Category: Nevin Manimala

Neuron. 2024 Jul 10:S0896-6273(24)00446-X. doi: 10.1016/j.neuron.2024.06.011. Online ahead of print.

ABSTRACT

Every day, hundreds of thousands of people undergo general anesthesia. One hypothesis is that anesthesia disrupts dynamic stability-the ability of the brain to balance excitability with the need to be stable and controllable. To test this hypothesis, we developed a method for quantifying changes in population-level dynamic stability in complex systems: delayed linear analysis for stability estimation (DeLASE). Propofol was used to transition animals between the awake state and anesthetized unconsciousness. DeLASE was applied to macaque cortex local field potentials (LFPs). We found that neural dynamics were more unstable in unconsciousness compared with the awake state. Cortical trajectories mirrored predictions from destabilized linear systems. We mimicked the effect of propofol in simulated neural networks by increasing inhibitory tone. This in turn destabilized the networks, as observed in the neural data. Our results suggest that anesthesia disrupts dynamical stability that is required for consciousness.

PMID:39013467 | DOI:10.1016/j.neuron.2024.06.011

Immunity. 2024 Jul 6:S1074-7613(24)00319-4. doi: 10.1016/j.immuni.2024.06.013. Online ahead of print.

ABSTRACT

Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host, Mastomys rodents. Efforts to create vaccines and antibody therapeutics must account for the evolutionary variability of the Lassa virus’s glycoprotein complex (GPC), which mediates viral entry into cells and is the target of neutralizing antibodies. To map the evolutionary space accessible to GPC, we used pseudovirus deep mutational scanning to measure how nearly all GPC amino-acid mutations affected cell entry and antibody neutralization. Our experiments defined functional constraints throughout GPC. We quantified how GPC mutations affected neutralization with a panel of monoclonal antibodies. All antibodies tested were escaped by mutations that existed among natural Lassa virus lineages. Overall, our work describes a biosafety-level-2 method to elucidate the mutational space accessible to GPC and shows how prospective characterization of antigenic variation could aid the design of therapeutics and vaccines.

PMID:39013466 | DOI:10.1016/j.immuni.2024.06.013

Pharm Stat. 2024 Jul 16. doi: 10.1002/pst.2423. Online ahead of print.

ABSTRACT

Finding an adequate dose of the drug by revealing the dose-response relationship is very crucial and a challenging problem in the clinical development. The main concerns in dose-finding study are to identify a minimum effective dose (MED) in anesthesia studies and maximum tolerated dose (MTD) in oncology clinical trials. For the estimation of MED and MTD, we propose two modifications of Firth’s logistic regression using reparametrization, called reparametrized Firth’s logistic regression (rFLR) and ridge-penalized reparametrized Firth’s logistic regression (RrFLR). The proposed methods are designed by directly reducing the small-sample bias of the maximum likelihood estimate for the parameter of interest. In addition, we develop a method on how to construct confidence intervals for rFLR and RrFLR using profile penalized likelihood. In the up-and-down biased-coin design, numerical studies confirm the superior performance of the proposed methods in terms of the mean squared error, bias, and coverage accuracy of confidence intervals.

PMID:39013454 | DOI:10.1002/pst.2423

Eur J Dent. 2024 Jul 16. doi: 10.1055/s-0044-1787820. Online ahead of print.

