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Biomolecules Jun 2024Incidences of drug-resistant tuberculosis have become common and are rising at an alarming rate. Aminoacyl t-RNA synthetase has been validated as a newer target against...
Incidences of drug-resistant tuberculosis have become common and are rising at an alarming rate. Aminoacyl t-RNA synthetase has been validated as a newer target against . Leucyl t-RNA synthetase (LeuRS) is ubiquitously found in all organisms and regulates transcription, protein synthesis, mitochondrial RNA cleavage, and proofreading of matured t-RNA. Leucyl t-RNA synthetase promotes growth and development and is the key enzyme needed for biofilm formation in Mycobacterium. Inhibition of this enzyme could restrict the growth and development of the mycobacterial population. A database consisting of 2734 drug-like molecules was screened against leucyl t-RNA synthetase enzymes through virtual screening. Based on the docking scores and MMGBSA energy values, the top three compounds were selected for molecular dynamics simulation. The druggable nature of the top three hits was confirmed by predicting their pharmacokinetic parameters. The top three hits-compounds (ZINC000001543916), (ZINC000001554197), and (ZINC000008214483)-were evaluated for their binding affinity toward leucyl t-RNA synthetase by an isothermal titration calorimetry study. The inhibitory activity of these compounds was tested against antimycobacterial activity, biofilm formation, and LeuRS gene expression potential. Compound (Macimorelin) was found to be the most potent molecule, with better antimycobacterial activity, enzyme binding affinity, and significant inhibition of biofilm formation, as well as inhibition of the LeuRS gene expression. Compound , the top hit compound, has the potential to be used as a lead to develop successful leucyl t-RNA synthetase inhibitors.
Topics: Mycobacterium tuberculosis; Ligands; Antitubercular Agents; Leucine-tRNA Ligase; Molecular Docking Simulation; Enzyme Inhibitors; Calorimetry; Molecular Dynamics Simulation; Tuberculosis; Computer Simulation; Protein Binding; Humans
PubMed: 38927114
DOI: 10.3390/biom14060711 -
Chemosphere Jun 2024In the present work, an analytical method for the quantification of per and poly fluoroalkyl substances (PFAS) in rice and maize has been developed and then validated...
In the present work, an analytical method for the quantification of per and poly fluoroalkyl substances (PFAS) in rice and maize has been developed and then validated with a metrological approach. PFAS are a group of human-made chemicals used in a variety of industries and consumer products for their water- and grease-resistant properties. Studies have shown that PFAS can contaminate soil and water, and there is concern about their bioaccumulation in edible plants, fruits, and cereals. The presence of PFAS has been identified in rice and other food products, including maize, as indicated by studies and scientific literature. This is particularly alarming since some PFAS have been associated with adverse health effects and rice and maize account for over 20% of the annual food intake worldwide. Despite this evidence, the regulation currently in place is not covering cereal matrices and limits of quantification for matrices encompassed by the current legislation are defined for a small group of PFAS. In this study an UHPLC-HRMS/MS based method was validated, obtaining a LOQ (Limit Of Quantification) ranging between 2 ng/kg and 32 ng/kg and robustness in line with EU guidelines and recommendation for PFAS in food. Additionally, a metrological approach was employed to estimate the uncertainty budget, utilizing modeling and experimental methods, and comparing the outcomes, aiming to characterize with high accuracy PFAS in rice and maize and support control bodies to assess contamination in suspected areas. A comparison of uncertainty of different approaches was conducted after applying the method to 30 real samples.
PubMed: 38925520
DOI: 10.1016/j.chemosphere.2024.142690 -
Journal of the International AIDS... Jun 2024Evidence-based intervention strategies to improve adherence among individuals living with chronic conditions are critical in ensuring better outcomes. In this systematic...
INTRODUCTION
Evidence-based intervention strategies to improve adherence among individuals living with chronic conditions are critical in ensuring better outcomes. In this systematic review, we assessed the impact of interventions that aimed to promote adherence to treatment for chronic conditions.
METHODS
We systematically searched PubMed, Web of Science, Scopus, Google Scholar and CINAHL databases to identify relevant studies published between the years 2000 and 2023 and used the QUIPS assessment tool to assess the quality and risk of bias of each study. We extracted data from eligible studies for study characteristics and description of interventions for the study populations of interest.
