Concurrent Acute Ischemic Stroke and Myocardial Infarction Associated With Atrial Fibrillation.

An 85-year-old man was admitted with dysarthria. Electrocardiography showed atrial fibrillation and prominent ST-segment elevation in V2-V6. Multiple acute cerebral infarctions were observed in brain images. Coronary angiography showed total occlusion of the mid left anterior descending artery. After thrombus aspiration, no atherosclerotic changes were observed on intravascular ultrasound.

Impacts of Temperature on the Growth, Feed Utilization, Stress, and Hemato-Immune Responses of Cherry Salmon (Oncorhynchus masou).

Cherry salmon (Oncorhynchus masou) hold commercial value in aquaculture, and there is a need for controlled laboratory studies to isolate the specific effects of temperature on their growth, feeding, and well-being. We examined the effects of different temperatures (10 °C, 14 °C, 18 °C, and 22 °C) on juvenile cherry salmon (average mass 29.1 g) in triplicate tanks per treatment over eight weeks. The key parameters assessed included growth rate, feed efficiency, stress response, and hemato-immune responses. Our objectives were to determine the most and less favorable temperatures among the four designated temperatures and to assess the adverse effects associated with these less favorable temperatures. The results showed that body weight, growth rates, feed intake, and feed efficiency were significantly higher at 10 °C and 14 °C compared to 18 °C and 22 °C. Reduced appetite and feeding response were observed at 22 °C. Red blood cell parameters were significantly lower at 22 °C. At 10 °C, the results showed significantly increased plasma cortisol levels, gill Na+/K+-ATPase activity, body silvering, and decreased condition factors, suggesting potential smoltification. The potential smoltification decreased with increasing temperatures and disappeared at 22 °C. Furthermore, the plasma lysozyme concentrations significantly increased at 18 °C and 22 °C. In conclusion, our study identifies 10 °C and 14 °C as the temperatures most conducive to growth and feed performance in juvenile cherry salmon under these experimental conditions. However, temperatures of 22 °C or higher should be avoided to prevent compromised feeding, reduced health, disturbed immune responses, impaired growth, and feed performance.

Relationship between childhood trauma and resilience in patients with mood disorders.

BACKGROUND: Childhood trauma has lasting negative impacts on individuals' psychological functioning. However, there is limited empirical evidence on the association between childhood trauma and resilience and none examining such relationship among diverse clinical populations. This study aimed to investigate the relationship in patients with major depressive disorder, bipolar I disorder, bipolar II disorder, and a comparison group. METHODS: In total, 787 psychiatric patients and 734 people from the general population participated in the study. The Childhood Trauma Questionnaire-Short Form and Connor-Davidson Resilience Scale were used to assess childhood trauma and resilience, respectively. RESULTS: Individuals with childhood trauma showed lower levels of resilience in all subjects; among them, those who experienced emotional abuse and emotional neglect exhibited even stronger associations than other types of childhood trauma. There was a significant difference in the negative relationship between childhood trauma and resilience by group, where the association was more prominent in the comparison group than in MDD and BD II patient groups. LIMITATIONS: The generalizability of our results may be limited due to unproportionate patient sample size. Also, we could not examine the causal relationship between childhood trauma and resilience. CONCLUSION: Childhood trauma and resilience had a significantly negative association. Our results suggest that people who have experienced emotional abuse and emotional neglect should be closely assisted to develop resilience. Interventions that promote resilience should be provided to individuals predisposed to psychological risks as a result of childhood trauma.

Efficacy and safety of daily home-based transcranial direct current stimulation as adjunct treatment for bipolar depressive episodes: Double-blind sham-controlled randomized clinical trial.