ABSTRACT

The objective of this review is to expose the main genetic changes and genetic polymorphisms that may or may not be associated with greater susceptibility to reduced survival of dental implants and, consequently, to their loss. Case-control studies that fully portrayed the specific types of genetic polymorphisms that may be associated with dental implant failure were included by searching in the PubMed, Scopus, and Web of Science databases from 2010 to 2023. The following descriptors and their combinations in English were used to search for articles: “dental implants,” “bone genes,” “genetics,” “polymorphism genetics,” “genetic risk factor,” and “interleukin.” The initial search resulted in 107 results (PubMed n = 47, Scopus n = 14, and Web of Science n = 46). After a manual search, reviewing each article’s title and abstract, and excluding duplicates, systematic reviews, and literature reviews, 30 articles were selected. After reading these 30 articles in full, 18 studies that did not describe the specific genetic polymorphism in relation to dental implant survival were excluded. Therefore, 12 articles were included in this review. The genetic polymorphisms of interleukin (IL)-1A, IL-1B, IL-4, IL-6, IL-10, IL-1 receptor antagonist, tumor necrosis factor-α, receptor activator of nuclear factor kappa B legend, and cluster of differentiation 14 were analyzed in the included studies. In seven of the studies, a statistically significant correlation between genetic polymorphisms and dental implant failure was observed. Of the polymorphisms studied, IL-1A (-899), IL-1B (+3954), and IL-4 (+33) showed a greater association with dental implant loss.

PMID:39013451 | DOI:10.1055/s-0044-1787820

Eur J Dent. 2024 Jul 16. doi: 10.1055/s-0044-1787105. Online ahead of print.

ABSTRACT

OBJECTIVES: Combining a three-dimensional scaffold with growth factors before implantation is one method used to increase scaffold bioactivity in bone tissue engineering. The mesenchymal stem cell (MSC)-conditioned medium (CM), called secretome, contains many proteins and growth factors required for tissue repair and growth. This study evaluated the bioactivity of a bovine bone scaffold combined with the secretome of human umbilical cord MSCs (hUC-MSCs) by analyzing MC3T3-E1 cell adhesion and viability on the scaffold.

MATERIALS AND METHODS: This in vitro laboratory study evaluated the effect of hUC-MSC secretome applied to bovine bone scaffolds processed using various techniques on MC3T3-E1 cell adhesion and viability. The three experimental groups included deproteinized bovine bone mineral-secretome (DBBM-CM), freeze-dried bovine bone-secretome (FDBB-CM), and decellularized FDBB-CM, whereas the control group was treated with DBBM alone. The cell adhesion test was performed using the centrifugation method after 6 and 24 hours, whereas the cell viability test was conducted using the trypan blue exclusion method after 24, 48, and 72 hours. Cell attachment was visualized after 4′,6-diamidino-2-phenylindole staining and viewed under inverted fluorescence microscopy.

STASTICAL ANALYSIS: Statistical analyses were performed using one-way analysis of variance, followed by a post hoc test in cases of significant differences.

RESULTS: Statistical analyses showed significantly greater adhesion of the preosteoblasts to the FDBB-CM scaffold at 6 hours (p = 0.002). The results of the adhesion test at 24 hours and the viability tests at all observation times showed no significant differences (p > 0.05). This study found that the average MC3T3-E1 cell adhesions and viabilities were highest for the FDBB-CM and DBBM-CM scaffolds. DBBM scaffolds with the secretome had better cell adhesion and viability than those without the secretome.

CONCLUSION: The addition of MSC secretome increased bovine bone scaffold bioactivity especially in DBBM and FDBB scaffolds.

PMID:39013448 | DOI:10.1055/s-0044-1787105

Eur J Dent. 2024 Jul 16. doi: 10.1055/s-0044-1786864. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this article was to evaluate the effects of modifying glass ionomer cement (GIC) with carboxymethyl chitosan (CMC) on surface morphology and remineralization outcomes by examining dentin morphology and calcium ion composition changes.

MATERIALS AND METHODS: Thirty holes in a cylindrical acrylic mold were filled with three groups of restorative materials: GIC, GIC modified with CMC (GIC-CMC) 5%, and GIC-CMC10%. The surface morphology of each group’s materials was observed using scanning electron microscopy (SEM). The compressive strength measurement was performed using a universal testing machine. The dentin remineralization process was performed by applying GIC, GIC-CMC5%, and GIC-CMC10% materials for 14 days on demineralized dentin cavities treated with 17% ethylenediamine tetraacetic acid (EDTA) for 7 days. A morphological evaluation was conducted using SEM. The calcium ion composition and calcium-to-phosphorous (Ca/P) ratio were examined using an energy-dispersive X-ray (EDX).

