bluuebunny/crossref_metadata_2025 huggingface dataset:
Central adiponectin induces trabecular bone mass partly through epigenetic downregulation of cannabinoid receptor CB1
Authors: Jiang Hua , Wu Yuwei , Valverde Paloma , Murray Dana , Tang Jin , Yao Qi , Han Qianqian , Zhang Jin , Zhang Lan , Sui Lei , Tang Yin , Tu Qisheng , Chen Jake
Published: November 2018

Central adiponectin (APN) in either the globular (gAPN) or full‐length forms decreases sympathetic tone and increases trabecular bone mass in mice through the hypothalamus. It is known that cannabinoid type‐1 (CB1) receptors are expressed in the hypothalamic ventromedial nucleus and participate in energy metabolism by controlling sympathetic activity. However, whether central APN could influence endocannabinoid signaling through CB1 receptor to regulate bone metabolism has not been characterized. Here we demonstrate that gAPN downregulated CB1 expression in embryonic mouse hypothalamus N1 cells in vitro. gAPN intracerebroventricular (icv) infusions also decreased hypothalamic CB1 expression and bone formation parameters in APN‐knockout (APN‐KO) and wild‐type mice. Most importantly, mice pretreated with icv infusions with the CB1 receptor agonist arachidonyl‐2′‐chloroethylamine or antagonist rimonabant attenuated or enhanced respectively central APN induction of bone formation. We then investigated whether epigenetic signaling mechanisms were involved in the downregulation of hypothalamic CB1 expression by gAPN. We found gAPN enhanced expression levels of various histone deacetylases (HDACs), especially HDAC5. Furthermore, chromatin immunoprecipitation assays revealed HDAC5 bound to the transcriptional start site transcription start site 2 region of the CB1 promoter. In summary, our study identified a possible novel central APN‐HDAC5‐CB1 signaling mechanism that promotes peripheral bone formation through epigenetic regulation of hypothalamic CB1 expression.
Human breast cancer decellularized scaffolds promote epithelial‐to‐mesenchymal transitions and stemness of breast cancer cells in vitro
Authors: Liu Gang , Wang Biao , Li Shubin , Jin Qin , Dai Yanfeng
Published: November 2018

Breast cancer, with unsatisfactory survival rates, is the leading cause of cancer‐related death in women worldwide. Recent advances in the genetic basis of breast cancer have benefitted the development of gene‐based medicines and therapies. Tissue engineering technologies, including tissue decellularizations and reconstructions, are potential therapeutic alternatives for cancer research and tissue regeneration. In our study, human breast cancer biopsies were decellularized by a detergent technique, with sodium lauryl ether sulfate (SLES) solution, for the first time. And the decellularization process was optimized to maximally maintain tissue microarchitectures and extracellular matrix (ECM) components with minimal DNA compounds preserved. Histology analysis and DNA quantification results confirmed the decellularization effect with maximal genetic compounds removal. Quantification, immunofluorescence, and histology analyses demonstrated better preservation of ECM components in 0.5% SLES‐treated scaffolds. Scaffolds seeded with MCF‐7 cells demonstrated the process of cell recellularization in vitro, with increased cell migration, proliferation, and epithelial‐to‐mesenchymal transition (EMT) process. When treated with 5‐fluorouracil, the expressions of stem cell markers, including Oct4, Sox2, and CD49F, were maximally maintained in the recellularized scaffold with decreased apoptosis rates compared with monolayer cells. These results showed that the decellularized breast scaffold model with SLES treatments would help to simulate the pathogenesis of breast cancer in vitro. And we hope that this model could further accelerate the development of effective therapies for breast cancer and benefit drug screenings.
Inhibition of miR‐124 improves neonatal necrotizing enterocolitis via an MYPT1 and TLR9 signal regulation mechanism
Authors: Yin Yiyu , Qin Zhenfang , Xu Xiaobing , Liu Xu , Zou Huaxin , Wu Xiaole , Cao Junhua
Published: November 2018

Backgrounds

Necrotizing enterocolitis (NEC) was one of the main causes of morbidity and mortality in neonates. Our objective was to detect the mechanism of miR‐124 in small bowel tissues of NEC.

Methods

Hematoxylin and eosin (H&E) staining was used to detect the repair of the damaged tissues in rat NEC model. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to evaluate the cell apoptosis level in intestinal tissue. Reverse transcription polymerase chain reaction (RT‐PCR) was used to detect the messenger RNA (mRNA) expression level of miR‐124, Rho‐associated coiled‐coil‐containing protein kinase 1 (ROCK1), myosin phosphatase target subunit 1 (MYPT1), and Toll‐like receptor 9 (TLR9) in NEC tissues and IEC‐6 cells. Luciferase reporter assay was used to verify whether ROCK1 is a direct target of miR‐124.

Results

miR‐124 was overexpressed in the NEC tissues, while ROCK1 and MYPT1 was downregulated in the NEC tissues. Inhibition of miR‐124, suppressed the intestinal cell apoptosis and promoted the expression of ROCK1 and MYPT1. What is more, overexpression of miR‐124 could inhibit the expression of ROCK1, TLR9, and MYPT1. Luciferase assay confirmed that miR‐124 can regulate the transcriptional activity of ROCK1 through binding its 3′‐UTR region.

