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1.
Journal of Pharmaceutical Negative Results ; 13:758-764, 2022.
Article in English | Web of Science | ID: covidwho-2111713

ABSTRACT

Background: Educators and learners at all levels including nursing students have been impacted by Covid-19 pandemic with rapid adaptations to online learnings. While struggling to face the challenges, a learning innovation is needed to improve students confidence and critical thinking. This study explored the impact of an inquiry-based learning approach using podcast in a first-year undergraduate nursing students on acquisition of knowledge, self-confidence, critical thinking.Methods: The researchers in this study used a hybrid approach. We will evaluate the effectiveness of this course by a combination of a pre -and post-test in a quasi-experimental design and an in-depth interview to gauge students' knowledge gains, self-assurance, and critical thinking progress.Results: The quantitative results revealed an enhancement in students' self confidence and knowledge acquisition. After the intervention, students who were highly self-confident increased from 52% in pre-simulation to 91%, while the the average of online midterm and final exam test score was 8.6/10 +/- 1 (n 27) and 95% +/- 5% (n 27) for students in the intervention group compared to only 6.0/10 +/- 1 (n 27) and 65% +/- 5% (n 27) for students in the control group. The students from the intervention group found the combination of podcast media in learning methods very helpful, beneficial and reported their satisfaction.Conclusions: The inquiry learning method experience in combination with podcasts was an accepted form of learning innovation and provided new teaching strategies for students in times of pandemic to acquire knowledge more actively and develop their critical thinking.

2.
Majalah Kedokteran Bandung ; 54(3):177-183, 2022.
Article in English | Web of Science | ID: covidwho-2111179

ABSTRACT

COVID-19 is an acute respiratory disease caused by the SARS-CoV-2 virus that has caused a pandemic with symptoms of upper respiratory infection, respiratory failure, and even mortality. Several asymptomatic patients, with no shortness of breath, were found to experience impaired oxygenation in examination for objective data (happy hypoxia). Thus, objective data are needed, including data on inflammatory parameters (TLC, NLR, LDH, CRP, D-dimer and PCT) to monitor the severity and prognosis of COVID-19 patients. This study aimed to evaluate the inflammatory parameters in the initial days of treatment for COVID-19 patients between intubated and non-intubated patients during hospitalization. The study was conducted in the COVID was a retrospective cross-sectional comparative analytical observational study that involved patients' first laboratory examination results. The statistical analysis was performed using Mann Whitney test for numerical data and Chi Square test for categorical data. There were significant differences in inflammatory parameters values in both groups (p<0.01). The TLC values of intubated patients were lower than those of non-intubated patients, while the NLR, LDH, CRP, D-dimer and PCT values of intubated COVID-19 patients were higher than those of non-intubated patients.

3.
Nat Biomed Eng ; 6(8): 944-956, 2022 08.
Article in English | MEDLINE | ID: covidwho-1991606

ABSTRACT

Rapid nucleic acid testing is central to infectious disease surveillance. Here, we report an assay for rapid COVID-19 testing and its implementation in a prototype microfluidic device. The assay, which we named DISCoVER (for diagnostics with coronavirus enzymatic reporting), involves extraction-free sample lysis via shelf-stable and low-cost reagents, multiplexed isothermal RNA amplification followed by T7 transcription, and Cas13-mediated cleavage of a quenched fluorophore. The device consists of a single-use gravity-driven microfluidic cartridge inserted into a compact instrument for automated running of the assay and readout of fluorescence within 60 min. DISCoVER can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in saliva with a sensitivity of 40 copies µl-1, and was 94% sensitive and 100% specific when validated (against quantitative PCR) using total RNA extracted from 63 nasal-swab samples (33 SARS-CoV-2-positive, with cycle-threshold values of 13-35). The device correctly identified all tested clinical saliva samples (10 SARS-CoV-2-positive out of 13, with cycle-threshold values of 23-31). Rapid point-of-care nucleic acid testing may broaden the use of molecular diagnostics.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19 Testing , Humans , RNA, Viral/genetics , SARS-CoV-2/genetics , Saliva
4.
Nat Genet ; 54(8): 1078-1089, 2022 08.
Article in English | MEDLINE | ID: covidwho-1960394

