The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 2019 has led to a global health crisis. Mutations of the SARS-CoV-2 genome have impeded the development ...of effective therapeutics and vaccines against SARS-CoV-2. Natural products are important for discovering therapeutics to treat the 2019 coronavirus disease (COVID-19). In the present study, we investigated the antiviral activity of herbal drug extracts from Polygala Root, Areca, and Quercus Bark and natural compounds derived from herbal drug such as baicalin and glabridin, with IC
50
values of 9.5 µg/ml, 1.2 µg/ml, 5.4 µg/ml, 8.8 µM, and 2.5 µM, respectively, against SARS CoV-2 infection in vitro. Certain herbal drug extracts and natural compounds were found to inhibit viral RNA levels and infectious titers of SARS-CoV-2 in a dose-dependent manner. Furthermore, viral protein analyses showed that herbal drug extracts and natural compounds effectively inhibited SARS-CoV-2 in the various entry treatments. Our study revealed that three herbal drugs are good candidates for further in vivo and clinical studies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Systematic reviews (SRs) and meta-analyses (MAs) are commonly conducted to evaluate and summarize medical literature. This is especially useful in assessing in vitro studies for consistency. Our ...study aims to systematically review all available quality assessment (QA) tools employed on in vitro SRs/MAs.
A search on four databases, including PubMed, Scopus, Virtual Health Library and Web of Science, was conducted from 2006 to 2020. The available SRs/MAs of in vitro studies were evaluated. DARE tool was applied to assess the risk of bias of included articles. Our protocol was developed and uploaded to ResearchGate in June 2016.
Our findings reported an increasing trend in publication of in vitro SRs/MAs from 2007 to 2020. Among the 244 included SRs/MAs, 126 articles (51.6%) had conducted the QA procedure. Overall, 51 QA tools were identified; 26 of them (51%) were developed by the authors specifically, whereas 25 (49%) were pre-constructed tools. SRs/MAs in dentistry frequently had their own QA tool developed by the authors, while SRs/MAs in other topics applied various QA tools. Many pre-structured tools in these in vitro SRs/MAs were modified from QA tools of in vivo or clinical trials, therefore, they had various criteria.
Many different QA tools currently exist in the literature; however, none cover all critical aspects of in vitro SRs/MAs. There is a need for a comprehensive guideline to ensure the quality of SR/MA due to their precise nature.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To estimate the proportion of participants in clinical trials who understand different components of informed consent.
Relevant studies were identified by a systematic review of PubMed, Scopus and ...Google Scholar and by manually reviewing reference lists for publications up to October 2013. A meta-analysis of study results was performed using a random-effects model to take account of heterogeneity.
The analysis included 103 studies evaluating 135 cohorts of participants. The pooled proportion of participants who understood components of informed consent was 75.8% for freedom to withdraw at any time, 74.7% for the nature of study, 74.7% for the voluntary nature of participation, 74.0% for potential benefits, 69.6% for the study's purpose, 67.0% for potential risks and side-effects, 66.2% for confidentiality, 64.1% for the availability of alternative treatment if withdrawn, 62.9% for knowing that treatments were being compared, 53.3% for placebo and 52.1% for randomization. Most participants, 62.4%, had no therapeutic misconceptions and 54.9% could name at least one risk. Subgroup and meta-regression analyses identified covariates, such as age, educational level, critical illness, the study phase and location, that significantly affected understanding and indicated that the proportion of participants who understood informed consent had not increased over 30 years.
The proportion of participants in clinical trials who understood different components of informed consent varied from 52.1% to 75.8%. Investigators could do more to help participants achieve a complete understanding.
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CEKLJ, DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Habitual snoring is a prevalent condition that is not only a marker of obstructive sleep apnea (OSA) but can also lead to vascular risk. However, it is not easy to check snoring status at home. We ...attempted to develop a snoring sound monitor consisting of a smartphone alone, which is aimed to quantify snoring and OSA severity.
