Category: Nevin Manimala

Prostate. 2021 May 25. doi: 10.1002/pros.24171. Online ahead of print.

ABSTRACT

BACKGROUND: Current preclinical models of metastatic prostate cancer (PCa) require sophisticated technologies and/or genetically engineered cells for the noninvasive monitoring of tumors in remote sites, such as bone. Recent developments in circulating tumor DNA (ctDNA) analysis provide an alternative method for noninvasive tumor monitoring at a low cost. Here, we sought to evaluate human Alu and LINE-1 ctDNA for the longitudinal measurement of subcutaneous and intratibial human PCa xenograft growth and response to ionizing radiation (IR) through comparison with standard slide caliper and bioluminescence measurements.

MATERIAL AND METHODS: Intratibial and subcutaneous xenografts were established in male athymic nude mice using LNCaP cells that stably express firefly luciferase. A subset of tumors was treated with a single dose of IR (CT-guided focal IR, 6 Gy). Tumor measurements were simultaneously taken by slide caliper (subcutaneous only), in vivo bioluminescence imaging, and quantitative real-time PCR (qPCR) of human-specific Alu and LINE-1 ctDNA for several weeks.

RESULTS: Levels of ctDNA and bioluminescence increased concordantly with subcutaneous and intratibial tumor growth. A statistically significant correlation (Spearman) was observed between ctDNA and subcutaneous tumor volume (LINE-1, r = .94 and Alu, r = .95, p < .0001), ctDNA and bioluminescence (LINE-1, r = .66 and Alu, r = .60, p < .002), and bioluminescence and tumor volume (r = .66, p = .0003). Bioluminescence and ctDNA were also significantly correlated in intratibial tumors (LINE-1, r = .82 and Alu, r = .81, p < .0001). Following external beam IR, the tumor responses varied briefly by method of measurement, but followed a similar trend. Statistically significant correlations were maintained between ctDNA and slide caliper measurement in irradiated subcutaneous tumors (LINE-1, r = .64 and Alu, r = .44, p < .02), and ctDNA and bioluminescence in intratibial tumors (LINE-1, r = .55, p = .018).

CONCLUSIONS: Real-time qPCR of circulating human Alu and LINE-1 DNA provides an accurate measurement of subcutaneous and intratibial xenograft burden that is comparable with conventional bioluminescence imaging and slide caliper measurement. Transient differences in measurements were observed following tumor-targeted IR, but overall all measurements mirrored tumor growth and response.

PMID:34032307 | DOI:10.1002/pros.24171

J Chemother. 2021 May 25:1-10. doi: 10.1080/1120009X.2021.1923153. Online ahead of print.

ABSTRACT

The main objective is to define the mortality of patients with cancer admitted to our hospital, their clinical and demographic characteristics, investigate the risk of COVID-19 for patients with cancer, and determine factors that affect the mortality rates of patients with cancer dying of COVID-19. A total of 2401 patients were admitted to our hospital with the diagnosis of COVID-19 from March 11th, 2020, to May 31st, 2020. Ninety-two out of a total of 112 cancer patients were included in this study based on the planned inclusion/exclusion criteria. The clinical, demographic, and laboratory features and treatments provided were studied, and their effect on mortality rates was analyzed. In our study the median age of the patients was 67 years, and 55.4% were male. More than half (56.5%) of our patients had metastasis. The mortality rate was 6.2% in the overall population with COVID-19, whereas it was 23.9% in patients with cancer. The mortality rate in patients with metastasis was statistically significantly higher compared with those without metastasis (34.0% vs. 10.3% P = 0.008). The mortality rate in patients still smoking was statistically significantly higher than in non-smokers (37.5% vs. 12.5% P = 0.033). The mortality rates of patients with high average C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and D-dimer levels were statistically significantly higher than in those without, and the mortality rates of patients with lower average albumin and hemoglobin levels were statistically significantly higher than those without (P < 0.001, P = 0.006, P = 0.041, P < 0.001, P < 0.001, and P = 0.028, respectively). Having metastases concurrent with COVID-19 was a statistically significant factor predictive of prognosis. Also, high CRP, ferritin, LDH, and D-dimer, and low albumin and hemoglobin were related to increased mortality rates. The predictive and prognostic role of possible factors related to prognosis is still unknown and further large, multicenter prospective studies are needed to confirm these results.

PMID:34032198 | DOI:10.1080/1120009X.2021.1923153

J Physiol. 2021 May 25. doi: 10.1113/JP281691. Online ahead of print.

