoms: OR = 1.761, p = 0.001;anxiety symptoms: OR = 2.619, p < 0.001;hostility symptoms: OR = 1.913, p = 0.001), participant in more than 3 times large-scale SARS-CoV-2 screenings and more than 36 h per week in SARS-CoV-2 nucleic acid testing. Conclusion A portion of laboratory technicians reported experiencing varying levels of psychological burden. During the COVID-19 pandemic, multiple interventions should be developed and implemented to address existing psychosocial challenges and promote the mental health of laboratory technicians.

3.
International Journal of Infectious Diseases ; 2022.
Article in English | ScienceDirect | ID: covidwho-2149855

ABSTRACT

Objective To describe the full scope of long-term outcomes and the ongoing pathophysiological alterations among the COVID-19 survivor. Methods We established a longitudinal cohort of 208 COVID-19 convalescents and followed them at 3.3 (IQR: 1.3, 4.4, visit 1), 9.2 (IQR: 9.0, 9.6, visit 2), and 18.5 (IQR: 18.2, 19.1, visit 3) months after infection, respectively. Serial changes in multiple physical and psychological outcomes were comprehensively characterized. We additionally explored the potential risk factors of SARS-CoV-2 antibody response and sequelae symptoms. Results We observed continuous improvement of sequelae symptoms, lung function, chest CT, 6-minute walk test, and the Borg dyspnoea scale, whereas sequelae symptoms (at least one) and abnormal chest CT patterns still existed in 45.2% and about 30% of the patients at 18.5 months, respectively. Both anxiety and depression disorders were alleviated for the convalescents, although the depression status was sustained for a longer duration. Conclusions Most COVID-19 convalescents had an overall improved physical and psychological health status, whereas sequelae symptoms, residual lesions on lung function, exercise impairment, and mental health disorders were still observed in a small proportion of the participants at 18.5 months after infection. Implementing appropriate preventive and management strategies for the ever-growing COVID-19 population is warranted.

4.
Composites Part B: Engineering ; : 110463, 2022.
Article in English | ScienceDirect | ID: covidwho-2149593

ABSTRACT

Carbon fibre and carbon fibre reinforced polymer matrix composites (CFRPs) are important lightweight materials for aerospace, automotive, rail transport, infrastructure, and renewable energy applications. This paper provides a comprehensive review on the history of carbon fibres and carbon fibre composites, the current global CFRPs consumption, and trends for future developments in the aerospace, wind turbine, automotive, pressure vessels, sports and leisure, and construction sectors. The history of carbon fibres and CFRPs is discussed over four representative periods including their early development (1950–60's), growth of carbon fibre composites industry (1970–80's), major adoption of carbon fibre composites (the first wave, 1990–2000's), and expanded use of carbon fibre composites (the second wave, 2010's and beyond). Despite a 37% decline of carbon fibre consumption in the aerospace industry in 2021 caused by COVID-19, the global CFRP demand was around 181 kt which more than doubled its value in 2014. There is tangible projected increase over the next five years and the demand for CFRPs is expected to reach 285 kt in 2025, mainly attributed from the fast expansion of non-aerospace industries such as the wind energy sector. Lower cost carbon fibres (e.g., large tow) and associated manufacturing technologies are continually evolving. Finally, the implications of emerging materials and manufacturing methods in conjunction with recycling and reuse for carbon fibre composites are discussed.

5.
BMC Med Educ ; 22(1): 813, 2022 Nov 28.
Article in English | MEDLINE | ID: covidwho-2139262

ABSTRACT

BACKGROUND: The lack of interaction and communication in pharmacology courses, especially since the onset of the coronavirus disease 2019 (COVID-19) pandemic, which required a fast shift to remote learning at medical schools, leads to an unsatisfactory learning outcome. New interactive teaching approaches are required to improve pharmacology learning attention and interaction in remote education and traditional classrooms. METHODS: We introduced bullet screens to pharmacology teaching. Then, a survey was distributed to first-, second- and third-year pre-clinical undergraduate medical and nursing students at the Shanghai Jiao Tong University School of Medicine from November 2020 to March 2022. We evaluated the essential features, instructional effectiveness, and entertainment value of bullet screens. Responses to structured and open-ended questions about the strengths and weaknesses of the bullet screen and overall thoughts were coded and compared between medical and nursing students. RESULTS: In terms of essential features, bullet screens have a high degree of acceptability among students, and this novel instructional style conveniently increased classroom interaction. Considering instructional effectiveness, bullet screen may stimulate students' in-depth thinking. Meanwhile, students tended to use bullet-screen comments as a way to express their support rather than to make additional comments or to express their different viewpoints. The entertainment value of bullet screen was noteworthy. The lack of ideas might lead to relative differences between medical and nursing students, indicating that guiding the appropriate use of bullet screen is necessary. CONCLUSIONS: The bullet screen may be popularized as an auxiliary teaching approach to promote interaction between teachers and students in the classroom as well as during remote education. It is an interesting and beneficial tool in pharmacology courses, yet there are several aspects of this device that should be improved for popularization.