The subjects included 50 patients who underwent diagnostic polysomnography (PSG), of which the data of 10 patients were used for developing the program and that of 40 patients were used for validating the program. A smartphone was attached to the anterior chest wall over the sternum. It acquired ambient sound from the built-in microphone and analyzed it using a fast Fourier transform on a real-time basis.
Snoring time measured by the smartphone highly correlated with snoring time measured by PSG (r = 0.93). The top 1 percentile value of sound pressure level (L1) determined by the smartphone correlated with the ambient sound L1 during sleep determined by PSG (r = 0.92). Moreover, the respiratory disturbance index estimated by the smartphone (smart-RDI) highly correlated with the apnea-hypopnea index (AHI) obtained by PSG (r = 0.94). The diagnostic sensitivity and specificity of the smart-RDI for diagnosing OSA (AHI ≥ 15) were 0.70 and 0.94, respectively.
A smartphone can be used for effectively monitoring snoring and OSA in a controlled laboratory setting. Use of this technology in a noisy home environment remains unproven, and further investigation is needed.
Streptococcus suis, a bacterium that affects pigs, is a neglected pathogen that causes systemic disease in humans. We conducted a systematic review and meta-analysis to summarize global estimates of ...the epidemiology, clinical characteristics, and outcomes of this zoonosis. We searched main literature databases for all studies through December 2012 using the search term "streptococcus suis." The prevalence of S. suis infection is highest in Asia; the primary risk factors are occupational exposure and eating of contaminated food. The pooled proportions of case-patients with pig-related occupations and history of eating high-risk food were 38.1% and 37.3%, respectively. The main clinical syndrome was meningitis (pooled rate 68.0%), followed by sepsis, arthritis, endocarditis, and endophthalmitis. The pooled case-fatality rate was 12.8%. Sequelae included hearing loss (39.1%) and vestibular dysfunction (22.7%). Our analysis identified gaps in the literature, particularly in assessing risk factors and sequelae of this infection.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Predictive markers represent a solution for the proactive management of severe dengue. Despite the low mortality rate resulting from severe cases, dengue requires constant examination and ...round-the-clock nursing care due to the unpredictable progression of complications, posing a burden on clinical triage and material resources. Accordingly, identifying markers that allow for predicting disease prognosis from the initial diagnosis is needed. Given the improved pathogenesis understanding, myriad candidates have been proposed to be associated with severe dengue progression. Thus, we aim to review the relationship between the available biomarkers and severe dengue.
We performed a systematic review and meta-analysis to compare the differences in host data collected within 72 hours of fever onset amongst the different disease severity levels. We searched nine bibliographic databases without restrictive criteria of language and publication date. We assessed risk of bias and graded robustness of evidence using NHLBI quality assessments and GRADE, respectively. This study protocol is registered in PROSPERO (CRD42018104495).
Of 4000 records found, 40 studies for qualitative synthesis, 19 for meta-analysis. We identified 108 host and viral markers collected within 72 hours of fever onset from 6160 laboratory-confirmed dengue cases, including hematopoietic parameters, biochemical substances, clinical symptoms, immune mediators, viral particles, and host genes. Overall, inconsistent case classifications explained substantial heterogeneity, and meta-analyses lacked statistical power. Still, moderate-certainty evidence indicated significantly lower platelet counts (SMD -0.65, 95% CI -0.97 to -0.32) and higher AST levels (SMD 0.87, 95% CI 0.36 to 1.38) in severe cases when compared to non-severe dengue during this time window.
