Background and Aims:The rising antimicrobial resistance in Proteus mirabilis, a primary contributor to catheter-associated urinary tract infections, underscores the urgent need to explore alternative therapeutic approaches. In this study, we evaluated the antibacterial and antivirulence potential of Rosmarinus officinalis L. extract (ROE) against P. mirabilis and concurrently assessed clinical isolates for the presence of key resistance and virulence genes. Methods:Forty multi-drug-resistant (MDR) P. mirabilis isolates were analyzed using multiplex PCR to detect carbapenemase genes (b l a NDM, b l a OXA family, b l a SIM-1, b l a VIM-1) and uniplex PCR to identify virulence determinants (mrpA, pmfA, rsbA, rsmA, luxS). ROE was extracted and analyzed using high-performance liquid chromatography (HPLC). The antibacterial, antibiofilm, and antiswarming effects of the extract were assessed. Results:All isolates carried all five virulence genes. Carbapenemase gene profiling revealed b l a VIM-1in 20% of isolates, while b l a OXA-23, b l a OXA-24, and b l a OXA-58 were detected in 10%, 2.5%, and 2.5% of isolates, respectively. Neither b l a SIM-1 nor b l a NDM was identified. HPLC analysis of ROE identified rosmarinic acid as the predominant compound. Although the agar well diffusion assay indicated no bactericidal activity, the broth microdilution method determined a minimum inhibitory concentration (MIC) of 8 mg/mL for both reference and MDR strains. At sub-MIC levels, ROE significantly inhibited swarming motility (up to 86% at 250 μg/mL) and biofilm formation (up to 78% in the reference strain and 76% in MDR isolates at 15.6 μg/mL) in a dose-dependent manner. Notably, biofilm eradication activity was observed only against preformed biofilms of the reference strain, achieving up to 53% reduction. MTT cytotoxicity assays confirmed that ROE in low concentrations (1000-15.6 μg/mL) was nontoxic to Vero cells. Conclusion:These results highlight the concerning prevalence of carbapenemase genes among clinical P. mirabilis isolates and identify ROE as a promising, nontoxic candidate for targeting motility and biofilm formation. These findings suggest ROE may offer a viable strategy for managing drug-resistant P. mirabilis infections.
High EBV load in peripheral blood (PB) of untreated patients with chronic lymphocytic leukemia (CLL) has been associated with shorter overall survival. We demonstrated previously that EBV infection of B cells upregulates CCR1 and CCR2. For 54 therapy-naïve CLL patients of the present study, we analyzed expression of CCR1, CCR2, and CD38 on circulating CD19+CD5+ lymphocytes, determined the EBV load (EBV DNA copy number) and the EBV transcripts (BZLF1, LMP1, LMP2A, and EBNA2) in PB mononuclear cells (PBMCs), and measured levels and avidity of IgG antibodies against the EBV capsid antigen (anti-EBV-CA-IgG). The BZLF1 transcript was determined in one patient; both LMP1 and EBNA2 transcripts were detected in two patients only, and, in these patients, the frequency of CD19+CD5+ lymphocytes that presented CCR1 or CCR2 was elevated by 2.5-, 4.3-, and 2.9-fold and by 2.1-, 1.2-, and 2.9-fold, respectively, relative to the median values in the EBV-positive group (> 5 EBV DNA copies in 105 PBMCs; n = 21). The levels and avidity of anti-EBV-CA-IgG were significantly higher in EBV-positive patients compared with the EBV-undetectable group (p = 0.007 and p = 0.018, respectively). Noteworthy, the high avidity of anti-EBV-CA-IgG, with the relative avidity index (RAI) range 61.0-94.6, was associated in EBV-positive patients with the increased 2.3-fold frequency of CCR2 on CD19+CD5+ lymphocytes, compared to patients with the highest avidity (RAI > 95.0; p = 0.006). In patients with the highest anti-EBV-CA-IgG avidity (RAI > 95.0; n = 13), indicative of the high rate of antigen presentation and a recent lytic viral reactivation, the frequency of the CCR2-presenting CD19+CD5+ PB lymphocytes was 1.7-fold lower than the median value of all high-avidity patients (n = 31; p = 0.032). We hypothesize that CCR2 directs the migration of leukemic lymphocytes from circulation into ligand-rich lymphoid organs, thereby underlying EBV's contribution to CLL progression.