ABSTRACT

KEY POINTS: Healthy older adults exhibit lower cardiorespiratory fitness (VO₂ peak) than young in the absence of any age-related difference in skeletal muscle mitochondrial capacity, suggesting central hemodynamics plays a larger role in age-related declines in VO₂ peak. Total physical activity did not differ by age, but moderate-to-vigorous physical activity was lower in older compared to young adults. Moderate-to-vigorous physical activity is associated with VO₂ peak and muscle oxidative capacity, but physical inactivity cannot entirely explain the age-related reduction in VO₂ peak.

ABSTRACT: Declining fitness (VO₂ peak) is a hallmark of aging and believed to arise from decreased oxygen delivery and reduced muscle oxidative capacity. Physical activity is a modifiable lifestyle factor that is critical when evaluating the effects of age on parameters of fitness and energy metabolism. The objective was to evaluate the effects of age and sex on VO₂ peak, muscle mitochondrial physiology, and physical activity in young and older adults. An additional objective was to assess the contribution of skeletal muscle oxidative capacity to age-related reductions in VO₂ peak and determine if age-related variation in VO₂ peak and muscle oxidative capacity could be explained on the basis of physical activity levels. 23 young and 52 older men and women completed measurements of VO₂ peak, mitochondrial physiology in permeabilized muscle fibers, and free-living physical activity by accelerometry. Regression analyses were used to evaluate associations between age and VO₂ peak, mitochondrial function, and physical activity. Significant age-related reductions were observed for VO₂ peak (P<0.001), but not muscle mitochondrial capacity. Total daily step counts did not decrease with age, but older adults showed lower moderate-to-vigorous physical activity, which was associated with VO₂ peak (R² = 0.323, P<0.001) and muscle oxidative capacity (R² = 0.086, P = 0.011). After adjusting for sex and physical activity, age was negatively associated with VO₂ peak but not muscle oxidative capacity. Healthy older adults exhibit lower VO₂ peak but preserved mitochondrial capacity compared to young. Physical activity, particularly moderate-to-vigorous, is a key factor in observed age-related changes in fitness and muscle oxidative capacity, but cannot entirely explain the age-related reduction in VO₂ peak. This article is protected by copyright. All rights reserved.

PMID:34032280 | DOI:10.1113/JP281691

Inquiry. 2021 Jan-Dec;58:469580211018285. doi: 10.1177/00469580211018285.

ABSTRACT

Hospital readmission of stroke elderly remains a need for detecting preventable risks. This study aims to develop a Readmission Stroke Screening Tool or RRST. The mixed research design was employed, phase1; systematic reviews from 193 articles extracting to be 14 articles, 9 experts’ consensus, and try out the RRST Internal consistency; IOC = .93, ICC = between .93 and .56, phase 2; Data collecting 150 of strokes patients in the stroke units during 2019 to 2020; 30 nurses employed the RRST to screen stroke elderly before discharge. Statistical analysis, Exploring Principal Factor Analysis to test the best predictor factor, and Confirmatory Factor Analysis to test the model identity were employed. Results: The multi-domain RRST; 4 factors: Intra, inter, and external factors of patients can predict the hospital readmission of Stroke elderly at a high level in 28 days. The ADL: Activities in the Daily life domain was the highest level of predicting (Eigen Value = 6.76, 1.15, Variances = 79.19%) significantly. 53.3% of user nurses reflected; the RRST tool’s effectiveness was achievable in usefulness, benefit, accuracy, and easy to use; however, the rest users identified to improve the RRST easier and quicker. Conclusion; The new RRST; can predict the high-risk readmission effectively = 92.5%. User nurses satisfied the RRST predicted quality. the multi-domain RRST could be detecting the Thai Stroke’s high-risk group for reducing avoidable risks, suggestion; more effort will be investigated prospectively in readmission by expanded volume of the Asian’ Stroke elderly for increasing accuracy predicting and extended tool quality utilized standard scored correctly.

PMID:34032150 | DOI:10.1177/00469580211018285

Integr Cancer Ther. 2021 Jan-Dec;20:15347354211019107. doi: 10.1177/15347354211019107.

ABSTRACT

OBJECTIVE: The purpose of this study is both to estimate the efficacy and the safety of Yukgunja-tang (YGJT) and to establish evidence for the use of herbal medicines in the management of patients with cancer-related anorexia.

