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Finding a chink in the armor: Update, limitations, and challenges toward successful antivirals against flaviviruses
Full text linkFlaviviruses have caused large epidemics and ongoing outbreaks for centuries. They are now distributed in every continent infecting up to millions of people annually and may emerge to cause future epidemics. Some of the viruses from this group cause severe illnesses ranging from hemorrhagic to neurological manifestations. Despite decades of research, there are currently no approved antiviral drugs against flaviviruses, urging for new strategies and antiviral targets. In recent years, integrated omics data-based drug repurposing paired with novel drug validation methodologies and appropriate animal models has substantially aided in the discovery of new antiviral medicines. Here, we aim to review the latest progress in the development of both new and repurposed (i) direct-acting antivirals; (ii) host-targeting antivirals; and (iii) multitarget antivirals against flaviviruses, which have been evaluated both in vitro and in vivo, with an emphasis on their targets and mechanisms. The search yielded 37 compounds that have been evaluated for their efficacy against flaviviruses in animal models; 20 of them are repurposed drugs, and the majority of them exhibit broad-spectrum antiviral activity. The review also highlighted the major limitations and challenges faced in the current in vitro and in vivo evaluations that hamper the development of successful antiviral drugs for flaviviruses. We provided an analysis of what can be learned from some of the approved antiviral drugs as well as drugs that failed clinical trials. Potent in vitro and in vivo antiviral efficacy alone does not warrant successful antiviral drugs; current gaps in studies need to be addressed to improve efficacy and safety in clinical trials
Kinetics of Thermal Decomposition of Particulate Samples of MgCO3: Experiments and Models
Full text linkIn this work, we study the kinetics of thermal decomposition of MgCO3 in the form of particles of known size. In the experiments, the material is heated to a known temperature in a vacuum oven, and it is characterized, both before and after heating, by infrared spectroscopy and gravimetry. The agreement between the results of the two techniques is excellent. These results are rationalized by means of a model based on Languir’s law, and the comparison with the experiments allows us to estimate the activation energy of the process. The reabsorption of atmospheric water by the oxide is shown spectroscopically, finding that is strongly influenced by the temperature of the process
A Photocatalytic Hydrolysis and Degradation of Toxic Dyes by Using Plasmonic Metal–Semiconductor Heterostructures: A Review
Full text linkConverting solar energy to chemical energy through a photocatalytic reaction is an efficient technique for obtaining a clean and affordable source of energy. The main problem with solar photocatalysts is the recombination of charge carriers and the large band gap of the photocatalysts. The plasmonic noble metal coupled with a semiconductor can give a unique synergetic effect and has emerged as the leading material for the photocatalytic reaction. The LSPR generation by these kinds of materials has proved to be very efficient in the photocatalytic hydrolysis of the hydrogen-rich compound, photocatalytic water splitting, and photocatalytic degradation of organic dyes. A noble metal coupled with a low bandgap semiconductor result in an ideal photocatalyst. Here, both the noble metal and semiconductor can absorb visible light. They tend to produce an electron–hole pair and prevent the recombination of the generated electron–hole pair, which ultimately reacts with the chemicals in the surrounding area, resulting in an enhanced photocatalytic reaction. The enhanced photocatalytic activity credit could be given to the shared effect of the strong SPR and the effective separation of photogenerated electrons and holes supported by noble metal particles. The study of plasmonic metal nanoparticles onto semiconductors has recently accelerated. It has emerged as a favourable technique to master the constraint of traditional photocatalysts and stimulate photocatalytic activity. This review work focuses on three main objectives: providing a brief explanation of plasmonic dynamics, understanding the synthesis procedure and examining the main features of the plasmonic metal nanostructure that dominate its photocatalytic activity, comparing the reported literature of some plasmonic photocatalysts on the hydrolysis of ammonia borane and dye water treatment, providing a detailed description of the four primary operations of the plasmonic energy transfer, and the study of prospects and future of plasmonic nanostructures