Individuals' conspiracy beliefs can influence their vaccination readiness, which may affect the annual vaccination uptake rate for infectious diseases such as influenza and COVID-19. To provide reliable and valid tools adapted to the Taiwanese context in assessing these two constructs, the present study validated the psychometric properties of four scales among Taiwanese adults: the COVID-19 Vaccination Readiness Scale (CVRS), Influenza Vaccination Readiness Scale (IVRS), Influenza Conspiracy Beliefs Scale (ICBS), and COVID-19 Conspiracy Beliefs Scale (CCBS). A total of 914 participants completed the online survey between October and November, 2024. Confirmatory factor analysis (CFA) was employed to confirm the model structures and factor loadings for the four scales. All fit indices for all the scales were acceptable, with CVRS and IVRS fitting well to a bifactor model-general and specific-(comparative fix index [CFI] = 0.936 and 0.943) and the CCBS and ICBS to a two-factor model (CFI = 0.961 and 0.973). The internal consistency assessed by Cronbach's alpha [α] and McDonald's omega [ω] was good among all scales (α = 0.87, 0.87, 0.93 and 0.96; ω = 0.90, 0.91, 0.95 and 0.97, for CVRS, IVRS, CCBS and ICBS). Moreover, conspiracy beliefs negatively correlated with vaccination readiness (r = -0.351 to -0.417, p < 0.01). The robustness of these scales was validated. Moreover, conspiracy beliefs were associated with vaccination readiness. Authorities may use these scales to understand individuals' thoughts on vaccination and inform promotion strategies. Future studies may consider these variables in other types of infectious diseases, such as Mpox.
Background:Bacterial meningitis (BM) remains a significant public health concern in Ethiopia, particularly due to diagnostic challenges posed by limited laboratory infrastructure, late patient presentation, and technical skills required for cerebrospinal fluid (CSF) sampling. Molecular diagnostic methods offer rapid, sensitive, and specific alternatives to conventional culture. Objective:This narrative review synthesizes available evidence on molecular diagnostics for BM in Ethiopia, evaluates their performance compared to conventional methods, and identifies barriers to implementation. Methods:A structured literature search was conducted in PubMed, Google Scholar, Scopus, and Web of Science (August 1977-September 2024) using the terms: Meningitis OR Bacterial meningitis AND Diagnostics OR Molecular diagnostics, including PCR, CRISPR, next-generation sequencing (NGS), and MALDI-TOF. The review used a repeatable research selection procedure, well-defined inclusion/exclusion criteria, and PRISMA reporting requirements. Studies from Ethiopia and other low-resource settings were included. After screening titles/abstracts and full texts, 66 articles were selected. Results:In Ethiopia, multiplex PCR detected bacterial DNA in 10%-22% of the CSF samples, whereas culture was positive in only 0.5%-1% of the cases, primarily due to pre-admission antibiotic use. Globally, molecular panels (e.g., BioFire FilmArray ME) show > 90% sensitivity and specificity. Advanced techniques (CRISPR-Cas, NGS, and MALDI-TOF) have not yet been implemented in Ethiopian routine diagnostics. Conclusion:Molecular methods vastly improve the detection of BM in Ethiopia, but high costs, infrastructure gaps, and shortage of trained personnel prevent widespread adoption. Molecular assays have outstanding analytical sensitivity, but culture remains the gold standard for confirmation of the viability of live pathogens. Implementation gaps require urgent targeted investment in point-of-care diagnostics and specialized transport networks.
Background:Acinetobacter baumannii is a major contributor to antimicrobial resistance (AMR), particularly in hospitals. Its rising resistance presents significant clinical and economic concerns. This study evaluated the national burden and economic impact of A. baumannii infections in Iran from 2000 to 2021 using GBD 2021 AMR data. Materials and Methods:We estimated mortality and disability-adjusted life years (DALYs) per 100,000 people with 95% UIs under two scenarios: resistant infections replaced by susceptible ones (attributable burden) and replaced by no infection (associated burden). Economic burden was calculated using GDP per capita and purchasing power parity (PPP)-adjusted estimates. Results:From 2000 to 2021, total associated DALYs declined from 90,391.9 (95% UI: 80,178.0-100,605.9) to 69,740.5 (65,132.4-74,348.6) and attributable DALYs from 35,284.5 (30,843.1-39,725.9) to 28,085.9 (25,415.9-30,755.9). However, associated deaths increased from 2019.5 (1870.3-2168.8) to 2523.7 (2322.5-2724.9), with neonates and individuals aged 50 years and older most affected. Bloodstream and lower respiratory infections contributed most to DALYs. Resistance remained highest for cephalosporins and carbapenems. The economic burden peaked in 2010 at 584.6 million PPP and decreased to 435.2 million in 2021. Conclusion:Although disease burden declined, rising mortality and resistance trends highlight the need for stronger infection control and stewardship to reduce A. baumannii-related AMR in Iran.
