Expedient approach for trans-esterification of β-keto esters under solvent free conditions using silica supported boric acid (SiO2–H3BO3) as a recyclable catalyst

A highly efficient trans-esterification of β-keto methyl/ethyl esters with primary, secondary, allylic, benzylic and chiral alcohols has been carried out in excellent yields under solvent-free conditions using silica supported boric acid as a heterogeneous catalyst. The surface morphology of the silica-boric acid catalyst (fresh and recycled) has been characterized by SEM and EDX techniques. This sustainable protocol resulted in a remarkable enhancement in the synthetic efficiency (87–95% yield) with high purity and eliminating the use of an environmentally toxic solvent. The work up procedure is very simple and the catalyst has been successfully recovered and recycled. The present methodology is also applicable for trans-esterification with chiral alcohols on a multi-gram scale without compromising the yield. Noteworthy features of this protocol are simple operational procedure, minimizing production of chemical waste, mild reaction conditions, easy preparation of the catalyst and its recyclability up to five cycles without any appreciable loss of catalytic activity.

A simple, mild, high yielding and minimizing chemical waste procedure for trans-esterification of β-keto methyl/ethyl esters with alcohol groups was developed under solvent-free condition using silica-boric acid as recyclable heterogeneous catalyst.     

A summary-statistics-based approach to examine the role of serotonin transporter promoter tandem repeat polymorphism in psychiatric phenotypes

In genetic studies of psychiatric disorders in the pre-genome-wide association study (GWAS) era, one of the most commonly studied loci is the serotonin transporter (SLC6A4) promoter polymorphism, a 43-base-pair insertion/deletion polymorphism in the promoter region (5-HTTLPR). The genetic association signals between 5-HTTLPR and psychiatric phenotypes, however, have been inconsistent across many studies. Since the polymorphism cannot be tested via available SNP arrays, we had previously proposed an efficient machine learning algorithm to predict the genotypes of 5-HTTLPR based on the genotypes of eight nearby SNPs, which requires access to individual-level genotype and phenotype data. To utilize the advantage of publicly available GWAS summary statistics obtained from studies with very large sample sizes, we develop a GWAS summary-statistics-based approach for testing the variable number of tandem repeat (VNTR) associations with various phenotypes. We first cross-verify the accuracy of the summary-statistics-based approach for 61 phenotypes in the UK Biobank. Since we observed a strong similarity between the predicted individual-level 5-HTTLPR genotype-based approach and the summary-statistics-based approach, we applied our method to the available neurobehavioral GWAS summary statistics data obtained from large-scale GWAS. We found no genome-wide significant evidence for association between 5-HTTLPR and any of the neurobehavioral traits. We did observe, however, genome-wide significant evidence for association between this locus and human adult height, BMI, and total cholesterol. Our summary-statistics-based approach provides a systematic way to examine the role of VNTRs and related types of genetic polymorphisms in disease risk and trait susceptibility of phenotypes for which large-scale GWAS summary statistics data are available.Subject terms: Behavioural genetics, Genetic association study     

Design,synthesis and docking study of Vortioxetine derivatives as a SARS-CoV-2 main protease inhibitor

PurposeVortioxetine an anti-depressant FDA-drug recently reported showing better in vitro efficacy against SARS-CoV-2.MethodsIn this study, we have synthesized ten new derivatives having alkenes, alkynes, benzyl, aryl, and mixed carbamate at the N-terminal of vortioxetine. Then the binding energy and interactions with the crucial amino acid residues in the binding pocket of main protease (M^pro) of SARS-CoV-2, of reported and ten newly synthesized vortioxetine derivatives (total thirty-one) in comparison with remdesivir are analyzed and presented in this paper.ResultsBased on the docking scores predicted by ADV and AD, most vortioxetine derivatives showed better binding efficiency towards M^pro of SARS-CoV-2 in comparison with remdesivir (an EUA approved drug against SARS-CoV-2 M^pro) and vortioxetine.ConclusionThis study shows that some vortioxetine derivatives can be developed into promising drugs for COVID-19 treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40199-022-00441-z.     

