bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigación básica y enfermedades respiratorias
Authors: Borzone Tassara Gisella , Gonzalez Bombardiere Sergio
Published: March 2018

Sin resumen
Caso anatomo-clínico
Authors: Gazitua Harmsen Ricardo , Pertuze Rivera Julio , Gonzalez Bombardiere Sergio , Lisboa Basualto Carmen
Published: March 2018

Sin resumen
La psiquiatría como disciplina médica
Authors: Labarca Rodrigo
Published: March 2018

Sin resumen
Modelo biopsicosocial-evolutivo en psiquiatría
Authors: Fischman Gluck Patricio
Published: March 2018

Sin resumen
El imperativo de la participación en costo-efectividad y control de calidad en nuestra institución
Authors: Rossi Fernández Ricardo
Published: March 2018

Sin resumen
Educación médica y relación costo-efecto
Authors: Moreno B, Rodrigo , Velasco F. Nicolas
Published: March 2018

Sin resumen
Sistemas actuales de la salud en Chile y sus posibles cambios en las próximas décadas
Authors: Bellolio R. Jaime
Published: March 2018

Sin resumen
Control de calidad y costo-efectividad en el manejo del enfermo con cáncer
Authors: Rossi F. Ricardo , Baeza B. Ramón , Leon R. Augusto , Alvarez Z. Manuel , Besa de C. Pelayo , Razmilic V. Dravn , Vial V. Loreto
Published: March 2018

Sin resumen
Desarrollo de una estrategia de crecimiento en la cirugía cardiaca. Etapa inicial: identificación de los costos
Authors: Cifuentes Luis , Musso Santiago , Cabero Cristian , Espejo Andres , Massanes Loreto , Oberli Chistian , Oliver Lorena
Published: March 2018

Sin resumen
Erradicación de Helicobacter pylori en Chiles: ¿Quiénes, cómo, para qué?
Authors: Rollan Rodriguez Antonio
Published: March 2018

Sin resumen
Enfrentando la patología pleural
Authors: Cruz Mena Edgardo
Published: March 2018

Sin resumen
Derrame pleural neoplásico
Authors: Pertuze Rivera Julio , Aparicio Ramírez Rodrigo
Published: March 2018

Sin resumen
Casos radiológicos
Authors: Piddo Mujaes Claudia , Ríos Olsen Guillermo , García Bruce Cristian
Published: March 2018

Sin resumen
Patología de la glándula prostática
Authors: Matínez Sanz Carlos
Published: March 2018

Sin resumen
Aspectos epidemiológicos de la patología prostática
Authors: Martinez Carlos
Published: March 2018

Sin resumen
Procesos inflamantorios prostáticos
Authors: Martinez Sanz Carlos
Published: March 2018

Sin resumen
Hiperplasia prostática benigna: fisiopatología, clínica y tratamiento no invasivo
Authors: Martinez Sanz Pedro
Published: March 2018

Sin resumen
Tamizaje o screening en cáncer de la próstata
Authors: Trucco Brito Cristian
Published: March 2018

Sin resumen
Cáncer de la próstata: detección precoz, clínica y decisiones de tratamiento
Authors: Troncoso Carrasco Pablo
Published: March 2018

Sin resumen
Manejo del cáncer de prostata, avanzado, recidivado
Authors: Velasco Palma Alfredo
Published: March 2018

Sin resumen
Embolia pulmonar: Fisiopatología y diagnóstico
Authors: Diaz Patiño Orlando , Andresen Hernandez Max
Published: March 2018

Sin resumen
Rol de la medicina nuclear en el diagnóstico de TEP
Authors: Olea Garcia Enrique
Published: March 2018

Sin resumen
Heparinas y cumarínicos
Authors: Pereira Garces Jaime
Published: March 2018

Sin resumen
A miR-29b Byproduct Sequence Exhibits Potent Tumor-Suppressive Activities via Inhibition of NF-κB Signaling in KRAS-Mutant Colon Cancer Cells
Authors: Inoue Akira , Mizushima Tsunekazu , Wu Xin , Okuzaki Daisuke , Kambara Nanami , Ishikawa Sho , Wang Jiaqi , Qian Yamin , Hirose Haruka , Yokoyama Yuhki , Ikeshima Ryo , Hiraki Masayuki , Miyoshi Norikatsu , Takahashi Hidekazu , Haraguchi Naotsugu , Hata Taishi , Matsuda Chu , Doki Yuichiro , Mori Masaki , Yamamoto Hirofumi
Published: March 2018

We previously demonstrated that miR-29b-3p is a hopeful miRNA-based therapy against colorectal cancer. In this study, we aimed to clarify a value of miR-29b-1-5p as a next-generation treatment, especially for KRAS-mutant colorectal cancer. RT-PCR assay showed that the expression of miR-29b-3p was high, and its partner strand, miR-29b-1-5p, level was only negligible in clinical colorectal cancer samples. Mimic-miR-29b-1-5p significantly inhibited proliferation of KRAS-mutant colorectal cancer cell lines DLD1 and SW480 and KRAS wild-type HT29 cells. Proliferative activity was further examined by either miR-29b-1-5p strand or its opposite complementary sequence because miR-29b-1-5p is a passenger miRNA and may have no physiologic function. We found that completely opposite complementary strand to miR-29b-1-5p, but not miR-29b-1-5p, possessed a potent antitumor effect and named this byproduct miRNA sequence “MIRTX.” MIRTX directly targeted the 3′-UTR of CXCR2 and PIK3R1 mRNA and suppressed the NF-κB signaling pathway in KRAS-mutated colorectal cancer cells. MIRTX induced apoptosis in DLD1 with downregulation of antiapoptotic BCL2, BCL-xL, and MCL1 and upregulation of cleaved caspase-3 and cleaved PARP. In mouse xenograft models, systemic administration of MIRTX using a super carbonate apatite as a delivery vehicle significantly inhibited tumor growth of DLD1 and HT29 cells without any particular toxicities. In conclusion, these findings indicate that inhibition of NF-κB signaling by this novel miRNA-based therapeutic could be a promising treatment against refractory KRAS-mutant colorectal cancer and KRAS wild-type colorectal cancer. Mol Cancer Ther; 17(5); 977–87. ©2018 AACR.
D-2-Hydroxyglutarate Is Necessary and Sufficient for Isocitrate Dehydrogenase 1 Mutant–Induced MIR148A Promoter Methylation
Authors: Li Tie , Cox Christopher D. , Ozer Byram H. , Nguyen Nhung T. , Nguyen HuyTram N. , Lai Thomas J. , Li Sichen , Liu Fei , Kornblum Harley I. , Liau Linda M. , Nghiemphu Phioanh L. , Cloughesy Timothy F. , Lai Albert
Published: March 2018