Conclusion

miR‐124 was a promoter of NEC, which promotes the intestine cell apoptosis and inflammatory cell infiltration through the inhibition of TLR9 expression by targeting ROCK1.
Cell fate regulation by reticulon‐4 in human prostate cancers
Authors: Zhao Hu , Su Weipeng , Zhu Changyan , Zeng Tengyue , Yang Shunliang , Wu Weizhen , Wang Dong
Published: November 2018

Reticulon‐4 (RTN4), a reticulon family protein localized in the endoplasmic reticulum, is reported to be involved in multiple physiological processes like neuroendocrine secretion and membrane trafficking in neuroendocrine cells. Previous studies have presented a great potential of RTN4 for the treatment of autoimmune‐mediated demyelinating diseases and spinal cord injury regeneration. While interaction with Bcl‐2 and Bcl‐2‐like family in apoptosis modulation implicated its possible role in various human cancers. However, the investigation of this gene in prostate cancer is mainly ignored. Here in our current study, we focused on its role in prostate cancer and found that RTN4 DNA copy numbers were higher in prostate cancer than normal prostate gland while its RNA and protein expressions were relatively lower. Chromosomal neighbor gene EML6 had similar expression patterns with RTN4 in prostate cancer tissues and cell lines, and further research found that they could be both targeted by miR‐148a‐3p. Lentivirus‐mediated RTN4 overexpression potently inhibited DU145 and LNCaP cells proliferation. Cell cycle was blocked in G2/M phase and significant cell senescence was observed in RTN4 overexpressed prostate cancer cells. Finally, interaction networks in the normal prostate gland and cancer tissues further revealed that RTN4 maybe phosphorylated by MAPKAPK2 and FYN at tyrosine 591 and serine 107, respectively. All these results implied that RTN4 might somehow participate in prostate tumor progression, and this elicits possibility to develop or identify selective agents targeting RTN4 for prostate cancer therapy.
Embryo quality, and not chromosome nondiploidy, affects mitochondrial DNA content in mouse blastocysts
Authors: Jing Ying , Li Li , Li Yuan‐Yuan , Ouyang Ying‐Chun , Sun Qing‐Yuan , Zhang Cui‐Lian , Li Rong
Published: November 2018

It has been shown recently that there is premature mitochondria biosynthesis in blastocysts from older women whose egg or embryo quality is poor and that aneuploid blastocysts also have a high number of mitochondrial DNA (mtDNA) copies. Whether nondiploidy/aneuploidy or reduced egg or embryo quality causes premature mitochondrial biosynthesis is not known. This study constructed haploid, diploid, triploid, and tetraploid blastocysts by parthenogenetic activation, intracytoplasmic sperm injection with one or two sperm heads, blastomere electrofusion, respectively, and generated reduced cytoplasm quality embryos from diabetic mouse and in vitro fertilization of aged oocytes, and examined whether nondiploidy or reduced cytoplasm quality causes premature mitochondrial biosynthesis. MtDNA numbers of each blastocyst from different models were tested by absolute quantitative real‐time polymerase chain reaction. It was found that mtDNA content in preimplantation embryos was not associated with their chromosome ploidy, while mtDNA copy numbers in embryos with suboptimal quality were increased. Therefore, it might be the reduced cytoplasmic quality, and not chromosome nondiploidy, that causes premature mitochondria biosynthesis in blastocysts.
Cholinergic activity regulates the secretome of epicardial adipose tissue: Association with atrial fibrillation
Authors: Couselo‐Seijas Marinela , López‐Canoa Jose N. , Agra‐Bermejo Rosa M. , Díaz‐Rodriguez Esther , Fernandez Angel L. , Martinez‐Cereijo Jose M. , Durán‐Muñoz Dario , Bravo Susana B. , Velo Alba , González‐Melchor Laila , Fernández‐López Xesus A. , Martínez‐Sande Jose L. , García‐Seara Javier , González‐Juanatey Jose R. , Rodriguez‐Mañero Moises , Eiras Sonia
Published: November 2018

Botulinum toxin injection on epicardial fat, which inhibits acetylcholine (ACh) release, reduced the presence of atrial fibrillation (AF) in patients after heart surgery. Thus, we wanted to study the profile of the released proteins of epicardial adipose tissue (EAT) under cholinergic activity (ACh treatment) and their value as AF predictors. Biopsies, explants, or primary cultures were obtained from the EAT of 85 patients that underwent open heart surgery. The quantification of muscarinic receptors (mAChR) by real‐time polymerase chain reaction or western blot showed their expression in EAT. Moreover, mAChR Type 3 was upregulated after adipogenesis induction (p < 0.05). Cholinergic fibers in EAT were detected by vesicular ACh transporter levels and/or acetylcholinesterase activity. ACh treatment modified the released proteins by EAT, which were identified by nano‐high‐performance liquid chromatography and TripleTOF analysis. These differentially released proteins were involved in cell structure, inflammation, or detoxification. After testing the plasma levels of alpha‐defensin 3 (inflammation‐involved protein) of patients who underwent open heart surgery (
n = 24), we observed differential levels between the patients who developed or did not develop postsurgery AF (1.58 ± 1.61 ng/ml vs. 6.2 ± 5.6 ng/ml;
p < 0.005). The cholinergic activity on EAT might suggest a new mechanism for studying the interplay among EAT, autonomic nervous system dysfunction, and AF.
Effects of nebulized N­‐acetylcystein on the expression of HMGB1 and RAGE in rats with hyperoxia‐­induced lung injury
Authors: Qiao Junying , Chen Lixia , Huang Xianjie , Guo Feifei
Published: November 2018

Objective

To investigate the role of high mobility group box 1 (HMGB1) and receptor for advanced glycation end product (RAGE) in the lungs of hyperoxia‐induced rats and the effect of N‐­acetlycystein (NAC).

Methods

A model of hyperoxic lung injury was established, rats in the NAC intervention, and control, hyperoxia group were given nebulized NAC aerosol, nebulized same volume of saline once a day for 7 consecutive days, respectively. Wet/dry (
W/
D) ratio of the lungs was determined to evaluate the edema of the lung tissues. Conventional hematoxylin–eosin (HE) staining was used to observe the pathological changes of lung tissues. Immunohistochemical staining was used to investigate the expression of HMGB1 and RAGE in the lung tissues. Quantitative reverse‐transcription polymerase chain reaction and western blot analysis were used to measured the changes in the messenger RNA (mRNA) and protein expression of HMGB1 and RAGE, respectively.

