bluuebunny/crossref_metadata_2025 huggingface dataset:
Plant DNases are potent therapeutic agents against Echis carinatus venom‐induced tissue necrosis in mice
Authors: Rudresha Gotravalli V. , Urs Amog P. , Manjuprasanna Vaddarahally N. , Suvilesh Kanve N. , Sharanappa Puttappa , Vishwanath Bannikuppe S.
Published: December 2018

Echis carinatus envenomation leads to severe tissue necrosis at the bitten site by releasing DNA from immune cells that blocks the blood flow. An earlier report has shown that exogenous DNase 1 offers protection against such severe local tissue necrosis. Tricosanthus tricuspidata is a medicinal plant and the paste prepared from its leaves has been used extensively for the treatment of snakebite‐induced tissue necrosis. Most studies including reports from our laboratory focused on plant secondary metabolite as therapeutic molecules against snakebite envenomation. However, the involvement of hydrolytic enzymes including DNase in treating snake venom‐induced tissue necrosis has not been addressed. Several folk medicinal plants used against snakebite treatment showed the presence of DNase activity and found to be rich in T. tricuspidata. Further, purified T. tricuspidata DNase showed a single sharp peak in reversed‐phase high‐performance liquid chromatography (RP‐HPLC) with an apparent molecular mass of 17 kDa. T. tricuspidata DNase exhibited potent DNA degrading activity performed using agarose gel electrophoresis, spectrophotometric assay, and DNA zymography. In addition, purified DNase from T. tricuspidata was able to neutralize E. carinatus venom‐induced mouse tail tissue necrosis and normalized elevated serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels 30 minutes post venom injection. T. tricuspidata DNase was also able to reverse E. carinatus venom‐induced histopathological changes and collagen depletion in mice tail tissue. All these observed pharmacological actions of T. tricuspidata DNase were inhibited by sodium fluoride (NaF). This study provides scientific validation of the traditional use of T. tricuspidata leaf paste in the healing of snakebite‐induced tissue necrosis and might be exploited to treat snake venom‐induced local toxicity.
ClC‐3 chloride channels are involved in estradiol regulation of bone formation by MC3T3‐E1 osteoblasts
Authors: Deng Zhiqin , Li Wencui , Xu Jianying , Yu Meishen , Li Duan , Tan Qiuchan , Wang Daping , Chen Lixin , Wang Liwei
Published: December 2018

Evidence has been reported by us and others supporting the important roles of chloride channels in a number of osteoblast cell functions. The ClC‐3 chloride channel is activated by estradiol binding to estrogen receptor alpha on the cell membranes of osteoblasts. However, the functions of these chloride channels in estrogen regulation of osteoblast metabolism remain unclear. In the present study, the roles of chloride channels in estrogen regulation of osteoblasts were investigated in the osteoblastic cell line MC3T3‐E1. Estrogen 17β‐estradiol enhanced collagen I protein expression, alkaline phosphatase activity, and mineralization were inhibited, by chloride channel blockers. Estradiol promoted ClC‐3 chloride channel protein expression. Silencing of ClC‐3 chloride channel expression prevented the elevation of osteodifferentiation in osteoblasts, which were regulated by estrogen. These data suggest that estrogen can regulate bone formation by activating ClC‐3 chloride channels and the activation of ClC‐3 chloride channels can enhance the osteodifferentiation in osteoblasts.
miR‐452 promotes cell metastasis and the epithelial to mesenchymal by targeting SOX7 in clear‐cell renal‐cell carcinoma
Authors: Liu Feng , Guo Lihua , Xin Guangda , Wang Zhixin
Published: December 2018

Clear‐cell renal‐cell carcinoma (ccRCC) is the most common renal cell carcinoma (RCC), representing 75%‐80% of the cases of RCC, and characterized by a high recurrence rate and poor prognosis. miR‐452 acts as a tumor promoter in several tumors, including ccRCC. The purpose of this study was to determine the role of miR‐452 in ccRCC. miR‐452 and SOX7 messenger RNA and protein levels were calculated by quantitative reverse transcription polymerase chain reaction and Western blot analysis. MTT and Transwell assays were utilized to measure proliferative and invasive abilities. The Kaplan‐Meier method was used to evaluate the association between the expression of miR‐452 or SOX7 and the overall survival of ccRCC patients. Our results showed that miR‐452 was overexpressed in ccRCC tissues and cells, and upregulation of miR‐452 predicted a poor 5‐year survival in ccRCC patients. In contrast, expression of SOX7 was low and downregulation of SOX7 predicted poor prognosis in ccRCC. In addition, miR‐452 promoted cell proliferation, invasion, and the EMT, while SOX7 reversed the function of miR‐452 on cell proliferation and invasion in 786‐O cells. In conclusion, miR‐452 was shown to inhibit cell proliferation, invasion, and the EMT through SOX7 in ccRCC, and the newly identified miR‐452/SOX7 axis provided novel insight into the pathogenesis of ccRCC.
microRNAs‐107 inhibited autophagy, proliferation, and migration of breast cancer cells by targeting HMGB1
Authors: Ai Hongyan , Zhou Wei , Wang Zeqiang , Qiong Guo , Chen Zhouxi , Deng Shungang
Published: December 2018

Purpose

To investigate the effects of microRNAs‐107 (miR‐107) on autophagy, proliferation, and migration of breast cancer cells and its mechanism by targeting high mobility group protein B1 (HMGB1).

