Category: Nevin Manimala

J Biomol Struct Dyn. 2023 Feb 28:1-16. doi: 10.1080/07391102.2023.2179542. Online ahead of print.

ABSTRACT

Cervical cancer (CC) is a global threat to women and our knowledge is frighteningly little about its underlying genomic contributors. Our research aimed to understand the underlying molecular and genetic mechanisms of CC by integrating bioinformatics and network-based study. Transcriptomic analyses of three microarray datasets identified 218 common differentially expressed genes (DEGs) within control samples and CC specimens. KEGG pathway analysis revealed pathways in cell cycle, drug metabolism, DNA replication and the significant GO terms were cornification, proteolysis, cell division and DNA replication. Protein-protein interaction (PPI) network analysis identified 20 hub genes and survival analyses validated CDC45, MCM2, PCNA and TOP2A as CC biomarkers. Subsequently, 10 transcriptional factors (TFs) and 10 post-transcriptional regulators were detected through TFs-DEGs and miRNAs-DEGs regulatory network assessment. Finally, the CC biomarkers were subjected to a drug-gene relationship analysis to find the best target inhibitors. Standard cheminformatics method including in silico ADMET and molecular docking study substantiated PD0325901 and Selumetinib as the most potent candidate-drug for CC treatment. Overall, this meticulous study holds promises for further in vitro and in vivo research on CC diagnosis, prognosis and therapies.Communicated by Ramaswamy H. Sarma.

PMID:36852684 | DOI:10.1080/07391102.2023.2179542

J Anim Sci. 2023 Feb 28:skad062. doi: 10.1093/jas/skad062. Online ahead of print.

ABSTRACT

Physiological and environmental stresses such as the transition into lactation and heat load contribute to gastrointestinal tract (GIT) dysfunction. The nonruminant gastrointestinal tract has mechanisms to cope with prooxidant and proinflammatory stressors arising from the gut lumen or within intestinal cells. One-carbon metabolism (OCM) contributes to antioxidant capacity via the production of glutathione (GSH) and taurine, and the synthesis of phospholipid, creatine, and the osmolyte glycinebetaine among others. A multipronged approach was used to assess the biological relevance of OCM and closely-related pathways on GIT function in dairy cows. Ruminal papillae (Rum) and scrapings from duodenum (Duo), jejunum (Jej), and ileum (Ile) were collected at slaughter from 8 multiparous Holstein cows averaging 128 ± 12 d in milk and producing 39 ± 5 kg·d -1. A MIXED model ANOVA with preplanned orthogonal contrasts was used for statistical analysis. Methionine adenosyl transferase 1 activity (MAT) was ~10-fold greater (P < 0.01) and cystathionine β-synthase activity doubled in Rum vs. small intestine. Total glutathione peroxidase (GPX) activity was greatest (P = 0.03) in Ile, but similar to Rum. Activity and mRNA abundance of betaine-homocysteine S-methyltransferase were undetectable. There was a 2.5-fold greater protein abundance of GPX1 (P < 0.01) and a ~2-fold greater abundance of GPX3 (P < 0.01) in Rum vs. small intestine. Among the various amino acids (AA) with roles in OCM or closely-related pathways (e.g. creatine synthesis), concentrations of arginine, aspartate, glutamine, methionine, and serine were lower (P < 0.01) in Rum vs. small intestine. Unlike AA, concentrations of OCM-related intermediates S-5′-adenosyl-homocysteine (SAH), glycinebetaine, carnitine, creatine (CRE), and cysteinesulfinic acid were greater (P < 0.01) while taurine was lower in Rum vs. small intestine. Intermediates of the folate cycle were undetectable. The fact that S-adenosylmethionine (SAM) was undetectable while MAT activity and SAH were greater in Rum suggested that availability of SAM (a methyl donor) is a key determinant of flux through the folate and methionine cycles in the GIT. Except for adenosine, concentrations of glutamate, glycine, α-ketoglutarate, hypotaurine, and GSH were lowest in Ile. Together, the data underscored unique differences in activity of one-carbon metabolism and related pathways across sections of the GIT.

PMID:36852676 | DOI:10.1093/jas/skad062

J Cachexia Sarcopenia Muscle. 2023 Feb 28. doi: 10.1002/jcsm.13199. Online ahead of print.

ABSTRACT

BACKGROUND: Systemic inflammation, the most representative tumour-host interaction, plays a crucial role in disease progression and prognosis in patients with non-small cell lung cancer (NSCLC). Few studies have compared the performance of existing haematological systemic inflammation biomarkers in predicting the prognosis of NSCLC patients. The purpose of this study was to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with NSCLC through a multicentre prospective study.