Mutant isocitrate dehydrogenase (IDH) 1/2 converts α-ketoglutarate (α-KG) to D-2 hydroxyglutarate (D-2-HG), a putative oncometabolite that can inhibit α-KG–dependent enzymes, including ten-eleven translocation methylcytosine dioxygenase (TET) DNA demethylases. We recently established that miRNAs are components of the IDH1 mutant–associated glioma CpG island methylator phenotype (G-CIMP) and specifically identified MIR148A as a tumor-suppressive miRNA within G-CIMP. However, the precise mechanism by which mutant IDH induces hypermethylation of MIR148A and other G-CIMP promoters remains to be elucidated. In this study, we demonstrate that treatment with exogenous D-2-HG induces MIR148A promoter methylation and transcriptional silencing in human embryonic kidney 293T (293T) cells and primary normal human astrocytes. Conversely, we show that the development of MIR148A promoter methylation in mutant IDH1–overexpressing 293T cells is abrogated via treatment with C227, an inhibitor of mutant IDH1 generation of D-2-HG. Using dot blot assays for global assessment of 5-hydroxymethylcytosine (5-hmC), we show that D-2-HG treatment reduces 5-hmC levels, whereas C227 treatment increases 5-hmC levels, strongly suggesting TET inhibition by D-2-HG. Moreover, we show that withdrawal of D-2-HG treatment reverses methylation with an associated increase in MIR148A transcript levels and transient generation of 5-hmC. We also demonstrate that RNA polymerase II binds endogenously to the predicted promoter region of MIR148A, validating the hypothesis that its transcription is driven by an independent promoter.

Implications: Establishment of D-2-HG as a necessary and sufficient intermediate by which mutant IDH1 induces CpG island methylation of MIR148A will help with understanding the efficacy of selective mutant IDH1 inhibitors in the clinic. Mol Cancer Res; 16(6); 947–60. ©2018 AACR.
USP28 Deficiency Promotes Breast and Liver Carcinogenesis as well as Tumor Angiogenesis in a HIF-independent Manner
Authors: Richter Kati , Paakkola Teija , Mennerich Daniela , Kubaichuk Kateryna , Konzack Anja , Ali-Kippari Heidi , Kozlova Nina , Koivunen Peppi , Haapasaari Kirsi-Maria , Jukkola-Vuorinen Arja , Teppo Hanna-Riikka , Dimova Elitsa Y. , Bloigu Risto , Szabo Zoltan , Kerkelä Risto , Kietzmann Thomas
Published: March 2018

Recent studies suggest that the ubiquitin-specific protease USP28 plays an important role in cellular repair and tissue remodeling, which implies that it has a direct role in carcinogenesis. The carcinogenic potential of USP28 was investigated in a comprehensive manner using patients, animal models, and cell culture. The findings demonstrate that overexpression of USP28 correlates with a better survival in patients with invasive ductal breast carcinoma. Mouse xenograft experiments with USP28-deficient breast cancer cells also support this view. Furthermore, lack of USP28 promotes a more malignant state of breast cancer cells, indicated by an epithelial-to-mesenchymal (EMT) transition, elevated proliferation, migration, and angiogenesis as well as a decreased adhesion. In addition to breast cancer, lack of USP28 in mice promoted an earlier onset and a more severe tumor formation in a chemical-induced liver cancer model. Mechanistically, the angio- and carcinogenic processes driven by the lack of USP28 appeared to be independent of HIF-1α, p53, and 53BP1.

Implications: The findings of this study are not limited to one particular type of cancer but are rather applicable for carcinogenesis in a more general manner. The obtained data support the view that USP28 is involved in tumor suppression and has the potential to be a prognostic marker. Mol Cancer Res; 16(6); 1000–12. ©2018 AACR.
Olaparib-induced Adaptive Response Is Disrupted by FOXM1 Targeting that Enhances Sensitivity to PARP Inhibition
Authors: Fang Pingping , Madden Jill A. , Neums Lisa , Moulder Ryan K. , Forrest M. Laird , Chien Jeremy
Published: March 2018

FOXM1 transcription factor network is activated in over 84% of cases in high-grade serous ovarian cancer (HGSOC), and FOXM1 upregulates the expression of genes involved in the homologous recombination (HR) DNA damage and repair (DDR) pathway. However, the role of FOXM1 in PARP inhibitor response has not yet been studied. This study demonstrates that PARP inhibitor (PARPi), olaparib, induces the expression and nuclear localization of FOXM1. On the basis of ChIP-qPCR, olaparib enhances the binding of FOXM1 to genes involved in HR repair. FOXM1 knockdown by RNAi or inhibition by thiostrepton decreases FOXM1 expression, decreases the expression of HR repair genes, such as BRCA1 and RAD51, and enhances sensitivity to olaparib. Comet and PARP trapping assays revealed increases in DNA damage and PARP trapping in FOXM1-inhibited cells treated with olaparib. Finally, thiostrepton decreases the expression of BRCA1 in rucaparib-resistant cells and enhances sensitivity to rucaparib. Collectively, these results identify that FOXM1 plays an important role in the adaptive response induced by olaparib and FOXM1 inhibition by thiostrepton induces “BRCAness” and enhances sensitivity to PARP inhibitors.