Results

Weight gain of the rats in the hyperoxia group was significantly slower than that in the control group and intervention group (p < 0.05). HE staining results showed lung tissues in the hyperoxia group were severely damaged compared with control group. W/D ratio in hyperoxia group was significantly higher than that in control group and intervention group (p < 0.05). Protein and mRNA expression of HMGB1 and RAGE in the hyperoxia group were significantly higher than control group and intervention group (p < 0.05).

Conclusion

HMGB1 and RAGE were involved in the pathogenesis of hyperoxia‐induced lung injury, inhalation of NAC might alleviate hyperoxia‐induced lung injury by regulating the expression of HMGB1 and RAGE.
Preparation of adriamycin gelatin microsphere‐loaded decellularized periosteum that is cytotoxic to human osteosarcoma cells
Authors: Chen Chuan , Dong Jianghui , Chen Hong , Wang Xin , Mei Jin , Wang Liping , Xian Cory J
Published: November 2018

The purpose of this study was to develop a novel approach to treat bone osteosarcoma using a multipurpose scaffold aiming for local drug delivery. The slowly releasing microspheres was designed to deliver the chemotherapy drug adriamycin (ADM) and a decellularized (D) periosteum scaffold (which is known to be able to promote bone regeneration) was used to carry these microspheres. D‐periosteum was obtained by physical and chemical decellularization. Histological results showed that the cellular components were effectively removed. The D‐periosteum showed an excellent cytocompatibility and the ability to promote adhesion and growth of fibroblasts. Two kinds of slowly releasing microspheres, adriamycin gelatin microspheres (ADM‐GMS) and adriamycin poly (dl‐lactide‐co‐glycolide) gelatin microspheres (ADM‐PLGA‐GMS), were prepared and anchored to D‐periosteum, resulting in two types of drug‐releasing regenerative scaffolds. The effectiveness of these two scaffolds in killing human osteosarcoma cells was tested by evaluating cell viability overtime of the cancer cells cultured with the scaffolds. In summary, a gelatin/decellularized periosteum‐based biologic scaffold material was designed aiming for local delivery of chemotherapy drugs for osteosarcoma, with the results showing ability of the scaffolds in sustaining release of the cancer drug and in suppressing growth of the cancer cells in vitro.
Induced pluripotent stem cell‐derived extracellular vesicles: A novel approach for cell‐free regenerative medicine
Authors: Taheri Behnaz , Soleimani Masoud , Fekri Aval Sedigheh , Esmaeili Elaheh , Bazi Zahra , Zarghami Nosratollah
Published: November 2018

In recent years, induced pluripotent stem cells (iPSCs) have been considered as a promising approach in the field of regenerative medicine. iPSCs can be generated from patients’ somatic cells and possess the potential to differentiate, under proper conditions, into any cell type. However, the clinical application of iPS cells is restricted because of their tumorigenic potential. Recent studies have indicated that stem cells exert their therapeutic benefit via a paracrine mechanism, and extracellular vesicles have been demonstrated that play a critical role in this paracrine mechanism. Due to lower immunogenicity, easier management, and presenting no risk of tumor formation, in recent years, researchers turned attention to exosomes as potential alternatives to whole‐cell therapy. Application of exosomes derived from iPSCs and their derived precursor provides a promising approach for personalized regenerative medicine. This study reviews the physiological functions of extracellular vesicles and discusses their potential therapeutic benefit in regenerative medicine.
Association between miRNAs expression and signaling pathways of oxidative stress in diabetic retinopathy
Authors: Satari Mahbobeh , Aghadavod Esmat , Mobini Moein , Asemi Zatollah
Published: November 2018

Diabetic retinopathy (DR) is a major cause of vision reduction in diabetic patients. Hyperglycemia is a known instigator for the development of DR, even though the role of oxidative stress pathways in the pathogenesis of DR is established. The studies indicate that microRNAs (miRNAs) are significant to the etiology of DR; changes in miRNAs expression levels may be associated with onset and progression of DR. In addition, miRNAs have emerged as a useful disease marker due to their availability and stability in detecting the severity of DR. The relationship between miRNAs expression levels and oxidative stress pathways has been investigated in several studies. The aim of this study is the examination of function and expression levels of target miRNAs in oxidative stress pathway and pathogenesis of diabetic retinopathy.
Poly (3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) improved osteogenic differentiation of the human induced pluripotent stem cells while considered as an artificial extracellular matrix
Authors: Hosseini Fatemeh Sadat , Soleimanifar Fatemeh , Aidun Amir , Enderami Seyedeh Elnaz , Saburi Ehsan , Marzouni Hadi Zare , Khani Mohammad‐Mehdi , Khojasteh Arash , Ardeshirylajimi Abdolreza
Published: November 2018

Cocell polymers can be the best implants for replacing bone defects in patients. The pluripotent stem cells produced from the patient and the nanofibrous polymeric scaffold that can be completely degraded in the body and its produced monomers could be also usable are the best options for this implant. In this study, electrospun poly (3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) nanofibers were fabricated and characterized and then osteogenic differentiation of the human‐induced pluripotent stem cells (iPSCs) was investigated while cultured on PHBV scaffold. MTT results showed that cultured iPSCs on PHBV proliferation were increased compared to those cultured on tissue culture polystyrene (TCPS) as the control. Alkaline phosphatase (ALP) activity and calcium content were also significantly increased in iPSCs cultured on PHBV compared to the cultured on TCPS under osteogenic medium. Gene expression evaluation demonstrated that Runx2, collagen type I, ALP, osteonectin, and osteocalcin were upregulated in iPSCs cultured on PHBV scaffold in comparison with those cultured on TCPS for 2 weeks. Western blot analysis have shown that osteocalcin and osteopontin expression as two major osteogenic markers were increased in iPSCs cultured on PHBV scaffold. According to the results, nanofiber‐based PHBV has a promising potential to increase osteogenic differentiation of the stem cells and iPSCs‐PHBV as a cell‐co‐polymer construct demonstrated that has a great efficiency for use as a bone tissue engineered bioimplant.
Long noncoding RNA NEAT1 promotes the growth of human retinoblastoma cells via regulation of miR‐204/CXCR4 axis
Authors: Zhong Wei , Yang Jingpu , Li Miyang , Li Lin , Li Aipeng
Published: November 2018

