Nevin Manimala

Environ Sci Pollut Res Int. 2023 Apr 20. doi: 10.1007/s11356-023-26813-9. Online ahead of print.

ABSTRACT

Exposure to arsenic even at low levels can lead to adverse health outcomes, however, there is a paucity of research from South Africa in relation to human exposure to arsenic. We investigated long-term exposure of residents in Limpopo province, South Africa, in a cross-sectional study by analysing water, soil and blood arsenic concentrations from two arsenic-exposed (high and medium-low exposure) villages and one non-exposed (control) village. There were statistically significant differences in the distribution of arsenic in water, soil and blood amongst the three sites. The median drinking water arsenic concentration in the high-exposure village was 1.75 µg/L (range = 0.02 to 81.30 µg/L), 0.45 µg/L (range = 0.100 to 6.00 µg/L) in the medium- / low-exposure village and 0.15 µg/L (range = < limit of detection (LOD) to 29.30 µg/L) in the control site. The median soil arsenic concentration in the high-exposure village was 23.91 mg/kg (range = < LOD to 92.10 mg/kg) whilst arsenic concentrations were below the limit of detection in all soil samples collected from the medium-/low-exposure and control villages. In the high-exposure village, the median blood arsenic concentration was 1.6 µg/L (range = 0.7 to 4.2 µg/L); 0.90 µg/L (range = < LOD to 2.5 µg/L) in the medium-/low-exposure village and 0.6 µg/L (range = < LOD to 3.3 µg/L) in the control village. Significant percentages of drinking water, soil and blood samples from the exposed sites were above the internationally recommended guidelines (namely, 10 µg/L, 20 mg/kg and 1 µg/L, respectively). Majority of participants (86%) relied on borehole water for drinking and there was a significant positive correlation between arsenic in blood and borehole water (p-value = 0.031). There was also a statistically significant correlation between arsenic concentrations in participants’ blood and soil samples collected from gardens (p-value = 0.051). Univariate quantile regression found that blood arsenic concentrations increased by 0.034 µg/L (95% CI = 0.02-0.05) for each one unit increase in water arsenic concentrations (p < 0.001). After adjusting for age, water source and homegrown vegetable consumption in multivariate quantile regression, participants from the high-exposure site had significantly higher blood concentrations than those in the control site (coefficient: 1.00; 95% CI = 0.25-1.74; p-value = 0.009) demonstrating that blood arsenic is a good biomarker of arsenic exposure. Our findings also provide new evidence for South Africa on the association between drinking water and arsenic exposure, emphasising the need for the provision of potable water for human consumption in areas with high environmental arsenic concentrations.

PMID:37079235 | DOI:10.1007/s11356-023-26813-9

Geroscience. 2023 Apr 20. doi: 10.1007/s11357-023-00785-7. Online ahead of print.

ABSTRACT

Cellular senescence is a state of permanent growth arrest that plays an important role in wound healing, tissue fibrosis, and tumor suppression. Despite senescent cells’ (SnCs) pathological role and therapeutic interest, their phenotype in vivo remains poorly defined. Here, we developed an in vivo-derived senescence signature (SenSig) using a foreign body response-driven fibrosis model in a p16-CreER^T2;Ai14 reporter mouse. We identified pericytes and “cartilage-like” fibroblasts as senescent and defined cell type-specific senescence-associated secretory phenotypes (SASPs). Transfer learning and senescence scoring identified these two SnC populations along with endothelial and epithelial SnCs in new and publicly available murine and human data single-cell RNA sequencing (scRNAseq) datasets from diverse pathologies. Signaling analysis uncovered crosstalk between SnCs and myeloid cells via an IL34-CSF1R-TGFβR signaling axis, contributing to tissue balance of vascularization and matrix production. Overall, our study provides a senescence signature and a computational approach that may be broadly applied to identify SnC transcriptional profiles and SASP factors in wound healing, aging, and other pathologies.

PMID:37079217 | DOI:10.1007/s11357-023-00785-7

Tissue Eng Regen Med. 2023 Apr 20. doi: 10.1007/s13770-023-00534-z. Online ahead of print.

ABSTRACT

BACKGROUND: In guided bone regeneration (GBR), there are various problems that occur in the bone defect after the wound healing period. This study aimed to investigate the enhancement of the osteogenic ability of the dual scaffold complex and identify the appropriate concentration of growth factors (GF) for new bone formation based on the novel GBR concept that is applying rapid bone forming GFs to the membrane outside of the bone defect.