Background:Candida esophagitis (CE) is a recognized opportunistic infection in immunocompromised individuals, but data from HIV-negative patients remain limited. This study aimed to determine the prevalence, clinical manifestations, risk factors, and molecular characteristics of CE in HIV-negative adults undergoing upper gastrointestinal endoscopy. Methods:In this cross-sectional study, 455 HIV-negative adults with upper gastrointestinal symptoms who underwent esophagogastroduodenoscopy were evaluated. An esophageal mucosal sample for fungal culture was collected from all patients, while biopsy for histopathology was performed only when endoscopic findings suggested Candida infection. Active CE was defined by compatible endoscopic lesions, histopathological evidence of tissue invasion, and a positive fungal culture. Candida species were identified using PCR-RFLP. Results:Candida was detected in 84 patients (18.5%), and histopathologically confirmed that CE was identified in 16 patients (3.5%). The most common symptoms among CE patients were epigastric pain (68.8%) and acid reflux (56.3%). Diabetes mellitus (OR = 6.19, p = 0.001), denture use (OR = 3.72, p = 0.020), corticosteroid use (OR = 4.54, p = 0.025), and antibiotic use (OR = 5.08, p = 0.018) were significantly associated with CE. Among patients with CE (n = 16), molecular analysis showed Candida albicans as the predominant species (81.3%), followed by C. glabrata (12.5%) and C. tropicalis (6.2%). Conclusions:CE is an uncommon yet clinically relevant condition in HIV-negative patients. Metabolic factors, medication exposure, and denture use significantly increase the risk of CE. Early identification of high-risk individuals and accurate species detection may support timely diagnosis and appropriate management.
Background:The extensive use of antibiotics for treating infectious diseases leads to their release into the environment, which in turn results in antibiotic pollution and thereby facilitates the dissemination of antibiotic-resistance genes (ARGs). Recently, despite the implementation of strict antibiotic usage restrictions, the accumulation of ARGs and multidrug-resistant bacteria in the aquaculture environment continues to show a trend of persistent spread. Methods:The W2 strain was isolated in the presence of 32 μg/mL doxycycline. A broth microdilution assay was employed to determine the minimum inhibitory concentrations. Whole-genome sequencing was conducted to characterize ARGs and their mobility through bioinformatics analysis. The spread of ARGs was detected by conjugation assays. Results:W2 strain was isolated from the wastewater of a crucian carp aquaculture plant in Jinan, China, and identified as Proteus mirabilis. W2 genome contained a 190,320 bp antibiotic-resistance-conferring integrative and conjugative element (ICE), named ICEPmiW2. ICEPmiW2 contains 21 ARGs, 14 conjugative transposon protein-encoding genes, and one complex type I integron. No transconjugants were obtained using W2 as the donor strain and Escherichia coli 25DN as the recipient strain. However, evolutionary analysis revealed that ICEPmiW2 likely evolved from ICEs of other P. mirabilis strains. Conclusions:The multiple-antibiotic-resistant P. mirabilis W2 strain with potential pathogenicity to aquatic animals was isolated, and the antibiotic-resistance-conferring ICEPmiW2 was identified in P. mirabilis W2. Our findings suggest that ICEPmiW2 of P. mirabilis W2 can potentially spread ARGs among environmental P. mirabilis strains.