Adding pharmacists to primary care teams reduces predicted long‐term risk of cardiovascular events in Type 2 diabetic patients without established cardiovascular disease: results from a randomized trial

Aim To determine the impact of adding pharmacists to primary care teams on predicted 10‐year risk of cardiovascular events in patients with Type 2 diabetes without established cardiovascular disease. Methods This was a pre‐specified secondary analysis of randomized trial data. The main study found that, compared with usual care, addition of a pharmacist resulted in improvements in blood pressure, dyslipidaemia, and hyperglycaemia for primary care patients with Type 2 diabetes. In this sub‐study, predicted 10‐year risk of cardiovascular events at baseline and 1 year were calculated for patients free of cardiovascular disease at enrolment. The primary outcome was change in UK Prospective Diabetes Study (UKPDS) risk score; change in Framingham risk score was a secondary outcome. Results Baseline characteristics were similar between the 102 intervention patients and 93 control subjects: 59% women, median (interquartile range) age 57 (50–64) years, diabetes duration 3 (1–6.5) years, systolic blood pressure 128 (120–140) mmHg, total cholesterol 4.34 (3.75–5.04) mmol/l and HbA_1c 54 mmol/mol (48–64 mmol/mol) [7.1% (6.5–8.0%)]. Median baseline UKPDS risk score was 10.2% (6.0–16.7%) for intervention patients and 9.5% (5.8–15.1%) for control subjects (P = 0.80). One‐year post‐randomization, the median absolute reduction in UKPDS risk score was 1.0% greater for intervention patients compared with control subjects (P = 0.032). Similar changes were seen with the Framingham risk score (median reduction 1.2% greater for intervention patients compared with control subjects, P = 0.048). The two risk scores were highly correlated (rho = 0.83; P < 0.001). Conclusion Adding pharmacists to primary care teams for 1 year significantly reduced the predicted 10‐year risk of cardiovascular events for patients with Type 2 diabetes without established cardiovascular disease.     

Quantitative MRI of articular cartilage and its clinical applications

Cartilage is one of the most essential tissues for healthy joint function and is compromised in degenerative and traumatic joint diseases. There have been tremendous advances during the past decade using quantitative MRI techniques as a noninvasive tool for evaluating cartilage, with a focus on assessing cartilage degeneration during osteoarthritis (OA). In this review, after a brief overview of cartilage composition and degeneration, we discuss techniques that grade and quantify morphologic changes as well as the techniques that quantify changes in the extracellular matrix. The basic principles, in vivo applications, advantages, and challenges for each technique are discussed. Recent studies using the OA Initiative (OAI) data are also summarized. Quantitative MRI provides noninvasive measures of cartilage degeneration at the earliest stages of joint degeneration, which is essential for efforts toward prevention and early intervention in OA. J. Magn. Reson. Imaging 2013;38:991–1008. © 2013 Wiley Periodicals, Inc.     

Arsenicosis and Dietary Nutrient Intake Among Men and Women

To determine the dietary intake of nutrients and its correlation with manifestations of arsenicosis and gender a cross-sectional study was conducted in India among two groups of participants, Group 1 (108 cases having skin lesions) and Group 2 (exposed controls, 100 cases not having skin lesions) with exposure to arsenic drawn from geographical areas known to have high level of arsenic in ground water (above permissible limit, i.e. >50 μg/L). For diet survey, combinations of two methods of diet study i.e. weighment of cooked food and the 24-h diet recall were followed. The nutrients in each food items and calorie consumption were calculated. The mean calorie intake of males was significantly less than that of females in both cases and controls. In both the sexes, mean protein consumption was significantly less than that of the controls. In females, intake of most of the nutrients like thiamin, riboflavin, niacin, magnesium, copper and zinc were less in comparison to controls. In both the sexes mean choline intake was lower significantly in comparison to exposed controls. Riboflavin, copper, zinc and vitamin B₆ consumption were below the RDAs in nearly 90 % of the study population. The strongest trend in ORs was for protein (4.28). The present study revealed that low socio-economic status along with dietary intake of calorie, protein and micronutrients like thiamine, riboflavin, niacin, zinc and choline may have a definite role in increasing the risk of development of arsenicosis.     

Trabecular Bone Architecture in the Distal Radius Using Magnetic Resonance Imaging in Subjects with Fractures of the Proximal Femur