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of symptoms in infected individuals, from mild respiratory illness to acute respiratory distress syndrome. A systematic understanding of host factors influencing viral infection is critical to elucidate SARS-CoV-2-host interactions and the progression of Coronavirus disease 2019 (COVID-19). Here, we conducted genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2. We uncovered proviral and antiviral factors across highly interconnected host pathways, including clathrin transport, inflammatory signaling, cell-cycle regulation, and transcriptional and epigenetic regulation. We further identified mucins, a family of high molecular weight glycoproteins, as a prominent viral restriction network that inhibits SARS-CoV-2 infection in vitro and in murine models. These mucins also inhibit infection of diverse respiratory viruses. This functional landscape of SARS-CoV-2 host factors provides a physiologically relevant starting point for new host-directed therapeutics and highlights airway mucins as a host defense mechanism.


Subject(s)
COVID-19 , Animals , COVID-19/genetics , Clustered Regularly Interspaced Short Palindromic Repeats , Epigenesis, Genetic , Humans , Mice , Mucins/genetics , SARS-CoV-2
5.
International Journal of Food Studies ; 11(1):85-97, 2022.
Article in English | Scopus | ID: covidwho-1847649

ABSTRACT

The partial lockdown during the Covid-19 pandemic in Indonesia pushed people to work from and spend more time at home. During this unprecedented time, many people pursued new hobbies in gardening, which proved to enhance physical and mental health. With anxieties regarding food insecurity, food gardens became a new urban trend. With a relatively tiny space available, it is possible to make an urban food garden in the front yard of a house using various cultivation techniques to maximize space. However, the implementation of food gardens in urban houses is quite challenging due to limited space. Then, we reflect on the practical process and personal benefits gained from developing a tiny food garden at home. The tiny food garden could produce a variety of vegetables and herbs, such as the spinach family, lettuce, Asian greens, the tomato family, eggplants, the basil family, mint, rosemary, moringas, and butterfly-pea flowers. It may support a household with few amounts of fresh emergency food in the worst scenario during the Covid-19 pandemic. Besides, developing a tiny food garden at home may also provide co-benefits such as enhanced subjective well-being, increased appreciation of food and the environment, motivating others to start gardening at home, and great personal satisfactions of consuming home-grown food. With all these socio-ecological co-benefits, home food garden must be integrated as a strategy to achieve urban sustainability and increase household food resilience. © 2022. ISEKI-Food Association (IFA)

6.
AAPS J ; 24(1): 33, 2022 02 07.
Article in English | MEDLINE | ID: covidwho-1673958

ABSTRACT

In vitro screening for pharmacological activity of existing drugs showed chloroquine and hydroxychloroquine to be effective against severe acute respiratory syndrome coronavirus 2. Oral administration of these compounds to obtain desired pulmonary exposures resulted in dose-limiting systemic toxicity in humans. However, pulmonary drug delivery enables direct and rapid administration to obtain higher local tissue concentrations in target tissue. In this work, inhalable formulations for thermal aerosolization of chloroquine and hydroxychloroquine were developed, and their physicochemical properties were characterized. Thermal aerosolization of 40 mg/mL chloroquine and 100 mg/mL hydroxychloroquine formulations delivered respirable aerosol particle sizes with 0.15 and 0.33 mg per 55 mL puff, respectively. In vitro toxicity was evaluated by exposing primary human bronchial epithelial cells to aerosol generated from Vitrocell. An in vitro exposure to 7.24 µg of chloroquine or 7.99 µg hydroxychloroquine showed no significant changes in cilia beating, transepithelial electrical resistance, and cell viability. The pharmacokinetics of inhaled aerosols was predicted by developing a physiologically based pharmacokinetic model that included a detailed species-specific respiratory tract physiology and lysosomal trapping. Based on the model predictions, inhaling emitted doses comprising 1.5 mg of chloroquine or 3.3 mg hydroxychloroquine three times a day may yield therapeutically effective concentrations in the lung. Inhalation of higher doses further increased effective concentrations in the lung while maintaining lower systemic concentrations. Given the theoretically favorable risk/benefit ratio, the clinical significance for pulmonary delivery of aerosolized chloroquine and hydroxychloroquine to treat COVID-19 needs to be established in rigorous safety and efficacy studies. Graphical abstract.


