Human Bloodstream Research Articles

Lapachol, a natural food component, interacts with human serum albumin: Insights of its impact on the pharmacokinetics of clinically used drugs

Lapachol (LAP), a natural 1,4-naphthoquinone used in popular medicine of South American, is an antioxidant and antimicrobial compound used as a food additive; however, its interactive profile with the main protein carrier of compounds in the human bloodstream (human serum albumin, HSA) was not still characterized. Additionally, the impact of LAP in binding clinically drugs to albumin is still unknown. Thus, the present work describes the interaction HSA:LAP using different biophysical techniques, i.e., 1H saturation-transfer difference nuclear magnetic resonance (1H STD-NMR), isothermal titration calorimetry (ITC), steady-state and time-resolved fluorescence measurements combined with molecular docking calculations. LAP interacts with subdomain region IIA (site I), mainly driven by enthalpy effects, while subdomain region IB (site III) was identified as the second binding site, mainly driven by entropy effects. The binding is spontaneous, strong (binding constant average, Kaverage ≈ 4.45 × 105 M−1), and there is a positive cooperativity in the presence of ibuprofen, with the LAP structure fully buried into the protein cavities. Overall, LAP might impact the residence time (pharmacokinetic profile) of drugs that bind to subdomains regions IIA and IB of albumin, e.g., warfarin, phenylbutazone, diflunisal, naproxen, camptothecin, doxorubicin, daunorubicin, suramin, and tyrosine kinase inhibitors.

An ovine septic shock model of live bacterial infusion

BackgroundEscherichia coli is the most common cause of human bloodstream infections and bacterial sepsis/septic shock. However, translation of preclinical septic shock resuscitative therapies remains limited mainly due to low-fidelity of available models in mimicking clinical illness. To overcome the translational barrier, we sought to replicate sepsis complexity by creating an acutely critically-ill preclinical bacterial septic shock model undergoing active 48-h intensive care management.AimTo develop a clinically relevant large-animal (ovine) live-bacterial infusion model for septic shock.MethodsSeptic shock was induced by intravenous infusion of the live antibiotic resistant extra-intestinal pathogenic E. coli sequence type 131 strain EC958 in eight anesthetised and mechanically ventilated sheep. A bacterial dose range of 2 × 105–2 × 109 cfu/mL was used for the dose optimisation phase (n = 4) and upon dose confirmation the model was developed (n = 5). Post-shock the animals underwent an early-vasopressor and volume-restriction resuscitation strategy with active haemodynamic management and monitoring over 48 h. Serial blood samples were collected for testing of pro-inflammatory (IL-6, IL-8, VEGFA) and anti-inflammatory (IL-10) cytokines and hyaluronan assay to assess endothelial integrity. Tissue samples were collected for histopathology and transmission electron microscopy.ResultsThe 2 × 107 cfu/mL bacterial dose led to a reproducible distributive shock within a pre-determined 12-h period. Five sheep were used to demonstrate consistency of the model. Bacterial infusion led to development of septic shock in all animals. The baseline mean arterial blood pressure reduced from a median of 91 mmHg (71, 102) to 50 mmHg (48, 57) (p = 0.004) and lactate levels increased from a median of 0.5 mM (0.3, 0.8) to 2.1 mM (2.0, 2.3) (p = 0.02) post-shock. The baseline median hyaluronan levels increased significantly from 25 ng/mL (18, 86) to 168 ng/mL (86, 569), p = 0.05 but not the median vasopressor dependency index which increased within 1 h of resuscitation from zero to 0.39 mmHg−1 (0.06, 5.13), p = 0.065, and. Over the 48 h, there was a significant decrease in the systemic vascular resistance index (F = 7.46, p = 0.01) and increase in the pro-inflammatory cytokines [IL-6 (F = 8.90, p = 0.02), IL-8 (F = 5.28, p = 0.03), and VEGFA (F = 6.47, p = 0.02)].ConclusionsThis critically ill large-animal model was consistent in reproducing septic shock and will be applied in investigating advanced resuscitation and therapeutic interventions.

The Plasmodium falciparum histone methyltransferase PfSET10 is dispensable for the regulation of antigenic variation and gene expression in blood-stage parasites.