Background: Although transcranial direct current stimulation (tDCS) is known to be a promising therapeutic modality for unipolar depression, the efficacy and safety of tDCS for bipolar depressive episodes (BD) are still unknown and clinical trials of home-based tDCS treatment are scarce. As a result, we set out to investigate the efficacy and safety of home-based tDCS for the treatment BD. Methods: Participants (n = 64), diagnosed as bipolar disorder as per the diagnostic and statistical manual of mental disorders (DSM-5), were randomly assigned to receive tDCS. Hamilton Depression Rating Scale (HDRS-17) scores were measured at the baseline, week 2, 4, and 6, and home-based tDCS (for 30 min with 2 mA) was self-administered daily. Results: Of the 64 patients (15.6% bipolar disorder I, 84.4% bipolar disorder II), 41 patients completed the entire assessment. In the intention-to-treat analysis, time-group interaction for the HDRS-17 [F (3, 146.36) = 2.060; p = 0.108] and adverse effect differences between two groups were not statistically significant, except the pain score, which was higher in the active group than the sham group (week 0-2: p < 0.01, week 2-4: p < 0.05, and week 4-6: p < 0.01). Conclusion: Even though we found no evidence for the efficacy of home-based tDCS for patients with BD, this tool was found to be a safe and tolerable treatment modality for BD. Clinical trial registration: [https://clinicaltrials.gov/show/NCT03974815], identifier [NCT03974815].

Plasma concentration of dopamine varies depending on breed, sex, and the genotype of DRD4 in horses.

Dopamine (DA) is known to be a key modulator of animal behaviors. Thus, the plasma concentration of DA might be used as a biomarker for the behavioral characteristics of horses. The behavioral characteristics of horses vary depending on the breed, age, and sex. Moreover, the DA receptor genotypes are also related to horse behaviors. Thus, the aim of this study was to investigate the DA concentration variations of horse plasma by breed, age, sex, or genotype of its receptor. The horses were divided by breed into Thoroughbred (n = 13), Pony (n = 9), Warmblood (n = 4), and Haflinger (n = 5). The age variable was divided into three different groups: post-pubertal (2-5 years, n = 6), adult (6-13 years, n = 19), and aged horses (15-24 years, n = 6). The sex variable was divided into geldings (n = 8) and mares (n = 23). Approximately 10 mL of blood was collected, and an ELISA kit was used to measure the plasma concentration of DA. Polymerase chain reaction analysis was performed to identify the genetic variation in the DA D4 receptor gene (DRD4). SPSS statistical software was used for statistical analysis. The DA concentrations in geldings were significantly lower than those in mares. There was no significant difference in DA concentrations among breed and age groups. Horses with the GG and GA genotypes had significantly higher plasma concentrations of DA compared to horses with the AA genotype for the G292A gene. Briefly, the plasma concentration of DA varied depending on the sex and genotype of G292A. These factors should be considered when the concentration of DA is used as a biomarker for the behavioral characteristics of horses. In conclusion, the DA concentration or DRD4 genotype of horse plasma has the potential to be used as a biomarker that can predict the behavioral characteristics of horses.

Effects of Stocking Density on Stress, Hematological Responses, and Growth of Black Rockfish Sebastes schlegelii.

The objective of the current study was to evaluate the effect of stocking density on juvenile Black Rockfish Sebastes schlegelii (average weight = 12 g) in terms of stress, hematological responses, and growth performance during a 4-month growth trial in a flow-through system. The initial stocking densities were 1.3 kg/m3 (low), 1.8 kg/m3 (medium), and 2.3 kg/m3 (high), and the final densities were 4.9 kg/m3 (low), 5.6 kg/m3 (medium), and 6.3 kg/m3 (high). At the end of the trial, the high stocking density significantly affected growth characteristics, levels of growth hormone and insulin-like growth factor 1, and hematological indices (hematocrit, red blood cell count, and hemoglobin level) compared to the medium and low stocking densities. The plasma cortisol and immunoglobulin-M levels were significantly higher at the high density than at the other two densities. Taken together, while the low and medium stocking densities (final densities of up to 5.6 kg/m3 ) did not affect stress and hematological indices or growth, the high stocking density (final density of 6.3 kg/m3 ) significantly impacted those variables, which suggests an allostatic load at that density. Thus, the use of a final stocking density less than 6.3 kg/m3 should be considered to avoid compromising the stress and health condition and growth of Black Rockfish at this size and temperature range.