Implications: FOXM1 inhibition represents an effective strategy to overcome resistance to PARPi, and targeting FOXM1-mediated adaptive pathways may produce better therapeutic effects for PARP inhibitors. Mol Cancer Res; 16(6); 961–73. ©2018 AACR.
Cholesterol Esterification Inhibition Suppresses Prostate Cancer Metastasis by Impairing the Wnt/β-catenin Pathway
Authors: Lee Hyeon Jeong , Li Jie , Vickman Renee E. , Li Junjie , Liu Rui , Durkes Abigail C. , Elzey Bennett D. , Yue Shuhua , Liu Xiaoqi , Ratliff Timothy L. , Cheng Ji-Xin
Published: March 2018

Dysregulation of cholesterol is a common characteristic of human cancers including prostate cancer. This study observed an aberrant accumulation of cholesteryl ester in metastatic lesions using Raman spectroscopic analysis of lipid droplets in human prostate cancer patient tissues. Inhibition of cholesterol esterification in prostate cancer cells significantly suppresses the development and growth of metastatic cancer lesions in both orthotopic and intracardiac injection mouse models. Gene expression profiling reveals that cholesteryl ester depletion suppresses the metastatic potential through upregulation of multiple regulators that negatively impact metastasis. In addition, Wnt/β-catenin, a vital pathway for metastasis, is downregulated upon cholesteryl ester depletion. Mechanistically, inhibition of cholesterol esterification significantly blocks secretion of Wnt3a through reduction of monounsaturated fatty acid levels, which limits Wnt3a acylation. These results collectively validate cholesterol esterification as a novel metabolic target for treating metastatic prostate cancer. Mol Cancer Res; 16(6); 974–85. ©2018 AACR.
Fluorescent Light-Guided Cystoscopy with 5-ALA Aids in Accurate Surgical Margin Detection for TURBO: A Case Report
Authors: Takamoto Daiji , Kawahara Takashi , Ohtake Shinji , Mochizuki Taku , Kuroda Shinnosuke , Nakaigawa Noboru , Izumi Koji , Miyoshi Yasuhide , Makiyama Kazuhide , Yao Masahiro , Sawazumi Tomoe , Inayama Yoshiaki , Ohta Junichi , Uemura Hiroji
Published: March 2018

Recent studies have revealed that transurethral resection in one piece (TURBO) has several benefits over standard transurethral resection of bladder tumor (TUR-Bt), including a higher rate of containing the bladder muscle tissue and single-block resection. Five-aminolevulinic acid (5-ALA) was approved for the detection of bladder tumor treated with TUR-Bt. A 71-year-old male patient who received right nephroureterectomy developed bladder tumor recurrence on routine cystoscopy follow-up. We planned TURBO using fluorescent light-guided cystoscopy with 5-ALA. We herein report a case of bladder tumor successfully treated with TURBO using fluorescent light-guided cystoscopy with 5-ALA to detect the tumor surgical margin.
Incidence and Risk Profile of Dementia in the Regions of Middle East and North Africa
Authors: Bhalla Devender , Lotfalinezhad Elham , Amini Fatemah , Salmannejad Mohsen , Reza Borhani Nezhad Vahid , Rezai Kooshalshah Seyedeh Fatemeh  , Delbari Ahmed , Fadayevatan Reza , Irmansyah I , Abdelrahman Abdalla , Bhatta Nanda Kumar , Gharagozli Kurosh
Published: March 2018

Background: The risk of dementia is reported as “epidemic” and “looming” over the Middle East and North Africa (MENA) region. For this, we performed a multi-language review and feasible analysis on the incidence of dementia to offer apt conclusions. Methods: Totally, 3 databases (Magiran, Scientific Information Database, and PubMed) and 1 non-database source (Google) were searched in French, English, and Persian by using specific keywords and their combinations. All searches were independent and had no restriction for the year or type of publication. We also calculated cumulative incidence of dementia for Egypt and Israel-Palestine from relevant prevalence estimates by using standard formula. Results: Little information on incidence was available, sparing Israel (2.4/100,000/year; pre-senile). Ten (48.0%) countries had none-to-little information (of any kind) on dementia, indicating considerable awareness deficit in this region. Cumulative incidence of dementia in Egypt and Israel-Palestine was 2.7% over 20 years (55 new cases) and 14.7% (130 new cases) over 6 years, respectively. In Lebanon, cumulative incidence was 7.5% over 20 years. Data looked across dementia-related factors (i.e., fertility rate, polygamy, violence, hypovitaminosis D, diabetes, hypertension, life expectancy, age structure) did not seem to support epidemic proportions of dementia for MENA. Conclusions: MENA is youthful and dementia here is neither likely to be an epidemic nor looming over. The only possible exception might be Arab pocket in Israel. To us, previous attributions on dementia do not seem to be based on the realities of this region and, therefore, may prevent pragmatic addressal of dementia. Lastly, values-based collaborations are invited to jointly fill the awareness deficit in a unique low-cost manner.
Hypothalamic Response to Kisspeptin-54 and Pituitary Response to Gonadotropin-Releasing Hormone Are Preserved in Healthy Older Men
Authors: Abbara Ali , Narayanaswamy Shakunthala , Izzi-Engbeaya Chioma , Comninos Alexander N. , Clarke Sophie A. , Malik Zainab , Papadopoulou Deborah , Clobentz Ailish , Sarang Zubair , Bassett Paul , Jayasena Channa N. , Dhillo Waljit S.
Published: March 2018

