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Mymensingh Medical Journal : MMJ Jul 2024In Intensive Care Units (ICUs) infection represents the most frequent complication leading to high mortality. Particularly the incidence of fungal infections, especially... (Observational Study)
Observational Study
In Intensive Care Units (ICUs) infection represents the most frequent complication leading to high mortality. Particularly the incidence of fungal infections, especially due to Candida spp., has been increasing during the last years. Over last two decades there is predominance of Non albicans Candida (NAC) infection with increased isolation of novel species and decreased susceptibility. Early identification of Candida species and determination of antifungal susceptibility pattern is essential for effective management. Therefore, the study was conducted to isolate and identify Candida species from the blood samples of the patients suspected of candidemia and assess their antifungal susceptibility pattern. This cross-sectional, descriptive type of observational study was conducted in the Department of Microbiology, Mymensingh Medical College, Bangladesh from March 2021 to February 2022. Venous blood was collected from clinically suspected patients admitted at ICU, Neonatal Intensive Care Unit (NICU), Mymensingh Medical College Hospital, Bangladesh. Primary blood culture was performed by automated method followed by sub-culture in Saboraud's Dextrose Agar (SDA) and blood agar media. Candida species were recognized by phenotypic and genotypic methods. Antifungal susceptibility testing was done by disk diffusion and broth microdilution method (BMD). Out of 125 blood specimens collected, Candida species were isolated from 39(31.0%) blood samples of which NAC species were 35(89.0%) whereas C. albicans was only 4(10.2%). Eight (8) different Candida species were identified of which C. parapsilosis was predominant 16(41.0%). Rare and emerging drug resistant species of C. ciferrii 23.0%, C. auris 7.7%, C. rugosa 10.3%, C. lusitaniae 2.6% were also isolated. Candidemia was highest in neonate 33(84.61%) with male predominance 24(61.54%). Use of broad-spectrum antibiotics, prolonged hospital stay, pre-maturity and low birth weight (LBW) were found to be important risk factors. In candidemia the highest resistance was to Fluconazole-33% and lowest to Voriconazole-5%. The study showed that NAC species were more common with emergence of rare and multidrug resistant species.
Topics: Humans; Bangladesh; Candidemia; Cross-Sectional Studies; Female; Male; Candida; Antifungal Agents; Intensive Care Units; Microbial Sensitivity Tests; Infant, Newborn; Adult; Drug Resistance, Fungal
PubMed: 38944705
DOI: No ID Found -
Obesity Research & Clinical Practice Jun 2024Personalised medicine is seen as an exciting opportunity to improve the health outcomes of people with obesity. As research on phenotyping and personalised treatment for...
OBJECTIVE
Personalised medicine is seen as an exciting opportunity to improve the health outcomes of people with obesity. As research on phenotyping and personalised treatment for obesity rapidly advances, this study sought to understand patient preferences and perspectives on personalised medicine for obesity.
METHODS
A participatory world café methodology was used to garner the perspectives of people living with obesity on the potential opportunities and limitations associated with a personalised approach to obesity risk identification and treatment. Data were recorded by participants on tablemats and analysed thematically using thematic analysis.
RESULTS
Patients expressed the hope that personalised medicine for obesity would reduce stigma, support understanding of obesity as a disease, and improve treatment outcomes and acceptance. They also expressed concern about the accuracy of personalised medicine for obesity, its implications for insurance and that further advances in individual, personalised medicine, would detract attention from social, environmental, economic and psychological drivers of obesity.
CONCLUSIONS
This study highlights how patients are generally very optimistic about the potential for personalised obesity medicine but also raise a number of legitimate concerns that will be of interest to clinicians, industry, and policy makers.
PubMed: 38944550
DOI: 10.1016/j.orcp.2024.06.004 -
Advances in Pediatrics Aug 2024Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic condition caused by various enzyme deficiencies that result in disruptions of pathways of adrenal... (Review)
Review
Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic condition caused by various enzyme deficiencies that result in disruptions of pathways of adrenal steroidogenesis. 21-hydroxylase deficiency is the most common form of CAH and has a variable phenotype which ranges a spectrum, from the most severe salt-wasting type to the simple-virilizing type and the least severe nonclassical form. Patients with CAH are at risk for various comorbidities due to the underlying adrenal hormone production imbalance as well as the treatment of the condition, which typically includes supraphysiologic glucocorticoid dosing. Children and adults require frequent monitoring and careful medication dosing adjustment. However, there are multiple novel therapies on the horizon that offer promise to patients with CAH in optimizing their treatment regimens and reducing the risk of comorbidities.