The malaria parasite Plasmodium falciparum employs antigenic variation of the virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1) to escape adaptive immune responses during blood infection. Antigenic variation of PfEMP1 occurs through epigenetic switches in the mutually exclusive expression of individual members of the multi-copy var gene family. var genes are located in perinuclear clusters of transcriptionally inactive heterochromatin. Singular var gene activation is linked to locus repositioning into a dedicated zone at the nuclear periphery and deposition of histone 3 lysine 4 di-/trimethylation (H3K4me2/3) and H3K9 acetylation marks in the promoter region. While previous work identified the putative H3K4-specific methyltransferase PfSET10 as an essential enzyme and positive regulator of var gene expression, a recent study reported conflicting data. Here, we used iterative genome editing to engineer a conditional PfSET10 knockout line tailored to study the function of PfSET10 in var gene regulation. We demonstrate that PfSET10 is not required for mutually exclusive var gene expression and switching. We also show that PfSET10 is dispensable not only for asexual parasite proliferation but also for sexual conversion and gametocyte differentiation. Furthermore, comparative RNA-seq experiments revealed that PfSET10 plays no obvious role in regulating gene expression during asexual parasite development and gametocytogenesis. Interestingly, however, PfSET10 shows different subnuclear localization patterns in asexual and sexual stage parasites and female-specific expression in mature gametocytes. In summary, our work confirms in detail that PfSET10 is not involved in regulating var gene expression and is not required for blood-stage parasite viability, indicating PfSET10 may be important for life cycle progression in the mosquito vector or during liver stage development.IMPORTANCEThe malaria parasite Plasmodium falciparum infects hundreds of millions of people every year. To survive and proliferate in the human bloodstream, the parasites need to escape recognition by the host's immune system. To achieve this, P. falciparum can change the expression of surface antigens via a process called antigenic variation. This fascinating survival strategy is based on infrequent switches in the expression of single members of the var multigene family. Previous research reported conflicting results on the role of the epigenetic regulator PfSET10 in controlling mutually exclusive var gene expression and switching. Here, we unequivocally demonstrate that PfSET10 is neither required for antigenic variation nor the expression of any other proteins during blood-stage infection. This information is critical in directing our attention toward exploring alternative molecular mechanisms underlying the control of antigenic variation and investigating the function of PfSET10 in other life cycle stages.

Preferred Lung Accumulation of Polystyrene Nanoplastics with Negative Charges.

With the increasing presence of nanoplastics (NPs) in the human bloodstream, it is urgent to investigate their tissue accumulation and potential health risks. This study examines the effects of the size and surface charges of polystyrene (PS) NPs on lung accumulation. Using magnetic separation, we identified the protein corona composition on iron-core PS NPs, revealing the enrichment of vitronectin and fibrinogen. The corona promotes integrin αIIbβ3 receptor-mediated uptake by lung endothelial cells, explaining that both the corona composition and protein structure determine preferred localization of negatively charged PS NPs in the lung. This study uncovers the role of protein corona in NP uptake and the way NPs enter the lung, emphasizing the need to consider interactions between nanoplastics with varying surface characteristics and biological molecules in the nanotoxicological field.

Curcumin-loaded lignin nanoparticles: Exploring sonication effects on drug loading and particle properties for future biomedical use

The present study investigates the effects of sonication and cross-linker (oxalic acid) concentration on drug loading and the properties of curcumin-loaded lignin nanoparticles. Selected samples were further assessed for their toxicity and antioxidant potential using the eukaryotic model organism Saccharomyces cerevisiae. Transmission electron microscopy analyses revealed the formation of spherical nanoparticles with diameters in the range of 39–49 nm. Differential scanning calorimetry experiments confirmed the encapsulation of curcumin. Factorial experimental design analyses indicated that sonication time, wave amplitude, cross-linker concentration, and their interactions significantly influenced both ζ-potential – from (−37.0 ± 1.7) mV to (−48.4 ± 0.6) mV – and curcumin loading – from (3.70 ± 0.32) % to (7.10 ± 0.57) %. These parameters are critical for biomedical applications as they relate to the clearance of nanoparticles from the human bloodstream and drug dosage optimization. Although sonication has been previously reported for the preparation of lignin nanoparticles, this study represents the first documented instance of manipulating drug loading by controlled sonication parameters. While none of the investigated factors significantly affected the mean particle diameter, observations from TEM micrographs suggest that cross-linker concentration and wave amplitude notably influence nanoparticle morphology. Moreover, the curcumin-loaded nanoparticles exhibited non-toxicity toward Saccharomyces cerevisiae and demonstrated the ability to enhance yeast cell tolerance to H2O2-induced oxidative stress, underscoring their antioxidant potential. Therefore, this research significantly contributes to the scientific understanding of how the control of sonication parameters and cross-linkers can modulate the properties of curcumin-loaded lignin nanoparticles for future biomedical applications.