Subject(s)
Antimalarials/administration & dosage , COVID-19 Drug Treatment , Chloroquine/administration & dosage , Hydroxychloroquine/administration & dosage , Models, Chemical , Administration, Inhalation , Animals , Antimalarials/pharmacokinetics , Antimalarials/toxicity , Cells, Cultured , Drug Evaluation, Preclinical , Humans , Hydroxychloroquine/pharmacokinetics , Hydroxychloroquine/toxicity , Male , Mice , Middle Aged , Rats
7.
Pharmaceutics ; 14(1)2022 Jan 08.
Article in English | MEDLINE | ID: covidwho-1631503

ABSTRACT

In vitro transcribed messenger ribonucleic acid (mRNA) constitutes an emerging therapeutic class with several clinical applications. This study presents a systematic comparison of different technologies-intradermal injection, microneedle injection, jet injection, and fractional laser ablation-for the topical cutaneous delivery of mRNA. Delivery of Cy5 labeled mRNA and non-labeled enhanced green fluorescent protein (eGFP) expressing mRNA was investigated in a viable ex vivo porcine skin model and monitored for 48 h. Forty 10 µm-thick horizontal sections were prepared from each skin sample and Cy5 labeled mRNA or eGFP expression visualized as a function of depth by confocal laser scanning microscopy and immunohistochemistry. A pixel-based method was used to create a semi-quantitative biodistribution profile. Different spatial distributions of Cy5 labeled mRNA and eGFP expression were observed, depending on the delivery modality; localization of eGFP expression pointed to the cells responsible. Delivery efficiencies and knowledge of delivery sites can facilitate development of efficient, targeted mRNA-based therapeutics.

8.
Pharm Res ; 39(1): 57-73, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1615473

ABSTRACT

PURPOSE: Chloroquine and hydroxychloroquine are effective against respiratory viruses in vitro. However, they lack antiviral efficacy upon oral administration. Translation of in vitro to in vivo exposure is necessary for understanding the disconnect between the two to develop effective therapeutic strategies. METHODS: We employed an in vitro ion-trapping kinetic model to predict the changes in the cytosolic and lysosomal concentrations of chloroquine and hydroxychloroquine in cell lines and primary human airway cultures. A physiologically based pharmacokinetic model with detailed respiratory physiology was used to predict regional airway exposure and optimize dosing regimens. RESULTS: At their reported in vitro effective concentrations in cell lines, chloroquine and hydroxychloroquine cause a significant increase in their cytosolic and lysosomal concentrations by altering the lysosomal pH. Higher concentrations of the compounds are required to achieve similar levels of cytosolic and lysosomal changes in primary human airway cells in vitro. The predicted cellular and lysosomal concentrations in the respiratory tract for in vivo oral doses are lower than the in vitro effective levels. Pulmonary administration of aerosolized chloroquine or hydroxychloroquine is predicted to achieve high bound in vitro-effective concentrations in the respiratory tract, with low systemic exposure. Achieving effective cytosolic concentrations for activating immunomodulatory effects and adequate lysosomal levels for inhibiting viral replication could be key drivers for treating viral respiratory infections. CONCLUSION: Our analysis provides a framework for extrapolating in vitro effective concentrations of chloroquine and hydroxychloroquine to in vivo dosing regimens for treating viral respiratory infections.


Subject(s)
Chloroquine/administration & dosage , Chloroquine/pharmacokinetics , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/pharmacokinetics , Respiratory Tract Infections/drug therapy , Virus Diseases/drug therapy , Administration, Inhalation , Aerosols , Algorithms , COVID-19 , Cell Line , Cytosol/metabolism , Humans , Hydrogen-Ion Concentration , Lysosomes/metabolism , Primary Cell Culture
9.
Nature ; : 1-6, 2021.
Article in English | EuropePMC | ID: covidwho-1489898