Methods

Real‐time polymerase chain reaction assay was used to detect the expression of miR‐107 in breast cancer and its cell lines. In MDA‐MB‐231 and MDA‐MB‐453 breast cancer cells, the expression of p62, Beclin1 protein, and the changes of cell proliferation and migration after overexpression of m miR‐107 were detected by Western blotting, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, and transwell assays. Target Scan online prediction, dual luciferase reporter gene, and Western blot were used to verify the targeting relationship between miR‐107 and HMGB1. The effects of silencing HMGB1 expression on p62, Beclin1 protein expression, cell proliferation, and migration ability were detected. The transfected MDA‐MB‐453 cells were inoculated into the right axilla of the nude mice, the tumor volume and weight were weighed, and the expression of miR‐107, HMGB1, p62, and Beclin1 in the tumor were detected.

Results

The expression of miR‐107 was downregulated in breast cancer tissues and cell lines (P < 0.01). The expression of p62 protein was upregulated (P < 0.01), while Beclin1 protein was downregulated (P < 0.01) and cell proliferation and migration ability were decreased (P < 0.01) after overexpressing miR‐107 in MDA‐MB‐231 and MDA‐MB‐453 cells. The results of TargetScan online prediction, dual luciferase reporter gene, and Western blot showed that miR‐107 could regulate HMGB1 expression. The expression of p62 protein was upregulated (P < 0.01), while Beclin1 protein was downregulated (P < 0.01) and cell proliferation and migration ability were decreased (P < 0.01) after silencing HMGB1 in MDA‐MB‐231 and MDA‐MB‐453 cells. The results of xenograft experiments showed that miR‐107 could delay tumor growth and inhibit autophagy.

Conclusion

miR‐107 could inhibit cell autophagy, proliferation, and migration of breast cancer cells by targeting HMGB1.
Human RNF113A participates of pre‐mRNA splicing in vitro
Authors: Gatti da Silva Guilherme H. , Jurica Melissa S. , Chagas da Cunha Julia P. , Oliveira Carla C. , Coltri Patricia P.
Published: December 2018

Pre‐messenger RNA (mRNA) splicing is an essential step in the control of eukaryotic gene expression. During splicing, the introns are removed from the gene transcripts as the exons are ligated to create mature mRNA sequences. Splicing is performed by the spliceosome, which is a macromolecular complex composed of five small nuclear RNAs (snRNAs) and more than 100 proteins. Except for the core snRNP proteins, most spliceosome proteins are transiently associated and presumably involved with the regulation of spliceosome activity. In this study, we explored the association and participation of the human protein RNF113A in splicing. The addition of excess recombinant RNF113A to in vitro splicing reactions results in splicing inhibition. In whole‐cell lysates, RNF113A co‐immunoprecipitated with U2, U4, and U6 snRNAs, which are components of the tri‐snRNP, and with proteins PRP19 and BRR2. When HeLa cells were CRISPR‐edited to reduce the RNF113A levels, the in vitro splicing efficiency was severely affected. Consistently, the splicing activity was partially restored after the addition of the recombinant GST‐RNF113A. On the basis on these results, we propose a model in which RNF113A associates with the spliceosome by interacting with PRP19, promoting essential rearrangements that lead to splicing.
microRNA‐193a‐5p inhibits migration of human HT‐29 colon cancer cells via suppression of metastasis pathway
Authors: Shirafkan Naghmeh , Shomali Navid , Kazemi Tohid , Shanehbandi Dariush , Ghasabi Mehri , Baghbani Elham , Ganji Maziar , Khaze Vahid , Mansoori Behzad , Baradaran Behzad
Published: December 2018

Purpose

Altered expression of microRNAs (miRNAs) is indicated strongly in colorectal cancer (CRC). This study aims to evaluate the inhibitory role of miR‐193a‐5p on epithelial‐mesenchymal transition markers in CRC lines. The cellular effects and potential mechanisms of
miR‐193a‐5p were also examined.

Methods

Quantitative reverse‐transcription polymerase chain reaction (RT‐PCR) was performed to determine the expression of miR‐193a‐5p in three CRC cell lines (HCT‐116, SW‐480, and HT‐29) and its impact on metastasis‐related genes (
vimentin and
CXCR4) before and after mimic transfection. Of those, the cell line with the highest changes was selected for the next upcoming experiments such as wound‐healing assay, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), and annexin‐V staining tests.

Results

Our results revealed that miR‐193a‐5p was significantly downregulated in three CRC cell lines and that HT‐29 displayed the most decrease (
P < 0.0001). The restoration of
miR‐193a‐5p in human HT‐29 cell line inhibited cell migration. But,
miR‐193a‐5p transfection did not affect cell viability and had no significant effect on apoptosis induction. Also, the quantitative RT‐PCR analysis of
miR‐193a‐5p mimic transfected cells revealed a significant increase in
miR‐193a‐5p messenger RNA (mRNA) expression level (
P < 0.0001) with reduction of
vimentin and
CXCR4 mRNA expression levels in HT‐29 cell line (
P < 0.01 and < 0.05, respectively).

