Hasil untuk "Microbiology"

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DOAJ Open Access 2025
Physics-informed AI with chemical master equation dynamics for driver-gene subclone detection and risk labeling

Komlan Atitey, Caitlin E. Hughes, Joseph C. Fusco

Subclonal populations shape progression and therapy response but are difficult to resolve in bulk transcriptomes, where rare signals are diluted by dominant clones. Existing methods often treat samples as static mixtures, infer lineages without expression-defined states, or rank genes without specifying when to evaluate, yielding unstable signatures. We propose magicSubclonal, a physics-informed framework that embeds driver-gene dynamics using a Chemical Master Equation. From gene expression, we estimate decay, burst initiation, and burst size; automatically select the time of maximal rare-state separation; and identify subclones whose extremes lie within calibrated predictive envelopes. Driver-timed states are then linked to non-driver genes with False Discovery Rate control, and clinical risk is assigned using bootstrap-stabilized Cox/logistic models. Applied to ovarian, lung, Ductal Carcinoma in Situ, and breast cohorts, fits yielded plausible half-lives and well-calibrated predictions. We introduce the Subclone Driver Relevance Score (SDRS), a bounded metric quantifying outcome alignment under a uniform operating point. Across cohorts, magicSubclonal achieved the highest SDRS and superior ROC and precision-recall performance, outperforming variant-allele clustering (sciClone), expression factorization (NMF), and two expression-only baselines: single-sample deconvolution (ss-Deconv) and a diagonal log-Gaussian mixture (MM). Gains were most pronounced at low false-positive rates and early-recall regions, reflecting added signal beyond static mixtures or unsupervised clustering. By integrating stochastic driver dynamics with population-level heterogeneity and outcome-anchored evaluation, magicSubclonal provides interpretable, reproducible subclone discovery and robust risk labeling. Sensitivity analyses confirmed that predictions are driven by burst initiation and size, with decay increasingly influential over longer horizons, supporting cross-cohort consistency under identical preprocessing.

DOAJ Open Access 2025
Detection of Class 1 Integron among Klebsiella pneumoniae Clinical Isolates in Baghdad Hospitals

Jasim S. Jasim, Alyaa R. Hussein

Background: Extensively drug-resistant Klebsiella pneumoniae (K. pneumoniae) is a significant problem currently due to the increasing prevalence of this pathogen. Objectives: To underscore the growing threat of antibiotic-resistant K. pneumoniae by investigating the prevalence of class 1 integrons among selected multidrug-resistant (MDR) clinical isolates, with the goal of emphasizing the need for strengthened surveillance and targeted antimicrobial strategies. Methods: Seventy-four K. pneumoniae isolates have been identified out of 200 clinical samples from different clinical sources (urine, burns, blood, sputum, wounds). Isolates were obtained from November 2024 to March 2025, in Al-Kadhimiya Teaching Hospital and the Laboratory at College of Science Microbiology Department, University of Baghdad. The isolates were first detected by biochemical testing, chromogenic agar and later confirmed using the VITEK 2 method. Antimicrobial susceptibility was evaluated utilizing the disc diffusion technique (Kirby-Bauer method). The presence of the class 1 integron gene was confirmed via conventional PCR. Results: A total of 200 clinical samples were collected from the 74 K. pneumoniae isolates; 51 (68.9%) exhibited multidrug resistance. Resistance to cefotaxime was observed in 86%, followed by tetracycline (80%), while imipenem exhibited the highest sensitivity at 84%. Class 1 integron gene was identified in 80% of the 10 selected multidrug-resistant isolates. Conclusion: The high incidence of class 1 integrons in multidrug-resistant K. pneumoniae clinical isolates highlights the essential role of integrons in the spread of antibiotic resistance. This indicates the worldwide emergence of K. pneumoniae pathogenic strains resistant to colistin and carbapenems, highlighting the imperative for ongoing molecular surveillance and efficient antibiotic stewardship.

