Welcome

Recently updated

1. Fulltext Variant GADL1 and response to lithium in bipolar I disorder

   Consortium on Lithium Genetics, Hou L, Heilbronner U, Rietschel M, Kato T, Kuo PH, et al.

   N. Engl. J. Med., 2014 05 08;370(19):1857-9.

   PMID: 24806176 DOI: 10.1056/NEJMc1401817

   MeSH terms: Bipolar Disorder/genetics*; Carboxy-Lyases/genetics*; Female; Humans; Lithium/therapeutic use*; Male; Antimanic Agents/therapeutic use*; Polymorphism, Single Nucleotide*
2. Fulltext Mandatory addiction treatment for people who use drugs: global health and human rights analysis

   Lunze K, Idrisov B, Golichenko M, Kamarulzaman A

   BMJ, 2016 Jun 09;353:i2943.

   PMID: 27284009 DOI: 10.1136/bmj.i2943

   MeSH terms: Humans; Human Rights/standards*; Russia/epidemiology; Global Health; Government Regulation
3. Fulltext Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study

   Qian F, Wang S, Mitchell J, McGuffog L, Barrowdale D, Leslie G, et al.

   J. Natl. Cancer Inst., 2019 Apr 01;111(4):350-364.

   PMID: 30312457 DOI: 10.1093/jnci/djy132

   Abstract

   BACKGROUND: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear.

   METHODS: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants. We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided.

   RESULTS: Observed height was positively associated with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P = 1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P = .47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m2 increase, HR = 0.94, 95% CI = 0.90 to 0.98; P = .007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P = .02). BMI was primarily associated with premenopausal breast cancer.

   CONCLUSION: Height is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management.
4. Phenotypic and molecular dissection of metaplastic breast cancer and the prognostic implications

   McCart Reed AE, Kalaw E, Nones K, Bettington M, Lim M, Bennett J, et al.

   J. Pathol., 2019 02;247(2):214-227.

   PMID: 30350370 DOI: 10.1002/path.5184

   Abstract

   Metaplastic breast carcinoma (MBC) is relatively rare but accounts for a significant proportion of global breast cancer mortality. This group is extremely heterogeneous and by definition exhibits metaplastic change to squamous and/or mesenchymal elements, including spindle, squamous, chondroid, osseous, and rhabdomyoid features. Clinically, patients are more likely to present with large primary tumours (higher stage), distant metastases, and overall, have shorter 5-year survival compared to invasive carcinomas of no special type. The current World Health Organisation (WHO) diagnostic classification for this cancer type is based purely on morphology - the biological basis and clinical relevance of its seven sub-categories are currently unclear. By establishing the Asia-Pacific MBC (AP-MBC) Consortium, we amassed a large series of MBCs (n = 347) and analysed the mutation profile of a subset, expression of 14 breast cancer biomarkers, and clinicopathological correlates, contextualising our findings within the WHO guidelines. The most significant indicators of poor prognosis were large tumour size (T3; p = 0.004), loss of cytokeratin expression (lack of staining with pan-cytokeratin AE1/3 antibody; p = 0.007), EGFR overexpression (p = 0.01), and for 'mixed' MBC, the presence of more than three distinct morphological entities (p = 0.007). Conversely, fewer morphological components and EGFR negativity were favourable indicators. Exome sequencing of 30 cases confirmed enrichment of TP53 and PTEN mutations, and intriguingly, concurrent mutations of TP53, PTEN, and PIK3CA. Mutations in neurofibromatosis-1 (NF1) were also overrepresented [16.7% MBCs compared to ∼5% of breast cancers overall; enrichment p = 0.028; mutation significance p = 0.006 (OncodriveFM)], consistent with published case reports implicating germline NF1 mutations in MBC risk. Taken together, we propose a practically minor but clinically significant modification to the guidelines: all WHO_1 mixed-type tumours should have the number of morphologies present recorded, as a mechanism for refining prognosis, and that EGFR and pan-cytokeratin expression are important prognostic markers. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
5. Case 263: Malaysian Charm Needles (Susuk)

   Martin JL, Vlachou PA

   Radiology, 2019 03;290(3):843-847.

