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Background: Pain is the main complaint felt by mothers during childbirth. Pain management can be done with non-pharma-cological techniques, one of which is using the Rebozo technique. Objective(s): This study aimed to determine the effectiveness of the rebozo technique for active phase 1 labour pain in primipa-rous women. Method(s): The study used a quasi-experimental design with a pretest and posttest control group. An accidental sampling technique divided a sample of 30 people into control and intervention groups. The intervention group received Rebozo therapy, a therapy using a traditional cloth wrapped around the pelvis and buttocks with the mother kneeling, then shaking it slowly. The pain was measured using the Visual Analogue Scale (VAS), ranging from 0-10. Bivariate test using Wilcoxon. Result(s): The majority of respondents were aged 21-29 years (56.7%), had high school education (83.3%) and were house-wives (50%). The majority of the control group showed moderate pain (53.3%), while the intervention group showed severe (60%). The reduction in pain in the intervention group was more significant than in the control group (2.27 > 0.73). Both the control group and the intervention group showed p < 0.001. Conclusion(s): The Rebozo technique effectively reduces labour pain in the active phase of the first stage in primiparous women. This technique is easy and inexpensive, so it can be an option for non-pharmacological therapy to treat labour pain.Copyright © 2023 Japan University of Health Sciences.
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This paper examines the presence of a contagion effect between Chinese and G20 stock markets as well as its intensity over a recent period from 1(st) January 2013 to 7 April 2022. The empirical study is conducted using the time-varying copula approach. The obtained results show strong evidence of a contagion effect between China and all countries except United States America, Argentina and Turkey during the COVID-19 period. In particular, the Chinese stock market exhibits the highest level of dependence with the Asian and European stock markets in addition to the greatest variability in dependence. These findings are interesting and have important implications for several financial applications.
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Introduction: de Quervain's syndrome is a painful condition commonly presented to hand therapists. Exercise is utilised as an intervention, but isometric exercise has not been investigated. We aimed to assess the feasibility and safety of isometric thumb extension exercise for de Quervain's syndrome and to explore differences between high-load and low-load isometric exercise. Method(s): This parallel-group randomised clinical feasibility trial included individuals with de Quervain's syndrome. All participants underwent a 2 week washout period where they received an orthosis, education, and range of motion exercises. Eligible participants were then randomised to receive high or low-load isometric thumb extension exercises, performed daily for 4 weeks. Feasibility and safety were assessed by recruitment and drop-out rates, adherence, adverse events, and participant feedback via semi-structured interviews. Secondary outcomes included patient-reported outcomes for pain and function, and blinded assessment of range of motion and strength. Result(s): Twenty-eight participants were randomised. There were no drop-outs after randomisation, and no serious adverse events. Adherence to exercise was 86.7%, with 84% of participants stating they would choose to participate again. There were clinically and statistically significant improvements in pain and function over time (p < 0.001) but not in range of motion or strength. There were no statistically significant between-group differences. Conclusion(s): Isometric thumb extension exercise within a multimodal approach appears a safe and feasible intervention for people with de Quervain's syndrome. A large multi-centre trial would be required to compare high- and low-load isometric exercises. Further research investigating exercise and multimodal interventions in this population is warranted.Copyright © The Author(s) 2023.