Medicine, Medicine (General)
DOAJ Open Access 2025
Evaluation of resistance modulation in MDR Pseudomonas aeruginosa and Klebsiella pneumoniae using peppermint oil nanoemulsion: integrating antibacterial assays and molecular modeling

Sardar Ali, Firasat Hussain, Tehmeena Nousheen et al.

IntroductionMultidrug-resistant urinary tract pathogens, primarily Klebsiella pneumoniae and Pseudomonas aeruginosa, represent a significant and growing public health challenge. The overuse of antibiotics has accelerated the development of resistance, creating an urgent need for alternative antimicrobial strategies. This study aimed to evaluate the antibacterial efficacy of a peppermint oil nanoemulsion (PEONE) against clinical multidrug-resistant (MDR) isolates of K. pneumoniae and P. aeruginosa, with a specific focus on its potential for resistance modulation and its mechanism of action.MethodsClinical isolates were obtained from patients with urinary tract infections and their antibiotic susceptibility profiles were determined. The PEONE was prepared using ultrasonic emulsification and characterized, revealing a droplet size of 190.21 ± 0.5 nm and a polydispersity index (PDI) of 0.15 ± 0.021. Antibacterial activity was assessed by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Membrane integrity was evaluated using DNA and protein leakage assays, and bacterial killing over time was measured with time-kill kinetics. Furthermore, molecular docking and 100 ns molecular dynamic simulations were performed against β-lactamase enzymes (PDB: 4EXY from K. pneumoniae, 6R73 from P. aeruginosa) to identify key bioactive components within the nanoemulsion.ResultsThe bacterial isolates were resistant to Levofloxacin, Penicillin G, Ceftazidime, and amoxicillin-clavulanic acid (AMC). PEONE demonstrated potent antibacterial activity, with an MIC of 0.1% v/v and an MBC of 0.14% v/v. DNA and protein leakage increased significantly (p < 0.05) with higher PEONE concentrations, indicating bacterial membrane disruption. Time-kill assays showed a sustained reduction in bacterial viability over 72 hours, with significant differences emerging after 12 hours of exposure. Molecular docking revealed that caryophyllene, a major component of peppermint oil, had the highest binding affinity against both β-lactamase targets (−9.2 kcal/mol for 4EXY; −7.1 kcal/mol for 6R73). The stability of this binding was confirmed through molecular dynamics simulations.DiscussionThe findings indicate that PEONE is effective at inhibiting and killing MDR K. pneumoniae and P. aeruginosa. The observed leakage of DNA and proteins suggests that the mechanism of action likely involves disruption of the bacterial membrane, leading to the loss of intracellular contents. This is further supported by the computational data, which identified caryophyllene as a key component with stable binding to resistance-associated β-lactamase enzymes. These results position PEONE as a promising, plant-based alternative for combating antibiotic-resistant urinary tract infections. Further in vivo studies are warranted to explore its clinical applicability and safety profile.

DOAJ Open Access 2025
Mapping social-ecological connectivity of small scale fisheries: A network-based study in Paraja Bay, Banten, Indonesia

Choiri Muhamad Fatin, Yulianto Gatot, Boer Mennofatria

The small-scale fisheries of Paraja Bay are a complex system that plays a vital role in people's livelihoods. This study aims to map the connectivity of social-ecological components in small-scale fisheries systems in Paraja Bay, Banten, Indonesia. Social-Ecological Systems Framework (SESF) approach was applied to identify key variables in the small-scale fisheries system. The SESF variables were then analyzed using Social- Ecological Networks Analysis (SENA) with the igraph program in R. The analysis revealed 33 nodes and 58 edges of interaction in the system. The analysis identified fishing activity (FishAktv) and regulation as the most central nodes, which are important links in the system. Nodes such as income, debt, and lift net owners also function as strategic nodes in connecting the social, economic, and institutional dimensions. The results show the importance of key elements such as economics and governance for intervention and policy in system networking. The combined SESF and SENA approach has proven to provide a more holistic understanding of the dynamics of small-scale fisheries systems.