Levofloxacin Use in Patients with Suspected Tuberculosis in a Community Hospital, Thailand: A Pilot Study
Full text linkBackground. Levofloxacin is one of the broad-spectrum antibiotics that is indicated for the second-line treatment of tuberculosis (TB). However, using levofloxacin as an empirical therapy for patients without confirmation of TB could still be observed. This descriptive retrospective study, therefore, aimed to investigate the number of levofloxacin use in patients suspected TB in a community hospital in Thailand. Methods. Patient medical charts of all patients who were admitted to a community hospital in Nakhon Si Thammarat, Thailand, from 2016 to 2017, were reviewed. Patients who were suspected TB and received any levofloxacin-containing regimens were included. Data on patient characteristics and the received regimens were descriptively analyzed and reported as percentage and frequency. Results. There were a total of 21 patients who received levofloxacin in the hospital. Six of them (28.57%) had the diagnosis of hepatitis. The most prescribed regimen as empirical therapy was levofloxacin, ethambutol, and amikacin (66.67%). After the confirmation of TB using acid-fast bacilli (AFB) test, ten patients (47.62%) still received levofloxacin-containing regimens. Conclusion. The results from this study indicated high usage of levofloxacin despite no evidence of drug-resistant TB or negative AFB results in a community hospital in Thailand. The results from this study will be further used for the investigation of the prevalence of antibiotic resistance and clinical outcomes of using second-line regimens for TB treatment
Antidiabetic Properties and Toxicological Assessment of Antidesma celebicum Miq: Ethanolic Leaves Extract in Sprague–Dawley Rats
Full text linkAntidesma is a genus of plants, and its several species are known to have antidiabetic properties. Leaves of Kayu Tuah (Antidesma celebicum Miq) have been proven to have the best α-glucosidase inhibition ability compared to other species in the Antidesma genus, as evidenced by the in vitro α-glucosidase inhibition test. However, no scientific studies have reported its antidiabetic properties and toxicity in vivo. Therefore, this research managed to verify the antidiabetic features and safety of ethanolic extract of A. celebicum leaves (EEAC) in Sprague–Dawley rats. Male rats (170–280 g) were induced diabetic with streptozotocin (35 mg/kg BW) and fed a high-fat diet comprising 24% fat, whereas control group rats were given a standard diet. Rats were treated with EEAC at 200 and 400 mg/kg BW doses for 28-days and 60 mg/kg BW acarbose for the control group. Determination of antidiabetic properties was done by analyzing lipid profiles as well as fasting blood glucose. After confirming the antidiabetic properties of EEAC, the toxicological assessment was determined using the fixed-dose method. General behavior changes, appearance, signs of toxicity, mortality, and body weight of animals were marked down during the observation period. When the treatment period ended, hematological, biochemical, and histological examinations of liver, kidneys, and heart sections were performed. The results confirmed that EEAC reduced fasting blood glucose levels and stepped forward lipid profiles of rats. Also, all animals survived, and no obvious destructive outcomes were noticeable during the study. As EEAC has promising results toward hyperglycemia and hyperlipidemia and has been proven safe through toxicity tests, it can be concluded that EEAC has good potential to be further developed into antidiabetic drugs
Identifying molecular mediators of the relationship between body mass index and endometrial cancer risk: a Mendelian randomization analysis
Full text linkEndometrial cancer is the most common gynaecological cancer in high-income countries. Elevated body mass index (BMI) is an established modifiable risk factor for this condition and is estimated to confer a larger effect on endometrial cancer risk than any other cancer site. However, the molecular mechanisms underpinning this association remain unclear. We used Mendelian randomization (MR) to evaluate the causal role of 14 molecular risk factors (hormonal, metabolic and inflammatory markers) in endometrial cancer risk. We then evaluated and quantified the potential mediating role of these molecular traits in the relationship between BMI and endometrial cancer using multivariable MR.