To determine whether magnetic resonance (MR)-derived measures of trabecular bone architecture in the distal radius are predictive for prevalent hip fractures, 20 subjects with hip fractures and 19 age-matched postmenopausal controls were studied. Bone mineral density (BMD) measures at the hip (dual-energy X-ray absorptiometry, DXA) and the distal radius (peripheral quantitative computed tomography, pQCT) were also obtained. We compared the MR-based structural measures derived in the radius with those in the calcaneus of the same patients. In the radius, images were acquired at an in-plane resolution of 156 μm and a slice thickness of 0.5 mm. Stereologic measures such as the apparent trabecular thickness (app. Tb.Th), fractional trabecular bone volume (app. BV/TV), trabecular spacing (app. Tb.Sp) and trabecular number (app. Tb.N) were derived from the images. Measures of app. Tb.Sp and app. Tb.N in the distal radius showed significant (p<0.05) differences between the two groups, as did hip BMD measures. However, radial trabecular BMD measures showed only a marginal difference (p= 0.05). Receiver operating curve analysis was used to determine the diagnostic efficacy of BMD, structural measures and a combination of the two. The area under the curve (AUC) for total hip BMD was 0.73, and for radial trabecular BMD was 0.69. AUC for most of the measures of trabecular bone structure at the distal radius was lower than for hip BMD measures; however, AUC for app. Tb.N at the radius was 0.69, comparable to trabecular BMD using pQCT. The AUC for combined BMD (hip) and structure measures was higher (0.87) when radius and calcaneus structure was included. Measures of trabecular architecture derived from MR images combined with BMD measures improve the discrimination between subjects with hip fractures and normal age-matched controls. Received: 22 December 1998 / Accepted: 12 February 1999     

Local differences in the trabecular bone structure of the proximal femur depicted with high-spatial-resolution MR imaging and multisection CT

RATIONALE AND OBJECTIVES: The authors performed this study to investigate structural variations in the trabecular bone of the proximal femur at high-resolution magnetic resonance (MR) imaging and high-resolution multisection computed tomography (CT). MATERIALS AND METHODS: Bone mineral density (BMD) was measured in 36 proximal human femur specimens by using dual x-ray absorptiometry. High-resolution MR imaging was performed at 1.5 T with an in-plane spatial resolution of 0.195 x 0.195 mm and a section thickness of 0.3 and 0.9 mm. Multisection CT was performed with an ultra-high-resolution protocol; images were obtained with an in-plane spatial resolution of 0.25 mm and a section thickness of 1 mm. In a subset of these specimens, micro CT was performed with an isotropic spatial resolution of 30 microm. Identical regions of interest (ROIs) were used to analyze images obtained with MR imaging, multisection CT, and micro CT. Trabecular bone structural parameters were obtained, and the parameters from the individual imaging modalities and BMD were correlated. RESULTS: Significant differences concerning the trabecular microarchitecture between the individual ROIs were demonstrated with multisection CT and MR imaging. A number of the correlations between structural parameters derived with multisection CT, MR imaging, micro CT, and BMD measurements were significant. For MR imaging, threshold technique and section thickness had an effect on structural parameters. CONCLUSION: Structural parameters obtained in the proximal femur with multisection CT and high-resolution MR imaging show regional differences. These techniques may be useful for depicting the trabecular architecture in the diagnosis of osteoporosis.     

Power Spectral Analysis of Vertebral Trabecular Bone Structure from Radiographs: Orientation Dependence and Correlation with Bone Mineral Density and Mechanical Properties

Trabecular bone structure and bone density contribute to the strength of bone and are potentially important in the study of osteoporosis. Fourier transforms of the textural patterns in radiographs of trabecular bone have previously been used for the measurement of trabecular bone structure in subjects, however, the relationship between these measures and biomechanical properties of bone have not previously been established. In this study radiographs were acquired of 28 cubic specimens of spinal trabecular bone along each of the three anatomic axes: cranio-caudal or superior-inferior (SI), medial-lateral (ML), and anterior-posterior (AP). The radiographs were digitized, background corrected, and uniformly aligned. The Fast Fourier transform (FFT) was performed on a region comprised solely of trabecular bone for each image. The zero (DC), first (FMO), and second moments (SMO) of the Fourier power spectrum and the fractal dimension (FD) as determined from the Fourier power spectrum were correlated with stereology measures, with bone mineral density (BMD) as well as with measured biomechanical properties [Young's elastic modulus (YM) and ultimate strength] of the cubes. The results show that the power spectra-based measures, when compared with structural parameters determined using 3D stereology, show good correlations with bone volume fraction, trabecular spacing, thickness, and number. These power spectral measures showed fair to good correlations with BMD and the biomechanical properties. Moreover, the correlations between the power spectral measures of trabecular structure and the BMD, YM, and stereology measures of structure depend on the orientation of the radiographic image. Specifically, these were significant differences in the measured biomechanical properties and the power spectral measures of the trabecular structure between the SI and ML and the SI and AP directions. In addition, depending on the spatial frequency range for analysis, the fractal dimension showed opposite trends with changes in BMD and biomechanical properties. Multivariate regression models showed the correlation coefficients increasing with the inclusion of some of the power spectral measures, suggesting that FFT-based texture analysis may play a potential role in studies of osteoporosis. Received: 8 July 1997 / Accepted: 11 May 1998