Microbiology, Physiology
DOAJ Open Access 2024
Psychological and educational aspects of students’ adaptation in the context of digitalization

Melkumyan Anahit, Sahakyan Maria

This article aims to identify the factors that influence the academic performance of undergraduate students, focusing on digital literacy, digital knowledge and skills, as well as personal characteristics in the digital economy. To identify these relationships, surveys were conducted among students using appropriate online questionnaires, and the Big Five Personality Traits (BFPT) testing methodology was chosen to assess the personal qualities of undergraduate students. The findings of the study are consistent with the research in the field indicating a correlation between digital skills and student academic success and simultaneously the inverse impact of social media on academic performance. In addition, the study showed that there is also a positive relationship between some personal traits as conscientiousness, agreeableness and academic performance outcomes. Research illustrates the significant role of gender in academic achievement, explaining how differences in male and female personality traits can influence academic performance and adaptability. The results confirm that academic success and, thus, the ability to adapt to the changing conditions can be explained by personal traits and digital technologies used while the other possible factors can include gender, professional and cultural background.

Microbiology, Physiology
DOAJ Open Access 2024
The Staphylococcus aureus regulatory program in a human skin-like environment

Flavia G. Costa, Krista B. Mills, Heidi A. Crosby et al.

ABSTRACTStaphylococcus aureus is a Gram-positive pathogen responsible for the majority of skin and soft tissue infections (SSTIs). S. aureus colonizes the anterior nares of approximately 20%–30% of the population and transiently colonizes the skin, thereby increasing the risk of developing SSTIs and more serious infections. Current laboratory models that mimic the skin surface environment are expensive, require substantial infrastructure, and limit the scope of bacterial physiology studies under human skin conditions. To overcome these limitations, we developed a cost-effective, open-source, chemically defined media recipe termed skin-like medium (SLM) that incorporates key aspects of the human skin surface environment and supports growth of several staphylococcal species. We utilized SLM to investigate the transcriptional response of methicillin-resistant Staphylococcus aureus (MRSA) following growth in SLM compared to a commonly used laboratory media. Through RNA-seq analysis, we observed the upregulation of several virulence factors, including genes encoding functions involved in adhesion, proteolysis, and cytotoxicity. To further explore these findings, we conducted quantitative reverse transcription-PCR (qRT-PCR) experiments to determine the influence of media composition, pH, and temperature on the transcriptional response of key factors involved in adhesion and virulence. We also demonstrated that MRSA primed in SLM adhered better to human corneocytes and demonstrated adhesin-specific phenotypes that previously required genetic manipulation. This improved adherence to corneocytes was dependent on both acidic pH and growth in SLM. These results support the potential utility of SLM as an in vitro model for assessing staphylococcal physiology and metabolism on human skin.IMPORTANCEStaphylococcus aureus is the major cause of skin diseases, and its increased prevalence in skin colonization and infections present a need to understand its physiology in this environment. The work presented here outlines S. aureus upregulation of colonization and virulence factors using a newly developed medium that strives to replicate the human skin surface environment and demonstrates roles for adhesins clumping factor A (ClfA), serine-rich repeat glycoprotein adhesin (SraP), and the fibronectin binding proteins (Fnbps) in human corneocyte adherence.

DOAJ Open Access 2024
Formulation and evaluation of a probiotic drink fortified chlorella for enhanced health benefits

Iriani Dian, Hasan Bustari, Warningsih Trisla et al.

Probiotics are microorganisms that have benefits when consumed, they can be found in yogurt. Yogurt commercially lack protein; the addition of chlorella is a solution due to chlorella contains high protein. The research aimed to determine the effect of chlorella fortification on the quality characteristics of yogurt and the best concentration of chlorella addition in the manufacturing of yogurt. The experimental method using a non-factorial Completely Randomized Design (CRD) consisting of 4 treatment levels: without the addition of chlorella (PC0), 0.75% of chlorella (PC1), 1% of chlorella (PC2), and 1.25% of chlorella (PC3). The parameters tested in this research were hedonic testing and quality, chemical composition, physical properties, and microbiological assay. The results showed that yogurt fortified with 1% chlorella was most favorable by consumer acceptance, with organoleptic characteristics: green and thick color, slightly characteristic aroma of chlorella, and slightly sour taste typical of chlorella. Meanwhile, the proximate composition of this yogurt contains 81.26% moisture, 3.77% protein, 2.30% fat, 0.89% ash, 1.47% fiber; physical properties of pH 4.65, Aw 0.75, viscosity 205.85 cP; and microbiological value of acid total 1.95%, and lactic acid bacteria 2.1×107 cfu/g. Therefore, the yogurt chlorella is suitable for consumption and can enhance health benefits.