Exploring uncatalogued genetic variation in antimicrobial resistance gene families in Escherichia coli: an observational analysis

Antimicrobial resistance (AMR) in Escherichia coli is a global problem associated with substantial morbidity and mortality. AMR-associated genes are typically annotated based on similarity to variants in a curated reference database, with the implicit assumption that uncatalogued genetic variation within these is phenotypically unimportant. In this study, we evaluated the performance of the AMRFinder tool and, subsequently, the potential for discovering new AMR-associated gene families and characterising variation within existing ones to improve genotype-to-susceptibility phenotype predictions in Ecoli. In this cross-sectional study of international genome sequence data, we assembled a global dataset of 9001 Ecoli sequences from five publicly available data collections predominantly deriving from human bloodstream infections from: Norway, Oxfordshire (UK), Thailand, the UK, and Sweden. 8555of these sequences had linked antibiotic susceptibility data. Raw reads were assembled using Shovill and AMR genes (relevant to amoxicillin-clavulanic acid, ampicillin, ceftriaxone, ciprofloxacin, gentamicin, piperacillin-tazobactam, and trimethoprim) extracted using the National Center for Biotechnology Information AMRFinder tool (using both default and strict [100%] coverage and identity filters). We assessed the predictive value of the presence of these genes for predicting resistance or susceptibility against US Food and Drug Administration thresholds for major and very major errors. Mash was used to calculate the similarity between extracted genes using Jaccard distances. We empirically reclustered extracted gene sequences into AMR-associated gene families (≥70% match) and antibiotic-resistance genes (ARGs; 100% match) and categorised these according to their frequency in the dataset. Accumulation curves were simulated and correlations between gene frequency in the Oxfordshire and other datasets calculated using the Spearman coefficient. Firth regression was used to model the association between the presence of blaTEM-1 variants and amoxicillin-clavulanic acid or piperacillin-tazobactam resistance, adjusted for the presence of other relevant ARGs. The performance of the AMRFinder database for genotype-to-phenotype predictions using strict 100% identity and coverage thresholds did not meet US Food and Drug Administration thresholds for any of the seven antibiotics evaluated. Relaxing filters to default settings improved sensitivity with a specificity cost. For all antibiotics, most explainable resistance was associated with the presence of a small number of genes. There was a proportion of resistance that could not be explained by known ARGs; this ranged from 75·1% for amoxicillin-clavulanic acid to 3·4% for ciprofloxacin. Only 18 199 (51·5%) of the 35 343ARGs detected had a 100% identity and coverage match in the AMRFinder database. After empirically reclassifying genes at 100% nucleotide sequence identity, we identified 1042unique ARGs, of which 126 (12·1%) were present ten times or more, 313 (30·0%) were present between two and nine times, and 603 (57·9%) were present only once. Simulated accumulation curves revealed that discovery of new (100% match) ARGs present more than once in the dataset plateaued relatively quickly, whereas new singleton ARGs were discovered even after many thousands of isolates had been included. We identified a strong correlation (Spearman coefficient 0·76 [95% CI 0·73-0·80], p<0·0001) between the number of times an ARG was observed in Oxfordshire and the number of times it was seen internationally, with ARGs that were observed six times in Oxfordshire always being found elsewhere. Finally, using the example of blaTEM-1, we showed that uncatalogued variation, including synonymous variation, is associated with potentially important phenotypic differences; for example, two common, uncatalogued blaTEM-1 alleles with only synonymous mutations compared with the known reference were associated with reduced resistance to amoxicillin-clavulanic acid (adjusted odds ratio 0·58 [95% CI 0·35-0·95], p=0·031) and piperacillin-tazobactam (0·50 [95% CI 0·29-0·82], p=0·005). We highlight substantial uncatalogued genetic variation with respect to known ARGs, although a relatively small proportion of these alleles are repeatedly observed in a large international dataset suggesting strong selection pressures. The current approach of using fuzzy matching for ARG detection, ignoring the unknown effects of uncatalogued variation, is unlikely to be acceptable for future clinical deployment. The association of synonymous mutations with potentially important phenotypic differences suggests that relying solely on amino acid-based gene detection to predict resistance is unlikely to be sufficient. Finally, the inability to explain all resistance using existing knowledge highlights the importance of new target gene discovery. National Institute for Health and Care Research, Wellcome, and UK Medical Research Council.