STATISTICAL ANALYSIS: The Kruskal-Wallis and post-hoc Mann-Whitney U tests were performed to compare all four groups of calcium ions (p < 0.05).

RESULTS: The modification of GIC with CMC affected the morphological changes in the materials in the form of reduced porosity and increased fractures. A significant difference was found in compressive strength between the GIC-CMC modification materials of GIC-CMC5% and GIC-CMC10% and the GIC control group. The dentin tubule morphology and surface changes were observed after applying GIC, GIC-CMC5%, and GIC-CMC10% materials for 14 days, as evaluated by SEM. The EDX examination showed an increase in calcium ion content and hydroxyapatite formation (Ca/P ratio) after applying the GIC-CMC10% material.

CONCLUSION: The surface porosity of the GIC modification material with the addition of CMC tended to decrease. However, an increase in cracked surfaces that widened, along with the rise in CMC percentage, was found. This modification also reduced the compressive strength of the materials, with the lowest average yield at 10% CMC addition. Therefore, the modification of GIC with CMC affects changes in morphology, calcium ion composition, and Ca/P ratio in demineralized dentin.

PMID:39013447 | DOI:10.1055/s-0044-1786864

Geriatr Nurs. 2024 Jul 15;59:159-169. doi: 10.1016/j.gerinurse.2024.06.035. Online ahead of print.

ABSTRACT

This study investigated factors associated with cognitive performance among Black caregivers of persons living with two chronic conditions: dementia or cancer. Fifty-six Black caregivers of people living with dementia or cancer were recruited from clinic and community sources. Variables measured included: depression, anxiety, stress, sleep, fatigue, and caregiver burden. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA). Descriptive statistics and non-parametric analyses were conducted to identify factors related to MoCA scores. Caregivers were 58.3 years of age and predominantly female. The average MoCA score was 25.23. Gender and education, along with positive appraisal of caregiving were significantly associated with cognitive performance. Several other factors approached significance including cohabitation with the care recipient, fatigue, and stress due to perceived individual and institutional racism. Our findings suggest several factors that warrant further investigation for understanding the relationship between caregiving and cognitive performance in Black caregivers of people living with cancer or dementia.

PMID:39013234 | DOI:10.1016/j.gerinurse.2024.06.035

Placenta. 2024 Jul 4;154:153-159. doi: 10.1016/j.placenta.2024.07.003. Online ahead of print.

ABSTRACT

INTRODUCTION: To assess the placental biometry, placental biomarkers and uterine artery Doppler in each trimester of pregnancy for prediction of early-onset fetal growth restriction (EO FGR).

METHODS: In this prospective cohort study placental biometry; biomarkers PAPP-A, sFLT-1, and PlGF along with the uterine artery blood flow evaluation was done serially at 11-14, 20-24 and 28-32 weeks of gestation. The above parameters were compared between women with early onset FGR and controls.

RESULTS: Out of 1008 fully followed cases, the small for gestational age fetuses were 227/1008 (22.5 %), and EO FGR were 84/1008(8.3 %).The placental length, volume, and PlGF levels were significantly lower, whereas the uterine artery PI(Ut PI) was significantly higher at all time points among cases. The sFLT-1 level showed a significant increase among cases, whereas it decreased among controls from the first to the second trimester. The detection rate using PV/UtA PI was 60 % in the first trimester and 66.7 % in the second trimester at 30 % FPR.

CONCLUSION: The PV/Ut PI in first and the second trimester was a good marker for the prediction of pregnancies at increased risk of developing EO FGR.