Microbiology, Physiology
DOAJ Open Access 2023
Computational Prediction of RNA–RNA Interactions between Small RNA Tracks from <i>Betacoronavirus</i> Nonstructural Protein 3 and Neurotrophin Genes during Infection of an Epithelial Lung Cancer Cell Line: Potential Role of Novel Small Regulatory RNA

Alexis Felipe Rojas-Cruz, Clara Isabel Bermúdez-Santana

Whether RNA–RNA interactions of cytoplasmic RNA viruses, such as <i>Betacoronavirus</i>, might end in the biogenesis of putative virus-derived small RNAs as miRNA-like molecules has been controversial. Even more, whether RNA–RNA interactions of wild animal viruses may act as virus-derived small RNAs is unknown. Here, we address these issues in four ways. First, we use conserved RNA structures undergoing negative selection in the genomes of SARS-CoV, MERS-CoV, and SARS-CoV-2 circulating in different bat species, intermediate animals, and human hosts. Second, a systematic literature review was conducted to identify <i>Betacoronavirus</i>-targeting hsa-miRNAs involved in lung cell infection. Third, we employed sophisticated long-range RNA–RNA interactions to refine the seed sequence homology of hsa-miRNAs with conserved RNA structures. Fourth, we used high-throughput RNA sequencing of a <i>Betacoronavirus</i>-infected epithelial lung cancer cell line (Calu-3) to validate the results. We proposed nine potential virus-derived small RNAs: two vsRNAs in SARS-CoV (Bats: SB-vsRNA-ORF1a-3p; SB-vsRNA-S-5p), one vsRNA in MERS-CoV (Bats: MB-vsRNA-ORF1b-3p), and six vsRNAs in SARS-CoV-2 (Bats: S2B-vsRNA-ORF1a-5p; intermediate animals: S2I-vsRNA-ORF1a-5p; and humans: S2H-vsRNA-ORF1a-5p, S2H-vsRNA-ORF1a-3p, S2H-vsRNA-ORF1b-3p, S2H-vsRNA-ORF3a-3p), mainly encoded by nonstructural protein 3. Notably, <i>Betacoronavirus</i>-derived small RNAs targeted 74 differentially expressed genes in infected human cells, of which 55 upregulate the molecular mechanisms underlying acute respiratory distress syndrome (ARDS), and the 19 downregulated genes might be implicated in neurotrophin signaling impairment. These results reveal a novel small RNA-based regulatory mechanism involved in neuropathogenesis that must be further studied to validate its therapeutic use.

DOAJ Open Access 2023
Evaluation of the diagnostic effectiveness of next generation sequencing in sepsis etiology: a systematic review and meta-analysis

Dong Li, Yinghao Yang, Ying Xie et al.

Introduction: Systematic evaluation of the diagnostic value of next generation sequencing (NGS) in sepsis etiology. Methodology: We conducted a systematic search on four databases (Web of Science, Cochrane, PubMed, and Embase) and compiled diagnostic experiments using NGS to evaluate sepsis etiology. Two researchers conducted research and obtained data independently. Results: Nine documents were included comprising 747 patients, 988 blood samples, 175 bronchoalveolar lavage fluid (BALF) samples, 16 cerebrospinal fluid samples, and one urine sample. The combined sensitivity of each study was 0.89 (95% CI: 0.82-0.95). The combined specificity was 0.40 (95% CI: 0.25-0.55). The combined positive likelihood ratio was 1.51 (95% CI: 1.18-1.98). The combined negative likelihood ratio was 0.28 (95% CI: 0.11-0.48). The diagnostic odds ratio (DOR) was 6.38 (95% CI: 2.53-15.32) and the area under the curve (AUC) was 0.84, (95% CI: 0.62-0.94). Conclusions: Based on the data we collected, we found that compared with the blood culture technology, NGS has the advantages of high sensitivity and wide detection range, but its specificity was low. Further study is needed to confirm the value of NGS in the etiological diagnosis of patients with sepsis.