Conclusion

Our results indicated that miR‐193a‐5p acts as a tumor suppressor miRNA and its downregulation plays an important role in metastasis via upregulation of metastasis‐related genes in CRC. Therefore, it can be considered as a potential therapeutic target for applying in CRC management in the future.
Lecithin soybean phospholipid nano‐transfersomes as potential carriers for transdermal delivery of the human growth hormone
Authors: Kateh Shamshiri Maryam , Momtazi‐Borojeni Amir Abbas , Khodabandeh Shahraky Mahvash , Rahimi Fatemeh
Published: December 2018

Pharmaceutical molecules such as peptides and proteins are usually injected into the body. Numerous efforts have been made to find new noninvasive ways to administer these peptides. In this study, highly flexible vesicles (transfersomes [TFs]) were designed as a new modern transdermal drug delivery system for systemic drug administration through the skin, which had also been evaluated in vitro. In this study, two growth hormone‐loaded TF formulations were prepared, using soybean lecithin and two different surfactants; F1_sodium deoxycholate and F
2_sodium lauryl sulfate. Thereafter, the amount of skin penetration by the two formulas was assessed using the Franz diffusion cell system. TF formulations were evaluated for size, zeta potential and in vitro skin penetration across the rat skin. Results indicated that vesicle formulations were stable for 4 weeks and their mean sizes were 241.33 ± 17 and 171 ± 12.12 nm in the F
1 and F
2 formulation, respectively. After application to rat skin, transport of the human growth hormone (hGH) released from the TF formulations was found to be higher than that of the hGH alone. Maximum amounts of transdermal hormone delivery were estimated to be 489.54 ± 8.301  and 248.46 ± 4.019 ng·cm−2 , for F
1 and F
2, respectively. The results demonstrate the capability of the TF‐containing growth hormone in transdermal delivery and superiority of the F
1 to F
2 TFs.
Cold exposure induces nuclear translocation of CRTC3 in brown adipose tissue
Authors: Xu Ziye , Liu Jiaqi , You Wenjing , Wang Yizhen , Shan Tizhong
Published: December 2018

In mammals, cold stress activates the cAMP‐protein kinase A (PKA) signaling pathway, increases brown adipose tissue (BAT) activity, and induces thermogenesis to maintain body temperature. The cAMP responsive element binding protein (CREB)‐regulated transcription coactivator 3 (CRTC3) plays important role in adipose development and energy metabolism. However, the effect of cold exposure on the intracellular localization of CRTC3 in BAT is unclear. Here, we report that cold‐treated mice have higher expression of uncoupling protein 1 (UCP1) in adipose tissues and lower body weights and fat masses. Notably, cold exposure results in the nuclear translocation of CRTC3 in BAT. Moreover, forskolin (FSK), the activator of PKA pathway, induces the nuclear translocation of CRTC3 in brown adipocytes. At the molecular level, cold exposure and FSK treatment decrease liver kinase B1 (Lkb1) expression in brown adipocytes, which is related to the nuclear localization of CRTC3. These results demonstrate that the localization of CRTC3 involves in regulating cold‐induced upregulation of UCP1 in BAT and provide useful information for understanding the molecular regulation of BAT thermogenesis induced by a cold environment.
Clinical significance of long noncoding RNA VIM‐AS1 and CTBP1‐AS2 expression in type 2 diabetes
Authors: Erfanian Omidvar Maryam , Ghaedi Hamid , Kazerouni Faranak , kalbasi Saeid , Shanaki Mehrnoosh , Miraalamy Ghasem , Zare Ali , Rahimipour Ali
Published: December 2018

Background/Aims

The risk of type 2 diabetes (T2D) is determined by a combination of genetic and environmental factors. Multiple studies have proposed that long noncoding RNAs (lncRNAs) are crucial molecules in regulating several biological processes and complex diseases. The study was aimed at investigating the association between the expression levels of lncRNA VIM‐AS1, lncRNA CTBP1‐AS2, and T2D susceptibility.

Methods

lncRNA VIM‐AS1 and lncRNA CTBP1‐AS2 in the peripheral blood mononuclear cell (PBMC) of 100 healthy individuals and 100 T2D patients were collected for Quantitative Real‐Time RT‐PCR analysis. A logistic regression was performed to understand whether the likelihood of T2D can be predicted based on the expression levels of lncRNA VIM‐AS1 and lncRNA CTBP1‐AS2. Receiver operating characteristic (ROC) analysis was also performed to determine the statistical analysis of VIM‐AS1 and CTBP1‐AS2 levels in 200 samples.

Results

Our results display that decreased levels of VIM‐AS1 and CTBP1‐AS2 in PBMC were associated with diabetes in Iranian population. The logistic regression revealed that Systolic blood pressure (SBP), low‐density lipoprotein cholesterol (LDL‐C), Fasting blood glucose (FBG) and CTBP1‐AS2 are substantial predictors of T2D. The ROC analysis of CTBP1‐AS2 revealed the area under the ROC curve (AUC) of 0.68 with a sensitivity of 58.7% and specificity of 75.3% in distinguishing nondiabetic from diabetic subjects. The ROC analysis of VIM‐AS1 determined AUC of 0.63 with a sensitivity of 56.1% and specificity of 68.37% in distinguishing the two diagnostic groups.

Conclusion

lncRNA VIM‐AS1 and lncRNA CTBP1‐AS2 expression levels are associated with T2D susceptibility.
Stem cell‐based cell therapy for neuroprotection in stroke: A review
Authors: Rikhtegar Reza , Yousefi Mehdi , Dolati Sanam , Kasmaei Hosein Delavar , Charsouei Saeid , Nouri Mohammad , Shakouri Seyed Kazem
Published: December 2018

