Category: Nevin Manimala

Theor Popul Biol. 2024 Jun 4:S0040-5809(24)00061-3. doi: 10.1016/j.tpb.2024.06.001. Online ahead of print.

ABSTRACT

Muller’s ratchet, in its prototype version, models a haploid, asexual population whose size N is constant over the generations. Slightly deleterious mutations are acquired along the lineages at a constant rate, and individuals carrying less mutations have a selective advantage. The classical variant considers fitness proportional selection, but other fitness schemes are conceivable as well. Inspired by the work of Etheridge et al. (2009) we propose a parameter scaling which fits well to the “near-critical” regime that was in the focus of Etheridge et al. (2009) (and in which the mutation-selection ratio diverges logarithmically as N→∞). Using a Moran model, we investigate the”rule of thumb” given in Etheridge et al. (2009) for the click rate of the “classical ratchet” by putting it into the context of new results on the long-time evolution of the size of the best class of the ratchet with (binary) tournament selection. This variant of Muller’s ratchet was introduced in González et al. (2023), and was analysed there in a subcritical parameter regime. Other than that of the classical ratchet, the size of the best class of the tournament ratchet follows an autonomous dynamics up to the time of its extinction. It turns out that, under a suitable correspondence of the model parameters, this dynamics coincides with the so called Poisson profile approximation of the dynamics of the best class of the classcial ratchet.

PMID:38844263 | DOI:10.1016/j.tpb.2024.06.001

J Ethnopharmacol. 2024 Jun 4:118426. doi: 10.1016/j.jep.2024.118426. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar (As₂S₂ or As₄S₄) is a traditional Chinese medicine (TCM) containing arsenic. Existing studies have shown that it has genotoxicity under long-term use with large doses. Niuhuang Jiedu (NHJD) is a Chinese medicine prescription containing realgar and seven other TCMs. Whether the multiple TCMs combination in NHJD can reduce the genotoxicity induced by realgar in equivalent doses is still unknown.

AIM OF THE STUDY: To research the effect of NHJD on realgar’s genotoxicity and the possible mechanism involved based on the arsenic methylation metabolic pathway.

MATERIAL AND METHODS: Six groups (control, realgar (0.8 g/kg), NHJD (12.48 g/kg), as well as Glycyrrhiza uralensis Fisch (GU), Scutellaria baicalensis Georg (SB), Rheum palmatum L(RP) plus equivalent doses of realgar, respectively) were set up. ICR mice were intragastric administered for 12 weeks. First, genotoxicology tests were conducted to evaluate the effect of NHJD, GU, SB, and RP on reducing realgar’s genotoxicity. The inorganic arsenic(iAs), dimethyl arsenic acid (DMA), and monomethyl arsenic acid (MMA) were determined by HPLC-AFS, and the iAs%, MMA%, DMA%, primary methylation index (PMI), etc. were calculated. Meanwhile, the S-adenosyl methionine (SAM) and arsenate reductase (ARR) levels, the arsenic(+3)methyltransferase (As₃MT), purine-nucleoside phosphorylase(PNP), glutathione S-transfer omega1 (GSTO1) gene expression were detected, aimed to explore the possible alleviation mechanisms of NHJD.

RESULTS: The combination of multiple TCMs in NHJD decreased the levels of MN‰, SPA%, and DNA damage caused by realgar, with similar effects observed when SB, RP, and GU were used separately with realgar. Notably, the iAs% significantly decreased, while DMA% and PMI notably increased in the NHJD and realgar+SB (or RP) groups compared to the realgar-only group (P<0.05). Increases in SAM and ARR levels were observed across various groups, but only the ARR increase in the NHJD group was statistically significant. Moreover, significant increases in As₃MT mRNA and GSTO1 mRNA were noted in the NHJD group, and PNP mRNA levels significantly rose in the realgar+SB group.

