bluuebunny/crossref_metadata_2025 huggingface dataset:
Divergent Activity of the Pseudogene PTENP1 in ER-Positive and Negative Breast Cancer
Authors: Yndestad Synnøve , Austreid Eilin , Skaftnesmo Kai Ove , Lønning Per Eystein , Eikesdal Hans Petter
Published: October 2017

Transcripts derived from the PTEN pseudogene (PTENP1) function as decoys to adsorb miRNAs targeting the PTEN tumor suppressor for degradation, and PTENP1 upregulation is known to inhibit growth in preclinical cancer models. Here, PTENP1 3′UTR transduction influences PTEN, AKT/mTOR signaling, and tumor progression in estrogen receptor (ER)-positive and -negative breast cancer cells. PTENP1 upregulation decreases PTEN gene expression in the ER-positive MCF7 and T47D human breast carcinoma cells and accelerates MCF7 tumor growth in vivo. Of note, PTENP1 transduction significantly decreases ERα (ESR1) mRNA and protein levels in MCF7 xenografts with a concomitant increase in hsa-miR-26a, a miRNA known to target ESR1. In the ER-negative MDA-MB-231 and C3HBA breast cancer cells, upregulation of PTENP1 increases PTEN gene expression with no influence on hsa-miR-26a, ESR1, or ERα expression. While PTENP1 transduction did not influence the growth rate of human MDA-MB-231 xenografts, PTENP1 upregulation profoundly reduces its metastatic propensity. Furthermore, PTENP1 significantly inhibits the growth rate of ER-negative C3HBA murine breast cancer xenografts. PTENP1 transduction had no influence on doxorubicin cytotoxicity in ER-positive MCF7 cells but an increase in doxorubicin sensitivity was observed in the ER-negative MDA-MB-231 cells. In summary, while PTENP1 upregulation decreased PTEN transcript levels and stimulated the growth of ER-positive breast cancers, increased PTEN transcript levels and inhibited tumor progression was observed in the ER-negative cells.

Implications: This report highlights the profound biological activity of PTENP1 in breast cancer, which is dictated by the hormone receptor status. Mol Cancer Res; 16(1); 78–89. ©2017 AACR.
Early Gastroenteropancreatic Neuroendocrine Tumors: Endoscopic Therapy and Surveillance
Authors: Scherübl Hans , Cadiot Guillaume
Published: October 2017

Neuroendocrine neoplasias (NEN) of the stomach, duodenum, pancreas, appendix, or rectum that are ≤1 cm in size as well as well-differentiated with World Health Organization grade 1 (G1) can be considered ‘early' neuroendocrine tumors; they have a very good prognosis. Regarding prognosis, neuroendocrine tumors (NET) G1 must be distinguished from well-differentiated NET G2 and poorly differentiated neuroendocrine carcinomas (NEC) G3. NET are increasing, with a rise in the age-adjusted incidence in the USA by about 700% in the last 40 years. Earlier diagnosis of NET is one of the main epidemiological changes of clinically detected NEN. The general availability of high-resolution endoscopy and advanced radiological imaging techniques has contributed to a shift in the discovery to smaller-sized (≤10 mm) gastrointestinal and pancreatic NET and earlier tumor stages at diagnosis. Thus, screening colonoscopy is effective in the early diagnosis not only of colorectal adenomas and adenocarcinomas but also of rectal NET. Endoscopic resection is the treatment of choice in NET G1 of the stomach, duodenum (despite gastrinoma), and rectum that are ≤10 mm in size, do not infiltrate the muscularis propria (T1), and do not show angioinvasion (V0, L0). Similarly, histologically proven, early pancreatic NET G1 (≤10 mm) may be managed conservatively by regular surveillance. In contrast, small (≤1 cm) NET G1 of the jejunum or ileum are not ‘early' tumors and have to be resected surgically with lymph node dissection.
Oral Lactobacillus Counts Predict Weight Gain Susceptibility: A 6-Year Follow-Up Study
Authors: Rosing Johanne Aviaja , Walker Karen Christina , Jensen Benjamin A.H. , Heitmann Berit L.
Published: October 2017

Background: Recent studies have shown an association between weight change and the makeup of the intestinal microbiota in humans. Specifically, Lactobacillus, a part of the entire gastrointestinal tract's microbiota, has been shown to contribute to weight regulation. Aim: We examined the association between the level of oral Lactobacillus and the subsequent 6-year weight change in a healthy population of 322 Danish adults aged 35-65 years at baseline. Design: Prospective observational study. Results: In unadjusted analysis the level of oral Lactobacillus was inversely associated with subsequent 6-year change in BMI. A statistically significant interaction between the baseline level of oral Lactobacillus and the consumption of complex carbohydrates was found, e.g. high oral Lactobacillus count predicted weight loss for those with a low intake of complex carbohydrates, while a medium intake of complex carbohydrates predicted diminished weight gain. A closer examination of these relations showed that BMI change and Lactobacillus level was unrelated for those with high complex carbohydrate consumption. Conclusion: A high level of oral Lactobacillus seems related to weight loss among those with medium and low intakes of complex carbohydrates. Absence, or a low level of oral Lactobacillus, may potentially be a novel marker to identify those at increased risk of weight gain.
Psoriasis als Ursache für Infertilität beim Mann: Eine unter vielen
Authors: Weisenseel Peter
Published: October 2017