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The ambition of this development study is to explore the opportunity to put the knowledge gained during the COVID-19 pandemic into practice in a blended, post-COVID, learning environment. The focus is to explore how a combination of digital and face-to-face activities may allow for fostering social presence among undergraduate students. The Social Presence model and the five elements of Affective Association, Community of Cohesion, Instructor Investment, Interaction Intensity, and Knowledge and Experience, encompass the theoretical framework of the study. The contextual setting is the first course of The Marketing Programme at Linnaeus University in Sweden, a bachelor program with a 50% Swedish intake and 50% international intake. Given the diverse background of the students in this course, challenges are typically encountered in relation to community building. Empirical data was collected during the fall of 2022 among the enrolled students using an online questionnaire. While the results from this study should be seen as preliminary, they offer an inspiring glimpse of how to nurture social presence in a blended learning environment. Copyright © 2023 by SCITEPRESS – Science and Technology Publications, Lda. Under CC license (CC BY-NC-ND 4.0)
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Introduction: As check-ups in healthcare facilities are much arduous during the pandemic including blood pressure (BP) control, an alternative is urgently needed to replace the use of disturbing cuff-based office and ambulatory BP monitoring (BPM) devices. With the advancement of telemedicine, real-time checking and reporting of blood pressure may be potentially achieved using photoplethysmography (PPG) technology in cuffless devices. Therefore, this study evaluated the accuracy of these devices compared to the cuff-based BPM devices. Method(s): This systematic review and meta-analysis was conducted based on the PRISMA 2020 guideline through multiple databases using Rayyan according to the prearranged inclusion and exclusion criteria, yielding six clinical studies to be included in the final review and analysis. Result(s): Overall fixed-effect meta-analysis of all studies (total of 319 subjects) presented small differences between cuffless and cuff-based devices, showing promising accuracy according to the current medical instrumentation guideline both in measuring systolic BP (SMD: 0.23 mmHg [95% CI: 0.07-0.39], p = 0.004;I2= 0%, p = 0.55) and diastolic BP (SMD: 0.27 mmHg [95% CI: 0.11-0.43], p = 0.0007;I2= 39%, p = 0.14). Discussion(s): PPG itself is a noninvasive technology, consisting of an infrared-emitting light source and a photodetector to measure the blood-reflected light intensity. Despite its ease in equipment, it measures BP accurately without being influenced by various positions and activities. Moreover, the data can be accessed real-time by both users and healthcare providers. Conclusion(s): In summary, cuffless PPG BPM devices have the potential in becoming a telemonitoring device for ambulatory patients for its accuracy. Its presence may be the answer to current restriction towards healthcare access during the COVID-19 pandemic. Therefore, in order to further confirm our findings, more clinical studies with various settings are encouraged to be held.
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Digital technology development caused the digital transformation of the economy and society. E-commerce, the most widespread among digital innovations, reached a significant share, particularly during the COVID-19 pandemic, impacting economic growth. The progress of digital technologies and the evolution of e-commerce can contribute to the more sustainable development of organizations and worldwide economies. This paper analyzed the influences of digital transformation and e-commerce on GDP and sustainable development. The study used the Eurostat database to gather the research variables for the EU countries. The paper used artificial neural networks and cluster analysis to reveal the significant influence of digital transformation and e-commerce on GDP and sustainable organizational development. Countries with a low level of digital transformation and e-commerce should propel these activities to increase economic performance sustainably.
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Radiotherapy-induced secondary malignancy is a well-known occurrence. During the COVID-19 pandemic, many people have undergone serial computed tomography (CT) imaging, and concerns have been raised regarding radiation-induced malignancies due to frequent scanning. Accordingly, various low and ultra-low-dose CT (LDCT) thorax protocols have been developed to reduce the dose of radiation. Major governing bodies worldwide have established guidelines regarding the indications for CT scans and chest X-rays during the pandemic. We, therefore, aimed to provide facts about the effects of radiation (both diagnostic and therapeutic). Through this article, we intend to break the myths and 'mithya' (misbeliefs) regarding diagnostic radiation and its association with cancer in this COVID-19 era. For this review, we performed a search in Google using specific keywords pertaining to imaging during COVID-19 and radiation risk. We also included the names of various global governing bodies in the Google search. We included only full text articles and guidelines from authentic websites. From this review, we conclude that if we follow the recommendations of various global governing bodies and use CT scan only in cases of moderate to severe COVID-related symptoms, adhere to the principle of 'as low as reasonably achievable' for radiation protection, and use LDCT scan protocols, we can significantly reduce the mean effective radiation dose delivered and the estimated cancer risk.Copyright © 2023 Cancer Research, Statistics, and Treatment. All rights reserved.
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Any form of physical activity, including exercise, has various benefits at the physiological (improving cardiac and respiratory functions, increasing skeletal muscle mass, and maintaining homeostasis) and psychological levels (improving cognitive function, reducing anxiety and depression) which help to combat any type of infection. In contrast, the infectivity ratio could reduce the physical activity of an individual, such as performing a habitual exercise. Adaptation to different exercise strategies including intensity and duration may better increase physical performance and improve the symptoms. For example, low to moderate intensity perhaps fails to induce this adaptive process, while high-intensity of exercise compromises immune health. This can aggravate the infection rate (Open window theory). However, high intensity with a shorter time produces various morphological alterations in the primary organs including the lungs and heart, which facilitate life support in COVID-19 patients. However, less information about exercise protocols failed to assure the benefits of exercise to COVID-19 patients, particularly post-COVID-19 conditions. Therefore, this review will answer how exercise intensity is crucial to reassure the exercise benefits for promoting safe participation before infection and post-COVID-19 conditions.
