Method: The mRNA expression of PI3K/AKT axis from 100 non-obese and obese participants with insulin sensitivity and insulin resistance states were compared in this study toward the understanding of obesity heterogeneity molecular mechanism.
Result: In present study, there was no statistically significant difference in gene expression levels of IRS1 and PTEN between groups, whereas PI3K, AKT2 and GLUT4 genes were expressed at a lower level in obese diabetic group compared to other groups and were statistically significant. PDK1 gene was expressed at a higher level in non-obese diabetic group compared to obese diabetic and non-obese non-diabetics groups. No statistically significant difference was identified in gene expression pattern of PI3K/AKT pathway between obese non-diabetics and non-obese non-diabetics.
Conclusion: The components of PI3K/AKT pathway which is related to the fasting state, showed reduced expression in obese diabetic group due to the chronic over-nutrition which may induced insensitivity and reduced gene expression. The pathogenesis of insulin resistance in the absence of obesity in non-obese diabetic group could be due to disturbance in another pathway related to the non-fasting state like gluconeogenesis. Therefore, the molecular mechanism of insulin signalling in non-obese diabetic individuals is different from obese diabetics which more investigations are required to study insulin signalling pathways in greater depth, in order to assess nutritional factors, contribute to insulin resistance in obese diabetic and non-obese diabetic individuals.
Experimental procedure: Thirty six virgin adult female rats (n = 6) were randomly divided into six groups; Group 1-3 were normal control (NC), Sham (SHAM) and ovariectomized group (OVX) respectively whereas group 4-6 were PPD rats forced-fed once daily with distilled water (PPD), fish oil (PPD + FO; 9 g/kg) and Fluoxetine (PPD + FLX; 15 mg/kg) respectively from postpartum day 1 and continued for 10 consecutive days. Rats behaviors were evaluated on postpartum day 10 through open field test (OFT) and forced swimming test (FST), followed by biochemical analysis of NLRP3 inflammasome proteins pathway in their brain and determination of neutrophil to lymphocyte ratio (NLR).
Results: PPD-induced rats exhibited high immobility and low swimming time in FST with increased inflammatory status; NLR, IL-1β and NFкB/NLRP3/caspase-1 activity in their hippocampus. However, administration of FO or fluoxetine reversed the aforementioned abnormalities.
Conclusion: In conclusion, 10 days supplementation with FO ameliorated the depressive-like behaviors in PPD rats by targeting the NFкB/NLRP3/caspase-1/IL-1β activity. This has shed light on the potential of NLRP3 as a therapeutic target in treatment of PPD in rats.
OBJECTIVE: Apply machine learning for the prediction and identification of factors associated with short and long-term mortality in Asian STEMI patients and compare with a conventional risk score.
METHODS: The National Cardiovascular Disease Database for Malaysia registry, of a multi-ethnic, heterogeneous Asian population was used for in-hospital (6299 patients), 30-days (3130 patients), and 1-year (2939 patients) model development. 50 variables were considered. Mortality prediction was analysed using feature selection methods with machine learning algorithms and compared to Thrombolysis in Myocardial Infarction (TIMI) score. Invasive management of varying degrees was selected as important variables that improved mortality prediction.
RESULTS: Model performance using a complete and reduced variable produced an area under the receiver operating characteristic curve (AUC) from 0.73 to 0.90. The best machine learning model for in-hospital, 30 days, and 1-year outperformed TIMI risk score (AUC = 0.88, 95% CI: 0.846-0.910; vs AUC = 0.81, 95% CI:0.772-0.845, AUC = 0.90, 95% CI: 0.870-0.935; vs AUC = 0.80, 95% CI: 0.746-0.838, AUC = 0.84, 95% CI: 0.798-0.872; vs AUC = 0.76, 95% CI: 0.715-0.802, p < 0.0001 for all). TIMI score underestimates patients' risk of mortality. 90% of non-survival patients are classified as high risk (>50%) by machine learning algorithm compared to 10-30% non-survival patients by TIMI. Common predictors identified for short- and long-term mortality were age, heart rate, Killip class, fasting blood glucose, prior primary PCI or pharmaco-invasive therapy and diuretics. The final algorithm was converted into an online tool with a database for continuous data archiving for algorithm validation.
CONCLUSIONS: In a multi-ethnic population, patients with STEMI were better classified using the machine learning method compared to TIMI scoring. Machine learning allows for the identification of distinct factors in individual Asian populations for better mortality prediction. Ongoing continuous testing and validation will allow for better risk stratification and potentially alter management and outcomes in the future.
RESULTS: Among the 253 cats included in this study, 12.3% of the whole blood samples tested positive for DCH. The detection rate was significantly higher in pet cats (16.6%, n = 24/145) compared to shelter cats (6.5%, n = 7/108). Liver tissues showed higher a DCH detection rate (14.9%, n = 13/87) compared to blood; 5 out of these 13 cats tested positive for DCH in their paired liver and blood samples. Serum alanine transaminase (ALT) was elevated (> 95 units/L) in 12 out of the 23 DCH-positive cats (52.2%, p = 0.012). Whole-genome sequence analysis revealed that the Malaysian DCH strain, with a genome size of 3184 bp, had 98.3% and 97.5% nucleotide identities to the Australian and Italian strains, respectively. The phylogenetic analysis demonstrated that the Malaysian DCH genome was clustered closely to the Australian strain, suggesting that they belong to the same geographically-determined genetic pool (Australasia).
CONCLUSIONS: This study provided insights into a Malaysian DCH strain that was detected from a liver tissue. Interestingly, pet cats or cats with elevated ALT were significantly more likely to be DCH positive. Cats with positive DCH detection from liver tissues may not necessarily have viraemia. The impact of this virus on inducing liver diseases in felines warrants further investigation.
RESULTS: The PFGE data was input into FPQuest software, and the dendrogram generated was studied for possible genetic relatedness among the isolates. All the isolates were found to belong to the Salmonella Enteritidis serotype with notable resistance to tetracycline, gentamycin, streptomycin, and sulfadimidine. The S. Enteritidis isolates tested predominantly subtyped into the ST11 and ST1925, which was found to be a single cell variant of ST11. The STs were found to occur in chicken meats, foods, and live chicken cloacal swabs, which may indicate the persistence of the bacteria in multiple foci.
CONCLUSION: The data demonstrate the presence of S. Enteritidis among chickens, indicating its preference and reservoir status for enteric Salmonella pathogens.