Hintergrund: Aktuelle Forschungsergebnisse deuten darauf hin, dass ein systemischer Entzündungszustand die Fruchtbarkeit beeinträchtigen könnte, doch es liegen nur wenig Daten zu Männern mit Psoriasis vor. Ziel: Das Ziel dieser Studie war die Beurteilung der Keimdrüsenfunktion bei Männern mit Psoriasis unter Anwendung unseres Wissens über Fertilität bei diesen Patienten. Methoden: Männer mit Psoriasis im Alter zwischen 18 und 55 Jahren und eine Gruppe nach Alter, BMI und geographischer Herkunft parallelisierter gesunder Probanden wurden in die Studie aufgenommen. Bei allen Teilnehmern wurden eine umfassende körperliche und andrologische Untersuchung, Standard-Spermaanalyse, vollständige mikrobiologische Analyse und Ultraschalluntersuchung der Geschlechtsdrüsen durchgeführt. Die suPAR-Konzentration im Sperma (soluble urokinase-type plasminogen activator receptor) sowie die Serumkonzentrationen von Testosteron, Estradiol (E2), SHBG (sex hormone-binding globulin), luteinisierendem Hormon und follikelstimulierendem Hormon wurden ebenfalls bestimmt. Ergebnisse: 50 Patienten und 50 Kontrollpersonen erfüllten die Einschlusskriterien und wurden in die Studie aufgenommen. Die Testosteron- und SHBG-Werte waren bei den Psoriasispatienten signifikant niedriger als in der Kontrollgruppe. Außerdem wurden in der Psoriasisgruppe höhere E2-Konzentrationen gemessen. Die Gesamtzahl und Motilität der Spermien sowie der Anteil Spermatozoen mit normaler Morphologie lagen bei den Patienten signifikant niedriger als bei den Kontrollpersonen. Die suPAR-Konzentration war bei den Patienten signifikant höher als bei den Kontrollpersonen und lag oberhalb des Referenzbereichs. Sonographische Anzeichen für eine Inflammation der akzessorischen Drüsen lagen bei 35 der 50 Psoriasispatienten und bei keiner der Kontrollpersonen vor. Schlussfolgerung: Unsere Studie deutet darauf hin, dass unbehandelte Psoriasis die männliche Fertilität beeinträchtigen könnte. Sie hat außerdem ergeben, dass dies in den Auswirkungen einer systemischen Inflammation auf das hormonelle Profil und die Inflammation der akzessorischen Geschlechtsdrüsen begründet sein könnte.
Fototoxizität von Arzneimitteln und das Problem der systematischen Datenerfassung
Authors: Prager Welf
Published: October 2017

Hintergrund: Eine der wichtigsten dermatologischen Nebenwirkungen von Doxycyclin ist erhöhte Lichtempfindlichkeit. Da Doxycyclin eine wichtige Rolle für die Malariaprophylaxe spielt und Malaria vor allem in sonnenreichen Ländern verbreitet ist, gebührt dieser Nebenwirkung besondere Aufmerksamkeit. Zwar liegen bereits zahlreiche Publikationen zur Fototoxizität von Tetrazyklinen im Allgemeinen vor, doch nur wenige befassen sich gezielt mit Doxycyclin. Das Ziel der vorliegenden systematischen Übersichtsarbeit war es, alle verfügbaren Berichte zu klinischen Manifestation, Einflussfaktoren wie UV- und Arzneimitteldosis sowie die Möglichkeiten der Prävention durch Sonnenschutz zusammenzufassen. Methoden: Die vorliegende Übersicht beruht auf einer systematischen Literatursuche in PubMed nach Artikeln in englischer und deutscher Sprache sowie einer manuellen Suche für den Zeitraum von 1990 bis 2015. Ergebnisse: Die Zahl der Publikationen ist gering. Die klinischen Symptome reichen von leichten sonnenbrandartigen Erscheinungen (brennendes Gefühl, Hautrötung) bis zu großflächiger Fotodermatitis. Auch Onycholyse kann vorkommen. Das auslösende UV-Spektrum scheint vorwiegend im UVA1-Bereich (340-400 nm) zu liegen, daher sollten Lichtschutzmittel angewandt werden, die diesen Bereich abdecken. Personen, die in tropische Regionen reisen und Doxycyclin als Malariaprophylaxe einnehmen, bedürfen eingehender ärztlicher Beratung, um potenziell schwerwiegende fototoxische Reaktionen zu vermeiden. Schlussfolgerung: Es bedarf einer verbesserten Evidenzbasis, um Reisende, die Doxycyclin einnehmen und dem Risiko hoher UV-Exposition unterliegen, zu angemessenen Präventionsmaßnahmen beraten zu können.
A Preclinical Evaluation Comparing the Performance of a Novel 19-G Flexible Needle to a Commercially Available 22-G EBUS-TBNA Sampling Needle
Authors: Czarnecka-Kujawa Kasia , Tremblay Alain , Yasufuku Kazuhiro , Sczaniecka Anna , Parthiban Sujeeth , Kunz Lawrence , Dillard David , Gonzalez Xavier
Published: October 2017