Methods
Genetic instruments to proxy 14 molecular risk factors and BMI were constructed by identifying single-nucleotide polymorphisms (SNPs) reliably associated (P < 5.0 × 10−8) with each respective risk factor in previous genome-wide association studies (GWAS). Summary statistics for the association of these SNPs with overall and subtype-specific endometrial cancer risk (12,906 cases and 108,979 controls) were obtained from a GWAS meta-analysis of the Endometrial Cancer Association Consortium (ECAC), Epidemiology of Endometrial Cancer Consortium (E2C2) and UK Biobank. SNPs were combined into multi-allelic models and odds ratios (ORs) and 95% confidence intervals (95% CIs) were generated using inverse-variance weighted random-effects models. The mediating roles of the molecular risk factors in the relationship between BMI and endometrial cancer were then estimated using multivariable MR
The Accuracy of Electrical Impedance Tomography for Breast Cancer Detection: A Systematic Review and Meta-Analysis
Full text linkIntroduction. Incidence of breast cancer (BC) in 2020 is about 2.26 million new cases. It is the first common cancer accounting for 11.7% of all cancer worldwide. Disease complications and the mortality rate of breast cancer are highly dependent on the early diagnosis. Therefore, novel human breast-imaging techniques play an important role in minimizing the breast cancer morbidity and mortality rate. Electrical impedance tomography (EIT) is a noninvasive technique to image the breast using the electrical impedance behavior of the body tissues. Objectives. The aims of this manuscript are as follows: (1) a comprehensive investigation of the accuracy of EIT for breast cancer diagnosis through searching pieces of evidence in the valid databases and (2) meta-analyses of the results. Methods. The systematic search was performed in the electronic databases including PubMed, Web of Science, EMBASE, Science Direct, ProQuest, Scopus, and Google Scholar without time and language limitation until January 2021. Search terms were “EIT” and “Breast Cancer” with their synonyms. Relevant studies were included based on PRISMA and study objectives. Quality of studies and risk of bias were performed by QUADAS-2 tools. Then, relevant data were extracted in Excel form. The hierarchical/bivariate meta-analysis was performed with “metandi” package for the ROC plot of sensitivity and specificity. Forest plot of the Accuracy index and double arcsine transformations was applied to stabilize the variance. The heterogeneity of the studies was evaluated by the forest plots, χ2 test (assuming a significance at the a-level of 10%), and the I2 statistic for the Accuracy index. Results. A total of 4027 articles were found. Finally, 12 of which met our criteria. Overall, these articles included studies of 5487 breast cancer patients. EIT had an overall pooled sensitivity and specificity of 75.88% (95% CI, 61.92% to 85.89%) and 82.04% (95% CI, 69.72% to 90.06%), respectively. The pooled diagnostic odds ratio was 14.37 (95% CI, 6.22% to 33.20%), and the pooled effect of accuracy was 0.79 with 95% CI (0.73, 0.83). Conclusions. This study showed that EIT can be used as a useful method alongside mammography. EIT sensitivity could not be compared with the sensitivity of MRI, but in terms of specificity, it can be considered as a new method that probably can get more attention. Furthermore, large-scale studies will be needed to support the evidence
What Factors Are Associated with Attitudes towards HPV Vaccination among Kazakhstani Women? Exploratory Analysis of Cross-Sectional Survey Data
Full text linkBackground. The high prevalence of HPV infection among Kazakhstani women and the absence of an HPV vaccination program are directly reflected in increasing rates of cervical cancer incidence and mortality. Kazakhstan made its first attempt at introducing the HPV vaccine in 2013, but was unsuccessful due to complications and low public acceptance. The attitudes of Kazakhstani women towards the vaccine were never measured. Therefore, this study aims to investigate the attitudes of women towards the HPV vaccine and determine factors associated with positive, negative, or neutral attitudes. Methods. A 29-item survey consisting of 21 demographic and contextual questions and 8 Likert-scale questions was distributed among women attending gynecological offices in four major cities of Kazakhstan from December 2021 until February 2022. Attitudes of women were measured based on their answers to the eight Likert-scale questions. Ordinal logistic regression was built to find associations between demographic characteristics and attitudes of women. Results. Two hundred thirty-three women were included in