Retinoblastoma (RB) is an aggressive eye cancer of infancy and childhood with high mortality. Studies have shown that long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) is closely related to the progression of multiple cancers. However, its role in RB remains unknown. This study aimed to investigate the role and underlying mechanism of NEAT1 in RB. We first detected the expression of NEAT1 in human RB tissues and cell lines. The effects of NEAT1 on the proliferation, migration, and apoptosis of RB cells were analyzed by loss‐of‐function. The underlying mechanism of NEAT1 in RB was mainly focused on the microRNA 204/C‐X‐C chemokine receptor type 4 (miR‐204/CXCR4) axis. In addition, the role and mechanism of NEAT1 in RB were further evaluated in a mouse xenograft tumor model. We found NEAT1 and CXCR4 expression levels were elevated, whereas miR‐204 expression was decreased in RB tissues and cells. Downregulation of NEAT1 significantly decreased the proliferation and migration but promoted the apoptosis of RB cells. NEAT1 functioned as a competing endogenous RNA for miR‐204 to regulate CXCR4 expression. Knockdown of NEAT1 suppressed the tumor volume, tumor weight, and CXCR4 expression, whereas increased miR‐204 expression in mice. In conclusion, NEAT1 promotes the development of RB via miR‐204/CXCR4 axis, which provides a new target for the treatment of RB disease.
EW‐7197 prevents ulcerative colitis‐associated fibrosis and inflammation
Authors: Binabaj Maryam M. , Asgharzadeh Fereshteh , Avan Amir , Rahmani Farzad , Soleimani Atena , Parizadeh Mohammad R. , Ferns Gordon A. , Ryzhikov Mikhail , Khazaei Majid , Hassanian Seyed M.
Published: November 2018

EW‐7197 is a transforming growth factor‐β type I receptor kinase inhibitor with potential anti‐inflammatory and antifibrotic properties. Here, we investigate the potential therapeutic effects of EW‐7197 in a murine model of ulcerative colitis. EW‐7197 attenuated the colitis disease activity index by improving rectal bleeding, body weight, and degree of stool consistency. EW‐7197 also reduced colorectal tissue damage and the colon histopathological score by reducing crypt loss, mucosal damage, and tissue inflammation. Moreover, EW‐7197 appeared to ameliorate the inflammatory and fibrotic responses by reducing oxidative stress, reducing submucosal edema and inflammatory cell infiltration, downregulating proinflammatory and pro‐fibrotic genes, and inhibiting excessive collagen deposition in inflamed and fibrotic ulcerative colitis tissues. These results suggest that EW‐7197 has potentially useful therapeutic properties against colitis, with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in patients with colitis.
Diversity and Stigmatized Identity in the Marketplace: Introduction to Research Dialogue
Authors: Shavitt Sharon
Published: November 2018

This article is part of a Research Dialogue: Chaney et al. (2019): https://doi.org/10.1002/jcpy.1075 Wooten & Rank‐Christman (2019): https://doi.org/10.1002/jcpy.1076 Lamberton (2019): https://doi.org/10.1002/jcpy.1077 Sanchez et al. (2019): https://doi.org/10.1002/jcpy.1078
A Facile Synthesis of Novel (Z)‐ethyl‐3‐(5‐substituted‐1‐alkyl/aryl‐1H‐indol‐3‐yl)‐2‐(1H‐tetrazol‐5‐yl)acrylate
Authors: Bakkolla Mahesh Goud , Taduri Ashok Kumar , Bhoomireddy Rama Devi
Published: November 2018

A novel route was developed for synthesis of high potential 1H‐tetrazoles by using conventional method. Tetrazole scaffold is a promising pharmacophore fragment, frequently used in the development of various novel drugs. Here, the novel (Z)‐3‐(N‐alkyl‐indol‐3‐yl)‐2‐(1H‐tetrazole‐5‐yl)acrylates 5 (a–i) have been synthesized from (Z)‐ethyl‐3‐(1H‐indol‐3‐yl)2‐(1H‐tetrazol‐5‐yl)acrylates 4 (a–c) by using various alkylating agents such as Dimethyl Sulphate (DMS), Diethyl Sulphate (DES), and benzyl chloride; 4 (a–c) were synthesized from sodium azide in the presence of copper sulfate in dimethylformamide; 3 (a–c) have been prepared by Knoevenagel condensation of indole‐3‐carbaldehyde 1 (a–c) and ethylcyanoacetate 2 in the presence of L‐Proline as a catalyst at room temperature in ethanol for an hour. This is an efficient and clean click chemistry method that has various advantages such as easy workup, higher yields, shorter reaction times, and more economical.
Synthesis of Ethyl 2‐Amino‐4‐benzoyl‐5‐oxo‐5,6‐dihydro‐4H‐pyrano[3,2‐c]quinoline‐3‐carboxylates by a One‐pot, Three‐Component Reaction in the Presence of TPAB
Authors: Poursattar Marjani Ahmad , Khalafy Jabbar , Farajollahi Ayda
Published: November 2018