Background: Needle samples may not provide sufficient diagnostic material for the assessment of mediastinal lymph nodes. Objective: The study compared the specimen size and diagnostic performance of a new 19-G endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) needle to that of a standard 22-G EBUS-TBNA needle in a swine model of granulomatous lymphadenopathy. Methods: Granulomatous inflammation was induced in mediastinal lymph nodes (LNs) of 10 domestic swine by injection of talc slurry. The affected LNs were sampled with the 19- and 22-G needles. Collected core tissue area and volume were determined using a specialized software and known needle internal diameter. The sample's quality was assessed using the biopsy core morphology grade (BCMG) as well as the biopsy diagnostic correlation grade (BDCG). Results: There was a significant increase in the average LN size from baseline (11.6 ± 3.2 to 15.2 ± 3.8 mm; p < 0.001) after talc injection. A total of 132 paired samples were collected from 38 LNs. The average mass and volume of the 19-G needle sample were larger than those of the 22-G needle sample: 33.78 ± 47.48 vs. 25.18 ± 32.08 mg (p < 0.002) and 11.40 ± 13.91 vs. 6.91 ± 6.42 mm3 (p < 0.0004), respectively. The pooled needle biopsy samples for the 19- and the 22-G needles had similar BCMG (1.38 ± 0.86 vs. 1.43 ± 0.87, p > 0.2) and BDCG (1.54 ± 0.93 vs. 1.57 ± 0.93, p > 0.2). The 19-G needle samples tended towards less blood contamination (p = 0.057), more often granuloma identification (46 vs. 32%, p = 0.2) and had more cartilage contamination (0.49 ± 1.46 vs. 4.81 ± 16.49% p < 0.003). Conclusion: In experienced hands, the 19- and the 22-G EBUS-TBNA needles have a similar diagnostic yield in the swine model of granulomatous lymphadenopathy. The samples collected by the 19-G needle are larger and may have less blood contamination.
Clinical and Angiographic Outcomes with the Combined Local Aspiration and Retriever in the North American Solitaire Stent-Retriever Acute Stroke (NASA) Registry
Authors: Malisch Tim W. , Zaidat Osama O. , Castonguay Alicia C. , Marden Franklin A. , Gupta Rishi , Sun Chung-Huan J. , Martin Coleman O. , Holloway William E. , Mueller-Kronast Nils , English Joey , Linfante Italo , Dabus Guilherme , Bozorgchami Hormozd , Xavier Andrew , Rai Ansaar T. , Froehler Michael , Badruddin Aamir , Nguyen Thanh N. , Taqi M. Asif , Abraham Michael G. , Janardhan Vallabh , Shaltoni Hashem , Novakovic Robin , Yoo Albert J. , Abou-Chebl Alex , Chen Peng Roc , Britz Gavin W. , Kaushal Ritesh , Nanda Ashish , Nogueira Raul G.
Published: October 2017

Background: Various techniques are used to enhance the results of mechanical thrombectomy with stent-retrievers, including proximal arrest with balloon guide catheter (BGC), conventional large bore proximal catheter (CGC), or in combination with local aspiration through a large-bore catheter positioned at the clot interface (Aspiration-Retriever Technique for Stroke [ARTS]). We evaluated the impact of ARTS in the North American Solitaire Acute Stroke (NASA) registry. Summary: Data on the use of the aspiration technique were available for 285 anterior circulation patients, of which 29 underwent ARTS technique, 131 CGC, and 125 BGC. Baseline demographics were comparable, except that ARTS patients are less likely to have hypertension or atrial fibrillation. The ARTS group had more ICA occlusions (41.4 vs. 22% in the BGC, p = 0.04 and 26% in CGC, p = 0.1) and less MCA/M1 occlusions (44.8 vs. 68% in BGC and 62% in CGC). Time from arterial puncture to reperfusion or end of procedure with ARTS was shorter than with CGC (54 vs. 91 min, p = 0.001) and was comparable to the BGC time (54 vs. 67, p = 0.11). Final degree of reperfusion was comparable among the groups (TICI [modified Thrombolysis in Cerebral Infarction] score 2b or higher was 72 vs. 70% for CGC vs. 78% for BGC). Procedural complications, mortality, and good clinical outcome at 90 days were similar between the groups. Key Messages: The ARTS mechanical thrombectomy in acute ischemic stroke patients appears to yield better results as compared to the use of CGCs with no significant difference when compared to BGC. This early ARTS technique NASA registry data are limited by the earlier generation distal large bore catheters and small sample size. Future studies should focus on the comparison of ARTS and BGC techniques.
Uveal Melanoma: 5-Year Update on Incidence, Treatment, and Survival (SEER 1973-2013)
Authors: Aronow Mary E. , Topham Allan K. , Singh Arun D.
Published: October 2017

Purpose: To analyze trends in incidence, treatment, and survival of uveal melanoma in the United States from 1973 to 2013 using the Surveillance, Epidemiology, and End Results database. Materials and Methods: Patients were identified using International Classification of Disease for Oncology codes: C69.3 (choroid), C69.4 (ciliary body and iris), and C69.2 (retina). Trends in age-adjusted incidence, treatment (surgery or radiation), and 5-year relative survival were calculated. Results: There were 4,999 cases of uveal melanoma. The majority (97.8%) were reported by hospital inpatient/outpatient clinics. Histopathologic confirmation was available in 67.8%. The mean age-adjusted incidence was 5.2 per million (95% CI 5.0-5.4). When the incidence was standardized for race, a small but statistically significant (p < 0.05) annual percentage change of 0.5% was detected in Whites. There was a decline in patients treated with surgery alone (94.2% from 1973 to 1975 vs. 24.7% from 2012 to 2013). A corresponding increase was observed in radiation as primary treatment selection (1.3% from 1973 to 1975 vs. 68.3% from 2012 to 2013). No change in the 5-year relative survival (80.9%) was observed. Conclusions: The age-adjusted incidence of uveal melanoma has remained stable with a minor increase in Whites. Despite a shift towards globe-preserving treatment, there has not been a concomitant improvement in survival.
The Role of the Mineralocorticoid Receptor in Inflammation: Focus on Kidney and Vasculature
Authors: Belden Zachary , Deiuliis Jeffrey A. , Dobre Mirela , Rajagopalan Sanjay
Published: October 2017