Subject(s)
COVID-19 , Medicine , Students, Nursing , Humans , China , Schools, Medical
6.
Frontiers in psychiatry ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2124851

ABSTRACT

Objective To evaluate the effect of mindfulness intervention on improving mental health among undergraduate nursing students during the coronavirus disease 2019 (COVID-19) pandemic in China. Methods An online mindfulness intervention course named Mindfulness Living With Challenge (MLWC) was developed by the research team, and a randomized controlled trial using MLWC among Chinese undergraduate nursing students was carried out. A total of 120 undergraduate nursing students were randomized into control (60 students) and intervention groups (60 students) via a WeChat mini program. Self-administered questionnaire surveys were conducted at pre- and post-intervention, measuring depression, anxiety, stress, mindfulness, and perceived social support. After intervention, the acceptance of the online mindfulness course among participants was assessed by employing the theory of technology acceptance model (TAM). Results Among the enrolled 120 participants, 86.67% (52/60) and 93.33% (56/60) of the intervention and control groups remained completed the trial and the questionnaire surveys. Compared with the control group, the reduction of anxiety and stress symptoms, as well as the improvement of mindfulness level and perceived social support in the MLWC intervention group were statistically significant (P < 0.05), while the change in depression was not statistically significant. The scores of the four dimensions in TAM ranged from (5.88 ± 0.94) to (5.91 ± 0.97). Conclusion Online mindfulness intervention implemented in this study is effective in improving mental health among undergraduate nursing students, and they were interested in this intervention. Clinical trial registration [www.ClinicalTrials.gov], identifier [ChiCTR2 200058103].

7.
PLoS One ; 17(11): e0276608, 2022.
Article in English | MEDLINE | ID: covidwho-2119220

ABSTRACT

OBJECTIVES: This study is intended to assess the prevalence of depression and anxiety in individuals who had recovered from COVID-19 and been discharged from hospital (RD hereafter) in Wuhan, China, and to explore the factors associated with these mental disorders. METHODS: Participants of this study were the RD who were infected at the beginning of the outbreak from 13 communities in Jianghan District of Wuhan City, Hubei Province, China by convenience sampling in mid-2021. The Generalized Anxiety Disorder Questionnaire, the Patient Health Questionnaire, the Short Version of COVID-19 Stigma Scale, the Peace of Mind Scale, the Resilience Style Questionnaire, and the Perceived Social Support Questionnaire were used to collect relevant information of the participants. Descriptive analyses, Pearson correlation analysis, and logistic regression analysis were used to describe and analyze the data and to examine the factors associated with the mental health status of this population. RESULTS: In total, we recruited 1601 participants from 3059 COVID-19 patients, and 1541 participants completed the questionnaire survey, with a response rate of 96.25%. Finally, 1297 participants met the inclusion and exclusion criteria in this study, of whom 28.8% and 37.9% reported mild to severe levels of anxiety and depression symptoms. Perceived better mental health status during hospitalization, higher frequency of alcohol use per week, peace of mind, higher education level, and resilience were negatively associated with anxiety, while stigma and history of psychological or emotional counseling before infection was positively associated with anxiety. More severe clinical classification of COVID-19 and stigma (AOR = 1.057, P<0.001) were both positively associated with depression, while perceived better mental health status during hospitalization (AOR = 0.564, P<0.001), higher frequency of alcohol use per week (AOR = 0.462, P = 0.004), peace of mind (AOR = 0.857, P<0.001), and social support (AOR = 0.972, P = 0.034) were negatively associated with depression. CONCLUSIONS: Tailored interventions on reducing stigma, enhancing mindfulness and social support should be taken into account to alleviate anxiety and depression among RD.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , SARS-CoV-2 , Patient Discharge , Cross-Sectional Studies , Anxiety/epidemiology , Anxiety/psychology , Anxiety Disorders , Surveys and Questionnaires , China/epidemiology
9.
Journal of Ethnopharmacology ; : 115853, 2022.
Article in English | ScienceDirect | ID: covidwho-2082427