In this research, in order to synthesize a series of ethyl 2‐amino‐4‐benzoyl‐5‐oxo‐5,6‐dihydro‐4H‐pyrano[3,2‐c]quinoline‐3‐carboxylates, a green and an efficient method is proposed through one‐pot three‐component reaction of substituted arylglyoxals, ethyl cyanoacetate, and 4‐hydroxyquinolin‐2(1H)‐one in the presence of terapropylammonium bromide as a catalyst in good yields. All synthesized new substances were characterized by FTIR, 1H‐NMR, and 13C‐NMR spectral data and elemental analysis.
Copper Catalyzed Synthesis of Thiomorpholine Derivatives: A New Entry of Multicomponent Reaction Between Terminal Alkynes, Isothiocyanates, and Aziridines
Authors: Samzadeh‐Kermani Alireza
Published: November 2018

Copper acetylide was reacted with isothiocyanate and aziridines to form 1,4‐thiomorpholine derivatives. Reaction outcome depends highly on the reaction conditions and the particular solvent employed. Optimum conditions are developed using copper iodide in hexafluoro‐2‐isopropanol at 60°C. Both the alkyl‐substituted and aryl‐substituted aziridines and terminal alkynes were studied.
Neonatal and infant diagnostic HIV‐PCR uptake and associations during three sequential policy periods in Cape Town, South Africa: a longitudinal analysis
Authors: Kalk Emma , Kroon Max , Boulle Andrew , Osler Meg , Euvrard Jonathan , Stinson Kathryn , Timmerman Venessa , Davies Mary‐Ann
Published: November 2018

Introduction

To strengthen the early infant diagnosis (EID) programmes and timeously identify and treat HIV‐infected infants, birth HIV‐PCR for some/all infants has been recommended in the Western Cape, South Africa since 2014. Operational data on the implementation of such programmes in low‐ and middle‐income countries are limited.

Methods

Utilizing the electronic records platform at primary care facilities, we developed an electronic register which consolidated obstetric and HIV‐related data, allowing us to track a cohort of HIV‐infected/exposed mother/infant dyads longitudinally from antenatal care through delivery to infant HIV‐PCR. We assessed guideline implementation and impact on EID of three sequential EID policies in a referral chain of facilities in Cape Town (primary‐tertiary care). Birth HIV‐PCR was indicated in period 1 if symptomatic; period 2 if meeting high‐risk criteria for transmission; and period 3 for all HIV‐exposed neonates.

Results

We enrolled 2012 HIV‐exposed infants; 89.2% had at least one HIV‐PCR at any point. The majority of birth tests were performed in hospital versus primary care regardless of policy period. Almost half of all infants (47.9%) had at least one high‐risk criterion for vertical infection; of these, 39.7% had a birth test. Infants with more risk factors were more likely to have birth EID. Receipt of a birth HIV‐PCR significantly reduced the likelihood of receiving a follow‐up test at six to ten weeks, even after adjusting for potential confounders (aOR 0.18 (0.12 to 0.26)). The proportion of infants tested at six to ten weeks old dropped from 92.9% (period 1) to 80.2% in period 3 and those receiving birth HIV‐PCR increased, peaking at 67.4% during period 3. The proportion of positive birth tests was highest (2.9%) when birth tests were restricted to infants meeting high‐risk criteria, with a low proportion positive for the first time at six to ten weeks. During period 3, the proportion positive at six to ten weeks was high (2.4%), highlighting the importance of follow‐up to detect intrapartum and early postpartum infections.

Conclusions

Over all policy periods, EID guidelines were incompletely implemented across all levels of care but especially in primary care. Birth HIV‐PCR reduced return for follow‐up testing, such follow‐up testing is critical for the effectiveness of the programme.
Buprenorphine: Therapeutic potential beyond substance abuse
Authors: Velasquez Stephani , Rappaport Jay
Published: November 2018

Discussion of buprenorphine and its potential utility for the treatment of inflammatory disorders.
Gene expression profiling of human tissue-resident immune cells: Comparing blood and liver
Authors: Boeijen Lauke L , van Oord Gertine W , Hou Jun , van der Heide-Mulder Marieke , Gaggar Anuj , Li Li , Fletcher Simon P , de Knegt Robert J , Boonstra André
Published: November 2018

In this study, we describe a method to reliably characterize intrahepatic leukocyte populations using flow cytometry and next-generation RNA sequencing on fresh human liver biopsies. Over the last decades, immune responses of viral hepatitis patients, and of other liver diseases, have been incompletely characterized. Most studies include peripheral blood samples only, foregoing the possibility to investigate the site of inflammation directly. Here, we show that with an optimized protocol that combines cell sorting and RNA sequencing, we can perform a side by side comparison of both intrahepatic and peripheral immune cells. Using core liver biopsies from chronic hepatitis B virus patients, we show that the expression levels of IFN-stimulated genes and leukocyte-specific genes are markedly different in the liver compartment as compared to the peripheral blood. These observations emphasize the need to sample the liver directly. The variation of gene expression profiles in these chronic hepatitis B patients was considerable, despite the uniform treatment with nucleotide analogs and absence of liver inflammation in these patients. Finally, we show that this method can provide a detailed characterization of previously undetected liver-specific effects of novel candidate therapeutic compounds.
Volatile compounds profiling by using proton transfer reaction‐time of flight‐mass spectrometry (PTR‐ToF‐MS). The case study of dark chocolates organoleptic differences
Authors: Deuscher Zoé , Andriot Isabelle , Sémon Etienne , Repoux Marie , Preys Sébastien , Roger Jean‐Michel , Boulanger Renaud , Labouré Hélène , Le Quéré Jean‐Luc
Published: November 2018