   PMID: 30789811 DOI: 10.1148/radiol.2019162113

   Abstract

   History A 58-year-old woman was seen in the rheumatology clinic for bilateral wrist and knee pain that was unresponsive to physiotherapy and intra-articular steroid injections. Remote fracture of the left tibia from a motor vehicle collision was reported and was previously treated with conservative management. Serologic work-up for inflammatory disease was negative. The patient reported no prior surgical or medical history. Social history revealed remote immigration from Malaysia. Radiographs of the hands and knees were obtained.
6. Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort

   Assi N, Rinaldi S, Viallon V, Dashti SG, Dossus L, Fournier A, et al.

   Int. J. Cancer, 2020 Feb 01;146(3):759-768.

   PMID: 30968961 DOI: 10.1002/ijc.32324

   Abstract

   Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by partial least square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor-positive tumors with respectively TE = 1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-standard deviation (1-SD) increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE = 1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone was associated with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association.
7. Phytochemical and anti-inflammatory properties of Scurrula ferruginea (Jack) Danser parasitising on three different host plants elucidated by NMR-based metabolomics

   Hong X, Mat Isa N, Fakurazi S, Safinar Ismail I

   Phytochem Anal, 2020 Jan;31(1):15-27.

   PMID: 31243835 DOI: 10.1002/pca.2861

   Abstract

   INTRODUCTION: Scurrula ferruginea (Jack) Danser is a hemi-parasitic shrub that is widely used as a traditional herbal medicine.

   OBJECTIVES: To elucidate the anti-inflammatory activity of S. ferruginea parasitising on three different hosts of Vitex negundo L., Micromelum minutum (G. Forst.) Wight & Arn. and Tecoma stans (L.) Juss ex HBK., as well as, to determine the metabolite differences related to their anti-inflammatory properties.

   MATERIALS AND METHODS: Two plant parts of S. ferruginea, stems and leaves, were extracted in water. The freeze-dried stem of S. ferruginea grown on T. stans was liquid-liquid partitioned into several solvents. Their potential anti-inflammatory activity was assessed via inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS) and interferon-γ (IFN-γ)-induced RAW 264.7 macrophage cells. The metabolite variation was examined using proton nuclear magnetic resonance (1 H-NMR) combined with multivariate data analysis (MVDA).

   RESULTS: Scurrula ferruginea stems parasitising on T. stans and V. negundo which were freeze dried exhibited higher anti-inflammatory activity with IC50 values of 114.47 ± 2.96 and 118.87 ± 2.31 μg/mL, respectively. The mid-polar ethyl acetate fraction of S. ferruginea hosted on T. stans displayed the highest NO inhibition with 84.80 ± 0.45% at 200 μg/mL. Principal component analysis (PCA) indicated notable and clear discriminations among the different plant parts and host plants based on the identified metabolites. Furthermore, partial least squares (PLS) regression model suggested the anti-inflammatory bioactivity might be associated with the presence of choline, isoleucine, catechin, leucine and chlorogenic acid.

   CONCLUSION: This study suggests S. ferruginea could serve as a potential anti-inflammatory agent, highlighting the importance of T. stans as the host plant.
8. Early Pleistocene enamel proteome from Dmanisi resolves Stephanorhinus phylogeny

   Cappellini E, Welker F, Pandolfi L, Ramos-Madrigal J, Samodova D, Rüther PL, et al.

   Nature, 2019 10;574(7776):103-107.