Background: The remarkable success of clinical trials in mineralocorticoid receptor (MR) inhibition in heart failure has driven research on the physiological and pathological role(s) of nonepithelial MR expression. MR is widely expressed in the cardiovascular system and is a major determinant of endothelial function, smooth muscle tone, vascular remodeling, fibrosis, and blood pressure. An important new dimension is the appreciation of the role MR plays in immune cells and target organ damage in the heart, kidney and vasculature, and in the development of insulin resistance. Summary: The mechanism for MR activation in tissue injury continues to evolve with the evidence to date suggesting that activation of MR results in a complex repertoire of effects involving both macrophages and T cells. MR is an important transcriptional regulator of macrophage phenotype and function. Another important feature of MR activation is that it can occur even with normal or low aldosterone levels in pathological conditions. Tissue-specific conditional models of MR expression in myeloid cells, endothelial cells, smooth muscle cells and cardiomyocytes have been very informative and have firmly demonstrated a critical role of MR as a key pathophysiologic variable in cardiac hypertrophy, transition to heart failure, adipose inflammation, and atherosclerosis. Finally, the central nervous system activation of MR in permeable regions of the blood-brain barrier may play a role in peripheral inflammation. Key Message: Ongoing clinical trials will help clarify the role of MR blockade in conditions, such as atherosclerosis and chronic kidney disease.
Impact of the Number of Metastatic Tumors Treated by Stereotactic Radiosurgery on the Dose to Normal Brain: Implications for Brain Protection
Authors: Rivers Charlotte , Tranquilli Marissa , Prasad Shefalika , Winograd Evan , Plunkett Robert J. , Fenstermaker Robert A. , Fabiano Andrew J. , Podgorsak Matthew B. , Prasad Dheerendra
Published: October 2017

Purpose/Objectives: The purpose of this study was to evaluate the effect of the number of brain lesions for which stereotactic radiosurgery (SRS) was performed on the dose volume relationships in normal brain. Materials and Methods: Brain tissue was segmented using the patient's pre-SRS MRI. For each plan, the following data points were recorded: total brain volume, number of lesions treated, volume of brain receiving 8 Gy (V8), V10, V12, and V15. Results: A total of 225 Gamma Knife® treatments were included in this retrospective analysis. The number of lesions treated ranged from 1 to 29. The isodose for prescription ranged from 40 to 95% (mean 55%). The mean prescription dose to tumor edge was 18 Gy. The mean coverage, selectivity, conformity, and gradient index were 97.5%, 0.63, 0.56, and 3.5, respectively. The mean V12 was 9.5 cm3 (ranging from 0.5 to 59.29). There was no correlation between the number of lesions and brain V8, V12, V10, or V15. There was a direct and statistically significant relationship between the brain volume treated (V8, V10, V12, and V15) and total volume of tumors treated (p < 0.001). In our study, the integral dose to the brain exceeded 3 J when the total tumor volume exceeded 25 cm3. Conclusions: The number of metastatic brain lesions treated bears no significant relationship to total brain tissue volume treated when using SRS. The fact that the integral dose to the brain exceeded 3 J when the total tumor volume exceeded 25 cm3 is useful for establishing guidelines. Although standard practice has favored using whole brain radiation therapy in patients with more than 4 lesions, a significant amount of normal brain tissue may be spared by treating these patients with SRS. SRS should be carefully considered in patients with multiple brain lesions, with the emphasis on total brain volume involved rather than the number of lesions to be treated.
Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit Model of Intrauterine Growth Restriction
Authors: Illa Miriam , Brito Verónica , Pla Laura , Eixarch Elisenda , Arbat-Plana Ariadna , Batallé Dafnis , Muñoz-Moreno Emma , Crispi Fatima , Udina Esther , Figueras Francesc , Ginés Silvia , Gratacós Eduard
Published: October 2017

Introduction: The structural correspondence of neurodevelopmental impairments related to intrauterine growth restriction (IUGR) that persists later in life remains elusive. Moreover, early postnatal stimulation strategies have been proposed to mitigate these effects. Long-term brain connectivity abnormalities in an IUGR rabbit model and the effects of early postnatal environmental enrichment (EE) were explored. Materials and Methods: IUGR was surgically induced in one horn, whereas the contralateral one produced the controls. Postnatally, a subgroup of IUGR animals was housed in an enriched environment. Functional assessment was performed at the neonatal and long-term periods. At the long-term period, structural brain connectivity was evaluated by means of diffusion-weighted brain magnetic resonance imaging and by histological assessment focused on the hippocampus. Results: IUGR animals displayed poorer functional results and presented altered whole-brain networks and decreased median fractional anisotropy in the hippocampus. Reduced density of dendritic spines and perineuronal nets from hippocampal neurons were also observed. Of note, IUGR animals exposed to enriched environment presented an improvement in terms of both function and structure. Conclusions: IUGR is associated with altered brain connectivity at the global and cellular level. A strategy based on early EE has the potential to restore the neurodevelopmental consequences of IUGR.
Inhibition of MicroRNA-21-5p Promotes the Radiation Sensitivity of Non-Small Cell Lung Cancer Through HMSH2
Authors: Song Yu , Zuo Yun , Qian Xiao-Lan , Chen Zhi-Peng , Wang Shao-Kai , Song Lei , Peng Li-Ping
Published: October 2017