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Rapid urbanization has gradually strengthened the spatial links between cities, which greatly aggravates the possibility of the spread of an epidemic. Traditional methods lack the early and accurate detection of epidemics. This study took the Hubei province as the study area and used Tencent's location big data to study the spread of COVID-19. Using ArcGIS as a platform, the urban relation intensity, urban centrality, overlay analysis, and correlation analysis were used to measure and analyze the population mobility data of 17 cities in Hubei province. The results showed that there was high similarity in the spatial distribution of urban relation intensity, urban centrality, and the number of infected people, all indicating the spatial distribution characteristics of "one large and two small" distributions with Wuhan as the core and Huanggang and Xiaogan as the two wings. The urban centrality of Wuhan was four times higher than that of Huanggang and Xiaogan, and the urban relation intensity of Wuhan with Huanggang and Xiaogan was also the second highest in the Hubei province. Meanwhile, in the analysis of the number of infected persons, it was found that the number of infected persons in Wuhan was approximately two times that of these two cities. Through correlation analysis of the urban relation intensity, urban centrality, and the number of infected people, it was found that there was an extremely significant positive correlation among the urban relation intensity, urban centrality, and the number of infected people, with an R2 of 0.976 and 0.938, respectively. Based on Tencent's location big data, this study conducted the epidemic spread research for "epidemic spatial risk classification and prevention and control level selection" to make up for the shortcomings in epidemic risk analysis and judgment. This could provide a reference for city managers to effectively coordinate existing resources, formulate policy, and control the epidemic.
Subject(s)
COVID-19 , Epidemics , Animals , Humans , Big Data , COVID-19/epidemiology , Disease Outbreaks , CitiesABSTRACT
OBJECTIVE: The purpose of this study was to compare high-intensity interval training (HIIT) with moderate-intensity continuous training (MICT) for feasibility, safety, adherence, and short- and long-term efficacy in improving functioning and health-related quality of life in survivors of coronavirus disease 2019 (COVID-19). METHODS: COVIDEX is a two-pronged, parallel-group, randomized controlled trial with an 8-week training intervention. The study participants will be 94 patients aged >18 years, admitted to a specialized post-COVID center. Participants will be randomized to HIIT (4 × 4 minutes of high-intensity work periods at 85% to 90% of peak heart rate) and MICT (47 minutes at 70% to 75% peak heart rate) groups for biweekly sessions for 8 weeks. The participants will undergo 2 phases of supervised training (phases 1 and 2) of 4 weeks each, in a public, specialized, post-COVID center. In phase 1, we will assess and compare the feasibility, acceptability, and short-term efficacy of HIIT and MICT intervention. In phase 2, the long-term efficacy of HIIT and MICT will be assessed and compared regarding function and health-related quality of life. To prevent any expectation bias, all study participants and assessors will be blinded to the study hypotheses. Group allocation will be masked during the analysis. All statistical analyses will be conducted following intention-to-treat principles. IMPACT: This study is the first randomized controlled trial that will compare the feasibility, safety, adherence, and efficacy of the HIIT and MICT intervention programs in this population. The findings will potentially provide important information and assist in clinical decision making on exercise to optimize the benefits of clinical health care in survivors of COVID-19.
Subject(s)
COVID-19 , High-Intensity Interval Training , Humans , High-Intensity Interval Training/methods , Quality of Life , Exercise/physiology , Survivors , Randomized Controlled Trials as TopicABSTRACT
AIMS: STRONG-HF examined a high-intensity care (HIC) strategy of rapid up-titration of guideline-directed medical therapy (GDMT) and close follow-up after acute heart failure (AHF) admission. We assess the role of age on efficacy and safety of HIC. METHODS AND RESULTS: Hospitalized AHF patients, not treated with optimal GDMT were randomized to HIC or usual care. The primary endpoint of 180-day death or HF readmission occurred equally in older (>65 years, n = 493, 74 ± 5 years) and younger patients (53 ± 11 years, adjusted hazard ratio [aHR] 1.02, 95% confidence interval [CI] 0.73-1.43, p = 0.89). Older patients received slightly lower GDMT to day 21, but same doses at day 90 and 180. The effect of HIC on the primary endpoint was numerically higher in younger (aHR 0.51, 95% CI 0.32-0.82) than older patients (aHR 0.73, 95% CI 0.46-1.15, adjusted interaction p = 0.30), partially related to COVID-19 deaths. After exclusion of COVID-19 deaths, the effect of HIC was similar in younger (aHR 0.51, 95% CI 0.32-0.82) and older patients (aHR 0.63, 95% CI 0.32-1.02, adjusted interaction p = 0.56), with no treatment-by-age interaction (interaction p = 0.57). HIC induced larger improvements in quality of life to day 90 in younger (EQ-VAS adjusted-mean difference 5.51, 95% CI 3.20-7.82) than in older patients (1.77, 95% CI -0.75 to 4.29, interaction p = 0.032). HIC was associated with similar rates of adverse events in older and younger patients. CONCLUSION: High-intensity care after AHF was safe and resulted in a significant reduction of all-cause death or HF readmission at 180 days across the study age spectrum. Older patients have smaller benefits in terms of quality of life.
