Category: Nevin Manimala

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

Zhonghua Zhong Liu Za Zhi. 2023 Apr 23;45(4):322-329. doi: 10.3760/cma.j.cn112152-20211008-00745.

ABSTRACT

Objective: To produce chimeric antigen receptor T cells (CAR-T) targeting human hepatocyte growth factor/c-Met (HGF/c-Met) protein and detect its cytotoxicity against non-small cell lung cancer (NSCLC) cells H1975 in vitro. Methods: The whole gene sequence of c-Met CAR containing c-Met single-chain fragment variable was synthesized and linked to lentiviral vector plasmid, plasmid electrophoresis was used to detect the correctness of target gene. HEK293 cells were transfected with plasmid and the concentrated solution of the virus particles was collected. c-Met CAR lentivirus was transfected into T cells to obtain second-generation c-Met CAR-T and the expression of CAR sequences was verified by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, and the positive rate and cell subtypes of c-Met CAR-T cells were detected by flow cytometry. The positive expression of c-Met protein in NSCLC cell line H1975 was verified by flow cytometry, and the negative expression of c-Met protein in ovarian cancer cell line A2780 was selected as the control. The cytotoxicity of c-Met CAR-T to H1975 was detected by lactate dehydrogenase (LDH) cytotoxicity assay at 1∶1, 5∶1, 10∶1 and 20∶1 of effector: target cell ratio (E∶T). Enzyme-linked immunosorbent assay (ELISA) was used to detect the release of cytokines such as TNF-α, IL-2 and IFN-γ from c-Met CAR-T co-cultured with H1975. Results: The size of band was consistent with that of designed c-Met CAR, suggesting that the c-Met CAR plasmid was successfully constructed. The results of gene sequencing were consistent with the original design sequence and lentivirus was successfully constructed. CAR molecules expression in T cells infected with lentivirus was detected by western blot and RT-qPCR, which showed c-Met CAR-T were successfully constructed. Flow cytometry results showed that the infection efficiency of c-Met CAR in T cells was over 38.4%, and the proportion of CD8(+) T cells was increased after lentivirus infection. The NSCLC cell line H1975 highly expressed c-Met while ovarian cancer cell line A2780 negatively expressed c-Met. LDH cytotoxicity assay indicated that the killing efficiency was positively correlated with the E∶T, and higher than that of control group, and the killing rate reached 51.12% when the E∶T was 20∶1. ELISA results showed that c-Met CAR-T cells released more IL-2, TNF-α and IFN-γ in target cell stimulation, but there was no statistical difference between c-Met CAR-T and T cells in the non-target group. Conclusions: Human NSCLC cell H1975 expresses high level of c-Met which can be used as a target for immunotherapy. CAR-T cells targeting c-Met have been successfully produced and have high killing effect on c-Met positive NSCLC cells in vitro.

PMID:37078213 | DOI:10.3760/cma.j.cn112152-20211008-00745

Zhonghua Zhong Liu Za Zhi. 2023 Apr 23;45(4):313-321. doi: 10.3760/cma.j.cn112152-20220604-00386.

ABSTRACT

Objective: To analyze the trends of incidence and age change for global female breast cancer in different regions of the world according to the database from Cancer Incidence in Five Continents Time Trends (CI5plus) published by the International Association of Cancer Registries (IACR). Methods: The recorded annual female breast cancer (ICD-10: C50) incidence data and corresponding population at-risk data (1998-2012) were extracted from CI5plus published by IACR. The annual change percentage and average annual change percentage (AAPC) were calculated to examine the trends of incidence. The age-standardized mean age at diagnosis and proportion of incidence cases by age were calculated to analyze the relationship between incidence and age. Results: For crude incidence, except in Northern America, all other regions showed an upward trend, with Asia showing the most obvious upward trend (AAPC: 4.1%, 95% CI: 3.9%, 4.3%). For age-standardized incidence, in Asia, Latin America and Europe, the rising trends had slowed down, in Oceania and Africa, the trends began to be stable, and in Northern America, the trend showed a downward trend (APPC: -0.6%; 95% CI: -1.0%, -0.1%). The mean age at diagnosis were increased from 1998 to 2012 in Asia, Latin America, Oceania and Europe, with an annual increase of 0.12 years, 0.09 years, 0.04 years and 0.03 years, respectively. But after age-standardized, only Europe still kept increasing year by year, with an annual increase of 0.02 years, while Northern America showed a decreasing trend, with an annual decrease of about 0.03 years. Conclusions: From 1998 to 2012, the trends of incidence and age change for global female breast cancer vary in different regions of the world, and the global population aging is widespread, which affects the trend of the actual age change. Prevention and control strategies should be targeted at different age groups in different regions.

PMID:37078212 | DOI:10.3760/cma.j.cn112152-20220604-00386