Background: This study aimed to explore the effects of microRNA-21-5p (miR-21-5p) on the radiation sensitivity of non-small cell lung cancer (NSCLC) and the involvement of human MutS homolog 2 (hMSH2) One hundred fourteen NSCLC patients at stage II or III who received surgery and postoperative radiotherapy were enrolled in this study. Methods: The patients were assigned into radiation-sensitive and -insensitive groups. NSCLC A549 cells were transfected to generate control, Negative control (NC), miR-21-5p inhibitor, miR-21-5p mimic, small interfering hMSH2 (sihMSH2), miR-21-5p inhibitor + sihMSH2 and hMSH2 overexpression groups. Immunohistochemistry was performed to detect the hMSH2 expression in transfected and irradiated cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to evaluate A549 miR-21-5p and hMSH2 expression in transfected and irradiated cells. A colony formation assay was adopted for cell survival analysis. The relationship between miR-21-5p and hMSH2 was verified by a luciferase reporter assay. Cell viability was measured by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and apoptosis was assessed by flow cytometry. NSCLC nude mouse models were established, and tumor volumes and tumor weights were recorded. Results: The radiation-sensitive group of patients exhibited lower miR-21-5p but higher hMSH2 expression than the insensitive group. For irradiated A549 cells, lower cell survival, higher apoptosis, increased miR-21-5p expression and decreased hMSH2 expression were observed at 6 and 8 Gy than at 0, 2 and 4 Gy; compared to 6 Gy, cell survival and hMSH2 expression were decreased and apoptosis and miR-21-5p expression were increased at 8 Gy. Additionally, miR-21-5p was found to target hMSH2. Compared with the control group, the cell survival rate was lower and the apoptosis rate higher in the miR-21-5p inhibitor group, whereas the opposite was observed for the miR-21-5p mimic and sihMSH2 groups. For the mouse model, decreased tumor volume and tumor weight and higher hMSH2 expression were found in the miR-21-5p inhibitor, radiation, hMSH2 overexpression, miR-21-5p inhibitor + radiation and hMSH2 overexpression + radiation groups compared with the control group. In addition, tumor volume and tumor weight were decreased and hMSH2 expression increased in the miR-21-5p inhibitor + radiation and hMSH2 overexpression + radiation groups compared with the radiation alone group. Conclusion: These findings indicate that inhibition of miR-21 can promote the radiation sensitivity of NSCLC by targeting hMSH2.
Beneficial Effects of n-3 Fatty Acids on Cardiometabolic and Inflammatory Markers in Type 2 Diabetes Mellitus: A Clinical Trial
Authors: Mazaherioun Maryam , Djalali Mahmoud , Koohdani Fariba , Javanbakht Mohammad Hassan , Zarei Mahnaz , Beigy Maani , Ansari Samaneh , Rezvan Neda , Saedisomeolia Ahmad
Published: October 2017

Objective: To determine the effect of supplementation with n-3 polyunsaturated fatty acids (PUFAs) on circulatory resistin and monocyte chemoattractant protein 1 (MCP-1) levels in type 2 diabetes mellitus (T2DM) patients. Subjects and Methods: This was a 10-week, placebo-controlled, double-blind, randomized trial of n-3 PUFAs (2,700 mg/day) versus placebo (soft gels containing 900 mg of edible paraffin). Forty-four T2DM patients were supplemented with n-3 PUFAs and another 44 patients received placebo (3 patients discontinued the trial). Serum resistin, MCP-1, and the lipid profile were measured before and after supplementation. The adiponectin-resistin index (1 + log10 [resistin] - log10 [adiponectin]) and atherogenic index (log10 triglyceride/high-density lipoprotein cholesterol) of plasma (an indicator of cardiovascular complications) were assessed. The independent Student t test was used to assess the differences between the supplement and placebo groups and the paired t test to analyze the before/after changes. Results: In this study, n-3 PUFAs reduced serum MCP-1 levels (from 260.5 to 230.5 pg/mL; p = 0.002), but they remained unchanged in the placebo group. n-3 PUFAs could not decrease serum resistin levels. The adiponectin-resistin index was significantly reduced after supplementation with n-3 PUFAs when compared to the placebo. The atherogenic index was also significantly improved after supplementation with n-3 PUFAs (from 1.459 to 1.412; p = 0.006). Conclusions: The MCP-1 levels and lipid profile were improved after supplementation with n-3 PUFAs, but resistin serum levels were not changed. Hence, the anti-inflammatory effects of n-3 PUFAs might be mediated by targeting MCP-1.
Presence, Characteristics, and Prognostic Associations of Carotid Plaque Among People Living With HIV
Authors: Janjua Sumbal A. , Staziaki Pedro V. , Szilveszter Balint , Takx Richard A.P. , Mayrhofer Thomas , Hennessy Orla , Emami Hamed A. , Park Jakob , Ivanov Alexander , Hallett Travis R. , Lu Michael T. , Romero Javier M. , Grinspoon Steven K. , Hoffmann Udo , Zanni Markella V. , Neilan Tomas G.
Published: October 2017

Background—

Data from broad populations have established associations between incidental carotid plaque and vascular events. Among people living with HIV (PLWHIV), the risk of vascular events is increased; however, whether incidental carotid plaque is increased and there is an association between incidental carotid plaque, plaque characteristics, and vascular events among PLWHIV is unclear.

Methods and Results—

Data from the multi-institutional Research Patient Data Registry were used. Presence and characteristics (high-risk plaque, including spotty calcification and low attenuation) of carotid plaque by computerized tomography among PLWHIV without known vascular disease were described. Data were compared with uninfected controls similar in age, sex, and cardiovascular risk factors, including diabetes mellitus, hyperlipidemia, and cigarette smoking to cases. Primary outcome was an atherosclerotic cardiovascular disease event, and secondary outcome was ischemic stroke. Cohort consisted of 209 PLWHIV (45±10 years, 72% male) and 168 controls. Using computerized tomography, PLWHIV without vascular disease had higher rates of any carotid plaque (34% versus 25%;
P
=0.04), noncalcified (18% versus 5%;
P
<0.001) and high-risk plaque (25% versus 16%;
P
=0.03). Over a follow-up of 3 years, 19 atherosclerotic cardiovascular disease events (9 strokes) occurred. Carotid plaque was independently associated with a 3-fold increase in atherosclerotic cardiovascular disease events among PLWHIV (hazard ratio, 2.91; confidence interval, 1.10–7.7,
P
=0.03) and a 4-fold increased risk of stroke (hazard ratio, 4.43; confidence interval, 1.17–16.70;
P
=0.02); high-risk plaque was associated with a 3-fold increased risk of atherosclerotic cardiovascular disease events and a 4-fold increased risk of stroke.