Internal medicine, Microbiology
DOAJ Open Access 2022
Household costs associated with seeking malaria treatment during pregnancy: evidence from Burkina Faso and The Gambia

Laetitia Duval, Elisa Sicuri, Susana Scott et al.

Abstract Background Malaria in pregnancy remains a major health threat in sub-Saharan Africa to both expectant mothers and their unborn children. To date, there have been very few studies focused on the out of pocket costs associated with seeking treatment for malaria during pregnancy. Methods A cross-sectional survey was undertaken in Burkina Faso and The Gambia to estimate the direct and indirect costs associated with outpatient consultations (OP) and inpatient admissions (IP). Direct costs were broken down into medical (admission fees, drug charges, and laboratory fees), and non-medical (transportation and food). Indirect costs reflected time lost due to illness. In total, 220 pregnant women in Burkina Faso and 263 in The Gambia were interviewed about their treatment seeking decisions, expenditure, time use and financial support associated with each malaria episode. Results In Burkina Faso 6.7% sought treatment elsewhere before their OP visits, and 27.1% before their IP visits. This compares to 1.3% for OP and 25.92% for IP in The Gambia. Once at the facility, the average direct costs (out of pocket) were 3.91US$ for an OP visit and 15.38US$ of an IP visit in Burkina Faso, and 0.80US$ for an OP visit and 9.19US$ for an IP visit in The Gambia. Inpatient direct costs were driven by drug costs (9.27US$) and transportation costs (2.72US$) in Burkina Faso and drug costs (3.44 US$) and food costs (3.44 US$) in The Gambia. Indirect costs of IP visits, valued as the opportunity cost of time lost due to the illness, were estimated at 11.85US$ in Burkina Faso and 4.07US$ in The Gambia. The difference across the two countries was mainly due to the longer time of hospitalization in Burkina Faso compared to The Gambia. In The Gambia, the vast majority of pregnant women reported receiving financial support from family members living abroad, most commonly siblings (65%). Conclusions High malaria treatment costs are incurred by pregnant women in Burkina Faso and The Gambia. Beyond the medical costs of fees and drugs, costs in terms of transport, food and time are significant drivers. The role of remittances, particularly their effect on accessing health care, needs further investigation.

Medicine (General)
DOAJ Open Access 2021
Orbital apex syndrome due to invasive aspergillosis in an immunocompetent patient

Grace D. Cullen, Tara M. Davidson, Zachary A. Yetmar et al.

Infection is a rare cause of orbital apex syndrome (OAS) and most commonly occurs in immunocompromised hosts. We report a case of OAS in an elderly immunocompetent female due to invasive aspergillosis and Staphylococcus aureus co-infection. The patient required both surgical debridement and prolonged courses of antibiotic and antifungal therapy. Invasive fungal disease must be considered in cases of OAS, even in patients without classic risk factors.

Infectious and parasitic diseases
DOAJ Open Access 2020
Consumption of Fermented Foods Is Associated with Systematic Differences in the Gut Microbiome and Metabolome

Bryn C. Taylor, Franck Lejzerowicz, Marion Poirel et al.