METHODS: The predictive accuracy of systemic inflammation biomarkers for prognostic assessment in NSCLC was assessed using C-statistics. Inter-group differences in survival were assessed using the log-rank test and visualized using the Kaplan-Meier method. A restricted cubic spline (RCS) curve was used to explore the association between the biomarkers and survival. Independent prognostic biomarkers for overall survival were determined using multivariable Cox proportional hazards regression analysis. Logistic regression analysis was used to determine independent predictors of 90-day outcomes, length of hospitalization, hospitalization expenses and cachexia.

RESULTS: The inflammatory burden index (IBI) had the highest C-statistic for predicting the prognosis of patients with NSCLC, reaching 0.640 (0.617, 0.663). Patients with a high IBI had significantly worse outcomes than those with a low IBI (35.46% vs. 57.22%; log-rank P < 0.001). The IBI was also able to differentiate the prognosis of patients with NSCLC with the same pathological stage. The RCS curve showed an inverted L-shaped dose-response relationship between the IBI and survival of patients with NSCLC. Multivariable Cox proportional hazards regression analysis showed that a high IBI was an independent risk factor for death of patients with NSCLC (hazard ratio = 1.229, 95% confidence interval [CI]: 1.131-1.335, P < 0.001). A high IBI was an independent predictor of 90-day outcomes (odds ratio [OR] = 1.789, 95% CI: 1.489-2.151, P < 0.001), prolonged hospital stays (OR = 1.560, 95% CI: 1.256-1.938, P < 0.001), high hospitalization expenses (OR = 1.476, 95% CI: 1.195-1.822, P < 0.001) and cachexia (OR = 1.741, 95%CI = 1.374-2.207, P < 0.001) in patients with NSCLC.

CONCLUSIONS: The IBI was independently associated with overall survival, 90-day outcomes, length of hospitalization, hospitalization expenses and cachexia in NSCLC patients. As an optimal systemic inflammation biomarker, the IBI has broad clinical application prospects in predicting the prognosis of patients with NSCLC.

PMID:36852672 | DOI:10.1002/jcsm.13199

J Med Virol. 2023 Feb 28. doi: 10.1002/jmv.28625. Online ahead of print.

ABSTRACT

Recombination is the main contributor to RNA virus evolution, and SARS-CoV-2 during the pandemic produced several recombinants. The most recent SARS-CoV-2 recombinant is the lineage labeled XBB, also known as Gryphon, which arose from BJ.1 and BM.1.1.1. Here we performed a genome-based survey aimed to compare the new recombinant with its parental lineages that never became dominant. Genetic analyses indicated that the recombinant XBB and its first descendant XBB.1 show an evolutionary condition typical of an evolutionary blind background with no further epidemiologically relevant descendant. Genetic variability and expansion capabilities are slightly higher than parental lineages. Bayesian Skyline Plot indicates that XBB reached its plateau around October 6, 2022 and after an initial rapid growth the viral population size did not further expand, and around November 10, 2022 its levels of genetic variability decreased. Simultaneously with the reduction of the XBB population size, an increase of the genetic variability of its first sub-lineage XBB.1 occurred, that in turn reached the plateau around November 9, 2022 showing a kind of vicariance with its direct progenitors. Structure analysis indicates that the affinity for ACE2 surface in XBB/XBB.1 RBDs is weaker than for BA.2 RBD. In conclusion, at present XBB and XBB.1 do not show evidence about a particular danger or high expansion capability. Genome-based monitoring must continue uninterrupted in order to individuate if further mutations can make XBB more dangerous or generate new subvariants with different expansion capability. This article is protected by copyright. All rights reserved.

PMID:36852665 | DOI:10.1002/jmv.28625

Hum Brain Mapp. 2023 Feb 28. doi: 10.1002/hbm.26251. Online ahead of print.

