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1.
Acc Chem Res ; 54(21): 4001-4011, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1475239

ABSTRACT

Since the U.S. Food and Drug Administration (FDA) granted emergency use authorization for two mRNA vaccines against SARS-CoV-2, mRNA-based technology has attracted broad attention from the scientific community to investors. When delivered intracellularly, mRNA has the ability to produce various therapeutic proteins, enabling the treatment of a variety of illnesses, including but not limited to infectious diseases, cancers, and genetic diseases. Accordingly, mRNA holds significant therapeutic potential and provides a promising means to target historically hard-to-treat diseases. Current clinical efforts harnessing mRNA-based technology are focused on vaccination, cancer immunotherapy, protein replacement therapy, and genome editing. The clinical translation of mRNA-based technology has been made possible by leveraging nanoparticle delivery methods. However, the application of mRNA for therapeutic purposes is still challenged by the need for specific, efficient, and safe delivery systems.This Account highlights key advances in designing and developing combinatorial synthetic lipid nanoparticles (LNPs) with distinct chemical structures and properties for in vitro and in vivo intracellular mRNA delivery. LNPs represent the most advanced nonviral nanoparticle delivery systems that have been extensively investigated for nucleic acid delivery. The aforementioned COVID-19 mRNA vaccines and one LNP-based small interfering RNA (siRNA) drug (ONPATTRO) have received clinical approval from the FDA, highlighting the success of synthetic ionizable lipids for in vivo nucleic acid delivery. In this Account, we first summarize the research efforts from our group on the development of bioreducible and biodegradable LNPs by leveraging the combinatorial chemistry strategy, such as the Michael addition reaction, which allows us to easily generate a large set of lipidoids with diverse chemical structures. Next, we discuss the utilization of a library screening strategy to identify optimal LNPs for targeted mRNA delivery and showcase the applications of the optimized LNPs in cell engineering and genome editing. Finally, we outline key challenges to the clinical translation of mRNA-based therapies and propose an outlook for future directions of the chemical design and optimization of LNPs to improve the safety and specificity of mRNA drugs. We hope this Account provides insight into the rational design of LNPs for facilitating the development of mRNA therapeutics, a transformative technology that promises to revolutionize future medicine.


Subject(s)
COVID-19 Vaccines/pharmacology , Gene Editing , Gene Transfer Techniques , Lipids/chemistry , Nanoparticles/chemistry , RNA, Messenger/pharmacology , COVID-19/drug therapy , COVID-19 Vaccines/chemistry , Genetic Therapy , Humans , RNA, Messenger/chemistry , SARS-CoV-2/drug effects
2.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(8): 822-830, 2021 Aug 28.
Article in English, Chinese | MEDLINE | ID: covidwho-1441380

ABSTRACT

OBJECTIVES: Public health emergencies have caused significant psychological burden on nurse and affect their mental health. After the coronavirus disease 2019 pandemic, the nurse's mental health has been paid much attention. This study aims to investigate status and influencing factors for anxiety, depression, and insomnia in nurses during the normalized epidemic period, and to further compare the risk of anxiety, depression, and insomnia among nurses at different levels of hospitals between front-line epidemic nurses and other nurses so as to provide a basis for mental health work, nursing management, and relevant study in hospital. METHODS: A total of 4 237 nurses from all levels of hospitals in Hunan Province participated in the survey in December 2020. A self-designed anonymous questionnaire was used in this study. Anxiety, depression, and insomnia were assessed using Generalized Anxiety Disorder-7 items (GAD-7), Patient Health Questionnaire-9 items (PHQ-9), and Insomnia Severity Index (ISI), respectively. Descriptive statistical analysis was used to evaluate nurses' anxiety, depression, and insomnia; t-test, analysis of variance, and multiple linear stepwise regression analysis were used to analyze the influencing factors of nurses' anxiety, depression, and insomnia. RESULTS: The scores of GAD-7 among 4 237 nurses were 4.44±4.20, with 10.3% of them experienced moderate to severe level anxiety. The scores of PHQ-9 were 6.03±4.76, with 17.5% of them experienced moderate to severe level depressive symptom. The scores of ISI were 8.37±5.42, with 12.3% of them experienced moderate to severe insomnia. There were significant differences in GAD-7, PHQ-9, and ISI scores among different groups of hospital levels, gender, professional title, position, education level, night shifts, and family monthly income (all P<0.05). Marital status, whether to participate in the front-line, and whether to participate in psychology training groups were not associated with anxiety, depression, and insomnia (all P>0.05). Gender, hospital level, professional title, educational background, more night shifts, and family monthly income were the influencing factors for the GAD-7 and PHQ-9 scores. Gender, length of service, position, hospital level, educational background, night shifts in the last year, and family monthly income were the influencing factors for ISI score. CONCLUSIONS: There is no difference in the scores of the GAD-7, PHQ-9, and ISI between nurses whether to participate in the front-line, indicating that series of measures for front-line medical staff are effective in China.Meanwhile, some nurses experienced anxiety, depression, and insomnia, and attention should be paid to nurses with low position, more night shifts, lower-level hospitals, and families with low income. It is recommended that management policies, psychological support, and human resource protection should be given to relieve the pressure and maintain the mental health of nurses. At the same time, it is necessary to make mental health knowledge training as a routine training when responding to public health emergencies.


