Category: Nevin Manimala

Methods Mol Biol. 2023;2698:163-181. doi: 10.1007/978-1-0716-3354-0_11.

ABSTRACT

Transcription factors that act within a gene regulatory network (GRN) often interact with other proteins such as chromatin remodeling factors, histone modifiers, and other co-regulators. Characterizing these interactions is crucial for understanding the function and mechanism of action of a transcription factor. Here, a method for the identification of protein-protein interactions of nuclear-localized, transcription-associated factors is described. The method is based on the immunoprecipitation (IP) of a fluorophore-tagged target, followed by mass spectrometry (MS), peptide identification, and quantification of interacting proteins. By applying label-free quantification to IPs and their input protein extracts, statistically controlled protein enrichment ratios uncover high-confidence interaction partners of the target. A complete step-by-step procedure, including sample preparation, MS settings, data analysis, and visualization is provided.

PMID:37682475 | DOI:10.1007/978-1-0716-3354-0_11

Eur J Drug Metab Pharmacokinet. 2023 Sep 8. doi: 10.1007/s13318-023-00853-5. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: All latanoprost formulations currently available for the treatment of glaucoma or ocular hypertension contain the same concentration of latanoprost (0.005%) but differ in excipients, which may affect corneal drug permeability or stability. This study aimed at comparing corneal penetration of three marketed latanoprost solutions with different excipient formulations in in vitro and in vivo drug permeability studies.

METHODS: Three latanoprost formulations were tested under good laboratory practice conditions: a formulation containing benzalkonium chloride (BAK) but no surfactant (Preserved latanoprost); the same formulation except preservative-free (PF) without BAK or surfactant (SF) (PF SF latanoprost); and a different formulation without BAK but containing a non-ionic surfactant (MGHS 40 at 5%) combined with thickening agents (Carbomer 974P, Macrogol 4000) (PF latanoprost). Corneal permeation of latanoprost acid (LAT) was first determined in vitro using a reconstructed human corneal epithelium tissue. Then, in vivo pharmacokinetic studies were performed on pigmented rabbits, for which LAT concentration was measured in the aqueous humour (AH) and iris-ciliary body (ICB).

RESULTS: In vitro, the cumulative transport of LAT was linear between 1 h and 4 h for preserved latanoprost and PF SF latanoprost, and LAT concentrations matched exactly at each timepoint. By contrast, the permeation of PF latanoprost was linear between 2 h and 12 h and was significantly lower than that of preserved latanoprost and PF SF latanoprost at 4 and 8 h (p < 0.001). In rabbits, the concentrations of LAT in AH and ICB were not statistically different between preserved latanoprost and PF SF latanoprost at each timepoint, except at 1 h in ICB (p = 0.005). By comparison, the LAT concentration of PF latanoprost was statistically (p < 0.05) lower than that of preserved latanoprost and PF SF latanoprost in AH and ICB from 0.5 to 3 h.

CONCLUSION: BAK did not influence the corneal penetration of latanoprost in in vitro and in vivo studies. The formulation containing a non-ionic surfactant resulted in lower and slower ocular penetration compared with preserved or PF SF formulations. This raises questions about the relevance of BAK and some surfactants in enhancing corneal penetration of ocular formulations.

PMID:37682463 | DOI:10.1007/s13318-023-00853-5

Ther Innov Regul Sci. 2023 Sep 8. doi: 10.1007/s43441-023-00563-9. Online ahead of print.

ABSTRACT

A Benefit Risk Assessment Plan (BRAP) describes the assessments planned to determine whether the benefits of an investigational drug outweigh the risks. The plan can have two sections, one with timelines for aligning resources with decision milestones and the other for pre-specifying assessments for decision milestones. Regulatory guidance recommends a proactive planning process over an ad-hoc process. However, very little has been published about proactive plans themselves. This article works through a hypothetical example visualizing a series of assessments across the drug development lifecycle. Based on a regulatory framework, the planning process starts with assessing the medical condition and current treatment options. These early assessments bring out major considerations in assessing the investigational drug.

PMID:37682462 | DOI:10.1007/s43441-023-00563-9

Res Child Adolesc Psychopathol. 2023 Sep 8. doi: 10.1007/s10802-023-01115-3. Online ahead of print.

ABSTRACT

Between 1 to 2 of every 1,000 children are born deaf or hard of hearing (DHH) and, of those, 30-50% have additional disabilities, including Autism Spectrum Disorder (ASD). Most measures assessing ASD characteristics rely on some degree of behavioral response to sound (e.g., responding to name, listening response), and may not be appropriate for use with children who are DHH. Further, ASD specific measures do not provide information on a child’s functional abilities across developmental domains. We conducted a cross-sectional analysis comparing mean T-scores on a standardized multidimensional measure, the Behavior Assessment System for Children, Third Edition, Parent Rating Scale (BASC-3 PRS), across three groups matched for age and sex: children who are DHH and diagnosed with ASD (DHH + ASD; n = 16); children who are DHH without ASD (DHH-ASD; n = 16); and children who are typically hearing with ASD (H + ASD; n = 16). Analyses revealed statistically significant differences across scales of Attention Problems, Atypicality, Withdrawal, Behavioral Symptoms Index, Social Skills, Leadership, Functional Communication, Activities of Daily Living, Adaptive Skills, Autism Probability Indices, and Developmental Social Disorders. Pairwise comparisons showed DHH + ASD and H + ASD mean T-scores were statistically similar and distinct from DHH-ASD mean T-scores on all these scales except for Withdrawal, Leadership, Functional Communication, and Activities of Daily Living, where pairwise comparisons varied. The findings add to the literature on ASD and DHH children and call for further exploration of the BASC-3 as a tool for both evaluation of ASD and the development of individualized treatment plans in this unique population.