ABSTRACT

The dearth of new medicines effective against antibiotic-resistant bacteria presents a growing global public health concern1. For more than five decades, the search for new antibiotics has relied heavily on the chemical modification of natural products (semisynthesis), a method ill-equipped to combat rapidly evolving resistance threats. Semisynthetic modifications are typically of limited scope within polyfunctional antibiotics, usually increase molecular weight, and seldom permit modifications of the underlying scaffold. When properly designed, fully synthetic routes can easily address these shortcomings2. Here we report the structure-guided design and component-based synthesis of a rigid oxepanoproline scaffold which, when linked to the aminooctose residue of clindamycin, produces an antibiotic of exceptional potency and spectrum of activity, which we name iboxamycin. Iboxamycin is effective against ESKAPE pathogens including strains expressing Erm and Cfr ribosomal RNA methyltransferase enzymes, products of genes that confer resistance to all clinically relevant antibiotics targeting the large ribosomal subunit, namely macrolides, lincosamides, phenicols, oxazolidinones, pleuromutilins and streptogramins. X-ray crystallographic studies of iboxamycin in complex with the native bacterial ribosome, as well as with the Erm-methylated ribosome, uncover the structural basis for this enhanced activity, including a displacement of the Structure-guided design and component-based synthesis are used to produce iboxamycin, a novel ribosome-binding antibiotic with potent activity against Gram-positive and Gram-negative bacteria.

10.
New Armenian Medical Journal ; 15(2):56-63, 2021.
Article in English | EMBASE | ID: covidwho-1481750

ABSTRACT

Background: The emergency, labor and delivery conditions in obstetric cases need a clinical decision in a timely manner. The identification of Covid-19 especially in asymptomatic obstetric cases with ease and rapid antibody test need further investigation. Objective: To analyze the usability and performance of rapid antibody test in obstetric cases. Methods: Case control study using medical record on Covid-19 obstetric cases over 9 months with paired nasopharyngeal reverse transcriptase polymerase chain reaction severe acute respiratory syndrome coronavirus 2 and rapid antibody test results. Results: There were 92 Covid-19 obstetric cases (incidence: 17.4%) and 210 reactive rapid antibody test (seroprevalence: 39.6%). The sensitivity, specificity, positive predictive value and negative predictive value of rapid antibody tests was 89%, 24%, 40%, 80%. Symptomatic cases have lower sensitivity (73% vs. 96%) and higher specificity (48% vs. 20%). The presence of Covid-19 symptoms (p<0.05) and reactive rapid antibody test (p<0.001) were associated with Covid-19. Rapid antibody test will identify larger Covid-19 obstetric cases compare with the presence of symptom only (89.4% vs. 27.7%. Conclusion: Screening by rapid antibody test had a high sensitivity but low specificity. This test will identify more Covid-19 cases compared by symptoms only due to majority asymptomatic obstetric cases. This simple, cheap and rapid antibody test still has a place in initial screening to help identify Covid-19 in areas with widespread transmission and has limited capacity to carry out universal screening.

11.
New Armenian Medical Journal ; 15(3):39-46, 2021.
Article in English | Scopus | ID: covidwho-1436936

ABSTRACT

Background: Covid-19 infection in vulnerable obstetric patients still requires a lot of re-search, especially in developing countries to help determine the best policy to manage it. Objective: To analyze the characteristic of Covid-19 infection in obstetric patients. Methods: In an East Java tertiary Covid-19 referral hospital, a case control analysis was conducted using medical records on obstetric cases of Covid-19 infection from March until November 2021. Results: Covid-19 was identified in 109 cases (9.3%) from 1170 patients who came to our obstetric room. Majority came in pregnancy state with 76% and had delivered 93.6%. Most patients were as-ymptomatic (68.8%) with minimal contact history (2.8%). Comorbidity found in 41.3% cases, obesity and hypertension in pregnancy dominated the cases. Symptomatic cases were associated with lower gestational age (p=0,005) and birthweight (p=0,015), low lymphocyte count (p=0,006), abnormal chest X-Ray (p<0,001), intensive care admission (p=0,002) and maternal death (p<0,001), while asymptomatic cases were associated with more reactive antibody test (p=0,002). Conclusion: There were a high number of Covid-19 obstetric cases with the majority as-ymptomatic and came for delivery. Significantly higher reactive antibody tests in asymptomatic cases may aid Covid-19 identification. Covid-19 symptoms should be given more consideration, because they are linked to a lower gestational age, birth weight, poor clinical parameters, the need for intensive care, and maternal mortality. © 2021, Yerevan State Medical University. All rights reserved.