ObjectiveSevere fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease characterized by high morbidity and mortality rates. Timely detection and prognosis prediction are critical for implementing effective clinical interventions. This study aimed to develop a binary classification machine learning model utilizing early clinical and laboratory indicators to predict the prognosis of SFTS patients, facilitating early clinical decision-making.MethodsWe conducted a retrospective study including 233 SFTS patients diagnosed from October 2021 to May 2024. Clinical and laboratory data at initial diagnosis were collected and subjected to baseline analysis and correlation analysis to identify significant indicators. Using the area under the receiver operating characteristic curve as an indicator of model performance, select the analytical model among machine learning (LR) models, XGBOOST, LightGBM, and random forest. A binary classification machine learning model for predicting survival outcomes was constructed using a logistic regression algorithm in conjunction with identified metrics. The model's performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). The model was externally validated using a separate cohort of 73 patients.ResultA total of 233 patients were included in this study, among whom 146 (62.7%) survived and 87 (37.3%) died, with 208 assigned to the internal cohort (177 to the training set and 31 to the test set) and the external validation cohort consisted of 73 patients, including 52 survivors (71.2%) and 21 mortality cases (28.8%). Based on the AUC, the LR model (0.750) is selected, where the values of XGBOOST, LightGBM, and random forest are 0.649, 0.661, and 0.716, respectively. The logistic regression model, incorporating age, lactate dehydrogenase (LDH), albumin, activated partial thromboplastin time (APTT), and platelet count, demonstrated robust predictive accuracy with an AUC of 0.913 (95% CI: 0.821-1.000) for the test set and 0.923 (95% CI: 0.842-1.000) for the external validation set. The model exhibited an accuracy of 0.863, with a sensitivity of 0.952 and an NPV of 0.977. The specificity and PPV were 0.827 and 0.690, respectively. These results indicate that the model maintains robust discriminative performance in an independent cohort, suggesting its potential utility as a screening tool with high sensitivity and favorable NPV.ConclusionThe model constructed using the first diagnostic indicators described above can accurately determine the patient's prognosis, which can help the clinician intervene earlier as well as take the necessary life-saving measures, and has the potential to improve the survival rate of SFTS patients.
Background:Achillea millefolium L. (yarrow) is one of the oldest known medicinal plants recognized for properties, such as wound healing, fever, common cold, liver problems, nosebleeding, toothache, and headache. Yarrow, being native to Europe, grows wild in the whole of Asia, Northern Europe, and North America and also occurs wild in Kashmir. Objectives:This study aimed to investigate the antioxidant and antimicrobial properties of Achillea millefolium L. (AM), focusing on its ethanolic extract and its fractions (hexane and ethyl acetate). Methods:The antioxidant activity of the extracts was assessed using reducing power and DPPH radical scavenging assays. The extract and its fractions (hexane and ethyl acetate) were evaluated for antimicrobial activity by the agar well diffusion method. Additionally, LC-MS was employed to analyze the chemical composition of the ethyl acetate fraction, and molecular docking studies were conducted to understand its mechanisms of action. Results:The ethyl acetate fraction showed the highest antioxidant activity with an IC50 value of 199.12 (μg/mL), antibacterial activity against B. subtilis, ZOI = 14.74 ± 0.16, and antifungal activity against C. neoformans 34.70 ± 0.58. LC-MS identified key compounds, including diosmin, pelargonin, and epicatechin. From the docking analysis, the highest binding affinity was monitored in the cases of diosmin with -10.7 kcal, followed by pelargonin (-9.3 kcal) and epicatechin (-8.6 kcal) with the EF-TU complex protein. Conclusion:In summary, this study highlights the antioxidant and antimicrobial capabilities of Achillea millefolium L. These findings will establish the groundwork for bioassay-guided separation of bioactive components that could serve as leads for future research to combat diseases caused by microbes that are resistant to drugs.
Introduction:There are limited therapeutic options available for treating aminoglycoside- and carbapenem-resistant Gram-negative bacteria. Therefore, there is an urgent need for novel effective antimicrobial agents. Numerous studies have reported the enhanced efficacy of antibiotic combinations against multidrug-resistant (MDR) strains compared to monotherapy. This study aimed to investigate the potential synergistic effects of amikacin in combination with imipenem and ciprofloxacin against clinical isolates of MDR Escherichia coli to identify the most promising antibiotic combinations for treating infections caused by these isolates. Methods:In this experimental study, 20 MDR E. coli isolates were examined. The minimum inhibitory concentration (MIC) and checkerboard method were determined for amikacin, imipenem, and ciprofloxacin. Results:MIC determination revealed ciprofloxacin MICs of 4-512 μg/mL, imipenem 0.125-32 μg/mL, and amikacin 1-128 μg/mL. Resistance rates were 55% (11/20) for amikacin, 100% (20/20) for ciprofloxacin, and 55% (11/20) for imipenem. Synergistic effects were observed between amikacin and imipenem in 50% of isolates (10/20) and between amikacin and ciprofloxacin in 40% (8/20), with no antagonistic interactions detected. Conclusions:The combination of amikacin with imipenem or ciprofloxacin resulted in synergistic and additive effects in some cases. These findings suggest that antibiotic combination therapy could serve as an effective strategy in managing infections caused by antibiotic-resistant isolates.