Direct‐injection mass spectrometry (DIMS) techniques have evolved into powerful methods to analyse volatile organic compounds (VOCs) without the need of chromatographic separation. Combined to chemometrics, they have been used in many domains to solve sample categorization issues based on volatilome determination. In this paper, different DIMS methods that have largely outperformed conventional electronic noses (e‐noses) in classification tasks are briefly reviewed, with an emphasis on food‐related applications. A particular attention is paid to proton transfer reaction mass spectrometry (PTR‐MS), and many results obtained using the powerful PTR‐time of flight‐MS (PTR‐ToF‐MS) instrument are reviewed. Data analysis and feature selection issues are also summarized and discussed. As a case study, a challenging problem of classification of dark chocolates that has been previously assessed by sensory evaluation in four distinct categories is presented. The VOC profiles of a set of 206 chocolate samples classified in the four sensory categories were analysed by PTR‐ToF‐MS. A supervised multivariate data analysis based on partial least squares regression‐discriminant analysis allowed the construction of a classification model that showed excellent prediction capability: 97% of a test set of 62 samples were correctly predicted in the sensory categories. Tentative identification of ions aided characterisation of chocolate classes. Variable selection using dedicated methods pinpointed some volatile compounds important for the discrimination of the chocolates. Among them, the CovSel method was used for the first time on PTR‐MS data resulting in a selection of 10 features that allowed a good prediction to be achieved. Finally, challenges and future needs in the field are discussed.
Protective effect of silkworm pupa oil on hydrochloric acid/ethanol‐induced gastric ulcers
Authors: Long Xingyao , Zhao Xin , Wang Wei , Zhang Yu , Wang Hongwei , Liu Xinqi , Suo Huayi
Published: November 2018

BACKGROUND

Silkworm pupae are a traditional Chinese food, rich in various saturated and unsaturated fatty acids. Unsaturated fatty acids have a certain protective effect against oxidative damage. The present study used an animal model to determine the protective effect of silkworm pupa oil on hydrochloric acid / ethanol‐induced gastric ulcer.

RESULTS

Silkworm pupa oil is rich in unsaturated fatty acids, including palmitoleic acid 63.4 g kg−1, oleic acid 249.1 g kg−1, linoleic acid 47.0 g kg−1, and linolenic acid 337.8 g kg−1, whereas its unsaturated fatty acid content is 700 g kg−1. Compared to a gastric ulcer control group, high and low doses of pupa oil reduced gastric ulcer area and gastric secretion, whereas gastric pH increased. It also increased serum antioxidant superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH‐Px) levels, somatostatin (SST), and vasoactive intestinal peptide (VIP) levels, and reduced serum interleukin‐6 (IL‐6), interleukin‐12 (IL‐12), tumor necrosis factor (TNF‐α), and interferon‐γ (IFN‐γ), motilin (MTL), and gastrin (GT) levels. RT‐qPCR and western blot analyses indicated that silkworm pupa oil significantly increased CAT, GSH‐Px, epidermal growth factor (EGF), Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), Cu/Zn‐SOD, Mn‐SOD, and NF‐kappa‐B inhibitor‐α (IκB‐α) expression and lowered nuclear factor‐kappa B (NF‐κB), B‐cell lymphoma‐2 (Bcl‐2), cyclooxygenase‐2 (COX‐2), and inducible nitric oxide synthase (iNOS) expression.

CONCLUSION

Silkworm pupa oil treatment reduced oxidative damage and inflammation in mice, and high‐dose silkworm pupa oil was superior to low‐dose silkworm pupa oil, following ranitidine. © 2018 Society of Chemical Industry
Cytotoxicity, antiprotozoal, and anti‐inflammatory activities of eight curry powders and comparison of their UPLC‐ESI‐QTOF‐MS chemical profiles
Authors: Sandjo Louis P , Zingue Stephane , dos Santos Nascimento Marcus VP , de Moraes Milene H , Vicente Geison , Amoah Solomon KS , Dalmarco Eduardo M , Frode Tania S , Creczynski‐Pasa Tânia B , Steindel Mario
Published: November 2018

BACKGROUND

Curry powder is a blend of spices that is extensively consumed worldwide and mainly in Central Asia. Its preparation is strictly related to each locality and, because of the health benefits of its constituents, eight commercial forms of this condiment were biologically and chemically investigated. This study aimed to compare their chemical profile as well as their anti‐inflammatory, cytotoxic, and antiparasitic activities.

RESULTS

Curry samples 1 and 7 inhibited leukocyte influx and myeloperoxidase activity, while only 7 was active on protein exudate and NOx species. 2, 6, and 8 displayed trypanocidal effect against Trypanosoma cruzi amastigote, whereas 6 showed antileishmanial activity on Leishmania amazonensis amastigote. 2, 6, and 8 also inhibited the growth of THP‐1 cells used as the parasite's host. Among the cytotoxic samples (4 and 6), curry sample 6 induced apoptosis in MDA‐MB‐231 cells. Nevertheless, 4 and 6 were unselectively cytotoxic to non‐tumoral and tumoral cells. The anti‐inflammatory, cytotoxicity, and antiparasitic assays were respectively performed by carrageenan‐induced pleurisy test, Alamar blue assay, and intracellular parasite–host cell model. Ultra‐performance liquid chromatographic–electrospray ionization mass spectrometric data from the spices revealed both similar and different metabolites in their composition.

CONCLUSION

The results obtained indicate that different formulations can contribute different health benefits as a result of their chemical composition. © 2018 Society of Chemical Industry
A 96‐hour continuous wound infiltration with ropivacaine reduces analgesic consumption after liver resection: A randomized, double‐blind, controlled trial
Authors: Peres‐Bachelot Véronique , Blanc Ellen , Oussaid Nadia , Pérol David , Daunizeau‐Walker Anne Laure , Pouderoux Stéphanie , Peyrat Patrice , Rivoire Michel , Dupré Aurélien
Published: November 2018

Background

Continuous wound infiltration (CWI) with local anesthetics to reduce morphine consumption in postoperative pain management after open liver resection in patients with cancer.