Conclusions—

There is an increase in incidental carotid plaque, noncalcified plaque, and high-risk plaque among PLWHIV, and the presence and characteristics of carotid plaque are associated with subsequent vascular events.
Mitochondrial Cardiomyopathy Caused by Elevated Reactive Oxygen Species and Impaired Cardiomyocyte Proliferation
Authors: Zhang Donghui , Li Yifei , Heims-Waldron Danielle , Bezzerides Vassilios , Guatimosim Silvia , Guo Yuxuan , Gu Fei , Zhou Pingzhu , Lin Zhiqiang , Ma Qing , Liu Jianming , Wang Da-Zhi , Pu William T.
Published: October 2017

Rationale:

Although mitochondrial diseases often cause abnormal myocardial development, the mechanisms by which mitochondria influence heart growth and function are poorly understood.

Objective:

To investigate these disease mechanisms, we studied a genetic model of mitochondrial dysfunction caused by inactivation of
Tfam
(transcription factor A, mitochondrial), a nuclear-encoded gene that is essential for mitochondrial gene transcription and mitochondrial DNA replication.

Methods and Results:

Tfam
inactivation by Nkx2.5
Cre
caused mitochondrial dysfunction and embryonic lethal myocardial hypoplasia.
Tfam
inactivation was accompanied by elevated production of reactive oxygen species (ROS) and reduced cardiomyocyte proliferation. Mosaic embryonic
Tfam
inactivation confirmed that the block to cardiomyocyte proliferation was cell autonomous. Transcriptional profiling by RNA-seq demonstrated the activation of the DNA damage pathway. Pharmacological inhibition of ROS or the DNA damage response pathway restored cardiomyocyte proliferation in cultured fetal cardiomyocytes. Neonatal
Tfam
inactivation by AAV9-cTnT-Cre caused progressive, lethal dilated cardiomyopathy. Remarkably, postnatal
Tfam
inactivation and disruption of mitochondrial function did not impair cardiomyocyte maturation. Rather, it elevated ROS production, activated the DNA damage response pathway, and decreased cardiomyocyte proliferation. We identified a transient window during the first postnatal week when inhibition of ROS or the DNA damage response pathway ameliorated the detrimental effect of
Tfam
inactivation.

Conclusions:

Mitochondrial dysfunction caused by
Tfam
inactivation induced ROS production, activated the DNA damage response, and caused cardiomyocyte cell cycle arrest, ultimately resulting in lethal cardiomyopathy. Normal mitochondrial function was not required for cardiomyocyte maturation. Pharmacological inhibition of ROS or DNA damage response pathways is a potential strategy to prevent cardiac dysfunction caused by some forms of mitochondrial dysfunction.
Improvement in Care and Outcomes for Emergency Medical Service–Transported Patients With ST‐Elevation Myocardial Infarction (STEMI) With and Without Prehospital Cardiac Arrest: A Mission: Lifeline STEMI Accelerator Study
Authors: Kragholm Kristian , Lu Di , Chiswell Karen , Al‐Khalidi Hussein R. , Roettig Mayme L. , Roe Matthew , Jollis James , Granger Christopher B.
Published: October 2017

Background

Patients with ST‐elevation myocardial infarction (
STEMI
) with out‐of‐hospital cardiac arrest (
OHCA
) may benefit from direct transport to a percutaneous cardiac intervention (PCI) hospital but have previously been less likely to bypass local non‐
PCI
hospitals to go to a
PCI
center.

Methods and Results

We reported time trends in emergency medical service transport and care of patients with
STEMI
with and without
OHCA
included from 171
PCI
‐capable hospitals in 16
US
regions with participation in the Mission: Lifeline
STEMI
Accelerator program between July 1, 2012, and March 31, 2014. Time trends by quarter were assessed using logistic regression with generalized estimating equations to account for hospital clustering. Of 13 189 emergency medical service–transported patients, 88.7% (N=11 703; 10.5%
OHCA
) were taken directly to
PCI
hospitals. Among 1486 transfer‐in patients, 21.7% had
OHCA
. Direct transport to a
PCI
center for
OHCA
increased from 74.7% (July 1, 2012) to 83.6% (March 31, 2014) (odds ratio per quarter, 1.07; 95% confidence interval, 1.02–1.14), versus 89.0% to 91.0% for patients without
OHCA
(odds ratio, 1.03; 95% confidence interval, 0.99–1.07; interaction
P
=0.23). The proportion with prehospital
ECG
s increased for patients taken directly to
PCI
centers (53.9%–61.9% for those with
OHCA
versus 73.9%–81.9% for those without
OHCA
; interaction
P
=0.12). Of 997 patients with OHCA taken directly to
PCI
hospitals and treated with primary
PCI
, first medical contact‐to‐device times within the guideline‐recommended goal of ≤90 minutes were met for 34.5% on July 1, 2012, versus 41.8% on March 31, 2014 (51.6% and 56.1%, respectively, for 9352 counterparts without OHCA; interaction
P
=0.72).