Background:Anaerobic infections remain clinically significant yet underrecognized due to diagnostic challenges and limited routine susceptibility testing in clinical laboratories. Among these pathogens, Bacteroides fragilis is a clinically important anaerobe associated with bloodstream and deep-seated infections. This study aimed to evaluate the epidemiology, clinical characteristics, and antimicrobial resistance patterns of Bacteroides fragilis bacteremia in a tertiary care hospital. Materials and Methods:This retrospective study included patients with blood cultures positive for Bacteroides fragilis between July 2018 and January 2023. Demographic characteristics, clinical features, infection sources, treatment regimens, and antimicrobial resistance patterns were analyzed. Results:Our analysis found a higher rate of Bacteroides fragilis bacteremia among cancer patients, likely linked to cancer treatments that compromise gastrointestinal defenses. Notably, both hospital-acquired infection (OR: 4.99, 95% CI: 1.3-19.07, p = 0.019) and respiratory tract infection (OR: 8.19, 95% CI: 1.21-55.35, p = 0.031) were associated with an increased risk of death within 30 days, highlighting the importance of vigilance in healthcare environments. Resistance to clindamycin was substantial, while ampicillin resistance was expected because of the intrinsic resistance profile of Bacteroides species. While carbapenem resistance was uncommon, its presence signals a shifting resistance pattern. Metronidazole remained effective, supporting its continued use. Conclusion:Bacteroides fragilis bacteremia is associated with significant mortality, particularly in nosocomial settings. Continuous surveillance and appropriate antimicrobial stewardship are essential for effective management.
Candidemia is a life-threatening bloodstream infection, most commonly caused by Candida albicans (C. albicans), and remains a significant concern in immunocompromised patients. Rapid and accurate species-level detection is essential for effective clinical management. Loop-mediated isothermal amplification (LAMP) is a robust nucleic acid amplification method that enables rapid pathogen detection under isothermal conditions. This study developed and evaluated an ITS2-targeted LAMP assay for the detection of C. albicans in human blood. Analytical sensitivity and specificity were assessed using tenfold serial dilutions of DNA from a standard C. albicans strain (1 ng-1 fg). Specificity was tested against six other fungal species commonly involved in bloodstream infections: C. tropicalis, C. krusei, C. neoformans, Fusarium spp., Aspergillus flavus, and A. niger. The assay detected C. albicans DNA at concentrations as low as 10 fg, surpassing conventional PCR, which detected down to 10 pg. No cross-reactivity was observed with non-albicans species tested. Performance in blood was evaluated using artificially spiked samples, in which the assay consistently detected C. albicans at 101 CFU/mL under controlled experimental conditions. These findings demonstrate that the ITS2-based LAMP assay provides a rapid and sensitive molecular approach for the detection of C. albicans under the experimental conditions evaluated and may have potential as a complementary tool for candidemia detection following further clinical validation.