Comparative Interrupted Time Series Analysis of Long-term Direct Medical Costs in Patients With Hip Fractures and a Matched Cohort: A Large-database Study.

BACKGROUND: Previous studies on medical costs in patients with hip fractures have focused on medical costs incurred for a short period after the injury. However, patients often had comorbidities before their hip fractures that would have affected medical costs even had they not sustained a fracture. Consequently, these studies may have overestimated the costs associated with hip fractures and did not characterize the duration of increased medical costs adequately. Without knowing this crucial information, it is difficult to craft thoughtful health policy to support these patients' needs. QUESTIONS/PURPOSES: (1) To compare the direct medical costs for 5 years before fracture and up to 5 years after injury in a group of patients who underwent hip fracture surgery with a matched group of patients who did not experience a hip fracture, (2) to analyze the duration over which the increased direct medical costs associated with a hip fracture continues, and (3) to analyze whether there is a difference in direct medical costs according to age group using a nationwide claims database in South Korea. METHODS: The National Health Insurance Service Sample cohort in South Korea consisted of 1 million patients who were selected using a systematic, stratified, random sampling method from 48,222,537 individuals on December 31, 2006. Under a compulsory social insurance system established by the National Health Insurance Act, all patients were followed until 2015. Patients with hip fractures and matched controls were selected from the National Health Insurance Service sample of South Korea. Patients with hip fractures were defined as those who were hospitalized with a diagnosis of femoral neck fracture or intertrochanteric fracture and who underwent surgical treatment. We excluded patients with hip fractures before January 1, 2007 to ensure a minimum 5-year period that was free of hip fractures. Patients with hip fractures were matched with patients of the same age and gender at the date of admission to an acute care hospital for surgery (time zero). If patients with hip fractures died during the follow-up period, we performed matching among patients whose difference from the time of death was within 1 month. This method of risk-set matching was repeated sequentially for the next patient until the last patient with a hip fracture was matched. We then sequentially performed 1:5 random sampling for each risk set. A total of 3583 patients in the hip fracture cohort (patients with hip fractures) and 17,915 patients in the matched cohort (those without hip fractures) were included in this study. The mean age was 76 ± 9 years, and 70% were women in both groups. Based on the Charlson comorbidity index score, medication, and medical history, the patients with hip fractures had more comorbidities. Person-level direct medical costs per quarter were calculated for 5 years before time zero and up to 5 years after time zero. Direct medical costs were defined as the sum of that insurer's payments (that is, the National Health Insurance Service's payments), and that patient's copayments, excluding uncovered payments. We compared direct medical costs between patients with hip fractures and the patients in the matched cohort using a comparative interrupted time series analysis. The difference-in-difference estimate is the ratio of the differences in direct medical costs before and after time zero in the hip fracture cohort to the difference in direct medical costs before and after time zero in the matched cohort; the difference in difference estimates were calculated each year after injury. To identify changes in direct medical cost trends in patients with hip fractures and all subgroups, joinpoint regression was estimated using statistical software. RESULTS: The direct medical costs for the patients with hip fractures were higher than those for patients in the matched cohort at every year during the observation period. The difference in direct medical costs between the groups before time zero has increased every year. The direct medical costs in patients with hip fractures was the highest in the first quarter after time zero. Considering the differential changes in direct medical costs before and after time zero, hip fractures incurred additional direct medical costs of USD 2514 (95% CI 2423 to 2606; p < 0.01) per patient and USD 264 (95% CI 166 to 361; p < 0.01) per patient in the first and second years, respectively. The increase in direct medical costs attributable to hip fracture was observed for 1.5 to 2 years (difference-in-difference estimate at 1 year 3.0 [95% CI 2.8 to 3.2]; p < 0.01) (difference-in-difference estimate at 2 years 1.2 [95% CI 1.1 to 1.3]; p < 0.01; joinpoint 1.5 year). In the subgroups of patients younger than 65, patients between 65 and 85, and patients older than 85 years of age, the increase in direct medical costs attributable to hip fracture continued up to 1 year (difference-in-difference estimate ratio at 1 year 2.7 [95% CI 2.1 to 3.4]; p < 0.01; joinpoint 1 year), 1.5 to 2 years (difference-in-difference estimate ratio at 1 year 2.8 [95% CI 2.6 to 3.1]; p < 0.01; difference-in-difference estimate ratio at 2 years 1.2 [95% CI 1.1 to 1.3]; p < 0.01; joinpoint 1.5 years), and 39 months to 5 years (difference-in-difference estimate ratio at 1 year 5.2 [95% CI 4.4 to 6.2]; p < 0.01; difference-in-difference estimate ratio at 5 years 2.1 [95% CI 1.4 to 3.1]; p < 0.01; joinpoint 39 months) from time zero, respectively. CONCLUSION: The direct medical costs in patients with hip fractures were higher than those in the matched cohort every year during the 5 years before and after hip fracture. The increase in direct medical costs because of hip fractures was maintained for 1.5 to 2 years and was greater in older patients. Based on this, we suggest that health policies should focus on patients' financial and social needs, with particular emphasis on the first 2 years after hip fracture with stratification based on patients' ages. LEVEL OF EVIDENCE: Level II, economic analysis.

