Category: Nevin Manimala

Pharm Res. 2022 Feb 10. doi: 10.1007/s11095-022-03175-4. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate a three-compartmental semi-physiological model for analysis of uptake clearance and efflux from brain tissue of the hydrophilic markers sucrose and mannitol, compared to non-compartmental techniques presuming unidirectional uptake.

METHODS: Stable isotope-labeled [¹³C]sucrose and [¹³C]mannitol (10 mg/kg each) were injected as IV bolus into the tail vein of awake young adult mice. Blood and brain samples were taken after different time intervals up to 8 h. Plasma and brain concentrations were quantified by UPLC-MS/MS. Brain uptake clearance (K_in) was analyzed using either the single-time point analysis, the multiple time point graphical method, or by fitting the parameters of a three-compartmental model that allows for symmetrical exchange across the blood-brain barrier and an additional brain efflux clearance.

RESULTS: The three-compartment model was able to describe the experimental data well, yielding estimates for K_in of sucrose and mannitol of 0.068 ± 0.005 and 0.146 ± 0.020 μl.min^-1.g^-1, respectively, which were significantly different (p < 0.01). The separate brain efflux clearance had values of 0.693 ± 0.106 (sucrose) and 0.881 ± 0.20 (mannitol) μl.min^-1.g^-1, which were not statistically different. K_in values obtained by single time point and multiple time point analyses were dependent on the terminal sampling time and showed declining values for later time points.

CONCLUSIONS: Using the three-compartment model allows determination of K_in for small molecule hydrophilic markers with low blood-brain barrier permeability. It also provides, for the first time, an estimate of brain efflux after systemic administration of a marker, which likely represents bulk flow clearance from brain tissue.

PMID:35146590 | DOI:10.1007/s11095-022-03175-4

J Digit Imaging. 2022 Feb 10. doi: 10.1007/s10278-022-00588-w. Online ahead of print.

ABSTRACT

Previous studies have demonstrated a frequent occurrence of screw/K-wire malpositioning during surgical fracture treatment under 2D fluoroscopy and a correspondingly high revision rate as a result of using intraoperative 3D imaging. In order to facilitate and accelerate the diagnosis of implant malpositioning in 3D data sets, this study investigates two versions of an implant detection software for mobile 3D C-arms in terms of their detection performance based on comparison with manual evaluation. The 3D data sets of patients who had received surgical fracture treatment at five anatomical regions were extracted from the research database. First, manual evaluation of the data sets was performed, and the number of implanted implants was assessed. For 25 data sets, the time required by four investigators to adjust each implant was monitored. Subsequently, the evaluation was performed using both software versions based on the following detection parameters: true-positive-rate, false-negative-rate, false-detection-rate and positive predictive value. Furthermore, the causes of false positive and false negative detected implants depending on the anatomical region were investigated. Two hundred fourteen data sets with overall 1767 implants were included. The detection parameters were significantly improved (p<.001) from version 1 to version 2 of the implant detection software. Automatic evaluation required an average of 4.1±0.4 s while manual evaluation was completed in 136.15±72.9 s (p<.001), with a statistically significant difference between experienced and inexperienced users (p=.005). In summary, version 2 of the implant detection software achieved significantly better results. The time saved by using the software could contribute to optimizing the intraoperative workflow.

PMID:35146612 | DOI:10.1007/s10278-022-00588-w

Environ Monit Assess. 2022 Feb 10;194(3):168. doi: 10.1007/s10661-022-09843-7.