Background:Cryptosporidium spp. is a major opportunistic pathogens in HIV/AIDS patients, contributing substantially to morbidity and mortality worldwide. Despite advances in HIV/AIDS management, the global burden, genetic diversity, and risk factors of cryptosporidiosis in this high-risk group remain incompletely understood. Methods:We conducted a systematic review and meta-analysis of cross-sectional and case-control studies published between January 1, 2017, and June 10, 2025, in accordance with PRISMA 2020 guidelines. Literature searches were performed in PubMed, Scopus, Embase, and Web of Science, supplemented by Google Scholar. Eligible studies reported the prevalence of Cryptosporidium spp. in HIV/AIDS patients, with or without comparison groups, using microscopy, serology, or molecular methods. Data extraction was performed independently by two reviewers, and study quality was assessed using the JBI checklist. Random-effects models were applied in Comprehensive Meta-Analysis software, with subgroup analyses and meta-regression conducted to explore prevalence and heterogeneity. Results:A total of 89 studies were included. The pooled prevalence of Cryptosporidium spp. among HIV/AIDS patients was 9.5% (95% CI: 7.6-11.8). Based on 17 case-control studies, HIV-positive individuals had a significantly higher risk of infection compared to HIV-negative controls (OR: 3.5, 95% CI: 2.1-5.9). Subgroup analyses revealed higher pooled prevalence in smaller studies, medium-HDI and lower-middle-income countries, and African and Central American settings. Pooled prevalence did not differ significantly across diagnostic methods. Among HIV/AIDS patients positive for Cryptosporidium spp., 39.8% were aged ≤ 30 years and 64.7% were > 30 years. Females represented 54.5% of positives, slightly higher than males at 45.8%. Most infected patients had CD4 counts ≤ 200 cells/μL (62.5%), compared to 43.2% with counts > 200. Diarrhea was present in 78.4% of positive cases, versus 43.8% among those without infection. Meta-regression confirmed a significant inverse association between sample size and prevalence (β = -0.0019, p = 0.003). Molecular data identified diverse species and subtypes, with C. hominis and C. parvum predominating but zoonotic species such as C. meleagridis, C. felis, C. viatorum, C. canis, C. suis, C. andersoni, and C. cuniculus also reported. Sensitivity analyses showed no single study significantly influenced the pooled prevalence. Funnel plot asymmetry and Egger's test indicated publication bias. Conclusions:This updated synthesis demonstrates that cryptosporidiosis remains a substantial health burden in HIV/AIDS patients, with notable genetic diversity reflecting both anthroponotic and zoonotic transmission routes. The strong association with immunosuppression, as evidenced by low CD4 counts and diarrheal symptoms, underscores its clinical relevance. These findings highlight the urgent need for improved surveillance, molecular epidemiology, and preventive interventions to mitigate the impact of Cryptosporidium spp. in vulnerable populations.
In nations with developing healthcare infrastructures, the dual burden of Type 2 diabetes mellitus (T2DM) and tuberculosis represents a critical health challenge. The aim of this study is to investigate the influence of T2DM on the development of multidrug-resistance tuberculosis (MDR-TB) in relation to genetic mutations of Mycobacterium tuberculosis in Ethiopia. A facility-based cross-sectional study was carried out between 2023 and 2024. Genetic mutations associated with drug resistance in both diabetic and nondiabetic groups were detected using line probe assays (LPAs). Diagnosis of T2DM was performed using fasting blood glucose and glycated hemoglobin levels. Data were analyzed with SPSS software, and logistic regression models were performed. Our findings revealed that 44 of the 182 participants (24.2%) were TB-T2DM, whereas 138 (75.8%) were TB with nondiabetic groups. Multivariate analysis displayed that the prior TB treatment history (aOR: 2.51, 95%CI: 1.02-6.19, p = 0.046) and a family history of T2DM (aOR: 2.25, 95% CI: 1.10-4.60, p = 0.031) were independently associated with an increased risk of TB-T2DM comorbidity. Genetic analysis identified a total of 50 mutations (22 rpoB, 22 katG, and 6 inhA promoter) associated with resistance to RIF and INH drugs among 31 drug-resistant M. tuberculosis isolates, which were significantly more common in TB-T2DM comorbid patients (p = 0.009). The rpoB S450L and katG S315T1 were the predominant mutations typically associated with high-level RIF and INH resistance, respectively, and high biological fitness, allowing for successful transmission within the community. Among the dual mutations identified in MDR-TB isolates, only the rpoB UN + katG S315T1 mutation was significantly more prevalent in nondiabetics (p = 0.04) compared to the TB-T2DM comorbid group. Multivariate analysis revealed that prior TB treatment history (aOR: 4.00, 95% CI: 1.31-12.50, p = 0.014) and TB-T2DM comorbidity (aOR: 3.12, 95% CI: 1.02-9.10, p = 0.042) were significantly associated with an increased likelihood of MDR-TB. This increased odd of resistance in comorbid patients highlights the need for bidirectional T2DM screening for all TB patients, particularly those with a history of prior TB treatment or a family history of diabetes. A genome-wide association study into the mutation patterns responsible for DR is crucial to inform the development of targeted, effective strategies moving forward.