the final analysis. A total of 54% of women had positive attitudes towards the vaccine. The majority of women did not trust or had a neutral attitude towards the government, pharmaceutical industry, and traditional and alternative media. However, the trust of women was high in medical workers and scientific researchers. Women’s age, education, number of children, effect of the 2013 HPV program, and trust in alternative medicine were included in the ordinal logistic model. Women with a low level of education, a high number of children, who believe in alternative medicine, and who were affected by the failed 2013 vaccination program were less likely to have a positive attitude towards the vaccine. Conclusions. Contrary attitudes towards HPV vaccination exist among Kazakhstani women, with approximately half having positive and almost half having negative or neutral attitudes towards the vaccine. An informational campaign that takes into consideration women’s levels of trust in different agencies, as well as targets those who are the most uninformed, might help in a successful relaunch of the HPV vaccination program. However, more studies that cover a higher number of women are require
Epidemiological and Clinical Characteristics of Respiratory Syncytial Virus Infections in Children Aged <5 Years in China, from 2014–2018
Full text linkRespiratory syncytial virus (RSV) is an important pathogen that causes acute respiratory tract infections in children. To understand the epidemiological and clinical characteristics of RSV in children, we analyzed the RSV diagnostic testing results from the 2014–2018 surveillance of acute respiratory infections in China. Among children aged <5 years, RSV incidence during 2014–2018 was 17.3% (3449/19,898), and 89.1% of RSV-positive individuals were inpatients. Children aged < 6 months had a high proportion in RSV infected individual (n = 1234; 35.8%). The highest RSV detection rate was in winter, RSV-A and RSV-B co-circulated year-round and jointly prevailed in 2015–2016. Cough was the common symptom of RSV infection 93.2% (3216/3449). Compared with older children, those aged <6 months were more likely to show breathing difficulty or lung rale that further developed into bronchopneumonia (p < 0.001). The symptoms such as cough, running nose, and diarrhea had significant differences between the RSV-A and RSV-B groups. The rate of RSV co-detection with other viruses or bacteria was 35.4%. Those coinfected with other viruses had a significantly higher incidence of fever, whereas those coinfected with bacteria had higher incidences of breathing difficulty and severe pneumonia. Our findings highlight the need for accumulating epidemiological information for the prevention and control of RSV
Safety of Vaccines against SARS-CoV-2 among Polish Patients with Multiple Sclerosis Treated with Disease-Modifying Therapies
Full text link(1) Background: The present study aims to report the side effects of vaccination against coronavirus disease 2019 (COVID-19) among patients with multiple sclerosis (MS) who were being treated with disease-modifying therapies (DMTs) in Poland. (2) Methods: The study included 2261 patients with MS who were being treated with DMTs, and who were vaccinated against COVID-19 in 16 Polish MS centers. The data collected were demographic information, specific MS characteristics, current DMTs, type of vaccine, side effects after vaccination, time of side-effect symptom onset and resolution, applied treatment, relapse occurrence, and incidence of COVID-19 after vaccination. The results were presented using maximum likelihood estimates of the odds ratio, t-test, Pearson’s chi-squared test, Fisher’s exact p, and logistic regression. The statistical analyses were performed using STATA 15 software. (3) Of the 2261 sampled patients, 1862 (82.4%) were vaccinated with nucleoside-modified messenger RNA (mRNA) vaccines. Mild symptoms after immunization, often after the first dose, were reported in 70.6% of individuals. Symptoms included arm pain (47.5% after the first dose and 38.7% after the second dose), fever/chills/flu-like symptoms (17.1% after the first dose and 20.5% after the second dose), and fatigue (10.3% after the first dose and 11.3% after the second dose). Only one individual presented with severe side effects (pro-thrombotic complications) after vaccination. None of the DMTs in the presented cohort were predisposed to the development of side effects. Nine patients (0.4%) had a SARS-CoV-2 infection confirmed despite vaccination. (4) Conclusions: Vaccination against SARS-CoV-2 is safe for people with MS who are being treated with DMTs. Most adverse events following vaccination are mild and the acute relapse incidence is lo