Methods

This single‐center randomized double‐blind study allocated patients requiring resection of liver metastases to receive a 3.75 mg/mL ropivacaine (ROP) infiltration, followed by a 2 mg/mL ROP CWI, or placebo (P) for 96 hours. Postoperative analgesia included acetaminophen and patient‐controlled analgesia morphine pump. The primary endpoint was to investigate the reduction of total morphine consumption (mg/kg) over the first 96 postoperative hours.

Results

Eighty‐five patients were recruited, and randomized (ROP: 42, P: 43) between 2009 and 2014. The median morphine consumption significantly decreased in the ROP arm in the first 96 postoperative hours (ROP: 1.0, P: 1.5 mg/kg;
P = 0.026). Twenty‐three (27%) patients had grade 3 adverse events (ROP: 14, P: 9) and four experienced grade 3 treatment‐related adverse events (ROP: mental confusion [n = 1], hallucinations [n = 2], P: hematoma [n = 1]). Two (5%) patients showed a wound inflammation (ROP: 1, P: 1). Nine (11%) patients experienced at least one serious adverse event (ROP: 6, P: 3); none related to treatment.

Conclusion

Preperitoneal CWI of 2 mg/mL ROP significantly reduces intravenous morphine consumption during the 96 postoperative hours resulting in an absolute reduction of 0.5 mg/kg.
Assessment of hospital‐level adjusted breast cancer sentinel lymph node positivity rates
Authors: Berger Elizabeth R. , Bilimoria Karl Y. , Kinnier Christine V. , Minami Christina A. , Bethke Kevin P. , Hansen Nora M. , Merkow Ryan P. , Winchester David P. , Yang Anthony D.
Published: November 2018

Background/Objectives

Proficiency of performing sentinel lymph node biopsy (SLNB) for breast cancer varies among hospitals and may be reflected in the hospital's SLNB positivity rate. Our objectives were to examine whether hospital characteristics are associated with variation in SLNB positivity rates and whether hospitals with lower‐than‐expected SLNB positivity rates have worse patient survival.

Methods

Using the National Cancer Data Base, stage I to III breast cancer patients were identified (2004‐2012). Hospital‐level SLNB positivity rates were adjusted for tumor and patient factors. Hospitals were divided into terciles of SLNB positivity rates (lower‐, higher‐, as‐expected). Hospital characteristics and survival were examined across terciles.

Results

Of 438 610 SLNB patients (from 1357 hospitals), 78 104 had one or more positive SLN (21.3%). Hospitals in the low and high terciles were more likely to be low volume (low: RRR, 4.40; 95% CI, 2.89‐6.57; P < 0.001; and high: RRR, 1.79; 95% CI, 1.21‐2.64; P < 0.001) compared to hospitals with as‐expected (middle tercile) SLNB positivity rates. Stage I patients at low‐ and high‐tercile hospitals had statistically worse survival.

Conclusions

There is a wide variation in hospital SLNB positivity rates. Hospitals with lower‐ or higher‐than‐expected SLNB positivity rates were associated with survival differences. Hospital SLNB positivity rates may be a novel ‘process measure’ to report to hospitals for internal quality assessment.
Updates in adjuvant systemic therapy for melanoma
Authors: Kwak Minyoung , Farrow Norma E. , Salama April K. S. , Mosca Paul J. , Hanks Brent A. , Slingluff Craig L. , Beasley Georgia M.
Published: November 2018

There has been a rapid increase in adjuvant therapies approved for treatment following surgical resection of stages III/IV melanoma. We review current indications for adjuvant therapy, which currently includes a heterogenous group of stages III and IV patients with melanoma. We describe several pivotal clinical trials of systemic immune therapies, targeted immune therapies, and adjuvant vaccine strategies. Finally, we discuss the evidence for selecting the most appropriate treatment regimen(s) for the individual patient.
Melanoma of unknown primary
Authors: Song Yun , Karakousis Giorgos C.
Published: November 2018

Formally described in the 1960s, melanoma of unknown primary (MUP) is characterized by the finding of metastatic melanoma within the lymph nodes, subcutaneous tissues, and other distant sites without an evident primary lesion. The most likely hypothesis of its etiology is an immune‐mediated regression of the primary after metastasis has occurred. In addition, patients with MUP appear to have equivalent or better outcomes compared with patients with known primaries of a similar stage.
New lymph node staging for rectal neuroendocrine tumors
Authors: Fields Adam C. , McCarty Justin C. , Ma‐Pak Linda , Lu Pamela , Irani Jennifer , Goldberg Joel E. , Bleday Ronald , Chan Jennifer , Melnitchouk Nelya
Published: November 2018

Background and Objectives

Current guidelines of the American Joint Commission on Cancer (AJCC) for rectal neuroendocrine tumors (NETs) classify tumor nodal status as N0/N1. This staging does not take into consideration the number of positive lymph nodes. The goal of this study is to determine how the number of positive lymph nodes affects the prognosis for patients with rectal NETs.

Methods

The National Cancer Database was used to identify patients with rectal NETs who underwent rectal resection. Nearest‐neighborhood grouping was used to classify patients by survival to create a new nodal staging system.

Results

There were 687 patients with rectal NETs. There were distinct 5‐year survival estimates for patients with N0 [81.8% (95%CI:77.1%‐85.6%)], N1 (1‐4 positive lymph nodes) [57.8% (95% confidence interval (CI: 51.2%‐63.9%)] and N2 (≥5 positive lymph nodes) [32.6% (95%CI:25.1%‐40.3%)] patients, P < 0.0001. Distinct 5‐year survival estimates using the new nodal staging system was apparent for patients in the external validation set. After adjusting for predictors of survival in multivariable analysis, the new nodal stage remained an independent predictor of overall survival.