12.
New Armenian Medical Journal ; 15(2):56-63, 2021.
Article in English | Web of Science | ID: covidwho-1405815

ABSTRACT

Background: Covid-19 infection in vulnerable obstetric patients still requires a lot of research, especially in developing countries to help determine the best policy to manage it. Objective: To analyze the characteristic of Covid-19 infection in obstetric patients. Methods: In an East Java tertiary Covid-19 referral hospital, a case control analysis was conducted using medical records on obstetric cases of Covid-19 infection from March until November 2021. Results: Covid-19 was identified in 109 cases (9.3%) from 1170 patients who came to our obstetric room. Majority came in pregnancy state with 76% and had delivered 93.6%. Most patients were asymptomatic (68.8%) with minimal contact history (2.8%). Comorbidity found in 41.3% cases, obesity and hypertension in pregnancy dominated the cases. Symptomatic cases were associated with lower gestational age (p=0,005) and birthweight (p=0,015), low lymphocyte count (p=0,006), abnormal chest X-Ray (p<0,001), intensive care admission (p=0,002) and maternal death (p<0,001), while asymptomatic cases were associated with more reactive antibody test (p=0,002). Conclusion: There were a high number of Covid-19 obstetric cases with the majority asymptomatic and came for delivery. Significantly higher reactive antibody tests in asymptomatic cases may aid Covid-19 identification. Covid-19 symptoms should be given more consideration, because they are linked to a lower gestational age, birth weight, poor clinical parameters, the need for intensive care, and maternal mortality.

13.
Pakistan Journal of Medical and Health Sciences ; 15(2):508-513, 2021.
Article in English | Scopus | ID: covidwho-1212306

ABSTRACT

Background: COVID-19 identification in obstetric emergency cases with limited resources is problematic, particularly in asymptomatic cases. Aim: To examine the screening strategies of COVID-19 obstetric emergency cases in low-resource health care settings. Method: A retrospective cohort design was carried out on patients with COVID-19 positive screening results. It was assessed based on symptoms, contact history, lymphocytopenia, chest X-rays, and rapid antibody tests compared to RT-PCR results SARS-COV-2. Result: Out of the 190 cases that came to the delivery room, the staff suspected 69 COVID-19 cases (36.3%) through the first screening protocol. Positive SARS-COV-2 RT-PCR was found in 23 cases with a majority asymptomatic (52.2%). The percentages of sensitivity and specificity from the parameters as follow: 48% and 74% in COVID-19 symptoms (febris or respiratory symptoms);9% and 100% in contact history;22% and 83% in lymphocytopenia;52% and 48% in chest x-ray;78% and 30% in rapid antibody test. Rapid antibody tests have the highest sensitivity to increase the identification of 12 asymptomatic cases. Conclusion: Other screening beyond symptoms and contact history such as lymphocytopenia, chest x-ray, and rapid antibody test can improve the identification, especially for asymptomatic cases in areas with the limited testing ability and high Covid-19 transmission. © 2021 Lahore Medical And Dental College. All rights reserved.

14.
F1000Research ; 9:1107, 2020.
Article in English | MEDLINE | ID: covidwho-916551

ABSTRACT

Background: The unpredictability of the progression of coronavirus disease 2019 (COVID-19) may be attributed to the low precision of the tools used to predict the prognosis of this disease. Objective: To identify the predictors associated with poor clinical outcomes in patients with COVID-19. Methods: Relevant articles from PubMed, Embase, Cochrane, and Web of Science were searched and extracted as of April 5, 2020. Data of interest were collected and evaluated for their compatibility for the meta-analysis. Cumulative calculations to determine the correlation and effect estimates were performed using the Z test. Results: In total, 19 papers recording 1,934 mild and 1,644 severe cases of COVID-19 were included. Based on the initial evaluation, 62 potential risk factors were identified for the meta-analysis. Several comorbidities, including chronic respiratory disease, cardiovascular disease, diabetes mellitus, and hypertension were observed more frequent among patients with severe COVID-19 than with the mild ones. Compared to the mild form, severe COVID-19 was associated with symptoms such as dyspnea, anorexia, fatigue, increased respiratory rate, and high systolic blood pressure. Lower levels of lymphocytes and hemoglobin;elevated levels of leukocytes, aspartate aminotransferase, alanine aminotransferase, blood creatinine, blood urea nitrogen, high-sensitivity troponin, creatine kinase, high-sensitivity C-reactive protein, interleukin 6, D-dimer, ferritin, lactate dehydrogenase, and procalcitonin;and a high erythrocyte sedimentation rate were also associated with severe COVID-19. Conclusion: More than 30 risk factors are associated with a higher risk of severe COVID-19. These may serve as useful baseline parameters in the development of prediction tools for COVID-19 prognosis.

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