Evaluation of Micro-RNA Expression Profiling Level as Biomarkers for Diagnosis and Gene Sequencing in Patients Suffering from Breast Cancer

Background: Human bloodstream microRNAs (miRNAs) have emerged as a promising predictive and diagnostic biomarker for a range of cancers, including breast cancer. Our objective was to look into new miRNA biomarkers for diagnosis in the serum of patients with breast cancer and track the expression levels at different stages using miRNA profiling.Methods: 53 breast cancer patients and 10 healthy controls had blood samples tested for three miRNAs. miRNAs were extracted from blood and evaluated using real-time quantitative polymerase chain reaction. After extracting genomic DNA, miRNA primer-produced PCR products were sequenced to discover point mutations that may contribute to the illness.Results: After examining miR195, miR200b, and miR331, breast cancer patients had a significantly lower miR195 level than healthy persons. In addition, miR200b expression levels were significantly lower in breast cancer patients than in healthy individuals. In advanced stages, miR331 expression was substantially higher than in healthy people.Conclusion: The findings of our study demonstrated a significant association between the expression of miRNAs and the prognosis of breast cancer. Additional research is necessary to study better the correlation between these circulating miRNAs and the stages of breast cancer.Keywords: Breast cancer; Circulating miRNAs; miR195; miR200b; miR331 RT PCR; Gene Sequencing

Evaluation of Hematotoxicity in Female Wistar Rats Following Sub-Acute Inhalation Exposure to Polyethylene Microplastic

Polyethylene (PE) becomes a source of microplastics that can be widely distributed through the digestive and respiratory systems. However, its effects on blood cells are still being investigated. This study aims to analyze the impact of Polyethylene Microplastic (PE-MPs) exposure on the blood of female rats, including erythrocytes, leukocytes, and platelets. This study used female Wistar rats, which were divided into control and PE-MP groups. PE-MP was administered via whole-body inhalation at a concentration of 15 mg/m³ for 4 hours daily for 28 days. The absorption of plastic particles detected in the human bloodstream is likely to occur through mucosal contact (either through ingestion or inhalation). After the exposure period, the rats were euthanized to collect blood samples through the heart. A complete blood count was performed using an automatic hematology analyzer, and blood morphology was analyzed using thin blood smears. This study used the Mann-Whitney test. PE-MP exposure increased erythrocyte and platelet counts without a corresponding rise in leukocytes. Erythrocytes showed abnormal morphology (12.73% with ovalocytes and tear-shaped cells). Erythrocyte indices (MCV, MCH, MCHC) showed no significant differences. Platelet count rose by 1.7% (p-value= 0.017). Leukocyte and neutrophil counts were lower (0.84 and 0.94 times lower, respectively), while lymphocytes and monocytes were higher (1.03 and 1.61 times higher, respectively) in the PE-MP group compared to controls. The neutrophil-to-lymphocyte ratio did not differ significantly. PE-MP exposure in rats disrupts blood parameters, altering erythrocyte morphology and increasing platelet counts. Potential causes include oxidative stress, immune responses, and compensatory mechanisms. Study limitations include a small sample size and exclusive focus on inhalation exposure. Integrating multiple exposure routes (inhalation, ingestion, dermal) could offer a broader view of microplastic impacts. Future research with larger samples, diverse doses and durations, and exploration of additional markers or organ-specific effects is crucial for understanding PE-MP toxicity in real-world scenarios.

Two novel Enterobacter species, Enterobacter chinensis sp. nov. and Enterobacter rongchengensis sp. nov., recovered from clinical samples carrying multiple virulence factors.