METHODS: We enrolled 40 patients with cancer-related anorexia. The enrolled participants were randomly allocated to 2 groups: the control group (n = 20), which received nutrition counseling, and the treatment group (n = 20), which received nutrition counseling and was administered YGJT at twice a day for 4 weeks (a total of 56 times @ 3.0 g each time). The primary outcome of this study was the score on the anorexia/cachexia subscale (ACS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary outcomes were the FAACT score with the ACS score excluded, the score on the Visual Analog Scale (VAS) for appetite, and the results on laboratory tests regarding appetite, such as leptin, tumor necrosis factors (TNF-α), interleukin-6 (IL-6), and ghrelin. All variables related to the safety assessment, such as vital signs, electrocardiography results, laboratory test results (complete blood cell count, chemistry, urine test), and adverse events, were documented on the case report form (CRF) at every visit.

RESULT: The difference in the primary outcome, that is, the score on the anorexia/cachexia subscale (ACS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT), between the control and the treatment groups was statistically significant (P = .023) as was the difference in the FAACT scores with the ACS score excluded, a secondary outcome, between the 2 groups; however, no statistically significant differences were noted in the scores on the VAS or the levels of leptin, TNF-α, IL-6, and ghrelin. In addition, no significant differences in the numbers and the types of adverse events or in the results on the laboratory tests between the control and the treatment groups were recorded.

CONCLUSION: These results obtained in this research confirmed the efficacy and the safety of using YGJT as a herb-medicine treatment option for patients with cancer-related anorexia.

PMID:34032151 | DOI:10.1177/15347354211019107

J Addict Dis. 2021 May 25:1-9. doi: 10.1080/10550887.2021.1926882. Online ahead of print.

ABSTRACT

BACKGROUND: Alcohol use disorder (AUD) is a psychiatric disorder characterized by excessive and uncontrolled drinking that causes distress and has damaging consequences for men and women of all ages. It is one of the four most disabling diseases and it affects approximately 14.6 million persons in Europe.

OBJECTIVES: Objective of this study is to investigate changes in platelet serotonin concentration after four weeks of alcohol abstinence in regards to the genotype of the serotonin transporter.

METHODS: A total of 154 patients with AUD were included in the study. Platelet serotonin concentrations were assessed by enzyme-linked immunosorbent assay. Genotype of serotonin transporter promoter polymorphism was determined by the polymerase chain reaction-based method.

RESULTS: We did not establish a statistically significant main effect of serotonin transporter polymorphism on platelet serotonin concentration after four weeks of abstinence.

CONCLUSION: Aforementioned finding is in line with previous research suggesting a complex relationship between serotonin transporter gene and platelet serotonin levels, and congruent with the well-established genotype interaction with numerous other factors, such as sex, ethnicity, education level, and stressful life events.

PMID:34032190 | DOI:10.1080/10550887.2021.1926882

J Comp Eff Res. 2021 May 25. doi: 10.2217/cer-2021-0026. Online ahead of print.

ABSTRACT

In 2008, the Programa Rede Farmácia de Minas (RFM, literally translated: ‘Minas Gerais Pharmacy Network’ program) was created as a strategy to expand access to medicines. Aim: Measure access to medicines in public pharmacies through comparison between municipalities that joined or not the RFM. Materials & methods: Cross-sectional, evaluative study, gathering information from a representative sample of the municipalities in Minas Gerais between July 2014 and May 2015. The Poisson regression results were obtained by calculating the prevalence ratios. Results: Adequate access to medicines in Minas Gerais was 69.9%, being 75.8% in municipalities with and 69.2% without the RFM. The municipalities with the RFM showed statistically higher percentages in the Availability, Adequacy/Accommodation, and Acceptability dimensions. Conclusion: RFM appears an efficient strategy for promoting access to medicines.

PMID:34032143 | DOI:10.2217/cer-2021-0026

Cleft Palate Craniofac J. 2021 May 25:10556656211012858. doi: 10.1177/10556656211012858. Online ahead of print.

ABSTRACT

OBJECTIVE: Utilize 3-dimensional (3D) photography to evaluate the nasolabial changes in infants with bilateral cleft lip and palate (BCLP) who underwent nasoalveolar molding (NAM) and primary reconstructive surgery.

DESIGN: This is a retrospective serial longitudinal study of consecutively enrolled infants from September 2012 to July 2016 with BCLP who underwent NAM before primary lip and nose reconstructive surgery. It included infants who had digital 3dMD stereophotogrammetry records at initial presentation (T1), completion of NAM (T2), and 3 weeks following primary repair (T3). Twelve infants fulfilled the inclusion criteria. 3dMD Vultus software was used to orient images and plot 16 nasolabial points with x, y, z coordinates to obtain the linear and angular measurements. Nasal form changes were measured and analyzed between T1 (0.5 months old), T2 (5 months old), and T3 (6 months old). Intraclass correlation coefficient was performed for intrarater reliability. Averaged data from the 3D images was statistically analyzed from T1 to T2 and T2 to T3 with Wilcoxon tests. Unaffected infant norms from the Farkas publication were used as a control sample.