Topics: Humans; Adrenal Hyperplasia, Congenital; Glucocorticoids; Child
PubMed: 38944479
DOI: 10.1016/j.yapd.2024.02.006 -
Journal of Hepatology Jun 2024Regression of cirrhosis has been observed in patients with viral and non-viral etiologies of liver disease in whom the underlying cause of liver injury was effectively...
BACKGROUND & AIMS
Regression of cirrhosis has been observed in patients with viral and non-viral etiologies of liver disease in whom the underlying cause of liver injury was effectively suppressed. However, the understanding of the factors contributing to reversibility of fibrosis and cirrhosis is limited. Our aims were to assess clinical factors, perform genotyping of known variants, and comprehensive metabolic phenotyping to characterize the regression of fibrosis in patients with compensated advanced chronic liver disease (cACLD).
METHODS
In a case-control pilot study with 81 cACLD patients, we compared individuals exhibiting histological or clinical evidence of cACLD regression ("regressors"; n=44) with those showing no improvement ("non-regressors"; n=37) after a minimum of 24 months of successful therapy of the cause of liver disease. Data were validated using an external validation cohort (n=30).
RESULTS
Regardless of the cause of cACLD, the presence of obesity (OR 0.267 95%CI:0.072-0.882; P=0.049), high liver stiffness (OR 0.960, 95%CI:0.925-0.995; P=0.032), and carriage of GCKR variant rs1260326 (OR 0.148, 95%CI:0.030-0.773; P=0.019) are associated with a reduced likelihood of fibrosis regression in a subgroup of 60 ACLD patients genotyped for known genetic variants. Using liver tissue transcriptomics, we identified metabolic pathways differentiating regressors from non-regressors, with top pathways associated to lipid metabolism -especially fatty acids, bile acids, phospholipids, triacylglycerides (biosynthesis), and the carnitine shuttle. In the entire discovery cohort, we further measured metabolites within the defined pathways, which led to identifying 33 circulating markers differentiating regressors from non-regressors after etiological therapy. The validation cohort confirmed 14 of the differentially expressed markers.
CONCLUSIONS
We identified and validated a group of lipid biomarkers associated with regression of fibrosis that could be used as non-invasive biomarker for detecting regression of fibrosis in cACLD.
PubMed: 38944391
DOI: 10.1016/j.jhep.2024.06.028 -
Genomics Jun 2024The lack of specific molecular targets and the rapid spread lead to a worse prognosis of triple-negative breast cancer (TNBC). Therefore, identifying new therapeutic and...
BACKGROUND
The lack of specific molecular targets and the rapid spread lead to a worse prognosis of triple-negative breast cancer (TNBC). Therefore, identifying new therapeutic and prognostic biomarkers helps to develop effective treatment strategies for TNBC.
METHODS
Through preliminary bioinformatics analysis, FOXCUT was found to be significantly overexpressed in breast cancer, especially in TNBC. Tissue samples were collected from 15 TNBC patients, and qRT-PCR was employed to validate the expression of FOXCUT in both TNBC patient tissues and TNBC cell lines. We also carried out the GSEA analysis and KEGG enrichment analysis of FOXCUT. Additionally, the effects of FOXCUT knockdown on TNBC cell malignant behaviors, and aerobic glycolysis were assessed by methods including CCK-8, Transwell, western blot, and Seahorse XF 96 analyses. Moreover, utilizing databases predicting interactions between ceRNAs, corresponding lncRNA-miRNA binding relationships, and miRNA-mRNA interactions were predicted. These predictions were subsequently validated through RNA immunoprecipitation and dual-luciferase reporter assays.
RESULTS
FOXCUT exhibited high expression in both TNBC tissues and cell lines, fostering cell malignant behaviors and glycolysis. FOXCUT was found to sponge miR-337-3p, while miR-337-3p negatively regulated the expression of ANP32E. Consequently, FOXCUT ultimately facilitated the malignant phenotype of TNBC by upregulating ANP32E expression.
CONCLUSION
This study elucidated the role of FOXCUT in elevating aerobic glycolysis levels in TNBC and driving malignant cancer cell development via the miR-337-3p/ANP32E regulatory axis.