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Tweets are the most concise form of communication in online social media. Wherein a single tweet has the potential to make or break the discourse of the conversation. Online hate speech is more accessible than ever, and stifling its propagation is of utmost importance for social media companies and users for congenial communication. Most of the research has focused on classifying an individual tweet regardless of the tweet thread/context leading up to that point. One of the classical approaches to curb hate speech is to adopt a reactive strategy after the hateful content has been published. This strategy results in neglecting subtle posts that do not show the potential to instigate hate speech on their own but may portend in the subsequent discussion ensuing in the post's replies. In this paper, we propose DRAGNET++, which aims to predict the intensity of hatred that a tweet can bring in through its reply chain in the future. Our model uses the semantic and propagating structure of the tweet threads to maximize the contextual information leading up to and the fall of hate intensity at each subsequent tweet. We explore three publicly available Twitter datasets – Anti-Racism contains the reply tweets of a collection of social media discourse on racist remarks during US political and COVID-19 background;Anti-Social presents a dataset of 40 million tweets amidst the COVID-19 pandemic on anti-social behaviours with custom annotations;and Anti-Asian presents Twitter datasets collated based on anti-Asian behaviours during COVID-19 pandemic. All the curated datasets consist of structural graph information of the Tweet threads. We show that DRAGNET++ outperforms all the state-of-the-art baselines significantly. It beats the best baseline by an 11% margin on the Person correlation coefficient and a decrease of 25% on RMSE for the Anti-Racism dataset with a similar performance on the other two datasets.
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The period of confinement due to the Covid-19 virus has not only affected the general population, but also sport in general. The objective of this study was to investigate the emotional and adaptive consequences of rowers who compete nationally and internationally. A quantitative descriptive study was carried out with a non-probabilistic sample, based on convenience sampling, known as a snowball. One hundred and ninety-three rowers who competed nationally and internationally participated in the study, with an average age of 19.49 years. The results showed that the rowers reacted with more unpleasant moods than the rowers. It was also found that stressful thoughts were associated with states of greater anxiety, anger or depressive feelings, while the best training conditions and the acceptance of confinement rules were inversely associated with negative mood states. Linear regression analysis showed that stressful thoughts, along with behavior and motivation problems during lockdown, predicted the level of total mood disturbance.
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The energy consumption structure is now shifting from using fossil fuels to using renewable energy. Thus it is crucial to research if decreasing energy use can genuinely boost green total factor productivity (GTFP) and how to reconcile the link between reducing energy consumption and GTFP using various technical approaches. This study proposes the two-way influence of Artificial Intelligence (AI) and natural resources market on GTFP. It comprehensively evaluates the effects of AI on green economic development using the instance of China and a pertinent mathematical model. We found that the impacts of AI on carbon intensity vary between industries and developmental phases. Compared to the 11th Five-Year Plan, AI significantly reduced carbon intensity during the 12th. Compared to capital-intensive businesses, labor- and technology-intensive industries likely have a more significant drop in carbon intensity due to AI and natural resources market.
