Proc Natl Acad Sci U S A. 2023 Apr 4;120(14):e2302318120. doi: 10.1073/pnas.2302318120. Epub 2023 Mar 27.
NO ABSTRACT
PMID:36972458 | DOI:10.1073/pnas.2302318120
Tag: nevin manimala
J Psychoactive Drugs. 2023 Mar 27:1-9. doi: 10.1080/02791072.2023.2192985. Online ahead of print.
ABSTRACT
The study aimed to assess and compare the serum brain derived neurotrophic factor (BDNF) levels in patients with alcohol dependence, depression and alcohol dependence with comorbid depression. Three groups each of 30 alcohol-dependent, depressive and alcohol-dependent with comorbid depressive patients seeking treatment were included. BDNF levels were estimated, and scales were administered to assess severity of alcohol dependence (using severity of alcohol dependence questionnaire, SADQ) and depressive symptoms (using Hamilton depression rating scale, HDRS). The mean BDNF value in ADS, depression and ADS with comorbid depression group was 16.4 ng/mL, 14.4 ng/mL and 12.29 ng/mL respectively, and the differences were statistically significant. In ADS group and ADS with comorbid depression groups significant negative association existed between BDNF and SADQ scores (r = -0.371, p = .043 and r = -0.0474, p = .008 respectively). There were significant negative association between BDNF and HDRS scores in depression and comorbid ADS and depression group (r = -0.400, p = .029 and r = -0.408, p = .025 respectively). The BDNF level was significantly lower in the ADS with comorbid depression group and was associated with severity of dependence and depression across the groups.
PMID:36972422 | DOI:10.1080/02791072.2023.2192985
J Agric Food Chem. 2023 Mar 27. doi: 10.1021/acs.jafc.2c08541. Online ahead of print.
ABSTRACT
A strategy for determining the bioaccessibility of bromine and iodine from edible seaweeds was proposed for the first time using microwave-induced combustion (MIC) and ion chromatography coupled to mass spectrometry (IC-MS) after in vitro digestion. The concentrations of bromine and iodine in edible seaweeds using the proposed methods (MIC and IC-MS) were not statistically different from those using MIC and inductively coupled plasma mass spectrometry (p > 0.05). Trueness was assessed by recovery experiments (101-110%, relative standard deviation <10%). Following an in vitro digestion protocol, MIC was proposed as sample preparation for bioaccessible and residual fractions. Using this strategy, the mass balance totaled from 97 to 111%. No statistical difference (p > 0.05) was observed between the total concentration of bromine or iodine and their concentration in bioaccessible and residual fractions for three edible seaweed species, indicating full analyte quantification in the fractions.
PMID:36972393 | DOI:10.1021/acs.jafc.2c08541
Hepatol Commun. 2023 Mar 24;7(4):e0079. doi: 10.1097/HC9.0000000000000079. eCollection 2023 Apr 1.
ABSTRACT
BACKGROUND: Using dynamic contrast-enhanced (DCE) MR perfusion and MR spectroscopy this study aimed to characterize the blood-brain barrier permeability and metabolite changes in patients with cirrhosis and without covert HE.
METHODS: Covert HE was defined using psychometric HE score (PHES). The participants were stratified into 3 groups: cirrhosis with covert HE (CHE) (PHES<-4); cirrhosis without HE (NHE) (PHES≥-4); and healthy controls (HC). Dynamic contrast-enhanced MRI and MRS were performed to assess KTRANS, a metric derivative of blood-brain barrier disruption, and metabolite parameters. Statistical analysis was performed using IBM SPSS (v25).
RESULTS: A total of 40 participants (mean age 63 y; male 71%) were recruited as follows: CHE (n=17); NHE (n=13); and HC (n=10). The KTRANS measurement in the frontoparietal cortex demonstrated increased blood-brain barrier permeability, where KTRANS was 0.01±0.02 versus 0.005±0.005 versus 0.004±0.002 in CHE, NHE, and HC patients, respectively (p = 0.032 comparing all 3 groups). Relative to HC with a value of 0.28, the parietal glutamine/creatine (Gln/Cr) ratio was significantly higher in both CHE 1.12 mmoL (p < 0.001); and NHE 0.49 (p = 0.04). Lower PHES scores correlated with higher glutamine/Cr (Gln/Cr) (r=-0.6; p < 0.001) and lower myo-inositol/Cr (mI/Cr) (r=0.6; p < 0.001) and lower choline/Cr (Cho/Cr) (r=0.47; p = 0.004).