Neurological disorders, such as stroke, are triggered by a loss of neurons and glial cells. Ischemic stroke remains a substantial problem for industrialized countries. Over the previous few decades our understanding about the pathophysiology of stroke has enhanced, nevertheless, more awareness is required to advance the field of stroke recovery. Existing therapies are incapable to adequately relief the disease outcome and are not appropriate to all patients. Meanwhile, the majority of patients continue to show neurological deficits even subsequent effective thrombolysis, recuperative therapies are immediately required that stimulate brain remodeling and repair once stroke damage has happened. Cell therapy is emergent as a hopeful new modality for increasing neurological recovery in ischemic stroke. Numerous types of stem cells from various sources have been identified and their possibility and efficiency for the treatment of stroke have been investigated. Stem cell therapy in patients with stroke using adult stem cells have been first practiced in clinical trials since 15 years ago. Even though stem cells have revealed a hopeful role in ischemic stroke in investigational studies besides early clinical pilot studies, cellular therapy in human is still at a primary stage. In this review, we summarize the types of stem cells, various delivery routes, and clinical application of stem cell‐based therapy for stroke treatment.
Trehalose administration attenuates atherosclerosis in rabbits fed a high‐fat diet
Authors: Sahebkar Amirhossein , Hatamipour Mahdi , Tabatabaei Sayed Abbas
Published: December 2018

Disruption of macrophage autophagy is a major contributor to macrophage dysfunction and subsequent inflammation leading to atherosclerosis. Trehalose is a natural disaccharide that is able to induce macrophage autophagy‐lysosomal biogenesis and reduce inflammation. Here, we studied the efficacy of intravenous trehalose administration in reducing atherosclerotic plaque burden in high‐cholesterol‐fed rabbits. Adult male New Zealand white Rabbits were fed with a high‐fat diet containing 1% cholesterol for 8 weeks followed by a cholesterol‐free diet for the next 4 weeks. In the latter 4‐week phase of the cholesterol‐free diet, one group received intravenous trehalose solution at a dose of 350 mg/kg, three times per week. In the control group, an equivalent volume of PBS (3 mL) was administered with the same protocol. At the end of the 12th week of the study, all rabbits were anesthetized and aortic arch sections were collected followed by hematoxylin and eosin staining and assessment of plaque grading. Fasting serum lipids were also measured using routine enzymatic methods. At the end of the 12th week, there were no significant differences in the body weight and blood lipids between the control‐ and trehalose‐treated groups. Intravenous trehalose administration significantly attenuated atherosclerotic plaque development as revealed by reduced plaque grading (
P = 0.048) and intima/media thickness ratio (
P = 0.017). Intimal thickening was also found to be reduced in the trehalose versus control group, though this reduction did not reach statistical significance. The present study provided evidence as to the efficacy of short‐term intravenous trehalose administration in regressing atherosclerotic plaque in high‐fat‐fed rabbits.
microRNA‐31 inhibition partially ameliorates the deficiency of bone marrow stromal cells from cleidocranial dysplasia
Authors: Xu Ling , Fu Yu , Zhu Weiwen , Xu Rongyao , Zhang Juan , Zhang Ping , Cheng Jie , Jiang Hongbing
Published: December 2018

Background

Cleidocranial dysplasia (CCD) in humans is an autosomal‐dominant skeletal dysplasia caused by heterozygous mutations of the runt‐related transcription factor 2 (RUNX2) and significantly increases the risk of osteoporosis. Increasing evidence demonstrates that the dysfunction of bone marrow stromal cells from CCD patients (BMSCs‐CCD) contributes to the bone deficiency, but the characteristics of BMSCs‐CCD and the mechanisms that underlie their properties remain undefined.

Methods

The clinical manifestations of three CCD patients were collected and the mutations of RUNX2 were analyzed. The properties of proliferation, osteogenesis, stemness, and senescence of BMSCs‐CCD were compared with that of BMSCs from healthy donors. The expression of microRNA‐31 (
miR‐31) between BMSCs‐CCD and BMSCs was measured and lentivirus‐carried
miR‐31 inhibitor was used to determine the role of
miR‐31 in BMSCs‐CCD both in vitro and in vivo. The molecular mechanisms underlying RUNX2‐miR31 and
miR‐31 targeting stemness and senescence of BMSCs‐CCD were also explored.

Results

We identified two mutation sites of RUNX2 via exome sequencing from 2 of 3 Chinese CCD patients with typical clinical presentations. Compared with BMSCs from healthy donors, BMSCs‐CCD displayed significantly attenuated proliferation, osteogenesis and stemness, and enhanced senescence. Meanwhile,
miR‐31 knockdown could ameliorate these deficiency phenotypes of BMSCs‐CCD by regulating
SATB2,
BMI1,
CDKN, and
SP7. Mechanistically,
RUNX2 directly repressed
miR‐31 expression, and therefore
RUNX2 haploinsufficiency in CCD leading to
miR‐31 upregulation contributed to the deficiency of BMSCs‐CCD.
miR‐31 inhibition in BMSCs‐CCD showed enhanced osteogenesis through heterotopic subcutaneous implantation in the nude mice.

Conclusions

Our results show the functional deficiencies of BMSCs‐CCD and a potential role of miR‐31 in BMSCs‐CCD deficiencies. The application of
miR‐31 inhibitor in BMSCs‐CCD might lend hope for developing BMSC‐based therapeutic approaches against CCD‐associated skeletal diseases.
Low expression of miR‐186‐5p regulates cell apoptosis by targeting toll‐like receptor 3 in high glucose–induced cardiomyocytes
Authors: Liu Ye , Zheng Wei , Pan Yue , Hu Jing
Published: December 2018