Subject(s)
COVID-19 , Nurses , Sleep Initiation and Maintenance Disorders , Anxiety/epidemiology , Anxiety Disorders/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Humans , Pandemics , SARS-CoV-2 , Sleep Initiation and Maintenance Disorders/epidemiology
3.
Front Psychiatry ; 12: 696823, 2021.
Article in English | MEDLINE | ID: covidwho-1295708

ABSTRACT

When a biological public health event breaks out, due to the characteristics of their work, doctors and nurses must face risks directly when the situation is unknown. Their difficulties and psychological pressure are unimaginable. However, few studies have investigated the difficulties encountered by those doctors and nurses and their requirements for psychological interventions. This study aimed to explore the difficulties and psychological intervention needs of doctors and nurses during the new biological public health events in China in 2019. We carried out a qualitative study using a phenomenological approach. We used convenience sampling to identify participants who provided direct care and treatment for patients with biological events such as coronavirus disease 2019 (COVID-19). They participated in semi-structured, in-depth face-to-face interviews. The interviews were transcribed and analyzed using Colaizzi's seven-step method. Analysis of this study was divided into the difficulties encountered by doctors and nurses and their mental health need. The difficulties encountered by doctors and nurses included four themes: being worried about the impact on others, lack of knowledge and skills, difficult patients, being socially isolated, and the feeling of uncertainty. The mental health need was summarized into two parts, needs expressed by doctors and nurses and needs observed by researchers. Doctors and nurses mostly did not feel that they needed any psychological support, but the researchers noticed several signs of stress or potential mental health problems among interviewees. Doctors and nurses faced significant complex and multidimensional difficulties. Many denied needing psychological support, even though the researchers noted signs that it might be helpful. Interventions and support strategies that involve mental health promotion activities should consider individual needs related to doctors and nurses' situation.

4.
Int J Environ Res Public Health ; 18(9)2021 04 26.
Article in English | MEDLINE | ID: covidwho-1231460

ABSTRACT

Worldwide commitment to disseminate Psychological First Aid (PFA) training to enable frontline workers to support distressed individuals and/or manage their own self-care is increasing, but the evidence base of PFA training is uncertain. METHOD: a scoping review was undertaken by searching seven databases and hand-searching grey literature to maximise coverage of potential studies. RESULTS: Twenty-three studies met the inclusion criteria. Three PFA training models were commonly used in research studies. A broad selection of PFA training outcomes were observed including learning, behavior, satisfaction and practice in crisis mental and behavior health preparedness. CONCLUSIONS: Research evidence of reasonable quality demonstrates that PFA training significantly improves knowledge of appropriate psychosocial response and PFA skills in supporting people in acute distress, thereby enhancing self-efficacy and promoting resilience. However, this review highlights inadequate guidance on how PFA training should be applied and adapted, significant shortcomings of reporting PFA training delivery, limited training evaluation and unclear training outcomes. Whilst behavioral, knowledge and system impact of the PFA training are promising, methodologically stronger evaluations which include systematic training adaptation and selection of sensitive outcome measures is needed to strengthen future implementation of PFA training and thereby enhance population preparedness for future emergencies.


Subject(s)
First Aid , Mental Disorders , Humans , Learning
5.
Disaster Med Public Health Prep ; : 1-8, 2021 Feb 16.
Article in English | MEDLINE | ID: covidwho-1085458

ABSTRACT

OBJECTIVE: The aim of this study was to assess the current status of disease-related knowledge and to analyze the relationship among the general condition, illness perception, and psychological status of patients with coronavirus disease 2019 (COVID-19). METHODS: A hospital-based cross-sectional study was conducted on 118 patients using convenience sampling. The general questionnaire, disease-related knowledge questionnaire of COVID-19, Illness Perception Questionnaire (IPQ), and Profile of Mood States (POMS) were used to measure the current status of participants. RESULTS: The overall average score of the disease-related knowledge of patients with COVID-19 was (79.19 ± 14.25), the self-care situation was positively correlated with knowledge of prevention and control (r = 0.265; P = 0.004) and total score of disease-related knowledge (r = 0.206; P = 0.025); the degree of anxiety was negatively correlated with the knowledge of diagnosis and treatment (r = -0.182; P = 0.049). The score of disease-related knowledge was negatively correlated with negative cognition (volatility, consequences, emotional statements) and negative emotions (tension, fatigue, depression) (P < 0.05); positively correlated with positive cognition (disease coherence) and positive emotion (self-esteem) (P < 0.05). CONCLUSIONS: It was recommended that we should pay more attention to the elderly and low-income groups, and increase the knowledge about diagnosis and treatment of COVID-19 and self-care in the future health education for patients.

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