Conclusions

Direct transport to
PCI
hospitals increased for patients with STEMI with and without
OHCA
during the 2012 to 2014 Mission: Lifeline
STEMI
Accelerator program. Proportions with prehospital
ECG
s and timely reperfusion increased for patients taken directly to
PCI
hospitals.
Benefits of Cardiac Rehabilitation on Cardiovascular Outcomes in Patients With Diabetes Mellitus After Percutaneous Coronary Intervention
Authors: Jiménez‐Navarro Manuel F. , Lopez‐Jimenez Francisco , Pérez‐Belmonte Luis M. , Lennon Ryan J. , Diaz‐Melean Carlos , Rodriguez‐Escudero J. P. , Goel Kashish , Crusan Daniel , Prasad Abhiram , Squires Ray W. , Thomas Randal J.
Published: October 2017

Background

Participation in cardiac rehabilitation (
CR
) is an essential component of care for patients with coronary artery disease. However, little is known about its benefit on cardiovascular outcomes in patients with diabetes mellitus (
DM
) who have undergone percutaneous coronary intervention. The aim of our study was to evaluate the impact of
CR
in this high‐risk group of patients.

Methods and Results

We performed a retrospective analysis of all patients with
DM
who underwent percutaneous coronary intervention in Olmsted County (Minnesota) between 1994 and 2010, assessing the impact of
CR
participation on clinical outcomes.
CR
participation was significantly lower in patients with
DM
(38%, 263/700) compared with those who did not have
DM
(45%, 1071/2379;
P
=0.004). Using propensity score adjustment, we found that in patients with
DM
,
CR
participation was associated with significantly reduced all‐cause mortality (hazard ratio, 0.56; 95% confidence interval, 0.39–0.80;
P
=0.002) and composite end point of mortality, myocardial infarction, or revascularization (hazard ratio, 0.77; 95% confidence interval, 0.60–0.98;
P
=0.037), during a median follow‐up of 8.1 years. In patients without
DM
,
CR
participation was associated with a significant reduction in all‐cause mortality (hazard ratio, 0.67; 95% confidence interval, 0.55–0.82;
P
<0.001) and cardiac mortality (hazard ratio, 0.67; 95% confidence interval, 0.47–0.95;
P
=0.024).

Conclusions

CR
participation after percutaneous coronary intervention is associated with lower all‐cause mortality rates in patients with
DM
, to a similar degree as for those without
DM
. However,
CR
participation was lower in patients with
DM
, suggesting the need to identify and correct the barriers to
CR
participation for this higher‐risk group of patients.
“We are the True Citizens of This Country”
Authors: Bal Ellen , Siraj Nasrin
Published: October 2017

Democracy has generally been understood the best remedy to prevent societal violence, as it gives different groups a channel to voice their interests and grievances. However, in this article, that focuses on the Chittagong Hills, which for many decades has formed one of the most violent spaces in Bangladesh, we argue that, in reality, democracy and violence can be two sides of the same coin. This is not to say that in Bangladesh, where full liberal democracy is not in place, ordinary citizens have no values and idea(l)s of democracy and citizenship. On the contrary, in order to make sense of the intricate connection between democratic idea(l)s, and violent imaginations and practices, we focus in particular on the process of what we call the vernacularisation of democratic politics. We connect this process to the appropriation of citizenship and nationalism, by ordinary but radically differently-positioned people, in their daily realities. We demonstrate that widely shared imaginations of Bangladeshi-ness, as Bengali-ness or Muslim-ness, and of Bengalis/Muslims as the true nation and citizens of Bangladesh, are intimately connected with popular understandings and practices of democracy, which are based on the exclusion of the not-genuine-Bengalis, with the legitimisation and continuation of violence, and the exclusion of ethnic minorities in the Chittagong Hills.
Examining the Geographic Distribution of Victim Nations in Stolen Data Markets
Authors: Smirnova Olga , Holt Thomas J.
Published: October 2017

The growth of electronic commerce and malicious software tools designed to compromise various payment systems and computer networks has led to concurrent increase in data breaches, phishing, and hacking incidents targeting sensitive financial information. As a function of this increase, an underground market economy has developed around the sale of consumers’ bank account details and other financial information. Recent research examining data markets operating on the Open Web demonstrate their basic functions and distribution of information sold. Emerging evidence suggests markets are now operating on the “Dark Web,” or encrypted web sites operating on Tor-based networks. Little research to date has compared the distribution of victim nations in stolen data markets nor examined any variations between Open and Dark Web operations. This study utilizes a rational choice framework to examine this gap using a sample of 18 forums and 15 shops hosted on the Open Web and Tor. Using statistical analyses to examining the geography of victimization, this study provides a preliminary test of the applicability of rational choice theory to market operations.
Channeling Hearts and Minds: Advocacy Organizations, Cognitive-Emotional Currents, and Public Conversation
Authors: Bail Christopher A. , Brown Taylor W. , Mann Marcus
Published: October 2017

Do advocacy organizations stimulate public conversation about social problems by engaging in rational debate, or by appealing to emotions? We argue that rational and emotional styles of communication ebb and flow within public discussions about social problems due to the alternating influence of social contagion and saturation effects. These “cognitive-emotional currents” create an opportunity structure whereby advocacy organizations stimulate more conversation if they produce emotional messages after prolonged rational debate or vice versa. We test this hypothesis using automated text-analysis techniques that measure the frequency of cognitive and emotional language within two advocacy fields on Facebook over 1.5 years, and a web-based application that offered these organizations a complimentary audit of their social media outreach in return for sharing nonpublic data about themselves, their social media audiences, and the broader social context in which they interact. Time-series models reveal strong support for our hypothesis, controlling for 33 confounding factors measured by our Facebook application. We conclude by discussing the implications of our findings for future research on public deliberation, how social contagions relate to each other, and the emerging field of computational social science.
Cut to the Quick: The Consequences of Youth Violent Victimization for the Timing of Dating Debut and First Union Formation
Authors: Warner Tara D. , Warner David F. , Kuhl Danielle C.
Published: October 2017