To investigate the effect and mechanism of microRNA‐186‐5p (miR‐186‐5p) on the apoptosis in high glucose (HG)–treated cardiomyocytes. Diabetic cardiomyopathy model was established in cardiomyocytes by stimulating with HG. The expressions of miR‐186‐5p and toll‐like receptor 3 (TLR3) were detected by quantitative polymerase chain reaction or Western blot analysis, respectively. Apoptosis was detected in HG‐treated cardiomyocytes by flow cytometry and Western blot analysis. The interaction between miR‐186‐5p and TLR3 was explored by bioinformatics analysis and luciferase activity assay. Results showed that miR‐186‐5p expression was downregulated in HG‐treated cardiomyocytes and its overexpression reversed HG‐induced apoptosis and cleaved caspase‐3 protein expression. Moreover, TLR3 was indicated as a target of miR‐186‐5p and regulated by miR‐186‐5p. Knockdown of TLR3 suppressed HG‐induced apoptosis and cleaved caspase‐3 protein expression. Besides, restoration of TLR3 ablated the effect of miR‐186‐5p on cell apoptosis. Collectively, miR‐186‐5p attenuated HG‐induced apoptosis by regulating TLR3 in cardiomyocytes, providing novel biomarker for treatment of diabetic cardiomyopathy.
The muscular sense in Russia: I. M. Sechenov and materialist realism
Authors: Smith Roger
Published: December 2018

Contemporary Russian sensory physiology and psychology uses the notion of a “dark sense,” referring to the background of bodily sensation, especially of the position and movement of the body. The physiologist Ivan Sechenov introduced this language in the 1860s in the context of arguing for a physiological basis for scientific psychology. The muscular sense (the term preceding modern notions of kinaesthesia and proprioception) thereafter featured in the many talks and journal articles he presented to spread scientific enlightenment. The paper describes the history and significance of this. It does so in the light of Soviet representations of Sechenov as a scientist who substantially contributed to the Leninist materialist–realist theory of knowledge. These representations assessed Sechenov’s discussions as a breakthrough in world science to the understanding of the human organism as a self‐regulating material system. It is necessary to understand the purposes and pressures driving Soviet historiography. The paper confirms the historical importance the sense of movement has had in realist theories of knowledge of the world; and it contributes a previously unknown chapter to the history of psychology.
The moral power of suggestion: A history of suggestion in Japan, 1900–1930
Authors: Wu Yu‐chuan
Published: December 2018

In Japan, as in the west, suggestion theory was the predominant theory of hypnosis, and suggestive therapy was one of the most important, if not the most important, form of psychotherapy in the early 20th century. While the use of suggestion was met with objections on both scientific and moral grounds in the west, it was seen in a more positive light and has had a significant influence on the development of psychotherapy in Japan. With regard to the contexts of suggestion, suggestive power, suggestibility, and the effects of suggestion, this study will examine the distinctive conceptions and practices of suggestion developed by analogy with existing ideas about interpersonal influence, particularly with the concept of kanka (assimilative transformation) in Japan. They provide an interesting comparison to the western ideas of suggestion, helping us understand the historical and cultural particularity of western dynamic psychiatry and psychotherapy, particularly their presumptions about interpersonal influence.
Synthesis of Some Novel Furan‐tagged Thienopyrimidine Derivatives as Antibacterial Agents
Authors: Abdel Hamid Atef M. , Shehta Wael
Published: December 2018

Cyclization of 2‐furan‐2‐yl‐4‐mercapto‐6‐methylpyrimidine‐5‐carbonitrile 1 with ethyl chloroacetate gave o‐aminoester thienopyrimidine derivative 3, which was reacted with a variety of reagents to give a series of novel thienopyrimidines including tetrazolyl thienopyrimidine, pyrrolylthienopyrimidine, pyrimidothienotriazine, and thienodipyrimidines. Some of the synthesized compounds were tested for their antibacterial activities against Gram‐positive and Gram‐negative bacteria.
Early antiretroviral therapy and daily pre‐exposure prophylaxis for HIV prevention among female sex workers in Cotonou, Benin: a prospective observational demonstration study
Authors: Mboup Aminata , Béhanzin Luc , Guédou Fernand A , Geraldo Nassirou , Goma‐Matsétsé Ella , Giguère Katia , Aza‐Gnandji Marlène , Kessou Léon , Diallo Mamadou , Kêkê René K , Bachabi Moussa , Dramane Kania , Geidelberg Lily , Cianci Fiona , Lafrance Christian , Affolabi Dissou , Diabaté Souleymane , Gagnon Marie‐Pierre , Zannou Djimon M , Gangbo Flore , Boily Marie‐Claude , Vickerman Peter , Alary Michel
Published: December 2018

Introduction

In sub‐Saharan Africa, HIV prevalence remains high, especially among key populations. In such situations, combination prevention including clinical, behavioural, structural and biological components, as well as adequate treatment are important. We conducted a demonstration project at the Dispensaire IST, a clinic dedicated to female sex workers (FSWs) in Cotonou, on early antiretroviral therapy (E‐ART, or immediate “test‐and‐treat”) and pre‐exposure prophylaxis (PrEP). We present key indicators such as uptake, retention and adherence.

Methods

In this prospective observational study, we recruited FSWs from October 4th 2014 to December 31st 2015 and followed them until December 31st 2016. FSWs were provided with daily tenofovir disoproxil fumarate/emtricitabine (Truvada®) for PrEP or received a first‐line antiretroviral regimen as per Benin guidelines. We used generalized estimating equations to assess trends in adherence and sexual behaviour.