Background: Male testosterone levels decline by 1% per year from the age of 40 years. Whilst a primary testicular deficit occurs, hypothalamic or pituitary dysregulation may also coexist. This study aimed to compare the hypothalamic response to kisspeptin-54 and the pituitary response to gonadotropin-releasing hormone (GnRH) of older men with those of young men. Methods: Following 1 h of baseline sampling, healthy older men (n = 5, mean age 59.3 ± 2.9 years) received a 3-h intravenous infusion of either vehicle, kisspeptin-54 0.1, 0.3, or 1.0 nmol/kg/h or GnRH 0.1 nmol/kg/h, on five different study days. Serum gonadotropins and total testosterone were measured every 10 min and compared to those of young men (n = 5/group) (mean age 28.9 ± 2.0 years) with a similar body mass index (24 kg/m2) who underwent the same protocol. Results: Kisspeptin-54 and GnRH significantly stimulated serum gonadotropin release in older men compared to vehicle (p < 0.001 for all groups). Gonadotropin response to kisspeptin-54 was at least preserved in older men when compared to young men. At the highest dose of kisspeptin-54 (1.0 nmol/kg/h), a significantly greater luteinising hormone (LH) (p = 0.003) response was observed in older men. The follicle-stimulating hormone (FSH) response to GnRH was increased in older men (p = 0.002), but the LH response was similar (p = 0.38). Serum testosterone rises following all doses of kisspeptin-54 (p ≤ 0.009) were reduced in older men. Conclusions: Our data suggest that healthy older men without late-onset hypo­gonadism (LOH) have preserved hypothalamic response to kisspeptin-54 and pituitary response to GnRH, but impaired testicular response. Further work is required to investigate the use of kisspeptin-54 to identify hypothalamic deficits in men with LOH.
ВИВЧЕННЯ РІВНЯ ЗНАНЬ І ПРАКТИЧНИХ НАВИЧОК ФАХІВЦІВ ОФТАЛЬМОЛОГІЧНОГО ПРОФІЛЮ ТА ЇХ ОСВІТНІ ПОТРЕБИ
Authors: Saksonov S. G.
Published: March 2018

Мета: визначення рівня кваліфікації лікарів офтальмологічного профілю та їх сучасних інформаційно-освітніх потреб.Матеріали і методи. Використано бібліографічний, соціологічний, медико-статистичний та інформаційно-аналітичний методи.Результати. Високо оцінюють рівень своєї кваліфікації 65,2±3,3 на 100 опитаних фахівці офтальмологічного профілю, низько – 12,4±2,3, утрималися від оцінки 22,3±2,9.Більше половини респондентів відвідували курси підвищення кваліфікації 1 раз на 5 років. При цьому, 18,6±2,7 на 100 опитаних робили це 2 і більше разів на рік, тоді як менше 1 разу на 5 років – 12,4±2,3, а 12,9±2,3 їх взагалі не проходили. Причинами низької частоти підвищення кваліфікації є неможливість відриву від роботи (42,2±3,3 на 100 опитаних), зменшення заробітку на період навчання (13,8±2,3), високу вартість витрат на проживання та дорогу (26,6±3,0), високу вартість деяких форм підвищення кваліфікації на комерційній основі (74,3±3,0).Підтвердили потребу у підвищенні кваліфікації 75,0±3,0 на 100 офтальмологів. Встановлено бажані форми підвищення кваліфікації лікарів офтальмологічного профілю.Висновки. Отримані результати щодо кваліфікації лікарів, їх сучасних інформаційно-освітніх потреб є важливою передумовою обґрунтування заходів з удосконалення надання офтальмологічної допомоги населенню.
АНТИОКСИДАНТНА ТЕРАПІЯ У ЖІНОК ІЗ БЕЗПЛІДДЯМ НА ФОНІ ГЕНІТАЛЬНОГО ЕНДОМЕТРІОЗУ
Authors: Khmil S. V. , Kulyk I. I. , Khmil A. S.
Published: March 2018

Мета: проаналізувати дані огляду літератури щодо впливу оксидативного стресу на якість яйцеклітин у жінок із безпліддям на фоні генітального ендометріозу та основні принципи антиоксидантної терапії.Матеріали і методи. У дослідженні застосовано бібліосемантичний метод – проаналізовано 37 джерел наукової літератури.Результати. За матеріалами використаних наукових досліджень встановлено прямий вплив оксидативного стресу на якість яйцеклітин і ембріонів та дію антиоксидантів на різні ланки патогенезу оксидативного стресу. Вплив оксидативного стресу на розвиток симптомів ендометріозу та доцільність використання антиоксидантів як допоміжного напрямку лікування ендометріозу, асоційованого з безпліддям.Висновки. Оксидативний стрес є однією з причин виникнення ендометріозу асоційованого з безпліддям. Приймання антиоксидантних препаратів знижує явища оксидативного стресу і покращує якість яйцеклітин та ембріонів, а отже результати лікування безпліддя.
Description of the first juvenile stage of the fiddler crab Minuca mordax (Smith, 1870) (Crustacea, Decapoda, Ocypodidae)
Authors: Martins Salise Brandt , Marochi Murilo Zanetti , Masunari Setuko
Published: March 2018