ABSTRACT

Ethnopharmacological relevance Scutellaria baicalensis Georgi. contains varieties of function compounds, and it has been used as traditional drug for centuries. Baicalein is the highest amount of flavonoid found in Scutellaria baicalensis Georgi., which exerts various pharmacological activities and might be a promising drug to treat COVID-19. Aim of the study The present work aims to investigate the metabolism of baicalein in humans after oral administrations, and study the pharmacokinetics of BA and its seven metabolites in plasma and urine. Materials and methods The metabolism profiling and the identification of baicalein metabolites were performed on HPLC-Q-TOF. Then a column-switching method named MPX™-2 system was applied for the high-throughput determination of BA and seven metabolites. Results Seven metabolites were identified using HPLC-Q-TOF, including sulfate, glucuronide, glucoside, and methyl-conjugated metabolites. Pharmacokinetic study found that BA was extensively metabolized in vivo, and only 5.65% of the drug remained intact in the circulatory system after single dosing. Baicalein-7-O-sulfate and baicalein-6-O-glucuronide-7-O-glucuronide were the most abundant metabolites. About 7.2% of the drug was excreted through urine and mostly was metabolites. Conclusion Seven conjugated metabolites were identified in our assay. A high-throughput HPLC-MS/MS method using column switch was established for quantifying BA and its metabolites. The method has good sensitivity and reproducibility, and successfully applied for the clinical pharmacokinetic study of baicalein and identified metabolites. We expect that our results will provide a metabolic and pharmacokinetic foundation for the potential application of baicalein in medicine.

10.
11.
Frontiers in pharmacology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2073353

ABSTRACT

Patients with colon adenocarcinoma (COAD) are at a higher probability of infection with COVID-19 than healthy individuals. However, there is no globally accepted treatment protocol for patients with COAD/COVID-19. Quercetin has been found to have significant antitumor, antiviral and anti-inflammatory effects in several studies. Therefore, this study sought to evaluate the potential of quercetin as the agent for COAD/COVID-19 and to explore its mechanisms. We used bioinformatics algorithms to obtain COAD/COVID-19-related genes (CCRG) from COAD-related transcriptome data and COVID-related transcriptome sequencing data, and used these genes to construct a COAD prognostic model. We intersected the CCRG with the therapeutic target genes of quercetin and obtained a total of 105 genes (potential target genes of quercetin for the treatment of COAD/COVID-19). By constructing a protein-protein interaction (PPI) network, we ascertained FOS, NFKB1, NFKB1A, JUNB, and JUN as possible core target genes of quercetin for the treatment of COAD/COVID-19. Bioinformatic analysis of these 105 genes revealed that the mechanisms for quercetin the treatment of COAD/COVID-19 may be associated with oxidative stress, apoptosis, anti-inflammatory, immune, anti-viral and multiple pathways containing IL-17, TNF, HIF-1. In this study, we constructed a prognostic model of COAD/COVID19 patients by using CCRG and elucidated for the first time the potential target genes and molecular mechanisms of quercetin for the treatment of COAD/COVID-19, which may benefit the clinical treatment of COAD/COVID-19 patients. However, no clinical trials have yet been conducted to further validate the findings, but this will be the future direction of our research.