Bayesian semiparametric mixed effects models for meta-analysis of the literature data : An application to cadmium toxicity studies.

We propose Bayesian semiparametric mixed effects models with measurement error to analyze the literature data collected from multiple studies in a meta-analytic framework. We explore this methodology for risk assessment in cadmium toxicity studies, where the primary objective is to investigate dose-response relationships between urinary cadmium concentrations and ß2 -microglobulin. In the proposed model, a nonlinear association between exposure and response is described by a Gaussian process with shape restrictions, and study-specific random effects are modeled to have either normal or unknown distributions with Dirichlet process mixture priors. In addition, nonparametric Bayesian measurement error models are incorporated to flexibly account for the uncertainty resulting from the usage of a surrogate measurement of a true exposure. We apply the proposed model to analyze cadmium toxicity data imposing shape constraints along with measurement errors and study-specific random effects across varying characteristics, such as population gender, age, or ethnicity.

Predicting the Number of Graphene-Like Layers on Surface for Commercial Fumed Nanodiamonds with Raman Spectra and Model Calculations.

Nanoscale carbon materials have a broad range of applications in the field of surface and material sciences. Each vibration mode of a Raman and Fourier transform infrared (FT-IR) spectra corresponds to a specific frequency of a bond in the core and surface of the crystal, thus it is highly sensitive to morphology, implying that every band is sensitive to the orientation of the bonds and the atomic weight at either end of the bond. Accordingly, in this study we apply transmission electron microscope (TEM), Raman spectroscopies, and model calculations to study the relative content of carbon-carbon (C-C) bonds to the anhydrous and weakly aggregated elementary nanoscale carbon particles of detonation nanodiamonds. One point of the Raman bands at approximately 1300 cm-1 established that there are highly uniform C-C bonds in a tetrahedral crystal field environment not unlike that of diamonds. Another point at approximately 1600 cm-1 would be a hexagonal graphene-like sheet. By analyzing the relative content of carbon bonds using the area of intensity of the Raman peaks and a simulation of crystal morphology, we suggest that the number of graphene surface layers would be monolayers in nanodiamonds, comprising two kinds of C-C bonds, one being sp3 bonds of diamond in the core and the other being sp2 bonds of graphene on the surface.

SCF-Slimb is critical for Glycogen synthase kinase-3ß-mediated suppression of TAF15-induced neurotoxicity in Drosophila.