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Intro: SARS-CoV-2 is a single-strand enveloped RNA virus belonging to the family Coronaviridae. It was first recognized in late 2019 as causing COVID-19, and later declared a pandemic. The development of this assay aided in the detection of positive cases early in the pandemic which in turn facilitated the isolation of infected individuals to minimize the spread. Method(s): The SARS-CoV-2 RNA detection by real time RT-PCR is a molecular in vitro diagnostic test that aids in the detection and diagnosis of SARS-CoV-2 in nasopharyngeal and oropharyngeal specimens. This test is based on nucleic acid extraction and amplification technology and uses oligonucleotide primers and dual-labeled hydrolysis probes. RNA is isolated and purified from specimens using the Abbott m2000sp. This technology uses magnetic particles to capture and purify the RNA. The bound RNA is eluted and transferred to a 96 deep-well plate and is ready for amplification. The master mix is prepared manually and is added to a PCR plate together with the extracted RNA. The RNA is reverse transcribed to cDNA and subsequently amplified in the Abbott m2000rt. In this process, the probe anneals to a specific target sequence located between the forward and reverse primers. During the extension step of the PCR cycle, the 5' nuclease activity of Taq polymerase degrades the probe, causing the reporter dye molecules to be cleaved from their respective probes, increasing the fluorescence intensity. Fluorescence intensity is monitored at each PCR cycle on the Abbott m2000rt instrument. Finding(s): The clinical evaluation was performed by testing patient samples in a blinded fashion. The performance of SARS-CoV-2 Assay was established using 60 clinical specimens. The positive and negative percent agreements were analyzed by comparing the SARS-CoV-2 Assay results to Seegene's AllplexTM 2019-nCoV which showed 100% concordance. Conclusion(s): This assay demonstrated accuracy and reproducibility for the detection of SARS-CoV-2.Copyright © 2023
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Purpose: Disability in knee osteoarthritis (KOA) is known to be largely due to pain, the mechanism of which is complex and multidimensional with alterations in nociceptive processing in the peripheral and central nervous system (CNS) leading to persistent pain. Current clinical practice guidelines for KOA provide strong recommendations for education and exercise including land-based or mind-body approaches. However, individually these strategies are only moderately effective. One potential reason for this is a lack of understanding of their underlying mechanisms and how their combination might impact nervous system modulation. Neuromuscular exercise is known to improve lower extremity strength. Mind-body approaches as well as pain neuroscience education (PNE) are uniquely positioned to potentially reverse CNS adaptations by inducing positive neuroplastic changes and improving descending modulation of pain resulting in decreased pain. To our knowledge, neuromuscular exercise, mind-body techniques, and PNE have not been studied in combination. We therefore aimed to establish the feasibility of an intervention consisting of these three elements referred to as Pain Informed Movement (PIM). The results of this study will inform necessary modifications for a two-arm pilot randomized controlled trial (RCT). Method(s): This study was a single-arm feasibility trial with a nested qualitative component and the primary feasibility outcome of complete follow up. Inclusion criteria: age >= 40 years, KOA clinical diagnosis or people fulfilling the NICE diagnostic criteria, and average pain intensity >=3/10 on the numeric pain rating scale. PIM consisted of twice weekly in-person exercise sessions and a third home exercise session for 8 weeks. In addition, PNE, provided as online videos, covered the following topics: purpose of pain, neurophysiological changes associated with pain, movement guidelines when pain persists, mind-body techniques to impact neurophysiology and support moving with ease that included breath awareness and regulation, muscle tension regulation, awareness of pain related thoughts and emotions, and relaxation. The mind-body techniques and the PNE topics were implemented during the group exercise sessions that included evidence-based neuromuscular exercises aimed at improving sensorimotor control and functionality of the knee joint. Participants completed questionnaires and in-person assessments at baseline and at program completion. Assessments included weight and height, chair stands as a measure of functional leg strength, and conditioned pain modulation to assess efficiency of the descending modulatory pathways. Participants also had their blood drawn to monitor changes in brain derived neurotrophic factor (BDNF), a marker of neuroplasticity. Questionnaires included the Pain Catastrophizing Scale, Hospital Anxiety and Depression Scale, the Knee Injury and Osteoarthritis Outcome Score - function and pain subscales, Chronic Pain Self Efficacy scale, pain intensity rated in the past 24 hours, the past week, and worst pain in the past 24 hours. Secondary feasibility outcomes included acceptability of the intervention, burden of assessments, recruitment rate, compliance rate, adherence rate, and self-reported adverse events. Feasibility