PubMed: 38944356
DOI: 10.1016/j.ygeno.2024.110892 -
Chemosphere Jun 2024Colistin is a polymyxin antimicrobic mainly used to treat infection caused by multi-drug resistant Gram-negative bacteria. Mechanisms of colistin resistance are linked...
Colistin is a polymyxin antimicrobic mainly used to treat infection caused by multi-drug resistant Gram-negative bacteria. Mechanisms of colistin resistance are linked to the mobile colistin resistance (mcr) genes, which are transferable within mobile plasmids. Currently, there is limited research on the environmental dissemination of these genes. The behavioural and morphological characteristics of Apis mellifera L. make honey bees effective environmental bioindicators for assessing the prevalence of antimicrobial-resistant bacteria. This study aims to evaluate the colistin phenotypic and genotypic resistance in environmental Gram-negative bacteria isolated from foraging honey bees, across a network of 33 colonies distributed across the Emilia-Romagna region in Italy. Phenotypic resistances were determined through a microdilution assay using the minimum inhibitory concentration (MIC) with dilutions ranging from 0.5 μg/ml to 256 μg/ml. Strains with MIC values gather than 2 μg/ml were classified as resistant. Also, the identification of the nine mcr genes was carried out using two separate multiplex PCR assays. The study found that 68.5% of isolates were resistant and the genus with the higher resistance rates observed in Enterobacter spp. (84.5%). At least one mcr gene was found in 137 strains (53.3%). The most detected gene was mcr5 (35.3%), which was the most frequently detected gene in the seven provinces, while the least observed was mcr4 (4.8%), detected only in two provinces. These results suggested the feasibility of detecting specific colistin resistance genes in environmentally spread bacteria and understanding their distribution at the environmental level, despite their restricted clinical use. In a One-Health approach, this capability enables valuable environmental monitoring, considering the significant role of colistin in the context of public health.
PubMed: 38944352
DOI: 10.1016/j.chemosphere.2024.142717 -
International Journal of Cardiology Jun 2024Heart failure is an important cause of mortality and morbidity worldwide. Heart failure with preserved ejection fraction (HFpEF) incidence and prevalence is increasing,... (Review)
Review
Heart failure is an important cause of mortality and morbidity worldwide. Heart failure with preserved ejection fraction (HFpEF) incidence and prevalence is increasing, and the phenotype associated with obesity is the most frequent. Epicardial adipose tissue (EAT) is directly associated with systemic obesity and several previous studies have shown a clear link between EAT and HFpEF. Moreover, the restriction induced by the pericardium is also linked to HFpEF. In this review we will describe the epidemiological association between the pericardium, EAT and HFpEF, how to quantify EAT, what are the pathophysiological mechanism to explain theses association and how can the pericardium and EAT be a treatment target in patients with HFpEF.
PubMed: 38944349
DOI: 10.1016/j.ijcard.2024.132303 -
Journal of Affective Disorders Jun 2024Growing evidence highlights the role of the spleen-brain axis in inflammation-associated depression. The α7-subtype of nicotinic acetylcholine receptor (α7 nAChR,...
BACKGROUND
Growing evidence highlights the role of the spleen-brain axis in inflammation-associated depression. The α7-subtype of nicotinic acetylcholine receptor (α7 nAChR, encoded by the Chrna7 gene) is implicated in systemic inflammation, with Chrna7 knock-out (KO) mice displaying depression-like behaviors. Yet, the influence of spleen nerve on depression-like behaviors in these KO mice remains to be elucidated.
METHODS
We investigated the effects of the splenic nerve denervation (SND) on depression-like behaviors, the protein expression in the prefrontal cortex (PFC), and the gut microbiota composition in Chrna7 KO mice.
RESULTS
SND markedly alleviated depression-like behaviors and the reduced expression of GluA1 and postsynaptic density protein-95 (PSD-95) in the PFC of Chrna7 KO mice. No changes in α-diversity of gut microbiota were noted among the control, KO + sham, and KO + SND groups. However, significant differences in β-diversity of gut microbiota were noted among the groups. Notable alterations in various microbiota (e.g., Fluviimonas_pallidilutea, Maribacter_arcticus, Parvibacter_caecicola) and plasma metabolites (e.g., helicide, N-acetyl-L-aspartic acid, α-D-galactose 1-phosphate, choline, creatine) were observed between KO + sham and KO + SND groups. Interestingly, correlations were found between the relative abundance of specific microbiota and other outcomes, including synaptic proteins, metabolites and behavioral data.