RESULTS
Of the 32,698 total studies/records screened, 2814 were eligible for abstract screening and of those, 497 were eligible for full-text screening. A total of 82 studies were subsequently included, describing a total of 58,043 patients. Of the total included studies, 58 (70.7%) were related to antiretroviral therapy for HIV, 6 (7.3%) were anti-hypertensive medication-related, 12 (14.6%) were anti-diabetic medication-related and 6 (7.3%) focused on medication for more than one condition. A total of 54/82 (65.9%) reported improved adherence based on the described study outcomes, 13/82 (15.9%) did not have clear results or defined outcomes, while 15/82 (18.3%) reported no significant difference between studied groups. The 82 publications described 98 unique interventions (some studies described more than one intervention). Among these intervention strategies, 13 (13.3%) were multifaceted (4/13 [30.8%] multi-component health services- and community-based programmes, 6/13 [46.2%] included individual plus group counselling and 3/13 [23.1%] included SMS or alarm reminders plus individual counselling).
DISCUSSION
The interventions described in this review ranged from adherence counselling to more complex interventions such as mobile health (mhealth) interventions. Combined interventions comprised of different components may be more effective than using a single component in isolation. However, the complexity involved in designing and implementing combined interventions often complicates the practicalities of such interventions.
CONCLUSIONS
There is substantial evidence that community- and home-based interventions, digital health interventions and adherence counselling interventions can improve adherence to medication for chronic conditions. Future research should answer if existing interventions can be used to develop less complicated multifaceted adherence intervention strategies.
Topics: Humans; Africa South of the Sahara; Chronic Disease; HIV Infections; Medication Adherence
PubMed: 38924296
DOI: 10.1002/jia2.26266 -
PloS One 2024Forests play a key role in the mitigation of global warming and provide many other vital ecosystem goods and services. However, as forest continues to vanish at an...
Forests play a key role in the mitigation of global warming and provide many other vital ecosystem goods and services. However, as forest continues to vanish at an alarming rate from the surface of the planet, the world desperately needs knowledge on what contributes to forest preservation and restoration. Migration, a hallmark of globalization, is widely recognized as a main driver of forest recovery and poverty alleviation. Here, we show that remittance from migrants reinforces forest recovery that would otherwise be unlikely with mere migration, realizing the additionality of payments for ecosystem services for China's largest reforestation policy, the Conversion of Cropland to Forest Program (CCFP). Guided by the framework that integrates telecoupling and coupled natural and human systems, we investigate forest-livelihood dynamics under the CCFP through the lens of rural out-migration and remittance using both satellite remote sensing imagery and household survey data in two representative sites of rural China. Results show that payments from the CCFP significantly increases the probability of sending remittance by out-migrants to their origin households. We observe substantial forest regeneration and greening surrounding households receiving remittance but forest decline and browning in proximity to households with migrants but not receiving remittance, as measured by forest coverage and the Enhanced Vegetation Index derived from space-borne remotely sensed data. The primary mechanism is that remittance reduces the reliance of households on natural capital from forests, particularly fuelwood, allowing forests near the households to recover. The shares of the estimated ecological and economic additionality induced by remittance are 2.0% (1.4%∼3.8%) and 9.7% (5.0%∼15.2%), respectively, to the baseline of the reforested areas enrolled in CCFP and the payments received by the participating households. Remittance-facilitated forest regeneration amounts to 12.7% (6.0%∼18.0%) of the total new forest gained during the 2003-2013 in China. Our results demonstrate that remittance constitutes a telecoupling mechanism between rural areas and cities over long distances, influencing the local social-ecological gains that the forest policy intended to stimulate. Thus, supporting remittance-sending migrants in cities can be an effective global warming mitigation strategy.
Topics: China; Forests; Conservation of Natural Resources; Transients and Migrants; Humans; Forestry; Ecosystem
PubMed: 38923961
DOI: 10.1371/journal.pone.0296751 -
Epidemiologia (Basel, Switzerland) Jun 2024The COVID-19 pandemic has disrupted global daily life, including the world of elite athletes. This paper examines the multifaceted impact the COVID-19 pandemic had on...
BACKGROUND
The COVID-19 pandemic has disrupted global daily life, including the world of elite athletes. This paper examines the multifaceted impact the COVID-19 pandemic had on elite swimmers and water polo athletes, specifically their mental health, their concerns over the virus, their intentions of getting vaccinated, and sleep disturbances that they may have faced.
METHODS
We conducted a cross-sectional study on elite swimmers and water polo players, using an anonymous questionnaire.
RESULTS
A total of 200 elite athletes participated. The majority of the participants reported a negative impact on their mental health, screened positive for insomnia (n = 107 (53.5%), with females (n = 101; 57.7%), swimmers (n = 100, 66.7%), and university students (n = 71, 71.7%) being more vulnerable ( < 0.001). Concerns about contracting the disease especially during important training or tournament periods and potential career disruption also affected their psychological well-being. While the majority (75%) had the intention of getting vaccinated, an alarming percentage was yet uncertain over its decision.