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder characterized pathologically by motor neuron degeneration and associated with aggregation of RNA-binding proteins. TATA-binding protein-associated factor 15 (TAF15) accumulates as cytoplasmic aggregates in neuronal cells, and clearance of these aggregates is considered a potential therapeutic strategy for ALS. However, the exact pathogenic mechanism of TAF15-induced neurotoxicity remains to be elucidated. Glycogen synthase kinase-3 (GSK-3) plays a critical role in the protection of ALS pathology. In the present study, we use a transgenic fly model over-expressing human TAF15 to study the protective effects of Shaggy/GSK3ß on TAF15-induced neuronal toxicity in Drosophila brain. Transgenic flies were examined for locomotor activity and lithium treatment. The expression level and solubility of TAF15 were assessed with western blotting, whereas immunohistochemistry was used to assess TAF15 aggregation in Drosophila brain. We have revealed that Shaggy/GSK3ß was abnormally activated in neurons of TAF15-expressing flies and its inhibition can suppress the defective phenotypes, thereby preventing retinal degeneration and locomotive activity caused by TAF15. We have also found that Shaggy/GSK3ß inhibition in neuronal cells leads to a reduction in TAF15 levels. Indeed, the F-box proteins Slimb and archipelago genetically interact with TAF15 and control TAF15 protein level in Drosophila. Importantly, SCFslimb is a critical regulator for Shaggy/GSK3ß-mediated suppression of TAF15-induced toxicity in Drosophila. The present study has provided an in vivo evidence supporting the molecular mechanism of GSK3ß inhibition for protection against TAF15-linked proteinopathies.

Differential Seawater Adaptability in Three Different Sizes of Under-yearling Steelhead Trout.

Seawater adaptability of steelhead trout increases along with the increase in the size of the fish, independent of parr-smolt transformation. Three 96 h seawater challenge tests were conducted to determine the size at which seawater adaptability of steelhead trout develops. Plasma Na+ and Cl- levels, moisture content, gill Na+/K+ ATPase activity, and mortality during the 96 h after direct transfer to seawater (32 ppt) were determined. Plasma Na+ and Cl- levels in 50 g fish continuously increased during the 96 h after the transfer to seawater (p<0.05), but the levels in 100 and 150 g fish leveled off after 24 h (p<0.05). Both 100 and 150 g size steelhead trout maintained muscle moisture content (%) better than 50 g size fish (p<0.05). Gill Na+/K+ ATPase activity in the 100 g size group increased in a time-dependent manner after transfer to seawater (p<0.05), whereas activity in the 50 and 150 g sizes did not increase (p>0.05), for which a possible explanation was discussed. A mere 2.6% mortality in both the 50 and 150 g size groups was observed. In conclusion, the current results indicate that 50 g size steelhead trout did not show development of a high level of hypoosmoregulatory capacity, whereas fish in the 100 and 150 g size groups showed a high level in our experimental conditions. Therefore, the steelhead trout larger than a 100 g size is recommended for transfer to seawater culture.

Recent Advances on the Role of GSK3ß in the Pathogenesis of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disease characterized by progressive motor neuron degeneration. Although several studies on genes involved in ALS have substantially expanded and improved our understanding of ALS pathogenesis, the exact molecular mechanisms underlying this disease remain poorly understood. Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine-protein kinase that plays a critical role in the regulation of various cellular signaling pathways. Dysregulation of GSK3ß activity in neuronal cells has been implicated in the pathogenesis of neurodegenerative diseases. Previous research indicates that GSK3ß inactivation plays a neuroprotective role in ALS pathogenesis. GSK3ß activity shows an increase in various ALS models and patients. Furthermore, GSK3ß inhibition can suppress the defective phenotypes caused by SOD, TDP-43, and FUS expression in various models. This review focuses on the most recent studies related to the therapeutic effect of GSK3ß in ALS and provides an overview of how the dysfunction of GSK3ß activity contributes to ALS pathogenesis.

Effects of Hemicastration on Testes and Testosterone Concentration in Stallions.