The findings suggest that alterations of platelet count and AST level-in the first 72 hours of fever onset-are independent markers predicting the development of severe dengue.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Two phenylpropanoid-conjugated iridoids, deglucosyl gaertneroside (
1
) and morindoidin (
2
), were isolated from the leaves of
Morinda morindoides
(Rubiaceae) by activity-guided fractionation using ...an anti-malarial activity assay. The known related iridoids molucidin (
3
) and prismatomerin (
4
), two lignans, abscisic acid, two megastigmanes, and two flavonol glycosides were also identified. The structures of isolated compounds were elucidated using spectroscopic analysis. The isolated compounds were evaluated for anti-malarial activity against the chloroquine/mefloquine-sensitive strains of
Plasmodium falciparum
together with cytotoxicity against adult mouse brain cells. Potent anti-malarial activity of
3
and
4
(IC
50
of 0.96 and 0.80 μM, CC
50
of 1.02 and 0.88 μM, and SI of 1.06 and 1.10, respectively) was shown, while new iridoids
1
and
2
and pinoresinol (
5
) displayed moderate activity (IC
50
of 40.9, 20.6, and 24.2 μM) without cytotoxicity (CC
50
> 50 μM). These results indicate that
1
–
5
may be promising lead compounds for anti-malarial drugs. In addition, our results imply the necessity of the quality control of the extract of
M. morindoides
leaves based on the contents of
1
–
5
in terms of the safety and efficacy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Three phenylpropanoid-conjugated iridoid glucosides, acetylgaertneric acid (
1
), acetyldehydrogaertneroside (
2
), and dehydrogaertneric acid (
10
), together with nine known related iridoid ...glucosides (
3
–
9
,
11
, and
12
), two coumaroyl alkaloids, one benzenoid, and three flavonoid glucosides were isolated from leaves of
Morinda morindoides
(Rubiaceae). Structures of these isolated compounds were determined using spectroscopic analysis. Compounds
1
–
18
and previously isolated compounds (
19
–
29
) were evaluated for anti-trypanosomal activity against
Trypanosoma cruzi
Tulahuen strain (trypomastigote and amastigote) together with cytotoxicity against host cells, new-born mouse heart cells. Among them, molucidin (
21
) and prismatomerin (
22
) exhibited good anti-trypanosomal activity (IC
50
of 4.67 and 5.70 µM, respectively), together with cytotoxicity (CC
50
of 2.76 and 3.22 μM, respectively). Compounds
1
–
18
did not show anti-malarial activity against a chloroquine/mefloquine-sensitive strain of
Plasmodium falciparum
.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The pathogenesis of dengue shock syndrome (DSS, grade 3 and 4) is not yet completely understood. Several factors are reportedly associated with DSS, a more severe form of dengue infection that ...reportedly causes 50 times higher mortality compared to that of dengue patients without DSS. However, the results from these reports remain inconclusive. To better understand the epidemiology, clinical manifestation, and pathogenesis of DSS for development of new therapy, we systematically reviewed and performed a meta-analysis of relevant studies that reported factors in both DSS and dengue hemorrhagic fever (DHF, grade 1 and 2) patients.
PubMed, EMBASE, Scopus, Google Scholar, Dengue Bulletin, Cochrane Library, Virtual Health Library, and a manual search of reference lists of articles published before September 2010 were used to retrieve relevant studies. A meta-analysis using fixed- or random-effects models was used to calculate pooled odds ratios (OR) or event rate with corresponding 95% confidence intervals. Assessment of heterogeneity and publication bias, meta-regression analysis, subgroup analysis, sensitivity analysis, and analysis of factor-specific relationships were further performed. There were 198 studies constituting 203 data sets that met our eligibility criteria. Our meta-regression analysis showed a sustained reduction of DSS/dengue hemorrhagic fever (DHF) ratio over a period of 40 years in Southeast Asia, especially in Thailand. The meta-analysis revealed that age, female sex, neurological signs, nausea/vomiting, abdominal pain, gastrointestinal bleeding, hemoconcentration, ascites, pleural effusion, hypoalbuminemia, hypoproteinemia, hepatomegaly, levels of alanine transaminase and aspartate transaminase, thrombocytopenia, prothrombin time, activated partial thromboplastin time, fibrinogen level, primary/secondary infection, and dengue virus serotype-2 were significantly associated with DSS when pooling all original relevant studies.
The results improve our knowledge of the pathogenesis of DSS by identifying the association between the epidemiology, clinical signs, and biomarkers involved in DSS.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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