ABSTRACT

Schizophrenia (SZ) is a severe mental disorder characterized by failure of functional integration (aka dysconnection) across the brain. Recent functional connectivity (FC) studies have adopted functional parcellations to define subnetworks of large-scale networks, and to characterize the (dys)connection between them, in normal and clinical populations. While FC examines statistical dependencies between observations, model-based effective connectivity (EC) can disclose the causal influences that underwrite the observed dependencies. In this study, we investigated resting state EC within seven large-scale networks, in 66 SZ and 74 healthy subjects from a public dataset. The results showed that a remarkable 33% of the effective connections (among subnetworks) of the cognitive control network had been pathologically modulated in SZ. Further dysconnection was identified within the visual, default mode and sensorimotor networks of SZ subjects, with 24%, 20%, and 11% aberrant couplings. Overall, the proportion of discriminative connections was remarkably larger in EC (24%) than FC (1%) analysis. Subsequently, to study the neural correlates of impaired cognition in SZ, we conducted a canonical correlation analysis between the EC parameters and the cognitive scores of the patients. As such, the self-inhibitions of supplementary motor area and paracentral lobule (in the sensorimotor network) and the excitatory connection from parahippocampal gyrus to inferior temporal gyrus (in the cognitive control network) were significantly correlated with the social cognition, reasoning/problem solving and working memory capabilities of the patients. Future research can investigate the potential of whole-brain EC as a biomarker for diagnosis of brain disorders and for neuroimaging-based cognitive assessment.

PMID:36852654 | DOI:10.1002/hbm.26251

Twin Res Hum Genet. 2023 Feb 28:1-5. doi: 10.1017/thg.2023.4. Online ahead of print.

ABSTRACT

An abnormal alanine aminotransferase (ALT) level is predictive of disease and all-cause mortality and may indicate liver injury. Using twin modeling, the genetic and environmental factors that affect human serum ALT levels have been well studied for the populations in the different countries, and the results showed moderate-to-high heritability. However, the heritability of ALT level has not been explored in Chinese population. Thus, we recruited 369 pairs of twins (233 monozygotic and 136 dizygotic) from the Qingdao Twin Registry in China with a median age of 50 years (40-80 years). Correlation analysis and a structural equation model (SEM) were conducted to evaluate the heritability of ALT level. The data for age, gender, body mass index and alcohol consumption were set as covariates. Intrapair correlation in monozygotic twins was 0.64 (95%CI [.56, .71]) and 0.42 (95% CI [.28, .55]) in dizygotic twins. The SEM analysis indicated that 65% (95% CI [57%, 71%]) of the variation in ALT levels can be explained by additive genetics and 35% (95% CI [29%, 44%]) of the variation is attributed to unique environmental factors or residuals. Shared environmental influences were not significant. In conclusion, serum ALT variations exhibited strong genetic effects. The variation could also be explained by unique environmental factors. However, shared environmental factors have a minor impact on the serum ALT level.

PMID:36852647 | DOI:10.1017/thg.2023.4

Nurs Open. 2023 Feb 28. doi: 10.1002/nop2.1657. Online ahead of print.

ABSTRACT

AIM: This study aimed to calculate the total daily nursing workload and the optimal number of nurses per general unit based on the nursing intensity.

DESIGN: This study was conducted using a cross-sectional study.

METHODS: Three units at one general hospital were investigated. Patient classification according to nursing needs was performed for over 10 days in each unit in September 2018. The direct and non-direct nursing time and nursing intensity scores were analysed using descriptive statistics.

RESULTS: For the internal medicine unit, the average direct nursing time per patient was 1.0, 1.5, 2.2 and 2.9 h for Groups 1, 2, 3 and 4, respectively. For the surgical unit, the average direct nursing time per patient was 0.9, 1.4, 2.1 and 2.6 h for Groups 1, 2, 3 and 4, respectively. 5 and 9 additional nurses were needed in the internal medicine and surgical nursing units.

PATIENT CONTRIBUTION: This study confirmed that the optimal number of nurses was not achieved and that the nursing intensity was very high. Long-term efforts, such as improving the nursing environment, should be made to ensure an optimal number of nurses in various nursing units.

PMID:36852629 | DOI:10.1002/nop2.1657

Inquiry. 2023 Jan-Dec;60:469580231155716. doi: 10.1177/00469580231155716.