ABSTRACT

How and to which extent terrain factors affecting the drainage area threshold (DAT) are disputable. This paper uses principal component analysis (PCA) and correlation analysis to study the influence degree of terrain factors on DAT. Firstly, 22 watersheds, locating in the severe soil erosion region (SSER) of Loess Plateau of China, are picked out as the example areas. The purpose of the mean change point method (MCP) to detect the relationship between DAT and gully density (GD) is to get a reasonable DAT. Secondly, nine terrain factors are calculated, and their statistical values are compared and put in the matrix to clear the different effects on DAT. Finally, the effects of statistical eigenvalues of terrain factors on DAT are compared with PCA and the correlation analysis. According to the PCA, the nine terrain factors are summarized into three principal components, which are slope, height variation, and relief factor. By calculating the score weighted by each factor coefficient matrix and eigenvalue, the result states that slope (S), terrain curvatures (K), and surface roughness (SR) are the factors that have great influence on DAT. Meanwhile, the results of correlation analysis indicate that S, SR, and K have exerted a great influence on the DAT, and the significance level was above 0.05. Both the results of PCA and correlation analysis make clear that the slope is the most direct and influential factor affecting DAT, while other factors are more or less related to slope directly and indirectly. The result implies that the vertical variation of terrain has a strong correlation with the slope, and also has a great influence on DAT. This research not only would be of great significance to recognize the mechanism of gully development, but also able to provide a scientific reference for soil and water conservation in the Loess Plateau.

PMID:35146588 | DOI:10.1007/s10661-022-09843-7

Abdom Radiol (NY). 2022 Feb 11. doi: 10.1007/s00261-022-03412-9. Online ahead of print.

ABSTRACT

PURPOSE: The identification of high recurrence risk stage II colon cancer patients was critical to adjuvant chemotherapy decision. However, current definition of high-risk features remains inadequate. This study aimed to construct a model for predicting recurrence risk based on tumor enhancement ratio (TER) on abdominal contrast-enhanced CT scan.

METHOD: 282 stage II colon cancer patients were included and randomly divided into training and validation sets in the ratio of 7:3. TER was calculated using maximum tumor attenuation value in contrast-enhanced CT scan divided by the minimum. Kaplan-Meier survival analyses were adopted to evaluate the prognostic value of variables. A model based on TER was built to predict recurrence risk through the LASSO Cox model. The recurrence risk score of patients was calculated based on this model.

RESULTS: The optimal cut-off value of TER was 1.83 derived from the time-dependent ROC (tdROC) curve. Patients with high-TER showed increasingly poorer disease-free survival (DFS) in both training (p < 0.001) and validation (p < 0.001) sets. A model was built based on TER demonstrated satisfactory performance to recurrence risk prediction (C-index: 0.784 in the training set and 0.725 in the validation set). Patients were regrouped into modified high-risk and non-high risk according to recurrence risk score (cut-off value: 1.75) and a significant DFS difference was observed (training set: p < 0.001; validation set: p < 0.001).

CONCLUSION: TER can serve as a high-risk feature of stage II colon cancer. And a model based on TER provided a new approach to assess recurrence risk of stage II disease.

PMID:35146573 | DOI:10.1007/s00261-022-03412-9

Protoplasma. 2022 Feb 10. doi: 10.1007/s00709-022-01741-6. Online ahead of print.

ABSTRACT

Parquetina nigrescens has been used for decades in ethnomedicine for its antioxidant, antimicrobial, anti-inflammatory, analgesic, and aphrodisiac properties. In this study, the cytotoxic and genotoxic effect of aqueous crude leaf extracts of P. nigrescens on the root meristematic cells of Allium cepa was examined. Volatile organic compounds (VOCs) present in the plant extract were also identified using gas chromatography-mass spectrometry (GC-MS). The extract was prepared with tap water as is locally practised by many Nigerians. Onion bulbs were exposed to 1, 5, 10, 20, and 50% concentrations of the extract for the analysis of root growth inhibition and chromosomal aberration. Lead nitrate (10 ppm) and tap water were used as the positive and negative controls, respectively. The result showed cytotoxicity which was observed as statistically significant (p <p0.05), concentration-dependent inhibition of root growth from 5 to 50% concentrations of the plant extract compared with the negative control. At 10 and 20% concentrations, the extract showed statistically significant (p < 0.05) genotoxicity by inducing different chromosomal aberrations such as fragments, disturbed spindle, delayed, and sticky chromosomes. The GC-MS analysis identified 14 VOCs of which 1, 2-benzenediol, 4H-pyran-4-one, 2, 3-dihydro-3,5-dihydroxy-6-methyl, and 5-hydroxymethylfurfural were believed to be responsible for the observed cytogenotoxicity. These results show that the aqueous crude leaf extracts of P. nigrescens at high concentrations are cytogenotoxic and therefore should be consumed with caution.