Two Enterobacter strains 170198T and 170250T were isolated from clinical blood samples from distinct patients in a hospital in Chengdu, China, in 2022. These isolates were subjected to whole-genome sequencing. A phylogenomic tree based on 2,096 concatenated core genes showed that the two strains were clustered within the genus Enterobacter. The average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values between each of the two strains and type strains of all currently known Enterobacter species were determined. The two strains belonged to two novel species as the highest ANI and isDDH values with type strains of all currently known Enterobacter species below the cutoff for species demarcation (96% for ANI and 70% for isDDH). Then the physiological and biochemical studies demonstrated that biochemical features and the profile of whole fatty acids of strains 170198T and 170250T were largely consistent with those known Enterobacter species. Nevertheless, the two novel species can be differentiated from all other Enterobacter species by certain biochemical characteristics. In conclusion, 170198T and 170250T represent two novel species of the genus Enterobacter, for which we propose Enterobacter chinensis sp. nov. and Enterobacter rongchengensis sp. nov., as the species names. The type strains of Enterobacter chinensis sp. nov., and Enterobacter rongchengensis sp. nov. are 170198T (=GDMCC 1.3549T=JCM 35826T) and 170250T (=GDMCC 1.3670T=JCM 36189T), respectively. The two novel species have clinical significance with the ability to cause bloodstream infections.IMPORTANCEEnterobacter is a group of bacteria comprising several common opportunistic pathogens and has a complicated taxonomy. Here, we reported two novel Enterobacter species. We demonstrated that the two novel species can be differentiated from other Enterobacter species by certain phenotypic characteristics and therefore provide information for designing tests for identification. We also showed that strains of the two novel species are able to cause human bloodstream infections and carry multiple virulence factors and therefore are of clinical significance. We highlight that the virulence of Enterobacter is less studied and warrants further exploration. We believe that the findings here are valuable for enhancing the appreciation toward Enterobacter, an important pathogen.

Narażenie dermalne – ważny aspekt bezpieczeństwa pracy z nanomateriałami

Dermal exposure – an important aspect of safety in working with nanomaterials Taking into account dermal exposure is an important aspect in ensuring safe working conditions with nanomaterials. Quantum dots and nanomaterials with a larger particle size, metallic or with a metallic component, have the highest probability of absorption through the skin. A crucial factor in the process of absorption of nanomaterials through the skin is the disruption of its protective function, which may result in an increased risk of penetration and permeation of nanomaterials into the dermis and the human bloodstream. Keywords: nanoparticles, nanomaterials, skin absorption, skin exposure

Regulation of thiamine and pyruvate decarboxylase genes by Pdc2 in Nakaseomyces glabratus (Candida glabrata) is complex.

Thiamine (vitamin B1) is essential for glucose catabolism. In the yeast species, Nakaseomyces glabratus (formerly Candida glabrata) and Saccharomyces cerevisiae, the transcription factor Pdc2 (with Thi3 and Thi2) upregulates pyruvate decarboxylase (PDC) genes and thiamine biosynthetic and acquisition (THI) genes during starvation. There have not been genome-wide analyses of Pdc2 binding. Previously, we identified small regions of Pdc2-regulated genes sufficient to confer thiamine regulation. Here, we performed deletion analyses on these regions. We observed that when the S. cerevisiae PDC5 promoter is introduced into N. glabratus, it is thiamine starvation inducible but does not require the Thi3 coregulator. The ScPDC5 promoter contains a 22-bp duplication with an AT-rich spacer between the 2 repeats, which are important for regulation. Loss of the first 22-bp element does not eliminate regulation, but the promoter becomes Thi3 dependent, suggesting cis architecture can generate a Thi3-independent, thiamine starvation inducible response. Whereas many THI promoters only have 1 copy of this element, addition of the first 22-bp element to a Thi3-dependent promoter confers Thi3 independence. Finally, we performed fluorescence anisotropy and chromatin immunoprecipitation sequencing. Pdc2 and Thi3 bind to regions that share similarity to the 22-bp element in the ScPDC5 promoter and previously identified cis elements in N. glabratus promoters. Also, while Pdc2 binds to THI and PDC promoters, neither Pdc2 nor Thi3 appears to bind the evolutionarily new NgPMU3 promoter that is regulated by Pdc2. Further study is warranted because PMU3 is required for cells to acquire thiamine from environments where thiamine is phosphorylated, such as in the human bloodstream.