Concentrated in adolescence, violent victimization is developmentally disruptive. It undermines physical, mental, and socioemotional well-being and compromises youths’ transitions into and progression through key life course tasks. Youth violent victimization (YVV) has been linked to precocious exits from adolescence and premature entries into adulthood. This includes early entry into coresidential romantic unions, which is but one stage of a relationship sequence generally beginning via dating debut. Using data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) and Cox regression, we examine the effects of YVV on the timing of dating debut and progression to first coresidential unions during adolescence and the transition to adulthood. We pay particular attention to how these effects may be structured by age and gender. Overall, we find that victims begin dating sooner and progress more quickly from dating to first unions than do non-victims. However, youths victimized in early adolescence withdraw from dating and union formation, whereas late adolescent victims appear to overinvest in relationships—at least temporarily—displaying accelerated entry into dating and rapid progression to first unions. We conclude by discussing the implication of these age-graded patterns for intervention efforts and youth well-being more broadly.
ISMP Medication Error Report Analysis
Authors: Cohen Michael R. , Smetzer Judy L.
Published: October 2017

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your in-service training programs. Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers’ names will be published if desired. ISMP may be contacted at the address shown below. Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters’ wishes as to the level of detail included in publications.
Mannitol Prescribing Practices With Cisplatin Before and After an Educational Newsletter Intervention
Authors: Corbin Morgan , Bossaer John B.
Published: October 2017

Background: Mannitol has been used in the past for the prevention of cisplatin-induced nephrotoxicity. Studies on its efficacy have conflicting results. An educational newsletter was designed for local oncologists on the conflicting data of mannitol use in preventing cisplatin-induced nephrotoxicity. Purpose: The purpose of this study was to determine whether a pharmacist-created newsletter intervention led to changes in the mannitol prescribing practices of local oncologists. Methods: A newsletter describing the paucity of evidence to support mannitol use to prevent cisplatin-induced nephrotoxicity was distributed via e-mail to local oncologists in October 2010. Mannitol prescribing rates were retrospectively evaluated before and after newsletter distribution. The Mann-Whitney U test was used to compare nonparametric continuous data. The chi-square test was used for nominal data. Descriptive statistics were performed for baseline demographics, and odds ratios were calculated for possible risk factors for acute kidney injury (AKI). The primary endpoint was a change in mean mannitol dose before and after the newsletter intervention. The secondary endpoint was the difference in the rate of AKI before and after the intervention. Data were collected for 67 patients with various malignancies. Results: There was a difference in the average mannitol dose before and after newsletter intervention ( P = .02). The rates of AKI before and after newsletter were similar. Conclusion: A pharmacist-led newsletter intervention was associated with significantly decreased rates of mannitol usage after intervention.
Postoperative Pain Management With Liposomal Bupivacaine in Patients Undergoing Orthopedic Knee and Hip Arthroplasty at a Community Hospital
Authors: Jacob Bobby C. , Peasah Samuel K. , Shogbon Angela O. , Perlow Ellen R.
Published: October 2017

Objective: The objective of this study was to assess the association between liposomal bupivacaine use in patients undergoing knee or hip arthroplasty and concurrent pain control, length of hospitalization, and physical therapy milestones. Methods: This was a retrospective chart review. Patients receiving liposomal bupivacaine during a 1-year period (study group) were compared with patients seen by the same surgeon in the previous year who did not receive liposomal bupivacaine (control group). Clinical outcomes included concurrent opioid use, average pain scores, length of stay, ambulation, and range of motion. Results: A total of 357 patients were included in the study. Knee study group patients received lower amounts of opioid (209 vs 248 mg; P = .02) and had a delayed time to first rescue medication (6.3 ± 4.7 vs 5.0 ± 4.4 hours; P = .02). Hip study group patients had a delay in time to first rescue medication (7.1 ± 6.3 vs 4.9 ± 4.0 hours; P = .046). Both knee and hip study group patients had higher average pain score during the 72-hour postoperative period (6.38 vs 6.06; P = .01, and 6.32 vs 5.80; P = .02, respectively) but decreased median length of stay (2.0 vs 3.0 days; P < .0001, and 2.0 vs 3.0 days; P = .04, respectively). Conclusions: Use of liposomal bupivacaine produced a modest decrease in opioid use among knee patients and a decreased length of stay in both knee and hip patients; however, this was accompanied by a non-clinically significant increase in pain scores for knee and hip patients suggesting limited utility for orthopedic procedures.
Highly Probable Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome Associated With Lenalidomide
Authors: Shanbhag Anusha , Pritchard E. Ryan , Chatterjee Kshitij , Hammond Drayton A.
Published: October 2017

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening hypersensitivity reaction to medications. We report a case of a 75-year-old African American female who presented with generalized rash with desquamation and malodorous secretions. She was febrile and hypotensive, and required vasopressors for hemodynamic instability. Sepsis secondary to skin or soft tissue infection was considered initially. However, she recently was started on lenalidomide for treatment of her multiple myeloma, and her white blood cell count of 17 K/µL with 55% eosinophils along with peripheral smear showing eosinophilia suggested lenalidomide-induced rash. Lenalidomide was discontinued, and methylprednisolone was initiated. Four days after lenalidomide discontinuation, vasopressors were discontinued. Blood cultures did not exhibit any growth. The Niranjo Adverse Drug Reaction Probability Scale score of 9 suggests lenalidomide was a highly probable cause of DRESS syndrome. The temporal relation of lenalidomide administration and development of symptoms plus improvement of rash with the discontinuation of lenalidomide and reappearance on restarting lenalidomide in the follow-up clinic strengthens our suspicion of lenalidomide-induced DRESS syndrome. Cases of lenalidomide-induced DRESS syndrome are sparse; however, DRESS syndrome is fatal in approximately 10% of patients. Providers should be aware and keep a vigilant eye out for this adverse reaction with lenalidomide.