CONCLUSIONS: This study revealed that NHJD could attenuate the genotoxic effects of realgar. The botanicals SB, RP, and GU within NHJD may be key contributors to this effect. Enhancements in arsenic methylation capabilities through increased levels of SAM and ARR and elevated gene expressions of As₃MT, PNP, and GSTO1 suggest potential mechanisms behind these findings.

PMID:38844250 | DOI:10.1016/j.jep.2024.118426

Sci Total Environ. 2024 Jun 4:173725. doi: 10.1016/j.scitotenv.2024.173725. Online ahead of print.

ABSTRACT

Trees contribute to bedrock weathering in a variety of ways. However, evaluating their full impact is complicated by a lack of direct observation of unexposed root systems of individual trees, especially when the scale of the analysis goes down to the level of microbiomes. In the present study, we investigated the contribution of tree root systems to bioweathering and soil production at the macro- and microscale. Soil profiles developed under trees on granite bedrock were investigated in two parts of the Sudety Mountains, SW Poland: the Rudawy Janowickie Mountains, and the Stołowe Mountains. Soil profiles were gradually excavated and soil samples collected from pre-defined positions of the root zone: 1) bulk soil, 2) rhizosphere, 3) cracks, 4) topsoil, and 5) control positions. In total, we analyzed 103 samples for soil chemistry and microbiological activity. In addition, we analyzed 19 samples using XRF (X-ray Fluorescence). Four parent rock samples, in the form of thin-sections, were the subject of mineralogical evaluation. Soil analyses included: total organic carbon (C) and nitrogen (N) content, soil pH_H2O, soluble iron (Fe_d), and aluminum (Al_d), non-crystalline (amorphous) iron (Fe_ox), and aluminum (Al_ox). For microbiological analyses, we used a Biolog (EcoPlate) system to determine the functional diversity of soil microorganisms. We evaluated the results on soil chemistry and microbiological activity statistically by principal component analysis (PCA) and redundancy analysis (RDA). Differences between soil sampling positions were assessed using a non-parametric Kruskal-Wallis (K-W) rank sum test and a post-hoc pairwise Dunn test. Trees developed different root architectures, likely shaped by the depth to bedrock and its pre-existing net of fractures and fissures. Tree roots were able to enter bedrock cracks at one study site (at Pstrążna, Stołowe Mountains). The soil profile was too deep for root system penetration at the second study site (Mt Jańska, Rudawy Janowickie Mountains, RJM). The rhizospheric soil along the roots had significantly different chemical properties compared to non-rhizospheric soil types. At Mt. Jańska, soil differed from the crack soil in terms of Al_ox (p_Holm-adj. < 0.0006) and Fe_ox (p_Holm-adj. < 0.004), and from the bulk soil (p_Holm-adj. < 0.02) and topsoil (p_Holm-adj. < 0.007). In addition, at Pstrążna, the soil differed from the control soil in terms of C (p_Holm-adj. < 0.009) and soil pH_H2O (p_Holm-adj. < 0.0008) and from the topsoil in terms of soil pH_H2O. The highest metabolic activity was in cracks at Mt. Jańska and in control samples from Pstrążna. In general, the spatial distribution of soil microbial activity, and the weathering that results from that portion of the soil biome, is spatially heterogeneous and appears to be partially determined by the interaction of root growth and bedrock fracture patterns.

PMID:38844241 | DOI:10.1016/j.scitotenv.2024.173725

J Control Release. 2024 Jun 4:S0168-3659(24)00351-1. doi: 10.1016/j.jconrel.2024.06.008. Online ahead of print.