ABSTRACT

The primary method for preventing health and health-related problems in diabetic people is glycemic control. Numerous studies have documented the importance of glycemic control and the factors that influence it. However, the results are dispersed. This study sought to identify the prevalence of poor glycemic control and associated factors in Ethiopia. Findings will be crucial to reduce the burden of poor glycemic control. Comprehensive search was performed from databases: PubMed, Global Health, CINAHL, IRIS, and FSTA. Gray literature sources were also explored. This document was prepared based on the PRISMA flowchart. The protocol is registered in PROSPERO (ID: CRD42022296583). STATA software was used for data analyses and I² test with Cochrane Q statistics, and forest plot were used to verify heterogeneity. When the I² value was higher than 50% and the p-value was 0.05, heterogeneity was deemed significant. To confirm publication bias, a funnel plot with an Egger’s regression test was performed. The factors related to poor glycemic control were reported using pooled odds ratios (POR) and a 95% confidence interval. In this study, 46 papers totaling 15 457 people were used to calculate the pooled estimates. It was determined that 32.6% (95% CI: 28.3, 36.9) and 61.92% (95% CI: 57.92, 65.92) of the subjects, respectively, had good and poor glycemic control. Being male protected against poor glycemic control, while poor diet adherence, lack of exercise, poor adherence to anti-diabetic medications, and smoking increased the likelihood of poor glycemic control. Lack of formal education, no family history of diabetes, lack of glucometer for blood glucose monitoring, comorbidity, being overweight and prolonged length of stay with diabetes all contributed to poor glycemic control. Ethiopia had a fairly high rate of poor glycemic control. The main determinants are lifestyle factors. Therefore, it is important to focus on behavioral interventions.

PMID:36852627 | DOI:10.1177/00469580231155716

Hum Brain Mapp. 2023 Feb 28. doi: 10.1002/hbm.26237. Online ahead of print.

ABSTRACT

Visual impairment and retinal neurodegeneration are intrinsically connected and both have been associated with cognitive impairment and brain atrophy, but the underlying mechanisms remain unclear. To investigate whether transneuronal degeneration is implicated, we systematically assessed the relation between visual function and retinal, visual pathway, hippocampal and brain degeneration. We analyzed baseline data from 3316 eligible Rhineland Study participants with visual acuity (VA), optical coherence tomography (OCT), and magnetic resonance imaging (MRI) data available. Regional volumes, cortical volume, and fractional anisotropy (FA) were derived from T1-weighted and diffusion-weighted 3 T MRI scans. Statistical analyses were performed using multivariable linear regression and structural equation modeling. VA and ganglion cell layer (GCL) thinning were both associated with global brain atrophy (SD effect size [95% CI] -0.090 [-0.118 to -0.062] and 0.066 [0.053-0.080], respectively), and hippocampal atrophy (-0.029 [-0.055 to -0.003] and 0.114 [0.087-0.141], respectively). The effect of VA on whole brain and hippocampal volume was partly mediated by retinal neurodegeneration. Similarly, the effect of retinal neurodegeneration on brain and hippocampal atrophy was mediated through intermediate visual tracts, accounting for 5.2%-23.9% of the effect. Visual impairment and retinal neurodegeneration were robustly associated with worse brain atrophy, FA, and hippocampal atrophy, partly mediated through disintegration of intermediate visual tracts. Our findings support the use of OCT-derived retinal measures as markers of neurodegeneration, and indicate that both general and transneuronal neurodegeneration along the visual pathway, partly reflecting visual impairment, account for the association between retinal neurodegeneration and brain atrophy.

PMID:36852616 | DOI:10.1002/hbm.26237

Minerva Dent Oral Sci. 2023 Feb 28. doi: 10.23736/S2724-6329.23.04774-5. Online ahead of print.

ABSTRACT

BACKGROUND: Dental caries still represents a major public health problem, as it is the most widespread noncommunicable disease. The enamel of deciduous teeth is less resistant than permanent dentition and for this reason demineralization, and consequent caries formation, progresses more rapidly. The purpose of this study is to investigate the correlation between the incidence of caries and intake of sugary drinks in pediatric patients.

METHODS: The study included 526 subjects (295 males, 231 females) between the ages of 2 and 15 years old. Several variables were examined, including: gender, age, separate values of the decay missing filled teeth (DMFT) epidemiological index (for both deciduous and permanent dentition), quantity and quality of sugary drinks taken daily, daily brushing frequency, parental nationality and socio-economic status. A multivariate analysis conducted (using a simple linear regression model) to verify the association between soft drink consumption and DMF, including a series of confounding variables (namely, sex, brushing frequency and parents’ nationality).

RESULTS: From the results of the statistical analysis of the variables examined, a correlation between the incidence of caries in children aged between 2 and 14 years and brushing frequency, consumption of sugary drinks and parents’ nationality was found.

CONCLUSIONS: It is important to raise awareness and properly inform patients and healthcare colleagues about the importance of oral health. Taking good care of our oral health represents part of implementation of the lifestyle and the quality of life of the future generations.

PMID:36852612 | DOI:10.23736/S2724-6329.23.04774-5