ABSTRACT Lifestyle factors, such as diet, strongly influence the structure, diversity, and composition of the microbiome. While we have witnessed over the last several years a resurgence of interest in fermented foods, no study has specifically explored the effects of their consumption on gut microbiota in large cohorts. To assess whether the consumption of fermented foods is associated with a systematic signal in the gut microbiome and metabolome, we used a multi-omic approach (16S rRNA amplicon sequencing, metagenomic sequencing, and untargeted mass spectrometry) to analyze stool samples from 6,811 individuals from the American Gut Project, including 115 individuals specifically recruited for their frequency of fermented food consumption for a targeted 4-week longitudinal study. We observed subtle but statistically significant differences between consumers and nonconsumers in beta diversity as well as differential taxa between the two groups. We found that the metabolome of fermented food consumers was enriched with conjugated linoleic acid (CLA), a putatively health-promoting molecule. Cross-omic analyses between metagenomic sequencing and mass spectrometry suggest that CLA may be driven by taxa associated with fermented food consumers. Collectively, we found modest yet persistent signatures associated with fermented food consumption that appear present in multiple -omic types which motivate further investigation of how different types of fermented food impact the gut microbiome and overall health. IMPORTANCE Public interest in the effects of fermented food on the human gut microbiome is high, but limited studies have explored the association between fermented food consumption and the gut microbiome in large cohorts. Here, we used a combination of omics-based analyses to study the relationship between the microbiome and fermented food consumption in thousands of people using both cross-sectional and longitudinal data. We found that fermented food consumers have subtle differences in their gut microbiota structure, which is enriched in conjugated linoleic acid, thought to be beneficial. The results suggest that further studies of specific kinds of fermented food and their impacts on the microbiome and health will be useful.

DOAJ Open Access 2020
Betalain exerts a protective effect against glaucoma is majorly through the association of inflammatory cytokines

Jiadi Wang, Dandan Zhang, Conghong Cao et al.

Abstract The present research aimed at evaluating the protective role of betalain on the in vitro glaucoma model using PC12 neuronal cells. The cultured neuronal cells in a customized pressurized chamber were analyzed for the onset of glutathione, myeloperoxidase (MPO), cathepsin, expression of inflammatory enzymes such as cyclooxygenase (COX-1), lipoxygenase (5- LOX), sPLA2 caveolin-1, glaucoma markers and other inflammatory cytokines in the presence and absence of betalain. The results have shown that a significant increase in the expression of oxidative stress with increased activity of cathepsin B and D. On the other hand, the activity of inflammatory enzymes such as COX-1, 5- LOX, sPLA2 were significantly increased in pressure exposed cells. In addition, glaucoma simulated cells demonstrated a significant increase in the VEGF, TGF-β, BDGF, and neuroserpin compared to control. Moreover, cells predisposed to hydrostatic pressure demonstrated an increase in (p < 0.01) inflammatory cytokines such as IL-6, CXCR4, IL-17, IL-1β, and TNF-α levels. However, cells pre-treated with betalain improved the glutathione levels with attenuated MPO activity. Simultaneously, the levels of inflammatory cytokines and other glaucoma marker genes found restored in drug pre-treated cells. Thus, the results of the present study demonstrate that the use of betalain on ocular cells can prevent the progression of the disease that can be a suggestive therapeutic for controlling glaucoma like conditions.

Biotechnology, Microbiology
DOAJ Open Access 2019
Effect of Gamma-Rays on the Growth and Penicillin Production of Penicillium chrysogenum

Mohammed M. Aljeldah, Hosam El-Sayyad, Nasreldin Elhadi et al.

This study aimed to investigate the effects of different doses (25, 50, 75, 100, 125, 150, 200, 250, 500, 1000 and 2000 Gy) of gamma radiation on spore germination in Penicillium chrysogenum and on the production and efficacy of penicillin in this fungus. A dose of 200 Gy of gamma radiation increased spore germination by 70.2% after 20 hours of incubation compared to control cultures. It was also found that penicillin yield increased by 95.2% at this dose of gamma radiation. The efficacy of penicillin was remarkably enhanced, resulting in a 99.6% reduction in the total count of Staphylococcus aureus treated with penicillin from irradiated P. chrysogenum compared with that of S. aureus treated with commercially available and purified penicillin from nonirradiated fungi. The results obtained highlighted the potential of this technology for production of penicillin.

DOAJ Open Access 2018
Assessment of disinfectant and antibiotic susceptibility patterns and multi-locus variable number tandem repeat analysis of Staphylococcus epidermidis isolated from blood cultures

Parisa Asadollahi, Fereshteh Jabalameli, Reza Beigverdi et al.