12.
BMC Infect Dis ; 22(1): 765, 2022 Oct 01.
Article in English | MEDLINE | ID: covidwho-2053871

ABSTRACT

BACKGROUND: COVID-19 vaccines have been administered in many countries; however, a sufficient vaccine coverage rate is not guaranteed due to vaccine hesitancy. To improve the uptake rate of COVID-19 vaccine, it is essential to evaluate the rate of vaccine hesitancy and explore relevant factors in different populations. An urgent need is to measure COVID-19 vaccine hesitancy among different population groups, hence a validated scale for measuring COVID-19 vaccine hesitancy is necessary. The present study aims to validate the COVID-19 vaccine hesitancy scale among different populations in China and to provide a scale measuring COVID-19 vaccine hesitancy with satisfactory reliability and validity. METHODS: Self-reported survey data were collected from different populations in China from January to March 2021. Based on the Parent Attitudes about Childhood Vaccines scale, 15 items were adapted to evaluate the COVID-19 vaccine hesitancy. Exploratory and confirmatory factor analysis were utilized to identify internal constructs of the COVID-19 vaccine hesitancy scale among two randomly split subsets of the overall sample. Reliability was analyzed with the internal consistency, composite reliability, and the test-retest reliability, and validity was analyzed with the criterion validity, convergent validity, and discriminant validity. RESULTS: A total of 4227 participants completed the survey, with 62.8% being medical workers, 17.8% being students, 10.3% being general population, and 9.1% being public health professionals. The exploratory factor analysis revealed a three-factor structure that explain 50.371% of the total variance. The confirmatory factor analysis showed that models consisting of three dimensions constructed in different populations had good or acceptable fit (CFI ranged from 0.902 to 0.929, RMSEA ranged from 0.061 to 0.069, and TLI ranged from 0.874 to 0.912). The Cronbach's α for the total scale and the three subscales was 0.756, 0.813, 0.774 and 0.705, respectively. Moreover, the COVID-19 vaccine hesitancy scale had adequate test-retest reliability, criterion validity, convergent validity, and discriminant validity. CONCLUSIONS: The COVID-19 vaccine hesitancy scale is a valid and reliable scale for identifying COVID-19 vaccine hesitancy among different population groups in China. Given the serious consequences of COVID-19 vaccine hesitancy, future studies should validate it across regions and time to better understand the application of the COVID-19 vaccine hesitancy scale.


Subject(s)
COVID-19 , Vaccines , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Child , China , Cross-Sectional Studies , Humans , Psychometrics/methods , Reproducibility of Results , Surveys and Questionnaires , Vaccination Hesitancy
13.
Lancet Microbe ; 3(6): e427-e434, 2022 06.
Article in English | MEDLINE | ID: covidwho-2050134

ABSTRACT

BACKGROUND: A dengue pre-vaccination test that is convenient, highly specific, and highly sensitive is still needed. The OnSite Dengue IgG rapid diagnostic test (RDT) is a new rapid diagnostic test specifically designed for pre-vaccination screening. We aimed to retrospectively assess the efficacy of a tetravalent dengue vaccine (CYD-TDV) in participants determined to be dengue seropositive by the OnSite IgG RDT and to evaluate assay performances. METHODS: This was a complementary study using pre-vaccination samples from two CYD-TDV efficacy trials done in five countries in the Asia-Pacific region (NCT01373281) and five countries in Latin America (NCT01374516). Baseline dengue serostatus was determined by the OnSite IgG RDT on samples from the immunogenicity subsets of the two trials. In participants who were test positive, we calculated CYD-TDV vaccine efficacy against symptomatic virologically confirmed dengue (VCD) over 25 months, and against hospitalisation with VCD over 72 months of follow-up after the first vaccination. We used a reference algorithm to determine the reference dengue serostatus for each sample, and sensitivity and specificity of the OnSite IgG RDT were calculated. Analyses were done on the whole population (aged 2-16 years), and on those aged 6 years or older and those aged 9 years or older. FINDINGS: Of 3983 participants in the immunogenicity subsets of the efficacy trials CYD14 and CYD15, 3962 had complete dengue reference test results enabling baseline serostatus classification and 3833 had sufficient serum samples remaining for evaluation with the OnSite IgG RDT. Of the samples tested, 2486 (64·9%) of 3833 were OnSite IgG RDT-positive. In participants aged 2-16 years who were OnSite IgG RDT-positive, vaccine efficacy was 84·1% (95% CI 71·6-91·1) against symptomatic VCD, and 69·2% (38·8-84·5) against hospitalisation with VCD, with similar findings in those aged 6 years or older and those aged 9 years or older. The OnSite IgG RDT showed very high sensitivity (91·1%, 89·9-92·1) and high specificity (92·8%, 91·2-94·2) in participants aged 2-16 years, with significantly higher specificity in those aged 9 years or older (96·6%, 94·9-97·8). INTERPRETATION: The OnSite IgG RDT should provide a valuable tool for screening for previous dengue infection at the point of vaccination. In individuals who were OnSite IgG RDT-positive, the vaccine efficacy of CYD-TDV was high across all three age groups. FUNDING: Sanofi Pasteur.