Upaya peningkatan pengetahuan dan pencegahan demam berdarah pada masyarakat kelurahan darma

Introduction: Dengue hemorrhagic fever or abbreviated as DHF is an acute febrile disease caused by the dengue virus. This virus enters the human bloodstream through the bite of mosquitoes from the Aedes genus, for example Aedes aegypti or Aedes albopictus. This disease is characterized by high fever continuously for 2 to 7 days and is accompanied by bleeding and shock which, if not treated immediately, can cause death Objective: The aim of this Community Service is to increase public knowledge about dengue fever and its prevention in Darma Environmental Batu-batu Village. Method: Knowledge increasing activities regarding increasing knowledge and preventing dengue fever were carried out. On Thursday, May 27 2024, 10.00 WITA, the opening of community service activities with the theme "Increasing Knowledge and Prevention of Dengue Fever" took place in the Darma Environmental Batu-batu sub-district. The media used is material in the form of leaflets and posters. The implementation of community service uses the community outreach method, namely involving the community and students during the implementation process. Result: From the results of the pre-test analysis, most of the community does not know about dengue fever and its prevention, but after counseling, the post-test results show that almost all people understand about dengue fever and its prevention. Conclusion: From the community service activities that have been carried out in the Darma Environmental Batu-Batu Subdistrict by the STIKES Bina Generasi Polewali Mandar community service team, it can be concluded that public knowledge regarding dengue hemorrhagic fever (DBD) needs to continue to be improved continuously, climate change, especially in the rainy season very vulnerable to the spread of dengue fever so it is necessary to empower the community in preventing dengue fever, one of which is through 3M and PSN

An automated, high-resolution phenotypic assay for adult Brugia malayi and microfilaria

Brugia malayi are thread-like parasitic worms and one of the etiological agents of Lymphatic filariasis (LF). Existing anthelmintic drugs to treat LF are effective in reducing the larval microfilaria (mf) counts in human bloodstream but are less effective on adult parasites. To test potential drug candidates, we report a multi-parameter phenotypic assay based on tracking the motility of adult B. malayi and mf in vitro. For adult B. malayi, motility is characterized by the centroid velocity, path curvature, angular velocity, eccentricity, extent, and Euler Number. These parameters are evaluated in experiments with three anthelmintic drugs. For B. malayi mf, motility is extracted from the evolving body skeleton to yield positional data and bending angles at 74 key point. We achieved high-fidelity tracking of complex worm postures (self-occlusions, omega turns, body bending, and reversals) while providing a visual representation of pose estimates and behavioral attributes in both space and time scales.

Evidence of Hyperglycemic Levels Improving the Binding Capacity between Human Serum Albumin and the Antihypertensive Drug Hydrochlorothiazide

Cardiovascular diseases (CVDs), especially arterial hypertension, stand as prominent contributors to global mortality. Regrettably, individuals with diabetes encounter a two-fold increase in the risk of mortality associated with CVDs. Hydrochlorothiazide (HCTZ) represents a primary intervention for hypertension, particularly in diabetic patients. Nevertheless, there has not yet been a comprehensive assessment of the biophysical characteristics regarding the impact of glucose levels on its binding affinity with human serum albumin (HSA). Thus, the present work reports the interactive profile of HSA/HCTZ in nonglycemic, normoglycemic (80 mg/dL), and hyperglycemic (320 mg/dL) conditions by time-resolved fluorescence, saturation transfer difference–nuclear magnetic resonance (STD-NMR), and surface plasmon resonance (SPR). There was a moderate ground state association of HSA/HCTZ with subdomain IIA that was affected in the presence of different glucose levels. The hyperglycemic condition decreased the binding affinity of HCTZ to subdomain IIA and increased the possibility of subdomain IB also being considered as a secondary binding site due to cooperativity and/or alterations in the protein’s structure. Overall, the glucose level under hyperglycemic conditions led to the cavities being more likely to receive more ligands, offering insights into the necessity of glucose control in the human bloodstream to not impact the residence time (pharmacokinetic profile) and pharmacotherapeutic potential of HCTZ.

Antimicrobial resistance patterns in Streptococcus dysgalactiae in a One Health perspective.