PMID:35146572 | DOI:10.1007/s00709-022-01741-6

Zhonghua Yan Ke Za Zhi. 2022 Feb 11;58(2):130-136. doi: 10.3760/cma.j.cn112142-20210320-00139.

ABSTRACT

Objective: To investigate the efficacy of mitomycin C (MMC) 0.02% for prevention of haze after transepithelial photorefractive keratectomy (Trans-PRK) for mild and moderate myopia. Methods: Retrospective cohort study. We reviewed medical records of 295 patients (588 eyes) who underwent Trans-PRK with or without use of MMC. There were 45 patients (90 eyes) in the mild myopia group (aged between 18 and 41 years; 37 males and 8 females; myopia diopter <3.00 D) and 250 patients (498 eyes) in the moderate myopia group (aged between 18 and 46 years; 168 males and 82 females; myopia diopter: 3.00 to 6.00 D). The two groups were divided into subgroups with MMC 0.02% and without MMC, respectively. The time of intraoperative application of MMC, if there was, was 15 s and 30 s in the mild myopia group and the moderate myopia group, respectively. The mean follow-up time was 6 months. Postoperative best corrected visual acuity (BCVA), spherical equivalent (SE) and haze were analyzed and compared using an independent Student t-test or Mann-Whitney U test between subgroups. Haze variables were compared using chi-square statistics. Results: Haze was quantified with Fantes from grade 0.5 to 4. In the mild myopia group, all haze grades were 0.5 within 3 months. The incidence of haze was 6.25% (2/32) in eyes treated with MMC and 8.62% (5/58) in eyes treated without MMC; there was no statistical significance (χ²=0.00, P>0.999). In the moderate myopia group, the incidence of haze was 9.19% (24/261) in eyes treated with MMC within 3 months; the grade was 0.5 in 91.67% (22/24) of eyes with haze and 1 in 8.33% (2/24). The incidence of haze was 29.53% (70/237) in eyes treated without MMC; the grade was 0.5 in 60.00% (42/70) of eyes with haze, 1 in 18.57% (13/70), and 2 in 5.71% (4/70) within 3 months, and 0.5 in 15.71% (11/70) after 3 months (χ²=12.36, P=0.002). In the mild myopia group, BCVA was 5.0(5.0, 5.1) versus 5.0(5.0, 5.1) in the subgroups with MMC and without MMC (Z=-0.34, P=0.733). In the moderate myopia group, BCVA was 5.0(5.0, 5.1) versus 5.0(5.0, 5.1) in the subgroups with and without MMC (Z=-2.05, P=0.040). In the mild myopia group, SE was (0.33±1.07) D versus (0.32±0.57) D in the subgroups with and without MMC (t=0.25, P=0.805). In the moderate myopia group, SE was (0.66±0.85) D versus (0.53±0.67) D in the subgroups with and without MMC (t=2.97, P=0.003). Conclusions: MMC 0.02% was effective in preventing haze after Trans-PRK in the treatment of moderate myopia. However, it was not effective in mild myopia.

PMID:35144353 | DOI:10.3760/cma.j.cn112142-20210320-00139

Zhonghua Yan Ke Za Zhi. 2022 Feb 11;58(2):112-119. doi: 10.3760/cma.j.cn112142-20210912-00423.