Conclusions

The number of positive locoregional lymph nodes is an independent prognostic factor in rectal NETs. The next AJCC edition should consider classifying patients with rectal NETs as N0, N1, and N2 to provide better estimates of survival for patients.
Desmoplastic melanoma
Authors: Nicolson Norman G , Han Dale
Published: November 2018

Desmoplastic melanoma (DM) is a rare melanoma variant that has unique biology and pathology compared with conventional melanoma (non‐DM). Importantly, DM is classified into pure and mixed histologic subtypes, which have been correlated with outcomes. Management of DM broadly mirrors that of non‐DM; however, there are unique considerations for DM that influence treatment approaches. This paper will provide a contemporary overview of this disease and will review the literature regarding the management of DM.
Validity of Indirect Ultrasound Findings in Acute Anterior Cruciate Ligament Ruptures
Authors: Mautner Ken , Sussman Walter I. , Nanos Katie , Blazuk Joe , Brigham Carmen , Sarros Emily
Published: November 2018

Objectives

Ultrasound (US) is increasingly being used as an extension of the physical examination on the sidelines, in training rooms, and in clinics. Anterior cruciate ligament (ACL) injury in sport is common, but the literature on US findings after acute ACL rupture is limited. Three indirect US findings of ACL rupture have been described, and this study assessed the validity of these indirect signs.

Methods

Patients with an acute knee injury (<6 weeks) underwent US examinations to determine whether there was evidence of a femoral notch sign, posterior cruciate ligament wave sign, or capsular protrusion sign. Ultrasound findings were compared to magnetic resonance imaging.

Results

Sixty‐nine patients were included (53 with ACL tears and 16 control patients). The posterior cruciate ligament sign had the highest sensitivity (84.9%), and the notch sign had the highest specificity (93.8%). If 2 or 3 of the signs were positive, the sensitivity was 86.8%, and the specificity was 87.5%.

Conclusions

A US examination is an easy‐to‐perform and noninvasive test, and the 3 indirect signs of an acute ACL tear had high positive predictive values ranging from 91.8% to 96.8%.
Use of Shear Wave Elastography in the Sonographic Triage of Thyroid Nodules: Feasibility Study in a Series of Lesions Already Selected for Fine Needle Aspiration
Authors: Ippolito Davide , Galimberti Stefania , Leni Davide , Vacirca Francesco , Nasr Ahmed , Bragazzi Nicola Luigi , Spiga Sara , Schiavone Valentina , Pincelli Angela Ida , Garancini Mattia , Leone Biagio Eugenio , Pagni Fabio
Published: November 2018

Objectives

The aim of this study was to evaluate the application of shear wave elastography (SWE) in the routine management of thyroid nodules, as a possible additional tool to the standard sonographic triage.

Methods

A total of 248 consecutive patients scheduled for ultrasound‐guided thyroid fine‐needle aspiration were included in the study. The presence of a pure colloid lesion was an exclusion criterion. Absolute and relative SWE stiffness measurements on color‐coded elastograms, expressed in kilopascals and meters per second, were correlated with radiologic and pathologic features.

Results

SWE values in thyroid nodules were significantly higher than normal thyroid tissue (P = .0001), proving the different elastic properties of the pathologic tissues. Regarding the radiologic characteristics of the nodules, SWE highest values were associated with the largest lesions (P = .0105) but independent from sonographic and Doppler findings. The SWE elasticity was not influenced by the characteristics of the biopsy smears. The final correlation between the SWE results and the pathologic diagnoses showed a trend in stiffness from tender tumors (follicular adenoma) to papillary thyroid carcinoma (P = .016).

Conclusions

SWE allows the identification of nodules within normal parenchyma; however, the present study does not confirm the potential role in differentiating between benign and malignant thyroid nodules.
Clinicopathologic and Ultrasound Variables Associated With a Heavy Axillary Nodal Tumor Burden in Invasive Breast Carcinoma
Authors: Li Jia‐wei , Tong Yu‐yang , Jiang Yi‐zhou , Shui Xu‐juan , Shi Zhao‐ting , Chang Cai
Published: November 2018

Objectives

To identify clinicopathologic and ultrasound (US) variables that were associated with a heavy nodal tumor burden, which was defined as 3 or more lymph nodes involved with metastasis to the axilla after invasive breast carcinoma.

Methods

With ethical approval, 621 patients with a pathologic diagnosis of invasive breast carcinoma were retrospectively analyzed for clinical, pathologic, and US data. Pathologic findings were ascertained by the final paraffin pathologic analysis. Ultrasound characteristics were evaluated on the basis of the American College of Radiology's Breast Imaging Reporting and Data System (BI‐RADS). Univariate and multivariate logistic regression analyses were used to assess the clinicopathologic and US variables that were associated with a heavy nodal tumor burden at the axilla.

Results

There were 107 cases (17.2%) of invasive breast carcinoma with a heavy tumor burden at the axilla. The independent clinicopathologic variables for a heavy tumor burden at the axilla included a tumor size of 2 to 5 cm (odds ratio [OR], 1.86; P = .036), the presence of lymphovascular invasion (OR, 23.52; P < .001), the presence of papillary invasion (OR, 2.93; P = .043), and a non–triple‐negative subtype (OR, 2.34; P = .04). The independent US features of breast tumors that were associated with a heavy tumor burden at the axilla included BI‐RADS category 5 (OR, 5.50; P = .024) and a posterior acoustic shadow (OR, 1.94; P = .024).

Conclusions

A large tumor size, lymphovascular invasion, papillary invasion, and a non–triple‐negative subtype on the pathologic analysis as well as BI‐RADS category 5 and a posterior acoustic shadow on a US assessment were associated with a heavy nodal tumor burden at the axilla. These US characteristics of the primary breast carcinoma might provide additional information to axillary US for the prediction of axillary nodal tumor loads.