Subject(s)
Biomedical Research , Dengue Vaccines , Dengue Virus , Dengue , Antibodies, Viral , Dengue/diagnosis , Humans , Immunoglobulin G , Retrospective Studies , Vaccination , Vaccines, Combined
14.
Pacific-Basin Finance Journal ; 75:101855, 2022.
Article in English | ScienceDirect | ID: covidwho-2042070

ABSTRACT

This research investigates the role that China's monetary policy has played in maintaining financial stability after crises in the 21st century. We construct a financial stability index (FSI) with eight variables from four characteristics that reflect variations in the financial stability of China, and analyze the dynamic impacts of China's monetary policies on financial stability with a time-varying parameter vector-autoregressive (TVP-VAR) model. The three major crises that China has been involved in the past 15 years (i.e., the 2008 global financial crisis, 2015 stock market crash in China, and the ongoing COVID-19 crisis) indicate that the scale of social financing, stock market performance, and the degree of financial deepening in China have great influences on financial stability. We observe supportive evidence, moreover, that both quantitative and price-based monetary policies can promote financial stability after crises in China, especially in the short term. The quantitative policy is more effective than price-based monetary policy and has become the main policy tool in China. At a time when the world economy is still suffering from the COVID-19 crisis, the quick economic recovery is an imperative task for all countries. It is of great theoretical and practical significance to understand the relationship between monetary policy and financial stability after crises.

15.
J Affect Disord ; 319: 437-445, 2022 Dec 15.
Article in English | MEDLINE | ID: covidwho-2041887

ABSTRACT

BACKGROUND: In the global pandemic of the coronavirus disease 2019 (COVID-19), depression and post-traumatic stress disorder (PTSD) have commonly occurred among COVID-19 patients, whose experiences of infection and subsequent treatment might develop negative consequences on their mental well-being even after recovery. Despite the general recognition of efficacy of mindfulness-based interventions in reducing psychological distress among various populations, there were insufficient studies on the relationship between mindfulness and mental health among individuals who have recovered from COVID-19. OBJECTIVE: The current study aims to identify the prevalence of common mental health challenges among recovered COVID-19 patients in Jianghan District, Wuhan, China and to explore the potential mechanism through which mindfulness alleviate depression and PTSD. METHODS: A cross-sectional survey on mental health was conducted among a convenience sample of adults recovered from COVID-19 in Jianghan District, Wuhan, China. The study participants completed questionnaires under the assistance of trained investigators. The questionnaire included Chinese version of Five Facets of Mindfulness Questionnaire-Short Form (FFMQ-SF), Generalized Anxiety Disorder Questionnaire (GAD-7), Resilience Style Questionnaire (RSQ), Impact of Events Scale-Revised (IES-R), and Patient Health Questionnaire (PHQ-9) to measure mindfulness, anxiety, resilience, PTSD, and depression respectively. Structural equation modeling was used to explore the relationship between mindfulness and mental health outcomes of this population. RESULTS: 1541 respondents (654 [42.4 %] men and 887 [57.6 %] women) completed the questionnaire between June 10 and July 25, 2021, of whom 36.2 % and 27.1 % had mild and severe levels of depressive and anxiety symptoms respectively, and 15.2 % was indicated with PTSD. The average score of mindfulness of the study participants was (3.100 ± 0.387), and that of resilience was (3.560 ± 0.877). The structural equation model fit the data well, demonstrating that mindfulness was negatively associated with depressive symptoms directly (ß = -0.031, P = 0.021) or indirectly through the mediation effect of resilience (ß = -0.019, P = 0.009) and anxiety symptoms (ß = -0.208, P < 0.001), and was negatively associated with PTSD through the mediation effect of anxiety symptoms (ß = -0.142, P < 0.001). CONCLUSION: Individuals who have recovered from COVID-19 commonly experienced psychological distress. Mindfulness is associated with alleviation of depressive and PTSD symptoms directly or indirectly. Interventions based on mindfulness are suggested to improve the mental well-being of this population.