ABSTRACT

The use of animal experiments can be minimized with computational models capable of reflecting the simulated environments. One such environment is intestinal fluid and the colloids formed in it. In this study we used molecular dynamics simulations to investigate solubilization patterns for three model drugs (carvedilol, felodipine and probucol) in dog intestinal fluid, in a lipid-based formulation, and a mixture of the two. We observed morphological transformations that lipids undergo due to the digestion process in the intestinal environment. Further, we evaluated the effect of bile salt concentration and observed the importance of interindividual variability. We applied two methods of estimating solubility enhancement based on the simulated data, of which one was in good qualitative agreement with the experimentally observed solubility enhancement. In addition to the computational simulations, we also measured solubility in i) aspirated dog intestinal fluid samples and ii) simulated canine intestinal fluid in the fasted state, and found there was no statistical difference between the two. Hence, a simplified dissolution medium suitable for in vitro studies provided physiologically relevant data for the systems explored. The computational protocol used in this study, coupled with in vitro studies using simulated intestinal fluids, can serve as a useful prescreening tool in the process of drug delivery strategies development.

PMID:38844179 | DOI:10.1016/j.jconrel.2024.06.008

J Affect Disord. 2024 Jun 4:S0165-0327(24)00932-7. doi: 10.1016/j.jad.2024.06.017. Online ahead of print.

ABSTRACT

BACKGROUND: Agentive steadfastness was identified as a potential trait marker with which to anticipate prognostically that a patient will persevere steadfastly and take congruent action in facing the demands of living. Taken as an enduring expression of personality, this study investigated agentive steadfastness among adult social media respondents (n = 511) in relation to temperament and character as captured in Cloninger’s psychobiological model of personality.

METHODS: Participants recruited though snowball sampling on social media platforms, applied the 27-item Agentive Steadfastness Index (ASI) and the 240-item Temperament and Character Inventory (TCI-R-240).

RESULTS: Agentive steadfastness was statistically predicted by the Self-directedness (β = 0.634), Self-transcendence (β = 0.119), Harm Avoidance (β = -0.142) and the Reward Dependence (β = 0.071) scales, accounting for 63.3 % of the variance in one stepwise regression model. In another stepwise model for the TCI-R-240 subscales, the Purposeful (β = 0.359), Anticipatory Worry (β = -0.353), and the Responsibility (β = 0.259) subscales accounted for respectively 56.8 %, 11.2 % and 2.8 % of the variance in ASI scores.

LIMITATIONS: Results are limited to adult social media respondents who were willing to participate.

CONCLUSIONS: Agentive steadfastness may serve as a trait marker of well-being and the good prognostic associations that have been established for high self-directedness, low harm avoidance, as well as resilience, and character strengths. It may be assessed clinically to anticipate prognostically the extent to which a patient will persevere steadfastly and take congruent action in facing the demands of living and adversity.

PMID:38844170 | DOI:10.1016/j.jad.2024.06.017

Osteoarthritis Cartilage. 2024 Jun 4:S1063-4584(24)01210-X. doi: 10.1016/j.joca.2024.05.012. Online ahead of print.

ABSTRACT

OBJECTIVE: We here explore whether observed treatment effects of a putative disease modifying osteoarthritis drug (DMOAD) are greater when cartilage morphometry is performed with rather than without knowledge of MRI acquisition order (unblinded/blinded to time point).

METHODS: In the FORWARD randomized controlled trial, 549 knee osteoarthritis patients were randomized 1:1:1:1:1 to three once-weekly intra-articular injections of placebo, 30µg sprifermin every 6 or 12 months(M), or 100µg every 6/12M. After year 2, cartilage segmentation of baseline through 24M MRIs was performed, with blinding to acquisition order. After year 5, 24 and 60M MRIs were analyzed together, with unknown relative order, but with segmented BL images as reference (24M unblinded vs. BL), by the same operators. Total femorotibial joint cartilage thickness (TFTJ_ThC) change was obtained for 352 participants analyzed under both conditions.

RESULTS: 24M data read unblinded to order revealed a -35±44 µm lower TFTJ_ThC than blinded analysis (all groups: lower/upper bounds -120/+51µm; correlation r²=97%). With unblinded analysis, the placebo group lost -46±57µm TFTJ_ThC over 24M, whereas 100µg/every 6M lost -2.2±73µm (difference=44µm [95%CI: 22,66]). With blinded analysis, placebo lost -11±53µm, whereas 100µg/every 6M gained 30±62µm (difference=40µm [95%CI: 21,60]). 100µg sprifermin injected every 6M showed statistically significant (p<0.001) treatment effects in TFTJ_ThC, with Cohen D=-0.66 for unblinded and D=-0.69 for blinded analysis.