The first stage of the fiddler crab Minuca mordax is described here. Zoea larvae obtained from four ovigerous female were reared in the laboratory until the development of the first crab stage. The development from zoea I to the first juvenile instar lasted 35 days after hatching. The first crab stage of Minuca mordax can be morphologically distinguished from those of Minuca burgersi and Leptuca cumulanta by a 2‑segmented antennule endopod (3‑segmented in M. burgersi, unsegmented in L. cumulanta), an unsegmented maxillule endopod (2‑segmented in M. burgersi and L. cumulanta), and a 4‑segmented first and second maxilliped endopod (respectively unsegmented and 5‑segmented in M. burgersi and L. cumulanta). The three species have the following characters in common: segmented peduncle of antennule 2; endopod of antennule unsegmented; presence of aesthetascs on the antennule; peduncle of antenna 3‑segmented; flagellum of antenna 6‑segmented; mandible 3‑segmented; maxilla with coxal and basal endite bilobed; first, second and third maxillae with exopod 2‑segmented and abdomen with six somites that are wider than long.
Idades U-Pb de zircão detríticos e suas implicações na proveniência de sedimentos da Formação Penedo, Bacia de Sergipe-Alagoas, NE Brasil
Authors: Melo Alice Maria Queiroz de , Rosa Maria De Lourdes da Silva , Conceição Herbet
Published: March 2018

A Formação Penedo representa um sistema fluviodeltaico de padrão entrelaçado pertencente ao estágio rifte da Bacia de Sergipe-Alagoas (BSA). Este trabalho foi realizado na seção aflorante, que deu o nome a esta unidade, localizada na cidade de Penedo, Estado de Alagoas, e denominada PDO-01. A metodologia de estudo envolveu análise de paleocorrente aliada à datação U-Pb de cristais de zircão detríticos por Espectrometria de Massa por Ablação a Laser (LA-ICP-MS). O registro sedimentar de paleocorrentes indicou aporte vindo de norte, enquanto os cristais analisados apresentaram idades variando do Mesoarqueano (3098 ± 33 Ma) ao Paleozoico (530 ± 12 Ma), que foram reunidas em cinco grupos (G1 a G5). Dessa análise conjunta foram propostas as seguintes fontes de proveniência: para o primeiro grupo (G1), os granitos neoproterozoicos (~670 Ma) pertencentes ao Domínio Pernambuco-Alagoas; para o segundo grupo (G2), as rochas do Complexo Cabrobó (~0,9 – 1,2 Ga); para o terceiro grupo (G3), as rochas do Complexo Arapiraca com idades paleoproterozoicas (~1,6 – 2,2 Ga); e para o quarto e o quinto grupos (G4 e G5), as rochas do Complexo Nicolau Campo Grande com idades neoarqueanas (~2,4 – 3,0 Ga).
Senescence Alters PPARγ (Peroxisome Proliferator–Activated Receptor Gamma)-Dependent Fatty Acid Handling in Human Adipose Tissue Microvascular Endothelial Cells and Favors Inflammation
Authors: Briot Anaïs , Decaunes Pauline , Volat Fanny , Belles Chloé , Coupaye Muriel , Ledoux Séverine , Bouloumié Anne
Published: March 2018

Objective—

Adipose tissue (AT) dysfunction associated with obesity or aging is a major cause for lipid redistribution and the progression of cardiometabolic disorders. Our goal is to decipher the contribution of human AT microvascular endothelial cells (ECs) in the maintenance of fatty acid (FA) fluxes and the impact of senescence on their function.

Approach and Results—

We used freshly isolated primary microvascular ECs from human AT. Our data identified the endothelial FA handling machinery including FATPs (FA transport proteins) FATP1, FATP3, FATP4, and CD36 as well as FABP4 (FA binding protein 4). We showed that PPARγ (peroxisome proliferator–activated receptor gamma) regulates the expression of FATP1, CD36, and FABP4 and is a major regulator of FA uptake in human AT EC (hATEC). We provided evidence that endothelial PPARγ activity is modulated by senescence. Indeed, the positive regulation of FA transport by PPARγ agonist was abolished, whereas the emergence of an inflammatory response was favored in senescent hATEC. This was associated with the retention of nuclear FOXO1 (forkhead box protein O1), whereas nuclear PPARγ translocation was impaired.

Conclusions—

These data support the notion that PPARγ is a key regulator of primary hATEC function including FA handling and inflammatory response. However, the outcome of PPARγ activation is modulated by senescence, a phenomenon that may impact the ability of hATEC to properly respond to and handle lipid fluxes. Finally, our work highlights the role of hATEC in the regulation of FA fluxes and reveals that dysfunction of these cells with accelerated aging is likely to participate to AT dysfunction and the redistribution of lipids.
Trajectories of Health-Related Quality of Life in Coronary Artery Disease
Authors: Sajobi Tolulope T. , Wang Meng , Awosoga Oluwagbohunmi , Santana Maria , Southern Danielle , Liang Zhiying , Galbraith Diane , Wilton Stephen B. , Quan Hude , Graham Michelle M. , James Matthew T. , Ghali William A. , Knudtson Merrill L. , Norris Colleen
Published: March 2018

Background:

Health-related quality of life (HRQOL) assessment is an important health outcome for measuring the efficacy of treatments and interventions for coronary artery disease (CAD). HRQOL is known to improve over the first year after interventions for CAD, but there is limited knowledge of the changes in HRQOL beyond 1 year. We investigated heterogeneity in long-term trajectories of HRQOL in patients with CAD.

Methods and Results:

Data were obtained from 6226 patients identified from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease with at least 1-vessel CAD who underwent their first catheterization between 2006 and 2009. HRQOL was assessed using the Seattle Angina Questionnaire, a 19-item disease-specific measure of HRQOL for patients with CAD. Group-based trajectory analysis was used to identify various subgroups of Seattle Angina Questionnaire trajectories over time while adjusting for missing data through a longitudinal multiple imputation model. Multinomial logistic regression was used to identify the predictors of differences among the identified subgroups. Our analysis revealed significant improvements in HRQOL across all the 5 domains of Seattle Angina Questionnaire overtime for the whole data. Multitrajectory analyses revealed 4 HRQOL trajectory subgroups including high (25.1%), largely increased (32.3%), largely decreased (25.0%), and low (17.6%) trajectories. Age, sex, body mass index, diabetes mellitus, previous history of myocardial infarction, smoking, depression, anxiety, type of treatment received, and perceived social support were significant predictors of differences among these trajectory subgroups.