Results

Among FSWs in the catchment area, HIV testing coverage within the study framework was 95.5% (422/442). At baseline, HIV prevalence was 26.3% (111/422). Among eligible FSWs, 95.5% (105/110) were recruited for E‐ART and 88.3% (256/290) for PrEP. Overall retention at the end of the study was 59.0% (62/105) for E‐ART and 47.3% (121/256) for PrEP. Mean (±SD) duration of follow‐up was 13.4 (±7.9) months for E‐ART and 11.8 (±7.9) months for PrEP. Self‐reported adherence was over 90% among most E‐ART participants. For PrEP, adherence was lower and the proportion with 100% adherence decreased over time from 78.4% to 56.7% (p‐trend < 0.0001). During the 250.1 person‐years of follow‐up among PrEP initiators, two seroconversions occurred (incidence 0.8/100 person‐years (95% confidence interval: 0.3 to 1.9/100 person‐years)). The two seroconverters had stopped using PrEP for at least six months before being found HIV‐infected. In both groups, there was no evidence of reduced condom use.

Conclusions

This study provides data on key indicators for the integration of E‐ART and PrEP into the HIV prevention combination package already offered to FSWs in Benin. PrEP may be more useful as an individual intervention for adherent FSWs rather than a specific public health intervention. E‐ART was a more successful intervention in terms of retention and adherence and is now offered to all key populations in Benin.

Study registration

ClinicalTrials.gov NCT02237
Attrition of HIV‐exposed infants from early infant diagnosis services in low‐ and middle‐income countries: a systematic review and meta‐analysis
Authors: Carlucci James G , Liu Yu , Friedman Halle , Pelayo Brenda E , Robelin Kimberly , Sheldon Emily K , Clouse Kate , Vermund Sten H
Published: December 2018

Introduction

Identification and retention of HIV‐exposed infants in early infant diagnosis (EID) services helps to ensure optimal health outcomes. This systematic review and meta‐analysis examines the magnitude of attrition from EID services in low‐ and middle‐income countries (LMICs).

Methods

We performed a comprehensive database search through April 2016. We included original studies reporting retention/attrition data for HIV‐exposed infants in LMICs. Outcomes included loss to follow‐up (LTFU), death and overall attrition (LTFU + death) at time points along the continuum of EID services. At least two authors determined study eligibility, performed data extraction and made quality assessments. We used random‐effects meta‐analytic methods to aggregate effect sizes and perform meta‐regression analyses. This study adhered to PRISMA reporting guidelines.

Results

We identified 3040 unique studies, of which 92 met eligibility criteria and were included in the quantitative synthesis. The included studies represent data from 110,805 HIV‐exposed infants, the majority of whom were from Africa (77%). LTFU definitions varied widely, and there was significant variability in outcomes across studies. The bulk of attrition occurred in the first six months of follow‐up, with additional losses over time. Overall, 39% of HIV‐exposed infants were no longer in care at 18 months. When restricted to non‐intervention studies, 43% were not retained at 18 months.

Conclusions

These findings underscore the high attrition of HIV‐exposed infants from EID services in LMICs and the urgent need for implementation research and resources to improve retention among this vulnerable population.
Reflections on the early invasive clinical cardiac electrophysiology era through fifty manuscripts: 1967–1992
Authors: Wang Norman C. , Lahiri Marc K. , Thosani Amit J. , Shen Sharon , Goldberger Jeffrey J.
Published: December 2018

In 1967, researchers in The Netherlands and France independently reported a new technique, later called programmed electrical stimulation. The ability to reproducibly initiate and terminate arrhythmias heralded the beginning of invasive clinical cardiac electrophysiology as a medical discipline. Over the next fifty years, insights into the pathophysiologic basis of arrhythmias would transform the field into an interventional specialty with a tremendous armamentarium of procedures. In 2015, the variety and complexity of these procedures were major reasons that led to the recommendation for an increase in the training period from one year to two years. The purpose of this manuscript is to present fifty manuscripts from the early invasive clinical cardiac electrophysiology era, between 1967 and 1992, to serve as an educational resource for current and future electrophysiologists. It is our hope that reflection on the transition from a predominantly noninvasive discipline to one where procedures are commonly utilized will lead to more thoughtful patient care today and to inspiration for innovation tomorrow. In the words of the late Dr. Mark E. Josephson, “It is only by getting back to the basics that the field of electrophysiology will continue to grow instead of stagnate.”
Global warming from 1.5 to 2 °C will lead to increase in precipitation intensity in China
Authors: Zhou Mengzi , Zhou Guangsheng , Lv Xiaomin , Zhou Li , Ji Yuhe
Published: December 2018

The impact of global warming on extreme precipitation over China is projected based on CMIP5 simulations under three representative concentration pathway scenarios. When global warming is 1.5 °C above pre‐industrial (1861–1890), precipitation intensity and frequency increase, which leads to an increase relative to the period 1986–2005 in total wet daytime precipitation in northeast China, north China, and the Qinghai–Tibet Plateau. However, south China and southwest China experience fewer precipitation days and less total precipitation despite increasing simple daily intensity (SDII). Under 2 °C of warming, the number of wet days (R1mm) increases north of 30°N and decreases to the south, whereas consecutive dry days (CDD) displays the opposite pattern. The other eight extreme precipitation events increase during the simulation period nationwide, with varying intensity. An increase in global warming from 1.5 to 2 °C is projected to lead to an increase in precipitation intensity over China, except for some scattered regions in the northwest and southwest of the country. More frequent extreme precipitation days are also expected, although decreases in R1mm are projected in north China and extend to northwest China. An overall small decrease in CDD is predicted for China. All annual regional‐mean precipitation events have an apparent linear relationship with global mean temperature, except for CDD. The rate of increase of extreme precipitation with temperature in the future on an annual scale is much faster than for a reference period (1986–2005), whereas no noticeable difference exists on a daily scale. The relationships between daily precipitation extremes and temperature for the present day and for the future show a quadratic polynomial structure, increasing up to 19 °C but decreasing at higher temperatures. There is a significant positive influence on extreme precipitation when warming is limited to 1.5 °C, compared with a limit of 2 °C.
Incidence and Effects of Feeding Intolerance in Trauma Patients
Authors: Virani Farrukh R. , Peery Travis , Rivas Orlyn , Tomasek Jeffrey , Huerta Ravin , Wade Charles E. , Lee Jenny , Holcomb John B. , Uray Karen
Published: December 2018

Background

Although feeding intolerance is a common complication in trauma patients, the incidence, development, and effects are poorly understood.