CONCLUSION: The dynamic contrast-enhanced MRI KTRANS measurement revealed increased blood-brain barrier permeability in the frontoparietal cortex. The MRS identified a specific metabolite signature with increased glutamine, reduced myo-inositol, and choline, which correlated with CHE in this region. The MRS changes were identifiable in the NHE cohort.
PMID:36972380 | DOI:10.1097/HC9.0000000000000079
Oncologist. 2023 Mar 27:oyad062. doi: 10.1093/oncolo/oyad062. Online ahead of print.
ABSTRACT
INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) can lead to chemotherapy dose reduction, delay, and discontinuation, and has limited effective prevention strategies. Our study aimed to identify patient characteristics associated with CIPN severity during weekly paclitaxel chemotherapy in people with early-stage breast cancer.
METHODS: We retrospectively collected baseline data including participants’ age, gender, race, body mass index (BMI), hemoglobin (regular and A1C), thyroid stimulating hormone, Vitamins (B6, B12, and D), anxiety, and depression up to 4 months prior to their first paclitaxel treatment. We also collected CIPN severity by Common Terminology Criteria for Adverse Events (CTCAE) after chemotherapy, chemotherapy relative dose density (RDI), disease recurrence, and mortality rate at the time of the analysis. Logistic regression was used for statistical analysis.
RESULTS: We extracted 105 participants’ baseline characteristics from electronic medical records. Baseline BMI was associated with CIPN severity (Odds Ratio [OR] 1.08; 95% CI, 1.01-1.16, P = .024). No significant correlations were observed in other covariates. At median follow-up (61 months), there were 12 (9.5%) breast cancer recurrences and six (5.7%) breast cancer-related deaths. Higher chemotherapy RDI was associated with improved disease-free survival (DFS, OR 1.025; 95% CI, 1.00-1.05; P = .028).
CONCLUSIONS AND RELEVANCE: Baseline BMI may be a risk factor for CIPN and suboptimal chemotherapy delivery due to CIPN may negatively impact disease-free survival in patients with breast cancer. Further study is warranted to identify mitigating lifestyle factors to reduce incidences of CIPN during breast cancer treatment.
PMID:36972359 | DOI:10.1093/oncolo/oyad062
Hum Brain Mapp. 2023 Mar 27. doi: 10.1002/hbm.26281. Online ahead of print.
ABSTRACT
Memory-related functional magnetic resonance imaging (fMRI) activations show age-related differences across multiple brain regions that can be captured in summary statistics like single-value scores. Recently, we described two single-value scores reflecting deviations from prototypical whole-brain fMRI activity of young adults during novelty processing and successful encoding. Here, we investigate the brain-behavior associations of these scores with age-related neurocognitive changes in 153 healthy middle-aged and older adults. All scores were associated with episodic recall performance. The memory network scores, but not the novelty network scores, additionally correlated with medial temporal gray matter and other neuropsychological measures including flexibility. Our results thus suggest that novelty-network-based fMRI scores show high brain-behavior associations with episodic memory and that encoding-network-based fMRI scores additionally capture individual differences in other aging-related functions. More generally, our results suggest that single-value scores of memory-related fMRI provide a comprehensive measure of individual differences in network dysfunction that may contribute to age-related cognitive decline.
PMID:36972323 | DOI:10.1002/hbm.26281
PLoS Comput Biol. 2023 Mar 27;19(3):e1010885. doi: 10.1371/journal.pcbi.1010885. Online ahead of print.