CONCLUSIONS
This study highlights the significant psychological distress faced by elite aquatic athletes during the pandemic. It emphasizes the difficulties faced by elite swimmers and water polo athletes and determines not only the importance of addressing the vaccination intentions of athletes, but also how critical it is to confront the challenges they face both for their personal health and for the restoration of world sports to their pre-pandemic state. More large-scale studies are required to inform policies targeted at minimizing disruption to the athletes' career, provision of information on preventive measures and vaccination, and improvement in psychological well-being in case of similar major public health issues in the future. Additionally, this study calls for further research to explore the unique challenges faced by aquatic athletes, such as those related to their training environments and fear of contagion, to better support them in future public health crises.
PubMed: 38920755
DOI: 10.3390/epidemiologia5020020 -
Biosensors Jun 2024Agricultural products are vitally important for sustaining life on earth and their production has notably grown over the years worldwide in general and in Brazil...
Agricultural products are vitally important for sustaining life on earth and their production has notably grown over the years worldwide in general and in Brazil particularly. Elevating agricultural practices consequently leads to a proportionate increase in the usage of pesticides that are crucially important for enhanced crop yield and protection. These compounds have been employed excessively in alarming concentrations, causing the contamination of soil, water, and air. Additionally, they pose serious threats to human health. The current study introduces an innovative tool for producing appropriate materials coupled with an electrochemical sensor designed to measure carbendazim levels. The sensor is developed using a molecularly imprinted polymer (MIP) mounted on a glassy carbon electrode. This electrode is equipped with multi-walled carbon nanotubes (MWCNTs) for improved performance. The combined system demonstrates promising potential for accurately quantifying carbendazim. The morphological characteristics of the synthesized materials were investigated using field emission scanning electron microscopy (FESEM) and the Fourier-transform infrared (FTIR) technique. The analytical curve was drawn using the electrochemical method in the range of 2 to 20 ppm while for HPLC 2-12 ppm; the results are presented as the maximum adsorption capacity of the MIP (82.4%) when compared with NIP (41%) using the HPLC method. The analysis conducted using differential pulse voltammetry (DPV) yielded a limit of detection (LOD) of 1.0 ppm and a repeatability of 5.08% ( = 10). The results obtained from the analysis of selectivity demonstrated that the proposed electrochemical sensor is remarkably efficient for the quantitative assessment of carbendazim, even in the presence of another interferent. The sensor was successfully tested for river water samples for carbendazim detection, and recovery rates ranging from 94 to 101% were obtained for HPLC and 94 to 104% for the electrochemical method. The results obtained show that the proposed electrochemical technique is viable for the application and quantitative determination of carbendazim in any medium.
Topics: Carbamates; Benzimidazoles; Pesticides; Nanotubes, Carbon; Electrochemical Techniques; Biosensing Techniques; Electrodes; Biomimetic Materials; Limit of Detection
PubMed: 38920608
DOI: 10.3390/bios14060304 -
Entropy (Basel, Switzerland) May 2024The road passenger transportation enterprise is a complex system, requiring a clear understanding of their active safety situation (ASS), trends, and influencing...
The road passenger transportation enterprise is a complex system, requiring a clear understanding of their active safety situation (ASS), trends, and influencing factors. This facilitates transportation authorities to promptly receive signals and take effective measures. Through exploratory factor analysis and confirmatory factor analysis, we delved into potential factors for evaluating ASS and extracted an ASS index. To predict obtaining a higher ASS information rate, we compared multiple time series models, including GRU (gated recurrent unit), LSTM (long short-term memory), ARIMA, Prophet, Conv_LSTM, and TCN (temporal convolutional network). This paper proposed the WDA-DBN (water drop algorithm-Deep Belief Network) model and employed DEEPSHAP to identify factors with higher ASS information content. TCN and GRU performed well in the prediction. Compared to the other models, WDA-DBN exhibited the best performance in terms of MSE and MAE. Overall, deep learning models outperform econometric models in terms of information processing. The total time spent processing alarms positively influences ASS, while variables such as fatigue driving occurrences, abnormal driving occurrences, and nighttime driving alarm occurrences have a negative impact on ASS.
PubMed: 38920443
DOI: 10.3390/e26060434 -
Frontiers in Oral Health 2024Inflammatory dysbiotic diseases present an intriguing biological paradox. Like most other infectious disease processes, the alarm bells of the host are potently...
Inflammatory dysbiotic diseases present an intriguing biological paradox. Like most other infectious disease processes, the alarm bells of the host are potently activated by tissue-destructive pathobionts, triggering a cascade of physiological responses that ultimately mobilize immune cells like neutrophils to sites of active infection. Typically, these inflammatory host responses are critical to inhibit and/or eradicate infecting microbes. However, for many inflammatory dysbiotic diseases, inflammophilic pathobiont-enriched communities not only survive the inflammatory response, but they actually obtain a growth when challenged with an inflammatory environment. This is especially true for those organisms that have evolved various strategies to resist and/or manipulate components of innate immunity. In contrast, members of the commensal microbiome typically experience a competitive growth disadvantage under inflammatory selective pressure, hindering their critical ability to restrict pathobiont proliferation. Here, we examine examples of bacteria-neutrophil interactions from both conventional pathogens and inflammophiles. We discuss some of the strategies utilized by them to illustrate how inflammophilic microbes can play a central role in the positive feedback cycle that exemplifies dysbiotic chronic inflammatory diseases.