This study aimed to evaluate the antimicrobial potential of the supernatant (conditioned medium) of mesenchymal stem cells-derived conditioned medium (MSCs CM), incorporated in chitosan nanoparticles (CS NPs), against multidrug-resistant (MDR) clinical isolates. Dynamic light scattering (DLS), zeta potential (ZP), and scanning electron microscopy (SEM) assays were used to characterize CS NPs. MSCs CM was incorporated into CS NPs, and its release pattern from the composite (MSCs CM-CS NPs) was evaluated. Antibacterial properties of MSCs CM-CS NPs, as well as MSCs CM and CS NPs, were assessed by the microbroth dilution technique. The average particle size of most CS NPs was 85.2 nm, and their zeta potential was 32.1 mV. SEM findings supported the morphology of the prepared CS NPs and the synthesized composite (MSCs CM-CS NPs). Entrapment efficiency of the new construct was 71%. The antimicrobial activity of the new construct (MSCs CM-CS NPs: 1000 μg/mL + 0.05%) against MDR bacteria was significantly higher compared with MSCs CM (1000 μg/mL) and CS NPs (0.05%) each alone. This composite exhibited the synergistic antibacterial activity of the combination of MSCs CM and CS NPs, resulting in a more potent dose-dependent antibacterial activity against MDR clinical isolates.
BackgroundSix decades have elapsed since the index case of monkeypox virus (MPXV) was reported. Unlike most DNA viruses characterized by slow mutation and spread, MPXV caused the global outbreak of 2022, and as expected, several studies prior and post the 2022 outbreak have emanated. Despite its ability to trigger a potential pandemic, there is no holistic quantitative and qualitative insight into MPXV research landscape globally.MethodsFollowing the Scientific Procedures and Rationales for Systematic Literature Review (SPAR-4-SLR protocol) applied to the Scopus database, studies were retrieved covering 1976-2025 on MPXV globally and screened using predefined criteria. The final dataset was analyzed using Biblioshiny, RStudio, and VOSviewer tool.ResultsOf the 8460 retrieved records, 5315 met the inclusion and exclusion criteria, comprising 79.98% original articles and 20.02% review articles, authored by 32,098 researchers across 1547 journals. Our analysis of the MPXV research revealed an average annual growth rate of 12.38%, with a pronounced surge after 2021, coinciding with the global 2022 outbreak. The United States dominated research output, authorship, funding, institutional leadership, and international collaborations, with the Centers for Disease Control (CDC) emerging as the most influential institution. China, India, and the United Kingdom also contributed substantially, while resource-poor settings were underrepresented. Keyword and thematic analyses revealed a transition from early virological and animal studies to recent emphasis on human transmission, epidemiology, vaccination, and therapeutics. Highly cited studies were concentrated in leading infectious disease journals. Overall, MPXV research has evolved rapidly, highlighting expanding global collaboration and shifting research priorities.ConclusionThe study demonstrates a sharp post-2021 expansion of MPXV research, dominated by high-income countries, particularly the United States. Strengthening research contributions, surveillance, and collaborations from MPXV-endemic regions in Africa is essential for balanced global preparedness and response efforts.
Advances in the epidemiology of seasonal coronavirus (CoV) are important for understanding CoV transmission dynamics and strengthening the strategies against emerging CoV infections. The epidemiology of CoV-NL63, a seasonal CoV discovered in 2003, is poorly understood, particularly before 2003. To analyze the seroprevalence of CoV-NL63 in Yamagata, Japan, we performed a microneutralization test using 146 to 379 serum samples collected from four age groups ranging from 0 to 4 years to ≥ 40 years in 1976, 1990, 2010, 2019, and 2022, as well as the Yamagata isolate. We only measured the neutralizing antibodies (NT Abs) against CoV-NL63, as methods for other seasonal CoVs had not yet been established. The total NT Ab-positive rate in each year was 68.0%-90.4%. The Ab-positive rates in 0-4-year age group were 21.3%-65.2% in each year, whereas the rates for individuals aged above 4 years old were between 73.3% and 100% throughout the study period. We do not understand the influence of cross-reactive immunity among seasonal CoVs. This study shows that seroprevalence against CoV-NL63 increased with age in the younger generation and then plateaued at a high level, suggesting that reinfection may occur and that CoV-NL63 was already transmitted among infants and children before CoV-NL63 had been identified.