Methods

We performed a retrospective study in which trauma patients were classified as having feeding intolerance based on time to reach feeding goal. Subsequently, we sorted patients by gastric residual volumes (GRVs) or symptoms of slowed gastrointestinal motility.

Results

One‐third of trauma patients experienced delayed time to reach feeding goal after diet initiation. Delayed feeding was associated with prolonged intensive care unit (ICU) stays, increased readmission rates, and increased incidence of sepsis. Patients with elevated GRV (>500 mL) had significantly prolonged ICU and hospital stays and increase incidence of sepsis. Patients with >2 symptoms of slowed gastrointestinal motility had prolonged ICU and hospital stays, delayed time to reach feeding goals, significantly increased readmission rates, increased incidence of infectious and thromboembolic complications and sepsis, decreased serum prealbumin levels, and increased CRP levels.

Conclusion

Decreased gastrointestinal motility in trauma patients is associated with worse outcomes and increased systemic inflammation.
Influence of nitrogen fertilization on yield and phenolic compounds in wheat grains (Triticum aestivum L. ssp. aestivum)
Authors: Stumpf Beate , Yan Feng , Honermeier Bernd
Published: November 2018

Nitrogen (N) is an important plant nutrient and is crucial for the plant growth and grain yield formation of field crops such as wheat (Triticum aestivum L. ssp. aestivum). However, little is known about the influence of N on secondary metabolites in wheat grains which are supposed to be beneficial for human health due to their antioxidant potentials. Therefore, we investigated the influence of N fertilization on plant growth and yield performance of winter wheat, as well as on total phenolic concentration, antioxidant capacity, and the accumulation of (in)soluble phenolic acids in wheat grains during the grain‐filling phase. It was found that ferulic acid was the predominant phenolic acid in wheat grains. As expected, higher amounts of N fertilizer led to increasing grain yields, whereas the concentration of soluble ferulic acid decreased. In contrast, insoluble bound ferulic acid, total phenolic content, and antioxidant capacity were not affected by the N treatment. Insoluble phenolic compounds seemed to be less susceptible to variations in N supply.
Testing for funnel plot asymmetry of standardized mean differences
Authors: Pustejovsky James E. , Rodgers Melissa A.
Published: December 2018

Publication bias and other forms of outcome reporting bias are critical threats to the validity of findings from research syntheses. A variety of methods have been proposed for detecting selective outcome reporting in a collection of effect size estimates, including several methods based on assessment of asymmetry of funnel plots, such as the Egger's regression test, the rank correlation test, and the Trim‐and‐Fill test. Previous research has demonstated that the Egger's regression test is miscalibrated when applied to log‐odds ratio effect size estimates, because of artifactual correlation between the effect size estimate and its standard error. This study examines similar problems that occur in meta‐analyses of the standardized mean difference, a ubiquitous effect size measure in educational and psychological research. In a simulation study of standardized mean difference effect sizes, we assess the Type I error rates of conventional tests of funnel plot asymmetry, as well as the likelihood ratio test from a three‐parameter selection model. Results demonstrate that the conventional tests have inflated Type I error due to the correlation between the effect size estimate and its standard error, while tests based on either a simple modification to the conventional standard error formula or a variance‐stabilizing transformation both maintain close‐to‐nominal Type I error.
Trophic interactions, toxicokinetics, and detoxification processes in a domoic acid‐producing diatom and two copepod species
Authors: Harðardóttir Sara , Hjort Ditte Marie , Wohlrab Sylke , Krock Bernd , John Uwe , Nielsen Torkel Gissel , Lundholm Nina
Published: December 2018

In costal ecosystems, copepods coexist with toxin‐producing phytoplankton. The presence of copepods can amplify the phytoplankton toxin production and thereby increase the overall toxicity of a bloom. Copepods are not always affected by the toxins and can vector the toxins to higher trophic levels. To investigate the interactions between toxin producers and their grazers, we determined the kinetics of grazer‐induced increases in toxin production and the subsequent toxin reduction in a domoic acid (DA)‐producing diatom, Pseudo‐nitzschia seriata. The cellular DA level of the diatom was within the range of in situ measurements. Ten days after removal of the copepods, 28% ± 8% of the cellular DA still remained in the cells. Simultaneously, we monitored the toxicokinetics of DA in two grazers; Calanus finmarchicus and Calanus glacialis. After 144 h of grazing on the toxic diet, the copepods accumulated and retained high concentrations of DA. Nine hours after exposure to the toxic diet was terminated, the copepods had depurated 70% ± 10% of the DA. The depuration lasted 4 ± 2 d and was independent of Calanus species and treatment. We explored the possible physiological responses in copepods after feeding on a purely toxic diet from gene expression profiles of C. finmarchicus. Expression of genes regulating several major metabolic and cellular processes was reduced in copepods feeding on DA‐containing diatoms, and we hypothesize that this is because of exposure to DA.
When is complemented in tensor products of ?
Authors: Morelli Cortes Vinícius , Medina Galego Elói , Samuel Christian
Published: December 2018