METHODS: Four bone defects with a diameter of 8 mm were formed in the calvaria of New Zealand white rabbits each to perform GBR. Collagen membrane and biphasic calcium phosphate (BCP) were applied to the bone defects with the four different concetration of BMP-2 or FGF-2. After 2, 4, and 8 weeks of healing, histological, histomorphometric, and immunohistochemical analyses were conducted.

RESULTS: In the histological analysis, continuous forms of new bones were observed in the upper part of bone defect in the experimental groups, whereas no continuous forms were observed in the control group. In the histomorphometry, The group to which BMP-2 0.5 mg/ml and FGF-2 1.0 mg/ml was applied showed statistically significantly higher new bone formation. Also, the new bone formation according to the healing period was statistically significantly higher at 8 weeks than at 2, 4 weeks.

CONCLUSION: The novel GBR method in which BMP-2, newly proposed in this study, is applied to the membrane is effective for bone regeneration. In addition, the dual scaffold complex is quantitatively and qualitatively advantageous for bone regeneration and bone maintenance over time.

PMID:37079199 | DOI:10.1007/s13770-023-00534-z

EJNMMI Phys. 2023 Apr 20;10(1):29. doi: 10.1186/s40658-023-00548-5.

ABSTRACT

PURPOSE: In this retrospective study, we compared the maximum standardized uptake values (SUVmax) of parathyroid lesions and the target-to-background ratio (TBR) of parathyroid lesions to thyroid tissue in early-phase single-photon emission computed tomography/computed tomography (SPECT/CT) versus delayed-phase SPECT/CT in patients with secondary hyperparathyroidism (SHPT) in order to determine the optimal timing of 99mTc- methoxyisobutylisonitrile (99mTc-MIBI) SPECT/CT imaging.

METHODS: Seventeen patients with a history of chronic kidney failure stage 5 on hemodialysis, underwent pre-operative parathyroid scintigraphy for detection and localization of parathyroid lesions. Retrospective analysis was conducted for lesions with focal accumulation of 99mTc-MIBI. All patients underwent dual-phase 99mTc-MIBI parathyroid scintigraphy and dual-phase SPECT/CT. SUVmax of parathyroid lesions and thyroid tissues was measured.

RESULTS: Mean SUVmax of parathyroid lesions was 4.86 on early-phase and 2.58 on delayed-phase SPECT/CT, respectively. Mean TBR was 1.14 on early phase and 1.48 on delayed-phase SPECT/CT, respectively. Statistically significant differences in SUVmax and TBR between dual-phase SPECT/CT were observed (P < 0.001).

CONCLUSIONS: Delayed-phase SPECT/CT in SHPT is required because of the better image contrast.

PMID:37079194 | DOI:10.1186/s40658-023-00548-5

Egypt Heart J. 2023 Apr 20;75(1):29. doi: 10.1186/s43044-023-00356-3.

ABSTRACT

BACKGROUND: Left atrium changes are implicated in atrial fibrillation (AF) substrate and are predictive of AF outcomes. Left atrial appendage (LAA) is an integral component of left atrial structure and could be affected by atrial cardiomyopathy. We aimed to elucidate the association between LAA indices and late arrhythmia recurrence after atrial fibrillation catheter ablation (AFCA).

METHODS: The MEDLINE database, ClinicalTrials.gov, medRxiv and Cochrane Library were searched for studies evaluating LAA and late arrhythmia recurrence in patients undergoing AFCA. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was pre-ablation difference in LAA anatomic or functional indices.

RESULTS: A total of 34 studies were found eligible and five LAA indices were analyzed. LAA ejection fraction and LAA emptying velocity were significantly lower in patients with AF recurrence post-ablation [SMD = – 0.66; 95% CI (- 1.01, – 0.32) and SMD = – 0.56; 95% CI (- 0.73, – 0.40) respectively] as compared to arrhythmia free controls. LAA volume and LAA orifice area were significantly higher in patients with AF recurrence post-ablation (SMD = 0.51; 95% CI 0.35-0.67, and SMD = 0.35; 95% CI 0.20-0.49, respectively) as compared to arrhythmia free controls. LAA morphology was not predictive of AF recurrence post-ablation (chicken wing morphology; OR 1.27; 95% CI 0.79-2.02). Moderate statistical heterogeneity and small case-control studies are the main limitations of our meta-analysis.