PMID:39013215 | DOI:10.1016/j.placenta.2024.07.003

Early Hum Dev. 2024 Jul 11;195:106078. doi: 10.1016/j.earlhumdev.2024.106078. Online ahead of print.

ABSTRACT

BACKGROUND: The study aimed to investigate the association of second and fourth-digit (2D:4D) ratios with metabolic syndrome (MS) and cardiovascular disease risk (CVR).

METHOD: This case-control study was conducted between February and March 2024 with 200 participants (100 patients +100 controls). Biochemical parameters (glucose, total cholesterol, HDL, LDL, triglycerides, haemogram, HbA1C) were recorded. All participants were evaluated in terms of MS diagnostic criteria. CVR was calculated with the ESC CVD Risk Calculator. Second-digit and fourth-digit measurements were performed and the 2D:4D ratio of both hands and the difference between 2D:4D of both hands (Dr-l) were obtained. The relationship between 2D:4D and MS, CVR, and gender was evaluated. p < .05 was considered statistically significant.

RESULTS: Forty-one percent of the study participants were male. The right-hand 2D:4D (R2D:4D) ratio was 1.009 ± 0.04 and the left-hand 2D:4D (L2D:4D) ratio was 0.991 ± 0.04 (p < .001). R2D:4D ratio was 1.010 ± 0.04 in women and 0.985 ± 0.03 in men (p = .019). R2D:4D (p < .001), Dr-l (p = .001), and CVR (p < .001) were significantly higher in men with MS (+) compared to MS (-).

CONCLUSION: In our study, the R2D:4D ratio was found to be associated with MS and CVR in men. Low intrauterine androgen exposure may affect the development of MS, but this effect is more prominent in males.

PMID:39013212 | DOI:10.1016/j.earlhumdev.2024.106078

Nutr Rev. 2024 Jul 16:nuae096. doi: 10.1093/nutrit/nuae096. Online ahead of print.

ABSTRACT

CONTEXT: Global Leadership Initiative on Malnutrition (GLIM) and Patient-Generated Subjective Global Assessment (PG-SGA) are commonly used nutrition assessment tools, whose performance does not reach a consensus due to different and imperfect reference standards.

OBJECTIVE: This study aimed to evaluate and compare the diagnostic accuracy of GLIM and PG-SGA, using a hierarchical Bayesian latent class model, in the absence of a gold standard.

DATA SOURCES: A systematic search was undertaken in PubMed, Embase, and Web of Science from inception to October 2022. Diagnostic test studies comparing (1) the GLIM and/or (2) PG-SGA with “semi-gold” standard assessment tools for malnutrition were included.

DATA EXTRACTION: Two authors independently extracted data on sensitivity, specificity, and other key characteristics. The methodological quality of each included study was appraised according to the criteria in the Quality Assessment of Diagnostic Accuracy Studies-2.

DATA ANALYSIS: A total of 45 studies, comprising 20 876 individuals evaluated for GLIM and 11 575 for PG-SGA, were included. The pooled sensitivity was 0.833 (95% CI 0.744 to 0.896) for GLIM and 0.874 (0.797 to 0.925) for PG-SGA, while the pooled specificity was 0.837 (0.780 to 0.882) for GLIM and 0.778 (0.707 to 0.836) for PG-SGA. GLIM showed slightly better performance than PG-SGA, with a higher diagnostic odds ratio (25.791 vs 24.396). The diagnostic performance of GLIM was most effective in non-cancer patients with an average body mass index (BMI) of <24 kg/m2, followed by non-cancer patients with an average age of ≥60 years. PG-SGA was most powerful in cancer patients with an average age of <60 years, followed by cancer patients with an average BMI of <24 kg/m2.

CONCLUSION: Both GLIM and PG-SGA had moderately high diagnostic capabilities. GLIM was most effective in non-cancer patients with a low BMI, while PG-SGA was more applicable in cancer patients.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration No. CRD42022380409.

PMID:39013202 | DOI:10.1093/nutrit/nuae096