Conclusions:

This study highlights variations in longitudinal trajectories of HRQOL in patients with CAD. Despite overall improvements in HRQOL, about a quarter of our cohort experienced a significant decline in their HRQOL over the 5-year period. Understanding these HRQOL trajectories may help personalize prognostic information, identify patients and HRQOL domains on which clinical interventions are most beneficial, and support treatment decisions for patients with CAD.
TBX20 Regulates Angiogenesis Through the Prokineticin 2–Prokineticin Receptor 1 Pathway
Authors: Meng Shu , Gu Qilin , Yang Xiaojie , Lv Jie , Owusu Iris , Matrone Gianfranco , Chen Kaifu , Cooke John P. , Fang Longhou
Published: March 2018

Background:

Angiogenesis is integral for embryogenesis, and targeting angiogenesis improves the outcome of many pathological conditions in patients. TBX20 is a crucial transcription factor for embryonic development, and its deficiency is associated with congenital heart disease. However, the role of TBX20 in angiogenesis has not been described.

Methods:

Loss- and gain-of-function approaches were used to explore the role of TBX20 in angiogenesis both in vitro and in vivo. Angiogenesis gene array was used to identify key downstream targets of TBX20.

Results:

Unbiased gene array survey showed that
TBX20
knockdown profoundly reduced angiogenesis-associated
PROK2
(prokineticin 2) gene expression. Indeed, loss of TBX20 hindered endothelial cell migration and in vitro angiogenesis. In a murine angiogenesis model using subcutaneously implanted Matrigel plugs, we observed that TBX20 deficiency markedly reduced PROK2 expression and restricted intraplug angiogenesis. Furthermore, recombinant PROK2 administration enhanced angiogenesis and blood flow recovery in murine hind-limb ischemia. In zebrafish, transient knockdown of
tbx20
by morpholino antisense oligos or genetic disruption of
tbx20
by CRISPR/Cas9 impaired angiogenesis. Furthermore, loss of
prok2
or its cognate receptor
prokr1a
also limited angiogenesis. In contrast, overexpression of
prok2
or
prokr1a
rescued the impaired angiogenesis in
tbx20
-deficient animals.

Conclusions:

Our study identifies TBX20 as a novel transcription factor regulating angiogenesis through the PROK2–PROKR1 (prokineticin receptor 1) pathway in both development and disease and reveals a novel mode of angiogenic regulation whereby the TBX20-PROK2–PROKR1 signaling cascade may act as a “biological capacitor” to relay and sustain the proangiogenic effect of vascular endothelial growth factor. This pathway may be a therapeutic target in the treatment of diseases with dysregulated angiogenesis.
Associations Between Ambient Particle Radioactivity and Blood Pressure: The NAS (Normative Aging Study)
Authors: Nyhan Marguerite M. , Coull Brent A. , Blomberg Annelise J. , Vieira Carol L.Z. , Garshick Eric , Aba Abdulaziz , Vokonas Pantel , Gold Diane R. , Schwartz Joel , Koutrakis Petros
Published: March 2018

Background

The cardiovascular effects of low‐level environmental radiation exposures are poorly understood. Although particulate matter (
PM
) has been linked to cardiovascular morbidity and mortality, and elevated blood pressure (
BP
), the properties promoting its toxicity remain uncertain. Addressing a knowledge gap, we evaluated whether
BP
increased with higher exposures to radioactive components of ambient
PM
, herein referred to as particle radioactivity (
PR
).

Methods and Results

We performed a repeated‐measures analysis of 852 men to examine associations between
PR
exposure and
BP
using mixed‐effects regression models. As a surrogate for
PR
, we used gross β activity, measured by the US Environmental Protection Agency's radiation monitoring network. Higher
PR
exposure was associated with increases in both diastolic
BP
and systolic
BP
, for exposures from 1 to 28 days. An interquartile range increase in 28‐day
PR
exposure was associated with a 2.95–mm Hg increase in diastolic BP (95% confidence interval, 2.25–3.66;
P
<0.001) and a 3.94–mm Hg increase in systolic BP (95% confidence interval, 2.62–5.27;
P
<0.001). For models including both
PR
and
PM
≤2.5 µm, the
PR
‐
BP
associations remained stable and significant. For models including
PR
and black carbon or
PR
and particle number, the
PR
‐
BP
associations were attenuated; however, they remained significant for many exposure durations.

Conclusions

This is the first study to demonstrate the potential adverse effects of
PR
on both systolic and diastolic
BP
s. These were independent and similar in magnitude to those of PM ≤2.5 µm, black carbon, and particle number. Understanding the effects of particle‐bound radionuclide exposures on
BP
may have important implications for environmental and public health policy.
Does Environmental Governance Matter for Foreign Direct Investment? Testing the Pollution Haven Hypothesis for Indian States
Authors: Kathuria Vinish
Published: March 2018

This paper attempts to examine the role of environmental governance on foreign direct investment by testing the pollution haven hypothesis for 21 Indian states for the period 2002–2010. To test for the hypothesis, this study computes an abatement expenditure index adjusted for industrial composition at the state level using Annual Survey of Industries plant-level data. The methodology used is based on that proposed by Levinson ( 2001 ). The index compares actual pollution abatement expenditures in a particular state, unadjusted for industrial composition, to predicted abatement expenditures in the same state. (The predictions are based on nationwide abatement expenditures by industry and each state's industrial composition.) If the adjusted index is low for a state, it implies that the state has poor environmental governance, which would be expected to induce foreign firms to invest. However, the results do not find any evidence of the pollution haven hypothesis in the Indian context. Other infrastructure and market-access-related variables are more important in influencing a foreign firm's investment decisions than environmental stringency.
Empowering Cities: Good for Growth? Evidence from the People's Republic of China
Authors: Mukim Megha , Zhu T. Juni
Published: March 2018