Subject(s)
COVID-19 , Mindfulness , Adult , Male , Humans , Female , COVID-19/epidemiology , Cross-Sectional Studies , SARS-CoV-2 , Depression/epidemiology , Depression/therapy , Depression/psychology , Anxiety/epidemiology , Anxiety/therapy , Anxiety/psychology , China/epidemiology
16.
Anticancer Drugs ; 33(8): 773-777, 2022 09 01.
Article in English | MEDLINE | ID: covidwho-2032194

ABSTRACT

The erb-b2 receptor tyrosine kinase 2 (ERBB2), also known as HER2, has long been recognized as an oncogenic driver in some breast and gastroesophageal cancers, and ERBB2-targeted therapies are standard for ERBB2-positive breast and gastric cancer. However, there are currently no standard therapies targeting the ERBB2 pathway in non-small cell lung cancer. Recently, somatic mutations in ERBB2 have been reported in 2-3% of patients with advanced lung adenocarcinoma, these mutations are trans-forming in lung cancer models and result in kinase activation, conferring some in-vitro sensitivity to trastuzumab. The ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate composed of trastuzumab joined via a stable linker to DM1. In this report, a 67-year-old male patient was diagnosed with advanced lung adenocarcinoma with multiple lymph node metastases, and multi-chemotherapy and immunotherapy were not effective. The results of genetic testing indicated a non-frameshift insertion mutation in exon 20 of the ERBB2 gene. The patients received T-DM1 at a dose of 3.6 mg/kg by intravenous infusion every 21 days until for 12 cycles. Partial response appeared in the tumor lesions after treatment for four cycles, and PET-computer tomography showed the tumor lesions were effectively controlled, and the efficacy evaluation was complete response after treatment for six cycles. Although the patient experienced second degree of thrombocytopenia during the treatment, the corresponding symptomatic treatment was taken, and the platelets could return to normal before the next cycle of T-DM1. Follow-up review showed the patient is in good health and the tumor has not recurred.


Subject(s)
Adenocarcinoma of Lung , Breast Neoplasms , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Maytansine , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Ado-Trastuzumab Emtansine , Aged , Breast Neoplasms/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Male , Maytansine/therapeutic use , Mutation , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Trastuzumab/therapeutic use
17.
Commun Biol ; 5(1): 958, 2022 09 14.
Article in English | MEDLINE | ID: covidwho-2028733

ABSTRACT

Hydroxychloroquine (HCQ), a drug used to treat lupus and malaria, was proposed as a treatment for SARS-coronavirus-2 (SARS-CoV-2) infection, albeit with controversy. In vitro, HCQ effectively inhibits viral entry, but its use in the clinic has been hampered by conflicting results. A better understanding of HCQ's mechanism of actions in vitro is needed. Recently, anesthetics were shown to disrupt ordered clusters of monosialotetrahexosylganglioside1 (GM1) lipid. These same lipid clusters recruit the SARS-CoV-2 surface receptor angiotensin converting enzyme 2 (ACE2) to endocytic lipids, away from phosphatidylinositol 4,5 bisphosphate (PIP2) clusters. Here we employed super-resolution imaging of cultured mammalian cells (VeroE6, A549, H1793, and HEK293T) to show HCQ directly perturbs clustering of ACE2 receptor with both endocytic lipids and PIP2 clusters. In elevated (high) cholesterol, HCQ moves ACE2 nanoscopic distances away from endocytic lipids. In cells with resting (low) cholesterol, ACE2 primarily associates with PIP2 clusters, and HCQ moves ACE2 away from PIP2 clusters-erythromycin has a similar effect. We conclude HCQ inhibits viral entry through two distinct mechanisms in high and low tissue cholesterol and does so prior to inhibiting cathepsin-L. HCQ clinical trials and animal studies will need to account for tissue cholesterol levels when evaluating dosing and efficacy.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Animals , COVID-19/drug therapy , Cell Culture Techniques , Cholesterol , HEK293 Cells , Humans , Hydroxychloroquine/pharmacology , Lipids , Mammals , Peptidyl-Dipeptidase A , SARS-CoV-2
18.
Cells ; 11(16)2022 08 22.
Article in English | MEDLINE | ID: covidwho-2023200