ABSTRACT

Objective: To investigate the early histological changes by confocal microscopy of patients with advanced keratoconus receiving collagen cross-linking therapy. Methods: In this prospective case series study, confocal microscopy was used to observe 23 patients (32 eyes) who were diagnosed with advanced keratoconus and treated with collagen cross-linking at the Department of Ophthalmology, Chinese PLA General Hospital from September 2017 to March 2019, aged (26±10) year. All patients were examined before and at 1 week, 1 month and 3 months after the therapy. The tissue structure changes, the density of nerve fibers, stromal cells and endothelial cells, and the depth of the corneal stroma were recorded and compared. The overall differences at different times were compared by repeated measurement analysis of variance or Friedman test, and the pairwise comparison was corrected by LSD-t test or Bonferroni test. Results: One week after collagen cross-linking, the epithelial cells were in the repair stage, showing an increased nucleolar size and an enhanced reflection, and the activated cells could be detected under the epithelium. The superficial corneal stroma was swollen and spongiform, while the deep corneal stroma was patchy or cord-like, scattered and with a strong reflection. One month after the therapy, epithelial cells recovered, subepithelial nerves began to grow, the superficial corneal stroma still showed a spongy structure, and the reflection was further enhanced. The activation of the deep corneal stroma exhibited as thicker plaques or cord-like structure. Three months after the therapy, the continuous elongation of single nerve fibers could be detected occasionally. There was statistically significant difference in the density of nerve fibers before and early after the therapy (F=233.30, P<0.001). Compared with the preoperative value [(14.60±2.57) mm/mm²], the density of subepithelial nerve fibers decreased significantly in the early postoperative period, which was (0.51±0.31), (3.65±2.21) and (8.50± 4.02) mm/mm², respectively, at 1 week, 1 month and 3 months, and there were significant differences between different time points (all P<0.05). There was also statistically significant differences in the density of anterior stromal cells before and early after the therapy (χ²=92.48, P<0.001). Compared with the preoperative value [347.00(345.00,395.75) cells/mm²] the density of anterior stromal cells decreased significantly in the early postoperative period, which was 2.00(1.00,5.75), 2.50(1.00,5.75) and 79.00(64.25,94.00) cells/mm², respectively, at 1 week, 1 month and 3 months, and there were significant differences between different time points (all P<0.05). Within 3 months after the therapy, the depth of the corneal stroma observed by confocal microscopy ranged from 245 to 536 μm, with an average of (400.56±86.12) μm. Histologically, the depth of the corneal stroma ranged from 245 to 536 μm [average, (402.13±89.20) μm], from 251 to 527 μm [average, (399.88±85.92) μm] and from 259 to 530 μm [average, (399.69±85.94) μm] at 1 week, 1 month and 3 months, respectively, with no significant difference (F=0.797, P=0.455). There was no significant difference in the density of posterior stromal cells [(260.6±33.2) cells/mm² preoperatively, (264.4±44.5) cells/mm² at 1 week, (263.9±37.6) cells/mm² at 1 month and (266.3±40.2) cells/mm² at 3 months] and endothelial cells [(2 707±152.6) cells/mm² preoperatively, (2 704±148.5) cells/mm² at 1 week, (2 705±152.6) cells/mm² at 1 month and (2 704±150.1) cells/mm² at 3 months] between different time points (F=1.380, 1.011; P=0.259, 0.351). Conclusions: Confocal microscopy is able to clearly document the early morphological characteristics after collagen cross-linking in the treatment of keratoconus, including the epithelial and subepithelial nerve injury repair, the spongiform superficial corneal stroma, the patchy or cord-like deep corneal stroma, and the relatively stable stromal depth change.

PMID:35144351 | DOI:10.3760/cma.j.cn112142-20210912-00423

Zhonghua Yi Xue Za Zhi. 2022 Feb 15;102(6):399-405. doi: 10.3760/cma.j.cn112137-20211009-02231.