Streptococcus dysgalactiae (SD) is an important pathogen in humans as well as in a broad range of animal species. Escalating rates of antibiotic resistance in SD has been reported in both human and veterinary clinical practice, but the dissemination of resistance determinants has so far never been examined in a One Health Perspective. We wanted to explore the occurrence of zoonotic transmission of SD and the potential for exchange of resistance traits between SD from different host populations. We compared whole genome sequences and phenotypical antimicrobial susceptibility of 407 SD isolates, comprising all isolates obtained from human bloodstream infections in 2018 (n = 274) and available isolates associated with animal infections from the years 2018 and 2019 (n = 133) in Norway. Antimicrobial resistance genes were detected in 70 (26%), 9 (25%) and 2 (2%) of the isolates derived from humans, companion animals and livestock, respectively. Notably, distinct host associated genotypic resistomes were observed. The erm(A) gene was the dominant cause of erythromycin resistance in human associated isolates, whereas only erm(B) and lsa(C) were identified in SD isolates from animals. Moreover, the tetracycline resistance gene tet(O) was located on different mobile genetic elements in SD from humans and animals. Evidence of niche specialization was also evident in the phylogenetic analysis, as the isolates could be almost perfectly delineated in accordance with host species. Nevertheless, near identical mobile genetic elements were observed in four isolates from different host species including one human, implying potential transmission of antibiotic resistance between different environments. We found a phylogenetic delineation of SD strains in line with host adapted populations and niche specialization. Direct transmission of strains or genetic elements carrying resistance genes between SD from different ecological niches appears to be rare in our geographical region.

Determining glucose supply in blood using the incomplete [formula omitted]-function

In this paper, we delve into the realm of mathematical modeling as a powerful theoretical tool to understand essential aspects of medical-biological phenomena. This study focuses on developing a mathematical model incorporating the incomplete I-function (IIF) and estimating glucose supply in the human bloodstream. The results of our investigations are far-reaching, revealing many exciting scenarios across the various parameters under investigation. These results are not only practical but can also play an essential role in the contexts of medical and biological fields.

Genomic characterization of Aeromonas spp. isolates from striped catfish with motile Aeromonas septicemia and human bloodstream infections in Vietnam.

Aeromonas spp. are commonly found in the aquatic environment and have been responsible for motile Aeromonas septicemia (MAS) in striped catfish, resulting in significant economic loss. These organisms also cause a range of opportunistic infections in humans with compromised immune systems. Here, we conducted a genomic investigation of 87 Aeromonas isolates derived from diseased catfish, healthy catfish and environmental water in catfish farms affected by MAS outbreaks in eight provinces in Mekong Delta (years: 2012-2022), together with 25 isolates from humans with bloodstream infections (years: 2010-2020). Genomics-based typing method precisely delineated Aeromonas species while traditional methods such as aerA PCR and MALDI-TOF were unable identify A. dhakensis. A. dhakensis was found to be more prevalent than A. hydrophila in both diseased catfish and human infections. A. dhakensis sequence type (ST) 656 followed by A. hydrophila ST251 were the predominant virulent species-lineages in diseased catfish (43.7 and 20.7 %, respectively), while diverse STs were found in humans with bloodstream infections. There was evidence of widespread transmission of ST656 and ST251 on striped catfish in the Mekong Delta region. ST656 and ST251 isolates carried a significantly higher number of acquired antimicrobial resistance (AMR) genes and virulence factors in comparison to other STs. They, however, exhibited several distinctions in key virulence factors (i.e. lack of type IV pili and enterotoxin ast in A. dhakensis), AMR genes (i.e. presence of imiH carbapenemase in A. dhakensis), and accessory gene content. To uncover potential conserved proteins of Aeromonas spp. for vaccine development, pangenome analysis has unveiled 2202 core genes between ST656 and ST251, of which 78 proteins were in either outer membrane or extracellular proteins. Our study represents one of the first genomic investigations of the species distribution, genetic landscape, and epidemiology of Aeromonas in diseased catfish and human infections in Vietnam. The emergence of antimicrobial resistant and virulent A. dhakensis strains underscores the needs of enhanced genomic surveillance and strengthening vaccine research and development in preventing Aeromonas diseases in catfish and humans, and the search for potential vaccine candidates could focus on Aeromonas core genes encoded for membrane and secreted proteins.

Vibrio cholerae Bacteremia: An Enigma in Cholera-Endemic African Countries.

