Mycobacterium tuberculosis (Mtb), an acid-fast bacillus that causes Tuberculosis (TB), is a pathogen that caused 1.5 million deaths in 2020. As per WHO estimates, another 4.1 million people are ...suffering from latent TB, either asymptomatic or not diagnosed, and the frequency of drug resistance is increasing due to intrinsically linked factors from both host and bacterium. For instance, poor access to TB diagnosis and reduced treatment in the era of the COVID-19 pandemic has resulted in more TB deaths and an 18% reduction in newly diagnosed cases of TB. Additionally, the detection of Mtb isolates exhibiting resistance to multiple drugs (MDR, XDR, and TDR) has complicated the scenario in the pathogen's favour. Moreover, the conventional methods to detect drug resistance may miss mutations, making it challenging to decide on the treatment regimen. However, owing to collaborative initiatives, the last two decades have witnessed several advancements in both the detection methods and drug discovery against drug-resistant isolates. The majority of them belong to nucleic acid detection techniques. In this review, we highlight and summarize the molecular mechanism underlying drug resistance in Mtb, the recent advancements in resistance detection methods, and the newer drugs used against drug-resistant TB.
Tuberculosis (TB) caused by the bacterial pathogen Mycobacterium tuberculosis (Mtb) remains a threat to mankind, with over a billion of deaths in the last two centuries. Recent advancements in ...science have contributed to an understanding of Mtb pathogenesis and developed effective control tools, including effective drugs to control the global pandemic. However, the emergence of drug resistant Mtb strains has seriously affected the TB eradication program around the world. There is, therefore, an urgent need to develop new drugs for TB treatment, which has grown researchers' interest in small molecule-based drug designing and development. The small molecules-based treatments hold significant potential to overcome drug resistance and even provide opportunities for multimodal therapy. In this context, various natural and synthetic flavonoids were reported for the effective treatment of TB. In this review, we have summarized the recent advancement in the understanding of Mtb pathogenesis and the importance of both natural and synthetic flavonoids against Mtb infection studied using in vitro and in silico methods. We have also included flavonoids that are able to inhibit the growth of non-tubercular mycobacterial organisms. Hence, understanding the therapeutic properties of flavonoids can be useful for the future treatment of TB.
The world is experiencing a life-altering and extraordinary situation in response to the COVID-19 pandemic. There are limited data and controversies regarding the relationship between vitamin D (Vit ...D) status and COVID-19 disease. Thus, this study was designed to investigate the association between Vit D levels and the severity or outcomes of COVID-19 disease.
A cross-sectional observational study was conducted in the Eastern province of Saudi Arabia from January to August 2021. All the admitted patients who were diagnosed with COVID-19 infection were distributed into three groups depending on their Vit D levels: normal, insufficiency, and deficiency. For the three groups, demographic data, and laboratory investigations as well as data regarding the severity of COVID-19 were collected and analysed.
A total of 203 diagnosed cases of COVID-19 were included in this study. The Vit D level was normal (>30) in 31 (15.3%) cases, insufficient in 45 (22.2%) cases and deficient in 127 (62.6%) cases. Among the included cases, 58 (28.6%) were critical cases, 109 (53.7%) were severe and 36 (17.7%) had a mild-moderate COVID-19 infection. The most prevalent comorbidity of patients was diabetes mellitus 117 (57.6%), followed by hypertension 70 (34.5%), cardiac disease 24 (11.8%), chronic kidney disease 19 (9.4%) and chronic respiratory disease in 17 (8.4%) cases. Importantly, the current study did not detect any significant association between Vit D status and COVID-19 severity (p-value=0.371) or outcomes (hospital stay, intensive care units admission, ventilation, and mortality rate) (p-value > 0.05), even after adjusting the statistical model for the confounders.
In hospital settings, Vit D levels are not associated with the severity or outcomes of COVID-19 disease. Further, well-designed studies are required to determine whether Vit D status provides protective effects against worse COVID-19 outcomes.
Background
Coinfection at various sites can complicate the clinical course of coronavirus disease of 2019 (COVID-19) patients leading to worse prognosis and increased mortality. We aimed to ...investigate the occurrence of coinfection in critically ill COVID-19 cases, and the predictive role of routinely tested biomarkers on admission for mortality.
Methods
This is a retrospective study of all SARS-CoV-2-infected cases, who were admitted to King Fahad Hospital of the University between March 2020 and December 2020. We reviewed the data in the electronic charts in the healthcare information management system including initial presentation, clinical course, radiological and laboratory findings and reported all significant microbiological cultures that indicated antimicrobial therapy. The mortality data were reviewed for severely ill patients who were admitted to critical care units.
Results
Of 1091 admitted patients, there were 70 fatalities (6.4%). 182 COVID-19 persons were admitted to the critical care service, of whom 114 patients (62.6%) survived. The in-hospital mortality was 13.4%. Coinfection was noted in 67/68 non-survivors, and Gram-negative pathogens (
Enterobacterales
,
Pseudomonas aeruginosa
, and
Acinetobacter baumanni)
represented more than 50% of the etiological agents. We noted that the serum procalcitonin on admission was higher for non-survivors (Median = 1.6 ng/mL ± 4.7) than in survivors (Median = 0.2 ng/mL ± 4.2) (
p
≤ 0.05).