The endocrine system is critical to the maintenance of testicular function. The homeostasis of sex hormone levels is orchestrated by positive and negative feedback systems controlled by the hypothalamic-pituitary-gonadal axis. This study investigated the long-term effects of hemicastration on testicular size and function in stallions. Four Thoroughbred stallions, 4-6 years of age, were included in this study. Several parameters, including testicular weight and volume, plasma testosterone concentrations, VASA-positive germ cell populations and cross-sectional areas of the seminiferous tubules were compared in stallions that underwent two hemicastrations, approximately 11 months apart. The weights and volumes of testes harvested at the second hemicastration were significantly higher than those of testes collected at the first hemicastration. However, VASA-positive germ cell populations and the cross-sectional areas of seminiferous tubules were not significantly different between testes harvested at the first and second hemicastrations. Similarly, plasma testosterone concentrations measured weekly for 3 weeks before the first hemicastration, 3 weeks after the first hemicastration, and 3 weeks before the second hemicastration were not significantly different. Our results suggest that hemicastration results in compensatory enlargement of the remaining testis and compensatory steroidogenesis to maintain normal reproductive function in stallions.

Effects of risk factor numbers on the development of the metabolic syndrome.

This study was performed to identify the factors affecting the develop-ment of metabolic syndrome by comparing the numbers of risk factors of the syndrome and by identifying the factors influencing the develop-ment of metabolic syndrome. Two hundred forty-eight health screening of examinee were used for the study (101 males, 147 females). Diagnostic basis ratio of metabolic syndrome risk factors showed that 35.1% of the subjects had abdominal obesity, 32.7% for high blood pressure, 66.1% for high insulin blood sugar, 43.1% for high triglyceride lipidemia, and 7.3% for low high-density lipoprotein lipidemia. No significant difference of the incidence of metabolic syndrome was found between gender. The diagnostic number for male was the highest with 1 risk factor (31.7%) while the highest with 2 factors (30.6%) in female. Significant differences were found in age and body mass index (BMI) between normal group with no risk factor and metabolic syndrome group. There was significant difference in BMI between the syndrome group with 1 risk factor and 3 risk factors. BMI was significantly higher (5.282 times) compared to their counterpart (P<0.001). Significant difference was found in BMI between 2 risk factors and the syndrome group with more than 3 risk factors and the incidence was higher (4.094 times) in the overweight group than their counterpart (P<0.001).

The adverse effects of selenomethionine on skeletal muscle, liver, and brain in the steelhead trout (Oncorhynchus mykiss).

Juvenile Oncorhynchus mykiss (average weight: 22.3 g) were fed one of five selenomethionine diets (1.09, 8.79, 15.37, 30.79, or 61.58 mg Se/kg diet). After 4 weeks, hepatic catalase activity over 15.37 mg Se/kg diets was significantly decreased, and the glutathione peroxidase activity over 30.79 mg Se/kg diets was elevated compared to the controls. In the brain, the dopamine levels at 61.58 mg Se/kg diet and the serotonin levels over 15.37 mg Se/kg diets were significantly increased, whereas the 3,4-dihydroxyphenylacetic acid, homovanillic acid, and dopamine turnover, and the 5-hydroxyindoleacetic acid and serotonin turnover over 30.79 mg Se/kg diets were decreased. In muscle, the 3-nitrotyrosine level over 15.37 mg Se/kg diets, acetylcholine esterase activity over 30.79 mg Se/kg diets, and histological alterations over 8.79 mg Se/kg diets were increased. Our current results showed that selenomethionine disrupted dopamine and serotonin metabolism in the brain and damaged the neuromuscular system in skeletal muscle.

Inhibition of biofilm and virulence properties of Pseudomonas aeruginosa by sub-inhibitory concentrations of aminoglycosides.