findings were evaluated against a-priori success criteria. In the qualitative component, participants were invited to an online focus group and were asked about their experience and perceptions of the program. Interview recordings were analyzed using thematic content analysis to identify suggestions for program modification. Result(s): In total, 19 participants (mean age 63.3 years (SD 10.5), 73% female) were enrolled, with a complete follow up rate of 74% (n=14) for our primary objective, indicating that modifications would be needed to proceed. Of the 5 dropouts, only one was study related. We will be adding additional inclusion criteria of: ability to get up and down from the floor independently, and no use of mobility aids. Adherence to in-person treatment sessions was 91%, hich indicates proceeding with the protocol for the next phase (i.e., pilot RCT). Some absences were due to unmodifiable factors (e.g., COVID-19). We will make protocol amendments for the purpose of improving the adherence rate to include 'no planned absences'. All other success criteria were met: recruitment rate, compliance to exercise sessions, program acceptability, duration, frequency, and delivery, likelihood of recommending the program to others and taking the program again, burden, and adverse events (Table 1). Analysis of the focus groups revealed that the video content pertaining to the mind-body techniques would benefit from on screen demonstrations by the instructor to assist with participants' execution of breath and muscle tension regulation. The majority of participants improved in most of the physical assessment outcomes and questionnaires (Table 2). Conclusion(s): The PIM program is feasible, acceptable, not burdensome, does not cause adverse events, and had an excellent compliance rate. Minor modifications are needed to optimize enrolment and adherence rates. Although improvements in pain, function, and psychological measures were observed, the feasibility nature of this study precludes any conclusions regarding efficacy. A pilot two-arm RCT will be conducted to establish the feasibility and explore potential effects of PIM when compared to conventional neuromuscular exercise and standard OA education. [Formula presented] [Formula presented]Copyright © 2023
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Due to the recent trend of sustainability and socio-economic changes and to expand the research on resilient supply chains in Korea, this study targets Korean venture companies to ensure their success and growth. This study aims to analyze the reliance factors affecting the business performance of Korean manufacturing venture enterprises by considering two types of business performance: technology and financial performance. Regarding the factors influencing business performance, this study analyzes five resilience factors: product structure intensity, brand intensity, research and development intensity, cooperation, and corporate social responsibility. Business years were used as control variables and the causal relationship between the factors was analyzed using SPSS 22. The results show that all resilience factors positively influenced technology performance. The results for the financial performance show research and development intensity and corporate social responsibility. However, cooperation only shows different results between technology performance and financial performance. Based on these results, this study provides implications and contributions for manufacturing venture enterprises.
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Background: Next-generation SARS-CoV-2 vaccines demonstrated that nanoparticle messenger ribonucleic acid (mRNA) delivery is effective and safe for in vivo delivery in humans. Current treatments for cystic fibrosis (CF) primarily focus on modulator drug therapies designed to correct malfunctioning CF transmembrane conductance regulator (CFTR) protein, but these modulators are ineffective for the 10% of people with CF with variants that do not allow protein production. Among these is the splice variant 3120 + 1G >A, the most common CF-causing mutation in native Africans. Gene editing would allow production of CFTR protein and enhancement of function using available CFTR modulators. We have demonstrated that electroporation of a modified CRISPR-Cas9 base editor to primary human bronchial epithelial cells carrying 3120 + 1G >A and F508del mutant alleles achieved 75% genome editing of the splice variant, resulting in approximately 40% wild-type (WT) CFTR function [1]. Here,we evaluate the effectiveness of several new nanoparticle formulations at delivering green fluorescent protein (GFP) mRNA to CF bronchial epithelial (CFBE41o-) cells. Using the optimal formulation,we then tested the efficacy correction of the 3120 + 1G >Avariant in a CFTR expression minigene (EMG) integrated into the genome of isogenic CFBE cells using mRNA and plasmid deoxyribonucleic acid (DNA) encoding adenine base editor (ABE) and guide (g)RNA. Method(s): GFP served as a reporter to evaluate transfection efficiency, cell viability, and mean fluorescence intensity (MFI) for three dosages (150, 75, 32.5 ng of mRNA), four polymer-to-mRNA to weight (w/w) ratios (60, 40, 30, 20), and four polymers (R, Y, G, B). 