This paper utilizes a countrywide process of county-to-city upgrading in the 1990s to identify whether extending the powers of urban local governments leads to better firm outcomes. The paper hypothesizes that since local leaders in newly promoted cities have an incentive to utilize their new administrative remit to maximize gross domestic product and employment, there should be improvements in economic outcomes. In fact, aggregate firm-level outcomes do not necessarily improve after county-to-city graduation. However, state-owned enterprises perform better after graduation, with increased access to credit through state-owned banks as a possible explanation. Importantly, newly promoted cities with high capacity generally produce better aggregate firm outcomes compared with newly promoted cities with low capacity. The conclusions are twofold. First, relaxing credit constraints for firms could lead to large increases in their operations and employment. Second, increasing local government's administrative remit is not enough to lead to better firm and economic outcomes; local capacity is of paramount importance.
Gamete Donation: Are Children Entitled to Know Their Genetic Origins? A Comparison of Opposing Views. The Italian State of Affairs
Authors: Montanari Vergallo Gianluca , Marinelli Enrico , di Luca Natale Mario , Zaami Simona
Published: March 2018

Medically assisted fertilization techniques give rise to a wide array of issues, such as the rights to secrecy, partial anonymity or to the full disclosure of information about the donors’ identities. The authors espouse the right of donor-conceived children to know their biological origins, and delve into opposing views, either in favour of the gamete donors’ right to anonymity or against it. Be that as it may, the right to know one’s biological origins has been gaining a foothold as part of the broader right to personal identity. The latter is in fact codified and upheld in numerous international treaties and conventions as a fundamental human right. The authors expound upon the Italian legislation, which is designed to enforce total donor anonymity. Against that backdrop, the authors weigh the suitability of further regulating access to sensitive, identifying information about the procreation methods involved in each case.
On Some Shortcomings of Shannon Entropy as a Measure of Information Content in Indirect Measurements of Continuous Variables
Authors: Petty Grant W.
Published: March 2018

Shannon entropy has long been accepted as a primary basis for assessing the information content of sensor channels used for the remote sensing of atmospheric variables. It is not widely appreciated, however, that Shannon information content (SIC) can be misleading in retrieval problems involving nonlinear mappings between direct observations and retrieved variables and/or non-Gaussian prior and posterior PDFs. The potentially severe shortcomings of SIC are illustrated with simple experiments that reveal, for example, that a measurement can be judged to provide negative information even in cases in which the postretrieval PDF is undeniably improved over an informed prior based on climatology. Following previous authors’ writing mainly in the data assimilation and climate analysis literature, the Kullback–Leibler (KL) divergence, also commonly known as relative entropy, is shown to suffer from fewer obvious defects in this particular context. Yet, even KL divergence is blind to the expected magnitude of errors as typically measured by the error variance or root-mean-square error. Thus, neither information metric can necessarily be counted on to respond in a predictable way to changes in the precision or quality of a retrieved quantity.
Improving the multifunctional behaviour of structural supercapacitors by incorporating chemically activated carbon fibres and mesoporous silica particles as reinforcement
Authors: Javaid A , Ho KKC , Bismarck A , Steinke JHG , Shaffer MSP , Greenhalgh ES
Published: March 2018

Novel structural supercapacitors have been fabricated which can simultaneously carry mechanical loads as well as store electrochemical energy. Structural supercapacitors are fabricated by impregnating activated carbon fibre mat electrodes and glass fibre mat separator with crosslinked polymer electrolytes using the resin infusion under flexible tooling method. Mesoporous silica particles are also used as reinforcements to further improve the electrochemical and mechanical performance of structural supercapacitors. The fabricated structural supercapacitors have been characterised through chronoamperometry method and impedance spectroscopy to evaluate the electrochemical performance and in-plane shear properties to evaluate the mechanical performance. A multifunctional structural supercapacitor, exhibiting simultaneously a power density of 34 W kg−1, an energy density of 0.12 Wh kg−1 and a shear modulus of 1.75 GPa, has been fabricated.
Analyzing the international trade-related food miles in Iran
Authors: Mosammam Hassan Mohammadian , Sarrafi Mozaffar , Nia Jamileh Tavakoli , Mosammam Ali Mohammadian
Published: March 2018

The aim of this article was to present a “snapshot” of Iran’s total import-related food miles and associated direct environmental costs in 1999 and 2013. Based on a customized model, the import-related “food miles” was calculated for 14 food groups. The methods used provide new insights to be obtained about how far agricultural products travel from their point of production to the main cities in Iran. We also calculated travel-related energy use and CO2 emissions based on different transport modes. Distance and agricultural products data were obtained from national and international sources. Produce arriving at the main cities in Iran were typically transported more than 15,456 km in 1999. In 2013, however, average food miles have fallen 47%, largely driven by indirect food imports. In terms of energy use, imported products accounted for 130,855 TJ of energy use in 1999; this was reduced by 10% in 2013. Moreover, these changes account for more than 10 and 9 Mt of food miles-related CO2 emissions in 1999 and 2013, respectively. There is an opportunity to re-legislate and revise policies regarding both imported and domestically grown food.
Sericin–copper-functionalized silk fabrics for enhanced ultraviolet protection and antibacterial properties using response surface methodology
Authors: Chitichotpanya Pisutsaran , Pisitsak Penwisa , Chitichotpanya Chayanisa
Published: March 2018