Aminoglycosides are a commonly used class of antibiotics; however, their application has been discontinued due to the emergence of multi-drug resistance bacterial strains. In the present study, the subinhibitory concentrations (sub-MIC) of several aminoglycosides were determined and tested as an antibiofilm and for their anti-virulence properties against Pseudomonas aeruginosa PAO1, which is an opportunistic foodborne pathogen. P. aeruginosa PAO1 exhibits multiple mechanisms of resistance, including the formation of biofilm and production of several virulence factors, against aminoglycoside antibiotics. The sub-MIC of these antibiotics exhibited biofilm inhibition of P. aeruginosa in alkaline TSB (pH 7.9). Moreover, various concentrations of these aminoglycosides also eradicate the mature biofilm of P. aeruginosa. In the presence of sub-MIC of aminoglycosides, the morphological changes of P. aeruginosa were found to change from rod-shaped to the filamentous, elongated, and streptococcal forms. Similar growth conditions and sub-MIC of aminoglycosides were also found to attenuate several virulence properties of P. aeruginosa PAO1. Molecular docking studies demonstrate that these aminoglycosides possess strong binding properties with the LasR protein, which is a well-characterized quorum-sensing receptor of P. aeruginosa. The present study suggests a new approach to revitalize aminoglycosides as antibiofilm and antivirulence drugs to treat infections caused by pathogenic bacteria.

Antibiofilm Action of ZnO, SnO2 and CeO2 Nanoparticles Towards Grampositive Biofilm Forming Pathogenic Bacteria.

BACKGROUND: The ability to form biofilm and produce several virulence factors has caused numerous human pathogens to become tremendously resistant towards traditional antibiotic treatments, thus, new alternative strategies are urgently in demand. One of the strategies that have recently been developed involves the application of metallic Nanoparticles (NPs). Up to the present, promising results in terms of antimicrobial and antibiofilm activities have been observed in a wide range of metal NPs. METHODS: The present study has selected three metal oxides such as ZnO, SnO2 and CeO2 NPs to comparatively investigate their antibiofilm and antibacterial properties against two Gram-positive human pathogens, which are Listeria monocytogenes and Staphylococcus aureus. RESULTS: The anti-biofilm activities of ZnO, SnO2 and CeO2 NPs against S. aureus and L. monocytogenes were assayed by crystal violet staining and confirmed by microscopic visualization using SEM. The synthesis of amyloid protein by S. aureus and exopolysaccharide by L. monocytogenes in the presence of ZnO, SnO2 and CeO2 NPs was evaluated by Congo red assay. DISCUSSION: Results have shown that ZnO, SnO2 and CeO2 NPs effectively inhibited biofilm formation of both L. monocytogenes and S. aureus. The microscopic analysis also confirmed the antibiofilm activity of these NPs. It was also found that only ZnO NPs inhibited cell growth as well as the production of amyloid protein in S. aureus. CONCLUSION: Overall, these results indicated that ZnO, SnO2 and CeO2 NPs can be considered as potential agents for treating the infections caused by L. monocytogenes and S. aureus, especially those associated with biofilm formation. Based on the present study, further studies are required to understand their mechanisms at both phenotypic and molecular levels, as well as their in vivo cytotoxicity, thereby enabling the applications of these metal oxide NPs in biomedical fields and food industry.

Streptomycin mediated biofilm inhibition and suppression of virulence properties in Pseudomonas aeruginosa PAO1.

Pseudomonas aeruginosa is known as an opportunistic pathogen whose one of the antibiotic resistance mechanisms includes biofilm formation and virulence factor production. The present study showed that the sub-minimum inhibitory concentration (sub-MIC) of streptomycin inhibited the formation of biofilm and eradicated the established mature biofilm. Streptomycin at sub-MIC was also capable of inhibiting biofilm formation on the urinary catheters. In addition, the sub-MIC of streptomycin attenuated the bacterial virulence properties as confirmed by both phenotypic and gene expression studies. The optimal conditions for streptomycin to perform anti-biofilm and anti-virulence activities were proposed as alkaline TSB media (pH 7.9) at 35 °C. However, sub-MIC of streptomycin also exhibited a comparative anti-biofilm efficacy in LB media at similar pH level and temperature. Furthermore, this condition also improved the biofilm inhibition and eradication properties of streptomycin, tobramycin and tetracycline towards the biofilm formed by a clinical isolate of P. aeruginosa. Findings from the present study provide an important insight for further studies on the mechanisms of biofilm inhibition and dispersion of pre-existing biofilm by streptomycin as well as tobramycin and tetracycline under a specific culture environment.