PMID:37682456 | DOI:10.1007/s10802-023-01115-3

Environ Sci Pollut Res Int. 2023 Sep 8. doi: 10.1007/s11356-023-29208-y. Online ahead of print.

ABSTRACT

Polycyclic aromatic hydrocarbons (PAHs) are one of the most important environmental pollutants. Urinary concentrations of 1-hydropyren metabolites of PAHs have been used as biomarkers of these chemicals’ exposure in humans. This cross-sectional study was conducted on 468 healthy Iranian adults over 25 years old and non-smokers in six provinces who were selected based on the clustering method. Fasting urine sampling and body composition and demographic measurements were performed. Urine samples were analyzed by GC-MS. The analysis included descriptive statistics and analytical statistics using multiple linear regression by Python software. 1-Hydroxypyrene was found in 100% of samples, and the mean (Reference Value 95%) concentration of 1-hydroxypyrene was 6.12 (RV 95%: 20) μg/L and 5.95 (21) μg/gcrt. There was a direct relationship between the amount of body composition (body fat, visceral fat), BMI, and age with the urinary concentrations of 1-hydropyren metabolites, and this relationship was significant for BMI with urinary concentrations of 1-hydropyren metabolites (P = 0.045). The amount of 1-hydroxypyrene in healthy Iranian adults has been higher than in similar studies in other countries. These results provide helpful information regarding the exposure of Iranian adults to 1-hydroxypyrene, and these data can be used to supplement the national reference values of human biomonitoring for the interpretation of biomonitoring results.

PMID:37682435 | DOI:10.1007/s11356-023-29208-y

Environ Monit Assess. 2023 Sep 8;195(10):1169. doi: 10.1007/s10661-023-11784-8.

ABSTRACT

Estuaries are among the most dynamic ecosystems in coastal regions and are facing serious threats due to increasing anthropogenic activities. The aim of the present study is to evaluate the water quality of the Rushikulya estuary by analyzing the abundance of pathogenic bacteria in both its water and sediment. Water and sediment samples were collected from five different stations at the mouth of the Rushikulya estuary during the monsoon and post-monsoon seasons. These samples were analyzed to assess the abundance of pathogenic bacteria and environmental parameters. The results revealed that bacterial abundance is significantly higher in the sediment than in the water, possibly due to a longer residence time of pathogenic bacteria in the sediment. Seasonal observations indicated an increase in pathogenic bacterial abundance during the monsoon season, suggesting an impact from monsoonal discharge. Escherichia coli-like organism, faecal coliforms, Shigella-like organisms, and Vibrio cholera-like organisms were the dominant pathogenic bacteria in both the water and sediment of the Rushikulya estuary. The higher abundance of these pathogens and the results of statistical analysis, which showed a strong correlation between Total Streptococci and BOD (r = 0.79), indicate the influence of human settlement and the mixing of untreated sewage in the Rushikulya estuary. The elevated levels of E. coli, faecal coliforms, and Shigella-like organisms in the Rushikulya estuary raise significant concerns that require immediate attention.

PMID:37682420 | DOI:10.1007/s10661-023-11784-8

Int J Cardiovasc Imaging. 2023 Sep 8. doi: 10.1007/s10554-023-02930-x. Online ahead of print.

ABSTRACT

The evaluation of cardiac magnetic resonance feature tracking may have great diagnostic value in hypertrophic cardiomyopathy and hypertensive heart disease. Exploring the diagnostic and clinical research value of cardiac magnetic resonance feature tracks in evaluation of myocardium deformation in patients with subclinical hypertrophic cardiomyopathy(SHCM)and subclinical hypertensive heart disease(SHHD). Cardiovascular Magnetic Resonance (CMR) scans were performed on a 1.5 T MR scanner in 33 patients with SHCM, 31 patients with SHHD, and 27 controls(NS). The CMR image post-processing software was used to analyze the characteristics of routine cardiac function, different global and regional myocardial strain in each group. Analysis of variance (ANOVA) was used to compare age, blood pressure, heart rate, routine cardiac function, body mass index (BMI), as well as the strain between different segments within each of the three groups. Once a significant difference was detected, a least significant difference (LSD) comparison would be performed. The diagnostic efficacy of different parameters in differentiating SHHD from SHCM was evaluated through receiver operating characteristic (ROC) curve analysis, and the best cut-off value was determined. There was no statistical difference among three groups (P>0.05) in routine cardiac function while significant statistical differences were found in the global myocardial strain parameters and the peak strain parameters of some segments (especially basal segments) (P < 0.05). The global radial peak strain (GRPS) was most effective (AUC = 0.885, 95% CI: 0.085-0.971, P<0.001) with a sensitivity and specificity of 84% and 88% at a cut-off value of 40.105, contributing to distinguishing SHCM from SHHD group. Cardiac magnetic resonance feature tracking could detect left ventricular deformation in patients with SHCM and SHHD group. The abnormality of strain has important research value for subclinical diagnosis and clinical evaluation.