7-AAD served as a live/dead stain to quantify viability, with flow cytometry results analyzed using FlowJo software. CFBE cells stably expressing the 3120 + 1G >A EMG were transfected with the optimized nanoparticle formulation to deliver ABE and gRNA at two dosages (150, 75 ng) of mRNA and DNA. CFTR function in CFBE cellswas measured by short circuit current, forskolin stimulation, and inh-172 inhibition as a measure of editing efficiency. Result(s): Flow cytometry showed that polymer R achieved more than 85% GFP transfection, compared with a maximum of approximately 35% for the other three polymers at the maximum 150-ng dose, with approximately 80% viability normalized to untreated cells. In addition, polymer R achieved GFP MFI more than one order of magnitude as high as other formulations (~30 000 vs 2700 MFI) for the other three polymers at 150-ng dose and 40 w/w ratio. CFBE cells transfected with polymer R nanoparticles containing ABE and guide RNA at 75 ng and 150 ng showed mean CFTR function increase to 10 muA 6 (standard error of the mean [SEM] 1.1 muA) (~10% of WT) and 6.3 muA (SEM 0.9 muA) (~6% of WT), respectively. Greater toxicity at the higher dose could explain the larger increase in CFTR current at the lower dose. DNA-encoded ABE plasmid and gRNA showed a less robust increase in CFTR function (2.9 muA [SEM 0.4 muA] for 75-ng dose;3.0 muA [SEM 0.4 muA] for 150-ng dose), which was probably a result of the nanoparticle formulation being optimized for RNA instead of DNA cargo or the additional intracellular barriers that must be overcome for successful DNA delivery. Conclusion(s): We demonstrated that an optimized nanoparticle formulation containing ABE and gRNA can correct splicing of isogenic cells bearing the 3120 + 1G >A CFTR variant, resulting in recovery of CFTR function. In ongoing work, we are adapting these nanoparticles for RNA- and DNAencoded ABE and gRNA delivery to primary human bronchial epithelial cells.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved
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Tuberculosis (TB) is second only to COVID-19 as the most lethal cause of death from a single infectious agent. Current primary methods for diagnosing TB infection present significant limitations such as lengthy time-to-result for phenotypic tests, the need for a priori knowledge of Mycobacterium tuberculosis (Mtb) resistance mutations, and prohibitive cost for molecular tests. Here, we present fluorogenic solvatochomic trehalose probes that enables rapid detection of live Mtb. In particular, we designed a 4-N,N-dimethylamino-1,8-naphtha-limide- conjugated trehalose (DMN-Tre) probe that undergoes >700-fold increase in fluorescence intensity when transitioned from aqueous to hydrophobic environments. This enhancement occurs upon metabolic conversion of DMN-Tre to trehalose monomycolate and incorporation into the mycomembrane of Actinobacteria. DMN-Tre labeling enabled the rapid, no-wash visualization of mycobacterial and corynebacterial species without nonspecific labeling of Gram-positive or Gram-negative bacteria.DMN-Tre labeling was detected within minutes and was inhibited by heat killing of mycobacteria. Furthermore, DMN-Tre labeling was reduced by treatment with TB drugs, unlike the clinically used auramine stain. Lastly, DMN-Tre labeled Mtb in TB-positive human sputum samples comparably to auramine staining, suggesting that this operationally simple method may be deployable for TB diagnosis.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
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Objective The objective of this study was to investigate the basic needs of medical staff during the coronavirus disease 2019 pandemic in a fever clinic, so as to provide a reference for the global epidemic medical teams. Methods A semi-structured qualitative interview outline was designed, including: (1) work level: Working hours, working intensity, and safety guarantee in a fever clinic;(2)life level: Diet, sleep, and physical comfort;(3)psychological level: Emotion, pressure, coping style, and interpersonal resources. The basic needs of the first batch of the fever clinic in Peking Union Medical College Hospital was studied by open telephone interviews. Results A total of 37 medical staff were interviewed, including 8 males (21.6%) and 29 females (78.4%). Among them, there were 16 doctors (43.2%), 19 nurses (51.4%), and 2 medical technicians (5.4%). In terms of work settings, the ideal continuous working time was 4-6 hours per shift. There should be pro re nata positions during extremely high workload, and sufficient personal protective equipment was the key to safety. In terms of living conditions, providing meals according to different shifts was important for dietary needs, and sleeping pills were temporarily needed for sleep. In terms of psychological reactions, nervousness and worrying were relatively common. Family and colleagues were important resources of support. Sport could help relieve physical and psychological stress, and psychological support from psychologists was helpful in reducing their negative emotions. Conclusions The basic needs of medical staff should be respected so as to keep the efficacy of their work. We suggest that medical staff can rest after each 4-6 h working shift. Personal protective equipment should be sufficient. Psychological support should be noted in all of them and provided when necessary.Copyright © 2021, Peking Union Medical College Hospital. All rights reserved.