CONCLUSIONS: These results do not reveal that detection of proposed DMOAD treatment is enhanced with MRIs read unblinded to order; rather, the sensitivity is similar to blinded analysis. Choices on blinded vs. unblinded analysis may thus be based on other criteria.

PMID:38844160 | DOI:10.1016/j.joca.2024.05.012

J Dent. 2024 Jun 4:105108. doi: 10.1016/j.jdent.2024.105108. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to propose a standardized protocol for the fabrication of three-dimensionally (3D)-printed curvature-adaptive splints (CASs) and assess the precision of CASs on dentitions with different depths of the curve of Spee (COS).

METHODS: 76 lower dental resin models, each exhibiting one of the four types of COS (0-, 2-, 4-, and 6-mm deep), were selected and digitally scanned. CASs were designed, 3D printed, and grouped into C0, C2, C4, and C6, corresponding to the four types of COS depths. To assess precision, the CASs occluded with the resin model were scanned as a whole and compared with the originally designed ones.

RESULTS: In terms of translational deviations observed in the CASs, the mean value of absolute sagittal deviation (0.136mm) was significantly higher than those of vertical (0.091mm) and transversal deviations (0.045mm) (P < 0.01). Regarding rotational deviations of the CASs, the mean deviation in pitch (0.323°) was significantly higher than those in yaw (0.083°) and roll (0.110°) (P < 0.01). However, when comparing the accuracy of CASs across C0, C2, C4, and C6 groups, no statistically significant difference was found. Additionally, the translational deviations, rotational deviations, and RMSE of all groups were significantly lower than the clinically acceptable limits of 0.5mm, 1°, and 0.25mm, respectively (P<0.01).

CONCLUSIONS: The depth of the COS has no significant impact on the precision of CASs, as evidenced by the absence of statistically significant differences in translational, rotational deviations, and RMSE among all groups (C0, C2, C4, and C6). Moreover, despite relatively high deviations in the sagittal dimension and pitch, all dimensional deviations and RMSE remained statistically significantly lower than the corresponding clinically acceptable limits (CALs) in all groups.

CLINICAL SIGNIFICANCE: This standardized protocol incorporating “curvature-adaptation” represents an optimized approach to fabricating diverse 3D-printed splints tailored to dentitions with different anatomical features in contemporary digital dentistry.

PMID:38844153 | DOI:10.1016/j.jdent.2024.105108

Am J Prev Med. 2024 Jun 4:S0749-3797(24)00174-0. doi: 10.1016/j.amepre.2024.05.018. Online ahead of print.

ABSTRACT

INTRODUCTION: Discrimination in medical settings (DMS) contributes to health care disparities in the United States, but few studies have determined the extent of DMS in a large national sample and across different populations. This study estimated the national prevalence of DMS and described demographic and health-related characteristics associated with experiencing DMS in seven different situations.

METHODS: Survey data from 41,875 adults participating in the All of Us Research Program collected in 2021-2022 and logistic regression were used to examine the association between sociodemographic and health-related characteristics and self-reported DMS among adults engaged with a health care provider within the past 12 months. Statistical analysis was performed in 2023-2024.

RESULTS: About 36.89% of adults reported having experienced at least one DMS situation. Adults with relative social and medical disadvantages had higher prevalence of experiencing DMS. Compared to their counterparts, respondents with higher odds of experiencing DMS in at least one situation identified as female, non-Hispanic Black, having at least some college, living in the South, renter, having other living arrangement, being publicly insured, not having a usual source of care, having multiple chronic conditions, having any disability, and reporting fair or poor health, p<0.05.