PubMed: 38919731
DOI: 10.3389/froh.2024.1413842 -
Frontiers in Pharmacology 2024Colorectal cancer (CRC) remains a significant global health concern, being the third most diagnosed cancer in men and the second most diagnosed cancer in women, with...
Colorectal cancer (CRC) remains a significant global health concern, being the third most diagnosed cancer in men and the second most diagnosed cancer in women, with alarming mortality rates. Natural phytochemicals have gained prominence among various therapeutic avenues explored due to their diverse biological properties. Curcumin, extracted from turmeric, and resveratrol, a polyphenol found in several plants, have exhibited remarkable anticancer activities. However, their limited solubility and bioavailability hinder their therapeutic efficacy. To enhance the bioavailability of these compounds, nanomaterials work as effective carriers with biogenic silica (BS) attracting major attention owing to their exceptional biocompatibility and high specific surface area. In this study, we developed Curcumin-resveratrol-loaded BS (Cur-Res-BS) and investigated their effects on colorectal cancer cell lines (HCT-116 and Caco-2). Our results demonstrated significant concentration-dependent inhibition of cell viability in HCT-116 cells and revealed a complex interplay of crucial proto-onco or tumor suppressor genes, such as , , , and , which are commonly dysregulated in colorectal cancer. Notably, Cur-Res-BS exhibited a synergistic impact on key signaling pathways related to colorectal carcinogenesis. While these findings are promising, further investigations are essential to comprehensively understand the mechanisms and optimize the therapeutic strategy. Moreover, rigorous safety assessments and studies mimicking the environment are imperative before advancing to experiments, ensuring the potential of Cur-Res-BS as an efficient treatment for CRC.
PubMed: 38919255
DOI: 10.3389/fphar.2024.1341773 -
Microbiology Spectrum Jun 2024Bacteremia is associated with significant morbidity and mortality. The emergence of bacteria with antimicrobial resistance (AMR) has further exacerbated the poor...
UNLABELLED
Bacteremia is associated with significant morbidity and mortality. The emergence of bacteria with antimicrobial resistance (AMR) has further exacerbated the poor outcomes associated with bacteremia. The Taiwan Surveillance of Antimicrobial Resistance (TSAR) program was established in 1998 to monitor bacterial epidemiology and antimicrobial resistance trends across all patient types and age groups. Between 2002 and 2020, a total of 14,539 non-duplicate bacteremia isolates were collected biennially from 29 hospitals during the months of July-September as part of the TSAR program. The three most common bacteremia agents were (31%), (13.6%), and (12.7%) overall. However, there was a steady increase in the proportions of and isolated from bacteremia cases (both < 0.001), while the proportions of spp. decreased. Regarding antimicrobial resistance, there was a notable increase in rates of third-generation cephalosporin and fluoroquinolone non-susceptibility among and , while the rates of carbapenem non-susceptibility were elevated but remained milder in these two species, especially in . Of concern is the alarming increase in vancomycin resistance among , rising from 10.0% in 2004 to 47.7% in 2020. In contrast, the prevalence of methicillin-resistant has remained stable at 51.2% overall. In conclusion, , with increasing third-generation cephalosporin and fluoroquinolone resistance, is the predominant cause of bacteremia in Taiwan during the 18-year surveillance. The escalating proportion of in bacteremia, coupled with a concurrent upsurge in vancomycin resistance, presents a therapeutic challenge in the recent decade.
IMPORTANCE
AMR surveillance not only enables the identification of regional variations but also supports the development of coordinated efforts to combat AMR on a global scale. The TSAR has been a biennial, government-endorsed, multicenter study focusing on pathogens isolated from inpatients and outpatients in Taiwan hospitals since 1998. Our report presents an 18-year comprehensive analysis on blood isolates in the 2002-2020 TSAR program. The study highlights an alarming increase in the proportion of causing bacteremia accompanied by elevated vancomycin resistance. It is worth noting that this trend differs from the observations in the United States and China. Understanding the composition of bacteria causing bacteremia, along with their prevalence of antimicrobial resistance, holds significant importance in establishing healthcare and research priorities. Additionally, this knowledge serves as a critical factor in evaluating the effectiveness of preventive interventions.
PubMed: 38916365
DOI: 10.1128/spectrum.00608-24