CONCLUSIONS: Our findings suggest that LAA ejection fraction, LAA emptying velocity, LAA orifice area and LAA volume differ between patients suffering from arrhythmia recurrence post-ablation and arrhythmia free counterparts, while LAA morphology is not predictive of AF recurrence.

PMID:37079174 | DOI:10.1186/s43044-023-00356-3

Ecotoxicology. 2023 Apr 20. doi: 10.1007/s10646-023-02645-8. Online ahead of print.

ABSTRACT

Highly imperiled unionids have a complex life cycle including the metamorphosis of an obligate parasite life stage, larval glochidia, to the juvenile stage. Despite the known vulnerabilities of both glochidia and juveniles to pollutants, little is known on how metamorphosis success may be affected by chemical stress. Disruption of the transformation process in which glochidia encyst on the gills of a host fish, could lead to lowered recruitment and population declines. Transformation rates of Lampsilis cardium on host fish Micropterus salmoides were empirically derived from experimental exposures to low, medium, or high concentrations of an agricultural or urban mixture of contaminants of emerging concern (CECs) over two exposure durations. Transformation was characterized by: (1) a zero-inflated Poisson general linear mixed effects model to compare difference in transformation between exposure durations and (2) time response curves to describe the transformation curve using long-term exposure data. Lampsilis cardium transformation was similar between exposure durations. When compared to controls, CEC stress significantly reduced juvenile production (p « 0.05) except for the agricultural medium treatment and tended to increased encapsulation duration which while statistically insignificant (p = 0.16) may have ecological relevancy. Combining the empirically derived reduction of transformation rates with parameters values from the literature, a Lefkovich stage-based population model predicted strong declines in population size of L. cardium for all treatments if these results hold in nature. Management focus on urban CECs may lead to best conservation efforts though agricultural CECs may also have a concentration dependent impact on transformation and therefore overall recruitment and conservation success.

PMID:37079163 | DOI:10.1007/s10646-023-02645-8

J Med Imaging (Bellingham). 2023 Sep;10(5):051806. doi: 10.1117/1.JMI.10.5.051806. Epub 2023 Apr 17.

ABSTRACT

PURPOSE: Lung transplantation is the standard treatment for end-stage lung diseases. A crucial factor affecting its success is size matching between the donor’s lungs and the recipient’s thorax. Computed tomography (CT) scans can accurately determine recipient’s lung size, but donor’s lung size is often unknown due to the absence of medical images. We aim to predict donor’s right/left/total lung volume, thoracic cavity, and heart volume from only subject demographics to improve the accuracy of size matching.

APPROACH: A cohort of 4610 subjects with chest CT scans and basic demographics (i.e., age, gender, race, smoking status, smoking history, weight, and height) was used in this study. The right and left lungs, thoracic cavity, and heart depicted on chest CT scans were automatically segmented using U-Net, and their volumes were computed. Eight machine learning models [i.e., random forest, multivariate linear regression, support vector machine, extreme gradient boosting (XGBoost), multilayer perceptron (MLP), decision tree, $k$ -nearest neighbors, and Bayesian regression) were developed and used to predict the volume measures from subject demographics. The 10-fold cross-validation method was used to evaluate the performances of the prediction models. $R$ -squared ( $R^2$ ), mean absolute error (MAE), and mean absolute percentage error (MAPE) were used as performance metrics.

RESULTS: The MLP model demonstrated the best performance for predicting the thoracic cavity volume ( $R^2$ : 0.628, MAE: 0.736 L, MAPE: 10.9%), right lung volume ( $R^2$ : 0.501, MAE: 0.383 L, MAPE: 13.9%), and left lung volume ( $R^2$ : 0.507, MAE: 0.365 L, MAPE: 15.2%), and the XGBoost model demonstrated the best performance for predicting the total lung volume ( $R^2$ : 0.514, MAE: 0.728 L, MAPE: 14.0%) and heart volume ( $R^2$ : 0.430, MAE: 0.075 L, MAPE: 13.9%).

CONCLUSIONS: Our results demonstrate the feasibility of predicting lung, heart, and thoracic cavity volumes from subject demographics with superior performance compared with available studies in predicting lung volumes.

PMID:37077858 | PMC:PMC10108239 | DOI:10.1117/1.JMI.10.5.051806

Pharmacol Res Perspect. 2023 Jun;11(3):e01075. doi: 10.1002/prp2.1075.