Conclusion
Coinfection is a serious complication for COVID-19 especially in the presence of co-morbidities. High levels of procalcitonin on admission may predict non-survival in critically ill cases in whom bacterial or fungal co-infection is likely.
Monkeypox virus (MPXV) core cysteine proteinase (CCP) is one of the major drug targets used to examine the inhibitory action of chemical moieties. In this study, an in silico technique was applied to ...screen 1395 anti-infective compounds to find out the potential molecules against the MPXV-CCP. The top five hits were selected after screening and processed for exhaustive docking based on the docked score of ≤ -9.5 kcal/mol. Later, the top three hits based on the exhaustive-docking score and interaction profile were selected to perform MD simulations. The overall RMSD suggested that two compounds, SC75741 and ammonium glycyrrhizinate, showed a highly stable complex with a standard deviation of 0.18 and 0.23 nm, respectively. Later, the MM/GBSA binding free energies of complexes showed significant binding strength with ΔG
from -21.59 to -15 kcal/mol. This report reported the potential inhibitory activity of SC75741 and ammonium glycyrrhizinate against MPXV-CCP by competitively inhibiting the binding of the native substrate.
Improper use of antimicrobials has resulted in the emergence of antimicrobial resistance (AMR), including multi-drug resistance (MDR) among bacteria. Recently, a sudden increase in ...Carbapenem-resistant Enterobacterales (CRE) has been observed. This presents a substantial challenge in the treatment of CRE-infected individuals. Bacterial plasmids include the genes for carbapenem resistance, which can also spread to other bacteria to make them resistant. The incidence of CRE is rising significantly despite the efforts of health authorities, clinicians, and scientists. Many genotypic and phenotypic techniques are available to identify CRE. However, effective identification requires the integration of two or more methods. Whole genome sequencing (WGS), an advanced molecular approach, helps identify new strains of CRE and screening of the patient population; however, WGS is challenging to apply in clinical settings due to the complexity and high expense involved with this technique. The current review highlights the molecular mechanism of development of Carbapenem resistance, the epidemiology of CRE infections, spread of CRE, treatment options, and the phenotypic/genotypic characterisation of CRE. The potential of microorganisms to acquire resistance against Carbapenems remains high, which can lead to even more susceptible drugs such as colistin and polymyxins. Hence, the current study recommends running the antibiotic stewardship programs at an institutional level to control the use of antibiotics and to reduce the spread of CRE worldwide.
Improper use of antimicrobials has resulted in the emergence of antimicrobial resistance (AMR), including multi-drug resistance (MDR) among bacteria. Recently, a sudden increase in ...Carbapenem-resistant Enterobacterales (CRE) has been observed. This presents a substantial challenge in the treatment of CRE-infected individuals. Bacterial plasmids include the genes for carbapenem resistance, which can also spread to other bacteria to make them resistant. The incidence of CRE is rising significantly despite the efforts of health authorities, clinicians, and scientists. Many genotypic and phenotypic techniques are available to identify CRE. However, effective identification requires the integration of two or more methods. Whole genome sequencing (WGS), an advanced molecular approach, helps identify new strains of CRE and screening of the patient population; however, WGS is challenging to apply in clinical settings due to the complexity and high expense involved with this technique. The current review highlights the molecular mechanism of development of Carbapenem resistance, the epidemiology of CRE infections, spread of CRE, treatment options, and the phenotypic/genotypic characterisation of CRE. The potential of microorganisms to acquire resistance against Carbapenems remains high, which can lead to even more susceptible drugs such as colistin and polymyxins. Hence, the current study recommends running the antibiotic stewardship programs at an institutional level to control the use of antibiotics and to reduce the spread of CRE worldwide.
