Alveolar soft part sarcoma of the retroperitoneum: A case report

Alveolar soft part sarcoma is a rare soft tissue tumor with uncertain histogenesis. It is a slow growing tumor with a high rate of metastasis. The tumor is not easily identified as clinical symptoms are not pronounced. The retroperitoneum is a rare location of tumor, with a few cases published in literature. Surgical excision is the mainstay of treatment. Here we describe a rare case of a large retroperitoneal Alveolar soft part sarcoma in a young female with radiological and histopathological findings.     

Prognostic impact of pre-operative albumin on short-term mortality and complications in patients with hip fracture

Low serum albumin may have prognostic value for morbidity and mortality in patients with hip fracture. The primary aim of the study was to evaluate the independent association between low serum albumin (<35 g/l) at hospital admission and short-term (in-hospital) mortality and post-operative complications of patients with hip fracture. We reviewed a prospective population-based cohort of 583 hip fracture patients who had pre-operative albumin values measured at hospital admission in one of the 3 tertiary hospitals in Northern Alberta, Canada. Patients with a primary diagnosis of hip fracture and 65 years or older were included. The primary outcomes were in-hospital mortality and any pre-specified post-operative complication. Mean serum albumin level was 33.8 ± 4.5 g/l (±S.D.), and overall 55% (n = 318) of patients had a low albumin. The in-hospital mortality was 8% (n = 46) and rate of any non-fatal post-operative complication rate was 31/100. Mortality was 11% (n = 35) among those with low albumin levels and 4% (n = 11) for those with normal values (unadjusted odds ratio (OR) 2.86, 95% CI = 1.42-5.74). After multivariate adjustment, the association between low serum albumin and mortality remained large and statistically significant (adjusted OR = 2.44, 95% confidence interval (CI) = 1.17-5.12). Low albumin levels were also significantly associated with post-operative medical complications (adjusted OR = 1.96, 95% CI = 1.36-2.83). We conclude that routine measurement of serum albumin provides valuable prognostic information for treating this frail population.     

Amyloid precursor protein regulates differentiation of human neural stem cells

Although amyloid beta (Abeta) deposition has been a hallmark of Alzheimer's disease (AD), the absence of a phenotype in the beta amyloid precursor protein (APP) knockout mouse, tends to detract our attention away from the physiological functions of APP. Although much attention has been focused on the neurotoxicity of Abeta, many studies suggest the involvement of APP in neuroplasticity. We found that secreted amyloid precursor protein (sAPP) increased the differentiation of human neural stem cells (hNSCs) in vitro, while an antibody-recognizing APP dose-dependently inhibited these activities. With a high dose of sAPP treatment or wild-type APP gene transfection, hNSCs were differentiated into astrocytes rather than neurons. In vivo, hNSCs transplanted into APP-transgenic mouse brain exhibited glial differentiation rather than neural differentiation. Our results suggest that APP regulates neural stem cell biology in the adult brain, and that altered APP metabolism in Down syndrome or AD may have implications for the pathophysiology of these diseases.     

The dexamethasone suppression test in chronic alcoholics with and without depression and its relationship to their hepatic status

Fifty consecutively admitted male alcoholics (mean age = 42.8 +/- 8.5 years) were selected. This study shows objectively that 31/50 chronic alcoholics (62%) were found to be severely depressed (Hamilton Depression Rating Scale (HRS) greater than 22); 12/50 (24%) moderately depressed (HRS = 16-22); and 7/50 (14%) were not depressed (HRS less than 15). According to dexamethasone suppression test (DST) results, 8 out of 50 patients showed escape from suppression with 2 mg dexamethasone while 42/50 showed normal suppression. Depression in alcoholics may be of neurotic type or it may be ethanol-induced reactive depression. Raised cortisol levels and abnormal DST response showed a definite tendency towards normalisation after total abstinence accompanied by clinical improvement of depressive symptomatology. The DST showed improvement on improvement of mood and sleep in these patients during total abstinence. An abnormal DST response in chronic alcoholics seems to be state-related and not trait-dependent; it seems to be a non-specific test for depression in alcoholics. Hepatic status was affected equally in both suppressors and non-suppressors of DST. It is therefore suggested that abnormal DST in alcoholics may be due to the abnormality of the hypothalamo-pituitary-adrenocortical (HPA) axis and not due to abnormal hepatic function or histological status.     

High-resolution MRI vs multislice spiral CT: which technique depicts the trabecular bone structure best?

The purpose of this study was to compare trabecular bone structure parameters obtained from high-resolution magnetic resonance (HRMR) and multislice computed tomography (MSCT) images with those determined in contact radiographs from corresponding specimen sections. High-resolution MR and MSCT images were obtained in 39 distal radius specimens. For HRMR the in-plane spatial resolution was 0.152×0.153 mm² with a slice thickness of 0.9 and 0.3 mm using a 3D T1-weighted spin-echo sequence. For MSCT the resolution was 0.247×0.247 mm² with a collimation of 1 mm. Using a diamond saw, 117 0.9- to 1-mm-thick sections were obtained from these specimens and contact radiographs were acquired. In the corresponding sections structure parameters analogous to bone histomorphometry were determined. Significant correlations between MR- and CT-derived structure parameters and those derived from the contact radiographs were found (p<0.01); r values of up to 0.75 were obtained for HRMR imaging and up to 0.70 for MSCT. On the average, structure parameters showed higher correlations for the MR- than for the CT-derived data. For the MR data the threshold algorithm used for binarizing the images substantially affected these correlations. In conclusion, trabecular bone structure parameters assessed in distal radius HRMR and MSCT images are significantly correlated with those determined in corresponding specimen sections (p<0.01). High-resolution MR-derived structure parameters, however, performed better in the prediction of trabecular bone structure. Electronic Publication     

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.     

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.