LIMITATIONS
The underlying mechanisms remain to be fully understood.
CONCLUSIONS
Our findings indicate that the splenic nerve contributes to depression-like phenotypes in Chrna7 KO mice via the spleen-gut-brain axis.
PubMed: 38944290
DOI: 10.1016/j.jad.2024.06.091 -
Current Problems in Cardiology Jun 2024Public health, personal/community health behaviors, health care delivery, and the scientific community have all been impacted by the COVID-19 pandemic and are... (Review)
Review
Public health, personal/community health behaviors, health care delivery, and the scientific community have all been impacted by the COVID-19 pandemic and are consequently poised to consider substantial paradigm shifts that will enhance disease prevention and public health resilience. The current analysis compares the newly developed Lifestyle Health Index (LHI) to U.S. county-level COVID-19 vaccination, infection, and mortality rates. We linked Centers of Disease Control PLACES, the U.S. Community Profile Report, and Nationhood lab databases through common zip-code identifiers to determine the association between county-level LHI scores and COVID-19 outcomes and vaccination status against the backdrop of U.S. regions with distinct cultural phenotypes. There was a statistically significant relationship between a poor LHI, lower COVID-19 vaccination rates and higher COVID-19 infection and mortality rates. There were clear differences in outcomes across the U.S. regions, suggesting distinct regional cultural characteristics may significantly influence health behaviors and outcomes. In the U.S., a syndemic comprising unhealthy lifestyle, chronic disease, and COVID-19 resulted in unnecessary hospitalizations and deaths. Politicization of the pandemic, socioeconomic inequity and regional cultural values meaningfully contributed to the uneven distribution of poor outcomes during this syndemic. Components of the syndemic were avoidable and should not be repeated. Condensed Abstract: The unhealthy lifestyle - chronic disease - COVID-19 U.S. syndemic resulted in unnecessary hospitalizations and deaths. Politicization of the pandemic, socioeconomic inequity and regional cultural values meaningfully contributed to the uneven distribution of poor outcomes during this syndemic. Components of the syndemic were avoidable and should not be repeated.
PubMed: 38944225
DOI: 10.1016/j.cpcardiol.2024.102728 -
Biotechnology Advances Jun 2024Constraint-based modeling (CBM) has evolved as the core systems biology tool to map the interrelations between genotype, phenotype, and external environment. The recent... (Review)
Review
Constraint-based modeling (CBM) has evolved as the core systems biology tool to map the interrelations between genotype, phenotype, and external environment. The recent advancement of high-throughput experimental approaches and multi-omics strategies has generated a plethora of new and precise information from wide-ranging biological domains. On the other hand, the continuously growing field of machine learning (ML) and its specialized branch of deep learning (DL) provide essential computational architectures for decoding complex and heterogeneous biological data. In recent years, both multi-omics and ML have assisted in the escalation of CBM. Condition-specific omics data, such as transcriptomics and proteomics, helped contextualize the model prediction while analyzing a particular phenotypic signature. At the same time, the advanced ML tools have eased the model reconstruction and analysis to increase the accuracy and prediction power. However, the development of these multi-disciplinary methodological frameworks mainly occurs independently, which limits the concatenation of biological knowledge from different domains. Hence, we have reviewed the potential of integrating multi-disciplinary tools and strategies from various fields, such as synthetic biology, CBM, omics, and ML, to explore the biochemical phenomenon beyond the conventional biological dogma. How the integrative knowledge of these intersected domains has improved bioengineering and biomedical applications has also been highlighted. We categorically explained the conventional genome-scale metabolic model (GEM) reconstruction tools and their improvement strategies through ML paradigms. Further, the crucial role of ML and DL in omics data restructuring for GEM development has also been briefly discussed. Finally, the case-study-based assessment of the state-of-the-art method for improving biomedical and metabolic engineering strategies has been elaborated. Therefore, this review demonstrates how integrating experimental and in silico strategies can help map the ever-expanding knowledge of biological systems driven by condition-specific cellular information. This multiview approach will elevate the application of ML-based CBM in the biomedical and bioengineering fields for the betterment of society and the environment.
PubMed: 38944218
DOI: 10.1016/j.biotechadv.2024.108400