This study investigated the enhancement of the ultraviolet (UV) protection and antibacterial properties of functionalized silk fabrics using a simple, inexpensive and environmental friendly approach. We demonstrated the in situ synthesis of copper nanoparticles (CuNPs) in a silk sericin (SS) matrix, using ascorbic acid as both a reducing agent and antioxidant. Development and optimization was achieved using a central composite design (CCD) in conjunction with the response surface methodology (RSM). The goal was to identify the concentrations of CuSO4 and SS that produced the optimal balance between UV protection and antibacterial activity, when tested against Escherichia coli and Staphylococcus aureus. The SS-CuNP bio-nanocomposites were characterized using scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. Statistical analyses indicated that an empirical second-order polynomial could accurately describe the UV protective factor, % reduction of S. aureus and % reduction of E. coli. The three-dimensional response surface graphs showed that the optimal concentrations of CuSO4 and SS were 2380 and 9500 ppm, respectively. To confirm that the levels identified using RSM were optimal in practice, performance evaluations were conducted. These investigated the durability and stability of UV protection and antibacterial activity after repeated washing cycles. The results suggest that these bio-nanocomposites have great potential for the multifunctionalization of silk fibers.
“Getting Better”
Authors: Fraser Suzanne , Ekendahl Mats
Published: March 2018

The alcohol and other drug field is characterized by great diversity in kinds of treatment and treatment philosophies. Even the kinds of problems treatment is expected to address vary significantly, although agreement seems to exist that the general purpose is to help people “get better.” This article considers this diversity, drawing on a qualitative project conducted in three countries: Australia, Canada, and Sweden. Inspired by the project’s multisite approach and the questions it raises about comparative research, the article critically engages with the notion of “comparison” to think through what is at stake in making comparisons. Analyzing 80 interviews conducted with policy makers, service providers, and peer advocates, the article maps key ways treatment is conceptualized, identifying in them a central role for comparison. Participants in all sites invoked the need to consider addiction a multifaceted problem requiring a mix of responses tailored to individual differences. Related notions of “holism” were also commonly invoked, as was the need to concentrate on overall improvements in well-being rather than narrow changes in consumption patterns. In conducting this analysis, this article poses a series of critical questions. What kinds of comparisons about quality of life, the self, and well-being do treatments for addiction put into play? What categories and criteria of comparison are naturalized in these processes? What kinds of insights might these categories and criteria authorize, and what might they rule out? In short, what does it mean to understand alcohol and other drug use and our responses to it as intimately intertwined with the need to “get better,” and what happens when we scrutinize the politics of comparison at work in getting better through addiction treatment? We conclude by arguing for the need to find new, fairer, ways of constituting the problems we presently ascribe to drugs and addiction.
Case Management Effectiveness on Health Care Utilization Outcomes: A Systematic Review of Reviews
Authors: Joo Jee Young , Huber Diane L.
Published: March 2018

Case management is a cost-effective strategy for coordinating chronic illness care. However, research showing how case management affects health care is mixed. This study systematically synthesizes and critically evaluates evidence in systematic reviews of health care utilization outcomes from case management interventions for the care of chronic illnesses. Results are synthesized from seven English language systematic reviews published between January 1990 and June 2017. Hospital readmissions, length of hospital stay, institutionalization, emergency department visits, and hospitals/primary care visits were all identified as health care utilization outcomes of case management interventions. There was evidence that these interventions positively reduced health care utilization; however, results were mixed. These results and the implications of this review of reviews may be valuable for clinical practitioners, health care researchers, and policymakers.
Mixed Reality in Science Education as a Learning Support: A Revitalized Science Book
Authors: Weng Cathy , Rathinasabapathi Abirami , Weng Apollo , Zagita Cindy
Published: March 2018

This study aimed to explore whether the integration of virtual reality and augmented reality used in a specially designed science book could improve the students' science concept learning outcomes. A true experimental research design was conducted to check the effectiveness of the specially designed book in terms of learners' achievement. The sample for this study consisted of 80 fifth-grade students, divided into a control and an experimental group. The results revealed that using mixed reality (augmented reality and virtual reality) as a learning supplement to the printed book could improve students' learning outcomes, particularly for low spatial ability students. Finally, recommendations for future practices and research are discussed.
Shifting toward a Constructivist Philosophy for Teaching Biblical Principles in K-12 Christian Schools
Authors: Knowlton Dave S. , Shaffer Suzanne C.
Published: March 2018

Traditionally, the Bible curriculum in many K-12 Christian schools is based on memory work. If students can correctly reproduce a passage of Scripture, then they are somehow considered to be “educated.” The authors of this paper suggest that a Bible curriculum should be shifted away from this traditional approach and towards an approach that is based in constructivist philosophy. Such a shift is necessary if the goal is to move students toward a mature and thoughtful Christian life. After establishing the need for this shift and describing what the shift would entail, the authors offer brief vignettes of classrooms where the constructivist approach is being used. These vignettes should provide readers with ideas for application of the constructivist approach.
Global Pedagogy “A Table Conversation”
Authors: Blevins Dean G.
Published: March 2018

Evangelical Christian education has historically been tied to a western, if not outright North American, worldview. However, missional efforts by evangelical churches, like the Church of the Nazarene, as well as a growing global awareness present new challenges for the task of disciple-ship. Competing concepts within globalization complicate the task. Concepts epitomized in Benjamin Barber's terms “McWorld” and “Jihad” may result in educational strategies resembling either commodity-based commercialism or tribal coercive violence. Christian educators must develop a pedagogical conversation based on alternative visions of diversity and unity, using redemptive images cultivated from ecclesial and family settings. This article proposes such an alternative sacramental/familial image, global pedagogy as table conversation, and projects how such a vision might overcome the educational challenges presented by commercial domination or violent reaction.