ABSTRACT
Surface antigens of pathogens are commonly targeted by vaccine-elicited antibodies but antigenic variability, notably in RNA viruses such as influenza, HIV and SARS-CoV-2, pose challenges for control by vaccination. For example, influenza A(H3N2) entered the human population in 1968 causing a pandemic and has since been monitored, along with other seasonal influenza viruses, for the emergence of antigenic drift variants through intensive global surveillance and laboratory characterisation. Statistical models of the relationship between genetic differences among viruses and their antigenic similarity provide useful information to inform vaccine development, though accurate identification of causative mutations is complicated by highly correlated genetic signals that arise due to the evolutionary process. Here, using a sparse hierarchical Bayesian analogue of an experimentally validated model for integrating genetic and antigenic data, we identify the genetic changes in influenza A(H3N2) virus that underpin antigenic drift. We show that incorporating protein structural data into variable selection helps resolve ambiguities arising due to correlated signals, with the proportion of variables representing haemagglutinin positions decisively included, or excluded, increased from 59.8% to 72.4%. The accuracy of variable selection judged by proximity to experimentally determined antigenic sites was improved simultaneously. Structure-guided variable selection thus improves confidence in the identification of genetic explanations of antigenic variation and we also show that prioritising the identification of causative mutations is not detrimental to the predictive capability of the analysis. Indeed, incorporating structural information into variable selection resulted in a model that could more accurately predict antigenic assay titres for phenotypically-uncharacterised virus from genetic sequence. Combined, these analyses have the potential to inform choices of reference viruses, the targeting of laboratory assays, and predictions of the evolutionary success of different genotypes, and can therefore be used to inform vaccine selection processes.
PMID:36972311 | DOI:10.1371/journal.pcbi.1010885
PLoS Comput Biol. 2023 Mar 27;19(3):e1010994. doi: 10.1371/journal.pcbi.1010994. Online ahead of print.
ABSTRACT
We introduce a new spatial statistic, the weighted pair correlation function (wPCF). The wPCF extends the existing pair correlation function (PCF) and cross-PCF to describe spatial relationships between points marked with combinations of discrete and continuous labels. We validate its use through application to a new agent-based model (ABM) which simulates interactions between macrophages and tumour cells. These interactions are influenced by the spatial positions of the cells and by macrophage phenotype, a continuous variable that ranges from anti-tumour to pro-tumour. By varying model parameters that regulate macrophage phenotype, we show that the ABM exhibits behaviours which resemble the ‘three Es of cancer immunoediting’: Equilibrium, Escape, and Elimination. We use the wPCF to analyse synthetic images generated by the ABM. We show that the wPCF generates a ‘human readable’ statistical summary of where macrophages with different phenotypes are located relative to both blood vessels and tumour cells. We also define a distinct ‘PCF signature’ that characterises each of the three Es of immunoediting, by combining wPCF measurements with the cross-PCF describing interactions between vessels and tumour cells. By applying dimension reduction techniques to this signature, we identify its key features and train a support vector machine classifier to distinguish between simulation outputs based on their PCF signature. This proof-of-concept study shows how multiple spatial statistics can be combined to analyse the complex spatial features that the ABM generates, and to partition them into interpretable groups. The intricate spatial features produced by the ABM are similar to those generated by state-of-the-art multiplex imaging techniques which distinguish the spatial distribution and intensity of multiple biomarkers in biological tissue regions. Applying methods such as the wPCF to multiplex imaging data would exploit the continuous variation in biomarker intensities and generate more detailed characterisation of the spatial and phenotypic heterogeneity in tissue samples.
PMID:36972297 | DOI:10.1371/journal.pcbi.1010994
Br J Dermatol. 2023 Mar 27:ljad098. doi: 10.1093/bjd/ljad098. Online ahead of print.
ABSTRACT
BACKGROUND: Plaque psoriasis (PsO) is an inflammatory skin disease driven, in part, by the activation of Janus kinase (JAK) signalling pathways.
OBJECTIVE: To assess the efficacy and safety of multiple doses of topical brepocitinib, a tyrosine kinase 2/JAK1 inhibitor, in participants with mild-to-moderate PsO.