ABSTRACT

Obesity is of concern to the population because it is known to cause inflammation and oxidative stress throughout the body, leading to patient predisposition for health conditions such as diabetes, hypertension, and some cancers. However, some proteins that are activated in times of oxidative stress may provide cytoprotective properties. In this study, we aim to gain further understanding of the interconnection between Nrf2 and Sesn2 during obesity-related stress and how this relationship can play a role in cardio-protection. Cardiomyocyte-specific Sesn2 knockout (cSesn2-/-) and Sesn2 overexpressed (tTa-tet-Sesn2) mice and their wildtype littermates (Sesn2flox/flox and tet-Sesn2, respectively) were assigned to either a normal chow (NC) or a high-fat (HF) diet to induce obesity. After 16 weeks of dietary intervention, heart function was evaluated via echocardiography and cardiac tissue was collected for analysis. Immunoblotting, histology, and ROS staining were completed. Human heart samples were obtained via the LifeLink Foundation and were also subjected to analysis. Overall, these results indicated that the overexpression of Sesn2 appears to have cardio-protective effects on the obese heart through the reduction of ROS and fibrosis present in the tissues and in cardiac function. These results were consistent for both mouse and human heart samples. In human samples, there was an increase in Sesn2 and Nrf2 expression in the obese patients' LV tissue. However, there was no observable pattern of Sesn2/Nrf2 expression in mouse LV tissue samples. Further investigation into the link between the Sesn2/Nrf2 pathway and obesity-related oxidative stress is needed.


Subject(s)
Heart Diseases , NF-E2-Related Factor 2 , Animals , Diet, High-Fat , GA-Binding Protein Transcription Factor , Humans , Mice , NF-E2-Related Factor 2/metabolism , Nuclear Proteins/metabolism , Obesity , Reactive Oxygen Species/metabolism , Sestrins
19.
Front Mol Biosci ; 9: 976705, 2022.
Article in English | MEDLINE | ID: covidwho-2022800

ABSTRACT

The antimicrobial resistance (AMR) crisis from bacterial pathogens is frequently emerging and rapidly disseminated during the sustained antimicrobial exposure in human-dominated communities, posing a compelling threat as one of the biggest challenges in humans. The frequent incidences of some common but untreatable infections unfold the public health catastrophe that antimicrobial-resistant pathogens have outpaced the available countermeasures, now explicitly amplified during the COVID-19 pandemic. Nowadays, biotechnology and machine learning advancements help create more fundamental knowledge of distinct spatiotemporal dynamics in AMR bacterial adaptation and evolutionary processes. Integrated with reliable diagnostic tools and powerful analytic approaches, a collaborative and systematic surveillance platform with high accuracy and predictability should be established and implemented, which is not just for an effective controlling strategy on AMR but also for protecting the longevity of valuable antimicrobials currently and in the future.

20.
J Math Biol ; 85(3): 23, 2022 08 20.
Article in English | MEDLINE | ID: covidwho-2014120

ABSTRACT

Nonmonotone incidence and saturated treatment are incorporated into an SIRS model under constant and changing environments. The nonmonotone incidence rate describes the psychological or inhibitory effect: when the number of the infected individuals exceeds a certain level, the infection function decreases. The saturated treatment function describes the effect of infected individuals being delayed for treatment due to the limitation of medical resources. In a constant environment, the model undergoes a sequence of bifurcations including backward bifurcation, degenerate Bogdanov-Takens bifurcation of codimension 3, degenerate Hopf bifurcation as the parameters vary, and the model exhibits rich dynamics such as bistability, tristability, multiple periodic orbits, and homoclinic orbits. Moreover, we provide some sufficient conditions to guarantee the global asymptotical stability of the disease-free equilibrium or the unique positive equilibrium. Our results indicate that there exist three critical values [Formula: see text] and [Formula: see text] for the treatment rate r: (i) when [Formula: see text], the disease will disappear; (ii) when [Formula: see text], the disease will persist. In a changing environment, the infective population starts along the stable disease-free state (or an endemic state) and surprisingly continues tracking the unstable disease-free state (or a limit cycle) when the system crosses a bifurcation point, and eventually tends to the stable endemic state (or the stable disease-free state). This transient tracking of the unstable disease-free state when [Formula: see text] predicts regime shifts that cause the delayed disease outbreak in a changing environment. Furthermore, the disease can disappear in advance (or belatedly) if the rate of environmental change is negative and large (or small). The transient dynamics of an infectious disease heavily depend on the initial infection number and rate or the speed of environmental change.


Subject(s)
Disease Outbreaks , Systemic Inflammatory Response Syndrome , Humans , Incidence , Models, Biological
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