ABSTRACT

The opioid epidemic has impacted over 10 million Americans in 2019. Opioids, like morphine, bind non-selectively in both peripheral tissue, leading to effective pain relief, and central tissue, resulting in dangerous side effects and addiction. The inflamed conditions of injured tissues have a lower pH (pH = 6-6.5) environment than healthy tissue (pH = 7.4). We aim to design a morphine derivative that binds selectively within inflamed tissue using molecular extension and dissection techniques. Morphine binds to the μ-opioid receptor (MOR) when the biochemically active amine group is protonated. Fluorination of a β-carbon from the tertiary amine group led to a reduced pKa of the derivative through induction. Through a decrease in the pKa, protonation is still statistically favored in lower pH environments of inflamed tissue but primarily deprotonated in healthy tissue. The cyclohexenol and N-methyl-piperidine rings of morphine are removed to increase conformational flexibility when binding while still maintaining the interactions required for analgesia. Electronic structure calculations were performed with Gaussian16 using the Keck Computational Research Cluster at Chapman University to determine the pKa. The theoretical pKa values are determined at the M06-2X(SMD)/aug-cc-pVDZ level of theory to calculate the ΔG°aq values for the amine deprotonation reactions. Fluoromorphine β-C2 was designed computationally and modeled within the MOR using Maestro: Schrödinger. This derivative exhibits a pKa reduction and enhanced ligand-protein interactions within the MOR. β-fluorination decreased the overall pKa values of the morphine derivatives (pKa: 6.1-7.83) relative to morphine, reducing binding within healthy, central tissue.

PMID:37078224 | DOI:10.1002/prp2.1075

Stat Med. 2023 Apr 30;42(9):1323-1337. doi: 10.1002/sim.9672. Epub 2023 Jan 27.

ABSTRACT

Covariate balance is one of the fundamental issues in designing experiments for treatment comparisons, especially in randomized clinical trials. In this article, we introduce a new class of covariate-adaptive procedures based on the Simulated Annealing algorithm aimed at balancing the allocations of two competing treatments across a set of pre-specified covariates. Due to the nature of the simulated annealing, these designs are intrinsically randomized, thus completely unpredictable, and very flexible: they can manage both quantitative and qualitative factors and be implemented in a static version as well as sequentially. The properties of the suggested proposal are described, showing a significant improvement in terms of covariate balance and inferential accuracy with respect to all the other procedures proposed in the literature. An illustrative example based on real data is also discussed.

PMID:37078360 | DOI:10.1002/sim.9672

Zhonghua Zhong Liu Za Zhi. 2023 Apr 23;45(4):330-334. doi: 10.3760/cma.j.cn112152-20220125-00059.

ABSTRACT

Objective: To investigate the relationship between miR-199b and clinicopathologic features and prognosis of patients with colorectal cancer. Methods: Cancer tissues and adjacent normal tissues of 202 patients with colorectal cancer treated in Cancer Hospital of Chinese Academy of Medical Sciences from March to December 2011 were collected. Reverse transcription-quantitative real-time polymerase chain reaction was used to detect the expression level of miR-199b in colorectal cancer tissues and corresponding adjacent normal tissues. Kaplan-Meier method and Log rank test were used for survival analysis, and receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of miR-199b in colorectal cancer patients. Results: The relative expression level of miR-199b in colorectal cancer tissues (-7.88±0.11) was lower than that in adjacent normal tissues (-6.49±0.12, P<0.001). The expression level of miR-199b in colorectal cancer tissues with lymph node metastasis (-7.51±0.14) was higher than that in colorectal cancer tissues without lymph node metastasis (-8.23±0.17, P<0.001). The relative expression levels of miR-199b in stage Ⅰ/Ⅱ, Ⅲ and Ⅳ colorectal cancer tissues were gradually increased, which were -8.26±0.17, -7.70±0.16 and -6.57±0.27, respectively, and the difference was statistically significant (P<0.001). The 5-year survival rates of patients with high and low expressions of miR-199b were 75.6% and 84.6%(P=0.045) respectively. ROC curve showed that when miR-199b was -7.965, the area under the curve was 0.578 (95% CI: 0.468, 0.688). Conclusion: The high expression of miR-199b in colorectal cancer tissues is associated with late TNM stage, lymph node metastasis and poor prognosis in colorectal cancer patients, and miR-199b may be used as a potential marker for postoperative progress and prognosis in colorectal cancer patients.

PMID:37078214 | DOI:10.3760/cma.j.cn112152-20220125-00059