ABSTRACT

Objective: To explore the prognosis of patients with leptomeningeal metastasis (LM) and epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC) treated with different kinds of tyrosine kinase inhibitors (TKIs). Methods: From January 2016 to June 2021, the clinicopathological data of 70 patients confirmed by histologically or cytologically EGFRm LM who received different types of TKIs in Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. According to treatment patterns, patients were divided into the first-and second-generation EGFR-TKIs treatment group and the third-generation EGFR-TKIs treatment group [Osimertinib 80 mg once a day], and the prognosis and prognostic factors (with Cox proportional hazards model) of patients in different treatment group were assessed. The next-generation sequencing (NGS) of paired samples of cerebrospinal fluid (CSF) and plasma from 64 patients at the time of LM diagnosis was performed simultaneously. Results: There were 20 males and 50 females in 70 EGFRm NSCLC patients with LM. The age ranged from 35 to 69 years, with a median age of 56 years. A total of 24 patients received the first-and second-generation EGFR-TKIs treatment, and 46 received the third-generation EGFR-TKIs treatment. Twenty-four patients developed disease progression on the first-and second EGFR-TKIs treatments, followed by treatment with the third-generation EGFR-TKIs (Osimertinib) in 12 cases, chemotherapy or anti-angiogenesis therapy in 4 cases, and the optimal supportive treatment in 8 cases. Among the 70 patients, 18 had partial response (PR), 48 had stable disease (SD), and 4 had progressive disease (PD). The objective response rate (ORR) and disease control rate (DCR) were 26% (18/70) and 94% (66/70), respectively. The median follow-up time was 16.5 months. The median progression-free survival (PFS) was 5.3 months(95%CI: 2.8-7.8)in the first-and second-generation EGFR-TKIs and 10.8 months (95%CI: 7.9-13.6) in the third-generation EGFR-TKIs, and the difference was statistically significant (P=0.019). The median overall survival (OS) was 14.9 months (95%CI: 9.7-20.0) and 15.7 months (95%CI: 13.3-18.1) in the two groups, respectively, but no statistical differences was observed (P=0.713). Univariate analysis showed that the PFS of patients with EGFRm LM were related to gender and different types of EGFR-TKIs (P˂0.05). Multivariate analysis demonstrated that male (HR=2.30, 95%CI: 1.31-4.03, P=0.004) and the first-and second-generation EGFR-TKIs (HR=2.03, 95%CI: 1.20-3.41, P=0.008) were independent risk factors for PFS in patients with EGFRm LM. The EGFR mutation was detected in 61 (95%) CSF and in 27 (42%) plasma samples. Conclusion: In EGFRm NSCLC patients with LM, the dose of Osimertinib 80 mg (once a day) has a significant PFS benefit compared with the first-and second-generation EGFR-TKIs.

PMID:35144338 | DOI:10.3760/cma.j.cn112137-20211009-02231

Zhonghua Yi Xue Za Zhi. 2022 Feb 15;102(6):418-422. doi: 10.3760/cma.j.cn112137-20210729-01684.

ABSTRACT

Objective: To investigate the risk factors for gestational diabetes mellitus (GDM) in elderly multipara women in the next pregnancy. Methods: A total of 219 elderly multipara women with 2 consecutive delivery records in Tianjin Binhai New Area Tanggu Obstetrics and Gynecology Hospital from January 2018 to May 2019 were included. Among them, 141 had normal glucose tolerance (NGT) and 78 of them had GDM. The clinical data of the previous and current pregnancy were collected to analyze the risk factors of GDM in elderly multipara women. Results: The average ages of 219 elderly women in previous pregnancy and this pregnancy were (31.9±2.2) and (36.7±1.5) years old, and the prevalence of GDM was 35.62% (78 cases). Compared to NGT group, GDM patients had higher fasting blood glucose(previous (5.51±1.43) vs (4.63±0.62) mmol/L; current (5.26±0.63) vs (4.59±0.30) mmol/L, 1 h blood glucose(previous (11.74±2.36) vs (9.50±1.82) mmol/L; current (11.03±2.03) vs (9.51±1.14) mmol/L) in 75 g oral glucose tolerance test (OGTT) in both previous and current pregnancy. The rates of cesarean section, in both previous and current pregnancy were higher in GDM group (previous 34.6% vs 4.3%; current 52.6% vs 22.0%). Furthermore, prenatal weight and body mass index (BMI) of the previous pregnancy, pre-pregnancy weight and BMI, and prenatal BMI of this pregnancy were also higher in GDM group, and the differences were all statistically significant (all P<0.05). Logistic multivariate regression analysis indicated cesarean section history (OR=10.80, 95%CI: (4.09-28.54)), GDM history of previous pregnancy (OR=10.64, 95%CI: (4.02-28.20)), 75 g OGTT fasting blood glucose≥ 4.86 mmol/L (OR=2.70, 95%CI: (1.27-5.70)), 1 h blood glucose after glucose administration ≥ 8.45 mmol/L (OR=1.78, 95%CI: (1.37-2.31)) were risk factors for GDM in elderly multipara women of this pregnancy. Conclusion: The risk of GDM in elderly multipara women with a history of cesarean section and GDM increases significantly. Results of OGTT in previous pregnancy also has predictive value.

PMID:35144341 | DOI:10.3760/cma.j.cn112137-20210729-01684