Let X be a Banach space, let I be an infinite set, let τ be an infinite cardinal and let . In contrast to a classical c0 result due independently to Cembranos and Freniche, we prove that if the cofinality of τ is greater than the cardinality of I, then the injective tensor product contains a complemented copy of if and only if X does. This result is optimal for every regular cardinal τ. On the other hand, we provide a generalization of a c0 result of Oja by proving that if τ is an infinite cardinal, then the projective tensor product contains a complemented copy of if and only if X does. These results are obtained via useful descriptions of tensor products as convenient generalized sequence spaces.
New county jail unit speaks to addressing mental health needs
Authors: Enos Gary
Published: December 2018

Leaders from a local mental health center and a county jail in western Minnesota are partnering to improve upon what can be a chaotic experience for detainees with mental illness.
Design of a fragment‐type UHF RFID tag integrated into printed circuit board
Authors: Tao Yonghui , Zang Xian , Wang Can , Yang Chenwei
Published: December 2018

A conformal radio frequency identification tag antenna can be integrated into printed circuit board (PCB) is presented. The simulation and experiment results indicate that the proposed tag can be reached as being applied on stacked PCB boards or separated PCB board. The design area of the proposed tag is 6 × 46 mm, which is small enough for most PCB boards. And it is also proved that the proposed tag can be used in PCB boards with different thicknesses. The maximum read range is measured to be 2.7 and 3.5 m as the tag is deployed on stacked PCB boards and separately placed PCB boards.
Naringenin Promotes Thermogenic Gene Expression in Human White Adipose Tissue
Authors: Rebello Candida J. , Greenway Frank L. , Lau Frank H. , Lin Yuan , Stephens Jacqueline M. , Johnson William D. , Coulter Ann A.
Published: December 2018

Objective

Naringenin, a citrus flavonoid, prevents diet‐induced weight gain and improves glucose and lipid metabolism in rodents. There is evidence that naringenin activates brown fat and increases energy expenditure in mice, but little is known about its effects in humans. The goal of this study was to examine the effects of naringenin on energy expenditure in adipose tissue.

Methods

Human white adipocyte cultures (hADSC) and abdominal subcutaneous adipose tissue (pWAT) were treated with naringenin for 7 to 14 days. Expression (quantitative real‐time polymerase chain reaction, immunoblotting) of candidate genes involved in thermogenesis and glucose metabolism was measured. Oxygen consumption rate was measured in hADSC using a Seahorse flux analyzer.

Results

In hADSC, naringenin increased expression of the genes associated with thermogenesis and fat oxidation, including uncoupling protein 1 and adipose triglyceride lipase, and key factors associated with insulin sensitivity, including glucose transporter type 4, adiponectin, and carbohydrate‐responsive element‐binding protein (P < 0.01). Similar responses were observed in pWAT. Basal, ATP‐linked, maximal and reserve oxygen consumption rate increased in the naringenin‐treated hADSC (P < 0.01).

Conclusions

Naringenin increases energy expenditure in hADSC and stimulates expression of key enzymes involved in thermogenesis and insulin sensitivity in hADSC and pWAT. Naringenin may promote conversion of human white adipose tissue to a brown/beige phenotype.
Kinetic solvent effects in organic reactions
Authors: Slakman Belinda L. , West Richard H.
Published: December 2018

This article reviews prior work studying reaction kinetics in solution, with the goal of using this information to improve detailed kinetic modeling in the solvent phase. Both experimental and computational methods for calculating reaction rates in liquids are reviewed. Previous studies, which used such methods to determine solvent effects, are then analyzed based on the reaction family. Many of these studies correlate kinetic solvent effect with one or more solvent parameters or properties of reacting species, but it is not always possible, and investigations are usually done on too few reactions and solvents to truly generalize. From these studies, we present suggestions on how best to use data to generalize solvent effects for many different reaction types in a high throughput manner.
Ring opening polymerization and copolymerization of L‐lactide and ɛ‐caprolactone by bis‐ligated magnesium complexes
Authors: Slattery Reile M. , Stahl Amanda E. , Brereton Kelsey R. , Rheingold Arnold L. , Green David B. , Fritsch Joseph M.
Published: December 2018

Seven magnesium complexes (1–7) were synthesized by reaction of new (L
3‐H–L
5‐H) and previously reported ketoimine pro‐ligands with dibutyl magnesium and were isolated in 59–70% yields. Complexes 1–7 were characterized fully and consisted of bis‐ligated homoleptic ketoiminates coordinated in distorted octahedral geometry around the magnesium centers. The complexes were investigated for their ability to initiate the ring opening polymerization (ROP) of l‐lactide (L‐LA) to poly‐lactic acid (PLA) and ɛ‐caprolactone (ɛCL) to poly‐caprolactone in the presence of 4‐fluorophenol co‐catalyst. For L‐LA polymerization, complexes containing ligand electron‐donating groups (1–5) achieved >90% conversion in 2 h at 100 °C, while the presence of CF3 groups in 6 and 7 slowed or resulted in no PLA detected. With ɛCL, ROP initiated with 1–7 resulted in lower percentage conversion with similar electronic effects. Moderate molecular weight PLA polymeric material (14.3–21.3 kDa) with low polydispersity index values (1.23–1.56) was obtained, and ROP appeared to be living in nature. Copolymerization of L‐LA and ɛCL yielded block copolymers only from the sequential polymerization of ɛCL followed by L‐LA and not the reverse sequence of monomers or the simultaneous presence of both monomers. Polymers and copolymers were characterized with NMR, gel permeation chromatography, and differential scanning calorimetry. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 48–59