Background: The protozoan parasite Toxoplasma gondii may cause serious illness in the immunocompromised. The Toxoplasma gondii seropositive prevalence in pregnant women in WHO Eastern Mediterranean ...Region countries is inconsistent in the literature and it is associated with outcomes that have not be fully elucidated, hence the need for a better understanding of the pooled seroprevalence and associated maternal and fetal outcomes. Objective: The objective was to conduct a systematic literature review and determine the pooled prevalence of WHO Eastern Mediterranean Regional countries’ pregnant women’s seroprevalence of Toxoplasma gondii and the maternal–fetal outcomes. Methods: This quantitative study examined WHO Eastern Mediterranean countries’ maternal–fetal outcomes and Toxoplasma gondii prevalence in pregnant women. The targeted population was pregnant women, while the primary outcome was seropositivity of Toxoplasma gondii, while other outcomes such as maternal and fetal associations and risk factors were determined PubMed, SCOPUS, MEDLINE, and Index Medicus for the Eastern Mediterranean Region (IMEMR) databases were searched up until 30 January 2023. The search terms used were “Toxoplasma gondii” OR “Toxoplasma infection” AND “Pregnant woman” or pregnan* OR Antenatal OR Prenatal OR Gravidity OR Parturition OR Maternal AND WHO Eastern Mediterranean Region). OpenMeta-Analyst and Jamovi were used to analyze the generated data. Results: In total, 95 of 2947 articles meeting the inclusion criteria examined Toxoplasma gondii prevalence in pregnant women from WHO Eastern Mediterranean countries. The pooled prevalence of Toxoplasma gondii in pregnant women was 36.5% (95%CI: 32.6–40.4) with a median value of 35.64%, range values of 1.38–75.30%, with 99.61% heterogeneity. The pooled seroprevalence of IgG of Toxoplasma gondii was 33.5% (95%CI: 29.8–37.2) with a median value of 33.51%, and a range values of 1.38–69.92%; the pooled seroprevalence of IgM was 3.6% (95%CI: 3.1–4.1)) with a median value of 3.62 and range values of 0.20–17.47%, while cases of pooled seroprevalence of both IgG and IgM positivity was 3.0% (95%CI: 1.9–4.4) with a median value of 2.05 and a range values of 0.05–16.62%. Of the Toxoplasma gondii seropositive women, 1281/3389 (34.8%) 174/1765 (32.9%), 1311/3101 (43.7%), and 715/1683 (40.8%) of them had contact with cats, drank unprocessed milk, ate raw or undercooked meat and ate unwashed raw vegetables, respectively. The maternal–fetal outcomes associated with Toxoplasma gondii seropositivity were a history of abortions, miscarriage, stillbirth, intrauterine fetal death, and premature birth, which were found in 868/2990 (32.5%), 112/300 (36.1%), 111/375 (25.7%), 3/157 (1.9%) and 96/362 (20.1%) of women who tested positive for Toxoplasma gondii antibodies. Conclusion: The study found a high proportion of Toxoplasma gondii seroprevalence in pregnant women in the WHO Eastern Mediterranean Region, which may be linked to poor outcomes for mothers and their babies. Thus, pregnant women require monitoring and comprehensive prevention strategies for Toxoplasma gondii infection.
The attitudes of physical education (PE) teachers toward inclusion are critical to the successful provision of inclusive teaching for students with disabilities. Therefore, the purpose of this study ...was to investigate the attitudes of Saudi Arabian PE teachers toward the inclusion of students with disabilities in PE classes and the effect of sociodemographic variables (e.g., gender and length of teaching experience) on their attitudes toward inclusion. A total of 1,314 PE teachers (
= 41.09, SD = 9.40, females = 42.8%) completed the Arabic version of the Sentiments, Attitudes, and Concerns about Inclusive Education-Revised Scale (SACIE-R). Analyses found that, in general, PE teachers had moderately positive attitudes toward the inclusion of students with disabilities in PE lessons. A significant difference was found between the two genders in their attitudes toward inclusion. Specifically, female PE teachers demonstrated more positive attitudes toward inclusion than males. Multiple linear regression analysis, meanwhile, showed that the length of teaching experience and the experience of teaching a student with a disability were significant predictors of participants' attitudes toward inclusion. Our findings highlighted the importance of reconsidering the quality of PE teachers' experiences and interactions with students with disabilities as a means to improving their attitudes, which in turn would translate into successful inclusion.
Context:
The emergence of neonatal invasive bacterial infections (IBIs) poses a formidable challenge to health-care providers worldwide. The combination of nonspecific clinical symptoms, in addition ...to the absence of an acceptable sensitive test, resembles a dilemma for clinicians to diagnose or safely rule out the presence of infections. A newly developed tool by Chen
et
al
. stratifies the risk of full-term neonates suspected of IBI. This model works by identifying neonates who need immediate antibiotic treatment from those who only need observational and continuous reassessment.
Aims:
The purpose of the study was to validate Chen
et
al
.’s risk stratification tool.
Settings and Design:
This is a retrospective cohort study.
Subjects and Methods:
The following parameters are required to utilize this tool: ill appearance, abnormal neurological signs, age at admission, white blood cell, neutrophil percentage, C-reactive protein, and procalcitonin (PCT).
Statistical Analysis Used:
Data management and analysis were carried out using SPSS version 25.
Results:
Out of 768 neonates screened for IBIs, we identified 100 babies suspected of IBI regardless of PCT availability. Out of those, 30 neonates were eligible to be entered into the calculator and used for the validation process. The number of neonates who had IBIs was found to be 14 babies. Neonatal IBI incidence in full-term babies was estimated to be 0.79/1000 live births. Specificity, negative predictive value, and accuracy of the validated tool were reported as 82.14% (95% confidence interval CI: 63.11%–93.94%), 99.9% (95% CI: 99.88%–99.91%), and 82.07% (95% CI: 63.81%–93.59%), respectively.
Conclusions:
Overall, the tool demonstrated a poor outcome in terms of detecting those with IBI but excellent outcomes in identifying healthy babies.
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