Background and Objectives: Variable number tandem repeat (VNTR) patterns and resistance against three commonly used hospital disinfectants [0.5% (w/w) chlorhexidine digluconate (CHG) and 75% (w/w) alcohol (A), CHG-A; Quaternary ammonium compounds (QACs) and biguanides (B), QAC-B; and 70% (w/w) isopropanol (ISP) and 0.25% (w/w) QACs, ISP-QAC], as well as frequently used antibiotics, were evaluated among 115 Staphylococcus epidermidis blood isolates recovered from a children’s hospital in Tehran, Iran. Materials and Methods: Multi-locus variable number tandem repeat analysis (MLVA) was performed using primers targeting 5 VNTR loci on the genome of S. epidermidis isolates. Micro-broth dilution method and detection of qacA/B and smr genes were carried out for evaluating resistance against the disinfectants. Results: Out of the 115 isolates, 115 (100%) and 113 (98.3%) were susceptible to linezolid and quinupristin/dalfopristin, respectively. A total of 55.7% of the isolates were found to be multidrug resistant (MDR). All isolates had MICs of CHG-A and ISP-QAC of 8 folds lower and MIC of QAC-B 6 folds lower than that suggested by the manufacturers. The genes qacA/B and smr were found in 28 (24.3%) and 14 (12.2%) isolates, respectively. MLVA typing of the S. epidermidis isolates resulted in 106 VNTR patterns and 102 MLVA types for the 112 S. epidermidis isolates, considering that 3 were not typeable. Conclusion: MLVA typing of S. epidermidis isolates show a great diversity and that the isolates are still susceptible to the concentrations of disinfectants recommended for use by the manufacturers. In addition, the relatively high percentage of the MDR S. epidermidis isolates could cause MDR infections and act as reservoirs to transfer resistance determinants to S. aureus population. Therefore, it is important that suitable infection control strategies are employed to avoid the distribution of MDR isolates between personnel and patients in this medical centre.

Microbiology
DOAJ Open Access 2018
Therapeutic potential of DNA methyltransferase inhibitors with immune checkpoint inhibitor therapy in breast cancer

Na Luo, Ayaka Sugiura, Justin M. Balko

Immune checkpoint inhibitor (ICI) therapy has changed the landscape of cancer treatment, particularly for high-mutation burden cancers. However, ICI therapy has thus far demonstrated limited efficacy in breast cancers, where tumor mutation rates are intermediate. Nonetheless, because of limited but positive signals in early trials, combinations of therapies to enhance anti-tumor immunity, and thus response to ICIs in breast cancer, are actively being sought. Our laboratory recently found that guadecitabine, a next-generation DNA methyltransferase inhibitor (DMTi), potentiated cytotoxic CD8+ T cell responses in breast cancer, which appeared to occur by the following mechanisms: (1) DMTi treatment hypomethylated and up-regulated both baseline and IFN-γ-induced MHC-I expression, thereby enhancing antigen presentation capacity, (2) DMTi treatment increased Cxcr3 ligands/chemokines (i.e., Cxcl9, Cxcl10, and Cxcl11) expression and recruited cytotoxic CD8+ T cells into the tumors and (3) DMTi treatment activated NFκB signaling, presumably through the expression of endogenous retroviral (ERV) sequences in tumor cells, initiating an innate response observed in other solid tumor types [Luo et al., Nat Commun 9(1):248]. Most importantly, DMTi treatment primed breast cancer and improved responses to anti-PD-L1 therapy.

Medicine, Biology (General)
S2 Open Access 2013
Human impact on the microbiological water quality of the rivers

E. Páll, M. Niculae, T. Kiss et al.

Microbiological contamination is an important water-quality problem worldwide. Human impact on this category of contamination is significant and several human-related activities, and also the population explosion, have affected and are still affecting dramatically the aquatic environment. Extensive industrialization and agriculture have led to increased pollution and hydromorphological changes in many river basins. The Danube river is one of the most affected by these changes where human involvement is undeniable, and subsequently, the Danube Delta Biosphere Reserve became one of the most vulnerable ecosystems. This review is an attempt to analyse the microbiological contamination and to identify the major role human activities play in altering the water quality of the rivers.

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