Cholera is highly endemic in many sub-Saharan African countries. The bacterium Vibrio cholerae is responsible for this severe dehydrating diarrheal disease that accounts for over 100,000 deaths each year globally. In recent years, the pathogen has been found to invade intestinal layers and translocate into the bloodstream of humans. The non-toxigenic strains of V. cholerae (non-O1/O139), also known as NOVC, which do not cause epidemic or pandemic cases of cholera, are the major culprits of V. cholerae bacteremia. In non-cholera-endemic regions, clinical reports on NOVC infection have been noted over the past few decades, particularly in Europe and America. Although low-middle-income countries are most susceptible to cholera infections because of challenges with access to clean water and inappropriate sanitation issues, just a few cases of V. cholerae bloodstream infections have been reported. The lack of evidence-based research and surveillance of V. cholerae bacteremia in Africa may have significant clinical implications. This commentary summarizes the existing knowledge on the host risk factors, pathogenesis, and diagnostics of NOVC bacteremia.

Multi-locus sequence typing of Escherichia coli isolated from clinical samples in Jordan.

Escherichia coli (E. coli) is the major cause of extraintestinal infections in the urinary tracts and bloodstream in humans in the community and health care institutions. Several studies on the genetic characterization of E. coli among clinical and environmental isolates were performed and revealed a wide diversity of sequence types (STs). In Jordan, phenotypic and genetic features of E. coli were extensively studied but there is still a need to identify the STs that inhabit the community. In this study, multi-locus sequence typing (MLST) was performed on archived clinical E. coli isolates collected from different hospitals in Jordan and the identified STs were extensively analyzed. Genotyping of 92 E. coli isolates revealed 34 STs and 9 clonal complexes. The frequencies of STs ranged between 1 to 23 observations. The most frequent STs among E. coli isolates were ST131 (n = 23), ST69 (n = 19), ST998 (n = 7), ST2083 (n = 5), and ST540 (n = 4). These five ST accounted for up to 60% of the 92 E. coli isolates. Based on the MLST database, the STs reported in this work were world widely recognized in humans, animals, and in the environment. This study has elaborated more knowledge about the genotypes of E. coli in Jordan, with recommendations for future studies to correlate its genotypes with virulence and resistance genes.

Spectroscopic and in silico characterization of the interaction between synthetic 2-substituted-naphtho-1,4-quinones and human serum albumin

The intermolecular interaction between 2-(N-phenyl-N-methyl)aminonaphtho-1,4-quinone (1) and 2-(4-N-methylaminophenyl)naphtho-1,4-quinone (2) and human serum albumin (HSA) was investigated using spectroscopic techniques combined with in silico calculations via molecular docking. Steady-state titration of HSA fluorescence by 1 and 2 (λexc 295 nm) in PBS at 305, 310, and 315 K, as well as studies employing time-resolved fluorescence emission, demonstrated that the HSA:1 and HSA:2 interaction occurs through a static quenching mechanism. The Stern-Volmer constant (Ksv) values, (1.56 ± 0.08) and (3.05 ± 0.10) × 104 L/mol at 310 K for HSA:1 and HSA:2, respectively, indicate a moderate binding affinity. Van't Hoff plots showed that HSA:1 and HSA:2 interactions are spontaneous (negative ΔGo) with a hydrophobic character (ΔSo value of 0.00707 ± 0.00106 and 0.0392 ± 0.0062 kJ/mol K for HSA:1 and HSA:2, respectively) and specific electrostatic interactions (ΔHo value of –22.7 ± 3.3 and −14.4 ± 1.9 kJ/mol for HSA:1 and HSA:2, respectively). Synchronous fluorescence results showed significant perturbation in the microenvironment of the tryptophan residue (Trp-214). Circular dichroism indicated that after interaction with naphthoquinones 1 and 2, the HSA structure remains predominantly in the α-helix form. Finally, molecular docking revealed the formation of hydrophobic, electrostatic, and hydrogen bond interactions with the surrounding amino acid residues in subdomain IIA of HSA, which contains the Trp-214 residue, validated with the experimental drug-displacement assays. Overall, spectroscopic and in silico characterization of HSA:1 and HSA:2 might reflect in a low half-life in the human bloodstream, indicating the necessity of methods to improve the bioavailability, e.g., studies on the type of administration (oral versus intravenous).