PMID:37682417 | DOI:10.1007/s10554-023-02930-x

Funct Integr Genomics. 2023 Sep 8;23(4):293. doi: 10.1007/s10142-023-01228-4.

ABSTRACT

Sporadic Alzheimer’s disease (AD) is a complex neurological disorder characterized by many risk loci with potential associations with different traits and diseases. AD, characterized by a progressive loss of neuronal functions, manifests with different symptoms such as decline in memory, movement, coordination, and speech. The mechanisms underlying the onset of AD are not always fully understood, but involve a multiplicity of factors. Early diagnosis of AD plays a central role as it can offer the possibility of early treatment, which can slow disease progression. Currently, the methods of diagnosis are cognitive testing, neuroimaging, or cerebrospinal fluid analysis that can be time-consuming, expensive, invasive, and not always accurate. In the present study, we performed a genetic correlation analysis using genome-wide association statistics from a large study of AD and UK Biobank, to examine the association of AD with other human traits and disorders. In addition, since hippocampus, a part of cerebral cortex could play a central role in several traits that are associated with AD; we analyzed the gene expression profiles of hippocampus of AD patients applying 4 different artificial neural network models. We found 65 traits correlated with AD grouped into 9 clusters: medical conditions, fluid intelligence, education, anthropometric measures, employment status, activity, diet, lifestyle, and sexuality. The comparison of different 4 neural network models along with feature selection methods on 5 Alzheimer’s gene expression datasets showed that the simple basic neural network model obtains a better performance (66% of accuracy) than other more complex methods with dropout and weight regularization of the network.

PMID:37682415 | DOI:10.1007/s10142-023-01228-4

Sports Med. 2023 Sep 8. doi: 10.1007/s40279-023-01926-w. Online ahead of print.

ABSTRACT

It has often been reported that mental exertion, presumably leading to mental fatigue, can negatively affect exercise performance; however, recent findings have questioned the strength of the effect. To further complicate this issue, an overlooked problem might be the presence of publication bias in studies using underpowered designs, which is known to inflate false positive report probability and effect size estimates. Altogether, the presence of bias is likely to reduce the evidential value of the published literature on this topic, although it is unknown to what extent. The purpose of the current work was to assess the evidential value of studies published to date on the effect of mental exertion on exercise performance by assessing the presence of publication bias and the observed statistical power achieved by these studies. A traditional meta-analysis revealed a Cohen’s d_z effect size of – 0.54, 95% CI [- 0.68, – 0.40], p < .001. However, when we applied methods for estimating and correcting for publication bias (based on funnel plot asymmetry and observed p-values), we found that the bias-corrected effect size became negligible with most of publication-bias methods and decreased to – 0.36 in the more optimistic of all the scenarios. A robust Bayesian meta-analysis found strong evidence in favor of publication bias, BF_pb > 1000, and inconclusive evidence in favor of the effect, adjusted d_z = 0.01, 95% CrI [- 0.46, 0.37], BF₁₀ = 0.90. Furthermore, the median observed statistical power assuming the unadjusted meta-analytic effect size (i.e., – 0.54) as the true effect size was 39% (min = 19%, max = 96%), indicating that, on average, these studies only had a 39% chance of observing a significant result if the true effect was Cohen’s d_z = – 0.54. If the more optimistic adjusted effect size (- 0.36) was assumed as the true effect, the median statistical power was just 20%. We conclude that the current literature is a useful case study for illustrating the dangers of conducting underpowered studies to detect the effect size of interest.

PMID:37682411 | DOI:10.1007/s40279-023-01926-w

J Autism Dev Disord. 2023 Sep 8. doi: 10.1007/s10803-023-06077-5. Online ahead of print.

ABSTRACT

Present study aimed to evaluate the relationship between self-compassion and psychological hardiness, and psychological well-being among mothers of children with autism. The research design was correlational, and its statistical population sample consisted of 101 mothers of children with an autism spectrum disorder. The results of a correlational analysis showed a significant positive relationship between self-compassion and psychological hardiness, and psychological well-being. Multiple regression analysis showed that among the variables of self-compassion and psychological hardiness, the variable of self-compassion had the largest share in predicting the psychological well-being of mothers. Concerning self-compassion, conscious awareness of self-kindness along with psychological hardship could predict the psychological well-being in these groups of mothers, such as raising a child with ASD.

PMID:37682408 | DOI:10.1007/s10803-023-06077-5