RESULTS: After NAM therapy, statistically significant changes in the position of subnasale and labius superius improved nasolabial symmetry. Both retruded after NAM were displaced downward after NAM and surgical correction with respect to soft tissue nasion. The nasal tip’s projection was maintained with NAM and surgical correction. The columella lengthened from 1.4 to 4.71 mm following NAM.

CONCLUSIONS: There was a significant improvement in the nasolabial anatomy after NAM, and this was further enhanced after primary reconstructive surgery.

PMID:34032145 | DOI:10.1177/10556656211012858

J Am Heart Assoc. 2021 May 25:e019343. doi: 10.1161/JAHA.120.019343. Online ahead of print.

ABSTRACT

Background Hypertriglyceridemia is associated with increased risk of coronary heart disease but the association is often attributed to concomitant metabolic abnormalities. We investigated the epidemiology of primary isolated hypertriglyceridemia (PIH) and associated cardiovascular risk in a population-based setting. Methods and Results We identified adults with at least one triglyceride level ≥500 mg/dL between 1998 and 2015 in Olmsted County, Minnesota. We also identified age- and sex-matched controls with triglyceride levels <150 mg/dL. There were 3329 individuals with elevated triglyceride levels; after excluding those with concomitant hypercholesterolemia, a secondary cause of high triglycerides, age <18 years or an incomplete record, 517 patients (49.4±14.0 years, 72.0% men) had PIH (triglyceride 627.6±183.6 mg/dL). The age- and sex-adjusted prevalence of PIH in adults was 0.80% (0.72-0.87); the diagnosis was recorded in 60%, 46% were on a lipid-lowering medication for primary prevention and a triglyceride level <150 mg/dL was achieved in 24.1%. The association of PIH with coronary heart disease was attenuated but remained significant after adjustment for demographic, socioeconomic, and conventional cardiovascular risk factors (hazard ratio [HR], 1.53; 95% CI, 1.06-2.20; P= 0.022). There was no statistically significant association between PIH and cerebrovascular disease (HR, 1.06; 95% CI, 0.65-1.73, P= 0.813), peripheral artery disease (HR, 1.27; 95% CI, 0.43-3.75; P= 0.668), or the composite end point of all 3 (HR, 1.28; 95% CI, 0.92-1.80; P=0.148) in adjusted models. Conclusions PIH was associated with incident coronary heart disease events (although there was attenuation after adjustment for conventional risk factors), supporting a causal role for triglycerides in coronary heart disease. The condition is relatively prevalent but awareness and control are low.

PMID:34032140 | DOI:10.1161/JAHA.120.019343

Huan Jing Ke Xue. 2021 Jun 8;42(6):2769-2777. doi: 10.13227/j.hjkx.202010216.

ABSTRACT

The soil and water assessment tool (SWAT) model is currently one of the most widely used watershed models in China. Since the model has been developed with distributed parameters and is customized to satisfy the environmental characteristics of the U.S.A., determining appropriate parameter values that reflect local features for model application in China is crucial. Some studies have proposed parameter values for the SWAT model by summarizing reported values in the literature; however, these studies neither differentiate the literature with respect to its quality nor consider non-uniformity in parameter values and the impact of extreme values. To address this, an indicator system for assessing the quality of SWAT model research was established, taking into account the process of model development, parameter calibration, and model validation as well as model performance. This screening approach was applied to a total of 428 journal articles on SWAT model research published between 2015 and 2017 were retrieved from the China National Knowledge Infrastructure database. The reported values of 15 model parameters involved in hydrology and sediment and nutrient simulation were extracted from highly credible articles and analysed in terms of statistical distributions, differences among geographic regions, and discrepancies between calibrated and default values. Results showed that the 129 highly credible journal articles screened generally followed good modelling practice and consisted of case studies from different regions across China. The statistical distributions of the 15 model parameters derived from the SWAT model studies exhibited a range of features including positive and negative skewness, and those of 4 parameters showed significant differences among regions where the watersheds are located. Furthermore, the calibrated values of 12 out of 15 parameters were significantly different from their default values. Considering the statistical characteristics of these model parameters, recommended parameter values for SWAT model application in China are proposed in the form of confidence intervals, and specific suggestions are also provided based on data availability.

PMID:34032076 | DOI:10.13227/j.hjkx.202010216