Background:Antibiotics, as a selection stress, could trigger specific responses in bacterial pathogens. This study aimed to investigate adaptive changes of E. coli SM10λpir (pUCP24T) under constant treatment of sub-MIC Gm (gentamicin). Methods:E. coli SM10λpir (pUCP24T) underwent continuous passage culture by serial transfer for 50 days on agar plates containing 30 μg/mL Gm to obtain E. coli SM10λpir (pUCP24T)-E. Two strains were compared for the horizontal gene transfer ability, stability of plasmid pUCP24T, fitness cost, and expression of conjugation-related genes. Based on whole genome and RNA sequencing data, functional enrichment analysis (GO and KEGG) was conducted, along with analyses of plasmid sequencing depth, SNPs, and differentially expressed genes (DEGs). Results:The conjugation frequency of E. coli SM10λpir (pUCP24T)-E with recipient PAO1 was higher, and its traI expression was significantly upregulated (p < 0.05). In the same strain, the growth rate and competition index were lower (p < 0.05); the sequencing depth of plasmid pUCP24T and the relative expression of the rep gene were much higher (p < 0.05), but the plasmid showed reduced stability. Functional enrichment analysis suggested a possible enhancement of certain physiological processes and metabolic pathways. A total of 1294 DEGs were detected, with obvious upregulation of hycB, hycD, nikE, cspA, and nanA, and obvious downregulation of gadB, gadC, yeiQ, and yjiH, transcription factors (appY, gadE), and sRNAs (arrS, isrC). Additionally, the expression of aerobic respiratory pathway genes (cyoABCDE) in E. coli SM10λpir (pUCP24T)-E increased significantly (p < 0.05). Conclusions:The enhanced conjugation frequency during adaptation may be attributed to increased expression of the transfer gene traI and an elevated copy number of plasmid pUCP24T. A heavier fitness cost was imposed on the host during this process. Aerobic respiration and metabolic efficiency were likely potentiated. sRNA isrC was hypothesized to inhibit aerobic respiration by targeting the cytochrome bo oxidase subunit cyoD.
Purpose:We aim to investigate which of the comorbidities is associated with prolonged viral RNA shedding among hospitalized patients with COVID-19 illness. Patients and Methods:We conducted a retrospective cohort study of COVID-19 patients in Hasan Sadikin General Hospital, Bandung, from March 2020 to April 2022. Data of ORF1b Ct value measurements were collected from the 1st week to the 5th week and presented in a line plot to see the changes in the Ct values across the course of the disease stratified to each comorbidity. Results:We included a total of 279 patients with a median age of 55-year-old, and male patients were the majority included. However, 68% of the original cohort was excluded due to having only a single Ct result. Based on the ORF1b Ct value data, most patients within each comorbidity group demonstrated increasing Ct values from Week 1 (n = 135) to Week 5 (n = 34). However, we found that the ORF1b Ct value in the HIV-AIDS (n = 12) and the autoimmune (n = 12) groups peaked and gradually declined. In the HIV-AIDS ORF1b, Ct values declined after 2 weeks (n = 2) with a statistically significant difference compared to patients without comorbidity (n = 65). Conclusion:This study shows that COVID-19 patients with HIV-AIDS have prolonged viral shedding compared to patients with other comorbidities.
Introduction:Helicobacter pylori (H. pylori) infection is highly prevalent worldwide and is associated with multiple gastroduodenal pathologies, including gastric cancer. The increasing pattern of drug resistance among H. pylori limits available treatment options. To overcome this challenge, drug repurposing and the use of current medications as adjuvant therapies have emerged as a valuable alternative strategy. Metformin is a commonly prescribed antidiabetic drug for Type 2 diabetes mellitus (T2DM); it has been shown to have antibacterial properties. This study aimed to investigate the anti-H. pylori activity of metformin and evaluate its potential to enhance the efficacy of six conventional antibiotics used to treat H. pylori infections. Methods:The antibacterial effect of metformin on H. pylori was evaluated using both clinical and reference laboratory strains by detecting the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Furthermore, a checkerboard assay was conducted to assess the combined effect of metformin with six conventional antibiotics used to treat H. pylori infection. Results:Metformin showed limited antibacterial activity against H. pylori, with MIC and MBC values ranging between 6.83 and 9.75 mM (1131-1615 μg/mL). MIC/MBC ratios and time-kill study suggested a bactericidal effect against the tested H. pylori strains. The fractional inhibitory concentration index (FICI) findings for the tested combinations were 0.52-1.0, including the MDR strain, indicating an additive effect. No synergistic or antagonistic interactions were observed. Conclusion:The additive effect and the bactericidal activity of metformin suggest a potential clinical relevance for diabetic patients already receiving this medication. However, comprehensive studies are needed to further evaluate safety, efficacy, and the underlying killing mechanism of metformin against H. pylori.