METHOD: This phase IIb, multicentre, randomised, double-blind study was conducted in two stages. In stage one, participants received one of eight treatments for 12 weeks: brepocitinib 0·1% once daily (QD), 0·3% QD or twice daily (BID), 1·0% QD or BID, 3·0% QD, or vehicle QD or BID. In stage two, participants received brepocitinib 3·0% BID or vehicle BID. The primary endpoint was the change from baseline in Psoriasis Area and Severity Index (PASI) score at week 12, analysed using analysis of covariance. The key secondary endpoint was the proportion of participants who achieved a Physician Global Assessment (PGA) response (score of clear (0) or almost clear (1) and an improvement of ≥2 points from baseline) at week 12. Additional secondary endpoints included the difference vs. vehicle in change from baseline in PASI, using mixed-model repeated measures (MMRM), and the change from baseline in Peak Pruritus Numerical Rating Scale (PP-NRS) at week 12. Safety was monitored.
RESULTS: Overall, 344 participants were randomised. Topical brepocitinib did not result in statistically significant changes from respective vehicle controls in the primary or key secondary efficacy endpoints for any dose group. At week 12, least squares mean (LSM) change from baseline in PASI score ranged from -1·4 to -2·4 for brepocitinib QD groups vs. -1·6 for vehicle QD, and from -2·5 to -3·0 for brepocitinib BID groups vs. -2·2 for vehicle BID. From week 8, change from baseline in PASI score separated from vehicle in all brepocitinib BID groups. Brepocitinib was well-tolerated with AEs occurring at similar rates across groups. One participant in the brepocitinib 1·0% QD group developed a treatment-related AE of herpes zoster in the neck area.
CONCLUSION: Topical brepocitinib was well-tolerated but did not result in statistically significant changes vs. vehicle when administered at the doses evaluated to treat signs and symptoms of mild-to-moderate PsO.
CLINICALTRIALS.GOV IDENTIFIER: NCT03850483.
PMID:36972293 | DOI:10.1093/bjd/ljad098
J Basic Clin Physiol Pharmacol. 2023 Mar 27. doi: 10.1515/jbcpp-2023-0004. Online ahead of print.
ABSTRACT
OBJECTIVES: In preclinical research, etodolac, a non-steroidal anti-inflammatory drug, affected transient receptor potential ankyrin 1 (TRPA1) activation. Yet, whether the in vitro interaction between etodolac and TRPA1 translates to altered TRPA1 functionality in vivo in human remains to be investigated.
METHODS: A randomized, double-blinded, celecoxib-controlled study was conducted to assess the effect of etodolac on TRPA1-mediated dermal blood flow (DBF) changes on the forearm of 15 healthy, male volunteers aged between 18 and 45 years. Over four study visits, separated by at least five days wash-out, a single or four-fold dose of etodolac 200 mg or celecoxib 200 mg was administered orally. Two hours post-dose, TRPA1 functionality was evaluated by assessing cinnamaldehyde-induced DBF changes. DBF changes were quantified and expressed in Perfusion Units (PUs) using laser Doppler imaging during 60 min post-cinnamaldehyde application. The corresponding area under the curve (AUC0-60min) was calculated as summary measure. Statistical analysis was performed using Linear mixed models with post-hoc Dunnett.
RESULTS: Neither the single dose of etodolac nor celecoxib inhibited the cinnamaldehyde-induced DBF changes compared to no treatment (AUC0-60min ± SEM of 17,751 ± 1,514 PUs*min and 17,532 ± 1,706 PUs*min vs. 19,274 ± 1,031 PUs*min, respectively, both p=1.00). Similarly, also a four-fold dose of both compounds failed to inhibit the cinnamaldehyde-induced DBF changes (19,235 ± 1,260 PUs*min and 19,367 ± 1,085 PUs*min vs. 19,274 ± 1,031 PUs*min, respectively, both p=1.00).
CONCLUSIONS: Etodolac did not affect the cinnamaldehyde-induced DBF changes, suggesting that it does not alter TRPA1 functionality in vivo in human.
PMID:36972286 | DOI:10.1515/jbcpp-2023-0004