   PMID: 31511700 DOI: 10.1038/s41586-019-1555-y

   Abstract

   The sequencing of ancient DNA has enabled the reconstruction of speciation, migration and admixture events for extinct taxa1. However, the irreversible post-mortem degradation2 of ancient DNA has so far limited its recovery-outside permafrost areas-to specimens that are not older than approximately 0.5 million years (Myr)3. By contrast, tandem mass spectrometry has enabled the sequencing of approximately 1.5-Myr-old collagen type I4, and suggested the presence of protein residues in fossils of the Cretaceous period5-although with limited phylogenetic use6. In the absence of molecular evidence, the speciation of several extinct species of the Early and Middle Pleistocene epoch remains contentious. Here we address the phylogenetic relationships of the Eurasian Rhinocerotidae of the Pleistocene epoch7-9, using the proteome of dental enamel from a Stephanorhinus tooth that is approximately 1.77-Myr old, recovered from the archaeological site of Dmanisi (South Caucasus, Georgia)10. Molecular phylogenetic analyses place this Stephanorhinus as a sister group to the clade formed by the woolly rhinoceros (Coelodonta antiquitatis) and Merck's rhinoceros (Stephanorhinus kirchbergensis). We show that Coelodonta evolved from an early Stephanorhinus lineage, and that this latter genus includes at least two distinct evolutionary lines. The genus Stephanorhinus is therefore currently paraphyletic, and its systematic revision is needed. We demonstrate that sequencing the proteome of Early Pleistocene dental enamel overcomes the limitations of phylogenetic inference based on ancient collagen or DNA. Our approach also provides additional information about the sex and taxonomic assignment of other specimens from Dmanisi. Our findings reveal that proteomic investigation of ancient dental enamel-which is the hardest tissue in vertebrates11, and is highly abundant in the fossil record-can push the reconstruction of molecular evolution further back into the Early Pleistocene epoch, beyond the currently known limits of ancient DNA preservation.

   MeSH terms: Amino Acid Sequence; Animals; Bayes Theorem; Dental Enamel/metabolism*; Fossils*; Humans; Male; Perissodactyla/classification*; Perissodactyla/genetics*; Perissodactyla/metabolism; Phosphorylation/genetics; Phylogeny*; Proteome/analysis; Proteome/genetics*; Amino Acid Motifs; Proteomics*; History, Ancient; DNA, Ancient/analysis*
9. Gelam honey promotes ex vivo corneal fibroblasts wound healing

   Md Yusof A, Abd Ghafar N, Kamarudin TA, Chua KH, Azmi MF, Ng SL, et al.

   Cytotechnology, 2019 Dec;71(6):1121-1135.

   PMID: 31606844 DOI: 10.1007/s10616-019-00349-8

   Abstract

   This study evaluated the effects of Gelam honey (GH) on ex vivo corneal fibroblast ulcer model via wound healing assay, gene expression and immunocytochemistry. Corneal fibroblasts from New Zealand white rabbits were culture expanded. The corneal fibroblast wound healing capacity was observed by creating a circular wound onto confluent monolayer cells cultured in basal medium (BM), BM with GH, serum-enriched basal medium (BMS) and BMS with GH respectively. Wound healing assay and phenotypic characterization of the corneal fibroblast were performed at different stages of wound closure. Expression of aldehyde dehydrogenase (ALDH), vimentin, α-smooth muscle actin (α-SMA), lumican, collagen I and matrix metalloproteinase 12 (MMP 12) were measured at day 1, day 3 and complete wound closure day. Corneal fibroblast cultured in BMS with GH demonstrated the fastest wound closure, at day 5 post wounding. The gene expressions of ALDH and vimentin were higher than control groups while α-SMA expression was lower, in GH enriched media. The expressions of lumican, collagen I and MMP 12 were also higher in cells cultured in GH enriched media compared to the control groups. GH was shown to promote in vitro corneal fibroblast wound healing and may be a potential natural adjunct in the treatment of corneal wound.
10. Fulltext Social Media in the Urology Practice | Opinion: NO

    Da Silva RD, Leow JJ, Abidin ZA, Linden-Castro E, Castro EIB, Blanco LT, et al.

    Int Braz J Urol, 2019 10 19;45(5):882-888.

    PMID: 31626517 DOI: 10.1590/S1677-5538.IBJU.2019.05.04

    MeSH terms: Confidentiality; Humans; Physician-Patient Relations; Practice Patterns, Physicians'/trends; Urology/methods; Urology/trends*; Health Communication/methods; Health Communication/trends; Social Media/trends*