CONCLUSIONS: The findings indicate a high prevalence of DMS, particularly among some population groups. Characterizing DMS may be a valuable tool for identifying populations at risk within the health care system and optimizing the overall patient care experience. Implementing relevant policies remains an essential strategy for mitigating the prevalence of DMS and reducing health care disparities.

PMID:38844146 | DOI:10.1016/j.amepre.2024.05.018

Am J Infect Control. 2024 Jun 4:S0196-6553(24)00532-7. doi: 10.1016/j.ajic.2024.05.018. Online ahead of print.

ABSTRACT

BACKGROUND: Peripheral intravenous catheters (PIVs) are the most frequently used invasive device in hospitalized patients. These devices are not benign and may put patients at risk of serious complications. However, clinician awareness of their presence is variable and poorly understood.

METHODS: We conducted a prospective, multi-center, observational point prevalence study to assess awareness of PIV presence among clinicians caring for hospitalized patients in four hospitals between 05/2018 and 02/2019 located in Michigan, United States of America. We first assessed patients for presence of a PIV then interviewed their providers. Differences in awareness by provider type was assessed via chi-square tests; p< 0.05 was considered statistically significant. Analyses were performed on Stata MP v16 (College Station, TX).

RESULTS: A total of 1,385 patients and 4,003 providers were interviewed. Nurses had the greatest awareness of overall PIV presence, 98.6%, while attendings were correct 88.1% of the time. Nurses were more likely to correctly assess PIV presence and exact location than physicians (67.7% vs. < 30% for all others). Awareness of PIV presence did not significantly vary among providers in patients with multiple vascular access device(s), on contact precautions, or those receiving active infusions.

CONCLUSIONS: Given the ubiquity of PIVs and known complications, variable awareness of vascular devices is problematic. Methods to increase awareness to ensure appropriate care and removal appear necessary.

PMID:38844143 | DOI:10.1016/j.ajic.2024.05.018

Eur J Vasc Endovasc Surg. 2024 Jun 4:S1078-5884(24)00469-6. doi: 10.1016/j.ejvs.2024.05.042. Online ahead of print.

ABSTRACT

OBJECTIVE: This retrospective cohort study aimed to confirm the previously reported inverse association between diabetes mellitus (DM) and abdominal aortic aneurysm (AAA) using large population based data. It also investigated the associations between AAA with impaired fasting glucose (IFG) and new onset DM (not yet treated).

METHODS: A representative dataset was obtained from the Korean National Health Insurance Service. Participants who were aged ≥ 50 years and received a national health examination in 2009 were included and followed until 31 December 2019. Glycaemic status was defined based on fasting plasma glucose level and the relevant diagnostic codes. AAA was ascertained using records of medical facility usage with relevant diagnostic codes or aneurysm repair surgery. A Cox proportional hazards model was used to examine the association between glycaemic status and AAA, with adjustment for confounders. Additionally, the interactions between glycaemic status and subgroups based on baseline characteristics were examined.

RESULTS: The study population comprised 4 162 640 participants. Participants with IFG or DM were significantly more likely to be male, older, and have comorbidities compared with normoglycaemic participants at baseline. The incidence of AAA was lower in participants with IFG or DM compared with normoglycaemic participants. The AAA risk was lower in patients with DM than in patients with IFG, and decreased linearly according to glycaemic status: the adjusted hazard ratio was 0.88 (95% confidence interval [CI] 0.85 – 0.91) for IFG, 0.72 (95% CI 0.67 – 0.78) for newly diagnosed DM, 0.65 (95% CI 0.61 – 0.69) for DM duration < 5 years, and 0.47 (95% CI 0.44 – 0.51) for DM duration ≥ 5 years compared with the normoglycaemia group. Both IFG and DM were related to reduced AAA risk in all subgroups, suggesting an independent association.

CONCLUSION: Both IFG and DM, even when not treated with antihyperglycaemic medication, were associated with a lower incidence of AAA. The AAA risk decreased linearly according to DM duration.

PMID:38844129 | DOI:10.1016/j.ejvs.2024.05.042