Chitooligosaccharides as Antibacterial, Antibiofilm, Antihemolytic and Anti-Virulence Agent against Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus nosocomial infections with a high mortality rate in human and animals have been reported to associate with bacterial biofilm formation, along with the secretion of numerous virulence factors. Therefore, the inhibition of biofilm formation and attenuation of virulence determinants are considered as a promising solution to combat the spread of S. aureus infections. Modern trends in antibiofilm therapies have opted for the active agents that are biocompatible, biodegradable, non-toxic and cost-effective. Owning the aforementioned properties, chitosan, a natural N-acetylated carbohydrate biopolymer derived from chitin, has been favorably employed. Recently, the chitosan structure has been chemically modified into Chitooligosaccharides (COS) to overcome its limited solubility in water, thus widening chitosan applications in modern antibiofilm research. In the present study, we have investigated the antibacterial, antibiofilm and anti-virulence activities against S. aureus of COS of different molecular weights dissolved in neutral water. METHODS: The study of bactericidal activity was performed using the micro-dilution method while the biofilm inhibition assay was performed using crystal-violet staining method and confirmed by scanning electron microscopic analysis. The inhibition of amyloid protein production was confirmed by Congo Red staining. RESULTS: Results showed that low molecular weight COS exhibited bactericidal activity and reduced the bacterial amylogenesis, hemolytic activity as well as H2O2 resistance properties, while slightly inhibiting biofilm formation. The present study provides a new insight for further applications of the water-soluble COS as a safe and cost-effective drug for the treatment of S. aureus biofilm-associated infections. CONCLUSION: Reducing the molecular weight of chitosan in the form of COS has become an effective strategy to maintain chitosan biological activity while improving its water solubility. The low molecular weight COS investigated in this study have effectively performed antibacterial, antibiofilm and antivirulence properties against S. aureus.

Synthesis and characterization of chitosan oligosaccharide-capped gold nanoparticles as an effective antibiofilm drug against the Pseudomonas aeruginosa PAO1.

The infection caused by Pseudomonas aeruginosa is a serious concern in human health. The bacterium is an opportunistic pathogen which has been reported to cause nosocomial and chronic infections through biofilm formation and synthesis of several toxins and virulence factors. Furthermore, the formation of biofilm by P. aeruginosa is known as one of the resistance mechanisms against conventional antibiotics. Natural compounds from marine resources have become one of the simple, cost-effective, biocompatible and non-toxicity for treating P. aeruginosa biofilm-related infections. Furthermore, hybrid formulation with nanomaterials such as nanoparticles becomes an effective alternative strategy to minimize the drug toxicity problem and cytotoxicity properties. For this reason, the present study has employed chitosan oligosaccharide for the synthesis of chitosan oligosaccharide-capped gold nanoparticles (COS-AuNPs). The synthesized COS-AuNPs were then characterized by using UV-Visible spectroscopy, Dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), Field emission transmission electron microscopy (FE-TEM), and Energy dispersive X-ray diffraction (EDX). The synthesized COS-AuNPs were applied for inhibiting P. aeruginosa biofilm formation. Results have shown that COS-AuNPs exhibited inhibition to biofilm as well as eradication to pre-existing mature biofilm. Simultaneously, COS-AuNPs were also able to reduce bacterial hemolysis and different virulence factors produced by P. aeruginosa. Overall, the present study concluded that the hybrid nanoformulation such as COS-AuNPs could act as a potential agent to exhibit inhibitory properties against the P. aeruginosa pathogenesis arisen from biofilm formation.